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Background Local excision (LE) after chemoradiotherapy is a new option in low rectal cancer, but morbidity has never been compared prospectively with total mesorectal excision (TME). Early and late morbidity were compared in patients treated either by LE or TME after neoadjuvant chemoradiotherapy for rectal cancer. Method This was a post-hoc analysis from a randomized trial. Patients with clinical T2/T3 low rectal cancer with good response to the chemoradiotherapy and having either LE, LE with eventual completion TME, or TME were considered. Early (1 month) and late (2 years) morbidities were compared between the three groups. Results There were no deaths following surgery in any of the three groups. Early surgical morbidity (20 per cent LE versus 36 per cent TME versus 43 per cent completion TME, P = 0.025) and late surgical morbidity (4 per cent versus 33 per cent versus 57 per cent, P Conclusion The rate of surgical complications after neoadjuvant chemoradiotherapy in the LE group was half that of TME group at 1 month and 10 times lower at 2 years. LE is a safe approach for organ preservation and should be considered as an alternative to watch-and-wait in complete clinical responders and to TME in subcomplete responders.

A raised C-reactive protein level should be used to prompt early detection of anastomotic leakage before development of clinical symptoms. Early biochemical diagnosis of anastomotic leakage and intervention mitigates the negative impact of leakage on oncological outcomes in patients with rectal cancer.

Background Laparoscopy, by its minimally invasive nature, has revolutionized digestive and particularly colorectal surgery by decreasing post-operative pain, morbidity, and length of hospital stay. In this trial, we aim to assess whether low pressure in laparoscopic colonic surgery (7 mm Hg instead of 12 mm Hg) could further reduce pain, analgesic consumption, and morbidity, resulting in a shorter hospital stay. Methods and analysis The PAROS trial is a phase III, double-blind, randomized controlled trial. We aim to recruit 138 patients undergoing laparoscopic colectomy. Participants will be randomly assigned to either a low-pressure group (7 mm Hg) or a standard-pressure group (12 mm Hg). The primary outcome will be a comparison of length of hospital stay between the two groups. Secondary outcomes will compare post-operative pain, consumption of analgesics, morbidity within 30 days, technical and oncological quality of the surgical procedure, time to passage of flatus and stool, and ambulation. All adverse events will be recorded. Analysis will be performed on an intention-to-treat basis. Trial registration This research received the approval from the Committee for the Protection of Persons and was the subject of information to the ANSM. This search is saved in the ID-RCB database under registration number 2018-A03028–47. This research is retrospectively registered January 23, 2019, at http://clinicaltrials.gov/ed under the name “LaPAroscopic Low pRessure cOlorectal Surgery (PAROS)”. This trial is ongoing.

Background and Aim: Anti-tumour necrosis factor [TNF] agents have dramatically improved the prognosis of inflammatory bowel disease [IBD]. However, despite their good safety profile, use of these agents may lead to paradoxical manifestations involving skin or joints. Pathogenesis of such side effects is poorly understood and may involve anti-TNF pharmacokinetics. The aim of the present study was to look for an association between infliximab trough levels [ITL] and cutaneous [CPM] or rheumatological [RPM] paradoxical manifestations. Methods: IBD patients receiving infliximab as maintenance therapy were included in a cross-sectional prospective monocentre study. At inclusion, patients had an ITL measurement [LISA-TRACKER®, Biomedical Diagnostics BMD] and were assessed for paradoxical manifestations: a CPM was defined by new onset or exacerbation of pre-existing psoriasis lesions during IFX therapy, and an RPM by new onset of severe poly-arthralgia during IFX therapy. Results: Among the 121 patients included [69 female; median age: 38.9 years; 92 with Crohn’s disease], 7% had CPM and 8% RPM. Median ITL values were 5.87 [range: 0.52–19.53] µg/ml in patients with CPM and 1.90 [0.00–13.5] µg/ml in those with RPM, as compared respectively with 5.12 [0.00–49.12] µg/ml in patients without CPM [ p = 0.56] and 5.57 [0.00–49.12] µg/ml in those without RPM [ p = 0.058]. No prognostic factor was associated with CPM. The single factor associated with RPM was elevated antinuclear antibodies. Conclusion: ITL were not elevated in IBD patients developing cutaneous or rheumatological paradoxical manifestations when receiving IFX as maintenance therapy. As suggested by the high level of antinuclear antibodies, RPM could be related to an induced autoimmune disorder.

