Luis Abreu

Double-guidewire technique for difficult bile duct cannulation: a multicenter randomized, controlled trial

BACKGROUND ERCP can be associated with serious complications. Difficulty in common bile duct (CBD) cannulation is one of the main risk factors for post-ERCP pancreatitis. The double-guidewire technique (DGT) has been considered a promising alternative approach in difficult cannulation situations. OBJECTIVE To compare the performance of DGT with the standard cannulation technique (SCT) in patients in whom CBD cannulation is difficult to perform. DESIGN Multicenter randomized, controlled trial. SETTING Six tertiary referral centers. PATIENTS A total of 188 patients with difficult CBD cannulation defined by completion of 5 unsuccessful cannulation attempts were enrolled. INTERVENTIONS Ninety-seven patients were assigned to the DGT group and 91 to the SCT group. Both techniques were compared for an extra 10 cannulation attempts. MAIN OUTCOME MEASUREMENTS CBD cannulation rate, number of attempts required to cannulate, and ERCP-related complications. RESULTS Successful CBD cannulation was achieved in 46 of 97 (47%) patients in the DGT group compared with 51 of 91 (56%) in the SCT group (OR 0.85; 95% CI, 0.64-1.12). The median number of attempts required for each group was 9 and 7, respectively (P = .128). The incidence of post-ERCP pancreatitis was 17% in the DGT group and 8% in the SCT group (OR 2.13; 95% CI, 0.89-5.05). LIMITATIONS Reduced number of enrolled subjects and a lack of detailed information regarding the number and extent of pancreatic duct contrast injections. CONCLUSIONS In patients with difficult CBD cannulation, DGT was not superior to SCT in achieving CBD cannulation. DGT might be associated with a higher risk of post-ERCP pancreatitis.

Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients

Aliment Pharmacol Ther 2011; 34: 544–554

Long-term Oral Tacrolimus Therapy in Refractory to Infliximab Fistulizing Crohn's Disease.A Pilot Study

Aims: To evaluate efficacy and safety of oral tacrolimus in cases of fistulizing Crohns disease (FCD), which is refractory to conventional therapy including infliximab. Methods: Patients with fistulas, previously and unsuccessfully treated with all conventional therapy (i.e., antibiotics, azathioprine, or 6‐mercaptopurine and infliximab), were enrolled in a prospective, uncontrolled, open‐label study of long‐term treatment with oral tacrolimus (0.05 mg/kg every12 h). The evaluation of the clinical response was complemented by use of the perianal Crohns disease activity index (PCDAI) and magnetic resonance imaging‐based score (MRS) with determined periodicity. Results: Ten patients were included in the study (enterocutaneous fistula, 3 patients; perianal fistula, 4 patients; rectovaginal fistula, 3 patients) with 6 to 24 months of follow‐up. Five patients were steroid‐dependent, and 4 patients needed maintenance treatment with immunosuppressant agents. Four patients (40%) achieved complete clinical responses, which were verified by PCDAI and MRS. Five patients (50%) achieved partial responses (i.e., important decreases in fistula drainage, size, discomfort, and PCDAI/MRS values). Decreases in both the PCDAI and MRS were statistically significant (P < 0.05). All steroid‐dependent patients stopped therapy with prednisone, and concomitant immunosuppressive therapy was tapered. The response was maintained, and no new flare‐up of the disease was observed. Only mild adverse events were detected (1 patient withdrew from treatment due to headache), and no case of nephrotoxicity or diabetes was detected. One patient had received no benefit from therapy after 6 months. Conclusions: Oral tacrolimus could be an effective and safe treatment for patients with FCD, even if there has been no response to infliximab treatment. Randomized studies are needed to compare oral tacrolimus with infliximab in terms of efficacy, safety, and costs.

Interferon and prednisone therapy in chronic hepatitis C with non-organ-specific antibodies

