Sunit K. Shukla

Predictors of survival in hepatitis B virus related decompensated cirrhosis on tenofovir therapy: an Indian perspective.

Decompensated cirrhosis has low survival rate compared to compensated state. Effective viral suppression due to antiviral therapy (tenofovir) has been shown to slow disease progression and may delay the burden of liver transplantation. We aimed to evaluate the usefulness of various prognostic indicators in predicting the 24-months survival in HBV related decompensated cirrhosis after tenofovir therapy and to evaluate the post-treatment outcome. Ninety-six HBV related decompensated patients on antiviral (tenofovir) therapy were prospectively studied for 24months survival and mortality. Cutoff levels for several prognostic indicators were generated by ROC. Prediction of overall probability of mortality was also calculated. The overall probability of survival observed at 12months was 0.947 whereas at 24months it was found to be 0.833. According to Cox proportional hazards model, the univariate analysis revealed cutoff of >7.4logcopies/ml for HBV DNA, >1.2mg/dl for serum creatinine, >3.7mg/dl for total bilirubin, ⩽0.75 for platelets count, >10 for CTP and >20 for MELD as predictors of poor survival. Multivariate analysis showed MELD score of >20 was the most robust predictor of mortality, with 58 times higher risk (HR: 58.73, p<0.001). Post-treatment response with tenofovir for 24months significantly improved the hepatic functions and reverses decompensation and showed incredible efficacy in improvement of hepatic functional status with reduced viremia in a great majority of decompensated cirrhosis subjects having high MELD and HBV DNA level.

Dendritic cell therapy in advanced gastric cancer: A promising new hope?

Advanced gastric cancer carries a very poor prognosis when the tumor becomes unresectable. Even with the best currently available chemotherapy regimens the survival rate remains dismal. A recent breakthrough in the treatment paradigm has been the approval of trastuzumab, a monoclonal antibody, in HER2-positive metastatic gastric cancer. A large number of trials are underway using dendritic cells (DCs) in a number of human malignancies and do show a ray of hope in management of these patients. This review attempts to summarize tumor immunology and the current data regarding use of DCs in gastric cancer therapy.

Ulcerative Colitis and Its Association with Salmonella Species

Ulcerative colitis (UC) is characterized by presence of ulcer in colon and bloody diarrhea. The present study explores the possibility of association between Salmonella and ulcerative colitis. The present study comprised 59 cases of UC, 28 of colon cancer (CC), 127 of irritable bowel syndrome (IBS), and 190 of healthy control. The serological study was done by Widal and Indirect Haemagglutination Assay (IHA) for ViAb. Nested PCR was performed targeting fliC, staA, and stkG gene for Typhi and Paratyphi A, respectively. A total of 15.3% patients were positive for Salmonella “O” antigen among them 18.6% UC, 35.5% CC, 12.6% IBS, and 15.3% healthy control. A total of 36.9% patients were positive for “H” antigen including 39.0%, 57.1%, and 67.7% UC, CC, and IBS, respectively. About 1.73% show positive agglutination for AH antigen including 3.4%, 3.6%, and 1.6%, UC, CC, and IBS. A total of 10.89% were positive for ViAb. While 6.8% of UC, 10.7% of CC, 11.0% of IBS, and 12.1% of healthy subjects were positive for the antibody, the PCR positivity rates for Salmonella specific sequences were 79.7% in UC, 53.6% in CC, 66.1% in IBS, and 16.3% in healthy controls. The present study suggested that higher prevalence of Salmonella might play important role in etiopathogenesis of UC, IBS, and CC.

