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Background: Several medicinal treatments for avoiding post-operative ileus (POI) after abdominal surgery have been evaluated in randomised controlled trials. This network meta-analysis aimed to explore the relative effectiveness of these different treatments on ileus outcome measures. Methods: A systematic literature review was performed to identify randomised controlled trials (RCTs) comparing treatments for post-operative ileus following abdominal surgery. A Bayesian network meta-analysis was performed. Direct and indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analysis. Results: A total of 38 randomised controlled trials were included in this network meta-analysis reporting on 6371 patients. Our network meta-analysis shows that prokinetics significantly reduce the duration of first gas (Mean difference (MD) (hours) – 16; credible interval - 30, - 3.1; surface under the cumulative ranking curve (SUCRA) 0.418), duration of first bowel movements (Mean difference (MD) (hours) -25; credible interval - 39, - 11; SUCRA 0.25) and duration of post-operative hospitalisation (Mean difference (MD) (hours) – 1.9; credible interval – 3.8, - 0.040; SUCRA 0.34). Opioid antagonists are the only treatment that significantly improve the duration of food recovery (Mean difference (MD) (hours) - 19; credible interval - 26, - 14; SUCRA 0.163). Conclusion: Based on our meta-analysis, the two most consistent pharmacological treatments able to effectively reduce POI after abdominal surgery are prokinetics and opioid antagonists. The absence of clear superiority of one treatment over another highlights the limits of the pharmacological principles available.

Aim Postoperative morbidity is high in patients operated on for Crohn's disease (CD) complicated by malnutrition. This study aimed to evaluate the impact of preoperative enteral nutritional support (PENS) on postoperative outcome in patients with CD complicated by malnutrition included in a prospective nationwide cohort. Method Malnutrition was defined as body mass index 10%. Failure of PENS was defined as the requirement for additional preoperative parenteral nutrition to PENS. Univariate analysis of the risk factors for PENS failure was performed. Propensity score matching (PSM) was used to compare the outcomes between 'upfront surgery' and 'PENS' groups. The primary endpoint was the rate of intra-abdominal septic morbidity and/or temporary defunctioning stoma. Results Among 592 patients included, 149 were selected. In the intention-to-treat population including 20 (13.4%) patients with PENS failure after PSM, 78 'upfront surgery' and 71 'PENS'-matched patients were compared, with no significant difference in the primary endpoint. Perforating CD and preoperative intra-abdominal fistula were associated with PENS failure [37.5 vs 16.1% (P = 0.047) and 41.2% vs 16.2% (P = 0.020), respectively]. After exclusion of these 20 patients, PSM was used to compare 45 'upfront surgery' and 51 'PENS'-matched patients, with a significantly decreased rate of intra-abdominal septic complications and/or temporary defunctioning stoma in the PENS group (19.6 vs 42.2%, P = 0.016). Conclusion Preoperative enteral nutritional support is associated with a trend but no conclusive evidence of a reduction in intra-abdominal septic complications and/or requirement for defunctioning stoma. Patients with perforating CD complicated with malnutrition are at risk of PENS failure.

Background and AimsFew prospective data exist on outcomes of surgery in Crohn’s disease [CD] complicated by an intra-abdominal abscess after resolution of this abscess by antibiotics optionally combined with drainage.MethodsFrom 2013 to 2015, all patients undergoing elective surgery for CD after successful non-operative management of an intra-abdominal abscess [Abscess-CD group] were selected from a nationwide multicentre prospective cohort. Resolution of the abscess had to be computed tomography/magnetic resonance-proven prior to surgery. Abscess-CD group patients were 1:1 matched to uncomplicated CD [Non-Penetrating-CD group] using a propensity score. Postoperative results and long-term outcomes were compared between the two groups.ResultsAmong 592 patients included in the registry, 63 [11%] fulfilled the inclusion criteria. The abscess measured 37 ± 20 mm and was primarily managed with antibiotics combined with drainage in 14 patients and nutritional support in 45 patients. At surgery, a residual fluid collection was found in 16 patients [25%]. Systemic steroids within 3 months before surgery [p = 0.013] and the absence of preoperative enteral support [p = 0.001] were identified as the two significant risk factors for the persistence of a fluid collection. After propensity score matching, there was no significant difference between the Abscess-CD and Non-Penetrating-CD groups in the rates of primary anastomosis [84% vs 90% respectively, p = 0.283], overall [28% vs 15% respectively, p = 0.077] and severe postoperative morbidity [7% vs 7% respectively, p = 1.000]. One-year recurrence rates for endoscopic recurrence were 41% in the Abscess-CD and 51% in the Non-Penetrating-CD group [p = 0.159].ConclusionsSurgery after successful non-operative management of intra-abdominal abscess complicating CD provides good early and long-term outcomes.

