Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship.

Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.

Predictors of Rebleeding in Non-variceal Upper Gastrointestinal Bleeding of Peptic Ulcer Etiology in Kashmiri Population.

Background Upper gastrointestinal bleeding (UGIB) represents a substantial clinical and economic burden and rebleeding is one of the most important predictors of morbidity and mortality. Identifying patients who are likely to rebleed is a critical component of effectively managing patients with bleeding peptic ulcers. So, the study was undertaken to look for predictors of rebleeding in patients with bleeding peptic ulcers and try to find out the new scoring system to predict rebleeding in our population. Material and methods A retrospective analysis of prospectively maintained hospital data of UGIB patients was done and 480 patients of endoscopically documented peptic ulcers whose complete data was available were taken for study. Results Among the studied patients, men constituted 84.6%, and most of the patients were in the third to sixth decade of life with a mean age of 40.9±15.9 years, 76% were from rural areas. Only males with a mean age of 38.4±19.8 rebled with a rebleeding rate of 2.9% only. Half of the patients who rebled were in shock at the time of presentation. Those who rebled received more units of blood transfusion (mean 3±1.8), had a large mean ulcer size of Forest class IIa and IIb and epinephrine injection monotherapy group with varied statistical significance. Among rebleeders (n=14), eight patients were managed by a second endoscopic therapy, and six (42.8%) rebleeders and 1.25% of patients in total needed surgery. Two patients ultimately died giving overall mortality of 0.4% and mortality of 14.3% among rebleeders. Conclusion Our study found a very low rebleeding rate and mortality which could be explained by a young population with fewer co-morbidities and better response to proton pump inhibitor therapy. The significant parameters related to rebleeding were shock at presentation, degree of smoking, units of blood transfused, ulcer size, and high-risk endoscopic stigmata.

Management of Helicobacter pylori infection: The Bhubaneswar Consensus Report of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.

Clinical Profile and Efficacy of Antivirals in Hepatitis B Virus Reactivation, in Patients With Cancer Receiving Chemotherapy.

BACKGROUND/PURPOSE: Hepatitis B virus reactivation (HBVR) is common in patients withcancer. The aim of the present study was to find out clinical profile of patients with cancer receiving chemotherapy with HBVR and to study the efficacy of entecavir (ETV) and tenofovir in the treatment of HBVR. METHODS: This is a prospective study in which all consecutive patients with cancer with evidence of HBVR were included. HBVR was defined as: New onset transaminitis with alanine aminotransferase (ALT) >3 times upper limit of normal and >10 fold increase in HBV DNA levels from baseline levels or detection of HBV DNA ≥100,000 IU/ml in patients with no baseline HBV DNA. Patients with HBVR were put on ETV or tenofovir and were closely monitored for efficacy and safety for minimum of 1 year. RESULTS: Of 204 Hepatitis B surface antigen (HBsAg)-positive patients with different cancers, 92 met the inclusion criteria. Of 92, 46 received ETV 0.5 mg/day and 46 received tenofovir disoproxil fumarate (TDF) 300 mg/day. At 6 months, there was 4.7 log reduction in HBV DNA level in the ETV group and 5.2 log reduction in the TDF group (P = 0.029). Proportion of patients with undetectable HBV DNA (75.7% vs 87.5%), ALT normalization (89.2% Vs 87.5%), HBsAg negativity (25% vs 28.1%), and seroconversion (2.8% vs 3.1%) at 1 year were almost similar in both groups with P value > 0.05 for all efficacy end points. There was no HBVR-related mortality in any group. CONCLUSION: Both ETV and tenofovir are very effective in the treatment of HBVR and reduce the liver-related mortality and morbidity in such patients.

Epidemiology of Taenia saginata taeniasis with emphasis on its prevalence and transmission in a Kashmiri population in India: A prospective study.

