The Six Best Abstracts B1 Long term oncological and clinical outcomes after extralevatory abdominoperineal resection and conventional abdominoperineal resection for rectal cancer: a nationwide study E. P. Colov1, M. Klein1 & I. G€ ogenur2 1 Herlev Hospital, Herlev, Denmark, 2Køge Hospital, Køge, Denmark Aim: Extralevator abdominoperineal excision (ELAPE) is used increasingly for low rectal cancers. The aim of this study was to perform a nationwide study to compare oncological and clinical outcomes in patients undergoing ELAPE compared with conventional abdominoperineal resection (APR). Method: Electronic medical reports of patients undergoing ELAPE or APR between 2009 to 2012 in Denmark were examined. Results: About 250 and 186 patients were operated with ELAPE and APR respectively. After ELAPE 44% and 39% had chronic wound complications and pain compared with 28% and 21% after APR (P < 0.001 and P < 0.0001 respectively). No significant difference was found in hernia rate between the two procedures (1.2% ELAPE and 1.6% APR). No statistically significant difference was found for rate of local recurrence (4.4% ELAPE and 3.2% APR). Rate of systemic recurrence was significantly higher after ELAPE 25% and APR 13% (P < 0.05). Conclusion: No significant difference exists in local recurrence or hernia rate between patients undergoing ELAPE or APR for rectal cancer. Significantly more patients had chronic wound complications, pain and systemic recurrence after ELAPE compared with APR.
B2 Long-term results of a randomised controlled trial comparing preoperative conventional chemoradiotherapy with short-course radiotherapy with delayed surgery for rectal cancer T. Latkauskas, H. Pauzas, L. Kairevice, R. Janciauskiene, Z. Saladzinskas, A. Tamelis, I. Gineikiene & D. Pavalkis Lithuanian University of Health Sciences, Kaunas, Lithuania Aim: This study assesses outcomes after long-course chemoradiotherapy (CRT) compared to short-term radiotherapy (RT) followed by delayed surgery in the treatment of rectal cancer. Method: One hundred and fifty patients diagnosed with stage II-III rectal cancer between 2007–2013 were randomised to two neoadjuvant treatment arms; conventional chemoradiotherapy (CRT) and short-term radiotherapy (RT) followed by surgery after 6–8 weeks. Primary endpoints of this trial were downstaging and pathological complete response rate. Secondary endpoints were local recurrence rate and overall survival. Results: Pathological complete response was found in 3 (4.4%) cases after RT and 8 (11.1%) after CRT (P > 0.05). Downstaging (stage 0 and I) was observed in 21 (30.9%) cases in RT group versus 27 (37.5%) cases in CRT group (P > 0.05). Median follow-up time was 39.7 (range 4.9–79.7) months. Three-years overall survival (OS) was 78% in RT group vs. 82.4% in CRT group (P = 0.145), while diseasefree survival (DFS) differed significantly – 59% in RT group vs. 75.1% in CRT group (P = 0.022). Hazard ratio of cancer progression for RT patients was 1.93 (95% CI: 1.08–3.43) compared to CRT patients. Conclusion: Three-years DFS was better in CRT group compared to RT group with no difference in OS.
