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Background and Objectives: Biosimilars are cost-effective alternatives to reference products for patients with inflammatory bowel diseases (IBD) and chronic inflammatory rheumatic diseases (CIRD), but patient beliefs can affect adherence to the transition. This study aimed to explore patient experience and satisfaction after switching to CT-P17, a high-concentration (100 mg/mL), citrate-free adalimumab biosimilar. Patients and Methods: This observational, multicenter, prospective French study included adult patients with IBD or CIRD who switched to CT-P17 from reference adalimumab (R-ADA; 100 mg/mL) or a low-concentration adalimumab biosimilar (ADA-BioS; 50 mg/mL). Patients completed online questionnaires to assess treatment perceptions, satisfaction, and tolerance at study inclusion (under previous treatment) and over 3 months of CT-P17 treatment. The primary criterion was overall patient satisfaction, which was assessed with the question, "What is your global satisfaction with the CT-P17 injection?", using a 7-point Likert scale. Multivariate logistic regression analysis was performed to identify factors associated with increased treatment satisfaction after switching to CT-P17. Results: The total analysis population included 232 patients (IBD 72.0%, CIRD 28.0%). Median patient age was 57.0 years (interquartile range [IQR] 46.0–63.0), 50.4% were men, and median disease duration was 9 years (IQR 5–16). Approximately half of the cohort (51.2%) switched to CT-P17 from an ADA-BioS (including 19.4% from an ADA-BioS with citrate) and half (48.7%) from R-ADA. The proportion of patients who were satisfied with treatment was stable between baseline (under previous treatment) and 3 months (under CT-P17). More patients reported increased satisfaction after switching to CT-P17 from an ADA-BioS (22.7% vs 8.0% when switching from R-ADA; p = 0.002), or from an ADA-BioS containing citrate (28.9% vs 12.3% when switching from a citrate-free ADA-BioS; p = 0.008). Independent prognostic factors for increased satisfaction were previous treatment with an ADA-BioS (odds ratio [OR] 2.88 [95% confidence interval 1.17–7.08]; p = 0.021) and pain at the injection site under previous treatment (OR 1.26 [1.08–1.47]; p = 0.004). Significantly fewer patients reported pain, redness, itching, and hematoma after 3 months of CT-P17 treatment versus baseline (p < 0.001). Conclusions: The majority of patients had stable or increased treatment satisfaction after switching from R-ADA or an ADA-BioS to CT-P17. In particular, switching to CT-P17 from a low-concentration ADA-BioS or an ADA-BioS containing citrate was associated with increased patient satisfaction. An improvement in overall tolerance with CT-P17 versus previous adalimumab treatment was also reported. Trial Registration: ClinicalTrials.gov identifier NCT05427942, registered June 22, 2022. [ABSTRACT FROM AUTHOR]

Copyright of Hépato-Gastro & Oncologie Digestive is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown. Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator. Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale. Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey's honest significant difference test. Results: The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%) and Hulio® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) (p < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) (p < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects. Conclusion: In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device. [ABSTRACT FROM AUTHOR]

Background: The planification of radiation therapy (RT) for pancreatic cancer (PC) requires a dosimetric computed tomography (CT) scan to define the gross tumor volume (GTV). The main objective of this study was to compare the inter-observer variability in RT planning between the arterial and the venous phases following intravenous contrast. Methods: PANCRINJ was a prospective monocentric study that included twenty patients with non-metastatic PC. Patients underwent a pre-therapeutic CT scan at the arterial and venous phases. The delineation of the GTV was performed by one radiologist (gold standard) and two senior radiation oncologists (operators). The primary objective was to compare the Jaccard conformity index (JCI) for the GTVs computed between the GS (gold standard) and the operators between the arterial and the venous phases with a Wilcoxon signed rank test for paired samples. The secondary endpoints were the geographical miss index (GMI), the kappa index, the intra-operator variability, and the dose-volume histograms between the arterial and venous phases. Results: The median JCI for the arterial and venous phases were 0.50 (range, 0.17–0.64) and 0.41 (range, 0.23–0.61) (p = 0.10) respectively. The median GS-GTV was statistically significantly smaller compared to the operators at the arterial (p < 0.0001) and venous phases (p < 0.001), respectively. The GMI were low with few tumors missed for all patients with a median GMI of 0.07 (range, 0-0.79) and 0.05 (range, 0-0.39) at the arterial and venous phases, respectively (p = 0.15). There was a moderate agreement between the radiation oncologists with a median kappa index of 0.52 (range 0.38–0.57) on the arterial phase, and 0.52 (range 0.36–0.57) on the venous phase (p = 0.08). The intra-observer variability for GTV delineation was lower at the venous phase than at the arterial phase for the two operators. There was no significant difference between the arterial and the venous phases regarding the dose-volume histogram for the operators. Conclusions: Our results showed inter- and intra-observer variability in delineating GTV for PC without significant differences between the arterial and the venous phases. The use of both phases should be encouraged. Our findings suggest the need to provide training for radiation oncologists in pancreatic imaging and to collaborate within a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Simple Summary: Crohn's disease (CD) is associated with an increased risk of small bowel neoplasia (SBN). We aimed to assess preoperative predictors of SBN in CD patients. We conducted a retrospective case-control study including CD patients who underwent surgery: cases were diagnosed with SBN on histopathological analysis in 12 tertiary centres and controls had no neoplasia. Preoperative cross-sectional imaging was reviewed by a panel of blinded expert radiologists. Fifty cases were matched to one hundred and fifty consecutive controls. Old age, long small bowel CD duration, and stricture predicted the presence of SBN, particularly adenocarcinoma when patients have digestive wall thickening > 8 mm on preoperative imaging. Crohn's disease (CD) is associated with an increased risk of small bowel neoplasia (SBN). We aimed to assess preoperative predictors of SBN in CD patients. We conducted a retrospective case-control study including CD patients who underwent surgery: cases were diagnosed with SBN on histopathological analysis and controls had no neoplasia. Preoperative cross-sectional imaging was reviewed by a panel of blinded expert radiologists. Fifty cases were matched to one hundred and fifty consecutive controls. In multivariable analysis, predictors of SBN were age ≥ 50 years (OR = 28, 95% CI = 5.05–206), median CD duration ≥ 17.5 years (OR = 4.25, 95% CI = 1.33–14.3), and surgery for stricture (OR = 5.84, 95% CI = 1.27–35.4). The predictors of small bowel adenocarcinoma were age ≥ 50 years (OR = 5.14, 95% CI = 2.12–12.7), CD duration ≥ 15 years (OR = 5.65, 95% CI = 2.33–14.3), and digestive wall thickening > 8 mm (OR = 3.79, 95% CI = 1.45–11.3). A predictive score based on the aforementioned factors was constructed. Almost 73.7% of patients with a high score had SBA. Old age, long small bowel CD duration, and stricture predicted the presence of SBN, particularly adenocarcinoma when patients have digestive wall thickening > 8 mm on preoperative imaging. [ABSTRACT FROM AUTHOR]

