Risk of incident cancer in patients with Inflammatory Bowel Disease with prior breast cancer: a multicenter cohort study.

BACKGROUND AND AIMS: Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD). The aim of our study was to evaluate incident cancer rate (recurrence or new-onset cancer) in a cohort of IBD patients with a history of breast cancer according to the subsequent IBD treatment provided. METHODS: A multicenter retrospective study included consecutive IBD patients with prior breast cancer. The inclusion date corresponded to the diagnosis of index malignancy. Follow-up lasted from cancer diagnosis until the occurrence of incident cancer. RESULTS: Among 207 patients included (median disease duration: 13 years [IQR 6 - 21]), first line treatment (median interval of 28 months [IQR 7 - 64]) was a conventional immunosuppressant in 19.3 % of patients, anti-TNF in 19.8 %, vedolizumab in 7.2 % and ustekinumab in 1.9 %. After a median follow-up of 71 months [IQR, 34 - 148], 42 (20%) incident cancers were observed (34 breast cancer recurrences). Adjusted incidence rates per 1000 person-years were 10.2 (95%CI 6.0- 16.4) for the untreated arm and 28.9 (95%CI 11.6-59.6) for exposed patients (p= 0.0519). There was no significant difference between treated patients and controls regarding incident-cancer free survival rates (p=0.4796). In multivariable analysis, factors associated with incident cancer were stage T4d (p=0.036), triple negative tumor (p=0.016) and follow-up of less than 71 months (p=0.005). CONCLUSION: We did not find a statistically significant increase in incident breast cancer related to IBD treatment beyond the already known poor prognostic factors of breast cancer.

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.

Assessment of long-term results of repeated dilations and impact of a scheduled program of dilations for refractory esophageal strictures: a retrospective case-control study.

INTRODUCTION: In patients with benign and refractory esophageal strictures (BES), repeating initial dilations in short intervals could be recommended, but little data are available to validate this strategy. Our aim was to evaluate long-term results of a scheduled program of repeated and sustained esophageal dilations in patients with refractory strictures. METHODS: Patients with BES requiring five or more dilations were retrospectively included and divided in two groups for analysis: a SCHEDULED group (SDG) where patients were systematically rescheduled for the 5 first dilations; ON-DEMAND group (ODG) where patients were dilated only in case of recurrence of the dysphagia. Comparison between SDG and ODG was done with a 1:1 matching analysis and etiology of stricture. Clinical success was defined as the absence of dysphagia for more than a year. RESULTS: 39 patients with refractory BES were included with post-operative stenosis in 51.2% and post-caustic injury 28.2%; 10 were in SDG and 29 in ODG. In overall analysis (39 patients), the follow-up was 64.4 ± 32 months, success rate was 79.5% and duration of treatment was 27.3 ± 20 months, and mean number of dilations was 11.7 per patient. The need for dilations decreased significantly after 18 months of treatment with an average of 0.56 dilations per semester. Self-expandable metallic stent insertion was associated with an increased rate of complications (5.9% vs 59.1% p = 0.001). In matched analysis (10 ODG vs 10 SDG patients), the duration of treatment was lower in SDG (18.8 vs 41.4 months, p = 0,032) with a higher probability of remission (survival analysis, Log-rank: p = 0,019) and the success rate did not differ between ODG and SDG patients (80% vs 90%; NS). CONCLUSION: Overall, long-term esophageal dilations resulted in a 79.5% success rate and the need for further dilatations decreased significantly in both groups after 18-month follow-up. A scheduled dilation program was associated with a higher probability of final success and lower treatment duration.

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.

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.

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.

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.

Autochthonous infections with hepatitis E virus genotype 4, France.

During January-March 2011, diagnoses of hepatitis E virus (HEV) infection increased in Marseille University hospitals in southeastern France. HEV genotype 4, which is described almost exclusively in Asia, was recovered from 2 persons who ate uncooked pork liver sausage. Genetic sequences were 96.7% identical to those recently described in swine in Europe.

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

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

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.

Clinical practice guidelines from the French National Society of Coloproctology in treating chronic constipation.