B3 A novel low rectal cancer stratification tool to predict the risk of circumferential resection margin involvement: data from the prospective MERCURY II study N. J. Battersby1, P. How1, S. Stelzner2, G. Branagan3, J. Strassburg4, P. Quirke5, G. Brown6 & B. Moran7, The MERCURY II Study Group1 1 Pelican Cancer Foundation, Basingstoke, UK, 2Dresden-Friedrichstadt General Hospital, Dresden, Germany, 3Salisbury NHS FT, Salisbury, UK, 4Vivantes Klinikum im Friedrichshain, Berlin, Germany, 5Leeds Institute of Cancer and Pathology, Leeds, UK, 6Royal Marsden Hospital, London, UK, 7North Hampshire Hospitals, Basingstoke, UK Aim: The MERCURY II study prospectively validated MRI assessment of the low rectal cancer resection plane. By combining MRI staging with optimal clinical management pathological circumferential resection margin (pCRM) involvement fell to 8.7%, significantly lower than previously published series. We investigate which preoperative factors predicted for pCRM involvement. Method: Between 2008 and 2012, 288 patients with adenocarcinoma 5 mm and >3 malignant nodes) and low rectal cancer resection plane ‘safety’, these were compared against pCRM outcome using binary logistic regression analysis. Results: There were four significant MRI predictors of pCRM involvement on multivariate analysis: anterior quadrant tumour invasion (OR2.6 [95%CI1.1–6.2]); mrEMVI (OR3.3 [95%CI1.3–8.3]); tumours ≤4 cm from anal verge (OR2.5 [95% CI1.0–6.3]) and an MRI ‘unsafe’ mesorectal fascia/distal TME plane (OR3.5 [95% CI1.3–8.9]). Depending on the number of factors present, the ‘pCRM involvement risk’ varied from 2% to 53% Conclusion: This information may allow a patient-tailored approach to low rectal cancer management. When no risk factors are present restorative-resection alone appears feasible but optimal management of patients with multiple risk-factors, particularly after restaging, requires further investigation.
B4 Multi-centre randomised placebo-controlled study of percutaneous tibial nerve stimulation in patients with faecal incontinence G. Giuliani2, C. Kubis3, S. O. Breukink1, I. Ferreira1, P. A. Lehur3, F. La Torre2 & C. G. M. I. Baeten1 1 Maastricht University Medical Centre, Maastricht, The Netherlands, 2Universita degli Studi di Roma “La Sapienza”, Rome, Italy, 3IMAD, University Hospital of Nantes, Nantes, France Aim: Percutaneous tibial nerve stimulation (PTNS) is presently the least invasive treatment option for faecal incontinence (FI) when conservative treatment fails. PTNS benefits remain however debatable. A placebo effect has been suggested. This study aims to demonstrate that the effect of PTNS on FI are objectively related to a true effect of tibial nerve electrical stimulation compared to placebo. Method: Three referral European centres participated in this single-blinded randomised placebo-controlled trial [NCT00974909]. Intervention group (GrA) had unilateral stimulation twice a week for 6 weeks, then once a week for 3 weeks. Placebo group (GrB) received the same treatment schedule, but had ankle test-punction only. Number of FI episodes/3 weeks, CCF-FI, SF-36 scores were compared at 9 weeks follow-up to baseline. Results: Fifty-six patients (GrA 26, GrB 30) were included, no loss to follow-up. Groups were comparable at baseline. Only minor side effects were observed. Median number of FI episodes decreased significantly (16 to 10, P < 0.05) in GrA and did not change in GrB. A significant decrease in CCF-FI score was observed in GrA but not in GrB (P < 0.05). SF-36 mental components score increased significantly in GrA (P < 0.01). Conclusion: In this sham-controlled trial PTNS showed significant improvement of FI and QoL compared to placebo.
B5 Novel technology assessment in early colorectal cancer: population level survival analysis of local excision versus major resection A. Bhangu1, R. Kiran2, S. Rasheed1, G. Brown1 & P. Tekkis1 1 Royal Marsden Hospital, London, UK, 2Columbia University Medical Centre, New York, USA Aim: Previous studies discourage local excision of rectal cancer in good-risk patients. This study evaluated survival differences after local excision and major resection for well versus moderately differentiated T1 colon and rectal cancer. Method: Patients with non-metastatic T1 colon or rectal adenocarcinoma undergoing surgery without radiotherapy between 1998 and 2010 were included from the SEER database. Five-year cancer specific survival for T1N0 tumours after local excision was compared with radical resection using adjusted hazard ratios (HR, 95% confidence interval). Results: From 37,494 T1 colorectal cancers treated, 27,760 underwent major resection with 8.5% being lymph node positive. Moderate differentiation was an independent risk factor for lymph node metastasis in colon (odds ratio [OR] 1.87, 1.65–2.12) and rectal cancer (OR 1.52, 1.16–2.00). For well-differentiated T1N0 colon cancer, local excision was oncologically equivalent to major resection (HR 1.07, 0.78–1.47) but was inferior for moderate differentiation (HR 1.30, 1.07–1.58). Similarly, local excision of well-differentiated T1N0 rectal cancer was equivalent to major resection (HR 1.11, 0.70–1.78) but was inferior for moderate differentiation (HR 1.41, 1.12–1.78). Conclusion: Long-term oncological outcome after local excision is comparable to major resection for well-differentiated T1N0 colorectal cancer. Wider use of local techniques can reduce use of radical surgery.
