Rajan Dhingra

Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis — A randomized, placebo-controlled, pilot study

BACKGROUND AND AIMS Curcumin, an active ingredient of turmeric with anti-inflammatory properties, has been demonstrated to be useful in experimental models of ulcerative colitis (UC). Its efficacy in humans needs to be investigated. METHODS A randomized, double-blind, single-centre pilot trial was conducted in patients with distal UC (<25 cm involvement) and mild-to-moderate disease activity. Forty-five patients were randomized to either NCB-02 (standardized curcumin preparation) enema plus oral 5-ASA or placebo enema plus oral 5-ASA. Primary end point was disease response, defined as reduction in Ulcerative Colitis Diseases Activity Index by 3 points at 8 weeks, and secondary end points were improvement in endoscopic activity and disease remission at 8 weeks. RESULTS Response to treatment was observed in 56.5% in NCB-02 group compared to 36.4% (p=0.175) in placebo group. At week 8, clinical remission was observed in 43.4% of patients in NCB-02 group compared to 22.7% in placebo group (p=0.14) and improvement on endoscopy in 52.2% of patients in NCB-02 group compared to 36.4% of patients in placebo group (p=0.29). Per protocol analysis revealed significantly better outcomes in NCB-02 group, in terms of clinical response (92.9% vs. 50%, p=0.01), clinical remission (71.4% vs. 31.3%, p=0.03), and improvement on endoscopy (85.7% vs. 50%, p=0.04). CONCLUSION In this pilot study we found some evidence that use of NCB-02 enema may tend to result in greater improvements in disease activity compared to placebo in patients with mild-to-moderate distal UC. The role of NCB-02 as a novel therapy for UC should be investigated further.

Fibroscan can avoid liver biopsy in Indian patients with chronic hepatitis B

Liver fibrosis is an established determinant of prognosis and therapy in chronic hepatitis B (CHB). The role of fibroscan in assessing fibrosis in CHB remains unclear. Present study was designed to correlate fibroscan with liver biopsy and determine whether fibroscan can avoid liver biopsy in patients with CHB.

Endoscopic and clinical responses to anti-tubercular therapy can differentiate intestinal tuberculosis from Crohn's disease

Differentiation between intestinal tuberculosis and Crohns disease is difficult and may require therapeutic trial with anti‐tubercular therapy in tuberculosis‐endemic regions.

Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis.

A recent genome-wide association study (GWAS) identified association with variants in X-linked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10-09; rs12008279—OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10-09; rs6622126—OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.

Serum Human Trefoil Factor 3 is a Biomarker for Mucosal Healing in Ulcerative Colitis Patients with Minimal Disease Activity

BACKGROUND The goals of treating ulcerative colitis (UC) have shifted from clinical remission to mucosal healing. Non-invasive biomarkers are required to assess mucosal healing as endoscopic assessment is inconvenient for patients. Enhanced expression of trefoil factor 3 (TFF3, a mucin-associated peptide) is observed after injury of the gastrointestinal tract. The present study was designed to evaluate TFF3 as a biomarker of mucosal healing in patients with UC. METHODS This cross-sectional study included consecutive patients with UC (18-65 years old, disease duration >3 months, either left-sided colitis or pancolitis) who had a Simple Clinical Colitis Activity Index (SCCAI) <6. Colonoscopy was done to assess the presence or absence of mucosal healing (defined using the Baron score) in all patients. Serum level of TFF3 was assessed in all patients and 20 healthy controls. RESULTS Seventy-four patients were included [mean age 37.2±10.9 years, 47 males, median disease duration 4.8 years (IQR 3-8.3), median SCCAI = 0] in the study. Forty-three patients had mucosal healing (Baron score 0 or 1) and 31 did not (Baron score 2 or 3). Median TFF3 level in patients without mucosal healing was significantly higher than that in patients with mucosal healing [1.5 (IQR 1.2-1.9) vs 1.1 (IQR 0.8-1.3) ng/ml, p = 0.01] and healthy controls [0.85 (IQR 0.7-1.2) ng/ml, p < 0.001]. A serum TFF3 level of <1.27 ng/ml (as determined by the receiver operating characteristic curve; area under the curve 0.73) had sensitivity, specificity, positive predictive value and negative predictive value of 70, 68, 75 and 62%, respectively, for identifying patients with mucosal healing. CONCLUSION Serum TFF3 can potentially be used as a biomarker to assess mucosal healing in UC patients.