Publication for promotion in medical academia

We read with interest the Editorial [1] by Aggarwal et al. We laud the effort by the editors to bring to fore some of the drawbacks in the MCI criteria for promotion in medical institutions. We wish to draw attention to few other aspects of publication criteria. Publication is the only other criteria besides minimum duration of service deemed essential for promotion on MCI website. Clinical data publishable as original article in prescribed journals are hard to collate within the time frame provided for promotions by MCI. Time-bound criteria for registering students for PhD, DM, or MD under junior faculty require 6 to 10 years of seniority. Again, whereas MOHfunded colleges have dynamic assured career progression (DACP), institutions in a university system have different policies and multiple hurdles. This creates a chasm in medical fraternity across government-funded institutions. Laboratory research which is often essential for early publication is limited by miniscule resources, autonomy, and collaborative culture within most peripheral medical institutions. Funding from UGC and ICMR is usually evaluationand priority-based. First authorship also assumes that the ICMJE recommendation for the work done on publication is followed. Clinical research requires simultaneous documentation which is often impossible for clinicians in course of duty unless backed by manpower and EHR which is mostly lacking for Indian clinical researcher. Given the above limitations, publishing meaningful original articles does seem like a herculean task. Paucity of indexed journals does not make this situation better. Medical science, like governance, is multifaceted. Basic sciences use theoretical philosophizing and experimentation, social sciences rely on studying Bconcepts^ through polls and surveys, and technology draws its strength from instrumentation and innovation. Medical specialities have the advantage of using all these facilities but within multiple constrains of timely availability of clinical material, consent process, ethics, and high expectations from consumers/patients. Although journals from reputed international publishers have preferential access to Indian libraries and institutions, hardly any article from Indian researcher gets published in them. Most of these journals have hefty subscription cost. Some open access publishers require hefty publication fee unavailable to our researchers. National society or institutional journals do not charge publication fee. However, they have limited circulation outside society members and require subscription, and many are not easily searchable online, often competing with many more popular publications on search engines. International journals have no method of verifying the veracity of methods adopted to conduct the study as reported. Analysis, statistics, positive result, and funding weigh over methodology and rigor, and so scientific Bfraud^ and duplication prosper. Many genuine laboratories in developing countries require Bauthenticating^ western collaborators for publication and may fail to publish because a similar study has recently been published or are not desired in targeted journal. In the absence of a suitable opportunity, many studies get published in less known and inaccessible journals. It is a common experience of faculty being informed of a Bnew^ journal which has accepted his/ her student’s paper. * Sunit Kumar Shukla sunitshuklabhu@gmail.com

Rare trematode infestation in irritable bowel syndrome: Pathogen or commensal?

A healthy young adult male presented with complaints of frequent (>3/day) formed stools and passage of excessive mucous in stool for 3 months. He did not complain of nocturnal motions, recent diarrhea, blood in stool, straining, weight loss, or pain abdomen. Stool test was normal. He was counseled and treated as a case of irritable bowel syndrome. Due to inadequate relief with empirical therapy, colonoscopy was performed in a subsequent visit. Club-shaped small, round organisms with moving proboscis were seen in the cecum. Organism was later identified as a trematode Gastrodiscoides hominis, a rare foodborne trematode. The patient was treated with praziquantel, without complete relief. Trematode infection might not be the cause of symptoms.

P-096 YI Comparative Response of Combination Therapy vs. Mono Therapy in Steroid Dependent Ulcerative Colitis Patients

Background:Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease (IBD) characterized by a chronic relapsing/intermittent clinical course. Steroids offer efficient and prompt relief of symptoms in a high proportion of ulcerative colitis (UC). Although most patients initially respond to corticosteroids, after 1 year, approximately 25% become steroid-dependent. The aim of this prospective study was to assess whether the administration the efficacy of azathioprine (AZA) and mesalamine combination to AZA monotherapy in maintaining remission of steroid-dependent ulcerative colitis (UC). Methods:The present study was carried out in the Department of Gastroenterology, IMS, BHU, Varanasi, India. A total of 136 patients age sex matched were included in the study after written informed consent fulfilling inclusion and exclusion criterias. Patients with steroid-dependent UC in remission were randomized to receive AZA alone (1.5 mg/kg) (group 1) or in combination with mesalamine (800 mg tid) (group 2). Each group had 59 patients. Patients were considered in remission when steroid was withdrawn, an Ulcerative Colitis Clinical Activity Index (UCCAI) score of <2, an Ulcerative Colitis Disease Activity Index (UCDAI) score of 0, and a negative colonoscopy and histology. Followup was carried out every monthly for 2 year. Clinical examination, hematological and biochemical test were carried out routinely. Sigmoidoscopy and completion of inflammatory bowel disease quality-of-life questionnaire (IBD-Q) and UCDAI every 3 months; and 3) total colonoscopy with biopsies at the end of the study. Results:Out of 136 patients 110 patients were analysed and rest 18 (13.23%) were lost in followup and 4 patients in each group developed side effects or poor compliance with treatment and were withdrawn from the study. Five patients receiving monotherapy (group 1) relapsed after the first year of the study and 3 after the second year of the study (14.54%). In the combination group (group 2) 2 patients relapsed after the first year of study and 2 after the second year of the study (7.27%) having statistically significant when compared with group 1 (p<0.05). Relapse rates were significant whether analyzed by intention-to-treat or per protocol. There were no significant differences between groups in time to relapse or discontinuation of treatment, UCCAI, UCDAI, or IBD-Q scores. Adverse events were similar both the groups and statistically non significant. Conclusions:Patients with steroid-dependent UC successfully maintained in remission on AZA and mesalamine and however relapse rate were more common in patients on azathioprine alone.

