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International audience; To evaluate whether systematic mesh implantation upon primary colostomy creation was effective to prevent PSH.Summary of background data: Previous randomized trials on prevention of PSH by mesh placement have shown contradictory results.Methods: This was a prospective, randomized controlled trial in 18 hospitals in France on patients aged ≥18 receiving a first colostomy for an indication other than infection. Participants were randomized by blocks of random size, stratified by center in a 1:1 ratio to colostomy with or without a synthetic, lightweight monofilament mesh. Patients and outcome assessors were blinded to patient group. The primary endpoint was clinically diagnosed PSH rate at 24 months of the intention-to-treat population. This trial was registered at ClinicalTrials.gov, number NCT01380860.Results: From November 2012 to October 2016, 200 patients were enrolled. Finally, 65 patients remained in the no mesh group (Group A) and 70 in the mesh group (Group B) at 24 months with the most common reason for drop-out being death (n = 41). At 24 months, PSH was clinically detected in 28 patients (28%) in Group A and 30 (31%) in Group B [P = 0.77, odds ratio = 1.15 95% confidence interval = (0.62;2.13)]. Stoma-related complications were reported in 32 Group A patients and 37 Group B patients, but no mesh infections. There were no deaths related to mesh insertion.Conclusion: We failed to show efficiency of a prophylactic mesh on PSH rate. Placement of a mesh in a retro-muscular position with a central incision to allow colon passage cannot be recommended to prevent PSH. Optimization of mesh location and reinforcement material should be performed.

Summary Background The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone. Methods We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18–70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov , NCT00769405 , and is now completed. Findings Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0–77·1), median overall survival was 41·7 months (95% CI 36·2–53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1–49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63–1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035). Interpretation Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases. Funding Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.

Background Spleen-preserving distal pancreatectomy with resection of the splenic vessels (VR-SPDP) is an effective procedure. However, hemodynamic changes in splenogastric circulation may lead to the development of gastric varices (GV) with a risk of gastrointestinal (GI) bleeding. This retrospective study aimed to assess the long-term postoperative clinical follow-up of patients and review the late postoperative abdominal computed tomography (CT) or endoscopic examination. Methods From 1988 to 2015, 48 consecutive VR-SPDP for benign or low-grade malignant disease were included. Late postoperative follow-up was undertaken with the use of a prospective database and assessment undertaken by CT and/or endoscopy. Results The median follow-up was 76 months (range: 12–334 months). Two patients were lost to follow-up. Gastrointestinal hemorrhage occurred in one patient. Endoscopy and abdominal CT showed submucosal GV in five patients. Ten patients had perigastric varices (27%), but none developed clinical complications from their varices. All varices occurred within one year after distal pancreatectomy and remained stable during follow-up. Discussion Asymptomatic varices frequently occurred in patients who underwent VR-SPDP, but bleeding risk seemed low. Abdominal CT could identify GV and distinguish submucosal varices with a higher risk of gastric bleeding.

Ventral mesh rectopexy (VMR) is a surgical option to treat rectal prolapse with pelvic floor dysfunction (PFD). Using synthetic surgical glue to fix the mesh to the anterior rectal wall after ventral dissection could be advantageous in comparison with sutured or stapled fixation. This study aimed to evaluate the safety and efficacy of synthetic surgical glue for mesh fixation compared with suture mesh fixation in VMR. This observational cohort study is a retrospective analysis conducted in a University Hospital Pelvic Surgery Center. All consecutive female patients (n = 176) who underwent laparoscopic or laparotomic VMR between January 2009 and December 2014 were included. Two groups were defined based on mesh fixation technique of the rectal wall: VMR with synthetic glue (n = 66) and VMR with suture (n = 110). The recurrence-free survival after VMR was determined by Kaplan–Meier method and multivariate analysis by Cox regression. Short-term postoperative complications, postoperative symptom improvement, the need for complementary treatment postoperatively, and procedure length were evaluated. A total of 176 females patients (mean age, 58.6 ± 13.7 years) underwent VMR with synthetic mesh. Mean recurrence-free survivals after VMR were 17.16 (CI 95% 16.54–17.80) and 17.33 (CI 95% 16.89–17.77) months in the glue group and the suture group, respectively (p > 0.05). Cox regression identified an independent effect on the recurrence risk of the external rectal prolapse, alone, or in combination with other anatomical abnormalities (HR = 0.37; CI 95% 0.14–0.93; p = 0.03). There was no significant difference of short-term postoperative morbidity, procedure length, postoperative symptom improvement, or need for complementary treatment postoperatively between suture versus glue groups (all p > 0.05). Use of glue to fix the mesh in VMR was safe and had no impact on outcomes. External prolapse was the unique significant predictive factor for recurrence.

