Rigorous Donor Selection for Fecal Microbiota Transplantation in Active Ulcerative Colitis: Key Lessons From a Randomized Controlled Trial Halted for Futility.

BACKGROUND & AIMS: Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated fecal microbiota transplantation (FMT) administration were hypothesized to improve FMT induction of remission in ulcerative colitis (UC). METHODS: The RESTORE-UC trial was a multi-centric, double-blind, sham-controlled, randomized trial. Patients with moderate to severe UC (defined by total Mayo 4-10) were randomly allocated to receive 4 anaerobic-prepared allogenic or autologous donor FMTs. Allogenic donor material was selected after a rigorous screening based on microbial cell count, enterotype, and the abundance of specific genera. The primary endpoint was steroid-free clinical remission (total Mayo ≤2, no sub-score >1) at week 8. A pre-planned futility analysis was performed after 66% (n = 72) of intended inclusions (n = 108). Quantitative microbiome profiling (n = 44) was performed at weeks 0 and 8. RESULTS: In total, 72 patients were included, of which 66 received at least 1 FMT (allogenic FMT, n = 30 and autologous FMT, n = 36). At week 8, respectively, 3 and 5 patients reached the primary endpoint of steroid-free clinical remission (P = .72), indicating no treatment difference of at least 5% in favor of allogenic FMT. Hence, the study was stopped due to futility. Microbiome analysis showed numerically more enterotype transitions upon allogenic FMT compared with autologous FMT, and more transitions were observed when patients were treated with a different enterotype than their own at baseline (P = .01). Primary response was associated with lower total Mayo scores, lower bacterial cell counts, and higher Bacteroides 2 prevalence at baseline. CONCLUSION: The RESTORE-UC trial did not meet its primary endpoint of increased steroid-free clinical remission at week 8. Further research should additionally consider patient selection, sterilized sham-control, increased frequency, density, and viability of FMT prior to administration. CLINICALTRIALS: gov, Number: NCT03110289.

A novel hybrid technique for the repair of an atrioesophageal fistula post-atrial radiofrequency ablation.

An atrioesophageal fistula is an uncommon complication of atrial ablation with a mortality rate of 40-100%. Uniform treatment guidelines have yet to be established. Herein, we illustrate the successful surgical management of an atrioesophageal fistula, avoiding the need for an oesophageal surgical intervention by sealing and clipping of the oesophagus. This novel single-step hybrid approach combining cardiac surgical and gastroenterological techniques provides a less aggressive strategy with potentially a more favourable prognosis.

Efficacy and safety of radiofrequency ablation of Barrett's esophagus in the absence of reimbursement: a multicenter prospective Belgian registry.

BACKGROUND: Radiofrequency ablation (RFA), combined with endoscopic resection, can be used as a primary treatment for low grade dysplasia, high grade dysplasia, and early esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE). The aim of the Belgian RFA registry is to capture the real-life outcome of endoscopic therapy for BE with RFA and to assess efficacy and safety outside study protocols, in the absence of reimbursement. PATIENTS AND METHODS: Between February 2008 and January 2017, data from 7 different expert centers were prospectively collected in the registry. Efficacy outcomes included complete remission of intestinal metaplasia (CR-IM), complete remission of dysplasia (CR-D), and durability of remission. Safety outcomes included immediate and late adverse events. RESULTS: 684 RFA procedures in 342 different patients were registered. Of these, 295 patients were included in the efficacy analysis, with CR-IM achieved in 88 % and CR-D in 93 %, in per-protocol analysis; corresponding rates in intention-to-treat analysis were 82 % and 87 %, respectively. Sustained remission was seen in 65 % with a median (interquartile range) follow-up of 25 (12 - 47) months. No risk factors for recurrent disease were identified. Immediate complications occurred in 4 % of all procedures and 6 % of all patients, whereas late complications occurred in 9 % of all procedures and in 20 % of all patients. CONCLUSIONS: Data from the Belgian registry confirm that RFA in combination with endoscopic resection is an efficient treatment for BE with dysplasia or early EAC. In the absence of reimbursement, more rescue treatments are used, not compromising outcome. Since there is recurrent disease after CR-IM in 35 %, surveillance endoscopy remains necessary.

