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Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR. We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated. From 2005 to 2020, 27 patients (Crohn's Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first (n = 2), second (n = 4) or third (n = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX. IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics. What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation. What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity. How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug. [ABSTRACT FROM AUTHOR]

Background: Acute gastrointestinal bleeding (GIB) may be a severe condition in immunocompromised patients and may require intensive care unit (ICU) admission. We aimed to describe the clinical spectrum of critically ill immunocompromised patients with GIB and identify risk factors associated with mortality and severe GIB defined by hemorrhagic shock, hyperlactatemia and/or the transfusion of more than 5 red blood cells units. Finally, we compared this cohort with a control population of non-immunocompromised admitted in ICU for GIB. Results: Retrospective study in 3 centers including immunocompromised patients with GIB admitted in ICU from January, 1st 2010 to December, 31rd 2019. Risk factors for mortality and severe GIB were assessed by logistic regression. Immunocompromised patients were matched with a control group of patients admitted in ICU with GIB. A total of 292 patients were analyzed in the study, including 141 immunocompromised patients (compared to a control group of 151 patients). Among immunocompromised patients, upper GIB was more frequent (73%) than lower GIB (27%). By multivariate analysis, severe GIB was associated with male gender (OR 4.48, CI95% 1.75–11.42, p = 0.00), upper GIB (OR 2.88, CI95% 1.11–7.46, p = 0.03) and digestive malignant infiltration (OR 5.85, CI95% 1.45–23.56, p = 0.01). Conversely, proton pump inhibitor treatment before hospitalization was significantly associated with decreased risk of severe GIB (OR 0.25, IC95% 0.10–0.65, p < 0.01). Fifty-four patients (38%) died within 90 days. By multivariate analysis, mortality was associated with hemorrhagic shock (OR 2.91, IC95% 1.33–6.38, p = 0.01), upper GIB (OR 4.33, CI95% 1.50–12.47, p = 0.01), and long-term corticosteroid therapy before admission (OR 2.98, CI95% 1.32–6.71, p = 0.01). Albuminemia (per 5 g/l increase) was associated with lower mortality (OR 0.54, IC95% 0.35–0.84, p = 0.01). After matching with a control group of non-immunocompromised patients, severity of bleeding was increased in immunocompromised patients, but mortality was not different between the 2 groups. Conclusion: Mortality is high in immunocompromised patients with GIB in ICU, especially in patients receiving long term corticosteroids. Mortality of GIB is not different from mortality of non-immunocompromised patients in ICU. The prophylactic administration of proton pump inhibitors should be considered in this population. [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]

Background: Predictors of the efficacy of endoscopic dilation for caustic esophageal stricture have been poorly studied.Methods: All patients undergoing an endoscopic dilation for an esophageal caustic stricture between 1990 and 2015 in a French national reference center were included. Success of dilation was defined by self-food autonomy without the need for reconstructive esophageal surgery.Results: During the study period, 894 patients were admitted after caustic ingestion. Among them, 101 patients developed esophageal stricture and 92 patients were eligible for analysis (missing data in 8 cases, 1 patient died before endoscopic dilation). In this cohort (median age 42 years, women 53%, strong alkali 74%, suicide attempt 77%, hydrostatic balloon use 93%), the overall success rate of dilation was 57% with a median number of 3 dilation sessions (274 sessions, range 1-17). Factors predicting the success of the procedure were: non-inflammatory stricture or non-inflammatory intercalated mucosa between stricture (88% vs 47%, p = 0.001), a single stricture versus 2 or more strictures (69% vs 47% vs 33%, respectively, p = 0.04), a stricture of less than 5 cm (70% vs 27%, p < 0.001) and the existence of mild/ moderately tight or very tight stricture (70% vs 21% of success, p < 0.001). Perforation rate was 6.5% (18/274) requiring emergency surgery in 2 cases.Conclusion: Several characteristics of caustic esophageal strictures are significantly associated with the success rate of endoscopic dilation. Our data may be useful for customizing treatment strategies in patients with a caustic stricture. [ABSTRACT FROM AUTHOR]