There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. We retrieved the full datasets of two observational, multicentre, retrospective studies of patients with UC for whom anti-TNF therapy failed and the patients were then treated with either vedolizumab or ustekinumab. The outcomes included steroid-free clinical remission, clinical remission, treatment persistence, colectomy, hospitalization, and serious and infectious adverse events. Propensity scores weighted comparison was applied. In total, 121 patients were included in the vedolizumab group and 97 were included in the ustekinumab group. At week 14 and week 52, in the weighted cohort, no difference was found between vedolizumab and ustekinumab for steroid-free clinical remission (OR = 0.55 [0.21–1.41], p =.21 and 0.94 [0.40–2.22], p =.89, respectively). There was no difference between vedolizumab and ustekinumab for secondary outcomes such as clinical remission, hospitalization, UC-related surgery, treatment persistence and serious and infectious adverse events. In patients with UC for whom anti-TNF therapy failed, no difference was found between vedolizumab and ustekinumab after propensity scores weighted comparison. Further studies are required to determine predictive factors of the efficacy of both biological agents. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with inflammatory bowel disease have an increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD). The study aims to determine the prevalence of CVD and VTE risk factors in a large population of patients with ulcerative colitis (UC). Methods: We conducted a cross-sectional study in 33 French and Belgium referral centers. A questionnaire was developed to explore self-reported risk factors for VTE and CVD, based on the latest international guidelines, in consecutive patients with UC. Results: A total of 1071 patients with UC were included. There were 539 women (50.3%), and the median age of patients was 44 years [32; 57]. The median disease duration was 10 years [6; 17]. In the cohort, 36.5% of patients reported no cardiovascular risk factor (CVRF) and 72% had ≤ 1 CVRF. Regarding cardiovascular risk markers (CVRM) 36.9% of patients reported no CVRM and 78% had ≤ 1 CVRM. Of the 1071 patients, 91.3% of patients reported no VTE strong risk factor and 96% had ≤ 1 VTE moderate risk factor. Conclusion: This is the first cohort specifically designed to assess both VTE and CVD risks in patients with UC. More than one third of patients with UC had no CVRF and around three quarters had ≤ 1 CVRF. In addition, more than nine out of ten patients had no VTE strong risk factor and ≤ 1 moderate risk factor. Physicians should be aware of these factors in their patients. [ABSTRACT FROM AUTHOR]

Objective The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-α therapy. We aimed to describe the association of IgAV and IBD. Methods We retrospectively analysed the association of IgAV and IBD through the implication of the GETAID and FVSG networks. Characteristics of IBD and IgAV were collected using a standardized case report form. Results Forty-three cases were included. IBD [mainly Crohn's disease (CD) in 58%] preceded IgAV in 38 (88%), with median interval of 9.2 (IQR 5.4–15.4) years. In these 38 patients, at IgAV diagnosis, five (13%) had active IBD and 28 (74%) were treated with anti-TNF-α for a median duration of 31.5 (IQR 19–56) months. Main IgAV manifestations were purpura all patients (100%), joints in 20/35 (57%), renal in 15/35 (43%) and gastrointestinal in 11/35 (31%) involvement. IgAV was treated with glucocorticoids in 25 (66%), colchicine in six (16%), CYC in six (16%) and anti-TNF-α were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-α blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-α cessation vs one (8%) in those continuing biologics. Anti-TNF-α were resumed in six (40%), with subsequent IgAV relapse in four (67%). Conclusions This large cohort suggests that TNF-α blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-α was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-α was associated with IBD remission but vasculitis relapse. [ABSTRACT FROM AUTHOR]

