PERFUSE: a French non-interventional study of patients with inflammatory bowel disease receiving infliximab biosimilar SB2: a 12-month analysis.

Background: FlixabiTM (SB2) is a biosimilar of the reference infliximab (IFX), Remicade®. Published evidence on long-term, real-world use of SB2 in patients either IFX naive or transitioned from prior IFX is scarce. Objectives: We evaluated persistence, effectiveness, and safety of SB2 over 12 months in adults with IBD [Crohn's disease (CD) and ulcerative colitis (UC)], participating in PERFUSE. Design: PERFUSE is a long-term, non-interventional, multicenter study of patients receiving SB2 at specialist sites across France. Methods: SB2 treatment was initiated in September 2017, either as first IFX treatment (IFX naive), after transition from treatment with reference IFX (IFX ref) or another IFX biosimilar (IFX bs), or both IFX ref and IFX bs (IFX multiswitch). Outcomes up to Month 12 (±2) include persistence on SB2 (primary outcome measure), SB2 dose, disease status, immunogenicity, and safety. Results: This final 12-month analysis of patients with IBD includes 569 with CD and 168 with UC. Persistence [95% confidence interval (CI)] at Month 12 was CD: 89% (77.2; 94.9), UC: 78.5% (58.2; 89.8) for IFX naive; CD: 94% (91.0; 96.1), UC: 92.8% (84.8; 96.7) for IFX ref; CD: 91.6% (86.0; 95.0), UC: 94.2% (83.1; 98.1) for IFX bs; and CD 100% (100; 100), UC 100% (100; 100) for IFX multiswitch. In the CD and UC cohorts, disease activity among IFX naive patients declined from baseline to Month 12; with any prior IFX, the proportions of patients in remission at baseline, Month 6, and Month 12 remained unchanged in the UC cohort, and were comparable or higher in the CD cohort. No immunogenicity or safety signals were detected. Conclusions: Patients with IBD can be initiated on SB2 or transitioned from IFX ref and/or IFX bs to SB2, with no loss of disease control or safety concerns, with >75% of naive and >90% of transitioned patients continuing on SB2 treatment at 12 months.

Upper gastrointestinal bleeding in adults treated with veno-arterial extracorporeal membrane oxygenation: a cohort study.

OBJECTIVES: Upper gastrointestinal bleeding (UGIB) is a common complication in adults treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock or cardiac arrest. We aimed to determine risk factors, prevalence and outcomes associated with VA-ECMO-associated UGIB in adult patients. METHODS: We conducted a retrospective cohort study (2014-2022) on consecutive VA-ECMO patients in the medical and infectious disease intensive care unit of Bichat-Claude Bernard University Hospital, Paris, France. UGIB was defined as (i) an overt bleeding (haematemesis, melena, haematochezia) or (ii) acute anaemia associated with a lesion diagnosed on upper gastrointestinal endoscopy. VA-ECMO-associated UGIB was defined as an UGIB occurring during VA-ECMO, or up to 10 days after decannulation in patients weaned off extracorporeal membrane oxygenation (ECMO). Cause-specific models were used to identify factors associated with UGIB and death, respectively. RESULTS: Among the 455 patients included, 48 (10%) were diagnosed with UGIB after a median of 12 [7; 23] days following ECMO cannulation. Mortality occurred in 36 (75%) patients with UGIB and 243 (60%) patients without. UGIB patients had longer intensive care unit stays (32 [19; 60] vs 18 [7; 37] days; P < 0.01), longer ECMO (14 [9; 18] vs 7 [4; 11] days; P < 0.01) and mechanical ventilation durations (21 [16; 36] vs 10 [5; 20] days; P < 0.01), as compared to non-UGIB patients. Ninety upper gastrointestinal endoscopies were performed, and the most frequent lesions detected were gastro-duodenal ulcers (n = 23, 26%), leading to 11/90 therapeutic procedures. By multivariable analysis, a history of peptic ulcer [cause-specific hazard ratio (CSHR) 2.93, 95% confidence interval (CI) [1.01; 8.51]], a dual antiplatelet therapy (CSHR 2.0, 95% CI [1.07; 3.72]) and extracorporeal cardiopulmonary resuscitation (CSHR 2.78, 95% CI [1.42; 5.45]) were independently associated with an increased risk of UGIB. CONCLUSIONS: In adult patients under VA-ECMO, a history of gastric ulcer, dual antiplatelet therapy and extracorporeal cardiopulmonary resuscitation were independently associated with an increased risk of UGIB. This study highlights the potential role of acute ischaemia-reperfusion injury in the pathophysiology of VA-ECMO-associated UGIB.

