Combined strategies following surgical drainage for perianal fistulizing Crohn's disease: failure rates and prognostic factors.

AIM: The medico-surgical strategy for the treatment of perianal fistulizing Crohn's disease (CD) following surgical drainage remains challenging and debated. Our aims were to describe the failure rate of therapeutic interventions after drainage of the fistula tract and determine the factors associated with failure to optimize medico-surgical strategies. METHOD: All consecutive patients with perianal fistulizing CD who underwent surgical drainage with at least a 12-week follow-up were included. Failure was defined as the occurrence of at least one of the following items: abscess recurrence, purulent discharge from the tract, visible external opening and further drainage procedure(s). RESULTS: One hundred and sixty-nine patients were included. The median follow-up was 4.0 years. The cumulative failure rates were 20%, 30% and 36% at 1, 3 and 5 years, respectively. The cumulative failure rates in patients who had sphincter-sparing surgeries or seton removal were significantly higher than in those who had a fistulotomy. Anterior fistula [hazard ratio (HR) = 2.52 (1.13-5.61), P = 0.024], supralevator extension [HR = 20.78 (3.38-127.80), P = 0.001] and the absence or discontinuation of immunosuppressants after anal drainage [HR = 3.74 (1.11-12.5), P = 0.032] were significantly associated with failure in the multivariate analysis model. CONCLUSION: Combined strategies for perianal fistulizing CD lead to a failure rate of 36% at 5 years. Where advisable, fistulotomy may be preferred because it has a lower rate of recurrence. The benefits of immunosuppressants require a dedicated prospective randomized trial.

Protocol of a multicentric prospective cohort study for the VALIDation of the IBD-disk instrument for assessing disability in inflammatory bowel diseases: the VALIDate study.

BACKGROUND: Inflammatory Bowel Diseases (IBD) affect psychological, family, social and professional dimensions of patients' life, leading to disability which is essential to quantify as part of Patient-Reported Outcomes (PROs) newly included in the targets to reach in IBD patients. Up to now, the IBD-Disability Index (IBD-DI) was the only validated tool to assess disability, but it is not appropriate for use in clinical practice. The IBD Disk was developed, a shortened and self-administered tool, adapted from the IBD-DI, in order to give immediate representation of patient-reported disability. However, the IBD Disk has not been validated yet in clinical practice. The aims of the VALIDate study are to validate this tool in a large population of IBD patients and to compare it to the already validated IBD-DI. METHODS: The VALIDate study is an ongoing multicentric prospective cohort study launched in April 2018 in 3 French University Hospitals (Nantes, Rennes, Angers), with an objective to reach a sample of 400 patients over a period inclusion of 6 months. Each patient will fill in the two questionnaires IBD Disk and IBD-DI at baseline, then between 3 and 12 months later, during a follow-up visit. Clinical and socio-demographic data will also be collected. During these two consultations, gastroenterologists and patients will evaluate disease activity thanks to a semi-quantitative 4-grade scale, named respectively PGA (Physician Global Assessment) and PtGA (Patient Global Assessment). This cohort will allow to evaluate the validity of the IBD Disk with respect to the IBD-DI in order to generalize its use for clinical practice. Other psychometric criteria of the IBD Disk will also be analysed as its reliability or its discriminant capacity. Close attention will nonetheless be needed to minimize the number of lost to follow-up patients between baseline and follow-up. DISCUSSION: The VALIDate study is the study designed to validate the IBD Disk, a visual tool easily useable in daily practice to assess disability in IBD patients. The results of this trial should enable the diffusion of this tool. TRIAL REGISTRATION: The trial is registered in ClinicalTrials.Gov with registration number NCT03590639. First posted: July 18, 2018.

Chronic pelvic pain and rectal prolapse invite consideration of enterocele.

