Intrarectal injections of botulinum toxin versus placebo for the treatment of urge faecal incontinence in adults (FI-Toxin): a double-blind, multicentre, randomised, controlled phase 3 study.

BACKGROUND: Non-randomised studies assessing intrarectal botulinum toxin type A (BoNTA) injections for faecal incontinence are promising. We aimed to evaluate the efficacy of BoNTA for the treatment of faecal incontinence in a randomised study. METHODS: In this randomised, double-blind, placebo-controlled study, we included adult patients who had at least one urgency or faecal incontinence episode per week for at least 3 months and who had experienced a failure of conservative or surgical treatment from eight French specialist hospital units with the skills to manage patients with faecal incontinence. Patients were randomly assigned (1:1) by a central web form to receive intrarectal submucosal injections of either 200 units of BoNTA (Botox; Allergan, Irvine, CA, USA; BoNTA group) or an equivalent volume of saline (placebo group), stratified by Cleveland Clinic Severity scores (CCS score; ≥12 or <12). Patients, investigators, study site staff, and sponsor personnel were masked to treatment allocation up to the 6-month visit. The primary endpoint was the number of episodes of faecal incontinence and urgency per day assessed using 21-day patient bowel diaries 3 months after the treatment. The primary analysis was performed using a modified intention-to-treat (mITT) approach (ie, in all the randomised patients who had received a treatment) with adjustment for baseline faecal incontinence and urgency episodes. After the final data collection at 6 months after injections, patients were unmasked and offered the BoNTA treatment if they were in the placebo group (rescue therapy) without masking, with an additional 6 months of safety follow-up. This trial is registered with ClinicalTrials.gov, number NCT02414425. FINDINGS: Between Nov 25, 2015, and Nov 25, 2020, we randomly assigned 200 patients to receive either BoNTA (n=100) or placebo (n=100) injections. Due to withdrawals before the injections, 96 patients were included in the BoNTA group and 95 patients were included in the placebo group (mITT analysis). The mean number of faecal incontinence and urgency episodes per day in the BoNTA group decreased from 1·9 (SD 2·2) at baseline to 0·8 (1·8) at 3 months after the injections, and from 1·4 (1·1) to 1·0 (1·0) in the placebo group, with a baseline-adjusted mean group difference at 3 months estimated at -0·51 (95% CI -0·80 to -0·21, p=0·0008). No serious treatment-related adverse events were reported in the trial. The most frequently reported non-serious adverse event (treatment related or not) following the BoNTA or placebo injections was constipation (reported in 68 [40%] of 169 patients who received the BoNTA injections and 38 [40%] of 95 patients who received placebo injections). INTERPRETATION: BoNTA injections are an efficacious treatment for urge faecal incontinence. Further research will define the optimum selection criteria, dose, site of injection, re-injection frequency, and long-term results. FUNDING: General Direction of Healthcare (French Ministry of Health).

Allogenic stem cells for Crohn's anal fistulas: Treating early improves the deep remission rate.

AIM: The aim of this study was to evaluate the real-life clinical and radiological efficacy of darvadstrocel injection into complex perianal fistulas in Crohn's disease. Secondary endpoints were to assess symptomatic efficacy, adverse effects and factors associated with complete combined clinical-radiological response (deep remission). METHODS: After marketing the product in France, all first patients treated consecutively were included. A complete clinical response was defined by a complete closure of all external openings with no discharge on pressure. A complete radiological response (MRI), evaluated at least after six months of follow-up, was defined by a completely fibrotic sequela without abscess. A deep remission was defined as the association of a complete clinical response with a complete radiological response. RESULTS: A total of 43 patients were included (M/F: 22/21, median age 37 [26-45] years). The fistulas were already drained with seton(s) and were on biologic treatment. After a median follow-up of 383 (359-505) days, 28 (65%) patients showed a clinical response (22 complete and 6 partial) and 16 (37%) achieved a deep remission. The Perineal Disease Activity Index decreased significantly after treatment: 39 (91%) patients reported symptomatic improvement in terms of discharge, pain, and induration, and 28 (65%) no longer had any perineal symptoms. No severe adverse events were reported. A short history of Crohn's disease <3 years was significantly associated with deep remission (OD 4.5 [1.0-19.1], p = 0.04). CONCLUSION: Darvadstrocel injection resulted in a clinical response for two thirds of patients and deep remission for one third. A shorter duration of Crohn's disease was associated with deep remission.