BACKGROUND: Taeniasis, caused by two major Taenia species, T. solium and T. saginata, is a worldwide foodborne zoonotic disease. T. solium is found in people who habitually eat raw or undercooked pork, while T. saginata is found in people who habitually eat raw or undercooked beef. Cattle rearing and beef consumption is an important socio-cultural feature in the Kashmir valley, India. This study's objectives were to evaluate the prevalence of foodborne taeniasis in Kashmir and explore the various risk factors for its transmission. METHODS AND MATERIALS: A detailed survey of the population in selected rural and semi-urban sites of Kashmir valley was carried out based on previous information. A total of 12,404 subjects (males=6364; females=6040) ranging from one to 85 years of age (mean age: 28.96±17.68) were included in this study. The parasite diagnosis was made through stool analysis (egg morphology) and anatomical characteristics of gravid proglottids obtained from infected cases. The data obtained were compiled for the parameters studied and statistically analyzed. RESULTS: The observations as estimated coprologically and based on gravid proglottids' anatomy revealed the presence of T. saginata infection. The prevalence was 2.74% with males significantly (p<0.01) more infected (3.40%) than females (2.05%). Similarly, the age group of >60 years showed greater prevalence (7.21% among males and 2.68% among females) at a significance value of p<0.05. Rural populatios were slightly more infected (2.84%) than semi-urban populations (2.36%) with a statistically significant difference (p<0.01). CONCLUSION: Our findings indicate that the Kashmiri population who consume raw or undercooked beef, harbor T. saginata infection; its prevalence was influenced by food eating habits, age, sex, and living conditions.

Endoscopic Yield, Appropriateness, and Complications of Pediatric Upper Gastrointestinal Endoscopy in an Adult Suite: A Retrospective Study of 822 Children.

BACKGROUND/AIMS: This study aimed to study the endoscopic yield, appropriateness, and complications of pediatric endoscopy performed by adult gastroenterologists in an adult endoscopic suite. METHODS: This a retrospective study in which records of all the patients less than 18 years of age who underwent endoscopy in the last 5 years were studied. The indications of endoscopy in children were categorized as appropriate or inappropriate per the latest guidelines by American Society for Gastrointestinal Endoscopy and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Positive endoscopic yield was defined as the presence of any abnormality on endoscopy. RESULTS: Among the total of 822 children (age <18 years), the most common indications were variceal surveillance/eradication in 157 (19.1%), followed by dyspepsia in 143 (17.4%), upper gastrointestinal (UGI) bleeding in 136 (16.5%), recurrent abdominal pain in 94 (11.4%), unexplained anemia in 74 (9%), recurrent vomiting in 50 (6.08%), chronic refractory gastroesophageal reflux disease in 34 (4.1%) and others; 780 out of 822 endoscopic procedures (94.9%) done in children were appropriate as per the guidelines. The endoscopic yield was 45.8%, highest in patients with UGI bleeding (71.3%), followed by variceal surveillance (54.8%), recurrent vomiting (38%), dyspepsia (37.8%), and recurrent abdominal pain (36%). Minor adverse events occurred in 7.3% of children. CONCLUSION: Pediatric endoscopy performed by an experienced adult gastroenterologist may be acceptable if done in cooperation with a pediatrician.

Entecavir is Safe and Effective in Long Term for the Treatment of Hepatitis B in Immunocompromised Children.

OBJECTIVE: Hepatitis B infection is common in patients with cancer, and prompt treatment is necessary; otherwise, it can result in life-threatening complications. The objective of this study was to assess the long-term safety and efficacy of entecavir in immunocompromised children with hepatitis B. METHODS: This single-center prospective study was conducted on children with different malignancies referred to our department with evidence of hepatitis B infection. Only those children were included in the study who had HBsAg positive and alanine aminotransferase (ALT) more than 2 times the upper limit of normal and whose hepatitis B virus (HBV) DNA was more than 20,000IU/ml. These children were put on entecavir and prospectively observed upto 192 weeks. Primary efficacy end point was the proportion of patients who achieved undetectable HBV DNA at 48 weeks of treatment. Other efficacy end points were the proportion of patients with HBeAg seroconversion, undetectable HBV DNA, and ALT normalization at weeks 48 and 96 weeks. RESULTS: A total of 41 children met the inclusion criteria, of which 5 children died because of malignancy and 5 were lost to follow-up. Mean log DNA was 7.67 at the start which after starting entecavir reduced to 4.1, 2.8, 1.19, 1.09, and 0.84 at 12, 24, 48, 72, and 96 weeks, respectively (P value < 0.0001). Mean ALT decreased from 332.5 which reduced to 190, 115, 63, and 46 at 4, 12, 24, and 48 weeks, respectively (P < 0.0001). 67.7% achieved the primary outcome and had undetectable DNA at 48 weeks which increased to 26 (83.9%) at 96 weeks. At 48 weeks, 80.6% patients achieved ALT normalization. Thirty percent developed HBeAg seroconversion. Two patients developed virological breakthrough, one at 96 weeks and another at 192 weeks. No significant adverse effects were observed. CONCLUSION: Entecavir is safe and effective in long term for the treatment of hepatitis B in immunocompromised children.

