Tofacitinib for Patients with Anti-TNF Refractory Ulcerative Proctitis: A Multicentre Cohort Study from the GETAID.

BACKGROUND: Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP. METHODS: We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year. RESULTS: All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis]. CONCLUSION: Tofacitinib may offer a therapeutic option for patients with refractory UP.

Risk of infection in elderly patients with inflammatory bowel disease under biologics: A prospective, multicenter, observational, one-year follow-up comparative study.

OBJECTIVES: The emergence of biologics has improved the course of inflammatory bowel diseases (IBD) in the elderly population despite a potential higher risk of infections. We conducted a one-year, prospective, multicenter, observational study to determine the frequency of occurrence of at least one infectious event in elderly IBD patients under anti-TNF therapy compared with that in elderly patients under vedolizumab or ustekinumab therapies. METHODS: All IBD patients over 65 years exposed to anti-TNF, vedolizumab or ustekinumab therapies were included. The primary endpoint was the prevalence of at least one infection during the whole one year follow-up. RESULTS: Among the 207 consecutive elderly IBD patients prospectively enrolled, 113 were treated with anti-TNF and 94 with vedolizumab (n=63) or ustekinumab (n=31) (median age 71 years, 112 Crohn's disease). The Charlson index was similar between patients under anti-TNF and those under vedolizumab or ustekinumab as well as the proportion of patients under combination therapy and under concomitant steroid therapy did not differ between both both groups. The prevalence of infections was similar in patients under anti-TNF and in those under vedolizumab or ustekinumab (29% versus 28%, respectively; p=0.81). There was no difference in terms of type and severity of infection and of infection-related hospitalization rate. In multivariate regression analysis, only the Charlson comorbidity index (≥ 1) was identified as a significant and independent risk factor of infection (p=0.03). CONCLUSION: Around 30 % of elderly patients with IBD under biologics experienced at least one infection during the one-year study follow-up period. The risk of occurrence of infection does not differ between anti-TNF and vedolizumab or ustekinumab therapies, and only the associated comorbidity was linked with the risk of infection.

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

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

Endoscopic treatment of nonmalignant tracheoesophageal and bronchoesophageal fistula: results and prognostic factors for its success.

BACKGROUND: Nonmalignant esophago-respiratory fistulas (ERF) are frightening clinical situations, involving surgery with high morbi-mortality rate. We described the endoscopic management of benign ERF. The aim of the study was to describe outcomes of endoscopic treatment of nonmalignant ERF and to analyze factors associated with its success. METHODS: This is a retrospective study involving patients managed for benign ERF in our center between 2012 and 2016. The ERFs were classified into three groups of sizes: (I) punctiform, (II) medium, and (III) large. The primary aim was to document the endoscopic success (= fistula's healing after 6 months). The secondary objectives were characteristics of endoscopic treatment, the functional success and death, and identifying factors associated with success and death. RESULTS: 22 patients were included. The etiologies of ERF were surgery in 12 patients, esophageal dilatation in 3, invasive ventilation in 3, radiation therapy in 2, and tracheostomy in 2. Ninety-three procedures were performed (mean of number: 4.2 ± 4.5/patient). Twenty-one patients had stent placement, eight over-the-scope clips (OTSC), and seven a combined therapy. The endoscopic success rate was 45.5% (n = 10; 67% in punctiform, 50% in medium, and 14% in large ERF), and the functional success was 55% (n = 12). Serious adverse events occurred in 9 patients (40.9%). Six patients died (27%). The persistence of the orifice after 6 months of endoscopic treatment was associated with failure (OR 44; IC95: 3.38-573.4; p = 0.004 multivariate analysis). The orifice's size was associated with mortality [71% of death if large fistulas (p = 0.001) univariate analysis]. CONCLUSION: Endoscopic treatment of ERF leads to 45.5% of successful endoscopic closure and 55.5% of functional success, depending on fistula's orifice size. After 6 months without healing, the chances for success dramatically decrease.

Esophageal Motor Disorders Are a Strong and Independant Associated Factor of Barrett's Esophagus.

