Summary Background Ciclosporin and infliximab are potential rescue treatments to avoid colectomy in patients with acute severe ulcerative colitis refractory to intravenous corticosteroids. We ...compared the efficacy and safety of these drugs for this indication. Methods In this parallel, open-label, randomised controlled trial, patients were aged at least 18 years, had an acute severe flare of ulcerative colitis defined by a Lichtiger score greater than 10 points, and had been given an unsuccessful course of high-dose intravenous steroids. None of the patients had previously received ciclosporin or infliximab. Between June 1, 2007, and Aug 31, 2010, patients at 27 European centres were randomly assigned (via computer-derived permutation tables; 1:1) to receive either intravenous ciclosporin (2 mg/kg per day for 1 week, followed by oral drug until day 98) or infliximab (5 mg/kg on days 0, 14, and 42). In both groups, azathioprine was started at day 7 in patients with a clinical response. Neither patients nor investigators were masked to study treatment. The primary efficacy outcome was treatment failure defined by absence of a clinical response at day 7, a relapse between day 7 and day 98, absence of steroid-free remission at day 98, a severe adverse event leading to treatment interruption, colectomy, or death. Analysis was by intention to treat. This trial is registered with EudraCT (2006-005299-42) and ClinicalTrials.gov ( NCT00542152 ). Findings 115 patients were randomly assigned; 58 patients were allocated to receive ciclosporin and 57 to receive infliximab. Treatment failure occurred in 35 (60%) patients given ciclosporin and 31 (54%) given infliximab (absolute risk difference 6%; 95% CI −7 to 19; p=0·52). Nine (16%) patients in the ciclosporin group and 14 (25%) in the infliximab group had severe adverse events. Interpretation Ciclosporin was not more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids. In clinical practice, treatment choice should be guided by physician and centre experience. Funding Association François Aupetit, Société Nationale Française de Gastroentérologie, and the International Organization for the study of Inflammatory Bowel Disease.
Background & Aims: The natural history of pediatric Crohn's disease and risk factors necessitating surgery have not been thoroughly described. Methods: In a geographically derived incidence cohort ...diagnosed from 1988 to 2002, we identified 404 Crohn's disease patients (ages, 0–17 years at diagnosis) with a follow-up time ≥2 years. Results: Median follow-up time was 84 months (range, 52–124 months). The most frequent disease location at diagnosis was the terminal ileum/colon (63%). Follow-up was characterized by disease extension in 31% of children. Complicated behavior was observed in 29% of children at diagnosis and 59% at follow-up. Kaplan–Meier survival estimates of the cumulative incidence of surgery were 20% at 3 years and 34% at 5 years from diagnosis. Multivariate Cox models showed that both structuring behavior at diagnosis (hazard ratio HR, 2.54; 95% confidence interval CI: 1.58–4.01) and treatment with corticosteroids (HR, 2.98; 95% CI: 1.64–5.41) were associated with increased risk for surgery, whereas treatment with azathioprine (HR, 0.51; 95% CI: 0.33–0.78) was associated with decreased risk. Azathioprine was introduced earlier in the course of disease in patients not undergoing surgery than in patients requiring surgery. Conclusions: Pediatric Crohn's disease was characterized by frequent occurrence, with time, of a severe phenotype with extensive, complicated disease. Immunosuppressive therapy may improve the natural history of this disease and decrease the need for performing surgery.