Noradrenaline versus terlipressin in the management of type 1 hepatorenal syndrome: A randomized controlled study.

BACKGROUND: Hepatorenal syndrome (HRS) occurs in decompensated liver disease and carries high mortality. Vasoconstrictors are the drug of choice. Terlipressin is widely used and is expensive. In this study, we compared noradrenaline and terlipressin in the management of type 1 HRS. METHODS: Sixty consecutive patients with type 1 HRS were managed with noradrenaline (Group A, n = 30) or terlipressin (Group B, n = 30) with albumin in a randomized controlled trial at a tertiary center. RESULTS: Reversal of type 1 HRS was achieved in 16 (53%) patients in group A and 17 (57%) in group B. There was statistically insignificant difference between the two groups in decreasing serum creatinine and increasing urine output (p > 0.05). On univariate analysis, Child-Turcotte-Pugh (CTP) score, serum sodium, serum urea, serum albumin, prothrombin time, International normalized ratio (INR), serum alanine aminotransferase (ALT), ascitic fluid protein, and history of bleeding were associated with response to treatment (noradrenaline/terlipressin). However, on multivariate analysis, only baseline CTP score, serum urea, serum albumin, and prothrombin time were independent predictors of response. All patients who responded were discharged alive with no mortality within 30 days. CONCLUSIONS: There is no difference in outcome of patients with type 1 HRS treated with noradrenaline or terlipressin. Thus, noradrenaline, which is cheaper, can be used instead of terlipressin (Clinical Trials Registry-India [CTRI] No. CTRI/2011/09/002032).

Antibiotic resistance in Helicobacter pylori: A mutational analysis from a tertiary care hospital in Kashmir, India.

Background: Helicobacter pylori infection is recognised as type 1 carcinogen by the International Agency of Research on Cancer. Previous studies in our hospital have revealed high prevalence of H. pylori in our population with a high recurrence rate after completion of treatment. This prompted us to undertake this study. Aim: This study aimed to determine common gene mutations leading to resistance to clarithromycin, metronidazole, tetracycline and quinolones in H. pylori in patients attending our hospital. Settings and Design: This is a cross-sectional hospital-based study. The study was approved by the Institutional Ethics Committee. Materials and Methods: This study was conducted on 196 adult dyspeptic patients with an indication for upper gastrointestinal endoscopy. Gastric biopsies collected from them were subjected to histopathological examination, rapid urease test (RUT) and culture. Of the 196 patients, 95 met the inclusion criteria. Drug susceptibility testing (DST) by various polymerase chain reaction-based methods was done for 47 RUT-positive biopsies and 13 H. pylori isolates. Results: Maximum resistance was seen to metronidazole (81.66%) followed by clarithromycin (45%) and quinolones (3.33%). No high-level resistance was seen to tetracycline. In clarithromycin-resistant cases, A2142G mutation was more prevalent than A2143G mutation. Multidrug resistance (resistance to metronidazole and clarithromycin) was seen in 41.66% of patients. Conclusions: Tetracycline and quinolones could be the antibiotics of choice in the eradication of H. pylori in this region, while recurrence of the infection with H. pylori could be expected among patients receiving either metronidazole or clarithromycin, for eradication therapy. DST should be done on a routine basis utilising both phenotypic and genotypic methods to prevent further emergence of resistance in this region.