AIM: Data on the pathogenesis and symptoms of enterocele are limited. The objectives of this study were to determine the clinical phenotype of patients with enterocele, to highlight the main functional and/or anatomical associations and to improve the accuracy of the preoperative assessment of pelvic floor disorders. METHOD: A total of 588 patients who were referred to a tertiary unit for an anorectal complaint completed a self-administered questionnaire and underwent physical examination, anorectal manometry and defaecography. Using defaecography, enterocele was defined as a radiological hernia of the small bowel into an enlarged rectovaginal space. One hundred and thirty-five patients with enterocele were age- and gender-matched with 270 patients without enterocele. Factors associated with enterocele were assessed using univariate and multivariate analysis models. RESULTS: Patients with enterocele were less frequently obese than patients without enterocele (8/135 vs 36/270; P = 0.02) and more frequently had a past history of pelvic surgery (51/135 vs 75/270; P = 0.04). They complained more frequently of pelvic pain on bearing down (29/135 vs 24/270; P = 0.003), anal procidentia (37/135 vs 46/270; P = 0.01) and more frequently had irritable bowel syndrome (83/135 vs 131/270; P = 0.01) and severe constipation according to the Kess score (104/135 vs 182/270; P = 0.04). Anorectal function was comparable between the two groups. Patients with enterocele had more frequent rectoceles and overt rectal prolapses than patients without enterocele. CONCLUSIONS: Enterocele should be investigated in patients with chronic pelvic pain, overt rectal prolapse and/or a past history of pelvic surgery.

Advancement flap procedure in Crohn and non-Crohn perineal fistulas: a simple surgical approach.

AIM: Rectal flap advancement is still a part of therapeutic management of anal fistulas. Data on the outcome of rectal flap advancement in patients with Crohn's disease (CD) is scarce. Our objective was to ascertain rates of failure of rectal flap advancement and to determine predictive factors for failure, with a special focus on CD METHOD: The patients' details, the characteristics of the fistula and the main clinical and therapeutic events were prospectively assessed among patients who underwent rectal flap advancement. All patients had a partial-thickness rectal flap advancement. Failure of primary rectal flap advancement was defined as the occurrence of at least one of the following: abscess, discharge, visible external opening, further drainage procedure. The rates of failure of rectal flap and the predictive factors of failure were assessed. RESULTS: Eighty-seven patients (34 patients with CD) were included. The median (interquartile range) follow-up was 13.3 (3.8-38.1) months. The cumulative failure rates were 15.9% (10.3-23.6), 23.0% (16.0-31.8), 31.6% (22.9-41.8) and 41.3% (30.5-53.0) at 3, 6, 12 and 24 months respectively. These data were comparable in Crohn's patients. Those with a supralevator fistula [hazard ratio 2.53 (1.01-7.71), P = 0.0476] and patients who had fewer than two fistula drainages before rectal flap [hazard ratio 3.19 (1.40-8.23), P = 0.005] were associated with higher rectal flap failure rates. In CD patients, the absence of biological therapy at referral was predictive of failure. CONCLUSION: Rectal flap advancement is a satisfactory option for the therapeutic management of anal fistula, including CD populations. Fistula drainage is needed before performing this surgical technique.

Sphincter-sparing surgery for complex anal fistulas: radiofrequency thermocoagulation of the tract is of no help.

AIM: To compare the rate of failure of radiofrequency thermocoagulation for anal fistula with that of rectal advancement flap in a case-matched study. METHOD: Patients who underwent radiofrequency treatment were compared with age- and sex-matched patients with Crohn's disease (CD) who underwent a rectal flap procedure. Fistula features, general characteristics and the main clinical events were recorded in a prospective database. Failure was defined by at least one of following: abscess, purulent discharge, visible external opening or further drainage procedure. RESULTS: A total of 62 patients [median age 45 (range 36.8-57.5) years; 22 women, 40 men; 22 with CD] were analysed. The failure rate of radiofrequency treatment was higher than that of rectal flap treatment (74.2% vs 32.2%; P = 0.004). The cumulative probabilities of failure of the radiofrequency treatment were 53.8% (38.8-68.3), 71.8% (55.3-84.0) and 87.4% (70.6-95.3) at 3, 6 and 12 months, respectively. Three patients in the radiofrequency group required drainage for an abscess and one had severe thermal ulceration. The Cox proportional hazards regression model (surgical procedure, obesity, CD) showed rectal flap treatment [3.48 (1.60-8.07); P = 0.001] and CD [2.60 (1.16-6.41); P = 0.02] to be the main independent predictors of healing. CONCLUSION: Radiofrequency thermocoagulation is a less satisfactory sphincter-sparing treatment for the management of anal fistula than a rectal flap procedure.

