Comparative analysis of copy number variations in ulcerative colitis associated and sporadic colorectal neoplasia.

BACKGROUND: The incidence of and mortality from colorectal cancers (CRC) can be reduced by early detection. Currently there is a lack of established markers to detect early neoplastic changes. We aimed to identify the copy number variations (CNVs) and the associated genes which could be potential markers for the detection of neoplasia in both ulcerative colitis-associated neoplasia (UC-CRN) and sporadic colorectal neoplasia (S-CRN). METHODS: We employed array comparative genome hybridization (aCGH) to identify CNVs in tissue samples of UC nonprogressor, progressor and sporadic CRC. Select genes within these CNV regions as a panel of markers were validated using quantitative real time PCR (qRT-PCR) method along with the microsatellite instability (MSI) in an independent cohort of samples. Immunohistochemistry (IHC) analysis was also performed. RESULTS: Integrated analysis showed 10 overlapping CNV regions between UC-Progressor and S-CRN, with the 8q and 12p regions showing greater overlap. The qRT-PCR based panel of MYC, MYCN, CCND1, CCND2, EGFR and FNDC3A was successful in detecting neoplasia with an overall accuracy of 54% in S-CRN compared to that of 29% in UC neoplastic samples. IHC study showed that p53 and CCND1 were significantly overexpressed with an increasing frequency from pre-neoplastic to neoplastic stages. EGFR and AMACR were expressed only in the neoplastic conditions. CONCLUSION: CNVs that are common and unique to both UC-associated and sporadic colorectal neoplasm could be the key players driving carcinogenesis. Comparative analysis of CNVs provides testable driver aberrations but needs further evaluation in larger cohorts of samples. These markers may help in developing more effective neoplasia-detection strategies during screening and surveillance programs.

Monocyte chemoattractant protein-1, transforming growth factor-beta1, nerve growth factor, resistin and hyaluronic acid as serum markers: comparison between recurrent acute and chronic pancreatitis.

BACKGROUND: Diagnostic parameters that can predict the presence of chronic pancreatitis (CP) in patients with recurrent pain due to pancreatitis would help to direct appropriate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta1 (TGF-beta1), nerve growth factor (NGF), resistin and hyaluronic acid (HA) in patients with recurrent acute pancreatitis (RAP) and CP to assess their ability to differentiate the two conditions. METHODS: Levels of serum markers assessed by enzyme-linked immunosorbent assay (ELISA) were prospectively compared in consecutive patients with RAP, CP and in controls, and stepwise discriminant analysis was performed to identify the markers differentiating RAP from CP. RESULTS: One hundred and thirteen consecutive patients (RAP=32, CP=81) and 78 healthy controls were prospectively enrolled. The mean (SD) age of the patients was 32.0 (14.0) years; 89 (78.8%) were male. All markers were significantly higher in CP patients than in the controls (P<0.001); MCP-1, NGF and HA were significantly higher in RAP patients than in the controls (P<0.001). Stepwise discriminant analysis showed significant difference (P=0.002) between RAP and CP for resistin with an accuracy of 61.9%, discriminant scores of ≤-0.479 and ≥0.189 indicating RAP and CP, respectively. The other markers had no differential value between RAP and CP. CONCLUSION: Serum resistin is a promising marker to differentiate between RAP and CP and needs validation in future studies, especially in those with early CP.

Pancreatic Calculus Causing Biliary Obstruction: Endoscopic Therapy for a Rare Initial Presentation of Chronic Pancreatitis.

INTRODUCTION: Biliary obstruction in chronic calcific pancreatitis (CCP) is often caused by inflammatory or fibrotic strictures of the bile duct, carcinoma of head of pancreas or less commonly by compression from pseudocysts. Pancreatic calculi causing ampullary obstruction and leading to obstructive jaundice is extremely rare. METHODS: The medical records of all patients with CCP or biliary obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP) over 4 years between 2010-2014 at Kasturba Medical College, Manipal were analyzed. RESULTS: Five patients of CCP with impacted pancreatic calculi at the ampulla demonstrated during ERCP were identified. All 5 presented with biliary obstruction and were incidentally detected to have CCP when evaluated for the same; 3 patients had features of cholangitis. All the patients were managed successfully by endoscopic papillotomy and extraction of pancreatic calculi from the ampulla with resolution of biliary obstruction. CONCLUSION: Pancreatic calculus causing ampullary obstruction, though very rare, should be considered as a possibility in patients with CCP complicated by biliary obstruction. Endoscopic therapy is affective in the resolution of biliary obstruction in such patients.

