Abstracts from the 2014 ISDE World Congress, September 22-24, 2014, Vancouver, Canada.

DISEASES OF THE ESOPHAGUS 2014-Vol. 27 Supplement

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Monday, September 22 – 13:30–15:00 O101: Esophageal Cancer: Pathology/Pathophysiology Room: Salon 2 O101.01: CYCLOOXYGENASE-2 (COX-2) AND METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) GENE POLYMORPHISMS IN ESOPHAGEAL CANCER Ulysses Ribeiro Jr, Evelise Pelegrinelli Zaidan, Michelle Tatiana Tomitão, Márcia Kubrusly, Adriana Vaz Safatle-Ribeiro, Evandro Sobroza De Melo, Rafael Mariano Da Rocha, Rubens Sallum, Ivan Cecconello University of Sao Paulo School of Medicine, Sao Paulo, SP/BRAZIL Background: Brazilian population presents very high levels of genomic diversity due to the multi-ethnicity, which have important clinical/genomic implications. Cyclooxygenase-2 (Cox-2) is induced in response to growth factors and cytokines; and is expressed in inflammatory diseases, premalignant and esophageal tumors. The product of folate metabolism by the enzyme methylenetetrahydrofolate reductase (MTHFR) acts in DNA synthesis. Alteration or inhibition of this enzyme increases the susceptibility to mutations, alter DNA methylation, and gene expression of the tumor suppressor genes and proto-oncogenes, leading to a potential risk factors for esophageal cancer. Cox-2 and MTHFR polymorphisms might modify the levels of protein expression and may have a considerable influence on disease phenotype, which may have important clinical/genomic implications. Aims: To evaluate single nucleotide polymorphisms (SNPs) in the Cox-2 and MTHFR genes and their prognostic value for patients operated on for esophageal cancer; and to investigate possible interactions between these genetic variations and clinicopathologic characteristics in esophageal cancer. Methods: Cox-2 and MTHFR SNPs were analyzed in 114 prospective patients who underwent surgical resection, and had a minimum of 5 years follow-up. DNA was isolated from leukocyte using extraction and purification kit, followed by amplification by polymerase chain reaction (PCR). Real-time analysis was used for genotyping Cox-2 and MTHFR SNPs through the TaqMan ® SNP Genotyping Assay. Results: There was no difference in Cox-2 and MTHFRA polymorphisms among cases and controls (without tumors). We determined frequencies of three Cox-2 polymorphisms (1195A>G/-1329A>G, 8437T>C, 1759G>A), with nine haplotypes; and two MTHFR biallelic polymorphisms (1298 A>C, 677 C>T), with six haplotypes. High frequency of the wild genotype Cox-21195GG was detected in adenocarcinoma tumors. Homozygous Cox-28437CC was associated to Caucasians and younger patients at diagnosis. Polymorphic wild genotype MTHFR-1298AA was increased in squamous cell carcinoma, and younger patients. Wild homozigous MTHFR-677CC was associated to improved survivalship, and to heavy active tobacco smoking patients. Wild homozygous genotype of Cox-2 and MTFHR were significantly correlated to a worst progression-free survival and overall survival when compared to the combined heterozygous or recessive genotypes in a multivariate analysis. Cox-2 immunoverexpression was detected in 70% of the squamous cell carcinoma, and the immunoexpression was not different among the haplotypes.

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Methods: We retrospectively reviewed patients who underwent RFA for Barrett’s dysplasia and or since its introduction in our regional Upper GI unit since July 2011. We prospectively collected data concerning indications, technique, post procedure complications and resolution of Barrett’s with dysplasia following RFA. Results: Twenty-one patients underwent RFA for HGD or LGD with BO at our institution between July 2011 and September 2013 (18 males, 85.7%, median Age = 69 years, Range = 40–87 years). The indication for RFA was HGD in 18 patients and LGD in the rest. Six patients (28.6%) had previously undergone EMR/ESD for treatment of nodules, and one (4.8%) underwent a previous oesophagectomy for a malignant stricture. The median length of Barrett’s segments was 5cm (range 2–12cm). The median number of RFA treatments was 1 (range = 1–2 treatments). Patients were followed up for 1a median of 12 months (range 3–17 months). Among patients who had HGD (n = 18); at 3 months HGD was cleared from 13 patients (72%), 3 of whom still had BO but no dysplasia. 5 patients (27.8%) had persistent HGD at 3 months post RFA. Fourteen patients had at least 12 months follow up, of whom 11 patients (79%) were free of HGD at one year. 3 patients (21%) have developed intra-mucosal cancers during follow up. The remaining 4 patients require further follow-up endoscopy. All three patients (100%) who initially displayed LGD had BO only at 3 months. 2 of these patients reached 12 months endoscopic follow up and they remained clear of dysplasia. Three patients developed intra-mucosal cancers during follow up. One patient underwent an oesophagectomy (histology T1bN1M0R0). One patient had complete resection of a T1aN0M0 oesophageal tumour through endoscopic submucosal dissection. One patient declined surgery and opted for routine follow-up only. All of these three patients remain alive 5 months post-initial RFA. At the time of data collection, 19 patients (90.5%) remain under clinic or endoscopic follow-up. There were 3 (14%) complications. One patient developed acute dysphagia secondary to stricture formation 2 weeks post-RFA. A further patient developed late stricture formation. Both of these patients required endoscopic dilatation of their stricture with good symptomatic relief. One patient developed severe chest pain post-RFA requiring an extended admission for additional investigations and pain management (48 hours postRFA). There was no evidence of perforation on CT and he was later discharged. At the time of data collection one patient has died and his cause of death is unrelated to RFA therapy. Discussion: Dysplasia clearance rates at 3 and 12 months following RFA to HGD, LGD on the background of Barrett’s are good and in accordance with previously published literature. RFA appears to be a safe procedure with low morbidity and no mortality. Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett oesophagus, RFA, dysplasia clearance, morbidity and mortality O101.03: ASSOCIATION BETWEEN BARRETT’S ESOPHAGUS LENGTH AND TOBACCO SMOKING Bashar Qumseya, Yazen Qumsiyeh, Michael Wallace, Herbert Wolfsen Mayo Clinic, Jacksonville/FL/UNITED STATES OF AMERICA

Discussion: 1. Wild homozygous Cox-2 and MTHFR SNPs were associated to disease progression and survival in patients with advanced esophageal cancer; 2. Cox-2 and MTFHR SNPs may be useful markers of aggressiveness in these patients, and may orientate the appropriate target therapy in novel clinical trials.

Background: Smoking has been associated with esophageal cancer and has been identified as a risk factor for Barrett’s esophagus. The effect of smoking on the length of Barrett’s esophagus segment has not been well studied. We aim to investigate the association between tobacco smoking and the length of BE among patients with history of BE.

Disclosure: All authors have declared no conflicts of interest.

Methods: We conducted a retrospective, observational, descriptive study of a large Barrett’s Esophagus database in a tertiary referral center. We extracted data on the length of BE segment, patient age, gender, race, in addition to smoking status (ever smoked vs. never smoked). Our primary outcome of interest was length of BE segment as measured during esophagogastroduodenoscopy (EGD). We used multivariable linear regression models to test for the association between BE length and smoking status while controlling for possible confounders. We used interaction terms to test for effect modification. The final model was tested to insure fulfilment of model assumptions.

Keywords: methylenetetrahydrofolate reductase (MTHFR), Esophageal cancer, clinicopathologic characteristics, Cyclooxygenase-2 (Cox-2) O101.02: RADIOFREQUENCY ABLATION FOR THE TREATMENT OF OESOPHAGEAL DYSPLASIA AND EARLY NEOPLASIA – OUTCOMES FROM A TERTIARY CENTRE IN THE UNITED KINGDOM Zaher Toumi1, Jiten Patel1, Larry Loo2, Jonathan Vickers1, Polobody Sibaprasad Senapati1, Regi George2, Yeng Ang2 1 Salford Royal NHS Foundation Trust, Manchester/UNITED KINGDOM, 2 Salford Royal Hospital, Salford/UNITED KINGDOM Background: Radiofrequency ablation (RFA) and endoscopic mucosal resection (EMR) are increasingly used in the treatment of Barrett’s Oesophagus (BO) with high or low-grade dysplasia (HGD, LGD) and early intramucosal neoplasia. We aim to study patient outcomes after undergoing RFA at a tertiary teaching hospital.

Results: Smokers and non-smokers were similar in mean age, gender, and race distribution. Results are further summarized in table 1. Smokers had a shorter BE segment length compared to non-smokers (median length 3cm vs 5cm, p < 0.0001). On multivariable linear regression modeling, smoking was associated with 1.8 cm (95% CI: 0.9–2.7, p = 0.0002) decrease in the length of BE when controlling for patients age, gender, and race.

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ABSTRACTS PRESENTED AT THE 2014 ISDE CONGRESS


5. Measurement of PGE2 production (pg/TPmg) in esophageal tissue PGE2 synthetic activity was significantly increased in the EDA group (691 ± 50) compared with the sham operated group (25 ± 5) (p < 0.01). Discussion: In this study, we demonstrated that bile reflux of duodenal contents induces COX2 and increases prostaglandin synthesis in dysplastic and cancer tissue.This result suggests a possible mechanism by which bile acids could promote esophageal cancer. Disclosure: All authors have declared no conflicts of interest. Keywords: Bile acids, COX2, Esophageal cancer, duodenoesophageal anastomosis O101.05: TUMOR BETA-1 INTEGRIN AS A POTENTIAL SURVIVAL PREDICTOR IN GASTROESOPHAGEAL CANCER – A CLINICAL CORRELATION Henry Jiang1, Sara Najmeh1, Stephen Gowing1, Monisha Sudarshan1, Ugo Mancini1, Roushika Perez2, Victoria Marcus1, Jonathan Cools-Lartigue1, Lorenzo Ferri1 1 McGill University, Montreal/QC/CANADA, 2University of Toronto, Toronto/ON/CANADA Discussion: Despite the increased risk of BE with smoking, smokers appear to have short BE segments when compared to non-smokers. The pathophysiology of such finding is not clearly understood. Larger studies are needed to verify this trend. Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett’s Esophagus, Smoking O101.04: EFFECT OF BILE ACID ON COX2 IN RAT MODEL OF DUODENOESOPHAGEAL ANASTOMOSIS Hashimoto Naoki Kinki University, Osaka/JAPAN Background: It is known that reflux of duodenal contents (bile acids) can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. We examined the expression of COX2 and prostaglandin E2 (PGE2) in rat esophageal lesions induced by duodenal contents reflux. Methods: Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animal underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy to elicit chronic esophagitis. In ten rats the sham (Control). The rats were sacrificed at the 40th week, their esophagi were examined for HE (Hematoxylin Eosin), COX2, PGE2, and PCNA, and total bile acids in the esophageal lumen was measured. Results: 1. Macroscopic findings The middle and lower esophagus of animals in the EDA group was wide and thickened. There was gross evidence of severe esophageal mucosal injury in the EDA group, which included epithelial thickening and extensive hyperplasia of the lower two thirds of the esophagus. There was a small polyploid tumor in the lower esophagus in the EDA group. The tumor was squamous cell carcinoma and adenocarcinoma. In addition, there was grossly normal tissue in the control group. 2. Microscopic Findings The esophagi of the control rats did not reveal any pathological findings, but various squamous cell lesions were observed in the middle and lower esophagus in the EDA group. All animals from the EDA group showed histological features of esophagitis, including marked hyperplastic changes with increased thickness of the squamous epithelium, hyperkeratosis and regenerative changes with papillomatosis, and basal cell hyperplasia. These features were not found in the control group. Columnar lined epithelium (CLE) and epithelial ulceration were frequently present adjacent to the anastomosis. CLE was observed in 40% at the 40th week. Sever dysplasia in the lower esophagus occurred in 100%, squamous cell carcinoma (SCC) was observed in 40% and adenocarcinoma (ADC) was observed in 30% at the 40th week. To assess the biological behavior of various squamous lesions, we performed immunohistochemical staining for PCNA because the proliferative index is often increased in dysplastic and cancerous tissues. The PCNA labeling index of dysplasia and cancer(75 ± 5%) was higher than that of control (30 ± 5%) (p < 0.05). 3. Total bile acid in the esophageal lumen (μmol/L) Total bile acid in the esophageal lumen was significantly increased in the EDA group(175 ± 5) compared with the sham operated rats (35 ± 5) (p < 0.05). 4. Immunohistochemistry of COX2 Every animal that suffered from reflux demonstrated COX2 protein expression in the lower esophagus. COX2 was abundantly expressed in both inflammatory and proliferative esophageal mucosa of rats exposed to chronic duodenoesophageal reflux (EDA). Some SCC and ADC epithelial cells strongly expressed the COX2 protein.

Background: Integrin expression on cancer cells has profound implications in tumor progression. Emerging work suggests that beta-1 integrin is a key mediator of adhesion between cancer cells and neutrophil extracellular DNA, which has been recently identified as a novel mechanism of cancer metastasis. To determine its clinical importance, we examined the relationship between the level of beta-1 integrin expression and survival in a group of 35 patients who underwent surgery for gastroesophageal (GE) cancer. Methods: We constructed a tissue microarray (TMA) using cores from paraffin embedded tumor blocks from 35 patients with adenocarcinoma of the GE junction. Immunohistochemistry was carried out to stain beta-1 integrin. All specimens were reviewed by a board certified pathologist. The stained slides were read by Image-Scope® and subsequently analyzed by Aperio® Image Analysis Software to yield raw beta-1 scores based on intensities of expression (3, 2, 1, 0) and percentage of cells within each intensity. The weighted beta-1 score is calculated as the sum of the product of the respective pairs of percentages and intensities. Kaplan-Meier plots and logrank tests were prepared using JMP® Statistical Software. Results: Of the 35 tumor cores in the TMA, only 26 contained sufficient cancer cell content for immunohistochemistry of beta-1 integrin. Of the 26 cores analyzed, 24 (92%) were positive for beta-1 integrin. The overall survival (OS) of patients with tumors expressing high beta-1 vs. low beta-1 integrin at 1, 3 and 5 years are 93%-vs.-91%, 67%-vs.-55%, and 60%-vs.-27%, respectively (p = 0.13, log-rank test). The disease free survival (DFS) of patients with high beta-1 vs. low beta-1 expressing tumors at 1, 3 and 5 years are 93%-vs.-64%, 53%-vs.-27%, and 53%-vs.-27%, respectively (p = 0.16, log-rank test). Although neither comparison is statistically significant, there appears to be a trend for high beta-1 expression to be associated with more death and recurrence. More death occurred one year after surgery in patients with high beta-1 expressing tumors, whereas more recurrence occurred within a year of surgery in the high beta-1 expressing group. These trends persisted 5 years after surgery. Discussion: Beta-1 integrin is highly expressed in human esophageal cancer tissue. Though our study with limited sample size did not demonstrate significant association between the expression of beta-1 and post-operative survival in patients with GE junction cancer, a trend appears to exist. By expanding our TMA database, we hope to elucidate the true clinical effect of beta-1 integrin. Disclosure: All authors have declared no conflicts of interest. Keywords: Beta-1 integrin, Gastroesophageal cancer, Adhesion and Metastasis, Post-operative recurrence O101.06: THE SURVIVAL PREDICTIVE SIGNIFICANCE OF HOXC6 AND HOXC8 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA Ke-Neng Chen, Ya-Bing Du, Lu-Yan Shen, Liang Dai, Bin Qin, Hong-Chao Xiong, Xiao-Zheng Kang, Zhen Liang, Wan-Pu Yan Beijing Cancer Hospital, Beijing/CHINA Background: Esophageal squamous cell carcinoma (ESCC), a common disease in China, is mainly treated surgically. We established a prospective database of patients with esophageal cancer between January 2000 and December 2010, including 486 subjects with ESCC who underwent surgical treatment. In this study, we explored the prognostic significance of the expression of HOXC6 and HOXC8, responsible for embryonic development, by studying the specimens collected from clinical subjects during strict follow-up periods. Methods: Immunohistochemistry (IHC) was used to detect the expressions of HOXC6 and HOXC8 in 274 ESCC subjects including 138 ESCC subjects treated with surgery alone and 136 ESCC subjects treated with neoadjuvant


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chemotherapy. Survival analysis was performed from the day of surgery to August 2013. Results: The 5-year survival rate of the 274 ESCC subjects was 44.2%, with a median survival time of 44.12 months. For the 274 ESCC subjects involved in the investigation of HOXC6 and HOXC8 expressions, the median survival time of subjects with high-level expression of HOXC6 and HOXC8 was shorter than that for subjects with low-level expression (P = 0.001, P < 0.001, respectively). Similar results were obtained from the analysis of the prognostic value of HOXC6 and HOXC8 in the group treated with surgery alone and the group treated with neoadjuvant chemotherapy. Multivariate analysis demonstrated that HOXC6 and HOXC8 expression were independent prognostic factors in patients with ESCC. Discussion: TNM stage were still the prognostic marker of ESCC. Whether TRG is used as the predictor of prognosis of patients with neoadjuvant chemotherapy remains further estimated. HOXC6 and HOXC8 expressions could be used to assist the determination of tumor sensitivity to chemotherapy. HOXC6 and HOXC8 can be considered prognostic factors in addition to the TNM stage to provide a reference for clinical work. However, this study has a few limitations. First, although the database was prospective, the study was retrospective actually. Second, the sample size was relatively small. Third, there was a poor match of clinical stages between the neoadjuvant chemotherapy group and the surgery only group. These limitations can be overcome in a future prospective study consisting of a large number of randomly grouped subjects with the same conditions. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal squamous cell carcinoma, HOXC6, HOXC8, Survival O101.07: CLINICAL AND BIOLOGICAL IMPACT OF CYCLINDEPENDENT KINASE SUBUNIT 2 (CKS2) IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA Yoshiaki Kita1, Hiroshi Okumura1, Yuka Nishizono1, Yasuto Uchikado1, Ken Sasaki1, Masataka Matsumoto1, Tetsuro Setoyama1, Kiyonori Tanoue1, Itaru Omoto1, Shinichiro Mori1, Tetsuhiro Owaki1, Sumiya Ishigami1, Hiroshi Nakagawa2, Koshi Mimori3, Masaki Mori4, Shoji Natsugoe1 1 Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima/ JAPAN, 2Division of Gastroenterology, Department of Medicine, Philadelphia/PA/UNITED STATES OF AMERICA, 3Department of Surgery, Bepppu Hospital, Beppu/JAPAN, 4Osaka University, Suita/ JAPAN Background: Cyclin-dependent kinase subunit 2 (CKS2) is a cyclin-dependent kinase subunit (CKS) family menber that participates in cell cycle regulation. Few studies have investigated its involvement in esophaeal squamous cell carcinoma (ESCC). The aim of this study was to assess the cliical significance of CS2 in ESCC. Methods: We used immunohstochmisry t sudy the clincopahologic significane of CKS2 prtn expression in 121 patients with ESCC. Using real time reverse transcriptase-polymrase chain reaction (RT-PCR), we examined the expression of CKS2 mRNA in tumors and the corresponding normal esophagel tissues that were obained from 62 patients. Finally, siRNA mediated attenuation of CKS2 expression was exained in vitro. Results: CKS2 protein expression was significantly correlated with depth of tumor invasion, clinical stage, lymphatic invasion, and distant metastasis (p = 0.033, 0.028, 0.041, and 0.009 respectively). CKS2 mRNA expresio was higher in cancer tissue than in corresponding normlal tissue (p < 0.001). Patients with positive CKS2 potein exprssion had a poorer five years suvival frequency than patients who did not express CKS2 protein (p = 0.025). In vitoro, siRNA mediated suppression of CKS2 slowe the grouth rate of ESCC cells compared control cells (p < 0.001). Discussion: We previously analyzed genes related to lymph node metastasis in ESCC. Using laser microdissection techniques and cDNA and oligo nucleotide microarray, several genes were identified simultaneously in comparisons of lymph node-positive and -negative primary tumors or primary tumors and lymph node metasasis. CKS2 was among the gene of interest that were identified. Moreover, our in vitro study implcated CKS2 may play an important role by inhibiting apoposis as observed in other cancers. In this study, CKS2 expression was associted with lymphatic invasion and distant metastasis. The evaluation of CKS2 expression is useful fo predicting the cause of maligant tumors and the prognosis of patient with ESCC. Disclosure: All authors have declared no conflicts of interest. Keywords: CKS2, Esophageal squamous cell carcinoma, prognosis, biomarker

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O101.08: DIFFERENT EXPRESSION OF LONG NONCODING RNAS AND THEIR FUNCTIONS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA Suqing Li, Yusuo Tong, Lei Tuo, Chunmei Wang, Haiwei Xie, Jin Lv, Lv Ji, Bin Zhu, Xiaobin Yang, Jinsong Wang, Weihong Shi, Xiufeng Cao Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing/CHINA Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive tumors, which is the leading cause of cancer-related death. Long noncoding RNAs (lncRNAs) are a novel class of mRNA-like transcripts without protein coding function, however, they play a variety of functions including roles in tumorigenesis and metastasis. Methods: To investigate the function of lncRNAs in ESCC, we performed the expression profile of lncRNAs in six pairs of clinical ESCC samples using microarray assay. The results were further validated in 109 ESCC patients by quantitative real-time PCR (qRT-PCR). Functional analysis of selected lncRNAs in ESCC carcinogenesis in vitro were also performed. Results: Our microarray analyses identified 2210 human lncRNAs were differentially expressed (greater-than or equal to 2-fold change) in ESCC samples compared with normal tissues, of which 952 lncRNAs were upregulated and 1258 lncRNAs were down-regulated. Five up-regulated lncRNAs (HUESCC-lncRNA1 (92/109, p < 0.01), HUESCC-lncRNA2 (80/109, p < 0.01), HUESCC-lncRNA3 (85/109, p < 0.01), HUESCClncRNA4 (84/109, p < 0.01), HUESCC-lncRNA5 (75/109, p < 0.01)) and seven down-regulated lncRNAs (HDESCC-lncRNA1 (88/109, p < 0.01), HDESCC-lncRNA2 (96/109, p < 0.01), HDESCC-lncRNA3 (89/109, p < 0.01), HDESCC-lncRNA4 (77/109, p < 0.01), HDESCC-lncRNA5 (75/109, p < 0.01), HDESCC-lncRNA6 (77/109, p < 0.01), HDESCC-lncRNA7 (87/109, p < 0.01)) were selected for further confirmation of microarray results by qRT-PCR, and a strong correlation was identified between the qRT-PCR results and microarray data. Through statistical analysis, we found that some of these twelve lncRNAs have relationships with clinicopathologic classifications. For example, HUESCC-lncRNA2 expression was found to be closely related to clinical stage (p < 0.05), while high expression of HUESCC-lncRNA5 was discovered to be significantly correlated with both N stage (p < 0.05) and clinical stage (p < 0.05). Moreover, overexpression of HUESCC-lncRNA5, was observed in ESCC cells. Small interfering RNA induced silence of HUESCC-lncRNA5 significantly reduced migration and invasion of ESCC cells in vitro, but had less effect on cell cycle, apoptosis and proliferation. Discussion: Our findings indicate that some lncRNAs are differently expressed and act as functional markers in esophageal squamous cell carcinoma. HUESCC-lncRNA5, biomolecule of HOX gene family, which is similar to HOTAIR, has an important impact on metastasis of tumor cells. Taken together, this study may provide potential targets for future diagnosis and treatment of ESCC and novel insights into cancer development and progression. Disclosure: All authors have declared no conflicts of interest. Keywords: matestasis, LncRNA Profile, microarray, ESCC

O101.09: PROTEASE-ACTIVATED RECEPTORS IN BARRETT’S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA Wayne Phillips, Shze Yung Koh, Nicholas Clemons Peter MacCallum Cancer Centre, Melbourne/VIC/AUSTRALIA Background: Chronic gastroesophageal reflux is a known risk factor for Barrett’s esophagus. The active agents in the refluxate are thought to be primarily acid and bile but reflux material also contains other biologically active molecules, including proteases such as trypsin and pepsin. Furthermore, the inflammatory milieu associated with Barrett’s esophagus contains a variety of proteases released by stromal cells and infiltrating inflammatory cells. While the traditional view of proteases is that they are blunt proteindegrading enzymes involved in the digestive process, it is becoming increasingly apparent in a number of physiological systems that proteases are also versatile and multifunctional hormone-like signaling molecules that can regulate cellular functions through their interaction with a large variety of targets, including specific receptors such as the protease-activated receptors (PARs). PARs are a family of seven-transmembrane G-protein-coupled receptors that mediate cellular signaling in response to extracellular proteases. The PARs have a unique mechanism of activation in that they effectively carry their own activating ligand in a masked state. Unmasking of the ligand, and activation of the receptor, is achieved through the proteolytic cleavage of a specific site on the extracellular N-terminal portion of the receptor. This allows the newly revealed ‘tethered ligand’ to bind to a specific extracellular domain on the receptor to trigger intracellular signaling. In this study, we have investigated the potential role of PARs in the pathophysiology of the Barrett’s esophagus. Methods: We have used quantitative real-time reverse transcriptase-PCR to assess the expression of PARs in normal esophagus, Barrett’s esophagus and

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esophageal adenocarcinoma tissues, and cell lines. PAR-mediated signaling was assessed by the protease-dependent mobilisation of calcium from intracellular stores using the Fluo-4 Direct™ calcium assay. Results: We found that human esophageal epithelial cells express both PAR1 and PAR2. While mRNA for PAR3 and PAR4 was detected in Barrett’s esophagus and esophageal adenocarcinoma tissues, we could not detect either in purified esophageal epithelial or fibroblast cell lines suggesting that the PAR3 and PAR4 may be derived from infiltrating inflammatory cells. Using a panel of Barrett’s esophagus (GihTERT, GohTERT, QhTERT) and esophageal adenocarcinoma (JH-EsoAd1, OE33, FLO1) epithelial cell lines, we further demonstrated that the release of calcium stimulated by the protease thrombin was significantly reduced by either the depletion of PAR1 by small interfering RNA or in the presence of a PAR1 antagonist, confirming PAR1-mediated signalling in these cells. Similarly, treatment of esophageal epithelial cells with trypsin or synthetic PAR2-activating peptides resulted in PAR2-mediated release of intracellular calcium. Discussion: Our results demonstrate the expression of functionally active PAR1 and PAR2 by esophageal epithelial cells. This, together with the known presence of proteases, such as trypsin, in the refluxate of patients with chronic gastroesophageal reflux disease raises the possibility of a role for PARs in the pathogenesis of Barrett’s esophagus and/or progression to esophageal adenocarcinoma. Disclosure: All authors have declared no conflicts of interest. Keywords: signaling, proteases, inflammation, calcium mobilisation

Monday, September 22 – 15:30–17:00 O102: Barrett’s Esophagus: Diagnosis and Management Room: Salon 2 O102.01: INFRARED SPECTRAL CYTOPATHOLOGY AS A DIAGNOSTIC TOOL IN SCREENING FOR BARRETT’S ESOPHAGUS Oliver Old1, Max Almond1, Doug Townsend2, Gavin Lloyd1, Kathleen Lenau2, Max Diem2, Hugh Barr1 1 Gloucestershire Royal Hospital, Gloucester/UNITED KINGDOM, 2 Northeastern University, Boston/UNITED KINGDOM Background: Screening for Barrett’s esophagus (BE) could allow early detection, enabling timely diagnosis and intervention for esophageal adenocarcinoma. Recent studies have shown the acceptability of a swallowed cytology brush (‘Cytosponge’) for cell collection. If introduced, cytological assessment would pose several challenges. Firstly, esophageal cytology is performed infrequently, and expertise in this field is correspondingly limited. Secondly, assessment of individual cells is challenging even for experienced cytopathologists, with a degree of interobserver variability. Thirdly, screening would require a great deal of cytopathology resources. Infrared (IR) spectroscopy identifies subtle biochemical differences in biological substrates based on differential IR absorption; applying multivariate statistical analysis and computer modelling can provide robust and rapid discrimination between pathological cell subtypes. We aimed to demonstrate the potential application of IR in analysis of esophageal cytology. Methods: Endoscopic cytology brushes were used to collect esophageal cells from patients undergoing planned endoscopy for BE. Cells were fixed in formalin, centrifuged and slides prepared. IR spectra were measured across the entire sample area. Pre-processing steps allowed spectra from individual cells to be reconstituted. Further pre-processing removed confounding effects and enhanced signal-to-noise ratios. Conventional cytology analysis was undertaken to provide a reference for developing a predictive model using IR data. Chemometric analysis was then undertaken using Partial Least Squares Discriminant Analysis (PLS1DA) and cross-validation performed. Results: 23 cytology brush samples were collected from 11 patients. 4 samples contained low cell counts and were excluded from analysis. 5536 cells (2339 normal squamous, 2511 BE and 686 dysplastic) were used to create and validate a predictive model. The predictive capability of the model is shown in the table below: Classification accuracy of Infrared spectroscopy Sensitivity Specificity

Normal Squamous

Barrett’s Esophagus

Dysplasia

100% +/− 1% 99% +/− 1%

96% +/− 2% 99% +/− 1%

94% +/− 3% 98% +/− 1%

Discussion: With such high accuracy demonstrated by our predictive model, IR spectral cytopathology shows great promise as a diagnostic tool for cytological analysis of esophageal cells. As an objective, automated system, this technique has potential as a future diagnostic tool, and could prove invaluable if a cytology-based screening programme were implemented for BE.


Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett’s Esophagus, screening, infrared spectroscopy, cytology O102.02: CLINICAL EVALUATION OF A NEW CRYOBALLOON FOCAL ABLATION SYSTEM FOR THE ELIMINATION OF BARRETT’S ESOPHAGUS Dirk Schölvinck1, Jacques Bergman2, Christine Kestens3, Peter Siersema3, Frank Vleggaar3, Marcia Canto4, Hilary Cosby4, Julian Abrams5, Charles Lightdale5, Elizabeth Tejeda-Ramirez5, Steven Demeester6, Christina Greene6, Blair Jobe7, Jeffrey Peters8, Bas Weusten1 1 St. Antonius Hospital, Nieuwegein/NETHERLANDS, 2Academic Medical Center Amsterdam, Amsterdam/NETHERLANDS, 3Universitary Medical Center, Utrecht/NETHERLANDS, 4John Hopkins Medical Institutions, Baltimore/MD/UNITED STATES OF AMERICA, 5Columbia University Medical Center, New York/NY/UNITED STATES OF AMERICA, 6 University of Southern California, Los Angeles/CA/UNITED STATES OF AMERICA, 7Canonsburg General Hospital, Canonsburg/PA/UNITED STATES OF AMERICA, 8University of Rochester, Rochester/NY/ UNITED STATES OF AMERICA Background: RFA has become the preferable method for eradication of BE, when indicated. Although highly effective, RFA suffers from drawbacks such as the need for precise sizing, multiple deployment steps, and large controller units.The aim was to assess the feasibility, safety, and doseresponse of a newly developed Cryoballoon Focal Ablation System (CbFAS) in patients with flat BE with or without dysplasia. The system was designed to address many of the limitations of current ablation techniques. Methods: In this ongoing multi-center, prospective non-randomized trial, up to 40 patients will be enrolled with each subject receiving up to 2 ablations using the CbFAS using two doses. The CbFAS consists of a TTS catheter with a balloon probe made of a conformable material obviating the need for sizing. The balloon is simultaneously inflated and cooled with cryogenic fluid delivered from a small disposable canister, resulting in ablations of approximately 2 cm2. Symptoms were assessed directly after and 2 days after CbFA. Followup endoscopy with photo documentation and biopsy of the treated areas was scheduled at 6–8 weeks. Primary outcomes were incidence of adverse events, pain, esophageal stricture formation, and ablation response by cryogen dose. Results: By March 2014, 49 ablations (6s in 10, 8s in 28, 10s in 11) were performed in 33 patients. Median (IQR) procedure time was 8 (3–10) min. Device malfunction was encountered in 2 additional patients. No major adverse events occurred, while 5 patients had minor mucosal lacerations that required no additional intervention. Mild pain was reported immediately after the procedure in 7 of 33 patients and in 6 patients at 2 days. At followup endoscopy full squamous regeneration was seen in 29 treated areas (6/10 areas treated with 6s; 23/28 areas treated with 8s with CbFA; 10s ablations pending follow up endoscopy). No strictures had developed. Discussion: Preliminary results of this multicenter prospective trial suggest that focal cryobablation of BE with the newly developed CbFAS is feasible, safe, and results in squamous regeneration in the majority of patients. Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett, Cryoablation, Cryotherapy O102.03: ADVANCED ENDOSCOPIC IMAGING OF BARRETT’S ESOPHAGUS: A FEASIBILITY STUDY OF RAMAN SPECTROSCOPY IN THE PRESENCE OF ENDOSCOPIC WHITE LIGHT AND NARROW BAND IMAGING Oliver Old, Max Almond, Gavin Lloyd, Catherine Kendall, Hugh Barr Gloucestershire Royal Hospital, Gloucester/UNITED KINGDOM Background: Raman Spectroscopy (RS) is an optical diagnostic technique which probes tissue biochemistry based on the scattering of light. Recent studies have demonstrated the ability of a Raman probe compatible with an endoscope to accurately identify pathological subgroups in Barrett’s esophagus (BE) in ex vivo tissue. To achieve the goal of translation to clinical use at endoscopy, one crucial step is ensuring feasibility of RS in the presence of white-light from the endoscope (WLE) and potentially other advanced imaging modalities. Narrow Band Imaging (NBI) illuminates mucosa with blue/green light to enhance the resolution of the mucosal surface to identify dysplasia/early cancer. This study aimed to assess the potential for endoscopic multi-modality imaging using RS, NBI and WLE. Methods: A 2-stage experiment was constructed: • Stage 1 aimed to identify the spectral interference caused by WLE and NBI. Raman spectra were measured (5 second acquisitions) in the presence of WLE and NBI: air background, polytetrafluoroethylene (PTFE) standard and fresh esophageal biopsies were measured, and repeated following exclusion of ambient light (control measurement). Resulting spectra were plotted and visually compared for areas of discrepancy representing spectral interference.


ABSTRACT SUPPLEMENT

• Stage 2 analysed the previously collected dataset of spectra from ex vivo tissue samples (collected without WLE or NBI) using only those wavenumbers not affected by spectral interference from WLE and NBI as determined in stage 1. The previous dataset included 798 ex vivo esophageal samples from 62 patients; 1-second spectra were acquired across the wavenumber range 400–1850 cm-1. Classification models were developed to discriminate pathological subgroups: Principal Component-fed Linear Discriminant Analysis algorithms tested using leave one spectrum out cross-validation. The results of the classification model using the truncated dataset were compared against the classification models developed using the entire wavenumber range.

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the cardia and proximal of the GF contained IM in 0% and 63% respectively. Discussion: In Western patients PV are frequently seen with the latest version NBI-system. PV are best observed under optimal insufflation. In a substantial subset of patients the GF and PV differ in location and IM can be detected in biopsies from this “zone of discordance”, whereas no IM is detected in biopsies distal to the PV. These results question the value of the GF as the distal margin of the Barrett’s segment. Disclosure: All authors have declared no conflicts of interest. Keywords: Palisade vessels, Barrett

Results: • Ex vivo Raman spectra were measured from 13 fresh esophageal biopsies collected from 3 patients. Consistent spectral interference in the wavenumber region 1460–1600cm-1 was noted for air background, PTFE and tissue spectra. • Wavenumbers above 1465cm-1 were excluded and classification models developed. Predictive capability of the truncated dataset is shown compared against the whole wavenumber datset in the table below: Classification accuracy of the truncated vs. whole dataset Dataset

Pathology subgroup

Sensitivity

Specificity

Truncated spectral range (400–1465)

Normal Squamous LGD/Barrett’s HGD/ Adenocarcinoma Normal Squamous LGD/Barrett’s HGD/ Adenocarcinoma

86% 73% 86%

95% 91% 86%

87% 72% 86%

96% 91% 88%

Whole spectral range included (400–1850)

Discussion: Classification performance remained high using a truncated spectral range. These findings demonstrate feasibility of RS in the presence of WLE and NBI and suggest promising potential for multimodality imaging using WLE, NBI and RS. Disclosure: All authors have declared no conflicts of interest. Keywords: Narrow Band Imaging, Barrett’s Esophagus, Advanced endoscopic imaging, Raman spectroscopy O102.04: ARE THE GASTRIC FOLDS STILL THE OPTIMAL LANDMARK FOR DEFINING THE DISTAL BORDER OF A BARRETT’S ESOPHAGUS IN A WESTERN POPULATION? Dirk Schölvinck1, Osamu Goto2, Kees Seldenrijk3, Jacques Bergman4, Naohisa Yahagi2, Bas Weusten3 1 St. Antonius Hospital, Nieuwegein/NETHERLANDS, 2Cancer Center, Keio University, School of Medicine, Tokyo/JAPAN, 3St. Antonius Hospital Nieuwegein, Nieuwegein/NETHERLANDS, 4Academic Medical Center Amsterdam, Amsterdam/NETHERLANDS Background: The definition of the esophagogastric junction (EGJ) for a diagnosis of Barrett’s esophagus (BE) is not uniform: according to Western guidelines, the EGJ is located at the top of the gastric folds (GF), assessed during expiration. In contrast, in Japan the EGJ is defined by the distal end of the palisade vessels (PV). However, PV are faint and often not clearly visible in Western patients. Narrow Band Imaging (NBI) enhances contrast in mucosal structures and vessels. The new Olympus EXERA III endoscopy system combines bright NBI with dual focal high-resolution endoscopy, and may more easily visualize PV, even in Western BE patients. The aim was to evaluate the detection rate of PV using the new EXERA III system, to quantify the discordance between the Western and Japanese criteria for the distal border of BE, and to evaluate the presence of intestinal metaplasia (IM) in this “zone of discordance” (ZoD), in Western BE patients. Methods: Consecutive Dutch patients with BE segment of ≥2 cm (no dysplasia or low-grade dysplasia) on previous endoscopy were enrolled. Endoscopies were performed by a Western expert endoscopist, assisted by a Japanese endoscopist. The distance of the GF and distal ends of PV (when visible) to the incisors were determined in in- and desufflated conditions. Any difference in distance between the top of the GF (assessed during expiration) and the distal end of the PV was considered a ZoD. Two biopsies were taken from the cardia (either 1 cm below the distal end of the PV, or 1 cm below the GF in case of absence of PV), two biopsies from the ZoD when present, and 4-quadrant biopsies starting 1 cm proximal of the GF to determine the presence of IM. Results: 25 patients (19 males, median 66 yrs, median BE C5M7) were included. PV were seen in 96%. They were more often visible during inspiration (96%) than in expiration (76%; p = 0.06). PV were located in a constant position during in- and expiration. In patients with visible PV, in 63% (n = 15) a ZoD was present during expiration with the GF median 1 cm (range 1–2) proximal to the PV. In patients with a ZoD, IM was present in 6/30 (20%) of the ZoD biopsies. This was more compared to the cardia biopsies (0/30; 0%; p = 0.01) and less compared to the biopsies obtained proximal of the GF (35/60; 58%; p < 0.001). In the 10 patients without ZoD biopsies of

O102.05: SEGMENT LENGTH REDUCTION TIME OF BARRETT’S ESOPHAGUS AFTER RADIOFREQUENCY ABLATION IS ASSOCIATED WITH REMISSION OF DYSPLASIA AND METAPLASIA Daniel Chan, Cadman Leggett, Emmanuel Gorospe, Lori Lutzke, Kenneth Wang Mayo Clinic, Rochester/MN/UNITED STATES OF AMERICA Background: Radiofrequency ablation (RFA) is widely used in the treatment of dysplastic Barrett’s esophagus (BE). There is empiric evidence to suggest that rapid reduction in BE segment lengths following RFA is associated with improved outcomes in achieving remission of dysplasia and metaplasia. We aim to validate and quantify this association. Methods: 268 patients enrolled in a BE surveillance program and treated with RFA from 2003 to 2013 at a tertiary medical center were included in the study. Pre-RFA histology included 39 patients with low-grade dysplasia (LGD), 183 with high-grade dysplasia (HGD) and 46 with intramucosal carcinoma (IMCa). Nodular lesions were removed with endoscopic mucosal resection and the remaining BE were treated with RFA. There were 95 patients with short segment BE (3 cm). Subjects were followed on average for 2.39 ± 1.64 years. Outcomes measured included complete eradication of dysplasia (CR-D) and metaplasia (CR-IM) defined by absence of dysplasia or intestinal metaplasia, respectively after two sequential follow-up endoscopies with biopsies. We evaluated for the time to achieve 50% reduction in BE segment length taking the difference between maximal extent BE segment lengths measured at initial RFA and subsequently during surveillance. 50% Segment Length Reduction (SLR) time was analyzed for association with CR-D and CR-IM outcomes. Results: Overall 227 (84.7%) patients achieved 50% SLR with a mean time of 7.87 ± 7.37 months from initial RFA. Kaplan-Meier analysis showed a significant association for achieving CR-D (p = 0.04, HR 1.38 95% CI 1.02, 1.89) and CR-IM (p < 0.0001, HR 1.74 95% CI 1.32, 2.32) in patients with shorter 50% SLR times (Figure 1). There was no association between 50% SLR time and aspirin or statin use. The degree of initial dysplasia (LGD, HGD, IMCa) was not significantly associated to 50% SLR times. There was a significant association between those with initial short segment BE achieving CR-D (p = 0.02, HR 1.68 95% CI 1.15, 2.40) and CR-IM (p < 0.0001, HR 2.03 95% CI, 1.36, 2.95) earlier than long segment BE respectively.

Discussion: In patients undergoing RFA, 50% SLR time is associated with CR-D and CR-IM and may be a marker of response to ablative therapy. Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett’s Esophagus, radio frequency ablation, dysplasia, segment length

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O102.06: TISSUE AND PLASMA LEVELS OF MIC-1/GDF-15 INCREASE DURING THE MALIGNANT TRANSFORMATION OF BARRETT’S ESOPHAGUS AND HIGH MIC-1 PLASMA LEVELS MAY BE ASSOCIATED WITH WORSE PROGNOSIS FOR PATIENTS WITH ESOPHAGEAL ADENOCARCINOMA Oliver Fisher1, Angelique Levert-Mignon1, David Brown1, Natalia Botelho1, Dan Falkenback2, Melissa Thomas1, Sarah Lord3, Yuri Bobryshev1, Samuel Breit1, Reginald Lord1 1 St. Vincent’s Centre for Applied Medical Research, Sydney/NSW/ AUSTRALIA, 2Lund University Hospital, Lund/SWEDEN 3 University of Notre Dame School of Medicine, Sydney/NSW/ AUSTRALIA Background: Macrophage inhibitory cytokine 1 (MIC-1/GDF-15) is a member of the TGF-β superfamily which has been detected in various mammalian tissues. It has been shown to play many – sometimes contradictory – roles in multiple pathologies, including cardiovascular disease, obesity, and inflammation as well as cancer. MIC-1 plasma levels predict disease progression in prostate, breast and colorectal cancer. In this novel study we investigated the biomarker potential of tissue and blood levels of MIC-1 in BE and EAC. Methods: 138 patients were studied: 45 normal esophagus/healthy controls (NE), 37 Barrett’s esophagus (BE IM) with no dysplasia, 16 BE low-grade dysplasia (LGD) and 40 esophageal adenocarcinoma (EAC) patients. Tissue levels were measured using multiplex qRT-PCR. Plasma levels were determined using a validated ELISA. Receiver-operator characteristics with corresponding AUC were generated to determine the diagnostic potential for MIC-1 in BE monitoring. Results: Median MIC-1 mRNA tissue expression increased a significant 25-fold from NE to BE and increased further in LGD tissues. MIC-1 tissue levels were significantly increased in EAC compared to both BE and NE. MIC-1 plasma values were significantly higher in patients with EAC when compared to patients with NE or BE. Plasma levels higher than 811 pg/ml were associated with a diagnosis of EAC with a sensitivity of 83% (95%CI 65% – 94%) and specificity of 62% (95%CI 50 – 74%; ROC AUC = 0.75 [95%CI 0.65 – 0.85]). In a multivariable Cox-regression model adjusting for patient age, BMI (associated with MIC-1 levels), and tumor stage, high MIC-1 plasma levels (over 1140pg/ml) were an independent predictor of worse survival for patients with EAC (HR 3.87, 95%CI 1.01 – 14.75; p = 0.047). Discussion: Plasma and tissue levels of MIC-1 are significantly elevated in patients with BE IM, LGD and EAC. There is a potential inverse association between high MIC-1 plasma levels and survival for patients with EAC. Plasma MIC-1 may have value in a panel with other markers as a diagnostic and monitoring tool for patients with BE or EAC. Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett’s Esophagus, Esophageal adenocarcinoma, prognosis, MIC-1/GDF-15 O102.07: THE GWENT BARRETT’S OESOPHAGUS REGISTRY – THE WELSH EXPERIENCE Kristof Nemeth, Varsha Shah, Ashraf Rasheed Royal Gwent Hospital, Newport/UNITED KINGDOM Background: Barrett’s Oesophagus (BO) is a metaplastic alteration of the normal oesophageal epithelium that is detected on endoscopic examination and is confirmed or corroborated on histological examination of the biopsies. BO is a predisposing factor for oesophageal adenocarcinoma (OAC) and the progression to cancer is a multi-steps accumulation of genetic mutations, accompanied by histologic changes from metaplasia to low grade (LGD) and high grade dysplasia (HGD) and finally carcinoma. This multisteps progression to malignancy is the basis for the current BO surveillance practice, in an attempt to detect cancer at an earlier stage to improve survival. Up until the end of 2013 the UK surveillance practice was based on the 2005 Guideline from the British Society of Gastroenterology (BSG). Endoscopic surveillance has several shortcomings including limited sampling of affected mucosa, the extensive time required to obtain the recommended number of biopsies, non-compliance, and relatively poor pathological inter-observer reproducibility. Methods: The main aim was to compare the current practice at the local health board with the 2005 guidelines on management of BO issued by the BSG. Secondary aims are the assessment of the efficiency of surveillance and


the progression rate from BO/Low-Grade Dysplasia (LGD) to High-Grade Dysplasia(HGD)/Adenocarcinoma. In the form of an observational study all cases coded in the local health board histopathology database as BO during the period from 2005 to 2012 have been identified. The histology reports were matched with the corresponding endoscopy reports. The accumulated data was used to build a registry and also to audit the surveillance practice against the 2005 BSG guidance. Results: 620 cases had BO, 406 males and 214 females, mean age of 63.50 years (SD 12.61,range 20–97years). Intestinal metaplasia was confirmed in 459/620 cases. Based on the histology reports 544/620 BO patients never progressed to any dysplasia stage. Only 178/544 (33%) had at least on followup appointment (mean follow-up 19.52 Months, SD 11.75, Median 23). We have identified 46/620 LGD cases 16 of which were prevalent cases present at index endoscopy. 37/46 cases had at least one follow up. The mean follow up for LGD was 17.55 months (SD 12.30, median 14) There were 14/620 cases of HGD with 11/620 being prevalent cases detected at or within a year of index endoscopy. The mean follow-up for HGD was 5.53 Months (SD 4.31, median 4.00). Discussion: The audit highlighted lacking compliance with BSG guidance for BO surveillance which is in keeping with published literature on the topic. Only 178 of the 544 (32.72%) simple Barrett’s Oesophagus cases were followed up. For LGD we had 37/46 cases (80%) followed up. All the HGD and OAC cases received follow-up. We have identified a need for compliance and quality improvement in our practice and have started using our registry to improve on the follow up strategy. Our department has also introduced dedicated endoscopy lists for Barrett’s Surveillance in order to improve the quality of sampling. Our surveillance practice will also be influenced by the new 2013 BSG Guidelines. Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett’s Esophagus, surveillance O102.08: SUCCESSFUL RECRUITMENT TO BARRETT’S OESOPHAGUS SURVEILLANCE STUDY (BOSS): YOU CAN RANDOMIZE TO ‘AT NEED’ ENDOSCOPY Oliver Old1, Clive Stokes1, Corran Roberts2, Sharon Love2, Chris Foy1, Julie Hapeshi1, Hugh Barr1 1 Gloucestershire Royal Hospital, Gloucester/UNITED KINGDOM, 2Centre for Statistics In Medicine, Oxford/UNITED KINGDOM Background: Barrett’s esophagus (BE) is a recognised pre-malignant condition which is readily identifiable at endoscopy. Consequently current international guidelines advise routine endoscopic surveillance for patients with BE to enable early detection of esophageal adenocarcinoma. However, evidence for improved outcomes from surveillance is weak and remains the subject of debate. To address these concerns, the BOSS trial aims to compare the benefits of 2-yearly surveillance endoscopy against endoscopy on an ‘at need’ basis only. As a large, multicentre trial with a 10-year follow-up period, this ambitious project faced a number of challenges to recruitment. Chief amongst these was the acceptability of randomizing to a control arm with no routine endoscopy, especially in sites where surveillance was wellestablished, and patients and clinicians may have been in favour of continued surveillance. Methods: Multi-centre randomized controlled trial (ISRCTN54190466). Inclusion criteria: patients over 18 with endoscopic and histologically proven BE > 1 cm. Exclusion criteria: patients unable to consent, unfit for endoscopy, high-grade dysplasia or cancer, or participation in AspECT trial. Target sample size: 3400. Recruitment: patients identified at local centres with new diagnosis, or existing diagnosis of BE and endoscopy within last 2 years. Follow-up will be for 10 years. Intervention arm will receive 2-yearly surveillance endoscopy, control arm will receive endoscopy on an ‘at need’ basis if symptomatic. Primary outcome: all cause mortality. Results: Recruitment began March 2009; target of 3400 was reached ahead of schedule in October 2011. 8457 patients assessed for eligibility, 4628 excluded (1607 did not meet inclusion criteria, 81 LGD, 1530 refused, 438 preferred endoscopy, 15 preferred no endoscopy, 50 on another trial, 907 no reason given). 347 consented to baseline data collection only, leaving 3455 to be randomised. A further 2 were subsequently found to be ineligible, therefore 3453 randomised and available for analysis (40.8% of assessed patients): 1734 in 2-yearly surveillance, 1719 in ‘at need’ arm. 127 hospitals were open to recruitment, though 3 withdrew from the study, recruitment was closed in one centre by the trial team, and 11 did not recruit any patients.


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ABSTRACT SUPPLEMENT

Disclosure: All authors have declared no conflicts of interest. Keywords: Stenting, Carcinoma, Palliation

Tuesday, September 23 – 8:00–9:50 O103: Esophageal Function Testing Room: Salon 2

Discussion: The successful recruitment to BOSS strongly supports the acceptability of randomization to the control arm, and patients’ willingness to participate in a long follow-up RCT. The large number of centres and enthusiastic principal investigators have shown continued success, and great promise for BOSS to answer key questions on the merits of Barrett’s surveillance and who may benefit. Disclosure: All authors have declared no conflicts of interest. Keywords: randomized controlled trial, Barrett’s Esophagus, surveillance, Endoscopy O102.09: SHOULD STENTING BE THE END-POINT OF PALLIATIVE TREATMENT FOR ESOPHAGEAL CANCER? John Watson, Adam Gorrie, Keith Harris, Daniel Swinson, Samir Mehta, Jeremy Hayden Leeds Teaching Hospitals NHS Trust, Leeds/UNITED KINGDOM Background: The majority of patients that develop oesophageal cancer are treated with palliative intent. The focus in these patients is to maximise survival whilst maintaining quality of life. We examined the outcome for patients who received a self-expanding metal stent for dysphagia as part of a palliative multimodality treatment pathway. Methods: We performed a retrospective audit of the outcome of 164 patients who had received an oesophageal stent for malignant dysphagia between 2008 and 2012. They were clinically staged by CT (100%), PET (54%) and EUS (12%) and treatment planned by a specialist multidisciplinary team. Patients were treated with palliative intent due to the presence of metastatic or non-resectable disease, poor performance status or patient preference. Results: There were 116 male and 48 female patients with a median age of 70 yr (range 37–99 yr) and 69 (42%) were clinical stage IV. Patients received oncological treatment prior to stent insertion in 108 (66%) and afterwards in 125 cases (76%). Of those receiving oncological treatment first, there was a significant difference in time to stenting depending on the type of treatment that was administered (chemotherapy, radiotherapy or both) (P = 0.000). Prior oncological treatment did not increase stent related complications. Moreover, for patients that had received oncological treatment before their stent there was no significant survival benefit from continuing oncological treatment afterwards (P = 0.105). Discussion: Oncological treatment for oesophageal cancer can delay the need for palliative stenting, but once patients are stented there is no evidence of further survival benefit from continuing oncological treatment.

Major Symptom Concordant Diagnoses Dysphagia 1 Dysphagia 2 Dysphagia 3 Reflux symptoms 4 Reflux symptoms 5 Dysphagia 6 Reflux symptoms 7 Reflux symptoms 8 Reflux symptoms 9 Discordant Diagnoses Reflux symptoms 10 Reflux symptoms 11 Chest-Pain 12 Reflux symptoms 13 Dysphagia 14 Dysphagia 15 Dysphagia 16 Dysphagia 17 Dysphagia 18 Chest-Pain 19 Dysphagia 20

O103.01: VALIDATION OF THE CHICAGO CLASSIFICATION FOR THE DIAGNOSIS OF PRIMARY ESOPHAGEAL MOTILITY DISORDERS BASED ON OUTCOME DATA – DATA FROM A PROSPECTIVE, RANDOMIZED, DOUBLE BLIND, CROSSOVER STUDY COMPARING THE SOLID-STATE AND WATERPERFUSED SYSTEM Edoardo Savarino1, Renato Salvador1, Giovanni Capovilla1, Loredana Nicoletti1, Giovanni Zaninotto2, Mario Costantini1 1 University of Padua, Padua/ITALY, 2Imperial College, London/UNITED KINGDOM Background: Early comparisons between conventional manometry and High Resolution Manometry (HRM) showed that high spatial resolution increases diagnostic yield and accuracy for clinically relevant esophageal motility disorders (EMD). Thus, a new classification of these disorders, the Chicago Classification (CC), has been created based on HRM studies carried out in a large group of healthy volunteers and patients who underwent the 36 solid-state (SS) pressure transducers HRM. However, limited data are available confirming its diagnostic accuracy and validating its effectiveness in terms of patients’ outcome. So far, we aimed to assess the diagnostic accuracy and clinical value of CC comparing the diagnoses of EMD formulated by using the 36-SS system and the 24-channel water perfused (WP) system in consecutive patients with esophageal symptoms and evaluating their clinical outcome after treating them based on CC findings. Methods: In this prospective, randomized, double blind, crossover study, 20 patients [11M/9F; 48 (43-55)] with esophageal symptoms underwent HRM with both 36-SS (Given Imaging, Los Angeles, CA) and 24-WP (EB Neuro, Firenze, Italy) systems, in random order. Two expert reviewers (RS, ES) performed a blindfolded analysis of the patients plots. Diagnoses based on CC were formulated. Inter-rater and inter-device agreement for each reviewer were evaluated. Then, according to CC-based diagnoses at 36-SS HRM studies, patients were empirically treated and followed-up for 1 year. Outcome was evaluated as positive (≥50% of symptomatic relief) or negative (30% distal IBT was associated with dysphagia (p = 0.030). Discussion: Decreased bolus transit in the distal esophagus is associated with dysphagia in patients with normal esophageal pressure topography, but not in patients with obvious manometric abnormalities. Proximal bolus transit does not add to HRM assessment. Disclosure: All authors have declared no conflicts of interest. Keywords: High-resolution manometry, Impedance, dysphagia O103.05: CLINICAL UTILITY OF PHARYNGEAL PH MONITORING IN PREDICTING THE RESPONSE OF LARYNGORESPIRATORY GERD SYMPTOMS TO FUNDOPLICATION Andreas Tschoner, Michal Lada, Michelle Han, Christian Peyre, Carolyn Jones, Thomas Watson, Jeffrey Peters University of Rochester Medical Center, Rochester/NY/UNITED STATES OF AMERICA Background: Treating patients with extraesophageal symptoms of gastroesophageal reflux disease (GERD) remains a challenge due to the unpredictable success rates noted with either medical or surgical therapy. A recently published study suggests that pharyngeal pH monitoring with the Restech® device is an appropriate diagnostic tool to predict successful surgical outcomes. The aim of our study was to assess the efficacy of pharyngeal pH monitoring, and to compare it to dual probe pH monitoring, in predicting the response of laryngorespiratory GERD symptoms to fundoplication. Methods: The records of all consecutive patients who underwent a pharyngeal pH study for evaluation of GERD between 5/1/09 and 10/31/13 were reviewed. 92/96 (96%) patients underwent concomitant dual probe pH monitoring. A positive result for the Restech® was defined as an increased RYAN score, while a positive result for the proximal sensor of a dual probe was defined as an elevated fraction time pH 15 mmHg) who do not meet criteria for achalasia are labeled as EGJ outflow obstruction. The aim of this study was to review clinical symptoms and characteristics in this group of patients. Methods: A retrospective review of a prospectively maintained database was conducted to identify patients who underwent HRM between September 2008 and December 2013. Only patients with an upper endoscopy within a week of HRM are included in the study. Patients with previous foregut surgery, achalasia, scleroderma, epiphrenic diverticulum, large hiatal hernia (>5cm), esophageal tumor or esophageal stricture were excluded. Symptoms were graded using a standard questionnaire with symptoms graded on a scale of 0–3. Results: One hundred thirty four patients met the inclusion criteria (mean age of 53.9 ± 14.1, 93 females). The most common symptoms were heartburn in 81 (60%), regurgitation in 73 (55%), dysphagia in 62 (46%), chest pain in 39 (29%) and respiratory symptoms in 55 (41%). In HRM findings, mean length of lower esophageal sphincter length was 2.9 ± 0.8 cm, mean lower esophageal sphincter pressure integral was 593.4 ± 343.4 mmHg-s-cm, mean lower esophageal sphincter pressure was 45.1 ± 18.1 mmHg and mean distal contractile integral (DCI) was 3852.0 ± 4223.9 mmHg-s-cm. Patients with dysphagia had lower incidence of pH positive and lower proportion of respiratory symptom than patients without dysphagia. Regarding IRP, there was no difference between patients with and without dysphagia. A Figure showed proportion of dysphagia based on IRP. On multivariate analysis, only pH negative was associated with dysphagia (p = 0.050). Forty-nine patients had treatment: eleven patients had Botox injection, three patients had endoscopic dilation, thirty-one patients had fundoplication, two patients had Heller myotomy, one patient had laparoscopic pyroloplasty and one patient had a sleeve gastrectomy.

Discussion: High IRP (>15 mmHg) is associated with wide array of symptoms with no clear clinical association. What is considered a normal IRP (in non-achalasia patients) needs to be re-evaluated and alternate criteria identified to have clinical relevance. Disclosure: All authors have declared no conflicts of interest. Keywords: Functional outflow obstruction, High-resolution manometry O103.07: IMPEDANCE-PH REFLUX PATTERNS AND POSITIVE SYMPTOM ASSOCIATION PREDICT THE PRESENCE OF MICROSCOPIC ESOPHAGITIS IN NON-EROSIVE REFLUX DISEASE PATIENTS Edoardo Savarino1, Patrizia Zentilin2, Luca Mastracci2, Pietro Dulbecco2, Nicola De Bortoli3, Santino Marchi3, Roberto Fiocca2, Vincenzo Savarino2 1 University of Padua, Padua/ITALY, 2University of Genoa, Genoa/ITALY, 3 University of Pisa, Pisa/ITALY Background: Microscopic esophagitis (ME) is frequently encountered in patients with erosive and non-erosive reflux disease (NERD). Recently, this histological finding has been regarded as the potential main mechanism in symptom generation in NERD. Impedance and pH (Imp-pH) testing detects both acid and non-acid reflux and is useful for evaluating symptom-reflux association and overall reflux patterns. To determine whether any symptom association or reflux pattern was associated with ME in patients with NERD. Methods: We evaluated 84 (39M/45F; mean age 45) consecutive patients with NERD while off-PPI therapy. During upper endoscopy

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multiple biopsies were taken at Z-line and 2 cm above it. Basal cell hyperplasia, papillae elongation, dilation of intercellular spaces and eosinophil (Eos) intraepithelial infiltration were measured [0 (absent), 1 (mild or 1 = 1 Eos), and 2 (marked or 2=>1 eos/HPF)] on hematoxylin–eosin-stained slides by two expert and blinded pathologists. A global score (GS) was calculated by summing up all the scores and dividing by the number of assessed lesions and was considered positive for ME when >0.35. Within 3 days from endoscopy, patients underwent impedance-pH testing. We measured esophageal acid exposure time (AET), mean acid clearance time (MACT), number of


impedance-detected reflux episodes (acid, nonacid) and symptom association probability (SAP; positive if ≥95%). Results: Reflux characteristics are summarized in the Table (univariate analysis). Overall, multivariate analysis showed that the factors associated with the presence of ME were: a positive symptom association probability [OR 3,485 (95%CI 1,045-11,626; p = 0,0423], a prolonged MACT [OR 4,322 (95%CI 1,473-12,678; p = 0,0077] and an abnormal number of reflux events [OR 3,485 (95%CI 1,029-8,833; p = 0,0443]. Patients with Abnormal Values

Reflux Features (upper limit of normal value) Total AET, % (n = 4,2%) MACT total, sec (n = 85) GER total, n (n = 54) Proximal Reflux, n (n = 30) SAP+ all reflux

Whole population (n = 84)

Patients with ME (n = 47)

Patients without ME (n = 37)

p value

2.8 (0.7–5.1) 69 (29–125) 51 (35–77) 22 (13–47) 61 (73%)

19 (40%) 27 (57%) 29 (62%) 23 (49%) 41 (87%)

6 (17%) 8 (22%) 9 (24%) 7 (19%) 20 (54%)

0.0235 0.0009 0.0006 0.0044 0.0007

Discussion: While confirming the importance of acid clearance in favouring the presence of esophageal microscopic damage in patients with NERD, impedance-pH data emphasize the major role of overall reflux episodes in promoting these histological lesions and further support the relevance of ME in symptom generation. Disclosure: All authors have declared no conflicts of interest. Keywords: microscopic esophagitis, impedance-pH monitoring, symptomreflux association, non-erosive reflux disease O103.08: IMPACT OF FUNDOPLICATION TYPE ON RADIAL PRESSURE OF THE ANTI-REFLUX BARRIER AND DYSPHAGIA Jennifer Myers1, Fermin Estremera-Arévalo2, Glyn Jamieson1, John Dent2 1 University of Adelaide, ADELAIDE/SA/AUSTRALIA, 2Royal Adelaide Hospital, ADELAIDE/SA/AUSTRALIA Background: Antireflux surgery carries the risk of post-operative dysphagia. We have shown recently from pre- and post-operative measurements that an impairment of esophageal body propulsive function is a significant risk factor for post-operative dysphagia i.e. mismatch of the timing of aborad advancement of esophageal peristaltic pressure relative to the flow of a viscous bolus along the esophagus.a We have now evaluated changes of the radial pressure pattern of esophago-gastric junction (EGJ) associated with two types of antireflux surgery and investigated whether the radial pattern of pressure within the EGJ could also contribute to post-operative dysphagia. Methods: EGJ pressures were evaluated by station pull-through of a catheter with 8 radial, 45o separated side-holes (in triplicate, mean). The validated Dakkak and Bennett composite dysphagia assessment scored the difficulty with swallowing 9 food types of increasing viscosity [scale 0 (none) to 45 (very severe)].b Pressure and dysphagia data were collected before and then 6 months after surgery. Results: All 34 patients with confirmed reflux disease (21M/13F; mean age 47 yrs, range 23–77) underwent a hiatal repair then either 90o anterior (new dysphagia 3/13, 23%) or 360o fundoplication (new dysphagia 10/21, 48%). Overall mean dysphagia score was low before and after surgery, 4.6 (0–22) vs. 7.1 (0–22) respectively. After 90o fundoplication, the magnitude, radial orientation and axial length of EGJ end-expiratory pressure was highest in the left anterior quadrant corresponding to the position of the partial fundal wrap. EGJ pressures were greater following 360o fundoplication cf. 90o fundoplication, however despite a complete circumferential fundal wrap, radial pressures were not uniform with higher pressure occurring consistently in the posterior aspect. Peak-inspiratory diaphragmatic squeeze pressure increased similarly for both types of fundoplication by a mean 35 mmHg in the L-lateral to L-anterior aspect. A comparison of 9 patients with no dysphagia before or after surgery (7x 360o, 2x 90o fundoplications) and 8 patients with new or worse dysphagia that was deemed clinically significant (6x 360o, 2x 90o fundoplications), revealed only a trend: after fundoplication, worse dysphagia was associated with a greater differential of asymmetrical radial peakinspiratory (p = 0.07) and end-expiratory (p = 0.08) EGJ pressure. Discussion: Antireflux surgery imposes changes of the EGJ radial pressure pattern that differ for the two types of surgery evaluated. In an expert centre for antireflux surgery, these alterations of EGJ mechanics appear to be a relatively minor contributor to post-operative dysphagia, when compared to the previously shown dysphagia risk due to the presence of a usually asymptomatic pre-surgery impairment of the timing of esophageal bolus transport relative to esophageal body peristalsis.a aMyers JC et al. Neurogastroenterol Motil 2012; bDakkak and Bennett. J Clin Gastroenterol 1992. Disclosure: All authors have declared no conflicts of interest. Keywords: fundoplication, manometry, esophagogastric junction, dysphagia

O103.09: MANOMETRIC AND DEMOGRAPHIC PREDICTORS OF INCOMPLETE BOLUS TRANSIT IN PATIENTS DIAGNOSED WITH INEFFECTIVE ESOPHAGEAL MOTILITY Christopher Andrews1, Sarah Pradhan2, Michelle Buresi1, Milli Gupta1, Michael Curley1, Lynn Wilsack1 1 University of Calgary, Calgary/CANADA, 2Royal College of Surgeons Ireland, Dublin/IRELAND Background: Ineffective esophageal motility (IEM), or frequent failed peristalsis in the Chicago Classification, is a common motility abnormality describing a non-specific manometric pattern of peristaltic failure. With the addition of multichannel intraluminal impedance technology to high resolution esophageal manometry (HRM), evaluation of bolus transit simultaneously with esophageal contraction is possible. However, manometric predictors of incomplete bolus transit (IBT) in the setting of IEM have not been fully characterized. Methods: REB-approved retrospective chart review of patients diagnosed with IEM at a regional gut motility centre. All subjects were clinically assessed prior to HRM with a detailed history containing the patient’s primary complaints, other pertinent symptoms and demographic information. HRM with impedance studies (Given Imaging, Inc) were performed by standard protocol. Summary (averaged) data from each patient was compared. To examine which manometric variables best predicted the percentage of swallows with incomplete bolus transit for any given patient, a multiple linear regression was performed using selected variables, and adjusted for age and gender (SPSS 21). All tests were two-sided and significance was set at the 95% level. Results: 230 patients (130 female; mean age 52 yr; range 18–82 yr) with a manometric diagnosis of IEM were included. The primary complaints of patients included dysphagia (33.9%), heartburn/reflux (33.0%), chest pain (11.7%), other (10.9%), and cough (8.7%). Many patients had more than one symptom; however there were no significant differences in baseline characteristics across primary symptom groups (data not shown). The multiple regression model fit was highly significant (F = 10.14, 9 df, p < 0.001) with an adjusted r square of 0.373. In the model, decreasing proportions of peristaltic contractions correlated significantly with decreased bolus transit (ie higher percentage of incomplete bolus transit). Similarly, higher intrabolus pressure correlated significantly with higher percentages of incomplete bolus transit. The remainder of the manometric variables were not significantly associated with IBT. Gender was not significant but increasing age was associated with less IBT (Table). Variable

B

95%CI Lower

95%CI Upper

P Value

Constant Female Age (Years) Mean LES Basal Pressure (mmHg) Mean LES Residual Pressure (4s IRP, mmHg) Proportion of peristaltic swallows (%) Mean Wave Amplitude (mmHg) Mean Wave Duration (s) Distal Contractile Integral (mmHg-cm-s) Intrabolus Pressure (mmHg)

129.2 −6.51 −0.43 −0.23

96.2 −15.21 −0.73 −0.53

162.2 2.19 −0.13 0.08

65 years reporting dysphagia (men/women, 24/23; mean age 73.0 years) (group A) were compared with those from 42 middle-aged patients with dysphagia (men/women, 18/24; mean age 56.5 years) (group B) and 27 younger patients with dysphagia (men/women, 15/12; mean age 36.1 years) (group C) in regard to symptoms, esophageal motility and health-related QOL (HRQOL). Each patient received ten 5-mL room temperature boluses of saline solution in combined multichannel intraluminal impedance-esophageal manometry examination. They all completed a selfadministered 7-point Likert scale questionnaire about their symptoms and HRQOL based on results of the SF-8. A symptom rated by the patient with a Likert scale score of 4 points or higher was defined as a significant symptom. Results: Although all patients had dysphagia as the significant symptom, more elderly patients reported globus sensation and more younger patients reported heartburn as their primary symptom, respectively. Manometric

diagnoses were generally similar among the three groups, although ineffective esophageal motility tended to be diagnosed more in group A compared to group B (Table 1). No significant differences in manometric parameters were detected (Table 2). There were no significant differences in HRQOL among the three groups. Table 1. Manometric diagnoses among the three groups NOTE: DES, diffuse esophageal spasm; IEM, ineffective esophageal motility; NE, Nutcracker esophagus GroupA GroupB GroupC

15A

ABSTRACT SUPPLEMENT


Achalasia

DES

IEM

NE

Others

Normal

8 (17.0%) 13 (31.0%) 8 (29.6%)

2 (4.3%) 4 (9.5%) 1 (3.7%)

14 (29.8%) 5 (11.9%) 7 (25.9%)

3 (6.4%) 1 (2.3%) 0 (0%)

0 (0%) 2(4.8%) 0 (0%)

20 (42.5%) 17 (40.5%) 11 (40.7%)

GroupA (n = 47)

CFV (cm/sec) DCI (mmHg. cm. sec) IRP (mmHg) Ratio of normal peristalsis (%) CBT (%)

3.8 1060 17.6 64.1 27.7

Discussion: Laparoscopic Heller myotomy with or without an anti-reflux procedure in children should be the treatment of choice in children with achalasia. Utilization of post-operative pneumatic dilatation may be necessary in some cases. More studies are needed to determine the need for an anti-reflux procedure during myotomy. Disclosure: All authors have declared no conflicts of interest. Keywords: achalasia, pediatric, children, Heller myotomy

Table 2. Comparison of esophageal motor function among the three groups NOTE: CFV, contractile front velocity; DCI, distal contractile integral; IRP, integrated relaxation pressure; CBT, complete bolus transit; LESP, lower esophageal sphincter pressure. Esophageal motor function

Twenty (80%) underwent a LHM with Dor fundoplication, 2 (8%) underwent a LHM with Toupet fundoplication, and 3 (12%) underwent a LHM without an antireflux procedure. Mean OR time was 124 minutes and length of stay was 2.7 days. One patient required revision of the Heller myotomy. Post-operative dysphagia was seen in 12.5% of the patients requiring single pneumatic dilatation. Most patients reported long term relief of symptoms with a median follow up time of 6 months.

O104.06: THE CHANGING FACE OF ACHALASIA Karthik Ravi, David Katzka, Joseph Murray Mayo Clinic, Rochester/MN/UNITED STATES OF AMERICA

GroupB (n = 42)

GroupC (n = 27)

P value

3.5 ± 1.3 945 ± 1274 22.9 ± 17.4 51.7 ± 37.6 30.9 ± 37.4

4.5 ± 1.3 732 ± 704 19.6 ± 26.4 52.4 ± 34.0 20.9 ± 33.4

N.S. N.S. N.S. N.S. N.S.

Background: High resolution manometry has expanded our understanding of achalasia by defining three distinct subtypes. However, despite these advances a reappraisal of the clinical presentation of achalasia is lacking.

Discussion: Despite differences in symptom patterns, broad manometric diagnoses and impairment of HRQOL in the elderly with dysphagia are similar to non-elderly dysphagia patients.

Methods: Patients referred to our institution between June 1, 2012 and August 30, 2013 with a diagnosis of achalasia were identified. Manometric tracings were re-assessed by a single investigator and clinical records reviewed.

± 1.6 ± 2945 ± 11.7 ± 36.9 ± 33.6

Disclosure: All authors have declared no conflicts of interest. Keywords: dysphagia, esophageal motility, Quality of Life O104.05: ACHALASIA IN CHILDREN: A SINGLE INSTITUTION EXPERIENCE Mikael Petrosyan1, Ashanti Franklin2, Anil Darbari2, Timothy Kane2 1 Children’s National Medical Center, Washington/DC/UNITED STATES OF AMERICA, 2Children’s National Hospital, Washington/DC/UNITED STATES OF AMERICA Background: Achalasia is a rare esophageal motility disorder in children and therefore ideal management of the disease in this population is not clearly defined. We conducted review of our experience to ascertain the ideal treatment and outcomes in pediatric population. Methods: A retrospective analysis at a tertiary free-standing children’s hospital from 2003–2014 was completed to determine the ideal surgical management and outcomes of Heller myotomy. Children ages 2–18 with a diagnosis of achalasia who underwent surgical intervention were included in the study. Demographics, presenting symptoms preoperative work up, medical and surgical treatment outcomes were reviewed. Statistical analysis was completed using the Student’s t-test and chi square analysis. Results: Twenty-five children with a mean age of 13, with a diagnosis of achalasia, underwent laparoscopic Heller myotomy (LHM) with or without an anti-reflux procedure. Preoperative manometry was done only in 38% of patients due to poor patient compliance. Only two patients received calcium channel blocker with only temporary relief of symptoms. Of the 25 patients, 4 underwent pneumatic dilatation and 2 had botulinum toxin injection.

Results: Fifty five patients with manometric criteria consistent with achalasia were identified. Similar to previous reports, there was no gender predominance, dysphagia was nearly universal, regurgitation was common, and diagnostic delay was common with an average symptom duration of 41.6 months prior to diagnosis. However, several new patterns in the clinical spectrum of achalasia were noted. Heartburn was a common symptom, with 45% (22/49) of patients complaining of persistent heartburn or requiring regular PPI. Strikingly, obesity was common in the population, with a mean body mass index (BMI) of 28.2 kg/m2 (18.5 to 49.3kg/m2) (Table 1). Further, 30% (16/54) and 72% (39/54) of patients had a BMI greater than 30kg/m2 and 25kg/m2 respectively. Perhaps most interesting, opiod use was common. Overall, 24% of achalasia patients were on chronic opiods, the need for which preceeded diagnosis and were unrelated to achalasia in all cases. Further, the opiod use varied among the subtypes, noted in 0% (0/4), 21% (9/43), and 50% (4/8) of types 1, 2, and 3 achalasia respectively (Table 2). Discussion: The clinical presentation of achalasia in this study differs from previous descriptions. Heartburn was a common finding and overall patients were obese despite signifcant dysphagia. In addition, preceeding chronic opiod use for unrelated reasons was common and therefore may have contributed to the observed manometric findings. These findings suggest clinical suspicion for achalsia should be expanded and further investigation into the effect of opiods on esophageal peristalsis is needed. Disclosure: All authors have declared no conflicts of interest. Keywords: achalasia, clinical presentation of achalasia, chronic opiods and achalasia, opiods and achalasia

Table 1. Clinical Presentation of Achalasia

Type 1 Achalasia Type 2 Achalasia Type 3 Achalasia All Achalasia

N

Female

Mean Age (years)

Mean BMI (kg/m2)

Mean Symptom Duration(months)

Dysphagia to solids and liquids

Regurgiation

Chest Pain

Heartburn

4 43 8 55

50% (2/4) 51% (22/43) 50% (4/8) 51% (28/55)

49.7 (29.6–74.8) 57.9 (18.6–87.8) 67.4 (48.5–78.4) 58.7 (18.6–87.8)

28.1 (21–33.5) 27.9 (18.5–49.3) 29.7 (20.8–43.1) 28.2 (18.5–49.3)

27.8 (9–60) 40.9 (4–424) 52.5 (6–120) 41.6 (4–424)

100% (4/4) 79% (33/43) 63% (5/8) 76% (42/55)

100% (4/4) 63% (25/40) 71% (5/7) 67% (34/51)

0% (0/4) 18% (7/38) 29% (2/7) 18% (9/49)

50% (2/4) 45% (17/38) 43% (3/7) 45% (22/49)

Table 2. Opiod use and Achalasia management Type 1 Achalasia Type 2 Achalasia Type 3 Achalasia All Achalasia

Opiod use

Normal Esophagram

Normal EGD

Heller myotomy/POEM

Pneumatic Dilation

0% (0/4) 21% (9/43) 50% (4/8) 24% (13/55)

0% (0/4) 0% (0/43) 0% (0/7) 0% (0/54)

0% (0/3) 17% (7/41) 25% (2/8) 17% (9/52)

100% (4/4) 71% (30/42) 57% (4/7) 72% (38/53)

0% (0/4) 7% (3/42) 14% (1/7) 8% (4/53)

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O104.07: ESOPHAGEAL SENSITIVITY AND VISCERAL PAIN PERCEPTION IN HEALTH IS NOT MODULATED BY ENDOGENOUS OPIOID RELEASE Charlotte Broers1, Ans Pauwels1, Chloé Melchior2, Veerle Boecxstaens1, Jan Tack1 1 University of Leuven, Leuven/BELGIUM, 2University Hospital, Rouen, Rouen/FRANCE Background: When gastro-esophageal reflux is causing symptoms (heartburn, regurgitation) or lesions (esophagitis), it is defined as gastro-esophageal reflux disease (GERD). A large group of patients does not present with esophageal lesions and are referred to as non-erosive reflux disease patients (NERD). Proton pump inhibitors (PPI) are effective in healing esophagitis, but a large group of NERD patients remains symptomatic while taking PPIs. In these patients, esophageal hypersensitivity is considered an important pathophysiological mechanism and this is often linked to defective functioning of descending anti-nociceptive pathways, although evidence to support this hypothesis is lacking. Endogenous opioids are key candidate mediators of descending anti-nociception. Our aim was to study the role of centrally acting and peripherally restricted μ-opioid receptor antagonists naloxone and methylnaltrexone respectively on esophageal sensitivity in healthy volunteers (HV).


Methods: Esophageal multimodal sensitivity was quantified after administration of naloxone (20μg/kg/h IV infusion after 0.4mg bolus), methylnaltrexone (12mg/0.6ml SC injection) and placebo (0.9% NaCl) in 12 HV (7m/5f, mean age 31 y [range 22–51]). After an overnight fast, a custom made probe with a balloon was positioned in the distal esophagus. Thermal (recirculating a heated solution through the balloon), mechanical (increasing balloon volume), electrical (2 stimulation electrodes) and chemical sensitivity (modified Bernstein) were tested. Perception scores were evaluated on Visual Analogue Scales (VAS). Stimulus intensities were evaluated for first perception (VAS 1), pain perception threshold (VAS 5) and pain toleration threshold (VAS 7). General mood was assessed by the Positive and Negative Affect Schedule (PANAS) and the State-Trait Anxiety Inventory (STAIstate) questionnaires before and after the stimulations. Results were analyzed using repeated measures ANOVA or the non-parametric Kruskal-Wallis test. P-values of 0.14 was significantly elevated n patients with RE compared with patients without RE(p < 0.01). 3) Simultaneous contraction >30% was frequently observed in patients with regurgitation symptom or with Grade C/D RE. In contrast, distal esophageal contraction 24-h delayed cases) to the present 5%. However, the disease related 3-month mortality of stented patients was 20%. The diagnostic delay over 24h was 27% in stented patients, 43% in the primary repair group and 55% in the esophaectomy group. Discussion: No single reason can explain the decrease of overall mortality over this lengthy period. Improvements in intensive care treatment and antiinfectious medication, earlier diagnosis, and more tailored treatment strategies contribute to improved outcome. In addition, many delayed cases earlier treated with esophagectomy can be treated successfully with primary repair and fundic reinforcement. Disclosure: All authors have declared no conflicts of interest. Keywords: Treatment strategies, 91 cases, results, Boerhaavés Syndrome O105.04: COLONIC INTERPOSITION FOR ESOPHAGEAL REPLACEMENT: CHANGING PATTERNS AND CURRENT INDICATIONS FROM A 28-YEAR SINGLE INSTITUTION EXPERIENCE Ilies Bouabdallah, Xavier Benoit D’Journo, Lucile Gust, Geoffrey Brioude, Bastien Orsini, Delphine Trousse, Christophe Doddoli, Pierre Fuentes, Pascal Thomas Aix-Marseille University, Marseille/FRANCE Background: To investigate if the indications and the early outcome of colon interposition for esophageal replacement have changed during the last decades. Methods: The medical records of all patients who underwent an esophageal replacement between 1985 to 2013 were retrospectively reviewed from a single institution prospective database. Over a 28-year period, 921 patients were screened. Among them, 158 consecutive patients underwent a colon interposition (17 %). This cohort constitutes the material of the present study. All the patients were divided in two cohorts: group A (1985–1995) and group B (1996–2013). Statistical tests were performed on these two cohorts to identify in each group: indications, technique of coloplasty and early results in term of mortality, morbidity and length of hospital stay. Results: Among the 158 colonic interpositions, there were 60 patients in group A (mean 6 patients/year) and 98 patients in group B (mean 5.5 patients/year). Among all operations performed for esophageal substitution, colon interposition represented 18.5% of for group A (60/325) and 16.4% for group B (98/596) (p = 0.43). There were 48 (80 %) males in group A and 66 (67 %) in group B (p = 0.08). The mean age was 52 ± 12 in group A and 50 ± 14 in group B (p = 0.85). Indications for colon interposition differ significantly between the group A and B (Table 1). An isoperistaltic conduit based on the left colonic artery could be used in 140 (89%) patients (group A: 52 and group B: 88, p = 0.54). An intrathoracic esophagocolic anastomosis was performed in 8 (13%) in group A and in 27 (27%) in group B (p = 0.03). The surgical route used was through the posterior mediastinum in 95 (60 %) (group A:38, B:57; p = 0.51), in a retrosternal position in 61 patients (38 %) (group A:21, B:40; p = 0.46), and under the skin in 2 patient (1 in each group). The postoperative course is summarized in Table 2. The mean length of hospital stay was 37 days ± 13 in group A and 35 days ± 16 in group B (p = 0.39).

18A



O105.06: COMPARING OUTCOMES OF OPEN VERSUS FLEXIBLE AND RIGID TRANS-ORAL ENDOSCOPIC TECHNIQUES FOR THE TREATMENT OF ZENKERS DIVERTICULUM Daniel Jones, Abdullah Aloraini, Stephen Gowing, Mara Leimanis, Roger Tabah, Lorenzo Ferri McGill University, Montreal General Hospital, Montreal/QC/CANADA

Discussion: Current indications of colonic interposition have changed confirming the epidemiologic changes observed during the two last decades. Indications for cancer are less frequent whereas indications for non malignant stenosis are increasing and notoriously in females. An isoperistaltic conduit in the posterior mediastinum supplied by the left colic artery remains the substitute of choice. Despite current progress, it remains a major procedure facing a high mortality and morbidity rate over time. Disclosure: All authors have declared no conflicts of interest. Keywords: caustic, esophagectomy, Colon interposition, Benign disease

O105.05: PROGNOSTIC FACTORS FOR SUCCESS OF LAPAROSCOPIC CARDIOMYOTOMY AS TREATMENT FOR END-STAGE ESOPHAGEAL ACHALASIA Sergio Szachnowicz, Rubens Sallum, Francisco Seguro, Valter Felix, Andre Duarte, Angela Falcão, Ivan Cecconello University of Sao Paulo, Sao Paulo SP/BRAZIL Background: Achalasia is a rare motor disease. In some countries, the majority of cases are due to Chagas disease and it is not so uncommon advanced dilated forms (over 10cm of esophageal diameter). Formerly, esophagectomy with cervical gastroplasty was the gold standard for treatment but with considerable morbimortality. However, with the facilities of laparoscopic cardiomiotomy and its low complication rates, this procedure was being implemented as a treatment option. The aim of this study is to analyze the long-term outcome of advanced End-stage patients with laparoscopic achalasia Cardiomyotomy and identify prognostic factors.

Background: Zenker’s diverticulum (ZD), a common cause of dysphagia and recurrent aspiration pneumonia in the elderly, is caused by a hypertensive cricopharyngeal muscle. Treatment of this condition centers primarily on disruption of this muscle via cricopharyngeal myotomy (CM). While conventional open surgical CM (OpenCM) was long considered the standard of care, less invasive trans-oral approaches (involving flexible or rigid endoscopy) are coming into favor. Endoscopic approaches can be achieved with either a rigid stapling device (RigidCM) or an electrosurgical needle knife passed through a standard gastroscope (FlexCM). The superiority of one technique over the other has not been established, therefore we sought to compare outcomes between OpenCM, RigidCM, and FlexCM for ZD. Methods: All patients undergoing treatment for ZD within the divisions of general and thoracic surgery at a single university-affiliated hospital between 5/92-5/13 were reviewed. Patient demographics, ZD size, post-operative complications (Clavien-Dindo classification), and length of stay (LOS) were compared between OpenCM, RigidCM, and FlexCM. Dysphagia scores (DS) (0 best-4 worst) and pneumonia incidence were assessed pre-operatively and post-operatively. Data presented as median (interquartile range). Chi-Square, non-parametric ANOVA and multi-linear regression were performed (significance set at p ≤ 0.05(*)). Results: 52 patients underwent open (33/52(63%)) or endoscopic (19/52(37%): 8 Rigid/11 Flexible) CM. Trans-oral CM (FlexCM 4cm(2.5-4), RigidCM 4cm(2-4)) had slightly larger ZD than OpenCM (3cm(2-3))(NS). CM reduced DS for all approaches [OpenCM:2(2-3)–0(0-0)*; RigidCM:2(2-2)– 0(0-0)*; FlexCM:3(3-3)–0(0-0)*]. Major post-operative complications (>grade2 Clavien-Dindo) occurred in 3/33(9%) OpenCM, 1/8(12%) RigidCM, and 0/11(0%) FlexCM (NS). Pneumonia incidence post CM was comparable between groups (NS). LOS was lower in FlexCM (2days(1-2) vs RigidCM (3days(3-6)*) and OpenCM (5days(4-7)*), but did not differ between RigidCM and OpenCM. Accounting for age, sex, and post-operative complications FlexCM remained a significant determinant of LOS*. Discussion: Cricopharyngeal myotomy is a highly effective method to manage ZD with comparable post-operative outcomes between techniques. However, FlexCM is associated with a significant reduction in LOS compared to other approaches and could be considered the preferred method of treatment for patients with moderate to large Zenker’s diverticulum. Disclosure: All authors have declared no conflicts of interest. Keywords: Length of stay, Zenker’s Diverticulum, cricopharyngeal myotomy, Endoscopic O105.07: WHEN SHOULD ESOPHAGECTOMY BE CONSIDERED IN THE TREATMENT OF ACHALASIA? Maximiliano Loviscek, Luis Loviscek Instituto Argentino de Diagnostico y Tratamiento (IADT), Buenos Aires/ ARGENTINA Background: Achalasia is an esophageal motility disorder of unclear etiology. A delay in diagnosis is the most important prognostic factor. The radiologic classification is a useful tool to classify the stage, predict surgical results with the myotomy and suggests an esophagectomy.

Methods: Between 2000–2012, 653 patients were submitted to cardiomyotomy at our institution, 47 of them identified at advanced End-stage presentation (dilation > 10 cm). Data of those patients (age, chagasic or idiopathic origin, length of esophageal dilatation, manometric findings, comorbidities, operative morbidity, presence of dysphagia) were analyzed. Results: The mean follow-up was 8 years and the mean age of patients was 61 years. 35 patients had Chagas disease and 12 idiopathic form. Laparoscopic approach was chosen for 80% of the cases (feasible in all). Morbidity and mortality was absent. There was recurrence of dysphagia in 31%, but idiopathic cases had in only 8%. Patients with Chagas disease had 4.38 times more (OR) risk of recurrence than idiopathic patients (p = 0.03). The presence of other manifestations of Chagas (cardiac disease) were also related to increased risk. Other data were not associated to higher risk of recurrence. From the 14 (29.7%) patients that late recurred some degree of dysphagia; esophagectomy was necessary in only 2 cases(4.2%). Other 9 (19.1%) cases were resolved with endoscopic dilation and in 3(6.3%) of them was necessary redo the myotomy. Discussion: Laparoscopic Cardiomyotomy is a safe and effective procedure for the treatment of End-stage Esophageal Achalasia patients. This procedure avoided esophagectomy in all except 2 patients (4.2%). Chagasic are into higher risk of recurrence of dysphagia (OR 4.38) than Idiopathic forms. Disclosure: All authors have declared no conflicts of interest. Keywords: achalasia, myotomy, prognostic factor, motor disorder

Methods: We study retrospectively 146 patients with diagnosis of achalasia confirmed with manometry and treated surgically between 2003–2012. The argentinian radiologic classification was used (Resano-Malenchini) to classify the stages before surgery. This classification consists in four stages (I–IV) regarding the grade of esophageal dilatation and tortuosity. Laparoscopic Heller myotomy (LHM) and esophagectomy were the surgical approaches. We evaluated the results after a LHM with a symptoms questionnaire using a score


ABSTRACT SUPPLEMENT

0–4 (Likert scale) and with an esophagogram to study the esophageal emptying at 1-2-5 minutes, analyzing the surgical success and in which cases an esphagectomy was necessary. Success was considered with symptoms improvement, clear better esophageal emptying at the esophagogram and gain weight. Results: 146 patients: 67 males and 79 women. Median age: 48 (range 18–79). 75/146 (52%) patients had a straight esophagus (stage I–II) and 71 (48%) tortuous esophagus. 47/146 (32%) with one distal curve (stage III) and 24/146 (16%) with more than one curve (stage IV). 137/146 patients had been treated with a LHM and 9/146 were treated directly with an esophagectomy because of their young age and advanced stage (IV). Success after LHM was evident in 95% of patients with stage I-II, 89% with stage III and 50 % in stage IV. 3/15 (20%) patients with stage IV treated with LHM required an esophagectomy. Discussion: In achalasia early diagnosis is crucial. The esophagogram is useful to classified and predict prognosis. The successful outcomes after Heller myotomy were clearly better in those patients with an early stage and straight esophagus. Esophagectomy should be considered when all the attempts to preserve the esophagus have failed and in those young patients with a radiological stage IV with tortuous megaesophagus. Disclosure: All authors have declared no conflicts of interest. Keywords: achalasia, Radiologic classification, End Stage Achalasia, esophagectomy O105.08: PERIOPERATIVE OUTCOMES OF LAPAROSCOPIC HIATAL HERNIA REPAIR USING RELAXING INCISION OF THE DIAPHRAGM Geoffrey Chow, Eric Hungness, Nathaniel Soper Northwestern University Feinberg School of Medicine, Chicago/IL/ UNITED STATES OF AMERICA Background: Laparoscopic hiatal hernia repair is a complex operation that requires detailed knowledge of gastroesophageal anatomy and physiology. Despite advances in technique and increased surgeon experience with repair of these complex hernias, objective recurrence rates upwards of 50% have been reported. Inadequate esophageal length and tension on the crural closure are two factors that may contribute to hernia recurrence. In patients with widely splayed and/or stiff crura primary closure of the hiatus may be facilitated by a relaxing incision in the diaphragm. This study evaluates the perioperative outcomes for patients who underwent diaphragmatic relaxing incisions during laparoscopic repair of giant hiatal hernias. Methods: Medical records were reviewed from patients who underwent laparoscopic hiatal hernia repair with diaphragmatic relaxing incisions. Perioperative details and post operative course were described. Results: From July 2011 to February 2014, 79 patients underwent laparoscopic repair of paraesophageal hernias. Of these, 16 patients (20%) underwent hernia repair with diaphragmatic relaxing incisions to allow a tension-free primary closure of the hiatus. Thirty eight percent of the patients were male, the median age was 58 (range 35–85), and the mean BMI was 29 (range 21–39). All relaxing incisions were performed on the right side of the hiatus, and all operations were completed laparoscopically. Mean operative time was 135+/−39 min, and mean postoperative length of stay was 2.2+/−1.7 days. The operation was a primary procedure in 11 (69%) of patients, and a reoperation in 5. Three patients (19%) required a Collis gastroplasty for short esophagus. A Nissen fundoplication was performed in 75% of patients, a Dor in 19%, and a Toupet in 6%. Bio-A™ mesh was used to cover the relaxing incision defect in 13 patients, lesser omentum was used in 1 patient, and no additional tissue or mesh was used in 2 patients. Three patients (19%) developed intra-thoracic fluid collections requiring percutaneous drainage: One patient developed a symptomatic mediastinal seroma, 1 had a unilateral right sided effusion, and 1 developed bilateral chylous effusions requiring percutaneous embolization of the thoracic duct. Discussion: Durable repair of large paraesophageal hernias is limited by tension on the hiatal closure, and the use of mesh at the hiatus is problematic. Recurrent hernias and those with widely splayed crura add complexity to surgical repair. Relaxing incisions can facilitate primary hiatal closure. Intra-thoracic fluid collections complicate 1/5 of these procedures, but can usually be managed by minimally invasive techniques. The short term morbidity of relaxing incisions is limited, and long term outcomes will clarify the utility of this technique. Disclosure: All authors have declared no conflicts of interest. Keywords: laparoscopic foregut, paraesophageal hernia, hiatal hernia, relaxing incision O105.09: ESOPHAGEAL REPLACEMENT IN CHILDREN BY COLONIC GRAFT. Saidkhassan Bataev, Abdumanap Alkhasov, Alexander Razumovsky, Zorikto Mitupov, Victor Rachkov, Roman Ignatiev, Nikita Stepanenko, Ekaterina Ekimovskaya, Konstantin Tcilenco Filatov Children’s Hospital, Russian State Medical University, Moscow/ RUSSIAN FEDERATION Background: Since 1960 more than 740 esophageal replacements have been performed at the Filatov Children’s Hospital (Moscow). The aim of this

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study to present the modificated technique of esophageal replacement in children. Methods: For the last 10 years 124 colonic interpositions have been performed. All operation was carried out with the use of 3 main principles: 1. Esophageal substitution were made using isoperistaltic transverse colonic graft. 2. Retrosternal or posteriomediastinal rout channel had been chosen for graft realization. 3. Original antireflux anastomosis between the colon graft and the stomach had been used Results: Graft necrosis – 4 children (24%) leakage from the cervical anastomosis – 49 (33,3%), Strictures of the cervical anastomosis 19 (19,9%). Discussion: Colonic interposition is the method of chose in esophageal substitution in children. antireflux anastomosis between the colon graft and the stomach allows us to achieve the higher quality of life to our patients. Disclosure: All authors have declared no conflicts of interest. Keyword: Esophageal replacement in children

Tuesday, September 23 – 15:30–17:00 O106: Benign Esophageal Diseases: Surgery II Room: Salon 2 O106.01: UPPER DIGESTIVE TRACT RECONSTRUCTION FOR CAUSTIC INJURIES Mircea Chirica, Marie Dominique Brette, Matthieu Faron, Nicolas Munoz Bongrand, Emile Sarfati, Pierre Cattan Saint Louis Hospital, Paris/FRANCE Background: Simultaneous esophageal and pharyngeal reconstruction by colopharyngoplasty allows regaining nutritional autonomy in patients with severe pharyngoesophageal caustic injuries. The aim of the study was to compare the short and long term outcomes of colopharyngoplasty and esophagocoloplasty for caustic injuries of the upper digestive tract Methods: Patients who underwent upper digestive tract reconstruction for caustic injuries by colopharyngoplasty (n = 116) and esophagocoloplasty (n = 122) between 1993 and 2012, were included. Survival and functional outcomes were analyzed. Success was defined as nutritional autonomy after removal of the jejunostomy and tracheotomy tubes. Quality of life was assessed using the QLQ-OG25 and SF12v2 questionnaires. Results: Overall Kaplan –Meyer survival at 1-, 5-, 10 years after colopharyngoplasty and esophagocoloplasty were 92%, 74%, 67% and 92%, 83%, 73%, respectively (p = 0.56). Quality of life and functional results (success: 57% vs. 95%, p < 0.0001) were impaired after colopharyngoplasty. On multivariate analysis older age (OR: 0.94; CI 0.91-0.97, p < 0.0001) and pharyngeal reconstruction (OR: 0.05; CI 0.02-0.13, p < 0.0001) were associated with failure. The decline in success with age was more pronounced after colopharyngoplasty with only one (7%) of 15 patients operated after the age of 55 being self-sufficient for eating and breathing. Laryngeal resection during colopharyngoplasty had no influence on success (54% vs. 58%, p = 0.67). Discussion: In conclusion, colopharyngoplasty is a safe and reliable reconstruction technique in patients with severe caustic esophageal and pharyngeal injuries. Age is the main predictor of failure and pharyngeal reconstruction should probably be withheld in patients aged over 55. Disclosure: All authors have declared no conflicts of interest. Keywords: colopharyngoplasty, esophagocoloplasty, caustic ingestion O106.02: MUCOSAL PERFORATION DURING LAPAROSCOPIC HELLER MYOTOMY DOESN’T INFLUENCE THE FINAL OUTCOME OF THE TREATMENT Renato Salvador1, Mario Costantini1, Longo Cristina1, Francesco Cavallin2, Lisa Zanatta1, Loredana Nicoletti1, Giovanni Capovilla1, Francesca Galeazzi3, Edoardo Savarino3, Giovanni Zaninotto1 1 University of Padova, Padova/ITALY, 2IOV-IRCCS, Padova/ITALY, 3 University of Padua, Padua/ITALY Background: Laparoscopic Heller-Dor (LHD) is the currently accepted treatment for esophageal achalasia. The most common intraoperative complication (2–33%) is inadvertent mucosal perforation. There are no studies to determine whether the mucosal perforation affects the final outcome of LHD. The aim was to evaluate the final outcome in patients (pts) with accidental perforation detected during the operation or by the routine postoperative contrast-swallow. Methods: 713 pts underwent LHD between 1992–2013 by 6 staff surgeons alternatively. Mucosal perforation was detected in 22 pts (Group A). The pts who underwent the operation uneventfully were defined Group NP. Furthermore, two different patient groups were considered: Group B pts operated by the same surgeon immediately before and Group C immediately after a perforation occurred. Pts were evaluated preoperatively by a detailed

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symptom questionnaire, manometry, endoscopy and barium-swallow. Treatment failure was defined as a postoperative symptom score >10th percentile of the preoperative score (i.e. > 8). Pts with a previous myotomy were excluded. Results: LHD was the primary treatment for 567 pts; 146 (20.5%) had a previous endoscopic treatment. There were 22 perforations (3.1%): 19 (86.5%) were recognized and repaired during the operation, 2 (9%) were detected by contrast- swallow in the 1st POD and 1 (4.5%) was recognized in 3rd POD. The median follow-up was 35 months (IQR:15-79). Perforation was not related to the symptoms score or duration, age, radiological-grade, manometric pattern or surgeon’s experience. The LES residual pressure was the only variable associated to perforation risk (Group NP: 10mmHg vs Group A: 18 mmHg, p = 0.03). A previous endoscopic treatment (146 pts, 20.5%) didn’t increase the perforation rate (3/146 vs 19/567, 2% vs 3.3%, p = 0.59). The post-operative findings are presented in the table. Symptoms recurred in 4 pts of group A (18,2%), 2 pts of group B (10%) and 3 pts of group C (15%) (p = 0.99). The post-operative median symptom score was similar in all the 3 groups. The was no-difference in the median procedure time between group B (148 min) and group C (138 min, p = 0.38). Group NP (691 pts)

Group A (22 pts)

p-value

Hospital stay (days)

5 (4–6)

10 (10–15)

6 per year and stricture tightness (unable to pass an 11mm or larger size dilator) (p = 0.043, p < 0.01, p < 0.01 and p = 0.046 respectively) were more likely to end up with surgery. Overall, there were 33 patients underwent surgery. All had long segment left side colon bypass or interposition with cervical anastomosis (31 with substernal route). Some degree of gastric strictures were presented in all which precluded using stomach as an esophageal substituition. Eleven had concomitant esophageal resection. There was one (3%) hospital mortality. Overall anastomosis leakage was 12%(4/33) and stricture was 30% (10/33). Head clavicle and part of manubrium were resected in 23 patients. Three out of 23 (13%) patients with head clavicle resection and 7 out of 10 (70%) without resection had cervical anastomosis stricture (p = 0.001). Upper anastomoses were pharyngo-colostomy in 11 and esophago-colostomy in 22 patients. Patients with concomittant laryngeal stenosis requiring tracheostomy and with cervical pharyngo-colostomy anastomosis had significantly higher incidence of difficult swallow and aspiration postoperatively comparing to those who had not (p < 0.05). At the median follow up of 32 months, 29 of 33 patients can eat solid food via mouth without using feeding enterostomy. Overall good to excellent outcome was 81% after colon bypass or interposition. Discussion: Majority of patients with corrosive esophageal injury from suicidal attempt are severe. Endoscopic esophageal dilatations were ultimately failed in more than half of patients. Substernal colonic bypass or interposition using long segment left side colon with resection of head clavicle and part of manubrium sterni provides good outcome in corrosive esophageal stricture after failed dilatation. Disclosure: All authors have declared no conflicts of interest. Keywords: corrosive esophageal stricture, substernal colonic bypass

O106.05: PERFORATION OF ESOPHAGEAL ACHALASIA: THORACOSCOPIC REPAIR IN THE PRONE POSITION Tetsuji Nobuhisa Red Cross Hospital, Himeji/JAPAN Background: Several options are available for the treatment of esophageal achalasia, and balloon dilatation is one of the effective procedures. On the other hand, the most serious complication of balloon dilatation is a creation of large hole that requires emergency operation. We report a case of the minimally invasive thoracoscopic approach in the prone position in patient admitted for the esophageal perforation occurred in the esophageal achalasia by endoscopic balloon dilatation. Methods: We herein describe a 44-year-old female with the esophageal perforation occurred in the esophageal achalasia by fourth endoscopic balloon dilatation. Computed tomography scan showed the hole was in left-sided lower esophagus. The procedures of our surgical techniques were as follows: (1) The patient was placed in prone position. (2) Three 12mm-trocars were used in the left-sided thoracic cavity. (3) A big incision was made in the mediastinal pleura for incisional drainage. (4) The presence of the


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esophageal perforation was affirmed. (5) The divided layer of mucosa was sutured together, but the separated layer of muscle was left open. (6) Ten liter of saline was used for pleural lavage. (7) Two drainage tubes were placed into the pleural cavity for saline irrigation. Results: Operative time was 140 min. Blood loss was 0 g, and no perioperative transfusion was required. Postoperative recovery was uneventful. Esophageal dysphagia is removed, and esophageal transit is much smoother than before. Discussion: The described procedure for the esophageal perforation occurred in the esophageal achalasia by endoscopic balloon dilatation is a minimally invasive alternative to the conventional thoracotomy that looks promising.

