Asian pacific digestive week, november 22, 2014, bali, indonesia.

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Journal of Gastroenterology and Hepatology (2014) 29 (Suppl. 3)

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Biliary Tract

Biliary Tract

O-001 Who needs surgery after endoscopic treatment of primary and refractory postcholecystectomy biliary leaks? A multicenter review of 178 patients Presenting Author: JORGE CANENA Additional Authors: DAVID HORTA, JOÃO COIMBRA, LILIANE MEIRELES, PEDRO RUSSO, MARQUES INÊS, LEONEL RICARDO, CATARINA RODRIGUES, TIAGO CAPELA, DIANA CARVALHO, RAFAELA LOUREIRO, ANTÓNIO DIAS, GONÇALO RAMOS, CARLOS COUTINHO, CARLOS ROMÃO Corresponding Author: JORGE CANENA Affiliations: H. Amadora-Sintra, H. Capuchos, H. Pulido Valente, H. Capuchos, H. Pulido Valente, H. Amadora-Sintra, H. Amadora-Sintra, H. Capuchos, H. Capuchos, H. Capuchos, H. Capuchos, H. Capuchos, H. Pulido Valente, H. Pulido Valente

O-002 Analysis of demographic, clinical, and sonographic factors related to clinical outcomes of acute acalculous cholecystitis in children Presenting Author: EUN JAE CHANG Additional Authors: DAE YONG YI, JI YOUNG KIM, HYE RAN YANG Corresponding Author: EUN JAE CHANG Affiliations: Seoul National University Bundang Hospital, Seoul National University Bundang Hospital, Seoul National University Bundang Hospital

Objective: This study evaluated the clinical effectiveness of endotherapy for postcholecystectomy biliary leaks as well as the optimal and efficacy of rescue endotherapy for refractory biliary leaks. Methods: This was a multicenter, retrospective study of 178 patients who underwent endoscopic management of postcholecystectomy biliary leaks with a combination of biliary sphincterotomy and the placement of a large-bore (10-French) plastic stent. Data were collected to analyze the clinical outcomes and technical success, efficacy of the rescue endotherapy and the need for surgery, adverse events and prognostic factors for clinical success of endotherapy. Results: Endotherapy was possible in all of the patients. Following endotherapy, closure of the leak was accomplished in 162 patients (89.9%). A high-grade leak (P < 0.01) and a leak located at the common bile duct/common hepatic duct (associated with bile duct injury) (P = 0.017) were shown to be significant predictors of initial treatment failure in univariate analysis. The remaining 16 patients were treated with multiple plastic stents (MPSs) with a success rate of 62.5% (10 patients). The use of fewer than 3 plastic stents (P = 0.023) and a high-grade biliary leak (P = 0.034) were shown to be significant predictors of treatment failure with MPSs in refractory bile leaks. The 6 patients in whom the placement of MPSs failed were retreated with a fully cover self-expandable metallic stent (FCSEMS), resulting in closure of the leak in all cases. Conclusion: Endotherapy of biliary leaks with a combination of biliary sphincterotomy and the placement of a large-bore plastic stent is associated with a high rate of success (90%). However, refractory biliary leaks should be treated with FCSEMS especially in patients with high-grade leaks. Surgery is usually not necessary for the management of postcholecystectomy biliary leaks. Key Word(s): 1. biliary leak; 2. refractory biliary leak; 3. multiple plastic stents; 4. fully cover metallic stents

Objective: To evaluate the relationship between demographic factors and ultrasonographic gallbladder findings suggesting acute acalculous cholecystitis (AAC), regarding clinical outcomes of AAC in children. Methods: From March 2004 through February 2014, clinical features and ultrasonography (USG) findings were retrospectively reviewed in 131 children with AAC diagnosed by USG. The subjects were divided into the 4 age groups and clinical factors associated with AAC were evaluated. Results: Gender discrepancy was observed in the numbers of patients who underwent operation (p = 0.042) and in the distribution of underlying diseases showing the most prevalent etiology as Kawasaki disease in boys and systemic infection in girls (p = 0.031). Different age groups were associated with different etiologic diseases, revealing the most prevalent etiology as Kawasaki disease in infancy and early childhood and as systemic infection in middle childhood and adolescence (p = 0.000). Most ICU admissions were noted in children younger 2 years than in other age groups, which was not significant (p = 0.063). Gallbladder wall thickening was more commonly noted in systemic infection and not in Kawasaki disease (p = 0.002), whereas gallbladder distension on USG was more frequent in Kawasaki disease which was not common in systemic infection (p = 0.000). Septic shock and transfer to the ICU were related to the presence of ascites along with GB abnormality on USG (77.9% vs. 37.7%, p = 0.030) and the duration of admission was longer in patients with ascites along with AAC (11.6 ± 10.7 vs. 8.0 ± 6.6 days, p = 0.020). Conclusion: Gender and age were important factors associated with the etiologic diseases of AAC and worse clinical course including ICU admission. Sonographic findings of gallbladder wall thickening and gallbladder distension were respectively associated with different disease spectrum as etiology. Ascites on USG along with gallbladder findings of AAC indicated worse clinical course in children. Key Word(s): 1. acalculous cholecystitis; 2. ultrasonography; 3. gallbladder; 4. ascites; 5. age; 6. gender; 7. child

Journal of Gastroenterology and Hepatology 2014; 29 (Suppl. 3): 1–50 © 2014 The Authors. Journal of Gastroenterology and Hepatology © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd

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Biliary Tract O-003 Efficacy and safety of endoscopic papillary large balloon dilation following with an endoscopic sphincterotomy (EPLBD+EST) for large or multiple common bile duct stones (CBDS) Presenting Author: TANIGUCHI YOHEI Additional Authors: TETSURO INOKUMA, YAMASHITA YUKITAKA Corresponding Author: TETSURO INOKUMA Affiliations: Kobe City Medical Center General Hospital, Japanese Red Cross Society Wakayama Medical Center Objective: EPLB+EST has been proposed as an alternative modality for the endoscopic extraction of large or multiple CBDS. It has been reported to have a high success rate and acceptable complication rate. The aim of this study was to evaluate the efficacy and safety of EPLBD+EST. Methods: A total of 122 patients who underwent EPLBD+EST from May 2010 to February 2014 were analyzed retrospectively in Kobe City Medical Center General Hospital and Japanese Red Cross Society Wakayama Medical Center. Results: The mean diameter and number of the stone was 13.2 mm and 3.3. Overall complete stone removal rate was 96.7%, with 79.5% achieved in one session. The number of treatment was 1.24 on average. Mechanical lithotripsy was required in 14 patients. The overall rate of complication was 3.3%. There are no pancreatitis in patients. Bleeding occurred in three patients (2.5%). Laceration in diverticulum occurred in one patient (0.8%). The increase of amylase occurred in two patients (1.6%). Conclusion: EPLBD is safe and effective in patients with large or multiple CBDS. Key Word(s): Na

Biliary Tract O-004 Management of biliary ascariasis with live and dead worms: a comparative study Presenting Author: BIMAL CHANDRA SHIL Additional Authors: MADHUSUDAN SAHA, RANJIT KUMAR BANIK, SHASANKA KUMAR SAHA, MD HABIBUR RAHMAN, SWAPAN CHANDRA DHAR Corresponding Author: BIMAL CHANDRA SHIL Affiliations: North East Medical College, Sir Salimullah Medical College, Sir Salimullah Medical College, Sir Salimullah Medical College, Sir Salimullah Medical College Objective: Ascaris lumbricoids infect more than 25% of the total world population. Ascariasis is highly endemic in Bangladesh (82%) and in some states of India (30–70%). It creates serious problems when it enters the hepatobiliary and pancreatic system. The aim of the study was to compare the clinical features, complications and management of hepatobiliary and pancreatic ascariasis (HPA) with live and dead worms. Methods: A total of 146 patients of HPA diagnosed on the basis of ultrasound were included for the study over a period of 4 years in three hospitals of Bangladesh. All were admitted in the hospital with abdominal pain. Clinical assessment with history taking and investigations like CBC, LFT, abdominal ultrasound and endoscopy were carried out. Conservative treatment consisting of nothing by mouth, I/V fluids, antibiotic and analgesic was given to each patient initially. Oral diet including albendazole was given when the patients were improved. Serial ultrasonography was performed during the stay. Follow up assessment and ultrasonography was done for 2–4 weeks after the discharge. Results: The patients were 15–60 years of age with highest prevalence at 20–40 years. Biliary ascariasis was found to be more

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common in females (69.2%). One hundred and eight patients had living worms and 38 had dead worms. Common presentations (HPA with live vs dead worms) were biliary colic (98% vs 89%) (p < 0.05), vomiting (81% vs 79%) (p > 0.10) and worm emesis (32% vs 28%) (p > 0.10) but pyrexia was more common in HPA with dead worms (9% vs 76%) (p < 0.01). Complications (live vs dead worms) included acute cholangitis (16.6% vs 73.7%) (p < 0.01), obstructive jaundice (8.3% vs 42.1%) (p < 0.01), acute cholecystitis (4.6% vs 15.78%) (p < 0.05), and acute pancreatitis (1.8% vs 5.2%) (p > 0.10). But liver abscess (5.2%), hepatobiliary lithiasis (7.9%) and stricture of bile duct (2.6%) were associated only with dead worms. Ultrasound provided the definitive diagnosis in most cases. Majority of the patients (92, 85.2%) with live worms responded to the conservative management within 3–7 days but only 2 (5.2%) patients with dead worms responded to it (p < 0.01). ERCP extraction of worms was needed in 41 (28.8%) patients. Conclusion: In endemic areas, biliary ascariasis is a frequent diagnosis in patients presenting with acute upper abdominal pain. Ultrasonography is a reliable diagnostic modality. Most of the patients respond to conservative treatment. Biliary ascariasis with dead worms is more harmful than live biliary ascariasis. Prompt treatment should be started in all cases. Key Word(s): 1. biliary ascariasis; 2. acute upper abdominal pain; 3. ultrasonography; 4. conservative treatment

Colonic and Anorectal Disorders O-005 Iohexol versus diatrizoate for fecal/fluid tagging in CT colonography performed with cathartic preparation Presenting Author: BOHYUN KIM Additional Authors: SEONG HO PARK, GIL SUN HONG, JU HEE LEE, JIN CHEON KIM, CHANG SIK YU, JONG SEOK LEE, HYUN JIN KIM, AH YOUNG KIM, HYUN KWON HA Corresponding Author: BOHYUN KIM Affiliations: Asan Medical Center, Asan Medical Center, National Cancer Center, Asan Medical Center, Asan Medical Center, Asan Medical Center, Asan Medical Center, Asan Medical Center, Asan Medical Center Objective: Iohexol is more palatable and causes less clamping and diarrhea than diatrizoate. This study was to compare iohexol and diatrizoate used for fecal/fluid tagging for CT colonography (CTC) regarding technical quality and image quality. Methods: Forty prospective consecutive patients (M : F, 23:17; 63 years ± 11.6) who were suspected of having colonic neoplasia and underwent CTC using iohexol for fecal/fluid tagging (iohexol group) were compared with an age- and gender-matched retrospective cohort of 40 patients (M : F, 23:17; 63 years ± 11.5) (diatrizoate group) randomly chosen from 358 past clinical CTC patients who had undergone CTC for the same reason and using the same methods except for the use of diatrizoate for tagging. Patients underwent colon cleansing with 4 L polyethylene glycol followed by tagging with an intake of 50 mL (350 mgl/mL) iohexol (iohexol group) or 100 mL meglumine diatrizoate (diatrizoate group). Images were reviewed after removal of all identifications and randomization. The two groups were compared regarding the general quality of preparation/tagging, per-patient and per-segment (average number of 17 3- to 4-cm-long colonic segments sampled in each patient for analysis) semi-quantitative scores of colonic bubbles, ranging from 0 (no bubbles) to 5 (the largest amount), the amount of residual colonic fluid, and CT attenuation value (Hounsfield units, HU) of the fluid in each colonic segment seen on CTC. Results: The two groups were comparable in terms of general quality of preparation/tagging. Iohexol group showed significantly greater amount of colonic luminal bubbles than


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diatrizoate group: mean per-patient score ± SD of 1.2 ± 0.8 vs. 0.7 ± 0.6, respectively (P = .003). Eighty-five (12.9%) of 659 segments in iohexol group showed ≥grades 3 colonic bubbles, whereas only 11 (1.6%) of 695 segments in diatrizoate group showed grade 3 with no segments showing ≥grades 4 (P < .001). The residual colonic fluid was significantly smaller in iohexol group than in diatrizoate group: 138.8 ± 73.9 mL vs. 181.0 ± 93.3 mL, respectively (P = .041). The overall HU was comparable between two groups. Conclusion: Iohexol used for fecal/fluid tagging causes significantly more colonic bubbles, which may hamper diagnostic performance of CTC, but leaves smaller amount of residual colonic fluid than diatrizoate. Other parameters are similar between the two agents. Key Word(s): 1. CT colonography; 2. oral contrast agent

Colonic and Anorectal Disorders O-006 Prospective evaluation of the incidence of sessile serrated adenoma/polyps in hyperplastic polyps diagnosed by pan-chromo with high definition magnifying colonoscopy Presenting Author: WATARU SANO Additional Authors: YASUSHI SANO, MINEO IWATATE, NORIAKI HASUIKE, SANTA HATTORI, HIDEKAZU KOSAKA, TARO IKUMOTO, MASAHITO KOTAKA, TAKAHIRO FUJIMORI Corresponding Author: WATARU SANO Affiliations: Sano Hospital, Sano Hospital, Sano Hospital, Sano Hospital, Sano Hospital, Sano Hospital, Sano Hospital, Shinko Hospital Objective: Colorectal sessile serrated adenoma/polyps (SSA/Ps) are considered precancerous lesions. However, their precise incidence is unclear, and the current treatment strategies for serrated lesions still remain controversial. Through the use of recent image enhancing technique, the accuracy rate for differential diagnosis between non-neoplastic and neoplastic colorectal lesions improved over 90% in real-time histology. The aim of this study was to clarify the incidence of SSA/Ps in hyperplastic polyps (E-HPs) diagnosed by pan-chromo with high definition magnifying colonoscopy. Methods: During colonoscopy, 0.05% indigo carmine dye was sprayed throughout the entire colorectum to highlight the lesions. All detected lesions were diagnosed by narrow-band imaging magnifying observation (260, 290 LUCERA system, OLYMPUS). All lesions were resected endoscopically or surgically, except for rectosigmoid E-HPs ≤5 mm. The number of rectosigmoid E-HPs ≤5 mm was recorded, and some of them were resected endoscopically as tissue samples to confirm the quality assurance of real-time histology in magnifying colonoscopy. Results: A total of 343 patients (male: 42.9%; median age: 61.5 years) participated in this study between June 2013 and May 2014. Among the 3,856 E-HPs (distal colorectum: 96.4%) detected in 294 patients, 792 E-HPs were resected and histopathologically analyzed. The overall incidence of SSA/Ps in E-HPs was 2.7% but increased with the size of the E-HPs (≤5 mm: 0.7%; 6–9 mm: 29.0%; ≥10 mm: 70%). The incidence of SSA/Ps in proximal E-HPs was higher than that in distal E-HPs (proximal colon: 10.9% vs distal colorectum: 0.9%), and there was no SSA/P with cytological dysplasia. The diagnostic accuracy was 95.5% for rectosigmoid lesions resected endoscopically. Conclusion: SSA/Ps are more common in the proximal colon, and their incidence increases with the size of E-HPs. SSA/Ps with cytological dysplasia may be rare in community practice. Key Word(s): 1. hyperplastic polyp; 2. sessile serrated adenoma/polyp

Colorectal cancer mutation detection in clinical practice O-007 Differences in the genetic pathway(s) between Vietnamese and Japanese colorectal cancers Presenting Author: TORU HIYAMA Additional Authors: DUC TRONG QUACH, TOMOHIRO MIWATA, HUY MINH LE, HA NGOC THI HUA, SHIRO OKA, SHINJI TANAKA, KOJI ARIHIRO, MASAHARU YOSHIHARA, KAZUAKI CHAYAMA Corresponding Author: TOMOHIRO MIWATA Affiliations: Na Objective: The incidence of early-onset (in patients under 50 years of age) colorectal cancer (CRC) in Vietnamese patients has been reported to be high. To clarify the characteristics in genetic alterations in Vietnamese CRCs, we investigated the mutations of K-ras and mitochondrial DNA (mtDNA), and high-frequency microsatellite instability (MSI-H) in Vietnamese CRCs and Japanese CRCs as the comparison. Methods: Enrolled were 60 Vietnamese and 233 Japanese patients with invasive CRCs. K-ras mutations were examined with PCR-single-strand conformation polymorphism analysis. mtDNA mutations and MSI-H were examined with microsatellite analysis using D310 and BAT-26, respectively. Results: The frequency of K-ras and mtDNA mutations in the Vietnamese CRCs was significantly higher than that in the Japanese CRCs (8 of 24 [33%] vs 5 of 55 [9%], p = 0.048; 19 of 44 [43%] vs 11 of 133 [9%], p < 0.001, respectively). The frequency of MSI-H in the Vietnamese CRCs was also significantly higher than that in the Japanese CRCs (6 of 27 [22%] vs 10 of 130 [8%], p = 0.030, respectively). Conclusion: These results indicate that Vietnamese CRCs may involve significantly frequent changes in various genes compared with Japanese CRCs, indicating that the genetic pathway(s) of Vietnamese CRCs may differ from that of Japanese CRCs. Key Word(s): 1. colorectal cancer; 2. Vietnamese; 3. Japanese

Endoscopy and Imaging O-008 The usefulness of single-balloon endoscopy for the small bowel lesions Presenting Author: TEPPEI ADACHI Additional Authors: RIE TANAKA, MITSUNARI YAMADA, MASAKI TAKAYAMA, HIROMASA MINE, TOMOYUKI NAGAI, MASANORI KAWASAKI, YUTAKA ASAKUMA, YOSHIHISA OKAZAKI, YORIAKI KOMEDA, TOSHIHARU SAKURAI, SHIGENAGA MATSUI, HIROSHI KASHIDA, MASATOSHI KUDO Corresponding Author: TEPPEI ADACHI Affiliations: Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine Objective: Recently, various forms of endoscopy for the small intestinal examination have been developed. Our purpose is to clarify the usefulness of single-balloon endoscopy for the small bowel lesions. With the advent of balloon enteroscopy and video capsule endoscopy, we now have more