Accuracy of computed tomographic features in differentiating intestinal tuberculosis from Crohn's disease: a systematic review with meta-analysis

Abdominal computed tomography (CT) can noninvasively image the entire gastrointestinal tract and assess extraintestinal features that are important in differentiating Crohns disease (CD) and intestinal tuberculosis (ITB). The present meta-analysis pooled the results of all studies on the role of CT abdomen in differentiating between CD and ITB. We searched PubMed and Embase for all publications in English that analyzed the features differentiating between CD and ITB on abdominal CT. The features included comb sign, necrotic lymph nodes, asymmetric bowel wall thickening, skip lesions, fibrofatty proliferation, mural stratification, ileocaecal area, long segment, and left colonic involvements. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (DOR) were calculated for all the features. Symmetric receiver operating characteristic curve was plotted for features present in >3 studies. Heterogeneity and publication bias was assessed and sensitivity analysis was performed by excluding studies that compared features on conventional abdominal CT instead of CT enterography (CTE). We included 6 studies (4 CTE, 1 conventional abdominal CT, and 1 CTE+conventional abdominal CT) involving 417 and 195 patients with CD and ITB, respectively. Necrotic lymph nodes had the highest diagnostic accuracy (sensitivity, 23%; specificity, 100%; DOR, 30.2) for ITB diagnosis, and comb sign (sensitivity, 82%; specificity, 81%; DOR, 21.5) followed by skip lesions (sensitivity, 86%; specificity, 74%; DOR, 16.5) had the highest diagnostic accuracy for CD diagnosis. On sensitivity analysis, the diagnostic accuracy of other features excluding asymmetric bowel wall thickening remained similar. Necrotic lymph nodes and comb sign on abdominal CT had the best diagnostic accuracy in differentiating CD and ITB.

Development and validation of visceral fat quantification as a surrogate marker for differentiation of Crohn's disease and Intestinal tuberculosis.

Crohns disease (CD) and intestinal tuberculosis (ITB) have close phenotypic resemblance. Mesenteric fat (a component of visceral fat [VF]) hypertrophy and fat wrapping, which is visible radiologically as fibrofatty proliferation, is seen more commonly in CD than in ITB.

Long‐term pain relief with optimized medical treatment including antioxidants and step‐up interventional therapy in patients with chronic pancreatitis

Abdominal pain is difficult to treat in patients with chronic pancreatitis (CP). Medical therapy including antioxidants has been shown to relieve pain of CP in the short‐term. Our aim was to study the long‐term results of optimized medical and interventional therapy for pain relief in patients with CP with a step‐up approach.

Frequency, natural course and clinical significance of symptomatic terminal ileitis

Treatment guidelines for managing symptomatic terminal ileitis (TI) are lacking. We followed up a cohort of symptomatic TI patients to conduct an algorithm for their management.

Role of random biopsies in surveillance of dysplasia in ulcerative colitis patients with high risk of colorectal cancer.

Background/Aims Recent data suggest that the incidence of ulcerative colitis (UC) related colorectal cancer (CRC) in India is similar to that of West. The optimum method for surveillance is still a debate. Surveillance with random biopsies has been the standard of care, but is a tedious process. We therefore undertook this study to assess the yield of random biopsy in dysplasia surveillance. Methods Between March 2014 and July 2015, patients of UC attending the Inflammatory Bowel Disease clinic at the All India Institute of Medical Sciences with high risk factors for CRC like duration of disease >15 years and pancolitis, family history of CRC, primary sclerosing cholangitis underwent surveillance colonoscopy for dysplasia. Four quadrant random biopsies at 10 cm intervals were taken (33 biopsies). Two pathologists examined specimens for dysplasia, and the yield of dysplasia was calculated. Results Twenty-eight patients were included. Twenty-six of these had pancolitis with a duration of disease greater than 15 years, and two patients had associated primary sclerosing cholangis. No patient had a family history of CRC. The mean age at onset of disease was 28.89±8.73 years and the duration of disease was 19.00±8.78 years. Eighteen patients (64.28%) were males. A total of 924 biopsies were taken. None of the biopsies revealed any evidence of dysplasia, and 7/924 (0.7%) were indefinite for dysplasia. Conclusions Random biopsy for surveillance in longstanding extensive colitis has a low yield for dysplasia and does not suffice for screening. Newer techniques such as chromoendoscopy-guided biopsies need greater adoption.