BACKGROUND/AIMS: Esophageal motor disorder (EMD) has been shown to be associated with gastroesophageal reflux disease (GERD). However, the association of EMD with a Barrett's esophagus (BE) is controversial. Our objective was to evaluate whether the presence of EMD was an independent factor associated with BE. METHODS: A retrospective case-control study was conducted in GERD patients who all had oeso-gastroduodenal endoscopy and high-resolution esophageal manometry. The clinical data collected was known or potential risk factors for BE: male gender, smoking and alcohol consumption, age, body mass index, presence of hiatal hernia, frequency, and age of GERD. EMD were classified according to the Chicago classification into: ineffective motor syndrome, fragmented peristalsis and absence of peristalsis, lower esophageal sphincter hypotonia. RESULTS: Two hundred and one patients (101 in the GERD + BE group and 100 in the GERD without BE) were included. In univariate analysis, male gender, alcohol consumption, presence of hiatal hernia, and EMD appeared to be associated with the presence of BE. In a multivariate analysis, 3 independent factors were identified: the presence of EMD (odds ratio [OR], 3.99; 95% confidence interval [CI], 1.71-9.28; P = 0.001), the presence of hiatal hernia (OR, 5.60; 95% CI, 2.45-12.76; P ＜ 0.001), Helicobacter pylori infection (OR, 0.08; 95% CI, 0.01-0.84; P = 0.035). CONCLUSIONS: The presence of EMD (particularly ineffective motor syndrome and lower esophageal sphincter hypotonia) is a strong independent associated factor of BE. Searching systematically for an EMD in patients suffering from GERD could be a new strategy to organize the endoscopic follow-up.

Endoscopic treatment of fistulas after sleeve gastrectomy: a comparison of internal drainage versus closure.

BACKGROUND AND AIMS: Fistulas after sleeve gastrectomy are major adverse events of bariatric surgery. The endoscopic management strategy evolved from closure to internal drainage after 2013. The main objective of our study was to evaluate and compare these different approaches. METHODS: This retrospective study included all patients treated for fistulas after sleeve gastrectomy in a referral center. Closure management was defined as initial treatment that used a covered metal stent and/or endoclips. Internal drainage management was defined as initial treatment by nasocystic drain and/or a double-pigtail stent. RESULTS: A total of 100 patients (women N = 78, mean [± standard deviation {SD}] age 42 ± 12 years) were included between 2007 and 2015. The mean (± SD) delay between sleeve gastrectomy and the first endoscopy was 82 ± 125 days. The overall success of endoscopic treatment was 86% within 6 ± 27 months. Two patients died. The primary success of internal drainage and closure management occurred in 19 of 22 (86%) and 49 of 77 (63%) patients, respectively. Among patients in failure for closure management, 22 had secondary internal drainage (18 being successful). Success of initial management was significantly higher for internal drainage (P = .043). Factors associated with failure of closure management were in multivariable analysis: collection >5 cm (P = .013). Factors associated with a time >6 months for achieving leakage closure were in multivariable analysis: reoperation before endoscopy (P = .044) and purulent flow at endoscopy (P = .043). CONCLUSIONS: Endoscopic management of fistulas after sleeve gastrectomy was successful in 86% of cases. In cases of collections >5 cm, internal drainage should be proposed first. Surgical reintervention before endoscopy delays treatment success.

Prevalence of Fecal Incontinence in Adults with Cystic Fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) are deemed at risk of developing urinary incontinence (UI) due to repeated coughing and other factors causing increased pressure on the pelvic floor. Fecal incontinence (FI) is probably derived from the same mechanism, but only very few data are available on its frequency. AIMS: The aim of this study was to determine the prevalence of FI in an adult population with CF. METHODS: This retrospective study was conducted from January 2012 to June 2014. Patients were recruited from Marseille referral center for adult CF. They were asked to fill in a self-completed anonymous questionnaire for symptom assessment of UI and FI. Clinical data and a detailed history of CF were also recorded. RESULTS: A total of 155 out of 190 patients (92 females) of mean age 30.5 ± 11 years completed the survey. Seventy-three patients (47%) were lung transplanted. Forty patients (25.8%) reported FI with a mean St Mark's score of 4.9 ± 2. Thirty-five patients (22.6%) reported UI. Eighteen patients (11.6%) reported both FI and UI. FI was significantly more frequent in older patients (34.27 vs. 29.54 years, p = 0.03) and in patients with associated UI (p = 0.001). No relationship was found between respiratory, bacterial, nutritional status, transplantation, pancreatic status, practice of physiotherapy, delivery history, and FI. CONCLUSIONS: The high prevalence of FI in CF and its negative impacts need to integrate this symptom in the overall treatment of this pathology. The systematic early detection of FI may allow its rapid management and limit their consequences.

