Venkatakrishnan Leelakrishnan

Runt-Related Transcription Factor 3: Single Nucleotide Polymorphism rs760805, Gene Expression, and Methylation Status in Helicobacter pylori-Infected Patients for Determination of Gastric Cancer Risk

PurposeRepression of Runt-related transcription factor 3 (Runx3) gene, a tumor suppressor, has been known to be involved in Helicobacter pylori (H. pylori)-associated gastric carcinogenesis and cancer development. The present study was undertaken to study the Runx3 intronic T/A polymorphism (rs760805) in H. pylori-infected patients and uninfected controls of Tamil Nadu region, South India. Also, Runx3 gene expression, HK alpha (H,K-ATPase) gene expression and the methylation status of the Runx3 CpG island was determined.MethodsIn a prospective study, tissue biopsies were collected from 40 H. pylori-infected patients and 40 infection negative controls. Single nucleotide polymorphism analysis was carried out by polymerase chain reaction (PCR)-single-strand conformational polymorphism, and DNA sequencing. Gene expression analysis of Runx3 and HK alpha was carried out using semiquantitative reverse transcriptase-PCR. Methylation analysis of Runx3 CpG island was undertaken using methylation-specific restriction digestion-PCRResultsThe homozygous TT genotype was found to be the predominant genotype in positive samples and negative controls. No significant variation in gene expression was observed in positive samples and controls with respect to Runx3 and Hk alpha genes. Methylation analysis suggested that there was a lack of methylation except in a few subjects studied.ConclusionThe present study, first from this region, could neither detect significant repression of the Runx3 and HK alpha genes nor methylation in positive patients studied suggesting a lack of involvement of this tumor suppressor as a risk factor in the H. pylori-associated gastric carcinogenesis in the South Indian population studied.

Role of noninvasive markers to predict the presence of esophageal varices in cirrhosis: Pilot study

Cirrhosis of liver leads to portal hypertension and development of esophageal varices (EV), rupture of which results in spontaneous hematemesis. Upper gastrointestinal (UGI) bleeding is a catastrophic presentation of EV. Endoscopy remains the standard procedure for diagnosis [1] and esophageal variceal ligation as treatment of varices for decades; but with each passing day, the demand to develop noninvasive methods to diagnose varices is increasing. This pilot study aimed to find the association between esophageal varices, liver stiffness, spleen stiffness, and platelet counts and also to assess whether these indicators can be used to establish benchmarks in the future as noninvasive predictors of portal hypertension. A cross-sectional observational study was done at a tertiary health center from February 2014, to January 2015. Adult patients of ages ≥ 18 years of either sex with newly diagnosed chronic liver disease (CLD) and portal hypertension were included. The patients underwent routine biochemical and radiological investigations. Patients underwent an UGI and esophageal varices were graded as per Baveno V consensus. Liver stiffness (LS) and spleen stiffness (SS) values were assessed in patients with Acoustic Radiation Force Impulse (ARFI) (Siemens Acuson S2000TM). Individual readings were taken for the liver and spleen, the mean of which was taken as a final value expressed in meters per second. For LS, the METAVIR scoring system was used. Toshiba SSA-70 was used to carry out ultrasound examination. Fifty patients (with mean age of 50.44 ± 13.11 years were taken. OnUGI endoscopy, the presence of EVwas noted in 39 (78%) patients. Thirty-two (94.12%) patients had platelet count < 150,000/mm and 7 (5.88%) patients had platelet count ≥ 150,000/mm (p < 0.001). Sixteen patients (41.03%) had liver size ≥ 14.6 cm and 23 patients (58.97%) had liver size < 14.60 cm. However, this difference was statistically not significant. The diagnostic accuracy of liver size in predicting EV was 38% with 41.03% sensitivity, 27.27% specificity, and 0.56 positive likelihood ratio. Twenty-six had LS ≥ 2.09 while 11 patients (had LS < 2.09 [p = 0.104]. LS had an accuracy of 68% in predicting EV with 71.79% sensitivity and 54.55% specificity and positive likelihood ratio was 1.58. SS was ≥ 2.87 in a significantly higher number of patients (26 patients; 89.66%) compared to those who had < 2.87 (13 patients; 61.9%) (p = 0.023). SS had an accuracy of 68% for EV, with sensitivity of 66.67%. Among the 39 patients with EVs, a majority of the patients had LS of ≥ 2.09, that is 28 (71.8%) patients and 11 patients (28.2%) who did not have EV, but the difference was statistically not significant (p = 0.104). However, the sensitivity of LS in predicting EV was slightly high, that is 71.79% but less specific 54.55% resulting in diagnostic accuracy of 68% and positive likelihood ratio of 1.58. There is a wide variation of LS values in the literature that ranges from 2.5 to 75 kPa. These values are altered by gender, BMI, etiology, and necroinflammatory change [2, 3]. Normal TE values are 3.8 to 8 kPa in men and 3.3 to 7.8 kPa in women while in fibrosis (METAVIR fibrosis stage ≥ 2) the values are 7 to 8 kPa and in cases with cirrhosis, the values are 13 to 17 kPa [4]. Platelet count has been reported as the most sensitive and specific noninvasive parameter for predicting * Shiran Shetty drshiran@gmail.com