Screening for spondyloarthritis in patients with inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs) can be associated with various musculoskeletal (IBD-MSK) manifestations that could be difficult to classify for gastroenterologists. We aimed to evaluate the characteristics of patients with IBD-MSK and the prevalence of spondyloarthritis (SpA). In this observational cross-sectional study, we included patients with IBD-MSK complaints (peripheral or back pain). All patients underwent a standardized rheumatology evaluation including clinical, biological and imaging evaluations (MRI of spine and sacroiliac joints and ultrasonography of enthesis). We included 183 IBD patients (60.7% women; median [interquartile range] age 45 [36-56] years); 159 (87%) had joint pain. In 43 (23.5%) and 25/175 (14.3%) patients, enthesis abnormalities were found on ultrasonography and sacroiliitis on MRI, respectively. SpA was diagnosed in 54 (29.5%) patients. IBD-related arthralgia and degenerative spine disease were diagnosed in 105 (57.4%) and 72 (39.3%) patients. Sixteen (29.6%) SpA patients initiated a new conventional synthetic disease modifying anti-rheumatic drug (DMARD). A biologic DMARD was initiated in 10 patients or changed in 3. More than half of IBD-MSK patients had IBD-related arthralgia, and about one-third had definite SpA. Ultrasonography of enthesis and systematic MRI of sacroiliac joints seem useful for SpA classification and differential diagnosis in these patients who often have musculoskeletal pain complaints. Therapeutics were changed in most patients, which highlights the need for a multidisciplinary approach for managing IBD with extra-intestinal symptoms.

Staple Line Intrathoracic Migration After Sleeve Gastrectomy: Correlation between Symptoms, CT Three-Dimensional Stomach Analysis, and 24-h pH Monitoring.

PURPOSE: Migration of the staple line is the definition of sliding hiatus hernia in sleeve gastrectomy patients. The main aim was to determine the frequency and measurement of intrathoracic staple line migration and its correlation with GERD symptoms and pH monitoring. MATERIALS AND METHODS: This was a prospective clinical trial including all patients who underwent sleeve gastrectomy more than 1 year previously. All the patients underwent computed tomography (CT) imaging, and migration of the proximal end of the suture above the level of the hiatus was measured in mm. All the patients with symptoms suggestive of GERD were assessed using the GERD impact scale (GIS), and wireless 24-h esophageal pH and symptom association monitoring (SAP) were carried out. Analysis of risk factors for postoperative staple line migration was performed. RESULTS: Between March 2018 and December 2018, 194 patients were evaluated (mean age 45.1 ± 11.2 years; 161 females); 88/194 (45.4%) presented an average intrathoracic migration of 16.2 ± 6.9 mm. Thirty-eight of 194 (19.5%) patients presented symptoms suggestive of gastroesophageal reflux. There was a significant relationship between staple line intrathoracic migration and postsleeve GERD symptomatology (p = 0.0004, OR = 4.25 [1.92-9.39]). However, there was no significant correlation between positive 24-h pH monitoring and intrathoracic migration of the staple line (p = 0.1). CONCLUSION: A migration greater than 17 mm was strongly correlated with postsleeve GERD symptoms but not with positive 24-h pH monitoring.

Relationship between clinical remission of perianal fistulas in Crohn's disease and serum adalimumab concentrations: A multi-center cross-sectional study.