Diagnosis of acute severe colitis.

It is important to assess the severity of ulcerative colitis (UC) in order to decide the intensity of treatment and predict outcome. The criteria instituted by Truelove and Witts almost 60 years back are still being used. However, they lack a scoring system and offer no clear definition for the moderate group. The criteria with scoring system and endoscopic criteria (Mayo Score) seems to be more useful clinically. Endoscopic assessment is very important and a cautious attempt should always be made even if it enables a limited colonoscopic examination. Proctosigmoidoscopy is advocated at initial stages and after 5 to 7 days. The criteria for severity in general are same for pan-colitis and limited disease.

Assessing the Impact of Medication and Stenting on the Quality of Life of Patients With Chronic Pancreatitis: A Prospective Study.

This research aimed to assess the effect of pharmacotherapy alone versus the combination of pharmacotherapy and endoscopic stenting on the quality of life (QoL) outcomes of chronic pancreatitis patients. Chronic pancreatitis, an inflammatory disease, often presents with persistent pain, affecting patients' quality of life. Thirty patients treated either with pharmacotherapy alone or with the addition of endoscopic stenting were analyzed. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was used to gather data on the patients' QoL. Results showed that both treatment groups experienced improvements in global health, role functioning, fatigue, and abdominal pain scores over follow-ups. Specifically, the stenting group saw notable enhancements in global health and role functioning. The study's conclusions provide valuable insights into the potential benefits of both treatments, with stenting offering significant improvements in certain QoL parameters. However, the sample size and source limit generalizability, suggesting the need for more extensive research across diverse settings.

Use of thiopurines in inflammatory bowel disease: an update.

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.

Kayser-Fleischer-like rings in patients with hepatic disease.

Purpose: The aim of this work was to study Kayser-Fleischer [KF]-like rings in patients with hepatic or cholestatic liver disease and to find out the relation between serum bilirubin level and the presence of KF like ring in these patients. Methods: In this study, we evaluated patients with hepatic and cholestatic liver diseases with total Serum bilirubin levels >10 mg/dl. These patients were evaluated for the presence or absence of KF like ring. Results: A total of 67 patients with total bilirubin >10 mg/dl were included in the study. Patients were divided into 3 groups based on total S. bilirubin level: Group 1 with S. bilirubin >30 mg/dl, Group 2 with S. bilirubin >20 - <30 mg/dl and Group 3 with S. bilirubin >10 - <20 mg/dl at baseline evaluation. On follow-up they were divided into 3 groups based on the serum bilirubin level. Group 1- >20 mg/dl, Group 2- >10 - <20 mg/dl, Group 3- <10 mg/dl. KF like ring was seen in 98.5% of patients with high total S. bilirubin level. KF like ring disappeared in 87.5% of patients with reduction in the total S. bilirubin level to less than 10 mg/dl. Conclusion: KF like ring was seen in 98.5% of patients with high total S. bilirubin, disappeared in 87.5% of patients with reduction in the total S. bilirubin level to less than 10 mg/dl. There was no significant difference between the Total S. bilirubin levels, age, gender and KF Like Ring.

Colitis and Crohn's Foundation (India): a first nationwide inflammatory bowel disease registry.