Anoperineal lesions in Crohn's disease: French recommendations for clinical practice.

BACKGROUND: Anoperineal lesion (APL) occurrence is a significant event in the evolution of Crohn's disease (CD). Management should involve a multidisciplinary approach combining the knowledge of the gastroenterologist, the colorectal surgeon and the radiologist who have appropriate experience in this area. Given the low level of evidence of available medical and surgical strategies, the aim of this work was to establish a French expert consensus on management of anal Crohn's disease. These recommendations were led under the aegis of the Société Nationale Française de Colo-Proctologie (SNFCP). They report a consensus on the management of perianal Crohn's disease lesions, including fistulas, ulceration and anorectal stenosis and propose an appropriate treatment strategy, as well as sphincter-preserving and multidisciplinary management. METHODOLOGY: A panel of French gastroenterologists and colorectal surgeons with expertise in inflammatory bowel diseases reviewed the literature in order to provide practical management pathways for perianal CD. Analysis of the literature was made according to the recommendations of the Haute Autorité de Santé (HAS) to establish a level of proof for each publication and then to propose a rank of recommendation. When lack of factual data precluded ranking according to the HAS, proposals based on expert opinion were written. Therefore, once all the authors agreed on a consensual statement, it was then submitted to all the members of the SNFCP. As initial literature review stopped in December 2014, more recent European or international guidelines have been published since and were included in the analysis. RESULTS: MRI is recommended for complex secondary lesions, particularly after failure of previous medical and/or surgical treatments. For severe anal ulceration in Crohn's disease, maximal medical treatment with anti-TNF agent is recommended. After prolonged drainage of simple anal fistula by a flexible elastic loop or loosely tied seton, and after obtaining luminal and perineal remission by immunosuppressive therapy and/or anti-TNF agents, the surgical treatment options to be discussed are simple seton removal or injection of the fistula tract with biological glue. After prolonged loose-seton drainage of the complex anal fistula in Crohn's disease, and after obtaining luminal and perineal remission with anti-TNF ± immunosuppressive therapy, surgical treatment options are simple removal of seton and rectal advancement flap. Colostomy is indicated as a last option for severe APL, possibly associated with a proctectomy if there is refractory rectal involvement after failure of other medical and surgical treatments. The evaluation of anorectal stenosis of Crohn's disease (ARSCD) requires a physical examination, sometimes under anesthesia, plus endoscopy with biopsies and MRI to describe the stenosis itself, to identify associated inflammatory, infectious or dysplastic lesions, and to search for injury or fibrosis of the sphincter. Therapeutic strategy for ARSCD requires medical-surgical cooperation.

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. METHODS: A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). RESULTS: The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. CONCLUSIONS: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.

Prevalence and predictive factors of the need for surgery for advanced colorectal adenoma.

AIM: Endoscopic resection is the primary treatment for colorectal adenoma, but in some cases surgery is necessary. The aim of this retrospective study was to define the prevalence and predictive factors for surgery in patients with advanced colorectal adenoma managed in a referral endoscopy centre. METHOD: Consecutive patients diagnosed with advanced adenoma (Class 4 in the Vienna classification) during a colonoscopy from 2007 to 2009 in the endoscopy centre of the University Hospital of Rennes were included. Predictive factors of surgery were determined by univariate and multivariate analysis. RESULTS: Two-hundred and twelve (135 male) patients with a mean age of 65.8 years were included. The reason for colonoscopy was for diagnosis in 63.2%, surveillance in 25.5% and screening in 11.3%. These referred patients amounted to 20.8% of all patients having colonoscopy. Surgery was performed in 13.7% of the 212 patients and in 16 (8.3%) of the 192 patients in whom endoscopic removal was attempted. In the subgroup of 192 patients, univariate analysis revealed that body mass index (P = 0.04), histology (P = 0.002), size (P = 0.03) and macroscopic appearance (P < 0.001) of the polyp were associated with surgery. Multivariate analysis revealed that the macroscopic appearance and histology only were significantly associated with surgery. CONCLUSION: Surgery was needed in 13.7% of patients with an advanced adenoma, but in only 8.3% of the subgroup of 192 patients in whom endoscopic removal was attempted. Factors associated with surgery included macroscopic appearance and histology.

