Anne Dubois

Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6)

Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the effect of increasing the interval between the end of RCT and surgery on the pCR rate. Methods GRECCAR6 was a phase III, multicenter, randomized, open-label, parallel-group controlled trial. Patients with cT3/T4 or Tx N+ tumors of the mid or lower rectum who had received RCT (45 to 50 Gy with fluorouracil or capecitabine) were included. Patients were randomly included in the 7-week or the 11-week (11w) group. Primary end point was the pCR rate defined as a ypT0N0 specimen (NCT01648894). Results A total of 265 patients from 24 centers were enrolled between October 2012 and February 2015. The majority of the tumors were cT3 (82%). After RCT, surgery was not performed in nine patients (3.4%) because of the occurrence of distant metastasis (n = 5) or other reasons. Two patients underwent local resection of the tumor scar. A total of 47 (18.6%) specimens were classified as ypT0 (four had invaded lymph nodes [8.5%]). The primary end point (ypT0N0) was not different (7 weeks: 20 of 133, 15.0% v 11w: 23 of 132, 17.4%; P = .5983). Morbidity was significantly increased in the 11w group (44.5% v 32%; P = .0404) as a result of increased medical complications (32.8% v 19.2%; P = .0137). The 11w group had a worse quality of mesorectal resection (complete mesorectum [I] 78.7% v 90%; P = .0156). Conclusion Waiting 11 weeks after RCT did not increase the rate of pCR after surgical resection. A longer waiting period may be associated with higher morbidity and more difficult surgical resection.

Peng’s Binding Pancreaticojejunostomy After Pancreaticoduodenectomy: A French Prospective Study

BackgroundPancreatic fistula (PF) is the single most important complication after pancreaticoduodenectomy. Recently, a 0% rate of PF was reported using a binding pancreaticojejunostomy with intussusception of the pancreatic stump. The aim of this study was to assess the safety of this new binding pancreaticojejunostomy in condition most susceptible to PF, i.e. soft pancreas and non-dilated main pancreatic duct.MethodsForty-five consecutive patients with soft pancreas and non-dilated main pancreatic duct underwent a binding pancreaticojejunostomy. Post-operative PF was defined according to the International Study Group of Pancreatic Fistula.ResultsFour patients (8.9%) developed a PF. In one case, PF developed on post-operative day 3 due to a technical deficiency. In the three other cases, pancreatic fistula developed after the tenth post-operative day; all the patients had local and/or general co-morbidities before PF occurrence.ConclusionsBinding pancreaticojejunostomy according to Peng is a safe and secure technique that improves the rate of pancreatic fistula, especially in case of soft texture of the pancreas remnant. However, a 0% rate seems to be hard to achieve because other abdominal and general complications are frequent and can lead to secondary leakage of the pancreatic anastomosis.

Cost-effectiveness of New Surgical Treatments for Hemorrhoidal Disease: A Multicentre Randomized Controlled Trial Comparing Transanal Doppler-guided Hemorrhoidal Artery Ligation With Mucopexy and Circular Stapled Hemorrhoidopexy

Objective: To compare Doppler-guided hemorrhoidal artery ligation (DGHAL) with circular stapled hemorrhoidopexy (SH) in the treatment of grade II/III hemorrhoidal disease (HD). Background: DGHAL is a treatment option for symptomatic HD; existing studies report limited risk and satisfactory outcomes. DGHAL has never before been compared with SH in a large-scale multi-institutional randomized clinical trial. Methods: Three hundred ninety-three grade II/III HD patients recruited in 22 centers from 2010 to 2013 were randomized to DGHAL (n = 197) or SH (n = 196). The primary endpoint was operative-related morbidity at 3 months (D.90) based on the Clavien-Dindo surgical complications grading. Total cost, cost-effectiveness, and clinical outcome were assessed at 1 year. Results: At D.90, operative-related adverse events occurred after DGHAL and SH, respectively, in 47 (24%) and 50 (26%) patients (P = 0.70). DGHAL resulted in longer mean operating time (44±16 vs 30±14 min; P < 0.001), less pain (postoperative and at 2 wks visual analogic scale: 2.2 vs 2.8; 1.3 vs 1.9; P = 0.03; P = 0.013) and shorter sick leave (12.3 vs 14.8 d; P = 0.045). At 1 year, DGHAL led to more residual grade III HD (15% vs 5%) and a higher reoperation rate (8% vs 4%). Patient satisfaction was >90% for both procedures. Total cost at 1 year was greater for DGHAL [&OV0556;2806 (&OV0556;2670; 2967) vs &OV0556;2538 (&OV0556;2386; 2737)]. The D.90, incremental cost-effectiveness ratio (ICER) was &OV0556;7192 per averted complication. At 1 year DGHAL strategy was dominated. Conclusions: DGHAL and SH are viable options in grade II/III HD with no significant difference in operative-related risk. Although resulting in less postoperative pain and shorter sick leave, DGHAL was more expensive, took longer, and provided a possible inferior anatomical correction suggesting an increased risk of recurrence.