Aliment Pharmacol Ther 2011; 34: 462–469 Summary Background Faecal calprotectin is a reliable tool for predicting Crohn’s disease (CD) relapse in patients with sustained remission. Prediction of relapse with faecal calprotectin has been less studied in patients with severe CD treated with anti-TNF. Aim To identify an association between faecal calprotectin concentration and CD clinical relapse in patients achieving remission with infliximab (IFX). Methods From February 2007 to October 2008, consecutive patients with refractory luminal CD were prospectively included when they received three IFX infusions (5 mg/kg at weeks 0, 2 and 6) followed by maintenance with an immunomodulator alone. Faecal calprotectin and C-reactive protein (CRP) were measured at entry and at week 14 (w14). Results Sixty-five patients (43W; median age: 30.4 years) were included, and 50 (77%) were in clinical remission off steroids at w14; twenty-three of fifty (46%) experienced CD clinical relapse during the first year of follow-up. Median faecal calprotectin level at w14 was similar in patients with and without CD clinical relapse (200 and 150 μg/g respectively). When considering two suggested faecal calprotectin cut-offs to predict CD relapse, sensitivities and specificities were 61% and 48% for 130 μg/g, respectively, and 43% and 57% for 250 μg/g. Neither faecal calprotectin nor CRP at baseline and at w14 could predict relapse even when CD location subgroup analysis was considered. Conclusion In patients responding to an infliximab induction regimen, faecal calprotectin measurement at w14 cannot predict Crohn’s disease clinical relapse at 1 year.

Aliment Pharmacol Ther 2011; 33: 714–721 Summary Background Mucosal healing has become a new therapeutic goal in Crohn’s disease and can be achieved with azathioprine (AZA) or biologics. Methotrexate (MTX) is an effective drug for both the induction and maintenance of remission in Crohn’s disease. However, mucosal healing with MTX has been poorly investigated. Aim To assess the mucosal healing rate in patients with Crohn’s disease with clinical response to MTX as compared with AZA or infliximab (IFX). Methods From October 2007 to May 2009, consecutive patients with Crohn’s disease were prospectively enrolled into a single-centre study when they met the following criteria: previous identification of mucosal ulcerations with ileo-colonoscopy, clinical remission within at least 3 months with MTX, AZA or IFX monotherapy, usual indication for colonoscopy in Crohn’s disease (dysplasia/cancer screening, suspected stenosis) excluding assessment for mucosal healing. Mucosal healing was defined as absence of mucosal ulceration in all segments. Results Fifty-one patients with Crohn’s disease (38 female; median age: 42 years) were included: 18 receiving MTX, 18 AZA and 15 IFX. Mucosal healing was achieved in 2/18 (11%) with MTX, in 9/18 (50%) with AZA (P = 0.011 vs. MTX) and in 9/15 (60%) with IFX (P = 0.008 vs. MTX). Conclusion In patients with Crohn’s disease in sustained clinical remission, mucosal healing is less frequently achieved with MTX as compared with AZA or IFX.

Approximately 20% of patients have persistent symptoms of gastro-oesophageal reflux despite proton pump inhibitor (PPI) therapy. The aim of this study was to assess the determinants of reflux perception in patients on PPI therapy.20 patients with typical gastro-oesophageal reflux symptoms (heartburn and/or regurgitation) despite double-dose PPIs (twice daily) were included in this study. Ambulatory 24 h pH-impedance studies were performed in all patients. The characteristics of symptomatic and asymptomatic reflux episodes were compared. Symptoms were considered globally and separately for heartburn and regurgitation.A total of 1273 reflux episodes were detected including 243 (19.1%) acidic, 1018 (80.0%) weakly acidic and 12 (0.9%) weakly alkaline reflux episodes. Overall, 312 (24.5%) reflux episodes were symptomatic. The only factor associated with reflux perception was high proximal extent (p = 0.037). Compared with regurgitation, reflux episodes associated with heartburn were more frequently pure liquid (p = 0.009) and acidic (p = 0.027), had a lower nadir pH (p0.001), were more frequently preceded by acid reflux episodes (p0.001) and had a longer reflux bolus clearance time (p0.001).High proximal extent of the refluxate is the only factor associated with reflux perception in patients on double-dose PPI. However, compared with regurgitation, composition of the refluxate, sensitisation of the oesophagus by preceding acid exposure and delayed bolus clearance appear to play a role in heartburn perception.

