Govind K. Makharia

The Probiotic Preparation, VSL#3 Induces Remission in Patients With Mild-to-Moderately Active Ulcerative Colitis

BACKGROUND & AIMS Probiotics can maintain ulcerative colitis (UC) in remission effectively, but little is known of their ability to induce remission. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of a high-potency probiotic, VSL#3, for the treatment of mild-to-moderately active UC. METHODS Adult patients with mild-to-moderate UC were assigned randomly to groups that were given 3.6 x 10(12) CFU VSL#3 (n = 77) or placebo (n = 70), twice daily for 12 weeks. The primary end point was a 50% decrease in the Ulcerative Colitis Disease Activity Index (UCDAI) at 6 weeks. The secondary end points included remission by 12 weeks and reduction in total individual UCDAI parameters from baseline at 12 weeks. Intention-to-treat analysis was performed. RESULTS At week 6, the percentage of patients with an improvement in UCDAI score that was greater than 50% was significantly higher in the group given VSL#3 (25; 32.5%) than the group given placebo (7; 10%) (P = .001). At week 12, there were 33 patients given VSL#3 (42.9%) who achieved remission, compared with 11 patients given placebo (15.7%) (P < .001). Furthermore, significantly more patients given VSL#3 (40; 51.9%) achieved a decrease in their UCDAI that was greater than 3 points, compared with those given placebo (13; 18.6%) (P < .001). The VSL#3 group had significantly greater decreases in UCDAI scores and individual symptoms at weeks 6 and 12, compared with the placebo group. CONCLUSIONS VSL#3 is safe and effective in achieving clinical responses and remissions in patients with mild-to-moderately active UC.

Asia Pacific consensus recommendations for colorectal cancer screening

Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5–9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.

Usefulness of intralesional triamcinolone in treatment of benign esophageal strictures

INTRODUCTION The cornerstone treatment for benign esophageal strictures is endoscopic dilation. There are reports suggesting that intralesional corticosteroid injection decreases the frequency of endoscopic dilation. METHODS Seventy-one patients (mean age 42.39 [17.52] years; range, 13-78 years) with benign esophageal strictures (corrosive 29, peptic 14, anastomotic 19, radiation-induced 9) were recruited for this study. All were being managed with a program of intermittent endoscopic dilation by using over-the-wire polyvinyl dilators. All patients were treated by intralesional injections of triamcinolone acetonide (40 mg/mL diluted 1:1 with saline solution) by using a 23-gauge, 5-mm long sclerotherapy needle in aliquots of 0.5 mL. At each session, 4 injections (4 quadrants) were made at the proximal margin of the stricture with another 4 injections into the strictured segment itself whenever possible. The intervals between dilations and frequency of dilations were calculated before and after triamcinolone injections. A periodic dilation index (defined as number of dilations required per month) before and after the triamcinolone injections was calculated. RESULTS The overall mean (SD) duration of treatment before intralesional injection was 10.9 (19.8) months (range, 1-120 months) and the mean number (SD) of esophageal dilations required was 9.67 (13.06) (range, 1-70). The mean number of sessions of intralesional injection was 1.4 (0.62). After initiation of intralesional injections mean follow-up was 8.1 (5.6) months (range 3-30 months) and the mean number of esophageal dilations was 3.8 (3.0) (range 0-16). The periodic dilation index decreased significantly from 1.24 (0.05) (range 0.13-3.16) before injection to 0.5 (0.33) (range, 0-2) after injection (p < 0.001). For each category of stricture, the periodic dilation index decreased significantly: corrosive, 1.24 (0.5) to 0.53 (0.34) (p < 0.001); peptic, 0.92 (0.44) to 0.42 (0.2) (p < 0.001); anastomotic, 1.24 (0.49) to 0.51 (0.4) (p < 0.001); and radiation-induced, 1.32 (0.6) to 0.6 (0.3) (p < 0.02). CONCLUSION Intralesional injections of triamcinolone augment the effects of dilation in patients with benign esophageal strictures.