ª 2014 The Authors Colorectal Disease ª 2014 The Association of Coloproctology of Great Britain and Ireland. 16 (Suppl. 3), 1–2
The Six Best Abstracts B6 The healing effect of mesenchymal adipose-tissue-derived stem cells on colonic anastomosis under ischaemic condition T. W. C. Mak1, D. W. C. Chin1, J. F. Y. Lee1, P. B. S. Lai3, A. W. I. Lo2, P. K. Lam1 & S. S. M. Ng1 1 Division of Colorectal Surgery, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong, 2Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong, 3Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Aim: Anastomotic leak following colorectal surgery carries significant risks of morbidity and mortality. Stem cell therapy, with its potential for repair and regeneration may help to reduce anastomotic leak under ischaemic condition.This study assesses the potential of mesenchymal adipose-tissue-derived stem cells (ADSCs) on the healing of ischaemic colonic anastomosis in rats. Stem cell delivery method to target site is also assessed. Method: Forty Sprague-Dawley SD rats underwent segmental colonic resection, with an ischaemic protocol, followed by single-layer interrupted 6/0 polydioxanone anastomosis. They were evenly divided into four groups: (i) topical application of ADSCs and fibrin; (ii) fibrin alone; (iii) subserosal injection of ADSCs; (iv) control. Results: Animals were sacrificed on postoperative day 3 and 7. The bursting pressures in groups I and III (ADSCs group) were significantly higher than groups II and IV (P < 0.006). Histologically, less inflammation, increased fibroblastic proliferation, collagen deposition and angiogenesis were observed in the anastomosis treated with ADSCs. Conclusion: The use of adipose-derived stem cells has proven effective for anastomotic colonic healing under ischaemic condition. Topical application of stem cells with fibrin glue may provide a non-invasive method of stem cell delivery to target site.
Japanese Visiting Fellow Paper Area-specific prognostic values of mesothelin in Stage II colorectal cancer: a tissue-microarray based approach E. Shinto1, H. Ueno1, A. Shikina1, T. Kubo1, S. Fukazawa1, H. Tsuda2, J. Yamamoto1 & K. Hase1 1 Department of Surgery, National Defense Medical College, Saitama, 2Department of Pathology, National Defense Medical College, Saitama Aim: Mesothelin is expressed on normal mesothelial cells lining the pleura, pericardium and peritoneum. The biological functions of mesothelin are not clearly understood, but recent studies have suggested that the expression of mesothelin is related to an unfavorable patient outcome in several cancer types. Tissue microarray (TMA) technique may facilitate large-scale cohort study. In the present study, we used a unique TMA construction method particular about sampling areas and investigated prognostic values of mesothelin expression, whose clinical value in colorectal cancer (CRC) patients has been unclear. Method: Using formalin-fixed paraffin-embedded sections of 314 patients with Stage II CRC, we took 4 core specimens from the submucosal invasive front (Fr-sm), subserosal invasive front (Fr-ss), central area (Ce) and rolled edge (Ro) in each tumour and constructed TMA blocks. Using these TMA sets, mesothelin expression was surveyed immunohistochemically, and area-specific prognostic values were investigated.
Results: The rates of positive expression were 6.0%, 5.9%, 4.8% and 5.8% in Fr-sm, Fr-ss, Ce and Ro. Analyses of cancer-specific survival revealed that mesothelin expression showed significant prognostic values in Fr-sm (5-year survival of 78% in positive cases vs 97% in negative, P = 0.0001), in Fr-ss (78% vs 96%, P = 0.001) , in Ce (80% vs 95%, P = 0.04) , and in Ro (77% vs 96%, P = 0.02). These 4 area-specific values were evaluated by multivaliate analysis, which disclosed that mesothelin immunoreactivity in Fr-sm (HR 5.9, P = 0.0007) was an independent prognostic indicator. Conclusion: Area-specific four-point TMA analyses disclosed the prognostic significance of mesothelin expression in Fr-sm of Stage II CRCs.