Copyright of Hépato-Gastro & Oncologie Digestive is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background: Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real‐life long‐term data are currently available. Aims: To assess the real‐world effectiveness and safety of ustekinumab in patients with UC. Methods: From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score ≤2. Results: We included 103 patients with UC (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) with an insufficient response to immunosuppressants, anti‐TNFs and/or vedolizumab. At week 52, 45 (44%) patients had discontinued ustekinumab mainly due to lack of effectiveness (n = 41). The cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7% and 58.4% after 3, 6, 9 and 12 months respectively. The overall steroid‐free clinical remission rate at week 52 was 32% of whom 71% had subscores of null for rectal bleeding and stool frequency. Ten patients underwent colectomy within a median of 6.7 [4.3‐10.6] months. Adverse effects were observed in 15 (16.9%) patients; 4 (4.5%) were severe, including one patient who died from a myocardial infarction. Conclusion: After 52 weeks, over one‐half of patients with refractory UC were still treated by ustekinumab and one‐third were in steroid‐free clinical remission. [ABSTRACT FROM AUTHOR]

Summary: Background: Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In patients hospitalised for severe flare, who previously experienced multiple drug failures, including steroids and anti‐TNF agents, new quick‐acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid onset of action. Aim: To evaluate effectiveness and safety of tofacitinib as rescue therapy in patients hospitalised for UC flare. Methods: We conducted an observational and multicentre study with both retrospective and prospective collections in 14 GETAID centres. The primary objective was to assess the survival without colectomy following tofacitinib initiation in patients hospitalised for a UC flare. We determined rates of clinical response, clinical remission, and steroid‐free clinical remission at week 6 and week 14 and safety. Results: Fifty‐five patients were included (49 with prior infliximab failure and 19 previously exposed to ciclosporin). With a median follow‐up of 6.5 months (interquartile range [IQR] [3‐12.3]), rate of colectomy‐free survival was estimated at 78.9% (95 CI [68.5‐90.9]) and 73.6% (95 CI [61.9‐87.3]) at 3 and 6 months, respectively. Rates of clinical response, clinical remission and steroid‐free clinical remission were 60%, 45.5% and 37.5% at week 6 and 41.8%, 34.5% and 32.7% at week 14. Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zoster infections occurred in patients aged over 60 years old. No venous thrombotic or major adverse cardiovascular events occurred. Conclusion: Tofacitinib appears as a promising option in patients hospitalised with a UC flare but needs further validation in controlled trials. [ABSTRACT FROM AUTHOR]

Background: Surgical resection with adjuvant chemotherapy is the only treatment that can provide long term survival in localized pancreatic ductal adenocarcinoma (LPDAC). Notwithstanding, recurrence occurs in the vast majority of patients and a better stratification of preoperative therapies is required. This study aimed to investigate preoperative immunological and nutritional factors to predict relapse-free survival (RFS) in patients with LPDAC. Methods: Analyses were derived from all consecutive LPDAC patients treated with surgical resection at Besancon University Hospital, France, between January 2006 and December 2014 (n=146). Biological and nutritional parameters were recorded before and after surgery. The association of 24 baseline parameters with RFS was evaluated using univariate and multivariate Cox analyses. Based on the final model, a prognostic score was developed. Results: Lymphocyte count and body composition were available for 94 patients. In multivariate analysis, preoperative lymphopenia and sarcopenia (or a low muscle mass) were identified as independent prognostic factors for RFS. The score determined three groups with a median RFS of 5.6 months (95% confidence interval [CI] = 4.3 to 9.6 months) for high-risk group, corresponding to patients with lymphopenia; 11.5 months (95%CI = 9.8 to 13.9 months), and 21.2 months (95%CI = 9.9 to 55.3 months), for intermediate-(patient with sarcopenia without lymphopenia), and low-risk groups (no risk factor), respectively (p <0.001). Preoperative sarcopenia predicts the occurrence of postoperative lymphopenia in patients with a preoperative lymphocyte count above 1,000/mm3 (p = 0.0029). Conclusions: Preoperative lymphopenia and sarcopenia are pejorative prognostic factors in LPDAC and should be considered in the preoperative evaluation to stratify death risk in patients with LPDAC. [ABSTRACT FROM AUTHOR]