Summary Background Mucosal healing can be achieved with infliximab (IFX). Aim To assess the impact of mucosal healing on long-term outcomes in patients with ulcerative colitis (UC) when treated with infliximab (IFX) beyond 1 year. Methods All consecutive adult patients with refractory UC receiving maintenance treatment with IFX in five French referral centres were analysed retrospectively. Only patients who had endoscopic evaluation between 6 and 52 weeks following IFX initiation were included. According to their Mayo endoscopic sub-score, patients were categorised into mucosal healing (sub-score: 0–1) and no mucosal healing (2–3). Outcome measures were colectomy and IFX failure defined by drug withdrawal due to secondary failure among primary responders. Results Of the 63 patients (30 women; median age: 38 years), 30 (48%) achieved mucosal healing. The median follow-up duration was 27 (3–79) months. Colectomy-free survival rates at 12, 24 and 36 months were, respectively, 100%, 96% and 96% in patients with mucosal healing. The corresponding figures were, respectively, 80%, 65% and 65% in patients without mucosal healing (P = 0.004). By multivariate analysis, mucosal healing was the only factor associated with colectomy-free survival, with an odds ratio of 18.01 (95%CI: 1.58–204.92). IFX failure-free survival rates at 12, 24 and 36 months were, respectively, 76%, 69% and 64% in patients with mucosal healing, and 44%, 25% and 21% in those without mucosal healing (P = 0.003). Conclusion Patients with refractory UC who achieved mucosal healing after IFX initiation had better long-term outcomes, with significantly less colectomy and less IFX failure.

Objectives The aim of this study was to assess oncological outcomes in patients treated with pancreaticoduodenectomy for advanced pancreatic head adenocarcinoma after preoperative chemoradiotherapy and to compare these with outcomes in patients treated with surgery alone. Methods From 2004 to 2009, patients treated with pancreaticoduodenectomy for pancreatic head adenocarcinoma were included in a retrospective comparative study. Patients with locally advanced adenocarcinoma were treated with preoperative chemoradiotherapy (CRT group) and were compared with those treated with surgery alone (SURG group). Results A total of 111 patients were included; these comprised 72 patients in the SURG group and 39 patients in the CRT group. The median follow‐up was 21 months. Patients in the CRT group presented with a more advanced tumoral status. Microscopic resection rates were similar in both groups, but nodal status and vascular or lymphatic emboli were lower in the CRT group. At 3 years, the SURG and CRT groups exhibited similar overall (36% and 51%, respectively) and disease‐free (35% and 37%, respectively) survival ( P = 0.10). Conclusions In patients with advanced pancreatic head adenocarcinoma, a good response after preoperative chemoradiotherapy results in a survival rate similar to that in patients treated with surgery alone in whom the initial prognosis is better.

Faecal calprotectin is a reliable tool for predicting Crohn's disease (CD) relapse in patients with sustained remission. Prediction of relapse with faecal calprotectin has been less studied in patients with severe CD treated with anti-TNF.To identify an association between faecal calprotectin concentration and CD clinical relapse in patients achieving remission with infliximab (IFX).From February 2007 to October 2008, consecutive patients with refractory luminal CD were prospectively included when they received three IFX infusions (5mg/kg at weeks 0, 2 and 6) followed by maintenance with an immunomodulator alone. Faecal calprotectin and C-reactive protein (CRP) were measured at entry and at week 14 (w14). Sixty-five patients (43W; median age: 30.4years) were included, and 50 (77%) were in clinical remission off steroids at w14; twenty-three of fifty (46%) experienced CD clinical relapse during the first year of follow-up. Median faecal calprotectin level at w14 was similar in patients with and without CD clinical relapse (200 and 150μg/g respectively). When considering two suggested faecal calprotectin cut-offs to predict CD relapse, sensitivities and specificities were 61% and 48% for 130μg/g, respectively, and 43% and 57% for 250μg/g. Neither faecal calprotectin nor CRP at baseline and at w14 could predict relapse even when CD location subgroup analysis was considered.In patients responding to an infliximab induction regimen, faecal calprotectin measurement at w14 cannot predict Crohn's disease clinical relapse at 1year.