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It was also observed that those patients had higher mortality (9 deaths) in long-term follow up due to cardiac Chagasic disease. Discussion: The remiotomy in achalasia is feasible by laparoscopic approach, safe and satisfactory in patients who do not respond to dilatation, especially in patients with idiopathic form of the disease. This procedure proved to be also safe for recurrence of dysphagia in Chagasic patients who have not demonstrated a very long survival. Disclosure: All authors have declared no conflicts of interest. Keywords: myotomy, redo, laparoscopic, achalasia O106.07: LARGE CRURAL DEFECTS IN COMPLEX PARAOESOPHAGEAL HERNIATION IS ASSOCIATED WITH OESOPHAGEAL DYSMOTILITY AND SYMPTOMATIC RELAPSE James Brewer1, Paul Mackenzie1, Lorna Harries2, Shahjehan Wajed1 1 Royal Devon and Exeter Hospital, Exeter/UNITED KINGDOM, 2 University of Exeter, Exeter/UNITED KINGDOM Background: The aim of surgical intervention in symptomatic para-oesophageal herniation primarily is to restore normal anatomical configuration of the foregut, and secondly to permanently repair the crural defect responsible, hence eliminating significant clinical symptoms. Long term success is linked to the integrity of this repair, but despite this, some patients report new, or relapse of perceived original symptoms. This study evaluated possible causes for this apparent failure. Methods: A retrospective analysis of patients who underwent laparoscopic repair of large and complex para-oesophageal hernia was performed utilizing the prospectively maintained oesophago-gastric database at the Royal Devon and Exeter Hospital between October 2004 and December 2013. Crural repair was carried out in accordance with our local protocol to ensure minimal tension closure, and either primary sutured or biological mesh reinforced cruroplasty was performed dependent on the extent of actual diaphragmatic defect. Patients were clinically evaluated routinely after surgery and then on an annual basis, once primary symptoms had resolved. Patients were offered open access to return in case of any problems or concerns. These were investigated with endoscopy and radiology to assess for integrity of repair, and establish a cause for the symptoms.

Disclosure: All authors have declared no conflicts of interest. Keywords: achalasia, Perforation, dilatation, thoracoscopic O106.06: LAPAROSCOPIC RE-CARDIOMYOTOMY AS A SAFE TREATMENT FOR RECURRENCE OF DYSPHAGIA IN ESOPHAGEAL ACHALASIA Rubens Sallum, Sergio Szachnowicz, Francisco Seguro, Julio Rocha, Edno Bianchi, Ary Nasi, Ivan Cecconello University of Sao Paulo, Sao Paulo SP/BRAZIL Background: Esophageal achalasia admits several therapeutic options as endoscopic and surgery. Currently the surgical one still remains the gold standard. However, recurrence of symptoms occurs in about 10% in five years, and almost 30% in 30 years. The aim of this study was to demonstrate the results of reoperation in patients with recurrent symptoms after surgical treatment of achalasia and identify prognostic factors. Methods: In the period 2000–2013, 30 patients, with reccurence of dysphagia after surgical treatment and that failed to endoscopic dilatation were referred to reoperation. Data of those patients (age, chagasic or idiopatic origin, lenth of esophageal dilatation, ethiology of recurrence, manometric findings, comorbidities,laparoscopic or open reoperation, presence of dysphagia) were analysed. Results: Half of the procedures was performed by laparoscopic approach and the results were similar to open procedure. No influence on postop. dysphagia was observed according to the radiological classification of esophageal diameter (10cm = 10%). Chagas disease was the ethiology in 21 patients and 9 were idiopathic. The ethiology of reccurence was: incomplete myotomy (33%), myotomy fibrosis/ progression of disease (60%) and technical problems with hiatus or fundoplication (7%). There was no perioperative mortality. Disphagia was controled in all patients at the early follow up but 7 had necessity of endoscopic dilatation at the late period and Chagas disease was proved to be an important risk factor (p = 0.05).

Results: A total of 119 patients were included in our initial database; 68 (57.1%) had undergone standard laparoscopic cruroplasty, 51 (42.9%) patients had an extensive crural defect and required an augmented repair incorporating biologic mesh. The majority of patients (84.9%) reported resolution in their primary symptom at first follow-up (6 weeks after surgery). A total of 47 patients (39.5%) underwent further investigations post-operatively, of these 27 (22.3%) requested early clinical review due to concerns about symptoms prior to planned annual follow-up. We observed that patients with extensive defects and who underwent biologic mesh repair were more likely to re-attend open follow up with symptoms after initial discharge from clinic (mesh = 31.4%, sutured 16.2%, p = 0.05), with more patients requiring investigation (mesh = 33.3%, sutured 19.1%, p = 0.07). There were no significant differences in rates of recurrence (n = 3; 2 mesh, 1 sutured), tight wrap (n = 6; 4 mesh, 2 sutured), or significant reflux related conditions (n = 2; 1 mesh, 1 sutured) We did however identify a significant increase in those diagnosed with oesophageal dysmotility amongst those who had undergone biological mesh repair (18%), compared to sutured repair (1.4%) (p = 0.001). Conversely there was an increased association between sutured repair (n = 10) and functional bowel disorders compared to biologic mesh repair (n = 3) (p = 0.025). Discussion: Complex Para-oesophageal Hernia Repairs requiring use of biological mesh re-inforced cruroplasty due to large area of crural defect are associated with oesophageal dysmotility and increased symptomatic relapse. We hypothesise this is due to the increased size of the crural defect and need for extensive mediastinal dissection. Disclosure: All authors have declared no conflicts of interest. Keywords: Para-esophageal Hernia, Hiatus Hernia, Cruroplasty, Biologic Mesh O106.08: PER-ORAL ENDOSCOPIC MYOTOMY (POEM) FOR NON-ACHLASIA NEUROMUSCULAR DISORDERS OF THE ESOPHAGUS. Ahmed Sharata1, Christy Dunst1, Radu Pescarus2, Eran Shlomovitz3, Kevin Reavis1, Lee Swanstrom1, Emily Speer3 1 The Oregon Clinic, PORTLAND/UNITED STATES OF AMERICA, 2 Portland Providence Medical Center, Portland/OR/UNITED STATES OF AMERICA, 3Portland Providence Cancer Center, Portland/OR/UNITED STATES OF AMERICA Background: Per-Oral Endoscopic Myotomy (POEM) has recently been described as an alternative to conventional myotomy for neuromuscular disorders of the esophagus. While efficacy and outcomes in achalasia are

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good, there is a paucity of literature in Non-Achalasia Neuromuscular Disorders (NAND). Historically, laparoscopic myotomies are followed by unpredictable and generally poor outcomes for NAND. The aim of this study is to review our experience with POEM in NAND patients. Methods: Comprehensive data was collected prospectively on all patients undergoing POEM for NAND between 11/2010 and 11/2013. Patients were classified as having diffuse esophageal spasm (DES), hypertensive nonrelaxing lower esophageal sphincter (LES), nutcracker esophagus with/withoutrelaxing LES based on manometry. Pre/postoperative symptom scores and high resolution manometry data were collected. Operative data was compared to a separate cohort of achalasia POEM patients. Results: Twenty-five patients underwent POEM for NAND with a median age was 64 years (range, 36–83 years). Twelve had nutcracker esophagus with/without nonrelaxing LES, eight had hypertensive nonrelaxing LES, and five patients had DES. There was no mortality. There were no conversions to laparoscopy or thoracoscopy, no mediastinitis. Mean operative time was 128 mins. The incidence of inadvertent mucosotomy was 8% (2/25 patients) and capnoperitoneum requiring Veress decompression was 12% (3/25 patients). These were not different from POEM for achalasia despite the increased length of myotomy (11 cm NAND, 8 cm achalasia). Patients with DES had longer myotomies (12–23). Median follow up was 20 months (range, 7–36 months). Complete resolution of dysphagia was obtained in 70% (pre/post median score 3/0) and chest pain in 71.5% (pre/post median score 1/0). Two patients (one nutcracker esophagus and one DES) underwent unremarkable laparoscopic Heller myotomy for refractory symptoms. Five patients underwent endoscopic dilations (1–2 episodes) for occasional dysphagia or chest pain and two other patients underwent multiple dilatations. Average LES resting pressure decreased from 44.2 to 26.6mmHg (p = 0.01). Average DECA decreased from 126.7mmHg to 53.7mmHg (p = 0.0009). Heartburn and regurgitation scores were unchanged by POEM (p = 0.94; p = 0.12) with objective reflux rate of 35%. Discussion: Conclusion The POEM approach is ideal for long esophageal myotomies as it avoids the traditional mediastinal exposure required for the treatment of patients with Non-Achalasia Neuromuscular Disorders (NAND) such as diffuse esophageal spasm and nutcracker esophagus. This early experience suggests POEM is a safe and effective treatment option for a majority of NAND patients. Disclosure: All authors have declared no conflicts of interest. Keywords: Endoscopic Therapy, Esophageal Motility Disorder, POEM, Esophageal Myotomy O106.09: MINIMALLY INVASIVE ESOPHAGECTOMY WITH INTRACORPOREAL ANASTOMOSIS FOR GIANT ESOPHAGEAL LEIOMYOMA Akio Kaito, Hisayuki Matsushita, Tomoka Mizuguchi, Hideaki Shimizu Tochigi Cancer Center, Utsunomiya/JAPAN Background: The majority of esophageal submucosal tumors (SMT) are leiomyomas, but important differential diagnosis includes gastrointestinal stromal tumors (GIST), for which surgical resection is the only treatment that can provide complete cure. Video-assisted thoracoscopic surgery (VATS) for esophageal tumor has come into widespread use as a minimally invasive esophagectomy. We would like to report a case of gigantic esophageal SMT which was preoperatively diagnosed as an esophageal GIST and underwent VATS esophagectomy. Methods: A 42-years-old male referred to our hospital due to a mediastinal tumor identified on upper gastrointestinal series. Esophagogastroduodenoscopy showed smooth mucosal elevation at the lower thoracic esophagus. Endoscopic ultrasoundscopy showed SMT originating from the fourth layer of the lower thoracic esophagus. Computed tomography (CT) revealed a well demarcated poorly enhanced mass with calcification that surrounded 3/4 of the lower thoracic esophagus to the EG junction, with a diameter of 8.1 cm at most. VATS esophagectomy was performed in prone positionusing 4 ports. Theports were positionedin the 5th,6th and 7th inter costal space of the middle axillary line and one in the medial border line of the right scapula. The thoracic pressure was maintained at 6 to 10mmHg and single lung ventilation was used to obtain good view. Results: The esophageal SMT was located at the lower esophagus and was attached to the surrounding organs (vertebra, descending aorta and pericardium) but could be dissected easily. Medial and lower esophagus was mobilized with non-touch technique of the tumor and was resected at the level of bifurcation of the trachea. The tumor was extracted without injury of the capsule through the esophageal hiatus with HALS technique in a supine position. Esophagogastric anastomosis was performed with video assisted overlap method in prone position. A 45mm linear stapler was used for sideto-side anastomosis and the entry hole was closed by hand sewing. The operating time was 531 minutes and blood loss was 44ml. The postoperative course was uneventful and the patient was discharged on postoperative day 15. Pathological examination revealed the mass to be a leiomyoma of the esophagus with a Ki-67 index less than 1%.


Discussion: VATS is thought to be a feasible and safe surgical procedure for experienced thoracic surgeons with reduced invasiveness compared to conventional open esophagectomy. In this case, the tumor was preoperatively diagnosed as an esophageal GIST but pathological results revealed it to be a leiomyoma. When preoperative diagnosis is not accurate, it is vital to not to break the capsule of the SMT due to the possibility of it being a GIST. It is still controversial whether VATS esophagectomy is a safe approach for surgical resection of giant GISTs. We performed VATS esophagectomy in prone position, followed by laparoscopic gastric pull up and intracorporeal anastomosis for giant esophageal SMT which was preoperatively diagnosed as as esophageal GIST. Such methods for giant esophageal SMT has not been reported so far and is thought to be a safe and feasible method for experienced surgeons of VATS, therefore we would like to report this case with video presentation. Disclosure: All authors have declared no conflicts of interest. Keywords: video assisted thoracoscopic surgery, submucosal tumor, leiomyoma, Prone position

Wednesday, September 24 – 8:00–9:50 O107: Benign Disease: GERD I Room: Salon 2 O107.01: THE DIAGNOSTIC VALUE OF SYMPTOMS OF GERD AND DETECTION OF PEPSIN AND BILE ACIDS IN THE BRONCHOALVEOLAR LAVAGE FLUID AND EXHALED BREATH CONDENSATE IN THE IDENTIFICATION OF LUNG TRANSPLANT PATIENTS WITH GERD-INDUCED ASPIRATION P. Marco Fisichella, Nicholas Reder, Christopher Davis, Elizabeth Kovacs Loyola University, Maywood/UNITED STATES OF AMERICA Background: Gastroesophageal reflux disease (GERD) is thought to lead to aspiration and bronchiolitis obliterans syndrome (BOS) after lung transplantation. Unfortunately, the identification of those patients with GERD who aspirate still lacks clear diagnostic indicators. We hypothesized that symptoms of GERD and the detection of pepsin and bile acids in the bronchoalveolar lavage fluid (BAL) and exhaled breath condensate (EBC) are effective for identifying lung transplant patients with GERD-induced aspiration. Methods: From November 2009 to November 2010, 85 lung transplant patients undergoing surveillance bronchoscopy were prospectively enrolled. In these patients we correlated self-reported symptoms of GERD with levels of pepsin and bile acids in the BAL and EBC, and with GERD status assessed by 24-hour pH-monitoring. Sensitivity and specificity of pepsin and bile acids in the BAL and EBC were also compared to the presence of GERD on 24-hour pH-monitoring. Results: Typical symptoms of GERD (heartburn and regurgitation) had modest sensitivity and specificity for detecting GERD and aspiration; atypical symptoms of GERD (aspiration and bronchitis) showed better identification of aspiration as measured by detection of pepsin and bile acids in the BAL. The sensitivity and specificity of pepsin in the BAL when compared to GERD by 24-hour pH-monitoring were 60% and 45%, whereas the sensitivity and specificity of bile acids in the BAL were 67% and 80%, respectively. Discussion: These data indicate that the measurement of pepsin and bile acids in the BAL can provide additional data for identifying lung transplant patients at risk for GERD-induced aspiration when compared to symptoms or 24-hour pH-monitoring alone. These results support a diagnostic role for detection of markers of aspiration in the BAL, but must be validated in larger studies. Disclosure: All authors have declared no conflicts of interest. Keywords: Lung transplantation, Gastroesophageal reflux disease, Aspiration, Pepsin O107.02: DETECTION OF PEPSIN IN SALIVA AS A BIOMARKER OF OESOPHAGEAL SENSITIVITY TO REFLUX Daniel Sifrim1, Jamal Hayat2, Shirley Gabieta-Somnez1, Andrew Woodcock3, Peter Dettmar3, Jerry Mabary4, Etsuro Yazaki1, Jin-Yong Kang2, Qasim Aziz1 1 Barts and the London School of Medicine and Dentistry, Queen Mary University of, London/UNITED KINGDOM, 2St George’s Hospital, London/UNITED KINGDOM, 3Technostics Ltd, Hull/UNITED KINGDOM, 4Sandhill Scientific, Colorado/CO/UNITED STATES OF AMERICA Background: The relationship between individual gastroesophageal reflux episodes and symptoms is not completely understood. Perception of reflux is associated with oesophageal acidification, proximal extent of reflux and presence of gas in the refluxate. Patients wit GORD and hypersensitive oesophagus (HO) may have a positive reflux-symptom association with high or normal oesophageal acid exposure. Detection of pepsin in saliva suggests reflux with high proximal extent. We hypothesized that increased pepsin in saliva might be related to increased perception of reflux symptoms. We determined saliva pepsin concentration in patients presenting refluxattributed typical symptoms.


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Methods: 100 healthy subjects and 111 pts with heartburn and/or regurgitation) underwent impedance-pH (MII-pH) monitoring and simultaneous saliva sampling. Subjects collected expectorated saliva on waking, one hour after lunch and dinner. Pepsin was detected and concentration quantified using a lateral flow test with two unique monoclonal antibodies to pepsin (Peptest™, RDBiomed Ltd). Results: Patients were divided into 4 phenotypes based on MII-pH results. 1) GORD with +ve SAP (increased AET (9.35%+/-1.3, n = 58). 2) GORD with –ve SAP (increased AET (13.16+/-3, n = 21. 3) Hypersensitive oesophagus (HO)(normal AET (1.94%+/-1.2) and SAP +ve, n = 26) and 3) Functional Heartburn (FH)(normal AET (1.27%+/-0.24) and SAP -ve for acid/ non-acid reflux, n = 27). Saliva pepsin was more likely to be detected in the post-prandial periods, particularly in patients with GORD and HO. (OERD, 21% morning vs 57.8% post-prandial, p < 0.03) and (HO 23% vs 69.2%, p < 0.0002). GORD pts and HO pts had more postprandial proximal reflux events (GERD, 38 (19-58) and (HO, 20(12-28) than controls (5(2-10) or FH pts 10(4-18). The maximal pepsin concentration (max pep.) out of the three samples was highest in HO (237(52-311)ng/ml followed by GORD (121ng/ ml(29-252) compared to controls 0(0-59)ng/ml or FH 0(0-40)ng/ml, p < 0.0001. Patients with GORD +ve SAP had higher pep max (127ng/ml (30256) than GORD –ve SAP (45ng/ml(42-138) (trend but ns). All patients who were SAP +ve, (GORD or HO), had significantly higher pepsin concentration, 162(46-263)ng/ml, than those who were SAP -ve or had no symptoms, 50(0-240)ng/ml, p < 0.009. Discussion: Patients with a positive reflux-symptom association and particularly those with HO, have a high concentration of pepsin in saliva. This finding suggests that reflux perception in these patients might be related to increased volume/proximal extent of reflux. Alternatively, they may have oesophageal sensitivity to refluxates with high pepsin concentration. The reason for increased saliva pepsin in HO is under investigation (postprandial gastric pepsin and saliva secretion). We propose that high saliva pepsin concentration might be a biomarker of oesophageal hypersensitivity. Disclosure: All authors have declared no conflicts of interest. Keywords: gastro-oesophageal reflux, Pepsin, impedance-pH, oesophageal hypersensitivity O107.03: ESOPHAGEAL BASELINE IMPEDANCE VALUES CORRELATE WITH PRESENCE AND SEVERITY OF MICROSCOPIC ESOPHAGITIS IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE Edoardo Savarino1, Nicola De Bortoli2, Patrizia Zentilin3, Manuele Furnari3, Santino Marchi2, Luca Mastracci3, Roberto Fiocca3, Vincenzo Savarino3 1 University of Padua, Padua/ITALY, 2University of Pisa, Pisa/ITALY, 3 University of Genoa, Genoa/ITALY Background: In patients with Gastro-Esophageal Reflux Disease (GERD) levels of baseline impedance (BI) are impaired due to reduced mucosal integrity. Microscopic esophagitis (ME) has been associated to tight junction alterations and has been shown to be able to distinguish patients with GERD from those without. The aim of our study was to determine whether levels of BI correlate with presence and severity of ME. Methods: We evaluated 104 consecutive GERD patients. During upper endoscopy multiple biopsies were taken at Z-line and 2 cm above it. Basal cell hyperplasia, papillae elongation, dilation of intercellular spaces and intraepithelial neutrophils/eosinophil infiltration were semi-quantitatively measured (0 = absent, 1 = mild, 2 = marked) by two expert and blinded pathologists. A global score was calculated by summing up all the scores and dividing by the number of assessed lesions and was considered positive for ME when >0.35 (range 0–2). Within 3 days from endoscopy, patients underwent impedance-pH testing off-therapy. We evaluated BI values at 3 and 5cm above the LES, during the overnight rest, for at least 30 minutes after excluding swallows and reflux induced changes. Twenty healthy volunteers (HVs; 11F/9M) were also enrolled. Results: We included 20 patients with erosive esophagitis (EE; endoscopy +; 11F/9M), 65 with non-erosive reflux disease (NERD; endoscopy −, abnormal esophageal acid exposure or normal esophageal acid exposure but positive reflux-symptom association; 34F/31M) and 19 with functional heartburn (FH; endoscopy −, normal esophageal acid exposure, negative reflux-symptom association and negative response to acid suppressive therapy; 11F/8M). ME was more frequent (p < 0.001) in EE (95%) and in NERD (75%) than in FH (11%) and in HVs (15%). At 3 and 5 cm above the LES, patients with ME had lower BI levels compared to patients without ME (1482 vs. 2577 and 1411 vs. 2515; p < 0.0001). As shown in the Table, at both sites BI levels were lower in EE (p < 0.0001) compared to NERD, FH and HVs. Moreover, BI values were lower in NERD (p < 0.0001) compared to FH and HVs. No differences were found between FH and HVs (p = 0,3324). A negative correlation between BI levels and ME score was found at 3 (r = −0.629; p < 0.0001) and 5cm (r = −0.643; p < 0.0001).

EE

NERD

FH

HVs

P value

BI Levels at 3 cm, 934 (560– 1747 (840– 3342 (2530– 3515 (2950– 210ng/ml pepsin suggested the presence of GORD/HO with 95% probability. Discussion: In patients with symptoms suggestive of GORD, salivary pepsin can be used to confirm or reject the diagnosis before empirical PPI treatment. This may lessen the use of unnecessary anti-reflux therapy and the need for further invasive and expensive diagnostic methods. Disclosure: All authors have declared no conflicts of interest. Keywords: Pepsin, gastro-oesophageal reflux, impedance-pH monitoring


ABSTRACT SUPPLEMENT

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O108.02: LONG-LASTING ESOPHAGEAL MUCOSAL PROTECTION WITH ALGINATES: A POTENTIAL FOR TOPICAL MUCOSAL THERAPY IN GASTROESOPHAGEAL REFLUX Philip Woodland1, Chung Lee1, Sean Preston1, Peter Dettmar2, Daniel Sifrim1 1 Barts and the London School of Medicine and Dentistry, London/UNITED KINGDOM, 2Technostics Ltd, Hull/UNITED KINGDOM

for motility disorders and each EGJ was classified as: Type I, no separation between the LES and the CD; Type II, minimal separation (>1 and 2 cm separation between the LES and the CD. The patients also underwent impedance-pH testing off-therapy. We measured the esophageal acid expsosure time (AET), number of total impedance-detected reflux episodes and symptom association analysis using symptom association probability (SAP+ if ≥95%) and symptom index (SI+ if ≥50%).

Background: Patients with non-erosive reflux disease (NERD) exhibit impaired esophageal mucosal integrity in the form of dilated intercellular spaces and low transepithelial electrical resistance (TER). Such refluxateinduced changes to the mucosal integrity may underlie increased sensitivity to perception of reflux events, even on PPI, and could potentially be modified by application of topical solutions. Sodium alginate solutions are used in treatment of GERD, with proposed mechanisms of action including acid buffering, displacement of the gastric acid pocket, and reduction of GER events. We have recently described that in vitro topical application of a sodium alginate solution is able to protect mucosal biopsies against impairment of esophageal mucosal integrity when exposed to acidic solutions shortly after application. The potential durability of this protection is unclear. We aimed to assess the protective effect and physical location of a topically applied sodium alginate solution 1 hour after application.

Results: We enrolled 53 [28M/25F; mean age 53 (21–76)] consecutive GERD patients. At upper endoscopy, 12 patients had erosive esophagitis, 2 had Barrett esophagus and 39 had no mucosal breaks. Based on CC, we identified 21 (40%) patients with Type I EGJ, 19 (36%) with Type II EGJ and 13 (24%) with Type III EGJ. Patients with Type III EGJ had an higher median number of reflux episodes [61 (12-305) vs. 38 (4-109) vs. 30 (6-98), respectively; p < 0.01)], a greater mean AET [20.6 (4.4-43.4) vs. 14.1 (0.2-48.3) vs. 11.9 (0.1-54.3), respectively; p < 0.01)] and had more frequently a positive symptoms association [9 (69%) vs. 9 (47%) vs. 11 (52%), respectively; p < 0.05)] compared to patients with Type II and Type I EGJ. Moreover, patients with Type II EGJ tended to have a higher median number of reflux episodes and mean AET compared to patients with Type I EGJ, but statistically significance was not reached (p = 0.06).

Methods: 3 mucosal biopsies were taken from the distal oesophagus (3 cm above the z-line) in 15 patients attending the Royal London Hospital for gastroscopy examination. All biopsies were transferred immediately to Krebs buffer pH 7.4. Biopsies were then each placed in a specially adapted Ussing chamber and bathed in Krebs pH 7.4 (neutral) solution for 20 minutes to equilibrate. The luminal surfaces of 2 biopsies were coated with 200 μl of either a sodium alginate solution (Gaviscon Advance, Reckitt Benckiser, Hull, UK) or a viscous control solution (of same viscosity, but without alginate). The biopsies were mechanically washed with 5 ml Krebs, then returned to the chambers then bathed in neutral solution for a further 1 hour. The luminal aspect of the biopsy was then exposed for 30 min to an acidic solution pH 2 + 1 mg/ml pepsin + 1 mM taurodeoxycholate. Percentage changes in TER from baseline at the end of exposure were recorded. For the 3rd biopsy sodium alginate solution containing fluorescein-labeled alginate was used, and after 1 hour bathing in neutral solution the biopsy was fixed for immunohistological examination of the location of the alginate. Results: Our previous experiments have demonstrated that exposure of unprotected biopsies to the acidic solution results in a −14.4 ± 2.9% change in TER from baseline. I hour after protection with alginate solution the same exposure caused a −8.2 ± 4.2% change in TER compared to −15.9 ± 3.0% change after protection with the viscous control (p < 0.05). Labeled alginate could be seen coating the luminal surface in all cases. Discussion: In vitro, alginate solutions can adhere to the esophageal mucosa for up to 1 hour and exert a topical protectant effect against refluxate like solutions. This suggests that durable topical protectants can be further explored and developed as first-line/add-on therapies for GERD. Disclosure: All authors have declared no conflicts of interest. Keywords: GERD, Alginates, Mucosal integrity

O108.03: ESOPHAGOGASTRIC JUNCTION MORPHOLOGY MAY BE USEFUL TO PREDICT A POSITIVE IMPEDANCE-PH MONITORING IN PATIENTS WITH GERD Edoardo Savarino1, Chiara De Cassan1, Renato Salvador1, Francesca Galeazzi1, Elisa Marabotto2, Moira Rigato1, Manuele Furnari2, Patrizia Zentilin2, Nicola De Bortoli3, Santino Marchi3, Romeo Bardini1, Giacomo Carlo Sturniolo1, Vincenzo Savarino2 1 University of Padua, Padua/ITALY, 2University of Genoa, Genoa/ITALY, 3 University of Pisa, Pisa/ITALY Background: High-resolution manometry (HRM) provides a better representation of the esophagogastric junction (EGJ) making it possible to isolate the crural diaphragm (CD) contraction from expiratory lower esophageal sphincter (LES) pressure. According to the Chicago Classification (CC), three different EGJ morphologic subtypes can be detected based on the separation between the LES and the CD. Recently, these EGJ subtypes have been positively correlated with the objective evidence (i.e. endoscopy+ or pH-metry+) of gastro-esophageal reflux disease (GERD). To date, data on the correlation between EGJ subtypes and esophageal acid exposure as well as impedance-detected reflux episodes are lacking. So far, the aim of our study, was to correlate the different EGJ subtypes with impedance-pH findings in GERD patients. Methods: Consecutive patients with heartburn and/or regurgitation and a recent endoscopic assessment were enrolled. All patients underwent a 36-Solid State HRM with a 5-min baseline recording to assess the EGJ and 10 single water swallows (5 mL) at 30-s intervals to evaluate the esophageal peristalsis and EGJ function. The tracings were analyzed based on the CC

Discussion: With increasing separation between the LES and the CD, from Type I to Type III EGJ, patients had a gradually and significantly increase of reflux episodes and esophageal acid exposure. Thus, EGJ morphology may be useful to predict an abnormal impedance-pH testing in patients with GERD. Disclosure: All authors have declared no conflicts of interest. Keywords: impedance-pH, reflux episodes, High-resolution manometry, esophagogastric junction O108.04: REOPERATION AFTER FAILED ANTI-REFLUX PROCEDURES Andre Brandalise, Nelson Brandalise, Nilton Aranha, Claudia Lorenzetti Hospital Centro Medico de Campinas, Campinas/BRAZIL Background: As laparoscopic anti-reflux surgery gained popularity as an option for treating a considerable number of patients suffering from chronic gastroesophageal reflux disease (GERD), the number of patients needing a re-intervention after this kind of surgeries also raised. We present our series and results of patients submitted to reoperations after anti-reflux surgeries Methods: From May/1993 to Feb/2014, 181 patients underwent a reoperation by our group. The mean age was 46 years old (1–78). Twenty four (13.3%) of them were first operated by laparotomy and 157 (86.7%) by laparoscopy. The first operation was performed by our group in 46 cases (out of 2400 anti-reflux procedures) We divided the patients into 3 groups regarding the main reason for reoperation: GERD recurrence, dysphagia and paraesophageal hernias. There were 78 (43.1%) patients in dysphagia group, 74 (40.9%) in recurrence group and 29 (16%) in paraesophageal hernia group. Results: In the dysphagia group, the procedures in the reoperation were: take down of fundoplication and new total fundoplication in 35 (44.9%) patients, myotomy plus partial fundoplication in 25 (32.0%), partial fundoplication in 14 (17.9%) and other procedures in 4 (5.1%). Follow up interview was possible in 56 (71.8%) patients, mean follow up was 29 months and 41 (73.2%) are asymptomatic, 8 (14.2%) complain of reflux and 7(12.5%) still experience some dysphagia. In the recurrence group, a total fundoplication was done in 73 (98.6%) cases. One patient was treated with a Roux-en-Y gastric bypass. Follow up interview was possible in 56 patients (75.6%) with an average of 30 months. Forty-nine (87,5%) patients are asymptomatic, 4 still complain of reflux and 2 present dysphagia. One patient with a new recurrent paraesophageal hernia complains of thoracic pain. In the paraesophageal hernia group, a mesh was used to reinforce the hiatus in 15 (51.7%) patients. 13 were treated with total fundoplication, 1 with gastric bypass and simple suture of the hiatus was done in an immediate reoperation after vomiting in the first post-operative day. Objective follow up was done in 19 (65.5%) patients. Normal endoscopy was found in 12 (63.2%) and small paraesophageal hernias in 7 (36,8%), six of them are asymptomatic. Discussion: There are many causes for a new operation following failed antireflux procedures. In our country reoperation rates for persistent dysphagia are still very high. That is, in our vision, due to technical mistakes, performing the fundoplication with the body of the stomach, not the fundus. This group has very good outcomes. Recurrence of the disease is growing in incidence, it can be due to the natural history of the fundoplication or more advanced disease (Barrett, stenosis). A new fundoplication is the best approach but, depending on the severity of the disease, other techniques (Collis-Nissen, Gastric bypass) must be used, also with very good results. Paraesophageal hernias are usually asymptomatic an require no reoperations, but when bothersome symptoms occur, the results are not so good as the previous groups. Possible explanations are shortened esophagus or large hiatal defects with thin muscle.

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Disclosure: All authors have declared no conflicts of interest. Keywords: reoperation, fundoplication, hiatal hernia, GERD O108.05: RABEPRAZOLE PROTECTS REFLUX ESOPHAGITIS AFTER TOTAL GASTRECTOMY IN RAT MODEL Hashimoto Naoki Kinki University, Osaka/JAPAN Background: Reflux of duodenal content into the esophagus has a role in the pathogenesis of esophageal inflammatory lesions. As little is known about effective therapy, we studied the effect of proton pump inhibitor (PPI) therapy on esophageal bile reflux in esophagitis after total gastrectomy.The purpose of this study is to clarify the effect of PPI (Rabeparazole) on reflux esophagitis. Methods: Sixteen 8-week old male Wistar rats were underwent total gastrectomy and esophagoduodenostomy to induce esophageal reflux of biliary and pancreatic juice. In 5 rats the sham operation induced a midline laparatomy alone (Sham). One week following surgery, they were treated with saline (Control) (n = 8) PPI(Rabeprazole)(n = 8)(30mg/kg/day)ip for 2 weeks. 3 weeks after operation, all rats were killed and the esophagus was evaluated histologically. Esophageal injury was evaluated by macroscopic, microscopic findings and expression of COX2 and PGE2. Measurement of bile acids in esophageal washing and common bile duct. Results: 1. Macroscopic findings In control rats, longitudinal ulcerations located primarily in the middle and lower thirds of the esophagus were observed. However, the gross appearance of esophagus from PPI group, all showed only scattered erosions or mild hemorrhage spots with whitish exudates scattered along the esophagus. 2. Microscopic findings Control group revealed evident thickening of epithelium, elongation of lamina papillae, and basal cell hyperplasia in the esophageal mucosa. Marked leukocyte infiltration in the submucosa was observed in the control group. However, the ulcer length, the degree of inflammatory cell infiltration, and the degree of hyperplasia were significantly decreased in the PPI group. 3. Total bile acid in the esophageal lumen (μmol/L) Total bile acid in the esophageal lumen was significantly increased in the control group (175 ± 5) compared with the sham operated rats (35 ± 5). The treatment with PPI (45 ± 5) significantly (p < 0.05) inhibited the increase in total bile acid activity in the esophageal lumen. 4. Total bile acid (mmol/L) of bile juice aspirated from the common bile duct There is no difference between control group (23.2 ± 3.4) and PPI group (23 ± 2.4). 5. Expression of COX2 COX2 was not detected in normal esophagus. However, COX2 was abundantly expressed in the inflamed esophageal mucosa of rats exposed to chronic duodenoesophageal reflux. The expression of COX2 was significantly (p < 0.05) increased by immunostain in the control group compared with the PPI group. 6. Measurement of PGE2 production (pg/TPmg) in esophageal tissue PGE2 synthetic activity was significantly increased in control group (691 ± 50) compared with sham group (25 ± 5). These increase were significantly (p < 0.05) decreased in PPI group (372 ± 30). 7. Esophageal epithelial proliferation in rat esophagus The PCNA L I was significantly increased in the control (65 ± 10%) compared with the sham operated group (30 ± 5%). These increase were significantly (p < 0.05) decreased in the PPI group (40 ± 5%). Discussion: With this model, we have demonstrated that Rabeprazole is an effective therapy for reflux esophagitis after total gastrectomy due to bile reflux. These results indicate that bile acid, which is inhibited by Rabeprazole, plays an important role in the mucosal damage induced by duodenal reflux and that it can be therapeutic target in patients with reflux esophagitis. Disclosure: All authors have declared no conflicts of interest. Keywords: Reflux esophagitis, Rabeprazole, esophagoduodenostomy, Bile acids


O108.06: ESOPHAGEAL MOTILITY AND PH METRY IN PATIENTS WITH LARYNGEAL-TRACHEAL STENOSIS: A PRELIMINARY STUDY Sergio Szachnowicz1, Angela Falcao2, Paulo Cardoso1, Ary Nasi3, Helio Minamoto1, Ana Carolina Dantas1, Rubens Sallum3, Paulo Pego-Fernandes1, Ivan Cecconello3 1 University of Sao Paulo Medical School, Sao Paulo/BRAZIL, 2University of Sao Paulo Medical School, Sao Paulo/BRAZIL, 3University of Sao Paulo, Sao Paulo SP/BRAZIL Background: Laryngeal-tracheal stenosis is a management problem that requires multiple surgical/endoscopic procedures for its correction. An increasing number of recalcitrant, mostly high airway stenosis and late post-operative recurrences led us to investigate other causes as Gastro esophageal reflux disease (GERD). Laryngeal-tracheal stenosis is a management problem that requires multiple surgical/endoscopic procedures for its correction. An increasing number of recalcitrant, mostly high airway stenosis and late post-operative recurrences led us to investigate other causes as Gastro esophageal reflux disease (GERD). The aim of this study is to assess the prevalence of pathologic GER in this patient population. Methods: Patients above 18 years with idiopathic, post-intubation stenosis or with recurrence of the stenosis following laryngeal-tracheal resections were included. Exclusion criteria were advanced age, previous surgery of the upper digestive tract. Patients were submitted to stationary manometry using an eight-channel perfused catheter connected to a low compliance pneumohydraulic pump (Multiplex II, Alacer Biomedica, Brazil). The assessment included lower esophageal sphincter (LES) position and pressure, motility and pressures of the esophageal body and upper esophageal sphincter pressure. The 24-hour pH study used a dual channel antimony electrode catheter and a logger (AL-3, Alacer Biomedica, Brazil). Results: 80 patients (50 males) with 44+16 years of age were assessed. Twenty-nine patients (36%) presented with typical GER symptoms. Esophageal manometry revealed normal LES pressure (21.3 ± 9mmHg; normal = 14mmHg-34mmHg) and 24.6% presented with a hypotonic LES. The distal esophageal body average pressure was normal (100mmHg) with only 10.9% of the cases with hypomotility (less than 30mmHg). Esophageal pH study was performed in 74 patients and 50% showed abnormal acid reflux exposure in the distal electrode with an average of 5,2% of total monitoring time (normal less than 4,5%) and a DeMeester score of 21,2 (normal less than 14,7). There was a predominance of supine GER (4.3%; normal less than 3,5%). Thirty patients (40.5%) presented with supraesophageal acid reflux as detected by the proximal esophageal pH electrode (average of 1.2 episodes/patient). Discussion: This preliminary study in patients with laryngotracheal stenosis reveals a high prevalence of abnormal acid reflux predominantly in supine position, and with prevalent upper esophageal acid exposure. This has occurred with low incidence of typical GER symptoms in the presence of essentially normal esophageal motility in the majority of the patients. A larger prospective study is under way to investigate the role of acid and non-acid reflux in a larger cohort of patients with upper airway stenosis and its effects on the outcome. Disclosure: All authors have declared no conflicts of interest. Keywords: GERD, LARYNGO-TRACHEAL STENOSIS, esophageal motility, supraesophageal reflux disease

O108.07: ENHANCED PERCEPTION OF PROXIMAL GASTRO-OESOPHAGEAL REFLUX: IMPAIRED MUCOSAL INTEGRITY OR DISTINCT SENSORY INNERVATION? Philip Woodland, Chung Lee, Rubina Aktar, Sean Preston, L Blackshaw, Daniel Sifrim Barts and the London School of Medicine and Dentistry, London/UNITED KINGDOM Background: In patients with GERD, including refractory disease, reflux events reaching the proximal esophagus are more likely to be perceived than those only reaching the distal esophagus. There is also experimental data suggesting an increased sensitivity of the proximal esophagus relative to the distal. As such, the proximal esophagus is likely to be highly significant in the pathogenesis of GERD symptoms. Reasons for this proximal esophageal sensitivity are not clear, but may include reflux volume, impairment in mucosal integrity or changes in sensory innervation. It has recently been shown that the distal mucosal integrity is more vulnerable to acid exposure in GERD than in controls. The integrity of the proximal esophagus has not been tested. To our knowledge, there are no studies evaluating mucosal afferent innervation of the distal and proximal esophagus. We aimed to compare mucosal integrity and afferent nerve


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ABSTRACT SUPPLEMENT

distribution in the proximal and distal esophagus in patients with heartburn without esophagitis.

gastric bypass are good alternatives in these cases. No complications related to the mesh were found in the follow-up period.

Methods: In 23 patients with heartburn and 10 healthy volunteers baseline proximal and distal esophageal impedance was measured in vivo. Oesophageal mucosal biopsies from the distal and proximal oesophagus were taken and baseline transepithelial electrical resistance (TER) was measured in Ussing chambers. Biopsies were examined immunohistochemically for presence and location of calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres.


Results: Baseline impedance was higher in the proximal than in the distal esophagus in healthy volunteers (2935 ± 204 Ω vs. 2234 ± 290 Ω, p < 0.05) and in patients (2949 ± 183Ω vs.1945 ± 235Ω, p < 0.001). However, baseline TER was not significantly different between proximal and distal esophagus, or between patients with heartburn and healthy volunteers. Mucosal CGRPimmunoreactive nerves were located more superficially in the proximal esophagus compared to the distal oesophagus in healthy controls (12.3 ± 0.9 vs. 23.8 ± 1.2 cells from lumen, p < 0.001) and in patients (5.7 ± 0.7 vs. 22.2 ± 2.7 cells from lumen, p < 0.0001). Moreover, these nerves were located closer to the lumen in patients with heartburn compared to asymptomatic controls (5.7 ± 0.7 vs. 12.3 ± 0.9, p < 0.001). Discussion: The baseline mucosal integrity of the proximal esophagus is not more impaired than that of the distal, nor is it more impaired in patients with heartburn symptoms versus healthy controls. Increased sensitivity of the proximal esophagus in GORD may instead be associated with a more superficial location of mucosal afferent nerves. Topical protection of the proximal esophageal mucosa is a potential treatment strategy to reduce this sensitivity. Disclosure: All authors have declared no conflicts of interest.

Keywords: Polypropylene, mesh, paraesophageal hernia O108.09: NORMAL VALUES OF 24H MULTICHANNEL INTRALUMINAL IMPEDANCE-PHMETRY (MIIPH) IN AN OBESE POPULATION Dimitrios Theodorou, Georgia Doulami, Stamatina Triantafyllou, Maria Natoudi, Zoi Vrakopoulou, Konstantinos Albanopoulos, Emmanouil Leandros, Georgios Zografos University of Athens, Athens/GREECE Background: Obesity and gastro-esophageal reflux disease (GERD) have been related and many pathophysiological mechanisms have been described. 24h multichannel intraluminal impedance-pHmetry (MIIpH) has been recently introduced in the diagnostic algorithm of patients with GERD. However, normal values of MIIpH have only been described in non obese healthy volunteers. Our aim is to describe the normal values of MIIpH in an obese population without GER symptoms. Methods: Twenty obese volunteers without GER symptoms underwent 24h MIIpH study. Data were analyzed with a statistical package and mean and 95thpercentiles are described. Results: Mean body mass index of the population was 47.31 kg/m2 and mean age was 41.7 years old. Mean DeMeester score was 13.95 and 95th percentile was 34.73. Table 1 contains mean and 95th percentiles of DeMeester’s subscores, impedance characteristics and reflux episodes.

Keywords: GERD, innervation, mucosa

O108.08: SAFE USE OF POLYPROPYLENE MESH IN LARGE HIATAL HERNIAS Andre Brandalise, Nilton Aranha, Nelson Brandalise, Claudia Lorenzetti Hospital Centro Medico de Campinas, Campinas/BRAZIL Background: Minimally invasive surgery has rapidly gained an important role in the treatment of gastroesophageal reflux disease. However, the best method to treat large hernias and paraesophageal hernias (type II and IV) is still under discussion. The use of prosthetics for enhancing the crural repair has been proposed by several authors in order to reduce the high relapse rates found in these patients Methods: A polypropylene mesh was used to reinforce the hiatal closure in large hernias – types II to IV – with primary or recurrent hiatal defect diamter greater than 5 cm. The prosthesis was done cutting the mesh in a “U”-shape, adapted to the dimensions found in the intraoperative field and coating the inner edge (which would have direct contact with the esophagus) with a silicon catheter. This was achieved by removing a small longitudinal segment of the catheter and then inserting the edge of the cut mesh, fixing with running nylon 5–0 suture. After cruroplasty, the mesh was placed as an onlay patch and fixed with staples. The fat tissue from the omentum was then fixed over the mesh to avoid its contact with the gastric fundus and fundoplication. Results: From 1999 to 2014, this technique was used in 90 patients. There were 63 females and 27 males, aged 30–84 years (mean 62 years). In 63 (70%) patients, paraesophageal hernia was primary and in 27 (30%), relapse after antireflux surgery. The only case of death in this series (1.0%) occurred on 22nd postoperative day in one patient (74 y) that had a laceration of the sutures on the fundoplication, causing gastropleural fistula and death. There was no relationship with the use of the prosthesis. A followup of six months or more was achieved in 72 patients (80%), ranging from six to 146 months (mean 48,4 months). All patients have at least one follow-up endoscopy or esophageal contrast examination, and a clinical interview. There were 9 cases of hernia reccurence. Three in 52 patients (5.7%) with primary hernias and six in 20 patients (30%) with reccurent paraesophageal hernias. In this follow-up period, no cases of complications related to the prosthesis (stenosis or erosion) were observed. In the clinical interview, 60 patients (83%) are asymptomatic, seven (9.7%) complain of GERD symptoms and five (7%) refer mild dysphagia. In the 9 patients in whom a reccurence occured, four (44.4%) are asymtomatic and five (55.6%) present pirosis or reflux. Discussion: The application of mesh-reinforced hiatal closure has resulted in a significant reduction in recurrence rates and has been an option adopted by some surgeons. However, serious complications had been described, mainly fibrosis, esophageal stenosis and intraluminal erosion, which causes dysphagia and may lead to major ressections. The model presented by the authors leads to low reccurence rates in primary hernias. The reccurent hernias still have high rates of a second reccurence, even using mesh as reinforcement. Other procedures such as Collis gastroplasty or Roux-en-Y

Upright time in reflux Recumbent time in reflux Total time in reflux Episodes over 5 minutes Longest episode (min) Total episodes Bolus exposure- All reflux percent time Median bolus clearance All reflux upright distal activity All reflux recumbent distal activity All reflux upright proximal activity All reflux recumbent proximal activity Postprandial all reflux activity Preprandial all reflux activity

Mean value

95th percentile

3.95% 3.08% 3.62% 1.46 7.74 50.15 1.8% 10.04 55.07 12.3 24.69 4.93 35.57 31.28

7.69% 13.13% 9.15% 6.72 38.05 103.52 4.43% 18.4 92.1 53.8 56.8 15 67.5 61.6

Discussion: Mean values and 95th percentiles of MIIpH in obese non GER patients are different from the published normal values of non obese healthy patients. More precisely, obese volunteers without symptoms of GER have increased recumbent reflux activity. Disclosure: All authors have declared no conflicts of interest. Keywords: Obesity, GERD, impedance pHmetry, DeMeester score

Wednesday, September 24 – 13:30–15:00 O109: Esophageal Cancer: Salvage Esophagectomy and Palliative Therapy Room: Salon 2 O109.01: INDICATION FOR SALVAGE ESOPHAGECTOMY AFTER DEFINITIVE CHEMORADIOTHERAPY IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS Masayuki Watanabe, Shinji Mine, Kojiro Nishida, Yasuhiro Okumura, Hironobu Shigaki, Akira Matsumoto Cancer Institute Hospital, Tokyo/JAPAN Background: Definitive chemoradiotherapy (dCRT) is a curative intent treatment for patients with esophageal cancer. However, the long-term outcome of patients with residual or recurrent tumors is dismal. Although salvage esophagectomy is almost the only treatment strategy that offers any chance of long-term survival to such patients, high morbidity and mortality rates have been reported. The aim of this study was to clarify who really benefits from the high risk surgery. Methods: Sixty-three patients who underwent salvage esophagectomy after chemoradiotherapy or radiotherapy with radiation dose of more than 50Gy at Cancer Institute Hospital between April 1988 and October 2013 were enrolled in this study. Short-term outcomes were evaluated by reviewing postoperative complication, Clavien-Dindo classification, length of hospital stay after surgery, and mortality. Survival rates were calculated by the Kaplan-Meier method, and statistical significance was determined by the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analysis of the overall survival.

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Results: Short-term outcome: Postoperative complication occurred in 41 patients (65.1%). Pulmonary complications and anastomotic leakage were observed in 23 (36.5%) and 10 (10.9%) cases, respectively. The mortality rate was 7.9%. Univariate analysis revealed that depth of invasion before dCRT (cT3/T4), positive lymph node metastasis before dCRT, advanced stage (cStage III/IV), and residual tumor after dCRT are the significant factors for the mortality. Long-term outcome: The 3- and 5-year overall survival rates were 29.8% and 15.0%, respectively. Among the preoperatively recognized variables, residual tumor after dCRT, the disease-free interval, and ycStage were the significant prognostic factors. However, multivariate analysis identified no independent prognostic factor. When we included pathological findings into the variables, residual disease (R1, 2) and depth of tumor invasion (ypT3/4) were the independent factors for poor prognosis. Discussion: When we consider the safety of surgery and the long-term outcomes, patients with tumors limited within T2 and those who have once achieved complete response to dCRT were the good candidates for salvage esophagectomy. Disclosure: All authors have declared no conflicts of interest. Keywords: Salvage esophagectomy, indication, definitive chemoradiootherapy O109.02: CATHEPSIN E IS REMARKABLY OVEREXPRESSED IN BARRETT’S INTESTINAL METAPLASIA AND DYSPLASIA TISSUES BUT LACKS PROMISE AS A DIAGNOSTIC BIOMARKER IN BLOOD. Oliver Fisher1, Angelique Levert-Mignon1, Natalia Botelho1, Araluen Freeman1, Melissa Thomas1, Dan Falkenback2, Sarah Lord3, Antony Wettstein4, Yuri Bobryshev1, Reginald Lord1 1 St. Vincent’s Centre for Applied Medical Research, Sydney/NSW/ AUSTRALIA, 2Lund University Hospital, Lund/SWEDEN, 3University of Notre Dame School of Medicine, Sydney/NSW/AUSTRALIA, 4 St. Vincent’s Clinic, Sydney/NSW/AUSTRALIA Background: The identification of clinically relevant biomarkers for patients with Barrett’s esophagus (BE) or esophageal adenocarcinoma (EAC) remains an unsolved problem. Cathepsin E (CTSE) is an aspartic proteinase and possible oncofetal antigen that is differentially expressed in the metaplasia-dysplasia-neoplasia sequence of gastric and colon cancer and is overexpressed in almost all pancreatic ductal adenocarcinomas. Increased CTSE levels are linked to improved survival in lung, bladder and breast cancer. Cathepsin B & C are up-regulated in BE & EAC. We therefore evaluated CTSE in BE/EAC. Methods: 273 pre-treatment tissues from 199 patients were analyzed (31 normal squamous esophagus (NE) from non-GERD patients, 29 BE IM, 31 BE with dysplasia, 108 EAC). CTSE relative mRNA expression was measured by multiplex tandem RT-PCR, and protein expression by immunohistochemistry. Cathepsin E serum levels were determined by ELISA. Results: CTSE mRNA expression levels were more than 1,000-fold higher in BE IM and BE dysplasia tissues compared to NE (Fig. 1). CTSE levels dropped significantly in EAC tissues but remained significantly higher than NE levels. A similar expression pattern was present in IHC, with absent staining in NE, intense staining in IM and dysplasia, and less intense EAC staining. CTSE serum analysis failed to discriminate patient groups. In uniand multivariable Cox proportional hazards modeling CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 42% relative risk reduction for death (HR 0.58, 95% CI 0.27 – 1.21, p = 0.15).


Discussion: Cathepsin E mRNA expression is upregulated more than any known gene in Barrett’s IM and dysplasia tissues. Protein expression is similarly highly intense in IM and dysplasia tissues. Disclosure: All authors have declared no conflicts of interest. Keywords: Cathepsin E, Esophageal adenocarcinoma, Barrett’s Esophagus O109.03: TRACHEO-ESOPHAGEAL FISTULA IN ADVANCED SQUAMOUS CELL CARCINOMA OESOPHAGUS – A SINGLE CENTRE EXPERIENCE OF 31 CASES John Grifson, Servarayan Murugesan Chandramohan, D Kannan, Jasper Sandeep Rajasekar, Rajendran Vellaisamy, D Bennet, A Amudhan, T Perungo, R Prabhakaran, Madeswaran Chinnathambi, Jeyasudhahar Jesudason Madras Medical College, Chennai/INDIA Background: Among patients with advanced carcinoma Oesophagus, the development of airway – oesophageal fistula alters the natural history dramatically with a rapid downhill course leading onto mortality in untreated cases. In this paper we analyse our experience in management of this rare disease and the outcomes following treatment. Methods: All patients diagnosed with tracheo-esophageal fistula (TEF) secondary to Carcinoma oesophagus from August 2010 to February 2013 were included in the study. At presentation demographic data was recorded, accurate history taking and physical examination was done and documented. The performance status was assessed according to ECOG. A chest radiograph was taken to document the respiratory complications. The status of disease was assessed by endoscopy, fiber-optic bronchoscopy and contrast enhanced CT scan of the neck and chest. Each patient was individually assessed and treatment was tailored according to their performance status and nature of disease. SEMS placement was performed by endoscopy over a guide wire under fluoroscopic guidance. Results: Thirty-one patients with a diagnosis of TEF due to advanced squamous cell carcinoma oesophagus were included in the study. Eighteen patients (58%) had received no treatment previously. Thirteen patients (42%) were under various treatment for squamous cell carcinoma oesophagus and TEF developed following Chemo-Radiotherapy in 5 patients (16.1%), following radiotherapy in 5 patients (16.1%) and following chemotherapy in 3 patients (9.7%).The performance status was good in 12 patients (38.7%) and poor in 19 (61.3%). On endoscopic evaluation the fistula was located in middle third of oesophagus in 26 patients (83.9%) and in 5 patients (16.1%) endoscopy could not clearly delineate the location. The growth was not negotiable in 9 patients (29%). Respiratory complications were present in 26 patients (84%). Lung metastases were found in 4 patients (12.9%). Assessment of the tracheal end of fistula with fiber-optic bronchoscopy was possible in 28 patients (90.3%). The location of fistula at the tracheal end was above the carina in 18 patients (64.3%) and below the carina in 6 patients (21.4%). In 4 patients (14.2%) the fistula site could not be properly delineated. Treatment with SEMS was feasible in 14 (45.1%) patients. Eleven patients (35.4%) were too sick for any treatment and hence were advised best supportive care (8 patients in this group had FJ done elsewhere).Six patients (19.5%) with minimal lung sepsis and small fistula received chemo-radiation. The technical success rate of oesophageal stenting was 86%. In the stented patients 94% had clinical relief of dysphagia. Following stenting, bleeding (n = 1, 0.7%), pain (n = 2, 1.4%), aspiration (n = 4, 28.6%) and stent migration (n = 2, 14.3%) were the complications observed. Discussion: In patients with advanced squamous cell carcinoma oesophagus with TEF it is difficult to offer any surgical therapy. In advanced disease SEMS has helped our patients to take food via naturalis. In some patients who are terminally ill best supportive care is the only treatment that can be offered. Disclosure: All authors have declared no conflicts of interest. Keywords: Malignant tracheoeospphageal fistula, advanced Squamous cell carcinoma esophagus, Self-expanding metallic stent, Palliation O109.04: RETHORACOPSCOPY AS A SALVAGE PROCEDURE AFTER ESOPHAGOGASTRECTOMY WITH INTRATHORACIC ANASTOMOSIS Palanivelu Chinnusamy, Praveen Raj Palanivelu, Senthilnathan Palanivelu, Parthasarathi Ramakrishnan, Sivalingam Perumal GEM Hospital & Research Centre, Coimbatore/INDIA

Figure 1. CTSE expression in tissue.

Background: Leakage after intrathoracic anastomosis is a dreaded complication after esophagectomy. The rates have been mentioned from 0% to 28.5%. in our series leak rates of 0.77% was found. Outcomes of conservative


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management are often disappointing and may lead to loss of salvagibility. Improperly managed cases may lead to septic shock and even death of the patient.

of microscopic residual tumor left undetected, prophylactic esophagectomy should be an optional treatment after definitive chemoradiation for locally advanced squamous cell thoracic esophageal cancer.

Methods: Here we describe the Re Thoracoscopic management of 4 cases of anastomosis leak. 2 cases (1 lap transhiatal and 1 ThoracoLap Ivor Lewis esophagectomy) had presented with persistent tachycardia, tachypnea and unsettled course, which on CT Scan was found to have loculated Abscess on 12th and 15th post operative day. Re thoracoscopy was done, abscess cleared up, ICD Tubes changed, Removable SEMS Placed and Ryles tube passed to stomach for feeding purposes. 1 case of Minimally invasive Ivor Lewis esophagectomy was found to have anastomosis leak on the gastric conduit site on UGIEndoscopy at 5th Postoperative day. Another case of Minimally invasive Ivor Lewis esophagectomy was diagnosed with leak during CT scan on 9th post operative day. In both cases, rethoracopy was done, previous anastomosis dismantled, edges trimmed till good vascularity was reached and reanastomosis done.


Results: All 4 patients thereafter had an uneventful recovery. Discussion: Re thoracopscopy is a viable alternative for salvage in cases of intrathoracic anastomosis leak. Disclosure: All authors have declared no conflicts of interest. Keywords: Rethoracopscopy, salvage, Esophagogastrectomy, leak O109.05: OUTCOME OF PROPHYLACTIC ESOPHAGECTOMY AFTER DEFINITIVE CHEMORADIATION IN LOCALLY ADVANCED SQUAMOUS CELL ESOPHAGEAL CANCER Chadin Tharavej, Patpong Navicharoen, Suthep Udomsaweangsup, Supa-Ut Pungpapong Chulalongkorn University, Bangkok/THAILAND Background: Definitive chemoradiation (dCRT) has been gaining in popularity for treatment of locally advanced squamous cell esophageal cancer. Esophagectomy has been reserved for persistent or recurrent disease (salvage surgery). However, recent reports have shown that number of patients with salvage surgery is significantly lower than expected candidates. Only 20% of patients with persistent or recurrent disease after dCRT were candidates for salvage esophagectomy. Majority of patients had concomitant distant metastasis or vital structure invasion when local disease was diagnosed which preclude esophageal resection. To date, no sensitive investigation can early detect persistent or recurrent disease. We have known form German trial that approximately two-third of patients had loco-regional recurrence within 2 years after dCRT. Only some of them were candidates for salvage surgery. Nevertheless, operative mortality was high (10–20%) which may result from poor patient performance status during disease recurrence. However, successful patients had prolonged survival. We consider that watchful waiting until recurrent disease is obvious is too late for salvage surgery. Early prophylactic esophagectomy may provide cure or prolonged survival in patients treated with dCRT. We hypothesized that significant number of patients have microscopic residual disease after definitive chemoradiation which worth undergoing prophylactic esophagectomy and secondly, in contrast to salvage surgery, resectability rate should be significantly higher and operative mortality should be significantly lower with early prophylactic esophagectomy. We conducted this prospective study to test our hypothesis. Methods: Patients with locally advanced squamous cell thoracic esophageal cancer (tumor length >5cm with T3-T4/N0-1/M0) were included. All patients had planned radical 2-field esophagectomy 3 months after concurrent 64 Gy of radiotherapy with 2 cycles of 5FU and cis-platin. Contraindications for esophagectomy included distant metastasis, vital structure invasion, poor performance status and refused surgery. Studies for detection of residual tumor after chemoradiation included endoscopy, CT and PET scan. Exclusion criteria were patients who had esophagectomy because of residual disease detected (salvage surgery) preoperatively. Pretreatment feeding jejunostomies were performed in all patients. Treatment outcome and histopathological study of esophagectomized specimens were examined.

Keywords: definitive chemoradiation, squamous cell esophageal cancer, esophagectomy O109.06: THE TREATMENT STRATEGY AND CLINICAL OUTCOMES FOR SALVAGE ESOPHAGECTOMY AFTER DEFINITIVE CHEMORADIOTHERAPY Shin Yamamoto, Kosuke Narumiya, Masaho Ota, Kenji Kudo, Masakazu Yamamoto, Hiroko Ide, Harushi Osugi Tokyo Women’s Medical University, Tokyo/JAPAN Background: Definitive chemoradiotherapy for esophageal cancer which was unresectable tumor has become common therapy. In recently, we have perform chemoradiotherapy for resectable tumor because esophagectomy for esophageal cancer is an invasive surgical procedure. But some cases were recurrent. We examined the treatment strategy and clinical outcomes of salvage esophagectomy after definitive chemoradiotherapy for esophageal cancer. Methods: We reviewed 51 cases of subjects with esophageal cancer who underwent salvage esophagectomy after definitive chemoradiotherapy with more than 50Gy of radiation from 1992 to 2013. We exam (1)Background (2)Term after Chemoradiotherapy (3)Surgical procedure (4)Complication (5)Prognosis Results: Age 63.0(36-82), Male:Female = 42:9, Location: Upper/Middle/ Lower = 13/27/11, T1/T2/T3/T4 = 9/2/19/21, M0/M = 41/10, (2)Within 6months/More than 6 months = 23/28 (3) Neck digection/Right thoracotomy : Left thoracotomy : laparotomy = 7:28:10:6, Stomach/colon/ jujenum = 39:3:9 Mediastinal rute/Ante/Retro = 15:21:15(4) Anastleakage/ Pneumonia/Abcess/Meningitis/Fluid in the thoracic cavity = 11:9:4:1:8 (4)5years survival rate was 20%. Hospital death was 3.9% Discussion: There were high rate complications for salvage esophagectomy after definitive chemoradiotherapy for esophageal cancer. Patients should be carefully selected for salvage esophagectomy. Surgeons should consider the indications and techniques for esophageal surgery to increase cure rates and decrease morbidity. Disclosure: All authors have declared no conflicts of interest. Keywords: Salvage esophagectomy, Definitive chemoradiotherapy, invasive surgical procedure, Hospital death O109.07: THE OUTCOME OF A SALVAGE SURGERY FOR T4 ESOPHAGEAL CANCER AFTER DOWN-STAGING. Yasunori Akutsu1, Tsuguaki Kono1, Masaya Uesato1, Isamu Hoshino2, Kentaro Murakami1, Masayuki Kano1, Takeshi Toyozumi1, Hiroshi Suito1, Masahiko Takahashi1, Yasunori Matsumoto1, Hisahiro Matsubara1 1 Chiba University, Graduate School of Medicine, Chiba/JAPAN, 2Graduate School of Medicine, Chiba University, Chiba/JAPAN Background: Recently, the outcome of chemoradiotherapy (CRT) has improved in esophageal cancer, and CRT is an appropriate modality for T4 esophageal cancer without distant metastases. Following CRT, such tumors can become resectable (downstaging) in some cases. Among these cases, it is unclear whether the outcome of late responders who underwent salvage esophagectomy after definitive chemoradiotherapy differs from those of early responders.

Results: There were 35 patients (median age = 58y, M:F = 33:2) who had no evidence of residual disease after definitive chemoradiation (clinical complete response). Esophagectomies with 2-field lymphadenectomies were performed. Operative mortality was 3% (1/35). R-0 resection was 89% (31/35). Incidence of pathological complete response (pCR) was 43% (15/35) and 57% of patients had microscopic residual tumor in esophagectomized specimens or lymph nodes. Five-year survival was 31.5% (50% for pCR and 20% for non-pCR). Eighty one percent of cause of deaths resulted from distant metastases. Endoscopic findings, CT or PET-CT can not accurately detect pCR or microscopic residual disease.

Methods: First, patients with distant metastases were excluded from this study. Then, those with double cancers, those who did not undergo curative esophagectomy with right thoracotomy, those with a poor performance status, and those who received radiation alone or the best supportive care were excluded. Between 2001 and 2012, 153 patients with T4 TESCC were selected and treated with CRT in Chiba University Hospital. Ten patients (6.5%) withdrew from treatment, and the remaining 143 patients (93.5%) completed CRT (40 Gy), after which the first evaluation for downstaging was performed. Of these, 28 patients (18.3%) exhibited downstaging of the primary tumor, and these patients underwent subsequent surgery (early responders). Among the remaining 115 patients, additional CRT was performed, and finally 12 (7.8%) achieved downstaging and then underwent salvage surgery (late responders). In total, 40 patients (26.1%) (early responders + late responders) achieved downstaging and underwent surgery. Various factors and survival were compared between early and late responders.

Discussion: Almost 60% of patients with advanced squamous cell esophageal cancer with clinical complete response after definitive chemoradiation had microscopic residual disease. Prophylactic esophagectomy after dCRT was safe. Resectability and R-0 resection rate was high. Overall survival was comparable to that of successful salvage surgery. Because of high incidence

Results: As for pathological effectiveness of CRT in resected specimens, primary tumors displayed a Grade 3 response in 6 (21.4%) of the early responders and 2 (16.7%) of the late responders and there was no statistical differences. The 5-year OS rates of the early and late responders were 25.9 and 36.5%, respectively, and the MSTs of these groups were 24.8 and 24.3

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months (P = 0.925). Unexpectedly, these results indicate that the duration of response does not affect patient outcome.The 5-year cause-specific survival rates in the early and late responder groups were 61.5% and 72.9% (P = 0.425), respectively. The patterns of recurrence after surgery in the early and late responder groups were evaluated. Postoperative recurrence occurred in 13 (46.6%) of the early responders and 6 (50.0%) of the late responders, and the frequency of recurrence did not differ between the groups (P = 0.544). In the patients with recurrence, lymphatic recurrence was the most frequent type of recurrence among the early responders (76.9%), whereas 50.0% of the recurrences among the late responders were lymphatic recurrences. Hematological recurrence was observed in 6 (46.2%) of the early responders and 3 (50%) of the late responders. Dissemination was observed in 3 (23.0%) of the early responders. The recurrence patterns not differ statistically between the groups (P = 0.680). Discussion: Our study revealed that the outcome of salvage surgery for T4 TESCC is not poor. For T4 cases, residual primary tumor is the primary concern for curative treatment, and salvage surgery should be re-considered. Therefore, if downstaging of the primary tumor can be achieved and patients can undergo subsequent surgery, then better survival can be expected. Disclosure: All authors have declared no conflicts of interest. Keywords: salvage surgery, chemoradiotherapy, downstaging

O109.08: BI-MODAL SALVAGE TREATMENT CONSISTING OF DOCETAXEL, CISPLATIN, AND S-1 (DCS) CHEMOTHERAPY AND ESOPHAGECTOMY FOR T4 ESOPHAGEAL CANCER NOT RENDERED RESECTABLE BY FULL-DOSE INDUCTION CHEMORADIOTHERAPY Tadashi Nishimaki, Hideaki Shimoji, Hiroyuki Karimata University of the Ryukyus, Nishihara, Okinawa/JAPAN Background: Prognosis of patients having persistent T4 esophageal tumor insufficiently responding to full-dose chemoradiotherapy is dismal, and their quality of life will be extremely impaired due to fistula formation involving the respiratory or cardiovascular organs unless the tumor is removed. We hypothesized that docetaxel, cisplatin, and S-1 (DCS) chemotherapy might maintain active effects even on persistent T4 esophageal tumor after full-dose chemoradiotherapy, and, resultantly, subsequent R0 esophagectomy would become feasible. Such a bi-modal salvage treatment has not yet been reported. Methods: Consecutive three patients having persistent T4 esophageal tumor insufficiently responding to full-dose chemoradiotherapy (nedaplatin/5FU/ 66 Gy) were included in the study, and the treatment outcomes were evaluated. All patients had initially unresectable esophageal tumor invading the aorta and left main bronchus. Three courses of the DCS chemotherapy consisting intravenous docetaxel and cisplatin (both, 35 mg/m2) and oral S-1 (40 mg/m2) followed by 2-staged esophagectomy were planned. At the time of tumor resection performed as the first operation, a pedicled intercostal musculopleural flap was constructed to cover the membranous wall of the trachea and bronchus, intending to prevent fistula formation due to ischemia of these structures. Results: All patients completed three courses of the DCS chemotherapy. Grade 3 neutropenia developed during the chemotherapy in all patients, although easily manageable with G-CSF use. The tumor volume reduction rate after the DCS chemotherapy was 21% and 12% compared with the tumor before the chemoradiotherapy and the DCS chemotherapy, respectively, in the first patient. They were 38.2% and 35.6% in the second patient. However, no tumor shrinkage was observed in the third patient. R0 esophagectomy was performed in the two patients showing tumor shrinkage after the DCS chemotherapy. A scalpel was needed to mobilize the tumor from the aorta and bronchus in both patients. They had uneventful postoperative course after the first resection and subsequent reconstruction surgery, and recovered normal swallowing function. Although yp-stage was T3N1 in the first patient, pathological complete response was observed in the second patient. After the discharge, the two patients undergoing esophagectomy have been maintaining normal swallowing function and good quality of life, whereas esophagobronchial fistula developed soon after the DCS therapy in the third patient who did not undergo esophagectomy. Discussion: The results of this study suggest that the DCS chemotherapy is safe and feasible, and still has a power to further reduce the volume of persistent T4 esophageal tumor insufficiently responding to full-dose chemoradiotherapy. Furthermore, subsequent esophagectomy could be safely performed if the esophageal surgery is performed as 2-staged operation. A pedicled intercostal musculopleural flap covering the trachea and bronchus may be useful in preventing postoperative fistula formation between these structures and the mediastinum. In conclusion, initially unresectable T4 esophageal cancer can be successfully treated by bi-modal salvage treatment consisting of DCS chemotherapy and esophagectomy even after ineffective full-dose induction chemoradiotherapy. The efficacy and safety of bi-modal salvage treatment should be confirmed by accumulation of treatment experience and, ultimately, by phase II clinical trials.


Disclosure: All authors have declared no conflicts of interest. Keywords: chemoradiotherapy, DCS chemotherapy, T4 esophageal cancer, Salvage esophagectomy

Wednesday, September 24 – 15:30–17:00 O110: Benign Esophageal Diseases Room: Salon 2 O110.01: USING A CLINICAL PATHWAY APPROACH TO SIMULATION-BASED TRAINING IN FOREGUT SURGERY Kiyoyuki Miyasaka, Joseph Buchholz, Denise Lamarra, Giorgos Karakousis, Rajesh Aggarwal University of Pennsylvania, Philadelphia/PA/UNITED STATES OF AMERICA Background: Simulation is a required component of surgery education, and governing bodies for residency programs like the ACGME encourage innovation in implementation of simulation-based curricula. We designed a novel integrated educational module for first-year surgery residents in foregut surgery that utilizes a clinical pathway approach. While conventional surgical simulation training focuses on isolated technical skills, our pathway approach features a series of immersive high-fidelity simulations that follow a single patient from outpatient visit through surgery and post-operative follow-up. This approach allows faculty to observe, evaluate, and teach residents’ technical and non-technical skills in a standardized, repeatable fashion within a realistic clinical context over the course of a simulated patient care pathway. Methods: The three-day module for groups of six residents comprises a combination of standardized patient (SP) encounters, didactic sessions, and hands-on training supervised by surgery faculty. A summative simulation “pathway” is repeated on days 1 and 3. The pathway is a sequence of three simulated encounters that follow a single patient through a disease process. First, the resident sees an SP in clinic presenting with symptoms of distal gastric cancer. The SP is interviewed, examined, counseled and consented for surgery based on findings and provided diagnostic information. The resident then enters an operating room to perform a gastro-jejunostomy as part of the operative management of the same patient. A porcine tissue model simulates the patient in a fully immersive environment complete with confederates standing in as an assistant and anesthesiologist. Finally, the resident engages in a simulated post-operative day 10 visit with the same SP. Surgery faculty observe and rate resident performance on live video feeds. Ratings are on standardized assessment forms endorsed by the American Board of Surgery: CAMEO for the pre-operative outpatient consultation, OPRS for the operative encounter, and Mini-CEX for the post-operative follow-up. Residents also provide self-assessments using the same forms, as well as their self-confidence in meeting 13 defined learning objectives for the module. Results: Eleven residents have undergone this training to date. Resident self-assessments indicated significant improvements in performance for all areas compared pre to post-training: pre-operative (median 3 vs 4 out of 5, p < 0.001), intra-operative (3 vs 3 out of 5, p < 0.001), and post-operative (5 vs 7 out of 9, p < 0.001). Resident scores of confidence in meeting the learning objectives increased from 3 to 4, p < 0.001. Faculty ratings of resident performance were not significantly improved pre to post-training. Discussion: Our novel pathway approach targets an important gap in training methodologies by placing both technical and non-technical skills in their clinical context as part of managing a surgical patient from initial presentation through surgery and post-operative follow-up. The module provides protected time for residents to have close interactive teaching from faculty outside of the pressures of their usual clinical duties, while remaining in a realistic patient care environment. While we did not see an improvement in faculty ratings of resident performance over the three-day training period, resident self-assessment and confidence were significantly improved and support continued implementation to educate first-year residents in foregut surgery. Disclosure: All authors have declared no conflicts of interest. Keywords: Education

Simulation,

Residency

program,

Standardized

patient,

O110.02: EOSPHAGEAL LICHEN PLANUS: 17 CASES BEFORE AND AFTER VISCOUS BUDESONIDE THERAPY Magnus Halland, Karthik Ravi, Sue Helling, David Katzka, Debra Geno, Lori Kryzer, Jeffrey Alexander Mayo Clinic, Rochester/MN/UNITED STATES OF AMERICA Background: Esophageal lichen planus (LP) is a rare esophageal disorder and small case series of various agents exist to guide therapy. There have


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been a few reports of response to topical steroid therapy in esophageal LP; and it is likely the first line agent in treatment of this disease. The actual effectiveness and tolerance of topical steroid therapy in LP has not been defined. We aimed to evaluate the effectiveness and tolerance of topical budesonide-Rincinol in the treatment of esophageal LP. Methods: We reviewed the Mayo Clinic patient database for patients diagnosed with esophageal lichen planus and evaluated in the esophageal clinic at Mayo Clinic Rochester between 2006–2014. Patients who were prescribed budesonide at a dose of 3 mg twice daily for at least 6 weeks and who had clinical and endoscopic follow up were included in the analysis. We collected data on age, gender and findings on structured barium esophagography measuring the maximal and minimal esophageal diameter. We assessed the severity of dysphagia as described in the initial esophageal physicians note along with endoscopic findings to determine response to therapy. A complete response was defined as resolution of dysphagia and normalization of esophageal mucosa. Those patients where clinical and endoscopic improvement was present, but additional therapy was required were deemed partial responders. A lack of response was defined as no clinical or endoscopic improvement. Results: We identified 17 patients in whom budesonide-Rincinol therapy had been used to treat esophageal lichen planus; 12/17 (71%) were female and 5/17 (29%). The mean age was 66 years (range 54–77). The mean duration of symptoms at diagnosis was 7 years (range 2–15). 7 of the patients had a diffusely narrowed esophagus on the esophagram whereas the other 10 patients had focal strictures with mean length of 7 cm (range 2–10 cm). The mean maximal and minimal esophageal diameter was 13 and 6 mm respectively. All patients reported severe dysphagia. In 2 patients (12%) no response to budesonide-Rincinol was found. A partial response was noted in 11/17 (64%) and 4 patients (24%) had a complete response. Among those with partial response a wide variety of immunosuppressive medications such as tacrolimus, methotrexate, mycophenolate, prednisone and azathioprine were added on a case by case basis. Budesonide was well tolerated, but 4/17 developed oral and/or esophageal candidiases. Discussion: Esophageal lichen planus is a rare esophageal disorder, which causes severe esophageal narrowing and dysphagia. Most patients are female and many patients have symptoms for a number of years prior to diagnosis. Oral viscous budesonide appears to be of modest benefit and induced a complete response in almost a quarter of our patients. However, in our experience the majority of patients appear to require therapy beyond viscous budesonide. Our data suggest that a quarter of patients may not need systemic immunosuppression to manage their esophageal symptoms. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal stricture, treatment outcomes, esophageal lichen planus, benign esophageal disease O110.03: SUPERIOR MESENTERIC ARTERY SYNDROME AS POTENTIAL CAUSE OF ANTIREFLUX SURGERY FAILURE Romeo Bardini1, Angelica Ganss1, Lisa Zanatta1, Imerio Angriman1, Edoardo Savarino2, Renato Salvador1 1 University of Padova, Padova/ITALY, 2University of Padua, Padua/ITALY Background: Superior mesenteric artery syndrome (SMAS) is characterized by upper gastrointestinal symptoms, such as nausea, food regurgitation, vomiting, post prandial epigastric pain and weight loss. SMAS is commonly not recognized and many patients are considered as affected by gastroesophageal reflux disease or specific gastrointestinal motility disorders. For this reason its diagnosis is frequently delayed, resulting in ineffective symptomatic therapies and inappropriate investigations. We aimed to investigate the occurrence of this misdiagnosis in a large group of patients who underwent surgical treatment for SMAS. Moreover, we assessed medical history and final outcome of these patients. Methods: 27 consecutive SMAS patients who underwent surgical correction (duodenojejunostomy or duodenojejunostomy+duodenum resection) between 2008–2013 have been enrolled in this study. Six patients had a previous fundoplication which had been performed elsewhere. Two patients had more than one antireflux procedure. Demographic and clinical data (weight, BMI, medical therapy, symptom duration) were prospectively collected. Symptoms were scored by using a detailed lickert-scale based questionnaire for vomiting, nausea, epigastric pain, regurgitation and post-prandial bloating. Before the surgical treatment for SMAS, all patients have been investigated with CT and/or MR angiography with multi-planar three-dimensional reconstructions, endoscopy, barium swallow, esophageal manometry and 24 hour pH-monitoring. Results: All six patients were PPI no-responders before the antireflux surgery and had persistent symptoms after the previous fundoplication. The median of symptom duration was 90 months. At SMAS preoperative evaluation, 5 patients had negative 24 hour pH-monitoring and normal LES resting pressure. Mean aorto-mesenteric angle was 21° +/-1.8 and distance 6 +/- 2.1 mm.

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In all patients a duodenojejunostomy was performed: in 5 patients a distal duodenum resection was added. The morbidity and mortality of SMAS surgery were nil. At a median follow-up of 48 months (IQR 37-55), the median of symptom score was significantly lower after surgery (28 vs 8; p < 0.001). In all patients the symptoms score increased after SMAS surgery. There was a significant improvement in patients’ weight (52+/-1 kg vs 57+/-9 kg p < 0.01) and BMI (18.5+/-3.4 kg vs 20.6+/-3.4 kg; p < 0.01) and there was a significant decrease of anti-reflux medications use (p < 0.01). Discussion: Patients with long lasting nausea, vomiting and gastroesophageal reflux who are not responding to PPI therapy should be carefully considered for possible SMAS before performing an antireflux procedure. Moreover, patients who underwent a fundoplication and still remained symptomatic reporting gas-bloat syndrome or persistent reflux should be addressed to a study of the duodenum for a possible presence of SMAS. Disclosure: All authors have declared no conflicts of interest. Keywords: Superior mesenteric artery syndrome, gastroesophageal reflux, fundoplication O110.04: DOES PRE-OPERATIVE PNEUMATIC DILATION AFFECT THE SURGICAL OUTCOME OF ELDERLY PATIENTS WITH ESOPHAGEAL ACHALASIA? Kazuto Tsuboi, Nobuo Omura, Fumiaki Yano, Masato Hoshino, Seryung Yamamoto, Shunsuke Akimoto, Takahiro Masuda, Koji Nakada, Hideyuki Kashiwagi, Katsuhiko Yanaga The Jikei University School of Medicine, Tokyo/JAPAN Background: Pneumatic dilation (PD) and surgery are effective management for esophageal achalasia. Generally, PD is able to ameliorate dysphagia in up to 70% of patients with esophageal achalasia. Although the effectiveness of PD in elderly patients is superior to that in young patients, some require repeated PDs for recurrent dysphagia. Meanwhile, laparoscopic Heller-Dor procedure (LHD) is a gold standard of treatment for esophageal achalasia, and LHD is associated with good outcome in patients with failed PD. The aim of this study is to evaluate the effect of pre-operative PD on surgical outcome in elderly patients with achalasia. Methods: The patients more than 60 years of age who underwent LHD in our institution were extracted from the database. These patients were divided two groups: LHD after pneumatic dilation in Group A and LHD without pre-operative PD in Group B. We analyzed the patients’ background including timed barium esophagogram (TBE), pre- and post-operative symptom scores, and surgical results. Before and after surgery, the standardized questionnaire was used to assess the degree of frequency and severity of symptoms (dysphagia, vomiting, chest pain and heartburn). Moreover, satisfaction with operation was evaluated using the standardized questionnaire. Results: Seventy-one patients met our inclusion criteria. Their mean age was 67.1 (60 to 83) years and 30 of them were male. The patients in Group A were older and had longer symptoms compare to those in patients in Group B (p = 0.0373, 0.0446, respectively). Between the two groups, there were no differences in surgical results such as operative time, blood loss, occurrence of peri-operative complications. However post-operative symptom score and patient satisfaction were comparable between the two groups, while the patients in Group B had better clearance of lower part of the esophagus by TBE. Discussion: LHD is a safe and effective surgical technique even in elderly patients with pre-operative PD. However, clearance of lower part of the esophagus was superior to patients without pre-operative PD in elderly patients. Disclosure: All authors have declared no conflicts of interest. Keywords: achalasia, surgical outcome, pneumatic dilation, elderly patient O110.05: ESOPHAGEAL TUBERCULOSIS – A MIMICKER OF MALIGNANCY Jasper Sandeep Rajasekar, Servarayan Murugesan Chandramohan, D Kannan, Rajendran Vellaisamy, T Perungo, John Grifson, Jeyasudhahar Jesudason, A Amudhan, D Bennet, R Prabhakaran, Madeswaran Chinnathambi, M Kanagavel, Asmita Chandramohan, Selvarathinam Palanisamy Madras Medical College, Chennai/INDIA Background: Even in countries with a high incidence of tuberculosis, esophageal tuberculosis is a rare diagnosis Esophageal tuberculosis (ET) is considered primary when there is no other detectable tuberculous site and secondary when the esophagus is involved by spread from adjacent organs or by hematogenous spread from a distant site. The natural history, clinical and endoscopic features, complications, and treatment of this condition is often unclear. We present our experience with ET encountered from 1996 to 2013 and highlight the tendency of ET to form a ulcerovegetative lesion thereby mimicking a neoplastic process.

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Methods: In our analyses, tuberculosis presenting with dysphagia can be broadly categorized into an ulcer group (UG, n = 21) and an extrinsic compression group (n = 10). The ulcerative form of ET which is often misdiagnosed as malignancy is reviewed. History and physical findings were noted. Chest radiographs, Upper GI endoscopy (including biopsies of esophageal lesions)with endoscopic Ultrasound, biopsies or FNA cytology of lymph nodes, bronchoscopy, contrast esophagogram, and thoracic CT were performed. Diagnosis was made with histological proof of epithelioid cell granulomas with marginally polygonal Langhans-type giant cells and/or the presence of acid-fast bacilli. Results: Dysphagia was the predominant symptom in the ulcer group (n = 18, 85.71%) followed by cough after oral intake (n = 7, 33.33%). In the 21 patients who presented with esophageal ulcers, the clinicopathological spectrum included: • • • •

Primary form of tuberculosis (with no lesion elsewhere) (n = 6) Ulcer associated with Tuberculosis elsewhere (n = 6) Ulcer associated with an Tracheoesophageal fistula (TEF) (n = 8) Ulcer associated with Esophagocervical sinus due to nodal suppuration (n = 1)

Twelve patients with ET (57.14%) responded to a full course (6–12 months) antituberculous pharmacotherapy alone. The patients who had esophageal ulcers had complete healing after a mean treatment period of 6 months. However, esophageal diverticula in 2 patients persisted. For patients with TEF, a temporary retrievable stent for mean period of 6 weeks was used in 3 patients (14.3%). Surgery by transthoracic approach was required in 5 patients (23.8%) (management of TEF in 4 patients and TEF following mediastinal drainage for suppuration in 1 patient). Open drainage of cervical nodal suppuration was done in 1 patient. Patients were followed for a period of 2 months to 3 years with minimal morbidity and no mortality. Discussion: This study shows that esophageal involvement is not isolated in most patients (n = 17, 71.42%) in our study. It is not uncommon to find esophageal tuberculosis misdiagnosed as malignancy during endoscopy. Tuberculous involvement was confirmed by pathological examination in all patients. Although antituberculous therapy is the mainstay of treatment, surgery is reserved for complications like persistent fistula and suppuration despite adequate therapy. Disclosure: All authors have declared no conflicts of interest. Keywords: Tuberculosis, Esophageal ulcer, Tracheo-oesophageal fistula, Malignancy mimicry

O110.06: LARGE ASSOCIATION STUDY OF EXONIC VARIANTS IN IDIOPATHIC ACHALASIA Ines Gockel1, Jessica Becker2, Stefan Niebisch1, Mira Wouters3, Henning Schulz4, Michaela Müller5, Hauke Lang1, Guy Boeckxstaens3, Markus Nöthen2, Michael Knapp2, Johannes Schumacher2 1 University Medical Center of Mainz, Mainz/GERMANY, 2University of Bonn, Bonn/GERMANY, 3Catholic University of Leuven, Leuven/ BELGIUM, 4Protestant Hospital Castrop-Rauxel, Castrop-Rauxel, Castrop-Rauxel/GERMANY, 5German Clinic for Diagnostics, Wiesbaden/ GERMANY


controls in order to confirm the contribution of these variants to the development of achalasia. Disclosure: All authors have declared no conflicts of interest. Keywords: achalasia, genetic O110.07: DILATION OF AN ESOPHAGEAL STRICTURE USING A BALLOON WITH INTEGRATED IMPEDANCE PLANIMETRY IMAGING. Johannes Lenglinger, Erwin Rieder, Ildiko Mesteri, Sebastian Schoppmann Medical University of Vienna, Vienna/AUSTRIA Background: Eosinophilic esophagitis (EoE) is a chronic, immune mediated condition frequently complicated by esophageal strictures. We report our first dilation of an esophageal stenosis in a patient with EoE using the EsoFLIP®, a device incorporating impedance planimetry imaging of balloon diameter. Methods: A 19 year old male with a 3 year history of EoE reported recurrence of dysphagia after discontinuation of topical budesonid. Videofluoroscopy showed an esophageal stricture with impaction of a 14 mm tablet. Esophagogastroscopy, impedance planimetry and dilation of the stricture were performed under general anesthesia. The EsoFLIP® ES-330 dilation catheter is fitted with a 30 mm dilation balloon acting as functional lumen imaging probe (FLIP). The catheter is connected to a motor syringe filled with a conductive solution. Voltage measurements by electrodes at 5 mm intervals over 7 cm are converted to estimations of corresponding balloon diameters and displayed in real time. Intraballoon pressure is monitored by a manometer connected via a 3-way valve. The EsoFLIP® catheter was used to dilate the stricture and for estimating esophageal lumen. Diameters at the level of the stenosis were measured at 20, 30, 40, and 50 ml filling volumes before and after dilation. Results: Endoscopy showed longitudinal furrows, mucosal rings and whitish plaques along the entire esophagus. The stenosis at 36 cm from the incisors was passed with slight pressure. The EsoFLIP® catheter was inserted until the balloon was centered at the level of the stenosis, confirmed by an hourglass shape of the balloon. Before dilation diameters at the level of the stricture were 9.0, 10.3, 11.4, and 12.7 mm at filling volumes of 20, 30, 40, and 50 ml, respectively. During dilation with 75 ml volume the balloon assumed a 30 mm cylindrical shape at 1 bar pressure. Post dilation diameters were 13.9, 18.0, 22.8, and 21.3 mm, respectively (image 1). No mucosal injury was visible after the procedure. Microabscesses and up to 60 eosinophilic granulocytes per high power field were apparent in biopsies from distal, middle and proximal esophagus. One week after the procedure dysphagia had resolved completely.

Background: Idiopathic achalasia is a severe disorder of the lower esophageal sphincter (LES) with a lifetime prevalence of 1:10,000. The disease is characterized by the degeneration of neurons in the myenteric plexus leading to the development of a megaesophagus with irreversible loss of LES function. On the etiological level, achalasia represents a multifactorial disorder with environmental and genetic factors being risk-associated. Methods: The aim of the present study was to determine the role of exonic variants in the development of achalasia. We performed an association study using Illumina’s Exomechips which have been developed based on the data of 12,000 exomes. The chip contains more than 240,000 – mainly functionalrelevant – markers. We genotyped 674 patients with idiopathic achalasia and 2,316 population-based controls from Central Europe and after quality control (QC) steps 106,417 markers remained for association testing. Results: The analysis yielded a strong association signal within the HLA region (P < 5x10-08). As achalasia association within the HLA region has been reported previously, we next focused on variants outside the HLA region and identified 139 markers reaching a P < 10×-03. In total, 33 of the 139 markers are common variants (MAFcontrols > 5%, best hit P = 1.55×10-05). In contrast, 48 are low-frequent markers (MAFcontrols < 5%) and the minor allele is more frequent in patients compared to controls (best hit P = 6.89×1006). Furthermore we used the INTERSNP-RARE software to test if there is an enrichment of rare, associated variants within specific genes. This analysis revealed an overload within the genes EDNRB and PLBD1 (P < 8×10-5). Discussion: The present study provides evidence that low-frequent and common exonic variants play a role in the pathophysiology of achalasia. Currently, we genotype a subset of the associated variants identified in this study in an independent sample of > 400 achalasia patients and > 1,000

Discussion: Our first dilation of an esophageal stricture using the EsoFLIP® catheter had excellent short-term success. Real time imaging of the balloon seems to be an advantage in regard to catheter placement and monitoring of the extent of dilation. Additionally, the effect of treatment can be measured in the same session. Disclosure: All authors have declared no conflicts of interest. Keywords: stricture, dysphagia, impedance planimetry, eosinophilic esophagitis O110.08: LAPAROSCOPIC DIVERTICULECTOMY WITH THE AID OF INTRAOPERATIVE GASTROINTESTINAL ENDOSCOPY TO TREAT EPIPHRENIC DIVERTICULUM Lei Yu, Ji-Xiang Wu Beijing Tongren Hospital, Capital Medical University, Beijing/CHINA Background: Most researchers believe that the presence of large epiphrenic diverticulum (ED) with severe symptoms should result in consideration of surgical options. The choice of minimally invasive techniques and whether

ABSTRACT SUPPLEMENT


Heller myotomy with antireflux fundoplication should be employed after diverticulectomy became debating focuses. The aim of this study was to describe how to perform laparoscopic transhiatal diverticulectomy (LTD) and esophagomyotomy with the aid of intraoperative GI endoscopy and investigate when the esophagomyotomy should be performed after LTD. Methods: From 2008 to 2012, 11 patients with ED underwent laparoscopic transhiatal diverticulectomy (LTD) with the aid of intraoperative gastrointestinal (GI) endoscopy at our department. Before surgery, four patients were successfully undertaken on esophageal manometry: esophageal dysfunction and an increase of the lower esophageal sphincter pressure (LESP) were found in 2 patients. Results: There were 2 cases of conversion to an open transthoracic procedure. 6 patients underwent LTD, Heller myotomy and Dor fundoplication; and 3 only undergoing LTD. Dysphagia and regurgitation 11 patients having before surgery improved significantly. Motor function studies showed that there was no esophageal peristalsis in 5 patients during followup, while 6 patients showed seemingly normal esophageal motility. Discussion: LTD represents a safe and valid approach for ED patients with severe symptoms. The requirement for myotomy and antireflux surgery after diverticulectomy depends on the observation of intraoperative GI endoscopy. During follow-up, there was no esophageal peristalsis in one case after LTD, Heller myotomy and Dor fundoplication.