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]

Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC). Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3). Patients received monotherapy based on 5-FU (n = 1068), a cytotoxic doublet (n = 395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n = 727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0–1 (OR 2.57; 95% CI [1.16, 5.73]; p = 0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p = 0.02), alkaline phosphatase > 300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p < 0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p = 0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80–0.96]; p = 0.004). ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation. • Severe drug toxicity has a negative impact on prognosis in metastatic colorectal cancer. • Early toxicity within 3 months after first-line regimen initiation may be a key factor. • Early grade III or more toxicity is a new prognostic marker. • Some baseline characteristics are associated with ET3 occurrence. • Early grade III or more toxicity correlates with poorer overall survival. [ABSTRACT FROM AUTHOR]

Aim: The treatment of perianal fistulas in Crohn's disease remains challenging. Fibrin glue injection has previously shown short‐term efficacy in a randomized controlled trial. No long‐term data are available to assess the benefit of this treatment. Methods: This retrospective multicentre study included all patients with drained fistulas treated by at least one fibrin glue injection between January 2004 and June 2015 in three tertiary French centres. The primary end‐point was the rate of complete clinical remission at 1 year after injection defined by the closure of all fistula tracts with no need for iterative anal surgery or for optimization of immunosuppressants and/or biologics. Results: In all, 119 patients (median age 33 years, complex fistulas 65%, median previous anal surgery two, median Harvey Bradshaw score 3, immunosuppressants exposure 50%, anti‐tumor necrosis factor exposure 60% with median time of administration of 1.1 year) were analysed with a median follow‐up of 18.3 months. The complete clinical remission rate at 1 year was 45.4%. The primary end‐point was achieved in 63% of the cases in the combination therapy group and 37% in other patients. The only predictor of complete clinical remission at 1 year was combination therapy at the time of injection (P = 0.01). The rate of early reintervention after glue injection was 2.5%. The cumulative incidence of iterative anal surgery and ostomy in the whole population was 54% and 5.6% respectively at 5 years. Conclusion: An adjunct of fibrin glue to conventional medical therapy may be an effective and safe treatment for perianal fistulas in patients with Crohn's disease. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Anal squamous cell carcinoma is associated with multiple risk factors, including infection with human papillomavirus and human immunodeficiency virus, immunosuppression, multiple sex partners, receptive anal sex and tobacco smoking. The aim of our study was to identify prognostic factors associated with poor outcomes after radiotherapy for anal cancer. We analysed retrospectively the medical records of 171 patients treated by (chemo)radiotherapy for non-metastatic anal cancer in our institution from 2000 to 2015. Patients and tumour characteristics, treatments (chemotherapy, radiotherapy [RT] and surgery) and outcomes were reported. Colostomy-free survival (CRF), disease-free survival and overall survival (OS) at 5 years were studied. Univariate and multivariate analyses were performed by logistic regression to determine factors associated with poor progression-free survival (PFS). Patients' characteristics were as follows: median age, 62 years (range = 36–89); gender, 45 men (26%) and 126 women (74%); HIV serology, positive: 21 patients (12%); tobacco smoking, 86 patients (50%), among whom 28 patients and 58 patients were current and former smokers, respectively. Tumours were classified as locally limited (T1–2, N0, M0) for 86 patients (50%) and locally advanced (T3–4 or N+, M0) for 85 patients (50%). The median total dose was 64.4 Gy (range = 54–76.6), and 146 patients were treated by concurrent chemoradiotherapy. Factors associated with poor PFS in univariate analysis were as follows: tumour size >4 cm, lymph node involvement, tobacco smoking, no initial surgical excision and anal warts at diagnosis. In multivariate analysis, only tobacco smoking status was significantly associated with poor PFS (hazard ratio = 2.85, 95% confidence interval [1.25–6.50], p = 0.013). Five-year PFS for non-smokers, former smokers and current smokers was 88.1%, 76.7% and 73.8%, respectively (p = 0.038). Tobacco smoking was also associated with poor overall survival (p = 0.03), locoregional relapse-free survival (LRFS; p = 0.05) and CFS (p = 0.02). Tobacco smoking status is associated with poor OS, LRFS, PFS and CFS in patients treated for anal cancer by high RT dose ± chemotherapy. • The patients's smoking status is associated with increased risk for anal cancer recurrence, colostomy and death. • The patient's smoking history (current smoker; ex-smoker; never smoker) is also associated with patient's outcome. • The patient's smoking status overcomes all prognostic factors in anal cancer treated by radiotherapy. [ABSTRACT FROM AUTHOR]