Summary Objectives In France, seton drainage followed by fistulotomy is currently the standard treatment for high cryptoglandular fistula-in-ano. Biological or synthetic glues, such as Glubran ® 2, have been recently proposed for sealing the fistula tract. The purpose of this study is to determine the healing rate with glubran 2 and to assess the functional outcome after cure of fistula-in-ano. Patients and methods From July 2006 to July 2008, 34 patients (20 males; median age 48.5 years, range 22–55 years) with high cryptoglandular anal fistulas were treated with glubran 2. Patients were seen for physical examination at 1, 3 and 6 months, then interviewed by telephone at 1 and 2 years, and in September 2009. The Fecal incontinence severity index (FISI) score was used to assess continence. Results The healing rate at 1 month was 67.6% (23 patients); the fistula failed to heal in 11 patients. All 23 patients with a healed fistula remained recurrence-free, with no continence disorders noted, during the median 34-month follow-up period (range 21–43 months). One patient was lost to follow-up after 6 months. Conclusion Glubran 2 provides an effective treatment for high fistula-in-ano, with no change in continence. In future, a randomized comparison of this agent with fibrin glues should be useful.

PURPOSE: Abdominoperineal resection, with iliac colostomy, remains the gold standard treatment for very low-lying rectal cancer, but it alters patients' quality of life. Alternatives to iliac colostomy need to be experimented. Antegrade enemas via a cecal access (Malone operation) obtains a colonic emptying and improves continence for incontinent patients. Continence and quality of life after abdominoperineal resection and perineal colostomy associated to a Malone antegrade continence enema were studied. METHODS: After abdominoperineal resection for cancer, 18 patients had a digestive reconstruction by perineal colostomy and Malone antegrade continence enema. Patients performed antegrade enemas every 24 to 48 hours with tap water. After six months, continence (Cleveland Clinic score) and quality of life (Fecal Incontinence Quality of Life scale) were recorded. RESULTS: Morbidity was 5 percent (1 appendix necrosis). All patients could perform antegrade enemas by themselves. Mean continence score was 6.41/20 (standard error, 2.31). Fecal Incontinence Quality of Life scores were: lifestyle 3.18/4 (standard error, 0.83); coping/ behavior 2.99/4 (standard error, 0.83); depression/self-perception 3.11/4 (standard error, 0.83); embarrassment 2.84/4 (standard error, 0.63). CONCLUSIONS: After abdominoperineal resection, Malone antegrade continence enema associated to perineal colostomy provided an acceptable continence. It preserved patients' body image and resulted in a satisfying quality of life. It could become an alternative to iliac colostomy in selected patients.

Background Recommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed. Aims We investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers. Methods Colorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer. All tumours underwent an MisMatch Repair test combining microsatellite instability analysis and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair-deficient tumour were offered germline testing. Results Of the 307 patients fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient tumour. Amongst them 27 were identified as Lynch carriers (20 with germline mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of genetic testing). The simplified clinical criteria selected a population whose MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome. Conclusion This bio-clinical strategy based on simplified clinical criteria combined with an MisMatch Repair test efficiently detected LS cases and is easy to use in clinical practice, outside expert centres.

Abdominoperineal resection has a high rate of postoperative morbidity of the perineal wound. This study aimed to determine the effects of perineal colostomy on perineal morbidity after abdominoperineal resection.All patients who underwent an abdominoperineal resection for rectal adenocarcinoma between 1993 and 2007 were studied. Two groups were identified and compared who had undergone either an iliac colostomy or a perineal colostomy.The analysis included 110 patients (iliac colostomy group, n = 41; perineal colostomy group, n = 69). There were fewer instances of pelviperineal morbidity (P = .008) and fewer instances of wound dehiscence (P = .02) in the perineal colostomy group, which resulted in a shorter time to healing (35.3 vs 45.1 d, respectively; P = .04). There was no specific postoperative morbidity in any patient and no difference between the 2 groups regarding long-term perineal morbidity. The benefits from perineal colostomy were statistically significant in patients who received radiation therapy in terms of pelviperineal morbidity (P = .01) and healing time (50.8 vs 35.9 days, respectively; P = .02), whereas no difference was found in patients who had not received radiation therapy.Perineal colostomy is a safe and functionally acceptable procedure for perineal reconstruction after abdominoperineal resection for rectal adenocarcinoma. In the present study, there was no additional morbidity related to perineal colostomy, and this procedure was associated with a decrease in perineal morbidity and healing time compared with primary perineal closure, in particular, after radiotherapy treatment.

International audience; AIMS: The aim of the present study was to assess the clinical fate of, and to gain new insights into, branch duct and mixed (predominantly main duct type) forms of intraductal papillary mucinous neoplasia of the pancreas (IPMN). METHODS: During a 17-year period, 99 successive IPMN patients (52 men, 47 women; mean age, 64 years) were included and divided into two groups for further comparison: one group had branch duct IPMN, whereas the other had mixed IPMN. RESULTS: Patients from the mixed IPMN group (n = 52) displayed a greater rate of symptoms (83% vs 55%, P = 0.004), pancreatic resection (67% vs 38%, P = 0.007), malignancy (35% vs 13%, P = 0.017) and death (15% vs 4%, P = 0.09) than those from the branch duct IPMN group. A 38-month follow up of non-operated, symptom-free patients confirmed that more than 85% of branch duct IPMN patients were asymptomatic without evidence of malignancy. Borderline lesions and carcinoma are found in up to 50% of symptomatic resected branch duct IPMN cases. CONCLUSION: Patients with the mixed form of IPMN as well as with symptomatic branch duct IPMN should require pancreatic resection because of symptoms and the risk for malignancy. In silent branch duct IPMN without radiological signs of malignancy, a non-operative watch-and-wait strategy can be discussed.