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prolonged need for mechanical ventilation even with the use of the usual cuff inflation volumes. Management is complex and the outcome depends on multiple factors. We report our experience with 6 cases of PITEF managed in a single center over a period of 3 years (2009–2013). Methods: Six patients (male: female -1:5) presented with PITEF. Median age of presentation was 30 years (range, 25 to 43). Causes for prolonged intubation were consumption of organ phosphorus poison with suicidal intent in 5 and following tuberculous cervical spine surgery in 1. The median duration of mechanical ventilation was 16 days (range, 9–50) The patients were referred to our center after a median period of 14 weeks (range, 10 – 30) and at presentation all patients were debilitated from either pulmonary complications of aspiration (n = 3, 50%) and malnutrition (n = 3, 50%). Patients were evaluated with Upper GI endoscopy (n = 6, 100%), bronchoscopy (n = 4, 66.6%), MRI neck (n = 2, 33.3%) and CECT neck (n = 4, 66.6%). The TEF was resected with primary repair of the tracheal and oesophageal defect in single layer in 4 patients (66.6%) and resection and reconstruction of the trachea with primary oesophageal repair in 2 (33.3 %). All repairs were buttressed by interposing pedicled sternocleidomastoid muscle flaps (100%). Anaesthetic management was difficult in 2 patients due to difficult intubation (33.3 %). Results: The defect was in the proximal trachea in all patients measuring a mean diameter of 1.7 cm (range, 0.6–3.0) and associated with tracheal stenosis in 2 patients. Preoperative nutrition optimisation was given for all patients for a mean of 11 weeks (range, 8–16). Preoperative nutritional support was managed with PEG (n = 1, 16.6 %), nasojejunal tube (n = 2, 33.3%) and feeding jejunostomy (n = 3, 50%). Postoperative complications developed in 2 patients (n = 33.3%). The 30-day mortality was one (16.6%) in a patient who underwent tracheal resection with repair. Median post operative hospital stay was 15 days (range, 8–20 days). Median follow-up was 6 months (range, 4 1/2 months to 2 years). Fistula closure was thus ultimately successful in 5 patients (83.3%) with no evidence of recurrent TEF or tracheal stenosis during follow-up. All patients resumed oral intake without complications. Discussion: 1. Proper assessment of TEF is necessary to assess the location, size and the adjacent tracheal lumen before planning definitive surgery. 2. Nutritional and respiratory status of the patient should be optimised prior to surgery. 3. Primary repair of the tracheal and oesophageal defects can be done where there is no luminal compromise of the tracheal lumen with successful outcome. Disclosure: All authors have declared no conflicts of interest. Keywords: Postintubation, pedicled flap, primary repair, Tracheoesophageal fistula

Two years after LTD, Heller myotomy and Dor fundoplication, esophagoscopy and barium esophagram showed that the lumen of distal esophagus was widening unevenly.

O201.02: ETIOLOGY, SURGICAL TECHNIQUE AND MORTALITY IN PATIENTS OPERATED FOR ESOPHAGEAL PERFORATION Karl-Erik Johansson, Ingvar Halldestam, Stefan Redéen, Per Gullstrand, Per Sandström University Hospital, Linköping/SWEDEN Background: The outcome after esophageal perforation is affected by many factors; the cause of the injury, location, underlying esophageal disease, duration before operation and comorbidity. Methods: During the years 1991–2013, 87 patients were operated with laparotomy and/or thoracotomy and/or cervical incision due to esophageal perforation. The same senior surgeon (K-E J) performed or supervised these operations. 63% of the patients were admitted from other hospitals.

O201.01: SURGICAL MANAGEMENT OF POST INTUBATION TRACHEOESOPHGEAL FISTULAE T Perungo, Jasper Sandeep Rajasekar, Servarayan Murugesan Chandramohan, D Kannan, Selvarathinam Palanisamy, Jeyasudhahar Jesudason, Rajendran Vellaisamy, John Grifson, Madeswaran Chinnathambi, A Amudhan, R Prabhakaran, D Bennet, T. M. Balakrishnan Madras Medical College, Chennai/INDIA

Results: 26 patients (30%) had spontaneous perforation, 3 of these to the pericardium. Of these 26 patients 15 had primary suture with fundoplication, 9 esophagectomy and 2 patients drainage operation. Mortality 10/26 (38%). The cause of death was multiple organ failure (4), acute myocardial infarction (2) and respiratory failure (2). Two patients died due to persistent leakage. One patient died after secondary gastric pull-up. In this case also nephrectomy and liver resection was performed. In 38 patients the esophagus was injured from the inside, by endoscopic diagnostic procedures (7), dilatation (18), treatment of esophageal varices (2), stents (3) and corpus alienum (8). The 38 patients were operated with reinforced primary suture (14), esophagectomy (19) and drainage (5). One patient died after transesophageal echocardiography and two patients after perforation at ERCP. One patient died in myocardial infarction after esophageal dilatation. Mortality 4/38 (11%). In 23 patients the esophagus was injured due to “external causes” as fundoplication (11), operation for Zenker diverticulum (2), lung surgery (2), mediastinoscopy (2), trauma (1) and spinal abscess (2). Three patients died after perforation due to treatment of descending aortic aneurysm. Mortality 3/23 (13%). The remaining 20 patients survived after primary suture (10), esophagectomy (6) and drainage operation (4).

Background: Despite advances in anaesthesiology care, post intubation Tracheoesophageal fistula (PITEF) is reported to be one of the common cause of Adult Benign Tracheo esophageal fistula (TEF). This is attributed to the

Discussion: Mortality after spontaneous esophageal perforation is high despite active surgical treatment. Many patients has also cardio-pulmonal failure. Better education in endoscopy might reduce the incidence of esophageal injure after diagnostic procedures.

Disclosure: All authors have declared no conflicts of interest. Keywords: Laparoscopy, diverticulum

Diverticulectomy,

Endoscopy,

Epiphrenic

Monday, September 22 – 13:30–15:00 O201: Esophageal Surgery: Iatrogenic Complications Room: Salon 3

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Disclosure: All authors have declared no conflicts of interest. Keyword: esophageal perforation O201.03: SHARP FOREIGN BODIES IN ESOPHAGUS – OUR EXPERIENCE IN 11 SURGICALLY TREATED PATIENTS Jeyasudhahar Jesudason, Servarayan Murugesan Chandramohan, Madeswaran Chinnathambi, Jasper Sandeep Rajasekar, T Perungo, Rajendran Vellaisamy, John Grifson, A Amudhan, D Kannan, R Prabhakaran, D Bennet, Sugaprakash Sankareswaran, Asmita Chandramohan, M Kanagavel Madras Medical College, Chennai/INDIA Background: Foreign bodies in the esophagus are common in extremes of age group. Though smooth and small foreign bodies invariably passes off on its own or retrieved easily by endoscopy, sharp foreign bodies pose

problems. They can get stuck in the esophagus at levels of constriction; injure the esophagus per se or during attempts at endoscopic removal warranting surgical intervention not only for removing the foreign body but also to manage the esophageal injury. We report our experience with 11 patients who warranted surgical intervention in our department. The analysis includes the common age, sex, type of foreign body, time from ingestion to presentation, previous attempts, time of referral to our department, type of management and outcome. Methods: We evaluated 11 cases of sharp foreign bodies impacted in the esophagus. All cases were attempted endoscopic removal by other departments and were referred to us. We approached esophagus at various levels depending upon the lodgment of the foreign body. All patients had good outcomes except 2 leaks which were managed conservatively and one death. This study does not include the foreign bodies which have been successfully treated by non surgical methods.

Department

Time ingestion to referral to our department

Previous Attempt

Our management

outcome

ENT Thoracic ENT Thoracic ENT ENT MGE ENT Thoracic ENT MGE

27 days 7 ½ years 6 weeks 2nd day One day 7 days

Endoscopic removal Endoscopic removal Endoscopic removal Endoscopic removal Diagnostic endoscopy Endoscopic removal

Transthoracic removal Transthoracic removal Transthoracic removal Trans Cervical Thoraco Abdominal Thoraco abdominal

Good Good Good Good Good (Had leak Settled) Explored post op Mediastinal Sepsis Good

Age

Sex

FB

Time from Ingestion to presentation

1 2 3 4 5 6

35 33 53 13 35 63

M M M M M M

Denture Denture Denture Crab Clip Blade Denture

23 days 7 ½ years 3 weeks One day One day One day

7

67

M

Denture

One day

MGE

2 days

8 9

55 63

M F

Needle Denture

Not known Not known

ENT MGE MGE

-

Endoscopic removal, pushed to GE Jn Endoscopic removal Diagnositic endoscopy

10

68

M

Denture

One week

ENT MGE

One week

Endoscopic removal

11

65

F

Denture

2 days

ENT

3 days

Endoscopic removal

S.No


Results: There was one mortality. Incidence was more common in males. Most common sharp foreign body was dentures. The most common site of impaction was the middle esophagus. Discussion: Sharp Foreign bodies in Esophagus always pose problems because of potential possibility of injury to Esophagus and producing irregular injury/perforation in attempts at removal by endoscopy. There can be difficulty in extraction even at surgery; repair will be difficult especially if they present late after multiple attempts at removal and require guarded approach for a good outcome. Disclosure: All authors have declared no conflicts of interest. Keywords: foreign bodies, dentures, sharp, needle O201.04: ENDOSCOPIC CLOSURE OF BOERHAAVE SYNDROME PERFORATIONS Radu Pescarus1, Eran Shlomovitz1, Ahmed Sharata2, Christy Dunst2, Kevin Reavis2, Lee Swanstrom2 1 Portland Providence Medical Center, Portland/OR/UNITED STATES OF AMERICA, 2The Oregon Clinic, PORTLAND/UNITED STATES OF AMERICA Background: Full-thickness perforation of the esophagus in the context of forceful vomiting known as Boerhaave syndrome often results in mediastinitis or peritonitis leading to sepsis and potentially death. Concomitant upper gastrointestinal bleeding is common. The classic surgical treatment involving thoracotomy and laparotomy with debridement, drainage and potential enteric diversion carries substantial morbidity. In so far as most Boerhaaves undergo an endoscopy to diagnose or confirm the diagnosis, and as there are today endoscopic modalities available for the closure of full thickness esophageal perforations we postulated that definitive endoscopic treatment would be possible at the time of the initial diagnostic upper endoscopy. Boerhaave type esophageal perforations present unique challenges due to their challenging location in proximity to the gastroesophageal junction (GEJ), their large size and commonly associated bleeding. We present our experience with treatment of Boerhaave syndrome using ‘overthe-scope-clip’ technology at the time of initial diagnostic endoscopy.

Transabdominal Transcervical Transabdominal removal+repair And fundal wrap Transthoracic Leak settled Transcervical

Good Good Good Good

performed after ruling out distal obstruction. In all cases the perforation was identified at the GEJ on the greater curvature side. The tears were 2 to 3 cm in length and extended across the GEJ. In two of the three cases significant bleeding was associated. Complete closure of the perforation and satisfactory hemostasis was obtained in all cases with a single OTSC (Ovesco AG, Tubingen, Germany) clip placed either in antegrade or retrograde fashion. One patient presented with a mediastinal abcess post intervention that was drained percutaneously. One other patient had aspirated prior to his intervention in the context of his bleeding and later died of respiratory complications. No complications related to the endoscopic procedure were noted and successful closure and hemostasis was confirmed. Discussion: Distal esophageal perforations encountered in patients with Boerhaave syndrome are technically difficult to treat. Surgical approaches are morbid. Endoscopic treatment carries less morbidity, yet has inherent limitations. The location of the perforations and the presence of bleeding makes them challenging to approach. The size of the perforation often precludes the use of through the scope clips. Endoscopic stents often migrate and provide suboptimal durable coverage of the distal GEJ. Endoscopic suturing of the GEJ in a retroflexed position is ergonomically and technically difficult. Over the scope full thickness clips appear reliable and safe for patients with Boerhaave syndrome in which closure of the perforation and control of the bleeding are imperative for patient stabilization and recovery. Disclosure: All authors have declared no conflicts of interest. Keywords: Boerhaave, esophageal perforation, OTSC, therapeutical endoscopy O201.05: MANAGEMENT OF PERFORATION FOLLOWING TREATMENT FOR ACHLASIA CARDIA: FACTORS INFLUENCING OUTCOME: EXPERIENCE WITH 8 CASES Rajendran Vellaisamy, Servarayan Murugesan Chandramohan, Jasper Sandeep Rajasekar, T Perungo, Asmita Chandramohan, M Kanagavel, John Grifson, D Kannan, A Amudhan, D Bennet, Madeswaran Chinnathambi, R Prabhakaran, Jeyasudhahar Jesudason Madras Medical College, Chennai/INDIA

Methods: A retrospective analysis of all patients referred to our surgical endoscopy service with an esophageal perforation from 03/2012 to 03/2014 was performed. Three patients were diagnosed with Boerhaave syndrome on the basis of their clinical symptoms and confirmed with computed tomography (CT).

Background: Perforation is the most feared complication while managing patients with Achlasia cardia by Pneumatic Dilatation or Surgical cardiomyotomy.Timely recognition and appropriate management are the two key factors in successful management. We report our experience with 8 Patients managed in our centre over 5 years.

Results: Different etiologies were identified in each of the three cases: gastroparesis, chronic alcohol abuse and cyclic vomiting syndrome. The interventions were performed under general anesthesia and with a high definition endoscope. A thorough examination of the esophagus and stomach was

Methods: Between 2009 and 2013 we have managed 8 patients.The age range was between 23 and 45. The demographic data, type of achalasia therapy, time of detecton of perforaion and referral, management and outcome was analysed.

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ABSTRACT SUPPLEMENT


Results: The male and female ratio was 3:5. There were three patients in surgical myotomy group (Two open, One Lap). They were managed with completion of myotomy, repair of injury and anterior fundoplication. All of them recovered and went home well. In the Pneumatic dilatation group (n = 5). Three were recognized at the time of procedure, one on day 2 and one on day 5. Of these patients, two had minor trivial injury which was managed conservatively and reassurance. Third patient was referred on day 5 with diffuse

mediastinal and retroperitoneal sepsis managed with multiple drainage, diversion and enteral access. She expired on day 11 after intervention. Fourth patient was referred on day 9 with mediastinal and chest collection, underwent emergency Transhiatal Esophagectomy and was discharged on day 22. Fifth patient was referred on day 10 with mediastinal and chest collection with atelectasis and ICD in situ. She underwent Transthoracic esophagectomy with cervical Reconstruction and she was discharged on day 35.

Patient characteristics, Management and Outcome After Achalasia Perforation No

Age

Sex

Therapy

Detection

Referral

Management

Outcome

Hospital Stay

1 2 3 4 5 6 7 8

45 25 37 35 38 39 23 43

M M F F F F M F

Open Myotomy Lap Myotomy Open Myotomy Pneumatic dilatation Pneumatic dilatation Pneumatic dilatation Pneumatic dilatation Pneumatic dilatation

At surgery At surgery At surgery Immediate Immediate Day 2 Immediate Day 5

On table On table On table Immediate Immediate Day 5 Day 9 Day 10

Repair, completion myotomy,anterior fundoplication Repair, completion myotomy,anterior fundoplication Repair, completion myotomy,anterior fundoplication Conservative Conservative Drainage, Enteral access THE TTE

Good Good Good Good Good Expired Discharged Discharged

5 days 5 days 7 Days 5 days 5 days 11 Days 22 Days 35 Days

Discussion: In our series, timely intervention, proper assessment and timely referral appear to be the key factors for a good outcome with less morbidity. Disclosure: All authors have declared no conflicts of interest. Keywords: Pneumatic dilatation, Perforation, cardio myotomy, Achalasia cardia O201.06: SPONTANEOUS ESOPHAGEAL PERFORATIONS MIMICKING CARDIO-PULMONARY PATHOLOGY PRESENTING TO PHYSICIANS WITH DELAYED REFERRAL TO G.I. SURGEONS- STRATEGIES ADOPTED AND OUTCOME OF MANAGEMENT John Grifson, Servarayan Murugesan Chandramohan, Jasper Sandeep Rajasekar, Madeswaran Chinnathambi, Rajendran Vellaisamy, T Perungo, D Bennet, R Prabhakaran, A Amudhan, D Kannan, M Kanagavel, Asmita Chandramohan, R Shashank, Raghu Nandhan, Jeyasudhahar Jesudason, Selvarathinam Palanisamy Madras Medical College, Chennai/INDIA Background: Spontaneous esophageal perforation or Boerhaave’s syndrome is associated with a high morbidity and mortality. Patients who do not have typical manifestations may report to physicians as cardiac or pulmonary emergency. Here we report a series of 11 patients who were initially treated as non oesophageal chest pain and diagnosis of esophageal perforation was recognised late.

was present in 4 patients (36.3%). The site of perforation was in the lower one third of the esophagus in all our patients(n = 11,100%). On evaluation by contrast study and CT scan, the perforation was draining into the left pleural cavity in six patients (54.5%), into the right pleural cavity in three patients (27.2%) and into both the pleural cavities in two patients (18.1%). All of our patients were hemodynamically stable on transfer in to our department. After investigation and optimization, one patient was managed conservatively (9%), six patients underwent Trans-Hiatal Esophagectomy (54.5%),three patients underwent Abdominal and Right TransThoracic Esophago-gastrectomy (27.3%) and one patient underwent Left Thoraco-Abdominal Esophagectomy (9%). One patient developed anastamotic neck stricture and is doing well following revision of the anastamosis. After a median follow up of 30 months, all our patient are alive and symptom free. Discussion: Spontaneous Esophageal Perforations are well known for high morbidity and mortality. We postulate that the probable reason for successful outcome in these 11 patients could be either due to small size of injury; initial management by physicians with antibiotic therapy; contained contents and presenting to us without gross sepsis enabling definitive therapy. Disclosure: All authors have declared no conflicts of interest. Keywords: spontaneous esophageal perforation, Boerhaave’s syndrome, Cardio-pulmonary emergency, Delayed referral

Methods: This is our analysis of 11 patients who were referred to us from the Medical Intensive Care Unit (MICU). All of them were admitted with possible diagnosis of cardiac or pleuritic pain in MICU. They have undergone evaluation to rule out cardiac, pulmonary and non-esophageal thoracic cause. They were referred to our department only after diagnostic aspiration of pleural fluid or intercostal drain content was suspicious of oesophageal perforation. The average time of presentation, evaluation done, modalities adopted and outcome were analysed.

O201.07: MANAGING ESOPHAGEAL INJURIES: “EAST OR WEST – NECK IS THE BEST OF THE WORST”OUR EXPERIENCE WITH 16 SUCCESSFULLY MANAGED PATIENTS – A SINGLE CENTER EXPERIENCE. Jeyasudhahar Jesudason, Servarayan Murugesan Chandramohan, Jasper Sandeep Rajasekar, D Kannan, Madeswaran Chinnathambi, D Bennet, T Perungo, Rajendran Vellaisamy, A Amudhan, R Prabhakaran, John Grifson, M Kanagavel, Asmita Chandramohan Madras Medical College, Chennai/INDIA

Results: Data of 11 men in the age group 22 to 54 years (median= 38 years), who presented with spontaneous esophageal perforation was analysed. The commonest symptom at presentation was chest pain (n = 11,100%) followed by respiratory distress (n = 10, 90.9%). The diagnosis of esophageal perforation was made out following drainage of food particles through the intercostals drain tube or by the high amylase content of the drain fluid. From the onset of symptom to diagnosis the median delay in diagnosis was 16 days (range 11–40 days). Six men were alcoholic (54.5%) and a history of vomiting

Background: History of esophageal injuries always portrayed a gloomy outcome till the last decade. Maturation of the scientific principles and concepts in the pathology and management of esophageal injuries have reached its zenith in the current era. Esophageal injuries span its spectrum from cervical and thoracic to abdominal territories. Our study analyzes the various etiologies and mode of treatment strategies we exercised in managing cervical esophageal injuries.

Methods: Etiology

SNo.

Age

Sex

Time of Detection

Management

Duration

Outcome

Cervical Spine Injuries

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

33 43 65 45 59 65 62 13 55 63 33 60 45 23 33 37

Male Male Male Male Male Male Male Male Male Male Female Female Male Male Male Male

Post op Post op 2months 4 months Post op Post op Post op 1 day Not known Immediate 2 days Immediate 1 hour 2 hours Managed elsewhere Managed elsewhere

Wait & watch/Removal of implant Wait & watch Implant Removal Implant Removal Observation- Implant Removal Observation Observation Cervical Extraction Trans cervical removal Conservative Conservative Conservative/neck drain Tracheostomy/Esophageal Repair/Stent Tracheostomy/Esophageal Repair/Rt Jugular ligation Tracheostomy – wait and watch Tracheostomy – wait and watch

2 ½ years 6 months 3 ½ months 5 months 3 months 3 weeks 2 weeks One week One week 3 days 10 Days 2 weeks 3 weeks 3 weeks 3 months 3 months

Good Good Good Good Good Good Good Good Good Good Good Good Good Good Good Good

Total Thyroidectomy for Ca Crab clip Needle Endoscopy Cut Throat

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We analysed 16 patients who presented with cervical esophgeal injuries. We evaluated the etiology, demography, time of detection of injury, management and outcome. Results: Widespread notion that esophageal injuries are always fatal is countered in this study which crystal clearly depicts the following inference. The cervical esophageal injuries have the best prognosis after abdominal esophageal injuries and lastly thoracic injuries carry the worst prognosis. This study highlights the importance of timely diagnosis, masterly inactivity, nutritional support, control of extra luminal contamination and well-timed decision of when to operate. Discussion: Running the gamut from cervical and thoracic to abdominal esophageal injuries the prognosis is always the best for cervical injuries. The factors determining conservative or surgical management include location of the injury, cause of the injury, delay in the diagnosis, sepsis and comorbidities. The presentation ends with emphasis on wise management of oral intake, intra venous fluids, antibiotics and drainage. The final word is that treating surgeon should hone his knowledge and skills in the management of esophageal injuries to bring out the best outcomes. Disclosure: All authors have declared no conflicts of interest. Keywords: cut throat, post thyroidectomy, Esophageal Injuries, Iatrogenic injury O201.08: SEVERE ANASTOMOTIC LEAKS AFTER ESOPHAGECTOMY – DO INTRAOPERATIVE VARIABLES MATTER? Alessandra Melis, Uberto Fumagalli, Jana Balazova, Valeria Lascari, Emanuela Morenghi, Riccardo Rosati Humanitas Research Hospital, Rozzano (Milano)/ITALY Background: Placement of an epidural catheter in patients undergoing esophagectomy has become a common practice with the aim of improving postoperative pain control and splanchnic blood flow. There are however controversies regarding mainly the effect of epidural analgesia on splanchnic blood flow and the possible detrimental effect of hypotension during catheter use. Aim of this work is to evaluate hypotensive episodes (HE) during esophagectomy (E) and to evaluate the postoperative course of patients experiencing intraoperative HE in terms of anastomotic leakage (AL) after E. Methods: 84 patients underwent E with gastric pull-up between March 2012 and November 2013 (16 with cervical and 68 with thoracic anastomosis). Intraoperative data were prospectively collected. HE were defined as a decrease in systolic blood pressure of more than 30% of its basal value, lasting more than 5 minutes. HE were treated with fluids and of vasopressive agents. 70 patients had an epidural catheter positioned which was used either during surgery or only postoperatively at discretion of the anesthesiologist. Fischer’s exact test or Wilcoxon test was used to analyze statistical association. Results: 19 patients had at least one HE during surgery (22,6%). HE were significantly more frequent in patients undergoing E in prone position (p = 0.001) and in patients in whom the epidural catheter was used during surgery (p = 0.04). Patients with HE had consequently significantly more liquid infusions (median 7.3 vs 8.8 ml/kg/h; p = 0.04). HE were rare when the catheter was not used (8,3%). Among 19 patients who had HE, 15 were treated with vasopressors. During the postoperative course, there were 13 anastomotic leaks: 6 were severe leaks, requiring surgery (Clavien Dindo 3b). Severe leaks were significantly more common in patients who had intraoperative HE (21% vs 3,1%; p = 0.02), mainly in patients with HE treated with vasopressive agents (20% vs 0; p = 0.008). Discussion: A good perfusion of the gastric tube is essential for a correct anastomotic healing. Various variables (pre, intra and postoperative) can influence perfusion and the occurrence of AL after esophagectomy. Epidural analgesia can positively affect splanchnic blood flow. However the intraoperative use of epidural catheter can also be detrimental to gastric blood flow due to the possible occurrence of HE. In our experience, independently from many other factors influencing the occurrence of AL, a higher incidence of severe AL was found in patients experiencing intraoperative HE. Although several factors can be responsible of intraoperative HE, the perioperative use of epidural catheter should be questioned. Disclosure: All authors have declared no conflicts of interest. Keywords: leak, epidural, intraoperative, esophagectomy O201.09: STAPLED ESOPHAGOGASTRIC ANASTOMOSIS IN NECK AFTER ESOPHAGECTOMY, IS IT BETTER THAN HAND SEWN ANASTOMOSIS? Ashish Goel, Kapil Kumar, Veda Padma Priya Selvakumar Rajiv Gandhi Cancer Institute Delhi, New Delhi/INDIA Background: Cervical esophagogastric anastomosis is often troubled by anastomotic dehiscence & leak often leading to sepsis and


respiratory morbidity during the initial post operative period and the resultant prolonged hospitalization and swallowing disability. Nearly 50% of cervical anastomotic leaks may lead to strictures and subsequently require repeated endoscopic dilatations. The choice of anastomotic technique is often debated, but there is little evidence to suggest the use of one technique over the other. Methods: We compared the cervical esophagogastric anastomotic outcomes in patients undergoing Mckeowns’ Esophagectomy & Transhiatal Esophagectomy in our Institute over the last five years. Anastomotic outcomes were analyzed by the leak rates and the need for serial dilatations in each group resulting from anastomotic strictures on longer followup. Total of 106 patients were available for analyses from July 2009 to December 2013; to include Mckeowns’ Esophagectomy (97) & Transhiatal Esophagectomy (9). Sixty-seven patients were males and the rest were females. The most common pathology on biopsy was squamous cell carcinoma (88.67%); with mid third esophageal lesions being the most common (62.26%). Sixty two patients underwent surgery after preoperative chemoradiation, while the rest underwent upfront surgery according to the stage at presentation. Results: Seventy three patients had a hand sewn end to end anastomosis in the left neck using 3-0 PDS suture by a continuous single layer technique; while thirty three underwent a totally mechanical stapled side to side anastomosis using a linear cutter stapler (No 55 or 75). The anastomotic leak rate was almost similar in the two groups; 10.95% in the stapled group & 12.1% in the hand sewn group. The slightly higher rate in stapled group was due to the learning curve during the initial cases. While 8.2% patients developed narrowing of anastomosis after hand sewn anastomosis, there was none after stapled anastomosis. Cardiac and respiratory morbidity was higher in the hand sewn anastomosis group, but there was no difference between hospital stay, ICU stay or recurrent laryngeal nerve injury in the two groups. Patients with stapled anastomosis had better overall swallowing function and lesser requirement for anastomotic dilatations. Discussion: Although there was no significant difference in anastomotic leak rate, hospital stay & ICU stay between the two groups, hand sewn anastomosis with continuous suture resulted in a significantly higher chance of anastomotic stricture with frequent requirement for endoscopic dilatation. Use of preoperative chemoradiation was the only factor found to be associated with higher anastomotic complications in hand sewn group. To conclude side to side totally mechanical cervical esophagogastric anastomosis is the preferred technique following gastric tube transposition after Mckeowns’ or Transhiatal Esophagectomy. Disclosure: All authors have declared no conflicts of interest. Keywords: stapled anastomosis, hand sewn anastomosis, esophagectomy

Monday, September 22 – 15:30–17:00 O202: New Technologies/Techniques in the Esophagus Room: Salon 3 O202.01: IMPEDANCE PLANIMETRY (ENDOFLIP®) MEASUREMENTS AT THE ESOPHAGO-GASTRIC JUNCTION DISTINGUISH NEUROMUSCULAR DISEASE FROM FIBROTIC LESIONS IN DYSPHAGIA PATIENTS. Johannes Lenglinger, Petra Schwaiger, Martina Scharitzer, Erwin Rieder, Martin Riegler Medical University of Vienna, Vienna/AUSTRIA Background: Impaired opening of the esophago-gastric-junction (EGJ) is a frequent cause of dysphagia. The underlying etiology may be of neuromuscular origin or due to fibrosis. Separating these etiologies may be decisive for the choice of treatment. Methods: For this retrospective study of EGJ distensibility 35 EndoFLIP® procedures were analyzed. The EndoFLIP® EF-320 catheter is fitted with a 25 mm balloon acting as functional lumen imaging probe (FLIP). The catheter is connected to a motor syringe filled with a conductive solution. Voltage measurements by electrodes at 5 mm intervals over 8 cm are converted to estimations of corresponding balloon diameters. Intraballoon pressure is monitored by a solid state pressure transducer, facilitating the calculation of compliance data. The EndoFLIP® catheter was inserted into the stomach transnasally and retracted until it was centered across the esophagogastric junction. Catheter position was initially choosen according to EGJ location data from HR-manometry and adapted during the measurements to maintain the hourglass shape of the balloon which was displayed in real time. EGJ distensibility measurements over 30 seconds were performed with balloon filling volumes of 20, 30, 40, and 50 ml volumes, respectively. Estimations of diameter and the distensibility index (DI, cross sectional area in mm2 divided by intraballoon pressure in mm Hg) were used as parameters. Based on endoscopy, histopathology, HR-manometry and videofluoroscopy dysphagia was ascribed to neuromuscular (NM) or fibrotic (F) etiology. We tested the hypothesis that EndoFLIP® measurements of

ABSTRACT SUPPLEMENT


EGJ distensibility device allow a distinction between neuromuscular disease and fibrotic lesions in dysphagia patients. Results: The NM group comprised 20 subjects (4 females). Diagnoses were achalasia in 7, hypertensive lower esophageal sphincter (LES) in 4, and impaired LES relaxation upon swallowing in 9 patients. In the F group of patients (1 female) 4 had eosinophilic esophagitis, 5 a Schatzki-ring, and 6 a peptic stenosis. Results of distensibility measurements are summarized in Table 1.

Age (yrs) EGJ diameter 30 ml (mm) EGJ diameter 50 ml (mm) DI 30 ml (mm2/mm Hg) DI 50 ml (mm2/mm Hg) Distensibility Index Quotient (DI 50 ml/DI 30 ml)

NM n = 20

F n = 15

p-value

42.1 ± 19.4 6.2 (5.0–7.9) 11.6 (8.7–12.7) 1.4 (0.9–2.4) 2.1 (1.5–2.7) 1.4 (1.0–2.0)

52.9 ± 17.8 7.2 (6.5–10.0) 9.3 (8.7–10.7) 2.3 (1.7–3.0) 1.3 (0.9–1.6) 0.6 (0.5–0.9)

n.s. 0.007 n.s. n.s. n.s. 0.001

Discussion: Except for a slightly higher EGJ diameter at 30 ml filling volume in the group of patients with fibrotic lesions no significant differences in distensibility parameters were found. In patients with neuromuscular disorders DI remained constant or increased with filling volume, whereas a decrease was encountered in patients with fibrosis. In this study we have shown that a new parameter, the distensibility index quotient (DI 50 ml/DI 30 ml), can be used to distinguish neuromuscular disease from fibrotic lesions at the EGJ. This might have implications for finding optimal treatment. Disclosure: All authors have declared no conflicts of interest. Keywords: achalasia, Endoflip, dysphagia, eosinophilic esophagitis O202.02: DETECTION OF BURIED BARRETT GLANDS AFTER RADIOFREQUENCY ABLATION (RFA) WITH VOLUMETRIC LASER ENDOMICROSCOPY (VLE) Anne-Fré Swager1, David Boerwinkel1, Daniel De Bruin1, Dirk Faber1, Ton Van Leeuwen1, Bas Weusten1, Sybren Meijer2, Jacques Bergman1, Wouter Curvers1 1 Academic Medical Center, Amsterdam/NETHERLANDS, 2Academic Medical Center Amsterdam, Amsterdam/NETHERLANDS Background: The prevalence and clinical relevance of Buried Barrett’s (BB) epithelium after radiofrequency ablation (RFA) in Barrett’s esophagus (BE) is questioned. Recent studies using small optical coherence tomography (OCT) catheters for scanning underneath the neosquamous epithelium demonstrated a high prevalence of tissue structures that might correspond to BB. Histological correlation, however, is lacking. Volumetric Laser Endomicroscopy (VLE) is a novel balloon-based OCT imaging technique that provides a 6-cm long circumferential volumetric scan of the esophageal wall layers to a depth of 3 mm with a resolution comparable to low-power microscopy. Aim: To evaluate if post-RFA subsquamous structures, detected with VLE, actually correspond to BB and to pursue direct histological correlation of VLE images. Methods: In-vivo VLE was performed to detect subsquamous structures suspicious for BB in patients with 100% endoscopic regression of dysplastic Barrett’s epithelium after RFA. Areas with suspicious subsquamous VLE structures were marked with electrocoagulation after which in-vivo VLE was repeated to confirm that the correct area was demarcated. These areas were subsequently resected endoscopically, followed by immediate ex-vivo VLE scanning to reconfirm the presence of the subsquamous VLE structures. Extensive histological sectioning was then performed and all histopathology slides were evaluated by an expert BE pathologist (blinded for VLE images). Results: In 9 patients, 6 areas with suspicious subsquamous structures were seen on in-vivo VLE and resected. Ex-vivo VLE of these 6 ER specimens reconfirmed the presence of these subsquamous structures in 5 ER specimens. Extensive histological sectioning of these areas showed BB in one area. The other subsquamous VLE structures corresponded to dilated (ducts of) (sub)mucosal glands or blood vessels. Discussion: Conclusion: VLE may potentially detect BB under endoscopically normal appearing neosquamous epithelium. However, most post-RFA subsquamous structures identified by in-vivo VLE did not correspond to BB. Further studies are required to identify VLE features that allow for differentiation of BB from normal subsquamous structures. Disclosure: All authors have declared no conflicts of interest. Keywords: Buried Barrett’s, Volumetric Laser Endomicroscopy

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O202.03: QUALITATIVE EVALUATION OF GOAT ESOPHAGUS AS A NEW MODEL OF AN FUNCTIONAL ARTIFICIAL ESOPHAGUS Kurodo Kamiya1, Yasunori Taira2, Yasuyuki Shiraishi3, Hidekazu Miura3, Takashi Kamei1, Go Miyata1, Tomoyuki Yambe3 1 Tohoku University, School of Medicine, Sendai/JAPAN, 2Tohoku University, Sendai/JAPAN, 3Institute of Development, Aging and Cancer, Tohoku University, Sendai/JAPAN Background: The main function of the esophagus is to transport swallowed food into the stomach. The esophagus is not a simple muscular tube, but is rather inhomogeneous. Functional disorders commonly occur in patients who undergo esophagectomy and gastric tube reconstruction for thoracic esophageal cancer, which is very invasive surgical procedure. However, artificial esophagi with functional peristalsis can solve these issues and reduce the surgical stress. We have already developed the artificial esophagus with peristalsis, but the function is not enough. The regional differences of the esophagus must be investigated to unravel the mechanisms of peristalsis before functional artificial esophagi can be developed. In this study, we analyzed the biomechanical and histological properties of goat esophagus. Methods: Esophagi were harvested from adult female goats used for other acute experiments, immediately after sacrifice. To evaluate the structural properties, we divided the esophagus into four segments. At every segment, we injected saline while concurrently measuring the inner pressure, and analyzed the pressure and volume relationship by the use of the Stiffness Parameter, a parameter intrinsic in a tissue expressing rigidy. To evaluate the histological characteristics, we measured the areas of mucosa, submucosa and muscularis propria, including the longitudinal and circular muscle layers, in circumferential section preparations with five parts and compared the data with each other. Results: The biomechanical experiment was performed using four esophagi. We found that the pressure of the distal segment was higher than that of the proximal segment in the low volume experiment, whereas the difference was reversed with increased volumes of saline. The data of the stiffness parameter were as follows sequentially from proximal part. (segmentI, β ＝0.54 ± 0.16; II, β = 0.43 ± 0.03; III, β = 0.38 ± 0.08; IV, β = 0.32 ± 0.11). The histological investigation was performed using six esophagi. Upon microscopic observation, the inner muscle seemed to run more longitudinally, whereas the outer muscle seemed to run more circularly. The areas of mucosa, submucosa, and the muscularis propria were not different among five parts. However, in the proximal segment, the ratios of the outer-to-total and innerto-total muscular layers were significantly larger, ratios as follows sequentially from proximal part (A, 0.39 ± 0.06; B, 0.40 ± 0.06; C, 0.38 ± 0.53; D, 0.41 ± 0.07; E, 0.52 ± 0.11) and smaller(A, 0.62 ± 0.06; B, 0.56 ± 0.07; C, 0.56 ± 0.05; D, 0.55 ± 0.06; E, 0.46 ± 0.11), respectively, than those in the distal part. Discussion: In this study, we found that the upper esophagus tended to be more rigid than the lower esophagus and that the circular muscles dominated the proximal segment, whereas the longitudinal muscles dominated the distal segment. These results suggest that the different regions of the esophagus have different functions, with the stiff, strong oral side being responsible for closing the lumen and the flexible anal side generating longitudinally shortening. Based on the above result, we propose a new model of artificial esophagus with functional peristaltic movement for simplyfying the procedure and reducing the surgical agression of esophagectomy. Disclosure: All authors have declared no conflicts of interest. Keywords: peristalsis, regional difference, artificial esophagus

O202.04: PROGRESSION OF DYSPLASIA IN BARRETT’S ESOPHAGUS DURING RADIOFREQUENCY ABLATION Swapna Devanna, Emmanuel Gorospe, Michele Johnson, Kenneth Wang, Prasad Iyer Mayo Clinic, Rochester/MN/UNITED STATES OF AMERICA Background: Barrett’s esophagus (BE) is the precursor lesion of esophageal adenocarcinoma. Endoscopic mucosal resection of nodular BE lesions and radiofrequency ablation (RFA) is a safe and effective therapy for dysplastic BE. The progression of Barrett’s dysplasia during RFA has not been reported from a large patient cohort. Aim: To assess the occurrence, predictors and outcomes of BE patients with disease progression during RFA. Methods: We identified BE patients who received RFA at our tertiary referral center using a prospectively-maintained database. Patient who developed worse grades of dysplasia during RFA were classified as progressors. Nonprogressors either remained the same, had histological improvement or achieved complete remission of intestinal metaplasia (CRIM), defined as eradication of intestinal metaplasia after 2 consecutive endoscopies with biopsies. We randomly selected age-matched non-progressors with the same

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grades of dysplasia to progressors in a 2:1 ratio. Other clinical and endoscopic characteristics were compared using non-parametric statistics. Outcomes of patients with dysplastic progression were collected from our database. Histologic diagnosis was confirmed by a gastrointestinal pathologists with expertise in BE. Results: There were 285 BE patients who received RFA of which 11 subjects had disease progression. Table 1 presents a comparison of clinical and endoscopic characteristics between progressors and non-progressors. Progression to intra-mucosal carcinoma (IMca) occurred in 7 (64 %) with pre-RFA high-grade dysplasia (HGD). Progression to HGD occurred in 2 patients who had pre-RFA low grade dysplasia (LGD). Progression to LGD occurred in 2 patients who had non-dysplastic BE, pre-RFA. The outcomes and management of patients with disease progression during RFA are summarized in Table 2. There was no statistical difference in the proportion of progressors (54%) and non-progressors (54%) who achieved CRIM (p = 1.00).


Table 1. Baseline Characteristics of Progressors and Non-Progressors Characteristics Median Age (range) % Male Median BMI (range) Median Length of BE (range) % HGD Median length of hiatal hernia (range) % of cases with nodular BE Median no. of RFA sessions (range) Median no. of EMR sessions (range)

Progressors (n = 11)

Non-Progressors (n = 22)

p-Value

70 (54–95) 100% 28 (22–41) 6 (0–11) 64% 4 (2–5)

70 (48–90) 86% 31 (23–44) 6 (1–14) 64% 4 (1–10)

0.57 0.19 0.23 0.76 1.00 0.67

45% 3 (1–4)

41% 2 (1–6)

0.81 0.45

1 (0–6)

1 (0–8)

0.96

Table 2. Outcomes and management in Progressors Progressors HGD to IMca (stageT1a) 1 2 3 4 5 6 7 LGD to HGD 1 2 NDB to LGD 1 2 Total = 11

Time between initial RFA and progression in months

Post progression RFA

Post progression EMR

Surgical resection

Post surgical staging

CRIM achieved

Final pathology

4 4 33 6 11 13 5

Yes No No Yes No Yes Yes

Yes Yes Yes Yes Yes Yes Yes

No No Yes No No No No

T3N0 -

No No No Yes Yes Yes

HGD HGD EAC Sq Sq Sq Sq

4 14

Yes No

Yes No

No No

-

Yes No

Sq Sq

13 5

No No

Yes No

No No 1

-

Yes Yes 6

Sq Sq

Discussion: Progression of disease though uncommon, can occur during RFA. In our cohort of 285 patients with BE, 11 progressed to worse grades of dysplasia. There were no baseline clinical or endoscopic predictors of progression during RFA. Therefore, surveillance endoscopy with biopsies is necessary to detect dysplastic progression and ensure appropriate early therapy. Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett’s Esophagus, Progression, Radiofrequency ablation O202.05: VIDEO-ASSISTED MEDIASTINOSCOPIC SURGERY FOR ESOPHAGEAL CANCER (VAMS-E) Takashi Fukuda, Yoichi Tanaka, Daiji Oka, Kazuhisa Ehara, Tatsuya Yamada, Yoshiyuki Kawashima Saitama Cancer Center, Saitama/JAPAN Background: Since 1996, we usually adopted the right thoracoscopic surgery for the patients with thoracic esophageal cancer (VATS-E) instead of conventional right thoracotomic surgery, mainly because to achieve the precise and complete removal of the tumor and to minimize the surgical invasiveness. Only for the patients with superficial esophageal cancer and no obvious mediastinal lymph node (LN) metastasis, we have intended the video assisted mediastinoscopic surgery (VAMS-E) as less invasive surgical procedure. Methods: The patient having clinical stage 1 cancer (cT1 N0) underwent VAMS-E operation which consisted of the cervical and laparotomic procedures. First from the cervical wound under direct vision or mediastinoscopy, we isolated the upper thoracic esophagus and exposed the surrounding structure to dissect the LNs to the subcarinal and bilateral hilar regions, using conventional electric cautery and ultrasonic coagulating shears, carefully avoiding the damage to bilateral recurrent laryngeal nerves. As a mediastinoscope we diverted the endoscopic vein harvesting system (Vein Harvest®) equipped with a 45-degree oblique perspective rigid endoscope and blunt peaked trenching apparatus, which provided an optimal operative field in the mediastinum. The important landmarks of dissecting boundaries were the membranous trachea and main bronchi, the left subclavian artery, the aortic arch, the azygos vein, the right bronchial artery and the inner surface of the mediastinal pleura. Next, through the esophageal hiatus from the upper laparotomy, mid and lower thoracic esophagus and the relevant tissues were separated from the surroundings. The dissection plane from below was finally connected to that from above. Then the en bloc removal of the esophagus and the regional LNs was completed.

Results: We performed VAMS-E for 27 patients with superficial thoracic esophageal cancer from 2010 to 2013. The preoperatively estimated depth of the primary tumor was submucosa (T1b) in 22 patients, and mucosa (T1a) in other 5 patients. Pathology revealed mediastinal lymph node metastasis in 5 patients, but fortunately no mediastinal recurrence has been detected in them. Although transient palsy of the left recurrent laryngeal nerve occurred in 23 patients (85%), none of them continued longer than a year after operation. Discussion: VAMS-E is a useful and safe surgical procedure for patients with superficial esophageal cancer but no mediastinal LN metastases. However, a comprehensive understanding of surgical anatomy is important for performing this procedure. Disclosure: All authors have declared no conflicts of interest. Keywords: mediastinoscopic surgery, Esophageal cancer, Minimally Invasive, surgical treatment O202.06: ENDOSCOPIC DILATATION IMPROVES ORAL INTAKE BUT HAS LIMITED NUTRITIONAL IMPACT IN PATIENTS WITH RADIOTHERAPY INDUCED OESOPHAGEAL STRICTURES Cuong Duong, Steve Lau, Yui Kaneko, John Spillane, Amber Kelaart Peter MacCallum Cancer Centre, Melbourne/VIC/AUSTRALIA Background: Dysphagia with poor oral intake secondary to radiotherapy induced non-malignant oesophageal strictures can cause significant morbidity. Endoscopic dilatation with balloon or bougie is the mainstay of treatment. However there is limited data on the efficacy of this therapeutic modality in improving nutritional status for these patients. Methods: Patients with radiotherapy induced non-malignant oesophageal strictures undergoing endoscopic dilatation were retrospectively analysed between 1st June 2001 to 1st June 2011 at Peter MacCallum Cancer Centre, Melbourne, Australia. Exclusion criteria included malignant strictures, reflux induced strictures and post-surgical anastomotic strictures. Results: A total of 38 patients with symptomatic radiation-induced oesophageal stricture underwent endoscopic dilatation. The mean maximal diameter at end of dilation correlated with symptomatic relief was 11mm. There was no mortality and two patients who had oesophageal perforation were successfully managed conservatively. High dose radiotherapy (60–79Gy) was associated with earlier initial presentation of dysphagia (mean of 9 weeks), as well as the development of more severe strictures that required a greater number of dilatations (mean of 4.8 dilatations). Improved dietary intake post dilatation was achieved in 89% (34/38) of cases, with 31 patients able


ABSTRACT SUPPLEMENT

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to tolerate a solid diet. Nonetheless, more than 50% of cases still had ongoing weight loss with the majority of this group remained malnourished or at risk of malnutrition. Overall, 26.3% (10/38) of cases required ongoing nutritional support via PEG or nasogastric tube post dilatation.

Discussion: The MSA-ICG migrated to more than one SLN and its signal was not diminished for at least 4 h during near-infrared imaging guided SLN mapping in esophagus. Therefore, the MSA-ICG is considered to be a potential tracer for SLN identification in esophagus cancer.

Discussion: Endoscopic dilatation can be performed safely and is effective in providing symptomatic relief for majority of patients with radiationinduced oesophageal strictures. However, close surveillance and ongoing nutritional support are still required.



O202.08: ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) OF ESOPHAGEAL CANCER USING THE NEW DEVICE FOR THE NARROW DIAMETER SCOPE Akiyoshi Ishiyama1, Tomohiro Tsuchida1, Makoto Kobayashi2, Kiyoaki Honma3 1 Cancer Institute Hospital, Tokyo/JAPAN, 2Yokkaichi Municipal Hospital, Mie/JAPAN, 3Nihonkai General Hospital, Yamagata/JAPAN

Keywords: radiation induced stricture, nutritional impact, endoscopic dilatation, oesophageal stricture O202.07: MERGED NEAR INFRARED FLUORESCENT IMAGEGUIDED SENTINEL NODE DETECTION IN ESOPHAGUS; COMPARISON BETWEEN INDOCYANINE GREEN AND MANNOSYLATED HUMAN SERUM ALBUMIN-INDOCYANINE GREEN CONJUGATE Hyun Koo Kim1, Yu Hua Quan1, Yujin Oh2, Yun-Sang Lee3, Beop-Min Kim2, Jae Min Jeong3, Young Ho Choi1 1 Korea University Guro Hospital, Seoul/SOUTH KOREA, 2Korea University, Seoul/SOUTH KOREA, 3Seoul National University College of Medicine, Seoul/SOUTH KOREA Background: Radical esophagectomy with 3-field lymph node dissection has been recognized as the standard treatment procedure, even for clinically node-negative cases. However, this procedure has been related to a significant increase in patient morbidity and mortality and reduced quality of life. Moreover, its effect on prognosis remains controversial. The sentinel lymph node (SLN) is an essential point for esophageal cancer surgery to avoid unnecessary radical lymph node dissection. Several pre-clinical trials are known to use fluorescent indocyanine green (ICG) to selectively detect SLNs. In this study, we used mannosylated human serum albumin (MSA)ICG conjugate as a new SLN targeting tracer to investigate esophageal SLN mapping using Combined Color and Near-infrared Fluorescence Imaging System (CCNFIS). Methods: Rabbits underwent thoracotomy, and free-ICG or premixed MSA-ICG was injected to the esophageal submucosa. The migration of free-ICG or MSA-ICG in esophageal lymphatic system was recorded and evaluated over a 2 h period by CCNFIS, and SLN biopsy was performed. Additionally, 5 Yorkshire pigs underwent submucosal injection of premixed MSA-ICG with esophagoscope (Fig. 1). The distribution of premixed MSA-ICG in SLN of pig esophagus was investigated by CCNFIS.

Keywords: Esophageal cancer, lymph node dissection, Sentinel lymph node, Near infrared Fluorescence

Background: Endoscopic subumucosal dissection (ESD) permits en bloc removal of superficial esophageal squamous cell carcinoma. In recent years, the report of the usefulness over cicatricial-stenosis prevention of steroid administration has appeared here and there. However, in the example of a recurrence after general chemo-radiotherapy and a circumferential mucosal defect involving over three fourths the circumference of the esophagus after ESD, we may be experienced that a scope does not pass stenosis. Although the case which stenosis has canceled by the endoscopic dilatation has performed endoscopic resection until now, has performed the coagulation to the difficult case using the argon plasma coagulation (APC) probe for the narrow diameter scopes. Although the treatment results in which coagulation is also in general good were acquired, since pathology assessment’s being impossible and a local recurrence case were experienced, medical treatment in endoscopic resection was desired. Methods: Device: SB Knife Jr. (Sumitomo Bakelite Co., Ltd.) is scissors type monopolar ESD knife. We improved this knife in the size which can be inserted in the forceps hole (2 mm diameter) of the narrow diameter scope. We named this knife SB Knife Pico. Design: Case series. Setting: Endoscopy department in our hospital. Patients and Methods: From May 2012 to February 2014, we enrolled a total of 6 consecutive patients who had superficial esophageal cancer with stenosis in the mouth side which a scope does not pass after the endoscopic dilatation. One patient used GIF-XP260N (5mm diameter, Olympus Co., Ltd.) scope and five patients used GIF-PQ260 (7.9mm diameter). The marking used the APC probe of 1.5 mm diameter (ERBE Co., Ltd.) and we performed ESD used improved SB Knife Pico. It was the same procedure as SB Knife Jr. and ESD continued by SB Knife Pico at circumference incision, and performed submucosal dissection, and arrest-of-hemorrhage operation was possible for it similarly. A setup of high-frequency power source equipment was considered as the same as SB Knife Jr. Results: All patients were possible to perform en-bloc resection of ESD without complication, such as bleeding and perforation. Discussion: It was thought that adaptation to the case of having been difficult for ESD would spread by improvement of a disposal implement if it is the former while collateralizing safety. Disclosure: All authors have declared no conflicts of interest. Keywords: Endoscopic submucosal dessection (ESD), New device for ESD, SB Knife (scissors type knife)

Results: The lymphatic vessel and SLN were successfully visualized using CCNFIS in rabbits. The SLN was detected within 15 min after injection of free-ICG or MSA-ICG, and the MSA-ICG provided significantly higher signal to background ratio (SBR) than free-ICG at esophageal SLN in rabbits. In porcine esophagus, SLN was detected from 15 min after injection of MSA-ICG. In three out of four trials, two SLNs were identified (Fig. 2).

O202.09: THE EFFICACY OF STEROID ADMINISTRATION FOR THE PREVENTION OF ESOPHAGEAL STRICTURE AFTER ENDOSCOPIC SUBUMUCOSAL DISSECTION FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA. Akiyoshi Ishiyama, Tomohiro Tsuchida, Hiroki Osumi, Chika Taniguchi, Akihiko Tomita, Hideomi Tomida, Kenjirou Morishige, Yusuke Horiuchi, Natsuko Yoshizawa, Hirotaka Ishikawa, Junko Fujisaki, Masahiro Igarashi, Keishou Chin, Shinji Mine, Masayuki Watanabe Cancer Institute Hospital, Tokyo/JAPAN Background: Endoscopic subumucosal dissection (ESD) permits en bloc removal of superficial esophageal squamous cell carcinoma. A circumferential mucosal defect involving over three fourths the circumference of the esophagus after ESD was significantly associated with the subsequent development of esophageal stenosis. So, it is necessary to prevent postprocedure stricture after ESD. In recent years, the report of the usefulness over cicatricial-stenosis prevention of steroid administration has appeared here and there. About the steroid administration method, an effect is expectable by the method of taking orally and both of injection, there is no unified view.

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Methods: Purpose: To evaluate of the efficacy of steroid administration for the prevention of esophageal stricture after ESD. Design: Case series. Setting: Endoscopy department in our hospital. Patients: From October 2011 to December 2013, a total of 36 consecutive patients who had an over three fourths mucosal defect that arose after ESD for superficial esophageal squamous cell carcinoma were enrolled in this study. 24 patients were in the oral group and 12 patients were in the injection group. Methods: In the oral group, prednisolone was used and the triamcinolone was used in the injection group. Pre-emptive endoscopic balloon dilation (EBD) was not started until stenosis occurs. Esophageal stenosis was defined when a standard endoscope (9.8mm in diameter) failed to pass through the stenosis. Oral prednisolone was started at 30 mg/day on the first day postESD. The prednisolone gradually tapered off and then was canceled eight weeks. The quantity of drug and schedules referred to an existing report. Injection considered it as the deed immediately after ESD or on the 1st day of after ESD (only in case of one case), and the amount of injection was 80 mg once. Main outcome measurements: Incidence of stricture and frequency of required EBD. Results: 7 of 24 patients (29%) was happened stricture in the oral group, and the number of EBD required was 3.2(0-16) on these patient. A complication was happened, the perforation related to EBD itself in one patient. 5 of 12 patients (41.7%) was happened stricture in the oral group, and the number of EBD required was 1.7(0-7) on these patient. There were no complication related to injection and EBD itself in 12 patients. Discussion: This study suggests that prednisolone taking orally and triamcinolone injection method are effective for prevention of post-ESD esophageal stricture. The variation of procedure does not occur, and patient’s acceptance is high, so oral administration is excellent. However, in the oral group, it needs to be cautious of the happening of complications, such as perforation. On the other hand, since it was completed by one injection when quality control was collateralized, the triamcinolone injection method is excellent. Disclosure: All authors have declared no conflicts of interest. Keywords: Prevention of esophageal stricture, After endoscopic subumucosal dissection, Oral prednisolone, Triamcinolone injection

Tuesday, September 23 – 8:00–9:50 O203: Management of HGD and Early Invasive Cancer Room: Salon 3 O203.01: PREVALENCE OF METASTASES IN EARLY ESOPHAGEAL ADENOCARCINOMA Dietmar Lorenz1, Christina Oetzmann Von Sochaczewski2, Thomas Haist1, Michael Pauthner1 1 Sana Klinikum Offenbach, Offenbach/GERMANY, 2HSK Dr. Horst Schmidt Kliniken, Wiesbaden/GERMANY Background: Early esophageal adenocarcinoma (eACEs) has a certain risk of lymph node metastases (LNM). Although endoscopic resection (ER) is accepted in eACEs limited to mucosa, the risk of LNM rises with increasing infiltration depth. Recently our group defined histopathological risk factors on the ER specimen, making it possible to define eACEs that have a high risk for LNM and thus cannot be cured by ER. The objective of this study was to assess the prevalence and pattern of lymphatic spread and to determine the overall risk of metastases in operatively resected eACEs. Methods: We analyzed the results of 186 consecutive patients with pT1 eACEs who underwent transthoracic esophagectomy and two-field lymphadenectomy. Tumor infiltration depth was subdivided into seven categories (m1, m2, m3, m4, sm1, sm2 and sm3). The influence of tumor infiltration depth, LNM, tumor differentiation (G1/2 vs 3) and lymphatic or venous vessel infiltration (L+ or V+) on overall and tumor-specific survival were determined by multivariate analysis. Furthermore the pattern of lymphatic spread and overall rates for LN metastases, locoregional recurrences, distant recurrences and the outcome were investigated. Results: Lymphatic spread occurred in 36 of 186 patients (19,4%). Infiltration depth-dependent incidences of LNM were: none in m1 and m2; 6.7% (1/15) in m3; 25% (5/20) in m4; 7.7% (3/39) in sm1; 26.8% in sm2 and 25.4% in sm3. The distribution of lymph node metastases in most of the cases was limited to the lower mediastinum, the paracardial region and along the lesser gastric curvature; 3 of 36 N+ patients (8,33%) had lymphatic spread in the upper mediastinum. Sixteen of 36 T1N+ patients (44,4%) developed recurrences. Moreover, in 10 of 150 T1N0 patients (6,7%) the tumor recurred.


Only 4 patients (2,2%) developed isolated locoregional tumor recurrences, whereas 13 patients (7%) suffered from locoregional and distant, and 9 (4,8%) from only distant recurrences. The overall rates for metastases were: None in m1 and m2, 20% (3/15) in m3; 25% (5/20) in m4; 7.7% (3/39) in sm1; 29.3% (12/41) in sm2 and 26.5% (23/63) in sm3 stages. On multivariate analysis only tumor infiltration depth and lymphatic invasion were independent predictors for metastases. Discussion: This is the first report on predictive markers for the overall risk for locoregional and distant metastases as well as recurrence pattern in patients with eACEs. Our analysis is based on the to our knowledge largest cohort of patients with eACEs treated with transthoracic esophagectomy and systematic two-field lymphadenectomy in a single center institution. Disclosure: All authors have declared no conflicts of interest. Keywords: overall risk for metastases, recurrence pattern, eACE, early Barrett Carcinoma O203.02: THE USE OF TISSUE-ENGINEERED CELL SHEETS IN A EUROPEAN SETTING TO PREVENT ESOPHAGEAL STRICTURES AFTER ENDSOCOPIC SUBMUCOSAL DISSECTION (ESD) Peter Elbe1, Eduard Jonas1, Sebastian Sjöqvist2, Makoto Kondo3, Nobuo Kanai3, Takeshi Ohki3, Teruo Okano3, Jenny Enger2, Maria Enger2, Heidi Pettersson4, Mime Egami3, Pontus Blomberg4, Matthias Löhr2 1 Division of Surgery, CLINTEC, Karolinska Institutet, Stockholm/ SWEDEN, 2Karolinska Institutet, Stockholm/SWEDEN, 3Tokyo Women’s Medical University, Tokyo/JAPAN, 4Karolinska Insitutet, Stockholm/ SWEDEN Background: Extensive dissection with Endoscopic Submucosal Dissection (ESD) often leads to postoperative esophageal strictures. Transplantation of tissue-engineered autologous oral mucosal epithelial cellsheets in the esophagus after ESD has been shown to prevent the development of strictures in Japanese studies. In Japan ESD in the esophagus is primarly done because of early squamous lesions. In the Western world is Barrett′s esophagus (BE) much more common and ESD is thus more used in patients with early adenocacrinomas or BE with high grade dysplasia (HGD). In this study we investigated the safety and efficacy of endoscopic transplantation of tissue engineered utologous oral mucosal epithelial cell sheets in preventing formation of strictures after ESD in a European setting. Methods: 5 patients were included. 4 patients with Barrett′s esophagus (BE) and visible lesions, where an ESD more than ⅔ of the circumference was expected were included. 1 patient with a squamous HGD was also included. Squamous cells from patients’ oral mucosa were cultured for 16 days in temperature-responsive cell culture surfaces. After ESD the cellsheets were endoscopically transplanted on the raw surfaces. All patients were followed up by endoscopy and confocal endoscopy (Cellvizio®) once a week for a four week period. Results: The patient with squamous HGD underwent an 8 cm long long circumferential resection, The healing was initially but the patient developed over time a stricture which was dilated six months later. The first patient with BE and HGD underwent a 5 cm long ESD of 75% of the esophageal circumference. Duringfollow-up the patient had complete re-epithelialization. The post-operative course was uneventful.The second patient with BE underwent a 5cm long long circumferential resection, He developed a stricture which was dilated four times. The third BE patient underwent a 10 cm long circumferential resection, PAD showed T1b adenocaricom with doubtful radicality at depth. He developed strictures that were dilated five times. This patient later underwent surgery. The fourth BE patient underwent a 4 cm long ESD of 30% of the circumference. This patient is just treated but after 4 weeks the resection area is healing well with squamous epithelium. Discussion: Transplantation of cell sheets with squamous cells can be used in a western population. The method is safe and seems to facilitate healing of the esophagus after ESD. Further studies are needed to see how the reflux disease, which most patients with Barrett’s esophagus have, affects the healing with cell sheets. Disclosure: All authors have declared no conflicts of interest. Keyword: ESD, Cellsheet, Barrett’s espohagus, esophageal strictures O203.03: CLINICAL OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL ADENOCARCINOMA OF BARRETT’S ESOPHAGUS. Masaki Tanaka, Naomi Kakushima, Kohei Takizawa, Noboru Kawata, Hiroyuki Ono Shizuoka Cancer Center, Nagaizumi/JAPAN Background: Endoscopic submucosal dissection (ESD) for superficial neoplasms of the esophagus and stomach has become a standard treatment in Japan. However, because of the low prevalence of Barrett’s esophagus, only a few reports of ESD for superficial adenocarcinoma of Barrett’s esophagus


ABSTRACT SUPPLEMENT

(sABE) have been reported. The aim of this study was to assess the safety of ESD for sABE and clarify the treatment outcomes. Methods: We conducted a retrospective review of our clinical database for sABE that included patients who underwent ESD between October 2002 and December 2013. Clinicopathological features of the lesions, en bloc resection rate, R0 resection rate, operation time, perioperative complications, and clinical course were assessed. Mid-term outcomes including 3-year overall survival rate were analyzed in patients who were followed-up over 6 months. Results: Forty two sABE lesions in 35 consecutive patients were enrolled. Twenty six lesions (74%) developed from short-segment Barrett’s esophagus and 9 lesions developed from long-segment Barrett’s esophagus. Median tumor size was 21 mm (range 4–95 mm). Macroscopic type included 8 protruded (19%), 12 elevated (29%), 3 flat (7%), and 19 depressed (45%) types. Circumferential extent of the tumor was under half of the lumen in 40 lesions (95%), and 26 lesions (62%) were located at 12 to 3 o’clock. Four patients had multiple lesions (synchronous 4, metachronous 1). Pathological tumor depth included 8 superficial muscularis mucosa (19%), 7 lamina propria mucosa (17%), 17 deep muscularis mucosa (40%), 5 submucosal invasion less than 200 micrometers (12%), and 5 submucosal massive invasive tumors (12%). The en bloc resection rate was 100% (35/35), and pathological R0 resection rate was 95% (40/42). One case was horizontal margin positive because of misdiagnosis of lateral tumor spread and the other case was vertical margin positive because of intra-lesional cutting during ESD. The median procedure time was 41 minutes (range, 4–258 minutes). Delayed bleeding and perforation occurred in one patient each, and both were treated conservatively. Postoperative stricture occurred in 3 patients and were managed by endoscopic dilatation. Twenty three patients were followed-up more than 6 months. During the median follow-up periods of 31 months (range, 6–86 months), there was no local recurrence. Lymph-node metastasis occurred in 2 patients. One patient died of Barrett’s adenocarcinoma 39 months after ESD, and 2 patients died of other disease. Three-year overall survival rate was 100%. Discussion: ESD for sABE achieved a high en bloc resection rate and good local control with an acceptable safety profile. ESD could be a standard treatment for sABE. Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett’s Esophagus, ESD, Clinical outcome O203.04: TREATMENT OF BARRETT’S ESOPHAGEAL ADENOCARCINOMA Kosuke Narumiya, Masaho Ota, Kenji Kudo, Yuji Shirai, Shin Yamamoto, Hiroko Ide, Harushi Osugi, Masakazu Yamamoto Tokyo Women’s Medical University, Tokyo/JAPAN Background: The mainly histologic type of esophageal carcinoma in japan is squamous cell carcinoma. The incidence of Barrett’s esophageal adenocarcinoma in our Japanese institute was 1.0% between 1990 and 1994 but it rised until 4.7% between 2005 and 2009. Although the incidence of Barrett’s esophageal adenocarcinoma has increased remarkably in the Europe or America, it remains relatively rare in Japan.The reason why are the rate of Helicobacter Pylori bacillus infection and physical constitution without reflux esophagitis. Methods: The purpose of this study was to evaluate the treatment of Barrett’s esophageal adenocarcinoma. Between 1992 and 2013, 33patients were diagnosis of Barrett’s esophageal adenocarcinoma. We exam (1) Back ground (2)Treatments (3)Location of the Lymph node metastasis (4)Prognosisthe (5)Type of the recurrence (6) Neoadjuvant therapy. Results: (1) Age 65.4(33–90), Male:Female = 30:3, Sympton, None : Swallowing difficulty : Heart burn : Epigastralgia = 17:9:7:3, T1/T2/T3 = 19/4/10, N0/N1 20/13, StageI/II/III/IV = 17/8/6/2, middle/low/EG junction= 3/14/16, Length of the tumor 45.2mm(12-105), Length of the Barrett’s mucosa 36.9mm(5.0-124), Short segment Barrett esophagus : Long segment esophagus = 24:9, Pathology Well:poorly = 25:8, HP bacillus infection rate was 44.4% (2) Surgery:ESD = 29:4, Right thoracotomy : Left thoracoabdominal incision : laparotomy =6:14:9 (3) Neck : upper Mediastainal : Middle : Low: Abnominal = 3.5%, 7.0%, 10.5%, 14.0%, 42.0% (4) 5-years survival rate for early cancer was 82%, for advanced cancer was30%. (5) Metastasis of the liver : Lymph node : Metastasis of the Bone : Dissemination = 7:4:1:1 (6) Chemotherapy before operation: Chemotherapy after operation : Chemoradiotherapy after operation = 1:8:2. Discussion: The survival rate was very poor in the Barrett’s esophagus adenocarcinoma as like as usual esophageal cancer. Surgical resection has been mainstream treatment but the effect was not satisfactory because the location of the metastasis of the lymph node was same as useal esophageal cancer which was squamous carcinoma. We started the Chemo-radiotherapy before the operation as a neoadjuvant therapy with taxane. In order to prevent the Barrett’s esophageal adenocarcinoma, we must make a schedule of the exam for patients who have the Barrett’s mucosa.

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Disclosure: All authors have declared no conflicts of interest. Keywords: Barrett’s esophageal adenocarcinoma, Reflux esophagitis, Short segment Barrett esophagus, neoadjuvant therapy O203.05: OUTCOME OF ENDOSCOPIC MUCOSAL RESECTION AND ENDOSCOPIC SUBMUCOSAL DISSECTION OF DYSPLASTIC BARRETT’S OESOPHAGUS AND EARLY ESOPHAGEAL ADENOCARCINOMA Larry Loo1, Zaher Toumi2, Jonathan Vickers2, Polobody Sibaprasad Senapati2, Regi George1, Yeng Ang1 1 Salford Royal Hospital, Salford/UNITED KINGDOM, 2Salford Royal NHS Foundation Trust, Manchester/UNITED KINGDOM Background: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are recent modalities, being used to treat high-grade dysplastic (HGD) Barrett’s oesophagus (BE) or intramucosal cancer. The aim of our study is to analyse outcome from a prospectively collected database following EMR or ESD in the background of Barrett’s in a large tertiary teaching hospital. Methods: We collected data on 29 patients (mean age, 70.9 years; 69% male) with BE and early neoplasia (28% with intramucosal cancer, 55% with HGD, 17% with LGD) who presented at a tertiary hospital in the United Kingdom from September 2011 to December 2013. Following discussion of these cases in our specialist multidisciplinary meeting, these patients underwent EMR, ESD or hybrid procedure (circumferential resection followed by snare resection). Outcomes such as complete endoscopic response and complications from EMR, ESD or a hybrid EMR/ESD were assessed. Results: Eighteen patients (62%) underwent EMR, 9 patients (31%) underwent ESD and 2 patients (7%) underwent hydrid EMR/ESD procedures. Median follow up duration was 16 months (range 1 to 26 months). Median size of the lesion was 2 cm (range 0.4 to 3 cm). Out of the 18 EMR cohort patients, 14 patients (77%) who had EMR achieved a complete endoscopic response. One patient required endoscopic re-treatment, which was successful. Oesophagectomy was required in 2 patients (11%) after submucosal tumour invasion was detected on histology. One patient underwent radiotherapy following detection of submucosal tumour invasion as deemed unfit for curative surgery. Out of the 9 ESD cohort, 7 patients (77%) who had ESD achieved a complete endoscopic response; of the remaining 2 patients, 1 patient required subsequent oesophagectomy due to submucosal tumour invasion and the other procedure was abandoned due to intra-operative bleeding from lesion (patient required admission for observation but no blood transfusion was required). One out of 2 patients who underwent hybrid EMR/ESD achieved a complete response. The other patient was referred for oesophagectomy due to presence of submucosal tumour invasion. Overall, 14 patients (48%) underwent radiofrequency ablation of the remaining Barrett’s segment following their initial endoscopic resection of the lesion. Metachronous lesions were detected in 4 patients (14%) during follow-up, all of which underwent re-EMR with complete endoscopic response. Except one minor bleeding there were no other major complications in this cohort of patients. Discussion: Our study has shown that EMR, ESD or combination of both, are effective methods for removing nodular lesions and both demonstrate an excellent safety profile. Coupled with radiofrequency ablation of residual dysplastic Barrett’s oesophagus, this dual modality therapeutic endoscopic approach is proving to be a reliable and effective management option for BE with HGD or intramucosal cancer. Disclosure: All authors have declared no conflicts of interest. Keywords: Endoscopic mucosal resection, endoscopic submucosal dissection, Esophageal cancer, Barretts esophagus: High-grade dysplasia O203.06: THORACOLAPAROSCOPIC DISSECTION OF ESOPHAGEAL LYMPH NODES IS FEASIBLE IN HUMAN CADAVERS, AND SAFE IN A PORCINE SURVIVAL STUDY Hannah Künzli1, Mark Van Berge Henegouwen2, Suzanne Gisbertz2, Kees Seldenrijk1, Karel Kuijpers1, Erik Hazebroek1, Sjoerd Lagarde2, Sybren Meijer2, Jacques Bergman2, René Wiezer1, Bas Weusten1 1 St. Antonius Hospital Nieuwegein, Nieuwegein/NETHERLANDS, 2 Academic Medical Center Amsterdam, Amsterdam/NETHERLANDS Background: Low-risk early esophageal adenocarcinoma (EAC) can safely be managed endoscopically. In case of high-risk early EAC (i.e. submucosal invasion >500 nanometers, poor differentiation grade and/or presence of lymphovascular invasion), esophagectomy with lymph node dissection is currently advocated given the relatively high rates of lymph node (LN) metastases. However, esophagectomy is associated with substantial morbidity and mortality and a reduced quality of life (QoL). Endoscopic radical (R0) local resection, followed by thoracolaparoscopic dissection of LNs involved in the drainage of the esophagus, without concomitant esophagectomy, could be an alternative. In this study, we evaluated the feasibility and

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safety of thoracolaparoscopic dissection of LNs involved in the drainage of the esophagus in (1) human cadavers, (2) living swine, and (3) two pilot-cases. Methods: (1) In human cadavers, thoracolaparoscopic dissection of LNs involved in drainage of the esophagus was performed. Thereafter, esophagectomy was performed and the esophagectomy specimen (ES) was analysed for any retained LNs. Outcome parameters included the number of dissected LNs, the number of retained LNs in the ES and technical success, which was defined as a ratio ≥ 0.9 between the number of dissected LNs during lymphadenectomy and the total (resected plus retained) number of LNs. (2) In swine, a thoracolaparoscopic LN dissection was performed. 28 days after the procedure, the swine were sacrificed and esophagectomy was performed. Outcome parameters included the presence of ischemia or stenosis in the ES (safety parameters), and other complications. (3) In the first human pilotcases, thoracolaparoscopic LN dissection was performed, directly followed by esophagectomy with gastric tube reconstruction (same session). Outcome parameters included the number of dissected LNs during lymphadenectomy, the number of tumor-positive LNs, and the number of retained LNs in the ES. Results: (1) In 5 human cadavers, a median of 26 LNs (IQR 22-46) was dissected. In 2 ES, 1 retained LN was found. Technical success rate was 100%. (2) None of the 7 porcine ES showed signs of ischemia or stenosis. One swine died because of ventricular fibrillation during surgery; during follow-up no complications were observed. (3) In 2 patients with early EAC (T1bN0M0), 23 and 43 LNs were dissected, all without evidence of metastasis. In the ES, 2 and 1 retained paraesophageal LNs were found, proximal and distal, respectively. In conclusion, thoracolaparoscopic dissection of LNs involved in the drainage of the esophagus is feasible. The porcine survival study suggests that the esophageal vascularity is not severely compromised by this procedure. Discussion: As anatomy differs between swine and humans, safety of the procedure will have to be investigated thoroughly before applying this new technique as the treatment of choice. Furthermore, we did not investigate efficacy of the procedure and the influence of the procedure on GI-tract functioning and QoL. We expect this procedure to be effective, safe and to retain QoL of patients post-operatively. Disclosure: All authors have declared no conflicts of interest. Keywords: Lymphadenectomy, surgical treatment, early esophageal cancer O203.07: PREDICTORS OF POSTOPERATIVE STRICTURE AFTER ESD FOR SUPERFICIAL ESOPHAGEAL CARCINOMA Akihiro Yamada, Toshiro Iizuka, Daisuke Kikuchi, Mitsuru Kaise Toranomon Hospital, Tokyo/JAPAN Background: Postoperative stricture after esophageal ESD of widespread mucosal resection is a major complication. In this study, we investigated the characteristics of lesions and predictors of postoperative stricture with a large number of cases. Methods: From April 2005 to December 2012, 215 patients who underwent >3/4 circumferential ESD for superficial esophageal carcinoma were enrolled. 8 patients who underwent operation after ESD and 18 patients who underwent steroid injection were excluded. Predictors of postoperative stricture were investigated by comparing results from 73 patients who developed strictures from 116 patients who did not. Results: Significant differences were observed in the location of the lesion (U/M/L: 24/26/23 vs 11/62/43), histologic depth (m/sm: 69/4 vs 92/24), procedure time (120.9 ± 53.1 vs 92.3 ± 43.7), the proportion of extension to the whole circumference of the lumen (3/4 1cm at EGD (p = 0.01), higher rates of multifocal EAC (p = 0.03), and positive deep and lateral margins for EAC on EMR (p < 0.05 and p = 0.01, respectively). On multivariate analysis only multifocal HGD was an independent factor for surgery (OR 5.29; 95% CI 1.23-22.8; p = 0.03). Following esophagectomy R0 resection rates for Barrett’s and cancer were both 100%. Surgical pathology showed a pTstage higher than T1a in 11 patients (22%; T1b n = 7, T2 n = 3, T3 n = 1) and positive nodal metastases were found in 4 patients (8%). Incidence of surgical treatment decreased over the study period from 85% to 40% while multiple EMR (≥3 per patient) increased from 21% to 55%. All ET patients had EMR (100%) and 28 patients (78%) underwent additional ablative therapies for BE. Eradication of EAC occurred in 33 patients (92%), dysplasia in 29 patients (81%), and BE in 19 patients (53%). Morbidity was not significantly different between groups (ST 51% vs ET 39%, p = 0.31). In-hospital, thirty- and ninetyday mortality rates were zero in each group. Recurrence rates in ST and ET group were 2% and 11%, respectively (p = 0.08). In the ET group, 2 patients with endoluminal cancer recurrence after complete eradication underwent esophagectomy. Age-adjusted overall survival was comparable (p = 0.211) with 80% in the ST group and 78% in the ET group (mean follow-up 70 and 42.6 months, respectively). Multivariate survival analysis revealed age (HR = 1.12; 95% CI 1.01-1.21; p = 0.02) and Charlson score (HR = 1.61; 95% CI 1.13-2.29; p = 0.01) as independent prognostic factors. Discussion: ST and ET of clinical T1a EAC are both safe and effective. Some patients remain understaged, even following EMR, and esophagectomy should remain an option in high volume centers. Endoscopic management is an excellent option in selected patients but treatment decisions should be made in multidisciplinary tumor board and appropriate longterm follow-up protocols need to be developed for patients treated endoscopically. Disclosure: All authors have declared no conflicts of interest. Keywords: early esophageal cancer, endoscopic mucosal resection, esophagectomy, Barrett’s O203.09: DEFINING PATHOLOGIC CRITERIA FOR THE ASSESSMENT OF NODAL METASTASIS RISK IN SUPERFICIAL (T1) ESOPHAGEAL ADENOCARCINOMA Jon Davison1, Michael Landau2, Douglas Landsittel3, James Luketich2, Katie Nason2 1 University of Pittsburgh School of Medicine, Pittsburgh/PA/UNITED STATES OF AMERICA, 2University of Pittsburgh School of Medicine, Pittsburgh/PA/UNITED STATES OF AMERICA, 3University of Pittsburgh, Pittsburgh/PA/UNITED STATES OF AMERICA Background: Nodal metastasis is a major determinant of therapeutic strategy and prognosis for superficial (stage T1) esophageal adenocarcinoma (EAC). Previous studies have established depth of invasion, tumor grade, lymphovascular invasion and tumor size as factors influencing the risk of nodal metastasis. In part because the pathologic criteria remain ambiguous, the pathologic evaluation of T1 EAC is not standardized. In this study we aimed to define and test a set of pathologic criteria for estimating the risk of lymph node metastasis in a large single institution cohort of T1 EAC.


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Methods: We scored four pathologic risk factors (depth of invasion, tumor grade, lymphovascular invasion and tumor size) using defined histopathologic criteria in 211 T1 EAC treated by esophagectomy without induction therapy at a single institution. These four risk factors were combined to generate a nodal metastasis risk score for each tumor using multivariate logistic regression. Tumors with similar scores were grouped as very low (20%) risk of nodal metastasis. Clinical follow up data were abstracted from the medical record. Time to recurrence and overall survival were assessed by comparing differences in Kaplan-Meier survival functions. Results: Nearly all (70 of 72, 97.2%) intramucosal (T1a) cancers had very low or low node metastasis risk scores. Twenty-seven of 138 (19.6%) submucosal (T1b) EAC had a low risk score, the remainder were intermediate (38/138, 27.5%) or high risk (73/138, 52.9%). Increasing risk scores had a strong positive association with the actual prevalence of nodal metastasis at esophagectomy (p < 0.0001, chi squared test). Higher risk scores were associated with worse overall survival (p < 0.0001, log rank test) and accelerated time to recurrence (p = 0.001, log rank test). Discussion: Tumor pathologic characteristics based on defined criteria can be used to generate a risk score that is strongly associated with nodal metastasis at esophagectomy and survival outcomes in superficial (T1) EAC. These criteria can be applied to endoscopically or surgically resected T1 EAC in order to facilitate risk stratification and clinical decisions in the pre- and post-operative setting. Disclosure: All authors have declared no conflicts of interest. Keywords: Superficial adenocarcinoma, lymph node metastasis, Pathology O203.10: THE ROLE OF ENDOSCOPIC MUCOSAL RESECTION IN THE MANAGEMENT OF EARLY OESOPHAGEAL CANCER: EXPERIENCE FROM A SINGLE UK CENTRE Barry Dent, Rhys Jones, Lorna Dunn, Shajahan Wahed, Arul Immanuel, S Michael Griffin Royal Victoria Infirmary, Newcastle upon Tyne/UNITED KINGDOM Background: Endoscopic mucosal resection (EMR) allows for the accurate diagnosis and treatment of oesophageal dysplasia and early cancer. Longterm outcomes from surgery for early oesophageal cancer are excellent and it is essential that the use of EMR does not lead to under treatment of these patients. We reviewed the introduction of EMR in a single UK oesophagogastric cancer surgical unit and its role in the management of patients with early oesophageal cancer. Methods: All patients undergoing oesophageal EMR in our unit since 2009 were included in the study. Patients were identified from a prospectively maintained database. All procedures were performed using the suction cap technique by a single consultant surgeon. Patients found to have invasive adenocarcinoma in the resection specimen were managed according to the depth of tumour invasion. Surgical resection was discussed with all patients with submucosal involvement (due to the risk of nodal metastasis) or positive deep or circumferential resection margins. Results: In total 86 oesophageal EMRs were performed on 66 patients. The median age of patients was 71 years (range 38–84). Sixteen patients underwent multiple resections for synchronous or metachronous lesions. The overall complication rate was 3.5% (3/86). Two patients had radiological evidence of a perforation following the procedure and were managed conservatively. A single patient required a repeat endoscopy to treat bleeding post-procedure. Invasive adenocarcinoma was identified in 33 EMR specimens. Depth of invasion was mucosal (T1a) in 23 and submucosal (T1b) in ten. In nine of these patients the pre-EMR histology was high grade dysplasia (HGD) only. Eight patients with mucosal and five with submucosal disease were found to have tumour involvement of deep or circumferential resection margins. Of the patients with mucosal disease and positive margins, three underwent surgical resection whilst the remaining five were unfit for surgery and were treated with radical radiotherapy (n = 3) or repeat EMR (n = 2). The remaining patients with mucosal disease underwent endoscopic surveillance only. Of the ten patients with submucosal disease, four were not fit for surgery and two patients chose to be managed conservatively. The remaining four patients underwent surgical resection. Of the seven patients who underwent surgical resection three had no evidence of tumour within the resection specimen. A single patient had pT1N2 disease. The remaining patients all had pT1N0 histology. A further three patients with mucosal disease underwent surgical resection after an initial period of endoscopic surveillance due to tumour recurrence at the EMR site (15, 17 and 27 months following EMR). In all cases, operative histology revealed pT1N0 disease. A single T1b patient treated originally with surgery (no residual disease in specimen) developed metastatic recurrence at 24 months following EMR. Discussion: EMR offers a potentially curative strategy with minimal morbidity in appropriate patients with early oesophageal cancer. Surveillance following EMR is essential to allow successful treatment of disease recurrence.

Care must be taken in particular with submucosal lesions as they have the potential for nodal and metastatic dissemination. Disclosure: All authors have declared no conflicts of interest. Keywords: Cancer, Endoscopic mucosal resection, Oesophageal O203.11: INTER-OBSERVER VARIABILITY IN THE INTERPRETATION OF ENDOSCOPIC MUCOSAL RESECTION SPECIMENS Stephanie Worrell1, John Vallone1, Parakrama Chandrasoma1, Jeffrey Hagen1, Corey Johnson1, Michal Lada2, Brian Louie3, Daniel Oh1, Jeffrey Peters2, Thomas Watson2, Steven Demeester1 1 USC, Pasadena/CA/UNITED STATES OF AMERICA, 2University of Rochester Medical Center, Rochester/NY/UNITED STATES OF AMERICA, 3Swedish Medical Center and Cancer Institute, Seattle/AL/ UNITED STATES OF AMERICA Background: Endoscopic resection to stage and potentially treat superficial esophageal adenocarcinoma has become a standard therapy. Accurate pathologic evaluation of the depth of invasion is critical to determine whether endoscopic therapy and esophageal preservation or esophagectomy is the most appropriate oncologic therapy for the patient. The aim of this study was to assess the inter-observer variability in pathologic assessment of endoscopic resection specimens. Methods: A retrospective study was performed of endoscopic resection specimens from three institutions. The endoscopic resections were all done for superficial esophageal adenocarcinoma. The original endoscopic resection slides were re-reviewed by two expert (study) gastrointestinal pathologists with experience interpreting endoscopic resection specimens who were blinded to the original report and to the other expert’s findings. None of the original reports were generated by either of the expert study pathologists. The original report was compared to the individual findings by the expert pathologists for the depth of tumor invasion, tumor grade and presence of lymphovascular invasion (LVI). Results: There were 18 endoscopic resection specimens re-evaluated for this study, with 8, 3 and 7 specimens coming from the 3 institutions. Compared to the original report, re-review by the two expert study pathologists disagreed on the depth of tumor invasion in 9 of the 18 specimens (50%) [Table]. In all but 1 case the original pathologist had over-staged the lesion. There was concordance between the expert study pathologists on the depth of invasion in all but 1 case. There was disagreement between the original pathologist and the expert study pathologists in 3 of 11 cases where tumor grade had been reported and in none of the 8 cases where LVI had been reported. There was concordance between the expert pathologists in all cases of LVI and in all but 1 case on tumor grade. Interpretation

T1a

T1b

T2

Original report Expert 1 (JV) Expert 2 (PC)

7 12 13

10 6 5

1 0 0

Discussion: There is a disturbingly high rate of disagreement (50%) on the depth of tumor invasion by expert pathologists compared to the original pathologic interpretation of endoscopic resection specimens of superficial adenocarcinomas. Most of the discrepancy was related to over-staging on the original interpretation, and in most cases this was related to mistaking the deep layer of a duplicated muscularis mucosa for muscularis propria. Expert review of endoscopic resection specimens is recommended to ensure patients are not subjected to a potentially unnecessary esophagectomy. Disclosure: All authors have declared no conflicts of interest. Keywords: endoscopic resection, Superficial adenocarcinoma

Tuesday, September 23 – 10:20–11:50 O204: Pediatrics Room: Salon 3 O204.01: THORACOSCOPIC CORRECTION OF ESOPHAGEAL ATRESIA IN CHILDREN Saidkhassan Bataev, Roman Ignatiev, Alexander Razumovsky, Victor Rachkov, Abdumanap Alkhasov, Ekaterina Ekimovskaya, Zorikto Mitupov, Nikita Stepanenko, Konstantin Tcilenco Filatov Children’s Hospital, Russian State Medical University, Moscow/ RUSSIAN FEDERATION Background: Advanced thoracoscopic technique of long-gap esophageal atresia (EA) treatment in children. Methods: 56 newborns (33 boys) with EA underwent surgery since 2008. Mean gestational age of the patients was 37 weeks, mean body weight – 2551 g, combined congenital malformations were observed in 42,9% of

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children. The newborns were divided into 3 groups according to L.Spitz Classification: I – 62,5%, II – 32%, III – 5,5%. All children were operated by a thoracoscopic approach.Thoracoscopic technique: 1. Mobilization of the upper and lower ends of an esophagus was made without coagulation by blunt dissection. 2. We didn’t cross v. azygous. 3. The oral end of the esophagus was mobilized up to the thoracic outlet. 4. We evaluated an actual tension between the ends of the esophagus. In case the diastasis was of more than 2,5 sm mobilized the lower end of the esophagus to the necessary extent (28 cases) or even up to the diaphragm (6 cases). 5. Distal part of the oral end of the esophagus was cut up to 2 mm. 6. Anastomosis was made to the right of v. azygous in order to separate suture line to avoid possible recanalization of the TE fistula.

Results: Clinical evaluation, endoscopy and X-ray study showed good results of the operation in all 18 causes. No signs of GER were found during 24-hours pH study. In the long term follow up there were no symptoms of recurrent dysphagia and gastroesophageal reflux. We believe the Dor type of gastropexy to be an appropriate partial fundoplication after esophagocardiomyotomy for achalasia treatment. In order to prevent a recurrence of dysphagia we advocate the technique of extended myotomy which has created good results in our study.

Results: 28 patients had diastases of esophageal ends of more than 2,5 sm and up to 5 sm. We succeed in 93% with the help of our advanced technique of total mobilization of the aboral end of the esophagus. Mean operational time was 83 ± 7 min., mortality rate was 10,7%. Survival rate in groups was: I – 100 %, II – 78 %, III – 33 %. Postoperative complications: anastomosis dehiscence – 10,7%, anastomosis stenosis – 32%, recanalization of the thracheoesophageal fistula – 3,6%.


Discussion: Extended mobilization of the aboral end of the esophagus does not lead to significant increase of postoperative complications in children with long-gap EA. Disclosure: All authors have declared no conflicts of interest. Keyword: Esophageal Atresia Children Thorocoscopic O204.02: LAPAROSCOPIC TREATMENT OF THE ESOPHAGEAL ACHALASIA IN CHILDREN Zorikto Mitupov, Alexander Razumovsky, Saidkhassan Bataev, Abdumanap Alkhasov, Victor Rachkov, Roman Ignatiev, Nikita Stepanenko, Ekaterina Ekimovskaya, Konstantin Tcilenco Filatov Children’s Hospital, Russian State Medical University, Moscow/ RUSSIAN FEDERATION Background: Achalasia is rare in children. Recently, injection of botulinum toxin into the lower esophageal sphincter has been studied as an alternative to esophageal pneumatic dilatation or surgical myotomy as treatment for achalasia. In the current study we present our experience of the laparoscopic treatment for achalasia. Methods: From 2004 to 2013 18 children from 4 to 15 years (mean 9 years) with achalasia of the esophagus were treated at The Filatov Children’s Hospital (Moscow, Russia). All 18 children underwent a laparoscopic cardiomyotomy with gastropexy.

Discussion: We suggest the laparoscopic cardiomyotomy combined with a gastropexy is the operation of choice for achalasia patients since it has all the advantages of minimally invasive approaches and gives the same good results as offen procedures do. Keyword: Esophageal Achalasia in Children O204.03: RADIATION EXPOSURE AND THE RISK OF CANCER IN PATIENTS WITH ESOPHAGEAL ATRESIA Robert Baird1, Yasmine Youssef2, Linda Sun2 1 Montreal Children’s Hospital, Montreal/QC/CANADA, 2McGill University, Montreal/QC/CANADA Background: Children with esophageal atresia (EA) undergo considerable amounts of diagnostic imaging and consequent radiation exposure throughout the course of their initial admission and follow-up. Patients with esophageal atresia are also known to have an increased risk of developing esophageal cancer. This study evaluates the radiological procedures preformed on patients with EA and estimates their cumulative radiation exposure and attributable lifetime cancer risk. Methods: With IRB approval (11-267-PED), patients with EA managed at a tertiary care center from 2001–2013 were investigated. Details regarding patient demographics, EA subtype and number and type of radiological investigations were gathered. Existing normative data was used to estimate the cumulative radiation exposure per imaging modality as well as the lifetime cancer risk per patient. Results: There were 72 children evaluated over the study period, 57 patients with type C EA. The mean follow up per patient was 3.6 years. Table 1 demonstrates the amount of imaging and effective radiation dose during admission and through follow-up, with an overall median 6.47 mSv dose/ patient. This represents 3 times the annual total normative radiation dose estimated at 2.1 mSv. On average, radiation exposure in the neonatal period was 5.7 mSV, correlating with an estimated cumulative lifetime mortality risk of cancer of 1:200 per infant.

Table 1. Summary of radiology and effective dose administration for cohort of patients with esophageal atresia Imaging

During Admission Median (Mean +/− SD)

During Follow Up Median (Mean +/− SD)

Total Median (Mean +/− SD)

Estimated effective dose/study (mSv)

Total Median effective dose (mSv)

Plain CXR Plain AXR Esophagram Other Flluoroscopy

7 (13.2 +/−19.4) 2 (3.6 +/−5.3) 1 (0.9 +/−1) 0 (0.9 +/−1.2)

4 (9.1 +/−12.2) 0 (1.5 +/−3.5) 0 (0.7 +/−0.9) 1 (1.4+/−1.6)

17 (22.3 +/−24.4) 2 (5.1 +/−7.2) 1 (1.6 +/−1.4) 1 (2.3 +/−2.6)

0.02* 0.02* *from Puch-Kapst et al. 2009 5.44** 0.65** From Dimitradis et al. 2011

0.34 0.04 5.44 0.65

Discussion: Children with EA are exposed to significant amounts of radiation during hospitalization and throughout follow-up, which may contribute to the documented increased esophageal cancer rate in these patients. Elimination of superfluous imaging appears warranted, as does direct dosimetry measurements for at-risk patients. Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal atresia, Carcinogenesis, radiation O204.04: THORACOSCOPIC TRACTION TECHNIQUE IN LONG GAP ESOPHAGEAL ATRESIA: ENTERING A NEW ERA David Van Der Zee UMC Utrecht, Utrecht/NETHERLANDS Background: Long gap esophageal atresia remains a challenge for pediatric surgeons. Over the years several techniques have been described to deal with the problem of the distance between the proximal and distal esophagus. More recently a traction technique has been advocated. With the advent of minimal invasive surgery the thoracoscopic elongation technique has been developed. The objective is to describe the evolution from delayed management of long gap esophageal atresia to thoracoscopic treatment directly after birth without the placement of a gastrostomy. Methods: Retrospective description of a single center experience with the thoracoscopic treatment of patients with long gap esophageal atresia over a 7 year period.


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Results: Between 2007 and 2013 eleven children with long gap esophageal atresia were treated by thoracoscopic elongation technique. In two children the procedure failed. In another two direct anastomosis was possible with the use of intrathoracic traction. Seven children succesfully underwent thoracoscopic traction with delayed primary anastomosis. Initially all patients had a gastrostomy. During the course the technique evolved into delayed primary anastomosis directly after birth without the use of a gastrostomy.

density and visual findings shows that eosinophil density increased with an increase in the number of visual abnormalities (Figure 1). Eosinophil density in patients with exudates, edema or furrowing was significantly lower in proximal compared to the mid and distal esophagus (p < 0.05). The presence of exudates irrespective of whether it was in the proximal, mid or distal esophagus was significantly associated with increased eosinophil density compared to those that lacked the finding (p < 0.05).

Discussion: Visual findings were strongly correlated with histology. Our findings suggest in conjunction with clinical symptoms and histology, visual findings may be an important biomarker in the assessment of EoE. Further longitudinal studies are needed to evaluate if changes in visual findings correspond to changes in esophageal eosinophilia with response to treatment. Disclosure: All authors have declared no conflicts of interest. Keywords: Visual findings, Eosinophil density, Esophageal eosinophilia, Histology Discussion: Thoracoscopic elongation technique in long gap esophageal atresia is not only feasible, it can nowadays also be performed directly after birth without the use of a gastrostomy. With this development we have entered a new era in the management of long gap esophageal atresia. Disclosure: All authors have declared no conflicts of interest. Keywords: thoracoscopic elongation, neonatal period, esophageal atresia, long gap O204.05: VISUAL CHARACTERISTICS IN CHILDREN WITH EOSINOPHILIC ESOPHAGITIS Joshua Wechsler1, Kristin Johnson1, Katie Amsden1, Alejandro Llanos-Chea1, Hector Melin-Aldana1, Amir Kagalwalla2 1 Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago/IL/ UNITED STATES OF AMERICA, 2Northwestern University Feinberg School of Medicine, Chicago/IL/UNITED STATES OF AMERICA Background: Diagnosis of eosinophilic esophagitis (EoE) is based on clinical symptoms and histology. Multiple abnormal visual findings described in EoE have not undergone vigorous prospective stratification in children. Utilizing a structured format, we studied the relative frequency of the different visual findings, assessed if abnormal visual findings correspond to the established histologic threshold of ≥15 eosinophils per high power field and established the relationship between the specific visual finding and eosinophilia. Methods: Children who met the 2011 consensus diagnostic guidelines were prospectively recruited and their visual findings at the time of diagnostic endoscopy and esophageal histology were reviewed for the purposes of this study. Results: Eighty-two children (75.6% male) with mean age 8.6 years (range 1.2–17.5 years) were included. Average duration of symptoms prior to diagnosis was 31.1 months (range 1.2–154.0). Abnormal visual endoscopic findings were found in 76 (92.7%) patients. The peak eosinophil count in children with abnormal visual findings was significantly higher than in those with normal findings (67 ± 37 vs. 40 ± 27, p < 0.05). Furrowing (78.0%), edema (59.8%) and exudates (51.2%) were the most common findings. Rings were present in 13.4% and one patient presented with a stricture. Patients with only furrowing (14.6%) had a mean peak eosinophil count of 67. In patients with two abnormal findings, furrowing and edema was the most common combination (15.9%). These patients had a peak eosinophil count of 56. In patients with three abnormal findings; furrowing, edema, and exudates was most common (28.0%). These patients had a peak eosinophil count of 77. A preliminary estimate of the relationship between eosinophil

O204.06: TREATMENT OUTCOMES FOR EOSINOPHILIC ESOPHAGITIS IN CHILDREN WITH ESOPHAGEAL ATRESIA Usha Krishnan1, Lijuan Chan2, Felipe Briglia1, Cathy Clarkson1 1 Sydney Children’s Hospital, Sydney/NSW/AUSTRALIA, 2University of New South Wales, Sydney/AUSTRALIA Background: Eosinophilic esophagitis (EoE) has been reported to be more prevalent in esophageal atresia (EA) patients compared to the general pediatric population. To date, little has been reported regarding the treatment outcome in this group of patients. The aim of this study is to evaluate the responses to EoE treatment in children with EA. Methods: A retrospective chart review was performed on children with EA and EoE who were diagnosed and treated between January 2000 and September 2013 at the Sydney Children’s Hospital. Data collected included details of the patient’s treatment, post-treatment endoscopy, symptoms and nutrition. Results: 23 patients were identified, 4 were excluded due to loss to follow-up. Median age at diagnosis was 26 month (8–103 months) and mean time from diagnosis to last follow-up was 33 months (2–111 months). 8 patients were treated with budesonide slurry, 5 with swallowed fluticasone, 1 with elimination diet and 5 with either budesonide or fluticasone in combination with elimination diet. All patients were on proton-pump inhibitor (PPI) at time of diagnosis which was continued. Mean peak intraepithelial eosinophil count reduced significantly from 35/HPF (15-80/HPF) to 13/HPF (0-60/ HPF) (median time for improvement = 22 months) (p = 0.001). Of the 4 patients who had furrowing at diagnosis, there was complete resolution in 2 (median time = 22 months).Table below shows improvement in histology, symptoms and nutrition with treatment of EoE.