Incontinence in full-thickness rectal prolapse: low level of improvement after laparoscopic rectopexy.

AIM: The study aimed to quantify incontinence before and after laparoscopic rectopexy in patients suffering from rectal prolapse. METHOD: Eighty-five patients underwent laparoscopic rectopexy to treat rectal prolapse between 2003 and 2009. Symptomatic and functional data were collected prospectively before and after surgery by self-administered questionnaires including the Cleveland Clinic Fecal Incontinence Score (CCIS) and constipation, gastrointestinal quality of life and urinary incontinence questionnaires. Incontinence was considered to be present when the CCIS remained at ≥ 5 after surgery. RESULTS: After a mean follow-up period of 36 months after surgery, 83% of the patients reported good to excellent results. Continence was improved in 58 (68%), with a significant decrease in the continence score (-3.4 ± 5.8, P = 0.001). However, 50 (58.9%) patients remained incontinent: 47 (55%) reported urge incontinence and 27 (32%) had passive leakage. Incontinence for liquid stool, incontinence for solid stool and the need for protection was seen in 43 (51%), 35 (41%) and 43 (51%) patients. Manometry, defaecography and ultrasonography were not associated with any improvement. In contrast, the patients' average age (60.2 ± 15.8 vs 46.9 ± 15.5 years; P = 0.003), symptom duration before surgery (58.1 ± 70.1 vs 29.5 ± 33.3 months; P = 0.011), preoperative urinary incontinence score (10.7 ± 10.8 vs 4.2 ± 5.7; P = 0.0131) and faecal incontinence score (12.9 ± 4.9 vs 7.1 ± 6; P < 0.0001) were significantly higher in patients suffering from postoperative incontinence. CONCLUSION: Despite some continence improvement in two-thirds of patients who underwent surgery for rectal prolapse, the level of improvement remained low in more than half of the patients.

Underlying functional bowel disorder may explain patient dissatisfaction after haemorrhoidal surgery.

AIM: The aim of this study was to assess patient dissatisfaction and functional symptoms following haemorrhoid surgery, aspects of which are seldom covered in other published series. METHOD: A self-administered questionnaire was mailed to 359 consecutive patients (prospective database; 198 men, 161 women; median follow up, 59 [1-120] months) who underwent either Milligan-Morgan haemorrhoidectomy (n=205) or stapled haemorrhoidopexy (n=154). RESULTS: The response rate was 72%; 2.4% of patients had no opinion, 13.6% were dissatisfied, 33.0% were satisfied, and 51.0% were very satisfied with the treatment. Dissatisfied patients were more likely to be women and more likely to have a long history of constipation and irritable bowel syndrome. The duration of surgery and the rates of pre- and postoperative complications did not differ between groups. Residual bleeding (49% vs 32%), prolapse (67% vs 31%) and pain (91% vs 55%) occurred more frequently in the dissatisfied group compared with the satisfied group (P<0.001). Incontinence (4 [0-16] vs 1 [0-15]; P=0.0003) and constipation (19 [1-34] vs 8 [0-31]; P<0.0001) scores were significantly higher in the dissatisfied group compared with satisfied patients. Anal pain was the predominant symptom associated with dissatisfaction in a logistic regression model. CONCLUSION: Persistent pain remains the major long-term factor associated with dissatisfaction after surgery for haemorrhoids.

How to Manage Inflammatory Bowel Disease Patients When They Withdraw Anti-Tumour Necrosis Factor [Anti-TNF] Due to Severe Anti-TNF-Induced Skin Lesions? A Multicentre Cohort Study.