Résumé: L'ingestion de caustiques représente une urgence médico-chirurgicale. Chez l'adulte, elle est le plus souvent à visée suicidaire et sa gravité dépend de la nature et de la quantité du produit ingéré. La prise en charge doit être multidisciplinaire. L'enjeu initial est d'identifier les patients qui nécessitent une résection chirurgicale d'urgence pour nécrose transmurale du tube digestif mettant en jeu leur pronostic vital. L'endoscopie digestive haute n'a plus de place à la phase aiguë de l'ingestion. L'algorithme décisionnel repose désormais sur le scanner injecté avec une classification dédiée et une bonne reproductibilité inter-observateur. L'apport de l'imagerie a permis d'étendre les indications de traitement conservateur qui peut être réalisé chez environ trois quarts des patients. Dans ce cas, la réalimentation doit être très précoce. Il n'y a pas de traitement médicamenteux validé pour favoriser la cicatrisation des lésions. En cas de survenue ultérieure d'une sténose œsophagienne, la dilatation endoscopique représente le traitement de première intention. Ingestion of caustics represents a medical and surgical emergency. In adults, it is most often suicidal and its severity depends on the nature and quantity of the ingested product. Management should be multidisciplinary. The initial challenge is to identify patients requiring emergency surgical resection for life-threatening transmural necrosis of the gastrointestinal tract. Upper gastrointestinal endoscopy has no longer a place in the acute phase of ingestion. The decisional algorithm is now based on the injected CT scan with a dedicated classification and good inter-observer reproductibility. The contribution of imaging has made possible to extend the indications for conservative treatment, which can be carried out in about three quarters of the patients. In this case, re-feeding must be very early. There is no validated drug treatment to promote wound healing. If esophageal stenosis occurs later, endoscopic dilatation is the first-line treatment. [ABSTRACT FROM AUTHOR]

Résumé: L'endoscopie d'urgence s'adresse à des maladies graves à toute heure de prise en charge. Les indications sont essentiellement le traitement de l'hémorragie digestive et l'extraction des corps étrangers supérieurs. Mais elle peut aussi être nécessaire en cas de volvulus du sigmoïde et de syndrome d'Ogilvie résistant au traitement médical. La plupart des indications urgentes doivent conduire à une endoscopie dans les 24 heures mais, dans de rares cas, le délai doit être de moins de 12 heures voire de moins de 2 heures. Elle est souvent réalisée en dehors des heures ouvrables, la nuit, le week-end et les jours fériés. Elle doit cependant être réalisée dans de bonnes conditions avec une équipe entraînée. La bonne connaissance des indications des endoscopies d'urgence, ainsi que du délai et de ses modalités de réalisation est nécessaire à tout hépato-gastroentérologue pour prendre les bonnes décisions avec les correspondants urgentistes, réanimateurs, radiologues et chirurgiens et conduire à une prise en charge optimale du patient. Emergency endoscopy is mandatory at all times for critically ill patients. Emergency endoscopy is mainly performed for the management of digestive bleeding and for the extraction of foreign bodies. But it may also be necessary in case of sigmoid volvulus and Ogilvie syndrome resistant to medical treatment. Most urgent indications must lead to an endoscopy within 24 hours, and in rare cases within 12 hours or even less than 2 hours. It is therefore often be carried out outside working hours; at night, weekends and holidays. However, it should be performed by a properly trained team in an adequate environment. A knowledge of validated indications for emergency endoscopies, appropriate timing and procedures should therefore be mastered by any hepatogastroenterologist on duty, in order to take the appropriate decisions with emergency intensivists, radiologists and surgeons, and to obtain an optimal care for patients. [ABSTRACT FROM AUTHOR]