Eos/HPF Furrowing Stricture Dilatation (mean number/ patient annually) Dysphagia Food bolus impaction Dying spells Reflux symptoms Gastrostomy Weight z-score (mean)

Pretreatment (No. of patients)

Posttreatment (No. of patients)

35 4 12 1.9

13 2 2 1.1

13 1 2 11 6 −1.27

1 0 0 2 2 −1.14

Median time to Improvement (months) 22 22

12.0

p-value 3). On final histopathology, sixteen patients had pCR (Grade-0; No residual tumor), five had Grade1 response with minimal residual disease, fourteen with moderate response (Grade-2) while six had poor response (Grade-3). The correlation between metabolic and histopathologic response is as follows (Table 1) Tumor Regression Grade

Complete Metabolic Response

Significant Metabolic Response

Partial Metabolic Response

Progressive Metabolic Disease

Total

0 1 2 3 Total

0 0 0 0 0

15 5 8 1 29

1 0 6 5 12

0 0 0 0 0

16 5 14 6 41

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Discussion: Metabolic response precedes changes in tumor size and hence FDG18 PET-CT fares better in response assessment compared to conventional CECT. In our study we found that metabolic response by FDG18 PET-CT correlated well with pathological response as shown in the table above. Although the study is retrospective and confers to a small sample size, FDG18 PET-CT still remains the gold standard for response assessment after neoadjuvant chemoradiation or chemotherapy. Disclosure: All authors have declared no conflicts of interest. Keywords: PET CT, response assessment, preoperative chemoradiation

Wednesday, September 24 – 10:20–11:50 O208: Hiatus Hernia Room: Salon 3 O208.01: LAPAROSOPIC REPAIR OF VERY LARGE HIATUS HERNIA WITH SUTURES VS. ABSORBABLE VS. NONABSORBABLE MESH – A RANDOMIZED CONTROLLED TRIAL David Watson1, Sarah Thompson2, Peter Devitt2, Lorelle Smith2, Simon Woods3, Ahmad Aly4, Susan Gan1, Philip Game2, Glyn Jamieson2 1 Flinders University, Bedford Park/SA/AUSTRALIA, 2Adelaide University, Adelaide/AUSTRALIA, 3Cabrini Hospital, Malvern/VIC/AUSTRALIA, 4 University of Melbourne, Heidelberg/AUSTRALIA


Results: PEH subtypes were similarly distributed between the study groups with type II 0.8% vs 0%, type III in 89.6% vs 90% and type IV in 9.6% vs. 9.7% with and without dysphagia, respectively. Baseline characteristics were comparable between groups, except for a higher mean BMI in patients without dysphagia (30.4 ± 5.2 kg/m2 vs 28.4 ± 4.5 g/m2, p = 0.033). Manometric assessment showed no significant differences between dysphagia and non-dysphagia groups for mean esophageal length (16.1 ± 2.5 cm vs. 16.5 ± 2.4 cm), mean lower esophageal sphincter integrated residual pressure (LESIRP) (10.1 ± 7.6 vs 8.3 ± 7.3) and mean DCI (1419.2 ± 1153.3 vs 1567.3 ± 1139.0). The pressure inversion point (PIP) could not be located in the majority of the patients (74% dysphagia vs 71% non-dysphagia, p = 0.71). In these patients, the mean percentage of LESR was calculated and used as a surrogate for the LES-IRP. Mean %LESR was significantly lower in the dysphagia group (37.8% vs. 43.8%, p = 0.024). Patients in whom the PIP was located, no significant difference in mean %LESR was seen (33.3% dysphagia vs 41.8 % non-dysphagia, p = 0.12). Of note, there was an inverse correlation between mean LES-IRP and mean %LESR in the PIP located group but not in the PIP not located group. Similar motility abnormalities based on the Chicago Classification were seen in the dysphagia and non dysphagia groups but the numbers were too small in each group to make a comparison except in the normals (normal: 55% vs 66%; distal esophageal spasm: 13% vs 7%; EGJ outflow obstruction: 10% vs 3%, failed peristalsis: 5% vs 3%; weak peristalsis: 20% vs 16%). There was a non-significant trend of motility disorders being more commonly seen in the dysphagia group (45% vs 34%, p = 0.21).

Background: Sutured repair of very large hiatus hernia is associated with high recurrence rates, and to improve outcomes mesh repair has been recommended. This trial was conducted to determine whether use of absorbable or non-absorbable mesh reduces the risk of recurrence compared to repair with sutures.

Discussion: Performing HREM in patients with giant PEH is technically challenging, especially the positioning of the catheter and location of the PIP. This study suggests that a lower BMI and the mean %LESR may be predictive of dysphagia in this patient population. However, the main contributor to dysphagia may be the hernia itself.

Methods: Multicentre prospective double blind randomized trial. 3 repair methods were compared; sutures vs. absorbable mesh vs. non-absorbable mesh. The primary outcome was hernia recurrence at 6 months assessed by barium meal and endoscopy. Secondary outcomes were clinical symptom scores at 1, 3, 6 and 12 months.


Results: 126 patients were enrolled – 43 repair with sutures, 41 absorbable mesh and 42 non-absorbable mesh. 96.0% were followed to 12 months, and objective follow-up was available for 92.9%. A recurrent hernia (any size) was identified in 23.1% in the suture repair group, 30.8% for absorbable mesh, and 12.8% for non-absorbable mesh (p = 0.161). Clinical outcomes were similar at all follow-up points, except less heartburn at 3 & 6 months and less bloating at 12 months in the non-absorbable mesh group, and higher scores for heartburn at 3 months, and more frequent odynophagia at 1 month, nausea at 3 & 12 months, wheezing at 6 months, and inability to belch at 12 months in the absorbable mesh group. The magnitude of the clinical differences were unlikely to be clinically significant. Discussion: No significant differences were seen for recurrent hiatus hernia at radiology or endoscopy, and the clinical outcome differences between the 3 techniques were unlikely to be clinically significant. The results of this trial do not support the routine use of mesh for repair of large hiatus hernias. Disclosure: All authors have declared no conflicts of interest. Keywords: laparoscopic fundoplication, randomized trial, hiatus hernia repair, mesh repair O208.02: PREDICTORS OF DYSPHAGIA IN PATIENTS WITH GIANT PARAESOPHAGEAL HERNIAS Carol Murakami1, Sabine Roman2, Henner Schmidt3, Danielle La Selva4, Donald Low3 1 Virgnia Mason Medical Center, Seattle/WA/UNITED STATES OF AMERICA, 2Hospices Civils de Lyon, Lyon/FRANCE, 3Virgina Mason Medical Center, Seattle/WA/UNITED STATES OF AMERICA, 4Virginia Mason Medical Center, Seattle/WA/UNITED STATES OF AMERICA Background: Dysphagia is a common symptom in patients presenting with giant paraesophageal hernias (PEH). However, currently it is unclear whether this is related to the configuration of the PEH or an underlying motility disorder of the esophagus. The focus of this retrospective analysis of pre-operative high resolution esophageal manometry studies is to objectively assess this issue. Methods: From 2008–2013, 121 consecutive patients undergoing PEH repair were included in an IRB approved database. In all paients, pre-operative high resolution esophageal manometry (HREM) was performed and retrospectively analyzed using Manoview 3.0. The following were measured on each swallow for all patients: esophageal length, inegrated residual pressure (IRP), distal contractil integral (DCI), segmental defects in peristalsis, distal latency, and percentage of lower esophageal sphincter relaxation (LESR). The Chicago Classification for HREM was then applied. Fifty-nine patients with dysphagia (49%) were compared to 62 patients without dysphagia (51%).

Keywords: analysis of HREM and patient characteristics, dysphagia in giant paraesophageal hernias O208.03: COULD THE INCREASE IN NUMBER OF REPAIRS OF GIANT HIATUS HERNIA BE EXPLAINED BY CENTRALISATION OF CANCER AND EMERGENCY SERVICES? Zaher Toumi, Yan Li Goh, Paul Turner, Kishore Pursnani, Jeremy Ward, Ravindra Date Royal Preston Hospital, Preston/UNITED KINGDOM Background: There is an increased number of operations performed for giant hiatus herniae. The reasons for this increase are not clear. We speculated that the centralisation of upper GI cancer services to our trust led to increase in emergency and elective referral of patients with giant hiatus hernia from the peripheral hospital. This study tests our hypothesis. Methods: We performed a retrospective review of patients who underwent repair of giant hiatus hernia over a 13-year period from 2000–November 2013. We collected data related to the distance between their place of residence and our hospitals and the urgency of the operation (elective, emergency and semi-elective after emergency admission). We have two hospital sites. Cancer and Emergency surgical services are based on one site and elective benign services (where most repairs were performed) are based on the other site. Results: Seventy patients underwent repair of giant hiatus hernia between 2000 until November 2013, of whom, 63 patients (90%) underwent their operations since April 2009 when oesophagogastric cancer services were centralised to our trust. The median distance between the patient’s residence and the elective hospital where most operations were performed was 9.9 miles (range 4.6–27.3) before April 2009 and 11.8 miles (range 1.2–260 miles). The difference was not significant (p = 0.7). The distance between the patient’s residence and the hospital in which emergency and cancer services are based was 10.4 miles (median, range 2.60–12.50) prior to April 2009 and 12.1 miles (median, range 0.5–249 miles). The difference again was not significant (p = 0.3). All operation which were done before April 2009 were elective (n = 7), while 56 out of 63 operations performed after April 2009 (89%) were elective. The difference again was not significant (p = 0.4). Discussion: There is an increase in the number of operations performed for giant hiatus herniae in the recent years. This increase could neither be explained by centralisation of cancer services nor by increase in emergency and urgent operations. Other reasons (including increase incidence and increase use of imaging) should be explored. Disclosure: All authors have declared no conflicts of interest. Keywords: giant hiatus hernia, centralisation


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O208.04: MAGNETIC SPHINCTER AUGMENTATION BROADENS THE APPEAL OF SURGICAL INTERVENTION IN CHRONIC REFLUX SUFFERERS James Brewer, Paul Mackenzie, Roberto Pezzuto, Teresa Royles, Antonio Manzelli, Shahjehan Wajed Royal Devon and Exeter Hospital, Exeter/UNITED KINGDOM Background: Magnetic bead esophageal sphincter augmentation device (MSAD) offers an alternative to tissue fundoplication (TF) in the management of gastro esophageal reflux disease (GERD). This study evaluates patients’ clinical characteristics and decision pathways involved in the selecting one of these available surgical options. Methods: Consecutive patients with chronic GERD who underwent surgical intervention for definitive treatment were enrolled in the study. The selection criteria for MSAD procedure included objective evidence of GERD, good esophageal motility, absence of a large hiatus hernia and long segment Barrett’s esophagus. Pre-operative symptoms, esophageal physiology, reflux related quality of life scores (HRQL) and the reason for selection of a surgical technique were obtained from a prospectively collected database. A statistical comparative analysis of these variables between the MSAD and the TF group was performed. Results: A total of 42 patients were included in the study. Thirty patients were suitable for MSAD, of which 28 (93%) elected to undergo the procedure. Two patients (7%) declined MSAD and opted for TF, along with 12 patients who failed to meet the inclusion criteria for MSAD. Distal esophageal acid exposure was significantly higher in the TF group (DeMeester score median 52.6 [22–74]) than in the MSAD group (DeMeester score median 34.4 [16–55] (p = 0.011). The HRQL score however were similar for both groups (TF 23.9; MSAD 25.8; p = 0.55) Patients requesting MSAD felt that the main reason was because the procedure was less invasive,(20/28, 71%) and secondarily because they perceived it to be associated with less side effects (3/28, 11%). In the TF group 9 patients (64%) felt that the surgeon had influenced their choice of surgical technique, 3 patients however (23%) elected for TF because it was an established procedure with extensive clinical experience. Discussion: MSAD offers an innovative and reliable alternative to patients with GERD instead TF or chronic drug dependency. The perception that it represents a less invasive, less problematic but definitive procedure, is an attractive option for patients who may not otherwise have considered more radical surgery. There was no clear correlation with the extent of distal esophageal acid exposure and the impact of this on patient health related quality of life, suggesting that debilitating symptoms can still occur with relatively modest degrees of reflux. The option of MSAD as a sphincter augmentation rather than a gastric reconstruction procedure may broaden the spectrum of patients willing to undergo surgical rather than medical therapy. Disclosure: All authors have declared no conflicts of interest. Keywords: Magnetic Bead Augmentation, Gastro Esophageal Reflux, health related quality of life, Tissue Fundoplication O208.05: GEOMETRIC ANALYSIS OF PARA-ESOPHAGEAL HERNIATION AND ITS ASSOCIATION WITH CLINICAL SEQUELAE James Brewer1, Roberto Pezzuto2, Simon Harries2, Roy Powell2, Lorna Harries1, Shahjehan Wajed1 1 University of Exeter, Exeter/UNITED KINGDOM, 2Royal Devon and Exeter Hospital, Exeter/UNITED KINGDOM Background: The clinical consequences of para-esophageal herniation (PEH) are unique. While most other herniae mainly affect the herniated structures, large PEH can compromise vital mediastinal organs causing severe symptoms and complications. We aim to characterise the dimensions of the crural defect and large PEH and its impact on the development of symptoms. Methods: Intra-operative measurements of the crural defect (see figure 1) and the depth of mediastinal intrusion (axial depth) were collected during consecutive complex laparoscopic PEH repairs at the Royal Devon and Exeter Hospital between January 2013 and February 2014. Clinico-pathological characteristics obtained from a prospectively collected database were correlated with the geometric findings. The Area of the Crural Defect (ACD) was calculated following the diagram and formula described in Figure 1. Two independent observers measured radiological axial, coronal and sagittal lengths (RAL, RCL and RSL) on pre-operative contrast swallows; the average was used to estimate the PEH Radiological Volume (RV) (see Figure 1). The measurements were normalised calculating their ratios, allowing the estimation of the average PEH sac shape.

Results: A total of 24 patients with large PEH were included in the study. The calculated ACD ranged from 3.3–20.63 cm2 (median 8.13 cm2). The axial depth ranged from 5–13 cm (median 8.33 cm). The RV obtained from 19/24 patients ranged from 11.1–441.7 cm3 (median 157.9 cm3). The mean value of normalised radiological length ratios were RAL : RSL = 1.14 (SD 0.29) RCL : RAL = 1.05 (SD 0.03) and RSL : RCL 0.88 (SD 0.2) The most common presenting symptoms included dysphagia 8/24 (33.3%), volume regurgitation 6/24 (24%) and heart burn 4/24 (16.6%). Seventy five per cent of patients presenting with dysphagia had an ACD > 7.5 cm2 (p = 0.010), conversely 75% of patients presenting with volume regurgitation had an ACD < 7.5 cm2 (p = 0.023) Patients presenting with volume regurgitation had significantly smaller RV (median 91.4 cm3) than patients without (median 176.2 cm3) (p = 0.015). Discussion: The area of the crural defect and the mediastinal projection of PEH have an important bearing in the development of symptomatology. The average shape of the PEH sac is a near-spherical ellipsoid. Patients with large crural defects appear to present with obstructive symptoms whereas small crural defects are associated with volume reflux. We hypothesise that the smaller defect may restrict intra-mediastinal stomach emptying, resulting in increased intra luminal pressure and reflux. Smaller hernia volumes are more associated with regurgitation than with dysphagia. Disclosure: All authors have declared no conflicts of interest. Keywords: Para-esophageal Hernia, Diaphragmatic Crura, Volume reflux, Ellipsoid

O208.06: GIANT HIATUS HERNIAE: THE TYPE OF REPAIR DOES NOT AFFECT RECURRENCE RATE Yan Li Goh, Zaher Toumi, Jeremy Ward, Paul Turner, Kishore Pursnani, Ravindra Date Royal Preston Hospital, Preston/UNITED KINGDOM Background: The management of giant hiatus hernia is surgically challenging with risk of recurrence of symptoms and reoperation after primary repairs. This study aims to find out whether the type of repair affect recurrence and reoperation rate. Methods: We performed a retrospective review of patients who underwent repair of giant hiatus hernia over a 13-year period from 2000–2013. We collected data related to the presenting symptoms, operative technique, and post – operative recurrence and redo-operations. Results: Seventy patients underwent repair of giant hiatus hernia between 2000 until November 2013. Following oral contrast study performed post – operatively, two patients had redo surgery during the same admission due to primary failure of hiatal repair. During follow up, 12 patients had recurrence of symptoms when they presented with similar pre – and post – operative reflux symptoms. Of these, five patients underwent re-do surgery. Redo surgery was warranted in another patient with symptom recurrence but was not performed as the patient was unfit for surgery due to her obesity. Eventually, her symptoms settled with medical therapy. In the remaining 6 patients with symptom recurrence that did not have surgery, their symptoms improved with medical therapy, left alone as investigations including OGD was normal or they were referred to other specialties for further management of dysphagia. Three patients had different reflux symptoms post operatively and they had redo operations. While the majority of patients had crural repair with no mesh, had Nissen fundoplications and had no gastropexy, there was no significant difference in regards to recurrence of hiatus herniae or reoperation rate between those who underwent Nissen Fundoplications and those who had anterior wrap (recurrence rate was 20% vs. 0%, P = 0.3, reoperation rate was 15% vs. 20%, p = 0.8), those who had gastropexy and those who haven’t (recurrence rate was 11% vs. 20%, p = 0.4 and reoperation rate was 26% vs. 10%, p = 0.08) and those who had crural repair with mesh

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and crural repair without mesh (recurrence rate was 0% vs. 19%, p = 0.2) and reoperation rate was 0% vs. 16%, p = 0.3).

haemorrhage. Following oral contrast study performed post – operatively, two patients had redo surgery during the same admission.

Discussion: Adding gastropexy, crural repair with mesh or replacing full wrap with anterior wrap when repairing giant hiatus herniae did not seem to result in a significant difference in regards to recurrence of symptoms or reoperation rate.

Discussion: The risk of serious complications after giant hiatus hernia repair is low. Surgical management of giant hiatus hernia is still recommended.

Disclosure: All authors have declared no conflicts of interest. Keywords: giant hiatus hernia, type of repair, recurrence O208.07: SPECTRUM AND CLINICAL PATTERNS ASSOCIATED WITH PRESENTATION OF SYMPTOMATIC PARAOESOPHAGEAL HERNIATION James Brewer1, Paul Mackenzie1, Lorna Harries2, Shahjehan Wajed1 1 Royal Devon and Exeter Hospital, Exeter/UNITED KINGDOM, 2 University of Exeter, Exeter/UNITED KINGDOM Background: The aetiology and pathogenesis of complex (giant) paraoesophageal herniae is a topic of debate. Often described as the ‘great mimic’, it presents with atypical features and its disease associations not clear. Theories to explain its pathogenesis include degeneration of supporting tissues, increased intra-abdominal pressure and oesophageal shortening. This study evaluated clinical and symptomatic associations of para-oesophageal herniation in a consecutive cohort of patients with this condition. Methods: A retrospective analysis of patients who underwent laparoscopic repair of large and complex para-oesophageal hernia was performed utilizing the prospectively maintained oesophago-gastric database at the Royal Devon and Exeter Hospital between October 2004 and December 2013. Clinical, symptomatic, pathological and surgical parameters were investigated and analyzed for association. Results: A total of 121 patients with giant PEH were included in our database, 87 females (71.9%), age range 26–91. There was a significant difference in the age of presentation between females and males (female: median 76, range 52–91, male: median 67, range 26–82) p = 0.001. Prevalence of degenerative conditions in our cohort included; diverticular disease (N = 31, 26.5%), abdominal wall hernias (N = 17, 14.5%), osteoarthritis (N = 29, 24.8%), rectocoeles (N = 4, 3.4%), cystocoeles (N = 12, 10.3%), which was consistent with population prevalence when adjusted for age and geographical location of our cohort. Discussion: Symptomatic para-oesophageal is a condition that prominently affects an older age group, but appears to occur approximately a decade later in female patients. The reason for earlier onset of this condition in males is unknown. There does not appear to be a strong association with other common age related conditions and PEH, suggesting that the aetiology of the pathogenesis of PEH is more complex than degeneration alone. Disclosure: All authors have declared no conflicts of interest. Keywords: Paraoesophageal Hernia, PEH, Hiatus Hernia O208.08: MORBIDITY AND MORTALITY AFTER REPAIR OF GIANT HIATUS HERNIA Yan Li Goh, Zaher Toumi, Kishore Pursnani, Paul Turner, Jeremy Ward, Ravindra Date Royal Preston Hospital, Preston/UNITED KINGDOM Background: The management of giant hiatus hernia is surgically challenging. This study aims to review the mortality and morbidity after surgical repair of giant hiatus herniae in our tertiary centre. Methods: We performed a retrospective review of patients who underwent repair of giant hiatus hernia over a 13-year period from October 2000– October 2013. We collected data related to post – operative complications and mortality. Results: Seventy patients underwent repair of giant hiatus hernia between 2000 until November 2013. Of whom, fourteen patients reported general post – operative complications and five patients reported surgery related complications and both types of complications were reported in one patient. General complications include acute urinary retention (1 case), poor analgesic control (1 case), chest infection and poor analgesic control (1 case), nausea (1 case), diarrhoea (1 case), chest infection (4 cases), post – operative anaemia of Hb77 (pre-operative Hb 144) requiring transfusion (1 case), post – operative pyrexia that responded to antibiotics (2 case), opiate toxicity (1 case) and hypotension (1 case). Five separate cases of surgery related complications include wound infection, bloating, dysphagia, left sided hydropneumothorax requiring surgical chest drain and gastrointestinal bleeding (this was managed endoscopically). Another patient had chest infection and persistent hiatus hernia (on post-operative barium swallow and CT). 2 patients died post-operatively, 1 had previous sigmoidopexy and colopexy died from faecal peritonitis due to perforation of the transverse colon that was consequently operated on; while the other patient (who was diagnosed post – operatively with metastatic myeloma) died from subdural

Disclosure: All authors have declared no conflicts of interest. Keywords: giant hiatus hernia, mortality, morbidity O208.09: TWO-YEAR CLINICAL, RADIOLOGICAL AND QUALITY OF LIFE RESULTS AFTER COLLIS-NISSEN OPERATION FOR SHORT ESOPHAGUS IN PATIENTS WITH PARAESOPHAGEAL HERNIA: A PROSPECTIVE STUDY Manuel Pera, Xenia Crous, Sonia Puig, Juan Sanchez-Parrilla, Jose Ramon, Luis Grande Hospital Universitario del Mar, Barcelona/SPAIN Background: The use of a Collis wedge gastroplasty has been advocated to reduce the rate of recurrences after open or laparoscopic repair of paraesophageal hernias. The aim of this study was to determine clinical and quality of life outcomes after this technique and the postoperative radiographic data. Methods: Since 2009, all patients with paraesophageal hernias and short esophagus (≤2.5 cm intra-abdominal segment measured after full esophageal mobilization) underwent a Collis-Nissen operation (wedge fundectomy technique). A non permanent mesh was selectively used to reinforce the crural closure. Symptoms and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaires and barium swallow were evaluated before and 12 and 24 months after the operation. Dysphagia was scored by a validated dysphagia score (0, no dysphagia, 45 severe dysphagia) Radiological findings were classified as non anatomical recurrence, migration of the fundoplication and dilation and/or diverticula formation in the proximal portion of the gastroplasty. Results: Thirty-eight patients [27 female, median age 71 years] were assessed. A laparoscopic approach was performed in 35 patients and a mesh was added in 12 cases. Primary type III-IV hernias (12 with volvulus) were present in 34 patients (89%), being recurrences after previous repair in the remaining cases. Indications were oppressive chest pain (16), reflux symptoms (12), anemia (6) and acute volvulus (4). Morbidity occurred in 8% with no mortality. Prevalence of preoperative heartburn, regurgitation, dysphagia and chest pain were 47%, 76%, 45%, and 66%, respectively. At 2 years follow-up, heartburn, regurgitation and chest pain were reduced to 16%, 14% and 30%, respectively. However, the percentage of patients with dysphagia remained stable (mean score of 10). Barium studies were performed in 95% and 87% of patients at 12 and 24 months. A normal post-fundoplication anatomy was confirmed in 21/33 (64%) of the cases. Migration of the fundoplication (750 IU/L for elevated amylase achieved the highest accuracy for the diagnosis of anastomotic leakage. Leakage was defined as any intrathoracic leakage of the reconstructed gastro-intestinal tract as found during re-operation, at endoscopy or on a CT-scan. Results: A total of 57 patients were included between March 2013 and March 2014. The median age was 66 years (range: 43–80) and 81% was male. Anastomotic leakage occurred in 7 patients (12.3%), all confirmed by endoscopy. Three patients had a leakage at the stapler line of the gastric conduit (5.3%), all confirmed by endoscopy. Of all patients with elevated amylase levels (N = 6), 5 patients had an intrathoracic leakage (positive predictive value 83.3%, 95% CI 36.1–97.2%). Of all patients with normal amylase levels (N = 51), 46 patients showed no intrathoracic leakage (negative predictive value 90.2%, 95% CI 78.6–96.7%). The overall test-accuracy was 89.5%. Discussion: Daily measurements of amylase levels in drain fluid of a drain close to the anastomosis is a simple, inexpensive and easy to use tool that may be used to screen for anastomotic leakage early after esophagectomy. Further prospective studies including sufficient patients are needed for validation and determination of the ideal cut-off value to increase the overall test accuracy. Disclosure: All authors have declared no conflicts of interest. Keywords: Intrathoracic leakage, Amylase, Drain fluid, esophagectomy

Wednesday, September 24 – 8:00–9:50 O307: Esophageal Cancer: Surgical Treatment VII Room: Cypress O307.01: SURGICAL TREATMENT OF ADENOCARCINOMAS OF THE ESOPHAGOGASTRIC JUNCTION Kevin Parry, Leonie Haverkamp, Jelle Ruurda, Richard Van Hillegersberg University Medical Center Utrecht, Utrecht/NETHERLANDS Background: Patients with adenocarcinoma of the esophagogastric junction (EGJ) may undergo either an esophagus-cardia resection or total extended gastrectomy depending on the site of the tumor. The aim of this study was to evaluate the outcome of surgical therapy with regard to postoperative outcome and survival. Methods: A prospective database of 266 consecutive patients with surgically resectable esophageal and gastric adenocarcinomas from 2003–2013 was analyzed. The choice of surgical approach was based on pre-operative imaging as well as intra-operative tumor localization. Either an esophaguscardia resection or an extended total gastrectomy was performed. Results: According to the histopathological analysis, 67 patients (25%) had a Siewert type I tumor, 176 patients (66%) a type II tumor, and 16 patients (6%) a type III tumor. In total 86% were treated with esophagectomy and 14% with gastrectomy. Overall 5-year survival (38%) did not differ significantly on multivariate analysis between esophagectomy and gastrectomy (p = 0.702). There were no significant differences in radicality of resection, mortality or disease recurrence between both procedures. The overall morbidity was significantly higher in the esophagectomy group (p = 0.028), due to a higher incidence of pneumonia (47% versus 25%; p = 0.015). In patients with type II tumors, upper mediastinal nodal involvement (subcarinal,


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paratracheal and aortapulmonary window) was present in 11% of the patients. The majority of the lymph node metastases were found at the lesser curvature (56%) and paracardial (24%) for type II tumors. For the paraesophageal lymph nodes, in patients treated with transhiatal or transthoracic esophagectomy, 34% contained metastases, whereas in patients treated with gastrectomy, only 5% contained metastases. Discussion: This study did not show any significant differences in overall 5-year survival, radicality of resection or mortality rate between esophagectomy and gastrectomy in patients with a Siewert type II tumor. Although esophagectomy is associated with higher morbidity than gastrectomy, the high prevalence of mediastinal nodal involvement in type II tumors indicates that a full lymphadenectomy of these stations should be considered to perform a radical en bloc tumor resection. Furthermore, esophagectomy provides for a more complete lower mediastinal lymphadenectomy compared to gastrectomy. We therefore suggest that an esophageal-cardia resection is the surgical therapy of choice in patients with a type II tumor. Disclosure: All authors have declared no conflicts of interest. Keywords: cardia, Siewert type II tumors, surgical treatment, esophagogastric junction O307.02: PROGRESSING TOWARDS CURE OF ESOPHAGEAL ADENOCARCINOMA: AN ANALYSIS OF MODERN SURVIVAL TRENDS AFTER ESOPHAGEAL RESECTION Michal Lada, Andreas Tschoner, Michelle Han, Christian Peyre, Carolyn Jones, Thomas Watson, Jeffrey Peters University of Rochester Medical Center, Rochester/NY/UNITED STATES OF AMERICA Background: Cure of esophageal carcinoma has been viewed as rare, with reported overall 5-year survival rates of approximately 17%. With improvements in staging modalities, more liberal use of (neo) adjuvant therapy, and advancements in surgical and endoscopic resection techniques, the outcomes of patients with this lethal disease have improved but have not been well described in the literature. The aim of this study was to analyze modern survival trends after resection for esophageal adenocarcinoma (EAC) at a high-volume center. Methods: The study population consisted of 357 consecutive patients undergoing esophagectomy for EAC at a university-based medical center between 2000 and 2012. Patients who underwent esophagectomy for high-grade dysplasia (n = 29) or those found to have metastatic disease at exploration (n = 5) were excluded. Clinical variables for three groups based on date of esophagectomy were compared (Group 1: 2000–2003, Group 2: 2004–2008, Group 3: 2009–2012). Survival was compared via the Kaplan-Meier (KM) method. Results: The median age of the 357 patients was 64.4 years (range:31.0–86.2) and 87% were male. The majority underwent transhiatal esophagectomy (n = 217, 61%). En bloc esophagectomy (n = 67, 19%) was utilized increasingly over time (0% group 1, 24% group 2 and 26% group 3, p = 0.001). Neoadjuvant therapy (n = 123, 34%) was also utilized increasingly over time (0% Group 1, 17% Group 2 and 72% Group 3, p < 0.001) as was PET/CT (n = 199, 56%; 0% Group 1, 52% Group 2 and 95% patients Group 3, p < 0.001). Compared to Group 1, a smaller proportion of patients in Group 3 were AJCC pathologic Stage I and an increasing proportion were Stage III (Stage I: 20% vs. 31%; Stage III: 49% vs. 43%, respectively, p = 0.145). The median survival for the entire cohort was 29.3 months (range:0.3–150.0) with 5-year KM survival of 31% for Group 1, 37% for Group 2 and 49% for Group 3 (p = 0.007, Figure). Inclusion of 24 patients who underwent endoscopic resection for intramucosal carcinoma between 2009–2012 resulted in improvement of the 5-year KM survival to 57% from 49%, p = 0.378, for those with resectable disease. Discussion: This analysis reveals an improvement in 5-year survival after esophagectomy from 31% to 49% over the past decade. Better staging and neoadjuvant therapy, as well as advancements in surgical technique, likely have played a vital role in this trend. Five-year survival rates for the most recent cohort, 2009–2012, approach 60% when patients with EAC treated endoscopically are included. Patients undergoing resection for EAC can expect a good cure rate, much better than what historically has been reported.

Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal adenocarcinoma, Survival

O307.03: MEASURING MICROCIRCULATION AT THE SITE OF ANASTOMOSIS BEFORE GASTROESOPHAGEAL RESECTION Michael Achiam Rigshospitalet, Copenhagen University Hospital, Copenhagen East/DENMARK Background: Gastroesophageal resection because of gastroesophageal junction (GEJ) malignancy is a massive surgical intervention, but is the only treatment of choice with significant long-term survival. The surgery is associated with numerous potentially dangerous post-operative complications. Anastomotic leakage has been reported in up to 30 %. The Ivor Lewis procedure used at our center is associated with up to 12 % anastomotic leakage, with mortality up to 20 %. A recent work at our department by Kofoed et al. [19] demonstrated that patients experiencing anastomotic leakage after gastroesophageal cancer resection have a significantly reduced long-term survival, even when early death and other postoperative complications were accounted for. The overall 5-year survival rates in patients with and without anastomotic leakage were 20 and 35 %, respectively. The causes for the diminished long-term survival are still to be elucidated. Reduced microcirculatory blood flow in the region of anastomosis is known to be a significant cause of anastomotic leakage. Therefore, intra-operative monitoring of the gastric microcirculation may reduce the risk of anastomotic deshiscence. By a new technique, “laser speckle contrast imaging” (LSCI), a real-time and non-touch measurement of microcirculation can be made. The aim of this presentation is to present data from an ongoing study and to show the feasibility of a method for assessing the changes in the microcirculatory blood flow as a consequence of the surgical procedure of mobilizing and creating the gastric conduit used for the gastro-esophageal anastomosis. Methods: Hemodynamic assessments were according to standardized methods. LSCI was used to measure the microcirculation just below the site of the anastomosis (the body) on the stomach: 1) when the peritoneum is first entered, 2) after 15 min. of surgery, 3) after the mobilization of stomach. The camera is placed at a distance of 25 cm and measures the relative flow (flux) at a depth of 1–2 mm by infrared light reflected from circulating erythrocytes in the micro-vessels. Results: 20 consecutive patients selected for open surgery due to GEJ adenocarcinoma were analyzed. The flux of the body were statistically different at the three measurements (P = 0.05, Friedmans test), but especially between measurement 2 and measurement 3 (P < 0.029, Friedmans, test). Discussion: Our data shows the feasibility of assessing the microcirculation with a LSCI. A significant difference between the first two measurements and the third measurement was found. The substantial decrease in microcirculation was despite a stable mean arterial blood pressure and is partly due to the ligation of the arteries in the upper part of the stomach. However, the decrease is also speculated to be multi-factorial, caused by e.g. the mesenteric traction reflex, changes in vasoactive substances, like ANP and prostacyclin, and the activation of the epidural catheter, causing a sympathic nerve system blockage due to thoracic epidural neuroaxial anesthesia. An optimization of the intraoperative handling with sustained blood flow in the splanchnic system is hypothesized to be a significant factor in the healing process of the anastomosis and presumably reduces the risk of anastomotic insufficiency. Thus, LSCI may be an important new tool for gastroesophageal cancer surgery Disclosure: All authors have declared no conflicts of interest. Keywords: Gastroesophageal anastomosis, Microcirculation, Anastomosis leakage, Gastroesophageal cancer

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O307.04: SPATIAL LOCATION OF THE POSITIVE CIRCUMFERENTIAL RESECTION MARGIN PREDICTS SURVIVAL IN PATIENTS UNDERGOING SURGERY FOR OESOPHAGEAL CANCER John Watson, Paul Jose, Samir Mehta, Heike Grabsch, Jeremy Hayden Leeds Teaching Hospitals NHS Trust, Leeds/UNITED KINGDOM Background: The presence of cancer cells at or close to the oesophageal circumferential resection margin (CRM-positive) is associated with poorer prognosis in patients with oesophageal and junctional carcinoma, although there is debate as to whether it acts as a truly independent predictor of survival. In this study we have sought to analyse the importance of CRM involvement in more detail by examining its spatial location in relation to the oesophagus. Methods: We examined the specimens of patients who underwent 2 stage oesophagectomy at our institution between 2009 and 2012. From 2009 resection specimens were prospectively orientated during surgery with marking sutures in order to identify anterior and right lateral (pleura) positions for the histopathologist. Specimens that were CRM-positive were categorised based on the presence of cancer cells close (within 1 mm) to the inked anterior, right, left or posterior resection margins of the resection specimen. We then performed a Cox regression analysis to determine the relationship of spatial location to survival. Results: 146 patients underwent oesophagectomy with resection specimen orientation during the time period. The median age was 63 yrs. 131 patients underwent neoadjuvant treatment prior to resection. 72 patients (49%) were CRM-positive. Overall, CRM was a predictor of survival in univariate analysis (p = 0.002). However, when the 4 spatial subgroups were analysed separately only when tumour cells were close to the anterior margin was this strongly predictive of poorer survival (p = 0.006). Discussion: Our results suggest that spatial location of CRM is important, with a positive anterior margin highly predictive of poorer survival. We hypothesise that tumour cells in this location could have a higher propensity to disseminate into the lymphovasculature. Disclosure: All authors have declared no conflicts of interest.


Table 1. Operative outcome N = 178

MIE (83)

Pathological Stage 31 (37.34%) 28 Stage 0/1 Stage 2 (33.73%) 23 (27.7%) 1 Stage 3 Stage 4 (1.2%) R0 resection 74 (89.1%) LN retrieval 23 (0–62)** LN positive 0 (0–41) OR time (min) 380 (260–570)# Blood Loss (ml) 400 (75–4500)* 32 (38.5%) Overall severe post-op complications In-hospital or 5 (6%) 30-day mortality Pulmonary 22 (26.5%) complications Anastomotic leak 14 (16.8%) Chyle leak 18 (21.6%)** New Atrial 23 (27.7%) Fibrillation Immediate mortality 5 (6%) Hospital stay (days) 15 (3–92)

TTE (48)

THE (47)

p-value

14 (29.1%) 16 (33.3%) 17 (35.4%) 1 (2%) 41 (85.4%) 23 (11–61)*** 1 (0–15) 450 (310–600) 675 (150– 4000)*** 22 (45.8%)

22 (46.8%) 9 (19.1%) 12 (25.5%) 4 (8.5%) 43 (91.4%) 12 (0–32) 0 (0–12) 320 (180–540) 500 (100–2000)

0.2 0.17 0.52 0.07 0.63 0.05); Lymph node metastasis in esophageal squamous cell carcinoma of Fas protein positive expression rate was 38.1% (8/21), without lymph node metastasis was 66.7% (22/33) (P < 0.05); Various clinical stages of esophageal squamous cell carcinoma of Fas positive expression rate: Phase IIa 61.9% (13/21), phase IIb 50.0% (5/10), phase III 52.2% (12/23) (P > 0.05). 2. In tumor specimen the positive rate of methylation of Fas gene 61.1% (33/54) is higher than 22.2% (12/54) in corresponding paracancerous tissues (P < 0.05). Different degree of differentiation of esophageal squamous cell carcinoma of Fas gene methylation ratewell-differentiated 63.2% (12/19), in the differentiation of 59.3% (16/27), poorly differentiated 62.5% (5/8) (P > 0.05); the pathologic types of esophageal squamous cell carcinoma medulla, Tanumbrella, ulcers and narrowing between the various types of Fas gene methylation rates were 59.3%(16/27), 61.5%(8/13), 66.7%(4/6) and 62.5% (5/8) (P > 0.05); Depth of invasion (T stage) in esophageal squamous cell carcinoma of Fas gene methylation rate: T2 of 59.3% (16/27), T3 60.0% (15/25), T4 100% (2/2) (P > 0.05); Lymph node metastasis in patients with esophageal squamous cell carcinoma of Fas gene methylation rate: 61.9% (13/21), without lymph node metastasis:60.6 % (20/33) (P > 0.05); The clinical staging of esophageal squamous cell carcinoma of the Fas gene methylation rates were as follows: Phase IIa 61.9% (13/21), phase IIb 60.0% (6/10), III 60.9% (14/23) (P > 0.05). Discussion: 1. The expression of Fas protein in esophageal squamous cell carcinoma is down-regulation, Fas gene is Hypermethylation. Fas expression was negatively correlated with the Fas gene hypermethylation performance. 2. Fas expression has relations with the degree of differentiation and lymph node metastasis. In well differentiated Fas expression is higher than in poorly differentiated (P < 0.05). Disclosure: All authors have declared no conflicts of interest. Keywords: Fas protein, Fas gene, Methylation, Esophageal squamous cell carcinoma O308.07: ABNORMAL CELL PROLIFERATION IN THE P75NTRPOSITIVE BASAL CELL COMPARTMENT OF THE ESOPHAGEAL EPITHELIUM DURING SQUAMOUS CARCINOGENESIS Tomoyuki Okumura1, Yutaka Shimada2, Tetsuji Yamaguch1, Katsuhisa Hirano1, Toru Watanabe1, Koki Kamiyama1, Isaya Hashimoto1, Kazuto Shibuya1, Shozo Hojo1, Ryota Hori1, Koshi Matsui1, Isaku Yoshioka1, Shigeaki Sawada1, Toru Yoshida1, Takuya Nagata1, Kazuhiro Tsukada1 1 University of Toyama, Toyama/JAPAN, 2Kyoto University, Kyoto/JAPAN Background: The low affinity neurotrophin receptor p75NTR is known to be expressed in the mitotically quiescent basal layer (BL) of the normal esophageal epithelium. The aim of the present study was to detect oncogenic changes in the p75NTR-positive BL during esophageal squamous carcinogenesis. Methods: The normal epithelium (NE), low-grade intraepithelial neoplasia (LGN), high-grade intraepithelial neoplasia (HGN), and esophageal squamous carcinoma (SCC), in which invasion was limited to the muscularis mucosa, were obtained from surgically-removed esophagi. The expression of p75NTR, the proliferation marker ki67, hTERT, and p53 was examined immunohistochemically. Results: The expression of p75NTR was detected in these tissues with average staining indexes (number of stained cells/100 nucleated cells: SI) of 1.00, 0.99, 0.81, and 0.73, respectively. The expression of ki67 in the BL significantly increased with the progression from LGN to HGN. The expression of hTERT and p53 significantly increased with the progression from NE to LGN, and then increased in a stepwise manner in HGN and SCC, with SI (hTERT/p53) of 0.10/0.11, 0.32/0.45, 0.50/0.72, and 0.65/0.61, respectively. A correlation was observed between the expression of ki67 and p53 (P = 0.005), while a negative correlation was found between p75NTR and hTERT (P = 0.01).


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Discussion: Our results demonstrated that phenotypic changes from quiescent to active proliferation in the p75NTR-positive BL occurred during the progression from LGN to HGN, which suggested that the basal cell ki67 immunoreactivity may help us to establish early detection of malignant transformation. The altered expression of hTERT and p53 in the BL was detected in LGN, which suggested that additional oncogenic events that disrupt mitotic regulation in the p75NTR-positive quiescent basal layer may play a crucial role in malignant transformation. Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal carcinogenesis, Basal layer, stem cell O308.08: IMMUNO SURVEILLANCE IN ESOPHAGEAL INFLAMMATION- DRIVEN CARCINOGENESIS Rita Alfieri1, Marco Scarpa1, Melania Scarpa1, Andromachi Kotsafti1, Bogdan Filip2, Matteo Cagol1, Tiziana Morbin3, Stefano Realdon1, Marina Bortolami3, Giorgio Battaglia1, Ignazio Castagliuolo4, Carlo Castoro1 1 Veneto Institute of Oncology, Padova/ITALY, 2University of Jasi, Jasi/ ROMANIA, 3University of Padova, Padova/ITALY, 4University of Padova, Padova/ITALY Background: Esophageal adenocarcinoma (EAC) is an increasingly common cancer with a poor prognosis. EAC microenvironment is characterized by lack of cytokines with anti-cancer effect and by high expression of immunosuppressive factors. The expression of costimulatory molecules CD80 and CD86 in the esophageal cancer tissue is significantly lower than in the mucosa of healthy patients and it is inversely correlated to the expression of TGFbeta1 and IL-10. This may be one of the mechanisms of impaired function of dendritic cells and immune escape of cancer cells in the esophageal cancer. The aim of the study is to investigate the interplay between epithelium and CD8 T cells that characterizes the immune environment of EAC. Methods: Fresh biopsies (n = 32) obtained from healthy esophagus, Barrett’s esophagus, esophageal dysplasia and adenocarcinoma were analysed by flow cytometry to quantify the expression of CD80 on esophageal epithelial cells and, its receptor CD28 and the lymphocytes activation marker CD38 on CD8 infiltrating lymphocytes. Mucosa samples from cancer and from healthy esophagus were obtained during esophagectomy from 58 patients affected by EAC and 12 patients affected by squamous cell cancer (SCC). Frozen samples were analysed with Real Time qPCR for innate immunity (Tlr4, Myd88), costimulatory molecules (Cd80, Cd86), and lymphocytes activation (Cd38, Cd69) genes expression. Immunohistochemistry for CD8 and NK cells cytolytic activity (CD107a) of tumor infiltrating lymphocytes and for CD80 was performed. Non parametrical statistics was used. Results: Flow cytometric analysis revealed a significant increase of CD80+ esophageal epithelial cells in metaplasia during inflammatory esophageal carcinogenesis. Moreover, Real Time qPCR showed a significant upregulation of Tlr4, MyD88, Cd80, Cd86, Cd38 and Cd69 gene expression in EAC tissues compared to their matched normal tissues. CD80, CD8 and CD107a proteins expression was higher in the cancer tissue of patient who underwent neoadjuvant therapy. Finally, the number of intraepithelial CD107a+ cells resulted inversely correlated with tumor differentiation and Mandard tumor regression grade. Discussion: In inflammation-driven esophageal carcinogenesis there is evidence of an early active immune surveillance process mediated by CD80 overexpression on metaplastic esophageal epithelial cells. Overall, EAC microenvironment shows an inflamed phenotype characterized by the presence of functionally inhibited CD8+ T-cells. Notably, patients who underwent neoadjuvant CT-RT show an increased tumor infiltration of degranulating (CD107+) CD8+ and NK cells. Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal carcinogenesis, immune surveillance O308.09: INFLUENCE OF LIFE STYLE IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS IN SOUTH INDIAN POPULATION Kalaimani Elango, Servarayan Murugesan Chandramohan, Jasper Sandeep Rajasekar, Sachdev Meenakshi, Kavin Kaliappan, Mohammed Nishar Samiullah, Chidambaram Ramasamy, Jeyasudhahar Jesudason, T Perungo, Madeswaran Chinnathambi, Rajendran Vellaisamy, John Grifson, D Kannan, R Prabhakaran, D Bennet, A Amudhan Madras Medical College, Chennai/INDIA Background: Cancer of the esophagus has a major impact on patient’s nutritional status by virtue of the organ inherent digestive functions. Squamous cell carcinoma of esophagus is the result of multi-factorial etiology. In western population obesity, reflux and Barret’s pathway leads to adeno carcinoma. In India malnutrition, smoking, alcohol intake and life style

factors play a significant role in causing squamous cell carcinoma. This study was conducted to analyze the pre-diagnosis modifiable behavioral factors & present nutritional status of oesophageal cancer patients at Madras Medical College & Rajiv Gandhi Government General Hospital and it’s attached institutes in Chennai, India. Methods: This is a retrospective case-control study. 102 subjects including both sexes between 20–70 years of age were selected by purposive sampling. 51 were esophageal cancer patients and the remaining 51 were controls. The interview schedule was designed to elicit demographic data, subjective and objective data. Dietary pattern was obtained using a pre structured questionnaire and anthropometric measurements were taken. PGSGA was carried out to assess the present nutritional status of the selected subjects. S. No 1 2 3 4 5 6 7 8 9 10 11

Modifiable Factors Analyzed

% of Test Exposed

Reheating of cooking oil Consumption of red meat rarely PGSGA – Stage B & C (moderately & severely malnourished) Intake of calorie and protein < RDA Consumption of more than 10 g salt per day Low intake of fruits & vegetables Smoking Alcohol Very hot liquids regularly Sodium rich sun dried vathal as a meal accompaniment Wood & kerosene as fuel for cooking

90% 84% 78% 77% 69% 68% 61% of males 55% of males 55% 45% 43%

Results: Among the test group, 70.6% were males. Logistic regression analysis showed that among males smoking and alcohol were positively associated with an odds ratio of 20.7143 (95% CI 6.2142–69.0487) and 14.5 (95% CI 4.6393–45.3196). Eating street foods and pickles also showed significant association with an odds ratio of 61.702 (95% CI 4.881–780.068) and 6.900 (95% CI 1.144–41.623) respectively. Discussion: In India, incidence of smoking is least common in female population. Hence our study showed statistically significant association of smoking and cancer in males. Unhealthy food practices, consumption of Asian pickled vegetables and smoking were predominant and need to be aggressively tackled. Inspite of poor red meat consumption, Indian population may be at risk of oesophageal cancer because of eating street foods. Street foods in South India basically contain food additives and reused oil as ingredients. This oil is rich in saturated & trans fat which are suspected to be the carcinogens. Indirect consumption of carcinogens in the form of wood and kerosene as alternative economical fuels & decreased intake of phytonutrients and fiber in their daily diet also contributes to oesophageal cancer. Poor socio economic status and compounded oesophageal cancer acts as a double edged sword in further worsening of the existing nutritional status thereby confirming the statistical results of PGSGA. Disclosure: All authors have declared no conflicts of interest.

Wednesday, September 24 – 15:30–17:00 O310: Esophageal Cancer: Surgical Treatment Room: Cypress O310.01: RESECTION FOR ESOPHAGEAL CANCER Egil Johnson, Dag Førland, Thor Jacobsen, Else Marit Løberg, Hans-Olaf Johannessen Oslo University Hospital, Oslo/NORWAY Background: The aim was to report mortality, serious complications, reoperations and pathology data for patients resected for esophageal cancer during the periods 1983–92, 1993–2002 and 2003–12. Methods: Retrospective and prospective examination based on data from patient files and a a question form. Relevant data was registered in a data base. The patients had Ivor-Lewis esophagectomy using a gastric- (n = 219), jejunal (n = 8) or colonic conduit (n = 4) with either thoracic- (n = 226) and cervical (n = 5) anastomosis. 33 of 265 patients (12.5%) were inoperable. Results: 231 of potentially 232 patients (186 men) with median age 63 years (range 37–79) were resected. Hybrid (laparoscopy and thoracotomy) minimal invasive esophagectomy was performed in 87 of the patients (37.5%). 30-day and in-hospital mortality (n = 232) for the whole period (1983–2012) was 3.9% (n = 9) and 4.7% (n = 11). Corresponding figures for period 1 (1983–92) (n = 48), 2 (1993–2002) (n = 47) and 3 (2003–12) (n = 137) were 12.5% and 12.5%, 4.3% and 6.4% and 0.4% and 1.5% (p = 0.04), respectively. Causes of death were lung failure (n = 2), perioperative hemorrhage (n = 2), anastomotic leakage (n = 2), myocardial infarction (n = 1), ischemic colonic conduit (n = 1), MOF (n = 1) and exhaustion (n = 1). 5.6% (n = 13) had anastomotic leakage, for periods 1–3 in 2.1%, 6.4% and 6.6%, respectively, of whom two died (15.4%). 16 patients (6.9%) were reoperated, 12.5%, 10.6% and 3.6% (p = 0.03) during the respective periods.

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Reoperations were for chylothorax (n = 3), bleeding/hematoma (n = 4), anastomotic leakage/-perforation (n = 3), ARDS (n = 1), ischemic colonic conduit (n = 1), pleurocutaneous fistula (n = 1), wound dehiscense (n = 1) and retention of gastric conduit (n = 1). Proportion of curative resections (R0) for periods 1–3 were 75% (n = 36/48), 76.6% (n = 36/47) and 90.5% (n = 124/137) (p = 0.02). Patients with adenocarcinoma increased from 33.4% to 74.5% (p < 0.0001) and 81.8% (p < 0.0001), respectively. Median (spread) tumor length (cm) was unaltered during these periods, respectively 3.8 (1–8), 3.5 (0.3–10.5) og 4.0 (0–9). Proportion of gastroesophageal junction tumors (Siewert II) increased from 20.8% to 59.6% and 54.7%. Respective figures for proximal tumors at or above carina was reduced from 22.9% to 14.9% and 5.1% (p = 0.001). Percentage distribution of tumor stage T1–T4 were not significantly altered during these time periods. Respective figures were for T1 14.6/10.6/16.9, T2 35.4/31.9/26.2, T3 43.8/48.9/54.6 and T4 6.3/8.5/2.3. Number of lymph nodes in the resected specimen from 92.2% (n = 214) of the patients increased from 3 (1–14) to 5.5 (1–22) (p = 0.006) and 11 (0–38) (p < 0.0001), respectively. Proportion of metastatic lymph nodes were 37.1%, 60.9% (p = 0.04) and 56.4% (p = 0.05), respectively. Annual number of resections for periods 1–3 were 4.7, 4.8 and 13.0, respectively. Discussion: The results from 30 years with resection for esophageal cancer demonstrated an improvement of outcome concerning mortality, reoperations, lymph node harvest and fraction of curative resections. Moreover, the proportion of proximal tumors and squamous epithelial carcinomas were considerably reduced during this period. The improvement of these results may be owing to several factors, including i) increased case load per surgeon, ii) more extensive lymph node dissection and better evaluation of the resected specimen iii) introduction of minimal invasive hybrid surgery and iv) better postoperative patient care. Disclosure: All authors have declared no conflicts of interest. Keywords: mortality, morbidity, lymph nodes O310.02: TREATMENT FOR SUBMUCOSAL TUMOR ON THE ESOPHAGO-GASTRIC JUNCTION Hirofumi Kawakubo1, Hiroya Takeuchi1, Osamu Goto2, Rieko Nakamura1, Tsunehiro Takahashi1, Norihito Wada3, Yoshiro Saikawa3, Tai Omori3, Yuko Kitagawa3 1 Keio University School of Medicine, Tokyo/JAPAN, 2Cancer Center, Keio University, School of Medicine, Tokyo/JAPAN, 3Keio University School of Medicine, Tokyo/JAPAN


base. The patients had Ivor-Lewis esophagectomy with gastric- (n = 140), jejunal (n = 8) and colonic conduit (n = 4) with thoracic- (n = 148) and cervical anastomosis (n = 4), respectively. Two field lymph node dissection was performed in upper adomen and in low and middle mediastinum. 23 of 176 patients (13.1%) were inoperable. Hybrid (laparoscopy and thoracotomy) and total (laparoscopy and thoracoscopy) minimal invasive esophageal resection were performed in 17 and 1 cases, respectively. Results: 152 of potentially 153 resectable patients (110 men) with median age 63 years (range 37–79) were resected. Overall survival was compared between periods 1 (1983–92) (n = 48), (1993–2002) (n = 47) and 3 (2003–09) (n = 58). Different perioperative neoadjuvant therapies were received by 56.3%, 23.4% and 13.8% of patients in respective consecutive periods. Corresponding figures for adjuvant treatment were 10.4%, 10.6% and 20.7%. Survival in months and percentage at 5 years after curative resection (R0) for adenocarcinoma (n = 76) and squamous cell carcinoma (n = 48) in periods 1–3 were 11 (0.75–184) (n = 37) and 8.1%, 19 (1–214) (n = 35) and 14.2% and 42.4 (0.03–126) (n = 52) and 44.1% (see table 1). There was no significant difference in survival after R0 resection between adenocarcinoma and squamous cell carcinoma (data not shown). Distribution of tumor stage T1–4 for the period 2003–09 (n = 57/58) were 11.1%, 34.6%, 47.7% and 5.9%, which was comparable to the periods 1983–92 and 1993–2002 (see another abstract). Number of lymph nodes harvested from periods 1–3 increased from 3 (1–14) to 5.5 (1–22) (p = 0.006) and 7 (0–22) (p = 0.0001). In consecutive periods were distributions of R1–2 resections 22.9%, 25.5% and 10.3% and gastroesophageals junction tumors 20.8%, 59.6% and 53.4%, respectively. Corresponding in-hospital mortality were 12.5%, 6.3% and 1.7% (p = 0.04). Table 1. Survival Time period

No. of patients (%)

Resection

Suvival (months) median/average (range)

Survival 5 years (%)

1983–2012

153 29 134 48 (31.4) 11 37 47 (30.7) 12 35 58 (37.9) 6 *52

R0–2 R1–2 R0 R0–2 R1–2 R0 R0–2 R1–2 R0 R0–2 R1–2 R0

17/35.7 (0.03–214) 11/20.1 (0.03–79) 19.5/39.4 (0.03–214) 10.5/22.2 (0.03–184) 9/15.5 (0.25–48) 11/24.2 (0.75–184) 17/35.9 (1–214) 12/20.4 (1–54) 19/41.2 (1–214) 36.5/46.9 (0.03–126) 20.5/27.8 (3–79) 42.5/49.0 (0.03–126)

20.7 3.4 24.8 6.3 – 8.1 10.6 – 14.2 41.2 16.7 44.1

1983–92 1993–2002 2003–09

Background: Endoscopic treatment and endoscopic surgery for submucosal tumor of the esophagus and stomach have been developed. However treatment of submucosal tumor on the esophagogastric junction is technically difficult, because excessive resection may result in postoperative transformation of the esophagogastric junction and cause stenosis, and intervention to lower esophageal sphincter may result in gastroesophgaeal reflux. The purpose of this study was to examine the usefulness and effectiveness of endoscopic treatment and endoscopic surgery for submucosal tumor on the esophago-gastric junction.

*One included patient was not resected because of death from hemorrhage.

Methods: From January 2012 to December 2014, endoscopic treatment (ESD) or endoscopic surgery (laparoscopic wedge resection) was performed on 7 cases of submucosal tumor on the esophago-gastric junction. Extraluminal type is indication of laparoscopic wedge resection using CLEAN-NET method. Intraluminal type is indication of ESD (partially all layer resection and closure by clipping) or LECS (all layer resection by endoscopy and closure by laparoscopy). Tumor over 5 cm is indication for open surgery.

Keywords: resection, survival, time periods

Results: Three of seven patients underwent laparoscopic wedge resection using CLEAN-NET method. Two patients underwent LECS. One patient underwent ESD. One patient underwent open proximal gastrectomy because tumor size is over 5 cm. All lesions were completely resected. Pathological diagnoses are leiomyoma for six cases and bronchogenic cyst for one case. There are no complications after treatment. There were no long-term complications such as stenosis and gastro-esophageal reflux in all patients. Discussion: The results indicated the usefulness and effectiveness of endoscopic treatment and endoscopic surgery. Disclosure: All authors have declared no conflicts of interest. Keywords: SMT ECJ ESD LECS O310.03: SURVIVAL AFTER RESECTION FOR ESOPHAGEAL CANCER Egil Johnson, Dag Førland, Thor Jacobsen, Else Marit Løberg, Hans-Olaf Johannessen Oslo University Hospital, Oslo/NORWAY Background: The aim was to report survival after resection for esophageal cancer in the period 1983–2009. Methods: Retrospective and prospective examination based on data from patient files and a a question form. Relevant data was registered in a data

Discussion: Overall survival after resection for esophageal cancer has improved considerably over the time periods 1983–92, 1993–2002 and 2003– 09. Plausible explanations include reduction of mortality, morbidity and need for reoperations as well as increased lymph node harvest and proportion of gastroesophageal junction tumors. The role of heterogenous neoadjuvant treatment can not be assessed from this patient material. Disclosure: All authors have declared no conflicts of interest.

O310.04: TUMOR STROMA RATIO (TSR) IN ESOPHAGEAL ADENOCARCINOMA BIOPSIES IN THE PREDICTION OF RESPONSE TO NEOADJUVANT THERAPY AND OVERALL SURVIVAL Maarten Anderegg1, Charlotte Hetterschijt1, Sjoerd Lagarde2, Rachel Blom2, Hanneke Van Laarhoven1, Sybren Meijer2, Suzanne Gisbertz2, Mark Van Berge Henegouwen2 1 Academic Medical Center, Amsterdam/NETHERLANDS, 2Academic Medical Center Amsterdam, Amsterdam/NETHERLANDS Background: The incidence of esophageal carcinoma has been rising over the past decades. Surgical resection remains an important part of curative treatment. Several studies have demonstrated a survival benefit for patients receiving neoadjuvant therapy compared to patients that underwent surgical resection alone. Identification of non responders at an early stage could prevent patients from the toxicity of neoadjuvant therapy and avoid a possible fatal delay in the performance of potentially curative surgery. Tumor stroma ratio (TSR) in primary tumor biopsies taken before neoadjuvant therapy and surgery proved to be a prognostic factor for patient’s survival. The aim of this study was to evaluate the prognostic value of the TSR in biopsies of esophageal adenocarcinomas taken before neoadjuvant therapy and surgery, in correlation to the response to neoadjuvant therapy prior to esophagectomy. In addition the correlation of the tumor stroma ratio with overall survival was evaluated. Methods: In a retrospective study, we selected 141 patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiotherapy prior to esophageal resection between 2004 and 2011. The haematoxylin-eosin (H&E) stained sections of the tumor biopsies were reanalysed. TSR was


ABSTRACT SUPPLEMENT

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scored as TSR low (50% carcinoma). Response to neoadjuvant therapy was determined in the resected specimen based on the tumor regression grade (TRG). The chi-square and Fisher’s exact tests were used to evaluate the correlation of TSR with TRG. Survival was calculated from the date of surgery using the Kaplan–Meier method. Results: 141 patients were analysed. 55 (39%) patients were defined as responders (TRG 1 and 2) and 86 (61%) as non-responders (TRG 3 and 4). Estimation of the TSR was performed successfully in all the tumors (100%). 104 (74%) patients were classified as TSR high and 37 (26%) patients as TSR low. The correlation of TSR with TRG was not significant (P = 0,537). The correlation of TSR with overall survival was not significant (P = 0,793). Discussion: Our results suggest that the TSR in biopsies of esophageal adenocarcinomas does not have a prognostic value in correlation to the response to neoadjuvant therapy prior to esophagectomy. Moreover, according to our results TSR is not a prognostic characteristic for overall survival. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, Tumor stroma ratio, Neoadjuvant treatment O310.05: PROGNOSTIC VALUE OF LYMPH NODE METASTASES IN PATHOLOGIC T0 (YPT0) PATIENTS RECEIVED NEOADJUVANT CHEMORADIATION THERAPY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA Hyun Jin Cho1, Yong-Hee Kim2, Hyeong Ryul Kim2, Dong Kwan Kim2, Seung-Il Park2, Jong Hoon Kim2, Sung-Bae Kim2 1 Gachon University Gil Medical Center, Incheon/SOUTH KOREA, 2Asan Medical Center, University of Ulsan College of Medicine, Seoul/SOUTH KOREA Background: Although patients who received neoadjuvant chemoradiotherapy for esophageal cancer show complete response of the primary tumor, some patients may still have residual nodal metastases. We analyzed the prognosis according to lymph node metastases in pathologic T0 patients who received neoadjuvant chemoradiotherapy followed by surgery for esophageal squamous cell carcinoma. Methods: We retrospectively studied prospectively-collected data from the patients who underwent prospectively protocol-based esophageal resection and reconstruction after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma from 2000 to 2010 at Asan Medical Center. We analyzed overall survival (OS), recurrence-free survival (RFS), and risk factors for ypT0N1, and compared with ypT0N0. Results: 211 patients underwent prospectively protocol-based esophageal resection and reconstruction after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma. 123 of them had pathologic complete response of primary tumor and were enrolled in this study. There were ypT0N0 in 103 patients and ypT0N1 in 20 patients. Two groups did not show significant differences in gender, initial clinical stage, tumor location, and histologic grade. Recurrence occurred in 13 patients (12.6%) of ypT0N0 and 6 patients (30.0%) in ypT0N1, respectively (p = 0.083). 5-year OS and RFS of ypT0N1 was 42.8 ± 13.9% and 41.7 ± 12.8%, respectively. In comparison of survival using log-rank test between two groups, there were no significant differences for OS and RFS (p = 0.234 and p = 0.165, respectively).

Discussion: Residual lymph node metastases do not significantly influenced on prognosis in pathologic T0 patients who received neoadjuvant chemoradiotherapy followed by surgery for esophageal squamous cell carcinoma. We suppose that to achieve a complete surgical resection of primary tumor and lymph node is important for prognosis. Disclosure: All authors have declared no conflicts of interest. Keywords: lymph node metastasis, Esophageal cancer, neoadjuvant therapy

O310.06: THE OPTIMAL SURGICAL TREATMENT FOR ESOPHAGOGASTRIC JUNCTION CANCER Ryo Morisue, Masafumi Kataoka, Takaomi Takahata, Toshikazu Kimura, Futoshi Uno, Kotaro Uemura, Ryohei Shoji, Tomoya Masuda, Kokichi Miyamoto, Motohiko Yamada, Teruki Kobayashi, Toshihiro Ogawa, Yoshihiko Ogawa, Yasuhiro Komatsu, Yurie Kudo, Shuichi Sakamoto, Yasutaka Kudo, Isao Yasuhara, Hironobu Kawamoto, Toru Kojima, Masanobu Maruyama, Yasuki Nitta, Takefumi Niguma, Yoshihiro Akazai, Yoshitaka Nishiyama, Tetsushige Mimura, Hideyuki Kimura, Nobumasa Tsutsui, Toshinori Ohara Okayama Saiseikai General Hospital, Okayama/JAPAN Background: The incidence of esophagogastric junction cancer (EGJC) is increasing, but its surgical treatment remains a challenge. We aimed to determine the optimal surgical approach, in particular the range of lymph node dissection, for treating EGJC by using clinico – pathological characteristics and clinical outcomes. Methods: A total of 86 patients who had undergone curative surgery (R0) for EGJC at Okayama Saiseikai General Hospital from 2004 to 2012 were investigated retrospectively. Patients with residual gastric cancers or multiple cancers were excluded. Specimens were categorized into typesI, II, and III according to their location based on Siewert’s classification, which is based on topographic anatomical criteria for esophagogastric junction adenocarcinomas. Results: This study included 81.4% men and 18.6% women; their median age was 68.5 years (46–84). Adenocarcinomas (AD), including Barrett’s cancer (3 cases) and squamous cell carcinomas (SQ, 19 cases), was the main histology in 67 cases. The transthoracic approach was performed in 24 patients (subtotal esophagectomy: 21 cases, middle and lower esophagectomy: 3 cases), and the non-transthoracic (transabdominal) approach in 62 patients (transhiatal esophagectomy and total/proximal gastrectomy: 21 cases, total gastrectomy: 28 cases, proximal gastrectomy: 13 cases). No significant differences were noted in the prevalence of lymph node metastasis between histology types (p = 0.1380) or among cancer location (p = 0.2210). In all, 37 patients (43.0%) had nodal metastasis. With regard to the location of lymph node metastasis, pericardial and lesser curvature nodes were more frequently seen. On the other hand, greater curvature, supra/infra pyloric, and splenic hiatal nodes had an extremely low incidence of metastasis. Six patients had mediastinal nodal metastasis, and 2 had cervical nodal metastasis. Patients with typeIII EGJC had neither cervical nor mediastinal nodal metastasis. Only one patient with type I SQ had paraaortic lymph node metastasis. Twenty-seven patients had disease recurrence. The patterns of initial recurrences were local in 4 cases, nodal in 7 cases, distant organs in

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8 cases and dissemination recurrence in 8 cases. Six of 8 patients with nodal recurrences had paraaortic lymph node metastasis. Discussion: The transthoracic approach with mediastinal lymph node dissection is necessary for type I EGJC, whereas the transabdominal approach is reasonable for types II and III EGJC. It is important to dissect the pericardial and lesser curvature nodes in all types of EGJCs. Paraaortic lymph node dissection should be considered in case of advanced disease. It is unnecessary to excise the spleen for dissecting splenic hilum lymph nodes in patients with EGJCs. Disclosure: All authors have declared no conflicts of interest. Keywords: lymph node dissection, Esophageal cancer, esophagogastric junction cancer, gastric cancer O310.07: VALIDATION OF THE STEYERBERG’S SCORING SYSTEM IN THE PREDICTION OF THE POSTOPERATIVE MORTALITY AFTER ESOPHAGECTOMY FOR CANCER: A NATIONWIDE STUDY Xavier Benoit D’Journo1, Julie Berbis1, Jacques Jougon2, Pierre Yves Brichon3, Jérome Mouroux4, Gilbert Massard5, Olivier Tiffet6, Pascal Thomas1, Marcel Dahan7 1 Aix-Marseille University, Marseille/FRANCE, 2CHU Bordeaux, Bordeaux/ FRANCE, 3CHU Grenoble, Grenoble/FRANCE, 4CHU Nice, Nice/ FRANCE, 5CHU Strasbourg, Strasbourg/FRANCE, 6CHU Saint Etienne, Saint Etienne/FRANCE, 7CHU Toulouse, Toulouse/FRANCE Background: The estimation of risk-adjusted in-hospital mortality is essential to allow each surgical team to be compared with national benchmarks. This study aims at investigating the reliability of the Steyerberg’s scoring system in the prediction of the in-hospital mortality after esophagectomy for cancer. Methods: Data were extracted from the national database of the French Society of Thoracic and Cardiovascular Surgery (EPITHOR). We retrospectively compared the predicted to the observed postoperative 30-day, 90-day and in-hospital mortality rate in all patients operated for an esophagectomy for cancer of the esophagus and of the gastro-esophageal junction. Steyerberg’s scoring system was calculated on the basis of four variables considered: age, comorbidity, neoadjuvant therapy, and hospital volume. The sum of these factors as a score was entered into a logarithmic formula to calculate the predicted mortality risk as percentage. Deviation of observed from theoretically expected number of deaths was assessed using a chi-square goodness of fit test. Area under receiver operating characteristic (ROC) curve was calculated to assess the discriminative power on the hospital mortality of the Steyerberg’s scoring system. Results: From 2002 to 2013, 1039 consecutive patients underwent a scheduled esophageal resection performed over 40 institutions. Among them, 18 centers were intermediate or high volume centers (>1 procedure/year) and 22 were low volume centers (≤1 procedure/year). The mean age was 62.3 ± 10 years. Neoadjuvant therapy was administrated in 420 patients (40%). One comorbidity was present in 261 patients (25%), 2 in 264 patients (25%), 3 in 383 patients (36%) and 4 in 5 patients (1%). The 30-day, 90-day and inhospital mortality rate were respectively 5.6% (n = 59), 9.2% (n = 96) and 9.6% (n = 100). The main causes of postoperative deaths were due to: respiratory complications (44%), complications of the gastric tube (28%), cardiologic complications (5%) and thromboembolism events (5%). The study population was divided in 10 deciles of equal 104 patients. For the in-hospital mortality, the predicted/observed mortalities were compared in each decile. There were no significant differences between predicted/observed mortalities in each decile. For the 30-day mortality, the Steyerberg’s scoring system overpredicted the observed mortality rate. Area under ROC curve indicated 0.63 (CI95%: 0.58–0.69) in prediction of the in-hospital mortality.


Discussion: Steyerberg’s scoring system is a reliable predictive score of the postoperative in-hospital mortality among a national database taking into account relevant criteria such as hospital volume. This score seems easily reproducible and applicable to others institution performing such surgery. Disclosure: All authors have declared no conflicts of interest. Keywords: esophagectomy, mortality, complication, predictive score O310.08: MICRO RNA PROFILE TO PREDICT POSTOPERATIVE PROGNOSIS IN PATIENTS WITH PRIMARY SMALL CELL CARCINOMA OF THE ESOPHAGUS Tomoyuki Okumura1, Yutaka Shimada2, Tetsuji Yamaguch1, Katsuhisa Hirano1, Toru Watanabe1, Koki Kamiyama1, Isaya Hashimoto1, Kazuto Shibuya1, Shozo Hojo1, Koshi Matsui1, Isaku Yoshioka1, Shigeaki Sawada1, Toru Yoshida1, Takuya Nagata1, Kazuhiro Tsukada1 1 University of Toyama, Toyama/JAPAN, 2Kyoto University, Kyoto/JAPAN Background: Primary small cell carcinoma of the esophagus (SCCE) is a rare but a very aggressive disease with poor prognosis. The standard therapy has been not established and the role of surgery in its multimodality treatment is controversial. The aim of this study was to identify molecular signature to predict postoperative outcome in patient with SCCE. Methods: We first summarized clinicopathological characteristics of the SCCE patients who underwent surgery in our hospital between 1983 and 2009. Then we extracted RNA from formalin-fixed paraffin-embedded samples of the surgically removed specimens to detected expression of micro RNA (miRNA) using a miRNA oligo chip on which 885 genes were mounted. The difference of the miRNA expression between two variables was analyzed by the Student’s t-test. Hierarchical clustering analysis was performed with the Ward’s method. P < 0.05 was used for significance. Results: Totally six cases underwent surgery for SCCE. The median age of the patients was 60.5 years (range: 54–80 years). The TNM classification of the disease was stage 1–2 in two cases and stage 3–4 in four cases. All the patients underwent radical surgery with no residual tumors and received postoperative chemotherapy or chemo-radiotherapy. Three patients showed long term disease free survival with the median observation period of 144.7 months (range: 56.1–173.0), while the other three patients died of tumor relapse rapidly after surgery with the median observation period of 5.1 months (range: 1.7– 8.5). There were no significant association between tumor relapse and any chlinicopathological characteristics of the tumors. After quality assessment of the extracted RNA, samples from five of the six cases were forwarded to miRNA expression analysis. Comparison between the average expression level of miRNAs in the five SCCE tumors and that in the five corresponding normal tissues demonstrated up regulation of 22 miRNAs, including miR-17, miR-21, miR-25, miR-93 and miR-1290, and down regulation of 3 miRNAs, such as miR-145, miR-4328 and miR-203, in the tumors compared to the normal counterparts with more than 2 fold difference. Hierarchical clustering based on the all examined miRNAs revealed two discrete clusters which were identical to the cases with and without postoperative tumor relapse, respectively. When the expression of miRNAs were compared between the two subgroups, high expression of 8 miRNAs, such as miR-4323, miR-625, miR-3619-3p, miR-4419b, miR-1249, miR-4648, miR-4664-3p and miR-1203, were associated with postoperative tumor relapse with statistical significance (p < 0.01). Discussion: These results suggested that combination therapy including surgery improve survival of a distinct subpopulation of the SCCE patients. The expression profile of miRNAs in the tumor was suggested to be a novel predictor for postoperative outcome in patients with SCCE. Disclosure: All authors have declared no conflicts of interest. Keywords: small cell carcinoma, miRNA, Surgery, Prognostic marker O310.09: AN ESOPHAGOGASTRIC ANASTOMOSES WITH PURSE STRING INSTRUMENT AND PROLONGED MUCOSA IN CONTINUOUS 1140 PATIENTS WITH NO ANSTOMOTIC LEAKING FOR SURGICAL TREATMENT OF ESOPHAGEAL CARCINOMA Shiying Zheng1, Ben Chen2, Dong Jiang1, Kevin Wang2, Tracy Yin2 1 The First Affiliated Hospital of Soochow University, Suzhou/CHINA, 2 Touchstone International Medical Science Co. Ltd., Suzhou/CHINA Background: Esophageal anastomotic leaking is the severe complications after the resection of esophageal cancer and cardia cancer. Exploring the effective methods to promote healing of the anastomosis and to prevent anastomotic leaking is still the hot point in these fields nowadays. From May 2007 to march 2014, 1140 esophageal and stomach cardia cancer patients treated by intrathoracic esophagogastric anastomosis with purse string instrument and esophageal mucosa extended varied in plane were retrospectively analyzed. Methods: One thousand one hundred and forty cases were retrospectively analyzed, 862 being male and 278 female from the age of 37–80 years. The


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patients from 45 to 70 years old accounted for 78.6%. These 1140 cases included 810 patients of middle segment cancer of the esophagus, 210 patients of inferior segment cancer and 120 patients of cardia cancer. In 920 cases of esophageal or cardia cancer the operation was carried through left thoracic cavity. 980 cases were treated by intrathoracic esophagogastric anastomosis (860 anastomosis were done above the aortic arch and 120 cases under the arch). 220 cases of esophageal cancer were treated by tumorectomy through right thoracic cavity and esophagogastric anastomosis through intrathoracic cavity. Esophagoesophageal anastomosis with purse string instrument and esophageal mucosa extended varied in plane. The main points of the operation are: One more centimeter should be retained on side of the esophageal. Results: In our study, there were no anastomotic leaking postoperatively. The follow up visit was up to 3–6 months postoperatively. Of the 745 patients with records, 709 patients had the normal diet (97.2%) and 36 patients soft diet (7.8%). Discussion: Though there were several methods of operation for esophagogastric or esophagoesophageal anastomosis, they can be classified into two groups: full-thickness and purse string instrument and esophageal mucosa extended anastomosis. These two kinds of methods were analyzed in this study. The former was the method used rather popularly. The purse string instrument and esophageal mucosa extended anastomosis was regarded as the better one, for the incidence of anastomotic leaking was dramatically lower than the former method. Many researchers have done a lot of study to prevent the incidence of anastomotic leaking. Since the operation of esophagogastric purse string instrument and esophageal mucosa extended anastomosis conforms to the above anatomical characters, healing will be achieved in a short time. The purse string instrument and esophageal mucosa extended anastomosis we used could prevent the anastomotic leaking effectively, which shows that the occurring of leaking is related to the modus operation. Compared to the traditional anastomosis, it has the following advantages: (1) Each layer of the organ can be annealed concinnously, especially the layer of mucosa and underlayer. (2) The extension of the mucosa layer may reduce the tension, which supplies good healing conditions. (3) One centimeter of the free edge is enough in esophageal mucosa shorten spontaneously. Disclosure: All authors have declared no conflicts of interest. Keywords: Anstomotic Leak;, Purse String Instrument, Prolonged Mucosa, Esophagogastric Anastomoses

Tuesday, September 23 – 08:00–15:45 P1: Tuesday Poster Session Room: Foyer P1.01.01: ASSOCIATION BETWEEN OBESITY AND BARRETT’S ESOPHAGUS IN A JAPANESE POPULATION Shota Fukui1, Jiro Watari1, Maki Kawanaka1, Noriko Kamiya1, Akio Tamura1, Tomohiro Ogawa1, Masato Taki1, Tomoaki Kohno1, Katsuyuki Tozawa1, Hisatomo Ikehara1, Yoshio Ohda1, Toshihiko Tomita1, Hirokazu Fukui1, Tadayuki Oshima2, Kazutoshi Hori1, Hiroto Miwa1 1 Hyogo College of Medicine, Nishinomiya/JAPAN, 2Hyogo Collage of Medicine, Nishinomiya/JAPAN Background: Although obesity may be an independent risk factor for Barrett’s esophagus (BE) in the West, the association between obesity and BE remains unclear in a Japanese population. Some studies show that proton pump inhibitors (PPIs) may induce regression and normalization of BE. We investigated the epidemiological and molecular pathological association of BE with obesity among individuals not taking PPIs. Methods: A prospective study of 1241 consecutive individuals who underwent upper gastrointestinal endoscopy was conducted, evaluating the prevalence of endoscopically suspected BE (ESBE). Obesity was evaluated by body mass index (BMI, ≥25 kg/m2) and waist circumference (WC) (males, ≥85 cm; females, ≥90 cm). As for the analyses of molecular alterations, microsatellite instability (MSI) at five microsatellite loci based on the revised Bethesda panel and the promoter methylation at hMLH1, E-cadherin, p16, and APC were also investigated from ESBE biopsy samples. Results: The prevalence of ESBE was 25.2% for ultra-short ESBE (5mins) and the reflux time in Group 1 were less than those in Group 2 (P = 0.00), while the longest episode of reflux in Group 1 were longer than that in Group 2 (P = 0.00). Discussion: Due to the application of minimally invasive techniques and neoadjuvant therapy, there is no significant difference in postoperative morbidity and overall survival between trans-hiatal and cervicothoracoabdominal esophagectomy for upper esophageal carcinoma. However, laryngo-pharyngeal reflux after combined thoracoscopic and laparoscopic esophagectomy was more severe than that after laparoscopic trans-hiatal surgery, which may influence patients’ quality of life. Disclosure: All authors have declared no conflicts of interest. Keywords: upper esophageal carcinoma, Laparoscopic transhiatal esophagectomy, combined thoracoscopic and laparoscopic esophagectomy, postoperative laryngo-pharyngeal reflux P1.09.11: ESOPHAGECTOMY BY VIDEO ASSISTED THORACOTOMY MIGHT REDUCE RESPIRATORY COMPLICATION IN ELDERLY PATIENTS WITH ESOPHAGEAL CANCER Katsunobu Sakurai, Naoshi Kubo, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Masaichi Ohira, Kosei Hirakawa Osaka City University Graduate School of Medicine, Osaka/JAPAN Background: With the extension of life expectancy, aging progresses and opportunities for medical care for the elderly over the age of 75 is increasing. The aim of this study is to clarify the safety of esophagectomy for elderly patients with esophageal cancer. Methods: This retrospective study selected 39 patients (elderly group) who underwent an esophagectomy for 75 age and more patients with esophageal cancer from January 2000 to December 2013. As a control group, 131 patients at the age of 60–69 who underwent esophagectomy at the same period were selected to compare the clinicopathological finding and perioperative outcome. Results: Preoperative respiratory examination revealed normal pattern in 15 cases, obstructive pattern in 18 cases, restricted pattern in 2 cases and mixed pattern in 2 cases in elderly group and normal pattern in 84 cases, obstructive pattern in 41 cases, restricted pattern in 4 cases and mixed pattern in 2 cases in control group. 72% in elderly group have preoperative comorbidity more than 60% in control group. Surgical procedure was open thoracotomy (24 cases), video assisted thoracotomy (VATS) (11 cases) and only open laparotomy (4 cases) in elderly group and open thoracotomy (82 cases), VATS (49 cases) in control group. Mean operative time was 510 min in elderly

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group significantly less than 571 min in control group (p < 0.05). Mean blood loss was 591 ml in elderly group significantly less than 802 ml in control group (p < 0.05). Whole postoperative complication was not significantly different from 74% in elderly group and 66% in control group. However respiratory complication was significantly 49% in elderly group more than 29% in control group (p < 0.05). In elderly group, respiratory complication of open thoracotomy and VATS were 54% and 45%. Respiratory complication in VATS tended to be lower rate than in open thoracotomy. Mean postoperative stay was 54 days in elderly group and 40 days in control group. There was no difference from both groups, but postoperative stay was longer in elderly group than in control group. Postoperative hospital death was 7.7% in elderly group and 1.5% in control group. There was no difference between both groups, but death rate was higher in elderly group than that in control group. Discussion: Respiratory complication risk was high at elderly patients. VATS might reduce respiratory complication of elderly patients with esophageal cancer. Disclosure: All authors have declared no conflicts of interest. Keywords: elderly patients, Esophageal cancer, VATS, complication P1.09.12: ROBOT ASSISTED THORACOSCOPIC ESOPHAGECTOMY IS SAFE AND FEASIBLE AFTER NEOADJUVANT CHEMORADIATION Ashish Goel, Kapil Kumar, Veda Padma Priya Selvakumar Rajiv Gandhi Cancer Institute Delhi, New Delhi/INDIA Background: Since more than seventy five percent cases of esophageal cancers are locally advanced at presentation; the use of neoadjuvant chemoradiation followed by surgery is gradually becoming the standard of care. However there is lot of hesitation among surgeons in performing Robot Assisted or Video Assisted Thorascopic Esophagectomy in patients who have received neoadjuvant chemoradiation. Most often there are concerns of adequate wide surgical resection, lack of tactile sensation in minimal invasive approaches and the fear of increased morbidity after neoadjuvant chemoradiation. Worldwide there is limited experience in Robot Assisted Thoracoscopic Esophagectomy (RATE) after neoadjuvant chemoradiation. We present our initial experience of robot assisted thoracoscopic esophagectomy in patients who have undergone preoperative chemoradiation. Methods: A total of 15 patients underwent Minimal Invasive Mckeowns’ Esophagectomy with a hybrid technique, i.e. robot assisted thoracic mobilization of esophagus and a mix of laparoscopic assistance or laparotomy for the abdominal procedure. They were eleven males and four females with mean age of 57.4 years (range 47–73 years). Five patients had lower third lesion & ten had mid third lesion. Biopsy was adenocarcinoma in four and squamous cell carcinoma in eleven. Ten cases received preoperative concurrent chemoradiation and one had preoperative chemotherapy alone; while four patients proceeded for surgery directly given their early stage disease. Preoperative assessment with FDG PET-CT suggested partial response with residual growth in five patients and significant response in rest six patients. Results: Robotic Assisted Thoracoscopic mobilization of esophagus was done in semi prone position with standard four ports. The median operative time was 362 minutes (range 315–400 minutes) with a median estimated blood loss of 200 ml. The average ICU stay was 5.7 days and hospital stay was 13.5 days (range 11–15 days). Overall there were two conversions to thoracotomy, one for intraoperative bleed and the other for tracheal injury from cautery burn. Both these complications occurred during the initial cases. All patients underwent gastric tube mobilization by abdominal approach with esophagogastric anastomosis by side to side stapling technique in left neck. Immediate surgical complication included anastomotic leak in three patients with chyle leak and recurrent laryngeal nerve injury in one case each. There were no significant cardiac or pulmonary complications. Postoperative histopathology suggested pCR in five cases (45.4%). Discussion: Robot assisted transthoracic mobilization of esophagus is feasible and can be safely performed even after neoadjuvant CTRT. Although there is a steep learning curve there are definite advantages in terms of equivalent surgical outcome, minimal blood loss and shorter hospital stay. In our single institution experience we have found Robot Assisted Esophagectomy to allow radical surgery with acceptable morbidity, shorter length of stay and good oncological outcomes, making this procedure as our standard approach even after neoadjuvant chemoradiation. Disclosure: All authors have declared no conflicts of interest. Keywords: Robotic esophagectomy, neoadjuvant chemoradiation

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P1.09.13: THE APPROPRIATENESS OF EARLY ENTERAL FEEDING WITH AN ELEMENTAL DIET FOR PATIENTS WITH THORACIC DUCT LIGATION FOLLOWING ESOPHAGEAL CANCER SURGERY Satoshi Aiko, Yasumasa Koyama, Shingo Maeda, Masanori Odaira Eiju General Hospital, Tokyo/JAPAN Background: Early enteral nutrition (EEN) with commonly used products is of limitted benefit for patients with esophageal cancer whose thoracic ducts (TDs) have been ligated during surgery. In these cases, an acute disturbance in the absorption of long-chain fatty acids, a main fat source in enteral nutrition (EN) products, can cause hemodynamic deterioraton in the early postoperative period. This study was conducted to determine whether EEN with an elemental diet containing negligible fat is beneficial for patients who underwent TD ligation (TDL) during surgery for esophageal cancer. Methods: Seventeen patients with esophageal cancer who underwent TDL during surgery were given an elemental diet (Elental) according to the postoperative EEN schedule. Biochemical values, lymphocytes counts, phytohemagglutinin (PHA)-induced lymphocyte transformation test values, and hemodynamic stability were compared among this group of patients (EL-TDL group) and two other groups who also underwent TDL during surgery; these included nine patients who received EEN with standard EN products (EN-TDL group) and nine patients who received total parenteral nutrition (PN-TDL group). To assess the impact of TDL two groups with preserved TDs were added for further comparisons; these included eleven patients who received EEN with the same standard EN products (EN-TDP group) and twelve patients who received parenteral nutrition (PN-TDP group). Patients who had a history of neoadjuvant therapy or had used corticosteroids were excluded from the study. Results: Total lymphocyte count showed an early recovery in the EN-TDP group and a significant difference was observed between the EN-TDP and PN-TDP groups on postoperative day (POD) 3. In TDL cases, a gradual increase, rather than an early recovery of the total lymphocyte count, was observed in the EN-TDL and EL-TDL groups, and there were significant differences among these groups and the PN-TDL group on POD 7. There were no significant differences in the PHA-induced lymphocyte transformation test values among all groups. Serum total bilirubin was significantly increased in both PN groups compared with the EEN groups. Significant differences were observed between patient groups with and without TDL. The EN-TDP group exhibited a more stable daily fluid balance calculated based on differences between fluid intake and fluid excretion compared with the PN-TDP group. However, fluid balance in the EN-TDL group changed widely and decreased to the lowest level on POD 3, while in the EL-TDL group fluid balance was maintained at a constant level between 700–1300ml during the week after surgery. There was a significant difference in the fluid balance on POD 3 between the EN-TDL group and the EL-TDL group.


esophagostomy were performed, and in April 2012 antethoracic route esophagogastrostomy was performed. Results: The urinary protein levels were negative by the 86th day of hospitalization, and the patient progressively improved and was discharged on the 91st hospital day. There has been no recurrence of esophageal cancer or relapse of nephrotic syndrome at 18 months following the operation. Discussion: In esophageal cancer patients with nephrotic syndrome, surgical treatment should be undertaken because the remission of nephrotic syndrome may be expected following tumor resection. For this purpose, selecting the appropriate operative procedures and careful perioperative management, including nutritional management, are of profound importance. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, Nephrotic Syndrome P1.09.15: ENDOCRINE CELL CARCINOMA OF THE ESOPHAGUS: 5 CASE REPORTS Hiroyuki Tada, Hitoshi Fujiwara, Hirotaka Konishi, Shuhei Komatsu, Atsushi Shiozaki, Daisuke Ichikawa, Kazuma Okamoto, Chouhei Sakakura, Eigo Otsuji Kyoto Prefectural University of Medicine, Kyoto/JAPAN Background: Endocrine cell carcinoma of the esophagus (ECC) is very rare with extremely poor prognosis because it is often difficult to diagnose ECC at the pretreatment examination and no standard treatment protocol has been established. Methods: The purpose of this study was to summarize the clinicopathological features of ECC in patients who underwent esophagectomy at our institution. Results: Case reports: The patients were 3 men and 2 women with a median age of 67 (58–72) years. One patient was preoperatively diagnosed with ECC by endoscopic biopsy and underwent neoadjuvant chemotherapy. The preoperative diagnoses of the other patients were squamous cell carcinoma, adenocarcinoma, and sarcoma, with an unknown diagnosis in the remaining patient. The clinical stages were II (n = 2) and III (n = 3). All patients underwent esophagectomy with curative intent as initial treatment. Postoperative pathological examination revealed that the tumors of the 4 patients who had not been diagnosed with ECC preoperatively were ECCs, and R0 resection was performed in 4 of 5 patients. Postoperatively, the recurrencefree survival of 2 node-negative patients was 8 months and 7 years without postoperative adjuvant chemotherapy, and 3 node-positive patients experienced early recurrence (multiple lymph node or organ metastases) within 3 months following esophagectomy that resulted in early death (6 months, 6 months, and 1.8 years) despite multimodal treatment.

Discussion: As with patients without TDL, patients with TDL obtained benefits from postoperative EEN, such as an increase in lymphocyte number and prevention of postoperative hyperbilirubinemia. EEN with the elemental diet did not cause the type of hemodynamic disturbance observed when standard EN products, containing large amounts of long-chain fatty acid, were administered. These results suggest that EEN with the elemental diet is appropriate for the nutritional management of patients with TDL following esophageal cancer surgery.

Discussion: Recently, some reports indicated better postoperative survival after R0 resection in patients with no regional lymph node metastasis than in those with lymph node metastasis. However, 70% of patients with ECC experienced lymph node metastasis, with a 1-year survival rate of 10%, and the median survival period of patients treated with curative resection was 6.2 months. Therefore, careful selection of appropriate treatment after precise pretreatment diagnosis is important.


Keywords: surgical treatment, Endocrine cell carcinoma of the esophagus

Keywords: Esophageal cancer, enteral nutrition, thoracic duct, elemental diet

P1.09.14: A CASE OF ESOPHAGEAL CANCER SHOWING COMPLETE REMISSION OF NEPHROTIC SYNDROME AFTER ESOPHAGECTOMY Yoshihiko Naritaka, Takeshi Shimakawa, Shinichi Asaka, Kentaro Yamaguchi, Asako Shimazaki, Atuko Usuda, Hiroko Tagawa, Minoru Murayama, Akira Miyaki, Hajime Yokomizo, Kazuhiko Yoshimatsu, Shunichi Shiozawa, Takao Katsube Tokyo Women’s Medical University Medical Center East, Tokyo/JAPAN Background: Nephrotic syndrome associated with a malignant tumor may remit following resection of the tumor. This report documents a case of esophageal cancer with concurrent nephrotic syndrome in which a surgical resection of the cancer resulted in a complete remission of nephrotic syndrome. Methods: A 78–year-old male patient noticed edema of his lower legs in February 2012 and was diagnosed with nephrotic syndrome. An endoscopic examination revealed an indented lesion with a nearly semiannular low elevation on the posterior wall of the esophagus at 31 to 34 cm from the upper incisors, and a diagnosis of esophageal cancer was made. A twostage operation was planned. In March 2012, a subtotal resection of the thoracic esophagus through a right thoracic approach and cervical external


P1.09.16: COMPARATIVE TRIAL OF ESOPHAGECTOMY VERSUS DEFINITIVE CHEMORADIOTHERAPY FOR POTENTIALLYRESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA Susumu Sueyoshi1, Toshiaki Tanaka2, Satoru Matono2, Naoki Mori2, Haruhiro Hino2, Takeshi Nagano3, Tatsuji Tsubuku1, Kazuo Shirouzu2, Hiromasa Fujita4 1 Omuta City Hospital, Omuta/JAPAN, 2Kurume University School of Medicine, Kurume/JAPAN, 3Kurume University School of Medicine, Kurume/JAPAN, 4Fukuoka Wajiro Hospital, Fukuoka/JAPAN Background: Outcomes after esophagectomy are compared with those after definitive chemoradiotherapy (dCRT) to determine the optimal treatment for potentially-resectable esophageal cancer. Methods: A consecutive series of 159 patients with a squamous cell cancer in the thoracic esophagus were treated in the Kurume University Hospital during the period from 2003 to 2009. After informed consent on preoperative staging and risk analysis, each patient him/herself chose esophagectomy or dCRT. Multivariate analysis was used to investigate the following prognostic factors; staging, risk, treatment, treatment effect and other clinical factors. Results: Among these 159 patients, 122 patients underwent esophagectomy (the surgery group), and 37 patients underwent dCRT (the dCRT group). In the surgery group, curative R0 resection was performed for 95 (78%)


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patients. In the dCRT group, 19 (51%) patients were complete responders to dCRT. The mortality rate was 1.6% (2/122) in the surgery group, and 2.7% (1/37) in the dCRT group. The 5-year-survival rate in the surgery group was significantly higher than that in the dCRT group (50% vs 22%, p < 0.001). There was no significant difference in the 5-year-survival rate between those undergoing curative R0 resection in the surgery group and the complete responders in the dCRT group (56% vs 37%, p = 0.274). There was significant difference in the 5-year-survival rate between those undergoing non-curative palliative R1/R2 resection in the surgery group and the non-complete responders in the dCRT group (26% vs 6%, p = 0.013). Among the various clinical and pathological factors, only three factors including ‘stage’, ‘treatment method’ and ‘effect of treatment’ were defined as prognostic by multivariate analysis. Discussion: For potentially-resectable esophageal cancer, these findings suggested that esophagectomy was more recommended than dCRT as the initial treatment, when practicable. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, esophagectomy, Definitive chemoradiotherapy P1.09.17: A CASE OF EARLY ADENOID CYSTIC CARCINOMA OF THE ESOPHAGUS Shoko Kato, Norihiro Yuasa, Takeuchi Eiji, Yasutomo Goto, Hidemasa Nagai, Masaoki Hattori, Kanji Miyata, Masahiko Fujino Japanese Red Cross Nagoya Daiichi Hospital, Nagoya/JAPAN Background: Adenoid cystic carcinoma (ACC) commonly originates in the major salivary glands and respiratory tract, but extremely rarely in the oesophagus. There are two hypotheses on the cellular origin of ACC of the esophagus: esophageal gland or esophageal epithelium origin. Several authors reported that ACC of the esophagus has much more aggressive behaviour than that of salivary gland. However, there have been a few of literature reporting early ACC of the esophagus. Methods: We report a case of early ACC of the esophagus. Results: A 71-year-old man came to our hospital for heartburn. He had atrial fibrillation and chronic hepatitis with hepatitis C virus antibody. He was a heavy smoker and hardened drinker. Blood tests including tumor marker revealed no particular abnormal finding. Barium esophagography showed a smooth elevated lesion 15 mm in length with central depression in the middle esophagus. Upper gastrointestinal endoscopy revealed an elevated tumor with predominantly subepithelial growth in the posterior wall of the middle esophagus. Biopsy specimen obtained from central depression of the tumor demonstrated squamous cell carcinoma composed mainly by basaloid cells. CT scan showed no findings suggesting lymph node or remote metastasis. FDG-PET showed no high FDG-accumulation in the esophagus, lung, or liver. We diagnosed this case as early esophageal cancer and performed subtotal esophagectomy with two field (abdomen and mediastinum) lymph node dissection followed by gastric tube reconstruction. Macroscopic finding of the resected specimen showed a 0-Isep tumor 14 × 10 mm in size. Histopathological examination revealed that atypical adenoepithelial and myoepithelial cells invaded to the deep submucosal layer with a cribriform or glandular structure containing PAS (periodic acid-Schiff) and alcian blue stain positive material. These atypical cells were positive for collagen IV, smooth muscle actin, and p63. No metastasis was found in the dissected lymph nodes. So, this case was diagnosed as early ACC: T1b (SM2), INFb, IM0, ly0, v0, N0. Thirty-six months after the operation, he was alive without evidence of relapse. Discussion: ACC of the esophagus accounts for less than 0.1% of all esophageal neoplasms (Suzuki and Nagayo, 1980). Although several authors reported that ACC of the esophagus has aggressive behaviour, its prognosis can be favourable if complete resection is performed in early stage. Disclosure: All authors have declared no conflicts of interest. Keywords: adenoid cystic carcinoma, early esophageal cancer, esophageal carcinoma P1.09.18: THORACOSCOPIC PRONE POSITION ESOPHAGECTOMY FOR CANCER: THE EXPERIENCE OF TUTORSHIP IN A HIGH VOLUME LAPAROSCOPIC CENTRE Mattia Berselli1, Eugenio Cocozza1, Lorenzo Livraghi1, Lorenzo Latham1, Luca Farassino1, Noemi Pasqua1, Claudio Cortelezzi1, Marco Parravicini1, Sergio Segato1, Roberto Petri2 1 Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi, Varese/ ITALY, 2Ospedale Santa Maria della Misericordia, Udine/ITALY Background: Minimally invasive esophagectomy in prone position is an appraising technique. Encouraging results regarding learning curve and postoperative management were reported. Few experiences were described about the tutorship and its more important issues. In this paper the acquisition of the technique by an experienced laparoscopic surgeon is narrated.