An Involuntary and Unexpected Treatment of Nutcracker Esophagus.

A 76-year-old woman complained of painful dysphagia and loss of weight. Esophagoscopy results were negative, whereas computed tomography (CT) disclosed a 25-mm mediastinal tumor without a connection to the esophagus. A diagnosis of nutcracker esophagus was made on high-resolution esophageal manometry. Peroral endoscopic esophageal myotomy failed to improve the symptoms. Right video thoracoscopy allowed resection of the tumor, which looked like a neurogenic tumor of the posterior mediastinum that developed from the right vagus nerve. The patient's dysphagia dramatically improved postoperatively. Because the pathologic examination disclosed a benign solitary fibrous tumor of the pleura, we hypothesize that the motility disorder would have been resolved by the unilateral vagotomy.

Gastric per-oral endoscopic myotomy with antropyloromyotomy in the treatment of refractory gastroparesis: clinical experience with follow-up and scintigraphic evaluation (with video).

BACKGROUND AND AIMS: Gastroparesis is a chronic, debilitating condition. We report an experience conducting gastric per-oral endoscopic pyloromyotomy (G-POEM) with objectives to assess clinical efficacy, gastric emptying evolution, and procedural adverse events. METHODS: This was a clinical pilot series on 12 consecutive patients who underwent G-POEM for refractory gastroparesis in our tertiary center between February 2014 and August 2015. Patients included had severe disease as defined by elevated Gastroparesis Cardinal Symptoms Index (GCSI) score and delayed gastric emptying scintigraphy (GES). G-POEM was performed by mucosal incision upstream the pylorus followed by submucosal tunnel and antropyloromyotomy with subsequent access closure. Efficacy was assessed at 5 days, 1 month, and 3 months, based on GCSI score, and individualizing (Likert scale) the main symptoms (nausea, vomiting, abdominal pain, early satiety, and anorexia). GES was performed 2 months after the procedure. RESULTS: G-POEM was successfully performed in all 12 patients, yielding a technical success rate of 100%. Significant improvements in GCSI were observed: 3.5 ± .8 versus .9 ± .9 (1 month) and 1.1 ± 1.5 (3 months), respectively (P < .001), as well as the severity of main symptoms at 3 months. Clinical efficacy was 85% (10/12). GES normalized in 75% of cases, with improvement of half emptying time (222 ± 90 minutes vs 133 ± 90 minutes; P = .03) and retention at 2 hours (76% ± 20% vs 44% ± 26%; P = .009). There were no adverse events related to the procedure. CONCLUSION: We report a single-center study evaluating G-POEM for refractory gastroparesis, demonstrating its feasibility, reproducibility, and safety with promising clinical and scintigraphic efficacy.

Complications of submucosal endoscopy.

Submucosal endoscopy essentially regroups peroral endoscopic esophageal myotomy (POEM) and, more recently, pyloromyotomy and tunnel tumor resections. The complication rate of POEM is between 5% and 10%. Complications include gas-related complications, mucosal tears, and bleeding, and are usually managed conservatively or with non-surgical procedures. Only one case of death has been reported. The most commonly identified risk factors for complicated procedures in POEM are short experience with the technique and sigmoid-type esophagus. The rate of gastro-esophageal reflux (GERD) is between 10% and 30% depending on the definitions, with a good clinical response to proton pump inhibitors. For the techniques other than POEM, the number of cases reported is too small to allow identification of the complications, which, in addition, probably vary depending on the organ involved. The management of gas-related complications is conservative and sometimes requiring percutaneous exsufflation (capnoperitoneum) or drainage. The endoscopic management of mucosal tears essentially involves clip placement and, in case of bleeding, the usual hemostasis techniques including stent placement. Importantly, following a rigorous and appropriate learning program is essential to minimize the risk of complications, particularly for specialists with a short experience in the technique.