BACKGROUND/AIMS: The national registry for inflammatory bowel disease (IBD) was designed to study epidemiology and prescribing pattern of treatment of IBD in India. METHODS: A multicenter, cross-sectional, prospective registry was established across four geographical zones of India. Adult patients with ulcerative colitis (UC) or Crohn's disease (CD) were enrolled between January 2014 and December 2015. Information related to demographics; disease features; complications; and treatment history were collected and analyzed. RESULTS: A total of 3,863 patients (mean age, 36.7 ± 13.6 years; 3,232 UC [83.7%] and 631 CD [16.3%]) were enrolled. The majority of patients with UC (n = 1,870, 57.9%) were from north, CD was more common in south (n = 348, 55.5%). The UC:CD ratio was 5.1:1. There was a male predominance (male:female = 1.6:1). The commonest presentation of UC was moderately severe (n = 1,939, 60%) and E2 disease (n = 1,895, 58.6%). Patients with CD most commonly presented with ileocolonic (n = 229, 36.3%) inflammatory (n = 504, 79.9%) disease. Extraintestinal manifestations were recorded among 13% and 20% of patients in UC and CD respectively. Less than 1% patients from both cohorts developed colon cancer (n = 26, 0.7%). The commonly used drugs were 5-aminosalicylates (99%) in both UC and CD followed by azathioprine (34.4%). Biologics were used in only 1.5% of patients; more commonly for UC in north and CD in south. CONCLUSIONS: The national IBD registry brings out diversities in the 4 geographical zones of India. This will help in aiding research on IBD and improving quality of patient care.

Colitis and Crohn's Foundation (India) consensus statements on use of 5-aminosalicylic acid in inflammatory bowel disease.

Despite several recent advances in therapy in inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) therapy has retained its place especially in ulcerative colitis. This consensus on 5-ASA is obtained through a modified Delphi process, and includes guiding statements and recommendations based on literature evidence (randomized trials, and observational studies), clinical practice, and expert opinion on use of 5-ASA in IBD by Indian gastroenterologists. The aim is to aid practitioners in selecting appropriate treatment strategies and facilitate optimal use of 5-ASA in patients with IBD.

Endoscopic treatment as first-line therapy for pancreatic ascites and pleural effusion.

BACKGROUND: Ascites and pleural effusion are well recognized complications of pancreatic diseases. Drug therapy of these is limited by high cost, prolonged hospitalization and failure rates; surgery is invasive and is associated with considerable morbidity and mortality. OBJECTIVE: To analyze the data on patients with pancreatic ascites and/or pleural effusion treated endoscopically over a ten-year period. METHODS: Patients with symptomatic ascites/pleural effusion for at least 3 weeks with a fluid amylase level of > 1000 S units/dl and underlying pancreatic disease were included. The interventions were a 5 mm sized pancreatic sphincterotomy and placement of a 7 Fr pancreatic stent. Somatostatin/octreotide and parenteral nutrition were not used after endoscopic therapy. RESULTS: Of the 28 patients included (22 men), 17 (60.7%) had chronic pancreatitis. The causes were tropical pancreatitis (13, 46.4%), alcohol abuse (10, 35.7%), idiopathic acute pancreatitis (4, 14.3%) and resective surgery for gastric cancer (1, 3.6%). Ascites alone was seen in 15, pleural effusion alone in 6 and both in 7 patients. Ten patients (35.7%) had 14 pseudocysts. Endotherapy was successful in 27 (96.4%). Twenty-six (92.8%) patients had complete resolution of ascites/effusion over a median 5 weeks. The stents were removed 3-6 weeks later without any recurrence over the next 6-36 (median = 17) months. Complications (7, 25%) included severe pain in 2 (7.1%) and fever in 5 (17.8%) of which 3 (10.7%) had infection of residual fluid collections. No patient died. CONCLUSION: Endoscopic therapy offers an excellent therapeutic alternative in patients with pancreatic ascites and pleural effusion.

Prevalence of and Factors Associated With Minimal Hepatic Encephalopathy in Patients With Cirrhosis of Liver.

