ERCP practice at a tertiary care hospital in Kashmir, North India: a large single-center cross-sectional study with focus on quality indicators, success rate, and indications.

Endoscopic retrograde cholangiopancreatography (ERCP) is the most technically demanding endoscopic procedure with significant adverse events that mandate appropriate training, competence and careful decision-making. The American Society for Gastrointestinal Endoscopy (ASGE) and the European Society of Gastrointestinal Endoscopy (ESGE) updated a list of quality indicators and performance measures for pancreatobiliary endoscopy. Nevertheless, real-life data are scarce, especially from developing countries. The study aimed to assess overall quality, procedural success, and indications of ERCP at our center. Methods: An audit of our endoscopy center at the start of the study for quality and performance indicators and a retrospective analysis of the 4 years of the prospectively maintained data of patients who underwent ERCP regarding procedural success and indications was done. Results: The study showed that ERCP is performed by meeting good quality standards, but structured training, sedation practice, and microbiological surveillance are subpar. A total of 3544 procedures were carried out with successful cannulation of the naive papilla in 93%, with 60% of procedures carried out on females, 80.5% of procedures done for benign diseases, and 19.5% on suspected or proven malignancy (47% men and 53% women) with perihilar obstruction being commonest in both sexes (32-33%) followed by carcinoma gallbladder in women (21%) and distal cholangiocarcinoma in men (27%). Among benign diseases (2711), 12% had benign pancreatic diseases, and 64.8% had common bile duct (CBD) stones, with 31% of CBD stones requiring more than one session for clearance. Conclusion: ERCP at our center is performed by meeting quality standards and by competent endoscopists with good procedural success. Improving sedation strategies, microbiological surveillance, and training programs remains an unmet need.

Clinicopathological Profile of Non-small Cell Lung Cancer and the Changing Trends in Its Histopathology: Experience From a Tertiary Care Cancer Center in Kashmir, India.

Background The overall frequency and incidence of different cancers across the globe, including lung cancer, are marked by ethnic and geographical variations. Lung cancer is the most commonly diagnosed cancer worldwide that inflicts most of the cancer deaths. Non-small cell lung cancer (NSCLC) constitutes most lung cancer cases. The aim of this study was to find the frequency and clinicopathological characteristics of NSCLC in high incidence zone of Kashmir, an ethnically and geographically distinct area in Northern India. Material and methods The study was conducted to evaluate the clinicopathological profile of NSCLC at a tertiary care cancer center, Sher-I-Kashmir Institute of Medical Sciences (SKIMS). The patients and case records were analyzed for clinical presentation and demographic features, smoking status, radiological features, histopathological type, and stage of their disease at presentation. Results The study included 1557 NSCLC patients registered over a period of seven years, i.e., 2008-2014. Most of the patients belonged to rural areas (70%). The median age of the whole cohort was 58.0 years (ranges 22-95 years), and the male-to-female ratio was 3.7:1 (male = 1231 and female = 326). Smokers comprised 77.39% of cases, and Hookah was the most common form of smoking (65.06%). The ratio of squamous cell carcinoma and adenocarcinoma was 3.7:1 (67.5% vs. 24.9%). Stage III and IV disease accounted for 93% of cases (30.6% and 62.7%, respectively). Squamous cell carcinoma histopathology was dominant in smokers (74.3%) compared to adenocarcinoma (19%), while squamous cell carcinoma and adenocarcinoma histopathology ran parallel in nonsmokers (45.1% and 44%, respectively). Most of the patients had an Eastern Cooperative Oncology Group (ECOG) performance status between 1 and 2 (79%).  Conclusion We conclude Kashmir region is a very high-risk area for lung cancer, with NSCLC showing a high incidence. Most of our patients present in advanced stages, and the frequency of adenocarcinoma is showing an increasing trend over the years from 2008-2014.

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.

Dietary valine improved growth, immunity, enzymatic activities and expression of TOR signaling cascade genes in rainbow trout, Oncorhynchus mykiss fingerlings.

This study was conducted to determine the effects of dietary valine (Val) on growth, hemato-biochemical parameters, immunity, enzymatic activities, antioxidant status and expression of target of rapamycin (TOR) and 4E-BP genes in rainbow trout, Oncorhynchus mykiss (1.57 ± 0.03 g; 5.10 ± 0.34 cm). Six isonitrogenous (450 g kg-1) and isoenergetic (20.90 kJ 100 g-1, gross energy) diets were designed to represent varied Val levels (10.5, 13.0, 15.5, 18.0, 20.5 and 23.0 g kg-1 dry diet basis). Growth parameters improved significantly (P < 0.05) with the amelioration of dietary Val level up to 18.0 g kg-1. Highest (P < 0.05) body protein content was noted at 18.0 g kg-1 dietary Val. Significant differences in hematological, intestinal enzymatic activities and antioxidant parameters were noted. However, plasma variables did not show any significant differences except aspartate transaminase and uric acid. Total protein content increased significantly, while the albumin and globulin content did not show any significant (P > 0.05) difference. Moreover expression of TOR mRNA and elF4E-binding protein (4E-BP) was observed higher (P < 0.05) at 18.0 g kg-1 Val. On the basis of results, optimum dietary Val requirement for maximal growth of rainbow trout was determined to be 18.19 g kg-1 of dry diet, corresponding to 40.42 g kg-1 of dietary protein.

Haematological and serum biochemical reference values of snow trout, Schizothorax labiatus habiting in river Sindh of Indian Himalayan region.