ASCRS Visiting Fellow Paper Recurrence and survival in patients with UT2UN0 rectal cancer (RC) treated with neoadjuvant chemoradiation (CRT) and local excision (LE): results of the ACOSOG Z6041 trial J. Garcia-Aguilar1, L. A. Renfro2, C. R. Thomas Jr3, E. Chan4, P. Cataldo5, M. Jorge6, D. Medich7, C. Johnson8, S. Oommen9, B. Wolff2, A. Pigazzi10, M. McNevin11, R. Pons12 & R. Bleday13 1 Memorial Sloan-Kettering Cancer Centre, New York, NY, USA, 2Mayo Clinic, Rochester, MN, USA, 3Oregon Health and Science University, Portland, OR, USA, 4 Vanderbilt University Medical Centre, Nashville, TN, USA, 5University of Vermont, Burlington, VT, USA, 6Tampa General Hospital, Tampa, FL, USA, 7University of Pittsburgh Medical Centre, Pittsburgh, PA, USA, 8St. Francis Hospital, Tulsa, OK, USA, 9John Muir Medical Centre, Concord, CA, USA, 10University of California, Irvine, Irvine, CA, USA, 11Holy Family Hospital, Spokane, WA, USA, 12Hialeah Hospital, Hialeah, FL, USA, 13Brigham and Women’s Hospital, Boston, MA, USA Aim: LE alone is an effective treatment for selected uT1uN0 RCs; however, for uT2uN0 RCs LE results in a higher local recurrence rate and lower survival compared to total mesorectal excision (TME). The Z6041 phase II trial (NCT00114231) investigates the efficacy of CRT and LE for treating uT2uN0 RC. Here we report the oncologic outcomes. Method: Patients (pts) with ultrasound-staged T2N0, ≤4 cm diameter, RC located within 8 cm of the anal verge, and ECOG PS ≤2 were treated with capecitabine (825 mg/m2 days 1–14 and 22–35) and oxaliplatin (50 mg/m2 weeks 1, 2, 4 and 5) during radiation (RT) (total dose 54 Gy) followed by LE. Due to toxicity, the dose of RT was reduced to 50.4 Gy and capecitabine to 725 mg/m2 (5 days/week/ 5 weeks). Local and distant recurrences were recorded. Disease free survival at 3 years was calculated using Kaplan–Meier analysis. Results: Of the 90 pts accrued, 11 were considered ineligible or withdrew consent. Of the 79 eligible pts, 1 had TME and 2 had no surgery. Of the 76 pts who had LE, 3 had ypT3 tumours and 1 had positive margins. They were considered inevaluable from primary endpoint analysis per study protocol. The 72 evaluable pts were followed for a mean 4.2 (0.5–6.4) years. At the end of follow-up 2 (3%) pts had developed local recurrence after LE; both were salvaged with an R0 abdominoperineal excision (APE) of the rectum, but 1 developed recurrence after APE. Five (7%) pts have developed distant metastasis (lung 3, liver 1, uterus 1). Six pts have died from unrelated causes during follow-up. The 3-year disease-free survival for the evaluable pts was 0.87 (0.79–0.95, 95% CI). Conclusion: The treatment of uT2uN0 rectal cancer with CRT and LE is associated with a low rate of local recurrence, but a higher rate of distant metastasis. The 3-year disease-free survival falls above the unacceptable level and close to levels deemed promising as defined by the study design. Therefore, CRT and LE may be considered as an alternative to TME for selected patients with uT2uN0 distal RC.
ª 2014 The Authors Colorectal Disease ª 2014 The Association of Coloproctology of Great Britain and Ireland. 16 (Suppl. 3), 1–2