Background: There is no consensual definition for gastric linitis plastica (GLP). We aim to construct a diagnostic score to distinguish this rare tumor from usual gastric adenocarcinomas. Methods: In this retrospective study, all patients who had gastrectomy for cancer between 2007 and 2017 in French tertiary centers were included. The outcome was a diagnosis of GLP based on pathological review of the surgical specimen. The diagnostic score was created by using variables that were most frequently associated with GLP using penalized logistic regression on multiply imputed datasets. We used discrimination measures to assess the performances of the score. Internal validation was performed using bootstrapping methods to correct for over-optimism. Results: 220 patients including 71 linitis plastica (female 49%, median age 57 years) were analyzed. The six parameters retained in the diagnosis score were the presence of large folds and/or parietal thickening on at least one segment, pangastric infiltration and presence of gastric stenosis on the upper endoscopy, circumferential thickening on at least one segment and thickening of the third hyperechogenic layer on endoscopic ultrasound and the presence of signet ring cells on endoscopic biopsies. The area under the ROC curve (AUC) was 0.967 with a sensitivity of 94% [89.9–97.3] and a specificity of 88.7% [81.7–95.8] for a threshold of 2.75. After internal validation, the corrected AUC was 0.959. Conclusion: It is the first study validating a pre-therapeutic diagnostic score (Saint Louis linitis score) with an excellent ability to discriminate GLP from non-GLP adenocarcinomas. An external validation is necessary to confirm our data. [ABSTRACT FROM AUTHOR]

Summary: Background: The long‐term outcome of patients with acute severe ulcerative colitis (ASUC) responding to intravenous steroids (IVS) has been poorly reported. Aims: To assess relapse‐free survival in patients with ASUC responding to IVS. Methods: Between January 2006 and December 2017, 142 consecutive patients with ASUC (according to modified Truelove‐and‐Witts criteria) responding to IVS were included in this multicentre retrospective study. Relapse was defined by a partial Mayo Clinic score >4 and/or the need for another maintenance therapy. Results: Among the 142 included patients (100 naïve of immunomodulator and/or biological agent) hospitalised for ASUC, 59 (41.5%) were treated at discharge with 5‐aminosalicylic acid, 60 (42%) with immunomodulators, 18 (13%) with anti‐tumour necrosis factor (TNF) agents and 5 (3.5%) with vedolizumab. After a median follow‐up of 4.8 (2.6‐7.3) years, 90 (63.4%) had relapsed and 12 (8.5%) had required colectomy. The probabilities of relapse‐free survival were 58%, 48% and 40% at 1, 2 and 5 years respectively. The multivariate analysis demonstrated that patients with <6 liquid stools per day at day 3 (hazard ratio 0.56, 95%CI [0.34‐0.91]), a partial Mayo Clinic score <2 at day 5 (0.41 [0.21‐0.80]) and anti‐TNF maintenance therapy (0.37 [0.16‐0.87]) were less likely to relapse. The probabilities of colectomy‐free survival were 96%, 95% and 91% at 1, 2 and 5 years respectively. Conclusion: Despite a high relapse rate, patients with ASUC responding to IVS had a low rate of colectomy after 5 years of follow‐up. Early response to IVS and maintenance therapy with biological agents were associated with a lower rate of relapse. [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]

Background: Identifying patients with metastatic colorectal cancer who will have an early disease progression during induction chemotherapy (IC) and identifying patients who may have a chemotherapy-free interval (CFI) after IC are two major challenges.Methods: A logistic model was used to identify factors associated with early progression during IC and with short duration of the first CFI in 488 patients enrolled in the PRODIGE 9 trial. Independent factors were defined with a threshold 0.10.Results: In multivariate analysis, baseline leukocytes >10 × 109/L (OR = 1.98 [1.02-3.8], p = 0.04), and stable or increasing CEA at 2 months (OR = 3.61 [1.68-7.75], p = 0.01) were independent factors associated with progression during IC. Male gender (OR = 1.725 [0.92-3.325], p = 0.09) and no tumour response at first evaluation (OR = 1.90 [0.96-3.76], p = 0.07) were significantly associated with a short CFI. The presence of BRAF V600E mutation was also associated with short CFI (OR = 4.59 [0.95; 22.3], p = 0.058).Conclusion: High baseline leukocyte count and the lack of CEA decrease level at first evaluation were associated with early progression, and could be in favour of early chemotherapy intensification. Male gender, no tumour response at first evaluation and BRAF mutation are associated with a short CFI, and may be considered for maintenance chemotherapy after IC.Clinical Trial Number: NCT00952029. [ABSTRACT FROM AUTHOR]