The aim of this study was to assess recurrence risk factors following ileocolonic resection (ICR) for Crohn disease (CD) in a nationwide cohort study SUMMARY BACKGROUND DATA:: Recurrence rate after ICR for CD can be up to 60%, but its predictive factors have never been evaluated in large prospective cohort studies.From 2013 to 2015, 346 consecutive patients undergoing ICR for CD and a postoperative ileocoloscopy within 6 to 12 months after surgery at 19 academic French centers were included prospectively.Twelve-month postoperative endoscopic (Rutgeerts score ≥i2) and clinical recurrence rates were 57.6% [95% confidence interval (CI), 54.2-61.0] and 11.3% (95% CI, 9-13.6), respectively. A total of 185 patients (54%) had a postoperative CD prophylaxis, comprising thiopurine in 69 (20%), or anti-tumor necrosis factor (TNF) therapy in 93 (27%). In multivariate Cox regression analysis, absence of postoperative smoking {odds ratio [OR] = 0.60 (95% CI, 0.40-0.91); P = 0.016}, postoperative prophylaxis [OR = 0.60 (95% CI, 0.41-0.88); P = 0.009], and penetrating disease behavior [OR = 0.58 (95% CI, 0.39-0.86); P = 0.007] were the only independent predictors of reduced endoscopic recurrence risk. Postoperative prophylaxis [OR 0.31 (95% CI, 0.15-0.66); P = 0.002), and penetrating behavior [OR = 00.36 (95% CI, 0.16-0.81); P = 0.013), were the only independent predictors of reduced clinical recurrence risk. Postoperative anti-TNF therapy was associated with a significant reduction of both 12-month risks of endoscopic (P0.001) and clinical (P = 0.019) recurrences.Absence of postoperative smoking, CD prophylaxis, and penetrating disease behavior could be independent predictors of reduced postoperative recurrence after ICR for CD. Prophylactic anti-TNF therapy reduces both endoscopic and clinical recurrence rates. It suggests that upfront surgery followed by postoperative anti-TNF therapy is probably the best therapeutic approach for complex CD (penetrating disease behavior).

Simple Summary Abdominoperineal resection (APR) and pelvic exenteration (PE) for the treatment of cancer (mainly anal and rectal cancers) require extensive pelvic resection with a high rate of postoperative complications. The objective of this work was to systematically review and meta-analyze the effects of vertical rectus abdominis myocutaneous flap (VRAMf) and mesh closure on perineal morbidity following APR and PE. The studies were distributed as follows: Group A comparing primary closure (PC) and VRAMf, Group B comparing PC and mesh closure, Group C comparing PC and VRAMf in PE. The meta-analysis of Groups A and B showed PC to be associated with an increase in the rate of total and major perineal wound complications. PC was associated with a decrease in total and major perineal complications in Group C. Abstract Background. Abdominoperineal resection (APR) and pelvic exenteration (PE) for the treatment of cancer require extensive pelvic resection with a high rate of postoperative complications. The objective of this work was to systematically review and meta-analyze the effects of vertical rectus abdominis myocutaneous flap (VRAMf) and mesh closure on perineal morbidity following APR and PE (mainly for anal and rectal cancers). Methods. We searched PubMed, Cochrane, and EMBASE for eligible studies as of the year 2000. After data extraction, a meta-analysis was performed to compare perineal wound morbidity. The studies were distributed as follows: Group A comparing primary closure (PC) and VRAMf, Group B comparing PC and mesh closure, and Group C comparing PC and VRAMf in PE. Results. Our systematic review yielded 18 eligible studies involving 2180 patients (1206 primary closures, 647 flap closures, 327 mesh closures). The meta-analysis of Groups A and B showed PC to be associated with an increase in the rate of total (Group A: OR 0.55, 95% CI 0.43–0.71; p < 0.01/Group B: OR 0.54, CI 0.17–1.68; p = 0.18) and major perineal wound complications (Group A: OR 0.49, 95% CI 0.35–0.68; p < 0.001/Group B: OR 0.38, 95% CI 0.12–1.17; p < 0.01). PC was associated with a decrease in total (OR 2.46, 95% CI 1.39–4.35; p < 0.01) and major (OR 1.67, 95% CI 0.90–3.08; p = 0.1) perineal complications in Group C. Conclusions. Our results confirm the contribution of the VRAMf in reducing major complications in APR. Similarly, biological prostheses offer an interesting alternative in pelvic reconstruction. For PE, an adapted reconstruction must be proposed with specialized expertise.