Prevalence of celiac disease in the northern part of India: A community based study

Background and Aim:  While celiac disease is estimated to affect about 1% of the worlds population, it is thought to be uncommon not only in India but in Asia also. There is a lack of studies on the prevalence of celiac disease from Asian nations. The aim of the present study was to estimate the prevalence of celiac disease in the community.

Asian consensus on irritable bowel syndrome.

Background and Aims:  Many of the ideas on irritable bowel syndrome (IBS) are derived from studies conducted in Western societies. Their relevance to Asian societies has not been critically examined. Our objectives were to bring to attention important data from Asian studies, articulate the experience and views of our Asian experts, and provide a relevant guide on this poorly understood condition for doctors and scientists working in Asia.

Clinical, Endoscopic, and Histological Differentiations Between Crohn's Disease and Intestinal Tuberculosis

OBJECTIVES:The clinical, endoscopic, and histological features of Crohns disease (CD) and intestinal tuberculosis mimic each other so much that it becomes difficult to differentiate between them. The aim was to find out clinical, endoscopic, and histological predictor features for differentiation between CD and intestinal tuberculosis.METHODS:We recruited 106 patients, 53 each with CD and intestinal tuberculosis, in this study. The clinical, histological, and endoscopic features were subjected to univariate, bivariate, and multivariate analyses. On the basis of regression coefficients of the final multivariate logistic model, a score to discriminate between CD and intestinal tuberculosis was devised. For the validation of the score, the same model was tested on 20 new patients, each with CD and intestinal tuberculosis.RESULTS:On univariate analysis, although longer duration of disease, chronic diarrhea, blood in stool, perianal disease, extra-intestinal manifestations, involvement of left colon, skip lesions, aphthous ulcers, cobblestoning, longitudinal ulcers, focally enhanced colitis, and microgranulomas were significantly more common in CD, partial intestinal obstruction, constipation, presence of nodular lesions, higher number, and larger granulomas were significantly more common in intestinal tuberculosis. On multivariate analysis, blood in stool (odds ratio (OR) 0.1 (confidence interval (CI) 0.04–0.5)), weight loss (OR 9.8 (CI 2.2–43.9)), histologically focally enhanced colitis (OR 0.1 (CI 0.03–0.5)), and involvement of sigmoid colon (OR 0.07(0.01–0.3)) were independent predictors of intestinal tuberculosis. On the basis of regression coefficients of the final multivariate logistic model, a score that varied from 0.3 to 9.3 was devised. Higher score predicted more likelihood of intestinal tuberculosis. Once the cutoff was set at 5.1, then the sensitivity, specificity, and ability to correctly classify the two diseases were 83.0, 79.2, and 81.1%, respectively. Area under the curve for receiver-operating characteristic (ROC) to assess the ability of these features to discriminate between CD and intestinal tuberculosis was 0.9089. The area under ROC in the validation data set was 89.2% (95% CI 0.79–0.99). With a similar cutoff score of 5.1, sensitivity and specificity in the validation model were 90% (95% CI 66.9–98.2) and 60% (95% CI 36.4–80.0), respectively.CONCLUSIONS:Blood in stool, weight loss, focally enhanced colitis, and involvement of the sigmoid colon were the most important features in differentiating CD from intestinal tuberculosis.

Predictors of unsuccessful mechanical lithotripsy and endoscopic clearance of large bile duct stones.

BACKGROUND Mechanical lithotripsy is used to break large bile duct stones. This study investigated the predictors of unsuccessful mechanical lithotripsy. METHODS Consecutive patients with bile duct stones underwent endoscopic retrograde cholangiography, sphincterotomy, and basket removal of stones. Mechanical lithotripsy was performed for stones of large size (>15 mm diameter) that precluded extraction intact. Success was defined as complete clearance of the duct. Various predictive factors, including size and number of stones, stone impaction, serum bilirubin, presence of cholangitis, and bile duct diameter were analyzed in relation to the success or failure of lithotripsy. RESULTS A total of 669 patients underwent endoscopic retrograde cholangiography for suspected choledocholithiasis, which was found in 401 patients. Of the latter patients, 87 had large stones that required mechanical lithotripsy. Lithotripsy was successful in 69 (79%) patients. Impaction of the stone(s) in the bile duct was the only significant factor that predicted failure of lithotripsy and consequent failure of bile duct clearance. Other factors, including stone size, were not significant. CONCLUSIONS Mechanical lithotripsy is successful in about 79% of patients with large bile duct stones. The only significant factor that predicts failure of mechanical lithotripsy is stone impaction in the bile duct.