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

BACKGROUND: Vedolizumab is a recently available monoclonal antibody targeting α4ß7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). OBJECTIVE: The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. METHODS: A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician's global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. RESULTS: Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. CONCLUSION: Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

Cystic Lymphangioma: Are Triglycerides Always Measurable?

The presence of chylous fluid with high triglycerides levels on endoscopic ultrasound- (EUS-) guided fine needle aspiration (FNA) is very pathognomonic for the diagnosis of cystic lymphangiomas of the pancreas. In our case report the puncture of the pancreatic cyst showed a typical milky fluid though measurable triglyceride concentrations were absent in the laboratory. Two possible explanations were found. First of all grossly lipemic samples show a slower rate of color development than do clear serums which can produce a false negative result if the sample is insufficiently diluted. Secondly, high lipase levels can divide triglycerides in glycerol and fatty acids, making the concentration of triglycerides undetectable.

Increasing Infliximab Dose Based on Symptoms, Biomarkers, and Serum Drug Concentrations Does Not Increase Clinical, Endoscopic, and Corticosteroid-Free Remission in Patients With Active Luminal Crohn's Disease.

BACKGROUND & AIMS: A combination of infliximab and immunomodulators is the most efficacious treatment for Crohn's disease (CD). Patients have the best outcomes when their serum concentrations of these drugs are above a determined therapeutic threshold. We performed a prospective, randomized trial to determine whether therapeutic drug monitoring (TDM) to maintain serum levels of infliximab above 3 µg/mL produced higher rates of clinical and endoscopic remission than adapting dose based only on symptoms. METHODS: We performed a double-blind trial in which 122 biologic-naïve adult patients with active CD (71 female, median age 29.8 years) received induction treatment with infliximab in combination with an immunosuppressant, from July 2012 through September 2015 at 27 centers in Europe. At week 14 of treatment, patients were randomly assigned (1:1:1) to 3 infliximab maintenance groups: dose increases (2 maximum) in steps of 2.5 mg/kg based on clinical symptoms and biomarker analysis and/or serum infliximab concentrations (dose intensification strategy [DIS]1 group); dose increase from 5 to 10 mg/kg based on the same criteria (DIS2 group); dose increase to 10 mg/kg based on clinical symptoms alone (controls). Patients' CD activity index scores, levels of C-reactive protein, fecal levels of calprotectin, and serum concentrations of infliximab were determined at baseline and at weeks 2, 4, 6, 12, and 14 of treatment, and then every 4 weeks thereafter until week 54. The primary endpoint was sustained corticosteroid-free clinical remission (CD activity index <150) from weeks 22 through 54 with no ulcers at week 54. RESULTS: The primary endpoint was reached by 15 (33%) of 45 patients in the DIS1 group, 10 (27%) of 37 patients in the DIS2 group, and 16 (40%) of 40 patients in the control group (P = .50). CONCLUSIONS: In a prospective randomized exploratory trial of patients with active CD, we found increasing dose of infliximab based on a combination of symptoms, biomarkers, and serum drug concentrations does not lead to corticosteroid-free clinical remission in a larger proportion of patients than increasing dose based on symptoms alone. EUDRACT NUMBER: 2011-003038-14.

[A man with a strange mass in his defecation]. / Een man met een vreemde massa in zijn ontlasting.

A 56-year-old patient underwent a preventive colonoscopy. We found a large mass in his colon with a benign aspect. The 'unroofing' technique was used for further diagnosis and we suspected the diagnosis of 'lipoma'. Nine days after the colonoscopy, a part of the lipoma was evacuated through the stool. Histopathological examination of this tissue confirmed the diagnosis of 'lipoma'.

Pancreatic panniculitis: a rare complication of pancreatitis secondary to ERCP.