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chance to encounter various small intestinal diseases. The aim of this study is to clarify the present status of small intestinal examination in our institute. Methods: The enteroscopy we use is OLYMPUS SIF TYPE Q260. The capsule is OLYMPUS EC TYPE 1. We evaluated 352 patients who received a total of 561 sessions of single balloon enteroscopy in our hospital from January 2005 to July 2014 (per oral 288 sessions, per anal 273 sessions). Results: The average age was 58 years old (9–89 years old). Male-to-female ratio was 142:92. Main reasons for the examination were OGIB in 190 sessions, Crohn’s disease in 107, suspicion of small bowel tumor in 58, intestinal obstruction in 40 and Peutz-Jeghers syndrome in 26. In OGIB cases, ulcer or erosion was found in 21%, angioectasia in 12%, diverticula in 5%, polyps in 2%, small bowel cancer in 1 patient, and no lesion was detected in 42% of the sessions. The bleeding was treated by clipping in 17% and by APC in 6% of the patients, surgery in 1 patient, and subsided spontaneously in 74% of the cases. In Crohn’s disease, 85 sessions were performed in 37 patients. Stricture was detected in 32% of the examinations. Balloon dilation was conducted in 3 patients. Conclusion: The small bowel examination using single-balloon enteroscopy have been almost established in our hospital. It is especially useful because it can be directly followed by the treatment as hemostasis or dilatation. Key Word(s): 1. small bowel endoscopy; 2. single balloon endoscopy

Endoscopy and Imaging O-009 Comparison of impact of reinforced education between telephone and short message service on the quality of bowel preparation: a prospective, colonoscopist-blinded, randomized, controlled study Presenting Author: KWANG BUM CHO Additional Authors: KYUNG SIK PARK, EUN SUN KIM, EUN SUNG CHOI, SANG MIN LEE Corresponding Author: KWANG BUM CHO Affiliations: Keimyung University Dongsan Medical Center, Keimyung University Dongsan Medical Center, Keimyung University Dongsan Medical Center, Keimyung University Dongsan Medical Center Objective: High-quality bowel preparation is essential for a successful colonoscopy. This study aimed to compare the impact of reinforced education between telephone and short message service on the quality of bowel preparation. Methods: A prospective, endoscopist-blinded, randomized, controlled study was conducted at a tertiary hospital. All subjects received regular instructions on the day of their colonoscopy appointment. Reinforced group was provided with additional education for reminding by telephone (TRE) or short message service (SMS) a day before colonoscopy. The primary outcome was the quality of the bowel preparation according to the Boston Bowel Preparation Scale (BBPS). The secondary outcomes included polyp detection rate (PDR), patients’ compliance and subjective feelings. Results: 390 subjects were included in the study (TRE 126, SMS 127, control 137). Mean scores of BBPS were 7.09 ± 1.15, 6.76 ± 1.29, and 6.31 ± 1.43 in TRE, SMS and control group, respectively (p 80% amount of purgative ingestion (OR, 5.75, p = 0.003) and interval of preparation to colonoscopy time 28 mg/dL (54.6% vs 20.5%, p < 0.0001) was associated with significantly higher intervention rate and MCV 0.05). Conclusion: Most patients of cirrhosis, irrespective of etiology, have vitamin D deficiency. The vitamin D levels further decreases as the severity of cirrhosis progresses from CTP class A to CTP class B and C. These patients may have increased risk of osteoporosis and fractures, and response to vitamin D supplementation should be further studied. Key Word(s): 1. cirrhosis; 2. chronic liver disease; 3. vitamin D deficiency

Liver O-044 The role of VEGF/sVEGFR-2 serum ratio as biomarker angiogenesis in chronic liver disease and hepatocellular carcinoma Presenting Author: NENENG RATNASARI Additional Authors: SITI NURDJANAH, AHMAD HAMIM SADEWA, MOHAMMAD HAKIMI MOHAMMAD HAKIMI Corresponding Author: NENENG RATNASARI Affiliations: Faculty of Medicine Gadjah Mada University, Faculty of Medicine Gadjah Mada University, Faculty of Medicine Gadjah Mada University Objective: The vascular endothelial growth factor (VEGF) ligand and its receptor (VEGFR) are important in angiogenesis process in chronic liver

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disease (CLD) and hepatocellular carcinoma (HCC). Increasing expression of angiogenesis factors in blood or tissue is associated with poor prognosis. The aim of the study is to investigate difference of ratio VEGF/sVEGFR-2 serum as biomarker of progressing disease in CLD and HCC. Methods: A prospective study was conducted in adult (>18 year) subjects who suffered chronic hepatitis (CH) viral (B and C), liver cirrhotic (LC) and HCC. All subjects were enrolled during 2 years study (2012–2013) at Dr. Sardjito General Hospital Yogyakarta Indonesia. Diagnosis was performed based on clinical, laboratory and serologic marker, and liver imaging. The exclusion criteria were severe sepsis, heart failure, renal failure, and non-liver tumor. Serum of VEGF and sVEGFR-2 were examined using Quantikine® HS kit human immunoassay (R&D System, Minneapolis, MN, USA). Data were analyzed by STATA. Kruskall–Wallis and two-sample Wilcoxon rank-sum (Mann–Whitney) test, ROC curve with AUC analyses, and prevalence ratio (PR) were calculated with significant value p < 0.05. Results: There were 77 subjects who agreed to enroll in the study (21 HCC, 19 LC, 20 CH, and 17 healthy. 51 male (66.23%) and 26 female (33.77%), with mean of age 52.12 ± 13.10 year). There was significant difference of serum level of sVEGF-2 and VEGF, and also ratio VEGF/sVEGFR-2 between groups. The mean of ratio VEGF/sVEGFR-2 serum were 0.035 ± 0.018 in CH, 0.034 ± 0.024 in LC, 0.101 ± 0.075 in HCC, and 0.033 ± 0.02 in healthy subject (p = 0.0013). However, significant difference of VEGF/sVEGFR-2 was shown in HCC compared with non HCC (CH, LC and healthy). Based on AUROC curve 0.793 7, showed cut of 0.04 1 (sensi 71.43%; spesi 71.79%) and PR 6.36. Conclusion: There was significance difference of ratio VEGF/sVEGFR-2 in HCC compared with non HCC. In the future, ratio VEGF/sVEGFR-2 can be a biomarker angiogenesis in CLD and HCC. Key Word(s): 1. ratio VEGF/sVEGFR-2; 2. biomarker angiogenesis; 3. chronic liver disease; 4. hepatocellular carcinoma

Liver O-045 Shorter duration of pegylated interferon plus ribavirin therapy for chronic hepatitis c genotype 1 patients who achieve early virological response Presenting Author: GOYAL OMESH Additional Authors: AJIT SOOD, VANDANA MIDHA Corresponding Author: GOYAL OMESH Affiliations: D.M.C. and Hospital, D.M.C. and Hospital Objective: Standard treatment for patients with chronic hepatitis C genotype 1 (CHC G-1) infection includes pegylated interferon plus ribavirin (PEG-RBV) for 48 weeks. Shorter treatment regimen would be more acceptable due to lower cost and fewer side-effects. We aimed to compare the efficacy of 36 week PEG-RBV therapy with standard 48 week therapy in CHC G-1 patients who achieve complete early virological response (cEVR). Methods: Consecutive treatment-naïve patients with CHC G-1 were treated with pegylated interferon α2b (1.5 μg/kg/week) or α2a (180 μg/week) and weight based ribavirin were enrolled. Patients who achieved cEVR at 12 weeks [undetectable HCV RNA irrespective of RVR (rapid virological response)] were randomized into group A (48 weeks therapy) and group B (36 weeks therapy). Primary end-point was achievement of sustained virological response (SVR) at 24 weeks of follow up. Results: Out of the total 166 patients started on PEG-RBV treatment, 112 (69.3%) achieved cEVR, and were randomized into group A (n = 59) and group B (n = 53). Fifty-five (93.2%) patients in group A and 50 (94.3%) in group B completed therapy. The overall SVR rate in group A was 79.6% (47/59) and in group B was 84.9% (45/53) (p = 0.622). SVR rates in the two groups were comparable in all patient sub-groups according to factors like viral load (≤ or >400,000 IU/ml), RVR (achieved/not achieved), age (≤


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or >40 years), body mass index (≤ or >27) and cirrhosis (present/absent). Group B had lower incidence of side-effects as compared to group A. Conclusion: In chronic hepatitis C genotype 1 patients who achieve cEVR, 36 weeks PEG-RBV therapy is as effective as standard 48 week therapy, irrespective of other host or virological factors. Key Word(s): 1. early virological response; 2. shorter therapy; 3. sustained virological response; 4. thirty-six weeks

Liver O-046 The role of coagulopathy variables of bleeding tendency in liver cirrhotic Presenting Author: NENENG RATNASARI Additional Authors: FAHMI INDRARTI, CATHARINA TRIWIKATMANI, PUTUT BAYUPURNAMA, SUTANTO MADUSENO, SITI NURDJANAH SITI NURDJANAH Corresponding Author: NENENG RATNASARI Affiliations: Faculty of Medicine Gadjah Mada University, Faculty of Medicine Gadjah Mada University, Faculty of Medicine Gadjah Mada University, Faculty of Medicine Gadjah Mada University, Faculty of Medicine Gadjah Mada University Objective: Hemostatic abnormalities (coagulopathy) can increase the risk of bleeding in liver cirrhotic (LC) patients, and INR is a predictor of bleeding tendency. Esophageal varices (EV) is one of bleeding site with an annual rate of 5–8%; even the large enough varices have a risk of bleeding in only 1–2% of cases. The aim of study is to investigate correlation between INR and coagulopathy variables of bleeding tendency in liver cirrhotic with or without EV. Methods: 46 adult LC patients with or without EV were agree enrolled the study during a two year period (2012– 2013), at Internal Medicine ward Dr. Sardjito Hospital Yogyakarta, Indonesia. The diagnosis of LC was based on clinical symptoms and liver ultrasound. Exclusion criteria: liver cancer, sepsis, liver congestive, hematology disorder (leukemia, aplastic anemia, idiopathic thrombocytopenia, etc.). Coagulopathy variables that were calculated: INR, thrombocyte, fibrinogen, transaminase enzyme, bilirubin and albumin. Data were analyzed by t-test, correlation, and linear regression, with significant value p < 0.05. Results: Only 42 LC patients were eligibly enrolled into the study, with mean of age 55.17 ± 11.19 year and 31 male patients (73.8%). There were no significant difference mean of INR, thrombocyte, fibrinogen, transaminase enzyme, bilirubin, and albumin in LC with or without EV (p > 0.05). By linear regression using backward method, there were significant correlation between INR with age, thrombocyte, fibrinogen, albumin, and spleen size (p < 0.05) with regression equation: INR = 3.484–0.017(age)-0.002(thrombocyte)-0.001(fibrinogen)-0.162 (albumin)-0.009(spleen size). Conclusion: INR has significant correlation with age, thrombocyte, fibrinogen, albumin, and spleen size. Key Word(s): 1. coagulopathy variables; 2. esophageal varices; 3. bleeding tendency; 4. liver cirrhotic

Liver O-047 Acute on chronic liver failure due to acute hepatic insult: an eastern perspective Presenting Author: SHALIMAR Additional Authors: DHARMENDRA KUMAR, PADMAPRAKASH KADAVOOR VADIRAJ, BAIBASWATA NAYAK, BHASKAR THAKUR, SUBRAT KUMAR ACHARYA Corresponding Author: SHALIMAR Affiliations: All India Institute of Medical Sciences, All India Institute of Medical Sciences, All India Institute of Medical Sciences, All India Institute of Medical Sciences, All India Institute of Medical Sciences Objective: In acute on chronic liver failure (ACLF), the effect of distinct etiologies, underlying silent or overt chronic liver disease and other predictors of prognosis, is not clear in eastern patients. Methods: In a prospective study, 213 consecutive ACLF patients were evaluated until death or discharge. Etiology of acute hepatic insult, underlying silent or overt chronic liver disease (CLD), organ failure (OF), other complications and disease outcomes were evaluated, and prognostic scores including model for end stage liver disease (MELD), acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) were calculated. Results: The most common causes of acute hepatic insult were alcohol, hepatitis B virus (HBV) and hepatitis E virus (HEV) in 77 (33.3%), 42 (19.7%) and 39 (18.3%) cases respectively. The etiology of CLD was alcohol, HBV and cryptogenic in 85 (40%), 52 (24%) and 50 (23%) cases. The mortality in HEV-ACLF was significantly lower (12.8% versus 33%-54% in other etiologies; p < 0.001). With similar SOFA, APACHE II and MELD scores, the mortality was 33.9% in the silent CLD group (112, 52.6% cases) as compared with 53.5% in the overt CLD group (101, 47.4%; p = 0.005). Independent predictors of mortality included hepatic encephalopathy (early, OR: 6.01; advanced, OR: 18.36), renal failure (creatinine > 1.5 mg/dl, OR: 9.68), elevated serum arterial ammonia (>92 μmol/L, OR: 4.30) and etiology of acute hepatic insult (HBV, OR: 10.266; alcohol, OR: 35.52 and cryptogenic, OR: 10.39). With increasing number of organ failures, the mortality increased linearly (p = 0.001). Conclusion: The etiology of acute hepatic insult, silent underlying CLD and occurrence of OF are important predictors of outcome in ACLF. Important causes include alcohol and hepatitis viruses. Key Word(s): 1. hepatitis E virus; 2. organ failure; 3. superinfection; 4. ammonia; 5. reactivation

Liver O-048 Indocyanine green as a predictor of development of post transarterial chemoembolisation liver failure Presenting Author: SHALIMAR Additional Authors: SUSHIL JAIN, SHIVANAND RAMACHANDRA GAMANAGATTI, SHASHI PAUL, SUBRAT KUMAR ACHARYA Corresponding Author: SHALIMAR Affiliations: All India Institute of Medical Sciences, All India Institute of Medical Sciences, All India Institute of Medical Sciences, All India Institute of Medical Sciences Objective: Post transarterial chemoembolisation (TACE) liver failure occurs in up to 60% of hepatocellular carcinoma (HCC) patients. No


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objective parameter predicts the risk. In a prospective study, we assessed the role of Indocyanine green (ICG) in predicting post TACE liver failure. Methods: ICG test was done on the day of the TACE. ICG-PDR and R-15 were recorded and assessed as predictors of development of liver failure post procedure. Results: 58 patients were included, mean age ± SD was 54.6 ± 12.8 years, 50 (86%) were males and all patients had underlying cirrhosis. The most common etiology of cirrhosis was hepatitis B in 60%, followed by hepatitis C and alcohol in 17% and 7% respectively. The child class was A in 55% and B in 45% patients. Post TACE liver failure developed in 28% patients. The median ± SD plasma disappearance rate (PDR) in patients developing liver failure was 7.7 ± 3.9%/min versus 13.4 ± 6.0%/min in those who did not develop liver failure (p = 0.001). The median R15 value in patients developing liver failure was 35.9 ± 18.2% vs 19.2 ± 14.4% in those who did not develop liver failure (p = 0.001). The area under the curve for R15 as a predictor of liver failure was 0.77. A cut off value of 23.4% predicts the development of liver failure with a sensitivity of 68.8% and specificity of 70%. Conclusion: ICG is a useful predictor of development of liver failure in patients undergoing TACE. Key Word(s): 1. TACE; 2. liver failure; 3. ICG; 4. PDR; 5. R15

Liver O-049 Acute liver failure due to hepatitis e virus infection has a better survival rate Presenting Author: SHALIMAR Additional Authors: SUBRAT KUMAR ACHARYA Corresponding Author: SHALIMAR Affiliations: All India Institute of Medical Sciences Objective: Acute liver failure (ALF) is associated with a high mortality. The difference in outcomes between different etiologies is not clear. We analysed the outcomes of consecutive ALF patients admitted at a single tertiary-care centre over a period of 25 years. Methods: All consecutive patients of ALF patients were managed till death or discharge. Results: A total of 1393 patients were evaluated. Out of these 787 (56.5%) were females. The mean age ± SD was 28.4 ± 11.7 years. Among the different etiologies of ALF, non A non E hepatitis viruses were the most common (38.1%), followed by hepatitis E virus (28.3%), hepatitis B virus (8.2%), antitubercular drugs (4.7%) and hepatitis A virus (1.4%). Only chronic markers were present in 9.6% and no etiological data were available in 5% of the patients. A total of 822 (59.0%) patients died. The survival among different etiologies was as follows: hepatitis A virus (65.0%), hepatitis E virus (53.3%), acute hepatitis B virus (33.3%), Non-A, Non-E hepatitis viruses (38.2%), dual infection (30.8%), ATT (29.2%) and in those with only chronic markers (29.1%)(p < 0.001). Conclusion: Hepatitis E virus infection is an important cause of ALF among adults and, among the different viral etiologies, it is associated with a better survival rate. Key Word(s): 1. hepatitis E; 2. non A-non E; 3. hepatitis A