The Role of Biochemical Variations and Genotype Testing in Determining the Virological Response of Patients Infected with Hepatitis C Virus.

BACKGROUND: In hepatitis C virus (HCV), infection viral and IL28B genotype along with many clinical and biochemical factors can influence response rates to pegylated interferon plus ribavirin (Peg-IFN-a/R) therapy and progression to chronic hepatitis C (CHC). AIMS: The present study was conducted to determine the effect of biochemical and risk factors on treatment outcome in CHC patients in relation to their viral and host genotype. SETTINGS AND DESIGN: The present study was a prospective Pe- IFN efficacy study consisting of Peg-IFN-a/R therapy for 24-48 weeks including 250 HCV infected patients. MATERIALS AND METHODS: Biochemical parameters were determined by Beckman Coulter AU680 automated analyzer. HCV and Interleukin 28B (IL28B) genotyping were carried out by polymerase chain reaction-restriction fragment length polymorphism and viral load was determined by quantitative real-time PCR. RESULTS: Wild outnumbered the variant genotypes in rs12979860, rs12980275, and rs8099917 SNP of IL28B gene. Sustained virological response (SVR) SVR and viral genotype were significantly associated with age, hepatic steatosis, low-grade varices, and serum aspartate transaminase levels (at the end of treatment) (P < 0.05). In addition, SVR was significantly influenced by body mass index (BMI), insulin resistance, serum low-density lipoprotein , and ferritin levels (P < 0.05). Viral genotype 1 infected patients had higher serum cholesterol and triglyceride levels (P < 0.05). CONCLUSIONS: Although the IL28B sequence variation is the major factor that can influence response rates to antiviral therapy, viral and biochemical factors also have a definite role to play in the diagnosis, etiology, and treatment outcome in HCV-infected patients.

Impact of IL28B genetic variant's and viral genotype on treatment outcome of hepatitis C infected patients.

INTRODUCTION: Viral genotype and variation in host genes involved in the immune response may predict the treatment response in patients infected with HCV. The present study was designed to determine the distribution pattern of HCV and host genotypes in Chronic Hepatitis C (CHC) patients and their association with virological response and other risk factors. METHODOLOGY: Two hundred and fifty (n = 250) HCV positive patients were included in the study. HCV and Interleukin 28B (IL28B) genotyping was carried out by PCR-RFLP. RESULTS: Viral genotype 3 was the predominant genotype seen in 187 (74.8%) patients. Wild genotype predominated in rs12979860, rs12980275 and rs8099917 SNP of IL28B gene. A significant difference was found in end stage virological response (EVR) between HCV genotype 1 infected patients with wild and variant genotype for rs12980275 and rs8099917 SNPs respectively (P < 0.05). On multivariate analysis all the SNPs were found to be associated with each other (P < 0.05) with rs12980275 SNP associated with history of Jaundice (P < 0.05). Viral genotype 3 was significantly associated with age (< 50 years) and rapid virological response (RVR) while as viral genotype 1 was significantly associated with history of surgery on multivariate analysis (P < 0.05). CONCLUSIONS: The viral genotype and IL28B polymorphisms are important factors to personalize antiviral therapy of patients with CHC.

Prevalence, risk factors and consequences of overweight and obesity among schoolchildren: a cross-sectional study in Kashmir, India.