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The organisational set-up with the more important technical skills are described. Methods: The experience started in 2009 due to a surgical meeting of our tutor, the head of an important centre of esophageal surgery in the north of Italy. He explained the technique of total esophagectomy with prone position thoracoscopic approach. During the following months we visit many times the operative room to look at this innovative technique. At the end of 2009 the tutorship has been started-up: the tutor came to our Hospital to perform with our assistance two esophagectomies with prone position thoracoscopic approach. A one-year well-experienced and helpful tutorship was performed. In 2011 we started our experience in thoracoscopic esophagectomy: the tutor was in our operative room to show the way. At the end of 2011 we perform our first total thoracoscopic esophagectomy without the presence of the tutor: he was 400 kilometers far from our hospital, but he was on call if needed. The tuthorship proceeded in the following months with a close comparison and in 2012 and 2013 we has been called to tell our experience in an important Italian teaching center for minimally invasive surgery. All the patients were treated after a multidisciplinary discussion and according to international guidelines. Perioperative chemoradioterapy was administered if needed. Thoracoscopy was performed in prone position and the patients were intubated with a single-lumen endotracheal tube in the standard conventional manner. Three trocars were placed in the right hemithorax. Two-field lymphadenectomy was performed. Stomach placed in anatomical prevertebral position was the method of reconstruction. A cervical stapled end-to-side anastomosis was carried out. The cervical drain was removed in 10th postoperative day after performing a soluble contrast swallow. Results: Seven patient (5 males and 2 females) underwent thoracoscopic prone position total esophagectomy. The median age was 62 years. One patient with an history of kidney transplantation died in the postoperative period by a renal failure. In the others patients no postoperative complications occurred. After a median follow-up of 29,5 months two patients died for disease progression, one patient is alive and in good condition with disease relapse, three patient are alive and disease free. Discussion: Minimally invasive esophagectomy in prone position technique can be learned by an experienced laparoscopic surgeon through an adequate and qualified tutorship. This technique can be useful in esophageal cancer management. The mininvasive approach to esophageal cancer is feasible after a long-term experience in mininvasive surgery for malignancies: we started our experience after performing hundreds of colon and rectal cancer with laparoscopic approach. It’s difficult to say how the learnig curve would be without a tutorship and an experience in minimally invasive surgery like that. An adequate selection of patients and a multidisciplinary approach are needed. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, Prone position, Minimally Invasive Esophagectomy, Thoracoscopy P1.09.19: PROGNOSTIC IMPACT OF METASTATIC LYMPH NODE NUMBER AND RATIO IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER NEOADJUVANT CHEMORADIOTHERAPY FOLLOWED BY ESOPHAGECTOMY Chao-Yu Liu1, Po-Kuei Hsu2, Chia-Chuan Liu3 1 Far Eastern Memorial Hospital, New Taipei City/TAIWAN, 2Taipei Veterans General Hospital, Taipei/TAIWAN, 3Sun Yat-Sen Cancer Center, Taipei/TAIWAN Background: The prognostic impact of number of metastatic lymph nodes (LNs) in esophageal squamous cell carcinoma (ESCC) has been validated. The N-staging in 7th edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system for esophageal cancer is based on pathologic lymph node number from esophageal cancers treated by surgery alone. However, the prognostic value of metastatic LNs and ratio in ESCC after neoadjuvant chemoradiotherapy (nCRT) has been less investigated. The purpose of this study was to evaluate the prognostic impact of metastatic lymph node number and ratio in ESCC patients receiving primary surgery and nCRT. Methods: The data were obtained from the Taiwan Cancer Registry, Ministry of Health and Welfare. We reviewed the clinicopathologic profiles from 2151 patients with ESCC who underwent esophagectomy with or without nCRT between 2008 and 2011 in Taiwan. Patients were stratified into primary surgery without prior treatments (n = 1301), and nCRT followed by esophagectomy (n = 850). A Cox proportional hazard model and KaplanMeier curve estimated the survival function using LNs number categorized into 0, 1–2, 3–6, ≧7 and ratio into 0, >0 ≦0.2, and >0.2. Results: In surgery group, the 3-year survival rates of patients categorized by LN number were 58.2% for LN = 0, 38.4% for LNs = 1–2, 25.5% for LNs = 3–6, and 12.3% for LNs≧7; by LN ratio were 56.4% for ratio = 0, 35.1% for ratio >0 ≦0.2, and 19.2% for ratio >0.2. Accordingly, in nCRT group,

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the 3-year survival rates were 51.4%, 30.0%, 18.3%, and 0% in LN number categorized into 0, 1–2, 3–6, and ≧7, respectively; the 3-year survival rates were 50.4% 28.6%, and 0% in LN ratio categorized into 0, >0 ≦0.2, and >0.2, respectively. In multivariate analysis, the LN number and ratio were all independent prognostic factors in both surgery group and nCRT group.

and fourteen trans-hiatal procedures were carried out. The following complications were observed in G1: cervical fistula (11), pneumonia (12), pleural effusion (4), necrosis of gastric tube (1) and death (8–20%). The complications observed in G2 were: cardyogenic shock (2), pulmonary embolism (1), cervical fistula (2) and death (2–10%).

Discussion: LN number and ratio remain independent prognostic factors for survival in patients receiving nCRT followed by esophagectomy. With the widespread use of multimodality treatment for ESCC, effort should be done to reduce metastatic LN number and gain an adequate number of resected LNs.

Discussion: Considering that all the patients were operated by the same team, we conclude that the few favourable results observed in patients with esophageal cancer are due to following factors: a) advanced age; b) metabolic disturbances caused by high consumption of alcohol and tobacco; c) peculiar characteristics of the consumption disease.



Keywords: Lymph Node Number, Ratio, Esophageal squamous cell carcinoma, Neoadjuvant chemoradiotherapy

Keywords: esophagectomy; esophageal cancer; benign diseases

P1.09.20: DOSE THE NUMBER OF RESECTED LYMPH NODES PREDICT SURVIVAL IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER NEOADJUVANT CHEMORADIOTHERAPY FOLLOWED BY ESOPHAGECTOMY? Chao-Yu Liu1, Po-Kuei Hsu2, Chia-Chuan Liu3 1 Far Eastern Memorial Hospital, New Taipei City/TAIWAN, 2Taipei Veterans General Hospital, Taipei/TAIWAN, 3Sun Yat-Sen Cancer Center, Taipei/TAIWAN Background: There have been controversies regarding optimum lymphadenectomy in esophageal cancer surgery. This study was designed to determine the prognostic impact of the number of resected lymph nodes (LNs) on survival in esophageal squamous cell carcinoma (ESCC) patients who received primary esophagectomy or neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. Methods: We reviewed the clinicopathologic profiles from 2151 patients with ESCC who underwent esophagectomy with or without nCRT between 2008 and 2011 in Taiwan. The data were obtained from the Taiwan Cancer Registry, Ministry of Health and Welfare. Patients were stratified into primary surgery without prior treatments (Surgery group, n = 1301), and nCRT followed by esophagectomy (nCRT group, n = 850). A Cox proportional hazard model and Kaplan-Meier method were used to determine the association between the number of LNs resected and survival. Results: The resected LNs number were categorized into 0, 1–10, 11–20, 21–30, 31–40, and >40. Cox regression analysis showed a more LNs number resected was associated with a trend predicting a better survival. A best survival function was seen in a LNs number of 31 to 40 obtained among both surgery group and nCRT group. LNs resected more than 40 did not show a better survival in both groups. The resected number of LNs presented an independent predictor of survival only when a 31 to 40 LNs were obtained in patients receiving nCRT followed by esophagectomy. Discussion: The number of LNs resected is not an independent predictor of survival in ESCC patients. However, the patients receiving nCRT followed by esophagectomy would benefit most in survival when lymphadectomy including a LNs number between 31 to 40 was performed.

P1.09.22: OUR APPROACHES IN SURGICAL TREATMENT OF ESOPHAGEAL CANCER Andrii Sydiuk, Yuri Dumansky, Alexandr Popovych Donetsk National Medical University, Donetsk/UKRAINE Background: Meta-analysis of literature over the past 15 years has shown that the most significant prognostic factor in the treatment of esophageal cancer is R0 resection in combination with adequate lymphadenectomy. In order to ensure the above conditions requires surgical access, which allows surgeons to perform curative surgery under visual control. According to the literature, another important factor is anastomosis between the esophagus and the small intestine or stomach. Anastomosis must meet the following requirements: to be the most reliable, easy to perform and functional, to minimize the number of early and late postoperative complications. Methods: 363 curatuve and palliative surgery for cancer of the esophagus and stomach cancer involving esophagus were performed from 2005 to 2012 in the Donetsk anticancer center. Results: In 21.2% of cases (77 patients) were combined operations: splenectomy – 42 cases, resection of the pancreatic tail – 24, subtotal pancreatectomy – 6, resection of the diaphragm – 16, liver resection – 8, colon resection – 6, lung resection – 5. Among postoperative complication was postoperative pneumonia – 3.3% (12 cases) and exudative pleuritis – 2.2 (8 cases). Postoperative mortality was 1.4% (5 patients). Causes of deaths: in two cases was the pulmonary embolism in 2 more cases – pancreatic and 1 acute cardiovascular failure. There were no leakage of esophageal-gastric and esophageal- intestinal anastomoses. In the study of the functional results of surgical treatment of esophageal cancer and gastric cancer involving esophagus, the frequency of reflux esophagitis was – 8%, anastomotic stenosis – 6%. Discussion: Thus, methods of surgical treatment of esophageal cancer wich were developed in Donetsk regional anticancer center are reliable and functional, with satisfactory rates of postoperative complications and mortality. Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal cancer, surgical treatment

Disclosure: All authors have declared no conflicts of interest. Keywords: Resected Lymph Nodes, Esophageal squamous cell carcinoma, Neoadjuvant chemoradiotherapy P1.09.21: EVALUATION OF ESOPHAGECTOMY INDICATED TO THE TREATMENT OF ESOPHAGEAL CANCER AND BENIGN DISEASES Maria Aparecida Henry School of Medicine, Botucatu/BRAZIL Background: Esophagectomy is one of the more complex procedures employed to the treatment of esophageal diseases. The aim of this research is to analyze the results of esophagectomy indicated to cancer treatment, and to esophageal benign diseases. Methods: A retrospective study of esophagectomy results in esophageal cancer patients (G1, n = 40), and with benign diseases (G2, n = 20) was carried out. Two types of esophagectomy was performed in the two groups: trans-thoracic and trans-hiatal procedures. Demographic aspects, complications and mortality were analyzed. Nutritional characteristics and, alcohol and tabacco consumption in the two groups were also studied. Results: Significant differences (P < 0.001) were found only concerning age (the mean age of G1 was 58 years-old, and of G2, 43 years-old) and gender (35 men and 5 women in G1, and 8 men and 11 women in G2). In relation to race, no diffference was found (P = 0.14). In G2, the diseases included: advanced stage megaesophagus (n = 10), caustic estenosis (n = 6), and iatrogenic lesion (n = 4). Body mass index and albumin presented no significant difference while that, when associated to alcohol and tobacco uses, G1 present higher values than G2 (P < 0.001). In G1, twenty trans-thoracic and twenty trans-hiatal procedures were performed. In G2, six trans-thoracic

P1.09.23: ANASTOMOTIC LEAK AFTER HAND-SEWN VERSUS LINEAR STAPLED INTRATHORACIC ESOPHAGOGASTRIC ANASTOMOSIS. Tomas Harustiak, Alexandr Pazdro, Martin Šnajdauf, Alan Stolz, Robert Lischke University Hospital Motol, Praha/CZECH REPUBLIC Background: Anastomotic leak after esophagogastrostomy is one of the most serious surgical complications of esophagectomy causing significant early postoperative morbidity and mortality. The aim of this study was to retrospectively compare the incidence and severity of postoperative leak after hand-sewn and linear stapled anastomosis after Ivor-Lewis esophagectomy for esophageal cancer. Methods: We performed a single-institutional retrospective analysis of consecutive series of transthoracic (Ivor-Lewis) esophagectomy patients operated between 2006–2012 for esophageal cancer. All patients had intrathoracic esophagogastric anastomosis either end-to-end hand-sewn (HS) or end-toside semi-mechanical (SM) using linear 45 mm endoscopic stapler depending on surgeon preference. Anastomotic integrity was rutinely examined on 7th postoperative day by means of esophagography with water-soluble contrast. In case of clinical suspicion contrast swallow was performed earlier in the postooperative course. Depending on radiographic appearance anastomotic leak was considered as contained (circumscript extralumination) or noncontained (free leakage of contrast to mediastinum or pleural cavity). Clinical condition in case of leak was judged according to physical signs and laboratory parameters as good or septic. According to the management of leak we distinguished conservative treatment (no oral nutrition with/without antibiotics) and interventional treatment (stent placement or drainage or re-operation).


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Results: There were 394 transthoracic esophagectomies with 135 hand-sewn and 259 stapled intrathoracic anastomoses. Anastomotic leak was detected in 53 patiens (13.4%). There was significantly lower incidence of over-all anastomotic leak after SM compared to HS (10% versus 20%, p = 0.006). Incidence of non-contained leak, leak associated with sepsis and leak requiring interventional treatment was not significantly different between SM and HS: 4,3% versus 6.7% (p = 0.30); 5% versus 7.4% (p = 0.34) and 5% versus 7.4% (p = 0.34), respectively. Postoperative mortality due to leak was also not significantly different between two groups: 1.2% after SM versus 2,2% after HS (p = 0.41).

P1.09.25: MINIMALLY INVASIVE ESOPHAGECTOMY: EXPERIENCE FROM A STARTING SINGLE CENTRE Luis Carlos Silva Corten1, Srdjan Rakic1, Pascal Steenvoorde2, Ewout A Kouwenhoven1 1 ZGT Almelo, Almelo/NETHERLANDS, 2MST Enschede, Enschede/ NETHERLANDS

Discussion: Semi-mechanical linear stapled end-to-side esophagogastric anastomosis was associated with significant reduction of incidence of anastomotic leak compared to hand-sewn end-to-end anastomosis. Decreased was especially the incidence of clinically favourable contained leak, whereas the incidence of septic leak and consequent mortality was not significantly changed. (Supported by IGA MZČR NT 12331-5.)

Methods: Between December 2010 and December 2013, 75 patients (60 male, 15 female) underwent a minimally invasive esophagectomy (MIE). All procedures consisted of a McKeown (55) or an Ivor Lewis approach (20) and were performed by two surgeons after proctorship program training, surrounded by a fixed nursing team. Thoracoscopic phase was performed in prone position. A gastric conduit was constructed during laparoscopic phase. Cervical anastomoses were manually sutured end-to-end, intrathoracic anastomoses were stapled side-to-side.

Disclosure: All authors have declared no conflicts of interest. Keywords: hand-sewn versus linear stapled anastomosis, Ivor-Lewis esophagectomy, anastomotic leak

P1.09.24: SURGERY OF SUPERFICIAL BASALOID CELL CARCINOMA OF THE ESOPHAGUS: A CASE REPORT Masaya Satake, Takeshi Shimakawa, Shinichi Asaka, Ryohei Nishiguchi, Asako Shimazaki, Kentaro Yamaguchi, Hajime Yokomizo, Kazuhiko Yoshimatsu, Takebumi Usui, Shunichi Shiozawa, Takao Katsube, Yoshihiko Naritaka Tokyo Women’s Medical University Medical Center East, Tokyo/JAPAN Background: Basaloid cell carcinoma originating in the esophagus is a rare disease classified as an epithelial malignancy. Compared with squamous cell carcinoma, basaloid cell carcinoma of the esophagus is generally associated with poor prognosis, involving extensive vascular invasion and causing extensive lymph node and hematogenous metastases. We report a case of surgically treated superficial basaloid cell carcinoma of the esophagus. Methods: A 69-year-old male patient with no chief complaint. An elevated lesion was found in the esophagus in the upper gastrointestinal contrast examination performed as part of the health checkup in January 2012. The patient was subsequently diagnosed with esophageal cancer based on an endoscopy performed at a nearby clinic and referred to our clinic in March 2012. Esophageal contrast examination: A 10 × 7 mm elevated squamous lesion was found at Lt. Esophageal endoscopy: A 10 mm diameter nodular, elevated lesion slightly dented at the center was found at 34 cm from the incisor. Biopsy: Tumor cells similar to poorly differentiated squamous cell carcinoma. Chest/abdominal CT: No lung, liver or lymph node metastasis. cStage I esophageal cancer (Lt, 0-IIa, T1b N0 M0) was diagnosed and surgically removed. Results: The surgical procedures included a right thoracolaparotomy followed by a subtotal excision of the esophagus, two regional lymph node dissection and anastomosis of the gastric tube to the esophagus via a upper intrathoracic route. The histopathology of the removed sample showed squamous cell carcinoma in the superficial epithelium and non-invaded part. The tumor cells had invaded the upper submucosal layer involving basaloid cell carcinoma. Based on the findings, superficial basaloid cell carcinoma of the esophagus was diagnosed (pT1b pN0 pM0 ly0 v0 pStage I). The patient had a good postoperative course and was discharged at about 3 weeks after surgery. No adjuvant chemotherapy has been performed. Currently at about 2 years postoperation, the patient is being followed up on an outpatient basis without recurrence. Discussion: Basaloid cell carcinoma of the esophagus is classified as an epithelial malignancy according to the Japanese Classification of Esophageal Cancer. It is a rare disease with an incidence of 0.068% of cases of resected esophageal cancer. It typically grows in the esophageal submucosa and advances with the formation of a large solid cancer nest. Most superficial cancer involves an elevated lesion covered with squamous epithelium that looks like submucosal tumor. A preoperative biopsy often fails to diagnose basaloid cell carcinoma as in this patient. Although the prognosis is considered poor, a prognosis comparable to regular esophageal cancer may be expected if the cancer is detected early. Long-term survival is hardly expected with advanced cancer, however. Survival for 2 years or longer has been reported in very few patients. Some studies reported patients treated for early stage esophageal cancer had recurrence in the liver and lymph nodes early postoperation, suggesting an advanced biological malignancy grade could be expected in some early cancer. Although this patient had superficial cancer with no lymph node metastasis, careful follow-up is considered necessary. Disclosure: All authors have declared no conflicts of interest. Keywords: superficial esophageal cancer, esophagectomy, basaloid cell carcinoma of the esophagus

Background: Surgical resection remains the gold standard for localized esophageal cancer. As a regional centre we report our starter’s experience with minimally invasive esophagectomy.

Results: Sixty-eight patients received neo-adjuvant chemoradiotherapy. Fifty-nine adenocarcinomas, 15 squamous cell carcinomas and 1 adenosquamous carcinoma were included. Median age was 65 (57–74). Mean operation time and blood loss were respectively 350 minutes and 157 ml. There were two conversions to laparotomy. Median ICU stay was 3 (3–5) days. Median hospital stay counted 11 (9–15) days. Most frequent peri-operative complications were pneumonia (26,7%), atrial fibrillation (17,3%), respiratory failure (10,7%), heart failure (4,0%). Surgical complications included anastomotic leakage (10,7%), chylothorax (4,0%), gastric conduit necrosis (2,7%), gastric conduit perforation (2,7%), temporary vocal cord paresis (2,7%). 2 patients deceased peri-operatively (2,7%). Seventy-three patients had a R0 resection, 2 patients R1. Mean lymph node harvest counted 17 nodes. Discussion: Although technically challenging, MIE can be carried out with reasonable operative times, minimal blood loss, a short length of hospital stay, a proper oncologic resection with thoracic lymphadenectomy and few complications, even when this procedure is newly implemented. Disclosure: All authors have declared no conflicts of interest. Keywords: esophagectomy, single centre, Minimally Invasive P1.09.26: THE INTENSE POSTOPERATIVE INFLAMMATORY RESPONSE CAUSES POOR SURVIVAL IN ESOPHAGEAL CANCER PATIENTS WHO UNDERWENT TRANSTHORACIC ESOPHAGECTOMY Satoru Matsuda, Hiroya Takeuchi, Hirofumi Kawakubo, Kazumasa Fukuda, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Yoshiro Saikawa, Tai Omori, Yuko Kitagawa Keio University School of Medicine, Tokyo/JAPAN Background: Transthoracic esophagectomy is one of the highly invasive surgeries and could induce postoperative inflammatory responses. Previously, the systemic inflammation was shown to facilitate angiogenesis or proliferation of cancer cells, leading poor prognosis in various solid tumors. The postoperative inflammatory response is usually induced by perioperative complications, including pneumonia and anastomotic leakage. However, in clinical practice, systemic inflammatory response was frequently obsereved without diagnosis of postoperative complications, and the prognosis of such patients remains to be elucidated. In this study, we revealed the intensity of the postoperative inflammation using C-reactive protein (CRP) and investigated the correlation with survival. Methods: We retrospectively reviewed 216 patients who underwent curative transthoracic esophagectomy in our institution between Janurary 2004 and December 2012. The postoperative serum CRP level during 14 days after esophagectomy was confirmed in 215 patients. We investigated patient charateristics, clinicopathological factors and surgical procedures. In terms of postoperative complications, the incidence of pneumonia and anastomotic leakage were evaluated. Based on Clavien-Dindo (C-D) classification, we diagnosed patients as pneumonia with higher than C-D grade 2 and as anastomotic leakage with higher than C-D grade 3. To evaluate postoperative inflammation using CRP, the timing of peak concentration of CRP in 14 days after surgery and the frequency of CRP elevation (>10 mg/dl) in 10 days after surgery were examined. Combining these indicators, patients who showed both delayed peak of CRP [postoperative day (POD) 3 or later] and longer duration of CRP elevation (longer than 5 days) were classified as high postoperative CRP group. Results: Mean age of patients was 63.1 years of age and 90% were male. In terms of location of primary tumor, 51% were located in middle thoracic esophagus. Ninety one percent of patients were diagnosed as squamous cell carcinoma. Distribution of postoperative pathological stage (pStage) of 0/1/2/3/4 was 0/70/58/66/16. The video assisted thoracoscopic esophagectomy was performed in 139 patients (65%). Regarding postoperative

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complications, 42 patients (20%) were diagnosed as pneumonia and 32 (15%) as anastomotic leakage. In postoperative course, the CRP level peaked out in POD 2 in 127 patients (59%), and 23% of patients showed elevated CRP level (>10 mg/dl) for longer than 5 days. Overall, 31 out of 215 patients (14%) were classified as postoperative high CRP group. In univariate analysis, advanced pStage and postoperative high CRP were correlated with poor overall survival (OS) significantly, but the incidence of postoperative pneumonia or leakage didn’t show negative impact on survival. In multivariate analysis, using Cox regression hazard model, pStage (P > 0.001) and postoperative high CRP level (HR: 2.180, P = 0.008) were shown to predict postoperative OS significantly.

P1.09.28: MEDIASTINOSCOPIC SUBAORTIC AND TRACHEOBRONCHIAL LN DISSECTION WITH A NEW CERVICO-HIATAL CROSSOVER APPROACH IN THIELEMBALMED CADAVERS Yutaka Tokairin, Kagami Nagai, Hisashi Fujiwara, Taichi Ogo, Masafumi Okuda, Yasuaki Nakajima, Kenro Kawada, Tomonori Suzuki, Akihiko Hoshino, Yutaka Miyawaki, Takuya Okada, Shunsuke Ohta, Tairou Ryoutokuji, Naoto Fujiwara, Katsumasa Saito, Keiichi Akita, Tatsuyuki Kawano Tokyo Medical and Dental University, Tokyo/JAPAN

Discussion: Postoperative high CRP level was remarkably correlated with overall survival after transthoracic esophagectomy. This indicator could include patients who were not diagnosed as postoperative complications but had postoperaive systemic inflammatory responses. In addition to multidisciplinary treatment which include chemotherapy and chemoradiotherapy, adequate postoperative managements which reduce postoperative inflammatory response might lead survival benefit in esophageal cancer patients.

Background: Cervical and abdominal procedures followed by thoracoscopic esophagectomy using the anterior phrenomediastinal approach (APMA) have been performed since 2000 for minimally invasive esophagectomy (MIE). The use of mediastinal surgery for MIE has been proposed; however, it is not performed as a radical surgical method because complete upper mediastinal dissection, including the left tracheobronchial lymph nodes (106tbL), is not feasible. We therefore developed a new method for complete dissection of the upper mediastinum.

Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, esophagectomy, Postoperative complication, Postoperative CRP

P1.09.27: LAPAROSCOPIC TOTAL GASTRECTOMY WITH MODIFIED D2 LYMPHADENECTOMY FOR TYPE III OESOPHAGO-GASTRIC JUNCTIONAL TUMOUR Polobody Sibaprasad Senapati Salford Royal Hospital, Manchester/UNITED KINGDOM Background: Video presentation showing the technical aspects of laparoscopic total gastrectomy with modified D2 lymphadenectomy for a type III oesophago-gastric junctional tumour. Methods: A 57years old male with oesophago-gastric junctional adenocarcinoma underwent staging investigations such as CT scan, pet-ct, eus and staging laparoscopy, which confirmed this as a T3N1M0 OG Junctional tumour. He then proceeded to receive 3 cycles of ECX neoadjuvant chemotherapy. Post chemotherapy CT showed the tumour had shrunk slightly. The patient developed weakness and further significant weight loss leading to a BMI of 15. He was considered not fit for major surgery by the preoperative anaesthetic and surgical assessment due to very low BMI and poor mobility. He received nutritional supplements by nasojejnunal feeding. In the subsequent 8 weeks he recovered from chemotherapy and gained weight leading to BMI of 21. He underwent CPEX (cardiopulmonary exercise testing) test, which was favourable, hence was reconsidered for major surgery. The operation was performed under general anaesthetic, using standard 5 ports (3 × 12 mm ports and 2 × 5 mm ports). The tumour was a mobile Type III junctional tumour with enlarged paraoesophageal nodes. The hiatal dissection was done first to mobilse the gastro-oesophageal junction. The dissection was extended into the mediastinum to include the paraoesphageal nodes in the lower third of the oesophagus. The highest paraoesophageal node visualised was sent for frozen section. This was negative for metastasis. An on-table gastroscopy was performed to assess the proximal extent of the tumour and assess the proximal resection margin. Having confirmed the feasibility of performing the procedure with good clearance, the rest of stomach was mobilized including the greater and lesser omentum. The left gastric artery and vein individually ligated and divided. The proximal resection was 4 cms above the OG junction. Distally the stomach was divided at the level of first part of duodenum. A modified D2 lymphadenectomy was performed. The Roux loop of jejunum formed 30 cms distal to the DJ flexure. A retrocolic stapled oesophago-jejunal anastomosis was performed with Orvil 25 mm circular stapling device. The roux-en-y jejuno-jejunostomy was performed 60 cms below the oesophago-jejunal anastomosis. The specimen was removed in a large specimen bag by extending the 12 mm camera port incision. The procedure took 7hours. The blood loss was 700 mls. The patient stayed for 48 hrs in high dependency ward and required 2 units of blood transfusion. Results: Postoperatively patient made steady recovery and was discharged home 10 days after surgery. The histology confirmed this as moderately differentiated adenocarcinoma T3N1 tumour with 1 lymph node involved out of 16 taken. This was a RO resection with clear margins. The patient continues to do well on regular follow-up and the last follow-up was 2 years ago. Discussion: Laparoscopic total gastrectomy has been performed with good outcome for gastric cancer. But we believe this is the first of its type for a type III oesophago-gastric junctional tumour. We conclude that laparoscopic total gastrectomy with modified D2 lymphadenectomy is a feasible operation in selective oesophagogastric junctional tumour patients. Disclosure: All authors have declared no conflicts of interest. Keywords: laparoscopic oesopagogastric junctional tumour

Methods: We developed a method for complete mediastinoscopic esophagectomy as radical surgery from the transcervical and transhiatal approach in five thiel-embalmed human cadavers. The cadavers were embalmed in a water-based solution containing salt with a small amount of formaldehyde for fixation, boric acid for disinfection, glycol, chlorocresol and ethanol. This precipitation results in tissue homogenization. The skin is life-like and the joints are fully flexible. Results: Procedures: ཰ Hand-assisted laparoscopic surgery (HALS) is used for gastric conduit mobilization. The pericardium, inferior bilateral pulmonary vein and inferior border of the carina tracheae and lymph nodes at the bifurcation (107) and left main bronchus (109L) are dissected. ཱ Open surgery on the left side is changed to the pneumomediastinum method after identifying the left recurrent nerve. The left subclavian artery and thoracic duct are exfoliated, and the dorsal side of left recurrent nerve is dissected up to the aortic arch. ི The right recurrent nerve is dissected. ཱི Using the pneumomediastinum method, the right recurrent nerve lymph nodes (106rR) are dissected. The esophagus is divided from the trachea. In the dissection of 106tbL, the front wall of the left main bronchus is dissected and initially depressed downward, obtaining a good view between the aortic arch and cartilage portion of the left bronchus. The 106tbL lymph nodes are dissected until the aortic arch is reached. Simultaneously, the 106tbL lymph nodes are dissected from the right cervical incision. This method is termed the “cross-over technique.” ཱུ Finally, the ventral side of the left recurrent nerve lymph nodes (106rL) is dissected. Discussion: It has traditionally been very difficult to dissect the 106tbL lymph nodes using the mediastinoscopic method because the mediastinal area is narrow and contains very important structures, including the bilateral main bronchus, recurrent nerve, aortic arch and pulmonary artery. Some reports have described methods for performing mediastinal esophagectomy, such as the use of an endodissector to eliminate “blind” mediastinal dissection or mediastinoscopy-assisted transhiatal esophagectomy (MATHE) with a mediastinoscope via the left neck. Another report employed the transcervical (left side only) approach with transhiatal esophagectomy using pneumomediastinum for either high-risk patients or for those with early esophageal carcinoma. However, complete dissection of the upper mediastinum, including the 106tbL lymph nodes, cannot be performed using these methods. We herein demonstrated that the upper mediastinum lymph nodes, including 106tbL nodes, can be dissected using the bilateral transcervical and transhiatal approach (cross-over technique) under pneumomediastinum. Mediastinoscopic esophagectomy with lymph node dissection (MELD) performed under pneumomediastinum using a bilateral transcervical and transhiatal approach is a useful modality based on our experience with thiel-embalmed human cadavers. Disclosure: All authors have declared no conflicts of interest. Keywords: Minimally Invasive Esophagectomy, Mediastinoscopic esophagectomy, Cross-over technique, Thiel P1.09.29: IVOR LEWIS ESOPHAGECTOMY AFTER NEOADJUVANT THERAPY: COMPARISON OF SHORT-TERM OUTCOMES WITH OPEN AND MINIMALLY INVASIVE TECHNIQUES Luis Tapias, Douglas Mathisen, Cameron Wright, John Wain, Henning Gaissert, Ashok Muniappan, Michael Lanuti, Dean Donahue, Christopher Morse Massachusetts General Hospital, Boston/MA/UNITED STATES OF AMERICA Background: Neoadjuvant therapy is integral in the treatment of locally advanced esophageal cancer. However, despite increasing acceptance of minimally invasive approaches to esophagectomy, there remain concerns


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about the safety and oncologic soundness in patients receiving neoadjuvant therapy. The aim of this study is to examine short-term outcomes in patients undergoing Ivor Lewis esophagectomy after neoadjuvant therapy by open (Open) and minimally invasive (MIE) approaches.

to provide favorable outcomes regarding survival. This effect could probably be enhanced with the concurrent application of neoadjuvant treatment.

Methods: Retrospective review of 130 patients with esophageal cancer undergoing Ivor Lewis esophagectomy with curative intention after neoadjuvant therapy at a tertiary academic center between 2008–2012.

Keywords: Esophageal cancer, esophagectomy

Results: Seventy-four (56.9%) patients underwent an open procedure while 56 (43.1%) had MIE. There were no significant differences in baseline characteristics among groups, except patients in the open group had a higher rate of previous abdominal surgery (36.5% vs. 14.3%, p = 0.004). Esophageal cancer staging distribution was similar with the majority of patients presenting with stage IIB and IIIA disease. All patients received chemotherapy, while 93.2% and 85.7% of patients in the open and MIE groups received radiotherapy, respectively (p = 0.237). There were no conversions to open with MIE. A pyloric drainage procedure was performed in 13.5% of patients having an open operation and in none of those having MIE (p = 0.005). There was a trend towards shorter overall surgical time with MIE (337.4 ± 48.3 vs. Open: 361.6 ± 83.1min, p = 0.055), which was the result of significantly shorter times during the thoracic portion of the operation (152.8 ± 26.9 vs. Open: 179.7 ± 47.1min, p = 0.0005). Median estimated blood loss was reduced in the MIE group (200cc [IQR 140–200] vs. 250cc [150–400], p = 0.0003). MIE patients had a shorter median stay in the ICU (p = 0.002), shorter duration of nasogastric drainage (p < 0.0001), underwent a routine contrast swallow earlier (p < 0.0001) and initiated oral intake faster (p < 0.0001). Hospital length of stay was shorter a median of 2 days in the MIE group (p < 0.0001), with a similar proportion of patients being discharged home when compared to open (p = 0.557). There were no significant differences in the overall occurrence of postoperative complications (open: 54.8% vs. MIE: 41.1%, p = 0.155). However, there was a significant reduction in observed pulmonary complications in patients after MIE (8.9% vs. Open: 29.7%, p = 0.004). Leak rate was similar (Open: 1.4% vs. MIE: 0%, p = 1.000). Mortality at 30 and 90 days was comparable (Open: 2.7% and 4.1% vs. MIE: 0% and 1.8%, p = 0.506 and p = 0.634, respectively). The rate of R0 resections was similar (Open: 98.7% vs. MIE: 100%, p = 1.000) as was the median number of harvested lymph nodes (Open: 20 [14–25] vs. MIE: 20 [16–25], p = 0.378).

P1.09.31: EUROPEAN EXPERIENCE: TECHNIQUE AND SHORTTERM OUTCOME OF MINIMALLY INVASIVE IVOR LEWIS ESOPHAGEAL RESECTION FOR DISTAL ESOPHAGEAL AND GASTRO-ESOPHAGEAL JUNCTION CANCERS Jennifer Straatman1, Kirsten Maas1, Joseph Roig2, Miguel Cuesta1, Suzanne Gisbertz3, Camiel Rosman4, Surya Biere1, Donald Van Der Peet1 1 VU Medical Centre, Amsterdam/NETHERLANDS, 2Hospital de Girona de Josep Trueta, Girona/SPAIN, 3Academic Medical Center Amsterdam, Amsterdam/NETHERLANDS, 4Canisius-Wilhelmina Hospital, Nijmegen/ NETHERLANDS

Discussion: MIE proves its safety after neoadjuvant therapy as it leads to significant reductions in estimated blood loss, ICU stay, hospital stay, duration of nasogastric drainage and time to initiation of oral intake while resulting in a decreased rate of postoperative pulmonary complications. Open and MIE appear equivalent with regards to perioperative oncologic outcomes following neoadjuvant therapy. Long-term oncologic outcomes need to be investigated. Disclosure: All authors have declared no conflicts of interest. Keywords: esophagectomy, Video-assisted thoracic surgery, Minimally Invasive, Esophageal cancer P1.09.30: SURGICAL TREATMENT OF ESOPHAGEAL CANCER, IS THERE ROOM FOR IMPROVING OUTCOME? RESULTS OF AN INDIVIDUALIZED PROTOCOL Dimitrios Theodorou, Georgia Doulami, Stamatina Triantafyllou, Nikolaos Tsagaropoulos, Eleftheria Kleidi, Nikolaos Memos, Stulianos Katsaragakis, Georgios Zografos University of Athens, Athens/GREECE Background: The extent of surgery and lymphadenectomy in surgical treatment of esophageal cancer (EC) between transhiatal esophagectomy with 1-field lymphadenectomy (THE-1FL) and transthoracic esophagectomy with 2-field lymphadenectomy (TTE-2FL) is still controversial. We evaluated the effect of optimal patient’s selection through individualized criteria for submission to each procedure, on patients’ overall survival. Methods: All patients with EC referred to our foregut surgical department were prospectively enrolled in a database. From January 2006, a protocol of individualized surgical treatment of EC (PISTEC) is applied to all patients with resectable disease. PISTEC is based on patient’s physical status (PO2 < 50 mmHg, PCO2 > 50 mmHg, FEV1 < 1L, ejection fraction 3) and disease stage, with intent to select the appropriate surgical procedure (THE-1FL vs TTE-2FL) for each patient. Results: Individualized surgical treatment according to PISTEC was applied on 61 patients with EC. Of them, 52.4% were submitted to THE-1FL and 31.1% to TTE-2FL. The 30-day mortality rate was 4.9% (n = 3). Mean follow up time was 49.5 months. The 5-year overall survival rate was 55.7% and recurrence was observed in 33.3% of patients. The estimated overall 5-year survival of patients with stage 0, I, II, III and IV was 100%, 100%, 85.7%, 45.8% and 0%, respectively. Discussion: The proposed algorithm aims at balancing perioperative risks and oncological benefit. Individualization of surgical treatment of EC seems


Background: Esophagectomy can be performed by a two-stage procedure with intrathoracic anastomosis, the Ivor Lewis esophagectomy. The increasing incidence of distal carcinomas of the esophagus and the esophagogastric junction induce more interest in this Ivor Lewis esophagectomy. Also minimally invasive procedures are increasingly being implemented in order to reduce postoperative complications. The study reported in this artivle involved a multi-centre analysis of minimally invasive Ivor Lewis esophagectomy for achieving short term results. Methods: During the period of 2010–2013, 103 patients in five different centers underwent minimally invasive Ivor Lewis esophagectomy for distal resectable cancer. Results: Most important complications were pulmonary complications (16%) and anastomotic leakage (15%) with or without thoracic empyema. Anastomotic leakage only occured after using the transoral stapler technique. Mortality rate was 2%. Discussion: Though Ivor Lewis minimally invasive esophagectomy is increasingly implemented, important problems remain. Questions arise how to standardize the operative technique and most important the type od anastomosis and therefore decreasing the rate of anastomotic leakage. Nonetheless, we recognize the advantage of starting the operation abdominally and keeping a long segment of the patient’s own esophagusas worthy reason for continual improvement. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, gastro-esophageal junction cancer, Minimally Invasive, Ivor Lewis esophagectomy P1.09.32: LONG-SEGMENT PEDICLED JEJUNAL FLAP WITH THE USE OF VASCULAR ANASTOMOSIS FOR THORACIC ESOPHAGEAL RECONSTRUCTION Hitoshi Kawasaki1, Naoki Wajima2, Akitoshi Kimura2, Harue Akasaka2, Nobukazu Watanabe1, Masaaki Endo1, Kenichi Hakamada2 1 Aomori City Hospital, Aomori/JAPAN, 2Hirosaki Graduate School of Medicine, Aomori/JAPAN Background: When the stomach is unavailable, the colon or jejunum is used as a substitute for reconstruction of the thoracic esophageal cancer operation. However, the frequency of anastomotic leakage and stenosis is high because of the limitations of the mesenteric blood supply. To overcome this disadvantage, we have extended the jejunum upward and positioned it with the aid of microvascular anastomosis. Methods: The proximal portion of the jejunum is extracted, and the appropriate vessel for anastomosis are identified. After test clamping of two to three mesenteric vessels proximal to this pedicle, mesenterium and an arcade between the first and second oral jejunal vessels are divided, then the jejunum is divided. The anterior chest wall is dissected as far as the midclavicular line. Three centimeter lengths of the second and third costal cartilages are resected, and pedicle of internal thoracic artery and vein are dissected. The second jejunal artery and vein are divided. The conduit is then brought through the chest in a posterior mediastinal position. A microvascular anastomosis is then performed. The esophagojejunal anastomosis is performed. Results: During the 5-year period, 10 patients were selected for this method. No vessel obstruction was detected, and the extended jejunums survived completely. Only one patient had an esophagojejunal anastomotic leak that healed spontaneously. Discussion: We believe that the extended jejunum with the aid of microvascular anastomosis is a good thoracoesophageal substitute, especially in the case of patients whose stomach cannot be used. Disclosure: All authors have declared no conflicts of interest. Keywords: Long-segment pedicled jejunal flap, vascular microanastomosis, Esophagogastrectomy

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P1.09.33: IT IS BENEFICIAL TO INCORPORATE LAPAROSCOPIC PROCEDURE INTO MINIMALLY INVASIVE ESOPHAGECTOMY Xiaoxia Jiang1, Hao Wang2, Yaxing Shen2, Mingxiang Feng2, Zongwu Lin2, Wei Jiang2, Lijie Tan2, Qun Wang2 1 Shanghai Punan Hospital, Shanghai/CHINA, 2Zhongshan Hospital, Fudan University, Shanghai/CHINA Background: The benefit of using the laparoscopic approach in minimally invasive esophagectomy (MIE) is still controversial. We therefore performed this study to compare the clinical outcomes of patients with esophageal cancer who underwent thoracoscopic MIE incorporating laparoscopy or laparotomy. Methods: Patients with esophageal cancer undergoing thoracoscopic threeincision minimally invasive esophagectomy with laparoscopy (n = 94) or laparotomy (n = 57) between 2011 and 2012 were analyzed from a prospective maintained database in our institution. Results: No significant difference was observed between the two groups in demographics. There was no significant difference on number of abdominal lymph nodes harvested, hospital stay, 30-d mortality, total rate of complications. The laparoscopy group had significantly less abdominal operative times (53.6 ± 18.9min vs 74.8 ± 19.0min, P < 0.001), less abdominal blood loss (38.7 ± 19.9ml vs 81.8 ± 40.7ml, P < 0.001), less abdominal wound infection (0 vs 5.26%, P = 0.025), less pulmonary complication (9.6% vs 17.5%, P = 0.152), earlier median time of ambulation (76.5h vs 116.5h, P = 0.039) and less complain of abdominal pain. Discussion: The utility of laparoscopic procedure in MIE might provide benefit by facilitating postoperative recovery and reducing the rates of pulmonary complications. However, further randomized controlled trials are required to confirm these findings. Disclosure: All authors have declared no conflicts of interest. Keywords: Laparoscopic Procedure, Minimally Invasive Esophagectomy P1.09.34: ARTIFICIAL PNEUMOTHORAX DURING MINIMALLY INVASIVE ESOPHAGECTOMY Yuichiro Kume, Yosuke Izumi, Kei Sakamoto, Yoshinori Kohira, Akinori Miura, Tsuyoshi Kato Cancer and Infectious Diseases Center Komagome Hospital, Tokyo/JAPAN Background: Minimally invasive esophagectomy (MIE) for esophageal cancer is increasingly being used with increasing skills and experience and advances of endoscopic technology such as high-resolution endoscopic system. The surgical requirement for thoracoscopic esophagectomy is a good view of the mediastinum. The esophagus is at the bottom of the operative field when the patients is in the left lateral decubitus position. The view tends to be obscured by the lung especially when approaching the lower mediastinum. Artificial pneumothorax (AP), insufflating carbon dioxide gas (C02), actively promotes lung collapse either during two-lung ventilation or one-lung ventilation. Older studies demonstrated negative hemodynamic effects on animals. Complications are clinically insignificant if C02 is used judiciously. Bilateral AP happens during MIE, but there has been no study on hemodynamic effect due to bilateral AP. Methods: The aim of this study is to investigate the efficacy and safety of AP during MIE and also investigate optimum anesthesia during AP or bilateral AP. Methods: Our current technique consists of laparoscopic gastric dissection under pneumoperitoneum, laparoscopic transhiatal dissection of the middle and lower thoracic esophagus under bilateral AP and a right thoracoscopic approach for mobilization of the intrathoracic esophagus and lymph node dissection in the paratracheal region under AP. 9 cases underwent MIE between January 2011 and January 2012 under AP using C02 at 8–10 mmHg. The end-tidal C02 pressure, arterial oxygen saturation, arterial pressure and heart rate were monitored. Peak inspiratory pressure (PIP), tidal volume and respiration rate were recorded. Measurements were determined at base line, at the time approaching the middle mediastinum under bilateral AP (pneumoperitoneum), at the initiation of one-lung ventilation and at the end of one-lung ventilation under AP. Results: The insufflation of C02 of 8–10 mmHg had significant effect on the end-tidal C02 pressure, arterial pressure and heart rate. Mean arterial pressure had a trend to decrease from 72 mmHg to 64.9 mmHg. Mean PIP significantly rose from 14.4 mmHg to 21.8 mmHg. Minute volume was required to raise up to 11% over usual volume during bilateral AP. Both lung were collapsed from laparoscopic view and membranous part of trachea caved in from thoracoscopic view during increased airway pressure, so barotraumas could not possibly happen even though airway pressure significantly rose. Hypercapnea over 60 mmHg was noted in 3 cases (33%). Subcutaneus emphysema was noted in 3 cases (33%). Discussion: Artificial pneumothorax with C02 during MIE did not have adverse hemodynamic effects in the clinical setting. Further investigation is required.


Disclosure: All authors have declared no conflicts of interest. Keywords: artificial pneumothorax, Minimally Invasive Esophagectomy P1.09.35: COMPARISON OF THE SURGICAL PROCEDURE AND SHORT TERM RESULTS OF THORACOSCOPIC ESOPHAGECTOMY IN THE LEFT LATERAL DECUBITUS POSITION AND IN THE PRONE POSITION FOR THE PATIENTS WITH THORACIC ESOPHAGEAL CANCER. Takashi Kamei1, Go Miyata2, Toru Nakano1, Shigeo Abe3, Kazunori Katsura3, Tadashi Sakurai3, Makoto Hikage3, Jin Teshima3, Hiroshi Okamoto4, Noriaki Ohuchi3 1 Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai/JAPAN, 2Tohoku University, Sendai/JAPAN, 3Tohoku University Graduate School of Medicine, Sendai/JAPAN, 4Tohoku University Hospital, Sendai/JAPAN Background: Traditional esophagectomy with thoracotomy for esophageal cancer is a highly invasive surgery. Over the last few decades, video assisted thoracoscopoic surgery for thoracic esophageal cancer has been spread with a minimally invasiveness, acceptable feasibility and good outcomes. We also undergo thoracoscopic esophagectomy and mediastinal lymphadenectomy as a standard procedure for resectable esophageal cancer patients. In recent years, the benefits of thoracoscopic esophagectomy in the prone position have been reported. We compared the surgical procedures and operative outcomes in patients who underwent thoracoscopic esophagectomy in the prone position or in left lateral position. Methods: Between November 2011 and August 2013, 42 patients in lateral position (group A) and 49 patients in prone position (group B) were undergone thoracoscopic esophagectomy. Back ground of patients was not different significantly. In group A, esophagectmy was performed under one-lung ventilation, and an assistant displaced right lung to maintain the operation field. We performed operation under two-lung ventilation with artificial pneumothorax by CO2 gas insufflation in group B. Both group underwent the reconstruction following esophago-gastric anastomosis at the neck. We retrospectively reviewed the perioperative clinical data including operation time, blood loss, pulmonary complication rate and hospital stay. Results: Blood loss was significantly lower in group B than in group A (38.7ml vs 215ml, P < 0.01). Pulmonary complication frequency was lower in group B than in group A (4% vs 21%) and also SIRS after surgery was rapidly improved in group B than in group A. Hospital stay was tend to shorter in group B. We had no experience of an emergent convert into thoracotomy in group B. Discussion: Thoracoscopic esophagectomy in the prone position may reduce the pulmonary complication and surgical invasiveness. This could be a standard procedure of minimally invasive surgery for esophageal cancer. Although in case of borderline resectable disease, it is better to choice the lateral position because of possibility of conversion into thoracotomy. Furthermore, we consider that it is important to simulate an emergency conversion from prone position into lateral position by major bleeding or unexpected organ injury. Disclosure: All authors have declared no conflicts of interest. Keywords: Prone position, pulmonary complication, Thoracoscopic esophagectomy P1.09.36: A 6 YEAR SERVICE REVIEW OF PRE-OPERATIVE DIETETIC INPUT FOR PATIENTS UNDERGOING OESOPHAGEAL RESECTION AT A REGIONAL UNIT Fiona Macharg, Alice Kidd, Emma Westmancoat, Shaun Preston Royal Surrey County Hospital, Guildford/UNITED KINGDOM Background: Oesophageal cancer patients frequently present with nutritional deficiencies. In order to limit complications from surgery and optimise recovery it is important to ensure patients are well nourished prior to surgery. At the Regional Oesophago-Gastric Unit in Guildford, UK 2.4 full time specialist dietitians are dedicated to ensuring all patients referred to the unit are nutritionally optimised. Surgical patients are assessed on diagnosis and receive intensive nutritional input during their neo-adjuvant treatments and throughout their surgical pathway. Methods: We carried out a service review to audit the level of nutritional input required by our surgical patient group. Data was collected on all patients who underwent oesophageal resection for cancer of the oesophagus or oesophago-gastric junction between January 2008 and December 2013. Patients were excluded if they had their neo-adjuvant treatment outside of the unit or who went straight to surgery and therefore not assessed or advised locally. Results: 236 patient records were reviewed (34 excluded). The review demonstrated that a variety of nutritional interventions were required for this patient group to ensure nutritional status was optimised prior to surgery.

ABSTRACT SUPPLEMENT


18% (range 0–29) where asymptomatic and only required advice to ensure healthy eating principles were followed and weight maintenance achieved. 62% (range 47–86) were able to meet their nutritional requirements following advice on texture modification and food fortification (32%, range 21–55) and using oral nutritional supplements (30%, range 26–38). However, an average 15% (range 10–20) of patients a year required enteral nutrition support via either naso-enteral or surgical jejunostomy. We also noticed an increasing incidence of obesity and more patients required advice on calorie restricted diets based on healthy eating principles to encourage healthy weight loss (increased from 0% to 8% in past 7 years). Discussion: This is a complex patient group who require specialist assessment and tailored advice from an experienced oesophago-gastric dietitian in order to optimise their nutritional status prior to surgical resection. Disclosure: All authors have declared no conflicts of interest. Keywords: pre-operative Oesophagectomy

optimisation,

nutrition

support,

dietitian,

P1.09.37: TIPS AND TRICKS REQUIRED FOR VIDEO ASSISTED UPPER MEDIASTINAL LYMPHADENECTOMY BY CERVICAL APPROACH Kazuhiko Mori, Yukinori Yamagata, Susumu Aikou, Yasuyuki Seto The University of Tokyo Graduate School of Medicine, Tokyo/JAPAN Background: To avoid thoracotomy related surgical complications, non transthoracic approach for esophageal cancer has been developed and attempted. Transcervical lymph dissection extending its dissection area into the upper mediastinal field has been also reported. However, frequent occurrence of the recurrent laryngeal nerve (RLN) palsy remarkably limits its potential utility. We have overcome this technical obstacle and succeeded in retrieving a comparable number of lymph nodes without increasing recurrent nerve palsy. Methods: Through an 8 cm collar incision, a 30 degree angle endoscope, long bladed retractors and other surgical devices are applied. Lymph nodes along the left RLN are dissected en bloc with RLN and esophagus from the adjacent structures. We have performed a totally non transthoracic esophagectomy with oncologically radical intention for thirty-four esophageal cancer patients. In the esophagectomy for this series of patients, the video assisted transcervical procedure was combined with robotic transhiatal surgery.

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P1.09.38: THE ANNUAL RISK OF POST-OPERATIVE VITAMIN & MINERAL DEFICIENCIES FOLLOWING OESOPHAGEAL AND GASTRIC CANCER SURGERY Alice Kidd, Fiona Macharg, Emma Westmancoat, Shaun Preston Royal Surrey County Hospital, Guildford/UNITED KINGDOM Background: Oesophagectomy (OG) and total gastrectomy (TG) are radical surgical treatments that may cure upper gastrointestinal carcinomas. Patients who have undergone these procedures are at risk of developing vitamin and mineral deficiencies (VAMD) due to altered anatomy, malabsorption, reduced nutritional intake and the effects of chemotherapy. Although we currently recommend that all post-operative patients take a daily complete multivitamin and mineral supplement, micronutrient levels are not routinely monitored unless symptomatic. An audit was carried out to monitor micronutrient levels in patients ≥12 months post-surgery and how rates of deficiency change over time. Methods: All patients attending the surgical outpatients clinic between October 2013 and April 2014 who had undergone either an OG or TG ≥ 12 months ago were selected. Each patient had a blood sample taken and the number of months post-surgery, nutritional supplementation and their use of pancreatic enzyme replacement therapy (PERT) recorded. Results: 82 subjects (71 post-OG and 11 post-TG) 12–90 months postsurgery, mean age 65 years (range 41–80 years). 37% patients were taking regular multivitamin and mineral supplement and 9% PERT. Deficiency was identified for iron (17%), serum ferritin (27%) and iron saturation (38%). Vitamin D was the only deficient fat soluble vitamin (82%). Mineral deficiencies were found in zinc (51%), selenium (39%) and calcium (10%). The percentage of patients deficient in iron, ferritin and the iron saturation rates increased with time, whilst deficiencies in selenium and calcium were highest 12–24 months post-surgery then declined slightly. Zinc and vitamin D deficiency remained high throughout. Discussion: VAMD was higher in this patient group than in the general UK population for ferritin, haemoglobin and vitamin D. Deficiencies were identified for selenium and zinc compared to reference levels, although no UK comparisons are available. Over time deficiencies relating to iron and iron storage increased. Patients appear to be at risk of becoming deficient in certain vitamins and minerals and may benefit from monitoring and supplementation to prevent long term effects on health and quality of life. Disclosure: All authors have declared no conflicts of interest. Keywords: Nutritional Deficiency, Surgery, Vitamin, Longterm P1.09.39: INITIAL EXPERIENCES OF AN ENHANCED RECOVERY PROTOCOL FOR MINIMALLY INVASIVE ESOPHAGECTOMY Daniel Pirchi, Roberto Cerutti, Matias Mihura, Leonardo Pankl, Gustavo Lyons Hospital Britanico de Buenos Aires, BUENOS AIRES/ARGENTINA Background: The implementation of enhanced recovery after surgery (ERAS) protocols decrease morbidity and duration of stay after colorectal surgery. The experience of ERAS in patients undergoing esophageal surgery has been minimal. No study has analyzed their role in minimally invasive, laparoscopic and thoracoscopic, esophagectomy (MIE). This study assessed the feasibility of a protocol-driven written clinical pathway for multidisciplinary perioperative management after MIE and examined the determinants affecting protocol compliance.

Results: A median of 13 (ranges 4 to 34) upper mediastinal lymph nodes were retrieved. Eight of the thirty four patients had metastatic node in the upper mediastinum. One patient required tracheotomy for the bilateral RLN palsy and two patients developed left unilateral palsy requiring hospital stay more than 20 days. We here illustrate the tips and tricks of this procedure. Discussion: A comparable number of lymph nodes along the left RLN could be retrieved by transcervical video assisted surgery with low incidence of RLN palsy. Disclosure: All authors have declared no conflicts of interest. Keywords: video assisted surgery, transcervical, upper mediastinal dissection, recurrent laryngeal nerve

Methods: Patients undergoing MIE from 2009 to 2013 were identified from a prospectively maintained database. All patients were enrolled in a 6-days ERAS protocol including preoperative nutrition, epidural analgesia, fluid restriction management, and structured early mobilization, diet and drain management. Compliance to protocol was registered and the causes of failure were analyzed. Satisfaction surveys were done at the time of hospital discharge and 2 weeks after surgery. Results: We identified 38 patients who underwent MIE with ERAS protocol. Only 20 of them had jejunostomy. Six patients (15,7%) had major complications, which included 3 anastomotic leaks (detected before oral intake). These patients were excluded of the protocol. Other 7 patients had minor complications (Clavien I-II); total in-hospital morbidity 34,2%. Complications could not be attributed to ERAS protocol. Median hospital stay was 8 days (6–25). Neither required readmission but 5 had late complications, 2 of them related to jejunostomy. Of the 32 patients without complications or with minor complications the median hospital stay was 6 (6–9). These patients were the study group for compliance. Ten patients (31,2%) had a protocol delay of 1 day. Compliance was 93,7% for 3-days-epidural analgesia, 68,7% for early mobilization, 81,2% for early oral intake (liquids on POD4), 43,7% for semisolids on POD5 and 71,8% for hospital discharge on POD6. Aside from major complications, other factors influencing the compliance to protocol were analyzed. Age over 70 years and avoiding jejunostomy were factors that had a negative influence on compliance and duration of stay. All other factors analyzed (ASA, smoking, tumor location,

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histology, stage, neoadjuvant therapy and total vs subtotal MIE) were not significant. Ninety-three percent reported excellent satisfaction with their hospital stay and discharge. Discussion: MIE allow ERAS management with early mobilization (walk on POD2), oral intake on POD4 and hospital stay of 6 days. The compliance to protocol of 71,8% and 93% excellent satisfaction show the importance of the multidisciplinary team committed to the structured clinical written pathway. Major complications and age over 70 are the most important factors against protocol compliance and hospital stay. Jejunostomies allow early feeding and discharge but are associated with its own complications. Disclosure: All authors have declared no conflicts of interest. Keywords: postoperative care, hospital stay, Minimally Invasive Esophagectomy, Enhanced Recovery P1.09.40: VIDEO-ASSISTED THORACOSCOPIC AND LAPAROSCOPIC ESOPHAGEAL SURGERY FOR THORACIC ESOPHAGEAL CANCER Hisayuki Matsushia, Akio Kaito, Tomoka Mizuguchi, Hideaki Shimizu Tochigi Cancer Center, Utsunomiya City/JAPAN Background: Video-assisted thoracoscopic surgery (VATS) spread for minimally invasive surgery not only in Japan, but around the world as well. We performed thoracic mobilization of the esophagus in the prone position and laparoscopic reconstruction with gastric roll as a minimally invasive esophagectomy (MIE) in cases of thoracic esophageal cancer since 2009. The aim of this study was to evaluate the feasibility and efficiency of thoracoscopic esophagectomy following laparoscopic reconstruction. Methods: 22 consecutive operations were performed between September 2009 and January 2014. Operative time, estimated blood loss, and complications were evaluated. Results: Mean operative time was 698 min (range 518–1044). There were no cases of conversion to open surgery. Mean blood loss was 196 g (range 55–592). Paralysis of recurrent laryngeal nerve occurred in two cases. Minor leakage occurred in one case. All patients were able to walk the day after the operation and there was no pneumonia after surgery. On the other hand, our rate of paralysis of recurrent laryngeal nerve and leakage were 8% by open method. Discussion: MIE is a feasible and safe surgical procedure with reduced invasiveness compared to conventional esophagectomy, although the operation takes a long time. Disclosure: All authors have declared no conflicts of interest. Keywords: Surgery, video-assisted thoracoscopic surgery, Esophageal cancer, Minimally Invasive Esophagectomy P1.10.01: MICROVESSEL DENSITY IN SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA USING ANTICD34 AND ANTI-CD105 ANTIBODY Youichi Kumagai1, Jun Sobajima1, Morihiro Higashi2, Toru Ishiguro1, Minoru Fukuchi1, Keiichiro Ishibashi1, Hiroyuki Baba1, Erito Mochiki1, Tatsuyuki Kawano3, Hideyuki Ishida1 1 Saitama Medical Center, Kawagoe, Saitama/JAPAN, 2Saitama Medical Center, Saitama Medical University, Saitama/JAPAN, 3Tokyo Medical and Dental University, Tokyo/JAPAN Background: The esophagus is the only organ where changes in the superficial microvasculature from normal squamous epithelium to invasive cancer are evident by magnifying endoscopy. We investigated in detail the features of angiogenesis in early-stage esophageal cancer using CD34 and CD105 immunostaining, and also the correlation between angiogenesis and inflammatory cell infiltration. Methods: Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia, and 45 samples of superficial esophageal cancer (M1: 12 lesions, M2: 7 lesions, M3: 7 lesions, SM1: 5 lesions, SM2: 3 lesions, SM3: 11 lesions), we determined the MVD at hot spots showing positive staining for CD34 and CD105. We observed the histological features of CD34- and CD105-positive microvessels that corresponded to observations made by magnifying endoscopy. We then investigated the correlation between microvessel density (MVD) and each histological situation (normal, low grade intraepithelial neoplasia, M1 and M2 cancer, M3 or deeper cancer) or the grade of inflammatory cell infiltration (Class 1: inflammatory cell infiltration absent or weak. Class 2: aggregates of inflammatory cells present, but no evident follicle formation. Class 3: inflammatory cell infiltration with follicle formation. Class 4: Severe and diffuse aggregation of infiltrated inflammatory cells). Results: The histological features of CD34- and CD105-positive microvessels were able to explain the morphological changes in the microvasculature during cancer progression observed by magnifying endoscopy. MVD assessed on the basis of CD34 or CD 105 positivity, being lowest for normal squamous


epithelium, followed in ascending order by LGIN, M1-M2 cancer, and M3 or deeper cancer, and the correlation was significant but weak (P < 0.001 rS = 0.51, P < 0.001 rS = 0.76, respectively). Correlations between CD105-positive MVD and CD34-positive MVD demonstrated a significant but weak correlation (P = 0.003, rs = 0.38). Inflammatory cell infiltration at CD105 hot spots was most frequent in M1 and M2 cancer (94.7%). The CD105-positive MVD increased in the order of inflammatory cell infiltration grade 1 through 4, and the correlation was significant (P < 0.001 rS = 0.49). Discussion: We have previously reviewed and reported the profiles of angiogenic factors at the early stage of progression of esophageal squamous cell cancer, and proposed a hypothesis of ‘multi-step angiogenesis’ in early-stage esophageal squamous cell carcinoma. The MVD based on CD34 and CD105 immunostaining can be used to corroborate observations of superficial esophageal squamous cell carcinoma made by magnifying endoscopy. Inflammatory cell infiltration may play an important role in angiogenesis at the early stage of cancer progression. Disclosure: All authors have declared no conflicts of interest. Keywords: angiogenesis, microvessel density, Esophageal cancer, squamous cell carcinoma P1.10.02: PROGNOSTIC IMPORTANCE OF THE MITOSIS SPECIFIC MARKER ANTI-PHOSPHOHISTONE H3 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA Shingo Nakashima, Atsushi Shiozaki, Daisuke Ichikawa, Hitoshi Fujiwara, Shuhei Komatsu, Hirotaka Konishi, Ryo Morimura, Yasutoshi Murayama, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Masayoshi Nakanishi, Kazuma Okamoto, Chouhei Sakakura, Eigo Otsuji Kyoto Prefectural University of Medicine, Kyoto/JAPAN Background: Mitosis counting is a traditional and practical method to determine proliferative activity. Recently, the immunohistochemical staining of phosphohistone H3 (PHH3) has been reported to facilitate mitosis counting and predict the prognosis of different tumors. However, it has not been evaluated in esophageal squamous cell carcinoma (ESCC). The aims of this study were to evaluate the prognostic impact of PHH3 and compare the results with clinicopathological features. Methods: The number of anti-phophohistone H3-positive nuclei (PHH3 mitotic index (MI)) was calculated by immunohistochemistry in 50 primary tumor samples obtained from ESCC patients who underwent curative esophagectomy. Results: The PHH3 MI per 10 high-power fields (HPF) ranged from 1 to 72 (median: 15.5). When the patients were divided into 2 groups using a cut-off value of 10, the 5-year survival rate of the patients with PHH3 MI ≤ 10 was 88.2%, which was significantly higher than that of the patients with PHH3 MI > 10 (54.4%). The percentage of differentiated SCC was significantly higher among the patients with PHH3 MI ≤ 10 (94.4%) than among the patients with PHH3 MI > 10 (59.4%). No correlation was found between PHH3 MI and the Ki-67 or p21 LI. Multivariate analysis indicated PHH3 MI to be an independent prognostic factor, as were pN categories. Discussion: The expression of PHH3 is correlated with histological type and impacts the prognosis of patients with ESCC. Disclosure: All authors have declared no conflicts of interest. Keywords: phosphohistone h3, Esophageal cancer, prognostic factor P1.10.03: METACHRONOUS ESOPHAGEAL SQUAMOUS CELL CANCER AFTER GASTRECTOMY FOR GASTRIC CANCER Hironori Sakita1, Hiroshi Okumura2, Sumiya Ishigami2, Yasuto Uchikado2, Takaaki Arigami2, Yoshikazu Uenosono2, Yuko Kijima2, Tetsuhiro Owaki2, Hiroyuki Shinchi2, Shinichi Ueno2, Shoji Natsugoe2 1 Izumi Regional hospital, Akune/JAPAN, 2Kagoshima University, Kagoshima/JAPAN Background: The clinical and biological characteristics of metachronous esophageal squamous cell cancer (ESCC) after gastrectomy for gastric cancer have yet to be sufficiently elucidated. The aim of the present study was to examine carcinogenesis in such patients. Methods: Subjects comprised 11 patients with metachronous carcinoma in whom ESCC occurred after gastric cancer (metachronous ESCC), 9 patients with simultaneously occurring gastric cancer and ESCC (simultaneous ESCC) and 52 patients with ESCC alone. We investigated the clinicopathological findings and biological properties using p53, p21 and cyclin D1 expression. Results: The positive rate for the intraepithelial spread of tumor was higher for metachronous ESCC than for simultaneous ESCC (p\0.05). The number of dysplastic lesions in metachronous ESCC, simultaneous ESCC and ESCC alone was 56, 41 and 44, respectively. The rate of positive p53 expression in dysplasia was significantly higher for metachronous ESCC than for ESCC alone (p = 0.03).


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Discussion: Positive expression of p53 was found in not only the primary tumor, but also intraepithelial neoplasia around the tumor in metachronous ESCC. Chronic gastroesophageal reflux due to gastrectomy may be involved in the process of carcinogenesis in addition to environmental and genetic factors for metachronous ESCC. Further studies of a larger number of patients with metachronous ESCC and a history of gastrectomy are warranted. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, Gastrectomy, Carcinogenesis, Cyclin D1 p53 p21WAF1/Cip1 P1.10.04: DOWNREGULATION OF ST6GALNAC1 ON CHROMOSOME 17Q25.1 IS ASSOCIATED WITH THE DEVELOPMENT OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA Takeshi Iwaya1, Yuji Akiyama1, Masafumi Konosu1, Yusuke Kimura2, Fumitaka Endo1, Keisuke Koeda1, Akira Sasaki1, Koshi Mimori3, Go Wakabayashi1 1 Iwate Medical University, Morioka/JAPAN, 2Iwate Medical University School of Medicine, Morioka/JAPAN, 3Department of Surgery, Bepppu Hospital, Beppu/JAPAN Background: Tylosis is an autosomal dominant skin disorder that is associated with the early onset of esophageal squamous cell carcinoma (ESCC) in several families from UK, USA, German, Spain, and Finland. The tylosis esophageal cancer (TOC) gene locus has been mapped to chromosome 17q25.1 using linkage analyses of pedigrees of such families. This region is also frequently lost in sporadic ESCC. Therefore, genes involved in the development of esophageal cancer may exist in the TOC region on 17q25.1. Methods: Gene expression profiles of the 1500-Kb region on 17q25, including the TOC locus, in tumor and corresponding normal tissue samples from 3 ESCC patients were analyzed using RNA-seq analysis. We validated the expression status of candidate genes in samples from 90 ESCC patients using qRT-PCR. Direct sequence and loss of heterozygosity (LOH) analyses were performed on the candidate gene, ST6GALNAC1, in 46 and 26 samples from ESCC patients, respectively. The methylation status of ST6GALNAC1 was evaluated in 5 ESCC cell lines, KYSE150, KYSE270, TE6, TE9, and TE10, by 5-aza-dC treatment. Results: Four genes, ACOX1, C17orf106, EVPL, and ST6GALNAC1, were found to be significantly downregulated in tumor samples compared with corresponding normal tissues using RNA-seq analysis. Significant downregulation of ST6GALNAC1 and EVPL expression in cancer tissues was confirmed (p < 0.0001 and p = 0.0023, respectively) using qRT-PCR. Frequent nucleotide variants (7/46) were observed in exon 2 of ST6GALNAC1. Three of these variants were missense mutations, with the remaining 4 containing a 3-base deletion [14522–14524 (CCA)]. These mutations were not tumor-specific and were also observed in corresponding normal tissue samples of each case. LOH was observed at least 1 marker of the 3 microsatellite markers in ST6GALNAC1 locus in 17 of 26 (65%) cases. ST6GALNAC1 expression was significantly upregulated in 5-aza-dC treatment groups compared with control in the 5 esophageal cancer cell lines. Discussion: Although ST6GALNAC1 contains no CpG islands in its promoter region, it has been reported that ST6GALNAC1 is hypermethylated 2 bp upstream of the transcription start in some breast cancer cases. Our results suggest that downregulation of ST6GALNAC1 via hypermethylation and LOH are associated with the development of ESCC. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, tylosis, ST6GALNAC1 P1.10.05: THE ANTITUMOR EFFECT OF METFORMIN ON ESOPHAGEAL SQUAMOUS CELL CARCINOMA CELLS Nobufumi Sekino, Isamu Hoshino, Yasunori Akutsu, Naoki Akanuma, Yuka Isozaki, Kentaro Murakami, Tetsuro Maruyama, Takeshi Toyozumi, Hiroshi Suito, Masahiko Takahashi, Yasunori Matsumoto, Hisahiro Matsubara Graduate School of Medicine, Chiba University, Chiba/JAPAN Background: Currently, it was pointed out that the antitumor efficacy of insulin sensitizer metformin which is widely used for diabetes mellitus in various cancer cells. Indeed, it has been elucidated that metformin could reduce the proliferation and/or epithelial mesenchymal transition (EMT) activities. There are few reports about the antitumor efficacy of metformin on esophagus squamous cell cancer. Besides, there is no report which shows the correlation between EMT and metformin. In this study, we examined the antitumor effects and the suppression of EMT activity by metformin on esophagus cancer cell lines. Methods: We used the human esophageal squamous cell lines, TE2 and T.Tn. TE2 and T.Tn cells were exposed to various concentrations of

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metformin and antiproliferative effects were determined using Cell Counting Kit-8 (Dojindo, Kumamoto, Japan). Moreover, TE2 was exposed to IC50 metformin for 24 hours and mRNA expression levels of various EMT markers were determined by real-time RT-PCR. TE2 and T.Tn cells were exposed to metformin for 24 hours and protein expression levels of E-cadherin were determined by western blotting. Results: Metformin induced the growth inhibition on esophagus squamous carcinoma cell lines in a dose dependent manner (IC50 concentrations of TE2 and T.Tn were 3.8 mM and 3.3 mM, respectively.). Metformin induced the elevation of E-cadherin mRNA expression level in TE2. Metformin induced E-cadherin protein expression level in a dose dependent manner in several esophagus squamous cancer cell lines. Discussion: These results suggested that metfomrin could induce cell growth inhibition and suppress EMT ability in esophageal squamous carcinoma cells. Disclosure: All authors have declared no conflicts of interest. Keywords: Metformin, epithelial mesenchymal transition, E-cadherin P1.10.06: EXPRESSION OF BETA-1 INTEGRIN MAY PREDICT SURVIVAL IN PATIENTS WITH GASTROESOPHAGEAL CANCER Henry Jiang1, Sara Najmeh1, Stephen Gowing1, Monisha Sudarshan1, Ugo Mancini1, Roushika Perez2, Victoria Marcus1, Jonathan Cools-Lartigue1, Lorenzo Ferri1 1 McGill University, Montreal/QC/CANADA, 2University of Toronto, Toronto/ON/CANADA Background: Integrin expression on cancer cells has profound implications in tumor progression. Emerging work suggests that beta-1 integrin is a key mediator of adhesion between cancer cells and neutrophil extracellular DNA, which has been recently identified as a novel mechanism of cancer metastasis. To determine its clinical importance, we examined the relationship between the level of beta-1 integrin expression and survival in a group of 35 patients who underwent surgery for gastroesophageal (GE) cancer. Methods: We constructed a tissue microarray (TMA) using cores from paraffin embedded tumor blocks from 35 patients with adenocarcinoma of the GE junction. Immunohistochemistry was carried out to stain beta-1 integrin. All specimens were reviewed by a board certified pathologist. The stained slides were read by Image-Scope® and subsequently analyzed by Aperio® Image Analysis Software to yield raw beta-1 scores based on intensities of expression (3, 2, 1, 0) and percentage of cells within each intensity. The weighted beta-1 score is calculated as the sum of the product of the respective pairs of percentages and intensities. Kaplan-Meier plots and Fischer’s exact tests were prepared using JMP® Statistical Software. Results: Of the 35 tumor cores in the TMA, only 26 contained sufficient cancer cell content for immunohistochemistry of beta-1 integrin. Of the 26 cores analyzed, 24 (92%) were positive for beta-1 integrin. The overall survival (OS) of patients with tumors expressing high beta-1 vs. low beta-1 integrin at 1, 3 and 5 years are 91%-vs.-93% (p = 0.68), 55%-vs.-67% (p = 0.41), and 27%-vs.-60% (p = 0.10), respectively. The disease free survival (DFS) of patients with high beta-1 vs. low beta-1 expressing tumors at 1, 3 and 5 years are 64%-vs.-93% (p = 0.08), 27%-vs.-53% (p = 0.18), and 27%vs.-53% (p = 0.18), respectively. Although neither comparison is statistically significant, there appears to be a trend for high beta-1 expression to be associated with more death and recurrence. More death occurred one year after surgery in patients with high beta-1 expressing tumors, whereas more recurrence occurred within a year of surgery in the high beta-1 expressing group. Discussion: Beta-1 integrin is highly expressed in human esophageal cancer tissue. Though our study with limited sample size did not demonstrate significant association between the expression of beta-1 and post-operative survival in patients with GE junction cancer, a trend appears to exist. By expanding our TMA database, we hope to elucidate the true clinical effect of beta-1 integrin. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, Beta-1 integrin, Post-operative Survival, recurrence P1.11.01: AN ANALYSIS OF A METHOD TO IDENTIFY CANCER STEM-LIKE CELLS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA Kentaro Murakami, Isamu Hoshino, Yasunori Akutsu, Takayuki Nishimori, Naoyuki Hanari, Takeshi Toyozumi, Hiroshi Suito, Masahiko Takahashi, Hisahiro Matsubara Graduate School of Medicine, Chiba University, Chiba/JAPAN Background: Esophageal squamous cell carcinoma (ESCC) is a highly malignant cancer with a poor prognosis. In recent years, the existence of cancer stem-like cells and their treatment-resistance have been noted in

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gastrointestinal cancer. It is thought that cancer stem-like cells are major contributors to cancer relapse, and removing the cancer stem-like cells might improve the radical cure rate. However, there have been only a few reports on the cancer stem-like cells of esophageal squamous cell carcinoma. Theoretically, the cancer stem-like cells can be treated by either actively removing them or making them differentiate into cells that are sensitive to chemotherapy. However, no such strategies have been established yet. Methods: As a pre-planning stage for novel treatment strategies focused on ESCC cancer stem-like cells, we identified the cancer stem-like cell fraction and then elucidated their characteristics, using ESCC cell lines (T.Tn and TE series). Results: During the sphere formation assay, spheres were formed in cultures of the ESCC cell lines T.Tn, TE1 and TE2. We dissociated the spheres and cultured the resulting cells under non-adherent conditions. The spheres were formed again, so the capacity of the cells for self-renewal was confirmed. Furthermore we examined the sensitivity of the cells making up the spheres to an anticancer agent using the MTT assay. The cells showed resistance to CDDP. It is believed that the cells making up the spheres included cells with stem-like cell properties, so we analyzed these cells for their expression of CD24, 44, 133 and EpCAM, which were reported to be stem cell markers in other cancers, by flow cytometry. Compared to the ratio in the total cells, the proportion of positive cells in the cells making up the spheres was similar or lower. Therefore, we examined the expression of CD90, which has been reported to be a marker of liver cancer, in the same way. The percentage of positive cells in the cells making up the spheres was slightly increased compared to the overall cell population, but few CD90-positive cells were detected in the spheres by immunohistochemistry. It is therefore thought that CD24, 44, 90, 133 and EpCAM may not be suitable markers for ESCC-associated cancer stem cells. Discussion: The ESCC cell lines T.Tn, TE1 and TE2 form spheres, so these were considered to be useful in the present experimental system. However, separation by cell surface markers was difficult, so we are currently considering separation by functional markers, including ALDH enzyme activity. We will analyze the cancer stem cell markers continuously and identify an ESCC cancer stem-like cell fraction.


Disclosure: All authors have declared no conflicts of interest. Keywords: lymph node metastasis, CT lymphography, esophago-gastric junctional carcinoma P1.12.02: CLINICAL SIGNIFICANCE OF SERUM P53 ANTIBODY FOR ESOPHAGEAL CANCER AND CORRELATIONS WITH OTHER TUMOR MARKERS. Masahiro Noda, Hiroshi Okumura, Yasuto Uchikado, Yoshiaki Kita, Itaru Omoto, Tetsuhiro Owaki, Yoshikazu Uenosono, Sumiya Ishigami, Shoji Natsugoe Kagoshima University, Kagoshima/JAPAN Background: Recent the serum p53 antibody is reported to be a useful tumor marke in detecting or mntoring treatment outcome of patients with eophageal squamous cell carcinma (ESCC). In this sudy we examined th correlations between the serum p53 antibody, SCC, CEA level of ESCC patients and clinicopathologic factors. Methods: We examined the relations between tumor markers and the clinicopathologic factors. The study group consisted of 100 patients who were measured tumor markers (serum p53 antibody, SCC, CEA) before treatments. Among 100 patients, 58 patients underwent operation, and 37 patients were treated with chemotherapy or chemoradiotherapy. The others were given best supportie care. Cut off levels for each tumor marker was 1.3 U/ml for p53, 1.5 ng/ml for SCC, and 5.68 ng/ml for CEA, respectively. Results: The positive rate in p53, SCC and CEA was 32%, 54%, and 14%, respectively. The positive rates according to clinical stage I/II/III/IV were 13/6/50/31% for p53, 13/11/1/35% for SCC, 14/7/21/57% for CEA, respectively. p53 or SCC-positive rates were 71%, which indicated the best combination pattern. In addition, twelve patients with high level-p53 (more than 20 U/ml) had clinical advanced stage. Among them, eight patients had tumor with resistance to the treatments and worse outcome.


Discussion: The serum p53 antibody was useful marker in detecting esophageal cancer patients, and high level of p53 might become the marker for resistance of treatment and prediction for prognosis.

Keywords: cancer stem-like cell, Esophageal squamous cell carcinoma

Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, tumor marker, p53, SCC

P1.12.01: SENTINEL LYMPH NODE NAVIGATION SURGERY USING PREOPERATIVE CT LYMPHOGRAPHY FOR ESOPHAGOGASTRIC JUNCTIONAL CARCINOMAS Takahiro Yoshida1, Yoshihito Furukita1, Takeshi Nishino1, Hirokazu Takechi1, Yasuhiro Yuasa1, Yota Yamamoto1, Masakazu Goto1, Takuya Minato1, Seiya Inoue1, Satoshi Fujiwara1, Toru Sawada1, Naoya Kawakita1, Miyuki Kanematsu1, Hiromichi Yamai1, Junichi Seike1, Takanori Miyoshi2, Akira Tangoku1 1 The University of Tokushima, Tokushima/JAPAN, 2Tokushima Municipal Hospital, Tokushima/JAPAN Background: Selection criteria of a right thoracic approach or an abdominotranshiatal approach are still controversial for esophago-gastric junctional carcinoma. We have developed preoperative CT lymphography (CTLG) providing position and number of sentinel lymph nodes (SLNs) with their afferent lympatic vessels for superficial esophageal carcinoma. The purpose of this study is to evaluate the availabilty of CTLG for esophgo-gastric junctional carcinoma. Methods: Five patients clinically diagnosed with esophago-gastric junctional carcinomas were examined. Three-dimensional multi-detector computed tomography was performed to identify SLNs with lymphatic routes. Five minutes after endoscopic submucosal injection of 2 ml (0.5 ml each) iopamidol around the primary lesion using a 23-gauge endoscopic scleotherapy needle with a four-quadrant injection pattern. Results: CTLG was performed in 5 patinets with esophago-gastric junctional carcinomas prior to initial treatment. Case 1: Siewert type II, Squamous cell carcinoma (Sq), cT1b, SLNs (110, 3). Case 2: type I, Sq, cT1b, SLN (3). Case 3: type I, Adenocarcinoma (Ad), cT1b, SLNs (1, 3). Case 4: type I, Sq, cT1b, SLN (106tbL). Case 5: type II, Ad, cT1b, SLNs (107, 3). Four patients underwent esophagectomy except for case 1 treated by photodynamic therapy. Lymph node metastasis was patholocically confirmed in only case 3 and a small metastatic lesion was identified in one of 2 SLNs. Discussion: Case 3 who had a lymph node metastasis was diagnosed with invasion to adventitia (pathological T3). In this case 3, subtotal esophagectomy with 2-fied lymph node dissection excluding the para-aortic lymph nodes was conducted based on the reults of enhanced CT and CTLG. The para-aortic lymph node metastatic rates were reported to be 10–20% in advanced esophago-gastric junctional carcinomas. Lymphatic routes to the para-aortic lymph nodes were not detected in our 5 cases. In cnclusion, preoperative CTLG could visualize the precise SLNs with lymphatic routes and more accurate imaging diagnosis for lymph node metastasis in esophago-gastric junctional carcinomas.

P1.13.01: LONG-TERM OUTCOME OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA DIAGNOSED WITH PT1B WITHOUT CLINICAL LYMPH NODE METASTASIS FOLLOWING ENDOSCOPIC SUBMUCOSAL DISSECTION Satoru Hashimoto1, Manabu Takeuchi2, Kazuya Takahashi3, Kenichi Mizuno1, Masaaki Kobayashi1 1 Niigata University Medical and Dental Hospital, Niigata/JAPAN, 2 Niigata University Graduate School of Medical and Dental Sciences, Niigata/JAPAN, 3Niigata University Medical and Dental Hospital, Niigatashi/JAPAN Background: Few studies have investigated the long-term outcome of esophageal squamous cell carcinoma (EC) diagnosed with pT1b without clinical lymph node metastasis following endoscopic submucosal dissection (ESD). This study aimed to evaluate the long-term outcome of EC diagnosed with pT1b without clinical lymph node metastasis after ESD. Methods: This was a retrospective study from a single institution. From February 2003 to December 2010, 40 patients diagnosed with pT1b without clinical lymph node metastasis were included from a total of 357 consecutive patients who underwent ESD for EC. Cases of metachronous recurrences following chemoradiotherapy (CRT) were excluded. Our treatment strategy after ESD was as follows. All cases were classified into pSM1 (≤200 μm from the muscularis mucosa) and pSM2 (>200 μm from the muscularis mucosa) according to tumor depth of invasion. For cases without lymphovascular involvement or poor differentiation at the invasion front in the pSM1 group, neck-chest-abdominal computed tomography and endoscopy were performed every 6 months. Additional surgery or CRT was performed for the other patients in the pSM1 group and all patients in the pSM2 group in principle. CRT consisted of 40-Gy irradiation for cases with negative vertical resection margin or 60-Gy irradiation for cases with positive vertical resection margin, combined with 5-fluorouracil and cisplatin. All patients were followed-up for 3 years or until death. Overall survival, disease-specific survival, and recurrence rate were evaluated as the long-term outcome. Results: There were 36 men and four women with a median age of 69 years (range, 42–90 years). In the pSM1 group (n = 13), CRT was performed for 3 of 6 patients with lymphovascular involvement. During the median observation time of 60 months (range, 44–101 months), 2 (15.4%) patients who did not receive additional treatment experienced lymph node recurrence. No patients died; therefore the cumulative 3-year overall survival rate was 100%. In the pSM2 group (n = 27), CRT was performed for 9 patients, surgery was performed for 1 patient, and the others underwent no additional treatment


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because of advanced age or presence of risk factors. During the median observation period of 58 months (range, 6–97 months), 5 (18.5%) patients experienced lymph node recurrence, 1 (3.7%) experienced local recurrence, and 1 (3.7%) experienced bone metastasis. Six of 7 patients with recurrence received no additional treatment. Two (7.4%) patients who received no additional treatment after ESD died from causes related to EC, and the cumulative 3-year disease-specific survival rate was 92.3%. Three (11.1%) patients died from other carcinomas, 4 (14.8%) died from other diseases such as ischemic heart disease or liver cirrhosis, and 1 (3.7%) patient died from an unknown cause. The cumulative 3-year overall survival rate was 61.5%. Discussion: Our findings demonstrated that additional treatment is preferable for patients diagnosed with pT1b without clinical lymph node metastasis following ESD for EC. It is also appropriate to perform close follow-up for older patients with severe comorbidities who did not undergo surgery. Disclosure: All authors have declared no conflicts of interest. Keywords: esohageal squamous cell carcinoma, endoscopic submucosal dissection, pT1b, Long-term outcome P1.13.02: SIGNIFICANCE OF PROPHYLACTIC TREATMENT AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA Tomohiro Tsuchida, Akiyoshi Ishiyama, Hiroki Osumi, Akihiko Tomita, Kenjirou Morishige, Hideomi Tomida, Hirotaka Ishikawa, Yusuke Horiuchi, Natsuko Yoshizawa, Masami Omae, Toshiaki Hirasawa, Yoshiyuki Yoshio, Yorimasa Yamamoto, Junko Fujisaki, Masahiro Igarashi Cancer Institute Ariake Hospital, Tokyo/JAPAN Background: Recent endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) enables us to remove by “en block” and gives us a detailed histopathological assessment. Although the prophylactic treatment after ER is necessary for T1a-MM and T1b ESCC because of lymph node metastasis (∼40%), some patients are over-treated by the prophylactic treatment. However there are still few reports about the prognosis after ESD for T1a-MM and T1b ESCC. The aim of this study is to inspect a risk factor of metastasis of T1a-MM and T1b ESCC and the effect of the prophylactic treatment. Methods: In the cases of histopathological T1a-MM or T1b ESCC undergoing ESD in our hospital, I examined the relations with metastasis of vascular invasion (ly or v factor) and Droplet infiltration (DI). The DI, the infiltrative growth pattern that the nest of cancer infiltrates, is thought that it is one of the risk factor of metastasis. Furthermore, I was investigated the presence or absence of prophylactic treatment and the prognosis. Results: In 50 cases of T1a-MM ESCC, there were 9 cases (18%) of vascular invasion-positive, 7 cases (14%) of DI-positive, and 3 cases (6%) both-positive. CRT was performed in 3 cases, surgical operation in 4 cases, and the other 6 cases were observed without the prophylactic treatment. A recurrence was not observed in these cases. Although 43 cases of vascular invasion-negative and the DI-negative had been observation without prophylactic treatment, lymph node recurrence was observed in 1 case. In 5 cases of SM1 ESCC, there were 2 cases (40%) of vascular invasion-positive, no case of DI-positive. CRT was performed to 2 cases, 3 cases were observed without the prophylactic treatment. All are during no recurrence survival. In 13 cases of SM2 ESCC, there were 8 cases (62%) of vascular invasion-positive, 5 cases (38%) of DI-positive. CRT was performed in 3 cases, surgical operation in 7 cases. 2 cases have been other died of an illness. Discussion: If either risk factor is positive, the prophylactic treatment is necessary for the cases of histopathological T1a-MM or SM1 ESCC undergoing ESD. However, if vascular invasion and DI were both-negative, it was suggested that the prophylactic treatment was not necessary. Although it is considered issue is whether to select any prophylactic treatment, it is possible that the adaptation of ESD may be expanded to T1 b-SM2 ESCC. Disclosure: All authors have declared no conflicts of interest. Keywords: superficial esophageal squamous cell carcinoma, ESD, prophylactic treatment, risk factor P1.13.03: A CASE OF SUPERFICIAL VERRUCOUS CARCINOMA OF THE ESOPHAGUS TREATED WITH ENDOSCOPIC SUBMUCOSAL DISSECTION Tairo Ryotokuji, Kenro Kawada, Yasuaki Nakajima, Yutaka Tokairin, Yutaka Miyawaki, Takuya Okada, Naoto Fujiwara, Hisashi Fujiwara, Katsumasa Saito, Taichi Ogo, Masafumi Okuda, Kagami Nagai, Tatsuyuki Kawano, Takashi Ito, Hiroshi Kawachi, Yoshinobu Eishi Medical Hospital of Tokyo Medical and Dental University, Tokyo/JAPAN Background: In Japan, squamous cell carcinoma comprises 90% or more of the malignant neoplasms. Verrucous carcinoma is a subtype of squamous cell carcinoma, but the characteristics of these tumors are poorly understood.

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Methods: A 74-year-old male with abnormal findings during a routine medical screening underwent esophagogastroduodenoscopy (EGDS) at another clinic. The initial EGDS found a mucosal abnormality with a flat protruded lesion in the middle to distal esophagus. Despite strong suspicion of malignancy, the endoscopic biopsies failed to reveal any cancer cells. The patient was therefore diagnosed with chronic esophagitis. The patient underwent repeated endoscopic examinations four times in one year. During the fourth biopsy, malignant potential was noted, so the patient was referred to our hospital. EGDS revealed a superficially-spreading abnormal area with slight protrusion from 33 to 40 cm from the upper incisors. Endoscopic biopsies revealed squamous cell carcinoma. We suspected early verrucous carcinoma, especially based on the characteristic clinical course. Esophageal endoscopic submucosal dissection (ESD) was performed with the diagnosis of superficial esophageal cancer (cT1a (LPM), cN0, cM0, cStageIA, according to the TMN classification (7th edition) published by the UICC. The resected specimen measured ϕ73 × 51 mm. Results: Histologically, the well-differentiated squamous cell carcinoma had papillary proliferation of the hyperplastic epithelium. These findings led to a diagnosis of esophageal verrucous squamous carcinoma. Finally, the histological findings were pTis (EP), pN0, pM0, identified as p-stage 0. There has been no cancer recurrence as of six months post-ESD. Discussion: This case is a very interesting case in terms of its clinicopathological features. At this meeting, we will present a case report of superficial verrucous carcinoma of the esophagus treated with endoscopic submucosal dissection. Disclosure: All authors have declared no conflicts of interest. Keywords: Verrucous Carcinoma of the Esophagus, Verrucous Carcinoma, ESD, Superficial Verrucous Carcinoma P1.14.01: REG1A, A CANDIDATE OF THE NOVEL CHEMORADIOSENSITIVITY MARKER OF ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA Yusuke Sato, Satoru Motoyama, Kei Yoshino, Tomohiko Sasaki, Akiyuki Wakita, Yushi Nagaki, Kazuhiro Imai, Hajime Saito, Yoshihiro Minamiya Akita University Graduate School of Medicine, Akita/JAPAN Background: Identification of reliable markers of chemoradiosensitivity and the key molecules that enhance chemoradiosensitivity in ESCC has been highly desirable and sought. We previously reported that the positive expression status of REG1A was predictive of chemoradiosensitivity in patients treated with preoperative chemoradiotherapy before esophagectomy or with definitive chemoradiotherapy. To further confirm the utility of REG1A as a chemosensitivity marker, we carried out an additional retrospective clinical study aimed at determining whether REG1A is a reliable chemosensitivity marker in patients treated with esophagectomy followed by adjuvant chemotherapy. Methods: A total of 177 patients with T2–4 thoracic esophageal squamous cell carcinoma received curative surgery without preoperative treatment at Akita University Hospital between 2001 and 2011. A tissue microarray was constructed, and REG1A expression status was analyzed immunohistochemically. We then statistically analyzed the relationships between REG1A expression status and 5-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Results: Results. In the adjuvant group (n = 105), REG1A-positive patients showed significantly better prognoses than REG1A-negative patients. (5-year OS, p = .0022; DSS, p = .0004; and DFS, p = .0040). However, there were no significant differences between REG1A-positive and REG1A-negative patients in the surgery group (n = 72). Univariate and multivariate analyses showed REG1A expression status to be a significant prognostic factor affecting 5-year DSS, comparable to lymph node metastatic status. Discussion: The present study suggests REG1A expression status has the potential to be a highly reliable and clinically useful chemosensitivity marker in patients treated with advanced thoracic esophageal squamous cell carcinoma. REG1A expression status will provide a good indication of treatment strategy and enable more individualized treatment for patients. (Ann Surg Oncol 2013) Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, Adjuvant chemotherapy, Sensitivity marker, REG1A P1.14.02: NEOADJUVANT THERAPY FOR CLINICAL STAGE T2–3 N0 ESOPHAGEAL CANCER PATIENTS Norihisa Uemura, Tetsuya Abe, Ryosuke Kawai, Jiro Kawakami, Masayuki Shinoda Aichi Cancer Center Hospital, Nagoya/JAPAN Background: Although neoadjuvant therapy has been proven to be very important and is widely used for advanced esophageal cancer, it remains

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unclear whether patients with clinical stage T2–3 N0 (cT2–3 N0) esophageal cancer should be administered induction therapy with surgical intervention or surgical intervention alone.

response status was significantly correlated with ETR (p < 0.001) and was the sole independent prognostic predictor in both patient groups using multivariate analyses.

Methods: In this retrospective cohort study, we examined patients with cT2–3 N0 esophageal cancer undergoing induction therapy, followed by surgical resection or resection alone, at the Aichi Cancer Center Hospital from 2000 to 2010. Kaplan-Meier analysis was used to compare the all-cause mortality between the patients who had resection alone and those who had induction therapy followed by resection.

Discussion: ETR and high toxicity grading during induction chemotherapy or chemoradiotherapy suggest that T4 esophageal tumors are highly sensitive to induction therapies. ETR is a reliable surrogate marker of ultimate response status of tumor to induction therapy. ETR is a significant and useful clinical parameter predicting long-term survival in patients with T4 esophageal cancer undergoing induction therapy and subsequent surgery. Better selection of adequate treatment could be done in these patients according to the ETR status determined early after initiation of induction chemotherapy or chemoradiotherapy.

Results: We identified 66 patients who were divided into two groups: 37 patients (56%) received induction therapy (induction-resection group) and 29 (44%) did not (resection-only group). On univariate analysis, the pretreatment factor age (60 years vs. 65 years; p < 0.01) was found to be significantly greater in the resection-only group compared to the induction-resection group. Postoperative adjuvant chemotherapy was administered to 1 patient (3%) in the resection-only group and 10 patients (34%) in the induction-resection group. The 5-year survival rate did not significantly differ between the two groups (resection-only group, 54%; induction group, 65%; p = 0.96). More than 60% of patients with cT2–3 N0 esophageal cancer in the resection-only group were understaged during postoperative pathologic staging. Discussion: For patients with cT2–3 N0 esophageal cancer, the benefits of neoadjuvant therapy remain unclear. Induction therapy for cT2–3 N0 did not yield a significant improvement in survival. However, neoadjuvant therapy is beneficial for patients with lymph node metastases. Although cT2–3 N0 esophageal carcinoma is difficult to accurately diagnose, improvement in the clinical diagnostic accuracy would be essential for establishing an appropriate treatment strategy. Disclosure: All authors have declared no conflicts of interest. Keywords: lymph node metastases, clinical diagnostic accuracy, Esophageal cancer, neoadjuvant therapy P1.14.03: EARLY TUMOR RESPONSE TO INDUCTION CHEMOTHERAPY OR CHEMORADIOTHERAPY IS A SIGNIFICANT PROGNOSTIC PREDICTOR IN PATIENTS WITH INITIALLY UNRESECTABLE T4 ESOPHAGEAL CANCER FOLLOWING SUBSEQUENT SURGERY Hideaki Shimoji, Hiroyuki Karimata, Tadashi Nishimaki Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa/JAPAN Background: In a previous study, we demonstrated that survival rates of patients with T4 esophageal cancer were comparable to those of patients with immediately resectable esophageal cancer if R0 resection could be performed following induction chemotherapy or chemoradiotherapy (World J Surg 2013). However, esophagectomy for T4 esophageal cancer after induction treatment was associated with higher mortality rates. Therefore, it is important to determine prognostic predictors of these patients. The purpose of this study was to evaluate the hypothesis that early tumor responses (ETR) to induction chemotherapy or chemoradiotherapy would be significant prognostic predictors in patients with initially unresectable T4 esophageal cancer. Methods: Forty-eight patients with suspected T4 esophageal cancers were enrolled in this prospective study to test the efficacy of preoperative induction chemotherapy or chemoradiotherapy followed by esophagectomy, which was feasible in only 37 patients. We performed nested analysis of ETR as a prognostic predictor, using univariate and multivariate analyses. Other preoperative parameters which may correlate with ETR included initial tumor size, serum levels of squamous-cell-carcinoma–related antigen before and after induction therapy, initial growth patterns of tumors, tumor ulceration, before the treatment, modality of induction therapy, sex, age, histological tumor grading on initial biopsy, final response status to induction therapy, post-therapy improvement of dysphagia, induction therapy toxicity grading, body-mass index, and serum albumin levels before and after the treatment. ETR was added to the 16 aforementioned clinical parameters as another variable that can affect patients’ long-term survival. Results: Univariate analyses revealed that the final tumor response status (p < 0.001), ETR (p < 0.001), dysphagia improvement (p = 0.002), and post-therapy serum albumin levels (p = 0.025) were significant prognostic predictors in the 48 patients. Pretreatment serum squamous-cell-carcinoma–related antigen levels (p = 0.008), final response status (p < 0.001), ETR (p = 0.004), and induction therapy toxicity grading (p = 0.031) were found to be prognostic predictors in 37 patients. ETR absence was associated with an unfavorably short median survival duration in both the 48 (6.4 months) and 37 patients (10.2 months). The 5-year survival rate of showing ETR was 63.5%, whereas the 5-year survival rate and MST of the 15 patients without ETR were 22.5% and 10.2 months, respectively. Final

Disclosure: All authors have declared no conflicts of interest. Keywords: T4 esophageal cancer, induction therapy, early tumor response

P1.14.04: INDUCTION CHEMOTHERAPY USING FAP (5-FU, ADR AND CDDP) FOR PATIENTS WITH CLINICAL STAGE II AND III SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS Shigeyuki Tamura, Atsushi Takeno, Hirokazu Taniguchi, Yoshinori Kagawa, Yoshiteru Katsura, Hideki Sakisaka, Shin Nakahira, Yutaka Takeda, Takeshi Kato Kansai Rosai Hospital, Amagasaki/JAPAN Background: Patients with locally advanced esophageal carcinoma with lymph node metastasis have a poor prognosis. The aim of this study was to evaluate the feasibility and effectivity of chemotherapy using fluorouracil, adriamicin, and cisplatin (FAP) in patients with clinical stage II and III squamous cell carcinoma of the esophagus. Methods: Patients received 30 mg/m2 adriamicin and 70 mg/m2 cisplatin on day 1, and 700 mg/m2 5-fluorouracil on days 1–5 every four weeks. Forty-one patients were treated with 2 courses of FAP in principle. Following chemotherapy, eligible patients underwent esophagectomy, the others received definitive radiation therapy. Results: Thirty-two men and nine women were enrolled (mean age 69.1 years). Partial response was achieved in 22 patients (54% including the patients with PR-in), 18 patients had stable disease, and one had progressive disease with bone metastasis. Seventeen patients with PR and 11 with SD underwent surgery (resection rate: 66%). Other 13 patients received CRT or chemotherapy for several reasons (refuse operation: 6 patients, poor PS: 5 patients, diagnosis of other cancer and progressive disease: each 1 patient). Grade 3 or 4 toxicities developed in 7 patients (17%) with leucopenia, 23 (56%) with neutrophilia, 3 (7%) with thrombocytopenia and 2 (5%) with SIADH during chemotherapy. The 3 and 5-year survival rates of all patients were 58%, 49%, respectively. Patients with good response (22 cases) to chemotherapy had better prognosis than those with poor response (19 cases) with 3 and 5-year survival rate of 74% and 40% vs. 61% and 40% (p = 0.048). Discussion: Chemotherapy with FAP for patients with clinical stage II and III squamous cell carcinoma of the esophagus is effective and feasible and surgery may provide additional benefit for patients with good response to induction chemotherapy. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, esophagectomy, induction chemotherapy

P1.14.06: SYMPTOM DISTRESS, ANXIETY AND DEPRESSION IN PATIENTS WITH ESOPHAGEAL CANCER UNDERGOING ADJUVANT CHEMOTHERAPY AFTER RADICAL ESOPHAGECTOMY Xiaoxia Jiang1, Jianwei Tang2 1 Shanghai Punan Hospital, Shanghai/CHINA, 2Jinshan Hospital, Fudan University, Shanghai/CHINA Background: The aim of this study was to investigate the symptom distress, anxiety and depression in patients with esophageal cancer undergoing adjuvant chemotherapy after radical esophagectomy. Methods: A total of 84 patients undergoing adjuvant chemotherapy from January 2012 to December 2013 after radical esophagectomy were enrolled. The M.D. Anderson Symptom Inventory (MDASI) and the Hospital Anxiety and Depression Scale (HADS) were used to assess the patients, symptom distress, anxiety and depression condition. Results: The patients averagely scored 3.18 points in symptom items, and 2.81 points in interference items, with the scores being positively correlated with anxiety and depression respectively (P < 0.01 for both). The patients mainly reported symptoms of alopecia, lack of appetite, weight loss, reflux of gastric contents, etc.