BACKGROUND/AIMS The relationship between hepatitis C virus and autoimmunity is controversial. The issue is particularly relevant in those patients with hepatitis C virus infection and serum autoantibodies in whom steroids can exacerbate viral replication and interferon can lead to decompensated liver disease. The aim of this study was to evaluate the response to a course of prednisone or interferon-alpha 2b. METHODS/RESULTS The 12 study patients had biopsy-proven chronic hepatitis, serum HCV-RNA (by nested polymerase chain reaction) and non-organ-specific antibodies (eight with liver and kidney microsomal antibodies and four with antinuclear antibodies). Eight of these 12 patients received a 4-month course of prednisone (0.5 mg/kg per day), which increased alanine aminotransferase (mean +/- SE) (174 +/- 31 vs 252 +/- 18 U/l, p < 0.05) and bilirubin levels (0.96 +/- 0.17 vs 1.42 +/- 0.18 mg/dl, p = 0.09), without changing liver histology (Knodell index, 13.6 +/- 0.4 vs 13.1 +/- 0.3). Subsequent treatment with interferon in the 12 patients reduced serum alanine aminotransferase levels (170 +/- 20 vs 41 +/- 7 U/l, p < 0.0001) and portal and lobular inflammation (Knodell index, 13.8 +/- 0.5 vs 8.4 +/- 0.2, p < 0.001). A complete response to interferon was observed in ten of these patients (83%), eight of whom had previously been treated with prednisone. Serum HCV-RNA level decreased in interferon responders. A sustained response 1 year after withdrawal of interferon was seen in only five patients (41%). CONCLUSIONS Patients with chronic hepatitis C and autoantibodies show a favorable response to interferon, but not to prednisone. The latter regimen can exacerbate liver necrosis in these subjects. The presence of autoantibodies in hepatitis C patients does not modify the response to interferon.

I.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life

AIM To determine the dose-related effects of a novel probiotic combination, I.31, on irritable bowel syndrome (IBS)-related quality of life (IBS-QoL). METHODS A multicenter, randomized, double-blind, placebo-controlled intervention clinical trial with three parallel arms was designed. A total of 84 patients (53 female, 31 male; age range 20-70 years) with IBS and diarrhea according to Rome-III criteria were randomly allocated to receive one capsule a day for 6 wk containing: (1) I.31 high dose (n = 28); (2) I.31 low dose (n = 27); and (3) placebo (n = 29). At baseline, and 3 and 6 wk of treatment, patients filled the IBSQoL, Visceral Sensitivity Index (VSI), and global symptom relief questionnaires. RESULTS During treatment, IBS-QoL increased in all groups, but this increment was significantly larger in patients treated with I.31 than in those receiving placebo (P = 0.008). After 6 wk of treatment, IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups, respectively (P = 0.041 and P = 0.023 vs placebo), but only 9 ± 3 in the placebo group. Gut-specific anxiety, as measured with VSI, also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics (by 10 ± 2 and 14 ± 2 points, high and low dose respectively, P < 0.05 for both vs 7 ± 1 score increment in placebo). Symptom relief showed no significant changes between groups. No adverse drug reactions were reported following the consumption of probiotic or placebo capsules. CONCLUSION A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea.

Predictors of response to infliximab in patients with fistulizing Crohn's disease

OBJECTIVE To evaluate the efficacy and toxicity of infliximab for the treatment of fistulizing Crohns disease. METHODS Consecutive patients with fistulizing Crohns disease receiving infliximab were prospectively enrolled. Partial response was defined as a reduction of 50% or more from base-line in the number of draining fistulae. Complete response was defined as the closure of all fistulae. The influence of different variables on the efficacy of infliximab was evaluated. RESULTS 108 patients were included. The disease was inflammatory plus fistulizing in 18% and only fistulizing in 82%. After the third infusion of infliximab the response was partial in 26% and complete in 57%. Response (%) rates (partial/complete) depending on fistula location were: enterocutaneous (25/68%), perianal (35/60%), rectovaginal (36/64%), and enterovesical (20/40%). None of the studied variables (including concomitant immunosuppressive therapy) correlated with efficacy of infliximab in the multivariate analysis. Incidence of adverse effects (21%) depending on the dose of infliximab was: first dose (5.6%), second (7.4%), and third (11.1%). CONCLUSIONS Infliximab is an efficacious treatment for fistulizing Crohns disease. Partial response was achieved in approximately one third of the patients, and complete response in more than half. No studied variable was predictive of response. Adverse effects were relatively infrequent and mild.

Increased IgM B cell differentiation lymphokine production by T lymphocytes from patients with primary biliary cirrhosis

Hypergammaglobulinemia, mainly due to increased serum immunoglobulin M concentrations, is a common and distinctive feature of primary biliary cirrhosis. T-B cell cooperation plays a pivotal role in the regulation of immunoglobulin secretion. In this paper, the production of regulatory B lymphokines by T cells, as well as the functional response of B lymphocytes to these molecules, was investigated in patients with primary biliary cirrhosis. T cells from patients with primary biliary cirrhosis have an enhanced ability to produce lymphokines that regulate the proliferation of B cells and their differentiation to immunoglobulins G- and M-secreting cells. In contrast, the cellular production of lymphokines involved in the induction of immunoglobulin A-secreting cells was normal. Simultaneously, the proliferation and differentiation of purified B cells in response to stimulation with surface immunoglobulin ligands and lymphokines were normal. These results suggest that the elevated serum levels of immunoglobulins M and G found in patients with primary biliary cirrhosis could be ascribed to an enhanced lymphokine-mediated T-B cooperation.