Background & Aims: We performed a meta-analysis of placebo-controlled trials to evaluate safety and efficacy of tumor necrosis factor (TNF) antagonists for Crohn’s disease. Methods: We searched ...MEDLINE, Cochrane Library, and EMBASE. The primary end points were clinical remission for luminal Crohn's disease and fistula closure at ≥2 consecutive visits. Deaths, serious infections, and malignancies were also analyzed by the methods of Peto and Der Simonian and Laird. Results: Fourteen luminal Crohn's disease trials enrolled 3995 patients. In overall analysis, anti-TNF therapy was effective for induction of remission at week 4 (mean difference, 11%; 95% confidence interval CI, 6%–16%; P < .001) and maintenance of remission at weeks 20–30 in patients who responded to induction therapy and in patients randomized before induction (mean difference, 23%; 95% CI, 18%–28% and mean difference, 8%; 95% CI, 3%–12%, respectively; P < .001 for all comparisons). Ten studies evaluated anti-TNF for treatment of fistulizing Crohn's disease, involving 776 patients. In overall analysis, anti-TNF therapy was effective for fistula closure only in maintenance trials after open-label induction (mean difference, 16%; 95% CI, 8%–25%; P < .001). In 21 studies enrolling 5356 individuals, anti-TNF therapy did not increase the risk of death, malignancy, or serious infection. Conclusions: Infliximab, adalimumab, and certolizumab are effective in luminal Crohn's disease. Efficacy of anti-TNF agents other than infliximab in treating fistulizing Crohn's disease requires additional investigations. A longer duration of follow-up and a larger number of patients are required to better assess the safety profile of TNF antagonists in Crohn's disease.
Introduction
The aim of this study was to evaluate the association between serum ustekinumab (UST) trough levels and response to induction and maintenance UST treatment in refractory Crohn’s Disease ...(CD) patients.
Methods
We performed a prospective study including CD patients who received UST from September 2015 to January 2017. Patients received 90 mg of UST subcutaneously at weeks 0, 4, and 12, then every 8 weeks. Two cohorts of patients were analyzed: an induction cohort and a maintenance cohort. We evaluated clinical, biological, and imaging/endoscopic response to UST treatment. UST trough levels and anti-UST antibodies were dosed at weeks 12 and 28 in the induction cohort, and at a single time point in the maintenance cohort.
Results
Forty-nine patients were enrolled in the maintenance cohort. Mean concentrations of UST were 1.88 ± 1.40 µg/mL. UST trough levels were not significantly different in patients with or without clinical, biological, or imaging/endoscopic responses to UST treatment (
p
> 0.11). Twenty-three consecutive patients were included in the induction cohort. At week 12, mean UST concentrations were 1.45 ± 1.15 µg/mL. Patients with a biological response to UST treatment had significant higher serum UST trough concentration (median 1.72 µg/mL) than non-responders (median 0.56 µg/mL,
p
= 0.02). A UST trough level ≥ 1.10 µg/mL at week 12 was associated with a biological response to UST treatment at 6 months.
Conclusion
UST trough levels were associated with a biological response at the end of the induction phase. In patients with low levels of UST, optimization treatment may be necessary to obtain a sustained response.
The hemostatic powder TC-325 (Hemospray; Cook Medical, Winston-Salem, North Carolina, USA) has shown promising results in the treatment of upper gastrointestinal bleeding (UGIB) in expert centers in ...pilot studies. The aim of this study was to evaluate the feasibility and efficacy of TC-325 in a large prospective registry of use in routine practice.
The data of all patients treated with TC-325 were prospectively collected through a national registry. Outcomes were the immediate feasibility and efficacy of TC-325 application, as well as the rates of rebleeding at Day 8 and Day 30. Multivariate analysis was performed to determine predictive factors of rebleeding.
A total of 202 patients were enrolled and 64 endoscopists participated from 20 centers. TC-325 was used as salvage therapy in 108 patients (53.5 %). The etiology of bleeding was an ulcer in 75 patients (37.1 %), tumor in 61 (30.2 %), postendoscopic therapy in 35 (17.3 %), or other in 31 (15.3 %). Application of the hemostatic powder was found to be very easy or easy in 31.7 % and 55.4 %, respectively. The immediate efficacy rate was 96.5 %. Recurrence of UGIB was noted at Day 8 and Day 30 in 26.7 % and 33.5 %, respectively. Predictive factors of recurrence at Day 8 were melena at initial presentation and use of TC-325 as salvage therapy.
These multicenter data confirmed the high rate of immediate hemostasis, excellent feasibility, and good safety profile of TC-325, which could become the treatment of choice in bleeding tumors or postendoscopic bleeding but not in bleeding ulcers where randomized studies are needed.
