MicroRNA profiling in periampullary carcinoma.

BACKGROUND: MicroRNA expression patterns in many physiological and oncogenic processes have been established. However, the role of aberrant miRNA expression in periampullary carcinoma (PAC) has not been elucidated. We hypothesize that PAC may have differential expression of miRNAs which may differentiate the tumor histological subtypes. METHODS: Fresh paired tumor and control samples were collected from the PAC patients undergoing Whipple's pancreaticoduodenectomy. Microarray miRNA profiling was performed utilizing tumor (n = 40) and control tissues; adjacent normal pancreas (n = 22), six each distal CBD, duodenum and ampulla. Data obtained was subjected to statistical and bioinformatic analysis. Differentially expressed miRNAs obtained were validated using qPCR in an independent set of samples. RESULTS: Comparison of PAC tissue samples with controls revealed 29 common and differentially expressed miRNAs (20 upregulated and 9 downregulated) with a higher statistical significance (p < 0.001) and fold change (log2 FC > 1.5). A subset of 16 miRNAs (15 overexpressed and 1 underexpressed) differed in expression levels between pancreatobiliary and intestinal subtypes. Among these, miR-375, miR-31 and miR-196a expressions varied significantly between histological subtypes. Differential expression profiles of miRNAs specific to TNM staging was also observed in PAC subtypes. Target gene prediction for the differentially expressed miRNAs in PAC revealed that target genes are enriched for certain pathways. Particularly, Wnt signaling pathway genes appear to be relevant targets for most of the differentially expressed miRNAs. CONCLUSION: Differentially expressed common miRNA signatures identified in PAC subgroups may have a role in pathogenesis of PAC and miR-375, miR-31 and miR-196a expression patterns may differentiate PAC subtypes.

Prediction, prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy: An update.

Achalasia cardia, the most prevalent primary esophageal motility disorder, is predominantly characterized by symptoms of dysphagia and regurgitation. The principal therapeutic approaches for achalasia encompass pneumatic dilatation (PD), Heller's myotomy, and the more recent per-oral endoscopic myotomy (POEM). POEM has been substantiated as a safe and efficacious modality for the management of achalasia. Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy, the incidence of gastroesophageal reflux disease (GERD) following POEM is notably higher than with the aforementioned techniques. While symptomatic reflux post-POEM is relatively infrequent, the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications. Contemporary advancements in the field have enhanced our comprehension of the risk factors, diagnostic methodologies, preventative strategies, and therapeutic management of GERD subsequent to POEM. This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux, potential modifications in the POEM technique to mitigate GERD risk, and the strategies for managing reflux following POEM.

CYP2C19 polymorphism as a predictor of personalized therapy in South Indian population.

OBJECTIVES: To study allelic variants of CYP2C19 gene in South Indians. METHODS: A total of 220 individuals (167 Males and 53 Females) confirmed to be healthy on the basis of their physical examination and laboratory studies were recruited in the study. Genotyping of CYP2C19*2 and *3 polymorphisms was performed by a Polymerase chain reaction-Restriction fragment length polymorphism method. RESULTS: The genotypic results of both CYP2C19*2 and CYP2C19*3 are considered to establish the frequency of poor metabolisers related to monooxygenase mediated drug metabolism. Individuals who were homozygous mutants for both m1 (m1/m1) and m2 (m2/m2) and heterozygous for both m1 and m2 (ml/m2) mutations were categorized as poor metabolisers. In the present study the frequency of Homozygous Extensive Metabolizers (HomoEM), Heterozygous Extensive Metabolizers (HetEM) and Poor Metabolizers (PM) are 32.2% (n = 71), 52.8% (n = 116) and 15.0% (n = 33) respectively. CONCLUSION: Since inter individual genetic variations play crucial role in variety of drugs, the identification of intermediate and poor drug metabolizers based on CYP2C19 polymorphism can be a basis for the standardization of personalized therapy.

Management of hepatitis B and C in special population.