Therapeutic management of complex anal fistulas by installing a nitinol closure clip: study protocol of a multicentric randomised controlled trial--FISCLOSE.

Introduction Complex anal fistulas are responsible for pain, faecal incontinence and impaired quality of life. The rectal mucosa advancement flap (RMAF) procedure to cover the internal opening of the fistula remains a strategy of choice. However, a new procedure for closing anal fistulas is now available with the use of a nitinol closure clip (OTSC Proctology, OVESCO), which should ensure a better healing rate. This procedure is currently becoming more widespread, though without robust scientific validation, and it is therefore essential to carry out a prospective evaluation in order to determine the efficacy and safety of this new medical device for complex anal fistulas. Methods and analysis The FISCLOSE trial is aimed at evaluating the efficacy and safety of a nitinol closure clip compared to the RMAF procedure for the management of complex anal fistulas. This trial is a prospective, randomised, controlled, single-blind, bicentre and interventional study. Patients (n=46 per group) will be randomly assigned for management with either a closure clip or RMAF. The main objectives are to improve the healing rate of the anal fistula, lessen the postoperative pain and faecal incontinency, enhance the quality of life, and lower the number of reinterventions and therapeutic management costs. The primary outcome is the proportion of patients with a healed fistula at 3 months. The secondary outcomes are anal fistula healing (6 and 12 months), proctological pain (visual analogue scale), the faecal incontinence score (Jorge and Wexner questionnaire), digestive disorders and quality of life (Gastrointestinal Quality of Life Index and Euroqol EQ5D-3 L) up to 1 year. Ethics and dissemination The study was approved by an independent medical ethics committee 1 (IRB00008526, CPP Sud-Est 6, Clermont-Ferrand, France) and registered by the competent French authority (ANSM, Saint Denis, France). The results will be disseminated in a peer-reviewed journal and presented at international congresses. Trial registration number NCT02336867; pre-result.

Systematic Review With Meta-Analysis: Anti-TNF Therapy in Refractory Pouchitis and Crohn’s Disease-Like Complications of the Pouch After Ileal Pouch-Anal Anastomosis Following Colectomy for Ulcerative Colitis

Background Inflammatory complications including chronic refractory pouchitis and Crohns disease (CD)-like complications of the pouch are common complications after ileal pouch-anal anastomosis (IPAA) following colectomy for ulcerative colitis (UC). We performed a systematic review and meta-analysis to evaluate the efficacy of anti-TNF therapy in distinguishing patients with chronic refractory pouchitis from those with CD-like complications of the pouch. Methods We performed a systematic literature search to identify articles and abstracts reporting anti-TNF agents efficacy in treating inflammatory complications of the pouch after IPAA for UC. Short-term and long-term remissions were evaluated at 8 weeks 95%CI[5-10] and 12 months 95%CI[12-18.5], respectively. Results We identified 21 articles and 3 abstracts including 313 patients treated either with infliximab (n = 194) or adalimumab (n = 119) for inflammatory complications of the pouch. The rates of short-term and long-term clinical remission were 0.50 (95%CI [0.37-0.63]; I2 = 0.57) and 0.52 (95%CI[0.39-0.65]; I2 = 0.59), respectively. The rate of remission after anti-TNF induction therapy seemed to be higher in CD-like complications of the pouch 0.64 (95%CI[0.5-0.77]; I2 = 0.18), compared to refractory pouchitis 0.10 (95%CI [0.00-0.35]; I2 = 0.00) (P = 0.06), whereas no such difference appeared after long-term maintenance therapy 0.57 (95%CI[0.43-0.71]; I2 = 0.32) and 0.37 (95%CI [0.14-0.62]; I2 = 0.47), respectively (P = 0.57). Sensitivity analyses suggested no difference in outcomes. No significant publication bias has been detected. Conclusion Anti-TNF agents have a clear trend to have higher and faster efficacy in CD-like complications of the pouch compared to refractory pouchitis, highlighting the need to differentiate these two entities both in daily practice and clinical trials.