To determine the risk factors of morbidity after surgery for ileocolonic Crohn disease (CD).The risk factors of morbidity after surgery for CD, particularly the role of anti-TNF therapy, remain controversial and have not been evaluated in a large prospective cohort study.From 2013 to 2015, data on 592 consecutive patients who underwent surgery for CD in 19 French specialty centers were collected prospectively. Possible relationships between anti-TNF and postoperative overall morbidity were tested by univariate and multivariate analyses. Because treatment by anti-TNF is possibly dependent on the characteristics of the patients and disease, a propensity score was calculated and introduced in the analyses using adjustment of the inverse probability of treatment-weighted method.Postoperative mortality, overall and intra-abdominal septic morbidity rates in the entire cohort were 0%, 29.7%, and 8.4%, respectively; 143 (24.1%) patients had received anti-TNF3 months prior to surgery. In the multivariate analysis, anti-TNF3 months prior to surgery was identified as an independent risk factor of the overall postoperative morbidity (odds-ratio [OR] =1.99; confidence interval [CI] 95% = 1.17-3.39, P = 0.011), with preoperative hemoglobin10 g/dL (OR = 4.77; CI 95% = 1.32-17.35, P = 0.017), operative time180 min (OR = 2.71; CI 95% = 1.54-4.78, P0.001) and recurrent CD (OR = 1.99; CI 95% = 1.13-3.36, P = 0.017). After calculating the propensity score and adjustment according to the inverse probability of treatment-weighted method, anti-TNF3 months prior to surgery remained associated with a higher risk of overall (OR = 2.98; CI 95% = 2.04-4.35, P0.0001) and intra-abdominal septic postoperative morbidities (OR = 2.22; CI 95% = 1.22-4.04, P = 0.009).Preoperative anti-TNF therapy is associated with a higher risk of morbidity after surgery for ileocolonic CD. This information should be considered in the surgical management of these patients, particularly with regard to the preoperative preparation and indication of temporary defunctioning stoma.

Background and AimsTo compare perioperative characteristics and outcomes between primary ileocolonic resection [PICR] and iterative ileocolic resection [IICR] for Crohn’s disease [CD].MethodsFrom 2013 to 2015, 567 patients undergoing ileocolonic resection were prospectively included in 19 centres of the GETAID chirurgie group. Perioperative characteristics and postoperative results of both groups [431 PICR, 136 IICR] were compared. Uni- and multivariate analyses of the risk factors of overall 30-day postoperative morbidity was carried out in the IICR group.ResultsIICR patients were less likely to be malnourished [27.2% vs 39.9%, p = 0.007], and had more stricturing forms [69.1% vs 54.3%, p = 0.002] and less perforating disease [19.9% vs 39.2%, p < 0.001]. Laparoscopy was less commonly used in IICR [45.6% vs 84.5%, p < 0.01] and was associated with increased conversion rates [27.4% vs 14.6%, p = 0.012]. Overall postoperative morbidity was 36.8% in the IICR group and 26.7% in the PICR group [p = 0.024]. There was no significant difference between IICR and PICR regarding septic intra-abdominal complications, anastomotic leakage [8.8% vs 8.4%] or temporary stoma requirement. IICR patients were more likely to present with non-infectious complications and ileus [11.8% vs 3.7%, p < 0.001]. Uni- and multivariate analyses did not identify specific risk factors of overall postoperative morbidity in the IICR group.ConclusionsSurgery for recurrent CD is associated with a slight increase of non-infectious morbidity [postoperative ileus] that mainly reflects the technical difficulties of these procedures. However, IICR remains a safe therapeutic option in patients with recurrent CD because severe morbidity including anastomotic complications is similar to patients undergoing primary resection.PodcastThis article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.

BACKGROUND Patients with a simultaneous pancreas-kidney transplant (SPKT), especially those with gastroparesis, often have gastro-intestinal (GI) disorders that can modify immunosuppressant pharmacokinetics. We compared the MPA 12-hours area under the curve (AUC(0-12)) in SKPT patients with severe gastroparesis receiving mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). MATERIAL/METHODS Fifteen SKPT patients having a severe gastroparesis were switched, at 182 (69-1523) days post-transplantation, from MMF to EC-MPS because of GI disorders. MPA AUC(0-12) values were obtained before and after the switch, ie, under MMF (500 mg b.i.d.) at 169 (51-1522) days post-transplantation and EC-MPS (360 mg b.i.d.) at 102 (26-355) days after the switch. RESULTS Mean MPA AUC(0-12) h did not differ significantly under MMF and EC-MPS, ie, 40.13±14 and 38.24±15.5 mg*h/L, respectively. Trough and maximal MPA concentrations were similar with both MPA formulations. Although all patients had GI disorders under MMF (100%), only 3 had persistent GI disorders under EC-MPS (20%) (p