Purpose Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. Patients and Methods After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m2 administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m2 [FFCD] × 5 days or FU 370 mg/m2 plus l-leucovorin 100 mg/m2 IV × 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). Results A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. Conclusion This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus–based regimen after complete resection of colorectal cancer metastases.

PURPOSE: Abdominal rectopexy is the preferred surgical technique for the treatment of total rectal prolapse. In many reported series, its results are impaired by induced constipation. Lateral rectal ligaments preservation could prevent constipation but increase recurrence rates. We report anatomic and functional results of abdominal Orr- Loygue ventral rectopexy with dissection limited to anterior and posterior rectal wall. METHODS: Consecutive patients with total rectal prolapse or intra-anal rectal prolapse associated to fecal incontinence or outlet obstruction were treated by abdominal rectopexy. Recurrences, correction of symptoms, and induced constipation were prospectively analyzed. RESULTS: Seventy-three patients were treated between 1993 and 2004. Recurrence was observed in 3 of 73 patients (4.1 percent) after a mean follow-up period of 28.6 (range, 6–84) months. Overall patient satisfaction (correction of prolapse, incontinence, and/or outlet obstruction) after the procedure was classified in three categories: Cured: n = 45 (61.6 percent); Improved: n = 24 (32.9 percent); Failure: n = 4 (5.5 percent). Postoperative constipation appeared in 2 of 36 (5.5 percent) preoperatively nonconstipated patients and worsened in 2 of 37 (5.4 percent) preoperatively constipated patients. CONCLUSIONS: Orr-Loygue abdominal ventral rectopexy with limited dissection and preservation of rectal lateral ligaments is a safe and effective procedure for the treatment of complete rectal prolapse, or internal prolapse associated with fecal incontinence or outlet obstruction. Preservation of lateral ligaments seems to prevent postoperative constipation without increasing the risk of prolapse recurrence

Proctectomy followed by straight coloanal anastomosis (CAA) often results in poor functional outcome known as the anterior resection syndrome. It is now based on evidence that a colonic J-pouch CAA improves outcome in the first 2 years. We assessed the very late functional outcome of CAA patients with or without a pouch. These results show that the functional benefit of the J-pouch anastomoses is sustained over the very long term.

Sporadic early onset colorectal carcinoma (EOCRC) which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC) with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45-60 years were excluded to help define "young" and "old" groups. Thirty-nine cases of sporadic EOCRC (patients ≤ 45 years with microsatellite stable tumors) were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years) and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p = 0.013). Genetic studies also showed the absence of BRAF mutations (p = 0.022) and the methylator phenotype (p = 0.005) in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF) and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p = 0.01). This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways including the TNFR1 pathway have been identified as potential biomarkers for both the diagnosis and treatment of this disease.

Objective The aim of this study was to analyze the profile of tumor recurrence for patients operated on for cancer of oesophagogastric junction or oesophagus by Ivor-Lewis oesophagectomy. Methods Patients undergoing potentially curative Ivor-Lewis oesophageal resection between January 1999 to December 2008 at a single center institution were retrospectively analyzed. Their clinical records, details of surgical procedure, postoperative course, pathological findings, recurrence and long term survival were reviewed retrospectively. Univariate and multivariate survival analyses were performed. Results One hundred and twenty patients were analyzed. Fifty three patients (44%) presented recurrence during median follow-up of 58 months. Five-year relapse free survival (RFS) rate was 51% (95%CI = [46; 65%]). On multivariate analysis, pT stage > 2 (HR = 2.42, 95%CI = [1.22; 4.79] p = 0.011), positive lymph node status (HR = 3.69; 95% CI = [1.53; 8.96] p = 0.004) and lymph node ratio > 0.2 (HR = 2.57; 95%CI = [1.38; 4.76] p = 0.003) were associated with a poorer RFS and their combination was correlated to relapse risk. Moreover, preoperative tumor stenosis was associated with an increased risk of local recurrence (HR = 3.46; 95% CI = [1.38; 8.70] p = 0.008) whereas poor or undifferentiated tumor was associated with an increased risk of distant recurrence (HR = 3.32; 95% CI = [1.03; 10.04] p = 0.044). Conclusion pT stage > 2, positive lymph node status and lymph node ratio > 0.2 are independent prognostic factors of recurrence after Ivor-Lewis surgery for cancer. Their combination is correlated with an increasing risk of recurrence that may argue favorably, in addition with preoperative tumor stenosis assessment, for adjuvant treatment or reinforced follow-up.