BACKGROUND: Crohn's disease (CD) is complicated by perianal fistulas in approximately 20% of patients. Achieving permanent fistula closure remains a challenge for physicians. An association between serum anti-tumor necrosis factor-α concentrations and clinical outcomes in patients with CD has been demonstrated; however, little information is available on serum adalimumab (ADA) concentrations and remission of perianal fistulas in such patients. AIM: To study the relationship between serum ADA concentrations and clinical remission of CD-associated perianal fistulas. METHODS: This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018. At the time of each serum ADA concentration measurement, we collected information about the patients and their fistulas. The primary study endpoint was clinical remission of fistulas defined as the absence of drainage (in accordance with Present's criteria), with a PDAI ≤ 4, absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center. We also assessed fistula healing [defined as being in clinical and radiological (magnetic resonance imaging, MRI) remission] and adverse events. RESULTS: The study cohort comprised 34 patients who underwent 56 evaluations (patients had between one and four evaluations). Fifteen patients had clinical remissions (44%), four of whom had healed fistulas on MRI. Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not [14 (10-16) vs 10 (2-15) µg/mL, P = 0.01]. Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas [11 (7-14) vs 10 (4-16) µg/mL, P = 0.69]. The adverse event rate did not differ between different serum ADA concentrations. CONCLUSION: We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

Protein Kinase CK2 Acts as a Molecular Brake to Control NADPH Oxidase 1 Activation and Colon Inflammation.

BACKGROUND & AIMS: NADPH oxidase 1 (NOX1) has emerged as a prime regulator of intestinal mucosa immunity and homeostasis. Dysregulation of NOX1 may cause inflammatory bowel disease (IBD). It is not clear how NOX1 is regulated in vivo under inflammatory conditions. We studied the role of CK2 in this process. METHODS: The NOX1 organizer subunit, NADPH oxidase organizer 1 (NOXO1), was immunoprecipitated from cytokine-treated colon epithelial cells, and bound proteins were identified by mass spectrometry analysis. Sites on NOXO1 phosphorylated by CK2 were identified by nanoscale liquid chromatography coupled to tandem mass spectrometry. NOX1 activity was determined in colon epithelial cells and colonoids in the presence or absence of CX-4945, a CK2 specific inhibitor. Acute colitis was induced by administration of trinitrobenzenesulfonic acid in mice treated or not with CX-4945. Colon tissues were analyzed by histologic examination, quantitative polymerase chain reaction, and Western blots. CK2 activity, markers of inflammation, and oxidative stress were assessed. RESULTS: We identified CK2 as a major partner of NOXO1 in colon epithelial cells under inflammatory conditions. CK2 directly binds NOXO1 at the C-terminus containing the Phox homology domain and phosphorylates NOXO1 on several sites. CX-4945 increased ROS generation by NOX1 in human colon epithelial cells and organoids. Strikingly, CK2 activity was reduced in trinitrobenzenesulfonic acid-induced acute colitis, and CX-4945 exacerbated colitis inflammation as shown by increased levels of CXCL1, ROS generation, lipid peroxidation, and colon damage. CONCLUSIONS: The ubiquitous protein kinase CK2 limits NOX1 activity via NOXO1 binding and phosphorylation in colonic epithelial cells and lessens experimental colitis. Loss of CK2 activity during acute colitis results in excessive ROS production, contributing to the pathogenesis. Strategies to activate CK2 could be an effective novel therapeutic approach in IBD.

Impact of HIV Infection on the Course of Inflammatory Bowel Disease and Drug Safety Profile: A Multicenter GETAID Study.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and human immunodeficiency virus (HIV) both impact innate and adaptive immunity in the intestinal mucosa. As it is a rare situation, the intersection between HIV and IBD remains unclear, especially the impact of HIV infection on the course of IBD, and the drug safety profile is unknown. METHODS: We conducted a multicenter retrospective cohort study between January 2019 and August 2020. All adult patients with IBD and concomitant HIV infection were included. Each IBD patient with HIV was matched to two HIV-uninfected IBD patients. RESULTS: Overall, 195 patients with IBD were included, including 65 HIV-infected patients and 130 without HIV infection. Of the 65 infected patients, 22 (33.8%) required immunosuppressants and 31 (47.7%) biologics. In the HIV-infected group, the need for immunosuppressants (p = 0.034 for CD and p = 0.012 for UC) and biologics (p = 0.004 for CD and p = 0.008 for UC) was significantly lower. The disease course, using a severity composite criterion, was not significantly different between the two groups for CD (hazard ration (HR) = 1.3 [0.7; 2.4], p = 0.45) and UC (HR, 1.1 [0.5; 2.7], p = 0.767). The overall drug safety profile was statistically similar between the two groups. CONCLUSION: Although HIV-infected patients receive less treatments, the course of their IBD did not differ than uninfected, suggesting that HIV infection might attenuate IBD. The drug safety profile is reassuring, allowing physician to treat these patients according to current recommendations.