Baseline circulating tumour DNA (ctDNA) is a potential prognostic marker in metastatic colorectal cancer (mCRC) patients. However, few studies have compared ctDNA with the usual prognostic factors, and no ctDNA cut-off has been proposed for daily use in clinical practice. Chemotherapy-naive patients with mCRC were prospectively included. Plasma samples were collected at diagnosis and analysed centrally by both NGS and methylation digital PCR. Baseline patient and disease characteristics, treatment regimens, and secondary surgeries were collected. The restricted cubic spline method was used to define the optimal cut-off of ctDNA mutated allelic frequency (MAF). Prognostic values were assessed on overall survival (OS) using Cox models. From July 2015 to December 2016, 412 patients were included. ctDNA was undetectable in 83 patients (20%). ctDNA was an independent prognostic marker for OS considering the whole study population. The optimal cut-off for ctDNA MAF was 20% with median OS of 16.0 and 35.8 months for patients with MAF ≥20% and<20%, respectively (hazard ratio = 0.40; 95% confidence intervals: 0.31–0.51; P < 0.0001). The independent prognostic value of ctDNA MAF at 20% was confirmed in subgroups defined by RAS/BRAF status or resectability of metastases. Combining ctDNA MAF and carcinoembryonic antigen levels allowed us to define three different prognostic groups with median OS of 14.2, 21.1, and 46.4 months (P < 0.0001). ctDNA with a MAF cut-off of 20% improves prognostication of chemotherapy-naïve mCRC patients and may be useful in the future for individualised therapeutic decisions and as a stratification factor in clinical trials. Trial registration: Clinicaltrials.gov, NCT02502656 • ctDNA at baseline was a strong prognostic biomarker. • An optimal mutated allelic frequency (MAF) cut-off of 20% was defined. • Prognostic value of ctDNA was found in all subgroups. • CEA and ctDNA MAF had an independent prognostic value and are not correlated. • CEA and MAF combination classified patients in three prognostic subgroups. [ABSTRACT FROM AUTHOR]

Summary: Background: Cohort studies have described the short‐term effectiveness and safety of vedolizumab in treating patients with Crohn's disease (CD) and ulcerative colitis (UC), but data beyond 1 year are lacking. Aim: To assess the effectiveness and safety of vedolizumab after 162 weeks in patients with UC and CD. Methods: Between June and December 2014, 294 patients including 173 patients with CD and 121 with UC were treated with vedolizumab induction therapy. Among them, 149 continued to be treated with vedolizumab beyond week 54 (78 patients with CD and 71 with UC). Disease activity was assessed using the Harvey‐Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid‐free clinical remission at week 162, computed for the whole population included at week 0. Results: Steroid‐free clinical remission rates at week 162 were 19.9% and 36.1% in patients with CD and UC respectively. Vedolizumab dose optimisation to 300 mg every 4 weeks instead of 300 mg every 8 weeks was at investigator's discretion and occurred in 58.7% and 52.1% of patients with CD and UC respectively. The 1‐, 2‐ and 3‐year persistence rates of vedolizumab were 48.5%, 31.4% and 26.3% respectively, in patients with CD and 61.0%, 49.9% and 42.9% respectively, in patients with UC. No new safety signal was identified. Conclusion: Vedolizumab is able to maintain steroid‐free clinical remission in patients with UC and CD up to week 162. Loss of response resulting in discontinuation of vedolizumab occurred in 10% of patients per year. [ABSTRACT FROM AUTHOR]