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Discussion: Symptom distress is commonly seen in patients with esophageal cancer undergoing adjuvant chemotherapy after radical esophagectomy. And symptom distress, anxiety and depression react upon each another. Therefore physicians should pay more attention to these patients, mental state and guide them to rationally release their emotions. Disclosure: All authors have declared no conflicts of interest. Keywords: chemotherapy, symptom distress, Esophageal cancer P1.15.01: IMPROVEMENT IN THE POSTOPERATIVE COURSE OF SALVAGE ESOPHAGECTOMY AFTER DEFINITIVE CHEMORADIOTHERAPY Takuya Sato Tokyo Womens Medical University Yachiyo Medical Center, Yachiyo-si/ JAPAN Background: The aim of this study was to assess the outcome of salvage esophagectomy with less extensive lymphadenectomy, which we have performed since 2003 to improve high mortality and morbidity of standard salvage esophagectomy. Methods: We retrospectively compared the surgical outcome of 15 patients who underwent standard salvage esophagectomy via right thoracotomy for thoracic esophageal cancer between 1993 and 2002 (earlier period) with the results of 11 patients between 2003 and 2011 (later period). Results: There were two mortalities in the earlier period, whereas no patient died in the later period, and there was a lower rate of morbidity. In the later period, there was a significantly shorter SIRS duration, lower CRP on postoperative days 1–5, and higher lymphocyte count on postoperative days 2–4. Long-term survival showed no significant difference between the two periods. Discussion: Salvage esophagectomy with less extensive lymphadenectomy might improve the surgical outcome while maintaining long-term survival. Disclosure: All authors have declared no conflicts of interest. Keywords: Definitive chemoradiotherapy, Esophageal cancer, Salvage esophagectomy, squamous cell carcinoma

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P1.16.01: RISK FACTORS FOR POSTOPERATIVE PULMONARY COMPLICATIONS AFTER SIMULTANEOUS RESECTION FOR ESOPHAGEAL AND COLORECTAL CANCER Makoto Kobayashi Hakodate Goryoukaku Hospital, Hakodate City/JAPAN Background: At our hospital, the incidence of postoperative pulmonary complications after simultaneous resection of esophageal and colorectal cancer is much higher compared with that after only transthoracic esophagectomy. Therefore, the aim of this study was to estimate the association of adverse impacts of additional surgical procedures, particularly colorectal resection, with the development of pulmonary complications. Methods: From 2004 to 2013, 142 patients underwent esophagectomy for cancer at our hospital. Of these, four patients simultaneously underwent extensive resection for colorectal cancer with esophagectomy, and three of the four patients experienced postoperative pulmonary complications. On the other hand, the complication rate of patients who underwent only esophagectomy was 6.5% (9/138). Parameters examined for a possible association with pulmonary complications included patient age, preoperative spirometry value, Brinkmann index, surgical duration, amount of blood loss, C-reactive protein value, intrapulmonary shunt ratio, intraoperative water balance, event of anastomotic leakage, and simultaneous surgery for colorectal cancer. The unpaired t-test and Mann–Whitney U-test were used for analysis of continuous variables and the chi-squared test was used for categorical variables identified by univariate analysis. Multivariate logistic regression analysis was used to identify perioperative parameters with a significant association with pulmonary complications. Results: Univariate analysis showed that surgical duration, amount of blood loss, occurrence of anastomotic leakage, and simultaneous procedure with colorectal cancer were significant risk factors for pulmonary complications. Logistic regression analysis clearly indicated that anastomotic leakage and the additional colorectal resection were independent risk factors with the development of pulmonary complications. The odds ratio (OR) of simultaneous colorectal surgery (OR = 20.55, p = 0.0261) was higher compared with that of a leakage event (OR = 6.153, p = 0.0190) (Table 1).

P1.15.02: SALVAGE LYMPHADENECTOMY AFTER DEFINITIVE CHEMO-RADIATION THERAPY Kazuhiko Yamada1, Shinji Mine2, Masayuki Watanabe2, Shuichiro Oya2, Hironobu Shigaki2, Kunihiro Yamasawa1, Chihaya Hinohara1, Ohki Miyake1, Masanori Hashimoto1, Hideaki Yano1, Toshio Shimizu1 1 National Center for Global Health and Medicine, Tokyo/JAPAN, 2Cancer Institute Hospital Ariake, Tokyo/JAPAN Background: To evaluate the short-term prognosis of salvage lymphadenectomy without esophagectomy for the lymph node recurrence after definitive chemo-radiation therapy (CRT) for esophageal cancer. Methods: We investigated a retrospective review of 14 patients who underwent salvage lymphadenectomy for lymph node recurrence after CRT at Cancer Institute Hospital and National Center for Global Health and Medicine between 2005 and 2013 for esophageal cancer. Radiotherapy doses ranged from 60 Gy (n = 14). One case performed radiotherapy only. Concurrent chemotherapy was 5-FU and CDDP in 13 patients. The endpoints of the present study were short-term overall survival and safety management. Results: Complete response and partial response after CRT were observed in 8 and 6 cases of the patients. The distribution of recurrent lymph node were neck (n = 6), mediastinal (n = 3), abodomen (n = 4), axillary (n = 1), respectively. 12 cases underwent salvage curative lymphadenectomy (R0 or R1), but 2 cases were not resected for adjacent invasion (common carotid artery and trachea). 3 cases of mediastinal lymph node underwent videoassisted thoracoscopic surgery (VATS). No post-operative complication was seen and intra-hospital stay was median 9 days. The 1 and 2-year overall survival was 75% and 45% in resectable cases. One case was survived more than 5 years. But, in non-resectable cases, the 1 and 2-year overall survival was poor (50% and 0%). Discussion: In our study, the method of salvage lymphadenectomy might have a better prognosis for short term and be a safety management. Disclosure: All authors have declared no conflicts of interest. Keywords: video-assisted thoracoscopic surgery (VATS), salvage lymphadenectomy, definitive chemo-radiation

Discussion: Postoperative pulmonary complications severely compromise treatment outcomes after esophagectomy with extensive lymphadenectomy for cancer. Although our results have limitations because this was a casecontrol study with a small number of cases, multivariate logistic regression analysis clearly suggested that esophagectomy combined with radical resection for colorectal cancer may be a risky surgical strategy regarding postoperative respiratory complications. In our series, simultaneous surgery for esophageal and colorectal cancer did not improve postoperative mortality. Our results identified specific postoperative pulmonary complications associated with increased hospital stay, contraindicating simultaneous esophagectomy and colorectal resection. Disclosure: All authors have declared no conflicts of interest. Keywords: esophagectomy, colorectal cancer, pulmonary complication P1.16.02: ESOPHAGEAL SECOND PRIMARY FOLLOWING DEFINITIVE CHEMORADIATION FOR CARCINOMA HYPOPHARNYX A SURGICAL CHALLENGE Kapil Kumar, Ashish Goel, S Veda Priya Rajiv Gandhi Cancer Institute Delhi, New Delhi/INDIA Background: Carcinoma of the Hypopharynx runs the highest risk of developing a second primary in the esophagus. Close surveillance helps in early diagnosis. We hereby report this case to emphasize the issues pertaining to management of esophageal second primary cancer following definitive chemoradiation for carcinoma hypopharynx. Methods: 61 year old hypertensive, hypothyroid male was diagnosed with carcinoma hypopharynx in 2009 for which he underwent definitive

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concurrent chemoradiation by IMRT to a dose of 56.43 Gy/28 Fr; with four cycles of weekly cisplatin. He presented to our Institute in August 2013 with an upper GI endoscopy with a friable growth at lower end of esophagus & GE junction. The biopsy report was moderately differentiated squamous cell carcinoma. CECT showed mild thickening at lower end esophagus without any metabolic uptake on FDG PET CT. Direct Laryngoscopy was normal. In view of prior history of CCRT for carcinoma hypopharynx, he underwent Ivor Lewis Esophagectomywith end to side stapled esophagogastrics. On 3rd postoperative day he developed anastamotic leak for which he was reexplored, with resuturing and buttressing with LD myocutaneous flap. Inspite of secondary intervention the leak persisted and subsequently endoscopic stenting with covered SEMS was done after three weeks interval. His leak initially improved only to worsen after a month; finally re-stented in December 2013 after which he recovered. Final histopathology reported as Squamous Cell Carcinoma (pT1aN0). He is therefore on follow up; alive and disease free as of date. Results: Issues of importance in this case: • UGIE showed features of esophagitis; FDG PET CT did not show any metabolic uptake, but biopsy confirmed it to be squamous cell carcinoma. Thus surveillance endoscopy is mandatory in follow up of carcinoma hypopharynx. • The high radiation dose of 56.43 Gy by IMRT to hypopharynx prodded us towards Ivor lewisesophagectomy in an attempt to decrease morbidity compared to Mckeowens’ Esophagectomy. • Intrathoracicanastamotic leakage is associated with high morbidity & mortality. Hence re-exploration, flap coverage and subsequent management by endoscopic stenting were adopted to manage the leak. • In view of T1a disease, no adjuvant therapy was required that would impact survival. Discussion: The management ofesophageal second primary following definitive chemoradiation for carcinoma hypopharnyx is a challenging situation and requires a high index of clinical suspicion for diagnosis, wisdom in decision making and diligence in managing complications. Disclosure: All authors have declared no conflicts of interest. Keywords: carcinoma hypopharynx, second primary P1.16.03: TRACHEOBRONCHIAL NECROSIS AFTER ESOPHAGECTOMY WITH THREE-FIELD LYMPHADENECTOMY FOLLOWING NEOADJUVANT CHEMORADIOTHERAPY IN THORACIC ESOPHAGEAL CANCER Masahiro Niihara, Keisuke Kawamorita, Nozomu Machida, Yasuhisa Ode, Katsuya Gorai, Masahiro Nakagawa, Yasuhiro Tsubosa Shizuoka Cancer Center, Sunto-gun/JAPAN Background: The tracheobronchial necrosis is one of the catastrophic complications of the esophagectomy that occurs after radiotherapy especially. Almost the patients that suffered the tracheobronchial necrosis were placed in otherwise life-threatening condition. This case was rescued from the tracheobronchial necrosis by using myocutaneous plombage with the left pedicled latissimus dorsi. Methods: A 62-year-old man affected by thoracic esophageal cancer with left tracheobronchial lymph node metastasis was treated by esophagectomy following concomitant chemotherapy ((75 mg/m2 of cisplatin on days 1 and 29, and 1000 mg/m2 of 5-fluorouracil on days 1–4 and 29–32) and radiotherapy (total dose 41.4 Gy). Surgery proceeded 40 days after the completion of neoadjuvant chemoradiotherapy (nCRT). This patient underwent threefield lymphadenectomy including the metastatic left tracheobronchial lymph nodes via right transthoracic approach. Ambilateral bronchial arteries were forced to be tied off. After 9 days of surgery, computed tomography (CT) revealed air bubbles around the trachea and left bronchus. Bronchoscopy revealed an extensive tracheobronchial necrosis. We performed myocutaneous plombage with the left pedicled latissimus dorsi via left transthoracic approach. Results: CT after 32 days of surgery revealed the pedicled muscle bulging outward into the left bronchus. Bronchoscopy revealed the defect of the posterior tracheal wall and the muscle flap occupying the most of tracheal lumen. In spite of the situation, the patient’s respiratory condition was maintained well. The patient was discharged on postoperative day 57. Discussion: The tracheobronchial necrosis was suspected to be due to the tracheal ischemia stemming from both nCRT and surgery. As comprehensive irradiation especially to the trachea and bronchus was received, the indication and surgical procedure must be carefully-examined. The plombage with the left pedicled latissimus dorsi was one of the useful options in surgical treatment of the tracheobronchial necrosis. Disclosure: All authors have declared no conflicts of interest. Keywords: muscle plombage, pedicled latissimus dorsi, tracheobronchial necrosis, Neoadjuvant chemoradiotherapy


P1.16.04: ENDOSCOPIC MANAGEMENT OF THE EARLY UPPER GASTROINTESTINAL BLEEDING FOLLOWING THE MINIMALLY INVASIVE IVOR LEWIS ESOPHAGECTOMY FOR AN ESOPHAGEAL CANCER CASE Renquan Zhang, Ning-Ning Kang, Wan-Li Xia, Zai-Cheng Yu, Hua Guang Pan, Wei Ge, An-Guo Chen, Jun Wan Anhui Medical University First Hospital, He Fei/CHINA Background: Minimally invasive esophagectomy is now accepted as a regular treatment modality for esophageal cancer. Upper gastrointestinal (GI) bleeding is one of the common postoperative complications of esophagectomy. In the literature, there are very few reports on the endoscopic management of early upper GI bleeding following an esophagectomy. Here we report such an early postoperative GI bleeding case, which we managed successfully using endoscopic titanium clips. Methods: The patient was a 62 year old male diagnosed as high grade intraepithelial neoplasia with carcinoma in some part of the lesion. We operated this case using minimally invasive Ivor Lewis esophagectomy with purse string-based anastomosis. The procedure was completed smoothly, and the intraoperative bleeding was about 50 mL. On postoperative day one, the patient developed intermittent hematemesis, and his GI decompression tube drained out large amount of dark bloody fluid. Chest X-ray showed the image of a distended intrathoracic stomach. The patient was initially managed with omeprazole, hemostatic agent, and gastric lavage using ice water containing epinephrine; however, patient’s condition failed to improve. Forty eight hours after the surgery, we performed gastroscopic bleeding control under general anesthesia. The blood clots were removed using repeated flushing. Two oozing spots were identified at the stump of the thoracic gastric conduit, close to the pylorus. These bleedings sites were sealed using 4 titanium clips. Results: The patient stopped hematemesis and the gastric drainage started to become clear. Chest X-ray revealed the image of a normal intrathoracic stomach. No anastomotic or stump leakage was found in GI lipiodol-water imaging. The patient was discharged two weeks after the procedure. Discussion: Early GI bleeding may develop following an esophagectomy, particularly minimally invasive Ivor Lewis esophagectomy, due to stress induced ulcer or mechanical anastomotic failure. The bleeding may be located at the anastomosis or remnant stomach, and these two are difficult to differentiate. Endoscopic bleeding control using titanium clips is commonly used for the management of upper GI bleeding among non-surgical patients. However, this approach is considered risky among the patients with GI bleeding early after an esophagectomy, because of the urgent nature of their condition. Our limited experience suggests that early upper GI bleeding following esophagectomy may be managed conservatively during the first 24 hours. If patient’s condition fails to improve, gastroscopic bleeding control can be tried once patient’s condition gets stabilized following active blood transfusion, fluid replacement, and anti-shock treatment. During the endoscopic bleeding management process, efforts shall be made to avoid injury to the anastomosis or the gastric conduit. Disclosure: All authors have declared no conflicts of interest. Keywords: Minimally Invasive Ivor Lewis Esophagectomy, Upper Gastrointestinal Bleeding, Endoscopic Management, Esophageal cancer P1.17.01: THE FUNCTIONAL ANALYSES OF NA(+)/K(+)/2CL(−) COTRANSPORTER 1 (NKCC1) IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA Yoshito Nako, Atsushi Shiozaki, Daisuke Ichikawa, Hitoshi Fujiwara, Hirotaka Konishi, Ryo Morimura, Yasutoshi Murayama, Shuhei Komatsu, Hisashi Ikoma, Yoshiaki Kuriu, Takeshi Kubota, Masayoshi Nakanishi, Kazuma Okamoto, Chouhei Sakakura, Mitsuo Kishimoto, Yoshinori Marunaka, Eigo Otsuji Kyoto Prefectural University of Medicine, Kyoto/JAPAN Background: Various studies have shown that ion channels and transporters play important roles in fundamental cellular functions in recent years. These studies indicate the important roles of Cl− channels/transporters in the proliferation of cancer cells. The objectives of the present study were to investigate the role of NKCC1, Na+/K+/2Cl− cotransporter 1, in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Methods: NKCC1 expression in human ESCC cell lines was analyzed by Western blotting. Knockdown experiments were conducted with NKCC1 siRNA, and the effect of NKCC1 knockdown on cell cycle progression and cell growth was analyzed. The gene expression profiles of cells were analyzed by microarray analysis. An immunohistochemical analysis was performed on 68 primary tumor samples obtained from ESCC patients that had undergone esophagectomy.


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Results: NKCC1 was highly expressed in KYSE170 cells. In these cells, the knockdown of NKCC1 using siRNA inhibited G2-M phase progression and cell growth. Microarray analysis identified 2527 genes whose expression levels in KYSE170 cells were altered by the knockdown of NKCC1. Pathway analysis showed that the top-ranked canonical pathway was the G2/M DNA Damage checkpoint regulation pathway, which involved MAD2L1, DTL, BLM, CDC20, BRCA1, and E2F5. Immunohistochemical staining showed that NKCC1 was mainly found in the cytoplasm of carcinoma cells, and that its expression was related to the histological differentiation degree of ESCC.

P1.17.03: CARCINOSARCOMA OF THE ESOPHAGUS: FOUR CASES TREATED WITH SURGERY AND CHEMORADIOTHERAPY Kenichi Takemoto, Atsushi Shiozaki, Hitoshi Fujiwara, Hiroki Shimizu, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Daisuke Ichikawa, Kazuma Okamoto, Ryo Morimura, Yasutoshi Murayama, Yoshiaki Kuriu, Hisashi Ikoma, Masayoshi Nakanishi, Chouhei Sakakura, Eigo Otsuji Kyoto Prefectural University of Medicine, Kyoto/JAPAN

Discussion: Conclusions : These results suggest that the expression of NKCC1 in ESCC may affect the G2/M checkpoint and be related to the histological differentiation degree of SCC. As a result, we have a deeper understanding of the role played by NKCC1 as a mediator and/or biomarker in ESCC.

Methods: We report four cases of carcinosarcoma of the esophagus treated with surgical resection and chemoradiotherapy.

Disclosure: All authors have declared no conflicts of interest. P1.17.02: MURINE DOUBLE MINUTE 2 PREDICTS RESPONCE OF ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA TO DEFINIIVE CHEMORADIOTHERAPY Hiroshi Okamoto, Go Miyata, Takashi Kamei, Toru Nakano, Shigeo Abe, Kazunori Katsura, Yusuke Taniyama, Tadashi Sakurai, Jin Teshima, Makoto Hikage, Noriaki Ohuchi Tohoku University Hospital, Sendai/JAPAN Background: Recently, definitive chemoradiotherapy (dCRT) has been one of the most effective therapies for esophageal squamous cell carcinoma (ESCC). However, there have been treatment failures after dCRT. If we could know the response of ESCC to dCRT before treatment, we may improve the clinical outcome by finding a new strategy for ESCC. On the other hand, by investigating surgical specimens of salvage esophagectomy after dCRT, our previous study suggested that murine double minute 2 (MDM2) and p16 are associated with chemoradioresistance in ESCC. Methods: We selected pretreatment biopsy specimens of ESCC patients from our prospective clinical study on dCRT. Eligible patients in the study were aged 20–80 years with previously untreated, T1-3N0-3M0, and histologically confirmed ESCC of the thoracic esophagus. Pretreatment biopsy specimens of 79 ESCC patients, histologically diagnosed as ESCC, were available. The CRT protocol of the prospective study basically followed the protocol of the Japan Clinical Oncology Group trial 9906. We immunohistochemically investigated these specimens using antibodies against MDM2, p53, p16, and Ki-67. Results: The patients included 68 males and 11 females with a mean age of 63.3 years (range, 43–79 years). The number of patients in each pathological stage was as follows: 22, pStageI; 17, pStageII (7, T3N0; 6, T1N1; 4, T2N1); and 40, pStageIII (35, T3N1; 5, T3N2). cT, cN, and cStage were significantly more advanced in the Failure group (including the patients with persistent and recurrent disease after dCRT) than in the CR group (patients evaluated as persistent CR after dCRT). The clinical stage positively correlated with the CR rate and inversely with the rescue rate after failure. The overall survival rate was worse in the patients with advanced cT, cN, and cStage, and in the Failure group. Regarding markers expression, MDM2 positivity was significantly higher in the Failure group than in the CR group in cStageIII (p = 0.014). The number of patients with negative p16 expression was higher in the Failure group than in the CR group in cStageIII (P = 0.010) but not in cStageI, and, cSatgeII. Moreover, MDM2 positivity tended to be higher in the p16-negative group than in the p16-positive group. No other significant correlations were observed among the markers evaluated in this study. Discussion: This study suggests that MDM2 and p16 are predictive markers for chemoradioresistance in cStageIII ESCC and that there is a correlation between p16 and MDM2. p16 is located on chromosome 9p21, where p14 that inhibits MDM2 is also located. We believe that these same results were not observed in cStageI and cStageII, because the evaluation of immunohistochemical staining is difficult in shallow tumors, especially carcinoma in situ, and because the number of patients was small. These issues requires further investigation. Disclosure: All authors have declared no conflicts of interest. Keywords: murine double minute 2, p16 INK4, Esophageal squamous cell carcinoma, chemoradiotherapy

Background: Carcinosarcoma of the esophagus is a rare malignant tumor.

Results: All 4 patients were male, mean age 61 years old, and presented with dysphagia at diagnosis. Endoscopic examination revealed type 1 tumors in all cases. We planned esophagectomy with extended lymphadenectomy for all patients; however, non-curative resection was performed in one patient with extended lymph node metastasis. Curative resection was performed in three patients, all cases showed pT1 wall invasion, and two had lymph node metastasis; hense one case of StageI, two of Stage II. Local recurrence was developed in one patient 13 months after curative resection. This patient was treated with chemoradiotherapy, with a clinically complete response. The patient remains alive without recurrence. The other two showed no recurrence. Therefore, three patients with curative resection survived beyond 5 years. The other patient with non-curative resection died of multiple organ metastasis 111 days postsurgery. Discussion: Many patients of carcinosarcoma of the esophagus are diagnosed earlier than in esophageal cancer because protuberant carcinosarcoma causes symptoms like dysphagia; however, lymph node metastasis was frequent with carcinosarcoma of the esophagus at diagnosis. Surgery with extended lymphadenectomy for carcinosarcoma of the esophagus is better prognostically, and chemoradiotherapy for recurrence is as effective as for esophageal cancer. Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal carcinosarcoma, Surgery, chemoradiotherapy P1.17.04: THE EFFICACY AND SAFETY OF NEDAPLATIN AND 5FU COMBINATION CHEMOTHERAPY IN PATIENTS WITH METASTATIC AND RECURRENT ESOPHAGEAL CARCINOMA Fukutaro Shimamoto1, Takayuki Kii1, Masahiro Gotoh1, Motoki Yoshida1, Shin Kuwakado1, Tetsuji Terazawa1, Ken Asaishi1, Kazuhide Higuchi2 1 Osaka Medical College Hospital, Osaka/JAPAN, 2Osaka Medical College, OSAKA/JAPAN Background: A combination chemotherapy with Cisplatin (CDDP) and 5FU is regarded as a standard chemotherapy for metastatic and recurrent esophageal carcinoma, but the administration of CDDP is limited because of accumulative and substantial toxicity such as nephrotoxicity and neurotoxicity. Nedaplaitn (CDGP) is a platinum analogue which was developed with the aim of decreasing these toxicity. We report the efficacy and safety of a combination chemotherapy with CDGP and 5FU (FN therapy) for the patients ineligible for CDDP. Methods: We retrospectively investigated 33 patients received FN therapy from August 2008 to July 2013 in our hospital. Each course of chemotherapy consisted of 80 mg/m2 of CDGP with a 120-minute infusion on day 1 and 800 mg/m2/day of 5-FU with continuous infusion for 24 hours on days 1 to 5. Results: Characteristics of the patients were median age of 68 (range: 44–83) and male/female: 31/2. 13 patients received FN therapy as first-line therapy because of poor performance status and renal dysfunction. The response rate was 25% and the time to treatment failure was 135 days. On the other hand, 20 patients had prior history of treatment with CDDP-based combination chemotherapy. 5 patients refractory to CDDP did not respond to CDGP, but 15 patients who discontinued CDDP because of renal toxicity and upper limit of administration of CDDP partially responded to CDGP. The response rate was 14% and the time to treatment failure was 104 days. Major toxic effects observed were hematotoxicity including Grade 4 neutropenia (12%) and thrombocytopenia (6%), and gastrointestinal toxicity such as Grade 3/4 anorexia (15%) and diarrhea (6%) and stomatitis (6%). No treatment-related deaths were observed. Discussion: FN therapy is suggested to be promising chemotherapy and generally well tolerated in patients with metastatic and recurrent esophageal carcinoma ineligible for CDDP except patients refractory to CDDP. Disclosure: All authors have declared no conflicts of interest. Keywords: Nedaplatin, 5FU, Esophageal cancer, chemotherapy

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P1.17.05: HISTONE DEMETHYLASE LSD1 INHIBITORS PREVENT CELL GROWTH BY REGULATING THE GENE EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA CELLS Isamu Hoshino, Yasunori Akutsu, Naoki Akanuma, Yuka Isozaki, Tetsuro Maruyama, Takeshi Toyozumi, Yasunori Matsumoto, Hiroshi Suito, Masahiko Takahashi, Nobufumi Sekino, Aki Komatsu, Takayoshi Suzuki, Hisahiro Matsubara Graduate School of Medicine, Chiba University, Chiba/JAPAN Background: Epigenetic changes, such as histone modification, are thought to underlie a wide range of diseases, including various cancers. The expression of genes can be influenced by the balance of histone acetylation and/or histone demethylation, with an imbalance of these processes possibly observed in many cancers. The histone demethylase LSD1 inhibitor activity is associated with selective transcriptional regulation and alterations in the gene expression. However, the exact mechanisms underlying the antitumor effects of LSD1 inhibitors are not fully understood. Methods: The antitumor effects of NCL1, an LSD1 inhibitor, in esophageal squamous cell cancer (ESCC) cell lines was evaluated. A comprehensive analysis of the changes in the gene expression in ESCC cell lines induced by NCL1 was carried out using a microarray analysis. A loss-of-function assay using a siRNA analysis was performed to examine the oncogenic function of the gene. Results: NCL1 strongly inhibited the cell growth of T.Tn and TE2 ESCC cells and induced apoptosis. According to the microarray analysis, 81 genes in the T.Tn cells and 149 genes in the TE2 cells were up- or downregulated 2-fold or more by NCL1 exposure. Among these genes, 27 were contained in both cell lines and exhibited similar expression patterns. PHLDB2, one of the genes downregulated by NCL1, was overexpressed in the ESCC tumor tissues. Moreover, a high expression level of PHLDB2 was found to be significantly correlated with a poor prognosis.


Discussion: Incidence of gastric tube cancer was a relatively high 2.8% in our hospital as a secondary cancer after resection for esophageal cancer. We should be processed in a minimally invasive when the gastric tube cancer occurs. Therefore, after resection for esophageal cancer, at intervals of one year or less, regular endoscopic examination should be recommended. Disclosure: All authors have declared no conflicts of interest. Keywords: eshophageal cancer, gastric tube cancer, double cancer, endoscopic resection P1.17.07: FEEDING DOUDENOSTOMY DECREASES THE INCIDENCE OF MECHANICAL ILEUS AFTER RADICAL ESOPHAGEAL CANCER SURGERY Hisaharu Oya, Masahiko Koike, Naoki Iwata, Daisuke Kobayashi, Yukiko Niwa, Mitsuro Kanda, Chie Tanaka, Suguru Yamada, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Shuji Nomoto, Michitaka Fujiwara, Yasuhiro Kodera Nagoya University Graduate School of Medicine, Nagoya/JAPAN Background: The impact of nutritional support on the outcome of gastroenterological surgery is well known and in highly invasive surgery such as esophageal cancer surgery, management by enteral nutrition effectively mitigates postoperative complications including ileus, which leads to relaparotomy and could be potentially life-threatening. To reduce these complications, we began to place the enteral feeding catheter via duodenostomy in 2009. Here we conducted a retrospective study to compare the new technique with the conventional jejunostomy feeding.

Keywords: Histone demethylase inhibitor, LSD1 inhibitor, PHLDB2, esophageal squamous cell carcinoma

Methods: Three hundred and seventy-eight patients with esophageal cancer who underwent radical esophagectomy with retrosternal or posterior mediastinal gastric tube reconstruction at Department of Gastroenteral Surgery (Surgery II), Nagoya University Hospital from January through December 2012 were indentified in the prospective databse. These patients were classified into 2 groups accoding to the feeding route: 111 cases of feeding via doudenostomy (FD) and 267 cases of feeding via jejunostomy (FJ). Records of all patients were reviewed and th following complications related to enteral feeding were analyzed: catheter site infection, catheter dislodgement, catheter-related peritonitis and mechanical ileus.

P1.17.06: A STUDY OF GASTRIC TUBE CANCER AFTER ESOPHAGECTOMY FOR ESOPHAGEAL CANCER Kenji Kobayashi1, Ko Takachi2, Taro Aoki2 1 Hyogo Prefectural Nishinomiya Hospital, Nishinomiya/JAPAN, 2Kinki Centaral Hospital, Itami/JAPAN

Results: Mechanical ileus was observed in 12 patients (4.5%) in the FJ group but none in the FD group (P = 0.023). Surgery was required in as many as 7 of the 12 cases (58.3%) of which bowel resection was needed in 2 cases due to strangulated ileus. Catheter site infection was seen in 14 cases (5.2%) among the FJ, of which 2 (14.2%) developed peritonitis following catheter dislocation, while only one case was seen among the FD group (0.9, P = 0.049).

Discussion: The present observations of the comprehensive analysis of the gene expression levels provide insight into the mechanisms underlying the antitumor effects of LSD1 inhibitors in ESCC patients. Disclosure: All authors have declared no conflicts of interest.

Background: Double cancer is often found in esophageal cancer. In particular, the merger with gastric cancer is often in esophageal cancer. We examine gastric tube cancer as a secondary cancer after esophagectomy, and report about the problems. Methods: Esophageal cancer patients who were admitted to the Kinki Central Hospital in 2000–2013 year were 332 people. The resection/reconstruction for esophageal cancer were 143 cases, the chemoradiotherapy were 113 cases and the endoscopic resection (EMR/ESD) were 76 cases. Double cancer was 31 cases (21.7%) of the 143 esophagectomies. When limited to gastric cancer, double cancer was 9 cases (6.3%). We found four cases of gastric tube cancers by regular postoperative endoscopic examination. We discuss the subject four cases gastric tube cancer (2.8%) after esophagectomy. Results: Histological type of all cases was differentiated adenocarcinoma. Case 1: 65-year-old man pT3N2M0 StageIIIB. No abnormalities in the examination in 25 months after esophagectomy. We found a IIc gastric tube cancer at 32 months later and EMR was performed. Intramucosal cancer, lyv0, 22 × 15 mm. He is alive for 161 months after esophagectomy. Case 2: 65-year-old man pT1N0M0 StageIA. No abnormalities in the examination in 68 months after esophagectomy. We found a type 3 gastric tube cancer at 85 months later and resected a gastric tube (pT3N1M0, 67 × 63 mm). After that, he died in systemic blood-borne metastasis. It was 100 months later after esophagectomy, and was 12 months later after resection of gastric tube. Case 3: 64-year-old woman pT1N0M0 StageIA. No abnormalities in the examination in 54 months after esophagectomy. We found a IIc gastric tube cancer at 60 months later and treated with endoscopic resection (ESD) (pT1aN0M0, 9 × 6 mm). She is alive for 67 months after primary surgery. Case 4: 74-year-old-man pT2N0M0 StageIB. No abnormalities in the examination in 36 months after esophagectomy. We found a IIc gastric tube cancer at 48 months later and treated with endoscopic resection (ESD) (pT1aN0M0, 24 × 15 mm). He is alive for 57 months after primary surgery.

Discussion: Various methods to create enterostomy using different intestinal tract implantation sites, fixation positions, and fixation methods have been proposed to prevent ileus. Despite due consideration given to proposals for jejunostomy in the literature, surgical complications were relatively frequent in the FJ group and even led to resection of a relatively large portion of the jejunum in one case. We eventually employed a new approach-creation duodenostmy. Neither mechanical ileus nor relaparotomy was seen during enteral feeding via duodenostomy. Hence, we believe that feeding via duodenostomy is superior to jejunostomy. Disclosure: All authors have declared no conflicts of interest. Keywords: Jejunostomy, Duodenostomy, enteral nutrition, Esophageal Cancer Surgery P1.17.08: ESOPHAGO GASTRIC HISTIOCYTIC SARCOMA – A RARE CASE OF DYSPHAGIA IN ADULT CAUSING DIAGNOSTIC AND THERAPEUTIC DILEMMA Jasper Sandeep Rajasekar, T Perungo, Servarayan Murugesan Chandramohan, Madeswaran Chinnathambi, John Grifson, Jeyasudhahar Jesudason, Rajendran Vellaisamy, D Kannan, A Amudhan, D Bennet, R Prabhakaran, S Babu Madras Medical College, Chennai/INDIA Background: Squamous cell carcinoma of the esophagus followed by corrosive stricture are the commonest causes of dysphagia that we encounter in our department. The most common cause of ulceroproliferaive lesion in stomach and Gastro Esophageal junction is adenocarcinoma. Here we report a very rare case of Esophago Gastric Histiocytic Sarcoma which eluded diagnosis in multiple centres and was managed successfully by our team. Methods: A 41 year old gentleman has visited multiple centres with dysphagia for a period of three months. All the three endoscopists have made a diagnosis of mitotic disease involving the esophagus and stomach but


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the biopsy did not confirm the diagnosis of either squamous cell carcinoma or adenocarcinoma. CECT of chest and abdomen had picture suggestive of malignancy involving the esophagus, GE junction and stomach. A diagnostic laparoscopy was performed which showed serosal involvement at GE junction and proximal stomach. An omental nodule found was biopsied and was found to be non – mitotic. A multidisciplinary team consisting of Gastro Intestinal surgeons, Medical Gastroenterologist, Radiation Oncologist and Medical Oncologist decided on surgery for removing the disease, definitive diagnosis and relief of dysphagia. After obtaining informed consent, the patient underwent subtotal esophagectomy and total gastrectomy with colon reconstruction with cervical anastomosis. The final pathology report was Histiocytic sarcoma. The patient is now on follow up radiotherapy Results: Histiocytic sarcoma is an extremely rare non – Langerhans histiocytic disorder of monocyte-macrophage lineage. It accounts for less than one percent of all nodal and extranodal lymphoid tissue tumours. Middle aged people (median age 46–55 years) are most commonly affected with no gender preponderance. The disease can be unifocal or multifocal with involvement of skin, soft tissues, bone, lymphnode, liver, spleen and central nervous system. Isolated involvement of Gastro intestinal tract involvement is common involving ileum, rectum, anus, stomach and esophagus. However the involvement of esophagus, Esophago Gastro junction and stomach as a whole like our case was never reported before. Diagnosis is made by Histopathological examination which shows large polygonal or ovoid cells with abundant eosinophilic cytoplasm and irregularly folded eccentrically placed pleomorphic nuclei. ImmunoHistochemistry staining is positive for markers CD163, CD 68, LYS and sometimes S-100 as in our case and are specifically negative for T and B cell markers. Radical surgery followed by adjuvant Radiotherapy gives the best results while adjuvant chemotherapy is reserved for inoperable cases. We decided to proceed with surgery as the patient had symptomatic operable tumour with undiagnosed pathology. A pre operative definitive diagnosis of Histiocytic sarcoma, would not have altered the line of our management. The prognosis depends on the stage of the disease. Discussion: This case is presented for its extremely rare diagnosis of Histiocytic sarcoma, and the first known case in the literature to the best of our knowledge to affect esophagus, Esophago Gastric junction and stomach in continuity. Disclosure: All authors have declared no conflicts of interest. Keywords: Histiocytic Sarcoma, Esophagogastrectomy, First case, esophagogastric junction

P1.17.09: SECOND PRIMARY GASTRIC CANCER IN THE GASTRIC TUBE AFTER ESOPHAGECTOMY Ju Sik Yun, Seung Ku Kang, Sang Yun Song, Kook Joo Na Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeollanam-do/KOREA Background: As the prognosis of patients who underwent esopahgectomy for esopahgeal cancer has improved recently, the incidence of second primary cancer arising from gastric tubes used for reconstruction has been increasing. We investigated 5 cases of gastric tube cancer (GTC) after esophagectomy followed by esophagogastrostomy to evaluate the appropriate treatment and their outcomes. Methods: Total 215 patients underwent esophagogastrostomy after esophagectomy for esophageal cancer at Hwasun Chonnam National University Hospital between 2004 and 2013. And 5 (2.3%) of them developed a second primary cancer in the gastric tube. We retrospectively reviewed the medical records of these patients. Results: All of them were male, with an age range of 55∼72 years at the time of esophagectomy. 3 patients underwent Ivor-Lewis esopahgectomy and 2 patients underwent 3-phase esopahgectomy. The median interval between esophagectomy and treatment of GTC was 32 months (range, 7∼45). All gastric tube cancers were diagnosed as adenocarcinoma, by periodic endoscopic examination. Endoscopic mucosal resection (EMR) was performed in 2 patients, total gastrectomy followed by colon interposition was performed in 3 patients, including 1 patient who underwent additional right hemicolectomy for synchronous colon cancer. Although 1 patient died of pneumonia 6 weeks after the surgery, and 1 patient treated endoscopically died for reasons other than cancer itself, the others are alive without any recurrence. The median follow-up period after treatment of GTC was 11 months (range, 1∼15).

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Discussion: Long-term follow-up including regular endoscopic examination is necessary to ensure of early detection of GTC. EMR is a less invasive, curative treatment option for gastric tube cancer. And surgery such as total gastrectomy followed by re-reconstruction using the colon graft is a potential treatment option if it doesn’t meet the indication for EMR. Disclosure: All authors have declared no conflicts of interest. Keywords: gastric tube cancer, esophagectomy P1.17.10: EPIDEMIOLOGICAL FEATURES OF ESOPHAGEAL CANCER: SQUAMOUS CELL CARCINOMA VERSUS ADENOCARCINOMA Maria Aparecida Henry School of Medicine, Botucatu/BRAZIL Background: The aim of the investigation was to analyze the epidemiological features of patients with esophageal cancer according to the histopathological types: squamous cell carcinoma or adenocarcinoma. Methods: A total of 100 patients with esophageal cancer, being 50 squamous cell carcinomas and 50 adenocarcinomas were analyzed for demographics, nutritional factors, lifestyle habits, benign pathological conditions associated, like Barrett’s esophagus and megaesophagus, tumor stage and survival rates. The nutritional factors evaluated included body mass index, percent weight loss, hemoglobin and albumin serums levels. Results: Esophageal cancer occurred more often in men over 50 years-old in both histological groups. No significant differences on age and gender were found between the histological groups. Squamous cell carcinoma was significantly more frequent in blacks than adenocarcinoma. Alcohol consumption and smoking were significantly associated with squamous cell carcinoma. Higher values of body mass index were seen in patients with adenocarcinoma. Barrett’s esophagus was found in 9 patients (18%) with adenocarcinoma, and megaesophagus in 2 patients (4%) with squamous cell carcinoma. The majority of patients were on stages III and IV in both histological groups. The mean survival rates were 7.7 +/− 9.5 months for patients with squamous cell carcinoma and 8.0 +/− 10.9 months for patients with adenocarcinoma. No significant differences on tumor stage and survival rates were detected between the histological groups. Discussion: Epidemiological features are distinct for the histopathological types of esophageal cancer. Squamous cell carcinoma is associated with black race, alcohol and smoking while adenocarcinoma is related to higher body mass index, white race and Barrett’s esophagus. Disclosure: All authors have declared no conflicts of interest. Keywords: epidemiology, esophageal cancer, squamous cell carcinoma, adenocarcinomaus cell P1.17.11: PRIMARY ESOPHAGEAL MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA TREATED BY ENDOSCOPIC SUBMUCOSAL DISSECTION Kenji Kudo, Kosuke Narumiya, Masaho Ota, Yuji Shirai, Takeshi Oki, Harushi Osugi, Masakazu Yamamoto Tokyo Women’s Medical University, TOKYO/JAPAN Background: Primary esophageal MALT lymphoma is rare. There have been few reports about early primary esophageal MALT lymphoma being treated endoscopically. Methods: A 66-year-old man had an esophageal lesion detected by upper gastrointestinal endoscopy during a routine medical check-up. The test for Helicobacter pylori antibody was negative. Endoscopy showed a whitish, longitudinal, flat-topped, elevated submucosal tumor (1.5 × 0.5 cm) on the posterior wall of the esophagus approximately 35 cm from the incisors. Lugol chromoendoscopy revealed a poorly-demarcated unstained streak. Narrow-band imaging magnified endoscopy revealed obscure whitish mucosa without any irregular microvessels. Endoscopic ultrasonography (2T-20 MHz) showed a hypoechoic mass in the submucosa, which was clearly demarcated from the muscle layer. Biopsy ya diagnosis of suspected lymphoma. There was no evidence of other lesions from the chest to the pelvis on computed tomography. Based on these findings, we performed ESD with a clip traction technique.

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Results: The procedure was completed in 50 minutes. The resected specimen measured 25 × 12 mm and the lesion itself was 15 × 5 mm in size. Histopathological examination showed that the lesion was composed of small atypical lymphoid cells. These cells were positive for CD20 and CD79a, but were negative for CD5 and CD10. The final diagnosis was primary esophageal MALT lymphoma with negative margins. The patient was on a liquid diet for 2 days postoperatively. He started solids on day 3, and he was discharged 5 days after resection. Discussion: The clinical profile of primary esophageal MALT lymphoma is currently unclear, so it is important to accumulate more information about early esophageal MALT lymphoma which must be detected at an early stage and this requires detailed knowledge of macroscopic tumor morphology. Endoscopic resection is one of the most effective treatments. Here we report the macroscopic appearance of the tumor the first successful case of ESD for extremely early esophageal MALT lymphoma. Disclosure: All authors have declared no conflicts of interest. Keywords: dissection

esophageal

MALT

lymphoma,

endoscopic

submucosal

P1.17.12: NARROW-BAND IMAGING VERSUS LUGOL CHROMOENDOSCOPY FOR DETERMINING THE LATERAL EXTENT OF SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA Manabu Takeuchi, Kazuya Takahashi, Satoru Hashimoto, Kenichi Mizuno, Masaaki Kobayashi Niigata University Medical and Dental Hospital, Niigata/JAPAN Background: Although esophageal Lugol staining remains the gold standard for diagnosis of delineation of superficial esophageal squamous cell carcinoma (ESCC), its spraying process has some problems. For example, it may suppress the operability of the endoscope at the time of making circumferential marks because of accelerating esophageal spasms, and it may show heterogeneous mucosal unstained coloration because of the time taken to make marks around a large esophageal carcinoma. Recent studies have reported narrow-band imaging (NBI) useful for detecting superficial ESCC, but determination of the lateral extent of superficial ESCC has not yet been described. Methods: The aim of this study was to clarify the diagnostic ability of endoscopy with NBI and Lugol chromoendoscopy for demarcation of superficial ESCC. Ninety consecutive lesions in 78 patients excluding local recurrence after CRT, were enrolled between August 2012 and July 2013. All lesions were resected using endoscopic submucosal dissection (ESD). First, lesion margins were delineated before ESD by recognition of brownish areas and/or microvascular irregularity by NBI and marking dots were made 1–2 mm outside the delineation. Second, lesions margins were determined using 0.6% iodine staining. If the unstained area was different from the lateral extent by NBI observation, additional markings were made. The diagnostic accuracy of the lateral extent between NBI and Lugol staining was analyzed prospectively. Results: The complete en bloc resection rate was 100% (90/90). The rate of accurate diagnosis using the NBI system and Lugol chromoendoscopy were 90% (81/90) and 100% (90/90) respectively. Histologically, all misdaignosed areas by NBI observation showed a carcinoma in situ with low grade atypia. The mean size of misdiagnosed areas was 15 mm (range 2–60 mm). With multivariate analysis, the risk of misdiagnosis using the NBI system was lesion color non-reddish (P = 0.009) and multiple Lugol voiding lesions (P = 0.014). Discussion: For determining the lateral extent of superficial ESCC, making marks is an acceptable method with NBI and subsequent Lugol chromoendoscopy. Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal chromoendoscopy

carcinoma,

Lateral

extent,

NBI,

Lugol

P1.17.13: DECREASED FOOD INTAKE, HEMATOTOXICITY AND GASTROINTESTINAL SYMPTOMS IN NEOADJUVANT CHEMOTHERAPY FOR ESOPHAGEAL CANCER Erika Naito1, Shinichi Asaka1, Takeshi Shimakawa1, Atuko Usuda1, Akira Miyaki1, Asako Shimazaki1, Minoru Murayama1, Kentaro Yamaguchi1, Takebumi Usui1, Hajime Yokomizo1, Shunichi Shiozawa1, Kazuhiko Yoshimatsu1, Takao Katsube1, Yasuyuki Terai2, Yoshihiko Naritaka1 1 Tokyo Women’s Medical University Medical Center East, Tokyo/JAPAN, 2 Tokyo Women’s Medical University Medical Center East, Tokyo/JAPAN Background: Food intake decreases in many patients with esophageal cancer during neoadjuvant chemotherapy. We evaluated the association among decreased food intake, hematotoxicity and gastrointestinal symptoms.


Methods: We examined the data of 13 esophageal cancer patients (a total of 26 chemotherapy cycles) who were able to eat and underwent 2 cycles of preoperative adjuvant chemotherapy with docetaxel, CDDP and 5-fluorouracil (DCF) in June, 2013 from November, 2009. Decreased food intake was defined as 50% ≤ decrease of food intake from baseline. Association among decreased food intake, blood biochemical tests (serum albumin [Alb], WBC, neutrophil count and serum sodium [Na]) and gastrointestinal symptoms (diarrhea and nausea) was evaluated for each treatment cycle. Results: Decreased food intake was noted in 69% (18/26). The frequency of decreased food intake was 85% (11/13) of patients with Alb < 3.5 g/dL, 54% (7/13) in those with Alb ≥ 3.5 g/dL, 73% (8/11) in those with WBC < 3,000/μL, 67% (10/15) in those with WBC ≥ 3,000/μL, 80% (8/10) in those with neutrophil count 5/50

Discussion: Enucleation is associated with R1 resection in our group of patients. Available data are insufficient for a statistically valid analysis of risk factors for disease progression, especially conserning type of surgery. However, it seems that enucleation may be adequate for tumors ≤ 5 cm. (Supported by the project by Ministry of Health, Czech Republic and University Hospital Motol 00064203) Disclosure: All authors have declared no conflicts of interest. P1.17.23: C-REACTIVE PROTEIN INHIBITS LYMPHANGIOGENESIS AND RESULTANT LYMPH NODE METASTASIS OF SQUAMOUS CELL CARCINOMA IN MICE Tomohiko Sasaki Akita University Graduate School of Medicine, Akita/JAPAN Background: Lymph node involvement is the most important prognostic factor in many solid cancers. Recently, we found that patients with esophageal and lung cancer carrying the C-reactive protein (CRP) 1846T/T genotype, which is associated with lower serum CRP levels, are more likely to have lymph node metastasis. We hypothesized that host CRP directly inhibits lymph node metastasis. Methods: We inoculated NR-S1M metastatic cells subcutaneously into the backs of C3H/HeN mice. Concurrently, 1 mg of recombinant mouse CRP or phosphate-buffered saline was injected subcutaneously every 3 days for 5 weeks, after which the mice were killed for evaluation. We evaluated lymph node metastasis and lymphangiogenesis in the implanted tumor by using immunohistochemical analysis with anti-pancytokeratin and antilymphatic vessel endothelial hyaluronan receptor-1 antibodies. Results: There was no substantial difference in tumor size between the 2 groups but the lymph nodes were smaller in the CRP group than the control group (P < .044). Immunohistochemical analysis confirmed inguinal lymph node metastasis in 70% (14/20) of control mice, but in only 30% (3/10) of mice in the CRP group. Moreover, the metastatic area within lymph nodes was less in the CRP group (P < .042) and tumoral lymphangiogenesis was decreased in the CRP group (P < .037). Discussion: CRP appears to inhibit tumoral lymphangiogenesis and lymph node metastasis in mice. These findings suggest that by inhibiting lymph node metastasis, CPR may have therapeutic potential for use against cancer. Disclosure: All authors have declared no conflicts of interest. Keywords: lymph node metastasis, squamous cell carcinoma, CRP, lymphangiogenesis P1.17.24: A CASE OF HERPES SIMPLEX VIRUS- 1 ENCEPHALITIS FOLLOWING CHEMO-RADIOTHERAPY FO ADVANCED ESOPHAGEAL CANCER Masaaki Saito, Hirokazu Kiyozaki, Daisuke Ishioka, Osamu Takata, Toshiki Rikiyama Saitama Medical Center, Jichi Medical University, Saitama/JAPAN Background: It is reported that systmic chemotheapy and seroids as a prophylactic antiemetics may induces immunosuppressive state.There are a few reports that Herpes siplex vius- 1(HSV-1) infection with such a states were ccured in small cel carcinoma afterchemoradiotherapy with brain irradation. In addition, we reported a case of HSV-1 encephalitis that occurred during chemoadiotherapy for adanced esophageal cancer. Methods: A 74-year-old-woman was administered chemoradiotherapy (5-FU 700 mg/m2, CDDP 70 mg/m2, RT total 60 Gy) for stage III esophaeal cancer. Radiation 60 Gy total dose started with two courses of chemotheray with dexametasone as prophylactic antiemetics. Results: Two days before four courses of chemotherapy completion she developed acute neurological symptoms of disorientation, clouding of consciousness and fever. MRI T2 weighted images showed high intensity area in bilateral temporal lobe inside cortexes and insular cortex. Furthermore, blood test showed high level oh HSV-1 IgG. A diagnosis of herpetic

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encephalitis HSV-1 was made. She gave intravenous administration of aciclovir for three weeks and state of consciousness was gradually improved and came to be able to condct smple mutual undertnding. Discussion: In advanced esophageal cancer patients, chemoradiotherapy and surgery are standard treatment. A primary infection or a reactivation of an endogenous latent HSV-1 in brain cortexes under chemoradiation therapy and steroid may compromise these benefits. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, chemoradiotherapy, Herpes simplex virus 1, encephalitis P1.17.25: EARLY SYSTEMATIC EXERCISE GUIDANCE IS BENEFICIAL TO REDUCE POSTOPERATIVE COMPLICATIONS FOR PATIENTS WITH ESOPHAGEAL CANCER Rujian Lu, Hongjun Chu, Hong Shen, Xiaojie Qi Nantong Third People’s Hospital, Nantong University, Nantong/CHINA Background: The aim of this study was to investigate the impact of early systematic exercise guidance on the postoperative complications for patients with esophageal cancer. Methods: A total of 140 postoperative patients were enrolled and divided into two groups: early experiment group (n = 70) and control group (n = 70). the patients in the early experiment group were given systematic exercise guidance since POD 1 in addition to the conventional thoracic postoperative care, while the patients in the control were not given any specific requirements for exercise. Results: No significant difference was observed between the two groups in demographics, operative time, blood loss and lymph nodes harvested. No 30-day mortality occurred in this series. The total rate of complications was lower in early systematic exercise group than control group (17.1% vs 31.4%, p = 0.049), including less occurence of pneumonia, venous thrombosis of lower limbs, gastric emptying dysfunction. Besides, the hospital stay was also shorter in early systematic exercise group than control group (10[7- 56] d vs12[9- 63]d, p = 0.037). Discussion: Early systematic exercise guidance could be beneficial to reduce the incidence of postoperative complications for patients with esophageal cancer. However, further randomized controlled trials are required to confirm these findings. Disclosure: All authors have declared no conflicts of interest. Keywords: Early Systematic Exercise, Postoperative Complications


Results: Details about tolerability are shown in the Table. Overall, HVs did not found any difference between the 2 systems, whereas patients tolerated better the SS procedure. Significantly higher set-up time (454sec vs. 222sec, p < 0.01) and plot analysis time (601sec vs. 345sec, p < 0.01) was required by the WP system compared to the SS system. No difference was observed between the WP and SS system in terms of tracing acquisition (483sec vs. 552sec, p = 0.6). The single-procedure cost was 58,48 € for the WP system and 79,18 € for the SS system. HVs (n = 20) WP System Symptoms Occurrence, n (%) None 4 (20%) Pain 4 (20%) Heartburn 4 (20%) Nausea and Vomiting 1 (5%) Globus 10 (50%) Presence of Discomfort, 17 (85%) n (%) Location of Discomfort, n (%) Nose 6 (30%) Throat 10 (50%) Chest 0 (0%) Stomach 1 (5%) HRM Better Tolerated, n (%) SS 9 (45%) WP 9 (45%) None 2 (10%)

Patients (n = 20) SS System

WP System

SS System

3 (15%) 3 (15%) 5 (25%) 1 (5%) 9 (45%) 11 (55%)

1 (5%) 6 (30%) 1 (5%) 4 (20%) 9 (45%) 16 (85%)

14 (70%) 2 (10%) 0 (0%) 3 (15%) 4 (20%) 7 (35%)

5 (25%) 6 (30%) 0 (0%) 0 (0%)

8 (40%) 7 (35%) 0 (0%) 1 (5%)

4 (20%) 3 (15%) 0 (0%) 0 (0%)

11 (55%) 3 (15%) 6 (30%)

Discussion: The SS system was better tolerated by patients and required shorter set-up and analysis time. This may be explained by a heightened patients sensitivity to water outflow. The procedure cost was though substantially higher for the SS system due to the higher price of the SS catheter. Disclosure: All authors have declared no conflicts of interest. Keywords: High Resolution Manometry, Chicago Classification, Primary Esophageal Motility Disorders, reproducibility

P2.02.01: A CASE OF PSEUDOACHALASIA CAUSED BY METASTATIC GASTRIC CANCER IN THE MUSCLE LAYER OF THE ABDOMINAL ESOPHAGUS Takahiro Masuda, Fumiaki Yano, Nobuo Omura, Kazuto Tsuboi, Masato Hoshino, Seryung Yamamoto, Shunsuke Akimoto, Koji Nakada, Yoshio Ishibashi, Hideyuki Kashiwagi, Katsuhiko Yanaga The Jikei University School of Medicine, Tokyo/JAPAN

Wednesday, September 24 – 08:00–15:45 P2: Wednesday Poster Session Room: Foyer

Background: Pseudoachalasia caused by metastatic gastric cancer is rare. We report a case of pseudoachalasia caused by metastatic gastric cancer in the muscular layer of the abdominal esophagus 5 years after distal partial gastrectomy.

P2.01.01: COMPARATIVE ASSESSMENT OF TOLERABILITY, DURATION AND COSTS OF SOLID-STATE VS. WATERPERFUSED SYSTEM FOR ESOPHAGEAL MOTILITY TESTING – DATA FROM A PROSPECTIVE, RANDOMIZED, DOUBLE BLIND, CROSSOVER STUDY Giovanni Capovilla, Renato Salvador, Edoardo Savarino, Loredana Nicoletti, Giovanni Zaninotto, Mario Costantini University of Padua, Padua/ITALY

Methods: A 68-year-old woman underwent distal partial gastrectomy for gastric cancer in August 2007. She suffered from dysphagia since March 2012. She was diagnosed as primary achalasia and referred to our hospital. The esophageal manometry examination was performed. The simultaneous waves were observed at her esophageal body during wet swallows, and these results fulfilled the diagnostic criteria of achalasia. The length of the narrow segment by timed barium esophagogram was longer than that of primary achalasia and computed tomography of the chest and abdomen showed thickening of the esophageal wall. Therefore, pseudoachalasia was highly suspected and we decided to perform surgery by laparotomy.

Background: High Resolution Manometry (HRM) is a new technique for intraluminal esophageal pressure measurement, performed with a multitude of closely spaced (30 mmHg, and type III was associated with spasm. Symptoms were analyzed by a structured self-reported questionnaire that focused on dysphagia and chest pain, especially with regard to the location, the timing, and the duration. Of the 52 patients, 41 patients who fully answered the questionnaire were analyzed with regard to their symptoms. Results: The 52 achalasia patients comprized 21 patients in type I, 27 in type II, and 4 in type III. HRM showed that the amplitude of contraction in the distal esophagus was significantly lower (ANOVA, p < 0.01) in type I (14.4 mmHg) than in the other types, while it was the highest in type III (116.9 mmHg) and intermediate in type II (28.3 mmg). Regarding symptoms, type I patients had less chest pain (4/13, 23%) than type II patients (12/24, 50%) and type III patients (3/4, 75%) (Fisher’s exact test, p = 0.081). There was a significant (p < 0.05) difference in the timing of dysphagia among the types, and type II patients more frequently described the occurrence of dysphagia “immediately” after swallowing than at other times. The duration of chest pain was also different (p = 0.056) among the types. All type III patients (100%) had a duration of 1–5 min, compared with 50% of type I and 25% of type II patients. “Vomiting after chest pain” was reported by 75% of type I patients and 25% of type II patients, but not by type III patients (0%). Discussion: The symptoms of patients with achalasia differed according to the CC types, probably reflecting differences of the pathophysiology and manometric characteristics. The CC seems to be suitable for clinical application in the management of achalasia. Disclosure: All authors have declared no conflicts of interest. Keywords: High Resolution Manometry, esophageal achalasia, dysphagia, Chicago Classification P2.02.04: TREATMENT PATIENTS WITH NEUROMUSCULAR ELECTRICAL STIMULATION (VOCASTIM®) IN NEUROLOGIC SWALLOWING DISORDERS Fernando Robledo Hospital Paroissien, Is¡idro Casanova/ARGENTINA Background: Swallowing is a complicated neurological reflex that involves a well orchestrated sequence of three major phases. Stroke is the leading cause of neurologic dysphagia. Approximately 51–73% of patients with stroke have dysphagia, which is the most significant risk factor for the development of pneumonia; this can also delay the patient’s functional recovery. The current conventional therapy for dysphagia usually employs techniques of compensatory strategy Objective: To evaluate the effectiveness of the skin neuroelectroestimulacion with the use of VocaSTIM in the correction of swallowing disorders. Methods: From March 2011 until May of 2013 were 38 treatments, only 26 completed all of the treatment (the remaining Twelve abandoned or did not complete due to family/partner) 26 Patients were included (16 men, 10 women) average age between 32 to 78 years. Its largely dysphagia by neurological sequelae (stroke, paralysis of the recurrent, sequels neurological postcirugias: Meningiomas etc.) other causes were (esophageal bolus, cricopharyngeal spasm,) We average between 8–10 sessions of 20 minutes average 2 times a week, was conducted all (VFSS): Videofluoroscopic Swallow Study initial and control as well as a home electrodiagnosis to objectively assess degree of denervation in some cases esophageal manometry and videoesofagogastroscopy and nasal fiberoptic endoscopic evaluation of swallowing (FEES). Measurements: To establish comparisons all held you a (VFSS) initial and control as well as an electro-Diagnostics of home and its completion to

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objectively assess the degree of denervation and x-ray of thorax and videoesofagogastroscopy and nasal fiberoptic endoscopic evaluation of swallowing (FEES), in the majority of cases esophageal manometry and in 2 cases carried out impedance measurement and in 6 cases pH 24/metry. Results: Response was assessed according to degree of clinical and scale as well as the corresponding electrodiagnosis dysphagia. This technique combines the attempt to carry out a voluntary contraction with the manual trigger of electro-stimulation by means of a push button. The following score were evaluated to determine the responses of the patients. Patient satisfaction/Values of electro-Diagnostics (finals) les/Score of speech/grade of dysphagia evaluation It was noted a degree of positive response (degree of satisfaction) in more of the 80 % patients as well as a superior response to the 90 % electrodiagnosis, speech evaluation is considered good to very good in more of the 80 % of the patients. High degree of response in diseases with neurological lesions (ACV, Sequels neurosurgery, TCE, etc) was observed in diseases neurodegenerative (ALS, Parkinson,) the response was considered poor (regular/good) with the exception of Neuropharyngeal dystrophy whose assessment was very good and bad in the dysphagia cause esophageal diseases (esophageal bolus, cricopharyngeal spasm) There was disparity between the clinical evolution and the video swallowing the electrodiagnostic usually accompanied the clinical response. Discussion: VocaSTIM ® can produce a different degree of satisfaction functional response in the majority of patients with dysphagia. As parameters to further evaluate in the future we see the best result of vocaSTIM ® is observed above muscles contractility improvements suprahyoid (l) e infrahyoid (2). Disclosure: All authors have declared no conflicts of interest. Keywords: Neuromuscular electrical stimulation. (NMES), Key words: Dysphagia, Electrostimulation, vocaSTIM ®. P2.03.01: A NEW PROPOSAL FOR THE TREATMENT OF THE GASTROESOPHAGEAL REFLUX DISEASE: THE “NISSENBARDINI” FUNDOPLICATION Romeo Bardini1, Renato Salvador1, Lisa Zanatta1, Edoardo Savarino2 1 University of Padova, Padova/ITALY, 2University of Padua, Padua/ ITALY Background: Laparoscopic Nissen fundoplication has become the surgical treatment of choice in patients with gastroesophageal reflux, but the percentage of redo-fundoplication for recurrence are still high (5–20%). The most frequent cause of failure is the disruption of the hiatal repair and a migration of the fundoplication. The reason of these complications can result from excessive tension during the primary suture placement or from the weakening of the crura tissues. This video shows a proposal to prevent these mechanisms of failure. Methods: The technique (“Nissen-Bardini” Fundoplicatio, NB) consisted in reinforcement of the crura with a 1/2 absorbable-1/2 no-absorbable mesh. The meshes were manually shaped to envelop the crura and secured to them with clips. The iatoplasty was performed. The esophagus was fixed to the crura through the mesh with 2 sutures in each side catching the muscular coat. Finally the Nissen fundoplication was performed with the traditional technique. The patients were evaluated befre and after surgery by a detailed symptoms and a Quality of Life (GERD-HRQL) questionnaires, esophageal manometry, 24 hour pH-Impedance monitoring, endoscopy and barium swallow. Results: 20 patients underwent NB (M : F 11:9, median age was 52 y, IQR 46–63 y); 12 patients had a NB as a primary treatment and 8 patients as a redo-fundoplication. Mortality and post-operative complication were nil. The median procedure time was 170 min. The median follow up was 12 months and radiologic, endoscopic or symptoms recurrences weren’t seen. No-one patient referred dysphagia. Discussion: The preliminary data of this study showed that NB is a safe and effective procedure for the treatment of gastroesophageal reflux disease and for the failure of previous fundoplicatio. NB could decrease the risk of recurrence. Disclosure: All authors have declared no conflicts of interest. Keyword: Gastroesophageal reflux, redo-fundoplicatio P2.03.02: A MODIFIED NISSEN FUNDOPLICATION FOR THE TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE TO REDUCE THE RISK OF FAILURE. PRELIMINARY RESULTS FROM A PROSPECTIVE, CONTROLLED STUDY Renato Salvador1, Lisa Zanatta1, Edoardo Savarino2, Francesco Cavallin3, Romeo Bardini1 1 University of Padova, Padova/ITALY, 2University of Padua, Padua/ ITALY, 3IOV-IRCCS, Padova/ITALY Background: Failures of Nissen Fundoplication (NF) occurs in 5–20% of the cases. Its most frequent cause is the disruption of the hiatal repair or the


migration of the fundoplication. This phenomenon is likely due to the excessive tension during the primary suture placement or the weakening of the crura tissues. Recently, our group proposed a modified-Nissen procedure approach in order to reduce the rate of failure (Nissen-Bardini Fundoplication, NBF). So far, the aim was to evaluate the clinical and pathophysiological findings, the feasibility and the final outcome of this new technique. Methods: The NBF consisted in reinforcement the crura with a 1/2 absorbable-1/2 no-absorbable mesh. The meshes were manually shaped to envelop the crura and secured to them with clips. The iatoplasty was performed. The esophagus was fixed to the crura through the mesh with 2 sutures in each side catching the muscular coat. Finally a traditional Nissen fundoplication was performed. We evaluated 27 consecutive patients: 20 underwent NBF and 7 who received a traditionally NF were the control group. Patients were evaluated before and after surgery by a detailed symptoms and Quality of Life (GERD-HRQL) questionnaires, esophageal-manometry, 24-hour pHImpedance monitoring off-therapy, endoscopy and barium-swallow. Surgical failures were defined as: (1) abnormal 24-hour pH-Impedance study; (2) recurrence of endoscopic esophagitis; (3) recurrence of hiatal hernia/slipped fundoplication at endoscopy/barium swallow; (4) postoperative symptomscore > 10th percentile of the preoperative score (i.e. > 10). Results:

Symtom score Dysphagia score GERD-HRQL score LES resting pressure (mmHg) LES residual pressure (mmHg) LES total length (mm) LES abdominal length (mm) Procedure time (minutes) Antireflux medication Failures

Group NBF

Group NF

p value

0 (0-3) 0 (0-0) 3 (0-5) 21.4 (16.7-31) 10.8 (7.3-18) 34 (26-37) 15 (9-21) 170 1/20 (5%) 0

3 (0-10) 0 (0-0) 4 (0-6) 29.7 (21-33.9) 8.7 (3.8-21) 38 (25-46) 29 (19-30) 145 1/7 (14.3%) 1

0.17 0.99 0.64 0.68 0.87 0.55 0.12 0.41 0.46 0.26

In the NBF group 12 patients had surgery as a primary treatment and 8 as a redo-fundoplication. In the NF group all patients had the fundoplication as a primary treatment. Mortality and post-operative complications were nil. The median of symptoms-score decreased from 19 (IQR 11–22) to 0 (IQR 0–4) for the NBF and from 31 (IQR 22–35) to 3 (IQR 0–10) for the NF. Dysphagia was absent in both groups (p = 0.99). All patients increased the Quality of Life after surgery. At a median of follow-up of 12 months no-statistically significant differences emerged between the 2 groups in term of symptoms and GERD-HRQL score, LES resting and residual pressure, total and abdominal LES length, 24-hour pH-impedance features and antireflux medication (Table). Failure of antireflux surgery wasn’t found in group NBF, whereas one patient in the NF group had a recurrent hernia. Discussion: The preliminary results showed that NBF is a safe and effective procedure for the treatment of gastroesophageal reflux disease and for previous surgical treatment failures. Moreover, it seems promising in preventing the risk of recurrence although further data are mandatory. Disclosure: All authors have declared no conflicts of interest. Keywords: Gastroesophageal reflux, fundoplication, recurrent hiatal hernia P2.03.03: REAL TIME CONTINUOUS HIGH RESOLUTION MANOMETRY DURING HELLER MYOTOMY- DOR FUNDOPLICATION FOR THE TREATMENT OF ACHALASIA. COULD IT GUIDE SURGICAL TECHNIQUE TOWARDS EXCELLENT RESULTS? Dimitrios Theodorou, Stamatina Triantafyllou, Georgia Doulami, Eleftheria Kleidi, Ioanna Papailiou, Nikolaos Kokoroskos, Vassiliki Xiromeritou, Georgios Zografos University of Athens, Athens/GREECE Background: High Resolution Manometry (HRM) is emerging to become the gold-standard diagnostic tool of achalasia of the esophagus. Surgical myotomy remains the most effective treatment. Nevertheless, 10% failure rate is recorded, which is mainly caused by either incomplete myotomy or tight fundoplication. In the past, conventional manometry has been used intraoperatively with various results. The use of intraoperative HRM gives us the advantage of simultaneous real time estimation of intraluminal pressures of the esophagus. This information may be used by the surgeon in order to extend myotomy or modify fundoplication. We aim to introduce the intraoperative use of HRM during Heller myotomy and Dor fundoplication in order to tailor surgical technique. Methods: Twelve patients with achalasia referred to our department. Eleven of the patients underwent laparoscopic surgery, while one with a history of previous myotomy and recurrent dysphagia underwent open surgery. All patients included had preoperatively completed at least one manometric study. We collected intraoperative manometry data. The patients are followed-up by Eckardt scores and a repeat manometric test at six months after surgery.


ABSTRACT SUPPLEMENT

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Results: The technique was successfully completed without any perioperative complications. All patients were discharged on the second postoperative day. Immediate results (on the first month) were successful in regards of dysphagia and lack of reflux symptoms (Eckardt score). Three patients have completed six-month follow-up with maintenance of the excellent result. All patients will have six month follow-up as well as postoperative HRM study.

P2.04.01: LUNG TRANSPLANT: PREVALENCE OF GERD AND OUTCOME OF FUNDOPLICATION Rubens Sallum1, Sergio Szachnowicz1, Angela Falcão1, Ary Nasi1, Rafael Carraro2, Ricardo Teixeira2, Jose Afonso Jr2, Paulo Fernandes2, Andre Duarte1, Ivan Cecconello1 1 University of Sao Paulo, Sao Paulo SP/BRAZIL, 2University of Sao Paulo, Sao Paulo/BRAZIL

Discussion: According to the literature, failure of surgical treatment of achalasia of the esophagus is estimated approximately 10%. However, HRM may be the key to the individual spectrum of the Heller-Dor technique. Thus, we introduce the simultaneous use of HRM during Heller myotomy and Dor fundoplication in order to further improve the results after surgery for achalasia treatment.

Background: Lung Transplantation became effective treatment for end stage lung disease. In those patients, the abnormal motility of the esophagus has been associated with worsening of pulmonary function and severe GERD is considered a risk factor for the development of chronic rejection after lung transplantation.

Disclosure: All authors have declared no conflicts of interest. Keywords: achalasia, High Resolution Manometry, myotomy, real time manometry

P2.03.04: COMPLETE THORACOSCOPIC ENUCLEATION OF LARGE ESOPHAGEAL LEIOMYOMA IN THE PRONE POSITION Masato Kondo, Hiroyuki Kobayashi, Yusuke Sakamoto, Hiromitsu Kinoshita, Kazuyuki Okada, Takehito Yamamoto, Satoshi Kaihara, Ryo Hosotani Kobe City Medical Center General Hospital, Kobe/JAPAN Background: Minimal invasive thoracic surgery can be done widely for esophageal tumors, but it is difficult to resect large tumors preserving esophagus. We report a case underwent complete thoracoscopic enucleation of large esophageal leiomyoma in the prone position. Methods: A 43-year-old female patient who complained dysphagia came to our hospital. CT scan showed 7-cm extraluminal tumor of the upper thoracic esophagus, and preoperative pathological diagnosis was leiomyoma by endoscopic biopsy. the patient underwent complete thoracoscopic enucleation of the tumor in the prone position. Under general anesthegia with a single-lumen endotracheal tube and in the prone position, 4 trocars were placed and pneumothorax was kept at 8 mmHg using CO2 insufflation. Esophagus was encircled at the proximal and distal side of the tumor after the pleura was cut along the esophgus, then the muscular layer could be dissected safely not to injure the mucosal layer. The tumor was enucleated and the musculer layer was closed continuously using a 3-0 barbed suture. Results: The total operation time was 4 hr 24 min and there was little bleeding. No postoperative complication was occured, and the hospital stay was 15 days. Pathological diagnosis was confirmed as esophageal leiomyoma. Discussion: In the prone position,complete thoracoscopic enucleation of large esophageal leiomyoma seems to be done safely and easily. This approach can make surgens more comfortable because of clear visualization and wide working space, and lead to the satisfaction of patients in terms of less invasive surgery. Disclosure: All authors have declared no conflicts of interest. Keywords: complete thoracoscopic enucleation, large miomyoma, Prone position

P2.03.05: THORACOSCOPIC ENUCLEATION FOR ESOPHAGEAL LIEOMYOMA Kenji Maki, Shinsuke Takeno, Ippei Yamana, Tatsuya Hashimoto, Ryosuke Shibata, Hironari Shiwaku, Kanefumi Yamashita, Yuichi Yamashita Fukuoka University Faculty of Medicine, Fukuoka/JAPAN Background: Surgical approach for leiomyoma of the esophagus has not been reached a consensus. The authors report a case of leiomyoma of the esophagus enucleated thoracoscopically. Methods: Patient was 36-year old man, esophageal submucosal tumor was pointed out on the periodical medical examination. Results: Computed tomography scans demonstrated a 4.5 ×3.5 cm-sized tumor in the middle thoracic esophagus. endoscopy revealed the presence of a esophagus submucosal tumor with (4 cm in diameter) in the middle thoracic esophagus. Surgical treatment was planed, and the submucosal tumor was enucleated under thoracoscopy with prone position. there was no remarkable event after surgery and the patient discharged from hospital on 12th day after surgery. Discussion: Final pathological diagnosis was leiomyoma of the esophagus without malignant feature. Disclosure: All authors have declared no conflicts of interest. Keywords: thoracoscopic surgery, leiomyoma, Prone position

Objective: To evaluate the prevalence of GERD and esophageal motility in patients after lung transplantation specially those submitted to GERD surgical repair. Methods: 19 consecutive patients undergone to single or double lung transplantation were evaluated. Clinical symptoms, pulmonary function, Endoscopy, Esophageal manometry, esophageal pH monitoring (dual sensor: the distal 5 cm above the LES and the proximal in the ESE) were performed 8 months to 4 years after Transplantation. In cases submitted to surgical antireflux repair, also time from transplantation to fundoplication, evolution of GERD, pulmonary function and BOSS index were also evaluated Results: GERD occurred in nine (47%) patients; eight (42%) with proximal esophageal reflux. Six patients presented a hypotensive LES (33%) and two (11%) had dyskinesia of the distal segment of the esophageal body. In 8 patients with registered proximal reflux, 4 had some degree of deterioration of lung function. Seven of those 8 patients were submitted to Nissen fundoplication. GERD and worsening of lung function were controlled in all except one case that required reoperation for symptomatic esophageal stasis (conversion from total to partial fundoplication). This patient died 5 moths after fundoplication due to lost of pulmonary graft. Average/median time from transplantation to fundoplication of all patients were 3.2/4.0 months against 52 months of the patient that died. Discussion: After lung transplantation, 47% of patients had pathologic GERD. Seven of them were submitted to surgical antireflux repair. All patients operated with fundoplication in this initial observational study achieved immediate improvement of GERD. The 2 patients who had some degree of graft rejection presented pulmonary function stabilization after surgery. The patient who died presented interval between transplantation and fundoplication far above the average of the group. Next steps of this study will evaluate the real role of surgical treatment of GERD in transplant patients and its effect on the index of graft rejection. Disclosure: All authors have declared no conflicts of interest. Keywords: Lung transplantation, GERD, fundoplication, pulmonary function P2.04.02: TWO CASES OF SEVERE REFLUX ESOPHAGITIS AFTER TOTAL GASTRECTOMY WITH SUCCESSFUL RECOVERY BY REOPERATION Hiromasa Yamashita, Norihiro Yuasa, Eiji Takeuchi, Yasutomo Goto, Hideo Miyake, Hidemasa Nagai, Masaoki Hattori, Kanji Miyata Japanese Red Cross Nagoya Daiichi Hospital, Nagoya/JAPAN Background: Reflux esophagitis can be observed in patients who undergo total gastrectomy followed by Roux-en Y reconstruction, however, there have been a few of literature reporting successful resolution by reoperation. Methods: We report two cases of severe reflux esophagitis after total gastrectomy with successful recovery by reoperation. Results: The first case is a 72 year-old man, who had undergone total gastrectomy followed by Roux-en Y reconstruction for gastric cancer (pT1, pN0). 4 months after the operation, he was admitted to our hospital for severe heartburn, appetite and weight loss (12 kg/4 months). Esophagoscopy showed severe reflux esophagitis (Grade D according to Los Angels’ classification). Bile reflux was positive in 33.4% of 24 hr with bilirubin monitoring. Upper gastrointestinal radiography showed the distance between the esophagojejunostomy and jejunojejunostomy to be short (30 cm). Reoperation was performed: the jejunojejunostomy was divieded and the oral jejunum was anastomosed to the jejunum 100 cm distal to the previous jejunojejunostomy. After the reoperation, heartburn subsided and bilirubin monitoring disclosed no bile reflux. Endoscopy 3 months after the reoperation showed no reflux esophagitis. The second case is a 56 year-old man, who had undergone total gastrectomy followed by Roux-en Y reconstruction for gastric cancer (pT2, pN0). 18 months after the operation, he was admitted for heartburn, difficulty swallowing and weight loss (10 kg/1year). Esophagoscopy showed severe reflux esophagitis (Grade D). Bile reflux was positive in 72.6% of 24 hr with bilirubin monitoring. Upper gastrointestinal radiography showed the distance between the esophagojejunostomy and

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jejunojejunostomy to be short (20 cm). The same reoperation as the first case was performed: the jejunojejunostomy was divided and the oral jejunum was anastomosed to the jejunum 50 cm distal to the previous jejunojejunostomy. After the reoperation, heartburn and difficulty swallowing disappeared and bilirubin monitoring disclosed no bile reflux. Endoscopy 3 months after the reoperation showed no reflux esophagitis.

predictor for disease progression after adjustments for age, sex, smoking, alcohol, diabetes, hypertension, Helicobacter pylori status, PPI medication (>6 month), difference of waist circumference, and SAT area (P for trend = 0.015).

Discussion: Esophageal 24-hour bilirubin monitoring was useful to objectively evaluate the duodeno-jejuno-esophageal reflux, and the reoperation lengthening the Roux-en Y limb was successfully performed for severe reflux esophagitis after total gastrectomy.



P2.04.05: CLINICAL CHARACTERISTICS AND NATURAL HISTORY OF ASYMPTOMATIC EROSIVE ESOPHAGITIS Sung Hoon Jung, Jung Hwan Oh, Sung-Goo Kang The Catholic University of Korea, Seoul/KOREA

Keywords: Reflux esophagitis, bile reflux, total gastrectomy P2.04.03: OUR STANDARD LAPAROSCOPIC ANTI-REFLUX SURGERY FOR GERD PATIENTS Tatsushi Suwa, Satoshi Inose, Kazuhiro Karikomi, Eishi Totsuka, Naokazu Nakamura, Keigo Okada, Tomonori Matsumura, Kenta Kitamura Kashiwa Kousei General Hospital, Kashiwa, Chiba/JAPAN Background: Laparoscopic anti-reflux surgery for GERD patients is still considered complicated among surgeons. Methods: SURGICAL PROCEDURE Setting Our 5-trocar setting with patients in the reverse Trendelenburg’s position for laparoscopic Nissen fundoplication is as follows. A 5 mm trocar was inserted just below the navel for a laparoscope (A). A 5 mm trocar was inserted in the upper right abdomen for a snake-retractor to pull up lateral segment of the liver. A 5 mm trocar was inserted in the upper right abdomen for operator’s right hand. A 5 mm trocar was inserted in the upper left abdomen (B). A 5 mm trocar was inserted in the middle left abdomen (C). Step 1 Under laparoscopic view, left part of the lesser omentum was cut with preserving the hepatic branch of vagus nerve. The right crus has been dissected free, and the esophagus is being recognized. The soft tissue at the posterior side of the abdominal esophagus was carefully dissected. Then the left crus of the diaphragma was recognized from the right side. Step 2 The branches of left gastroepiploic vessels and the short gastric vessels were divided with LCS. The left crus of the diaphragma was exposed and the window at the posterior side of the abdominal esophagus was widely opened. Step 3 The right and left crura are sutured with interrupted stitches to reduce the hiatus. From the right side, the stomach is grasped from behind the esophagus. Then the fornix of the stomach is pulled to obtain a 360 degree “stomach-wrap” around the esophagus (fundoplication). Using nonabsorbable braided suture, stitches are placed between both gastric flaps. THE CHARACTERISTIC FEATURES OF OUR PROCEDURE 1. Floppy Nissen fundoplication 2. No use of bougie device or taping technique for esophagus 3. Rotation of scope site

Discussion: Visceral obesity had independent causal associations with the progression of RE Keywords: visceral obesity, Reflux esophagitis

Background: This study was designed to investigate risk factors related to asymptomatic erosive esophagitis and the natural history of both endoscopic findings and reflux-related symptoms in subjects with asymptomatic erosive esophagitis. Methods: On a retrospective basis, data was gathered from patients with erosive esophagitis (Los Angeles classification ≥A) who had undergone endoscopic follow-up at St. Vincent hospital. Data from 313 subjects with erosive esophagitis were investigated. Results: Most patients had mild esophagitis (grade A or B, Los Angeles classification); 198 (63.3%) had reflux symptoms, and 115 (36.7%) lacked typical or atypical symptoms. Asymptomatic erosive esophagitis was associated with non-smoking (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.4–3.9), and lower body mass index (BMI; OR, 1.5; 95% CI, 1.0–2.4), while 26% of subjects had recurring reflux-related symptoms. Younger subjects were more likely to have reflux-related symptoms (P < 0.05). Discussion: Non-smoking and lower BMI are associated with asymptomatic reflux esophagitis. Most asymptomatic subjects with erosive esophagitis remained stable and exhibited unchanged endoscopic findings.

Results: This procedure needs 2 surgeons (the operator and the assistant (scopist)). The mean operation time was about 60 min. A favorable outcome was assessed by radiograms performed on 4–6 POD. Resolution of the symptoms was noted at 1 month postoperatively in mostly all cases. Discussion: We have simplified laparoscopic anti-reflux surgery and established a simple standard procedure. Disclosure: All authors have declared no conflicts of interest. Keywords: NISSEN, anti-reflux surgery, laparoscopic, GERD P2.04.04: VISCERAL OBESITY AS RISK FACTORS OF REFLUX ESOPHAGITIS: A LONGITUDINAL 5-YR FOLLOW-UP STUDY Donghee Kim, Su Jin Chung, Min Jung Park Seoul National University Hospital Gangnam Center, Seoul/KOREA

Figure. Kaplan–Meier symptom-free survival rates, for 96 patients with asymptomatic erosive esophagitis depending on age Table. Independent factors associated with asymptomatic esophagitis identified on multivariate analysis

Background: To investigate the potential roles of visceral adiposity on the natural course of reflux esophagitis (RE). Methods: 1500 screenees [750 patients with endoscopically proven RE vs age-, sex- and waist circumference (WC)-matched controls] who underwent abdominal computed tomography (CT) scan were followed at Seoul National University Hospital Healthcare System Gangnam Center between Oct 2005 and Dec 2012. The surface areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas measured by abdominal CT scan were calculated. Effects of visceral adiposity on the course of RE were estimated with hazard ratios (HRs) and 95% confidence intervals (CIs) using multiple logistic regression. Results: During the study periods, a total of 982 subjects underwent repeated upper endoscopy and were finally included [625 (63.6%) to No-change group, 92 (9.4%) to Progression group and 265 (27.0%) to Regression group] with a mean follow-up period of 4.6 yr (0.9 to 8.4 yr). VAT area increased the likelihood of progression of RE (HR = 1.87 and 1.85; 95% CI, 1.1–3.4 and 1.0–3.4, 3rd and 4th quartiles vs. lowest quartile, respectively) in univariate analysis. There were no specific correlations between SAT area and progression or regression of the disease. Increased VAT area still showed a

BMI >24 kg/m2 ≤24 kg/m2 Smoking Yes No LA classification LA-A LA-B

Estimated value

Standard error

Odds ratio

95% CI*

P value

0.433

0.217

1.54

1.01–2.36

0.046

0.857

0.259

2.36

1.41–3.91

0.001

0.654

0.366

1.92

0.93–3.94

0.074

Disclosure: All authors have declared no conflicts of interest. Keywords: Endoscopy, Gastroesophageal reflux disease, Esophagitis, natural course


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P2.05.01: INTRATHORACIC STOMACH TREATED BY TOUPET FUNDOPLICATION AFTER EMERGENCY SURGERY FOR GASTRIC PERFORATION: A CASE REPORT Fumiaki Yano, Nobuo Omura, Kazuto Tsuboi, Masato Hoshino, Seryung Yamamoto, Shunsuke Akimoto, Takahiro Masuda, Yujiro Tanaka, Masami Yuda, Akira Matsumoto, Yuichiro Tanishima, Katsunori Nishikawa, Koji Nakada, Yoshio Ishibashi, Hideyuki Kashiwagi, Katsuhiko Yanaga The Jikei University School of Medicine, Tokyo/JAPAN Background: Paraesophageal hiatal hernias (PEH) account for less than 5% of all hiatal hernias but are highly likely to develop complications if left untreated. PEH tend to enlarge with time, and, as such, a well-defined sac of the peritoneum develops. Giant PEH has been defined as more than onethird of the stomach in the thoracic cavity. A subset of these patients with greater than 75% of the stomach herniated above the diaphragm are labeled as having intrathoracic stomach (ITS). The common symptoms of ITS include postprandial discomfort, dysphagia, vomiting, hemorrhage, chest fullness, inability to belch, and anemia, but reflux alone is uncommon. Occasionally, the presentation is more dramatic: bleeding from acute ulceration, acute volvulus with obstruction, or possibly gangrene of the stomach with perforation. We herein report a case of ITS who required Toupet fundoplication after emergency surgery for gastric perforation. Methods: A 68-year-old male patient was referred to our department due to ITS in December 2012. His chief complaints were regurgitation and dysphagia of 2-year duration. His surgery was scheduled electively in February 2013. During the waiting period, his gastric corpus perforated and emergency surgery was performed at another hospital in December 2012, in which simple closure of the perforation site with omental implantation and peritoneal drainage were performed. His postoperative course was uneventful and he was transferred to our department on postoperative day 20. Results: Seven days later, laparoscopic Toupet fundoplication was performed as a radical operation for ITS which required conversion to open surgery due to severe adhesion around the hiatus. The duration of surgery was 301 minutes and the blood loss was 560 ml. His postoperative course was uneventful and he was discharged on postoperative day 9. As of 12 months after surgery, he never felt regurgitation or dysphagia after surgery and exhibits no evidence of recurrence. Discussion: We experienced a case of ITS treated by Toupet fundoplication after emergency surgery for gastric perforation. Disclosure: All authors have declared no conflicts of interest. Keywords: paraesophageal hiatal hernia, intrathoracic stomach, acute gastric volvulus, gastric perforation P2.05.02: LAPAROSCOPIC TREATMENT OF TYPE III AND IV HIATAL HERNIA Marcin Migaczewski, Agata Grzesiak-Kuik, Michał Pędziwiatr, Andrzej Budzyński Medical College Jagiellonian University, Cracow/POLAND Background: There are four types of hiatal hernias, and diagnosis is established on the basis of gastroscopy in the majority of cases. Type III represents a mixed type in which the abdominal esophagus as well as the gastric cardia and fundus protrude into the thorax through the pathologically widened esophageal hiatus. Type IV, the so-called upside down stomach, can be considered an evolutionary form of type III, and refers to herniation of nearly the whole stomach (except for the cardia and pylorus) into the thorax. Types III and IV of hiatal hernias represent a group of rare diaphragmatic defects; thus, most centers do not possess considerable experience in their treatment. Frequently, laparoscopic treatment is implemented, although, according to some authors, conversion to laparotomy, thoracotomy, or thoracolaparotomy is necessary in selected cases. Methods: A total of 25 patients diagnosed with type III and IV hiatal hernia were included in further analysis. All patients were qualified for laparoscopic plasty of the esophageal hiatus. Although the typical signs of reflux disease were not frequently documented in the analyzed group, we followed the general rule of completing each hernioplasty with Nissen fundoplication. Results: As many as 19 out of 25 patients (76%) assessed the outcome of the surgery as evidently positive and reported marked improvement in the quality of life. Six months after the primary procedure, recurrent hernia along with migration of the fundoplication band into the thorax was documented in 1 female patient (4%). The patient was re-operated laparoscopically on an elective basis. A decision on using polypropylene mesh was made intraoperatively due to considerable defibration of diaphragmatic crura. Discussion: Laparoscopic surgery has assumed the dominant position in the surgeryof benign conditions of the gastroesophageal junction. Precise exposure of the esophageal hiatus area is possible due to a different position of the surgical team ascompared to classical surgery, as well as due to the properties of the laparoscopic video channel itself. Due to the risk of

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incarceration and manifestations associated with the compression of thoracic structures, leading to dyspnea and stenocardial pain, the qualification is based on considerably stricter criteria in patients with type II, III, and IV hernias. According to many reports, the risk of manifestation of GERD in patients operated on due to hiatal hernia without simultaneous fundoplication can reach up to 65%. Of our findings as they suggest that simultaneous fundoplication should be obligatorily recommended. The use of surgical mesh for the repair of large hiatal hernias still remains controversial. The possibility of supporting defective and frequently defibrating diaphragmatic crura, which not infrequently can barely be connected with sutures, represents one argument for such an approach. However, in our opinion, the use of synthetic implants is rarely necessary and refers mostly to cases of recurrent hernia. In conclusions the laparoscopic technique constitutes an excellent and safe method of repair of even the most complex defects in the esophageal hiatus. Therefore, the minimally invasive technique combined with an anti-reflux procedure should be the method of choice in patients with type III and IV hernia. Disclosure: All authors have declared no conflicts of interest. Keywords: Laparoscopic Nissen Fundoplication, type III and IV hiatal hernia P2.05.03: GIANT HIATAL HERNIA WITH PANCREATIC PROLAPSE: REPORT OF A CASE Yoshinori Kohira, Yosuke Izumi, Yuichiro Kume, Kei Sakamoto, Akinori Miura, Tsuyoshi Kato Cancer and Infectious Diseases Center Komagome Hospital, Tokyo/JAPAN Background: A giant hiatal hernia is a hernia that includes at least 30% of the stomach in the chest, although a uniform definition does not exist. Most commonly, a giant hiatal hernia is a type III hernia with a sliding and paraesophageal component. Methods: 44 year-old man presented with fluminant epigastralgia and dypnea postprandially and was diagnosed as giant esophageal hiatal hernia by CT scan in a clinic. He was referred to our hospital for further examination and treatment. CT scan showed whole stomach, almost whole small intestine, right and transverse colon and pancreas prolapsed above diaphragm, and type IV esophageal hiatal hernia was diagnosed. We performed elective open hiatal hernia repair. Operative findings were a giant hiatal hernia, defined as a hiatal defect 10 cm, massive gastrointestinal prolapse and winding esophagus. We were able to pull the stomach, small intestine, colon fully back to abdominal cavity relatively easily, but pancreas together with the duodenum stuck on the left thoracic cavity was hard to deliver. The pancreas was carefully detached and finally delivered out of the thoracic cavity. We narrowed the hiatal arch, performed Nissen’s fundoplication and additional reinforcement of the crura with mesh. Results: He received operation 2years before, now he has no reccurence. Discussion: A giant hiatal hernia has a risk of volvulus and strangulation of the stomach though often undetected for years before this life-threatening event. Many reports for a giant hiatal hernia have been seen, but a giant hiatal hernia with pancreatic prolapse is extremely rare and delivering pancreas was thought to be most difficult point during the operative procedure. Disclosure: All authors have declared no conflicts of interest. Keywords: giant hiatal hernia, pancreatic prolapse P2.06.01: EXCLUSION AND DIVERSION METHOD IN MANAGEMENT OF OESOPHAGEAL PERFORATIONS Tamás Vass, Péter Kupcsulik, Ákos Balázs, László Harsányi Semmelweis University, Budapest/HUNGARY Background: Oesophageal perforation is a rare condition with a high mortality rate and its management is clouded with controversy. This retrospective single-institution study presents our esophageal exclusion and diversion strategy. Methods: A retrospective review of 45 cases presented to the 1st Department of Surgery of Semmelweis University during the period 2006–2014 was performed. Most of the patients (n = 42) had perforation in the lower third, and among them there was an extremely high incidence (n = 25) of spontaneous perforation (Boerhaave). Selected patients (n = 21) had exclusion of the oesophagus with non-absorbable staples, cervical oesophagostomy, primary closure of the perforation, mediastinal drainage, internal detensionation of the oesophagus (with continuous suction), fundoplication (if possible), and for nutrition we created alimentary jejunostomy. Results: Almost half of the patients (47,6%) didn’t need further surgical intervention. The closure opened spontaneously in four weeks and the cervical

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oesophagostomy closed during this time. Two patients (9,5%) developed oesophago-cutaneous fistula which had to be be closed with a second operation. In one patient (4,8%) stenosis evolved which could be treated with dilatation. The relatively high rate of operative mortality (30%) was due to late recognition of the condition’s onset and delay in its diagnosis. Type of perforation

No. of cases

Exitus

Days since perforation (n)

Iatrogen Spontaneously Tumour

18 25 2 45

7 8 1 16

4,9 2,1 7

Discussion: In cases with severe mediastinitis, operative management seems to be the most appropriate choice. The specific treatment of an esophageal perforation should be selected according to each individual patient. Oesophagus exclusion with non-absorbable staples, cervical oesophagostomy and adequate drainage is a safe and moderately aggressive method which can be recommended in selected cases.


the lower thoracic esophagus, and one patient in the cervical and thoracic esophagus (multiple site). For the surgical treatment of benign esophageal perforation, 5 patients underwent primary closure, one patient underwent primary closure with omental patch, one patient underwent partial resection of esophagus, and one patient underwent video assisted thoracoscopic drainage. For the surgical treatment of malignant esophageal perforation, one patient underwent thoracotomy for drainage and performed esophageal stenting (self-expanding metallic stent), one patient performed thoracic tube drainage and underwent subtotal esophagectomy and reconstruction using gastric tube and one patient performed naso-gastric tube drainage and underwent esophageal bypass using gastric tube. As for the post-operative complications, anastomotic leakage occurred in 2 patients (18%), pyothorax occurred in one patient (9%), wound infection occurred in one patient (9%), and the hospital mortality was 0 %.


Discussion: The etiologies of esophageal perforation and the conditions of patients were quite various, and the outcome of surgical management showed the relatively satisfactory results in our recent study. The treatment of an esophageal perforation should appropriately according to each individual patient.