BACKGROUND AND AIMS: Optimal management of patients with inflammatory bowel disease [IBD] after anti-tumour necrosis factor [TNF] discontinuation due to severe induced skin lesions is unclear. Our study aimed to describe dermatological and IBD evolution after anti-TNF discontinuation for this side effect. METHODS: We conducted a multicentre retrospective study including consecutive IBD patients who discontinued anti-TNF due to severe induced skin lesions. Our objectives were to determine factors associated with dermatological remission [complete disappearance of skin lesions] and with IBD relapse in patients with inactive disease at inclusion, notably the impact of an early switch to another biological agent within 3 months of anti-TNF discontinuation. RESULTS: Among the 181 patients [134 women, 160 Crohn's disease] included in the 13 participating centres, dermatological remission occurred in 110 [62%] patients with a median [interquartile range, IQR] interval of 8.0 [6.8-11.0] months. Scalp location was independently associated with less remission of skin lesions (hazard ratio [HR] = 0.64 [95% CI 0.43-0.94], p = 0.02) while early switch was independently associated with a higher probability of remission of skin lesions (HR = 1.64 [95% CI 1.1-2.5], p = 0.02). Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 [51%] patients with a median [IQR] interval of 26.0 [23.0-39.1] months. Survival rates without IBD relapse at 1 year were 85.8% [95% CI 77.5-94.9] in the early switch group and 59.3% [95% CI 48.9-71.9] in the other group [p < 0.01]. CONCLUSIONS: Early switch to a new biological is associated with a higher probability of healing of anti-TNF-induced skin lesions and significantly reduces the risk of IBD relapse.

Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis.

OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX. METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed. RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy. CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.

Early Transmural Response Assessed Using Magnetic Resonance Imaging Could Predict Sustained Clinical Remission and Prevent Bowel Damage in Patients with Crohn's Disease Treated with Anti-Tumour Necrosis Factor Therapy.

BACKGROUND: Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]. AIMS: We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. METHODS: All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52. RESULTS: Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7-34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3-13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037). CONCLUSION: Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.

[Intestinal motility disorders and visceral hypersensitivity in irritable bowel syndrome]. / Troubles de la motricité intestinale et hypersensibilité viscérale dans le syndrome de l'intestin irritable.

The pathophysiology of irritable bowel syndrome is complex, secondary to a dysregulation of the visceral neuromuscular system. Motor disorders and digestive hypersensitivity have been studied most: phasic and tonic abnormalities and visceral hypersensitivity associated with different types of receptors have been identified in patients with irritable bowel syndrome. For other patients, the combination of these disorders can explain abnormal physiological responses. Some records of various explorations are correlated with patient symptoms, such as pain, bloating, or bowel movement disorders. These sensorimotor disorders, probably not limited to the gut, are reviewed in this article.

Online training on how to diagnose anoperineal lesions of Crohn's disease: Do pictures matter? A nationwide randomized study.

Any gastroenterologist must be trained to properly diagnose anoperineal lesions in patients with Crohn's disease (APLOC). The aim of this study was to establish whether adding pictures would improve teaching effectiveness of the diagnosis of APLOC to French gastroenterology trainees. METHOD: Trainees were asked to answer a first web-based survey consisting of evaluating 12 pictures of APLOC with a closed answer questionnaire. They were then randomized in 2 groups. Group A received an online teaching with typical pictures and APLOC definitions and group B definitions only. Trainees were asked again seven days later to answer a second survey with 12 other pictures of APLOC and 14 experts also answered this survey. Diagnostic scores were expressed in %. The primary endpoint was the comparison of the score of survey 2 between the two groups of trainees. Secondary endpoints were to compare results of survey 2 between trainees of both groups and experts, and assess diagnosis of each lesion. RESULTS: Two hundred fourty eight trainees among 465 answered survey 1, and 195 survey 2. The diagnostic score was 71.9% for groups A and B and 74.6% for experts (differences NS). After training diagnosis of ulceration was 72% for group A and 72.9% for group B, fistulae 85.2% versus 85.8%, erythema 44.1% vs. 55.6%, anoperineal scars 67.5% vs. 65.6%, and abscess 100% (differences NS). CONCLUSION: There was no difference between the two teaching methods. Further research should be performed aiming at improving teaching material and quotation baremes.

Long-term efficacy and safety of ustekinumab in 122 refractory Crohn's disease patients: a multicentre experience.

BACKGROUND: Long-term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. AIM: To evaluate the long-term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure-free persistence in a cohort of anti-TNF refractory CD patients. METHODS: We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD-related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. RESULTS: Eighty-eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4-34.4) months. Forty-seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure-free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure-free persistence was identified. One severe adverse event was observed (anal adenocarcinoma). CONCLUSION: In this cohort of refractory CD patients receiving long-term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile.

