Vicente Lorenzo-Zúñiga

Impact of azathioprine on the prevention of postoperative Crohn's disease recurrence: Results of a prospective, observational, long-term follow-up study

Background: Postoperative recurrence (PR) occurs early after intestinal resection in >75% of Crohns disease (CD) patients. No well‐established strategy for long‐term PR prevention is available. The aim was to prospectively evaluate the long‐term endoscopic and clinical outcomes of postoperative CD on maintenance treatment with azathioprine (AZA), especially in patients who developed endoscopic lesions confined to the ileocolic anastomosis. Methods: Long‐term AZA therapy (2–2.5 mg/kg/day) was initiated immediately after surgery in 56 consecutive patients who underwent a curative intestinal resection. Clinical and biological assessments every 3 months, as well as yearly endoscopic evaluation, were performed until the end of the study or clinical PR (CPR). Results: Thirty‐seven patients (70%) showed mucosal lesions at endoscopy after a median of 12 months (range 12–60); however, in 15 of these patients lesions were confined to the anastomosis and only 6 showed endoscopic progression, but none of them developed CPR. Among the remaining 22 patients with endoscopic PR (EPR), 23% suffered a CPR during follow‐up. Thirty percent of patients remained free of EPR after a median follow‐up of 33 months (range 12–84). The cumulative probability of EPR was 44%, 53%, 69%, and 82%, at 1, 2, 3, and 5 years, respectively. No predictive factors of EPR were found. Conclusions: Early postoperative use of AZA seems to delay EPR development in comparison to historical series or placebo groups in randomized controlled trials. Although usually considered as endoscopic recurrence, those lesions confined to the ileocolonic anastomosis are not likely to progress or to become symptomatic in the short term.

Insulin-like growth factor-I improves intestinal barrier function in cirrhotic rats

Background and aims: In liver cirrhosis, disruption of the intestinal barrier facilitates bacterial translocation and spontaneous bacterial peritonitis. Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesised by hepatocytes that displays hepatoprotective activities and trophic effects on the intestine. The aim of this study was to investigate the effect of IGF-I on intestinal barrier function in cirrhotic rats. Methods: In rats with carbon tetrachloride induced cirrhosis, we investigated the effect of IGF-I therapy on: (a) portal pressure; (b) intestinal histology and permeability to endotoxin and bacteria; (c) intestinal expression of cyclooxygenase 2 (COX-2) and tumour necrosis factor α (TNF-α), two factors that influence in a positive and negative manner, respectively, the integrity of the intestinal barrier; (d) intestinal permeability to 3H-mannitol in rats with bile duct ligation (BDL); and (e) transepithelial electrical resistance (TER) of polarised monolayers of rat small intestine epithelial cells. Results: IGF-I therapy reduced liver collagen expression and portal pressure in cirrhotic rats, induced improvement in intestinal histology, and caused a reduction in bacterial translocation and endotoxaemia. These changes were associated with diminished TNF-α expression and elevated COX-2 levels in the intestine. IGF-I reduced intestinal permeability in BDL rats and enhanced barrier function of the monolayers of epithelial intestinal cells where lipopolysaccharide (LPS) caused a decrease in TER that was reversed by IGF-I. This effect of IGF-I was associated with upregulation of COX-2 in LPS treated enterocytes. Conclusions: IGF-I enhances intestinal barrier function and reduces endotoxaemia and bacterial translocation in cirrhotic rats. IGF-I therapy might be useful in the prevention of spontaneous bacterial peritonitis in liver cirrhosis.

Combining steroids with enteral nutrition: a better therapeutic strategy for severe alcoholic hepatitis? Results of a pilot study

Background Results of a previous randomized controlled trial comparing the outcome of patients with severe alcoholic hepatitis treated with total enteral nutrition (TEN) or corticosteroids suggest that these treatments act through different mechanisms and may be complementary. We report a pilot study of combined treatment with TEN and a shorter course of steroids in patients with severe alcoholic hepatitis. Methods Thirteen patients with severe alcoholic hepatitis were treated with systemic steroids and TEN. Steroid therapy started with 40 mg oral prednisolone daily, and was progressively tapered as soon as both serum bilirubin and prothrombin time decreased below 50% of their baseline values. TEN (2000 kcal, or 8374 kJ, daily) was administered throughout the hospital stay. Patients were followed for at least 12 months or until death. Results Tapering of prednisolone dose could be started after a mean (SD) of 15.4 (3.8) days, whereas TEN was maintained for 22 (3.8) days. TEN was tolerated in 10 of the 13 patients. The major adverse event attributable to therapy was hyperglycemia requiring insulin therapy, which occurred in 12 of 13 patients. Only two patients (15%) died during the treatment period. Another patient died within the first 2 months of follow-up. In no case was the death due to infectious complications, despite two-thirds of patients developing infections during the treatment period. Infections during follow-up occurred only in three patients. Conclusion This pilot study suggests that TEN associated with a short course of steroids could be a good therapeutic strategy for severe alcoholic hepatitis. This possibility deserves investigation in a randomized controlled trial.

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.

Endoscopist experience as a risk factor for colonoscopic complications

Aim  We aimed to determine the incidence of colonic perforation (CP) following colonoscopy and postpolypectomy bleeding (PPB) in a teaching hospital, assessing the influence of endoscopist experience as a risk factor.

Radiation dose to patients during endoscopic retrograde cholangiopancreatography.