Region-specific remodeling of the enteric nervous system and enteroendocrine cells in the colon of spinal cord injury patients.

Patients with spinal cord injury (SCI) suffer from major bowel dysfunction, whose exact pathophysiology, particularly the involvement of the enteric nervous system or epithelial dysfunction is poorly understood. Herein, we aimed to characterize the mucosal biopsies of the right and left colon in SCI patients vs controls (CT): (1) remodeling of key enteric neurotransmitters, (2) remodeling of enteroendocrine cells, and (3) mucosal inflammation compared to those in controls. In SCI, mucosal ACh concentration was lower in the right colon as compared to CT, but no change was observed in the left colon, and AChE expression was lower in both the right and left colons than in CT. While the VIP concentration was similar in the right and left colons, VIP mRNA expression was increased in the right colon and decreased in the left colon, in SCI patients as compared to CT. Interestingly, 5-HT concentration was reduced in the left colon but not in the right colon in SCI patients. Moreover, in SCI patients, as compared to CT, SERT mRNA expression was selectively increased in the left colon while TPH1 mRNA expression was increased in the right and left colons. Although mucosal TNFα and IL-1ß mRNA expression did not significantly differ between SCI and CT groups, we identified a significant positive correlation between TNFα and IL-1ß mRNA expression and left colon transit time in the SCI group. In conclusion, region-specific changes occur in the enteric neurotransmitter, serotonergic, and inflammatory pathways in the colon of SCI patients. The significant correlations between these pathways and clinical parameters in the left colon further set a scientific basis for designing therapeutic targets to improve colonic motor dysfunction in patients.Biobank information: Spinal cord injury patients: PHRC ConstiCAPE-clinical trial NCT02566746. Controls: Anosain-clinical trial NCT03054415 and biobank of the "Institut des Maladies de l'Appareil Digestif (IMAD)" registered under number DC-2008-402.

Evaluation of a scoring system for the detection of central sensitization among women with chronic pelvic pain.

BACKGROUND: Central sensitization is frequently associated with chronic pelvic pain and requires specific management. The pain is described as hypersensitivity to an innocuous stimulus that is both widespread and persistent. However, no study has evaluated if central sensitization can be measured objectively with neurophysiological tests in the pelvic and perineal area to prove this concept in women with chronic pelvic pain. OBJECTIVE: This study aimed to evaluate nociceptive thresholds (primary objective) and spatial and temporal diffusion of pain among women with chronic pelvic pain and high or low scores of central sensitization. STUDY DESIGN: This prospective, assessor-blinded, comparative study compared a cohort of women with chronic pelvic pain and a high (>5/10; n=29) vs low (<5/10; n=24) score of sensitization according to the Convergences PP criteria. Participants underwent a noninvasive bladder sensory test, a rectal barostat test, and a muscular (algometer) and a vulvar (vulvagesiometer) sensory test. Poststimulation pain (minutes), quality of life (Medical Outcomes Study 36-Item Short Form Survey), and psychological state, comprising anxiety (State-Trait Anxiety Inventory), depression (Beck Depression Inventory Short Form), and catastrophizing (Pain Catastrophizing Scale), were assessed. RESULTS: The participants mostly suffered from endometriosis (35.8%), irritable bowel syndrome (35.8%), bladder pain syndrome (32.1%), and vestibulodynia (28.3%). Baseline characteristics were similar. Women with a high sensitization score had more painful diseases diagnosed (2.7±1.3 vs 1.6±0.8; P=.002) and suffered for longer (11±8 vs 6±5 years; P=.028) than participants with a low score. The bladder maximum capacity was equivalent between participants (399±168 vs 465±164 mL; P=.18). However, the pain felt at each cystometric threshold was significantly increased in women with a high sensitization score. No difference was identified for the rectal pain pressure step (29.3±5.5 vs 30.7±6.5 mm Hg; P=.38). Rectal compliance was decreased in women with a high sensitization score with a considerable increase in pain felt. The average of pain pressure thresholds at the 5 vulvar sites tested was decreased in these participants (162.5±90.5 vs 358.7±196.5 g; P=.0003). Similar results were found for the average of the pain pressure thresholds at 6 muscles tested (1.34±0.41 vs 2.63±1.52 kg/m2; P=.0002). A longer period was needed for patients with high sensitization score to obtain a VAS <3 out of 10 after the stimulation of the bladder (4.52±5.26 vs 1.27±2.96 minutes; P=.01), the rectum (3.75±3.81 vs 1.19±1.23 minutes; P=.009), and the muscles (1.46±1.69 vs 0.64±0.40 minutes; P=.002). The psychological state was equivalent between groups. No association was found between the sensory thresholds and the psychological state results. The physical component of the quality of life score was reduced in women with high sensitization score (P=.0005), with no difference in the mental component. CONCLUSION: Using neurophysiological tests, this study showed that there are objective elements to assess for the presence of central sensitization, independently of psychological factors.