ClinicalTrials.gov (NCT02595853).
Purpose
Gastric leak occurs after sleeve gastrectomy (SG) in 2% of cases. Most staple-line disruptions (SLD) can be successfully treated with first-line endoscopic procedures. Less favorable ...situations may lead to more complex therapeutic strategies, like conversion to Roux-en-Y gastric bypass (RYGBP). The aim of our study is to predict the factors of endoscopic treatment failure and to assess the safety of conversion to RYGBP.
Methods
We included all patients treated in two centers of academic excellence (
n
= 100) between 2013 and 2017 who had a malignant SLD after SG. A “malignant” leakage met one of the following poor prognosis criteria suggested in the literature: unsuccessfully treated by the first-line endoscopic treatment; generalized peritonitis; anatomical anomalies; gastro-cutaneous or gastro-pleural fistula (GCF/GPF); or chronic leaks (> 4 weeks).
Results
No deaths occurred during the follow-up (20 ± 12 months). The endoscopy reported an anatomically abnormal gastric tube in 35 (35%) patients (stenosis
n
= 21 (21%), twist
n
= 9 (9%), or both
n
= 5 (5%)). We could maintain the SG in place in 92% of cases without stenosis, twist, or GCF/GPF. Conversion to RYGBP due to leakage was necessary in 37 (37%) patients. Stenosis, twist, or GCF/GPF significantly prevented healing in multivariate analysis (respectively:
p
= 0.020, OR = 0.17, and
p
< 0.001, OR = 0.07—logistic regression).
Conclusion
Endoscopy is the treatment of choice for the management of chronic leaks after SG. The association of anatomical anomalies and GCF/GPF should lead to consideration of conversion to RYGBP.
Background
The aim of the study was to identify factors associated with a radiological response and to assess the impact of radiological improvement in long-term outcomes in small bowel (SB) Crohn’s ...disease (CD) patients.
Methods
We performed a retrospective study from June 2011 to June 2017 in the tertiary center, Claude Huriez Hospital in Lille, France. All SB CD patients, who underwent two magnetic resonance enterographies (MRE) 3–12 months apart, with at least 1-year follow-up after the second MRE, were included. Signs of radiological inflammation were identified by two expert radiologists in CD. Patients were classified as radiological responders (RR) and non-responders (NR). Hospitalization rates, adjustment of treatment, and surgical or endoscopic interventions were assessed and compared between RR and NR. Factors associated with a radiological response were also studied using the Cox model.
Results
One hundred and fifteen SB CD patients were included with a median follow-up of 17 months (IQR 11.6–28.3). There were 54 (47%) RR and 61 (53%) NR. The risk of surgical or endoscopic intervention was higher in NR than RR (
p
= 0.04), and the median delay until a surgical or endoscopic intervention was shorter in NR (
p
= 0.04). Multifocal disease, a hypersignal on diffusion-weighted or dynamic contrast-enhanced imaging, a stricture, or a fistula was significantly associated with a decreased probability of a radiological response (
p
< 0.05).
Conclusion
This study shows that a radiological response is associated with a decreased risk of surgical or endoscopic intervention and should be considered as a therapeutic target in CD patients.
The aims of this retrospective multicenter study were to assess the technical success and adverse events of endoscopic retrograde cholangiopancreatography (ERCP) procedures in children in French and ...Belgian centers.
All children aged 1 day to 17 years who underwent ERCP between January 2008 and March 2019 in 15 tertiary care hospitals were retrospectively included.
271 children underwent 470 ERCP procedures. Clinical long-term follow-up was available for 72 % of our patients (340/470 procedures). The median age at intervention was 10.9 years. ERCP was therapeutic in 90 % (423/470) and diagnostic in cases of neonatal cholestasis in 10 % of the patients. The most common biliary indication was choledocholithiasis; the most common pancreatic indication was chronic pancreatitis. Biliary cannulation was successful in 92 % of cases (270/294); pancreatic cannulation in 96 % of cases (169/176); and planned therapeutic procedures in 92 % of cases (388/423). The overall complication rate was 19 % (65/340). The most common complication was post-ERCP pancreatitis (PEP) in 12 % of cases (40/340) and sepsis in 5 % (18/340). On univariate analyses, pancreatic stent removal was protective against PEP (odds ratio OR 0.1, 95 % confidence interval CI 0.01 - 0.75;
= 0.03), and sepsis was associated with history of liver transplantation (OR 7.27, 95 %CI 1.7 - 31.05;
= 0.01). Five patients had post-ERCP hemorrhage and two had intestinal perforation. All complications were managed with supportive medical care. There was no procedure-related mortality.