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Liver O-052 Trans-arterial chemoembolization as a viable alternative to radiofrequency ablation: a study on early to intermediate hepatocellular carcinoma in an Asian population Presenting Author: YOCK YOUNG DAN Additional Authors: JIA CHEN LIM, CHERN HAO CHONG, ALFRED KOW, SHRIDAR GANPATHI, STEPHEN CHANG, MAUREEN DA COSTA, KRISHNAKUMAR MADHAVAN, SENG GEE LIM, YOCK YOUNG DAN Corresponding Author: WEI RONG BENJAMIN TAY Affiliations: National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore Objective: Radiofrequency ablation (RFA) is the locoregional therapy of choice recommended by international guidelines for early unresectable tumours, with trans-arterial chemoembolization (TACE) reserved for intermediate unresectable tumors. In many centers, however, TACE has been used successfully for early unresectable tumors either due to technical limitation or following patients’ choice. Our study goes beyond the guidelines to compare real world clinical outcomes of early to intermediate HCC treated by TACE or RFA in an Asian cohort. Methods: Our study was a retrospective cohort analysis of 248 patients with unresectable BCLC stage A0 to B hepatocellular carcinoma at the National University Hospital Singapore. The decision for TACE or RFA was based primarily on tumor location, technical accessibility for RFA, patients’ choice and number of nodules. Tumor analysis was stratified for size, BCLC stage and nodularity. Outcome measures were complete response, number of treatments required, time to progression and overall survival. Results: From the cohort, 190 patients underwent TACE, while 58 were treated with RFA. Lesions less than 2 cm required 1.92 (SEM 0.12) locoregional treatments, while those larger than 3 cm required a mean of 2.14 (SEM 0.172). There was no significant difference between TACE and RFA for these sizes. RFA needed significantly fewer treatments for lesions 2–3 cm (p = 0.041) with a mean of 1.43 (SEM 0.138) compared to 2.02 (SEM 0.178) for TACE. The chance for complete response was significantly higher for RFA compared to TACE (3 cm, p = 0.001) by Chi-square tests. There was a significantly longer time to progression for TACE in lesions 3 cm. Finally, no significant difference in survival was noted across all tumor sizes and BCLC classes. Conclusion: RFA appears to be superior to TACE by providing a significantly better chance for immediate complete response for lesions of all sizes while requiring fewer number of treatments for lesions 2–3 cm. However, there is no survival advantage between the two treatment modalities. In addition, time to progression in TACE compared favorably in contrast to RFA in lesions 50 μmol/L (p = 0.015), cirrhosis at diagnosis (p = 0.026) and nonresponder according to Barcelona criteria (p = 0.04) were independent predictors of poor outcomes. Conclusion: This is the largest PBC cohort study in Singapore. Although PBC predominantly affects female, male patients have a worse prognosis. Baseline bilirubin >50 μmol/L and cirrhosis at diagnosis independently predict poorer transplant free survival. Barcelona criteria predict survival better than Paris 1 and 2 criteria in this Singapore cohort. Key Word(s): 1. primary; 2. biliary; 3. cirrhosis; 4. liver; 5. Singapore; 6. survival; 7. outcomes

Objective: Serum uric acid is significantly elevated in patients with nonalcoholic fatty liver disease (NAFLD). However, whether this elevation is causally or coincidentally associated with NAFLD remains uncertain, neither the mechanisms behind this association are unclear so far. Methods: For evaluating the effect of uric acid on development of hepatic steatosis, mice were randomly divided into four groups of eight each, feeding standard chow, high fat diet (HFD), hyperuricemia-inducing diet, or HFD combined with hyperuricemia-inducing diet, respectively. To establish a cellular model of hepatic steatosis, HepG2 cells were exposed to a mixture of free fatty acids (FFA) for 48 hours. For evaluating the effects of uric acid on development of hepatic steatosis, HepG2 cells were exposed to different concentrations of uric acid for 48 hours. The mRNA and protein expression of NLRP3 inflammasome-related molecules were detected using real-time PCR, Western blot and ELISA. Small interfering RNA(siRNA) was used to knock down NLRP3 level. Results: Mice fed 8 weeks of hyperuricemia-inducing diet showed significant higher serum uric acid and triglyceride levels than those in mice fed standard chow. Consistent with serum alterations, we observed a significant higher intrahepatic triglyceride content in mice fed hyperuricemia-inducing diet than that in mice fed standard chow. Furthermore, the supplementary of 2% oxonic acid and 3% uric acid to HFD induced more remarkable hyperuricemia, higher serum triglyceride level, and higher intrahepatic triglyceride content compared with the mice fed HFD alone. Increased intrahepatic fat accumulation was confirmed by H&E and Oil Red O staining of liver sections. In vitro, adding 500 μmol/L or 750 μmol/L uric acid to culture medium induced significant intracellular triglyceride accumulation in HepG2 cells. Further, uric acid dose-dependently aggravated FFA-induced intracellular triglyceride accumulation in HepG2 cells. Then, we found significant increases of NLRP3 inflammasome-related molecules, both mRNA and protein levels, including NLPR3, caspase-1, IL-1β, and IL-18, in HepG2 cells stimulated with uric acid compared with unstimulated control cells. To further examine the role of NLRP3 in uric acid induced fat accumulation, inhibition of NLRP3 expression significantly ameliorated uric acid-induced fat accumulation in HepG2 cells. Meanwhile, we also found that uric acid induced significant elevations of IL-1β and IL-18 levels in culture supernatants of HepG2 cells compared with those from unexposed controls. Consistent with in vitro results, mice fed 8 weeks of hyperuricemia-inducing diet resulted in significant up-regulation of hepatic mRNA and protein expressions of NLPR3, caspase-1, IL-1β and IL-18, and elevation of serum IL-1β and IL-18 levels in mice. The development of NAFLD is a complex process resulting from the interaction of multiple genetic, environmental and metabolic factors. We previously reported that serum uric acid levels are significantly elevated in patients with NAFLD, and an elevation of serum uric acid increases the risk for incident NAFLD. However, whether uric acid is causally or coincidentally


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associated with NAFLD remains to be determined. The current study shows that uric acid directly induces hepatocyte fat accumulation both in HepG2 cells and in mice, suggesting that uric acid has a causal effect on development of hepatic steatosis. The mechanism behind the association between uric acid and NAFLD is required to be explored. NLRP3 inflammasome activation is involved in pathogenesis of obesity, obesity related metabolic diseases such as diabetes, atherosclerosis, and NAFLD. Uric acid is reported to participate in NLRP3 inflammasome activation , indicating a potential association between uric acid and NLRP3 inflammasome in NAFLD. In this study, we found that uric acid induces NLRP3 inflammasome activation both in HepG2 cells and in mice, whereas inhibition of NLRP3 expression ameliorates uric acid induced fat accumulation in HepG2 cells. These data indicate that uric acid has a regulatory effect on NLRP3 inflammasome activation, and NLRP3 inflammasome activation may be essential for the regulatory effect of uric acid on fat accumulation in hepatocytes. Conclusion: Our results suggest that uric acid-NLRP3 inflammasome axis contributes to hepatic steatosis. Key Word(s): 1. fatty liver; 2. uric acid; 3. NLRP3 inflammasome

Liver O-054 IL28B and PNPLA3 polymorphisms and treatment response in patients infected with genotype 6 hepatitis C virus (HCV) Presenting Author: GRACE LAI-HUNG WONG Additional Authors: HENRY LIK YUEN CHAN, POLLY OI YING CHAN, JOE CHO YIU CHENG, JACKIE SIU WOON CHENG, SHARON HOI YING LAU, ELBERT KAM YEUNG LEE, JUSTIN MING YIN MA, CHI HANG TSE, VINCENT WAI SUN WONG Corresponding Author: GRACE LAI-HUNG WONG Affiliations: The Chinese University of Hong Kong, The Chinese University of Hong Kong, The Chinese University of Hong Kong, The Chinese University of Hong Kong, The Chinese University of Hong Kong, The Chinese University of Hong Kong, The Chinese University of Hong Kong, The Chinese University of Hong Kong, The Chinese University of Hong Kong Objective: To test the hypothesis that interleukin-28B (IL28B) and patatin-like phospholipase domain containing 3 (PNPLA3) polymorphisms are associated with the disease severity and treatment response in Chinese chronic hepatitis C (CHC) patients in Hong Kong. Methods: This was a retrospective-prospective cohort study. Consecutive patients infected by genotype 6 HCV were included in the study group, and those infected by genotype 1 HCV acted as the control group. Host IL-28B- associated single-nucleotide polymorphisms (SNPs: rs12979860 and rs8099917) and PNPLA3 genotype were tested. The primary outcome was sustained virologic response (SVR), defined as undetectable HCV RNA by a sensitive assay at the end of a 24-week follow-up period after treatment completion. Results: 37 patients infected by genotype 6 HCV and 66 by genotype 1 HCV were recruited. Their mean age was 57 years, 64% were male. Mean baseline HCV RNA was 5.93 log IU/ml; 74 patients (80%) received standard treatment of peginterferon and ribavirin for 24 to 48 weeks. The SVR for patients infected by genotype 1 and 6 HCV was 90% and 48%, respectively. The proportions of IL28B genotypes were 80%, 19%, and 1% for TT/TG/GG at rs8099917 and 82%, 17%, and 1% for CC/CT/TT at rs12979860, respectively. The proportions of PNPLA3 genotypes were 49%, 39%, and 12% for CC/GC/GG. IL28B genotype was significantly associated with SVR, with 91% of patients achieving SVR carried TT at rs8099917. Instead PNPLA3 genotype was not associated

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with SVR. Conclusion: IL28B gene with rs8099917 T allele and HCV genotype 6 were two strong predictors of SVR in Chinese CHC patients. Key Word(s): 1. hepatitis C; 2. IL-28B; 3. PNPLA3

H. pylori O-055 Comparison of Japanese primary and secondary regimen of Helicobacter pylori eradication Presenting Author: TEPPEI ADACHI Additional Authors: RIE TANAKA, MITSUNARI YAMADA, MASAKI TAKAYAMA, HIROMASA MINE, TOMOYUKI NAGAI, MASANORI KAWASAKI, YUTAKA ASAKUMA, YOSHIHISA OKAZAKI, YORIAKI KOMEDA, TOSHIHARU SAKURAI, SHIGENAGA MATSUI, HIROSHI KASHIDA, MASATOSHI KUDO Corresponding Author: TEPPEI ADACHI Affiliations: Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine, Kindai University Faculty of Medicine Objective: The eradication of H.pylori has been done frequently and successfully in many countries. However, increasing resistance to antibiotics has been reported recently. The aim of this study is to establish a more successful way of H. pylori eradication in the view of resistance to the antibiotics. Methods: We evaluated the 711 courses in 623 patients who underwent Helicobacter pylori eradication therapy from January 2011 to October 2013 in our hospital. As the primary eradication regimen, we used amoxicillin, clarithromycin (CAM), and Proton pump inhibitor (PPI). As the secondary eradication regimen, we used metronidazole (MNZ), amoxicillin, and PPI. The major outcome was positive or negative urea breath test 2 months after the treatment course. Results: The patients’ gastrointestinal morbidities were chronic gastritis in 244, peptic ulcer in 220, early gastric cancer (which was treated endoscopically) in 74, and others in 85 patients. Primary eradication was adopted in 489 courses, and secondary regimen in 222 courses. We calculated the yearly success rate of eradication. That for primary regimen in year 2011, 2012 and 2013 was 60.9%, 64.2% and 71.7% (the average was 65.6%). That for the secondary regimen was 93.8%, 93.5% and 88.4% (the average was 91.1%). The rate of resistance to CAM was increased every year. The success rate of eradication for the primary regimen was 85.2% in CAM susceptible cases, but it was significantly low at 21.8% in CAM resistant cases. On the other hand, that for the secondary regimen was not different in both CAM susceptible and resistant cases (91.5% vs. 92.3%). The resistance to MNZ was 2.6% (1/38). Conclusion: In order to eradicate H. pylori, susceptibility to antibiotics should be examined before the treatment and the secondary regimen should be selected from the beginning. Key Word(s): 1. H. pylori; 2. eradication


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O-056 Effect of bifidobacterium longum on PPI-based triple therapy for eradication of Helicobacter pylori: a prospective, randomized study Presenting Author: TANED CHITAPANARUX Additional Authors: SATAWAT THONGSAWAT, PISES PISESPONGSA, APINYA LEERAPUN, PHURIPONG KIJDAMRONGTHUM Corresponding Author: TANED CHITAPANARUX Affiliations: Chiang Mai University, Chiang Mai University, Chiang Mai University, Chiang Mai University

O-057 Eradication of H. pylori infection in patients allergic to penicillin Presenting Author: TAKAHISA FURUTA Additional Authors: MITSUSHIGE SUGIMOTO, MIHOKO YAMADE, TAKAHIRO UOTANI, SHU SAHARA, HITOMI ICHIKAWA, TAKUMA KAGAMI, YASUSHI HAMAYA, MORIYA IWAIZUMI, SATOSHI OSAWA, KEN SUGIMOTO Corresponding Author: TAKAHISA FURUTA Affiliations: Hamamatsu University School of Medicine, Hamamatsu University School of Medicine, Hamamatsu University School of Medicine, Hamamatsu University School of Medicine, Hamamatsu University School of Medicine, Hamamatsu University School of Medicine, Hamamatsu University School of Medicine, Hamamatsu University School of Medicine, Hamamatsu University School of Medicine,Hamamatsu University School of Medicine

Objective: The failure rate of Helicobacter pylori (H. pylori) eradication imposes the assessment of new options. The aim of this study was to evaluate whether the addition of Bifidobacterium longum to PPI-based triple therapy beneficially affects H. pylori eradication rates and the side effects of triple therapy. Methods: This was a prospective, randomized, double blind placebo controlled study including 63 dyspeptic patients with H. pylori infection. Patients were randomized into two groups: 32 patients (control group) and 31 patients (test group). Both groups were treated with the standard triple therapy (esomeprazole, amoxicillin, clarithromycin) for 7 days. In a double blind study, patients received placebo or Bifidobacterium longum in capsules, twice a day for 4 weeks. Successful eradication therapy was defined as a negative 13C urea breath test 4 weeks after completion of the treatment. Results: According to intention-to-treat analysis, the infection was eradicated in 28/31 (90.32%) from test group and in 22/32 (68.79%) from control group, respectively. Per-protocol analysis showed 28/30 (93.33%) from test group and 22/30 (73.33%) from control group to have been successfully treated. Significant differences were noted according to the results of the ITT and PP analysis. One (3.23%) patient in the test group and eight (25%) patients in the control group experienced diarrhea (P = 0.027). Nausea, taste disturbance and epigastric pain were similar in both groups. Conclusion: The supplementation of probiotic Bifidobacterium longum on standard PPI-based triple therapy for the eradication of H. pylori infection resulted in better eradication rate and improved anti-H. pylori antibiotherapy-associated diarrhea. Key Word(s): 1. Helicobacter pylori; 2. probiotics; 3. PPI-based triple therapy

Objective: Eradication of H. pylori in patients allergic to penicillin should be performed by the regimens without penicillin derivatives. We have treated such patients with the triple therapy with a proton pump inhibitor and two antimicrobial agents selected from clarithromycin, metronidazole, minocycline and sitafloxacin. We here report the results of eradication rates in patients allergic to penicillin. Methods: A total of 56 patients allergic to penicillin who underwent the H. pylori eradication therapy from June 2007 to June 2014 were analyzed retrospectively. Before November 2008, they were treated with a PPI bid, clarithromycin 200 mg bid and metronidazole 250 mg bid (Triple PPI/CAM/MNZ therapy) for 1 or 2 weeks when they were infected with clarithromycinsensitive strains of H. pylori. Patients infected with clarithromycinresistant strains were treated with a PPI bid, minocycline 100 mg bid and metronidazole 250 mg bid for 1 week (Triple PPI/MINO/MNZ therapy). After November 2008, most of them were treated with a PPI bid (or qid for CYP2C19 rapid metabolizers), sitafloxacin 100 mg bid and metronidazole 250 mg bid (Triple PPI/STFX/MNZ therapy) for 1–2 weeks. At 4–8 weeks after the treatment, they underwent the [ 13 C]-urea breath test for the judgment of success or failure of eradication. Adverse events were searched based on the medical records. Results: The over all eradication rate was 92.9% (52/56, 95% CI = 82.7%-98.0%). The eradication rates with the triple PPI/CAM/MNZ for 1 or 2 weeks were 86.7% (13/15, CI = 59.5%-98.3%) and 100.0% (2/2, CI = 22.3%-100.0%). That with the triple PPI/MINO/MNZ therapy for 1 week was 66.7% (2/3. CI = 9.4%-99.2%). That with the triple PPI/STFX/MNZ for 1 or 2 weeks was 95% (19/20, CI = 75.1%-99.9%) and 100.0% (16/16, CI = 82.9%100.0%). Moderate dizziness was observed in 2 of 3 patients in the triple PPI/MINO/MNZ therapy. Mild diarrhea was also observed in approximately half of patients in all regimens. Conclusion: Based on our previous results, the triple therapy with a PPI, metronidazole and sitafloxacin for 1 week is well tolerated and effective for eradication of H. pylori in patients allergic to penicillin. However, an appropriate prospective study is needed to verify our conclusion. Key Word(s): 1. H. pylori; 2. sitafloxacin; 3. penicillin allergy


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H. pylori O-058 12-day reverse hybrid therapy versus 12-day standard triple therapy for Helicobacter pylori infection – a multi-center, randomized, controlled trial Presenting Author: PING-I HSU Additional Authors: DENG CHYANG WU, SUNG SHUO KAO, FENG WOEI TSAY Corresponding Author: PING-I HSU Affiliations: Kaohsiung Medical University Hospital, Kaohsiung Veterans General Hospital, Kaohsiung Veterans General Hospital Objective: Hybrid therapy is a novel emerging method for H pylori eradication. Reversing the sequence of drug administration of hybrid therapy is beneficial for doctors to prescribe regimen and for patients to adequately take medicines. The aim of this study was to compare the efficacies of 12-day reverse hybrid therapy and 12-day standard triple therapy. Methods: Consecutive H pylori-infected subjects were randomly assigned to receive either a 12-day reverse hybrid therapy (pantoprozole plus amoxicillin, clarithromycin and metronidazole twice daily for 7 days followed by pantoprazole plus amoxicillin twice daily for an additional 5 days) or a 12-day standard triple therapy (pantoprazole plus amoxicillin and clarithromycin twice daily for 12 days). H pylori status was examined 6 weeks after the end of treatment. Results: 402 H pylori-infected participants were randomized to receive a reverse hybrid (n = 200) or a 12-day standard triple (n = 202) therapy. Reverse hybrid therapy achieved a higher eradication rate than standard triple therapy (95.5% vs 88.6%; P = 0.011) by intention-to-treat analysis. Per-protocol analysis showed similar results (95.9% vs 88.5%; P = 0.007). The two treatments exhibited similar frequencies of adverse events (15.0% vs 8.9%, respectively) and drug compliance (97.0% vs 99.0%, respectively). In the standard therapy group, the patients with clarithromycin-resistant strains had a lower eradication rate than those with clarithromycin-susceptible strains (28.6% vs 96.2%). In the hybrid therapy group, there were no differences in eradication rates between patients with clarithromycin-resistant and -sensitive strains (90.0% vs 98.5%). Conclusion: 12-day reverse hybrid therapy achieves a higher eradication rate than 12-day standard triple therapy. Key Word(s): 1. Helicobacter pylori; 2. hybrid therapy; 3. reverse; 4. sequential therapy; 5. antibiotic resistance