Interferential therapy for chronic constipation in adults: The CON-COUR randomizedcontrolled trial.

BACKGROUND: Chronic constipation (CC) is a frequent condition, and the first-line treatment includes dietary rules, the use of laxatives, and biofeedback for evacuation disorders. However, almost half of the patients are dissatisfied with their current treatment. We report the first double-blind randomized multicenter trial assessing the effectiveness of transabdominal electrical stimulation by interferential therapy (IFT) in the treatment of CC in adults. METHODS: A prospective, multicenter, randomized, double-blind, sham-controlled, parallel-group, phase 3 trial was conducted at 7 centers in France. The primary endpoint was 8-week efficacy as defined by the number of complete spontaneous bowel movements during the last 4 weeks of the 8-week stimulation period. Secondary endpoints included the evaluation of the effects of IFT on symptoms (Patient Assessment of Constipation Symptoms questionnair (PAC-SYM)), quality of life (QOL) (Patient Assessment of Constipation Quality of Life), Colonic transit time (CTT), anorectal manometry, and patient satisfaction. RESULTS: The proportion of 8-week responders was not significantly different between the two groups (73.2% in the IFT group vs. 67.1% in the sham group). After 8 weeks of stimulation, the mean overall PAC-SYM score and the mean reduction in the overall PAC-SYM score were significantly greater in the IFT group than in the sham group. No differences were observed concerning CTT, anorectal manometry, or patient satisfaction. CONCLUSIONS: Although the primary endpoint was not reached, IFT can significantly alleviate the symptoms and improve the QOL of CC patients. It can be assumed that new treatments require different modes of evaluation and that the assessment of patient-reported outcomes may become a priority among therapeutic targets of CC. Trial registration number NCT02381665.

Risk factors for upper urinary tract deterioration in adult patients with spina bifida.

PURPOSE: Neurogenic bladder associated with spina bifida disease remains a major cause for mortality or morbidity due to kidney damages. However, we currently do not know which urodynamic findings are associated with an higher risk of upper tract damages in spina bifida patients. The objective of the present study was to evaluate urodynamic findings associated with functional kidney failure and/or with morphological kidney damages. METHODS: A large single-center restrospective study was conducted in our national referral center for spina bifida patients using our patients' files. All urodynamics curves were assessed by the same examinator. Functional and/or morphological evaluation of the upper urinary tract were done at the same moment as the urodynamic exam (between 1 week before and 1 month after). Kidney function was assessed using creatinine serum levels or 24 h urinary creatinine levels (creatinine clearance) for walking patients, or with the 24 h urinary creatinine level for wheelchair-users. RESULTS: We included 262 spina bifida patients in this study. Fifty-five patients had a poor bladder compliance (21.4%) and 88 of them had detrusor overactivity (33.6%). Twenty patients had a stage 2 kidney failure (eGFR < 60 ml/min) and 81 patients out of 254 (30.9%) had an abnormal morphological examination. There were three urodynamic findings significantly associated with UUTD: bladder compliance (OR = 0.18; p = 0.007), Pdetmax (OR = 14.7; p = 0.003) and detrusor overactivity (OR = 1.84; p = 0.03). CONCLUSION: In this large series of spina bifida patients, maximum detrusor pressure and bladder compliance are the main urodynamic findings determinants of UUTD risk.