Summary: Background: After ileocaecal resection for Crohn's disease (CD), inflammatory lesions frequently recur on the anastomosis and/or on the neo‐terminal ileum. Aim: To identify predictors of early post‐operative endoscopic recurrence. Methods: From September 2010 to September 2017, the REMIND group conducted a prospective nationwide study in nine French academic centres. Data were collected at the time of surgery and endoscopy, performed 6‐12 months after surgery. Endoscopic recurrence was defined as a Rutgeerts score ≥i2. Baseline factors associated with endoscopic recurrence were searched by univariate and multivariate regression analysis. Results: Two hundred and eighty‐nine CD patients were included. Endoscopy within 1 year following surgery was performed in 225 (78%) patients (104M/121F). Mean age and disease duration were 35 (12.2) and 8.8 (8.9) years respectively. Seventy (32%) patients were active smokers at surgery. One hundred and forty‐two (63%) patients received at least one anti‐TNF therapy before surgery. After surgery, 40 (18%) patients received thiopurines and 66 (29%) received an anti‐TNF agent. Endoscopic recurrence occurred in 107 (47%) patients. In multivariate analysis, male gender (OR = 2.48 [IC 95% 1.40‐4.46]), active smoking at surgery (OR = 2.65 [IC 95% 1.44‐4.97]) and previous resection (OR = 3.03 [IC 95% 1.36‐7.12]) were associated with a higher risk of endoscopic recurrence. Inversely, post‐operative anti‐TNF treatment decreased the risk of endoscopic recurrence (OR = 0.50 [IC 95% 0.25‐0.96]). Conclusions: Male gender, active smoking at surgery and previous intestinal resection are associated with a higher risk of endoscopic post‐operative recurrence, while post‐operative anti‐TNF treatment is associated with a lower risk. Linked Content This article is linked to Yamamoto and Kotze, and Imperatore et al papers. To view these articles visit https://doi.org/10.1111/apt.14985 and https://doi.org/10.1111/apt.14989. [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]

Purpose To evaluate outcomes after exclusive salvage high-dose-rate (HDR) intraluminal esophageal brachytherapy given to previously irradiated patients with recurrent esophageal cancer. Methods and Materials We reviewed medical records of 30 patients who were treated by salvage HDR brachytherapy for local esophageal cancer. Brachytherapy delivered four to six fractions of 5–7 Gy at 5 mm from the applicator surface and 20 mm above and below the macroscopic tumor volume. Results Eighty percentage of patients received treatment as initially planned. Complete response rate, evaluated 1 month after brachytherapy by endoscopy and biopsy, was 53%. Squamous histology and complete endoscopic tumor response at 1 month were significantly associated with better local tumor control. Median local progression-free survival was 9.8 months. Overall survival was 31.5% and 17.5% at 1 and 2 years, respectively. On univariate analysis, preserved performance status and limited weight loss (<10%) before salvage brachytherapy were associated with better overall survival. Severe toxicity (Grade ≥3) occurred in 7 patients (23%). Conclusions Although esophageal cancer in previously irradiated patients is associated with poor outcomes, HDR brachytherapy may be a valuable salvage treatment for inoperable patients with locally limited esophageal cancer, particularly in the subset of patients with preserved performance status and limited weight loss (≤10%) before salvage brachytherapy. [ABSTRACT FROM AUTHOR]