H. Pylori O-059 Is standard triple therapy for H.pylori failing in Asia? Presenting Author: ANIL JOHN Additional Authors: AL KAABI SAAD, DOIPHODE SANJAY, PETER MALFERTHEINER, COSIMA LANGNER, RAFIE YACOUB, RAGESH BABU, HAMID WANI, KHALID EEIJJI, MANIK SHARMA, MOUTAZ DERBALA Corresponding Author: ANIL JOHN Affiliations: Hamad Medical Corporation, Hamad Medical Corporation, Otto-Von-Guericke University, Hamad Medical Corporation, Hamad Medical Corporation, Hamad Medical Corporation, Hamad Medical Corporation, Hamad Medical Corporation, Hamad Medical Corporation, Hamad Medical Corporation Objective: H. pylori eradication rates show a steady decline over the past decade attributable to antibiotic resistance. Maastricht 4 guidelines recom-

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mends mapping of local antibiotic resistance pattern and to avoid empirical standard triple therapy when clarithromycin reistance exceeds 20%. Our aim was to study our H. pylori eradication rates with standard triple therapy and study our local antibiotic resistance pattern. Methods: Patients who underwent gastroscopy and found to have positive rapid urease test were given empirical standard triple therapy and eradication rates assessed by urea breath test. We also isolated H. pylori strains by culture at a reference laboratory and antibiotic resistance pattern was studied. Results: 789 patients fulfilling inclusion criteria underwent gastroscopy during study period, of which 279 (35.35%) were rapid urease test positive. Of the 268 patients who were administered standard triple therapy, 115 returned for urea breath test, 4 weeks after stopping treatment. Only 81 patients had a negative test, indicating 70% eradication rates, which was suboptimal. Others are still awaiting the post-treatment 4 week period to elapse and then undergo urea breath test. Clarithromycin resistance was 21.2%, contributing to low eradication rates (Table 1). Conclusion: We have suboptimal eradication rates with standard triple therapy which can be attributed to high clarithromycin, resistance and we need to avoid indiscriminate and empirical use of standard triple therapy as first line therapy for H. pylori eradication in regions of high clarithromycin resistance. Key Word(s): 1. H. pylori; 2. clarithromycin resistance; 3. H. pylori eradication Table 1. Eradication therapies

N

Number of patients with H. pylori strains

Percentage of resistant isolates (%)

95% CI*

Amoxicillin Clarithromycin Metronidazole Levofloxacin Tetracycline Rifabutin

105 104 105 104 105 105

3 22 82 16 0 5

2.9 21.2 78.1 15.4 0.0 4.8

0.59–8.12 13.76–30.26 68.97–85.58 9.06–23.78 0.00–3.45 1.56–10.76

H. pylori O-060 Hybrid therapy versus sequential therapy: which one is better for h pylori eradication? – a meta-analysis of randomized controlled trials Presenting Author: SUNG SHUO KAO Additional Authors: FENG WOEI TSAI, KWOK HUNG LAI, DENG CHYANG WU, PING I HSU Corresponding Author: SUNG-SHUO KAO Affiliations: Kaohsiung Veterans General Hospital, Kaohsiung Veterans General Hospital, Kaohsiung Medical University Hospital, Kaohsiung Veterans General Hospital Objective: Background and Aims: Hybrid therapy and sequential therapy are two novel treatments for H pylori infection. Only in the past few years have well designed trials comparing the two therapies become available but the results are controversial. The aim of this study was to assess the efficacy of hybrid therapy with that of sequential therapy by a meta-analysis. Methods: A comprehensive literature search using PubMed, Ovid and HealthSTAR for randomized controlled studies comparing the efficacy of hybrid therapy with sequential therapy was performed. The eradication rates of hybrid therapy and sequential therapy were pooled, and odds ratios (OR) were calculated. The eradication rates were considered both on an intention-to-treat (ITT) and on a per-protocol (PP) basis. Results: We identified 5 randomized controlled trials (1244 subjects) comparing hybrid


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therapy (617 subjects) and sequential therapy (627 subjects). The PP eradication rates were 92.5% in hybrid therapy and 87.6% in sequential therapy. ITT eradication rates of hybrid and sequential therapies were 87.2% and 84.5%, respectively. Meta-analysis demonstrated that hybrid therapy was superior to sequential therapy by PP analysis (OR of 1.741; 95% CI: 1.173–2.584; P = 0.005). However, the superiority of hybrid therapy over sequential therapy was insignificant by ITT analysis (OR of 1.741; 95% CI: 1.173–2.584; P = 0.117). Conclusion: According to PP analysis, hybrid therapy appears to be more effective than sequential therapy. Key Word(s): 1. Helicobacter pylori; 2. hybrid therapy; 3. sequential therapy; 4. eradication rate

H. Pylori O-061 The trend in helicobacter pylori eradication rates by first-line triple therapy and related factors in eradication therapy Presenting Author: SUNG EUN KIM Additional Authors: MOO IN PARK, SEUN JA PARK, WON MOON, HYE JUNG KWON, YOUN JUNG CHOI, JAE HYUN KIM Corresponding Author: SUNG EUN KIM Affiliations: Kosin University College of Medicine, Kosin University College of Medicine, Kosin University College of Medicine, Kosin University College of Medicine, Kosin University College of Medicine, Kosin University College of Medicine Objective: Trends in successful eradication of Helicobacter pylori by first-line triple therapy, comprised of a proton pump inhibitor, amoxicillin, and clarithromycin, have been understudied. We will evaluate H. pylori eradication rates in a single center during the last ten years and identify risk factors related to eradication failure. Methods: This study included 1,413 patients who were diagnosed with H. pylori infection and received 7 days of triple therapy between January 2003 and December 2012. We retrospectively investigated H. pylori eradication rates with respect to the year of therapy as well as demographic and clinical factors. H. pylori eradication was confirmed by a 13C-urea breath test or a rapid urease test at least 4 weeks after the completion of triple therapy. Results: The overall H. pylori eradication rate was 84.9%. Annual eradication rates from 2003 to 2012 were 93.5%, 80.0%, 87.2%, 88.5%, 92.0%, 88.3%, 85.7%, 84.1%, 83.7%, and 78.8% respectively, by per-protocol analysis. The eradication rate in first-line triple therapy decreased during the last ten years (p = .015). Multivariate analysis showed that female sex (OR 1.69; 95% CI 1.12–2.55) and smoking (OR 1.61; 95% CI 1.05–2.47) were associated with the failure of H. pylori eradication therapy. Conclusion: The efficacy of first-line triple therapy for H. pylori infection has decreased during the last ten years, which suggests an increase in antibiotic resistant H. pylori strains. Therefore, other first-line therapies may be necessary for H. pylori eradication in the near future. Key Word(s): 1. Helicobacter pylori; 2. first-line triple therapy; 3. eradication rates

H. pylori O-062 Systemic review and meta-analysis: is a regimen containing tetracycline and amoxicillin suitable for Helicobacter pylori infection? Presenting Author: ZHIFA LV Additional Authors: ZHIFA LV, YONG XIE, FUCAI WANG Corresponding Author: YONG XIE Affiliations: First Affiliated Hospital of Nanchang University, First Affiliated Hospital of Nanchang University, First Affiliated Hospital of Nanchang University Objective: To conduct a systematic review and meta-analysis of clinical trials with treatment in one study arm including both tetracycline and amoxicillin for eradication of Helicobacter pylori, thus providing clinical practice guidelines for successful eradication worldwide. Methods: Pubmed, Embase, Cochrane Central Register of Controlled Trials, Science Citation Index,China National Knowledge Infrastructure, Wanfang, and Chinese Biomedical Literature databases and abstract books of major European, American, and Asian gastroenterological meetings were searched. All clinical trials that examined the efficacy of Helicobacter pylori eradication therapies and included both tetracycline and amoxicillin in one study arm were selected for this systematic review and metaanalysis. Statistical analysis was performed with Comprehensive MetaAnalysis Software (Version 2). Subgroup, meta-regression, and sensitivity analyses were also carried out. Results: Thirty-three studies met the inclusion criteria. The pooled odds ratio (OR) was 0.90 (95% confidence interval: 0.42, 1.78) for quadruple therapy with amoxicillin and tetracycline versus other quadruple regimens, and total eradication rates were 78.1% by intention-to-treat (ITT) and 84.5% by per-protocol (PP) analyses in the experimental groups. The pooled eradication rates of 14-day quadruple regimens with a combination of amoxicillin and tetracycline were 82.3% by ITT and 89.0% by PP, and those of 10-day regimens were 84.6% by ITT and 93.7% by PP. ORs by ITT were 1.21 (95% CI: 0.64, 2.28) for triple regimens with amoxicillin and tetracycline versus other regimens and 1.81 (95% CI: 1.37, 2.41) for sequential treatment with amoxicillin and tetracycline versus other regimens, respectively. Conclusion: The effectiveness of regimens employing amoxicillin and tetracycline for Helicobacter pylori eradication is not inferior to that of control regimens. Ten- or 14-day quadruple regimens with amoxicillin and tetracycline can achieve acceptable or good eradication rates and are suitable for the treatment of Helicobacter pylori infection. Key Word(s): 1. Helicobacter pylori; 2. amoxicillin; 3. tetracycline; 4. systemic review; 5. meta-analysis

H. pylori O-063 Meta-analysis: the efficacy and safety of probiotics as adjuvant agent for helicobacter pylori infection Presenting Author: ZHIFA LV Additional Authors: ZHIFA LV, BEN WANG, YONG XIE Corresponding Author: YONG XIE Affiliations: First Affiliated Hospital of Nanchang University, First Affiliated Hospital of Nanchang University, First Affiliated Hospital of Nanchang University Objective: To determine whether probiotics could help to improve the eradication rates and reduce side effects, and to investigate the appropriate time, and duration to add the probiotics during anti-H. pylori treatment,


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thus provide clinical practice for eradication success worldwide. Methods: By searching Pubmed, Embase, the Cochrane Central Register of Controlled Trials, and the Science Citation Index, we selected for meta analysis all the randomized control trials (RCTs) comparing probiotics as an adjuvant agent of standard triple regimes with placebo or no treatment during anti-H. pylori. Statistical analysis was performed with the Comprehensive Meta Analysis Software (Version 2). Subgroup, meta-regression and sensitivity analyses were also carried out. Results: Twenty-one RCTs involving a total of 3814 participants met the inclusion criteria. The pooled eradication rates of the probiotic group were 80.3% (1709/2128) by intention-to-treat (ITT) and 83.8% (1709/2039) by pro-protocol (PP), the pooled relative risk (RR) by ITT for probiotics supplementation versus without probiotics was 1.12 [95% confidence interval (CI): 1.06, 1.19]. There was also a reduced risk of overall H. pylori therapy-related adverse effects (RR = 0.60, 95% CI: 0.39, 0.92). The subgroup analyses showed that the supplement before or after regimens all improved eradication rates for H. pylori infection. The more than 2 weeks duration of probiotic treatment, lactobacillus and multiple strains made significant difference in efficacy. Conclusion: Supplementation with probiotics for H. pylori eradication may be effective in increasing eradication rates and decreasing therapy-related side effects. In addition, probiotics appear to have better effects on eradication rates in timing of before or after regimens; more than 2 weeks duration of probiotics administered appear to better eradication effectiveness. Key Word(s): 1. probiotics; 2. Helicobacter pylori; 3. adjuvant treatment; 4. meta-analysis

H. pylori O-064 Efficacy and safety of hybrid therapy for helicobacter pylori infection: a systematic review and meta-analysis Presenting Author: BEN WANG Additional Authors: YOU HUA WANG, YONG XIE, ZHI FA LV, HUI WANG, YANG YANG Corresponding Author: YONG XIE Affiliations: The First Affiliated Hospital of Nanchang University, The First Affiliated Hospital of Nanchang Universi, The First Affiliated Hospital of Nanchang University, The First Affiliated Hospital of Nanchang University, The First Affiliated Hospital of Nanchang University Objective: To assess the efficacy and safety of hybrid therapy compared to other pre-existing therapies and to new therapies. Methods: Through a search of PubMed, EMBASE, the Cochrane Library and abstracts of major gastroenterology conferences, two independent reviewers systemically identified randomized, controlled trials that compared hybrid therapy to other pre-existing and new therapies. Dichotomous data were pooled to obtain the relative risk (RR) of the eradication rate, with 95% confidence intervals (CIs). Results: We identified 6 studies, 3 of which compared hybrid therapy and concomitant therapy, and 5 of which compared hybrid therapy and sequential therapy. Pooled estimates of the 3 RCTs showed no significant differences between hybrid therapy and concomitant therapy; the intention to treat (ITT) pooled RR was 0.99 (95% CI: 0.89–1.10), and the per protocol (PP) pooled RR was 0.99 (95% CI: 0.89–1.10). Pooled estimates of the 5 RCTs showed no significant differences between hybrid therapy and sequential therapy; the ITT pooled RR was 1.02 (95% CI: 0.93–1.12), and the PP pooled RR was 1.03 (95% CI: 0.94–1.13). After consideration of all treatment arms, the ITT eradication rates with hybrid therapy, concomitant therapy and sequential therapy were 88.6%, 86.2% and 84.7%, respectively. And the PP eradication rates were 92.1%, 92.5%

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and 87.5%, respectively. No significant differences were observed between the groups in terms of side effects or compliance. Conclusion: Hybrid therapy could be an alternative to concomitant therapy and sequential therapy. All three of these therapies yielded good eradication rates. Additionally, the efficacy of hybrid therapy might be PPI-dose-dependent, but more RCTs are needed to confirm this finding. Key Word(s): 1. Helicobacter pylori; 2. hybrid therapy; 3. concomitant therapy; 4. sequential therapy; 5. meta-analysis

H. pylori O-065 Standard triple therapy for Helicobacter pylori infection in China: a meta-analysis Presenting Author: BEN WANG Additional Authors: BEN WANG, ZHIFA LV, YONG XIE Corresponding Author: YONG XIE Affiliations: First Affiliated Hospital of Nanchang University, First Affiliated Hospital of Nanchang University, First Affiliated Hospital of Nanchang University Objective: To assess the efficacy and safety of standard triple therapy compared to other pre-existing and new therapies in China. Methods: Literature searches were conducted in the following databases: PubMed, Embase, the Cochrane Central Register of Controlled Trials, the VIP database, the China National Knowledge Infrastructure database (CNKI), and the Chinese Biomedical Database (CBM). A meta-analysis of all randomized controlled trials (RCTs) comparing standard triple therapy for the eradication of Helicobacter pylori (H. pylori) with pre-existing and new therapies in China was performed using Comprehensive MetaAnalysis (CMA) 2.0. There were 49 studies that met our criteria and the q ualities of these studies were asse ssed using the Jadad scale. The MantelHaenszel method was used for pooling dichotomous data. We also conducted subgroup analyses according to age, duration of treatment and drug type. Sensitivity analyses and cumulative meta-analysis were also performed with CMA 2.0. The publication bias was evaluated using Egger’s test, Begg’s test or a funnel plot. Results: A total of 49 RCTs including 8332 patients were assessed. This meta-analysis showed that standard triple therapy with proton pump inhibitors (PPIs), amoxicillin (AMO) and clarithromycin (CLA) was inferior to sequential therapy [relative risk (RR) = 0.863; 95% confidence interval (CI): 0.824–0.904], but was not superior to quadruple therapy (RR = 1.073; 95% CI: 0.849–1.357) or other triple therapies (RR = 1.01; 95% CI: 0.936–1.089). The meta-analysis also suggested that standard triple therapy is slightly more effective than dual therapy (RR = 1.14; 95% CI: 0.99–1.31). However, the differences were not statistically significant. We removed the only trial with a regimen lasting fourteen days by sensitivity analysis and found that seven day standard triple therapy was superior to seven day dual therapy (RR = 1.222; 95% CI: 1.021–1.461). Moreover, a sub-analysis based on the duration of quadruple therapy indicated that the seven days and ten days standard triple therapies were inferior to sequential therapy (RR = 0.790; 95% CI: 0.718–0.868; RR = 0.917; 95% CI: 0.839–1.002, respectively). Additionally, there were no significant differences in cure rate or adverse events among standard triple therapy, quadruple therapy, and other triple therapies (RR = 0.940; 95% CI: 0.825–1.072; RR = 1.081; 95% CI: 0.848–1.378, respectively). The standard triple therapy had a higher occurrence of side effects than sequential therapy (RR = 1.283; 95% CI: 1.066–1.544). Conclusion: The eradication rates with a standard triple therapy consisting of PPI, AMO, and CLA are suboptimal in China, and new treatment agents need to be developed. Key Word(s): 1. Helicobacter pylori; 2. eradication; 3. combination drug therapy; 4. amoxicillin; 5. clarithromycin; 6. adverse effects; 7. metaanalysis


