Performance Characteristics of a Lumen-Apposing Metal Stent for Pancreatic Fluid Collections: A Prospective Cohort Study.

BACKGROUND: Endoscopic ultrasound-guided transmural drainage is the preferred management of pancreatic fluid collections (PFCs). Optimizing drainage is important and there remains debate as to the choice of stent. A recent trend towards the use of lumen-apposing metal stents (LAMS) has emerged. AIM: To evaluate the performance characteristics of a LAMS based on a prospective protocol (CT scan 1 week after placement to assess for resolution and need for necrosectomy followed by stent removal within 3 weeks). METHODS: This is a descriptive prospective cohort study performed at a single centre. The primary outcome was clinical success. Secondary outcomes were technical success, procedure time, total number of endoscopic procedures with or without necrosectomy, stent indwell time, stent functionality and adverse events. RESULTS: Thirty-seven patients (21 males, mean age 46.5 years) underwent placement of LAMS for 41 PFCs (median size 12 cm). There were 18 pseudocysts and 23 walled-off necrosis. Clinical success was seen in 33 of 41 (80%) PFCs. Of the remaining eight patients, six underwent surgery and two patients died from underlying malignant disease (although their PFC had completely resolved). Technical success and stent functionality were 100%. The median procedure time was 14 min (interquartile range 11 min to 20 min). Of the 23 walled-off necrosis, 9 (39%) required necrosectomy. The median stent indwell time was 19 days (interquartile range 14 to 22 days). There were no serious adverse events. CONCLUSIONS: Our protocol demonstrates excellent performance characteristics of LAMS. Their clinical efficacy and favourable safety profile suggest that they may be the preferred modality for endoscopic ultrasound-guided management of PFCs.

Enteral nutritional therapy for induction of remission in Crohn's disease.

BACKGROUND: Corticosteroids are often preferred over enteral nutrition (EN) as induction therapy for Crohn's disease (CD). Prior meta-analyses suggest that corticosteroids are superior to EN for induction of remission in CD. Treatment failures in EN trials are often due to poor compliance, with dropouts frequently due to poor acceptance of a nasogastric tube and unpalatable formulations. This systematic review is an update of a previously published Cochrane review. OBJECTIVES: To evaluate the effectiveness and safety of exclusive EN as primary therapy to induce remission in CD and to examine the importance of formula composition on effectiveness. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2017. We also searched references of retrieved articles and conference abstracts. SELECTION CRITERIA: Randomized controlled trials involving patients with active CD were considered for inclusion. Studies comparing one type of EN to another type of EN or conventional corticosteroids were selected for review. DATA COLLECTION AND ANALYSIS: Data were extracted independently by at least two authors. The primary outcome was clinical remission. Secondary outcomes included adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. We performed intention-to-treat and per-protocol analyses for the primary outcome. Heterogeneity was explored using the Chi2 and I2 statistics. The studies were separated into two comparisons: one EN formulation compared to another EN formulation and EN compared to corticosteroids. Subgroup analyses were based on formula composition and age. Sensitivity analyses included abstract publications and poor quality studies. We used the Cochrane risk of bias tool to assess study quality. We used the GRADE criteria to assess the overall quality of the evidence supporting the primary outcome and selected secondary outcomes. MAIN RESULTS: Twenty-seven studies (1,011 participants) were included. Three studies were rated as low risk of bias. Seven studies were rated as high risk of bias and 17 were rated as unclear risk of bias due to insufficient information. Seventeen trials compared different formulations of EN, 13 studies compared one or more elemental formulas to a non-elemental formula, three studies compared EN diets of similar protein composition but different fat composition, and one study compared non-elemental diets differing in glutamine enrichment. Meta-analysis of 11 trials (378 participants) demonstrated no difference in remission rates. Sixty-four per cent (134/210) of patients in the elemental group achieved remission compared to 62% (105/168) of patients in the non-elemental group (RR 1.02, 95% CI 0.88 to 1.18; GRADE very low quality). A per-protocol analysis (346 participants) produced similar results (RR 1.04, 95% CI 0.91 to 1.18). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no differences in remission rates. An analysis of 7 trials including 209 patients treated with EN formulas of differing fat content (low fat: < 20 g/1000 kCal versus high fat: > 20 g/1000 kCal) demonstrated no difference in remission rates (RR 1.03; 95% CI 0.85 to 1.26). Very low fat content (< 3 g/1000 kCal) and very low long chain triglycerides demonstrated higher remission rates than higher content EN formulas. There was no difference between elemental and non-elemental diets in adverse event rates (RR 1.00, 95% CI 0.63 to 1.60; GRADE very low quality), or withdrawals due to adverse events (RR 1.29, 95% CI 0.80 to 2.09; GRADE very low quality). Common adverse events included nausea, vomiting, diarrhea and bloating.Ten trials compared EN to steroid therapy. Meta-analysis of eight trials (223 participants) demonstrated no difference in remission rates between EN and steroids. Fifty per cent (111/223) of patients in the EN group achieved remission compared to 72% (133/186) of patients in the steroid group (RR 0.77, 95% CI 0.58 to 1.03; GRADE very low quality). Subgroup analysis by age showed a difference in remission rates for adults but not for children. In adults 45% (87/194) of EN patients achieved remission compared to 73% (116/158) of steroid patients (RR 0.65, 95% CI 0.52 to 0.82; GRADE very low quality). In children, 83% (24/29) of EN patients achieved remission compared to 61% (17/28) of steroid patients (RR 1.35, 95% CI 0.92 to 1.97; GRADE very low quality). A per-protocol analysis produced similar results (RR 0.93, 95% CI 0.75 to 1.14). The per-protocol subgroup analysis showed a difference in remission rates for both adults (RR 0.82, 95% CI 0.70 to 0.95) and children (RR 1.43, 95% CI 1.03 to 1.97). There was no difference in adverse event rates (RR 1.39, 95% CI 0.62 to 3.11; GRADE very low quality). However, patients on EN were more likely to withdraw due to adverse events than those on steroid therapy (RR 2.95, 95% CI 1.02 to 8.48; GRADE very low quality). Common adverse events reported in the EN group included heartburn, flatulence, diarrhea and vomiting, and for steroid therapy acne, moon facies, hyperglycemia, muscle weakness and hypoglycemia. The most common reason for withdrawal was inability to tolerate the EN diet. AUTHORS' CONCLUSIONS: Very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD. Protein composition does not appear to influence the effectiveness of EN for the treatment of active CD. EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient adherence with this therapy.