Panniculitis is an uncommon and rare complication of systemic fat necrosis in patients with pancreatic diseases. The skin manifestations are independent of the severity of the pancreatic pathology and can occur at any time. The lesions can precede, be concomitant with or rarely follow the pancreatic illness. We report a case of acute pancreatitis post Endoscopic Retrograde Cholangio Pancreatography (ERCP) for common bile duct stone, with subcutaneous panniculitis. We noted a complete resolution within two weeks after the treatment of the pancreatic pathology.

Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy.

BACKGROUND: This study examined whether fecal calprotectin can be used in daily practice as a marker to monitor patients with ulcerative colitis (UC) receiving infliximab maintenance therapy. METHODS: This prospective multicenter study enrolled adult patients with UC in clinical remission under infliximab maintenance therapy. Fecal calprotectin levels were measured every 4 weeks. Sigmoidoscopies were performed at inclusion and at study end. Relapse was defined as a clinical need for change in treatment or an endoscopic Mayo subscore of ≥2 at week 52. Sustained deep remission was defined as a partial Mayo score <3 at all points and an endoscopic Mayo score 0 at week 52. RESULTS: Full analysis was possible for 87 of 113 included patients with UC (77%). Of these patients, 30 (34.4%) were considered to be in sustained deep remission and 13 (14.9%) to have relapsed. Calprotectin levels in patients with sustained deep remission remained very low (median < 40 mg/kg at all time points). Patients who flared had significantly higher calprotectin levels (median > 300 mg/kg) already 3 months before the flare. Further receiver operator curve analysis suggested that a calprotectin level >300 mg/kg had a reasonable sensitivity (58.3%) and specificity (93.3%) to model flare. Two consecutive calprotectin measurements of >300 mg/kg with 1-month interval were identified as the best predictor of flare (61.5% sensitivity and 100% specificity). CONCLUSIONS: Fecal calprotectin can be used in daily practice to monitor patients with UC receiving infliximab maintenance therapy. Two consecutive measurements >300 mg/kg is more specific than a single measurement for predicting relapse.

Capsule endoscopy for detection of small bowel malignancies.

Capsule Endoscopy (CE) is a recent diagnostic tool for detection of small bowel disease. The tiny imaging capsule has to be swallowed by the patient, which allows transmission by radiofrequency two images each second, to sensors worn around the patient's abdomen. After eight hours, the pictures can be downloaded and read by a Gastroenterologist. CE allows for exploration of the entire small bowel mucosa, which involves segments not accessible by classical endoscopy. Moreover, it is the only technique that involves a visualization of the entire small bowel without sedation. Tumors of the small intestine are rather infrequent and could account for approximately 2% of gastrointestinal neoplasms. As symptoms of small bowel tumors are not specific, most published series include patients with bleeding or anemia of undetermined origin, the main indication for performing CE. Currently, no doubt exists of the ability regarding the CE to increase the diagnostic yield of small bowel tumors, or to alter their management and improve their outcome in the absence of metastases. Overall, tumors along the small intestine are located by CE in 2.5%-8.9% of patients who undergo this procedure. While being an evident improvement, CE has some limitations, such as the inability to treat lesions locally or take tissue specimens. This last point is an important shortcoming, because small bowel tumors can be malignant (approximately 2/3 of the cases) or benign. The future of CE is bright, and special capsule devices already exist to specifically explore the esophagus as well as the large intestine.

Antireflux transoral incisionless fundoplication using EsophyX: 12-month results of a prospective multicenter study.