P-157 YI Elevated Macrophage Migration Inhibitory Factor Sera Level in Ulcerative Colitis Patients

Background:Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) and is often confused with Irritable bowel Syndrome (IBS). Ulcerative colitis is treated as an autoimmune disease. A number of cytokines have been implicated in chronic inflammatory lesions of UC. It has been reported that inflammatory cytokines play important role in the development of the disease. Macrophage migration inhibitory factor (MIF) is important pro inflammatory cytokine and plays a critical role in regulating broad range of immune and inflammatory activities. Higher levels may be related to the pathogenesis and induction of inflammation in UC. Aim of the present study was to evaluate the serum concentration of MIF in patients with ulcerative colitis, Irritable Bowel Syndrome (IBS), colon cancer and healthy control. Methods:Study was carried out in the Department of Gastroenterology, IMS, BHU, Varanasi, India. A total of 275 subjects age sex matched (59 UC, 127 IBS, 28 colon cancer and 61 Healthy controls) were enrolled for the study fulfilling inclusion and exclusion criteria. Blood samples were obtained after informed consent for serum separation. Enzyme linked immune sorbent assay (ELISA) was performed using Bioassay Technology Laboratory kit for human macrophage migration inhibitory factor following the manufacturers protocol. A p value of less than 0.05 was considered significant. Statistical analysis was conducted by using SPSS 16.0 (SPSS, Chicago, IL). Results:MIF level in UC was found to be significantly higher (P < 0.0003) having mean SD 3.55 ± 1.3 (Z score = 3.36) when compared with healthy control having mean SD 0.89 ± 0.48 whereas in IBS patients MIF level was found to be significantly elevated (p < 0.0006) having mean SD 3.96 ± 1.39 (Z score = 3.19) when compared to healthy control and that of colon cancer was also found to be high (P < 0.00471) having mean SD 3.02 ± 1.76 (Z score = 2.59) when compared to healthy control. Conclusions:MIF concentration significantly elevated in UC, colon cancer and IBS in respect to control subject which may immobilize macrophages and can lead to production of several inflammatory cytokine which supports the claim that inflammation could be an effective factor in the pathogenesis of disease.

Analysis of wedge resection of gallbladder bed and lymphadenectomy on adequate oncologic clearance for gallbladder cancer

BACKGROUND Surgery (R0 resection) is the mainstay of treatment of gallbladder cancer (GBC) as GBC is relatively resistant to currently known chemotherapy and radiotherapy regimens. AIM to assess if wedge resection of the gallbladder bed achieves an adequate oncological clearance in GBC (namely T1 and T2) and some T3 GBC with minimal liver infiltration. PATIENTS AND METHODS Patients with GBC who underwent radical cholecystectomy (en bloc cholecystectomy, wedge resection of the gallbladder fossa with a ≥2 cm rim of nonneoplastic liver tissue, and regional lymph node dissection) between October 2012 and June 2015 after obtaining informed consent. RESULTS Of thirty patients, mean age of 52 years, 5 had T1b, 13 T2, and 12 T3 GBC. R0 resection was achieved in all thirty GBC patients. Hepatic invasion was found in seven patients. The depth of hepatic invasion ranged from 0 to 9 mm. Follow-up ranged from a minimum of 12 to 43 months. Nineteen (63%) patients had N0 and 11 (37%) had N1 GBC. Total lymph node (TLND) count ranged from 1 to 12/patient with a median of 3. There was no local recurrence or systemic relapse of the disease. CONCLUSION Wedge resection of the gallbladder bed achieves an adequate oncological clearance in early GBC. TLND counts remain poor even after a thorough standard lymph node dissection for resectable GBC.

Clinical Profile and Outcome in Acute on Chronic Liver Failure (ACLF)

Background and Aims: ACLF is defined as an acute deterioration of liver function in a patient with previously fairly well-compensated chronic liver disease. The aims of this study were to understand the natural history, etiology of acute insult and underlying chronic liver disease, prognostic outcome, and whether there was any subgroup of chronic liver disease which had a higher rate of decompensation. Materials and Methods: This was a prospective study conducted in the Gastroenterology department, Institute of Medical Sciences, BHU, Varanasi from December 2013 to November 2014. Data including demographics, clinical presentation, hospital course and outcome of 86 patients were recorded. The etiologies of superimposed acute event and chronic liver disease were investigated on the basis of routine investigations, viral markers, autoimmune markers, Wilson disease panel, serum ferritin and liver biopsy (if feasible). Study variables like coagulopathy, hepatic encephalopathy, sepsis, hyponatremia, renal failure, hepatorenal syndrome and various prognostic scores were considered. Results:Most of the patients were young adults (55%) and males were more common than females (M: F = 2.7:1). The most common presenting features were coagulopathy and ascites (95%) whereas encephalopathy (28%) and GI bleed were less common. The most common cause of acute insult leading to Fig. 1 Etiology of acute events.