Transanal irrigation is a better choice for bowel dysfunction in adults with Spina bifida: A randomised controlled trial.

AIM: To compare transanal irrigation with conservative bowel management for the treatment of bowel dysfunction in Spina bifida (SB) patients. METHODS: Patients with SB and bowel dysfunction were randomly assigned to receive either transanal irrigation or conservative bowel management. The effectiveness of the treatment was defined as a decrease of 4 points in the neurogenic bowel dysfunction (NBD) score at week 10. Data on incontinence (Cleveland scores; Jorge-Wexner [JW]) and constipation (Knowles-Eccersley-Scott Symptom Constipation Score [KESS]) were recorded at 10 and 24 weeks after inclusion. Data were analysed on an intention-to-treat basis. RESULTS: A total of 34 patients were randomised: 16 patients to conservative bowel management and 18 patients to transanal irrigation. A total of 19/31 (61%) patients improved at week 10, 13 (76%) in the transanal irrigation group versus six (43%) in the conservative group (p = 0.056). In the irrigation group, the decrease in NBD score was -6.9 (-9.9 to -4.02) versus -1.9 (-6.5 to -2.8) in the conservative group (p = 0.049 in univariate and p = 0.004 in multivariate analysis). The NBD, Cleveland (JW and KESS) and Rosenberg scores were significantly lower in the transanal irrigation group than in the conservative bowel management group at week 10. CONCLUSIONS: This prospective, randomised, controlled, multicentre study in adult patients with SB suggests that transanal irrigation may be more effective than conservative bowel management.

Peroral endoscopic myotomy: is it better to perform it in naive patients or as second-line therapy? Results of an open-label-controlled study in 105 patients.

BACKGROUND: Whether Peroral Endoscopic Myotomy (POEM) can be proposed as a second-line treatment in patients with achalasia remains to be confirmed in real-life series. OBJECTIVE: This study aimed to compare the efficacy, feasibility and safety of POEM between treatment-naïve patients and patients who had prior endoscopic or surgical therapies for achalasia. METHODS: All consecutive patients who underwent a POEM procedure for achalasia in our centre from June 2015 to September 2018 were included in this retrospective study. They were classified into treatment-naïve patients (POEM1) and patients who had at least one previous endoscopic and/or surgical treatment for achalasia (POEM2). RESULTS: A total of 105 patients were included, 52 in the POEM1 group and 53 in the POEM2 group. Clinical success (defined as an Eckardt score ≤ 3) at 6 months was observed in 93% of POEM1 patients and 84% of POEM2 patients (p = 0.18). Technical success rate was not significantly different between the two groups (100% vs 96%, respectively; p = 0.50). No significant difference was noted in terms of adverse event rate (19% vs 19%, respectively; p = 1.00). Post-procedure pain occurred in 12% of treatment-naive and 9% of non-naïve patients (p = 0.76). The median length of hospital stay was 3 days in both groups (p = 0.17). Symptomatic gastroesophageal reflux occurred in 25% of POEM1 patients and 16% of POEM2 patients (p = 0.24). CONCLUSION: Efficacy, feasibility and safety of POEM are not different between treatment-naïve and non-naïve patients. POEM is a valuable second-line approach in patients with persistent symptoms of achalasia after surgical or endoscopic treatments.

High proficiency of esophageal endoscopic submucosal dissection with a "tunnel + clip traction" strategy: a large French multicentric study.

BACKGROUND: Esophageal endoscopic submucosal dissection (ESD) is the gold standard for the treatment of precancerous lesions or superficial esophageal cancers. This procedure is currently performed by expert endoscopists only, and poorly standardized. We aimed to assess the technical results and outcomes of a "tunnel + clip" strategy for esophageal ESD procedures performed by less experienced operators for the treatment of superficial neoplasms. METHODS: All consecutive esophageal ESDs performed with the "tunnel + clip" technique for patients with early esophageal cancer in 3 centers were enrolled. Procedural characteristics, clinical outcomes, and complications were recorded. RESULTS: Among 195 esophageal ESD procedures performed, early adenocarcinomas or high-grade dysplasia complicating Barrett's esophagus were predominant (132/195, 67.7%) compared with early squamous cell carcinomas (63/195, 32.3%). The en bloc, R0 and curative resection rates were 100% (195/195), 78.5% (153/195) and 67.2% (131/195), respectively. The mean rate of ESD was 29.7 mm2/min. One (0.5%) perprocedural perforation and 7 (3.6%) postprocedural bleedings occurred, all managed endoscopically. No delayed perforation occurred. Overall, 31 patients (31/195; 15.9%) of patients developed stenosis. CONCLUSIONS: The "tunnel + clip" strategy is safe, and allows to achieve high en bloc, R0 and curative resection rates. This standardized procedure could be used by physicians with little experience and might help spreading esophageal ESD in Western countries.