Mucosal healing has become a new therapeutic goal in Crohn's disease and can be achieved with azathioprine (AZA) or biologics. Methotrexate (MTX) is an effective drug for both the induction and maintenance of remission in Crohn's disease. However, mucosal healing with MTX has been poorly investigated.To assess the mucosal healing rate in patients with Crohn's disease with clinical response to MTX as compared with AZA or infliximab (IFX).From October 2007 to May 2009, consecutive patients with Crohn's disease were prospectively enrolled into a single-centre study when they met the following criteria: previous identification of mucosal ulcerations with ileo-colonoscopy, clinical remission within at least 3 months with MTX, AZA or IFX monotherapy, usual indication for colonoscopy in Crohn's disease (dysplasia/cancer screening, suspected stenosis) excluding assessment for mucosal healing. Mucosal healing was defined as absence of mucosal ulceration in all segments.Fifty-one patients with Crohn's disease (38 female; median age: 42 years) were included: 18 receiving MTX, 18 AZA and 15 IFX. Mucosal healing was achieved in 2/18 (11%) with MTX, in 9/18 (50%) with AZA (P =0.011 vs. MTX) and in 9/15 (60%) with IFX (P=0.008 vs. MTX).In patients with Crohn's disease in sustained clinical remission, mucosal healing is less frequently achieved with MTX as compared with AZA or IFX.

Background No long-term advantage of the laparoscopic approach has been demonstrated in colorectal surgery. This study compared the risk of incisional hernia between laparoscopic and open surgery for rectal cancer. Methods Between 1994 and 2004, patients who had restorative mesorectal excision for rectal cancer by laparoscopy were compared with those treated by open surgery. Follow-up was prospective, and incisional hernia was considered to be any abdominal wound dehiscence occurring at the midline, extraction, trocar or ileostomy site. Cumulative risks of hernia were evaluated by the Kaplan–Meier method and compared with the log rank test. Results Some 155 patients had a laparoscopic and 165 an open procedure. The two groups were similar in terms of age, sex, body mass index, tumour stage, loop ileostomy and morbidity. The conversion rate was 20·6 per cent. The rate of incisional hernia in all patients was 11·4 per cent at 1 year, 21·1 per cent at 2 years and 23·7 per cent at 5 years. The rate of hernia at 5 years was significantly lower in the laparoscopic than in the open group (13·0 versus 33·0 per cent; P < 0·001). The rate of hernia due specifically to the laparoscopic procedure (extraction and trocar sites) was ten times less than that after a primary or secondary open procedure (2·1 versus 16·1–33·1 per cent; P < 0·001). Conclusion The laparoscopic approach decreases the risk of long-term incisional hernia following restorative mesorectal excision for rectal cancer. The benefit is most apparent in patients without conversion or postoperative complication.

To determine the presence of Helicobacter species DNA in the liver of chronic hepatitis C (CHC) patients with and without cirrhosis as compared to controls, and to identify the bacterial species involved.Seventy-nine consecutive patients (HBV and HIV negative) with a liver sample obtained after liver biopsy or hepatic resection were studied: 41 with CHC without cirrhosis, 12 with CHC and cirrhosis, and 26 controls (HCV negative). Polymerase chain reactions (PCRs) targeting Helicobacter 16S rDNA and species-specific were performed on DNA extracted from the liver. A gastric infection with H pylori was determined by serology and confirmed by 13C-urea breath test.Overall, Helicobacter 16S rDNA was found in 16 patients (20.2%). Although positive cases tended to be higher in CHC patients with cirrhosis (41.6%) than in those without cirrhosis (17.0%) or in controls (15.4%), the difference was not statistically significant (P = 0.08). H pylori-like DNA was identified in 12 cases and H. pullorum DNA in 2, while 2 cases remained unidentified. Gastric infection with H pylori was found in only 2 of these patients.Our results do not confirm the association of Helicobacter species DNA in the liver of CHC patients with advanced liver disease. The lack of correlation between positive H pylori serology and the presence of H pylori-like DNA in the liver may indicate the presence of a variant of this species.

of calcium homeostasis and inflammatory parameters in subjects with either active or inactive IBD. In the linear regression model, calprotectin was the strongest predictor of the disease activity, as expected [beta coefficient 0.75 (P< 0.001) in men and 0.42 (P< 0.05) in women, respectively], when adjusted for age and TNF-alpha inhibitor treatment. Ionized calcium and serum PTH did not demonstrate any significant associations with disease activity in the same regression model. Conclusions: IBD patients have an altered calcium homeostasis and ionized calcium levels are significantly lower in the active disease state. That may indicate that IBD patients with frequent relapses may suffer from underestimated calcium losses and could be at higher risk of osteoporosis.