Our cohort demonstrates that ERCP can be performed safely with high success rates in many pancreaticobiliary diseases of children. The rate of adverse events was similar to that in previous reports.
Anti-Saccharomyces cerevisiae antibodies (ASCAs) are present in 50-60% of patients with Crohn's disease (CD) and in 20-25% of their healthy relatives (HRs). The yeast, Candida albicans, has been ...shown to generate ASCAs, but the presence of C. albicans in the digestive tract of CD patients and their HRs has never been investigated. Therefore, we studied C. albicans carriage in familial CD and its correlation with ASCAs.
Study groups consisted of 41 CD families composed of 129 patients and 113 HRs, and 14 control families composed of 76 individuals. Mouth swabs and stool specimens were collected for isolation, identification, and quantification of yeasts. Serum samples were collected for detection of ASCAs and anti-C. albicans mannan antibodies (ACMAs).
C. albicans was isolated significantly more frequently from stool samples from CD patients (44%) and their HRs (38%) than from controls (22%) (P<0.05). The prevalence of ACMAs was similar between CD patients, their HRs, and controls (22, 19, and 21%, respectively, P=0.845), whereas the prevalence of ASCAs was significantly increased in CD families (72 and 34% in CD and HRs, respectively, in contrast to 4% in controls, P<0.0001). AMCA levels correlated with C. albicans colonization in all populations. ASCA levels correlated with C. albicans colonization in HRs but not in CD patients.
CD patients and their first-degree HRs are more frequently and more heavily colonized by C. albicans than are controls. ASCAs correlate with C. albicans colonization in HRs but not in CD. In HRs, ASCAs could result from an altered immune response to C. albicans. In CD, a subsequent alteration in sensing C. albicans colonization could occur with disease onset.
Fistula is the main complication of laparoscopic sleeve gastrectomy (LSG), for which healing is difficult to achieve. The aims of the study were to evaluate the efficacy of interventional endoscopy ...for post-LSG fistula treatment, to evaluate various endoscopic techniques used and identify their complications, and to identify predictive factors of healing following endoscopic treatment.
This retrospective multicenter study included patients with post-LSG fistula. Therapeutic procedures were evaluated, taking into account complications and healing times. Endoscopic procedures were considered to have promoted healing if no other surgical procedure was performed. Predictive factors of healing were identified by univariate and multivariate analysis.
A total of 110 patients were included, of whom 6 (5.5 %) healed spontaneously, 81 (73.6 %) healed following endoscopic treatment, and 19 (17.3 %) healed following surgery. Healing rates following endoscopic treatment were 84.4 % in the first 6 months of treatment (65/77), 52.4 % for treatment lasting 6 - 12 months (11/21), and 41.7 % after 12 months of treatment (5/12). A drainage procedure (surgical, endoscopic, or percutaneous) was performed in 92 patients (83.6 %). A total of 177 esogastric stents were placed in 88 patients (80.0 %). Surgical debridement, clip placement, glue sealing, and plug placement were also performed. Multivariate analysis identified four predictive factors of healing following endoscopic treatment: interval < 21 days between fistula diagnosis and first endoscopy (P = 0.003), small fistula (P = 0.01), interval between LSG and fistula ≤ 3 days (P = 0.01), no history of gastric banding (P = 0.04).
Endoscopic treatment facilitated healing of post-LSG fistula in 74 % of patients. Early endoscopic treatment increased the likelihood of success, and was most effective during the first 6 months of management. After this point, surgical treatment should be considered.