Prevalence and risk factors for scoliosis in adults with closed and open spina bifida: A large, cross-sectional study.

BACKGROUND: Scoliosis develops in a proportion of children with myelomeningocele; however, little is known about scoliosis in adulthood and in other forms of spina bifida (SB). OBJECTIVES: The aims of this study were to describe the prevalence of scoliosis and identify risk factors for its development in a large cohort of adults with open and closed SB. METHODS: This was a cross-sectional study of data from 580 adults with SB attending their first consultation at a French multidisciplinary referral centre for SB. Sex, anatomical location and type of SB (open or closed), neurological level, back pain and ambulatory status (new Functional Ambulation Classification [new FAC]) were compared in adults with and without scoliosis. These characteristics were used to determine scoliosis risk factors. RESULTS: In total, 331 adults fulfilled the inclusion criteria: 221 had open and 110 had closed SB. Of these, 176 (53%) had scoliosis: 57% open and 45% closed SB. As compared with individuals without scoliosis, those with scoliosis more frequently had open SB (p=0.03), more cranially located SB (p<0.0001), more severe neurological deficits (p≤0.02) and poorer walking ability (mean new FAC score 3.5 [SD 3.3] vs 6.1 [2.6], [p<0.0001]). In total, 69% had chronic back pain, with no difference in frequency between those with and without scoliosis. The odds of scoliosis was associated with asymmetrical motor level and a new FAC score <4 (odds ratio 0.46, p<0.006, and 0.75, p<0.0001, respectively). CONCLUSION: About half of adults with open and closed SB had scoliosis. Back pain was frequent in those both with and without scoliosis. Individuals with low walking ability and an asymmetrical motor level should be monitored early and continuously to limit the consequences of scoliosis during their lifetime. A major issue is to determine how scoliosis evolves and to determine appropriate monitoring and treatment strategies for individuals at risk.

Identification of the optimal medical and surgical management for patients with perianal fistulising Crohn's disease.

AIM: The aim of our study was to assess the best medical and surgical approaches for perianal Crohn's disease (PCD) in order to identify an optimal combined medical and surgical treatment. METHODS: Medical records of all patients with PCD treated with TNFα antagonists in two referral centres between 1998 and 2018 were reviewed. Predictors of long-term outcomes were identified using a Cox proportional hazard model. RESULTS: A total of 200 patients were included. Fifty-three patients (26.5%) were treated with adalimumab and 147 (73.5%) with infliximab. A combination of TNFα antagonist with an immunosuppressant and the presence of proctitis were independently associated with fistula closure. Seton was placed in 127 patients (63.5%) before starting biological therapy. Eighty patients (40%) underwent additional perineal surgery. Prior PCD surgery, seton positioning, additional perineal surgery, and additional surgery within 52 weeks of anti-TNFα treatment were associated with an increased rate of fistula closure. Finally, medical combination therapy (anti-TNFα plus immunosuppressant) along with seton placement and additional surgery within 1 year was the best management for PCD patients (p = 0.02). CONCLUSION: Combined medical and surgical management is required for the treatment of PCD patients. Medical combination therapy associated with seton placement and additional surgery within 1 year is the best management for PCD patients.

Prospective and multicentre study of radiofrequency treatment in anal fistula.