Fibrolamellar variant of hepatocellular carcinoma presenting during pregnancy: management dilemmas

The Fibrolamellar variant of Hepatocellular Carcinoma (FLHCC) is a rare form of liver cancer that presents in the 3rd decade of life, is rarely associated with cirrhosis or chronic Hepatitis B/C virus infection, and usually presents with normal serum alpha-fetoprotein (AFP) levels. FLHCC presenting during pregnancy is extremely rare, with only 4 cases reported. We present a case of FLHCC in pregnancy and discuss the dilemmas in management. A 26 year-old primigravida, 26 weeks of gestation presented with a months history of obstructive jaundice secondary. Investigations revealed a mass in the left lateral segment of the liver with extension down the left hepatic duct into the common bile duct. Following an emergency caesarean section at 31 weeks, she underwent a left hepatectomy with extrahepatic bile duct excision. The postoperative course was uneventful. Histopathology showed FLHCC. In conclusion, liver tumors presenting during pregnancy should be managed in a multidisciplinary setup with facilities for neonatal intensive care. Management depends on the presumed pathology, period of gestation and family preferences.

High-grade non-Hodgkin's lymphoma of ovary presenting as peritonitis

Primary ovarian lymphoma is rare, with ovary more commonly involved secondarily in generalized disease. Primary ovarian lymphoma presents as mass in the ovary with chronic symptoms; an acute presentation has not been described previously. A 75-year-old female presented with acute abdomen and features of peritonism. Computed tomography and magnetic resonance imaging demonstrated large mass in left ovary along with infiltration of adjacent sigmoid colon causing perforation and pneumoperitoneum. Few jejunal loops were also involved. Intraoperatively, there was left ovarian mass infiltrating the sigmoid colon with perforation and fecal peritonitis. Distal jejunal loops were adherent to the tumor. The involved sigmoid colon was resected with total abdominal hysterectomy, bilateral salpingo-oophorectomy and resection of adherent jejunal loops. Histopathology revealed ovarian tissue with necrotic neoplasm composed of small-to medium-sized round cells exhibiting nuclear irregularity and scanty cytoplasm, forming discohesive sheets with the neoplasm infiltrating the retroperitoneal remnant tissue and resected bowel. This case highlights an unusual presentation of primary ovarian lymphoma.

Jejunal Diverticulosis - Rare Cause of Gastrointestinal Bleed

Jejunal diverticulosis was first described by Somerling in 1794 and by Sir Astley Cooper in 1807. Jejunal diverticula are rare. Hemorrhage from jejunal diverticula usually presents as gastrointestinal bleeding. Here, we present a case of severe gastrointestinal bleeding presenting as malena due to jejunal diverticulosis.

Diffuse intestinal polypoid angiodysplasia

This 6-year-old boy presented with bleeding per rectum for two days. He was pale but hemodynamically stable. There were no mucocutaneous lesions. He had two similar episodes in the past treated conservatively elsewhere. Hemoglobin was 6 g/dL and other blood investigations were normal. Esophagogastroduodenoscopy, ultrasound abdomen and colonoscopy did not reveal any abnormal findings. Meckel’s isotope scan was negative. Laparoscopy assisted enteroscopy revealed diffuse bluish polypoid lesions in the jejunum with ooze in one particular segment (Fig. 1a). The oozing segment was surgically resected and end-to-end anastomosis was done (Fig. 1b). Histopathological examination showed foci of dilated, tortuous, thin-walled vascular channels and few arterial channels in the submucosa with focal

Esophageal lipoma presenting as a long tongue

A 42-year-old man presented with history of non progressive dysphagia both for solids and liquids for the past 2 years. He used to bring out a fleshy mass from mouth during retching, followed by choking. Upper gastrointestinal endoscopy revealed a soft, long, smooth, bulging lesion in the upper esophagus, extending for a length of 20 cm. Pillow-sign was positive. Patient coughed immediately after the procedure, and brought out a fleshy pink tubular mass with a blind end from the mouth (Fig. 1), which caused sudden choking. The mass was maneuvered back by the patient himself. Endoscopic ultrasound showed hyperchoic lesion arising from the third layer of esophageal wall suggestive of lipoma. His CT thorax showed submucosal elongated polypoidal lesion with feeding blood vessels, and luminal narrowing in the upper part of the esophagus (Fig. 2). Surgical excision of the