The Asia-Pacific consensus on ulcerative colitis

Inflammatory bowel disease (IBD) is increasing in many parts of the Asia‐Pacific region. There is a need to improve the awareness of IBD and develop diagnostic and management recommendations relevant to the region. This evidence‐based consensus focuses on the definition, epidemiology and management of ulcerative colitis (UC) in Asia.

Inherited prothrombotic defects in Budd-Chiari syndrome and portal vein thrombosis: a study from North India.

We studied 57 patients with Budd-Chiari syndrome (BCS) and 48 with portal vein thrombosis (PVT) for underlying inherited prothrombotic defects such as protein C, protein S, and antithrombin III deficiencies. Genetic mutations for factor V Leiden, prothrombin gene 20210A, and methyltetrahydrofolate reductase (MTHFR) C677T were studied in 29 patients in each group. Inherited prothrombotic defects were detected in 16 (28%) of 57 patients with BCS and 7 (15%) of 48 patients with PVT. Factor V Leiden mutation was the most common prothrombotic defect in BCS (5/29 [17%]) followed by protein C deficiency (7/57 [12%]) and protein S deficiency (4/57 [7%]), whereas in PVT, protein C deficiency was the most common inherited prothrombotic defect (4/48 [8%]) followed by protein S deficiency (2/48 [4%]). The factor V Leiden mutation was detected in only 1 (3%) of 29 cases of PVT. The heterozygous MTHFR C677T mutation was detected in 7 (24%) of 29 patients with BCS and 6 (21%) of 29 patients with PVT. Antithrombin III deficiency, homozygous MTHFR C677T mutation, and prothrombin G20210A mutation were not detected in any patients.

Safety of 3 Different Reintroduction Regimens of Antituberculosis Drugs after Development of Antituberculosis Treatment–Induced Hepatotoxicity

BACKGROUND Drug-induced hepatotoxicity (DIH) is the most common adverse drug reaction leading to interruption of antituberculosis treatment. Worldwide, different reintroduction regimens have been advocated, but no consensus guidelines are available. Reintroduction of antituberculosis drugs in patients with DIH has never been studied systematically. We aimed to compare the safety of 3 different reintroduction regimens of antituberculosis drugs in patients with antituberculosis DIH. METHODS A total of 175 patients with a diagnosis of antituberculosis DIH were randomized to receive 1 of 3 different predefined reintroduction regimens of antituberculosis drugs and were evaluated prospectively. Patients in arm I were given isoniazid, rifampicin, and pyrazinamide simultaneously at full dosage from day 1. In arm II, drugs were administered in a manner similar to that recommended in the American Thoracic Society guidelines for reintroduction. In arm III, drugs were administered in accordance with British Thoracic Society guidelines. RESULTS Nineteen patients (10.9%) had recurrence of DIH during follow-up. Eight, 6, and 5 patients had recurrence of hepatitis in arms I, II, and III, respectively (P = .69). Of all the clinical and laboratory parameters, pretreatment serum albumin level was the only statistically significant predictor of future recurrence of DIH on reintroduction of antituberculosis drugs (P < .01). CONCLUSIONS The recurrence rate of hepatotoxicity was not significantly different between the 3 groups. According to the findings of the present study, all 3 of the potentially hepatotoxic drugs (isoniazid, rifampicin, and pyrazinamide) can be reintroduced simultaneously at full dosage safely from day 1, especially for patients with bilateral extensive pulmonary tuberculosis, to halt disease transmission or to treat patients with life-threatening tuberculosis. TRIAL REGISTRATION ClinicalTrials.gov identifier number: NCT00405301.