Background: After ileocolic resection in Crohn's disease, studies concerning the influence of the laparoscopic or open approach on clinical and endoscopic recurrences are scarce. Patients and Methods: In a prospective database, we identified all patients operated on between 2004 and 2012 for primary ileocolic resection in Crohn's disease, with at least 6 months of follow-up. The rates of endoscopic recurrence during the first postoperative year and the clinical recurrence at any time during follow-up were measured and compared after the laparoscopic or open approach. Results: Sixty-two patients (mean±standard deviation age, 33.5±12.7 years; 35 females) were operated on through laparoscopy ( n=28) or laparotomy ( n=34). Medical treatment, evolution and phenotype of disease, and postoperative course were comparable in both groups. Mean±standard deviation follow-up was 3.5±1.9 years. Ileocolonoscopy was available in 46 (74.2%) patients. Normal endoscopy or minor recurrence (i0 or i1 grade) was significantly more frequent after laparoscopy (14/24 [58.3%]) versus laparotomy (5/22 [22.7%]) ( P=.019). Clinical recurrence was comparable at 1 year ( P=.116) and at the end of follow-up ( P=.799) after laparoscopy (28.6% and 50%, respectively) or laparotomy (11.8% and 55.9%, respectively). Conclusions: After resection, normal or minor endoscopic lesions (i0 or i1 grade) were more frequent after laparoscopy than after laparotomy. However, clinical recurrence was similar after both techniques. [ABSTRACT FROM AUTHOR]

Purpose: The best way to assess the response to chemoradiotherapy of locally advanced oesophageal carcinomas is not known. We used F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to evaluate the metabolic response during chemoradiotherapy and tried to correlate this response to survival. Methods: Patients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment (SUV1) and during chemoradiotherapy after two cycles of 5-fluorouracil (FU)/cisplatin and 20 Gy (SUV2). Metabolic response was defined as 1−(SUV2/SUV1). Surgery was discussed after 40 Gy and three cycles of chemotherapy. Results of interim PET were not considered for the therapeutic decision. Results: Among 72 patients who underwent a first FDG PET/CT before any treatment, 59 (82 %) could receive the second FDG PET/CT examination. Median survival was 22.2 months with 1-year and 2-year survivals of 70 and 46 %, respectively. Nineteen patients (32 %) underwent surgery. Mean SUV1 and SUV2 were 12.3 ± 6.2 and 6 ± 4.1, respectively ( p < 0.001). Using a cut-off for metabolic response of 50 %, sensitivity and specificity for survival were 0.7 and 0.58. The 2-year overall survival of good responders was 62 % as compared to 27 % for poor metabolic responders. A multivariate analysis was performed, including T and N stages, surgery, histology and metabolic response: only metabolic response was significantly ( p = 0.009) associated with 2-year survival. Conclusion: Early evaluation of metabolic response had a great prognostic value and could help identify good responders to chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background & Aims: Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms. Method: A cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations. Results: The NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30- 0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03). Conclusions: It is not recommended to genotype the studied polymorphisms in routine practice. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36–75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400–3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control. [ABSTRACT FROM AUTHOR]

Background: Both observational and aggressive surgical strategies have been advocated for the treatment of corrosive injuries of the upper gastrointestinal tract (UGT) but the optimal management is still a dilemma. The aim of this study was to report our experience with caustic UGT injuries in adult patients treated with a surgically aggressive, endoscopy-based therapeutic protocol over a 6-year period. Patients and methods: Between January 2002 and December 2007, 315 patients (138 men, mean age = 40 ± 15.5 years) were referred for corrosive UGT injuries. Emergency endoscopy was performed in all patients at admission. Patients with mild injuries (grades I-IIIa) were offered nonoperative management, whereas emergency surgery was performed for severe injuries (grades IIIb and IV). Esophageal reconstruction was offered to psychologically stable patients after emergency esophageal resection and for esophageal strictures that failed endoscopic dilation. Functional failure was defined as the impossibility to remove the jejunostomy or/and the tracheotomy tube. Results: At endoscopy 73 (23%) patients did not have UGT injuries, 158 (50%) patients had mild injuries eligible for nonoperative management and 84 (27%) patients had severe injuries. Nonoperative management was successful in 93% of patients with mild injuries. Surgical exploration was eventually performed in 88 (28%) patients and resection was undertaken in 76 of them. Emergency mortality was 7% and all fatalities were patients with initial severe injuries. After a median follow-up of 6 days (range = 1 day-8.5 years), functional failure was recorded in 9 (3%) patients, all of whom had initial severe injuries. Conclusion: Emergency endoscopic grading of caustic injuries is the main factor that conditions outcome after caustic ingestion. [ABSTRACT FROM AUTHOR]

The article discusses a study on the efficacy and tolerability of second-line chemotherapy with fluorouacil, leucovorin and irinotecan (FOLFIRI) regimen in patients with advanced small bowel adenocarcinoma (SBA). It notes that the patients involved in the study are those whose first-line platinum-based chemotherapy failed. Results show that the disease of half of the patients has been controlled after the second-line treatment. Consideration of other treatments is recommended as such chemotherapy only delivers median progression-free survival (PFS).