Summary: Background: The burden of inflammatory bowel disease (IBD) is rising worldwide. The goal of IBD treatment is to achieve clinical and endoscopic remission but also prevent disability. Aims: To identify the predictive factors of disability in a large population of patients with IBD. Patients and methods: We conducted a cross‐sectional survey in 42 tertiary centres in France and Belgium. A self‐administered questionnaire was designed to explore patients and their IBD characteristics. IBD‐disk is a validated tool to measure disability in patients with IBD. The IBD‐disk score was then calculated for each patient. Based on a previous study, an overall IBD‐disk score ≥40 was associated with moderate‐to‐severe disability. Results: Among the 2011 patients, 1700 were analysed, including 746 (44%) in self‐reported clinical remission and 752 (44.2%) declaring clinical activity. The patient global assessment of global remission was missing in 200 (11.8%) of 1700 patients. Moderate‐to‐severe disability was significantly increased in patients with BMI >25 kg/m2 (OR = 1.66; 95% CI [1.29‐2.14]), in those having perception of need for a psychotherapist (OR = 2.24; 95% CI [1.79‐3.05]) and social worker (OR = 1.54; 95% CI [1.08‐2.21]). Conversely, male gender (OR = 0.83; 95% CI [0.69‐0.99]), ulcerative colitis (OR = 0.69; 95% CI [0.53‐0.92]), self‐reported clinical remission (OR = 0.59; 95% CI [0.46‐0.77]) and employed or student occupational status (OR = 0.69; 95% CI [0.52‐0.92]) were inversely correlated with disability. Overall, 257 (34.5%) patients who declared being in clinical remission had disability. Conclusion: Determinants of IBD‐related disability include IBD‐related factors but also psychological and social factors. This highlights the importance of a multidisciplinary team in the management of patients with IBD. [ABSTRACT FROM AUTHOR]

Summary: Background: The prevalence of inflammatory bowel diseases (IBD) is high in women of childbearing age. Achieving clinical remission from conception to delivery using current medications is a major issue in IBD. Aims: To assess maternal and neonatal complications and management of vedolizumab or ustekinumab) in pregnant women with IBD receiving these agents. Methods: We performed a retrospective cohort study among GETAID centres including women with IBD who received ustekinumab or vedolizumab during pregnancy or within the 2 months before conception and compared outcomes to women exposed to anti‐TNF treatment during pregnancy. Results: Seventy‐three pregnancies in 68 women with IBD were analysed: 29 on ustekinumab resulting in 26 (90%) live births, two (7%) spontaneous abortions and one (3%) elective termination; 44 on vedolizumab resulting in 38 (86%) live births, five (11%) spontaneous abortions and one (3%) medical interruption. The control group included 88 pregnancies exposed to anti‐TNF in 76 women with IBD. The median age at conception, the proportion of women who smoked or in clinical activity at conception was comparable between groups. Only the proportion of patients exposed to >2 anti‐TNF agents was significantly increased among the ustekinumab and vedolizumab groups compared to control group (22% and 10% vs 3%, P < 0.005). Rates of prematurity, spontaneous abortion, congenital malformations and maternal complications were comparable between groups. Conclusion: We report 73 pregnancies in patients receiving vedolizumab or ustekinumab without a negative signal on maternal or neonatal outcomes. Further prospective studies are needed on the outcomes of pregnancies with new biologic drugs. [ABSTRACT FROM AUTHOR]

Résumé: Le cancer du canal anal représente 2,7 % des cancers digestifs et son incidence est en constante augmentation. Dans la grande majorité des cas, il s'agit d'un carcinome épidermoïde, qui est associé à l'infection par HPV notamment au génotype 16 dans 90 % des cas. Environ 30-40 % des patients présentent soit une maladie métastatique au diagnostic, soit une évolution vers une maladie avancée non résécable suite à une radiochimiothérapie pour une maladie initialement localisée. La chimiothérapie systémique est donc le traitement de choix. En France, la collaboration de groupes coopérateurs a permis de mener des essais de phase II dans les cancers du canal anal avancés, aboutissant à un changement de paradigme avec une validation prospective des protocoles dans cette situation orpheline. Le premier fruit de ce travail fut l'étude Epitopes-HPV02, qui a permis de valider le schéma modifié du DCF (docétaxel, cisplatine et 5-fluoruracile) comme un nouveau standard. Plus récemment, un réseau international a également validé l'intérêt des taxanes en première ligne. En deuxième ligne, les immunothérapies anti-PD1/PD-L1 semblent prometteuses, surtout en association. Plusieurs essais cliniques sont actuellement en cours. Anal canal carcinoma represents 2.7% of gastrointestinal cancers, and its incidence is steadily increasing. Squamous cell carcinoma is by far the most frequent subtype, and is associated with HPV infection, mostly the genotype 16 in 90% of cases. Approximately 30 to 40% of patients are in an advanced stage, either with metastatic disease at diagnosis or with non resectable recurrence after chemoradiotherapy for an initially localized disease. Systemic chemotherapy is then the standard of choice. In France, a national network was settled and made possible to perform large phase II trials in advanced anal carcinomas. This is a paradigm shift with prospective validation of new strategies in this rare clinical setting thanks to the collaboration of different groups. Its first fruit was the Epitopes-HPV02 trial which validated the modified DCF (docetaxel, cisplatin, and 5-fluorouracil) regimen as a new standard. More recently, an international network has also validated the interest of taxanes in first-line. In second-line, results with anti-PD1/PD-L1 check point inhibitors are encouraging, especially in association, and could be the next standard. Several clinical trials are ongoing [ABSTRACT FROM AUTHOR]