BACKGROUND: A novel transoral incisionless fundoplication (TIF) procedure using the EsophyX system with SerosaFuse fasteners was designed to reconstruct a full-thickness valve at the gastroesophageal junction through tailored delivery of multiple fasteners during a single-device insertion. The safety and efficacy of TIF for treating gastroesophageal reflux disease (GERD) were evaluated in a prospective multicenter trial. METHODS: Patients (n = 86) with chronic GERD treated with proton pump inhibitors (PPIs) were enrolled. Exclusion criteria included an irreducible hiatal hernia > 2 cm. RESULTS: The TIF procedure (n = 84) reduced all hiatal hernias (n = 49) and constructed valves measuring 4 cm (2-6 cm) and 230 degrees (160 degrees -300 degrees ). Serious adverse events consisted of two esophageal perforations upon device insertion and one case of postoperative intraluminal bleeding. Other adverse events were mild and transient. At 12 months, aggregate (n = 79) and stratified Hill grade I tight (n = 21) results showed 73% and 86% of patients with >or=50% improvement in GERD health-related quality of life (HRQL) scores, 85% discontinuation of daily PPI use, and 81% complete cessation of PPIs; 37% and 48% normalization of esophageal acid exposure; 60% and 89% hiatal hernia reduction; and 62% and 80% esophagitis reduction, respectively. More than 50% of patients with Hill grade I tight valves had a normalized cardia circumference. Resting pressure of the lower esophageal sphincter (LES) was improved significantly (p < 0.001), by 53%. EsophyX-TIF cured GERD in 56% of patients based on their symptom reduction and PPI discontinuation. CONCLUSION: The 12-month results showed that EsophyX-TIF was safe and effective in improving quality of life and for reducing symptoms, PPI use, hiatal hernia, and esophagitis, as well as increasing the LES resting pressure and normalizing esophageal pH and cardia circumference in chronic GERD patients.

Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial.

BACKGROUND: Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab. METHODS: We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710. FINDINGS: Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60.0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35.9%) of 64 controls, for an absolute difference of 24.1% (95% CI 7.3-40.8, p=0.0062). Corresponding rates at week 52 were 40/65 (61.5%) and 27/64 (42.2%) (absolute difference 19.3%, 95% CI 2.4-36.3, p=0.0278). 20 of the 65 patients (30.8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25.3%) controls (p=1.0). INTERPRETATION: Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn's disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.

Capsule endoscopy in paediatrics: multicentric Belgian study.

BACKGROUND AND STUDY AIMS: Capsule Endoscopy (CE) is a noninvasive procedure for evaluating small bowel disease. Data concerning children are scarce. The aim of the present report was to review all paediatric cases investigated by CE in Belgium. PATIENTS AND METHODS: The seven Belgian academic hospitals using the CE device (Given) were asked to collect information on CE performed in patients < or = 18 years. Main indications for performing VCE, former radiological and endoscopic procedures were collected, as well as final diagnosis and clinical impact of VCE findings. RESULTS: From November 2002 until December 2005, VCE was performed in 17 children (mean age : 11.9 years, range : 5-18). Indications were occult gastro-intestinal bleeding (OGIB) and/or iron deficiency anaemia (IDA) (10 cases) and chronic and/or recurrent abdominal pain (7 cases). Mean duration of symptoms was 8.6 months. The mean number of endoscopic and radiological procedures before performing CE was 4.2 per patient. Detected lesions were ulcerations (6 cases), jejunal varices (1), ileo-ileal invagination (2), active bleeding (1), and normal findings (7). In the indication of OGIB/IDA, relevant findings having an impact on the diagnosis were found in 60% of the cases. In the group with chronic and recurrent abdominal pain, CE brought relevant findings in 43%. CE findings had an impact on therapy in 44% of the patients. CONCLUSIONS: CE could be a useful tool for clinical work-up of difficult paediatric cases, not only in the indication of IDA/OGIB, but also for selected cases of recurrent abdominal pain, but prospective controlled trials including emerging techniques like CT enterography are mandatory.

The role of aminosalicylates in the treatment of ulcerative colitis.

Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their efficacy has been established. Since ulcerative colitis is limited to the distal colon in two thirds of the patients, topical therapy also plays an important role. In mild/moderate active disease 5-ASA 4 g/d is as effective as oral corticosteroids. Ulcerative proctitis is treated with 2 x 500 mg or 1 x 1 g suppositories and proctosigmoiditis with 1 to 4 g enemas. Oral 5-ASA is also safe in maintenance treatment and is generally well tolerated. The risk of colorectal tumours is increased in patients with longstanding ulcerative colitis and epidemiological evidence indicates that chronic 5-ASA treatment reduces this risk. However, at present there is insufficient evidence to maintain patients on life-long 5-ASA maintenance treatment for this indication.