Haematological and serum biochemical parameters are a valuable tool in determining the wellbeing status of different fish species and response in close association to various biological and environmental factors, therefore the aim of the present study was to establish sex-wise reference values of haemato-biochemical parameters of S. labiatus. The haematological parameters such as haemoglobin (Hb) concentration, total erythrocyte count (RBC), total leucocyte count (WBC), packed cell volume (PCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV) and serum biochemical parameters such as glucose, cholesterol, urea, total protein, albumin and globulin were analysed. The results revealed that the haematological parameters, i.e., Hb, RBC, WBC and PCV showed significant (P < 0.05) differences with respect to sex. Significantly (P < 0.05) higher values of Hb content (11.18 g dl-1 ), RBC count (1.88 × 106 mm-3 ) and PCV (36.15%) were noted in male fish than females throughout the study period, while significantly (P < 0.05) higher WBC count was noted in females (20.38 × 103 mm-3 ) compared to males. However, no significant (P > 0.05) difference was observed in erythrocyte indices like MCH, MCHC and MCV between sexes. The serum biochemical parameters, i.e., glucose, cholesterol and urea, also showed significant (P < 0.05) difference between the sexes, but no significant (P > 0.05) difference was noticed in total protein, albumin and globulin. Significantly (P < 0.05) highest values of glucose (116.76 mg dl-1 ) and urea (9.01 mg dl-1 ) were recorded in male S. labiatus, while highest value of cholesterol (223.53 mg dl-1 ) was noted in females. The information generated in the present study gives the basic reference values of haematological and serum biochemical parameters of S. labiatus which will be useful in monitoring the wellbeing status of fish populations. Moreover, the data will also be helpful to ascertain the occurrence of different clinical and subclinical diseases, which may in turn help to boost the overall production of this species.

Socioeconomic status and esophageal squamous cell carcinoma risk in Kashmir, India.

Studies have persistently associated esophageal squamous cell carcinoma (ESCC) risk with low socioeconomic status (SES), but this association is unexplored in Kashmir, an area with a high incidence of ESCC in the northernmost part of India. We carried out a case-control study to assess the association of multiple indicators of SES and ESCC risk in the Kashmir valley. A total number of 703 histologically confirmed ESCC cases and 1664 controls matched to the cases for age, sex, and district of residence were recruited from October 2008 to January 2012. Conditional logistic regression models were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals. Composite wealth scores were constructed based on the ownership of several appliances using multiple correspondence analyses. Higher education, living in a kiln brick or concrete house, use of liquefied petroleum gas and electricity for cooking, and higher wealth scores all showed an inverse association with ESCC risk. Compared to farmers, individuals who had government jobs or worked in the business sector were at lower risk of ESCC, but this association disappeared in fully adjusted models. Occupational strenuous physical activity was strongly associated with ESCC risk. In summary, we found a strong relationship of low SES and ESCC in Kashmir. The findings need to be studied further to understand the mechanisms through which such SES parameters increase ESCC risk.

Combined impact of polymorphism of folate metabolism genes; glutamate carboxypeptidase, methylene tetrahydrofolate reductase and methionine synthase reductase on breast cancer susceptibility in kashmiri women.

BACKGROUND: Folate and methionine play a crucial role in DNA synthesis, repair and the epigenetic profile of cell. Hence, the alterations in the folate metabolism can lead to aberrant proliferation leading to neoplasia. Most of the studies have associated polymorphisms in methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes with reduced risk of cervical and colorectal cancer. However, the association with breast cancer is still controversial. Further, the involvement of Glutamate carboxypeptidase II (GCPII) polymorphism in cancer is not known. In the present study, we analyzed if the individual and combined effects of polymorphisms in folate pathway genes viz., MTHFR 677C > T, MTHFR 1298A > C, MTRR 66A > G and GCP II 1561 C>T, have any role in altering the susceptibility to breast cancer. METHODS: The DNA of 35 female breast cancer patients and 33 healthy individuals, in the Kashmiri population from India, were analyzed using a PCR-RFLP approach for the above mentioned polymorphisms. RESULTS: Individuals carrying the MTHFR 677CT/TT and GCPII 1561 CT genotype showed a 3.5 (95% CI: 3.1-3.7, P<0.02) and 7.7 (95% CI: 6.7-9.1, P<0.001) fold decreased risk for breast cancer than the wild types (MTHFR 677CC and GCPII 1561 CC). Subjects with MTRR 66 G-allele showed a 4.5 fold decreased risk (OR: 0.22, 95% CI: 0.20, 0.24, P<0.0005) compared to the wild type (MTRR 66A). Further, subjects with combined polymorphisms in MTHFR, GCPII and MTRR loci revealed a significant reduction of breast cancer risk. CONCLUSION: This study indicates (i) a protective role of polymorphisms in MTHFR, GCPII, MTRR against breast cancer in the study subjects, and (ii) combined effect of polymorphisms is more pronounced than single genetic polymorphism, thereby emphasizing the role of gene-gene interaction in the susceptibility to breast cancer.

Mutations in epidermal growth factor receptor gene in esophageal squamous cell carcinoma patients in kashmir- a high incidence area of India.

Activating mutations in Epidermal Growth Factor Receptor (EGFR) are common in lung adenocarcinoma of never smokers but are rare in other types of cancer. Here we have analysed mutations in exons 19 to 21 of EGFR and in exons 19 and 20 of the EGFR homolog HER2 in 54 cases of Esophageal Squamous Cell Carcinomas (ESCC) from patients recruited in Kashmir, India, a region of high incidence for this cancer. We report the detection of 3 mutations (6%) in the ATP-binding regulatory loops of the tyrosine kinase domain of EGFR (deletion 746-750, P753L, G719D). No mutation was found in HER2. This is the first report of activating EGFR mutations in ESCC, of the same type as those detected in lung adenocarcinoma of never-smokers. This suggests that a small proportion of ESCC patients in this high incidence area may benefit from treatment with EGFR tyrosine kinase inhibitors.