Keywords: Perforation, management, exclusion

Disclosure: All authors have declared no conflicts of interest. Keyword: esophageal perforation, surgical management

P2.06.02: EIGHT CASES OF GASTRIC TUBE PERFORATION AFTER RADICAL ESOPHAGECTOMY FOR ESOPHAGEAL CANCER IN SINGLE INSTITUTION Naoki Iwata, Masahiko Koike, Hisaharu Oya, Yukiko Niwa, Daisuke Kobayashi, Mitsuro Kanda, Chie Tanaka, Suguru Yamada, Goro Nakayama, Tsutomu Fujii, Hiroyuki Sugimoto, Shuji Nomoto, Michitaka Fujiwara, Yasuhiro Kodera Nagoya University Graduate School of Medicine, Nagoya/JAPAN Background: Gastric tube is the first choice as an esophageal substitute for reconstruction after esophagectomy. As recent advances in the surgical technique and postoperative care have afforded better prognosis for esophageal cancer patients, postoperative complication in gastric tube have increased. Gastric tube perforation is rare but life-threatening complication due to non-malignant ulceration. Ulcer formation is often asymptomatic and so in some cases instances of hematemesis or shock. Methods: From 1995 to 2010, 8 cases of gastric tube perforation were encountered in Department of Gastroenterological Surgery (Surgery II), Nagoya University Hospital. Medical records of these 8 patients were retrospectively reviewed to determine demographic data, diagnosis, and perioperative course. Results: The reconstructive route was, in all patients, posterior mediastinum in route. The perforation occurred from 9 to99 months after initial surgery. In 4 of 8 patients, the site of perforation were part of cardiovascular system and all of them had died. The others had ulcer in the gastric tube penetrating into the right lung, main bronchus or thoracic cavity. Four cases of 8 underwent neoadjuvant chemotherapy or chemoradiotherapy. H2 blocker and NSAIDs had prescribed in 4 and 5 patients, respectively. Discussion: The frequency of peptic ulcer in reconstructed gastric tubes was reported to be 6.6%–19.4%. Helicobacter pylori infection, decreased blood supply, stasis or bile reflux have been suggested as a factor in ulceration, however, the etiology of gastric tube ulceration remains controversial. From these 8cases, it is impossible to find precise etiology of this serious complication. Whatever the etiological factors are, to avoid this live-threatening complication, careful management is necessary. Endoscopic surveillance could be a help to find peptic ulcer before perforation. What is most important is to explain to patients about serious complication; gastric tube ulcer. Once the patients understand its seriousness, they won’t hesitate to undergo endoscopy and may consider various risk factor, such as NSAIDs, smoking and stress. Disclosure: All authors have declared no conflicts of interest. Keywords: gastric tube, complication, Esophageal cancer, Perforation P2.06.03: SURGICAL MANAGEMENT AND OUTCOMES OF THE ESOPHAGEAL PERFORATIONS Noriaki Sadanaga, Hiroshi Matsuura Saiseikai Fukuoka General Hospital, Fukuoka/JAPAN

P2.07.01: “POLYURETHANE FOAMBEZOAR” – AN UNUSAL FOREIGN BODY OF ESOPHAGUS AND STOMACH – FIRST HUMAN CASE REPORT Madeswaran Chinnathambi, Jasper Sandeep Rajasekar, Servarayan Murugesan Chandramohan, T Perungo, John Grifson, Jeyasudhahar Jesudason, D Kannan, Rajendran Vellaisamy, A Amudhan, D Bennet, R Prabhakaran, Rajkumar Rathinasamy Madras Medical College, Chennai/INDIA Background: A variety of unusual foreign bodies have been reported in the literature including endotracheal tubes, speaking valves, and fork. But there is no report of poly urethane foam, which is formed by poly addition of di isocyanate and poly hydroxyl ester. We present our experience in managing one such case and we have coined the term” FOAM BEZOAR”. Methods: 21 yrs old male presented to our department with history of retro sternal and upper abdominal discomfort and dysphagia of one day duration. He has consumed a combination two liquids which is used in refrigerator. He has had initial treatment at ER, where a nasogastric tube insertion has been attempted and failed. Results: At presentation he had stable vitals, soft abdomen, except palpable hard, movable mass in epigastrium. Upper G.I. scopy revealed a mass occupying the entire Esophagus and Stomach taking its shape. Though it was not adherent to the walls, it could not be removed as it was hard. CECT of chest and abdomen confirmed the intra luminal mass lesion. He was taken up for surgery. Abdomen entered by upper abdominal incision and there was a hard movable mass occupying the entire stomach and could be palpated along the Esophagus. Transgastric removal of the entire mass was done and the gastrostomy closed (Fig. 1).

Discussion: Polyurethane foam is formed by mixture of di isocyante and poly hydroxyl ester, mainly used in refrigeration industry. As the two components are mixed, it produces expansion upto 30 times, exothermic reaction and foam formation which gets solidified over a period of 2–3 minutes and once it formed, it becomes inert as per the literature review. In our, in vitro analysis, after mixing two liquids, foam formed which expanded 20 times in a period of 3 minutes with exothermic reaction. Assessment of exothermic reaction by clinical thermometer failed as it broke and the temperature measured by industrial thermometer revealed, heat reached to 201 F. We are not able to explain how the mucosa of Esophagus and Stomach withstood such temperature. Patient is on regular follow up for one year and he is totally asymptomatic. Disclosure: All authors have declared no conflicts of interest.

Background: Esophageal perforation leads to local and systemic inflammation such as mediastinitis, pyothorax and sepsis with high morbidity and mortality rates. Therefore prompt and adequate diagnosis and treatment is needed. Methods: We performed a retrospective clinical review of 11 patients surgically treated for esophageal perforation at our hospital beteen 2005 and 2012. The clinical characteristis, etiolgy, surgical treatment and outcme of these patients were reviewed. Results: Median age was 65 years (range 16 to 97), with 9 men and 2 women. There were 5 iatrogenic perforation, 3 malignant perforation, 2 spontaneous perforation and one traumatic perforation. As for the site of perforation, 2 patients occured in the cervical esophagus, one patient in the uppe thoracic esophagus, 3 patients in the middle and lower thoracic esophagus, 4 patients in

P2.07.02: MEDIASTINAL DRAINAGE BY TRANSHIATAL APPROACH FOR THE TREATMENT OF SPONTANEOUS RUPTURE OF THE ESOPHAGUS: A CASE REPORT Hiroaki Nagata, Atsushi Shiozaki, Hitoshi Fujiwara, Hirotaka Konishi, Ryo Morimura, Yasutoshi Murayama, Shuhei Komatsu, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Masayoshi Nakanishi, Daisuke Ichikawa, Kazuma Okamoto, Chouhei Sakakura, Eigo Otsuji Kyoto Prefectural University of Medicine, Kyoto/JAPAN Background: Spontaneous rupture of the esophagus (Boerhaave syndrome) is a form of barogenic rupture caused by a sudden post-emetic rise in the


ABSTRACT SUPPLEMENT

intraluminal pressure in the distal esophagus. Esophageal perforation is extremely rare and has high mortality, which increases to 40%–60% when treatment is delayed beyond 48 h, leading to mediastinal sepsis and multisystem organ failure. The radical treatment for esophageal perforation is the surgery. Although open-chest approach for the esophagus has commonly performed, transhiatal approach has not been common for this disease. We report the efficacy of the transhiatal approach in the treatment for the esophageal perforation. Methods: A 72-year-old Japanese man was admitted to the ER with severe chest pain. Emergency computed tomography (CT) showed a pneumomediastinum and this was assumed due to esophageal perforation. Because of the septic shock, we decided to perform emergency operation and mediastinal dranage by transhiatal approach has been achieved. Results: To gain access to the mediastinum, we conducted a laparotomy with median upper abdominal incision. First esophagus hiatus was dissected from abdominal cavity, and a volume of dirty darkred discharge leaked from mediastinum. We observed that the perforated site was located on left side on the lower esophagus. We could observe whole view of the perforated site and the size was 15 to 20 mm, full-thickness laceration. We performed primary closure of the esophageal perforation site with T-tube drainage and insert two drainage tube inside the mediastinum and chest tube in both chest cavity. Discussion: The transhiatal approach for Boerhaave’s syndrome resulted in a good surgical view of the mediastinum, and thought to be a surgical choice before performing traditional approach. Disclosure: All authors have declared no conflicts of interest. Keywords: Boerhaave syndrome, transhiatal approach P2.07.03: THE CLINICAL FEATURES OF GASTRIC TUBE ULCERS AFTER ESOPHAGECTOMY Naoki Mori1, Toshiaki Tanaka1, Matono Satoru1, Haruhiro Hino1, Kazuo Shirouzu1, Susumu Sueyoshi2, Hiromasa Fujita3 1 Kurume University School of Medicine, Kurume/JAPAN, 2Omuta City Hospital, Omuta/JAPAN, 3Fukuoka Wajiro Hospital, Fuuoka/JAPAN Background: The aim of this study was to present the clinical features of a gastric tube ulcer after esophagectomy for esophageal diseases. Methods: We reviewed the medical records of patients with esophageal diseases who admitted to Kurume university hospital between 1985 and 2010. In this period, there were 826 patients who underwent esophagectomy followed by reconstruction using a gastric tube. Results: Of 826 patients, there were 30 patients who had developed gastric tube ulcer after esophagectomy. There were 28 men and 2 women, and the mean age was 63 years (range: 45–81 years). Primary diseases of 29 patients were esophageal cancer, and that of the other was esophageal achalasia. Ten patients (33%) had presence of history of peptic ulcer. Six patients were able to examine for Helicobacter pylori (H. pylori) infection, and all six had H. pylori infection. Twelve patients (40%) received postoperative treatment. The diagnoses of the gastric tube ulcer were performed by endoscopy in 19 patients (63%). Three patients (10%) developed ulcer perforation. Of 3 patients, two were recovered by tracheal stent replacement and surgical drainage. However, one patient died of massive bleeding from the gastric tube. Discussion: It has considered being important to follow-up by endoscopy regularly, because more than 60% patients were diagnosed by endoscopy without symptom. As perforation of gastric tube ulcer sometimes makes patient fatal condition, we recommend a subcutaneous route for esophageal reconstruction using a gastric tube in patients with a history of peptic ulcer and H. pylori infection. Disclosure: All authors have declared no conflicts of interest. P2.07.04: ACUTE ESOPHAGEAL MUCOSAL LESION TREATED WITH ENDOSCOPIC BALLOON DILATATION Yusuke Higuchi1, Koji Nakamichi2 1 Fukuoka Tokushukai Medical Center, Kasuga-shi, Fukuoka/JAPAN, 2 Fukuoka Tokushukai Medical Center, Kasuga-shi, Fukuoka/JAPAN Background: We often recognize erosive esophagitis on emergency endoscopy for upper gastrointestinal bleeding. Acute esophageal mucosal lesion (AEML) is a comprehensive disease that includes necrotizing esophagitis and acute erosive esophagitis. Most cases will rapidly improve with a proton pomp inhibitor (PPI). Methods: We experienced a case of AEML complicated with esophageal stenosis treated by endoscopic balloon dilatation repeatedly. Results: The patient was a 69-year-old man with the chief compliment of hematemesis. He had an addiction to alcohol. He had an anemia of Hb 10.9 g/dl and underwent emergency endoscopy. We recognized diffuse circumferential erosive and ulcerative lesion without active bleeding in the

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lower esophagus. He did not have corrosive injury, radiation therapy, viral infection, or chronic gastroesophageal reflux disease (GERD). We diagnosed AEML from the endoscopic finding and clinical feature. He had been treated with PPI. One month later esophageal ulcers were rapidly improved, but esophageal stenosis was induced due to the formation of scar tissue, so endoscopy could not pass through. He treated with endoscopic balloon dilatation (10-11-12 mm). After the dilatation, endoscopy could pass through and he was able to swallow without dysphagia. But 8 months later, he was admitted again because of difficulty of solid foods intake. Endoscopic finding revealed the esophageal stenosis got worse and endoscopy could not pass through again. He was received endoscopic balloon dilatation repeatedly and the stenosis was improved successfully. Discussion: AEML is a relatively new difined disease. AEML is considered a different disease from common GERD. Most cases improve with conservative management using PPI. In our case, esophageal stenosis and dysphagia was induced but successfully treated by endoscopic balloon dilatation repeatedly. In future, esophageal stenosis may recur again, it is necessary to check clinical course. It is precious the report of AEML complicated with esophageal stenosis. We also present a review of the literature. Disclosure: All authors have declared no conflicts of interest. Keywords: acute esophageal mucosal lesion, endoscopic balloon dilatation, esophageal stenosis P2.07.05: SURGICAL MANAGEMENT OF ZENKER’S DIVERTICULUM – OUR EXPERIENCE T Perungo, Selvarathinam Palanisamy, Jasper Sandeep Rajasekar, Jeyasudhahar Jesudason, John Grifson, Rajendran Vellaisamy, Madeswaran Chinnathambi, D Bennet, R Prabhakaran, A Amudhan, D Kannan, Servarayan Murugesan Chandramohan, Sathyamoorthy Balakumaran Madras Medical College, Chennai/INDIA Background: Management of Zenker’s diverticulum differs based on the size of diveticulum, presentation and expertise available. Myotomy is the key surgical step followed by either inversion, diverticulectomy or diverticulopexy. We present our series of 7 cases of Zenker’s diverticulum who underwent surgery, including one emergency Methods: During the time period January 2011 to December 2013, 7 patients, 6 males (85.7%) and 1 female (14.3%) presented with Zenker’s diverticulum. Median age of the patients was 57 to 62 years. All seven patients had history of dysphagia(100%). Three patients had weight loss(42.85%) and three had cough (42.85%). One patient (14.28%) presented acutely with diverticular perforation with neck pain, vomiting, neck swelling and crepitus. Average duration of symptoms was 2 years (3 months to 4.5 years). Upper GI endoscopy was done in six patients and one had an associated cervical web. Barium swallow was done for six patients which showed pharyngo esophageal diverticulum of varied sizes. Based on the size patients were grouped into three – small 1 to 3 cm, n = 2(28.57%), medium 3 to 5 cm,n = 0, and large > 5 cm, n = 4(57.13%). Emergency CT neck and CT chest done in case of perforation showed subcutaneous emphysema and pneumomediastinum respectively. All seven patients underwent cricopharyngeal myotomy through oblique left cervical incision. Diverticulum inversion was done in 2 patients (28.57%) and diverticulectomy in 5 patients(71.42%) – 2 stapled and 3 handsewn. All underwent intraoperative endoscopy and leak test was performed at the end of the procedure. Results: Six patients who underwent elective surgery had an uneventful post operative recovery. Oral feeds were started on 2nd POD. The average length of stay after surgery was 4 days. One patient who underwent emergency diverticulectomy had cervical leak(14.28%) in the post operative period. He was managed conservatively with naso jejunal feeding and the leak settled in two weeks. All patients are under regular followup, the period ranging between 6 months to 2.5 years. The quality of life after surgery is excellent with complete relief of symptoms in all 7 patients. Discussion: Surgery offers good postoperative outcome in small and large sized Zenker’s diverticulum Disclosure: All authors have declared no conflicts of interest. Keyword: Zenker, Diverticulum, Myotomy, Esophagus P2.07.06: COMPARIXON BETWEEN GASTOINTESTINAL STROMAL TUMOR AND LEIOMYOMA OF THE ESOPHAGUS: CT FINDINGS Hyun Joo Lee, Mi Young Kim Asan Medical Center, Seoul/KOREA Background: Differential dagnosis between rare esophageal GIST and common leiomyoma in contrast enhanced CT is usually dilemma in clinical routine practice. The purpose of this study was to describe the multidetector enhanced CT findings and to disclose the difference of the esophageal

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gastrointestinal stromal tumor (GIST) and the esophageal leiomyoma. Methods: From January 2001 to December 2012, 16 patients (11 men, 5 women; mean age, 51.3 ± 11.6 years) and 74 patients (55 men, 19 women; mean age, 46 ± 12.4 years) who had pathologically proven consecutive esophageal GIST and consecutive leiomyoma were retrospectively enrolled. CT images of two groups were analyzed by two radiologists, with final decisions reached by consensus. We analyzed the CT findings: 1) tumor’s size in long diameter, shape, location, 2) showing internal homogeneity, 3) the presence of intra-tumoral calcification, passage disturbance, and regional dilatation. We used Paired Student’s t-test and Chi-square teste as statistics. Results: 1) Mean size of GIST and leiomyoma were 43.8 ± 23 mm and 37.3 ± 21.4 mm, respectively, no significant difference. GIST and leiomyoma showed usually eccentric mass on CT images (87.5% and 85.1%), no significant difference. GIST located in upper (0%), mild (31.3%), and lower esophagus (68.7%) and leiomyoma located in upper (23.0%), mild (44.6%), and lower esophagus (28.4 %) with significant differerence (p = 0.002). 2) GIST and leiomyoma, showing heterogeneous enhancement (56.3%, 1.4 %) was significantly different (p < 0.001). 3) GIST and leiomyma regarding calcification (6.3%, 14.9%), regional dilatation (31.3%, 32.4%), and passage disturbance (6.3%, 1.4%), there were no significant differences. Discussion: Esophageal GIST mainly located in the middle or distal esophagus and emonstrated heterogeneous attenuation against leiomyoma on CT images. Above findings must e useful for proper differential diagnosis with diagnostic priority of esophageal submucosal tumor. Disclosure: All authors have declared no conflicts of interest. Keyword: benign disease, GIST, leiomyoma, CT


perioperative physiotherapy performed chiefly with early mobilization for the patients undergoing VATS-E. Methods: Sixty-nine patients who underwent VATS-E were surveyed retrospectively. Early mobilization was performed in 51 patients and not in other 18 patients. The day of initial walking and complications were compared in the patients with and without early mobilization. The postoperative complications on postoperative day seven (atelectasis and pneumonia) were also compared. Results: There was no significant difference in preoperative respiratory function between the two groups. In the early mobilization group, the day of initial walking was significantly earlier. Atelectasis was significantly less common in the early mobilization group. Discussion: The application of postoperative early mobilization took advantage of the decreased invasiveness of the VATS-E and contributed to the early recovery of the patients. Disclosure: All authors have declared no conflicts of interest. Keywords: Physiotherapy, Esophagus cancer, Early mobilization, Thoracoscopic esophagectomy P2.08.03: RELAPSE AFTER CURATIVE ESOPHAGECTOMY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA: PREDICTORS OF SURVIVAL AND OPTIMAL INTERVAL OF FOLLOW-UP Tetsuya Abe, Norihisa Uemura, Ryosuke Kawai, Masayuki Shinoda Aichi Cancer Center Hospital, Nagoya/JAPAN Background: It’s important to identify the factors of recurrence and to determine the appropriate methods and intervals of follow-up after esophagectomy.

P2.08.01: COMPARISON BETWEEN HAND-ASSISTED LAPAROSCOPIC SURGERY AND LAPAROSCOPIC SURGERY IN ESOPHAGECTOMY FOR PATIENTS WITH THORACIC ESOPHAGEAL CANCER Hiroyuki Kobayashi, Ryo Hosotani, Masato Kondo, Satoshi Kaihara Kobe City Medical Center General Hospital, Kobe City/JAPAN

Methods: Between 2000 and 2008, we reviewed records of 271 consecutive patients who underwent esophagectomy for esophageal squamous cell carcinoma with curative resection. Recurrence occurred in 101 (37%). Clinicopathological factors associated with recurrence were analyzed and predictors of survival after relapse were assessed using the Kaplan-Meier approach and Cox-proportional hazard model.

Background: Radical esophagectomy for esophageal cancer is one of the most invasive procedures in gastrointestinal surgery. Endoscopic surgery for abdominal lymph nodes dissection and construction of gastric conduit has become important as well as thoracoscopic procedure. Hand-assisted laparoscopic surgery (HALS) and Laparoscopic surgery without hand-assist (LA) are common procedures as laparoscopic esophageal surgery. Each method has advantages and disadvantages respectively.

Results: Median duration of follow-up was 40 months (3–123 months). (Time to recurrence) Recurrence was detected at a median of 8 months after surgery (2–84 months). Eighty-four percent of recurrence were detected within 2 years of resection in all of the relapsed patients. The interval of recurrence was not shortened in patients who received with neoadjuvant therapy (p = 0.22). Median time to recurrence based on the pathological stages of disease were 28 months in patients with Stage I, 15 months in Stage II, 7 months in Stage III, and 6 months in Stage IV. Recurrence was detected significantly earlier in patients with more advanced disease (p < 0.05). (Detection of recurrence) Recurrence was firstly suspected by Computed tomography (CT) in 46 (47%), symptoms in 31 (31%), and by physical examination in 12 (12%). (Type of recurrence) Type of recurrence was classified into the three groups; locoregional recurrence (local, cervical lymph nodes (LNs), mediastinal LNs, and abdominal LNs), systemic recurrence (hematogeneous, disseminated, distant metastases), mixed recurrence (both locoregional and systemic recurrences). Locoregional recurrence was occurred in 35, systemic recurrence in 41, and mixed in 25. There was no difference in the type of recurrence between patients who had neoadjuvant therapy or primary surgical resection. (Risk factor of recurrence after curative resection) On univariate analysis, pathological stage, pathologic T classification, number of positive nodes significantly affected time to recurrence. (Survival after relapse) Overall 5-year survival in patients with recurrence was 14%, and median survival time was 24months. Overall survival after recurrence was detected was 12 months.Overall survival was significantly longer in patients who had locoregional recurrence compared with those who had systemic and mixed recurrence (16 versus 5 and 11 months; p < 0.01). On multivariate analysis, type of recurrence (hazard ratio [HR], 2.63; p < 0.01), the interval of recurrence less than 9 months (hazard ratio [HR], 1.67; p = 0.03) were significant predictors of overall survival after recurrence.

Methods: From January 2005 to September 2013, 172 (HALS: 152, LA: 20) patients underwent esophagectomy and reconstruction with gastric tube in our department. HALS was done with 6 cm of midline incision and 2 ports. Kocher’s mobilization and ileostomy were performed through the midline incision. LA was done with 5 ports of trocar. To compare the advantages and disadvantages of HALS and LA, we retrospectively analyzed the periand post-operative factors such as operation time, blood loss, number of lymph nodes dissected, and so on. Results: There were no differences between two groups in clinicopathological findings such as age, sex, location of the tumor, and clinical stage. No differences were found in bleeding, complications, and the number of lymph nodes dissected. Operation time was significantly shorter in HALS group (69.8 ± 25.9 min, 129 ± 34.9 min each, p < 0.0001). The period of recovery of bowel motility and initiation of walking were not significantly different between two groups. Discussion: HALS has a benefit in operation time. LA has a cosmetic advantage. Surgeons should make a choice according to the characteristics of each method. Disclosure: All authors have declared no conflicts of interest. Keywords: HALS, Esophageal cancer, Surgery P2.08.02: EFFICACY OF EARLY MOBILIZATION ON POSTOPERATIVE PULMONARY COMPLICATIONS IN PATIENTS UNDERGOING VIDEO-ASSISTED THORACOSCOPIC SURGERY FOR ESOPHAGUS Masatoshi Hanada1, Kengo Kanetaka2, Ryo Kozu1, Masato Oikawa1, Susumu Eguchi2, Hideaki Senjyu2 1 Nagasaki University Hospital, Nagasaki/JAPAN, 2Nagasaki University Graduate School of Biomedical Science, Nagasaki/JAPAN Background: Esophagectomy had been performed under thoracotomy, which is assisted with massive stress and prolonged controlled ventilation after surgery. Recently, video-assisted thoracic surgery for the esophagus (VATS-E) has been introduced, making it possible to apply early mobilization for the patients due to the lower postoperative pain and minimal thoracic wall destruction. This study was performed to clarify the efficacy of

Discussion: Type of recurrence, time to recurrence less than 9 months were strongly related to tumor recurrence. CT was useful for the detection of recurrence after esophagectomy. Frequent early CT follow-up is necessary after esophagectomy because over 80% of recurrence will occur within the 2 years. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, squamous cell carcinoma, recurrence, follow-up


ABSTRACT SUPPLEMENT

P2.08.04: LYMPH-NODE DISSECTION ALONG THE LEFT RECURRENT LARYNGEAL NERVE AFTER ESOPHAGEAL STRIPPING AND ESOPHAGECTOMY IN PRONE POSITION VIDEO-ASSISTED THORACOSCOPIC SURGERY OF ESOPHAGUS, AND SAFE ANASTOMOSIS IN THE NARROW NECK OPERATIVE FIELD Hiroshi Makino1, Hiroshi Yoshida1, Hiroshi Maruyama1, Tadashi Yokoyama1, Ichiro Akagi1, Masahiro Hotta1, Natsuki Seki1, Rina Kanamaru1, Kazuhide Ko1, Eriko Shinozuka1, Teppei Miyashita1, Toshimitsu Miyasaka1, Tsutomu Nomura2, Takeshi Matsutani2, Nobutoshi Hagiwara2, Masao Miyashita3, Eiji Uchida2 1 Nippon Medical School, Tama-Nagayama Hospital, Tokyo/JAPAN, 2 Nippon Medical School, Tokyo/JAPAN, 3Nippon Medical School, ChibaHokusoh Hospital, Chiba/JAPAN Background: A clear operative view of the middle and lower mediastinum has been obtained in prone position VATS-E, but the working space in the upper mediastinum is limited and lymph node dissection along the left recurrent laryngeal nerve is difficult in prone position. It is also difficult to anastomose using circular stapler in the narrow neck field. We report to overcome the problems by our techniques. Methods: Sixty three patients (25 in left lateral and 38 in prone position), with esophageal carcinomas underwent VATS-E, respectively. At first the patients are fixed at semi-prone position so that left lateral position can be set for emergency thoracotomy. For an esophagectomy the patient is rotated so that the procedure is performed in the prone position. For an emergency thoracotomy, the patient is rotated from the semi prone position and the procedure performed in the left lateral position. Five ports (1 port at the 3rd, 5th, 7th and 9th and 1 more port at the 7th or 9th) are used inter-costal space. Esophagectomy and the lymph node dissection around the trachea and bronchus, above the diaphragm and along the bilateral recurrent laryngeal nerves are performed in prone position, owing to the working space created by gravity and pneumothorax. The esophagus is isolated, and both the esophagus and stomach tube in the esophagus of the upper mediastinum are cut away from the tumor using 60 mm linear stapler, and the stomach tube is removed through the nose. Simultaneously the residual esophagus is stripped in the reverse direction and retracted toward the neck, and we can obtain the space for lymph node dissection along the left recurrent laryngeal nerve. The esophago-gastric anastomosis was performed using a 25 mm anvil and circular stapler. At first the circular stapler is introduced into the gastric conduit and joined to an anvil, and close a little because anastomosis is performed in the narrow neck field. And then an anvil is placed into the proximal esophagus and secured by means of a pursestring suture. The gastric conduit opening is closed using an additional firing of a 60 mm linear stapler and the anastomosis is completed. Results: 1.The mean blood loss is about 17 ml in the chest procedure and mean operative time 272 minutes. 2.The rate of anastomotic leak, postoperative pneumonia and the rate of recurrent laryngeal nerve paralysis were 2.8%, 11% and 19%, respectively. Discussion: 1. Our result indicates that esophageal stripping in prone VATS-E allows for safe and straight forward lymph node dissection along the left recurrent laryngeal nerve. 2. The semi-prone position is better because both prone for VATS-E and left lateral for emergency thoracotomy positions can be set by rotating from the semi-prone position. 3. Our anastomotic technique is safe in the narrow neck field. Disclosure: All authors have declared no conflicts of interest. Keywords: VATS-E, stripping, Prone position, safe anastomosis

P2.08.05: THORACOSCOPIC ESOPHAGECTOMY WITH LYMPHADENECTOMY ALONG THE LEFT RECURRENT LARYNGEAL NERVE FOLLOWING NEOADJUVANT CHEMORADIOTHERAPY FOR SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS: FEASIBILITY AND SIGNIFICANCE Kalayarasan Raja, Gajendra Bhati, Biju Pottakkat JIPMER, Pondicherry/INDIA Background: Radical esophagectomy remains the primary curative treatment option for the management of esophageal carcinoma. With the advent of neoadjuvant therapy there is controversy in the extent of lymphadenectomy. Hence this prospective study was performed to determine the feasibility, short term outcomes and significance of thoracoscopic esophagectomy with lymphadenectomy along the left recurrent laryngeal nerve (RLN) following neoadjuvant chemoradiotherapy. Methods: Patients with resectable squamous cell carcinoma of the esophagus (cT1–3,N0–1, M0) were included in this prospective study. Neoadjuvant chemoradiation [weekly administration of carboplatin and paclitaxel for 5 weeks and concurrent radiotherapy of 41.4 Gy in 23 fractions] was given to all patients with clinical T2-3 and N1 tumor. In patients who received neoadjuvant chemoradiation, surgery was performed after an interval of 6–8

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weeks. For thoracoscopic esophagectomy patient was placed in the prone position after single lumen tracheal tube intubation. Four thoracoscopic ports were used; working ports in 5th and 9th intercostal space along scapular line, camera port in 7th intercostal space along posterior axillary line, tracheal retraction port in 4th intercostal space along midaxillary line to facilitate supracarinal lymph node dissection. Mobilisation of thoracic esophagus and total mediastinal lymphadenectomy was performed during thoracoscopic phase. Gastric mobilization and conduit formation was performed using midline laparotomy. Stapled cervical esophagogastric anastomosis was performed using modified collard technique. Results: During the study period from July 2013 to February 2014 (Interim analysis of the ongoing prospective study) 11 patients underwent thoracoscopic esophagectomy with total mediastinal lymphadenectomy after neoadjuvant chemoradiotherapy. Median (range) age of the patients in the study group was 53(41–72) and the majority were males (7/11). Of the 11 patients 1 had tumor in the upper thoracic esophagus, 4 had tumor in the middle thoracic esophagus and 6 had tumor in the lower thoracic esophagus. Median (range) operation time for thoracoscopic phase was 225 (170–310) minutes, median (range) blood loss was 75 (50–200) ml and there was no conversion to thoracotomy. All patients underwent R0 resection. Total median (range) lymph node count and median lymph node count along left RLN were 16 (11–32) and 5 (3–8) respectively. Four (36.4%) patients had complete pathological response. Of the remaining 7 patients 6 (85.7%) had T3 tumor and 1 (14.3%) patient had T2 tumor. Six patients had lymph node positive tumor and 2 (33.3%) patients had isolated lymph node metastasis along left RLN. There was no postoperative mortality and transient vocal cord palsy occurred in 4 (36.3%) patients. Discussion: Thoracoscopic esophagectomy with total mediastinal lymphadenectomy including dissection along left RLN is feasible after neoadjuvant chemoradiotherapy with acceptable incidence of postoperative vocal cord palsy. Dissection along left RLN improves lymph node yield and staging after neoadjuvant chemoradiotherapy. Long term follow up studies are required to determine the survival benefit of thoracoscopic total mediastinal lymphadenectomy after neoadjuvant chemoradiotherapy for squamous cell carcinoma of the esophagus. Disclosure: All authors have declared no conflicts of interest. Keyword: Thoracoscopic esophagectomy, mediastinal lymphadenectomy P2.08.06: CAN SUBCARINAL LYMPH NODE CLEARANCE BE SAFELY OMITTED FOR CT1BN0 ESOPHAGEAL SQUAMOUS CELL CARCINOMA? Hongwei Zhang, Fan Feng Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, Xi’an, Shaanxi/CHINA Background: Dissection of subcarinal lymph nodes (SLNs) is technically difficult in that it may cause main bronchus injury and prolong operation time. The aim of the present study was to evaluate the clinical outcomes of clinical T1bN0 esophageal squamous cell carcinoma (ESCC) patients with or without SLNs dissection. Methods: A total of 242 patients with ESCC had undergone three stage esophagectomy. The clinical and pathological features were collected and correlations with SLNs metastasis were analyzed. The survival rates of patients were also analyzed. Results: We found that tumor length, clinical and pathological T stages were associated with SLN metastasis. The survival of cT1bN0 patients with SLNs clearance was comparable to that without SLNs clearance. The survival of patients without metastasis and had more than 4 SLNs dissection was significantly higher than that of the patients without metastasis and had less than 4 nodes dissection (P < 0.05), while patients without metastasis and had less than 4 SLNs dissection had no survival benefit compared to that of the patients had SLN metastasis (P > 0.05). Discussion: In conclusion, for clinical T1bN0 ESCC patients, SLNs clearance may be unnecessary. For the rest ESCC patients, we recommend that at least 4 SLNs should be removed in order to improve patients’ survival. Disclosure: All authors have declared no conflicts of interest. Keywords: Metastasis, Lymphadenectomy, Esophageal squamous cell carcinoma, Subcarinal lymph node P2.08.07: LAPAROSCOPIC GASTRIC CONDUIT CREATION: FEASIBILITY OF A NOVEL APPROACH TO THE MOST CRANIAL SHORT GASTRIC ARTERY VIA THE LEFT GASTROPHRENIC LIGAMENT Ken Ishikawa Fujita Health University, Toyoake/JAPAN Background: Transection of the cranial part of the gastrosplenic ligament is the most difficult stage of gastric conduit creation, mainly because the more

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cranial the short gastric artery, the shorter its length. To solve this issue, we have developed a novel approach to the most cranial short gastric artery medially via the left gastrophrenic ligament. The objective of this study was to determine the feasibility of this method. Methods: Consecutive 15 patients with resectable esophageal squamous cell carcinoma who had not undergone prior gastrectomy were enrolled. In these patients, after thoracoscopic esophagectomy in the prone position was completed, 5 trocars were placed in the upper abdomen in the supine position. Carefully preserving the gastroepiploic arteries, omental bursa was opened and the root of the gastric branch of the left gastroepiploic artery was divided. Then, the left gastrophrenic ligament, which is composed of loose connective tissue between the upper part of the stomach and the left diaphragmatic crus, was dissected along the posterior aspect of the stomach up to the splenophrenic ligament. Once the splenophrenic ligament was ripped, the upper pole of the spleen was exposed and the most cranial short gastric artery stood upright on the splenic hilum. In this surgical field, short gastric arteries were easily divided in turn from the cranial to the caudal side at their roots, retaining as much blood supply to the greater curvature as possible. Results: Gastric conduit creation was completed laparoscopically in all the patients. Surgical outcomes were as follows: total operation time, min; time for gastric conduit creation, 147 (90–221) min; time for transection of the gastrosplenic ligament, 46 (16–93) min; total blood loss, 165 (25–525) mL. Four patients developed postoperative complications including partial splenic infarction (3 patients) and anastomotic leakage (1 patient). No pancreatic fistula and intraabdominal abscess took place. There was no inhospital mortality in this series. Discussion: Craniocaudal transection of the gastrosplenic ligament using the present approach might be feasible and safe. We believe this novel approach is taking the advantage of laparoscopic dorsoventral and caudocranial overlook. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, Gastric conduit, laparoscopic surgery, Gastrosplenic ligament P2.08.08: ANALYSIS OF SURGICALLY RESECTED CARCINOMAS OF ESOPHAGOGASTRIC JUNCTION (SIEWERT TYPE II), EXPERIENCE OF THE SINGLE INSTITUTION Kazuhiro Noma, Yasuhiro Shirakawa, Naoaki Maeda, Shunsuke Tanabe, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara Okayama University Medical School, Okayama/JAPAN Background: Recently the incidence of tumors of esophagogastric junction (EGJ) has been increased in US and other western countries, and same trend is occurred even in eastern countries, which could be caused by change of diet and increased incident of GERD. However at present, consensus of surgical procedure for tumors at EGJ has yet to be reached. Here we will report our recent analysis of surgically resected tumors of EGJ and introduce our new surgical procedure, which is left thoracoabdominal approach and hand-sewn esophagogastric anastomosis. Hand-sewn anastomosis is performed intrathoracic at posterior mediastinum and reconstructed like to native esophagogastric junction with opened flaps method. At last we will discuss the adequate surgical approach and anastomosis procedure, as well as our policy for the treatment of those carcinomas and the outcome of treatment. Methods: From January 2000 to December 2013, there are 70 cases of esophagogastric junction cancer (Siewert type II) underwent surgically resected. These 70 cases were the subjects of this study and analyzed their clinicopathological findings, their later prognosis and quality of life. As we measured distance of esophageal invasion (EI), EGJ was identified at changed circumference in resected esophagogastric speciemens. Results: Mean age was 66.8 years old. Adenocarcinoma was 50%. 51% cases were LN positive cases, of which 11 (15.7%) cases was node positive in mediastinum. The ratio of LN metastasis was trended to be higher than other upper GI cancer, which was 51.4% of tumors, since over T2 were 62.9% of them. A similar tendency was seen among T factors. The ratio of LN metastasis in each was T1a 0%, T1b 11.8%, T2 58.3%, T3 80.8% and T4 83.3%. Analysis of EI and mediastinal metastasis showed that EI of positive group was longer than negative significantly (p < 0.001). There were mediastinal metasitasis only in cases over EI 2cm and Mean was 4.35 cm in positive group, and 2.4 cm in negative. Only 2 cases showed upper mediastinal metastasis and were associated to multiple upper abdominal LNs metastasis. Discussion: From the above results, we focused on 2 trends. First, Lower mediastinal metastasis were trend to be associated to cardiac LNs metastasis and related to over EI 2 cm. Second, upper mediastinal metasitasis were related to multiple upper abdominal LN metastasis. According to the above trends, now we suggest individualized surgical procedures for each stage. That is prone VATS esophagectomy for “First cases”, left thoracoabdominal approach with radical resection of lower mediastinal LN for “Second


cases” and transhiatal approach for “Other early cases”. On the other hand, most of the type of recurrent was liver metastasis with vessel invasion in advanced cases. Then we are forward to neoadjuvant chemotherapy and investigating that NAC induction will lead improvement of prognosis for advanced cases. In conclusion, it is necessary to LN resection of lower mediastinum for cases, which tumor has esophageal invasion longer than 2 cm. And we suggest that LN resection of full mediastinum and multimodal therapy with NAC could lead improved prognosis for advanced cases especially with multi LN metastasis. Disclosure: All authors have declared no conflicts of interest. Keywords: esophagogastric junction, Barrett’s esophageal tumor, Siewert type II, esophagectomy P2.08.09: VISUALIZATION OF BLOOD SUPPLY ROUTE TO THE RECONSTRUCTED STOMACH BY INDOCYANINE GREEN FLUORESCENCE IMAGING DURING ESOPHAGECTOMY Yasushi Rino1, Norio Yukawa1, Tsutomu Sato1, Naoto Yamamoto1, Hiroshi Tamagawa1, Shinichi Hasegawa1, Tsutomu Hayashi1, Yuta Kumazu1, Takashi Oshima1, Takaki Yoshikawa2, Munetaka Masuda1, Toshio Imada3 1 Yokohama City University, Yokohama/JAPAN, 2Kanagawa Cancer Center, Yokohama/JAPAN, 3Saiseikai Yokohama Nanbu Hospital, Yokohama/JAPAN Background: Ensuring an adequate blood supply is essential to the safe performance of an anastomosis during esophagectomy and the prevention of anastomotic leakage. Recently, indocyanine green (ICG) fluorescence imaging has been used to visualize the blood supply when anastomosis is performed in vascular surgery. We used ICG fluorescence imaging to visualize the blood supply for reconstruction during esophagectomy. Methods: Since January 2009, we have performed ICG fluorescence imaging in 33 patients with thoracic esophageal cancer who underwent thoracic esophagectomy. After pulling up the reconstructed stomach, 2.5 mg of ICG was injected as a bolus. ICG fluorescence imaging was performed with a near-infrared camera, and the images were recorded. Results: ICG fluorescence was easily detected in all patients 1 min after injection. Vascular networks were well visualized in the gastric wall and omentum. The blood supply route was located in the greater omentum beside the splenic hilum in 22 (66.7%) of the 33 patients. Discussion: ICG fluorescence can be used to evaluate the blood supply to the reconstructed stomach in patients undergoing esophagectomy for esophageal cancer. On ICG fluorescence imaging, the splenic hiatal vessels were the major blood supply for the anastomosis in most patients. Disclosure: All authors have declared no conflicts of interest. Keywords: ICG, Esophageal cancer, blood supply route, splenic hiatal vessels P2.08.10: PROGNOSTIC SIGNIFICANCE OF EXTRACAPSULAR NODAL INVOLVEMENT IN ESOPHAGEAL CANCER WITH PREOPERATIVE TREATMENT Tatsuya Kinjo, Hideaki Shimoji, Hiroyuki Karimata, Tadashi Nishimaki Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa/JAPAN Background: Extracapsular involvement (ECI) of lymph node metastasis has been reported as an indicator of poor prognosis in patients with esophageal cancer undergoing immediate resection. However, the implication of ECI remains unclear in patients undergoing preoperative chemotherapy or chemoradiotherapy. The aim of the study was to evaluate prognostic significance of ECI of lymph node metastasis in esophageal cancer patients undergoing curative esophagectomy after preoperative treatment. Methods: Eighty five patients undergoing esophagectomy for esophageal cancer were included in this study. Of those, 39 had no preoperative treatment and the other 46 had preoperative treatment. Influence of ECI and other clinicopathologic factors upon the patients’ survival was evaluated using univariate and multivariate analyses. Results: The prevalence of ECI was 31.8%. The overall survival rate of the 85 patients was 53.1% at 5 years. On univariate analysis, presence of ECI was significantly predictive of poor survival in the patients receiving preoperative treatment, whereas ECI was not in the patients undergoing immediate surgery, although ECI were significant prognostic predictors in the all patient. On multivariate analysis, ECI was an independent prognostic predictor in the patients receiving preoperative treatment (p = 0.004, HR 4.527). The 5-year overall survival was 66.5% in patients without this factor, whereas it was 28.9% in patients with the factor. Discussion: The assessment of ECI status is useful because ECI is a potent prognostic predictor in esophageal cancer patients undergoing preoperative treatment.


ABSTRACT SUPPLEMENT

Disclosure: All authors have declared no conflicts of interest. Keywords: multidisciplinary treatment, extracapsular involvement, lymph node metastasis, prognostic predictor P2.08.11: INFLUENCE ONPOSTOPERTIVE ANASTOMOTIC COMPLICATIONS BY RECONSTRUCTION ROUTE ATER ESOPHAGECTOMY Katsunori Nishikawa1, Masami Yuda2, Yujiro Tanaka1, Akira Matsumoto1, Yuichiro Tanishima1, Fumiaki Yano1, Nobuo Omura1, Katsuhiko Yanaga1 1 Jikei University, Tokyo/JAPAN, 2The Jikei University School of Medicine, Tokyo/JAPAN Background: Recently, esophageal surgery has been performed safely with introduction of minimum invasive surgery and other medical technologies. In spite of advances in surgical techniques, that lead to reduction of post operative complications, the incidence of anastomotic complications such as anastomotic leak (AL) or stricture (AS) remain higher than other gastrointestinal surgeries. Poor vascularization of the esophageal substitute, a major reason for anastomotic complications, is affected not only by insufficient blood flow of the esophagedal substitute but also by anatomical factors such as anterior mediastinal space when the retrosternal route was chosen. We herein report the impact of anatomical factors on postoperative complications for esophageal reconstruction. Methods: Eighty-one patients who underwent esophagectomy and reconstruction with the gastric tube through the retrosternal route were enrolled in the study. All patients were eligible to undergo CT scan before and after surgery with sagittal reconstruction at thoracic section. The anterior mediastinal area (AMa), distance between the sternum and the trachea at suprasternal notch (STd), and anastomotic height from the jugular notch (Ah) were measured from the sagittal CT images. Correlation between those anatomical factors and anastomotic complications were then analyzed. Results: AL and AS occurred 9.8% and 19.8%, respectively. Preoperative mean AMa and STd were 30.5 cm2 (15.1∼19.9) and 14.3 mm (5.2∼26.3), respectively. Ah was measured postoperatively with a mean height of 9.2 mm (-27.4∼37.8). AL group had smaller AMa as compared with AS or uneventful (UE) group (AL/AS/UE: 6.4/311/30.8). As for STd, UE had significant long STd against AL and AS (AL/AS/UE: 11.8/12.6/15.2, P < 0.05). AL patients were anastomosed significantly at cephalad as compared to other groups (AL/AS/UE: 19.5/7.5/83, P < 0.05). Discussion: From these results, tight pretracheal space constituted by the suprasternal notch and the trachea may be a factor associated with that impaired blood flow of the gastric tube. Also, high esophagogastric anastomsis may cause poor vascularization in the above area of the gastric tube by compression from the jugular notch. To reduce anastmotic complications, we propose to change the reconstruction route when esophageal substitute was suspected to be inappropriate due to anatomical factors. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, reconstruction, retrosternal route, anastomotic complication P2.08.12: MINIMALL ACCESS ESOPHAGEAL RESECTION IN PIGS (EXPERIMENTAL MODEL TRAINING) Norberto Velasco Hernández, Hector Horiuchi, Tomas Grippo, Juan Occhiuzzi, Enrique Ortiz Faculty of Medical Sciences, La Plata University, Buenos Aires/ ARGENTINA Background: The porcine model has been used for training in numerous experimental surgeries. The esophageal hiatus laparoscopic surgery was the beginning to develop esophageal resections for thoracoscopic and well also the anatomical similarities to the humans Methods: Between March 2011 to December 2012, 12 pigs underwent thoracoscopic esophageal resection in prone position using 3 ports. The animals we used were 8.5 to 14.1 kg (mean 11.1 kg) with the assistance of a veterinarian. The first 5 cases prior sacrifice animal were made and the remaining 7 using living anesthetics and intravenous midazolam and ketamine. Results: The procedure was performed in prone position and all cases the resection of the esophagus was completed successfully. The intraoperative complications were: aorta injury with hook and right lung injury during the access. The average time was 23.7 min (range 15–37) Of the 7 pigs alive operated two died before completing the procedure for pneumothorax. The others were sacrificed at the end of surgery by veterinarian. Discussion: The pigs showed anatomical similarities of the mediastinum and esophagus to humans, therefore may be considered as a very good experimental model for esophageal resection for minimally invasive thoracic approach. Disclosure: All authors have declared no conflicts of interest.

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P2.08.13: THE ROLE OF STATINES IN THE TREATMENT OF ESOPHAGEAL CANCER PATIENTS Maarten Anderegg1, Sjoerd Lagarde2, Suzanne Gisbertz2, Sybren Meijer2, Maarten Hulshof1, Jacques Bergman2, Hanneke Van Laarhoven1, Mark Van Berge Henegouwen2 1 Academic Medical Center, Amsterdam/NETHERLANDS, 2Academic Medical Center Amsterdam, Amsterdam/NETHERLANDS Background: Recently, there has been an increasing interest in the potential influence of statins on therapeutic response rates and survival in different types of cancer. However, no studies explored the role of statins in the curative treatment of esophageal cancer. The aim of the present study is to investigate the effect of statins on pathologic complete response (pCR) rates and disease free survival in patients who are treated with neoadjuvant chemo(radio)therapy followed by esophagectomy. Methods: Between March 1994 and September 2013 all consecutive patients with cancer of the esophagus or gastroesophageal junction who underwent esophageal resection after neoadjuvant chemo(radio)therapy were included in the present study. Baseline demographic and clinical characteristics were compared between statin users and nonusers. Results: 463 patients were included, 93 (20.1%) used statines at the time of diagnosis. 88 (19%) underwent preoperative chemotherapy and 375 (81%) underwent neoadjuvant chemoradiation. 85 (18%) patients had a pCR (pyT0N0M0R0). pCR was not significantly different between statin users and nonstatin users (23% vs 17%, p = 0.239). Median disease free survival was not significantly different between statin users and nonstatin users (44 (95% CI 32.2–55.9) vs 41 (95% CI 30.0–53.7) months, p = 0.509). Discussion: Statin users did not experience different outcomes compared with non-users and statin use did not affect the efficacy of neoadjuvant therapy. These data do not support modification or discontinuation of statin therapy for patients with esophageal cancer. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, statin therapy, Neoadjuvant treatment P2.08.14: OUR NUTRITIONAL SCREENING PRIOR TO SURGICAL TREATMENT OF ESOPHAGEAL CANCER Takeshi Shimakawa, Yoshihiko Naritaka, Masano Sagawa, Shinichi Asaka, Asako Shimazaki, Kentaro Yamaguchi, Minoru Murayama, Souichi Konno, Hajime Yokomizo, Kazuhiko Yoshimatsu, Takebumi Usui, Shunichi Shiozawa, Takao Katsube Tokyo Women’s Medical University Medical Center East, Tokyo/JAPAN Background: In patients undergoing esophageal cancer surgery, perioperative nutritional management is important, so nutritional screening should be performed to understand each patient’s preoperative nutritional state. This study was performed to examine the relationship between nutritional screening indices on hospital admission and postoperative clinical courses. Methods: 158 patients were enrolled in the study. There were 144 males and 14 females aged between 39 and 88 years. 13 patients were in pStage 0 of cancer, 22 were in pStage I, 37 were in pStage II, 66 were in pStage III, and 20 were in pStage IV. The nutritional screening indices were: patients age 70 and over, concurrent diabetes mellitus, body mass index (BMI) of less than 18.5 or more than 25, Onodera’s prognostic nutritional index of less than 40, and serum albumin level of less than 3.6 g/dl. These nutritional screening indices were evaluated for a relationship with the incidence of postoperative complications, the number of postoperative hospital stay, and long-term hospitalization. Results: Incidences of postoperative complications were significantly higher in patients age 70 and over (61%) in comparison to those under 70 (39%). The number of postoperative hospital stay was also significantly greater for patients age 70 and over than in those under 70, and in those with a BMI of less than 18.5 than in those with a BMI of more than 25. 15 (36%) patients among those with a BMI of less than 18.5 experienced long-term hospitalization, while there was 6 (23%) patient among those with a BMI of more than 25, showing a significant difference between the two groups. Discussion: In nutritional screening prior to surgical treatment of esophageal cancer, indices regarding patients age 70 and over, patients with a BMI of less than 18.5 and Onodera’s PNI of less than 40 may be useful among those studied for predicting incidences of postoperative complications and the possibility of long-term hospitalization. Disclosure: All authors have declared no conflicts of interest. Keywords: surgical treatment, Esophageal cancer, nutritional screening

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P2.08.15: SURGICAL APPROACH FOR THE ELDER ESOPHAGEAL CANCER Keitaro Tashiro1, Masaru Kawai1, Sang-Woong Lee1, Satoshi Kawashima1, Ryo Tanaka1, Masako Hiramatsu2, Kazuhisa Uchiyama1 1 Osaka Medical College, Osaka/JAPAN, 2Takatsuki Red Cross Hospital, Osaka/JAPAN Background: Recently the number of elder patients who have esophageal cancer has been higher in Japan. Because the anesthesia and surgical technique are developing day by day, we can choose surgery as radical therapy for esophageal cancer in elder patients. But the percentage of complication after operation in elder person still should be higher compared to young person. We present the problems and the risks of surgery for elder esophageal cancer in our institution. Methods: 51 patients (over 75 years old) who had esophageal cancer underwent esophageal resection from 1998 to 2013 in Osaka Medical College, Japan. We divided these patients to 3 groups: open surgery; Group A, none open surgery (includes the esophageal resection via abdominal side); Group B, VATS; Group C, and assessed the amount of blood loss and surgical time during operation and the frequency of complication after operation. Results: Average age of patient in Group B was significantly higher than other groups (Group A: 78.7 y. o., Group B: 80.8 y. o., Group C: 77.0 y. o.). Surgical time in Group C (547.5 ± 28.0 min) was significantly longer than other groups (Group A: 380.0 ± 18.8 min, Group B: 297.1 ± 28.8 min). Blood loss during operation in Group B tended to be less than other groups (Group A: 572.2 ± 109.3 mL, Group B: 320.4 ± 61.0 mL, Group C: 495.8 ± 115.7 mL). The complication after surgery occurred in 20 patients (39.2%) in whole groups, including pneumonia (21.6%), recurrent nerve paralysis (7.8%), ischemia of gastric tube and/or small intestine (3.9%), deep venous thrombosis (3.9%) and empyema (2.0%). According to surgical approach, the occurring frequency of pneumonia after operation in Group C (16.7%) was most less than other group (Group A: 25.9%, Group B: 25.0%), but more recurrent nerve paralysis was occurred in Group C (25.0%) compared to other groups.


P2.08.17: OUR CURRENT TEAM MEDICAL CARE AND ITS PROSPECTS IN PERIOPERATIVE MANAGEMENT OF ESOPHAGEAL CANCER Takeshi Shimakawa, Yoshihiko Naritaka, Shinichi Asaka, Atuko Usuda, Akira Miyaki, Kentaro Yamaguchi, Minoru Murayama, Hajime Yokomizo, Kazuhiko Yoshimatsu, Takebumi Usui, Shunichi Shiozawa, Takao Katsube Tokyo Women’s Medical University Medical Center East, Tokyo/JAPAN Background: Because radical esophagectomy is highly invasive, postoperative complications frequently occur even with today’s improved surgical techniques and perioperative management. In particular, pulmonary complications greatly affect the prognosis. Although we have devised a surgical technique and ensured careful perioperative patient management to reduce pulmonary complications, our single-department effort has limitations. Now we are providing team medical care to our patients. We report the effect of oral care and nutrition management by the nutrition support team (NST) provided as part of our team medical care. We evaluated the effect of oral care provided under the supervision of the Department of Dentistry/ Oral Surgery and the nutritional management performed by the NST introduced about 3 years ago on the prevention of postoperative pulmonary complications. Methods: We examined the data of 30 esophageal cancer patients who underwent a right thoracolaparotomy followed by a subtotal excision of the esophagus, three regional lymph node dissection and anastomosis of the gastric tube to the cervical esophagus via a retrosternal route immediately before and after our team medical care was started, respectively. We compared the incidence of postoperative pneumonia, tracheotomy rate and surgery-related mortality between the patient groups. Results: The incidence of postoperative pneumonia, tracheotomy rate and surgery-related mortality before and after the introduction of team medical care were 23.3%, 6.7% and 0% and 10.0%, 0% and 0%, respectively.

Discussion: Lung diseases including pneumonia, particularly in elder patient, are one of the most critical and sometimes become a fatal complication after esophageal cancer surgery. VATS seems to be more safe and useful approach in elder esophageal cancer resection, but needs to be care for recurrent nerve paralysis.

Discussion: After the team medical care system was introduced, the incidence of postoperative pneumonia decreased. No tracheotomy was performed, and no surgery-related deaths were reported. The team medical care is thus considered to have been preventing serious pulmonary complications. With the increase in the number of elderly patients undergoing surgery, we are considering introducing a dysphagia rehabilitation program.



Keyword: elder esophageal cancer

Keywords: Esophageal management

P2.08.16: CERVICAL GASTROPLASTY ANASTOMOSIS IN ESOPHAGECTOMY FOR ADENOCARCINOMA OF ESOPHAGOGASTRIC JUNCTION: COMPREHENSIVE ANALYSIS OF RESULTS Flavio Takeda, Rubens Sallum, Julio Rocha, Ulysses Ribeiro Jr, Sergio Szachnowicz, Ivan Cecconello University of Sao Paulo, Sao Paulo SP/BRAZIL

P2.08.18: ENDOSCOPICALLY PLACED STENTS FOR LEAKS AFTER MINIMALLY INVASIVE ESOPHAGECTOMY Brenda Ernst1, Helen Ross1, Harshita Paripati1, Rahul Panalla1, Jonathan Ashman1, William Rule1, Kristi Harold2, Dawn Jaroszewski2 1 Mayo Clinic, Scottsdale/UNITED STATES OF AMERICA, 2Mayo Clinic Arizona, Phoenix/AZ/UNITED STATES OF AMERICA

Background: There is no consensus about the thoracic or cervical esophagogastric anastomotic after esophagectomy in adenocarcinoma of gastroesophageal junction (AGEJ). The aim of this study is to analyze the results of the cervical gastroplasty after esophagectomy for adenocarcinoma of the esophago-gastric junction Methods: We performed a retrospective analysis from 2000–2012 of 112 consecutives esophagectomies for AGEJ with cervical gastroplasty anastomosis. Type of anastomosis, rate and time to establish fistula diagnosis, anastomotic stricture, morbidity and mortality (global and related to the fistula) were analysed. Results: There were 112 patients 95(84.8%) male, mean age was 62 years (33 to 79). All patients were submitted to esophagectomy with gastroplasty and cervical anastomosis, 89.3% by transhiatal approach and 12 by thoracoscopic approach. Only 8.9% performed neoadjuvant therapy followed by esophagectomy. Linear side-to-side stapled (LS) was performed in 87.5% and 14 hand-sewn (HS). There were 17.8% anastomotic leakages, but no difference was found comparing LS and HS (p = 0.5). Mean time of fistula diagnosis was 5.6 days (3–10). Fistula occurred before 5 days, was associated to worse clinical complications (p < 0.05). The re-operative rate was 5.3% and mortality rate related to the fistula was 0.9%. The late follow-up showed 13.4% of anastomosis stricture mostly associated to previous fistula, but all of them solved with endoscopic dilatation (mean 3). Discussion: Cervical gastroplasty anastomosis is a safe procedure with low rate of severe complications or mortality. Early leakage anastomosis (before 5 days) was related to those severe complications and need a special management. Disclosure: All authors have declared no conflicts of interest. Keywords: cervical anastomosis, EGj adenocarcinoma, gastroplasty, fistula

cancer,

Team

medical

care,

perioperative

Background: Minimally invasive esophagectomy (MIE) is increasingly utilized for resection of advanced esophageal cancers. Postoperative leak rates may be increased in patients undergoing esophagectomy after neoadjuvant chemoradiotherapy (CRT). Optimal management of leaks at the anastomosis or at the gastric conduit in the post-operative period is not well defined. This study reports on the endoscopic management of leaks after MIE for both benign and malignant disease. Most resections occurred in patients with advanced malignancies in conjunction with preoperative chemoradiotherapy. Methods: Retrospective review of all patients undergoing MIE from November, 2006 to December, 2013 at Mayo Clinic Arizona. Leak was defined as any clinical or radiographic imaging suspicious for the loss of anastomotic or conduit integrity. Results: 129 patients underwent MIE. Mean age was 64.25 (range 26–88 years), and 111 (86%) were male. 117 (91%) patients were resected for cancer and 12 (9%) for benign etiologies. Pre-operatively, 85 (72.6%) of cancer patients were staged IIB or higher. 84 patients (71.7% of cancer patients) received neoadjuvant chemoradiotherapy and 29 (22%) patients underwent postoperative adjuvant therapy. 12 (9.3%) cervical anastomoses and 117 (90.6%) thoracic anastomoses were performed. Leaks were observed in 17 patients. 12.5% of cervical anastomoses versus 12.8% of thoracic anastomoses developed leaks requiring observation (2/17) or active management (15/17). 3 of 5 (60%) patients with gastric conduit leak and 7 of 12 (53.8%) with anastomotic leak required reoperation. 10 patients (58%) with leaks were managed with endoscopic stent placement an average of 12 days postoperatively (range 5–26). Stents were placed such that the fistula/leak was in the fully covered portion with the greater portion of the stent residing in the esophageal remnant, using the largest available diameter (most often 22 mm). Endoscopically placed stents were successful at sealing leaks in 9/10 patients. Stents were removed endoscopically in 9/10 patients after an


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average of 49 days (range 28–76). Strictures developed in 2 of 10 (20%) stented patients discovered between 79–91 days postoperatively (average 85) and in 22 of 112 (19.6%) patients without leaks or stent placement discovered 20–1324 days (average 168) postoperatively. Leaks developed in 6 (13%) patients that did not receive chemoradiation. Patients treated with neoadjuvant chemoradiotherapy had 11 (13%) leaks, 1 managed with observation, 3 with reoperation and 7 with stents. Stent complications occurred in 2 patients including one tracheoesophageal fistula and one stent migration.

pull-up via retrosternal route 7 years ago. Contrast study revealed a filling defect in the distal part of the reconstructed gastric tube. Nasopharyngeal cancer was detected at the same time. After chemoradiotherapy for nasopharyngeal cancer, operation was performed for gastric tube cancer. Because the radiation field included anastomotic site of pervious operation, resection of the distal part of the gastric tube was considered. For this purpose, we intraoperatively evaluated blood flow of the gastric tube as well as lymphatic flow along the gastric tube by using ICG fluorescence imaging.

Discussion: Anastomotic leaks are a known complication of esophagectomy and can be managed endoscopically for some patients. Neoadjuvant chemoradiotherapy was associated with similar leak rates as compared with those that did not receive CRT and the majority of those leaks were amenable to endoscopic stent management and did not negatively affect overall postoperative outcomes. Endoscopic stent placement is an effective management tool for postoperative leaks after MIE for advanced stage esophageal malignancies and may reduce rates of reoperation.

Results: Submucosal ICG injection around the tumor revealed lymphatic flow localized along right gastroepiploic artery. In addition, intravenous ICG injection revealed blood flow into the distal part from oral side of gastric tube. Based on this finding, we performed distal gastrectomy (resection of distal part of gastric tube) with Roux-en-Y reconstruction (gastrojejunal anastomosis). The post-operative course was uneventful. Histologically, the tumor was diagnosed pT1b(SM)N0M0, pStage IA.

Disclosure: All authors have declared no conflicts of interest. Keywords: MIE, stent, Esophageal adenocarcinoma, chemoradiotherapy P2.08.19: INSIGHTS IN WORK REHABILITATION AFTER MINIMALLY INVASIVE ESOPHAGECTOMY Luis Carlos Silva Corten1, Srdjan Rakic1, Pascal Steenvoorde2, Ewout A Kouwenhoven1 1 ZGT Almelo, Almelo/NETHERLANDS, 2MST Enschede, Enschede/ NETHERLANDS Background: Esophagectomy is a severely debilitating procedure, but still the gold standard as treatment for localized esophageal cancer. We investigate the impact of minimally invasive esophagectomy (MIE) on work rehabilitation. Methods: Between December 2010 and December 2013, 75 patients underwent a MIE in our centre. All patients who had employment pre-operatively were selected. Patients with cancer recurrence during follow-up were excluded. Data about work rehabilitation were collected from patient’s forms and a questionnaire. Interval to restart professional career was monitored, as well as grade of occupation (part-time/full time). Results: Nineteen patients (15 male, 4 female) had employment before surgery. Seventeen underwent a McKeown procedure and 2 an Ivor-Lewis procedure. Median age was 56 (52–58). Median ICU stay was 3 (2–7) days. Median hospital stay was 10 (9–15) days. At 3 months postoperatively 7 patients (7/19 – 37%) were able to restart their professional occupation; 1 patient restarted his job full-time, 6 part-time. The group reaching six months (18/19) of surveillance showed part time work rehabilitation in 56% (10/18) and still only 1 full time occupation. At one year of follow-up (14/19) patients restored working capacity in 64% (9/14): 29% (4/14) full time, 36% (5/14) part-time. At 18 months (11/19) follow-up 55% of the patients worked full time (6/11). So far 3 out of 19 patients were declared disabled. Discussion: Work rehabilitation after MIE is not just a matter of course. For half of patients it takes 6 months to restart their job; only 64% of the patients is able to practice their job within a year. More than 18 months is needed to get only half of these patients back on their full time occupation. It is important to prepare our patients for the impact of MIE on their professional capacities. Disclosure: All authors have declared no conflicts of interest.

Discussion: Invasion of Surgery for gastric tube cancer frequently become large and complications sometime occur. Intraoperative evaluation of blood and lymphatic flow by using ICG fluorescence imaging helps decision of area of gastric tube’s resection and lymph node dissection and is useful for minimally invasive surgery for cancer in the reconstructed gastric tube. Disclosure: All authors have declared no conflicts of interest. Keywords: gastric tube cancer, Indocyanine green fluorescence imaging, minimally invasive surgery P2.08.21: CLINICAL ANALYSIS OF APPLICATION OF DUODENAL FEEDING TUBE IN THORACOSCOPY-AND LAPAROSCOPYGUIDED ESOPHAGECTOMY FOR ESOPHAGEAL CARCINOMA Ming Du, Xu Huang, Huanwen Chen The First Affiliated Hospital of Chongqing Medical University, Chongqing/ CHINA Background: This study was aimed to investigate the safety and feasibility of applying duodenal fedding tube in thoracoscopy-and laparcoscopyguided esophagectomy for esophageal carcinoma. Methods: Clinical data of 73 esophageal carcinoma patients who underwent esophagectomy and received a duodenal fedding tube by thoracoscopy and laparoscopy from March 2011 to September 2012 were analyzed retrospectively. Modes of operation included the separation of the esophagus by thoracoscopy, separation of the stomach by laparoscopy, reconstruction of the digestive tract, and so on. Results: A duodenal feeding tube was carefully placed at the site of esophagectomy of the patient. Operation time lasted from 180 min to 410 min, with an average of 273 min. The duodenal fedding tube wai placed at 27 min into operation. Intra-operative blood loss ranged from 50 mL to 450 mL, with an average of 120 mL. No post-operative death was encountered among the cases. After surgery, anastomotic fistula and gastrointestinal discomfort occurred in 2 and 5 of the 73cases, respectively. Discussion: Placement of a duodenal feeding tube at the site of esophagectomy through thoracoscopy and laparoscopy is completely asfe and feasible. Disclosure: All authors have declared no conflicts of interest. Keywords: Laparoscopy, thoracoscpy

esophageal

carcinoma,

enteral

nutrition,

Keywords: work rehabilitation, Minimally Invasive, esophagectomy P2.08.20: A RESECTED CASE OF GASTRIC CANCER ARISING IN THE RECONSTRUCTED GASTRIC TUBE AFTER ESOPHAGECTOMY BASED ON BLOOD AND LYMPHATIC FLOW EVALUATION BY INDOCYANINE GREEN FLUORESCENCE IMAGING Yosuke Ariyoshi, Atsushi Shiozaki, Hitoshi Fujiwara, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Daisuke Ichikawa, Kazuma Okamoto, Ryo Morimura, Yasutoshi Murayama, Yoshiaki Kuriu, Hisashi Ikoma, Masayoshi Nakanishi, Chouhei Sakakura, Eigo Otsuji Kyoto Prefectural University of Medicine, Kyoto/JAPAN Background: The gastric tube cancer has increased in recent years with the progress of multimodal treatment for esophageal cancer, but the proper resection of gastric tube and lymph node dissection for advanced gastric tube cancer are unclear. Indocyanine green (ICG) fluorescence imaging has been widely used for detection of sentinel lymph node in breast cancer surgery and visualization of the blood supply after anastomosis in vascular surgery. We report a case of gastric tube cancer performed distal part resection of gastric tube based on blood and lymphatic flow evaluation by ICG imaging. Methods: A 69-year-old man was admitted to our hospital to treat gastric tube cancer detected by screening upper gastrointestinal endoscopy. He had undergone subtotal esophagectomy for esophageal cancer with gastric

P2.08.22: THE LONG-TERM OUTCOME AFTER THORACOSCOPIC ESOPHAGECTOMY WITH EXTENSIVE LYMPHADENECTOMY IN 525 PATIENTS WITH THORACIC ESOPHAGEAL CANCER Shigeru Lee, Satoru Kishida, Yushi Fujiwara, Ryouya Hashiba, Yasunori Matsuda, Ken Gyobu, Eijiro Edagawa, Harushi Osugi Osaka City Univ. Graduate School of Medicine, Osaka/JAPAN Background: The long-term prognostic impact and oncologic feasibility of video-assisted thoracoscopic esophagectomy (VATS- esophagectomy) with extensive lymphadenectomy for esophageal cancer have yet to be clarified. Since 1996, VATS-esophagectomy has been performed in 525 patients with thoracic esophageal cancer. The long-term efficacy of VATS-esophagectomy in the left lateral position was studied. Methods: VATS-esophagectomy was indicated for the patients with 1) no extensive pleural adhesion, 2) no contiguous tumor spread, 3) pulmonary function capable of sustaining single-lung ventilation, and 4) no previous radiotherapy. We use 4 ports around a 5 cm minithoracotomy on the 5th intercostal space. We laid emphasis on utilizing magnifying effect of video, obtained by positioning the camera at close vicinity to the dissection. Results: VATS-esophagectomy was converted to open surgery in 53 patients dew to pleural adhesion, T4, and etc. We had no emergence conversion. Curative operation was performed in 459 patients. Duration of thoracic procedure and retrieved mediastinal nodes were 192 min. and 34. The blood

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loss during thoracic procedure was 193 g. The reduction of %VC was 11%, 15% at 4 weeks and 12 weeks after surgery. The mean follow-up period was 729 days. One hundred twenty-one patients (26%) had recurrence of cancer after curative operation. The disease recurrence in 81 patients (67%) within 1 year after surgery, in 103 patients (85%) within 2 years after surgery, in 117 patients (97%) within 3 years after surgery and in 121 patients (100%) within 4 years after surgery. Ninety-nine patients (39%) with lymph node metastasis had recurrence and 22 patients (11%) without lymph node metastasis had recurrence. The initial patterns were hematogeneous in 57 patients (12%, lung; 24, liver; 17, bone; 9, brain; 7), lymphatic in 58 patients (13%) (36 were out of the mediastinum and 22 were in the mediastinum), pleural dissemination in 4 patients (0.9%) and local in 2 patients (0.4%). Therefore, the local control rate after thoracoscopic surgery was 94%. The overall 5-year survival rate of stage IA, IB, IIA, IIB, IIIA, IIIB, IIIC and IV (UICC, the 7th Edition) disease in the patients followed more than 2 years after VATS-esophagectomy was 92.8, 87.0, 78.2, 74.2, 55.2, 38.1, 19.7 and 48.2%, respectively. And the overall 5-year survival rate of stage I, II, III, and IVa (Guide Lines for the Clinical and Pathologic Studies on Carcinoma of the Esophagus, the 10th Edition, Japan Esophageal Society) disease in the patients followed more than 2 years after VATS-esophagectomy was 92.6, 74.1, 49.3, and 25.2%, respectively. Discussion: Conclusion: VATS-esophagectomy with extensive lymphadenectomy for thoracic esophageal cancer can be performed safely with efficacy in the survival. Disclosure: All authors have declared no conflicts of interest. Keywords: thoracoscopic surgery, Esophageal cancer P2.08.23: TIMELY MULTIMODALITY THERAPY CAN REALIZE LONG SURVIVAL FOR ADVANCED ESOPHAGEAL CANCER PATIENTS WITH ESOPHAGO-BRONCHEAL FISTULA Akira Tangoku Institute of Health Biosciences, Tokushima University Graduate School, Tokushima/JAPAN Background: Advanced upper and middle thoracic esophageal cancer often inhibits oral intake due to stenosis or obstruction and involves the neighboring organ such as the trachea, left main bronchus, and the aorta. Esophogobroncheal fistula (EBF) develops in 5–15% of patients with esophageal cancer. Recent advance of chemotherapy and chemoradio therapy realized complete response for the patients with esophageal cancer. Effective therapy often makes a EBF. This situation is not only life threatening, but also decrease patients’ Quality of Life (QOL) due to dysphagia, cough, fever and dyspnea from pneumonia, and continue of treatment becomes very difficult, therefore an emergency stenting is frequently indicated to prevent respiratory failure. Prognosis after these palliative procedures is far from satisfactory. Survival time is very short under such a life-threating condition. Methods: Herein we reported four cases of cT4 esophageal cancer with EBF obtained long survival over one year under extremely well QOL by the multimodality managements using effective chemoradiotherapy and nutritional support by timely bypass operation. Results: Postoperative therapy including chemoradiotherapy could be completed because nutrition, QOL and fighting spirits were maintained by allowing oral intake. Complete remission has realized in two cases. Discussion: Recent advances in chemotherapy and chemo-radiotherapy have increased response rate and the number of the patients obtained complete responses also increased. But effective therapy for locally advanced upper and middle thoracic esophageal cancer often makes esophago-broncheal fistula and it brings about serious cough, dyspnea, fever and pulmonary infection. Those conditions are very difficult to manage. Timely bypass operation maintain QOL and fighting spirit of the patients, it make a completion of the therapy and long survive. Disclosure: All authors have declared no conflicts of interest. Keywords: advanced esophageal cancer, esophago-broncheal fistula, multimodality therapy, bypass surgery P2.08.24: TWO CASES OF ESOPHAGECTOMY WITH GASTRIC TUBE RECONSTRUCTION FOR PATIENTS WHO PREVIOUSLY RECEIVED TOTAL PHARYNGOLARYNGOCERVICAL ESOPHAGECTOMY Shoichiro Hikami, Atsushi Shiozaki, Hitoshi Fujiwara, Takeshi Ishimoto, Ryo Morimura, Yasutoshi Murayama, Shuhei Komatsu, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Masayoshi Nakanishi, Daisuke Ichikawa, Kazuma Okamoto, Chouhei Sakakura, Eigo Otsuji Kyoto Prefectural University of Medicine, Kyoto/JAPAN Background: Nowadays, free jejunal all transfer (FJT) with total pharyngolaryngocervical esophagectomy (TPLCe) for head-and-neck cancer has been performed in many hospitals. Awareness has been raised about the occurence


of secondary esophageal cancer (EC) in patients who subsequently underwent FJT. Although surgical approach is the only treatment for long term disease control, it is more challenging because of an increase in the risk of operative morbidity and mortality. Methods: We performed salvage esophagectomy with gastric tube reconstruction in patients with thoracic EC who had previouly undergone TPLCe with FJT. Patient 1 was a 53-year-old woman who previously received definitive chemoradiotherapy (dCRT) for middle thoracic EC. She subsequently underwent TPLCe with FJT for hypopharyngeal cancer. However, the recurrence of EC was found in the middle thoracic esophagus. Patients 2 was a 64-year-old man who previously TPLCe wth FJT for hypophryngeal cancer. He subsequently underwent endoscopic submucosal dissection and dCRT for thoracic EC. He was readmitted with severe esophageal stricture following dCRT (no residual tumor or recurrence was evident in the esopagus). we performed salvage esophagectomy with lymphadenectomy for two patients. Right thoracotomy was performed in patient 1, whereas a laparoscopic transhiatal approach without thoracotomy was used in patient 2. After dissection of the thoracic esophagus, a cervical incision was made on the opposite side of the supplying vessels of the free jejunal flap (FJF) in both patients. The FJF was detected and its distal side was cautiously exposed without damaging its supplying vessels or those of the permanent tracheal stoma. A gastric tube was pulled up through a posterior mediastinal route, and an anastomosis was made between the FJF and gastric tube by hand. Results: Postoperative recovery was uneventful in patient 1, and she was discharged 17 days after the operation. Although minor anastomotic leakage was found in patient 2, it healed immediately after drainage treatment. Discussion: We reported two cases of EC who had previously undergone TPLCe with FJT, and successfully performed salvage esophagectomy with gastric tube reconstruction. The surgical approach for these patients must be chosen carefully in order to preserve the FJF, permanent tracheal stoma, and their blood supplies. Disclosure: All authors have declared no conflicts of interest. Keywords: esophagectomy, gastric tube reconstruction, free jejunal transfer P2.08.25: THE DEVICE OF THE LEFT DECUBITUS THORACOSCOPIC ESOPHAGUS RESECTION BY THREE PORT APPROACH Seiya Inoue, Takanori Miyoshi, Mariko Aoyama, Hashimoto Naoki, Shinichi Yamasaki, Masaru Tuyuguchi Tokushima Municipal Hospital, Tokushima/JAPAN Background: Previously, we had done the esophageal cancer surgery lateral thoracotomy, with thoracoscopic assistance. We introduced the lateral position thoracoscopic esophagectomy by 3-port with the aim of a good field of view and reduce surgical stress. We presented about the safety and ingenuity of surgical procedures. Methods: One monitor, three ports, use a perspective mirror 30 degrees 10 mm. The camera port inserts a 12 mm port in the axillary line out of the seventh intercostal, and make the port for operators at 4 cm in the axillary line in front of the fourth intercostals, and make the port for assistants at 2 cm after the sixth intercostal in the axillary line. The operator takes the ventral of the patient., and the assistant stands in the back side. We perform intrathoracic operation using forcepses more than two. The operation of the superior mediastinum holds the superior lobe lungs in check with the forceps from a ventral and performs lymph node dissection. After having exfoliated the esophagus, perform taping and perform lymph node dissection around the both sides recurrent laryngeal nerve, and perform cutting apart of azygos vein. The operator pulls the trachea to the ventral of the patient with a siphon, and the assistant pulls the adipose tissue including the lymph node in the back side with a forceps. In a good field of vision, the operator can debride No.106rec-L and tbL lymph node. Furthermore, debride No.101 in succession in No.106rec-R. After having transected the esophagus, I exfoliate the lower part esophagus and finish intrathoracic operation. The abdominal operation uses a laparoscope to exfoliate stomach, and make a small incision to an epigastric region and make a gastric tube, and reconstruct it with retrosternal route. Results: There is no case that shifted to thoracotomy by this operation, and there is not the postoperative death. The average of the thoracic cavity operation time was 233 minutes and the average of the intrathoracic amount of bleeding was 297 ml. Pneumonia and the one side recurrent laryngeal nerve paralysis developed in the postoperative complications, but were improved by follow-up. Discussion: Our method was safe and was superior in the securing of field of vision in an operator and an assistant using forcepses more than two. This method can support in the case of the advanced cancer such as T4. We repeat a case, and it will be necessary to examine safety and a maneuver in future.


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Disclosure: All authors have declared no conflicts of interest. Keywords: left decubitus, thoracoscopic esophagus resection, three port approach P2.08.26: CLINICAL RESULTS OF TRANSHIATAL ESOPHAGECTOMY FOR CARCINOMA OF THE LOWER THORACIC ESOPHAGUS Masaharu Higashida, Hideo Matsumoto, Hisako Kubota, Masafumi Nakamura, Toshihiro Hirai Kawasaki Medical School, Kurashiki/JAPAN Background: We generally choose transhiatal esophagectomy (THE) for early esophageal cancer patients with high risk for postoperative complications and carcinoma of the lower thoracic or abdominal esophagus even if the tumor is in the advanced stage. The merits of THE are a short operation time, less invasive method and quick recovery from the operative stress. On the other hand, the demerit of THE is the impossibility of lymph node dissection of the upper mediastinal area. The operative procedure of THE is as follows; The wound retractor was used to take a good visual field around the lower mediastinal area. Lymph node dissection around the middle or lower esophagus was performed. The whole stomach was used as an esophageal substitute and that was lifted up to the neck through the post-mediastinal route. The anastomosis with the whole stomach and the cervical esophagus was done by a hand-sutured. Methods: We investigated 124 THE cancer patients to reveal it’s curability. Results: In patients with stages 0, I, II, III and IV tumors, 5-year survival rates were 100%,96%, 78%, 33%, 7%, respectively. The sites of first recurrence were the lymphnodes (n = 15) and single organs (n = 6). Dissemination (n = 2) and local recurrence (n = 3) were also seen as a first recurrence. Discussion: In our conclusion, THE is not less-curative method for cases in stages 0, I, and II. Disclosure: All authors have declared no conflicts of interest. Keywords: Clinical results, Lower Thoracic Esophagus, 5-year survival rates, Transhiatal esophagectomy P2.08.27: PROGNOSTIC IMPACT OF TUMOR LOCATION IN PATIENTS WITH SURGICALLY RESECTED ESOPHAGEAL SQUAMOUS CELL CARCINOMA Shinsuke Takeno, Kenji Maki, Ippei Yamana, Tatsuya Hashimoto, Ryosuke Shibata, Hironari Shiwaku, Kanefumi Yamashita, Yuichi Yamashita Fukuoka University Faculty of Medicine, Fukuoka/JAPAN Background: The esophagus develops from a small area of endoderm between the tracheal diverticulum and stomach dilation of the foregut. Elongation of the esophagus initially occurs in the lower site, then in the upper part. Between 3 and 4 months after conception, lymphatic capillaries develop in the submucosa of the esophagus. We wondered whether tumor location might affect lymphatic spread or prognosis in patients with esophageal squamous cell carcinoma (ESSC) from the perspective of embryological differences. To clarify the prognostic impact of tumor location in patients with ESCC, we examined data from not only open thoracic esophagectomy but also thoracoscopic esophagectomy as this technique enables more meticulous harvesting of lymph nodes at our institute. Methods: Participants in this study comprised 228 patients with ESCC who underwent radical esophagectomy with harvesting of lymph nodes from three fields (neck, thorax and abdomen) without preoperative supplement therapies between January 1991 and December 2010. Of these, 199 patients were male and 29 were female, and the mean age was 64.0 years. Patients with cervical esophageal ESCC were excluded. The prognostic impact of tumor location was examined in detail using subgroups according to status of lymph node metastasis, surgical approach (open thoracotomy vs. thoracoscopic surgery) or or cancer stage (early or advanced stage). Results: The ME group showed a decreased frequency of lymph node metastasis compared to the other groups (p = 0.0057). Extrathoracic lymph node metastasis, which included abdominal nodes, showed significantly increased frequency according to lower sites (p = 0.0008), whereas recurrent laryngeal node metastasis showed significantly increased frequency according to upper sites (p = 0.016). In the analysis of the prognostic difference of tumor location according to surgical approach, no significant statistical difference was identified. In addition, subgroup analysis classified by cancer stage (0, 1 or 2, 3) was performed because the patients with more advanced stage increased in LE group significantly. However, tumor location was likewise not identified as a significant prognostic parameter in early or advanced stage. Discussion: The prognostic impact of tumor location on esophageal cancer remains controversial and no consensus has been reached, particularly for ESCC, which can arise from anywhere in the esophagus. The number of

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dissected recurrent laryngeal nodes was increased in the thoracoscopic approach group compared with the open thoracotomy group. While tumor location still had no significant prognostic impact by surgical approach group, upper group tended to show more favorable prognosis in the thoracoscopic surgery. These results suggest the importance of adequate lymph node dissection regardless of open or thoracoscopic surgical approach. In conclusion, the mode of lymphatic spread varied by tumor location, but adequate lymph node dissection regardless of an open or thoracoscopic approach might eliminate any prognostic impact of tumor location on ESCC. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal squamous cell carcinoma, tumor location, prognosis, lymph node metastasis P2.08.28: PREOPERATIVE PREDICTION OF PREFERABLE APPROACH TO THE MEDIASTINUM DURING MINIMALLY INVASIVE ESOPHAGECTOMY BY CT SCAN Hidetaka Kawamura, Yosuke Izumi Tokyo Metroporitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo/JAPAN Background: To establish the method to predict the method to predict the preferable approach, thoracoscopic or laparoscopic, to the lower mediastinum by preoperative CT scan. Methods: Between June 2007 and June 2009, minimally invasive esophagectomy (MIE) was performed in 57 patients, while laparoscopic transhiatal approach was intended to dissect up to the level of subcarinal lymph nodes, and gastric reconstruction via retrosternal route, thoracoscopic dissection in the paratracheal lymph nodes and bilateral neck dissection were performed. 35 out of 57 patients underwent laparoscopic dissectionof the subcarinal lymph nodes. The others underwent laparoscopic mediastinal dissection up to the level of lower pulmonary vein. We measured the thorax size on preoperative CT scan, which are thought to be related to difficulty of the operative procedure. Results: [Deviation of the esophagus to the left from the midline] Mean operative time of thoracoscopic procedure were 130 minutes in 8 cases with deviation < 20 mm, 185 minutes in 9 cases with deviation 25–30 mm and 130minutes in 9cases with deviatin > 35 mm, respectively. Mean operative time of thoracoscopic procedure was significantly shorter in patients with deviation < 20 mm or >35 mm, compared with patients with deviation 25–30 mm(P = 0.024, 0.015 respectively) [Length between vertebra and sternum] Mean operative time of laparoscopic procedure up to the level of subcarinal lymph nodes were 268 minutes in 14 cases (58% of 22 cases) with length < 10 cm and 267minutes in 21 cases (66% of 33 cases) with the length > 10 cm. They were not different. Rate of dissection up to the level of subcarinal lymph nodes was higher in patients with the length > 10 cm, not significantly different. Discussion: 1. Laparoscopic transhiatal procedure might be limited to the level of lower pulmonary vein in patients with the length between vertebra and sternum < 10 cm and deviation of the esophagus to the left from the midline < 20 mm. 2. Laparoscopic transhiatal procedure would be better to be done up to the level of subcarinal lymph nodes or upper in patients with the length between vertebra and sternum > 10 cm and deviation of the esophagus to the left from the midline 25–30 mm. 3. Laparoscopic transhiatal procedure could be done easily up to the level of subcarinal lymph nodes or upper in patinets with deviatin of the esophagus to the left from the midline > 35 mm irrespective of the length between vertebra and aternum. Disclosure: All authors have declared no conflicts of interest. Keyword: CT P2.08.29: COMPARATIVE STUDY OF MINIMALLY INVASIVE VERSUS OPEN ESOPHAGECTOMY FOR ESOPHAGEAL CANCER Juwei Mu, Zuyang Yuan, Ning Li, Fang Lv, Yousheng Mao, Qi Xue, Shugeng Gao, Jun Zhao, Dali Wang, Zhishan Li, Yushun Gao, Liangze Zhang, Jinfeng Huang, Kang Shao, Feiyue Feng, Liang Zhao, Jian Li, Guiyu Cheng, Kelin Sun, Guojun Huang, Rugang Zhang, Jie He Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing/CHINA Background: In order to minimize the injury reaction during the surgery and reduce the morbidity rate, hence reducing the mortality rate of esophagectomy, minimally invasive esophagectomy (MIE) was introduced. The aim of this study was to compare the postoperative outcomes in patients with esophageal squamous cell carcinoma undergoing minimally invasive or open esophagectomy (OE). Methods: The medical records of 182 consecutive patients, who underwent minimally invasive esophagectomy (MIE) between January 2009 and September 2013 in Cancer Institute & Hospital, Chinese Academy of Medical

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Sciences, were retrospectively reviewed. In the same period, 144 patients who underwent OE, either Ivor Lewis or McKeown approach, were selected randomly as controls. The clinical variables of paired groups were compared, including age, sex, Charlson score, tumor location, duration of surgery, number of harvested lymph nodes, morbidity rate, the rate of leak, pulmonary morbidity rate, mortality rate, and hospital length of stay (LOS). Results: The number of harvested lymph nodes was not significantly different between MIE group and OE group (median 18 vs. 16, P = 0.728). However, patients who underwent MIE had longer operation time than the OE group (375 vs. 300 minutes, P < 0.001). Overall morbidity, pulmonary morbidity, the rate of leak, in-hospital death, and hospital LOS were not significantly different between MIE and OE groups. However, patients who underwent minimally Ivor Lewis esophagectomy had longer duration of surgery and more anastomotic leaks than that of open Ivor Lewis esophagectomy. And patients who underwent minimally McKeown esophagectomy had longer duration of surgery and more overall morbidities but not major morbidities such as anastomotic and pulmonary morbidity than that of open McKeown esophagectomy. Multivariable analysis demonstrated that duration of surgery was the only independent factor predictive of postoperative morbidity, but not the approach of surgery. Discussion: MIE and OE appear equivalent with regard to early oncological outcomes. Disclosure: All authors have declared no conflicts of interest. Keywords: Comparative study, surgical procedures, Minimally Invasive, esophagectomy P2.08.30: LAPAROSCOPIC ESOPHAGECTOMY FOR CANCER: IMPACT ON POSTOPERATIVE INFLAMMATORY AND NUTRITIONAL STATUS Rita Alfieri, Luca Maria Saadeh, Marco Scarpa, Francesco Cavallin, Eleonora Pinto, Matteo Cagol, Anna Da Roit, Elisa Pizzolato, Giulia Noaro, Carlo Castoro Veneto Institute of Oncology, Padova/ITALY Background: The purpose of this case-control study was to evaluate the impact of laparoscopic gastric tubulization during esophagectomy for cancer on postoperative inflammatory and nutritional status. Methods: We retrospectively evaluated all consecutive patients undergoing laparoscopic gastric tubulization (LGT) during esophagectomy for cancer referred to our surgical unit between 2008 and 2013. A group of patients undergoing esophagectomy with open gastric tubulization (OGT) – matched for neoadjuvant therapy, pathological stage, gender and age – were enrolled as controls. Demographic data, tumor features and post-operative course were compared. In particular, systemic inflammatory and nutritional status were monitored during the postoperative hospital stay. Quality of life was evaluated at one month after surgery using EORTC QLQ-C30 functional scales, EORTC OES-18 Eating scale and EORTC BR23 Body Image scale. Results: We enrolled 34 patients per group, with similar demographic and tumor characteristics and ASA score. Patients in LGT group had longer procedure (p = 0.04). Postoperative course was similar in term of complication rate and severity and of functional result. ICU length of stay was shorter patients in LGT group (p = 0.002). In the first postop day LGT patients had lower C-reactive protein (CRP) levels (p = 0.001) and white cell blood count (p = 0.05), and higher albumin serum level (p = 0.001). In this group, albumin remained higher also at third (p = 0.06) and seventh (p = 0.008) postop day, and CRP resulted lower at third post day (p = 0.04). No difference was observed in term of quality of life. Discussion: LGT during esophagectomy for cancer significantly improved the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter ICU length of stay. Quality of life and esophageal function were comparable between LGT and OGT patients. Disclosure: All authors have declared no conflicts of interest. Keywords: esophagectomy, nutritional status, minimally invasive surgery P2.08.31: OCCUPATIONAL STATUS AFTER ESOPHAGECTOMY FOR CANCER Rita Alfieri, Eleonora Pinto, Marco Scarpa, Francesco Cavallin, Matteo Cagol, Luca Maria Saadeh, Silvia Mantoan, Carlo Castoro Veneto Institute of Oncology, Padova/ITALY Background: The purpose of the current study was to evaluate the impact of esophagectomy for cancer on patients’ occupation. We also evaluated the association between the job condition and perceived quality of life at one year after esophagectomy. Methods: We retrospectively evaluated all consecutive patients referring to our department between 2009 and 2012 for esophageal cancer. Inclusion criteria was esophagectomy for cancer. Patients not suitable for work (due to psychiatric disease or tetraplegia) and patients with missing information


about their job were excluded. Working condition at diagnosis, at one month before surgery and at one year after surgery was collected. Patient’s and tumor characteristics – along with therapeutic strategies – were also collected. Quality of life was evaluated at one year after surgery using Financial Difficulties (FI), Social Functioning (SF), Role Functioning (RF) and Global health status (QL2) scores of EORTC QLQ-C30 questionnaire. Results: One hundred twenty-six consecutive patients referred to our department between 2009–2012 for esophageal cancer and 89 of them underwent surgical resection. Fifty-one patients were active workers at the diagnosis, 29 were retired and 6 were housewives, whereas job information was not available in 3 patients. Among patients working at diagnosis, 64% still worked at one year after surgery whereas 36% quit their job. At one year after surgery, the SF score (92.9 ± 13.1 vs. 85.5 ± 17.6, p = 0.32), FI score (16.7 ± 27.9 vs. 24.6 ± 27.0, p = 0.53), RF score (71.4 ± 28.4 vs.87.7 ± 22.0, p = 0.12) and QL2 score (84.8 ± 18.3 vs. 83.2 ± 22.4, p = 0.55) were similar between patients who quit and those who not quit their job. Discussion: A considerable number of patients quit their job after esophagectomy for cancer. Adequate welfare strategy should be implemented for esophageal cancer survivors. Disclosure: All authors have declared no conflicts of interest. Keywords: esophagectomy, esopahgeal cancer, Quality of Life, occupational status P2.08.32: RECONSTRUCTION OF THE THORACIC ESOPHAGUS WITH PEDICLED JEJUNAL FLAP Yasuhiro Shirakawa, Naoaki Maeda, Shunsuke Tanabe, Kazuhiro Noma, Toshiyoshi Fujiwara Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama/JAPAN Background: Esophageal reconstruction using intestine is often performed for esophageal cancer patients in whom stomach cannot be used. We have previously performed reconstruction using ileocolon with supercharge and drainage as our first choice in those cases. However, a less invasive, safer, and simpler reconstructive technique using jejunum without vascular anastomosis has recently become popular at our facility. This study describes the technique of esophageal reconstruction with jejunum, compares the surgical outcomes to those of standard reconstruction using colon, and discusses the clinical significance of this new concept. Methods: Subjects comprised 60 patients (55 males, 5 females) who underwent esophageal reconstruction using jejunum between January 2008 and March 2014. Patient characteristics, technical details, and outcomes were compared with those of 51 subjects who had undergone esophageal reconstruction using colon. When making the pedicled jejunal flap, the first jejunal vascular arcade was preserved, which in most cases allowed it to be pulled up to the cervical region by processing and transection up to the second jejunal vascular branch. Results: The vascular anastomosis techniques were used in 80.4% (41/51) of esophageal reconstructions using colon, compared with only 26.7% (16/60) of reconstructions using jejunum. No difference in the frequency of postoperative adverse effects was seen between groups, but the frequency of diarrhea was significantly lower with reconstruction using jejunum. Discussion: Esophageal reconstruction using jejunum with the blood vessel processing technique results in both safer and simpler pulling up. Thus the need to perform supercharge and resuperdrainage is reduced. Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal reconstruction, Pedicled jejunal flap, Supercharge, Superdrainage P2.08.33: THE IMPACT OF POSTOPERATIVE COMPLICATIONS ON BODY WEIGHT LOSS AND MUSCLE WASTING AT THREE MONTHS AFTER ESOPHAGECTOMY: COULD ENTERAL NUTRITION MAINTAIN BODY WEIGHT AND MUSCLE MASS? Tsutomu Hayashi, Yasushi Rino, Yuta Kumazu, Shinichi Hasegawa, Hiroshi Tamagawa, Naoto Yamamoto, Tsutomu Sato, Norio Yukawa, Takashi Oshima, Takaki Yoshikawa, Munetaka Masuda Yokohama City University, Yokohama/JAPAN Background: Enteral nutrition using jejunostomy is a routine part of esophagectomy in a patient with esophageal cancer. Furthermore enteral nutrition using jejunostomy has become an accepted method of dealing with postoperative complications like an anastomotic leakage, pneumonia, and recurrent nerve palsy. The aim of this study was to evaluate whether enteral nutrition decreases body weight loss and muscle wasting for the patients with postoperative complications after esophagectomy. Methods: Thirty-two patients who underwent a thoracic esophagectomy for esophageal cancer at Yokohama City University Hospital between January


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2011 and December 2013 were included in this study. In all patients, feeding jejunostomy was placed at the time of esophagectomy and enteral nutrition (EN) was initiated within 24 hours after surgery. Enteral nutrition was continued even if postoperative complications occurred, until patients could maintain adequate oral intake. Muscle mass was measured by cross sectional area (CSA) of psoas muscle of CT images at the level of the L3/4 intervartebral disk. The decrease rate of body weight (%BW) and cross sectional area of psoas muscle (%CSA) between pre-surgery and 3 months after surgery were calculated as follows: 100 x ([pre-surgery BW or CSA value] – [post-3 months BW or CSA value])/pre-surgery BW or CSA value. Patients were classified into those with postoperative complications (C group) and those without postoperative complications (N group). Data analyze included patient demographics, serum albumin at 3 months after surgery, duration using enteral nutrition, %BW, and %CSA, compared between C group and N group. Results: Postoperative complications occurred in 14 patients (C group: 14 patients, N group: 18 patients). No significant differences in age (median: 72.5 years old in C group, and 69.5 years old in N group, p = 0.536), serum albumin (3 months after surgery) (median: 3.75 mg/dl in C group and 4.05 mg/dl in N group, p = 0.054), and %BW (median: 8.5% in C group, and 9.1% in N group, p = 0.779) were observed between C group and N group. The duration using enteral nutrition was significantly longer in the C group than in the N group (median: 142 days in C group and 65 days in N group, p = 0.025). The %CSA was significantly higher in C group than in N group (median: 18.5% in C group and 3.9% in N group, p < 0.001). Discussion: The loss of muscle mass at 3 months after surgery could be influenced by postoperative complications while the body weight loss could not be influenced. The postoperative complications could leads to loss of muscle mass at 3 months after surgery, while body weight loss was not influenced by postoperative complications. The enteral nutrition could contribute to maintenance of body weight, while this could not decrease muscle wasting from influence of postoperative complications. Disclosure: All authors have declared no conflicts of interest. Keywords: complication, muscle wasting, esophagectomy, enteral nutrition

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P2.08.35: EXPERIENCE OF MINIMALLY INVASIVE IVOR LEWIS ESOPHAGECTOMY IN PRONE POSITION IN A TERTIARY CARE CENTRE Palanivelu Chinnusamy, Praveen Raj Palanivelu, Senthilnathan Palanisamy, R Parthasarathi, Anshuman Deo GEM Hospital & Research Centre, Coimbatore/INDIA Background: there is a gradual and sustained rise in the incidence of Adenocarcinoma esophagus in previously predominantly Squamous Cell Cancer regions of the world, probably reflecting the increasing incidence of Barrett’s metaplasia. Minimally invasive Ivor Lewis Esophagectomy is a viable option of giving a desired lymphnodal and tumour clearance with minimal morbidity. Methods: Between 2005 to 2013, 70 cases of Adenocarcinoma esophagus involving the lower esophagus and OG junction were operated using Minimally Invasive Ivor Lewis Esophagectomy with intrathoracic anastomosis. Data was collected and analyzed retrospectively. Surgical Technique-Mobilization of stomach and lower end of the esophagus with D2 lymphadenectomy and gastric tube formation. Gastric tube placed in right pleural cavity. Patient turned into semiprone position enbloc mbilisation of esophagus done upto upper mediastinum. Esophagus divided and pushed into the peritoneal cavity. Gastric tube anastomosed to the lower end of the esophagus either using handsewn end to end anastomosis or stapler assisted technique. Results: there were 42 males and 28 females. Median age was 65 years(range-37–80). Mean operating time was 3.5 hrs (3–4.5 hrs). Median blood loss 150 ml (100–500 ml),Median ICU Stay was 3 days(2–15days) and Hospital stay 8 days(7–24 days).One mortality was present in the perioperative period. Anastomosis leak rate was 4.2% (n = 3). Re exploration 2 cases and conversion to open 1 cases as there was suspicion of Aortic cross stapling. Nodal Harvest was 26(18–34). Discussion: With rise of Adenocarcinoma in the predominantly Squamous cell carcinoma regions, Lap Ivor Lewis gives good results in experienced hands. Disclosure: All authors have declared no conflicts of interest.