Background: The natural history of CD of the pouch has not been characterized. Methods: All eligible patients with CD of the pouch were identified and included from our subspecialty Pouchitis Clinic between 2002 and 2009. Demographic & clinical variables were collected from a prospectively maintained database. Results: 206 pts with CD of the pouch consisted of 49 inflammatory, 40 fibrostenotic, and 117 fistulizing types. Pts with fistulizing CD were younger than those with fibrostenotic CD. The interval from IBD diagnosis and pouch construction was shorter in the fistulizing CD group. More pts with fistulizing CD had postoperative use of biologics (25.6% vs. 10.2% and 12.5%, p=0.028). More patients with fistulizing CD were hospitalized for pouch-related condition (21.4% vs. 15.0% and 2.0%, p=0.007). Progression of phenotypes and pouch survival are shown in Figures. Conclusions: Clinical phenotypes of Crohn's pouch can change over time. These phenotypes of CD were associated with different natural history and risk for pouch failure.

Background: Treatment with infliximab (IFX) can result in immunogenicity through the formation of human anti-chimeric antibodies (HACAs). These antibodies are associated with a decreased duration of response, whereas therapeutic levels of IFX are associated with durable clinical response. We evaluated the clinical utility of measuring serum IFX and HACA levels. Methods: We retrospectively reviewed charts of patients with inflammatory bowel disease who had IFX drug and HACA levels measured over a three-year period from 2005-2008. The clinical utility of these tests was assessed by determining whether the result affected clinical management. The management and subsequent clinical response to therapeutic changes based on test results was evaluated. Fisher's exact test and log-rank test for discontinuation were used for statistical analysis. Results: One hundred and fifty-five patients underwent IFX level and HACA status testing. The median time to initial testing after IFX initiation was 50 weeks (IQR: 22.7-120). The main indications for testing were: loss of response to IFX (50.3%), partial response after initiation of IFX (22.6%) and possible autoimmune/delayed hypersensitivity reaction (14.8%). HACAs were identified in 35 patients (22.6%) and therapeutic IFX levels were found in 51 (32.9%). Of 177 total tests assessed, the results impacted treatment decisions in 73.4% (95% CI: 66-80%). In those with positive HACAs, change to another anti-TNF was associated with a complete or partial response in 91.6% of patients whereas increasing the dose had a response of 16.7% (p

Background Epidemiological studies on risk factors for colorectal cancer (CRC) have mainly focused on diet, and being overweight is now recognized to contribute significantly to CRC risk. Overweight and obesity are defined as an excess of adipose tissue mass and are associated with disorders in lipid metabolism. Peroxisome proliferator-activated receptors (PPARs) and retinoid-activated receptors (RARs and RXRs) are important modulators of lipid metabolism and cellular homeostasis. Alterations in expression and activity of these ligand-activated transcription factors might be involved in obesity-associated diseases, which include CRC. Cyclooxygenase-2 (COX-2) also plays a critical role in lipid metabolism and alterations in COX-2 expression have already been associated with unfavourable clinical outcomes in epithelial tumors. The objective of this study is to examine the hypothesis questioning the relationship between alterations in the expression of nuclear receptors and COX-2 and the weight status among male subjects with CRC. Method The mRNA expression of the different nuclear receptor subtypes and of COX-2 was measured in 20 resected samples of CRC and paired non-tumor tissues. The association between expression patterns and weight status defined as a body mass index (BMI) was statistically analyzed. Results No changes were observed in PPARγ mRNA expression while the expression of PPARδ, retinoid-activated receptors and COX-2 were significantly increased in cancer tissues compared to normal colon mucosa (P ≤ 0.001). The weight status appeared to be an independent factor, although we detected an increased level of COX-2 expression in the normal mucosa from overweight patients (BMI ≥ 25) compared to subjects with healthy BMI (P = 0.002). Conclusion Our findings show that alterations in the pattern of nuclear receptor expression observed in CRC do not appear to be correlated with patient weight status. However, the analysis of COX-2 expression in normal colon mucosa from subjects with a high BMI suggests that COX-2 deregulation might be driven by excess weight during the colon carcinogenesis process.