BACKGROUND: Obesity among children and adolescents is a growing public health problem. The objective of this study was to evaluate the prevalence, risk factors and metabolic consequences of obesity among schoolchildren from Kashmir, India. METHODS: The study subjects (n=2024) included 870 boys and 1154 girls, aged between 6 and 18 years. Data were collected by interviewer-administered questionnaires. Information was obtained about different lifestyles, anthropometric parameters and dietary habits. Obesity was defined as body mass index (BMI) percentile as per the guidelines of Centers for Disease Control, 2000. For the evaluation of different clinical parameters, blood samples were collected from the subjects in the fasting state at 8 to 9 am after an overnight (10-12 h) fast. RESULTS: The highest representation of subjects was from fee-paying private schools. Out of the total subjects, 6.69% were overweight and 4.64% were obese. The hip circumference, abdominal circumference, BMI, blood pressure (BP), use of ready-made foods as well as the clinical parameters like glucose, phosphorous, cholesterol and triglycerides were found significantly higher among girls than boys (p<0.05). Boys were taller and were physically more active than girls (p<0.01). Compared to the boys (3.33%), the girls were found to be more obese (5.63%). Rural dwelling subjects (4.22%) exhibited a lower percentage of obesity than urban population (5.00%). The difference in obesity among the different age groups was found statistically significant (p<0.05). Additionally, children with active lives in the form of vigorous (10.59%) or moderate (10.34%) exercise decreased their chances of gaining weight substantially. CONCLUSIONS: Results from the present study have shown that prevalence of obesity among children was high in our population.

Prevalence and pattern of growth abnormalities in children with extrahepatic portal vein obstruction: Response to shunt surgery.

OBJECTIVE: Growth retardation is common in children with extrahepatic portal vein obstruction (EHPVO) and growth hormone (GH) resistance may play a dominant role. The aim of this study was to ascertain growth parameters and growth-related hormones in children with EHPVO, comparing with controls and to study the response of shunt surgery on growth parameters. MATERIALS AND METHODS: The auxological and growth-related hormone profile (GH; insulin-like growth factor binding protein-3 [IGFBP-3] and IGF-1) of thirty children with EHPVO were compared with controls. The effect of shunt surgery on growth parameters in 12 children was also studied. RESULTS: The mean height standard deviation score (HSDS) of cases (-1.797 ± 1.146) was significantly lower than that of controls (-0.036 ± 0.796); the mean weight SDS of cases (-1.258 ± 0.743) was also lower than that of controls (-0.004 ± 0.533). The mean GH level of cases (5.00 ± 6.46 ng/ml) was significantly higher than that of controls (1.78 ± 2.04 ng/ml). The mean IGF-1 level of cases (100.25 ± 35.93 ng/ml) was significantly lower as compared to controls (233.53 ± 115.06 ng/ml) as was the mean IGFBP-3 level (2976.53 ± 1212.82 ng/ml in cases and 5183.28 ± 1531.28 ng/ml in controls). In 12 patients who underwent shunt surgery, growth parameters significantly improved. CONCLUSIONS: Marked decrease in weight and height SDSs associated with GH resistance is seen in children with EHPVO, which improves with shunt surgery.

The efficacy of accelerated, multiple, double-dose hepatitis B vaccine against hepatitis B virus infection in cancer patients receiving chemotherapy.

BACKGROUND: Hepatitis B virus (HBV) infection in cancer patients receiving chemotherapy carries high morbidity and mortality. Conventional hepatitis B vaccination with three doses at 0, 1, and 6 months apart is ineffective in prevention of HBV infection. OBJECTIVES: To compare the efficacy of accelerated, multiple, double-dose HB vaccine with conventional HB vaccine in cancer patients receiving chemotherapy (CT). METHODS: Patients of cancer who were planned for CT were screened for HBV markers (HBsAg, total anti-HB core, anti-HBs antibody and HBV DNA). Patients with negative HBV serum markers received HB vaccine in two groups. Group A received three double doses (40 µg) of recombinant HB vaccine at 0, 1, and 3 weeks before CT and additional three double doses post CT. Group B received HB vaccine (20 µg) at 0, 1, and 6 months. Efficacy of vaccine in the two groups was compared by anti-HBs titers achieved at 3, 6, and 9 months and by HBsAg positivity following CT at 1 year follow up. RESULTS: Protective anti-HBs titers (>10 mIU/mL) at 3, 6, and 9 months in group A and B was 41.1 %, 66.2 %, and 76% and 26 %, 37.7 %, and 49% respectively (p = 0.001). Seven of 454 (1.5%) patients in group A became HBsAg positive after vaccination compared to 19/472 (4.0%) in group B (p = 0.022). CONCLUSION: Accelerated, multiple, double-dose HB vaccine increases seroprotection and is more effective than conventional HB vaccine in preventing HBV infection.