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H. pylori O-066 Ethyl pyruvate reduced h pylori-induced inflammation through inhibition of HMGB1/TLR4 pathways Presenting Author: FU CAI WANG Additional Authors: YONG XIE, NAN JIN ZHOU Corresponding Author: YONG XIE Affiliations: The First Affiliated Hospital of Nanchang University, Institute of Medical Sciences of Jiangxi Province Objective: High mobility group box 1 (HMGB1), an endogenous ligand of toll-like receptor 4 (TLR4), contributes to pathogenesis of many diverse inflammatory disorders, but their roles in H. pylori infection are still unclear. This study intends to explore the effect of ethyl pyruvate (EP), an HMGB1 inhibitor, on expressions of HMGB1/TLR4 pathways in GES-1 and THP-1 cells induced by H. pylori infection, and release of proinflammatory cytokines. Methods: (1) GES-1 were co-culturing with H. pylori for different times (0 h, 3 h, 6 h, 12 h, 24 h and 48 h) at different bacteria/cell ratio (MOI) (MOI = 0, 10, 25, 50, 100 and 200); (2) Pretreated for 1 h with EP at 5 mmol/L, GES-1 were co-cultured with H. pylori at MOI = 100.Then GES-1 and THP-1 cells were co-culturing with transwell system for 24 h. The cells and culture supernatant were harvested and subjected to detection for mRNA and protein expressions of HMGB1/ TLR4/p-NFκB p65 and release of HMGB1, IL-1β and TNF-α by RT-PCR, western blot and ELISA, respectively. Results: (1) Only at 12 h, 24 h and 48 h, or at MOI = 50, 100 and 200, H. pylori infection up-regulated the mRNA and protein expressions of HMGB1/TLR4/p-NFκB p65 in GES-1 cells and increased HMGB1 release; (2) EP down-regulated the mRNA and protein expressions of HMGB1/TLR4/p-NFκB p65 in GES-1 and co-cultured THP-1 cells, and decreased the release of HMGB1, IL-1β and TNF-α. Conclusion: EP reduces H. pylori-induced inflammation through inhibition of HMGB1/TLR4/p-NFκB p65 expressions and reduction of HMGB1, IL-1β and TNF-α release. Key Word(s): 1. H. pylori; 2. EP; 3. HMGB1; 4. TLR4; 5. inflammation

H. pylori O-067 The role of AcrAB-TolC efflux pump on antibiotic resistance of Helicobacter pylori clinical isolates Presenting Author: YONG XIE Additional Authors: YUAN WANG CHEN, NAN JIN ZHOU, DONG SHENG LIU, XIAO QUN LIU, HUI WANG Corresponding Author: YONG XIE Affiliations: The First Affiliated Hospital of Nanchang University, Institute of Medical Sciences of Jiangxi Province, The First Affiliated Hospital of Nanchang University, The First Affiliated Hospital of Nanchang University, The First Affiliated Hospital of Nanchang University Objective: To elucidate the role of AcrAB-TolC efflux pump in multidrug resistance (MDR) of Hp clinical isolates. Methods: (1) The 10 Hp MDR strains and 10 susceptible strains which are sensitive to 9 kinds of antibiotic were screened from 653 Hp clinical isolates; (2) The mRNA expression of genes related to AcrAB-TolC efflux pump (hefA, hefB, hefC, hefD, hefE, hefF, hefG, hefH and hefI) were detected by q-PCR; (3) The mutation of resistance genes which are implicated in Metronidazole (rdxA and frxA), Clarithromycin (23SrRNA), Levofloxacin (gyrA) resistance

were detected by gene sequencing; (4) Influence of efflux pump inhibitors (CCCP and PAβN) on the MDR of Hp were evaluated by testing MIC of antibiotics to Hp. Results: (1) There was no high expression of AcrABTolC efflux pump mRNA in all the susceptibal strains; 1, 2, 1, 2, 3, 2, 3 and 2 of the MDR strains respectively presented high expression of hefA, hefB, hefC, hefD, hefE, hefF, hefG and hefH mRNA. (2) The 8 MDR strains which were resistant to clarithromycin had mutations in the 23SrRNA gene. All the MDR strains had mutations in the gyrA, rdxA and frxA gene. (3) The MIC of Clarithromycin was decreased at least 4-fold in 4 MDR strains by PAβN; the MIC of Metronidazole and Clarithromycin respectively were decreased at least 4-fold in 4 and 2 MDR strains by CCCP. Conclusion: The MDR of H. pylori clinical isolates is the result of a combination of the AcrAB-TolC efflux pump system and the resistant genes. Key Word(s): 1. Helicobacter pylori; 2. multidrug resistance; 3. efflux pump system; 4. efflux pump inhibitors

IBD O-068 Clinical predictors of endoscopic mucosal healing in patients with quiescent ulcerative colitis: data from Nixon-TAM HK IBD Registry Presenting Author: HAI YUN SHI Additional Authors: KL FRANCIS CHAN, JESSICA CHING, TIFFANY CHUNG, FU HANG LO, STEVEN TSANG, SF ALEX SZE, YEE TAK HUI, HS EDWIN SHAN, KK MICHAEL LI, SIEW C NG Corresponding Author: HAI YUN SHI Affiliations: The Chinese University of Hong Kong, The Chinese University of Hong Kong, The Chinese University of Hong Kong, United Christian Hospital, Tseung Kwan O Hospital, Queen Elizabeth Hospital, Queen Elizabeth Hospital, Caritas Medical Center, Tuen Mun Hospital, The Chinese University of Hong Kong Objective: Endoscopic mucosal healing (EMH) is associated with better prognosis in ulcerative colitis (UC) patients. Our aim was to identify clinical factors that predict EMH in quiescent UC. Methods: In a multicenter cross-sectional retrospective study, quiescent UC patients (Mayo symptomatic subscore = 0) who had a colonoscopy from six centers in Hong Kong were reviewed. EMH was defined as Mayo endoscopic subscore of 0. Severity of mucosal inflammation was graded with Mayo endoscopic subscore: 1 (mild), 2 (moderate) and 3 (severe). Predictive model for EMH was built using backward stepwise logistic regression. Results: Of 639 UC patients reviewed, 237 had quiescent disease (mean age, 50.39 ± 14.10 years, male 56.5%; mean disease duration 9.26 ± 6.94 years). Proctitis/left side colitis [odds ratio (OR) 1.7; 95% confidence interval (CI), 1.0–2.9; P = 0.045 vs extensive colitis], mild/moderate inflammation on previous colonoscopy (OR 2.2; 95% CI, 1.2–4.0; P = 0.007 vs severe inflammation), clinical remission > 3 years (OR 2.8; 95% CI, 1.5–5.0; P = 0.001); and immunosuppressant use (OR 1.9; 95% CI, 1.0–3.6; P = 0.044) were associated with EMH. In multivariate analysis, independent factors for EMH were clinical remission > 3 years (OR 4.0; 95% CI, 1.2–13.1, P = 0.020), non-severe mucosal inflammation (OR 3.3; 95% CI, 1.3–8.5, P = 0.014), and immunosuppressant use (OR 4.6; 95% CI, 1.5–14.6, P = 0.009). Among patients who had ≥2 protective factors, 74% achieved EMH, while only 39% with 3 years, 30%, 45.9% and 62.9% achieved EMH, respectively. Proportion of patients who had EMH was higher in patients on immunosuppressants (33.3%, 68.4%, 72.7%, respectively) than those not on immunosuppressants (28.8%, 38.8%, 60.8%, respectively). Immunosuppressant therapy significantly favored early EMH (P = 0.025). In multivariate analysis, only prior Mayo endoscopic subscore was independently associated with early EMH. Patients with previous mild inflammation were more likely to achieve early EMH than those with moderate/severe inflammation (odds ratio = 2.8; 95% confidence interval, 1.2–6.2; P = 0. 015). Conclusion: The longer the duration of clinical remission, the more likely EMH can be achieved. Majority of UC patients achieve EMH after 3 years of clinical remission. Immunosuppressant and severity of prior mucosal inflammation can predict rate of EMH in UC. Key Word(s): 1. ulcerative colitis; 2. endoscopic mucosal healing; 3. duration of remission

IBD O-070 The effect of HMGB1 a – box on LPS/TLR pathway in sw480 and THP-1 cells Presenting Author: YONG XIE Additional Authors: JING XUAN PEI, NAN JIN ZHOU, FU CAI WANG Corresponding Author: YONG XIE Affiliations: The First Affiliated Hospital of Nanchang University, Institute of Medical Sciences of Jiangxi Province, The First Affiliated Hospital of Nanchang University Objective: To investigate the possibility of HMGB1-A box specific inhibition HMGB1/TLR signaling pathway, to provide theoretical and experi-

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mental evidence for HMGB1-A box is to target treatment IBD. Methods: The intestinal epithelial cell lines SW480 were transfected with pEGFP-N1-HMGB1-A box, and were co-cultured with monocytic cell line THP1 by Transwell system, investigating the influence of HMGB1-A box high expression on the HMGB1, TLR4/LPS signaling pathway and the secretion of cytokines. Results: (1) After THP-1 cells were co-cultured with SW480 cells, the HMGB1, TLR4, MyD88 and pNF-κB p65 expression were not significantly different among the without LPS-treated groups in THP-1 cells (P > 0.05). After LPS-treated, their expression in the A box-transfected group was significantly lower than the control group and empty plasmid group (P < 0.05). In addition to the A box-transfected group, their expression in the LPS-treated group were significantly higher than the corresponding non-LPS-treated group (P < 0.05, 0.01). (2) After THP-1 cells were co-cultured with SW480 cells, the HMGB1, IL-1 β, TNF-α and IL-6 level of culture supernatant were not significantly different among the without LPS-treated groups in THP-1 cells (P > 0.05). After LPS-treated, these cytokine levels in the A box transfection group was significantly lower than the control group and empty plasmid group (P < 0.05, 0.01). In addition to the A box-transfected group, these cytokine levels in the LPS-treated group were significantly higher than the corresponding non-LPS-treated group (P < 0.01). Conclusion: (1) LPS can activate TLR4 signaling pathway, up-regulate the expression of HMGB 1 in SW480 and THP-1 cells, and promote secretion of pro-inflammatory cytokine. (2) The SW480 cell with high expression of HMGB1-A box were co-cultured with THP-1 cells, which can inhibit the expression and secretion of HMGB1, the LPS/TLR4 signal pathways and secretion of proinflammatory cytokines of THP-1 cells. Key Word(s): 1. HMGB1-A box; 2. LPS/TLR4 signaling pathways; 3. SW480; 4. THP 1; 5. IBD

IBD O-071 The effect and mechanism of Tim3 over-expression on TLRs signaling pathway in macrophages Presenting Author: YONH XIE Additional Authors: JING YU, NAN JIN ZHOU, ZHI RONG MAO Corresponding Author: YONG XIE Affiliations: The First Affiliated Hospital of Nanchang University, Institute of Medical Sciences of Jiangxi Province, The First Affiliated Hospital of Nanchang University Objective: Macrophages play an important role in pathogenesis of IBD. Toll-like receptor 4 (TLR4) activated macrophages to secrete plenty of cytokines which regulated inflammation and immunity reaction; T-cell immunoglobulin and mucin-domain-containing molecule-3 (Tim-3), an important member of TIM family, was also expressed on macrophages and could impact macrophages function through interacting with TLR4 pathways. Until now, it is unclear how IBD impacts Tim-3 and TLR4 pathways in macrophages. Methods: (1) RAW264.7 cells were coincubated with different concentrations of LPS at 6 h, the mRNA expressions of Tim3\TLR4\MyD88 were measured by RT-PCR; (2) Tim-3-overexpressing RAW264.7 cells were constructed by transfer pLVX-IRES-ZsGreen-Tim-3 and coincubated with LPS(1 ug/ml). The mRNA and protein expressions of Tim-3\TLR4\MyD88 were determined by RT-PCR and Western Blot. The concentrations of cytokines (TNF-α, IL-6 and IFN-γ) in supernatants were measured by ELISA. Results: (1) The macrophage was stimulated with different concentration of LPS for 6 h, the expression of TLR4\MyD88\Tim-3 were gradually increased with increasing concentration of LPS. (2) LPS stimulation could up-regulate the expression of Tim-3


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in RAW264.7 or in Tim-3-overexpressing RAW264.7. (3) With LPS stimulation, the expressions of TLR4\MyD88\p-NF-κBp65 or the release of pro-inflammatory cytokines (TNF-α\IL-6\IFN-γ) were significantly higher in Tim-3-overexpressing RAW264.7 than in RAW264.7. But without LPS stimulation, there were significant differences between Tim-3overexpressing RAW264.7 and RAW264.7. Conclusion: (1) LPS can activate the MyD88-dependent TLR4 signaling pathway and upregulate the expression of Tim-3, and LPS can also promote the secretion of cytokines in a concentration dependent way. (2) Tim-3 over-expression could not significantly influence the TLR4 signaling pathway and the secretion of cytokines without any other effectors. (3) Tim-3 overexpression can enhance the activation of TLR4 signaling pathway and promote the secretion of cytokines when stimulated with LPS. Key Word(s): 1. Tim-3; 2. TLR/IL-1 signaling pathway; 3. macrophage cells; 4. IBD

IBD O-072 The effect and mechanism of lipoxin on TLR4/Nf-κB signaling pathway in macrophages Presenting Author: YONG XIE Additional Authors: LI XING HUANG, NAN JIN ZHOU Corresponding Author: YONG XIE Affiliations: The First Affiliated Hospital of Nanchang University, Institute of Medical Sciences of Jiangxi Province Objective: Macrophages play an important role in pathogenesis of IBD. TLR4/NF-κB activated macrophages to secrete plenty of cytokines which regulated inflammation and immunity reaction; lipoxin can alleviate inflammation by inhibiting the activation of NF-κB. Until now, It is unclear that how IBD impacts lipoxin and TLR4/NF-κB pathways in macrophages. Methods: Macrophages RAW264.7 were divided in the following groups: (1) Control group; (2) lipoxin group; (3) BML-111 group (lipoxin receptor agonist); (4) BOC-2 (lipoxin receptor antagonist) group, then treated with or without LPS. Cytotoxicity was detected by CCK-8 and we also observed the influence of LXs on the TLR4/NF-κB signaling, SOCS2 and the secretion of cytokines in macrophage cell strain Raw264.7. Results: (1) Lipoxin and its agonist could elevate the survival rate of macrophage in the presence of LPS. (2) In the absence of LPS, there was no difference in the expression of TRAF6, p-NF-κBp65 and the level of IL-6, IL-10 in each group. In the the presence of LPS, the expression of protein of TRAF6, p-NF-κBp65 and the level of IL-6 in lipoxin group and the agonist group was significantly lower than the contral group and the antagonist group (P < 0.05), while the level of IL-10 was higher than the contral group and the antagonist group (P < 0.05); moreover, there was no difference in the expression of mRNA and protein of TLR4 and the mRNA of TRAF6 from each other(P > 0.05). With or without LPS, the mRNA and protein expression of SOCS 2 in lipoxin group and the agonist group was significantly higher than the contral group and the antagonist group (P < 0.05). Conclusion: (1) Lipoxin can reverse the cytotoxicity of LPS. (2) Lipoxin could regulate the negative regulator of TLR4/NF-κB signaling, SOCS2, promote the degradation of TRAF6, inhibit the nuclear translocation of NF-κB and the secretion of pro-inflammatory cytokines, and promote the secretion of anti-inflammatory cytokines, thereby reducing inflammation. Key Word(s): 1. IBD; 2. lipoxin; 3. TLR4/Nf-κB signaling; 4. SOCS2

IBD O-073 Mir-19b reduces intestinal inflammation via down-regulation of colonic SOCS3 expression in Crohn’s disease Presenting Author: HONGJIE ZHANG Additional Authors: XIUQIN CHENG, JIEWEN SU Corresponding Author: HONGJIE ZHANG Affiliations: Affiliated Hospital of Nanjing Medical University, Affiliated Hospital of Nanjing Medical University Objective: The aim of our study was to investigate the contribution of SOCS3 expression-associated miRNA to modulate production of chemokine in intestinal epithelial cells and is associated with the pathogenesis of Crohn’s disease. Methods: miRNA-SOCS3 pairs were predicted by bioinformatic approaches and these miRNA-SOCS3 pairs were detected by quantitative PCR (qRT-PCR) in CD patients. SOCS3 expressions in the colonic mucosa were determined by qRT-PCR and western blot. Luciferase reporter plasmid containing either wild-type (wt) or mutant (mut) SOCS3 3′ UTR, pre-miR-19b, scrambled antisense oligonucleotides were transfected. Caco2 cells were used to validate as the genuine target of miR-19b experiments. The levels of chemokine produced by intestinal epithelial cells were determined by using chemokine array. Finally, we assessed the therapeutic effect of miR-19b in 2,4,6trinitrobenzene sulfonic acid (TNBS)-induced murine colitis. Results: We identified significant inverse correlation between miR-19b and SOCS3 in colon tissues from active CD patients. SOCS3 was deduced to be a miR-19b target by computational prediction and was experimentally validated as the genuine target of miR-19b by luciferase reporter assay and western blot analysis with over-expression or knockdown of miR-19b. Furthermore, over-expression of miR-19b led to decreased SOCS3 expression and an increase in chemokine of MIP-3α level in Caco2 cells. However, knockdown of miR-19b led to increased SOCS3 expression and a decreased MIP-3α level. Intracolonic delivered miR-19b decreases the severity of TNBS-treated colitis. Conclusion: miR-19b suppresses inflammatory response at least partly by inhibition of its target SOCS3 expression modulating production of chemokine in colonic epithelial cells, and this is involved in the pathogenesis of CD. Key Word(s): 1. SOCS3; 2. MIR-19B; 3. Crohn’s disease