Summary: Background: Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate‐to‐severe ulcerative colitis (UC), but few real‐world data are currently available. Aim: To assess short‐term effectiveness and safety of ustekinumab in patients with UC. Methods: From January to September 2019, all patients with UC treated with ustekinumab in 20 French GETAID centres were retrospectively included. The primary outcome was steroid‐free clinical remission (partial Mayo Clinic score ≤2) at weeks 12‐16 without a rectal bleeding subscore >1. Results: Among the 103 patients included, 70% had been previously exposed to ≥2 anti‐TNF agents and 85% to vedolizumab. At weeks 12‐16, steroid‐free clinical remission and clinical remission rates were 35.0% and 39.8% respectively; the absence of rectal bleeding with normal stool frequency was noted in 19.4% of patients. Two patients discontinued ustekinumab before the week 12‐16 visit and underwent surgery. In multivariable analysis, a partial Mayo Clinic score >6 at inclusion (18.6% vs 46.7%, P = 0.003) and a history of both exposure to anti‐TNF and vedolizumab therapies (27.3% vs 80.0%, P = 0.001) were negatively associated with steroid‐free clinical remission at weeks 12‐16. Adverse events occurred in 7.8% of patients and serious adverse events in 3.9% of patients. Conclusion: In a cohort of highly refractory patients with UC with multiple prior drug failures, ustekinumab provided steroid‐free clinical remission in one‐third of cases at weeks 12‐16. Clinical severity and previous use of anti‐TNF and vedolizumab therapies were associated with ustekinumab failure at weeks 12‐16. [ABSTRACT FROM AUTHOR]

Summary: Background: The management of Crohn's disease patients with perianal lesions and anti‐TNF failure is challenging. Aims: To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real‐life cohort. Methods: We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. Results: One hundred and fifty‐one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti‐TNF. The median follow‐up time was 52 weeks. Sixty‐eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04‐0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25‐18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. Conclusions: We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies. [ABSTRACT FROM AUTHOR]

Despite increasing use of immunosuppressants and anti-tumor necrosis factor (TNF) agents, approximately half of Crohn's disease (CD) patients still require surgery within 10 years after diagnosis. Surgery is not curative as postoperative relapse is very frequent in the absence of prophylactic treatment. Screening for known risk factors for postoperative recurrence allows patients to be stratified in order to consider appropriate therapy. A subsequent endoscopic evaluation and reassessment of treatment is currently the best strategy. Analyses of pooled data indicate that 5-aminosalicylic acid and thiopurines have only slight efficacy to prevent postoperative recurrence in CD. Nitroimidazole antibiotics are modestly effective, but long-term toxicity limits their use in clinical practice. Recently, anti-TNF agents have demonstrated the best efficacy profile to prevent endoscopic recurrence after surgery. As new treatment algorithms evolve towards increasing use of anti-TNF agents, this drives increased costs of management. However, this may be offset by the more widespread use of biosimilar versions of the anti-TNF agents. The increasing number of patients with previous exposure to numerous immunosuppressants and biologics at the time of surgery is a new challenge in postoperative management of CD, for which further data on new biologics are eagerly awaited. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Volkers et al papers. To view these articles, visit https://doi.org/10.1111/apt.17153 and https://doi.org/10.1111/apt.17407 [ABSTRACT FROM AUTHOR]

Résumé: Dans les maladies inflammatoires chroniques de l'intestin (MICI), la coloscopie est un examen-clé, répété pendant le suivi, pour l'évaluation de la maladie et de la réponse aux traitements. La coloscopie est aussi un examen indispensable pour la surveillance de la dysplasie dans les colites anciennes et étendues. La préparation colique doit être optimale en respectant les critères connus de qualité pour assurer des examens complets, de qualité, dans les meilleures conditions de sécurité. La description des lésions élémentaires, validées dans la maladie de Crohn et la rectocolite hémorragique, dans le compte-rendu d'endoscopie permet une évaluation précise et facile à partager. L'utilisation des scores les plus courants et/ou validés facilite la connaissance des lésions élémentaires et l'évaluation de l'efficacité des traitements dans le temps. Pour le dépistage de la dysplasie, il est recommandé d'utiliser des endoscopes haute définition et de nouvelle génération ; la chromoendoscopie au bleu reste actuellement le gold standard. In the era of tight control in inflammatory bowel disease management, colonoscopy is a key and repeated tool for disease evaluation and treatment efficacy assessment. Colonoscopy is also essential for screening of dysplasia in extensive and long-standing colitis. Bowel preparation should be optimal with respect to known quality criteria to insure complete, adequate and safe examinations. The description of validated elementary lesions in colonoscopy reports enables a precise and easy to share evaluation of the disease. Standard and validated endoscopic scores facilitate endoscopic description of mucosal lesions and treatment efficacy assessment. Chromoendoscopy with blue dying and high definition new generation endoscopes are recommended for screening of dysplasia in extensive and long-standing colitis. [ABSTRACT FROM AUTHOR]