Chronic viral hepatitis is one of the leading causes of cirrhosis worldwide. Chronic hepatitis B is more common in the Asia-Pacific region due to the larger population and lower screening availability. Hepatitis C predominates in the west due to injection drug abuse. The discovery of (oral) direct-acting antiviral agents (DAAs) has changed the landscape of chronic hepatitis C (CHC) management. Nucleos(t)ide analogs (NUCs) have also changed the approach to the treatment of chronic hepatitis B (CHB). Oral NUCs and DAAs have excellent efficacy and patient acceptance as well as a lower risk of resistance. However, certain populations have no robust data and safety and efficacy of such oral drugs is still evolving. In this review, we provide an overview of the management of CHB and CHC in special populations, such as those with chronic kidney disease, pregnant women, healthcare workers, and those undergoing chemo- or immunosuppressive therapy.

Hepatic cholesterol transporter ABCG8 polymorphisms in gallstone disease in an Indian population.

BACKGROUND AND AIM: Gallstone formation is characterized by the abnormal regulation of cholesterol trafficking and solubilization. The prevalence of gallstone disease (GSD) differs between ethnic groups sharing the common environment. These differences can be explained by a genetic predisposition to gallstone formation. Studies have identified single nucleotide polymorphisms (SNP) D19H and T400K in the cholesterol transporter gene ATP-binding cassette, subfamily G, member 8 (ABCG8) in patients with cholesterol gallstones. The aim of this study was to analyze the relationship between D19H and T400K polymorphisms in the ABCG8 gene and GSD in an Indian population, and the effects of these polymorphisms on cholesterol levels in sera and bile. METHODS: A total of 226 patients with GSD were analyzed for their lipid profile in plasma and bile. A total of 289 controls were recruited, and their plasma lipid profile was analyzed by standard protocols. The genotype of SNP D19H and T400K of ABCG8 was analyzed in 226 patients and 222 control samples. SNP D19H was analyzed by direct sequencing, and SNP T400K genotyping was assayed by the amplification refractory mutation system-polymerase chain reaction. RESULTS: There was no significant difference in the allelic distribution of SNP T400K between the GSD and gallstone-free groups (P > 0.05), but the distribution of the SNP variant, D19H, was significantly higher (P = 0.017, odds ratio = 2.274) in patients compared to controls. The analysis of serum and bile cholesterol followed a strong association with genotypes. CONCLUSION: SNP D19H, but not SNP T400K, in the ABCG8 gene is significantly associated with GSD in an Indian population.

Genotype distribution in relation to viral load in a large cohort of Indian patients with chronic hepatitis C virus infection: A retrospective analysis.

INTRODUCTION: Hepatitis C virus (HCV) displays high genetic diversity, characterized by regional variations in the prevalence of genotype posing challenges to the development of vaccines and definitive treatment. Very few reports exist on the distribution and frequency change of HCV genotypes in India. In the present retrospective study, we aimed to understand the distribution pattern of HCV genotypes and viral load among HCV-infected patients attending the Asian Institute of Gastroenterology, Hyderabad, India, a tertiary care hospital. METHODS: Patients referred to the Hepatology Department from January 2009 to December 2015 were screened for this study. Eight hundred and sixty-two chronic HCV patients were included in this study. Genotyping was performed using type-specific probe-based hybridization assay and viral load was estimated by real-time polymerase chain reaction. RESULTS: Out of 862 patients, genotype 1 was detected predominantly in 392 (45.5%), followed by genotype 3 in 344 (39.9%) patients; genotypes 4, 6, and 2 were detected in 115 (13.3%), 8 (0.9%), and 3 (0.3%) patients, respectively. The number of patients having genotype 1 increased in frequency while genotype 3 became less from the year 2009 to 2015. Patients having genotype 1 had significantly (p < 0.0001) higher viral load compared with the patients infected with other genotypes. CONCLUSION: Our study results demonstrate a change in HCV genotypic distribution pattern from genotypes 3 to 1 during the span of 7 years in patients referred to our hospital. In the light of the reported difference in the pathogenic potential of various HCV genotypes, detection of HCV genotype appears to be still essential for better patient management.