After proper optimization of carvedilol dose, do different child classes of liver disease differ in terms of dose tolerance and response on a chronic basis?

BACKGROUND/AIMS: Literature regarding safe doses of carvedilol is limited, and safe doses across different Child classes of chronic liver disease are not clear. PATIENTS AND METHODS: A total of 102 consecutive cirrhotic patients with significant portal hypertension were included in this study. Hepatic venous pressure gradient was measured at baseline and 3 months after dose optimization. RESULTS: A total of 102 patients (63 males, 39 females) with a mean age of 58.3 ± 6.6 years were included. Among these patients, 42.2% had Child Class A, 31.9% had Class B, and 26.6% had Child Class C liver disease. The mean baseline hepatic venous pressure gradient was 16.75 ± 2.12 mmHg, and after dose optimization and reassessment of hepatic venous pressure gradient at 3 months, the mean reduction in the hepatic venous pressure gradient was 5.5 ± 1.7 mmHg and 2.8 ± 1.6 mmHg among responders and nonresponders respectively. The mean dose of carvedilol was higher in nonresponders (19.2 ± 5.7 mg) than responders (18.75 ± 5.1 mg). However, this difference was not statistically significant (P > 0.05). The univariate analysis determined that the absence of adverse events, the absence of ascites, and low baseline cardiac output were significantly associated with chronic response, whereas, the etiology, Child class, variceal size (large vs small), and gender were not. On multivariate analysis, the absence of any adverse event was determined to be an independent predictor of chronic response (OR 11.3, 95% CI; 1.9-67.8). CONCLUSION: The proper optimization of the dose of carvedilol, when administered chronically, may enable carvedilol treatment to achieve a greater response with minimum side effects among different Child classes of liver disease.

Prolonged Impacted Denture in the Esophagus: A Case Report and Review of the Literature.

Foreign body ingestion and aspiration is among the most common causes of emergency department visit associated with high morbidity and mortality. Ingested and aspirated denture is rare conditions being scarcely reported in the literature. We herein report a 57-year-old man who presented with 2-day history of liquid and solid dysphagia who was diagnosed to have impacted denture in esophagus since 3 years prior to presentation. He was diagnosed to have esophagus adenocarcinoma and had undergone esophageal radiotherapy. The denture was removed successfully using esophagoscopy and the patient was discharged after 48-hour care with good condition. To prevent accidental ingestion, dentures should be made to fit properly. Damaged or malfitting dentures should be discarded and replaced. Patients should be strongly advised against wearing them during sleep-time.

Phospholipase C epsilon 1 (PLCE1) haplotypes are associated with increased risk of gastric cancer in Kashmir Valley.

BACKGROUND/AIM: Phospholipase C epsilon 1 (PLCE1) plays a crucial role in carcinogenesis and progression of several types of cancers. A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus. The aim of the present study was to investigate the role of three potentially functional SNPs (rs2274223A > G, rs3765524C > T, and rs7922612C > T) of PLCE1 in gastric cancer patients from Kashmir Valley. PATIENTS AND METHODS: The study was conducted in 108 GC cases and 195 healthy controls from Kashmir Valley. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed using c2 test and logistic regression models. A P value of less than 0.05 was regarded as statistically significant. RESULTS: The frequency of PLCE1 A2274223C3765524T7922612, G2274223C3765524T7922612 , and G2274223T3765524C7922612 haplotypes were higher in patients compared with controls, conferred high risk for GC [odds ratio (OR) =6.29; P = 0.001; Pcorr = 0.003], (OR = 3.23; P = 0.011; Pcorr = 0.033), and (OR = 5.14; P = 0.011; Pcorr = 0.033), respectively. Smoking and salted tea are independent risk factors for GC, but we did not find any significant modulation of cancer risk by PLCE1 variants with smoking or excessive consumption of salted tea. CONCLUSION: These results suggest that variation in PLCE1 may be associated with GC risk in Kashmir Valley.