Summary: Background: Genital fistulas represent a devastating complication of Crohn's disease. Only studies with small sample sizes have evaluated the efficacy of anti‐TNF therapy for this complication. Aims: To assess the efficacy of anti‐TNF therapy for genital fistulas complicating Crohn's disease and to identify predictive factors associated with clinical response at 1 year. Methods: Consecutive patients treated with anti‐TNF therapy for genital fistulas complicating Crohn's disease from 1999 to 2016 in 19 French centres from the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif were included in a retrospective cohort study. Outcome was clinical fistula closure at 1 year. Results: Among the 204 women with genital fistulas who received anti‐TNF therapy, 131 were analysed. The first anti‐TNF given was infliximab (79%), adalimumab (20%), or certolizumab (1%). At start of anti‐TNF therapy, 56% of patients had seton drainage and 53% had concomitant immunosuppressive treatment. A complementary surgery was performed during the first year in 10 patients (8%). At 1 year, 37% of patients had complete clinical fistula closure, 22% had a partial response, and 41% had no response. Among patients without complementary surgery, 34% (41/121) had complete clinical fistula closure. Only complementary surgery was associated with better response on multivariate analysis (adjusted relative risk: 2.02, 95% CI: 1.25‐3.26, P = 0.0043). Conclusions: In the anti‐TNF era, approximately one‐third of patients with genital fistula in Crohn's disease had complete fistula closure at 1 year. Collaboration between surgeons and gastroenterologists appears to be very important to improve the rate of fistula closure. [ABSTRACT FROM AUTHOR]

Summary: Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of severe infection due to daily pathogen exposure is controversial. Aim: To assess the risk of severe infection in healthcare workers with IBD in a large multicentre case‐control study. Methods: The study population comprised 482 healthcare workers with IBD from 17 centres who were matched for gender, age, disease subtype and year of diagnosis to 482 controls (non‐healthcare workers with IBD). The study period was between the date of diagnosis of IBD and June 2016. Severe infection was defined as any community‐acquired infection that required hospitalisation. Results: With a median follow‐up of 9.3 years, 139 severe infections were recorded among cases and controls, including 30 Clostridium difficile infections, 33 severe viral infections, nine tuberculosis infections, 21 community‐acquired pneumonia and 46 others. No difference was observed between healthcare workers and controls regarding the overall incidence rates of severe infection. An increased risk of tuberculosis was noted in healthcare workers. In multivariate analysis in the entire study population, severe infection was associated with current exposure to corticosteroids (OR = 3.05, 95% CI [2.06‐4.52], P < 0.001), immunosuppressants (OR = 1.98, 95% CI [1.38‐2.84], P < 0.001) and anti‐TNF agents (OR = 2.93, 95% CI [2.02‐4.27], P < 0.001) and reduced with Crohn's disease (OR = 0.63, 95% CI [0.43‐0.91], P = 0.01). Conclusions: Healthcare workers with IBD do not have an increased risk of severe infection compared with other patients with IBD, except for tuberculosis. Screening for tuberculosis exposure should be assessed in this high‐risk population when treated with anti‐TNF agents. [ABSTRACT FROM AUTHOR]

Background: Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels.Methods: In this multi-institutional study, we first examined the histological features displayed by each collected tumour (n = 74) and analysed their etiological relationship with human papillomavirus (HPV) infection. The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined. Finally, the prognostic significance of each clinicopathological variable was assessed.Results: Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma. The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities. Importantly, anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligand-receptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa.Conclusions: Taken together, the findings reported in the present article reveal, for the first time, that glandular neoplasms of the anal canal arise by HPV-dependent or independent pathways. These etiological differences leads to both individual immune profiles and mutational landscapes that can be targeted for therapeutic benefits. [ABSTRACT FROM AUTHOR]

Summary: The tumour‐like growth of larval Echinococcus multilocularis tissue (causing alveolar echinococcosis, AE) is directly linked to the nature/orientation of the periparasitic host immune‐mediated processes. Parasite‐mediated immune suppression is a hallmark triggering infection outcome in both chronic human and murine AE. So far, little is known about secondary systemic immune effects of this pathogen on other concomitant diseases, e.g. endogenous gut inflammation. We examined the influence of E. multilocularis infection on murine dextran sodium sulphate (DSS) ‐induced colitis. At 3 months after E. multilocularis infection (chronic stage), the mice were challenged with 3% DSS in the drinking water for 5 days plus subsequently with tap water (alone) for another 4 days. After necropsy, fixed tissues/organs were sectioned and stained with haematoxylin & eosin for assessing inflammatory reactions. Cytokine levels were measured by flow cytometry and quantitative RT‐PCR. Colitis severity was assessed (by board‐certified veterinary pathologists) regarding (i) colon length, (ii) weight loss and (iii) a semi‐quantitative score of morphological changes. The histopathological analysis of the colon showed a significant reduction of DSS‐induced gut inflammation by concomitant E. multilocularis infection, which correlated with down‐regulation of T helper type 1 (Th1)/Th17 T‐cell responses in the colon tissue. Echinococcus multilocularis infection markedly reduced the severity of DSS‐induced gut inflammation upon down‐regulation of Th1/Th17 cytokine expression and attenuation of CD11b+ cell activation. In conclusion, E. multilocularis infection remarkably reduces DSS‐induced colitis in mice by attenuating Th1/Th17‐mediated immune reactions. [ABSTRACT FROM AUTHOR]