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Nerve Gut and Motility O-074 High resolution oesophageal manometry with multiple rapid swallows and a solid test meal improves detection of oesophageal pathology: a prospective study Presenting Author: DAPHNE ANG Additional Authors: EMILY TUCKER, JEFF WRIGHT, KEVIN KNOWLES, MARK FOX Corresponding Author: DAPHNE SHIH WEN ANG Affiliations: Nottingham Digestive Diseases Centre, Nottingham Digestive Diseases Centre, Nottingham Digestive Diseases Centre, University Hospital Zurich Objective: The use of high resolution manometry (HRM) has revolutionized measurement of oesophageal motility. However, many patients with dysphagia do not receive a definitive diagnosis and explanation for their symptoms. This may possibly be attributed to the use of 5 mL single water swallows (SWS) in routine HRM as defined by the Chicago classification that may not be representative of symptomatic dysfunction that occurs during free drinking or a solid meal. This study assessed whether inclusion of multiple rapid swallows (MRS) and a solid test meal (STM) reproduced symptoms and enhanced the diagnostic yield of HRM. Methods: Retro-

spective analysis of a prospectively collected cohort study of patients referred for investigation of functional dysphagia between January 2010 and December 2013. Published versions of the Chicago classification for SWS and modified for use with STM were applied. MRS abnormalities included (i) failure of sphincter relaxation, (ii) pan-oesophageal pressurization (PEP); (iii) failure to suppress contractility and (iv) absent aftercontraction. The proportion of patients with abnormal findings and reproducible symptoms during SWS, MRS and STM were compared by chi-square tests. Results: 272 patients (125 [46%] male; age 53 ± 18 years) underwent 279 studies. Oesophageal dysfunction occurred in 212/ 279 (76.0%) studies by SWS, 133/259 (51.4%) studies using MRS and 234/260 (90.0%) studies using STM (SWS vs STM, p < 0.001). Typical symptoms were reproduced in 8/279 (2.9%) SWS; 80/260 (30.8%) MWS and 208/260 (80.0%) STM respectively (SWS vs STM, p < 0.001). Diagnosis was altered by application of STM in 151/260 (58.1%) studies (Table 1 shows comparison of HRM findings with solid swallows [horizontal column] and single water swallows [vertical column]). Conclusion: Addition of multiple rapid swallows and a solid test meal enhances the ability to associate symptoms with oesophageal dysmotility. It also improves the diagnostic yield, especially for outflow obstruction. This has significant clinical impact. Key Word(s): 1. dysphagia; 2. oesophageal dysmotility; 3. oesophageal manometry; 4. Chicago classification

Table 1. Solid Single water swallow Type I achalasia Type II achalasia Type III achalasia EGJ outflow obstruction Spasm/jackhammar Absent peristalsis Weak peristalsis Nutcracker Normal

Type I achalasia

Type II achalasia

2

2 24

1

Type III achalasia

1 9 1 1

EGJ outflow obstruction

2 29 6 24 48 7 43

Nerve Gut and Motility O-076 Clinical outcomes of weak peristalsis in high-resolution manometry Presenting Author: JIN KYU JUNG Additional Authors: MOO IN PARK, SEUN JA PARK, WON MOON, YOUN JUNG CHOI Corresponding Author: SUNG EUN KIM Affiliations: Kosin University College of Medicine, Kosin University College of Medicine, Kosin University College of Medicine, Kosin University College of Medicine Objective: Weak peristalsis was one of the esophageal motility disorders which was categorized by the updated Chicago Classification published in 2011. However, the treatments and the prognosis of the patients with weak peristalsis have not been well established so far. This study evaluated the clinical outcomes of the medical treatments in weak peristalsis patients from a single-center experience. Methods: A total of 399 patients underwent high-resolution manometry (HRM) from January 2009 to December 2013. We reviewed medical records and HRM findings of the patients who

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Spasm/ jackhammer

Absent peristalsis

Weak peristalsis

Nutcracker

Normal

1 4 1

6 18

11 2

1

1

14

were diagnosed as weak peristalsis according to the updated Chicago Classification published. And we checked the treatment responses from the enrolled patients who took the medication (at least 30 days) via telephone. Results: A total of 23 patients were identified as weak peristalsis. Fourteen patients (60.9%) were female and the mean follow-up period was 460.8 days (range, 38–1323 days). In terms of therapeutic methods, proton pump inhibitors (PPIs) with motility agents, PPIs alone, and motility agents alone were prescribed in 16 patients (72.7%), 3 patients (13.6%), and 3 patients (13.6%), respectively. When the response rate of the treatments was assessed, results showed complete response of 27.3%; satisfactory response (≥50%) of 31.8%; partial response ( 5000 mmHg·s·cm were Chicago NE, and DCI > 8000 mmHg·s·cm were Jackhammer. Patients that met GC but not Chicago criteria were s-HCs. Results: (1) 28 patients (51.8 ± 12.3 y) were c-NE (100%). Among them, five (17.9%) patients were Jackhammer and 2 NE (7.1%). The other 21 (75%) were Chicago normal patients, but considered as s-HCs. (2) Lengths (3.8 (3.3– 4.9) vs. 6 (5.5–9) cm, p = 0.023), durations (3 (2.6–3.2) vs. 4.8 (4.4–5.1) s, p < 0.001)), peak amplitudes (212.8 (203.8–233.6) vs. 304.9 (221.4– 347.7) mmHg, p = 0.001) of HCA in s-HCs were lower than Chicago abnormal patients. Mean pressure (132 (118–144.1) vs. 188.1 (179.6– 206.2) mmHg, p < 0.001) and duration (3.5 (3–3.8) vs. 4.9 (4.4–5.2) s, p < 0.001) of esophageal segments 3–7 cm above LES in s-HCs were lower than that of Chicago abnormal pantients. Negative correlation (r = −0.435, p = 0.021) between upper margin of HCA and DCI value were found, while the length (r = 0.634, p < 0.001), peak amplitude (r = 0.721, p < 0.001) and contraction duration (r = 0.819, p < 0.001) of HCA were positively correlated with DCI. Conclusion: Large proportion of c-NE diagnosed by GC was considered as “normal” in Chicago criteria because the HCs were segmental or short-time in patients with NCCP or dysphagia. Key Word(s): 1. nutcracker esophagus; 2. different diagnosis strategy; 3. segmental; 4. short-time; 5. Chicago criteria

to determine if insular HTR1A-NR2B pathway influences the activity of insula and mediates the VH induced by chronic stress in rats. Methods: Chronic water avoidance stress (WAS) was used to establish VH rat models. Visceral sensitivity was determined by measuring the visceromotor response (VMR) amplitude to 60 mmHg colorectal distention (CRD). The HTR1A agonist 8-OH-DPAT and the HTR1A antagonist WAY100635 were microinjected into the left or right insular cortex. The gene and protein expression levels were observed by RT-PCR, Western Blot or immunohistochemical staining. Results: Compared with sham WAS and normal rats, the expression levels of insular 5-HT and HTR1A in WAS rats were significantly lower (p < 0.05), but the expression levels of insular c-fos and NR2B were significantly higher in WAS rats (p < 0.05); see Figure 1 and Figure 2. After insular 8-OH-DPAT intervention, the VMR amplitudes significantly reduced in WAS rats (p < 0.01), but the VMR amplitudes have no significant changes in WAS rats before and a fter insular WAY100635 intervention (p > 0.05, see Figure 3). The expression levels of insular NR2B and c-fos in 8-OH-DPAT intervention group were significantly lower than that in WAY100635 intervention group (p < 0.05, see Figure 4). Conclusion: Through regulating the activity of insular neuron, HTR1A-NR2B pathway has a critical role in mediating the VH induced by chronic stress in rats. Key Word(s): 1. insular cortex; 2. HTR1A-NR2B pathway; 3. visceral hypersensitivity; 4. chronic stress

Nerve Gut and Motility O-078 Insular HTR1a-NR2B pathway mediate the visceral hypersensitivity induced by chronic stress in rats Presenting Author: LISHA YI Additional Authors: HUIHUI SUN, LU ZHOU, YING CHEN, YUANXI JIANG, PING WU, SHUCHANG XU Corresponding Author: SUN HUIHUI Affiliations: Tongji University School of Medicine, Tongji University School of Medicine, Tongji University School of Medicine, Tongji University School of Medicine, Tongji University School of Medicine, Tongji University School of Medicine

Figure 1

Objective: Some studies thought the abnormality of 5-HT1A receptor (HTR1A) in insular cortex may play an important role in visceral hypersensitivity (VH), in which insular HTR1A-NR2B pathway was inferred to be critical in mediating the VH induced by chronic stress. This study aimed


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Figure 4

Figure 2

Nutrition and Metabolism O-079 The Ramadan fasting decreased body fat but not protein mass in healthy individuals Presenting Author: CECEP SURYANI SOBUR Additional Authors: MURDANI ABDULLAH, DADANG MAKMUN Corresponding Author: ARI FAHRIAL SYAM Affiliations: Dr. Cipto Mangunkusumo General Hospital, Dr. Cipto Mangunkusumo General Hospital, Dr. Cipto Mangunkusumo General Hospital

Figure 3

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Objectives: The previous studies have shown the effects Ramadan fasting on wight and body composition in healthy individuals. The aim of this study was to evaluate the effect of Ramadan fasting on body composition in healthy Indonesian medical staffs. Methods: This longitudinal study was performed in August – October 2013. The subjects were 43 medical staffs (physicians, nurses and nutritionists) at Internal Medicine Ward Dr. Cipto Mangunkusumo General Hospital. We compared weight, body mass index (BMI), waist to hip ratio (WHR), body composition (bofy fat, protein, mineral and water) and calorie intake on first, 28th day of Ramadan and 4–5 weeks after Ramadan fasting. All 43 subjects completed measurements on 28th day of Ramadan but only 25 who completed measurements on 4–5 weeks after Ramadan. Results: Body weight, BMI, fat, water and mineral significantly decreased on 28th day of Ramadan. Protein body mass and calorie intake were not change significantly. The body weight and composition on 4–5 weeks after Ramadan increased to the same level as on the first day of Ramadan. Conclusion: The Ramadan fasting could decrease the weight but it was temporary and quickly regained. Ramadan fasting didn`t trigger the catabolism state which protein loss is significant. The further research is needed to evaluate the benefit of weight loss during Ramadan fasting in healthy individual.


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hospitalization (p < 0.001). ROC analysis got MST score >3 as the best cut-off for predicting hospital mortality in pulmonary tuberculosis patients (AUC 0.644; 95% CI 0.581–0.707). MST score >3 increased the risk of hospital mortality in pulmonary tuberculosis patients (RR 2.288; 95% CI 1.507–3.474, p < 0.001). Conclusion: MST score >3 associated with higher risk of hospital mortality in pulmonary tuberculosis patients. MST appears to be a reliable tool to identify hospitalized pulmonary tuberculosis patients who have risk of malnutrition and mortality. Key Word(s): 1. malnutrition; 2. screening; 3. MST; 4. pulmonary tuberculosis; 5. hospital mortality

Oncology Figure 1

Figure 2

Nutrition and Metabolism O-082 Role of malnutrition screening tool for predicting hospital mortality in pulmonary tuberculosis patients Presenting Author: IRWIN TEDJA Additional Authors: ARI FAHRIAL SYAM, CLEOPAS MARTIN RUMENDE Corresponding Author: IRWIN TEDJA Affiliations: Faculty of Medicine, University of Indonesia, Faculty of Medicine, University of Indonesia Objective: Pulmonary tuberculosis patients who are hospitalized have varying nutritional conditions. A simple nutrition screening method is needed to predict a poor prognosis, especially mortality. Malnutrition Screening Tool (MST) is a simple, rapid and valid nutrition screening method for identifying patients with malnutrition. This study was aimed to know the role of MST for predicting hospital mortality in pulmonary tuberculosis patients. Methods: This was a retrospective cohort study of 345 hospitalized pulmonary tuberculosis patients in Cipto Mangunkusumo Hospital between January 2011 and September 2013. MST scores were obtained at admission, then subjects were observed to evaluate their hospital mortality. Results: The hospital mortality rate was 25.8%. Median MST score of hospitalized pulmonary tuberculosis patients was 3 (range 0–5). There were significant differences in median MST score among hospitalized pulmonary tuberculosis patients who died and survived during

O-083 Association between serrated polyps and the risk of synchronous advanced colorectal neoplasia in average-risk individuals Presenting Author: JESSICA YL CHING Additional Authors: JESSICA YL CHING, VICTOR CW CHAN, MARTIN CS WONG, RAYMOND TANG, SUNNY WONG, ARTHUR KC LUK, THOMAS YT LAM, QINYAN GAO, ANTHONY WH CHAN, FRANCIS KL CHAN, JAMES YW LAU, JOSEPH JY SUNG Corresponding Author: SIEW CHIEN NG Affiliations: Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong, Chinese University of Hong Kong Objective: Serrated polyps of the colorectum have distinct histological features and malignant potential. The aim of this study is to assess the association between the presence of serrated polyps and synchronous advanced colorectal neoplasia. Methods: Amongst 5,819 asymptomatic Chinese individuals aged 50–70 years who underwent screening colonoscopy, 329 cases with advanced neoplasia (adenoma ≥ 1 cm, with tubulovillous/villous histology, with high-grade dysplasia, or invasive adenocarcinoma) were compared with 5,490 controls without advanced neoplasia for age, sex, smoking history, body mass index, family history of colorectal cancer, and the presence of serrated polyps. Independent predictors of advanced neoplasia were determined by multivariate logistic regression analysis. Results: The prevalence of advanced neoplasia and serrated polyps was 5.7% and 14%, respectively. Proximal serrated polyps were detected in 4.2% and large (≥10 mm) serrated polyps in 0.4% of screened individuals. Independent predictors of synchronous advanced neoplasia included the presence of sessile serrated adenomas (OR, 6.10; 95% CI, 3.65–10.18), proximal serrated polyps (OR, 2.72; 95% CI, 1.44– 3.31), large serrated polyps (OR, 52.51; 95% CI, 20.32–135.74) and one or more non-advanced tubular adenomas (OR, 95% CI, 3. 61–12.19). Proximal serrated polyps carried a higher risk for proximal advanced neoplasia (OR 2.35; 95% CI, 0.96–5.76) than distal advanced neoplasia (OR 1.29; 95% CI, 0.48–3.45). Conclusion: The detection of proximal, sessile and/or large serrated polyps at screening colonoscopy is independently associated with an increased risk for synchronous advanced neoplasia. These individuals should undergo surveillance colonoscopy at an earlier time frame. Key Word(s): 1. serrated colon polyps; 2. advanced neoplasia


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Oncology O-084 The oral iron chelator, deferasirox, may be a novel potential therapeutic agent for pancreatic cancer Presenting Author: HIROFUMI HARIMA Additional Authors: SEIJI KAINO, SHUHEI SHINODA, MICHITAKA KAWANO, SHIGEYUKI SUENAGA, NAOKI YAMAMOTO, TAKAHIRO YAMASAKI, ISAO SAKAIDA Corresponding Author: HIROFUMI HARIMA Affiliations: Yamaguchi University Graduate School of Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi University Graduate School of Medicine Objective: Iron is essential for cell proliferation and viability. Therefore, iron depletion by a chelator can be used as a new strategy for cancer therapy. Deferasirox (DFX) is an orally effective iron chelator that is currently used for the treatment of iron-overload disease, and has been implemented as an alternative to the gold standard chelator, desferrioxamine (DFO). Earlier studies demonstrated that DFO exhibits antitumor effects on pancreatic cancer. However, there have been no studies that have investigated the effects of DFX on pancreatic cancer. This study aimed to elucidate the in vitro and in vivo activity of DFX against pancreatic cancer cells. Methods: In vitro, three human pancreatic cancer cell lines (BxPC-3, Capan-2, SW 1990) were treated with DFX. The cell proliferation was evaluated by the MTT assay, and the cell cycle progression and apoptosis were analyzed by flow cytometry. The role of caspases in the DFX-induced apoptosis was investigated using a luminescent assay. In vivo, a BxPC-3 xenograft pancreatic cancer model in mice was established. The mice were gavaged with DFX or vehicle alone for treatment. Results: The MTT assay showed that DFX had concentration-dependent cytoxic effects. The cell cycle analysis showed that a low concentration of DFX increased the S phase fraction, while a high concentration of DFX increased the sub-G1 fraction. The induction of apoptosis was also confirmed by Annexin V and PI staining in the cells treated with a high concentration of DFX. The caspase 3/7 activities were increased in a concentration-dependent manner by DFX. When DFX was orally administered to mice on alternate days at 20 mg/kg for six weeks, significant tumor growth suppression was observed compared with that in mice gavaged with the vehicle alone (P < 0.05). Conclusion: We demonstrated that DFX is an orally effective agent that had activity against pancreatic cancer. Key Word(s): 1. deferasirox; 2. iron chelator; 3. pancreatic cancer

Oncology O-085 Proteins of vegetable origin in fish feed induce inflammation and carsinogenesis in salmonid fish Presenting Author: BJØRGEN HÅVARD Additional Authors: T. MOLDAL, M. KALDHUSDAL, E.O. KOPPANG, O.B. DATE Corresponding Author: BJØRGEN HÅVARD Affiliations: Norwegian Veterinary Institute, Norwegian Veterinary Institute, Norwegian School of Veterinary Science, Norwegian Veterinary Institute Objective: One of the major challenges in aquaculture production of salmonid fish is the bioavailability of marine ingredients for fish nutrition.

