Hepatology and Pancreatic Science

Electrical stimulation of the gastrointestinal tract has been touted as a possible therapy for intestinal motor dysfunction since 1963 when Bilgutay, et al., reported the use of transluminal electrical stimulation to induce peristalsis. In the late 1960???s and 1970???s the myoelectrical activity of the gastrointestinal tract was elucidated along with its relationship to gut contractility. Out of this initial research several clinical applications of gastrointestinal electrical stimulation have arisen. These include gastric electrical stimulation (GES) for treatment of gastroparesis, sacral nerve stimulation (SNS) for treatment of fecal incontinence and constipation and electrical stimulation of the lower esophageal sphincter (LES) for treatment of severe gastroesophageal reflux disease (GERD). GES is a low energy, high frequency system that stimulates the nerves that innervate the gastric antral muscle. GES improves nausea and vomiting, decreases medical costs, decreases hospital days and improves quality of life in patients with gastroparesis refractory to dietary and pharmacological interventions. SNS is a low energy, high frequency system that directly stimulates the third sacral nerve root. SNS significantly improves severe fecal incontinence and constipation compared with optimal medical therapy. Electrical stimulation of the LES for treatment of GERD is the newest electrical stimulation therapy. Studies published in the last two years demonstrate sustained improvement in GERD outcome and GERD-HRQL, elimination of the need for daily GERD medications and sustained normalization of esophageal acid exposure compared to standard medical therapy for severe GERD. Electrical stimulation of the gastrointestinal tract continues to have great potential for many GI disorders.

Introduction: Vedolizumab (VDZ) is a humanized monoclonal antibody ?4?7 integrin-receptor antagonist indicated for the treatment of patients with moderately to severely active ulcerative colitis or Crohn's disease. We want to show our modest experience with the use of vedolizumab as a rescue therapy when other medical therapies have failed. Methods: An observational study was carried out on patients with inflammatory bowel disease treated with VDZ for at one year. An evaluation was performed on the activity indices, fecal calprotectin, and C-reactive protein levels. Results: Our study included 7 patients (5 CD, 2 UC, mean age 40 years). Previous treatment failures with ??? 2 anti-TNFs. At one year, in all patient maintained the clinical response and remission. The C-reactive protein and fecal calprotectin decreased significantly in both CD and UC patients. Discussion: Our experience indicates that a long-term effect can be achieved, even beyond 1 year of treatment. Vedolizumab is generally well tolerated. Vedolizumab may be used as a rescue therapy in patients with medically refractory ulcerative colitis or Crohn's disease..

Esophageal squamous cell carcinoma (ESCC) is among the most common human cancers, with an overall fiveyear survival rate of around 20%. To improve the diagnosis and prognosis of ESCC, we performed systematic studies on the molecular alterations in the disease. Frequent gains of chromosomal bands 3q26, 8q24, 11q13, losses of 3p14 and 9p21, amplifications of genes CCND1, EMS1 (CTTN), EGFR, PLK1, SKP2, PRKCI (PKCiota), deletions of CDKN2A/B, FHIT and rearrangements of NTRK3, DTL and PTPRD were found. The mutation profiling was characterized and potential therapeutic targets were identified. We further investigated intratumor heterogeneity (ITH) of the molecular alterations and constructed phylogenetic trees for genomic evolution, in which the mutations of ERBB4, FGFR2, BRCA2, ATM, TP53 and copy number changes of 11q13 and 9p21 were early events and those of PI3K/MTOR pathway, KIT, AURKA, CCND2 and 3q26 were late. By proteomic techniques and immunohistochemistry, multiple proteins were observed with high expression in tumor tissues but negative/low expression in morphologically normal operative margins.
Especially, copy number alterations of ANO1, CDKN2A, and high expression of p63 and ANO1 were also present in precancerous lesions (dysplasia). We further explored the mechanisms underlying the development and progression of ESCC and revealed that CRT, CTTN, PKCiota, SKP2 and PLK1 enhanced cell motility and resistance to apoptosis and promoted tumor growth and metastasis via activating the PI3K-AKT pathway, inhibiting beta-catenin degradation and up-regulating the apoptosis suppressor Survivin. These findings extend our understanding of ESCC, providing theoretical foundation for elucidating the mechanisms underlying the tumorigenesis of the esophagus and progression of ESCC and for developing classification biomarkers and therapy targets for ESCC treatment.

Introduction: Gut microbiota cluster into three enterotypes named the Bacteroides, Prevotella and Ruminococcus. While each person???s microbial ???fingerprint??? is unique, there are specific patterns seen in those that are healthy and those that have specific illnesses.
Objective: The objective of the present study was to identify the enterotypes that are possibly associated with Type I Diabetes Mellitus (T1DM) Egyptian patients as well as their possible role in the course of the disease.
Subjects & Methods: The study included 40 T1DM patients as well as control group of 20 healthy subjects of matched age and sex. Stool specimens were taken from each. Quantitative SYBR Green Real-Time PCR was done for the identification and quantitation of Bacteroides, Prevotella and Ruminococcus which constitute the core of the three major enterotypes.
Results: Enterotype 1 was the most common enterotype detected in T1DM and control cases (75% versus 65% respectively) with no significant differences between the two groups (P=0.418). Regarding enterotype 2 no significant differences was noted between T1DM patients and control group (25% vs. 35% respectively P=0.324). For enterotype 3, it was detected neither in patients with T1DM nor in control cases.
Conclusion: There was no significant difference in the distribution of enterotypes in all study groups. Therefore, collapsing the whole microbiome variations into dominant enterotypes was not appropriate to identify disease association or to be used as a disease biomarker.

Background: The prevalence of GI and liver disease in the Pakistani population has increased remarkably over the recent years, reflecting an elevated burden on healthcare systems. Optimized health management and effective resource utilization in Healthcare facilities are based on timely documentation and reporting of disease patterns. Aims: To present data from the GODD (gastroenterology outpatient discharge diagnosis) registry, comparing annual trends of GI & liver disease incidence among patients presenting to the Aga Khan University Hospital. Methods: A review of electronic records was performed for all patients presenting to the Gastroenterology clinic, AKUH between 2013 and 2016. Collected information included patient characteristics and outpatient discharge diagnosis (primary and associated), based on a list of 72 approved diagnosis categories related to gastrointestinal and Liver Diseases. Annual variation in this data is presented in this paper. A single visit is counted for a specific year for each patient. Result: A total of 28,493 new patients were seen in the gastroenterology clinic. The mean age of the patients was 44.6+15.8 years with an overall higher representation of males (58%). The number of patients was seen to gradually increase during the study period from 6410 in 2013 to 8138 in 2016. Overall, 15,956 (56%) patients presented with GI disease which comprised APD(78.4%), FGID (14.98%) and others(6.62%), while patients with liver diseases were 12,535 (44%) and included HCV(50.3%), HBV(20.3%),HDV(7%),Hepatitis A(0.79%), Hepatitis E(0.59), NBNC(4.22%), NASH(5%), Hepatoma (1.80%), Others(10%). Conclusion: This report highlights annual trends in outpatient data from a major tertiary care center in Karachi, Pakistan. The analysis suggests a higher frequency of GI disorders, the majority of which is comprised of APD, GERD,gastritis. Among liver disorder, HCV, HBV was highest in our setting. Further efforts should focus on prioritization and effective management of these most commonly observed ailments.