Timing of Thiopurine or Anti-TNF Initiation Is Associated with the Risk of Major Abdominal Surgery in Crohn's Disease: A Retrospective Cohort Study.

INTRODUCTION Early stages of Crohns disease [CD] are predominantly inflammatory and early treatment could be useful to change the natural history of CD. We aimed to evaluate the impact of early treatment in our cohort of CD patients. METHODS We retrospectively reviewed clinical records of all CD patients at our centre who have received immunomodulators. Time from diagnosis to first CD-related major abdominal surgery or end of follow-up was considered. Dates of diagnosis, of starting immunomodulators (thiopurines / anti-tumour necrosis factor [TNF]), and of the first CD-related surgery when appropriate were collected. RESULTS Of 422 patients who received thiopurines, 189 operated patients started thiopurines after a median of 117 months (interquartile range [IQR] 44-196) since diagnosis; non-operated patients, after a median of 30 months [IQR 6-128], p < 0,005. Odds ratio [OR] for surgery was 1.006 (95% confidence interval [CI]1.004-1008) for each month of delay in starting thiopurines. Among 272 patients who received anti-TNFs, 137 operated patients started anti-TNFs after a median of 166 months [IQR 90-233] since diagnosis; non-operated patients after a median of 59 months [IQR 14-162]; p < 0,005. OR for surgery was 1.008 [95% CI 1.005-1.010] for each month of delay in starting anti-TNFs. Among 467 patients who received thiopurines and/or anti-TNF, 210 operated patients started any immunomodulator after a median of 120 months [IQR 48-197] since diagnosis and non-operated patients after a median of 30 months [IQR 6-126], p < 0,005. OR for surgery was 1.008 [95% CI 1.005-1.010] for each month of delay in starting immunomodulators. CONCLUSIONS In our experience, time between diagnosis and thiopurine or anti-TNF initiation was associated with the risk of major abdominal surgery in Crohns disease.

Severe splenic rupture after colorectal endoscopic submucosal dissection

Splenic rupture (SR) after colonoscopy is a very rare but potentially serious complication. Delayed diagnosis is common, and may increase morbidity and mortality associated. There is no clear relation between SR and difficult diagnostic or therapeutic procedures, but it has been suggested that loop formation and excessive torquing might be risk factors. This is a case of a 65-year-old woman who underwent endoscopic submucosal dissection (ESD) for lateral spreading tumor in the descending colon, and 36 h afterwards presented symptoms and signs of severe hypotension due to SR. Standard splenectomy was completed and the patient recovered uneventfully. Colorectal ESD is usually a long and position-demanding technique, implying torquing and loop formation. To our knowledge this is the first case of SR after colorectal ESD reported in the literature. Endoscopists performing colorectal ESD in the left colon must be aware of this potential complication.

Using of magnetic resonance enterography in the management of Crohn's disease of the small intestine: First year of experience

OBJECTIVE to describe the experience at two tertiary centres during the first year of use of magnetic resonance enterography (MRE) for the management of Crohns disease (CD): indications and influence of the technique in clinical decision making. MATERIALS AND METHODS retrospective descriptive study in which patients who underwent MRE were included consecutively. Epidemiological and clinical data were collected from the patients, as well as the indication for the study and how it influenced clinical decision making in the 10 days following the radiological study. RESULTS 24 MREs were performed in suspected CD and 126 known CD; partial bowel obstruction in 53 patients (42%), monitoring of medical treatment in 34 (27%), due to incomplete ileocolonoscopy in 16 (13%), extension study of the small intestine in 15 (12%) and suspected complicated CD in 8 patients (6%). The MRE influenced in a change in treatment in 83 (55.3%) patients: 16 (10.7%) started with immunosuppressants, 41 (27.3%) with anti-TNFα were started on or switched, 15 (10%) were ordered surgery and in 3 (2%) changed from combined therapy to monotherapy. The MRE had less influence on clinical decision making in the group in which the indication was suspected CD (p < 0.05). CONCLUSIONS the use of MRE helped on decision making in more than half of patients, especially with regards to decisions related to the use of biological therapies and the indication for surgery. MRE was less useful in suspected CD patients.