BACKGROUND: The most effective treatment for anal fistula is fistulotomy, but it involves a risk of anal incontinence. To reduce this morbidity, sphincter-sparing treatments have been developed, but their success in real life is often less than 50%. The aim is to determine the clinical healing rate 6 months after radiofrequency treatment. METHODS: We planned to evaluate 50 patients from three French proctology centres. Treatment efficacy was evaluated at 6 and 12 months by means of clinical and magnetic resonance imaging examination. We evaluated morbidity and healing prognostic factors. RESULTS: Fifty patients with a mean age of 51 years (22-82) were included. Eleven patients had a low trans-sphincteric fistula (LTS), 21 patients had a high trans-sphincteric fistula (HTS), eight had a complex fistula and nine had Crohn's disease fistula. After 6 months, 17 patients (34.7%) had a clinically healed fistula, including five (45.5%) with LTS fistula, seven (33.3%) with HTS fistula, one (12.5%) with complex fistula, four (44.4%) with Crohn's disease, with no significant difference between these fistula types (p: 0.142). At 12 months, the healing rate was identical. MRI in 15 out of 17 clinically healed patients showed a deep remission of 73.3% at 12 months. Energy power was associated with the success of the treatment. There was an 8.2% incidence of post-surgical complications with 4.1% being abscesses (one required surgical management). Postoperative pain was minor. No new cases or deterioration of continence have been shown. CONCLUSION: Radiofrequency is effective in 34.7% of the cases as an anal fistula treatment in this first prospective study, with low morbidity and no effect on continence. Clinical healing was deep (MRI) in three-quarters at 1 year. The increase in energy power during the procedure seems to be a key point to be analysed to optimise results.

Impact of antibiotic prophylaxis and conditioning modalities in per-oral endoscopic myotomy for esophageal motor disorders.

BACKGROUND AND AIMS: No recommendation regarding antibiotic prophylaxis and preparation modalities are available for patients with esophageal motor disorders who benefit from Per-Oral Endoscopic Myotomy (POEM). The aim of our study was to evaluate their impact on the POEM's safety. PATIENTS AND METHODS: This study was a comparative and multicentric retrospective analysis of a database prospectively collected. Patients over 18 years old with esophageal motor disorders confirmed by prior manometry, who underwent POEM were included. The primary endpoint was the occurrence of adverse events, as classified by Cotton, based on whether or not antibiotic prophylaxis was administered. RESULTS: A total of 226 patients (median age 52.9 ± 19.12 years [18-105], 116 women [51.3%]) were included. The indication for POEM was mainly type 2 achalasia (n = 135, 60.3%). Antibiotic prophylaxis was administered to 170 patients (75.2%) during 3.93 ± 3.46 days [1-21]. The overall adverse events rate was 9.3% (n = 21). Antibiotic prophylaxis was associated with the occurrence of adverse events (p = .003), but had no impact on their severity (p = .238). Antibiotic prophylaxis didn't influence the effectiveness of POEM (1 [0-4] vs 1 [0-9], p = .231). The use of a liquid diet in the 48 h prior to the procedure was significantly associated with a lower adverse events rate (3.1% vs 6.19%, p = .0002). CONCLUSION: The antibiotic prophylaxis during POEM does not prevent adverse events, had no impact on their severity and the efficacy of the procedure. A liquid diet before the procedure should be systematically proposed.

Long-term outcomes and predictors of disabling disease in a population-based cohort of patients with incident Crohn's disease diagnosed between 1994 and 1997.

BACKGROUND: The identification of early prognostic factors during Crohn's disease (CD) remains needed for physician decision-making to minimize structural bowel damage, which this study aimed to assess in a population-based setting. METHODS: All incident cases of CD were prospectively registered from 1994 to 1997 in Brittany, a limited area of France. All charts of patients were reviewed from the diagnosis to the last clinic visit in 2015. Disabling CD course was defined according to the Saint-Antoine criteria. RESULTS: Among the 331 incident cases of CD, 272 (82%) were followed-up for a median time of 12.8 years. The cumulative probability of developing stricturing or fistulizing CD was 66% at 15 years, and 107 (39%) patients underwent surgery. The cumulative probabilities of immunosuppressant and TNF antagonist use at 15 years were 37% and 22%, respectively. The cumulative risks for disabling disease and bowel damage were 74% and 71% at 15 years, respectively. Systemic symptoms and perianal lesions at diagnosis were independently associated with a disabling disease course. Perianal disease and short disease extension were associated with the onset of bowel damage. Deep ulcers was not predictive of any outcome. CONCLUSIONS: A disabling disease course and bowel damage occurred early in the course of CD, which suggests the need for early diagnosis and early treatment, particularly for patients with systematic symptoms and perianal disease.