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A common way to deal with this challenge has been to dilute the content of marine protein and oil with derivates of vegetable origin. Commercial feeds containing various plant proteins have shown to cause inflammation and neoplasms. The course of this development has multiple parallels with inflammatory bowel disease (IBD) in humans. The pathogenesis of IBD has been thoroughly researched; however, it is still poorly understood. An accepted thesis is that IBD results from a dysregulated mucosal immune response to environmental factors in the gastrointestinal tract in genetically predisposed individuals. This study is designed to recreate inflammation and carcinogenesis, by feeding the fish with a high-risk feed, containing an abundant amount of plant protein. Methods: The gut wall will be examined histologically, using standard staining, immunohistochemistry and immunofluorescence. Morfometric analysis will further explain the intestinal health status. Results: The results are expected to show that it is possible to experimentally reproduce inflammation and carcinogenesis. Conclusion: Further on, the results can be used to create an animal model, which could become an important tool in the further study and understanding of the pathogenesis of IBD. Key Word(s): 1. IBD; 2. cancer; 3. inflammation; 4. feed; 5. salmon

Oncology O-086 Epidemiology of colon and rectal cancer in two Chinese cities with different background of colorectal cancer incidences Presenting Author: WAI K LEUNG Additional Authors: LI GU, DA LONG, TERESA TONG, WEI QING CHEN Corresponding Author: WAI KEUNG LEUNG Affiliations: Chongqing Medical University, Chongqing Medical University, University of Hong Kong, Chongqing Medical University Objective: With the rapid socioeconomic development in Asia, the incidence of colorectal cancer (CRC) is rising rapidly in Hong Kong (HK) where it has now become the most common cancer. The age-standardized rate of CRC in HK is about two-times higher than the corresponding rate in China. We studied the epidemiology of colon and rectal cancers in two Chinese cities (HK and Chongqing (CQ)) with different background CRC incidences to gain further insight into the changing CRC epidemiology in Chinese. Methods: This was a retrospective study conducted in three large regional hospitals in HK and CQ. We identified all patients newly diagnosed to have CRC between 2003 and 2012. The baseline demographic of CRC patients and the colon/rectal cancer ratios (CR ratio) of the two cities were compared. Results: 3,664 new cases of CRC were diagnosed (1350 in HK and 2314 in CQ) within the 10-year study period. CRC was more common in men in both cities with a M : F ratio of 1.3. The mean age at diagnosis of CRC was significantly younger in the low prevalent area (CQ) than in the high prevalent area (HK) (62.1 vs 70.4 years; P < 0.001). The proportion of young ( 15 mm and 2 patients had stricture between 10–15 mm. Barium study showed residual stricture in most of the patients was non critical. Conclusion: Diagnosis of gastroduodenal tuberculosis can be made by endoscopic methods in majority of the patients. Combination therapy of dilatation and anti-tubercular therapy is an effective alternative to surgery and should be the SOC. Key Word(s): 1. abdominal tuberculosis; 2. endo therapy; 3. endoscopic mucosal resection; 4. benign strictures


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Therapeutic Endoscopy/Interventional Radiology


O-101 Treatment of bleeding from gastric fundal varices: comparison between EIS using cyanoacrylate and B-RTO Presenting Author: YOSHIHIRO FURUICHI Additional Authors: JUNICHI TAIRA, TAKATOMO SANO, KATSUTOSHI SUGIMOTO, YASUHARU IMAI, IKUO NAKAMURA, FUMINORI MORIYASU Corresponding Author: YOSHIHIRO FURUICHI Affiliations: Tokyo Medical University Hospital, Tokyo Medical University Hospital, Tokyo Medical University Hospital, Tokyo Medical University Hospital, Tokyo Medical University Hospital, Tokyo Medical University Hospital

O-102 Histological analysis of subepithelial extent of submucosal early gastric cancer in 60 surgical cases Presenting Author: OSAMU GOTO Additional Authors: AI FUJIMOTO, MASAYUKI SHIMODA, TATSUO MATSUDA, YASUTOSHI OCHIAI, HIROFUMI KAWAKUBO, TOSHIO URAOKA, HIROYA TAKEUCHI, KAORI KAMEYAMA, YUKO KITAGAWA, NAOHISA YAHAGI Corresponding Author: OSAMU GOTO Affiliations: Keio University, School of Medicine, Keio University, School of Medicine, Keio University, School of Medicine, Keio University, School of Medicine, Keio University, School of Medicine, Keio University, School of Medicine, Keio University, School of Medicine, Keio University, School of Medicine, Keio University, School of Medicine, Keio University, School of Medicine

Objective: Because of the usually massive bleeding from gastric fundal varices (GV), it is difficult to arrest the bleeding by EIS using ethanolamine oleate (EO) only, so that endoscopic cyanoacrylate (CA) injection method is required in addition. After temporary arrest of the hemorrhage with CA injection, we divided the patients into those who received additional treatment with EIS (using EO and CA) (Group A) and those who received additional treatment with B-RTO (Balloon-Occluded Transvenous Obliteration, Group B), and compared the data retrospectively. Methods: The subjects were 99 patients with liver cirrhosis who had presented with bleeding from GV (Group A, n = 45; Group B, n = 54). The items examined were as follows: the number of treatments, the amount of EO, the recurrence rate of GV, the bleeding recurrence rate, the survival rate, and the complication rate. Results: The treatments were succeeded in both groups. The mean number of treatments was 2.6 ± 1.3: 2.5 ± 0.8 (Group A: Group B), and the total injected amount of EO was 25.6: 32.4 (ml). The 5-year cumulative recurrence rate was 57%:0% and the 7-year recurrence rate was 100%:0%. In addition, in Group B, no case of recurrence was found over the observation period of up to 140 months. The 5-year cumulative bleeding recurrence rate was 46%:0%; namely, a superior result was obtained in Group B. The 5-year cumulative survival rate was 34%:65%, and the 7-year survival rate was 0%:56%. As a postoperative complication, hemoglobinuria was observed in both groups (55.2%:60.7%), with no significant difference in the incidence between the two groups. Conclusion: In the treatment for GV bleeding, temporary hemostasis with CA injection was required. However, as the additional treatment, B-RTO was superior to EIS (using EO and CA). Therefore, acquisition of skill not only in administering CA injection, but also in B-RTO is considered to be necessary for the treatment of GV bleeding. Key Word(s): 1. EIS; 2. B-RTO; 3. esophageal varices; 4. cyanoacrylate

Objective: There is no consensus regarding an optimal safety margin in endoscopic full-thickness resection (EFTR). In this study, we aimed to assess subepithelial extent (SE) of submucosal early gastric cancer (EGC) to determine how far a safety margin should be set in EFTR. Methods: In 60 surgically resected submucosal EGCs 4 cm or less in size, which could be candidates for non-exposed endoscopic wall-inversion surgery (NEWS), EFTR without transgastric access, with sentinel node basin dissection (SNBD), 595 hematoxylin and eosin stain sections were retrospectively assessed. We measured the distance between the edge where the tumor was intralumenally exposed and the edge where it protruded in the subepithelial layer. The relationship between the SE and histological features of the tumor was statistically analyzed. Results: The average and the median of the SE were 1.1 mm (SD, 1.78 mm) and 0.3 mm (range, 0–12.3 mm), respectively. The 99th percentile was 8.8 mm. In a histological type at the subepithelilal tumor edge, the medians of SE were 0 mm in an intestinal type and 0.8 mm in a diffuse type, respectively (p < 0.0001). In location of the subepithelilal tumor edge, the medians of SE were 0.3 mm in the mucosal layer and 2.6 mm in the submucosal layer, respectively (p < 0.0001). Conclusion: In most lesions, SE was less than 1 cm, although it was significantly longer in the diffuse type or the submucosal layer at the tumor edge. The safety margin can be shortened more in NEWS with SNBD for submucosal EGC than in standard gastrectomy. Key Word(s): 1. early gastric cancer; 2. endoscopic full-thickness resection; 3. non-exposed endoscopic wall-inversion surgery; 4. tumor extent

Therapeutic Endoscopy/Interventional Radiology O-103 Colorectal endoscopic submucosal dissection is useful and safe Presenting Author: HIROSHI KASHIDA Additional Authors: TEPPEI ADACHI, YORIAKI KOMEDA, TOSHIHARU SAKURAI, YUTAKA ASAKUMA, MASAKI TAKAYAMA, HIROMASA MINE, MASATOSHI KUDO Corresponding Author: HIROSHI KASHIDA Affiliations: Kinki University, Kinki University, Kinki University, Kinki University, Kinki University, Kinki University, Kinki University Objective: Endoscopic submucosal dissection (ESD) for colorectal neoplasms was developed in Japan but is now globally spreading. In our


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hospital the technique was started in the year 2010. The objective of this study is to evaluate the results of colorectal ESD procedures for the first 4 years. Methods: The subjects are 233 consecutive lesions in 208 patients which were treated with ESD technique. The indications for ESD in our hospital are: 1. Neoplasms larger than 20 mm but confined to the mucosa or invading minimally to the submucosal layer, 2. Those smaller than 20 mm but associated with fibrosis resulting in non-lifting sign. The instruments used are PCF-Q260AZI, PCF-Q260JI or GIF-Q260J (Olympus), Short ST Hood and Flush Knife (Fujifilm) and VIO 300D (Erbe). Results: Male : female ratio was 104:104 and the average age was 68.1 (39–90) years old. The location was proximal colon in two-thirds of the lesions. The final pathological diagnosis was sessile serrated adenoma/ polyp (SSA/P) in 20, adenoma in 76, mucosal cancer in 112, minimally invasive cancer (SM1) in 16 and deeply invasive cancer (SM2) in 8, neuroendocrine tumor in 1, and hamartoma in 1. The gross appearance of the adenomas and cancers was flat or laterally spreading tumor (LST) in 195, sessile or 0-Is in 14, and depressed or 0-IIc in 3. The LSTs were subdivided into 58 lesions of homogeneous granular-type (LST-G-H), 46 mixed-nodular type (LST-G-M), 46 flat-elevated type (LST-NG-FE), and 44 pseudo-depressed type (LST-NG-PD). The average size in LST-G-H, LST-G-M, LST-NG-FE, LST-NG-PD, 0-Is, 0-IIc, and SSA/P was 41.2 mm, 39.8 mm, 30.6 mm and 25.6 mm, 36.3 mm, 10.3 mm, and 24.0 mm, respectively. Invasive rates in these subtypes in order was 1.8%, 14.5%, 9.9%, 20.6%, 22.2%, 33.3%, and 0%. Post-procedure bleeding occurred in 3 cases (1.29%). Minor intra-procedure perforation was encountered in 6 cases (2.57%), but no emergency operation was required. Delayed pneumoperitoneum was witnessed in one case, but it was attributable to the ileus which was caused by the anal stricture the patient had had since before. If we divide the cases into 1st, 2nd, 3rd fifty lesions and thereafter, the en bloc resection rate was 78%, 88%, 98% and 99%. Local recurrence was witnessed in 3 cases (1.29%) in all of which the ESD procedure had resulted in piecemeal resection due to fibrosis, but the recurrent lesions were all small and removed endoscopically without difficulty. Conclusion: Endoscopic submucosal dissection is a useful and rather safe technique for en bloc resection of early colorectal neoplasms. Key Word(s): 1. colorectal neoplasm; 2. endoscopic submucosal dissection

Therapeutic Endoscopy/Interventional Radiology O-104 Long-term outcome and satisfaction survey after percutaneous endoscopic gastrostomy in a general hospital in Japan Presenting Author: CHIKA KUSANO Additional Authors: TAKUJI GOTODA, KENJI KIKUCHI, KENICHI ASAKURA, HASHIMOTO MASAHARU, MORIYASU FUMINORI Corresponding Author: CHIKA KUSANO Affiliations: Tokyo Medical University, Yuri Kumiai General Hospital, Yuri Kumiai General Hospital, Yuri Kumiai General Hospital, Tokyo Medical University Objective: Indications for selecting individuals for percutaneous endoscopic gastrostomy (PEG) for elderly patients remain unclear. Furthermore, satisfaction of family after PEG for patients who were unable to consent on their own to PEG placement is unclear. The aim of this study was to evaluate satisfaction of patients’ family questionnaire after PEG insertion. Methods: We reviewed existing data of all patients who had undergone PEG insertion at the Yuri Kumiai General Hospital (Akita, Japan) between February 2000 and December 2010. We send the questionnaire to all patients’ families. We asked the following: (1) indication; (2) whether patients were dead or alive; (3) did patients come to be able to

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swallow; (4) did family want to place PEG as patient in same situation? Results: 545 patients underwent PEG insertion. Among them, 315 patients (or patient’s family) answered the questionnaire, 161 males with a mean age of 78 year (range 24–98). Cerebrovascular disease was the most common diagnosis (44%, n = 139/315) and aspiration pneumonia was second common disease (23%, n = 71/315). In total, 264 deaths ware observed (84%, n = 264/315). 86% (n = 271/315) of patients went to another hospital or nursing facility. 17% (n = 54/315) of patients could swallow after PEG insertion. 29% (n = 90/315) of patient’s family wants to undergo PEG for themselves. Conclusion: There is a low prevalence of acquisition of the deglutition ability. Regardless of will of the patients themselves, PEG may become a means only to feed enteral nutrition and send patients to other institutions in Japan. The majority of patients’ families did not want PEG placement for themselves. Future studies regarding quality of life after PEG insertion should be performed and are needed to elucidate the ethical aspect of PEG in geriatric patients. Key Word(s): 1. percutaneous endoscopic gastrostomy

Therapeutic Endoscopy/Interventional Radiology O-105 Clinical outcomes of endoscopic submucosal dissection (ESD) for the treatment of rectal carcinoid tumors and comparison with endoscopic mucosal resection (EMR) Presenting Author: JAEBUM LEE Additional Authors: EUN JUNG LEE, DOO SEOK LEE, IN TAEK LEE, DO SUN KIM, DO HAN LEE, EUI GON YOUK Corresponding Author: JAE-BUM LEE Affiliations: Daehang Hospital, Daehang Hospital, Daehang Hospital, Daehang Hospital, Daehang Hospital, Daehang Hospital Objective: Rectal carcinoid tumors less than 10 mm can be treated by endoscopic resection. However, conventional endoscopic mucosal resection (EMR) often cannot result in histological complete resection due to the submucosal location of the tumor. Endoscopic submucosal dissection (ESD) may be effective in terms of complete resetion. The aim of this study was to evaluate the clinical usefulness of ESD by comparing with EMR. Methods: Between January 2009 and December 2013, 308 rectal carcinoid tumors without lymph node enlargement on CT scan were endoscopically removed by ESD or EMR. Rate of complete resection on histologic examination, procedure time, and complications were reviewed and compared between groups treated by ESD and EMR. Results: One hundred rectal carcinoid tumors were removed by EMR and 208 tumors were removed by ESD. There was no difference in patient’s age (50.8 ± 13.0 years vs. 50.6 ± 11.7 years, p = 0.88). The mean tumor diameter was significantly larger in ESD group (4.45 ± 1.86 mm vs. 6.24 ± 2.39 mm, p < 0.001) and the mean procedure time was significantly longer in the ESD group (268 ± 198 seconds vs. 1295 ± 726 seconds, p < 0.001). No procedure-related complications occurred during or after endoscopic resection in both groups. The overall complete resection rate was significantly higher in the ESD group compared with EMR group (95.7% vs. 82.0%, P < 0.001). However, complete resection rate for rectal carcinoid tumors less than 5 mm was not significantly different between the ESD group and the EMR group (98.1% vs. 93.8%, P = 0.244). Conclusion: ESD and EMR were effective and safe methods for treatment of rectal carcinoid tumors less than 5 mm. However, the higher complete resection rate of ESD suggest that ESD may be considered as the first option for the treatment of rectal carcinoid tumors with a size of 5 mm or larger. Key Word(s): 1. rectal carcinoid tumors; 2. endoscopic submucosal dissection (ESD); 3. endoscopic mucosal resectin (EMR)


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O-106 Effectiveness of self-expandable metal stent for afferent loop obstruction caused by cancer recurrence after pancreaticoduodenectomy Presenting Author: ARATA SAKAI Additional Authors: HIDEYUKI SHIOMI, SEIJI FUJIGAKI, KOUDAI YAMANAKA, TAKESHI EZAKI, YUICHI HIRATA, TAKAO IEMOTO, TAKASHI NAKAGAWA, YOUSUKE YAGI, TAKASHI KOBAYASHI, TOSHITATSU TAKAO, MAMORU TAKENAKA, YOSHIFUMI ARISAKA, HIROMU KUTSUMI, YOSHIHIRO OKABE, TAKESHI AZUMA Corresponding Author: ARATA SAKAI Affiliations: Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital

O-107 How to treat pancreatic pseudocyst and abscess by endoscopic pancreatic stenting (long eps) via duodenal papilla – our experience of 151 cases in 23 years – mainly about its usefulness, safety and long prognosis Presenting Author: TADAO TSUJI Additional Authors: Na Corresponding Author: TADAO TSUJI Affiliations: Na

Objective: Afferent loop obstruction caused by cancer recurrence after pancreaticoduodenectomy (PD) can be managed either by surgical or nonsurgical treatment. The general condition of the patients with recurrent pancreaticobiliary cancer are often not good enough to undergo a surgery, therefore, less-invasive nonsurgical treatment is desirable. Here, we report the case series of self-expandable metal stent (SEMS) use for afferent loop obstruction caused by cancer recurrence after PD. Methods: A total of 5 patients (3 men, 2 women, median age 66, range 56–82) who underwent SEMS placement for afferent loop obstruction caused by cancer recurrence after PD were identified. The diagnosis of afferent loop obstruction was based on clinical presentation, laboratory data and CT scans. Upper endoscopy was performed to confirm the diagnosis and to manage the cases. 8.5 Fr nasojejunal drain was inserted into the distended afferent loop over a neoplastic stenosis, which relieved obstructive jaundice and ascending cholangitis. After clinical conditions improved, SEMS placement was performed by standard Through-The-Scope (TTS) technique under conscious sedation. Results: No procedure related complications were encountered. Technical success was achieved in all cases. The mean time of treatment was 25 min (range 15–30 min). Clinical success was achieved in all cases. After this procedure, 2 of 5 patients could be received chemotherapy for primary diseases. Clinical suspicion of stent dysfunction was not occurred in all patients. Median survival time was 155 days (range 96–374 days). Conclusion: Our series indicate that SEMS could be an effective and less invasive treatment for afferent loop obstruction caused by cancer recurrence after PD. Key Word(s): 1. afferent loop obstruction; 2. SEMS; 3. endoscopy