Kidney function monitoring in inflammatory bowel disease: The MONITORED consensus.

BACKGROUND AND AIMS: Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD. METHODS: A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement. RESULTS: Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient. CONCLUSION: The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients.

Chronic persistent HHV-6B infection after sulfasalazine-induced DRESS with demonstration of HHV-6 encoded small noncoding RNAs (sncRNAs) in Crohn's-like colitis: Case report.

A sulfasalazine-induced DRESS (Drug Reactivation with Eosinophilia and Systemic Symptoms) was complicated by a Crohn's-like colitis. We demonstrated HHV-6 reactivation with presence of HHV-6 DNA and small noncoding RNA in colonic lesions. This observation confirms the major role of HHV-6 reactivation in DRESS manifestations and the importance of looking for HHV-6 reactivation in DRESS.

Bariatric surgery induces a new gastric mucosa phenotype with increased functional glucagon-like peptide-1 expressing cells.

Glucagon-Like Peptide-1 (GLP-1) undergoes rapid inactivation by dipeptidyl peptidase-4 (DPP4) suggesting that target receptors may be activated by locally produced GLP-1. Here we describe GLP-1 positive cells in the rat and human stomach and found these cells co-expressing ghrelin or somatostatin and able to secrete active GLP-1 in the rats. In lean rats, a gastric load of glucose induces a rapid and parallel rise in GLP-1 levels in both the gastric and the portal veins. This rise in portal GLP-1 levels was abrogated in HFD obese rats but restored after vertical sleeve gastrectomy (VSG) surgery. Finally, obese rats and individuals operated on Roux-en-Y gastric bypass and SG display a new gastric mucosa phenotype with hyperplasia of the mucus neck cells concomitant with increased density of GLP-1 positive cells. This report brings to light the contribution of gastric GLP-1 expressing cells that undergo plasticity changes after bariatric surgeries, to circulating GLP-1 levels.

Impact of abdominal or pelvic radiotherapy on disease activity in inflammatory bowel disease: a multicentre cohort study from the GETAID.

BACKGROUND: Abdominal or pelvic radiotherapy in inflammatory bowel disease (IBD) patients raises concerns regarding the risk of worsening of underlying disease. AIM: To assess the impact of radiotherapy on IBD course. METHODS: A retrospective multicentre study including IBD patients exposed to abdominal or pelvic irradiation was conducted, retrieving IBD activity by semester (6-month periods) before (from S-4 to S-1) and after (from S + 1 to S + 6) radiotherapy and IBD flare during follow-up. RESULTS: Sixty-one patients (32 women, mean age 59 years), with 467 patient semesters of follow-up, treated for digestive (n = 31), urinary tract (n = 23) and gynaecological cancers (n = 7) were included. Rates of IBD activity per semester were, respectively, 21% (95% CI: 16-27) from S-4 to S-1; 12% (7-19) from S + 1 to S + 3 (P = 0.15 vs S-4 to S-1) and 16% (10-25) from S + 4 to S + 6 (P = 0.45 vs S-4 to S-1). With a median follow-up of 156 weeks (interquartile range: 82-365), rates of survival without IBD flare at 1 and 3 years after radiotherapy were 82.5% (73.2-93.0) and 70.6% (58.8-84.7). Moderate-to-severe acute radiotherapy-induced gut toxicity and the absence of concomitant chemotherapy were independently associated with an increased risk of flare. CONCLUSION: Most patients with non-active IBD can be safely treated with abdominal or pelvic radiotherapy. Patients having acute gut toxicity and those without concomitant chemotherapy should be more closely monitored in the post-radiotherapy period.