Ano-rectovaginal fistula after obstetrical anal sphincter injury: Diverting stoma does not improve the surgical results.

AIM: Ano-rectovaginal fistulas (ARVF) are challenging for the surgeon. Most of the series mix aetiologies, leading to confusion with respect to the conclusion. The aim of this study was to assess the factors associated with the success of ARVF management following obstetrical anal sphincter injury (OASIS). METHODS: This retrospective multicentric study included all the patients undergoing surgery for ARVF identified by the hospital codes. Patients for whom the aetiology of ARVF was not OASIS were excluded. The major outcome measure was the success of the procedure. RESULTS: Sixty patients with treated ARVF due to OASIS were identified. The success of overall management was 91.7%. Female patients underwent a mean of 2.5 (±1.7) procedures. A diverting stoma was formed in 29 patients (48.3%) of which 26 were closed at the end of the management period (89.7%). Of the 148 surgical procedures, only 55 were successful (37.2%). The order of the procedures (OR = 1.38; 95% CI: 0.75-2.51) or the diverting stoma (OR = 1.46; 95% CI: 0.31-6.91) were not significantly associated with the success of the surgery. However, Martius flap (OR = 4.13; 95% CI: 1.1-15.54) and Musset procedures (OR = 5.79; 95% CI: 1.77-18.87) produced better results than the endorectal advancement flap (ERAF). The other procedures did not show a significant correlation with management success. CONCLUSION: A diverting stoma is not mandatory in the management of ARVF due to OASIS to improve the success of the surgical procedure. While the Martius flap procedure offers better results, the ERAF procedure may be preferred as a primary intervention in the absence of sphincter injury as it is less invasive. In cases of residual sphincter injury, the Musset procedure is most likely to be the best option.

Altered epithelial barrier functions in the colon of patients with spina bifida.

Our objectives were to better characterize the colorectal function of patients with Spina Bifida (SB). Patients with SB and healthy volunteers (HVs) completed prospectively a standardized questionnaire, clinical evaluation, rectal barostat, colonoscopy with biopsies and faecal collection. The data from 36 adults with SB (age: 38.8 [34.1-47.2]) were compared with those of 16 HVs (age: 39.0 [31.0-46.5]). Compared to HVs, rectal compliance was lower in patients with SB (p = 0.01), whereas rectal tone was higher (p = 0.0015). Ex vivo paracellular permeability was increased in patients with SB (p = 0.0008) and inversely correlated with rectal compliance (r = - 0.563, p = 0.002). The expression of key tight junction proteins and inflammatory markers was comparable between SB and HVs, except for an increase in Claudin-1 immunoreactivity (p = 0.04) in SB compared to HVs. TGFß1 and GDNF mRNAs were expressed at higher levels in patients with SB (p = 0.02 and p = 0.008). The levels of acetate, propionate and butyrate in faecal samples were reduced (p = 0.04, p = 0.01, and p = 0.02, respectively). Our findings provide evidence that anorectal and epithelial functions are altered in patients with SB. The alterations in these key functions might represent new therapeutic targets, in particular using microbiota-derived approaches.Clinical Trials: NCT02440984 and NCT03054415.

Ten-year Evaluation of a Large Retrospective Cohort Treated by Sacral Nerve Modulation for Fecal Incontinence: Results of a French Multicenter Study.