Background Although the rs2476601 polymorphism of PTPN22 has been reported to be a susceptibility gene for Crohn's disease (CD), results from different studies vary and remain inconclusive. Also, no association has been found between rs2476601 and the risk of ulcerative colitis (UC). The aim of this meta-analysis was to investigate the association between this PTPN22 polymorphism (rs2476601) and the risk of inflammatory bowel disease, UC and CD. Methods We performed a meta-analysis by identifying relevant candidate gene-based studies from EMBASE and MEDLINE. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the strength of associations between rs2476601 and inflammatory bowel diseases, using a fi xed effect or random effect model. Publication bias was also assessed. Results By pooling 14 different studies, 13,356 controls, 8182 patients with CD, and 8656 with UC were included. We found that the T allele of PTPN22 was not significantly associated with a higher risk of developing UC (OR 1.06, 95%CI 0.98-1.14) but was associated with a decreased risk of developing CD (OR 1.28, 95%CI 1.17-1.40). The T allele in rs2476601 lowered the risk of CD by 22%. Conclusion Th is study shows that PTPN22 (rs2476601) is significantly associated with the risk of developing CD, but has no association with UC. Th is suggests that these diseases have different pathways involved in their pathophysiology. [ABSTRACT FROM AUTHOR]

Introduction: The use of various types of invasive interventions combined with anti-infective drugs in the therapeutic strategy of alveolar echinococcosis (AE) has changed during the last 30 years. Areas covered: This article reviews the current respective indications of surgical, percutaneous and perendoscopic interventions in AE and proposes an integrative therapeutic strategy. Expert commentary: Hepatic resection is indicated whenever it is feasible and curative; palliative surgery should be avoided; percutaneous procedures are best adapted to the drainage of the necrotic cavity present in advanced cases; perendoscopic procedures with stenting are best adapted to alleviating the biliary complications that are common and life-threatening in AE patients. Continuous administration of albendazole or mebendazole, without interruption is mandatory in all cases, temporarily (recommended duration: 2 years) after radical lesion resection in patients without immune suppression; for life in all other cases. Long-term follow-up is essential. [ABSTRACT FROM AUTHOR]

Background: Pancreatic adenocarcinoma (PDAC) incidence is increasing worldwide. Several studies have shown that lymphopenia was correlated with a poor prognosis but the potential interest to measure lymphopenia in the pre and post-operative setting as well as its added value among conventional prognostic factors was never investigated. Methods: Data from two independent cohorts in whom patients underwent resection for pancreatic carcinoma were retrospectively recorded. We examined the association between perioperative findings, pre and post-operative lymphocyte counts and overall survival (OS) in univariate and multivariate analyses. Performance assessment and internal validation of the final model were evaluated with Harrell's C-index, calibration plot and bootstrap sample procedures. Results: Three hundred ninety patients were included in the analysis between 2000 and 2011. Pre and post-operative lymphocyte counts were independent prognostic factors associated with OS in multivariate analysis (p = 0.0128 and p = 0.0764, respectively). The addition of lymphocyte count variable to the conventional parameters identified in multivariate analysis (metastatic lymph node ratio, veinous emboli and adjuvant chemotherapy) significantly improved the model discrimination capacity (bootstrap mean difference = 0.04; 95 % CI, 0.01-0.06). The use of a threshold and combining the categorical (≥1000; <1000) information in pre and post lymphocyte counts permitted the identification of 4 subgroups of patients with different prognosis (p < 0.0001). Finally, the description of patients in long-term remission showed that only 3 of 65 (4.6 %) patients with post-operative lymphocyte count under 1000/mm³ were alive 4 years after surgery contrary to 54 of 236 (22.8 %) patients with a post-operative lymphocyte count above 1000/mm³. Conclusion: Pre and post-operative lymphopenia are independent prognostic factors for OS and they have an additive value regarding conventional prognostic factors for death-risk stratification and to predict long-term survival. Lymphopenia should be included as stratification factors in future clinical trial assessing overall survival in pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