Prevalence of gallstone disease in patients with type 2 diabetes and the risk factors in North Indian population: a case control study.

BACKGROUND: Age, female sex, and obesity are considered to be risk factors for gallstone disease. The role of type 2 diabetes (T2D) in gallstone formation is still uncertain, and data in Indians is limited. OBJECTIVES: This is a case-control study to determine the prevalence of gallstones (GS) in patients with T2D, risk factors, and the relative risk compared with subjects without diabetes, selected from the general population. METHODS: Among 450 cases with T2D of a ≥2-year duration, 377 (88.8 %) participated. Diagnosis of GS was made at ultrasonography and history of cholecystectomy for GS. Controls were selected from the general population and diabetes excluded by oral glucose tolerance test. Cases and controls were matched for age, gender, and body mass index (BMI). RESULTS: Gallstones were seen in 67 (17.7 %) cases compared to 40 (5.8 %) in controls (p = 0.001). Prevalence increased with increasing age with peak in the sixth decade (23.4 % in cases and 4.4 % in controls (p = 0.001) and was higher in women (27.9 %) in cases and (7.8 %) in controls, (p = 0.001). In univariate analysis, risk factors for GS included age, female sex, BMI, multiparity, family history of GS, and high triglycerides and cholesterol with low high-density lipoprotein cholesterol. In multivariate analysis, age, (relative risk [RR] 1.54, confidence interval [CI] 1.1-2.1), female sex (RR 1.6, CI 1.0-1.9), and BMI (RR 1.5, CI 1.3-2.5) were the independent risk factors in gallstone formation. CONCLUSION: Patients with T2D had higher probability of having GS compared to the general population. Increasing age, female sex, and higher BMI were independently associated with gallstone disease.

Phospholipase C epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T) polymorphisms and esophageal cancer risk in the Kashmir Valley.

BACKGROUND: Phospholipase C epsilon 1 (PLCE1) encodes a member of the phospholipase family of proteins that play crucial roles in carcinogenesis and progression of several cancers including esophageal cancer (EC). In two large scale genome-wide association studies (GWAS) single nucleotide polymorphisms (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel susceptibility loci of esophageal cancer (EC) in China. The aim of the present study was to investigate this finding in Kashmir Valley, a high risk area. MATERIALS AND METHODS: We determined genotypes of three potentially functional SNPs (rs2274223A>G, rs3765524C>T and rs7922612C>T) of PLCE1 in 135 EC patients, and 195 age and gender matched controls in Kashmiri valley by PCR RFLP method. Risk for developing EC was estimated by binary logistic regression using SPSS. RESULTS: The selected PLCE1 polymorphisms did not show independent association with EC. However, the G2274223T3765524T7922612 haplotype was significantly associated with increased risk of EC (OR=2.92; 95% CI=1.30-6.54; p=0.009). Smoking and salted tea proved to be independent risk factors for EC. CONCLUSIONS: Genetic variations in PLCE1 modulate risk of EC in the high risk Kashmiri population.

Wait-and-see policy versus cholecystectomy after endoscopic sphincterotomy for bile-duct stones in high-risk patients with co-existing gallbladder stones: a prospective randomised trial.

BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy (ES) is one of the most important advances in the treatment of common bile duct (CBD) stones. However, the use of ES to remove CBD stones in high-risk patients without cholecystectomy is still debatable. The aim of this study was to compare the efficacy of a wait-and-see policy versus cholecystectomy after ES for CBD stones in high-risk patients with co-existing cholelithiasis. PATIENTS AND METHODS: A total of 162 patients after undergoing ES with the clearance of CBD stones were randomised after informed consent to cholecystectomy or conservative management of their gallbladder stones. RESULTS: The results indicated that cholecystectomy after ES for CBD stones significantly reduced the biliary complications in high-risk patients. CONCLUSION: Every patient who has both CBD stones and gallstones with significant co-morbid illnesses, after clearance of CBD stones by ES, should undergo early cholecystectomy.