Impact of vedolizumab therapy on extra-intestinal manifestations in patients with inflammatory bowel disease: a multicentre cohort study nested in the OBSERV-IBD cohort.

BACKGROUND: The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut-specificity. AIM: To assess effectiveness of vedolizumab for EIM in patients with inflammatory bowel disease (IBD) in a large real-life experience cohort. METHODS: Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3-step scale: complete remission, partial response and no response. RESULTS: At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% [1.05-3.41], P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% [1.12-3.52], P = .02). During the follow-up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation. CONCLUSION: Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy.

Pathophysiology of fecal incontinence in obese patients: A prospective case-matched study of 201 patients.

BACKGROUND: Obesity is an emerging risk factor for fecal incontinence (FI). The aim of this study was to characterize pathophysiologic mechanisms of FI in obese patients compared with non-obese patients in a prospective case-matched study. METHODS: The general characteristics and data of the anorectal manometry and endosonography of patients who were evaluated for FI at a single institution from 2005 to 2015 were prospectively assessed. Fecal incontinence was defined by a Cleveland Clinic Incontinence Score (CCIS) >4. Obesity was defined by a body mass index ≥30 kg/m2 . Obese patients were case-matched with two age- and sex-matched non-obese patients. KEY RESULTS: A total of 201 patients were included (67 obese matched with 134 non-obese). The CCIS, Knowles-Eccersley-Scott Symptom Constipation Score and quality of life score were comparable between obese and non-obese patients with FI. Factors significantly associated with obesity in FI patients were cholecystectomy (odds ratio [OR]=3.45 [1.19-10.32], P=.0230), irritable bowel syndrome - diarrhea (OR=2.94 [1.22-7.19], P=.0158), upper part of the anal canal resting pressure ≥22 mm Hg (OR=3.45 [1.45-8.76], P=.0045), maximum rectal tolerable volume ≥240 mL (OR=3.14 [1.34-7.54], P=.0082), and abdominal pressure ≥28 mm Hg (OR=2.75 [1.13-7.33], P=.0248) by multivariate analysis. CONCLUSIONS & INFERENCES: Obese patients with FI had a comparable severity of FI to that of non-obese patients with FI. Regarding obesity in patients with FI, physicians should focus on stool consistency.

[Children with inflammatory bowel disease: Assessment of the transition from the pediatric to the adult care unit]. / Évaluation de la transition pédiatrie-gastroentérologie d'adultes des enfants atteints de maladie inflammatoire cryptogénique intestinale.

AIM: Assess the transition of children followed for inflammatory bowel disease (IBD) to the adult gastroenterology care unit and the development of joint medical visits (JMVs). PATIENTS AND METHOD: This study was conducted at the Rennes University Hospital (Brittany, France). All patients with IBD and relayed to an adult gastroenterologist (GE) between 2000 and 2014 were included. The following medical data were collected: age, gender, clinical status, disease activity, type of follow-up (freelance or at hospital), medical history, disease locations, and treatments received. Patients who were relayed in the same hospital attended a JMV with both the pediatric and adult gastroenterologists. Patients and parents were interviewed with a questionnaire sent by mail. They were asked how they had perceived the transition with questionnaires containing specific items about the JMV. The answers of the patients who attended JMVs were compared to those who did not attend. RESULTS: Eighty-two patients were included. The patient response rate was 56 % (parents, 59 %). The average age at transition was 18±0.8years. Fifty patients were relayed in the same hospital with 30 attending a JMV. These patients suffered from more severe disease than other patients. Thirty-nine patients felt ready to transition (87 %). The JMV was deemed beneficial or very beneficial (74 %) for both follow-up and the benefits of the GE's knowledge of the medical file. The parents' responses did not differ from the patients'. CONCLUSION: Development of the JMV enables a successful transition for pediatric patients with IBD. It could be improved by developing specific therapeutic education sessions based on transition training.

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study.

BACKGROUND: We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. AIMS: To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. METHODS: Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 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 54. RESULTS: At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. CONCLUSION: Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD.