Identificación de asociaciones clínico-patológicas e hipermetilación de genes supresores de tumores en cáncer gástrico difuso a través de análisis de Hierarchical clustering / Hierarchical clustering analysis to detect associations between clinical and pathological features of gastric tumors and hypermethylation of suppressor genes

Background:Methylation is an inactivation mechanism for tumor suppressor genes, that can have important clinical implications. Aim: To analyze the methylation status of 11 tumor suppressor genes in pathological samples of diffuse gastric cancer. Material and methods: Eighty three patients with diffuse gastric cancer with information about survival and infection with Epstein Barr virus, were studied. DNA was extracted from pathological slides and the methylation status of genes p14, p15, p16, APC, p73, FHIT, E-caderin, SEMA3B, BRCA-1, MINT-2 y MGMT, was studied using sodium bisulphite modification and polymerase chain reaction. Results were grouped according to the methylation index or Hierarchical clustering (TIGR MultiExperiment Viewer). Results: Three genes had a high frequency of methylation (FHIT, BRCA1, APC), four had an intermediate frequency (p15, MGMT, p14, MINT2) and four had a low frequency (p16, p73, E-cadherin, SEMA3B). The methylation index had no association with clinical or pathological features of tumors or patients survival. Hierarchical clustering generated two clusters. One grouped clinical and pathological features with FHIT, BRCA1, and APC and the other grouped the other eight genes and Epstein Barr virus infection. Two significant associations were found, between APC and survival and p16/p14 and Epstein Barr virus infection. Conclusions: Hierarchical clustering is a tool that identifies associations between clinical and pathological features of tumors and methylation of tumor suppressor genes.

Características clínico-moleculares del cáncer gástrico cardial asociado al virus Epstein Barr / Clinical and molecular features of cardial gastric cancer associated to Epstein Barr virus

Background: Mortality caused by cardial gastric cancer in Chile, is increasing. Previously we demonstrated an association between Epstein Barr virus and this specific location of gastric cancer. Aim: To perform a clinical and molecular characterization of cardial gastric cancer associated to Epstein Barr virus. Material and methods: Epstein Barr virus was identified in 93 cardial gastric tumors, by in situ hybridization. Clinical and pathological features, survival and expression of p53 and c-erbB2 were compared between tumors with or without the presence of the virus. Results: Twenty two (23.6%) tumors expressed Epstein Barr virus. No difference in sex or age of patients with tumors positive or negative for the virus was observed. Epstein Barr positive tumors had a tendency to have a higher frequency of Bormann III endoscopic appearance and a lower frequency of p53 accumulation (p=0.06). Five years survival was 67% and 42% of tumors positive and negative for the presence of the virus, respectively (p=0.57). Conclusions: Our results, although not significant, show a tendency towards unique characteristics of cardial gastric tumors associated to Epstein Barr virus.

Efectos de la infusión aguda de octreotido sobre la función renal en pacientes con cirrosis hepática e hipertensión portal / Effects of acute octreotide infusion on renal function in patients with cirrhosis and portal hypertension

Background: Octreotide is used in the treatment of acute variceal bleeding, based on its inhibitory effects of post-prandial splanchnic hyperemia and splanchnic venoconstriction. The consequences of these haemodynamic changes on renal circulation are not well known in cirrhotic patients. Aim: To evaluate the effects of acute octreotide administration on several parameters of renal function, including free water clearance, in patients with cirrhosis with or without ascites. Patients and Methods: Twenty cirrhotic patients, Child-Pugh A or B, with or without ascites, with esophageal varices, normal renal function and free of medications (vasoactive drugs or diuretics) were assigned to 2 different protocols. Protocol 1: 10 patients were randomized to receive octreotide or placebo, as a bolus followed by a continuous infusion. Glomerular filtration rate (GFR) and renal plasma flow (PRF) were measured, in basal conditions and during the drug or placebo administration. Protocol 2: 10 additional patients were randomized in the same way and free water clearance and urinary sodium excretion were again measured in the basal period and during the drug or placebo infusion. Results: After octreotide or placebo administration no significant changes were observed neither in GFR nor in PRF. The free water clearance decreased significantly during octreotide administration (3.12 ml/min±1.04 SE vs 0.88±0.39, p <.03). In both protocols no changes in mean arterial pressure were observed. Conclusions: Acute administration of octreotide to cirrhotic patients with portal hypertension, with or without ascites, did not produce any change in glomerular filtration rate or in estimated renal plasma blood flow. However the free water clearance decreased significantly. This effect, under chronic administration, could be clinically important and deserves further studies.