Emerging issues in the medical management of Crohn's disease.

PURPOSE OF REVIEW: This article describes why this review is timely and relevant. The medical management of Crohn's disease is complex, and is changing rapidly with the introduction of novel therapeutic agents and management strategies. RECENT FINDINGS: We have summarized and synthesized up-to-date evidence and opinion on the proper role and composition of combined immunosuppressive therapy in the management of Crohn's disease, the optimal time for introduction of immunomodulator and/or biologic therapies, and the benefits of therapeutic drug monitoring for biologic therapies. We also discuss the evidence supporting the benefits of the novel agents vedolizumab and ustekinumab, and discuss where they will fit into the therapeutic landscape. SUMMARY: The review will provide evidence to support decision making in patients with Crohn's disease requiring biologic and/or immunomodulator therapy.

Anti-TNFα therapies are safe during pregnancy in women with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: The use of TNFα antagonists is well described for inflammatory bowel disease (IBD), but their safety profile during pregnancy is yet to be fully elucidated. A systematic review and meta-analysis were performed to identify studies that explored the safety of anti-TNFα therapy during pregnancy in patients with IBD. METHODS: A systematic literature search was conducted to identify studies that investigated the pregnancy outcomes among women with IBD on anti-TNFα therapy. The primary outcome was the overall rate of unfavourable pregnancy-related outcomes among women with IBD on anti-TNFα therapy. Secondary outcomes included rates of abortions (spontaneous or elective), preterm delivery, low birth weight, and congenital malformations. Odds ratios (OR) with 95% confidence interval (CI) are reported. Eligible studies used an observational or interventional design, enrolled subjects with IBD on anti-TNFα therapy for at least 1 trimester and compared outcomes with appropriately matched controls. RESULTS: Overall, 5 studies with a total of 1216 participants were eligible for inclusion in the meta-analysis. There was no significant difference in the rates of total unfavourable pregnancy outcomes between pregnant women with IBD who were on anti-TNFα therapy and controls not on anti-TNFα therapy (OR, 1.00 [95% CI, 0.72-1.41]). Similarly, there were no statistically significant differences in the rates of abortion (OR, 1.53 [95% CI, 0.97-2.41]), preterm birth (OR, 1.00 [95% CI, 0.62-1.62]), low birth weight (OR, 1.05 [95% CI, 0.62-1.78]), or congenital malformation (OR, 1.10 [95% CI, 0.58-2.09]). CONCLUSIONS: The use of anti-TNFα therapy does not seem to increase the risk of unfavorable pregnancy outcomes among women with IBD, although the optimal timing of therapy through pregnancy and the postpartum period was not assessed in this analysis. These data can help counsel patients around family planning and perinatal management.

An audit of influenza vaccination status in adults with inflammatory bowel disease.

BACKGROUND: Several guidelines recommend influenza vaccination for high-risk patients, including those on immune-suppressing medications (IS). OBJECTIVE: To assess the vaccination status and immunization history of an outpatient inflammatory bowel disease (IBD) population for H1N1 and seasonal influenza. RESULTS: Among 250 patients, 104 (41.6%) had been immunized against H1N1 and 62 (24.8%) against seasonal influenza, and 158 (63.2%) were taking IS (azathioprine, 6-mercaptopurine, infliximab, adalimumab, methotrexate, cyclosporine or prednisone). Among subjects on IS, the presence of comorbidities warranting vaccination was associated with higher likelihood of H1N1 immunization (62.5% versus 35.8%; P=0.022) but not of seasonal influenza vaccination (25.0% versus 17.2%; P=0.392). Among patients without comorbidities warranting vaccination, IS was associated with a decreased likelihood of vaccination against seasonal influenza (17.2% versus 30.7%; P=0.036) but not H1N1 (35.8% versus 41.3%; P=0.46). The frequency of H1N1 vaccination was significantly higher among patients who visited a general practitioner at least once yearly (45.7% versus 20%; P=0.0027), with a similar trend for seasonal influenza vaccination (27.1% versus 12.5%; P=0.073). Among 91 patients on IS who declined vaccination, 39.6% reported fear of immediate side effects, 29.7% reported concerns about developing serious medical complications, 15.4% reported concerns about activating IBD and 15.4% were not aware that vaccination was indicated. CONCLUSIONS: Current strategies for vaccinating IBD patients on IS are inadequate. Primary care provider education, incentive programs and regular primary care contact may improve immunization uptake.