The objectives of the present study are to explore role of pyruvate kinase isoenzyme type M2 (PKM2) in progression of Kazakh's esophageal squamous cell carcinoma (ESCC) in Xinjiang, China, and to clarify mechanism of PKM2 in malignant phenotype. PKM2 expression was examined using immunohistochemistry (IHC) in 101 matched pairs of ESCC and normal adjacent tissues (NATs) and using enzyme-linked immunosorbent assay (ELISA) in 35 serum samples of Kazakh's ESCC and 8 serum samples of healthy subjects. To investigate mechanism, small interfering RNA (siRNA)-PKM2 was transfected into ESCC cells. Cell migration and invasion were evaluated by wound healing and Transwell assays. Apoptosis and cell cycle were analyzed by flow cytometry (FCM). PKM2 expression was significantly higher in ESCC tissues (77.2 %, 78/101) compared with matched NAT ( P = 0.003) and also higher in serum samples of Kazakh's ESCC patients (78.84 ng/mL) compared with healthy subjects (13.55 ng/mL) ( P = 0.001). Patients with overexpression of PKM2 had a poor prognosis ( P = 0.032). After knockdown of PKM2, cell proliferation, migration, and invasion were significantly reduced ( P = 0.001), apoptosis increased ( P = 0.001), and cell cycle was arrested at G1 phase. PKM2 overexpression was significantly correlated with the worse outcome of Kazakh's ESCC. Furthermore, PKM2 was involved in progression of ESCC by promoting proliferation and suppressing apoptosis, accelerating invasion, and influencing cell cycle. PKM2 could be a potential biomarker for molecular classification of ESCC. [ABSTRACT FROM AUTHOR]

Background and Objectives: Anti-hypertensive treatment with the angiotensin II receptor antagonist olmesartan is a rare cause of severe Sprue-like enteropathy. To substantiate the hypothesis that olmesartan interferes with gut immune homeostasis, clinical, histopathological and immune features were compared in olmesartan-induced-enteropathy (OIE) and in autoimmune enteropathy (AIE). Methods: Medical files of seven patients with OIE and 4 patients with AIE enrolled during the same period were retrospectively reviewed. Intestinal biopsies were collected for central histopathological review, T cell Receptor clonality and flow cytometric analysis of isolated intestinal lymphocytes. Results: Among seven olmesartan-treated patients who developed villous atrophy refractory to a gluten free diet, three had extra-intestinal autoimmune diseases, two had antibodies reacting with the 75 kilodalton antigen characteristic of AIE and one had serum anti-goblet cell antibodies. Small intestinal lesions and signs of intestinal lymphocyte activation were thus reminiscent of the four cases of AIE diagnosed during the same period. Before olmesartan discontinuation, remission was induced in all patients (7/7) by immunosuppressive drugs. After interruption of both olmesartan and immunosuppressive drugs in six patients, remission was maintained in 4 but anti-TNF-α therapy was needed in two. Conclusion: This case-series shows that olmesartan can induce intestinal damage mimicking AIE. OIE usually resolved after olmesartan interruption but immunosuppressive drugs may be necessary to achieve remission. Our data sustain the hypothesis that olmesartan interferes with intestinal immuno regulation in predisposed individuals. [ABSTRACT FROM AUTHOR]

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Despite an increasing use of immunosuppressants and anti-tumor necrosis factor (TNF) agents, approximately half of the patients with Crohn’s disease will require surgery within 10 years after diagnosis. Postoperative relapse is frequent and should be systematically assessed within the first year by endoscopy. Absence of prophylactic treatment is associated with a higher risk of relapse. Other risk factors include smoking, prior intestinal surgery, penetrating disease behavior, perianal location, and extensive small bowel resection. Pooled data indicate that 5-aminosalicylic acid and thiopurines have only slight efficacy to prevent postoperative recurrence in Crohn’s disease. Nitroimidazole antibiotics are modestly effective, but long-term toxicity limits their use in clinical practice. Recently, anti-TNF agents in this setting have demonstrated efficacy and dramatically contrast with other interventions, but rising costs are concerning. Anti-TNF agents are highly effective in the prevention of postoperative recurrence in these patients. A therapeutic strategy based on a risk stratification of patients, with further treatment step-up and adjustment if relapse occurs on the basis of ileocolonoscopy, is recommended in clinical practice. Should we move towards top-down strategies based on a wider use of anti-TNF agents even in patients who are not at high risk of postoperative recurrence? Ongoing clinical trials addressing this issue will dramatically change our clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Although the efficacy of TNF blockers has been demonstrated in hidradenitis suppurativa (HS), many paradoxical effects have also been described with TNF antagonists. We wished to describe patients with adalimumab (ADA)-induced paradoxical HS.Methods: This is a retrospective descriptive case series of four patients with ADA-induced paradoxical HS.Results: All the patients had a good response to TNFa antagonist therapy at the time of HS occurrence. The time from TNFa antagonist initiation to HS onset or exacerbation ranged from a few weeks to 24 months. The outcome of HS was variable. Systemic antibiotics were required in all the cases to control HS. TNF blockers were continued in three cases with a switch to another anti-TNF class in one case. Switch to ustekinumab was prescribed in one patient with SA and Crohn’s disease.Conclusion: Although the imputability of TNF blockers in paradoxical HS is still debatable, further research and observation are needed to confirm and distinguish patients with genetic and clinical predisposition in the onset or exacerbation of HS during anti-TNF treatment. [ABSTRACT FROM AUTHOR]

We report two cases of acute pancreatitis following the administration of pamidronate given as an anti-inflammatory agent for spondyloarthritis with a recurrence in one patient when the drug was reintroduced. The upper gastrointestinal toxicity of aminobisphosphonates is well known and this drug class could be added to the list of medications that are associated with the development of pancreatitis. [ABSTRACT FROM AUTHOR]