Introduction: Cancer disease inducing an acquired hypercoagulable state is a well-established feature. Venous thromboembolism (VTE) occurs in 4% to 20% of the patients and is the second cause of mortality in cancer; VTE incidence is four to six times higher in cancer patients compared to other patients. In the last 10 years, important randomised clinical trials have clearly demonstrated that long-term use of daily subcutaneous low molecular weight heparin (LMWH) is more efficient than Vitamin K antagonists to treat VTE in cancer patients. First Italian, then American and more recently French national guidelines recommend the use of LMWH for 3 to 6 months for curative treatment of VTE in cancer patients with a clearly high level (A) of evidence. Despite convincing data, many physicians have not yet modified their clinical practice, doubting the tolerability of such a long period of subcutaneous injections. In fact, LMWH long-term use appears well tolerated and may also increase cancer patient survival.Objectives: The aim of this review is to present the scientific rationale for long-term daily subcutaneous LMWH in cancer patients, and to reinforce the favourable benefit/tolerance tolerability ratio with this specific antithrombotic strategy. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 23-year-old man, non-smoking with no significant personal or familial past medical history presented an acute eruption on the face. Topics include magnetic resonance enterography after Infliximab (IFX) revealing a regression of small bowel thickening and disappearance of parietal enhancement on delayed phase; and dermatological examination revealing an itchy and very well limited erythematous papulosquamous eruption of the face and neck.

In patients with metastatic colorectal cancer (mCRC), RAS and BRAF mutations are currently determined by tumor sample analysis. Here, we report BRAF mutation status analysis in paired tumor tissue and plasma samples of mCRC patients included in the AGEO RASANC prospective cohort study. Four hundred and twenty-five patients were enrolled. Plasma samples were analyzed by next-generation sequencing (NGS). When no mutation was identified, we used two methylated specific biomarkers (digital droplet PCR) to determine the presence or absence of circulating tumor DNA (ctDNA). Patients with conclusive ctDNA results were defined as those with at least one mutation or one methylated biomarker. The kappa coefficient and accuracy were 0.79 (95% CI: 0.67–0.91) and 97.3% (95% CI: 95.2–98.6%) between the BRAF status in plasma and tissue for patients with available paired samples (n = 405), and 0.89 (95% CI: 0.80–0.99) and 98.5% (95% CI: 96.4–99.5%) for those with conclusive ctDNA (n = 323). The absence of liver metastasis was the main factor associated to inconclusive ctDNA results. In patients with liver metastasis, the kappa coefficient was 0.91 (95% CI, 0.81–1.00) and accuracy was 98.6% (95% CI, 96.5–99.6%). We demonstrate satisfying concordance between tissue and plasma BRAF mutation detection, especially in patients with liver metastasis, arguing for plasma ctDNA testing for routine BRAF mutation analysis in these patients. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 58-year old woman with hematochezia and acute anemia, who had small-bowel adenocarcinoma along with celiac disease in past.

Colorectal cancers (CRC) develop in the face of an important immune system associated with the intestinal mucosal tissue. The immune response against the tumor has been proposed to affect the prognosis of patients undergoing treatment for CRC. In this study T cells infiltrating the tumor were compared with T cells populating the unaffected neighboring mucosal tissue and cells from the peripheral blood. We observed that T cells from the tumor harbor an activated phenotype, with engagement of the NKG2D pathway in CD8 T cells. We show that mucosal and tumor-infiltrating T cells are enriched in NKG2D CD4 T cells, which exhibit cytotoxic functions. Finally, T cell populations in the tumor were modified according to its oncogenetic status, with higher percentages of CD8 T cells isolated from patients with microsatellite instable tumor status. [ABSTRACT FROM PUBLISHER]