This work was presented in part and orally at the European Crohn’s and Colitis Organization (ECCO) meeting in Copenhagen in 2014, at the Digestive Disease Week (DDW) in Chicago in 2014 and at the UEG week in Vienna in 2014.; International audience; Background: Aims Colonic strictures complicate inflammatory bowel disease (IBD) and often lead to surgical resection to prevent dysplasia or cancer. We assessed the frequency of dysplasia and cancer among IBD patients undergoing resection of a colorectal stricture. Methods We analyzed data from the Groupe d’études et thérapeutiques des affections inflammatoires du tube digestif study. This was a nationwide retrospective study of 12,013 patients with IBD in France who underwent surgery for strictures at 16 centers, from August 1992 through January 2014 (293 patients for a colonic stricture, 248 patients with Crohn’s disease, 51% male, median age at stricture diagnosis was 38 y). Participants had no preoperative evidence of dysplasia or cancer. We collected clinical, endoscopic, surgical, and pathology data and information on outcomes. Results When patients were diagnosed with strictures, they had IBD for a median time of 8 y (3−14 y). The strictures were a median length of 6 cm (4−10 cm) and caused symptoms in 70% of patients. Of patients with Crohn’s disease, 3 were found to have low-grade dysplasia (1%), 1 was found to have high-grade dysplasia (0.4%), and 2 were found to have cancer (0.8%). Of patients with ulcerative colitis, 1 had low-grade dysplasia (2%), 1 had high-grade dysplasia (2%), and 2 had cancer (5%). All patients with dysplasia or cancer received curative surgery, except 1 who died of colorectal cancer during the follow-up period. No active disease at time of surgery was the only factor associated with dysplasia or cancer at the stricture site (odds ratio, 4.86; 95% confidence interval, 1.11–21.27; P=.036). Conclusion In a retrospective study of patients with IBD undergoing surgery for colonic strictures, 3.5% were found to have dysplasia or cancer. These findings can be used to guide management of patients with IBD and colonic strictures.

International audience; The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77) months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody-mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B-cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient- and graft-survival rates did not differ between patients with and without DSAs. In conclusion, liver-transplant patients with liver abnormalities should be screened for DSAs and AMR.

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.

International audience; BACKGROUND: In human pathology, the "creeping fat" (CF) of the mesentery is unique to Crohn's disease (CD). CF is usually referred to as an ectopic extension of mesenteric adipose tissue (MAT). However, since no animal model developing CF has ever been established, very little is known about this type of fat-depot expansion and its role in the development of the disease. METHODS: We developed and standardized an experimental protocol in mice that reproducibly induces CF development when a severe colonic inflammation is obtained by intracolonic instillation of DNBS. RESULTS: Macro-microscopic observations revealed a fatty appearance of CF. Yet when compared to MAT from the same animals, CF contains very little triglycerides, few adipocytes, and we observed a very low expression and protein levels of both adipose markers (hormone-sensitive lipase, perilipin) and adipocytokines (leptin, adiponectin). The decreased expression of perilipin in CF was also observed by immunohistochemistry. Conversely, the expression of proinflammatory and fibrous markers (Pref-1) was much higher in CF than in MAT. These observations were fully consistent with those made on CF recovered from five CD patients and compared with subcutaneous and mesenteric fat from the same patients. CONCLUSIONS: Altogether, this work reports an original experimental mice model of CF. In this model we establish for the first time that CF only occurs in severe colonic inflammation and shows an inflammatory, fibrous but not an adipose pattern.

Encapsulating peritoneal sclerosis is a rare but serious complication in patients undergoing peritoneal dialysis. Its mortality rate is approximately 30%, despite treatment with total parenteral nutrition, surgery, tamoxifen, or immunosuppressants.Of 991 kidney transplants performed at our institution over 9 years, 50 patients were treated for chronic peritoneal dialysis at the time of transplant.Two cases of encapsulating, peritoneal sclerosis occurred in patients receiving pretransplant peritoneal dialysis. Both had received intensive posttransplant treatment for acute humoral rejection. Encapsulating peritoneal sclerosis occurred at 3 months and 4 months after the transplant. Both presented with intestinal pain and gut obstruction. They were given total parenteral nutrition plus tamoxifen (20 mg/d) for 3 months. Outcomes were favorable for 1, though there was no improvement for the second patient, who was then also given sirolimus. He died later from multiorgan failure secondary to digestive-related sepsis, and encapsulating, peritoneal, sclerosis-related symptoms.When encapsulating, peritoneal sclerosis occurs after kidney transplant, tamoxifen therapy could be implemented.