Low phospholipid-associated cholelithiasis syndrome: A rare cause of acute pancreatitis that should not be neglected.

BACKGROUND: Low phospholipid-associated cholelithiasis (LPAC) syndrome is a very particular form of biliary lithiasis with no excess of cholesterol secretion into bile, but a decrease in phosphatidylcholine secretion, which is responsible for stones forming not only in the gallbladder, but also in the liver. LPAC syndrome may be underreported due to a lack of testing resulting from insufficient awareness among clinicians. AIM: To describe the clinical and radiological characteristics of patients with LPAC syndrome to better identify and diagnose the disease. METHODS: We prospectively evaluated all patients aged over 18 years old who were consulted or hospitalized in two hospitals in Paris, France (Bichat University Hospital and Croix-Saint-Simon Hospital) between January 1, 2017 and August 31, 2018. All patients whose profiles led to a clinical suspicion of LPAC syndrome underwent a liver ultrasound examination performed by an experienced radiologist to confirm the diagnosis of LPAC syndrome. Twenty-four patients were selected. Data about the patients' general characteristics, their medical history, their symptoms, and their blood tests results were collected during both their initial hospitalization and follow-up. Cytolysis and cholestasis were expressed compared to the normal values (N) of serum aspartate and alanine transaminase activities, and to the normal value of alkaline phosphatase level, respectively. The subjects were systematically reevaluated and asked about their symptoms 6 mo after inclusion in the study through an in-person medical appointment or phone call. Genetic testing was not performed systematically, but according to the decision of each physician. RESULTS: Most patients were young (median age of 37 years), male (58%), and not overweight (median body mass index was 24). Many had a personal history of acute pancreatitis (54%) or cholecystectomy (42%), and a family history of gallstones in first-degree relatives (30%). LPAC syndrome was identified primarily in patients with recurring biliary pain (88%) or after a new episode of acute pancreatitis (38%). When present, cytolysis and cholestasis were not severe (2.8N and 1.7N, respectively) and disappeared quickly. Interestingly, four patients from the same family were diagnosed with LPAC syndrome. At ultrasound examination, the most frequent findings in intrahepatic bile ducts were comet-tail artifacts (96%), microlithiasis (83%), and acoustic shadows (71%). Computed tomography scans and magnetic resonance imaging were performed on 15 and three patients, respectively, but microlithiasis was not detected. Complications of LPAC syndrome required hospitalizing 18 patients (75%) in a conventional care unit for a mean duration of 6.8 d. None of them died. Treatment with ursodeoxycholic acid (UDCA) was effective and well-tolerated in almost all patients (94%) with a rapid onset of action (3.4 wk). Twelve patients' (67%) adherence to UDCA treatment was considered "good." Five patients (36%) underwent cholecystectomy (three of them were treated both by UDCA and cholecystectomy). Despite UDCA efficacy, biliary pain recurred in five patients (28%), three of whom adhered well to treatment guidelines. CONCLUSION: LPAC syndrome is easy to diagnose and treat; therefore, it should no longer be overlooked. To increase its detection rate, all patients who experience recurrent biliary symptoms following an episode of acute pancreatitis should undergo an ultrasound examination performed by a radiologist with knowledge of the disease.

Real-world use of therapeutic drug monitoring of CT-P13 in patients with inflammatory bowel disease: A 12-month prospective observational cohort study.