Endoscopic retrograde cholangiopancreatography (ERCP) is an important tool for the diagnosis and treatment of the hepatobiliary system. The use of fluoroscopy to aid ERCP places both the patient and the endoscopy staff at risk of radiation-induced injury. Radiation dose to patients during ERCP depends on many factors, and the endoscopist cannot control some variables, such as patient size, procedure type, or fluoroscopic equipment used. Previous reports have demonstrated a linear relationship between radiation dose and fluoroscopy duration. When fluoroscopy is used to assist ERCP, the shortest fluoroscopy time possible is recommended. Pulsed fluoroscopy and monitoring the length of fluoroscopy have been suggested for an overall reduction in both radiation exposure and fluoroscopy times. Fluoroscopy time is shorter when ERCP is performed by an endoscopist who has many years experience of performing ERCP and carried out a large number of ERCPs in the preceding year. In general, radiation exposure is greater during therapeutic ERCP than during diagnostic ERCP. Factors associated with prolonged fluoroscopy have been delineated recently, but these have not been validated.

Predictors of Clinical Response to Systemic Steroids in Active Ulcerative Colitis

Although systemic steroids remain as the gold standard for the treatment of acute moderate to severe active ulcerative colitis (UC), 15–57% of patients do not achieve clinical remission. We sought to identify clinical, biological, or radiologic predictive factors of response to steroid treatment in acute UC attacks. The medical records of 39 consecutive patients admitted for an acute attack of UC and treated with systemic steroids, were reviewed. Epidemiologic, demographic, and clinical data at baseline and clinical data 3 days after starting steroid treatment were registered. Treatment failure was defined as the need of IV cyclosporine or colectomy before hospital discharge. Twenty-four patients (62%) responded to systemic steroids. Thirteen out of the 15 nonresponders, were treated with IV cyclosporine, avoiding colectomy in 7 cases (54%). More than six bowel movements per day at the third day of treatment, blood in stools in the third day of therapy, extensive UC, and the presence of malnutrition were associated with steroid treatment failure, but only blood in stools (P=.04), and more than six movements per day (P=.012) after 3 days of treatment, were found to be independent predictive factors of steroid refractoriness. In conclusion, clinical evaluation 3 days after starting systemic steroids seems to be the best tool to assess short-term prognosis.

Does methotrexate induce mucosal healing in Crohn's disease?

To the Editor: Mucosal healing has been claimed to be 1 of the most relevant therapeutic endpoints in Crohn’s disease (CD) as far as it seems to be associated with a longer clinical remission and lower likelihood of diseaserelated hospitalizations and intestinal resection. However, clinical indexes poorly correlate with endoscopic lesions. For this reason, endoscopic monitoring to assess mucosal healing has been proposed as an important tool in order to establish the real efficacy of drug therapies in IBD. Among the available maintenance therapies for CD, mucosal healing has only been assessed for infliximab and thiopurines. Methotrexate (MTX) has proven to be effective in inducing and maintaining clinical remission in chronic active CD. Despite that its efficacy seems to be similar to that of azathioprine, it remains a second-line drug. The lack of data showing its potential in inducing mucosal healing may be 1 of the reasons for its limited use in CD. In this perspective, we aimed to assess mucosal healing among patients with clinical response to MTX. CD patients treated with MTX for steroiddependency who entered into clinical remission free of steroids after starting MTX were identified. Eight patients from whom 2 colonoscopies—before and after MTX—were available were included. Disease location was colonic in 4 patients, ileal in 2, and ileocolonic in the remaining 2. Three patients had undergone ileocecal resection in the past. Azathioprine had been initially prescribed for steroid-dependency, but had to be discontinued because of intolerance in 4 and therapeutic failure in the remaining 4 patients. No patient received biological agents. MTX was administered subcutaneously or intramuscularly at an initial dose of 25 mg/ week, for a total 16 weeks; then the dosage was decreased to 15 mg/week as a long-term maintenance treatment. Patients were clinically inactive at the moment MTX was started, as far as they also received prednisone. Endoscopic reports of IBD patients in our center routinely describe the severity of Crohn’s lesions by specifying the presence and location of ulcers, erosions, aphtae, stenosis, and mucosal friability and erythema. As previously used elsewhere, total endoscopic healing was defined by the disappearance of all endoscopic lesions, whereas persistence of minor aphthous ulcers or erosions in the setting of a clear endoscopic improvement was considered partial mucosal healing. Individual characteristics and endoscopic features of patients are shown in Table 1. After

Biodegradable stents in gastrointestinal endoscopy

Biodegradable stents (BDSs) are an attractive option to avoid ongoing dilation or surgery in patients with benign stenoses of the small and large intestines. The experience with the currently the only BDS for endoscopic placement, made of Poly-dioxanone, have shown promising results. However some aspects should be improved as are the fact that BDSs lose their radial force over time due to the degradable material, and that can cause stent-induced mucosal or parenchymal injury. This complication rate and modest clinical efficacy has to be carefully considered in individual patients prior to placement of BDSs. Otherwise, the price of these stents therefore it is nowadays an important limitation.

Improving the quality of colonoscopy bowel preparation using a smart phone application: A randomized trial

Getting ready for a colonoscopy is difficult and involves many steps. Information given to patients is very important for adherence to treatment. We created a novel smart phone application (SPA) aimed to increase bowel preparation quality and patient satisfaction.