BACKGROUND/OBJECTIVES: Minimal hepatic encephalopathy (MHE), though highly prevalent, is a frequently underdiagnosed complication of cirrhosis of the liver. Because lack of time is reported as the major reason for non-testing, identifying patients at high risk of MHE would help in targeting them for screening. We aimed to determine the factors associated with MHE to help identify patient subgroups with a higher risk of MHE for targeted screening. METHODS: Patients with cirrhosis of liver presenting between April 2015 and November 2016 were included. Those with a Psychometric Hepatic Encephalopathy Score (PHES) of ≤-5 points on psychometric testing were diagnosed to have MHE. Various demographic, clinical and laboratory parameters were included in a univariate and later multiple logistic regression models. RESULTS: Of the 180 (male = 166, 92.2%) patients included 94 (52.2%) had MHE. Though serum albumin, serum total bilirubin, serum aspartate aminotransferase, international normalized ration, Child-Turcotte-Pugh and Model-For-End-Stage-Liver-Disease scores were significant on univariate analysis, only CTP score was found to be significantly associated with MHE (P = 0.002) on multivariate analysis. A higher CTP class was associated with a higher risk of the presence of MHE. The Odds ratio for having MHE was higher with CTP classes of B (P ≤ 0.001) and C (P ≤ 0.001) compared to class A. CONCLUSIONS: MHE is a common complication in patients with cirrhosis of liver and higher CTP scores independently predict the presence of MHE. Patients with CTP class B and C have a higher risk of suffering from MHE than CTP class A. Screening of patients in CTP class B and C is likely to increase the MHE detection rates while saving time, although select CTP class A patients may also need screening in view of public safety or poor quality of life.

Video assisted patient education improves compliance with follow up and depression scores in Inflammatory Bowel Diseases.

OBJECTIVES: Patients with inflammatory bowel diseases (IBD) have to deal with a poor quality of life (QOL) and psychomorbidity resulting from an incurable illness. We aimed to study the effect of patient education on QOL, compliance, anxiety and depression in IBD. METHODS: Patients were prospectively enrolled over two years beginning July 2014 and divided into an interventional and usual care group. Both received the standard of care, but the former in addition received an 8 min session of video-assisted education. Compliance to drugs was defined as drug intake of > 80% of the prescribed dose, and adherence to scheduled follow up visits were also compared. Self-administered questionnaires namely Short IBD questionnaire (SIBDQ), Beck Anxiety and Depression Inventory (BAI, BDI-II), Hospital Anxiety and Depression Scale (HADS) were used to assess QOL, anxiety and depression respectively at baseline, 6 months and 1 year. RESULTS: Of the 91 patients enrolled, 84 [92.3%; male = 66 (78.57%)] completed the follow up. Significantly more patients were compliant to follow up visits in the intervention and usual care groups respectively at 6 months (88.4% versus 65.8% respectively; p < 0.01) and 1 year (72.1% versus 46.3% respectively; p < 0.01). The median (IQR) scores for HADS-Depression over 1 year were significantly better in the interventional group than usual care (p < 0.049). The differences in SIBDQ, BDI-II, BAI, HADS-Anxiety and compliance to drug therapy between the groups did not reach statistical significance. CONCLUSION: Video assisted patient education improved compliance to follow up visits and depression scores in IBD. Further modifications in the educational video content and delivery might improve compliance to drug therapy, QOL and anxiety scores.

Continuing episodes of pain in recurrent acute pancreatitis: Prospective follow up on a standardised protocol with drugs and pancreatic endotherapy.

AIM: To assess the outcomes of drug therapy (DT) followed by pancreatic endotherapy for continuing painful episodes in recurrent acute pancreatitis. METHODS: DT comprised of pancreatic enzymes and anti-oxidants failing which, endotherapy (ET; pancreatic sphincterotomy and stent placement) was done. The frequency of pain, its visual analogue score (VAS), quality of life (QoL), serum C peptide and faecal elastase were compared between baseline and after 1 year of follow up in all patients and in the two subgroups on DT and ET. Response was defined as at least 50% reduction in the severity of pain to below a score of 5. RESULTS: Of the thirty nine patients analysed, 21 (53.9%) responded to DT and 18 (46.1%) underwent ET. The VAS for pain (7.0 ± 2.0 vs 1.3 ± 2.5, P < 0.001) and the number of days with pain per month decreased [1.0 (1.0, 2.0) vs 1.0 (0.0, 1.0), P < 0.001], and the QoL scores [55.0 (44.0, 66.0) vs 38.0 (32.00, 51.00), P < 0.01] improved significantly during follow up. Similar significant improvements were seen in patients in the subgroups of DT and ET except for QoL in ET. The serum C-peptide (P = 0.001) and FE (P < 0.001) levels improved significantly in the entire group and in the two subgroups of patients except for the C peptide levels in patients on DT. CONCLUSION: A standardised protocol of DT, followed by ET decreased the intensity and frequency of pain in recurrent acute pancreatitis, enhanced QoL and improved pancreatic function.