BACKGROUND: Whether therapeutic drug monitoring (TDM) of infliximab should be implemented in daily practice is an ongoing controversy. AIMS: To assess the real-world use of TDM in an observational multicentre cohort study with consecutive patients with inflammatory bowel disease (IBD) treated with CT-P13. METHODS: Between September 2015 and December 2016, 364 patients with IBD were treated with CT-P13 in 13 gastroenterology departments and were followed up for 54 weeks. Disease activity, CT-P13 trough concentration and anti-CT-P13 antibody (ACA) were recorded. RESULTS: Steroid-free clinical remission rates at week 54 were 67.0% and 56.4% in patients with CD and UC, respectively. CT-P13 trough concentrations were measured in 70.7% of the patients. The mean CT-P13 trough concentration was 4.2±4.3µg/mL. The presence of ACA was observed in 53 (15.9%) patients. CT-P13 trough concentration was collected in a proactive approach in 62.8% of cases and in a reactive approach in 37.2%. Among patients who submitted to TDM, CT-P13 therapy was optimized in 88.7% of the reactive group and in 22.5% of the proactive group (P<0.001). CONCLUSION: In a real-world cohort of patients with IBD treated with CT-P13, more than two-thirds of the patients underwent TDM. CT-P13 optimization was much less common in the proactive approach than in the reactive approach.

NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells in inflammatory conditions.

Inflammatory bowel disease (IBD) is characterized by severe and recurrent inflammation of the gastrointestinal tract, associated with altered patterns of cytokine synthesis, excessive reactive oxygen species (ROS) production, and high levels of the innate immune protein, lipocalin-2 (LCN-2), in the mucosa. The major source of ROS in intestinal epithelial cells is the NADPH oxidase NOX1, which consists of the transmembrane proteins, NOX1 and p22PHOX, and the cytosolic proteins, NOXO1, NOXA1, and Rac1. Here, we investigated whether NOX1 activation and ROS production induced by key inflammatory cytokines in IBD causally affects LCN-2 production in colonic epithelial cells. We found that the combination of TNFα and IL-17 induced a dramatic upregulation of NOXO1 expression that was dependent on the activation of p38MAPK and JNK1/2, and resulted into an increase of NOX1 activity and ROS production. NOX1-derived ROS drive the expression of LCN-2 by controlling the expression of IκBζ, a master inducer of LCN-2. Furthermore, LCN-2 production and colon damage were decreased in NOX1-deficient mice during TNBS-induced colitis. Finally, analyses of biopsies from patients with Crohn's disease showed increased JNK1/2 activation, and NOXO1 and LCN-2 expression. Therefore, NOX1 might play a key role in mucosal immunity and inflammation by controlling LCN-2 expression.

Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated. METHODS: We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features of patients with IBD with and without AIP in a case-control analysis, using multivariate analysis. RESULTS: We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn's disease [CD]). Eighty-nine patients had type 2 AIP, and 2 patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7 ± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.3; P = .007) and colectomy (OR, 7.1; 95% CI, 2.5-20; P = .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03-0.77; P = .023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25-33.3; P = .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6-217; P = .0029). CONCLUSIONS: In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD.

Are random biopsies still useful for the detection of neoplasia in patients with IBD undergoing surveillance colonoscopy with chromoendoscopy?

BACKGROUND: Colonoscopy with pan-chromoendoscopy (CE) is superior to standard colonoscopy in detecting neoplasia in patients with IBD. Performing random biopsies in unsuspicious mucosa after CE remains controversial. METHODS: Consecutive patients with IBD who underwent surveillance colonoscopy using CE were prospectively included. The standardised procedure used CE, performed targeted biopsies or endoscopic resection on suspicious lesions and then quadrant random biopsies every 10 cm. A panel of five expert pathologists reviewed histological slides with dysplasia. Logistic regression model was used to evidence the factors associated with neoplasia in any or in random biopsies. RESULTS: 1000 colonoscopes were performed in 1000 patients (495 UC, 505 Crohn's colitis). In 82 patients, neoplasia was detected from targeted biopsies or removed lesions, and among them dysplasia was detected also by random biopsies in 7 patients. Importantly, in 12 additional patients dysplasia was only detected by random biopsies. Overall, 140 neoplastic sites were found in 94 patients, 112 (80%) from targeted biopsies or removed lesions and 28 (20%) by random biopsies. The yield of neoplasia by random biopsies only was 0.2% per-biopsy (68/31 865), 1.2% per-colonoscopy (12/1000) but 12.8% per-patient with neoplasia (12/94). Dysplasia detected by random biopsies was associated with a personal history of neoplasia, a tubular appearing colon and the presence of primary sclerosing cholangitis (PSC). CONCLUSIONS: Despite their low yield, random biopsies should be performed in association with CE in patients with IBD with a personal history of neoplasia, concomitant PSC or a tubular colon during colonoscopy. TRIAL REGISTRATION NUMBER: IRB 001508, Paris 7 University.