Chronic constipation is a common symptom that regularly affects the quality of life of adult patients. Its treatment is mainly based on dietary rules, laxative drugs, perineal rehabilitation and surgical treatment. The French National Society of Coloproctology offers clinical practice recommendations on the basis of the data in the current literature, including those on recently developed treatments. Most are noninvasive, and the main concepts include the following: stimulant laxatives are now considered safe drugs and can be more easily prescribed as a second-line treatment; biofeedback therapy remains the gold standard for the treatment of anorectal dyssynergia that is resistant to medical treatment; transanal irrigation is the second-line treatment of choice in patients with neurological diseases, but it may also be proposed for patients without neurological diseases; and although interferential therapy may be a new promising treatment, it needs further evaluation.

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.

Faecal incontinence: Current knowledges and perspectives.

Faecal incontinence (FI) is a disabling and frequent symptom since its prevalence can vary between 5% and 15% of the general population. It has a particular negative impact on quality of life. Many tools are currently available for the treatment of FI, from conservative measures to invasive surgical treatments. The conservative treatment may be dietetic measures, various pharmacological agents, anorectal rehabilitation, posterior tibial nerve stimulation, and transanal irrigation. If needed, patients may have miniinvasive approaches such as sacral nerve modulation or antegrade irrigation. In some cases, a surgical treatment is proposed, mainly external anal sphincter repair. Although these different therapeutic options are available, new techniques are arriving allowing new hopes for the patients. Moreover, most of them are non-invasive such as local application of an α1-adrenoceptor agonist, stem cell injections, rectal injection of botulinum toxin, acupuncture. New more invasive techniques with promising results are also coming such as anal magnetic sphincter and antropylorus transposition. This review reports the main current available treatments of FI and the developing therapeutics tools.

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.

CON-COUR study: Interferential therapy in the treatment of chronic constipation in adults: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of chronic constipation is about 15 % in Western countries with a significant impact on quality of life and health care costs. The first-line therapy, based on medical treatment combined with laxatives and dietary rules, is often disappointing. Interferential therapy is a new treatment that has demonstrated its efficiency in the treatment of chronic constipation in children and encouraging results in adults. The primary objective of this study is to assess the efficacy of interferential therapy during 8 weeks in adult patients. The secondary objectives are to assess this new and noninvasive therapy in terms of persistence of the clinical efficacy, colonic transit time, ano-rectal manometry, patient satisfaction and quality of life (QoL), and tolerance. DESIGN: multicenter, prospective, randomized, placebo-controlled, double blind, two-parallel groups study. SETTING: nine French adult gastroenterology centers. INCLUSION CRITERIA: adult patients with a history of chronic constipation refractory to medical treatment for at least 3 months. Treatment groups: (1) interferential-experimental group (effective stimulation); (2) placebo-control group (sham stimulation). RANDOMIZATION: 1:1 allocation ratio. Evaluation times: inclusion (T0, randomization), baseline assessment (T1), start of stimulation (T2), intermediary assessment (T3, 4 weeks), end of stimulation (T4, 8 weeks), follow-up (T5 and T6, 1- and 6-month). ENDPOINTS: (1) primary: short-term efficacy at T4 (treatment response defined as three or more spontaneous, complete bowel movements per week); (2) secondary: efficacy at T5 and T6, symptoms (Patient Assessment of Constipation Symptoms questionnaire), colonic transit time, anorectal manometry, patient satisfaction (analogical visual scale), patient QoL (Patient Assessment of Constipation Quality of Life Questionnaire), side/unexpected effects. SAMPLE SIZE: 200 individuals to obtain 80 % power to detect a 20 % difference in treatment response at T4 between the two groups (15 % of lost to follow-up patients expected). DISCUSSION: The randomized, double-blind, placebo-controlled design is the most appropriate to demonstrate the efficacy of a new experimental therapeutic (Evidence-Based Medicine Working Group classification). National and international recommendations could be updated based on the findings of this study. TRIAL REGISTRATION: Current controlled trials NCT02381665 (registration date: February 13, 2015).