OBJECTIVE: The aim of this study was to assess the effectiveness of sacral nerve modulation (SNM) in a large cohort of patients implanted for at least 10 years, quantify adverse event rates, and identify predictive factors of long-term success. SUMMARY BACKGROUND DATA: Few studies have evaluated the long-term success of SNM. METHODS: Data collected prospectively from patients implanted for fecal incontinence (FI) in 7 French centers between January 1998 and December 2008 were retrospectively analyzed. Patient FI severity scores were assessed before and 10 years after implantation. The main evaluation criterion was the success of SNM defined by the continuation of the treatment without additional therapies. The secondary evaluation criteria were the rate of device revisions and explantations. Preoperative predictors of success at 10 years were sought. RESULTS: Of the 360 patients (27 males, mean age: 59 ± 12 years) implanted for FI, 162 (45%) had a favorable outcome 10 years post-implantation, 115 (31.9%) failed, and 83 (23.1%) were lost to follow-up. The favorable outcome derived from the time-to-event Kaplan-Meier curve at 10 years was 0.64 (95% CI 0.58-0.69). FI severity scores were significantly better 10 years post-implantation compared to preimplantation (7.4 ± 4.3 vs 14.0 ± 3.2; P < 0.0001). During the 10-year follow-up, 233 patients (64.7%) had a surgical revision and 94 (26.1%) were explanted. A history of surgery for FI and sex (male) were associated with an increased risk of an unfavorable outcome. CONCLUSIONS: Long-term efficacy was maintained in approximately half of the FI patients treated by SNM at least 10 years post-implantation.

Surgical closure, mainly with glue injection and anti-tumour necrosis factor α, in fistulizing perianal Crohn's disease: A multicentre randomized controlled trial.

AIM: In patients with fistulizing perianal Crohn's disease (CD), the need for a secondary surgical step is not defined. The aim was to assess the efficacy of surgical closure compared to a single seton removal in patients with drained fistulizing perianal CD treated with adalimumab. METHODS: This was a multicentre, randomized controlled trial, comparing seton removal + surgical closure (closure group) to seton removal alone (control group) with a stratification according to the American Gastroenterological Association classification. The primary end-point was fistula closure at month 12 defined by the association of the following criteria: no seton, absence of a visible external opening, absence of discharge from the tract after finger compression, absence of an internal opening, absence of perianal pain/abscess and absence of fistula-related abnormalities. RESULTS: Among the 64 included patients (262 expected) (48 complex fistula, 75%), 33 were randomized to the closure group and 31 to the control group. In the closure group, 26 patients (78.8%) had glue. At month 12, overall fistula closure was achieved in 35 of the evaluable 58 patients (60%): 18/32 (56%) in the surgery group and 17/26 (65%) in the control group (P = 0.479). In the closure group, fistula closure was observed in 13/25 (52%) and 5/7 (71%) patients with complex and simple fistula respectively (P = 0.426), compared with 12/18 (67%) and 5/8 (63%), respectively in the control group (P = 1.000). CONCLUSIONS: Seton removal alone seems to be no more effective than a secondary surgical step (in particular glue injection) in patients having fistulizing perianal CD controlled by an initial drainage combined with adalimumab. The results should be interpreted with caution.

Natural History of Perianal Crohn's Disease: Long-term Follow-up of a Population-Based Cohort.

BACKGROUND AND AIMS: The natural history of perianal Crohn's disease (PCD) remains poorly described and is mainly based on retrospective studies from referral centers. The aim of this study was to assess the incidence, outcomes and predictors of the onset of PCD. METHODS: All incident cases of patients diagnosed with possible CD were prospectively registered from 1994 to 1997 in Brittany, a limited area in France. At diagnosis, the clinical features of perianal disease were recorded. All patient charts were reviewed from the diagnosis to the last clinic visit in 2015. RESULTS: Among the 272 out of 331 incident CD patients followed up, 51 (18.7%) patients had PCD at diagnosis. After a mean follow-up of 12.8 years, 93 (34%) patients developed PCD. The cumulative probabilities of perianal CD occurrence were 22%, 29%, and 32% after 1 year, 5 years, and 10 years, respectively. The cumulative probabilities of anal ulceration were 14%, and 19% after 1 year and 10 years, respectively. Extraintestinal manifestations were associated with the occurrence of anal ulceration. The cumulative probabilities of fistulizing PCD were 11%, 16%, and 19% after 1 year, 5 years, and 10 years, respectively. Extraintestinal manifestations, rectal involvement and anal ulceration were predictors of fistulizing PCD. The cumulative probability of developing anal stricture was 4% after 10 years. CONCLUSIONS: PCD is frequently observed during CD, in approximately one-third of patients. These data underline the need for targeted therapeutic research on primary perianal lesions (proctitis, anal ulceration) to avoid the onset of fistulizing perianal disease.