Objective: It is still controversial how to treat pancreatic pseudocyst and abscess. In the past 23 years, 162 cases of chronic pancreatitis with pseudocyst were treated. In our hospital, EPS via duodenal papilla (major and/or minor) is the preferred choice for their treatments. Small cases were treated by other method (percutaneous, transgastric, stone removal alone by ESWL and/or endoscopy and surgery). Evaluation of the usefulness, safety of EPS and analysis of the long prognosis of EPS treated group. Methods: 162 cases consisted of 135 alcoholic, 12 idiopathic, 4 autoimmune, 3 divisum, 2 hereditary, 2 hyperparathyroidism, 1 serous cystadenoma, 1 cbd stone induced, 1 post pancreas operation and 1 systemic vasculitis (male 135, female 27; 24–94 y/o; mean age 55.2 y/o). Stone (+) cases were 113. Pancreatic pleural effusion and ascites (+) cases were 10 and perforation to retroperitoneal space and choledochus were 1, respectively. There were 20 cases of pseudoaneurysma formation. Pseudocysts located in the head were 59 cases, in the body 34 cases, in the tail 60 cases, in the head + body + tail 7 cases, and 2 cases in outside of pancreas parenchyma. 3 cases were treated by percutaneous method alone, 1 by transgastric method alone, 10 by stone removal alone using ESWL or endoscopy, and 5 by operation. Results: In 151 cases, ERP revealed the conection between main pancreatic duct and lesions, so EPS was tried and succeeded in 147 (147/151 = 97%) without major complications. We usually use our original long EPS (5 or 7 Fr. maximum length 30 cm). Among those cases, 4 were treated finally surgically. So 143 cases were treated mainly by EPS (EPS alone 54, EPS + percutaneous or transgastric 89, via major papilla 145, and via minor papilla 17 cases). 4 months and 10 months later from the first treatment, EPS was withdrawn and in some cases with duct narrowing and/or residual pseudocyst, EPS was re-placed. In 42 cases, repeated (>4 times) stenting was done and still now EPS(+) cases were 77 (53.8%). The lesions of this repeated (>4 times) stenting group were located in the tail portion. Deaths were 1 pancreatic cancer and 2 cyst infection. Other 140 cases had good prognoses. Conclusion: When ERP revealed the connection between lesions and the main pancreatic duct, EPS is indicative. This method is the preferable treatment of pseudocysts, because it repairs the broken pancreatic duct and the pancreatic juice flow without any complications and had good prognoses. Key Word(s): 1. chronic pancreatitis; 2. pseudocyst; 3. endoscopic pancreatic stenting


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Biliary Tract

O-108 Feasibility of endoscopic submucosal dissection for the treatment of colorectal neoplasms on ileocecal valve Presenting Author: TETSUYA YOSHIZAKI Additional Authors: TAKASHI TOYONAGA, YOSHIKO OHARA, FUMIAKI KAWARA, DAISUKE WATANABE, SHINWA TANAKA, TSUKASA ISHIDA, NAMIKO HOSHI, YOSHINORI MORITA, EIJI UMEGAKI, TAKESHI AZUMA Corresponding Author: TETSUYA YOSHIZAKI Affiliations: Kobe University Graduate School of Medicine, Kobe University Graduate School of Medicine, Kobe University Graduate School of Medicine, Kobe University Graduate School of Medicine, Kobe University Graduate School of Medicine, Kobe University Graduate School of Medicine, Kobe University Graduate School of Medicine, Kobe University Graduate School of Medicine, Kobe University Graduate School of Medicine, Kobe University Graduate School of Medicine

O-109 Histologic effect of in vivo endoscopic papillary large balloon dilation on the bile duct in swine models of normal and dilated bile duct Presenting Author: BYOUNG GY CHAE Additional Authors: SEOK JEONG, DON HAENG LEE Corresponding Author: BYOUNG GY CHAE Affiliations: Inha Universtiy School of Medicine, Inha Universtiy School of Medicine

Objective: Endoscopic submucosal dissection (ESD) has been widely accepted as an effective treatment for colorectal tumors. However, removing tumors on ileocecal valve by ESD is often considered challenging due to its location, difficulty to control endoscope and less availability of data about clinical outcome of the treatment. Methods: This study was to clarify effectiveness and postoperative course of ESD for the tumors on the ileocecal valve. A total of 38 lesions treated by ESD in our hospital and an affiliated hospital between April 2004 and December 2013 were analyzed. Results: The male : female ratio of the patients was 21:17, and the mean age was 68. The macroscopic type of the tumor includes one case each of 0-Is and 0-IIa+IIc, 25 of laterally spreading tumor (LST)-granular type, and 11 of LST-non granular type. The mean tumor size was 35 mm in diameter (14–120). Fourteen lesions were located on the upper lip of the ileocecal valve, 12 lesions were on the lower lip, and 12 lesions spanned both lips. The histopathological diagnosis were 7 adenomas, 29 mucosal carcinomas, 2 carcinomas with submucosal invasion. En block resection and complete removable rates were 97% and 97%, respectively. Two patients had postoperative bleeding, but no blood transfusion was required. No perforation occurred during the procedure, as well as post-operatively. Nine cases required over 3/4 of circumferential mucosal removable of ileocecal valve; however, no case developed intestinal stenosis during the observed period without prophylactic treatment, such as steroid injection into the submucosa. Conclusion: This study shows that en bloc and complete resection for the lesions on ileocecal valve can be achieved safely without severe adverse events. Furthermore, no patient who underwent more than three quarter of circumferential dissection developed stenosis. Our data indicates that ESD would be a useful treatment for colorectal neoplasms on the ileocecal valve. Key Word(s): 1. endoscopic submucosal dissection; 2. ileocecal valve

Objective: Endoscopic papillary large balloon dilatation (EPLBD) has been suggested to be a useful technique to remove large bile duct stones. However, there are still safety concerns about this procedure. We investigated histologic effect of in vivo EPLBD in normal (NBD) and dilated bile duct (DBD) models of swine. Methods: Six mini pigs were used and allocated into two groups; DBD model group (n = 3) which are made by closure of the major duodenal papilla with a detachable snare, and another NBD model group (n = 3) with normal diameter of bile duct. EPLBD (12 mm-diameter, 3 atmosphere, 60 seconds, single session) was performed in all animals in vivo after endoscopic retrograde cholangiography (ERC). Cholangiogram was then obtained again after the procedure. All animals were sacrificed and the common bile duct (CBD) with major duodenal papilla was extracted one day later. ERC findings, gross and microscopic findings of the resected specimen were analyzed. Results: The mean values of maximum CBD diameters were 5.0 and 14.1 mm, respectively, in both NBD and DBD groups. Right after EPLBD, dye leaked out from the distal CBD in cholangiogram and the gross and microscopic findings revealed perforation in CBD of all three NBD models. However, in all DBD models, any dye leakage or CBD perforation was not observed. There was no bleeding in both groups. This is the first in vivo animal study that shows safety of EPLBD which is applicable in the patient with large bile duct stone and dilated bile duct. Conclusion: EPLBD is suggested to be safe method for dilated bile duct model of swine unless the balloon diameter exceeds its CBD diameter. Key Word(s): 1. endoscopic papillary large balloon dilatation; 2. bile duct; 3. swine

Endoscopy and Imaging O-110 A randomized controlled trial of comparison on time and rate of cecal and terminal ileal intubation according to adult-colonoscope length: intermediate versus long Presenting Author: SEUNG HWA LEE Additional Authors: DUCK JOO LEE, JOON KOO KANG Corresponding Author: SEUNG-HWA LEE Affiliations: Ajou University School of Medicine, Ajou University School of Medicine Objective: For a complete colonoscopic examination, a high intubation rate and a short intubation time have been demanded to colonoscopists, if possible. The aim of the present study was to compare these examination parameters, intubation time and rate, according to the length of colonoscope. Methods: This was a prospective, randomized, singleblinded controlled trial. A total of 507 healthy Korean subjects were randomly assigned into two groups: intermediate length adult-colonoscope (n = 254) and long length adult-colonoscope (n = 253). Cecal intubation time and rate, and terminal ileal intubation time and rate as well as other procedure-related outcomes (withdrawal time and total procedure time)

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were evaluated. Results: There were significant differences in cecal intubation time and in terminal ileal intubation rate according to the length of the colonoscope. Time-to-cecal intubation was shorter for the intermediate-scope group than for the long-scope group (234.2 ± 115.0 seconds vs 280.7 ± 135.0 seconds, P < 0.001). However, the success rate of terminal ileal intubation was higher in the long-scope group than in the intermediate-scope group (95.3% vs 84.3%, P < 0.001). There were no significant differences in other colonoscopic parameters between the two groups. Conclusion: The intermediate length adult-colonoscope decreased the time to reach the cecum, whereas the long-scope showed a success rate of terminal ileal intubation. In our study, these findings suggest that it is reasonable to prepare and use these two types of colonoscope appropriate to the needs of the patient and examination, instead of employing only one type of colonoscope. Key Word(s): 1. colonoscopy; 2. intubation time; 3. intubation rate; 4. colonoscope length

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Figure 1

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Figure 2


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Figure 4 (c)

IBD O-111 A DNN approach to distinguishing between Crohn’s disease and ulcerative colitis without endoscopy and pathology Presenting Author: LI JING Additional Authors: SHAO BIN, CHAOHUI YU, HONGZHANG LI, LIU YULAN Corresponding Author: LI JING Affiliations: Microsoft Research (Beijing), Zhejiang University, Zhejiang Sanmen County Hospital, Peking University People’s Hospital (d)

Figure 3

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Objective: Crohn’s disease (CD) and ulcerative colitis (UC) are two inflammatory bowel diseases (IBD) which largely share the same set of symptoms, such as abdominal pain, bloody stool and endoscopic mucosal lesions. The misdiagnosis rate of CD and UC is high due to the lack of discriminative biochemical markers and being histopathologically indistinguishable at the early stage of intestinal mucosa lesions. We aim to distinguish between CD and UC by a machine learning technology called deep neural network (DNN). This approach solely relies on commonly available biochemical test results. Methods: We have a real-life data set that consists of 232 CD cases and 187 UC cases collected from 3 independent hospitals. These 419 IBD cases have already been confirmed by endoscopy and pathology by endoscopy and pathology using classical guidelines. We selected 32 commonly available biochemical indicators as input signals, and designed a three-layered deep neural work to classify the 32-dimensional input vectors. Results: The cross validation error rate is lower than 5%. To the best of our knowledge, this is the first work that distinguishes between CD and UC with such a high degree of accuracy using serum tests only. Conclusion: The intrinsically complicated relationships between biochemical indicators make it almost impossible for


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humans to build a strong connection between the biochemical indicators and the inflammatory bowel diseases CD and UC. Confirmed by our experimental evaluation, the deep neural network based machine learning approach can classify CD and UC with a high degree of accuracy. Key Word(s): 1. inflammatory bowel diseases; 2. diagnosis; 3. machine learning; 4. deep neural network

IBD O-112 Epac1 control intestinal epithelial barrier function by regulating JAM-A trafficking via Rap2C-TNIK signaling pathway Presenting Author: IRSHAD ALI SHEIKH Additional Authors: PARAMITA SARKAR, TULTUL SAHA, JOYDEEP AOUN, MIRAJUL HOQUE KAZI Corresponding Author: IRSHAD ALI SHEIKH Affiliations: National Institute of Cholera & Enteric Diseases, National Institute of Cholera & Enteric Diseases, National Institute of Cholera & Enteric Diseases, National Institute of Cholera & Enteric Diseases Objective: Perturbation of epithelial tight junction (TJ) represents a hallmark of intestinal inflammation. Though cAMP is implicated to maintain TJ integrity, the possible regulatory mechanism by novel cAMP effector, exchange protein directly activated by cAMP (Epac1) remains unknown. Thus, we sought to investigate the role of Epac1 in maintaining TJ integrity. Methods: TJ integrity was studied by measuring trans-epithelial resistance (TER) and FITC-dextran flux rate in human T84 monolayers. Lentivirus-mediated shRNA was employed to knockdown various proteins in T84 wild-type (T84WT) cells. Confocal microscopy and surface biotinylation assay were used to study trafficking and quantification of various TJ proteins, respectively. To evaluate TJ barrier function upon bacterial infection, invasion assay was performed in T84WT vs. Epac1 knockdown T84 (Epac1KDT84) cells. Results: Reduced TER and increased flux of FITC-dextran were observed in Epac1KDT84 cells vs. T84WT cells. Confocal images revealed punctuated staining of major TJ protein, junctional adhesion molecule-A (JAM-A) into sub-apical compartment that don’t colocalize with apical surface marker, wheat germ agglutinin, due to Epac1KD. Biotinylation assay revealed reduced band intensity of JAM-A, while no similar change was observed in other TJ protein, such as occludin and claudin1 in Epac1KDT84 cells vs. T84WT cells. Silencing downstream Epac1 effector Rap2C and TNIK caused similar change in TER and FITC-dextran flux rate as observed in Epac1KDT84 cells. Preincubating T84WT cells with recycling endosome inhibitor, primaquine caused reduced surface expression of JAM-A. Shigella flexneri invasion significantly increased in Epac1KDT84 cells vs. T84WT cells. Conclusion: We conclude that Epac1 regulates JAM-A trafficking by a novel Rap2C-TNIK signaling pathway which may have potential therapeutic value in intestinal inflammation. Key Word(s): 1. Epac1; 2. tight junction; 3. inflammation

IBD O-113 BAHD1: gatekeeper to protect us from ulcerative colitis? Presenting Author: HUATUO ZHU Additional Authors: XINGYONG WAN, WENGUO CHEN, LIHUA CHEN, CHAOHUI YU, MIN YUE, YINING DAI Corresponding Author: HUATUO ZHU Affiliations: The First Affiliated Hospital, Zhejiang University, The First Affiliated Hospital, Zhejiang University, The First Affiliated Hospital, Zhejiang University, The First Affiliated Hospital, Zhejiang University, The First Affiliated Hospital, Zhejiang University, The First Affiliated Hospital, Zhejiang University Objective: It was recently reported that epigenetics might play an essential role in inflammatory bowel disease (IBD). Bromo adjacent homology domain containing (BAHD1), which is involved in category of epigenetics, can regulate cell differentiation and maintain homeostasis by promoting the process of heterochromatin formation. Our study aimed to investigate the effects and underlying mechanisms of BAHD1 on development of ulcerative colitis (UC), seeking a new therapeutic target for the inflammation-associated colon diseases. Methods: Experimental colitis was induced in eight-week-old C57BL/6 mice by oral dextran sulfate sodium (DSS) administration. Disease activity index (DAI) and hematoxylin&eosin staining(HE) of distant colon sections were used to evaluate the chemically induced murine models of intestinal inflammation. To simulate the intestinal inflammation microenvironment of epithelial cells (IECs), Caco-2 cells were exposed to a mixture of lipopolysaccharide (LPS), TNF-α, IL-1β, and IFN-γ for 24 h. BAHD1 expression was detected using real-time PCR, Western blot and immunohistochemistry (IHC) in both UC patients and mice model colon tissue. Small interfering RNA (siRNA) was used to knock down the BAHD1 level in Caco-2 cells and level of associated cytokines were detected by either real-time PCR or ELISA. Results: The DAI and H&E staining results showed that murine model of UC-like inflammation was successfully established. With the method of IHC, we found that BAHD1 existed in the normal internal crypt and surface epithelial cells ubiquitously. Furthermore, compared with the control group, BAHD1 expression in colon tissue was significantly decreased in both UC patients and mice model. Consistent with BAHD1, the relative mRNA level of other chromatin complex model factors, including SP1, KAP1, HP1, MBD1, and HDAC1/5, were markedly reduced in DSS-induced mice colitis distal colon. To further examine the role of BAHD1 in the vitro cell line model system, we found that the protein level of BAHD1 was decreased in the stimulated group. Moreover, siRNA group within stimulatory factors secreted more IL-6 and MCP-1 contents in the culture supernatant than control group (p < 0.05). Meanwhile, the mRNA expression of TNF-α, IL-6, and IL-8 were remarkably enhanced in the treated group (P < 0.05). Conclusion: Collectively, these findings provide evidence that BAHD1 might act as an indispensable safeguard to keep intestine immunological homeostasis. Key Word(s): 1. BAHD1; 2. IBD; 3. UC; 4. inflammation


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Liver O-114 Cost analysis of liver transplantation in National University Hospital, Singapore Presenting Author: CHERN HAO CHONG Additional Authors: READON TEH, SENG GEE LIM, BOON LENG, KIERON LIM, YOCK YOUNG DAN, GUAN HUEI LEE, MAUNG AYE THWIN, KRISHNAKUMAR MADHAVAN, WEI CHIEH, ALFRED KOW, SHRIDHAR GANPATHI IYER, STEPHEN CHANG, PRISCILLA WEE, HOW CHENG LOW Corresponding Author: CHERN HAO CHONG Affiliations: National University Hospital, Singapore, National University Hospital Singapore, National University Hospital, Singapore, National University Hospital, Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital Singapore, National University Hospital, Singapore, National University Hospital, Singapore, National University Hospital, Singapore Objective: Liver transplant (LT) has improved life expectancy and outcomes in patients with decompensated liver disease and hepatocellular carcinoma (within criteria) but it comes with high cost. The study sought to determine the overall cost of LT and factors influencing the cost in National University Hospital, Singapore. Methods: We retrospectively review patients’ electronic medical records, hospital admissions for liver transplant, etiology, Child-Pugh and MELD scores, BMI and creatinine clearance. Spearman’s rank correlation coefficient was used to examine the relationship of different variables with cost of transplant. Results: A total number of 77 adult liver transplant (AdLT) were performed between 2004 and 2013. Cost of transplant was significantly associated with MELD score (p = 0.02), Child’s score (p < 0.001), Length of ICU (p < 0.001) and hospital stay (p < 0.001). There was no significant association between age, BMI, and creatinine clearance. The highest total LT cost was noted in acute liver failure (ALF). However, when we averaged out the cost per day of LT for each etiology, highest per-day cost was among non-alcoholic steatohepatitis (NASH) cirrhosis transplant. The median cost for transplant is US$ 84,768.04 (SD US$ 69,212-$ 100,324). Conclusion: The length of stay has the highest correlation with overall cost in AdLT. A possible explanation is the lack of available liver for immediate transplant in ALF leading to prolonged hospitalization. However, NASH cirrhosis transplant has the highest cost per day possibly due to pre-existing comorbidities that leads to transplant complications. Key Word(s): 1. cost analysis; 2. liver transplantation; 3. Singapore; 4. Transplantation Table 1. Factors affecting cost of transplant

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MELD Child-Pugh Score Length of hospitalization Length of ICU stay Age BMI Creatinine clearance

Correlation coefficient

P value

0.344 0.447 0.640 0.724 −0.164 0.168 −0.180

0.02

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