Cirrhotic patients with portal hypertension-related bleeding and an indication for early-TIPS: a large multicentre audit with real-life results.

BACKGROUND: The Baveno VI consensus meeting concluded that an early TIPS must be considered in high-risk cirrhotic patients presenting with variceal bleeding (VB) (Child B + active bleeding at endoscopy or Child C10-13 patients). Whether this therapeutic approach is feasible in a real-life setting remains unclear. AIMS: To determine (1) the proportion of patients eligible for early-TIPS among cirrhotic patients with VB, (2) the proportion of these patients who underwent early-TIPS placement and the main reasons for discarding TIPS, and (3) the outcomes of patients who experienced early-TIPS placement in a large, national, prospective, multicentre audit including academic and non-academic centres. MATERIALS AND METHODS: All French centres recruiting gastrointestinal bleeding were invited to participate. All consecutive patients with cirrhosis and PHT-related bleeding were included. RESULTS: 964 patients were included (58 centres: 26 academic, 32 non-academic; patient characteristics: male sex, 77%; age, 59.6 ± 12.1 years; aetiologies of cirrhosis (alcoholic,viral/other, 67%/15%/18%); source of bleeding (EV/GV/other, 80/11/9%); active bleeding at endoscopy 34%; Child A 21%/B 44%/C 35%. Overall, 35% of the patients were eligible for early-TIPS, but only 6.8%, displaying less severe cirrhosis underwent early-TIPS placement. The main reason for discarding TIPS was a lack of availability. The actuarial probability of survival at one year was significantly increased in early-TIPS patients (85.7±0.07% vs 58.9±0.03%, p=0.04). The severity of liver disease was the only parameter independently associated with improved one-year survival. CONCLUSION: In this real-life study, one-third of the cirrhotic patients admitted for VB fulfilled the criteria for early-TIPS placement, whereas only 7% had access to TIPS. TIPS was restricted to patients displaying less severe cirrhosis. The severity of liver disease was the only parameter that influenced survival.

Risk of Rectal Neoplasia after Colectomy and Ileorectal Anastomosis for Ulcerative Colitis.

BACKGROUND AND AIMS: Colectomy can be required in the management of ulcerative colitis [UC]. While ileal-pouch anal anastomosis [IPAA] is the recommended reconstruction technique, ileorectal anastomosis [IRA] is still performed and might present some advantages. However, the risk of rectal neoplasia might limit its indication. The aims of our study were to determine the incidence of rectal neoplasias following IRA for UC and to identify risk factors associated with rectal carcinomas. METHODS: We performed a multicenter retrospective study including patients who underwent IRA for UC from 1960 to 2014 in 13 centers. Cox-proportional hazard models were used to determine carcinoma-associated risk factors. RESULTS: A total of 343 patients were included, with a median follow-up of 10.4 years after IRA. At the end of follow-up, 38 rectal neoplasias (including 19 carcinomas) were diagnosed, and 7 patients [2%] had either died from rectal carcinoma or had a metastatic disease. Incidences of rectal carcinoma after IRA for UC were estimated at 3.2% at 10 years and at 7.3% at 20 years, whereas incidences of neoplasia were estimated at 7.1% and 14% at 10 and 20 years, respectively. In multivariate analysis, age at IRA, IBD duration, primary sclerosing cholangitis [PSC] and history of prior colonic carcinoma were independently associated with the risk of rectal carcinoma following IRA. CONCLUSION: The risk of rectal carcinoma in patients with IRA for UC remains, and this justifies long-term endoscopic surveillance. Either IPAA or end ileostomy should be considered in 'high-risk' patients i.e. those with PSC and/or with prior colonic neoplasia.