P2.08.34: THE QUALITY OF LIFE IN PATIENTS WITH DIFFERENT GASTRIC TUBE RECONSTRUCTION AFTER THREE-INCISION ESOPHAGECTOMY: RETROSTERNAL VERSUS PREVERTEBRAL Rujian Lu, Hongjun Chu, Hong Shen, Xiaojie Qi Nantong Third People’s Hospital, Nantong University, Nantong/CHINA Background: The types of gastric tube reconstruction are considered to have impact on the quality of life in patients after three-incision esophagectomy. This study was to compare the quality of life(QOL) in patients with retrosternal or prevertebral gastric tube reconstruction after three-incision esophagectomy. Methods: A total of 76 patients with esophageal squamous cell carcinoma who underwent three-incision esophagectomy from January 2010 to December 2012 were enrolled in this study. There were 40 patients in the retrosternal group and 36 in the prevertebral group. The EORTC questionnaire QLQ C-30 together with OES-18 were applied to evaluate the QOL of the patients before surgery and in the follow up (2nd, 4th, 12th, 24th and 48th week after operation). Results: No significant difference was observed between the two groups in demographics, operative time, blood loss and lymph nodes harvested. No 30-day mortality occurred in this series. And the total rate of complications were similar, except that more anastomotic leakage occurred in retrosternal group than prevertebral group (22.5% vs 8.3%, p = 0.091). The baseline QOL scores were similar before surgery. And in the 2nd week after operation, retrosternal group had higher score on eating problem(46.9 ± 27.0 vs. 32.7 ± 22.7, p = 0.015) and lower score global health status(38.9 ± 12.3 vs. 46.7 ± 13.4, p = 0.032). However, higher scores on global health status were discovered in retrosternal group than in prevertebral group in the 12th week (62.9 ± 13.3 vs. 56.7 ± 12.9, p = 0.043), 24th week (65.0 ± 13.5 vs.57.9 ± 12.9, p = 0.037), and 48th week (66.5 ± 13.1 vs. 58.5 ± 12.7, p = 0.034),after operation. And lower scores of dysponea and duodenogastric reflux were also founded in retrosternal group than in prevertebral group at the same time. Discussion: In the early stage after operation, QOL is worse in retrosternal group than in prevertebral group because of the higher risk of anastomotic leakage. Whereas in the long-term, QOL is better in retrosternal group in virtue of the less influence of respiratory function and duodenogastric reflux. However, further randomized controlled trials are required to confirm these findings. Disclosure: All authors have declared no conflicts of interest. Keywords: esophagectomy, gastric tube reconstruction, Quality of Life

Keywords: ivor lewis, Prone position, esophagectomy, Minimally Invasive P2.08.36: TRANSHIATAL CHEST DRAINAGE FOR MINIMALLY INVASIVE ESOPHAGECTOMY Kei Sakamoto1, Yosuke Izumi1, Tairo Ryotokuji2, Yuichiro Kume1, Akinori Miura1, Tsuyoshi Kato1 1 Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo/JAPAN, 2Tokyo Medical and Dental University, Tokyo/ JAPAN Background: Patients receiving esophagectomy often requires left chest tube drainage on postoperative days 3–4 due to pleural effusion in the contralateral thoracic cavity of the right transthoracic procedure. However, in such case, transthoracic intercostal drain placement is a standard practice, this chest tube placement cause pain and hamper mobility, sometimes causing pulmonary complications and delaying recovery. For patients receiving minimally invasive esophagectomy (MIE), additional drainage tube insertion after surgery sometimes ruin the advantage of MIE. We introduce a novel transhiatal drainage for postoperative left pleural effusion. Methods: From September 2005 to August 2012, 77 patients underwent MIE. We placed 28Fr intrercostal chest tube for right thoracic cavity and transhiatal silastic drainage tube for left thoracic cavity intraoperatively in 42 patients without left subphrenic abdominal drainage (Group A). We placed 28Fr intercostal chest tube for right thoracic cavity and left subphrenic drainage tube in the abdomen in 35 patients (Group B). Results: No patients in Group A developed clinically significant pleural effusion in the left thoracic cavity requiring further drainage. 25 patients (71%) in Group B required additional drainage in the left thoracic cavity. No complications, associated with transhiatal chest tube and no drainage tube for abdominal cavity, were noted in Group A. Discussion: Transhiatal chest tube drainage of the left thoracic cavity is an effective and safe method for MIE. Elimination of additional intervention after MIE will give patients not a little advantage for faster recovery after surgery. This technique can also be applied to open esophagectomy. Disclosure: All authors have declared no conflicts of interest. Keywords: transhiatal chest drainage, Minimally Invasive Esophagectomy

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P2.08.37: JEJUNAL/COLONIC CONDUIT AFTER MINIMALLY INVASIVE TOTAL GASTRECTOMY AND ESOPHAGECTOMY FOR ADVANCED CANCER Palanivelu Chinnusamy, Praveen Raj Palanivelu, Senthilnathan Palanisamy, Parthasarathi Ramakrishnan, Bansal Saurabh Surajbhan GEM Hospital & Research Centre, Coimbatore/INDIA Background: In patients with esophageal cancer involving major portion of the stomach or in cases of gastric cancer colonic or jejunal interposition is a viable option. Advantages of colonic conduit includes its long length, acid resistance and good blood supply. Disadvantages are increased operative time and an additional anastomosis which is prone for leakage. Methods: Between 2005–2013 we performed 12 interpositions (7 colonic & 5 jejunal) for esophageal reconstruction. Data was collected and analyzed retrospectively. Due to extensive involvement total gastrectomy was performed in continuity with the esophagus. Cranially the lower end of esophagus was mobilized well beyond the growth. Colon was placed in isoperistaltic fashion in 2 using right colon and reverse peristaltic fashion in 5 using left colon. These colonic conduits were placed in retrosternal position and anastomosis performed in the neck. In case of jejuna conduits, long limb of Roux en Y loop of jejunum was placed in the posterior mediastinum and intra thoracic anastomosis performed. Results: Colon was placed retrosternally in all cases of colonic conduit while jejunum was placed in the posterior mediastinum. In five cases, left colon and in two cases, right colon were used. We studied the patient demographics, ASA, Tumour grade & stage, other comorbidities, multivisceral resection. Early and late complications(wound infection, anastomosis leak, graft necrosis, stenosis) and survivability. Discussion: Colonic/jejunal interposition provides a valid option for esophageal replacement where gastric conduit is either not available or is not reaching the desired anastomosis site. Disclosure: All authors have declared no conflicts of interest. Keywords: minimally invasive, total gastrectomy, Jejunal conduit, colonic conduit P2.08.38: APPROPRIATE EXTENT OF ABDOMINAL LYMPHADENECTOMY FOR ADVANCED SIEWERT TYPE II ADENOCARCINOMA OF THE CARDIA FROM THE ASPECT OF ABDOMINAL NODAL SPREAD: A MULTICENTER RETROSPECTIVE STUDY Yutaka Kimura1, Kazumasa Fujitani2, Isao Miyashiro3, Shoki Mikata4, Shigeyuki Tamura5, Hiroshi Imamura6, Johji Hara7, Yukinori Kurokawa8, Jyunya Fujita9, Kazuhiro Nishikawa10, Shuji Takiguchi7, Masaki Mori7, Yuichiro Doki7 1 Sakai City Hospital, Sakai/JAPAN, 2Osaka General Medical Center, Osaka/JAPAN, 3Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka/JAPAN, 4Osaka Rosai Hospital, Sakai/JAPAN, 5Kansai Rosai Hospital, Amagasaki/JAPAN, 6Toyonaka Municipal Hospital, Toyonaka/JAPAN, 7Graduate School of Medicine, Osaka University, Suita/ JAPAN, 8Osaka University Graduate School, Osaka/JAPAN, 9NTT West Osaka Hospital, Osaka/JAPAN, 10Osaka National Hospital, Osaka/JAPAN Background: It is not apparent whether total gastrectomy with radical lymphadenectomy is required for survival benefit in Siewert type II adenocarcinoma of the cardia. In this study, we examined the pattern of abdominal nodal spread in type II adenocarcinoma of the cardia and defined the appropriate extent of abdominal lymphadenectomy for type II adenocarcinoma. Methods: Eighty-six patients who underwent curative total gastrectomy for advanced Siewert Type II adenocarcinoma were retrospectively identified on their pathological specimens and recruited into this study from nine hospitals. Abdominal nodal spread was examined for each lymph node station and overall survival (OS) was defined. Multivariate analysis was performed to identify prognostic factors. The therapeutic value of lymph node dissection for each station was estimated by multiplying the incidence of metastasis by the 5-year survival rate of patients with positive nodes in that station. Results: The 5-year OS was 37.1 % and median survival time (MST) was 1,210 days. Multivariate analysis confirmed the independent prognostic value of age less than 65 years [hazard ratio (HR), 0.455 (95 % confidence interval (CI), 0.261–0.793)] and nodal involvement with pN3 as referent [HR for pN0, 0.129 (95 % CI, 0.048–0.344); for pN1, 0.209 (95 % CI, 0.097– 0.448); and for pN2, 0.376 (95 % CI, 0.189–0.746)]. Estimated benefit from lymph node dissection in perigastric nodes of the lower half of the stomach (no. 4d, 5, 6) and splenic hilum node (no. 10) was very low. In contrast, substantially higher therapeutic value was observed in the perigastric nodes of the upper half of the stomach (no. 1, 2, 3) as well as in the second-tier nodes in positions 7 and 11. Discussion: From the results of our multicenter retrospective study, limited lymphadenectomy with proximal gastrectomy could be an alternative to


extended lymphadenectomy with total gastrectomy for obtaining the potential therapeutic benefit in abdominal lymphadenectomy for advanced Siewert type II adenocarcinoma of the cardia. Disclosure: All authors have declared no conflicts of interest. P2.08.39: MODERN RESULTS OF ESOPHAGECTOMY FOR ESOPHAGEAL CANCER: IMPACTS OF MULTIMODALITY TREATMENT AND MINIMALLY INVASIVE APPROACH Daniel Tong1, Claudia Wong1, Desmond Chan1, Tsz Ting Law2, Simon Law1 1 The University of Hong Kong, Hong Kong/HONG KONG, 2The University of Hong Kong, Queen Mary Hospital, Hong Kong/HONG KONG Background: Management strategies for esophageal cancer have evolved. The aims of this study are to investigate the oncological outcome and prognostic factors after esophagectomy in the modern era of neoadjuvant chemoradiation (CTRT) and minimally invasive esophagectomy (MIE). Methods: During 2000–2013, 409 patients with intra-thoracic squamous cell esophageal cancer underwent esophagectomy. Surgical outcomes and prognosis were evaluated. Results: The median age was 65 years (range 21–89), and 329 (80.4%) patients were men. CTRT was given to 214 (52.5%) patients, and 146 (35.9%) underwent MIE. Neoadjuvant CTRT was given to 94 (64.4%) patients in the MIE group and 120 (45.6%) in the open surgery group, (p = 0.001). Three patients died after surgery (0.7%). The median number of lymph nodes (LN) harvested was 32 (range 0–107). It was similar in patients with MIE or open approach. R0 resection rate was 81.3% in patients with CTRT and was 72.8% in those without (p = 0.027). MIE achieved a R0 rate of 82.8% vs. 74.1% in those with open approach, (p = 0.028). CTRT resulted in complete pathological response of the primary tumor in 40.7% of patients; and pCR in 28.9%. Five-year survival was 42.6% and median survival was 41.9 months. R0 resection had better survival than R1/2 resection, 62.3 m vs. 12.2 m, (p < 0.001). Patients with early stage diseases (pCR, ypT0N1, stage 0/I/II) fared better than those with advanced stages (pT0N2, pT0N3, stage III/IV), 81.1 m vs. 16.2 m, (p < 0.001). Median survival was 58.9 m for MIE and 34 m for open surgery respectively, 58.9 m vs. 34.0 m, (p = 0.079). Subgroup analysis showed that patients who had surgery without CTRT survived longer with MIE vs. open approach, 62.3 m vs. 23.5 m, (p = 0.009). pT stage, R category (R0 vs R1/2: HR = 2.16, p < 0.001) and pathological stage of disease (early vs. late: HR 1.81, p = 0.001) were significant prognostic factors on Cox regression analysis. Discussion: Modern multidisciplinary approaches achieve low mortality rate and good survival. MIE can have comparable oncological outcome as open esophagectomy. The main determinants of prognosis are R0 resection and stage of disease. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophagectomy for esophageal cancer, multimodality treatment, Modern results, Minimally invasive surgical approach P2.08.40: HYBRID TRANSHIATAL RADICAL ESOPHAGECTOMY WITH LYMPHADENECTOMY FOR THORACIC ESOPHAGEAL CANCER Yukinori Yamagata, Kazuhiko Mori, Susumu Aikou, Yasuyuki Seto The University of Tokyo Hospital, Tokyo/JAPAN Background: Radical esophagetomy has been a standard procedure for an invasive thoracic squamous cell carcinoma. However, it usually employs thoracic approach which is harmful to respiratory system and related to airway complications occasionally developing to lethal consequences. Moreover, due to the excessive aggression of the esophagectomy, reduction of food intake and malnutrition are frequently observed after surgery. We have developed techniques of transhiatal mediastinal lymph node dissection with multiple procedure by using direct approach, mediastinoscope, laparoscope and robotic surgical system. Methods: Our transhiatal procedure was combined with the preceding cervical and abdominal maneuver including lymph node dissections in the cervical, upper mediastinal field and abdominal fields. At first, we start cervical dissection under direct approach and abdominal dissection under laparoscopic approach. Subsequently we perform transhiatal mediatinal dissection by the robotic system. Results: We underwent 18 patients with thoracic esophageal cancer underwent these procedures.The mean age of the patients was 65.9 (range 46–82). 16 of 18 patients were male, and two were female. The average of the operative time was 541 minutes (range 445–724), and the average of the amount of bleeding was 402 ml (range 30–890). In all cases, there were no intraoperative accidents and no need for the intraoperative blood transfusion. Discussion: Our non thoracic approach was able to be carried out surely and safely. Our non-transthoracic surgery may have a potential to replace the conventional transthoracic esophagectomy.


ABSTRACT SUPPLEMENT

Disclosure: All authors have declared no conflicts of interest. Keywords: transhiatal approach, Hybrid surgery, robotic surgery

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cTNM-stage. A volume at surgical treatment may be pland by 3D-modeling of esophageal cancer process. Disclosure: All authors have declared no conflicts of interest.

P2.08.41: CLINICOPATHOLOGICAL CHARACTERISTICS OF SEVEN CASES OF ESOPHAGEAL CARCINOSARCOMA TREATED WITH SURGICAL RESECTION Ken Koseki, Toru Nakano, Takashi Kamei, Yohei Ozawa, Noriaki Ohuchi Tohoku University School of Medicine, Sendai City/JAPAN Background: Carcinosarcoma of the esophagus is a relatively rare histological type in esophageal malignancies. Methods: We clinicopathologically analyzed consecutive seven cases diagnosed with carcinosarcoma of the esophagus pathologically and treated by the surgical resection during 2000 and 2013. Results: All patients were male with an average age of 71 years old. The main tumor location in three cases was in the lower, two cases in the middle, one case in the upper third of the thoracic esophagus; the remaining one case in the abdomen. Macroscopic type of the tumor was 0-Ip in four out of the seven cases. Histological depth of tumor invasion was T1b in three cases, T2 in two cases and T3 in two cases. Five patients underwent both esophagectomy and total gastrectomy. Lymph node metastasis was found in 57.1% of them. On immunohistological studies, the tumor cells were G-CSF positive in two out of seven cases. Five of seven patients have been free from the disease and three of them survive more than 5 years. One patient died of cerebral hemorrhage on postoperative day 30. One patient experienced lung metastasis which required chemotherapy one year after the surgery. Discussion: It should be considered that the treatment with a focus on esophageal resection with lymphadenectomy and adding chemotherapy or radiotherapy as needed for carcinosarcoma of the esophagus. Disclosure: All authors have declared no conflicts of interest. Keywords: G-CSF, carcinosarcoma of esophagus, Surgery P2.08.42: POSSIBILITY OF 3D-MODELING IN PREOPERATIVE EVALUATION OF LOCAL PREVALENCE OF TUMOR AND REGIONAL LYMPH NODES METASTASIS OF ESOPHAGEAL CANCER Dmitry Rusanov, Konstantin Pavelets, Olga Vavilova, Maria Antipova State Pediatric Academy, Saint-Petersburg/RUSSIAN FEDERATION Background: In Russia, despite the success of diagnosis, esophageal cancer reveal in 80–90% cases at III-IV stage. Localized spread of tumor is failure course from surgical treatment. Some authors only to 10–15% patients considering a surgical and combind treatment. Late diagnosis of esophageal cancer depends from in sufficient implementation of medical visualization. Purpose: 1. To evaluate sensitivity of 3D-models in pre surgery TNM-stage. 2. To evaluate efficiency of 3D-models from position of multiprofessional approach to patients with esophageal cancer. Methods: n the bases of work experience of surgical treatment of 90 patients with esophageal cancer. At pre-surgery stage to 39 (43,3%) CT to 24 (26,7%) EUS to 20 (22,3%) CT with 3D-modeling, to 7 (7,7%) MRI with 3d-modeling were performed. 3D-model of esophageal cancer make by MRI/CT research data, formed to stl-files by computer program PowerShapeE. Integration EUS-graphics data into 3D-model of esophageal cancer produced by program Autodesk 3ds Max. surgical treatment were consist subtotal esophagectomy, cardiac part of stomach and extended two-zone lymph dissection D2F with ligation of thoracic duct. 3D-models data compared with interoperating finds and histological research. Sensitivity was calculated by four-squares tables method. Results: By 3D-modeling was evaluated tumor localization, tumor length, tumor spread to anatomical mediastinal structures, severity of abdominal and thoracic lymph nodes involving. This dates allowed to clinical TNM-stage. In most cases, by 3D-models and surgery finds marveled middle and lower esophagus. Tumor length from 5 sm. to 10 sm. at 20 (74% 0 cases by 3D-model and at 19 (70,4%) patients by surgery. Evaluate tumor spread to mediastinal structures at 18 patients (66,6%). IN 18 (88,9%) and 17 (62,9%) marveled para esophageal and para aortal cellule, in 4 (22,3%) by 3d-model and surgery we seen tumor spread to mediastenal pleura, tumor invasion to thoracic duct in 5 (22,8%) and 4 (22,3%) cases. Marvel of mediastinal lymph nodes consist at 26 (92,6%) and 26 (96,2%) patients, mediastinal and abdominal lymph nodes involved in tumor process at 18 (66,7%). By 3D-model no metastasis in lymph nodes at 2 (7%), confirmed at 1 by histological research. At cTNM-stage we seen localized primary tumors: T3N3 at 5 (18,5%): T4N1 at 7 (26,0%): T4N2 at 6 (22,2%). Sensitivity cTNM-stage consist 88,8%. Discussion: Method of computer 3D-modeling, based on CT/MRI with EUS-data integration is sensitively in evalition of localized spreading of esophageal tumor, and pre-surgery with sensitivity 88,8%, helps to clarity

Keyword: esophageal cancer, CT, TNM-stage, 3D-modeling P2.08.43: REASONS FOR INOPERABLE OESOPHAGEAL CANCER AT PLANNED CURATIVE SURGERY – CAN WE DO BETTER? Keng Ang, Rebekah Webb, Shereen Ajab, Aron Ciesla, Emmanuel Addae-Boateng, John Duffy Nottingham City Hospital Thoracic Surgery, Nottingham/UNITED KINGDOM Background: Current UK guidelines recommend the use of CT, with endoscopic ultrasound (EUS) or staging laparoscopy for the staging of oesophageal cancer before undergoing curative treatment. The addition of PET-CT in the staging process further increases the sensitivity of detection of regional and distal diseases. Despite these recommendations, we still encountered patients with inoperable oesophageal cancer at the time of planned curative surgery. Therefore, we investigate the reasons why patients were inoperable in our centre, and explore whether any of those can be identified preoperatively with a different strategy. Methods: We reviewed the prospective collected audit data and operation notes of patients undergoing oesophagectomy in our department since 2009, whereby PET CT was introduced in additional to CT, as well as laparoscopy or EUS for staging before curative treatment. In patients receiving neoadjuvant chemotherapy (usually < 75 years old), a further CT scan was normally performed at end of their therapy to confirm their suitability for curative resection. Results: From 2009 to April 2014, 268 planned curative oesophagectomies were attempted in our department. 26 patients (median[interquartile rang] age of 73[62–79]years old; 18male:8females) were found to have inoperable middle or lower oesophageal cancer at the time of surgery The surgical approach used was a thoracolaparotomy in 15 cases, Ivor Lewis in 8, left thoracotomy with phrenotomy 2 and hybrid approach in 1. Eleven patients were inoperable due to intra-abdominal spread of oesophageal cancer. Of these, 4 had their laparoscopy prior to chemotherapy and intra-abdominal spread might have been detected if staging laparoscopy were repeated before curative surgery. Six patients had vascular invasion of major thoracic vessels. Eight patients were inoperable due to either lung metastases or direct invasion into pulmonary structures. One patient was found to have a separate lung primary small cell cancer at the time of surgery. Amongst these patients with intrathoracic causes of inoperability, at least 5 could have been diagnosed with thoracoscopy. Discussion: Our results demonstrate there are still limitations in our current staging strategies in determining patient’s operative suitability. It is still unable to identify a small portion of patients with inoperable intra-abdominal or intrathoracic involvement. As almost a third of patients had intraabdominal involvement, there is a case to perform re-staging laparoscopy in this group of patients after their neo-adjuvant chemotherapy. Thoracoscopy assessment may also be useful before proceeding to definitive resection to assess lung and thoracic vascular involvement. Despite these measures, we may have to accept some patients will need exploratory surgery to be given a chance for curative surgery. Disclosure: All authors have declared no conflicts of interest. Keyword: Oesophageal surgery P2.09.01: CLINICAL SIGNIFICANCE OF EPIDERMAL DIFFERENTIATION COMPLEX GENE EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA Po-Kuei Hsu1, Hua-Ling Kao1, Hsuan-Yu Chen2, Yu-Chung Wu1, Teh-Ying Chou1 1 Taipei Veterans General Hospital, Taipei/TAIWAN, 2Academia Sinica, Taipei/TAIWAN Background: The epidermal differentiation complex (EDC) is a 2.5 Mbp region on chromosome 1q21 locus containing a high density of structurally and functionally related genes involved in terminal epidermal differentiation. The genes present in this region can be classified into three femilies: (1) the fused gene family; (2) the cornified envelope gene family; and (3) the S100 calcium binding gene family. Many EDC genes have been reported to be associated with esophageal squamous cell carcinoma (ESCC) tumorigenesis and aggressiveness. However, reports on the clinical implication of EDC genes expression in esophageal cancer are limited. In this study, we aim to (1) perform integrated microarray analysis and investigate the expression of EDC genes; (2) explore the clinicopathological relevance and prognostic significance of EDC gene expression, including CRNN, a member of the fused gene family and SPRR3, a member of the cornified envelop gene family, in ESCC.

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Methods: We performed integrated microarray analysis of four publicly available microarray dataset GSE5364, GSE20347, GS23400, and GSE29001. To explore the clinicopathological relevance and prognostic significance of EDC gene expression in ESCC, the protein expressions of CRNN and SPRR3 were evaluated by immunohistochemical staining in 220 ESCC formalin-fixed paraffin-embedded tissue.

P2.09.03: THE EXPRESSION OF PTEN AND LIVIN IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AND CLINICAL SIGNIFICANCE Shiying Zheng, Dong Jiang The First Affiliated Hospital of Soochow University, Suzhou/CHINA

Results: We first selected the top 50 genes in each dataset with the highest normal-to-tumor ratio. The members of the fused gene family, CRNN and FLG, were in the top genes lists of all four datasets. The member of the cornified envelope gene family, SPRR3, was in the lists of two datasets. We selected CRNN and SPRR3 for further protein expression evaluation.

Background: The occurrence and development of malignant tumor with not only the abnormal proliferation of tumor cells and differentiation, and inhibition of apoptosis, deficiency is also associated with cell apoptosis, research on genes related to apoptosis and tumor occurrence, evolution of in-depth understanding of cancer pathogenesis is very important, to open up a new approach to cancer treatment and improving the cure rate has important practical significance and broad prospects.PTEN gene is a tumor suppressor gene recognized, its mechanism of anti-tumor effect mainly by promoting apoptosis, is considered as a control gene of apoptosis.Livin gene is an apoptosis inhibiting gene discovered in recent years, not only has the function of inhibiting cell apoptosis, and the expression has obvious tissue specificity and expression, now most tumors, has close relationship with tumorigenesis.This experiment detected the expression and correlation of Livin protein and PTEN protein in esophageal carcinoma tissue, to study the occurrence, in the development of esophageal cancer significance.

Immunohistochemical staining revealed negative CRNN and SPRR3 expressions in 77% (171/220) and 48.1% (104/216) of patients with ESCC tumors, respectively. Compared to patients with positive expression, patients with negative CRNN protein expression were associated with advanced tumor invasion depth (p = 0.002), advanced nodal involvement (p = 0.014), and longer tumor length (p = 0.037). Patients with negative SPRR3 protein expression were also associated with longer tumor length (p = 0.031). In the survival analysis, patients with negative CRNN expression (median survival: 14.0 months, 5-year survival rate: 20.5%) had poorer overall survival than those with positive expression (30.0 months and 40.3%, p = 0.006). Patients with negative CRNN expression (median survival: 12.0 months, 5-year survival rate: 20.1%) also had poorer overall survival than those with positive expression (22.0 months and 29.2%, p = 0.032). In multivariate analysis incorporating age, sex, tumor length, TNM stage, CRNN expression and SPRR3 expression, negative CRNN expression, along with nodal involvement and distant metastasis, remained significant prognostic factors for poor overall survival (CRNN: negative vs. positive, HR: 1.541, p = 0.028). Discussion: Our analysis highlights the clinical implication of EDC gene expression in ESCC. Loss of CRNN expression correlated with advanced tumor length, tumor invasion depth, lymph node metastasis, and poor survival in patients with ESCC. Disclosure: All authors have declared no conflicts of interest. Keywords: immunohistochemistry, microarray, squamous cell carcinoma P2.09.02: ROLES OF E2F5 IN HUMAN ESOPHAGEAL SQUAMOUS CELL CARCINOMA Atsushi Shiozaki, Takeshi Ishimoto, Hitoshi Fujiwara, Hirotaka Konishi, Ryo Morimura, Yasutoshi Murayama, Shuhei Komatsu, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Masayoshi Nakanishi, Daisuke Ichikawa, Kazuma Okamoto, Chouhei Sakakura, Mitsuo Kishimoto, Eigo Otsuji Kyoto Prefectural University of Medicine, Kyoto/JAPAN Background: The E2 promotor binding factor (E2F) family, which is a group of transcription factors involved in the regulation of cellular proliferation, consists of eight members. Although E2F5 is considered to act primarily as a transcriptional repressor in the cell cycle, its expression and role in esophageal squamous cell carcinoma (ESCC) have not been investigated. We examined whether the expression of E2F5 is related to the clinicopathological features and prognosis of patients with ESCC. Methods: The expression of E2F5 was analyzed by immunohistochemistry in 64 primary tumor samples obtained from patients with ESCC who had undergone esophagectomy. The total score was calculated by adding the intensity and proportion scores of each case (mean ± SD = 3.11 ± 1.18). Total scores of 4 or more were defined as the E2F5-positive group (27 cases) and scores of 3 or less were defined as the E2F5-negative group (37 cases). The relationship of various clinicopathological features and prognosis with E2F5 status were analyzed. Results: In the clinicopathological analysis, the proportion of poorly differentiated tumors was significantly higher in the E2F5-positive group than in the E2F5-negative group (p = 0.027). There were no significant differences in Ki-67 labeling index by E2F5 status. The 5-year survival rate of the E2F5positive group was 39.3%, which was significantly poorer than that of the E2F5-negative group (83.8%) (p = 0.006). In multivariate analysis, the expression of E2F5 was the strongest prognostic factor of all clinicopathological features after esophagectomy. Discussion: The expression of E2F5 in the cytoplasm was correlated with the histological grade of ESCC, and was one of the most significant prognostic factors. The expression of E2F5 may be an indicator of poor clinical outcome after esophagectomy and a novel therapeutic target for the future treatment of ESCC. Disclosure: All authors have declared no conflicts of interest. Keywords: E2 promotor binding factor, Esophageal squamous cell carcinoma

Methods: A, Selected specimens of esophageal carcinoma in 60 patients.The pathology slice after operation for esophageal squamous cell carcinoma were confirmed. 10 cases of normal esophageal tissues as control tissues.Every specimen paraffin serial sections of 2, respectively, PTEN and livin immunohistochemical staining, the expression of SP was used to detect the PTEN and livin.Two, result Standard Livin protein positive reaction to light yellow to brown granules, mainly located in the cytoplasm; PTEN protein positive reaction to yellow to brown granules in the cytoplasm. Three, statistics SPSS12.0 software was used for statistical analysis.The case group and control group PTEN and livin by X2 test. P < 0.05 has statistical significance. Results: 1, the positive expression of Livin protein in esophageal carcinoma tissues was significantly higher than that of normal esophageal tissues: the positive rate of Livin protein expression and TNM stage and lymph node metastasis of esophageal cancer patients, regardless of age, degree of differentiation. 2, PTEN protein in esophageal normal tissues was significantly higher than expression in esophageal cancer tissues; the degree of differentiation and lymph node positive expression rate of PTEN protein and esophageal carcinoma metastasis, and age and TNM in patients with esophageal cancer staging were independent. 3, in esophageal cancer, the positive expression of Livin protein and PTEN protein expression rate were negatively correlated. Discussion: 1, the high level expression of Livin protein in esophageal carcinoma, while no expression in normal esophageal tissues.Livin protein expression in esophageal carcinoma and TNM staging and lymph node metastasis are closely related, prompt development of Livin may be associated with esophageal cancer and malignant potential of the. 2, significantly decreased in the positive expression in esophageal carcinoma, and is associated with esophageal cancer differentiation degree and lymph node metastasis, suggesting loss of PTEN expression plays an important role in the occurrence and development of esophageal carcinoma. 3, upregulation of Livin expression may inhibit the activity of PTEN, PTEN protein deletion may promote the expression of Livin protein, two are involved in the occurrence and development of esophageal carcinoma. Disclosure: All authors have declared no conflicts of interest. Keywords: PTEN gene, livin gene, Esophageal squamous cell carcinoma P2.09.04: THE FUNCTIONAL SNP RS3746804 IN C20ORF54 MODIFIES SUSCEPTIBILITY TO ESOPHAGEAL SQUAMOUS CELL CARCINOMA Ai Ji1, Liang Ma2, Wu Wei2 1 Changzhi Medical College, Changzhi Shanxi/CHINA, 2Changzhi Medical College, Changzhi Shanxi/CHINA Background: In 2010, by genome-wide association study (GWAS) of 25,000 patients for the susceptibility loci to esophageal squamous cell carcinoma (ESCC) and health controls, we firstly identified C20orf54 as one of the susceptibility loci to ESCC[1].C20orf54, known as human riboflavin transporter 2, has a messenger RNA (mRNA) that includes 2716 bp (NM_033409.3) and encodes an open reading frame protein which contains 469 amino acids. We have detected and compared plasma concentrations of riboflavin in patients with esophageal squamous cell carcinoma (ESCC) Changzhi, health controls and immigrants of Linzhou living in Changzhi from our former study. The results showed the plasma riboflavin levels in patients with ESCC were significantly lower than those in the healthy controls and immigrants of Linzhou living in Changzhi. The aim of present study was to explore the C20orf54 functional SNP (Single Nucleotide Polymorphism) 1139C > T with the susceptibility to ESCC in ESCC patients in Changzhi and Linzhou, health controls in Changzhi and Linzhou and immigrants of Linzhou living in Changzhi.


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Methods: Genomic DNA Purified by using the Maxwell® 16 System. Rs3746804 in C20orf54 was detected by direct sequencing in 434 ESCC patients (include Shanxi and Henan cancer patients) and 554 healthy controls. Results: For rs3746804 gene, CT, CC genotype show significant difference among Shanxi ESCC patients, Shanxi healthy controls and some people emigrating from Linzhou to Changzhi (P < 0.05). Comparing with ESCC patients inLinzhou, TT, CC genotype show significant difference (P < 0.05). TT, CTand CC genotypes show significant difference between ESCC patients in Linzhou and some people emigrating from Linzhou to Changzhi (P < 0.05). Comparing with shanxi healthy controls, TT, CC genotype show significant difference (P < 0.01). Meanwhile, there exists significant difference between ESCC patients in Changzhi and Linzhou and healthy controls in Changzhi, Linzhou and people emigrating from Linzhou in CTand CC genotypes (P < 0.01). CT and CT + TT genotype significantly decreased the risk of ESCC compared with the CC genotype. Discussion: Here is closed connection between functional SNP rs3746804 in C20orf54 and susceptibility to esophageal squamous cell carcinoma. Disclosure: All authors have declared no conflicts of interest.

P2.10.01: EFFICACY OF DOCETAXEL, CISPLATIN AND 5-FLUOROURACIL CHEMOTHERAPY FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA Yutaka Miyawaki1, Yasuaki Nakajima2, Kenro Kawada1, Masafumi Okuda1, Taichi Ogo1, Katsumasa Saito1, Hisashi Fujiwara1, Naoto Fujiwara1, Tairou Ryoutokuji1, Takuya Okada1, Yutaka Tokairin1, Kagami Nagai1, Tatsuyuki Kawano1 1 Tokyo Medical and Dental University, Tokyo/JAPAN, 2Medical and Dental University, Tokyo/JAPAN Background: Currently, the anticancer efficacy of Docetaxel, Cisplatin and 5-fluorouracil chemotherapy (DCF) for advanced or relapsed esophageal squamous cell carcinoma (ESCC) has been reported as better than one of conventional regimens and it may be a standard therapy for advanced or relapsed ESCC. Nowadays, endoscopic resection such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), esophagectomy or chemoradiotherapy is usual selected as the therapy for superficial ESCC (sESCC) according to invasion depth, extent and ratio among lumina of tumor. Because it is extremely rare that chemotherapy is administered as treatment for sESCC alone, the effectiveness of DCF for sESCC is still unknown. However it seemed that the investigation of the anticancer efficacy of chemotherapy for early caner is significant from the clinical oncological standpoin and useful to understand treatment resistance in cancer development. It is a well-known fact that the patient with squamous cell carcinoma of the head and neck region including pharynx and larynx (HNSCC) has a high risk of synchronous and metachronous ESCC, attributed to the histological similarity, anatomical sequentiality and the presence of common risk factors. Esophagogastroduodenoscopy (EGD) is performed on a screening purpose, before the therapy for HNSCC is begun at our institution. When a synchronism sESCC coexisting for advanced HNSCC is detected by EGD, the therapy for HNSCC is given priority to. At the department of head and neck surgery in our institution, DCF is one of standard therapies for HNSCC as induction chemotherapy or chemotherapy combination together with radiation, so we experienced some such cases. Methods: This retrospective single-center analysis included 28 patients with sESCC who had received DCF for synchronous HNSCC from June 2007 to July 2013. Results: DCF was administered as induction chemotherapy and/or chemotherapy combination together with radiation. 15 of 28 patients were received DCF of three courses in total which consisted of induction DCF of one course and subsequent chemotherapy combination together with radiation of two courses. 17 patients (60.7%) achieved complete response (CR), 10 patients (35.7%) had incomplete response/stable disease (IR/SD) and one patient (3.6%) showed progressive disease (PD). The response rate was 60.7%. In 12 of 17 patients who had been judged CR, recurrence was confirmed eventually by follow-up EGD. The median RFS period were 5.8 months. The correlation between the clinical tumor depth before DCF therapy or the times of DCF therapy and the best overall response were not significant. Discussion: In a point of the response rate or the median RFS, our result turned out approximately similar to previous reports for advanced or relapsed esophageal cancer. It seemed that this result supports that the anticancer efficacy of chemotherapy is not depend on the volume of tumor but the drug sensitivity of the individual. This result suggests that treatment resistance is obtained also in early cancer like advanced cancer. Disclosure: All authors have declared no conflicts of interest. Keywords: chemotherapy, retrospective study, superficial cancer

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P2.10.02: DOUBLE-CHANNEL ESD METHOD USING EEMR-TUBE FOR SUPERFICIAL ESOPHAGEAL CARCINOMA: ITS TECHNICAL ADVANTAGEOUSNESS AND TREATMENT OUTCOMES Osamu Chino1, Hideo Shimada2, Tomoki Nakamura1, Yoichi Tanaka1, Masahiko Takechi1, Eisuke Ito3, Akihito Kazuno3, Kenichi Kamachi3, Soji Ozawa3, Seiei Yasuda3, Yasumasa Kondo1, Hiroyasu Makuuchi1 1 Tokai University School of Medicine, Tokyo Hospital, Tokyo/JAPAN, 2 Tokai University School of Medicine, Oiso Hospital, Kanagawa/JAPAN, 3 Tokai University School of Medicine, Kanagawa/JAPAN Background: Endoscopic submucosal dissection (ESD) has been performed to treat superficial esophageal cancers. However, it is difficult to secure a good endoscopic view for submucosal dissection. The technique of esophageal ESD requires considerable skill. We have developed a double channel ESD method using endoscopic esophageal mucosal resection (EEMR) tube (Create Medic. Tokyo, Japan) for safe esophageal ESD with a good field of view. The stable field of view of the esophageal ESD layer is able to expose constantly, and it is easy to handle blood vessels. We report the treatment outcome and its technical advantageousness. Methods: Between February 2010 and December 2013, we performed 104 cases of esophgeal ESD with double-channel ESD method using EEMRtube for esophageal cancer. Countertraction is achieved by maneuvering a fine W-shaped grasping forceps (FG-41-1; Olympus Optical) inserted through the side channel of the EEMR tube. We analyzed the 104 cases of superficial esophageal carcinoma resected by ESD clinicopathologically, and report treatment outcome of the ESD cases. Results: 104 lesions in 92 patient (78 males and 14 female) were included in the ESD. The patients ranged in age from 46 to 85 years, with a mean age 68 years. Location of the lesion; Ce : Ut : Mt : Lt : Ae = 7:11:63:20:3, tumor types of endoscopic classification; 0-IIa:0-IIb:0-IIc:0-I = 12:17:69:6, tumor size ranged from 5 mm to 70 mm, with a mean size 24.3 mm. 89 cases of ESD were performed under general anesthesia with intubation in the operation room, and the others were performed with sedation in the endoscopic room. We use short type of clutch cutter (Fujifilm) in all cases. Pathological findings of the ESD specimens as below; SCC: adenocarcinoma = 101:3, T1a-E P : T1a-LPM : T1a-MM : SM1 : SM2 : SM3 = 34:44:11:6:9:0 (accuracy rete of depth 89.4%). Ratio of en bloc resection 100%, Ratio of pathological complete resection 96.2%. Complication; post ESD bleeding 0%, perforation 1 case (0.9%), fibrotic stricture 3 cases (2.9%). There has been no local recurrence and metastasis yet. Discussion: We performed ESD with double-channel ESD method using EEMR-tube for esophageal cancer. It was possible to do the procedure safely without severe complications. This method is expected to shorten the ESD time and avoid complications because of good stable field of view in the esophageal submucosal layer under countertraction. The technique of double-channel ESD method using EEMR-tube is advantageous to safe procedure of esophageal ESD. Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal carcinoma, ESD, double-channel ESD method, EEMR-tube

P2.10.03: FEASIBILITY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL SQUAMOUS ESOPHAGEAL NEOPLASM (SSEN) IN KOREA Jeonguk Lim, Byung-Wook Kim The Catholic University of Korea, Incheon/KOREA Background: Endoscopic submucosal dissection (ESD) is a potential alternative in the treatment of superficial squamous esophageal neoplasms (SSEN). However, there has been no report on the outcomes of ESD for SSEN in Korea. The aim of this study was to evaluate the long-term outcomes of ESD for SSEN in Korea. Methods: A retrospective analysis of all patients with SSEN (dysplasia and noninvasive carcinoma or intramucosal carcinoma) resected with ESD method between January 2005 and December 2011 was carried out. Clinical and pathologic outcomes were analyzed. Results: ESD was performed in 29 patients. En bloc resection was performed in 26 patients (89.7%) and complete resection was achieved pathologically in 27 patients (93.1%). There was no patient who required transfusion due to bleeding. Pneumonediastinum was developed in one patient (3.4%). There was no procedure-related mortality in the entire series. Discussion: ESD can be accepted as a treatment modality for the treatment of SSEN in Korea. Disclosure: All authors have declared no conflicts of interest. Keywords: superficial squamous esophageal neoplasm, endoscopic submucosal dissection

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P2.10.04: CASE REPORT: ESPINOCELULAR CARCINOMA ARISING IN A PHARYNGEAL POUCH (ZENKER’S DIVERTICULUM) Sergio Szachnowicz, Rubens Sallum, Francisco Seguro, Henrique Joaquim, Edno Bianchi University of Sao Paulo, Sao Paulo SP/BRAZIL Background: Pharyngeal pouch (Zenker’s diverticulum) is a rare condition, with a prevalence of 0.06% to 3.6% in the general population, with a higher incidence in elderly. There is risk of malignancy due to chronic irritation of mucosa by food, inflammation and repeated injury. This risk is estimated to be around 1.1%. Preoperative diagnosis of a carcinoma in an esophageal diverticulum may be difficult, as symptoms may mimic those of the diverticulum or underlying motor disorder. Most patients with cancer in pharyngeal pouch should be managed in a manner similar to that for patients with ordinary cervical esophageal malignancy. However, when the tumor is well localized without full-thickness penetration, nodal metastasis, or extension to the line of resection, diverticulectomy alone can provide satisfactory control of cancer with minimal therapeutic risk. Methods: Case Report: a 74 year male, presenting with dysphasia in the last two years associated with a 20 Kg weight loss (20% of body weight), underwent an upper endoscopy, showing a pharyngeal pouch of 5 cm with food retention and no apparent mucosal injury. The patient also had a contrasted esophagogram, that found a pharyngoesophageal diverticulum of 10 cm, with normal mucosal aspect. The patient was submitted to a left cervicotomy, with diverticulectomy with stapler and cricomyotomy. There was no post operative complication and the patient started oral ingestion 7 days after surgery. Results: Histopathological study described a superficially invasive espinocelular carcinoma without perineural and angiolymphatic invasion. No further adjuvant therapy was made, once the finding was a very early cancer. The patient will be followed, with periodical CT scans and endoscopies. Discussion: The finding of cancer in a pharyngeal pouch is a very rare condition. In early stage tumors, with no deep invasion of the diverticulum wall and no signs of dissemination, diverticulectomy alone may be a reasonable option. Disclosure: All authors have declared no conflicts of interest. Keywords: Zenker diverticulum, Esophageal cancer, treatment P2.10.05: BARRETT’S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA. A SINGLE CENTER EXPERIENCE AND CHANGES OF MANAGEMENT Emanuele Russo1, Fabrizio Cereatti2, Pietro Bruschini1, Paolo Trentino2, Tiziano De Giacomo1, Giulia D’Amati2, Federico Venuta1, Federico Francioni1 1 University of Rome “Sapienza”, Rome/ITALY, 2University of Rome “Sapienza”, Rome/ITALY Background: In the west countries dramatically icreased the incidence of the adenocarcinoma of the esophagus, related with the mayor number of cases of barrett esophagus diagnosed with an increasing of the reflux symptoms. Methods: Between January 2000 to December 2012 4937 patients underwent esophageal examinations for gastro esophageal reflux to identify Barrett’s Esophagus (BE) and Adenocarcinoma (AC) in non symptomatic patients, this study doesn’t include the patients in whom the endoscopy has been performed for the suspect of neoplasia or with dysphagia. The treatment of BE, from 2000 until 2007 was conservative for the non dysplastic or low grade dysplasia patient with a strict follow up and an associated medical treatment with PPI, while the approach for the high grade dysplasia was aggressive with an esophagectomy; from the beginning of 2008 was started the radio frequency ablation for all dysplasia (either low or high grade), as well as the non dysplastic lesions not responding after one year of treatment with PPI. For the adenocarcinoma group until 2007 the radical surgery (either minimally invasive or open) has been performed in all cases (independently from the stage); from 2008 for the early stage of adenocarcinoma endoscopic approach such as a mucosectomy if the tumour doesn’t go beyond the muscolaris mucosa; if the sub mucosa looked histologically infiltrated was needed an endoscopic submucosal dissection. Just in case of demonstrated invasion of the cancer beyond the submucosa a radical esophagectomy was performed. Results: Barrett esophagus (BE) was identified in 279 cases (5,7%) and in 63 patients (1,3%) an adenocarcinoma of the esophagus was founded. Histology showed in the BE patients a non dysplastic lesion in 171 cases (61%), low grade dysplasia in 88 (32%) and in 20 cases (7%) was observed an high grade dysplasia lesion. The stage of the AC patients was T1 in 17 (27%), T2 in 40 (64%) and T3 in 6 (9%); 19 (31%) of them were staged N positive. No post operative mortality has been registered, in one case was reported a post anastomosis fistula, the number of paralysis of the inferior laryngeal nerve was more than 11%. The long term survival at 5 year has been of the


sixty-eight per cent, the mortality in case of lymph node metastasis in this group of patient increase dramatically after five years. Discussion: Comparison of survival between this group and all esophageal carcinoma of the same Hospital in the same range of time evidenced a better prognosis, probably related also with the early diagnosis of this cohort. Every patient with symptoms of gastro esophageal reflux might have an EGDS at least once in the life. About the endoscopic approach, further randomized studies are necessary. The endoscopic treatment doesn’t change the survival, it’s mandatory an accurate pre operative staging. This also reduces the in hospital stay without losing the radicality. About surgery, is still the first therapeutic option for T2 and T3, narrow gastric tube is the best option for esophageal reconstruction. Minimally invasive approach does not change survival but improves post operative course Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal adenocarcinoma, Barrett’s Esophagus, minimally invasive surgery, endoscopic resection P2.11.01: PROGNOSTIC IMPACT OF NEUTROPENIA AND HISTOLOGICAL RESPONSE TO NEO-ADJUVANT CHEMOTHERAPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA Hirotaka Konishi, Hitoshi Fujiwara, Atsushi Shiozaki, Hidekazu Hiramoto, Shuhei Komatsu, Takeshi Kubota, Daisuke Ichikawa, Kazuma Okamoto, Chouhei Sakakura, Eigo Otsuji Kyoto Prefectural University of Medicine, Kyoto/JAPAN Background: The standard therapeutic strategy for clinical Stage II/III esophageal squamous cell carcinoma (ESCC) in Japan is neo-adjuvant chemotherapy (NAC) followed by radical esophagectomy. Although adverse events or histological response are considered to be a predictor of the chemotherapeutic effect, this has yet to be confused. Methods: We analyzed 122 patients with clinical Stage II/III ESCC who received NAC and underwent radical esophagectomy in Kyoto Prefectural University of Medicine. All adverse events in 58 patients who received NAC at our hospital and neutropenia in all patients were recorded. The impact of neutropenia and histological responses on the clinicopathological features and prognoses was investigated. All patients were diagnosed with their progression of stage on the basis of the criteria of the Japanese Classification of Esophageal Cancer tenth edition and the tumor-node-metastasis classification of the International Union Against Cancer seventh edition (UICC) Results: Grade3/4 neutropenia was a major adverse event in 58 patients (37.9%) who received NAC at our hospital, and of all patients, neutropenia was observed in 58% (71/122) and Grade 3/4 was in 31% (38/122). We focused on neutropenia because it is major grade 3/4 adverse event. Grade 3/4 neutropenia correlated with only high grade histological response (p = 0.01) in some clinicopathological features. Univariate and multivariate analyses revealed poorly differentiation, negative venous invasion, and Grade 3/4 neutropenia were independent predictors of a high grade histological response (p = 0.02, 0.04 and 1 cm (SPR3). Results: Pathologists agreed to the reference in the definition of TRG class with a median of 49% (37–87%), while SPR median was higher, reaching 81% (62–100%). Discussion: Every classification of pathological response to treatment is good in defining the extremes, i.e. complete responders and patients with huge residual cancer. The main argue is about partial responders, which actually are the main target of surgery, where surgery plays the most relevant role. We previously used SPR and TRG in a single high-volume center with dedicated pathologists and SPR resulted more objective and easy to perform and interpret. We here tested the agreement of these classifications with difficult cases and non-dedicated pathologists. TRG classification was highly variable, with all but one cases where only 37–62% of the pathologists agreed. Pathologists agreed more frequently with SPR, where the median agreement was 81%. No classification is perfect, but an agreement for SPR of more than 80% by non-dedicated pathologists in difficult cases of patients with partial response is encouraging. A questionnaire with more cases to be sent to more pathologists is mandatory, but SPR seems to be a good tool in the definition of response to induction treatment with good inter-observer agreement. Disclosure: All authors have declared no conflicts of interest. Keywords: SPR classification, Mandard TRG, Pathology


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P2.14.08: EXPRESSION OF NQO1 IN ESOPHAGEAL CANCER CELLS AFTER NEOADJUVANT CHEMOTHERAPY Takashi Ishikawa1, Shin-Ichi Kosugi1, Hiroshi Ichikawa1, Takaaki Hanyu1, Tsutomu Suzuki2, Toshifumi Wakai1 1 Niigata University Graduate School of Medical and Dental Sciences, Niigata/JAPAN, 2Niigata University Graduate School of Health Sciences, Niigata/JAPAN Background: NAD(P)H: quinone oxidoreductase 1 (NQO1), one of the antioxidant proteins, has been suggested to be involved in malignant tumors’ resistance to chemotherapy. We report the relationship between cancer recurrence and NQO1 expression in the primary tumor tissue of esophageal cancer patients who underwent surgery after neoadjuvant chemotherapy. Methods: Between January 2001 and December 2012, 41 patients with advanced esophageal squamous cell carcinoma underwent radical resection of the esophagus after neoadjuvant chemotherapy. All patients received one or two courses of combination chemotherapy with 5-fluorouracil and cisplatin in the neoadjuvant setting. We evaluated the NQO1 expression in tumor tissues of 38 patients (three patients achieved pathological complete response and were not studied) by immunohistochemical staining using formalinfixed paraffin-embedded blocks. For each specimen, we first assigned a proportion score that represented the estimated proportion of positivestaining tumor cells (0, none; 1, 1%–20%; 2, 21%–80%; and 3, 81%–100%). Next, an intensity score was assigned to represent the average intensity of the positive tumor cells (0, none; 1, weak; 2, intermediate; and 3, strong). The proportion and intensity scores were then multiplied to obtain an NQO1 expression score (range 0 to 9); positive NQO1 expression was defined as a score of 3 or higher. The relationships between cancer recurrence and NQO1 expression and other clinicopathological factors were examined statistically. Results: For the 38 patients, the two-year recurrence-free survival rate was 56.0% and the two-year overall survival rate was 68.1%. Twenty-three patients (60.5%) showed positive NQO1 expression. The two-year recurrence-free survival rate of the NQO1-positive group was 47.8%, which was significantly worse compared to the 78.3% of the NQO1-negative group (P = 0.04). We also found that the pathological therapeutic effect was a significant risk factor for cancer recurrence. In a multivariate analysis, only NQO1 positivity was found to be an independent risk factor (hazard ratio = 3.88, 95% confidence interval = 1.10–13.69, P = 0.04). Discussion: NQO1 expression in tumor cells may be involved in the chemoresistance of esophageal carcinoma, since recurrence was common in the early postoperative period in the NPQ1-positive group. NQO1 is a promising biomarker protein for the prediction of the therapeutic effect of neoadjuvant chemotherapy, and further studies should be conducted to test the utility of its expression in biopsy specimens before treatment. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, neoadjuvant chemotherapy, chemoresistancy, NQO1

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surgery. In Group B, seven patients showed an improvement in albumin level and three patients displayed increased body weight preoperatively. Neoadjuvant chemotherapy was performed for two patients in Group A and five patients in Group B. Albumin level improved in almost all patients following enteral nutrition using PEG. Moreover, many patients in Group B had received neoadjuvant chemotherapy, and the sufficient nutritional support provided using PEG enhanced the effects of chemotherapy. Furthermore, for the all patients who were provided sufficient preoperative treatment, radical resections of esophageal cancer were performed. Discussion: Preoperative nutritional support using PEG is useful for the patients with advanced esophageal cancer or the patients with severe comorbidities. In particular, in patients who have difficulty with ingestion due to localized highly advanced cancer, active use of PEG, combined with both neoadjuvant chemotherapy and nutritional support, may lead to improved outcomes in cancer therapy. Disclosure: All authors have declared no conflicts of interest. Keywords: esophegeal cancer, nutrition P2.14.10: EVALUATING THE SYNCHRONOUS ESOPHAGEAL CANCER IN HEAD AND NECK CANCER PATIENTS USING LUGOL DYE CHROMOENDOSCOPY Somkiat Sunpaweravong, Supparerk Laohawiriyakamol, Vitoon Leelamanit, Kowit Pruegsanusak, Wattana Sinkijcharoenchai Prince of Songkla University Hospital, Hat Yai, Songkla/THAILAND Background: Routine screening for esophageal cancer in head and neck patients in Thailand is controversial because of concerns regarding the screening methods and cost effectiveness. Since Lugol dye chromoendoscopy is an effective technique for early detection of squamous cell carcinoma of the esophagus, the objectives of this study are to evaluate the synchronous esophageal cancer in head and neck cancer patients and the effectiveness of Lugol dye chromoendoscopy for routine screening. Methods: All newly diagnosed patients with head and neck cancer from 1 September 2011 to 30 June 2013 were recruited into the study. Both conventional esophagoscopy and Lugol dye chromoendoscopy were done by one endoscopist. The incidence of esophageal cancer was calculated. A statistical analysis was done to compare conventional esophagoscopy with Lugol dye chromoendoscopy and the risk factors that increased the likelihood of synchronous esophageal cancer. Results: There were 89 head and neck cancer patients in this study. The incidence of esophageal cancer in head and neck cancer patients was 12.4% (11/89). Conventional esophagoscopy found a highly suspicious malignant lesion in only 6 patients, while the Lugol dye chromoendoscopy detected all 11 esophageal cancers. The 3 significant factors that increased the likelihood of synchronous esophageal cancer were age less than 50 years, presence of dysphagia, and an unstained Lugol dye area ≥ 10 mm.

P2.14.09: CURRENT CONDITION PREOPERATIVE NUTRITIONAL SUPPORT FOR PATIENTS WITH ESOPHAGEAL CANCER USING PERCUTANEOUS ENDOSCOPIC GASTROSTOMY Shunsuke Tanabe, Yasuhiro Shirakawa, Naoaki Maeda, Kazuhiro Noma, Toshiyoshi Fujiwara Okayama University, Okayama/JAPAN Background: Many patients with advanced esophageal cancer develop malnutrition due to dysphagia resulting from stenosis caused by the tumor. While these patients were previously primarily treated using nasogastric feeding, nutritional management was sometimes hindered by pain, difficulties in management of the nutritional route, and other issues associated with the method. To avoid these issues, we are currently actively implementing percutaneous endoscopic gastrostomy(PEG). We report herein the actual condition of esophageal cancer patients who underwent PEG placement at our hospital. Methods: Among the 26 esophageal cancer patients who underwent PEG placement between April 2010 and October 2012, the utility of preoperative PEG placement was investigated in 14 patients who underwent surgery, including examination of albumin level, body weight, and complications. Results: The breakdown of the 26 esophageal cancer patients who underwent PEG placement was as follows. Twelve patients underwent PEG placement due to far advanced cancer that was inoperable; six patients with severe comorbidities underwent PEG placement for nutritional purposes during the period from esophagectomy to digestive tract reconstruction for the two-stage surgery (Group A); and the remaining eight patients were unable to ingest food and underwent PEG placement with the objective of improving preoperative nutritional status before undergoing surgery (Group B). In Group A, three patients showed improved albumin levels and one patient had an increase in body weight before the second stage of the two-stage

Figure 1. The conventional esophagoscopy showed normal esophageal mucosa.

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(p = 0.007). The rate of postoperative complication was significantly lower in women (28.6%) than in men (52.8%) (p = 0.015). The overall survival was significantly better in women than in men (p = 0.045). The 5-year overall survival rates were 46.2% in men and 76.7% in women. A multivariate analysis revealed gender (HR:0.097, p = 0.002) and T factor (HR:0.394, p = 0.036) to be an independent prognostic factor. Discussion: Present study showed gender differences in degree of exposure with carcinogen such as cigarette and alcohol. This might bring gender difference in mortality and morbidity after esophagectomy. Expression of p53 protein is caused by genetic mutation of p53 gene. It also was known as a useful biomarker to predict tolerance of chemotherapy and prognosis for some cancer. Present study suggested women have more sensitivity to the chemotherapy than men. Furthermore, this advantage may lead better prognosis to women with esophageal squamous cell carcinoma. Disclosure: All authors have declared no conflicts of interest. Keywords: Esohageal cancer, p53 protein expession, chemotherapy tolerance, Gender differences P2.14.12: LYMPHOVASCULAR INVASION IS A SIGNIFICANT PROGNOSTICATOR IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PATIENTS WHO RECEIVE PREOPERATIVE CHEMORADIOTHERAPY Yin Kai Chao Chang Gung Memorial Hospital, Taoyuan/TAIWAN

Figure 2. Lugol dye chromoendoscopy in the same patient showed many unstained areas with the largest one was at the abnormal mucosa area, histopathology found squamous cell carcinoma.

Discussion: Because of the high prevalence of synchronous esophageal cancer in head and neck cancer patients and the higher sensitivity of Lugol dye chromoendoscopy than conventional esophagoscopy; we recommend a routine esophagoscopy with Lugol dye chromoendoscopy screening in head and neck cancer patients. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, Head and neck cancer, Lugol dye chromoendoscopy, screening P2.14.11: GENDER DIFFERENCES IN CLINICOPATHOLOGIC FEATURES AND OUTCOMES OF ESOPHAGEAL CANCER PATIENTS Takeshi Nishino, Takahiro Yoshida, Yoshihito Furukita, Hirokazu Takechi, Yota Yamamoto, Yasuhiro Yuasa, Masakazu Goto, Takuya Minato, Seiya Inoue, Satoshi Fujiwara, Toru Sawada, Naoya Kawakita, Hiromichi Yamai, Junichi Seike, Takanori Miyoshi, Akira Tangoku University of Tokushima Graduate School, Tokushima/JAPAN Background: Previous studies have reported prior prognosis after esophagectomy in women to men. To clarify the reason of advantages in female esophageal cancer, many studies have investigated about differences of sex hormone expression or immune function, but they could not reveal clearly what brings an advantage in mortality, morbidity and survive following esophageal surgery. Purpose of this study was to clarify the gender advantages in the clinico-pathological features and prognosis. Especially, gender difference was also investigated in the group who received neo-adjuvant chemotherapy. Methods: A total of consecutive 170 Japanese patients with esophageal squamous cell carcinoma were newly diagnosed and underwent esophagectomy between January 2004 and March 2013. Among the 170 patients, 142 were male and 28 were female. We compared men and women with clinical backgrounds, clinico-pathological factors, and prognosis. Clinical and pathological response after neo-adjuvant chemotherapy was also compared. Furthermore, we performed immunohistochemical staining of the p53 protein that had been recognized useful biomarker to predict tolerance of chemotherapy and prognosis of esophageal cancer, with the pre-treatment biopsy specimen, and compared p53 labeling index between men and women. Results: Women undergoing esophagectomy for esophageal cancer showed lower frequencies of cigarette smoking and alcohol consumption compared to men (p < 0.001). Histological features, tumor location, tumor depth, node involvement, and clinical stage showed no statistical difference between men and women. The cases that presented high grade pathological responce after chemotherapy (>Grade2) was significantly higher in women (66.7%) than men (43.3%) (p = 0.032) in 84 patients who received neo-adjuvant chemotherapy. The results of immunohistochemical staining of the p53 protein showed significantly higher incidence in men compared with in women

Background: To investigate the prognostic significance of lymphovascular invasion (LVI) in esophageal squamous cell carcinoma(SCC) after chemoradiotherapy(CRT). Methods: From 1998∼2008, 416 consecutive esophageal SCC patients underwent surgical resection after CRT in Chang Gung memorial hospital. Excluding patients with non-R0 resection or no residual tumor (ypT0Nx), histological assessments of tumor specimens in 231 patients were made and the correlation of LVI with patient survival were evaluated by univariate and multivariate analysis. Results: The total rate of LVI was 36.8%. The presence of LVI significantly correlated with close circumferential resection margin (CRM), deeper tumor depth of invasion, poorly tumor differentiation and positive lymph node metastases (LNM). The 5 year overall survival (OS) of patients with LVI was significantly lower than that of patients without LVI expression (5 yr OS: 31% vs. 10%, P < 0.001). Furthermore, in a multivariate analysis by Cox regression model, LVI was confirmed to be an independent prognostic factor (HR:1.5; unfavorable, P = 0.002) for OS, while LNM (HR: 1.6; unfavorable, P = 0.007) was also a significant prognostic factor. The 5 year OS in patients with LVI(-)LNM(-), LVI(+)LNM(−), LVI(−)LNM(+) and LVI(+)LNM(+) were 35%, 21%, 20% and 5% respectively. (P < 0.001). Discussion: After CRT, the presence of LVI is an independent prognostic factor in esophageal SCC patients. The combination of LNM and LVI could be used to predict survival. Disclosure: All authors have declared no conflicts of interest. Keywords: invasion

Esophageal

cancer,

chemoradiotherapy,

lymphovascular

P2.14.13: THE CLINICAL SIGNIFICANCE OF SYNCHRONOUS TRIPLE PRIMARY CARCINOMAS INCLUDING ESOPHAGEAL CANCER Naotomo Higo, Hiroshi Okumura, Yasuto Uchikado, Itaru Omoto, Ken Sasaki, Yoshiaki Kita, Masataka Matsumoto, Tetsuhiro Owaki, Sumiya Ishigami, Shoji Natsugoe Kagoshima University, Kagoshima/JAPAN Background: The opportunities of the treatment for multiple primary cancers are increasing because of the advances of the diagnostic or curative treatment ability for the digestive cancer and the aging society. We should treat them carefully because they often have complications and, in the surgical treatments, we should decide the operative methods more carefully. In this study, we examined the clinical significance of the synchronous triple primary carcinomas including esophageal cancer in our department. Methods: There were total 1592 esophageal cancer patients who were treated in our hospital between 1980 and 2012. Among them, the patients with the synchronous triple primary carcinomas were 12 (0.8%). We evaluated their clinicopathological features, outcome and discuss about the appropriate treatment strategies. Results: The mean age of the 12 patients was 71 years and all of them were men. About the diagnosis of the synchronous triple primary carcinomas 4 cases were found through investigating esophageal cancer, 5 cases were pointed out through other cancer and 3 cases were not known in details. The overlap primary carcinomas were as follows: 5 hypopharyngeal and gastric, 4 lung and colorectal, 3 liver, and one oropharyngeal, anal canal, and


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bladder. As for the diagnosis of the esophageal cancer, all of them were thoracic esophageal squamous cell carcinoma. The number of patient with pT1a/1b/2/3/4 was 4/4/1/2/1, pN0/1/3/4 was 7/2/1/2 and pStage0/I/II/Iva was 4/2/3/3, respectively. As for the treatment of the esophageal cancer, chemoradiation therapy (CRT) were four, transhiatal esophagectomy were three, thoracoabdominal esophagectomy was one, endoscopic mucosal resection (EMR) were three, and no treatment was one. About the treatment of the other carcinomas, six patients underwent radical curative excision for both carcinomas. As for their prognosis, three patients are alive including two patients with more than two years, two patients died of the esophageal cancer, four patients died of other synchronous carcinoma, one patient died of metachronous leukemia, one patient died of benign disease, and one patients’ outcome was unknown. Discussion: In the treatment of the synchronous triple primary carcinomas including esophageal cancer, it is important to estimate the progression degree of the esophageal cancer and synchronous other primary carcinomas sufficiently and to decide the well-balanced treatment strategy.

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P2.14.15: SURGICAL RESECTION AND CHEMORADIOTHERAPY FOR METACHRONOUS PULMONARY METASTASIS OF BASALOID SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS Hirotaka Ishida, Toru Nakano, Yu Onodera, Hiroshi Okamoto, Makoto Hikage, Jin Teshima, Tadashi Sakurai, Yusuke Taniyama, Kazunori Katsura, Shigeo Abe, Takashi Kamei, Go Miyata, Noriaki Ouchi Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai/JAPAN Background: Basaloid squamous cell carcinoma of the esophagus (BSCCE) is a relatively rare esophageal malignancy. The standard treatment for BSCCE has not yet been established because of the limited number of cases, furthermore, for metastatic lesion. We report a successful case treated with chemoradiotherapy for the local recurrence after partial resection of solitary pulmonary metastasis of BSCCE. Methods: ‘not applicable’


Results: Case Report

Keywords: Esophageal cancer, synchronous triple primary carcinomas, multiple primary cancers, Esophageal squamous cell carcinoma

72-year-old male was admitted to our hospital with a complaint of dysphagia. Upper gastrointestinal examination and esophagogram revealed a Type 2 tumor of the middle third of thoracic esophagus. Computed tomography (CT) showed no evidence of invasion of the esophageal cancer to adjacent structures or metastasis to distant organs. Esophagectomy with lymphadenectomy was performed via a thoracoscopic approach followed by reconstruction by using gastric tube through retro-mediastinal route. Macroscopic findings of the resected specimen showed 40×35 mm of tumor at middle third of thoracic esophagus. Pathological examination revealed that the cancer cells with venous and lymphatic invasion had invaded the adventitia of the esophagus. Lymph node metastases were detected along the left recurrent nerve and the left gastric artery. The definitive diagnosis was BSCCE, T3N1M0, stageIIIA according to the TNM classification of malignant tumors. Fourteen months later, follow-up CT detected a nodule in the size of 10 mm in the upper lobe of the right lung, and the maximum standardized uptake value (SUV max) of the lesion was 2.0 at 18F-2-fluoro-2-deoxy-Dglucose positron-emission tomography. The level of SCC antigen was 2.3 ng/ ml(0.00–1.50 ng/ml). It was strongly suggested metastatic lung tumor of BSCCE. Because no other metastasis was found by systemic examination, partial resection of the upper lobe of right lung was performed via a thoracoscopic approach. Histological diagnosis was confirmed as lung metastasis of the BSCCE. Seventeen months after the second surgery, CT revealed a tumor in the right pulmonary apex, and SUV max of the lesion was 12.2. These results strongly suggested the tumor relapsed again after resection of metastatic lung tumor. Because the lesion was near to the right subclavian artery and vein, surgical resection was thought to be difficult. He was treated with chemoradiotherapy; the protocol was comprised two cycles of intravenous cisplatin infusions with continuous 5-fluorouracil infusion and concurrent irradiation with a total dose of 60 Gy. Metastatic lesion disappeared completely, and he is without any sign of recurrence 42 months later.

P2.14.14: PREVALENCE AND PROGNOSTIC VALUE OF EGFR (EPIDERMAL GROWTH FACTOR RECEPTOR), HER2NEU AND VEGF (VASCULAR ENDOTHELIAL GROWTH FACTOR) EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CANCER RESECTION SPECIMENS AND CONCORDANCE WITH EXPRESSION IN PREOPERATIVE BIOPSY Rajneesh Singh, Niraj Kumari, Narendra Krishnani, Rajan Saxena, Shaleen Kumar Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow/INDIA Background: EGFR, HER2neu and VEGF are potential receptors for targeted individualized therapy for esophageal cancer. Not much is known about the prevalence of these markers in Asian population or their prognostic value. There is not much data to show that the same results can be obtained with small preoperative biopsy specimens as with large resection specimens. Methods: Retrospective chart review of 46 consecutive esophageal squamous cell cancer patients was done from our Institutional medical records. All available pathology specimens (resections and biopsies) were reviewed and subjected to immunohistochemistry (IHC) for EGFR, HER2neu and VEGF. The histopathology and IHC results were interpreted by two individual pathologists and were reported by mutual agreement. The prevalence of these markers in resection specimens was correlated (Fisher exact test) with prognostic criteria (T-stage, N-stage, Tumour grade, Perineural invasion and Lymphovascular invasion). Concordance between resection and biopsy specimens was calculated (SPSS ver. 22). Results: There were 46 patients with resected squamous cell cancer esophagus with M : F ratio of 1.9:1, mean age of 52.5 years (SD 8.1). The treatment received was as follows: Neoadjuvant chemoradiotherapy followed by surgery (n = 18), Surgery alone (n = 6) and Surgery followed by adjuvant therapy (n = 22). IHC staining in the resection specimens (n = 46) showed EGFR expression in 86.9% patients, HER2neu expression in 8.6% and VEGF expression in 60.8%. None of the markers showed any significant correlation with any of the prognostic criteria evaluated. Eighteen patients had available preoperative endoscopic biopsy specimens on which IHC was performed. In these samples EGFR expression was seen in 77.7%, HER2neu in 16.6% and VEGF in 41.1% of the patients. The kappa values for concordance for IHC staining between the resection specimens and the biopsy samples were as follows – EGFR (Kappa = 0.47; p = 0.043), HER2neu (Kappa = 0; p = 1.0) and VEGF (Kappa = 0.43; p = 0.059). This shows that random biopsies, taken for diagnosis, show only a low level of concordance for EGFR expression and none for HER2neu and VEGF expression. Discussion: Esophageal SCC in the Asian population studied was highly positive for EGFR. The IHC staining pattern of random esophageal biopsies taken for diagnostic purpose are not representative of the resected tumour with regard to HER2neu and VEGF. A large number of biopsies from different part of the tumour may be required to obtain representative results for these markers. The small sample size and retrospective data collection are the main limitations of the study. Disclosure: All authors have declared no conflicts of interest. Keywords: HER2/neu, VEGF, targeted therapy, EGFR

Discussion: There have been few reports of case treated with surgical intervention for solitary pulmonary metastases of BSCCE. In addition, no treatment strategy for pulmonary metastases from BSCCE has been established because of the limited number of cases. To our knowledge, the case of pulmonary lesion recurring again after partial resection of lung has not yet been reported. In our case, the re-recurrent pulmonary lesion disappeared completely after chemoradiotherapy and he is without any sign of recurrence in long time survival. Resection of solitary metachronous pulmonary metastasis of BSCCE should be considered. Irradiation of lung metastasis offers a good prognosis and might be considered for unresectable metastasis of BSCCE. Disclosure: All authors have declared no conflicts of interest. Keywords: basaloid squamous cell carcinoma of the esophagus, metachronous pulmonary metastasis, surgical resection, chomoradiotherapy P2.14.16: EXTRANODAL METASTASIS IS A POWERFUL PROGNOSTIC FACTOR IN PATIENTS WITH ADENOCARCINOMA OF ESOPHAGOGASTRIC JUNCTION Hongdian Zhang, Zhentao Yu, Peng Tang Tianjin Medical University Cancer Institute and Hospital, Tianjin/CHINA Background: The purpose of this study was to estimate the impact of extranodal metastasis (EM) on recurrence and survival of adenocarcinoma of esophagogastric junction (AEG) patients after radical resection. Methods: The clinical data of 284 lymph node positive AEG patients who underwent curative resection were reviewed. Univariate and multivariate analyses were carried out to elucidate the impact of EM on recurrence-free survival (RFS) and overall survival (OS). Results: EM was detected in 70 (24.6%) of the 284 cases. It had a significant correlation with tumor size, Lauren type, histopathological grading, depth of tumor invasion, the number of metastatic nodes and TNM stage. The 5-year RFS and OS rates were 22.2% and 24.3%, respectively. The patients

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with EM had a significantly decreased RFS (16 vs. 36 months, P < 0.001) and OS (23 vs. 41 months, P < 0.001) compared with those without EM. Multivariate analysis identified EM as an independent prognostic factor (P = 0.004 and P = 0.002, respectively). Discussion: The presence of EM increases recurrence and reduces the overall survival of AEG patients with lymph node metastasis. It is a powerful prognostic factor reflecting a particularly aggressive biologic behavior. Better understanding of the EM status may help clinicians with treatment decision and prognosis evaluation. Disclosure: All authors have declared no conflicts of interest. Keywords: Adenocarcinoma of esophagogastric junction, Extranodal metastasis, lymph node metastasis, prognosis P2.14.17: THE BLOOD FLOW EVALUATION OF GASTRIC TUBE BY ICG FLUORESCENCE METHOD AND LASER DOPPLER METHOD IN ESOPHAGECTOMY FOR ESOPHAGEAL CANCER Yasuto Uchikado, Hiroshi Okumura, Itaru Omoto, Tetsuhiro Owaki, Masataka Matsumoto, Yoshiaki Kita, Ken Sasaki, Takaaki Arigami, Yoshikazu Uenosono, Sumiya Ishigami, Shoji Natsugoe Kagoshima University, Kagoshima/JAPAN Background: The anastomotic leak or gastric tube necrosis of gastric tube reconstruction after resection of esophageal cancer is not only delayed Meal start, but also caused anastomotic stricture. So it extend hospital stay. In this study, we assessed a blood flow of gastric tube by using the method of indocyanine green (ICG) fluorescence and laser Doppler in reconstruction of esophagectomy, and investigated problems and effectiveness. Methods: From March to August in 2013, there were fifteen patients of esophagectomy that could be evaluated a blood flow of gastric tube by using the method of ICG fluorescence and laser Doppler. We have created gastric tube of 3.5–4 cm diameter with automatic suturing device. In the method of ICG fluorescence, we observed top of gastric tube to venous phase from arterial phase using the infrared camera system (PDE neo, HAMAMATSU Co.) after 5 mg intravenous injection of ICG. In the method of laser Doppler, we measured at two points of the anastomosis and the site of 2 cm oral side from pylorus of gastric tube by a laser Doppler blood flow meter (ALF21, ADVANCE Co.). We examined difference about the presence of postoperative complication (especially anastomotic leakage or stricture) between the ICG fluorescence method and the laser Doppler. Results: The preoperative treatment were no treatment; 4 cases, chemotherapy; 4 cases, and chemoradiotherapy; 7 cases. There were ten patients received both the ICG fluorescence and the laser Doppler methods, five patients received only the laser Doppler method. The average enhanced time of gastric tube end was 12.6 seconds (11 s-14 s) in the ICG fluorescence method. The average blood flow was 4.53ml/min/100g (2.3–8.9), and the blood flow ratio of two point (anastomosis/near pylorus) was 51.1%(30.7– 66.3%) in the laser Doppler method. Ten patients received both the ICG fluorescence and the laser Doppler methods had no postoperative complication related to anastomosis. The blood flow ratio of all ten cases were greater than 40%. In five patients received only the laser Doppler method, there were two cases with anastomotic leakage. So the blood flow ratio of two cases were 30.7% and 37.3%, other cases were greater than 40%. Discussion: In the ICG fluorescence method, there is a merit that can be visualized but a demerit that cannot be quantified for the blood flow of gastric tube. On the other hand, there is no numerical criteria of safety margin in the laser Doppler method. So the blood flow measurement of gastric tube using a combination of the both methods is effective for prevention of anastomotic leakage and stricture. Disclosure: All authors have declared no conflicts of interest. Keywords: ICG fluorescence, laser doppler, Esophageal cancer, blood flow of gastric tube P2.14.18: PHASE II STUDY OF DOCETAXEL AND 5-FLUOROURACIL WITH CONCURRENT RADIOTHERAPY IN PATIENTS WITH UNRESECTABLE LOCALLY ADVANCED ESOPHAGEAL CANCER Ichiko Yamakita, Jun Hihara, Yuta Ibuki, Yoshiro Aoki, Junya Taomoto, Yoichi Hamai, Manabu Emi, Morihito Okada Hiroshima University, Hiroshima/JAPAN Background: Definitive chemoradiothrapy is the standard treatment for unresectable locally advanced esophageal cancer. We conducted the phase II clinical trial for definitive chemoradiotherapy using docetaxel (DOC) combined with 5-Fluorouracil (5-FU), based on th result of the phase I study to define the optimal dose of DOC as we reported formerly. This phase II study evaluated an antitumor effect, time to progression (TTP), local control ratio, survival and safety for unresectable locally advanced esophageal squamous cell carcinoma. Methods: The patient enrollment in this phase II study was started on July 1, 2005 and completed on February 29, 2008. Eleven patents of thoracic and 5 of cervical esophageal cancer were eligible. There were 12 males and 4 females, ranging in age from 44 to 74 years (median, 64 years). All patiens


had squamous cell carcinoma. Twelve patients had cStage III, 2 cStage IV, one cStage IVa and one cStage IVb esophageal cancer according to the 6th TNM classification. Patients received DOC (7.5 mg/m2) on days 1, 8, 22, 29 and 43. They were also given 5-FU 250mg/m2/day by continuous infusion on days 1–5, 8–12, 15–19, 22–26, 29–33, 36–40 and 43–45. Fractionated radiotherapy was performed with a total dose of 66 Gy. Results: All patients completed prescribed dose of radiotherapy. Seven patients (43.8%) could complete planned cycles of DOC (5 times) and 5-FU (more than 6 weeks), others needed to reduce one or two cycles of DOC and/or 5-FU mainly due to esophagitis. Dose reduction of chemotherapy was not done. Hematological toxicity was mild. As for nonhematological Grade 3 or higher adverse effects, esophagitis was most frequent (31.3%). Overall response rate was 93.8% with CR in 5 patients (31.3%) and PR in 10 (62.5%). The median TTP was 20.0 months and the median survival time (MST) was 18 months. The overall 3-year and 5-year survival rate were 43.8% and 31.3%. According to primary tumor site, MST and 5-year OS were 18 months and 20.0% in the cervical esophageal cancer, and 29 month and 36.4% in the thoracic esophageal cancer, respectively (p = 0.898). Discussion: Definitive chemoradiotherapy using weekly DOC and continuous infusion of 5-FU could be performed safely, and may have a favorate antitumor effect in patients with locally advanced esophageal squamous cell carcinoma. Esophageal cancer patients often combine impaired renal function and CDDP is not suitable for these patients. This CRT regimen will be indicated in such patients desiring to avoid bone marrow suppression and progression of renal dysfunction, but careful attention should be paid to esophagitis. Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal carcinoma, chemoradiotherapy, docetaxel, 5-FU P2.14.19: THE TRANSUTION OF THE OXIDATIVE STRESS AFTER THE ESOPHAGECTOMY BY THE RIGHT THORECOTOMY IN THE ESOPHAGEAL CANCER PATIENTS Tetsuhiro Owaki1, Hiroshi Okumura1, Yasuto Uchikado2, Ken Sasaki3, Itaru Omoto3, Youta Kawasaki1, Shoji Natsugoe1 1 Kagoshima University, Kagoshima/JAPAN, 2Kagoshima University, Kagoshima/JAPAN, 3Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima/JAPAN Background: CRP, IL-6, operative time, bleeding volume etc. are used for an evaluation of the infestation of the surgical operation. however, it is difficult to evaluate accurate infestation, and the quantification is difficult. We may evaluate infestation under the surgery bu volume of unternal oxidative stress. Threrfore we measure postoperative oxidative stress over time and judge it whether measurement of the oxidative stress is useful as an evaluation of the volume of the operative infestation. Methods: 26 esophageal cancer patients who underwent esophagectomy by the right thoracotomy from 2010–2013 in Kagoshima University Hoppital were enrolled inthis study. Oxidative stress was measured by a d-reactive oxygen metabolites (d-ROM) test and antioxidant potency was evaluated by a biological antioxidant potential (BAP) test in the Free Radical Analytical System (FRAS)-4 at pre operation, just after an esophagectomy and the post operative first day, the third day and the 7th day. As oxidative stress, we calculated the BAP/d-ROM ratio in particular and used it. Results: As for the ratio for the preoperative value of BAP/d-ROM, just after the esophagectomy 137.9%, the postoprative first day 122.4%, the third day 105.5%, the 7th day 100.9%. There was no relationship between BAP/dROM transition and CRP transition. Discussion: As for the ratio for the preoperative value of BAP/d-ROM in the laparoscopic gastrectomy cases of the same period, just after the opeation 109.3%, the postopeative first day9.2%,the third day 78.9%, the 7th day 74.4% In gastrc cancer addominal operation, 131., 121.4 104.4 88.7%, respectively. In colectmy or colon cancer, 107.6,103.2, 819, 88.2%, espectively.In the surical operaton method that infestation is thought to be lght fro our experience, we find that BAP/d-ROM is low. In the same operatve method, the judgemt that an evaluation of the operative infestation is possible by measument of BAP/d-ROM requres the accumultion of the case. Disclosure: All authors have declared no conflicts of interest. Keywords: oxidative stress, d-ROM, BAP, esophagectomy P2.14.20: EXPRESSION OF MIR-145 IN EAC CELLS ENHANCE ANOIKIS RESISTANCE AND CELL INVASION Mathieu Derouet, Gail Darling University Health Network, Toronto/ON/CANADA Background: Carcinoma of the esophagus has become one of the fastest growing solid tumors in the world over the past 20 years and the 6th most common cause of death in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC) pre and post induction therapy. Out of the miRNAs discovered, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold upon induction


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therapy however its expression was associated with shorter disease-free survival. This unexpected result was explored Methods: In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in 3 EAC cell lines (OE33, FLO-1, SK-GT-4). After validation of the expression of miR-145, several hallmarks of cancer such as cell proliferation, resistance to chemotherapy drugs or anoikis, cell invasion were analyzed. Results: There were no differences in cell proliferation and 5 FU resistance between miR145 cell lines (miR-145) and the control cell lines (pcmv). miR-145 expression had no effect on cisplatin resistance in two of the three cell lines (OE33 and FLO-1), but miR-145 appears to protect SK-GT-4 cells against cisplatin treatment (% survival: 21.68 ± 1.4 (pcmv) vs 26.94 ± 0.94 (miR-145),n = 6, p < 0.05). However, there was a significant difference in cell invasion and resistance to anoikis. The miR-145 cell lines exhibited more ability to invade than their respective control (OE33 pcmv: 1308 cells ± 70; OE33 miR-145: 1493 cells ± 69; FLO-1 pcmv: 3478 cells ± 354; FLO-1 miR145: 4718 cells ± 548; SK-GT-4 pcmv: 3902 cells ± 235; SK-GT-4 miR-145: 4691 cells ± 303; n = 20). Furthermore, the miR145 cell lines were able to survive longer in a suspension state and therefore create more colonies after 72 hours culture in suspension (OE33: 126.5 ± 11 colonies (miR-145) against 83.5 ± 9 colonies (pcmv), n = 6, p < 0.05). Discussion: While expression of miR-145 in ESCC stop proliferation and invasion, it appears that expression of miR-145 in EAC cells leads to enhanced invasion and anoikis resistance. Although more work is required to understand how miR-145 conveys these effects, EAC progression may be facilitated by expression of miR-145, which appears to enhance invasion and protect against anoikis, which could in turn facilitate distant metastasis. Disclosure: All authors have declared no conflicts of interest. Keyword: miR-145, cell invasion P2.14.21: A CASE REPORT OF SIMULTANEOUS MULTIFOCAL ESOPHAGEAL CANCER OF SQUAMOUS CELL CARICNOMA AND ADENOCARCINOMA Soichiro Yamamoto1, Hiroyasu Makuuchi1, Shuji Uda1, Hideo Shimada2, Osamu Chino3, Takayuki Nishi4, Tomoko Hanashi5, Akihito Kazuno6, Miho Nitta4, Soji Ozawa6 1 Tokai University Hachioji Hospital, Hachioji, Tokyo/JAPAN, 2Tokai University School of Medicine, Oiso Hospital, Kanagawa/JAPAN, 3Tokai University School of Medicine, Tokyo Hospital, Tokyo/JAPAN, 4Tokai University Oiso Hospital, Naka-gun, Kanagawa/JAPAN, 5Tokai University Tokyo Hospital, Shibuya, Tokyo/JAPAN, 6Tokai University School of Medicine, Kanagawa/JAPAN Background: Simultaneous multifocal lesions were often recognized in esophageal cancer. However, the presence of two different histogenesis of cancers is rare. Methods: We report a case of synchronous squamous cell carcinoma and adenocarcinoma in lower esophagus. Results: A 67-year-old man underwent endoscopy for heartburn. There were irregular part in the Barrett’s mucosa and reflux esophagitis in endoscopic findings. It was diagnosed with adenocarcinoma from biopsy specimen of the irregular mucosa. We performed surgical treatment for Barrett’s esophageal cancer. From the results of pathological diagnosis, there was signet ring cell carcinoma in contact with Barrett’s mucosa. Also erosive part diagnosed with reflux esophagitis was squamous cell carcinoma in situ. Discussion: To define the border of esophagus and stomach by plotting from the position of proper esophageal glands, both squamous cell carcinoma and adenocarcinoma were also diagnosed to be derived from cancer of the esophagus. Differntial diagnosis of squamous cell carcinoma and esophagitis has been difficult in this case. Disclosure: All authors have declared no conflicts of interest. Keywords: squamous cell carcinoma, synchronous cancer, signet ring cell carcinoma, case report P2.14.22: A CASE OF MIXED ADENONEUROENDCRINE CARCINOMA (MANEC) OF THE ESOPHAGOGASTRIC JUNCTION Shuji Uda1, Hiroyasu Makuuchi1, Miho Nitta2, Akihito Kazuno3, Soichiro Yamamoto1, Takayuki Nishi2, Osamu Chino4, Hideo Shimada2, Soji Ozawa3 1 Tokai University Hachioji Hospital, Hachioji,Tokyo/JAPAN, 2Tokai University Oiso Hospital, Naka-gun, Kanagawa/JAPAN, 3Tokai University School of Medicine, Kanagawa/JAPAN, 4Tokai University School of Medicine, Tokyo Hospital, Tokyo/JAPAN Background: A 63-year-old man who presented with dysphagia over 1month. Gastric endoscopy revealed a typeIII tumor at the abdominal esophagus.The tumor had invaded into the esophagogastric junction,and biopsy specimens taken from the tumor histopathologically revealed endocrine carcinoma.Computed tomography scan showed lymph nodes swelling around gastric cardia.

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Methods: We underwent partial resection of the lower esophagus, proximal gastrectomy. Results: On histopathological examination, the tumor showed two distinct components.The majority of tumor consisted of immunohistochemically positive for synaptophysin.The Ki-67 index was 40%.The other component consisted of adenocarcinoma that made up about 30% of the entire tumor mass.The diagnosis was mixed adenoneuroendocrine carcinoma(MANEC) according to the 2010 World Health Organization guidelines. Discussion: Thirteen months after stating treatment,the patient is well without any recurrence. Disclosure: All authors have declared no conflicts of interest. Keywords: Esophageal cancer, mixed adenoneuroendcrine carcinoma, MANEC

Wednesday, September 24 – 13:30–15:00 V309: Video Abstracts Room: Cypress V309.01: ILEO-COLIC INTERPOSITION AS A STANDARD RECONSTRUCTION PROCEDURE AFTER RADICAL ESOPHAGECTOMY Harushi Udagawa, Masaki Ueno, Hiisashi Shinohara, Shusuke Haruta, Seigi Lee, Kota Momose Toranomon Hospital, Tokyo/JAPAN Background: Gastric conduit is the commonest procedure of reconstruction after radical esophagectomy. It is the simplest and with high reliability in terms of vascularity and anastomotic healing. However, the esophageal reconstruction with gastric conduit is accompanied with decreased reservoir function of the stomach and ever-lasting increased risk of regurgitation and aspiration pneumonia. Methods: We started esophageal reconstruction with interposition of the ileo-colic segment brought up through the retrosternal tunnel between the cervical esophagus and the gastric remnant left in the peritoneal cavity in 2008 (Fig. 1). First, it was applied only to younger patients with expectedly better prognosis. Since June in 2012, we have been applying this as our standard procedure for reconstruction after radical esophagectomy as long as no abnormality is detected on colonoscopy and no additional risk factors of surgery are revealed. Results: We have applied this procedure to 46 patients with no operative mortality and with only 1 anastomotic leakage. In recent 13 patients, handassisted laparoscopic technique has been applied and the length of the abdominal wound has diminished to 7–8 cm (Fig. 2). No further surgical intervention was required except one early re-operation for postoperative enteritis and one laparotomy for mechanical bowel obstruction 7 months after esophagectomy. No reflux esophagitis in the cervical esophagus above the cervical esophago-ileal anastomosis has been observed. Discussion: Although there is no clear statistical evidence yet, we believe that this procedure will lead patients to decreased postoperative pneumonia and better nutritional preservation. We will present the detail of this procedure with video.

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Disclosure: All authors have declared no conflicts of interest. Keywords: esophageal reconstruction, ileo-colic interposition, ileo-colonic interposition, aspiration pneumonia due to regurgitaion V309.02: AUTONOMIC NERVE PRESERVING EN BLOC ESOPHAGECTOMY FOR THORACIC ESOPHAGEAL CANCER Tadashi Nishimaki, Hideaki Shimoji, Hiroyuki Karimata University of the Ryukyus, Nishihara, Okinawa/JAPAN Background: Esophagectomy remains the mainstay of curative treatment of esophageal cancer. It is generally accepted that en bloc esophagectomy is indispensable for the achievement of high cure rates in esophageal cancer patients. Esophageal cancer frequently metastasizes to the recurrent nerve lymph nodes, and therefore complete removal of these lymph nodes is one of the most important parts of en bloc esophagectomy. However, thorough lymphadenectomy along the recurrent nerves increases the risk of postoperative vocal cord palsy, leading to extremely impaired quality of patient’s life. To maintain laryngo-respiratory function of patients and to keep high quality of tumor resection, we have performed an autonomic nerve preserving en bloc esophagectomy in patients with esophageal cancer. In the video, we will show our surgical techniques of this operation with the short- and long-term results. Methods: Preserved nerves during the operation include the bilateral recurrent nerves, pulmonary branches of the bilateral vagus nerves, cardiac nerves of the vagus and sympathetic nerves, and tracheal and bronchial branches of the vagus nerve. The esophageal branches of the recurrent nerves and vagus nerves were divided at their origins. To avoid injury to the nerves that must be preserved, and to facilitate thorough lymphadenectomy along the nerves, the bilateral recurrent nerves and vagus nerves were encircled using a shortly looped vascular tape. The bronchial arteries were also preserved. We have performed this operation in 104 patients. Of the 104 patients, 40 underwent upfront esophagectomy for immediately resectable less advanced tumors (Category 1), 23 underwent induction chemotherapy or chemoradiotherapy for T4 tumors (Category 2), and 41 underwent neoadjuvant chemotherapy for esophageal tumors resectable but associated with extensive nodal metastasis (Category 3).


Collis gastroplasty technique performed from the left chest during laparoscopic hiatal hernia repair. A 10 mm, 45 degree extended length camera is advanced into the thorax after creating a left pleurotomy from the hiatus. A left chest port (1 cm) is created in the 4th intercostal space at the anterior mid-axillary line and an endoscopic stapler (45 mm variable height 4.5 mm) is guided from the chest into the abdomen under direct vision. The gastroplasty is created with a single staple load and a 44 Fr esophageal bougie. Radial diaphragmatic tension is assessed by utilizing a novel tension device while approximating the crura (see Figure 1). If tension is high (>10 decagrams), a right crural relaxing incision and/or intentional pneumothorax is induced prior to crural closure. If a crural relaxing incision is utilized, the defect and hiatal closure are covered with synthetic bioabsorbable mesh. Results: We have performed 7 left thoracoscopic assisted laparoscopic Collis gastroplasties. The crural tensiometer has been utilized to assess radial tension in 64 patients and adjunctive procedures were performed as follows: right crural relaxing incision (n = 21), intentional pneumothorax (n = 12) and both procedures (n = 5). There were no intraoperative or postoperative complications. Discussion: In summary, this video describes 2 useful surgical adjuncts to help mitigate axial and radial tension during hiatal hernia repair. First, the simplified left chest Collis gastroplasty has advantages over previously described gastroplasty techniques in that it requires only 1 camera and avoids the need for fundectomy. Second, the crural tensiometer provides the surgeon with objective data which is useful in determining the need for crural relaxation and/or intentional pneumothorax before hiatal closure.

Results: Mortality and morbidity rates were 0% and 43% in Category 1 patients. Respective rates were 18% and 64% in Category 2 patients, and 5% and 71% in Category 3 patients. R0 resection rates were 98%, 59%, and 83% in Category1, 2, and 3 patients, respectively. Postoperative vocal cord palsy developed in 5%, 18%, and 10% of Category 1, 2, and 3 patients, respectively. Postoperative pulmonary complications occurred in 28%, 46%, and 62% of Category 1, 2, and 3 patients, respectively. The 5-year overall survival rates of patients undergoing R0 resection were 66%, 53%, and 24% in Category 1, 2, and 3 disease, respectively. Discussion: The goal of the autonomic nerve preserving en bloc esophagectomy is the simultaneous achievement of high cure rates of esophageal cancer and high preservation rates of laryngo-respiratory function. In patients with less advanced esophageal cancer (Category 1 disease), outcome of this operation seems satisfactory because both of long-term survival rate and occurrence rate of postoperative vocal cord palsy are acceptable. However, further innovation in perioperative management and oncological treatment strategy may be needed to improve both short- and long-term results in patients initially having advanced esophageal cancer that requires preoperative chemotherapy or chemoradiotherapy (Category 2 and 3 diseases). Disclosure: All authors have declared no conflicts of interest. Keywords: esophagectomy, autonomic nerve preserving operation, vocal cord palsy, long-term survival

V309.03: SURGICAL ADJUNCTS IN THE MANAGEMENT OF PARAESOPHAGEAL HERNIA TO REDUCE AXIAL AND RADIAL TENSION Jennifer Wilson, Daniel Davila Bradley, Brian Louie, Ralph Aye, Eric Vallieres, Alexander Farivar Swedish Medical Center and Cancer Institute, Seattle/AL/UNITED STATES OF AMERICA Background: The high recurrence rates reported after laparoscopic paraesophageal hernia repair are believed to be due to increased axial tension on the esophagus and/or radial tension on the diaphragmatic closure. In this video, we describe a simplified left chest approach to laparoscopic Collis gastroplasty to reduce axial tension and a method for objectively measuring radial tension on the diaphragmatic closure, which can be utilized to determine the need for additional adjunctive procedures to reduce radial tension. Methods: Axial tension is assumed if

Abstracts of the Lupus 2014: new targets, new approaches Congress, September 18-20, 2014, Quebec City, Canada.

2014 ACAPS Congress: Abstracts.

Abstracts of the RCOG World Congress 2014, 28-30 March 2014, Hyderabad, India.

Abstracts of the WFH 2014 World Congress, May 11-15, 2014, Melbourne, Australia.

Abstracts of the IPA World Congress 2014, May 9-11, 2014, Athens, Greece.

Abstracts of the XV World Congress on Cancers of the Skin, 3-6 September 2014. Edinburgh, Scotland.

Abstracts from the 2nd International Joined OTIS - ENTIS Conference, September 18-21, 2014, Toronto, Canada.

Abstracts from the 3rd World Congress on Vascular Access, WoCoVA 2014, 18-20 June 2014, Berlin, Germany.

Abstracts of the AAGBI Annual Congress, 17-19 September 2014, Harrogate, UK.

Abstracts from the FEBS EMBO 2014 Conference, 30 August-4 September, 2014, Paris, France.

Abstracts from the Third Chinese Congress on Gerontology and Health Industry, September 12-14, 2014, Suzhou, China.

Abstracts of the Heart Failure Congress 2014 and the 1st World Congress on Acute Heart Failure, May 17–20, 2014, Athens, Greece.

Abstracts of the International Academy of Cardiology Annual Scientific Sessions 2014 19th World Congress on Heart Disease, July 25-28, 2014, Boston, Massachusetts., USA, july 25-28, 2014.

Multimodality imaging: bird's eye view from The European Society of Cardiology Congress 2014 Barcelona, August 30-September 3, 2014.

Abstracts of the 22nd Congress of the European Sleep Research Society, 16-20 September, 2014, Tallinn, Estonia.

[Abstracts of the 24th German Skin Cancer Congress and ADO Annual Meeting, 11-13 September, 2014, Frankfurt, Germany].

Abstracts of the XVIII International Congress of Neuropathology, Rio de Janeiro, Brazil, September 14 to 18, 2014.

Abstracts from the International Surgical Congress of the ASGBI, 30 April-2 May 2014, Harrogate, UK.

Abstracts 2014.

Abstracts of the 5th World Congress on Sleep Medicine, 28 September-2 October 2013, Valencia, Spain.

Abstracts from the 10th Palliative Care Congress, 12–14 March, 2014, Harrogate, UK.

Presidential address: World Transplant Congress 2014, San Francisco.

9th world stroke congress, 22-25 october 2014, istanbul, Turkey.

Editorial: International Plant Proteomics Organization (INPPO) World Congress 2014.