Extended intraoperative peritoneal lavage as prophylactic peritoneal recurrence for locally advanced gastric cancer: a prospective randomized trial.

BACKGROUND: To demonstrate whether extensive intraoperative peritoneal lavage (EIPL) could yield better results in overall survival and less recurrence, regardless of peritoneal cytology, compared to standard peritoneal lavage (SPL). METHODS: A prospective randomised multicenter study including 94 patients (47 per arm) to detect a 20% difference in 3-year overall survival in patients with locally advanced tumours without peritoneal carcinomatosis. Three samples of peritoneal fluid were obtained (at the beginning, the end of procedure and after the assigned peritoneal lavage). Clinicopathological and surgical data were analysed by group. Postoperative complications, location of recurrence and surgical approach were evaluated. Overall survival was calculated by the Kaplan-Meier method and the uni/multivariate analysis for prognostic factors was carried out using Cox regression analysis. RESULTS: A total of 86 patients were analysed (4 excluded per group). No statistical differences were observed in clinicopathological or surgical data between groups, considering both groups well-balanced for analysis. Overall survival at 3 years was 64.3% for SPL vs. 62.3% for EIPL (p 0.421). Only three patients had at least one positive peritoneal cytology (1:2). There were no differences regarding postoperative complications (SPL: 37.2% vs. EIPL: 32.5%, p 0.65) or between location of recurrence and number of recurrences. The number of recurrences did not differ between surgical approaches, but locoregional and peritoneal recurrences were fewer with the laparoscopic approach (p 0.048). CONCLUSIONS: The regular use of extensive peritoneal lavage in patients with locally advanced gastric cancer, regardless of peritoneal cytology, has not been effective as prophylaxis of peritoneal recurrence or better survival.

A multi-gene panel study in hereditary breast and ovarian cancer in Colombia.

Germline mutations in BRCA1 and BRCA2 account for approximately 50% of inherited breast and ovarian cancers. Three founder mutations in BRCA1/2 have been reported in Colombia, but the pattern of mutations in other cancer susceptibility genes is unknown. This study describes the frequency and type of germline mutations in hereditary breast and/or ovarian cancer genes in a referral cancer center in Colombia. Eighty-five women referred to the oncogenetics unit of the Instituto de Cancerologia Las Americas in Medellin (Colombia), meeting testing criteria for hereditary breast and ovarian cancer syndrome (NCCN 2015), who had germline testing with a commercial 25-gene hereditary cancer panel, were included in the analysis. Nineteen patients (22.4%) carried a deleterious germline mutation in a cancer susceptibility gene: BRCA1 (7), BRCA2 (8), PALB2 (1), ATM (1), MSH2 (1) and PMS2 (1). The frequency of mutations in BRCA1/2 was 17.6%. One BRCA2 mutation (c.9246dupG) was recurrent in five non-related individuals and is not previously reported in the country. Seventeen mutation-carriers had a diagnosis of breast cancer (median age of diagnosis of 36 years) and two of ovarian cancer. All BRCA1 mutation-carriers with breast cancer had triple negative tumors (median age of diagnosis of 31 years). Variants of unknown significance were reported in 35% of test results. This is the first report of a multi-gene study for hereditary breast and/or ovarian cancer in a Latin American country. We found a high frequency and a wide spectrum of germline mutations in cancer susceptibility genes in Colombian patients, some of which were not previously reported in the country. We observed a very low frequency of known Colombian founder BRCA1/2 mutations (1.2%) and we found mutations in other genes such as PALB2, ATM, MSH2 and PMS2. Our results highlight the importance of performing multi-gene panel testing, including comprehensive BRCA1/2 analysis (full gene sequencing and large rearrangement analysis), in high-risk breast and/or ovarian cancer patients in Colombia.

Patrón de apoptosis de células blancas de sangre de cordón umbilical (CBSCU) en cultivos in vitro producido por la carbamacepina, Metotrexate y Acido Fólico / Pattern of apoptosis of white cells of blood of umbilical cord (CBSCU) in cultivations in vitro taken place by the carbamacepina, Metotrexate and Folic Acid

Se evaluó el patrón de apoptosis de células blancas de sangre de cordón umbilical producido por la carbamecepina y metotrexate de potencial teratógénico conocido y ácido fólico con efecto protector de defectos de tubo neural, en cultivos in vitro. Se empleó un diseño completamente al azar con 9 repeticiones, el cual responde a un modelo lineal aditivo. Se estudió la acción protectora de ácido fólico en presencia de MTX y CBZ en cultivos in vitro de células blancas de cordón umbilical. Se demopstró que el anticonvulsivante CBZ y el agente anti-inflamatorio MTX inducen apoptosis a 100uM y 50uM respectivamente (dosis terapéutica). En este estudio se encontró que la presencia de ACF (o,1 - 10uM) protege a las células blancas de cordón umbilical contra la inducción de la apoptosis producida por la CBZ y MXT. Por el contrario el ACF no suprime la muerte celular debida al tiempo de cultivo. Entonces el ACF tiene un efecto robusto de protección contra la apoptosis en células blancas de cordón umbilical, esta propiedad provee una nueva vía para el estudio de los mecanismos moleculares y celulares de esta vitamina. Los datos reportados en este estudio son los primeros resultados generados sobre el efecto del MTX, CBZ y ACF y co-cultivos CBZ + ACF, MTX +ACF en cultivos de células blancas de sangre de cordón umbilical humano, demostándose que esta metodología in vitro es capaz de detectar el efecto de agentes protectores y teratogénicos justificándose estudios posteriores de validación de la técnica y evaluación de otros medicamentos para su aplicación.