Endoscopy-based management decreases the risk of postoperative recurrences in Crohn's disease.

AIM To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence. METHODS From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohns disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS From 205 patients who underwent surgery, 161 patients (follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence (HR = 0.30, 95%CI: 0.13-0.70, P = 0.006). CONCLUSION Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.

Myenteric plexitis is a risk factor for endoscopic and clinical postoperative recurrence after ileocolonic resection in Crohn's disease

BACKGROUND As surgical resection is not curative in Crohns disease, postoperative recurrence remains a crucial issue. The selection of patients, according to available risk factors, remains disappointing in clinical practice highlighting the need for better criteria, such as histologic features. AIMS To investigate whether submucosal and myenteric plexitis increase the risk of endoscopic, clinical and surgical postoperative recurrence in Crohns disease. METHODS From the pathology department database, we retrospectively retrieved the data of all the patients who have undergone ileocolonic resection for Crohns disease. Two pathologists, blinded from clinical data, reviewed all specimens to evaluate the presence of plexitis at the proximal resection margin. RESULTS Of the 75 included CD patients, 19 (25.3%) had histological involvement of resection margin. Inflammatory cells count for myenteric and submucosal plexus were performed in 56 patients. In multivariate analysis, the myenteric plexitis was a risk factor for endoscopic postoperative recurrence (HR 8.83 CI95% [1.6-48.6], p=0.012), and the presence of at least one myenteric lymphocyte (HR 4.02 CI95% [1.4-11.2], p=0.008) was predictive of clinical postoperative recurrence. We observed no histologic predictor for surgical postoperative recurrence. CONCLUSION Myenteric plexitis in proximal margins of ileocolonic resection specimens is independently associated with endoscopic and clinical postoperative recurrence in Crohns disease.

Previous radiation for prostate neoplasm alters surgical and oncologic outcomes after rectal cancer surgery

Previous radiation for prostate cancer (PC) contra‐indicates neoadjuvant chemoradiotherapy for rectal cancer (RC) because of risk of cumulative radiation dose toxicity. Postoperative outcomes after proctectomy have not been well studied in these patients who did not receive optimal treatment.

Sa1895 Myenteric Plexitis Is a Risk Factor for Endoscopic and Clinical Postoperative Recurrence After Ileocolonic Resection in Crohn's Disease

a b s t r a c t Background: As surgical resection is not curative in Crohns disease, postoperative recurrence remains a crucial issue. The selection of patients, according to available risk factors, remains disappointing in clinical practice highlighting the need for better criteria, such as histologic features. Aims: To investigate whether submucosal and myenteric plexitis increase the risk of endoscopic, clinical and surgical postoperative recurrence in Crohns disease. Methods: From the pathology department database, we retrospectively retrieved the data of all the patients who have undergone ileocolonic resection for Crohns disease. Two pathologists, blinded from clinical data, reviewed all specimens to evaluate the presence of plexitis at the proximal resection margin. Results: Of the 75 included CD patients, 19 (25.3%) had histological involvement of resection margin. Inflammatory cells count for myenteric and submucosal plexus were performed in 56 patients. In mul- tivariate analysis, the myenteric plexitis was a risk factor for endoscopic postoperative recurrence (HR 8.83 CI95% (1.6-48.6), p = 0.012), and the presence of at least one myenteric lymphocyte (HR 4.02 CI95% (1.4-11.2), p = 0.008) was predictive of clinical postoperative recurrence. We observed no histologic predictor for surgical postoperative recurrence. Conclusion: Myenteric plexitis in proximal margins of ileocolonic resection specimens is independently associated with endoscopic and clinical postoperative recurrence in Crohns disease.