Herencia y genética del cáncer ginecológico / The heredity and genetics of gynecological cancer

La mayoría de los cánceres ginecológicos son esporádicos, no hereditarios. Pese a ello, debemos tener en cuenta el papel de la herencia, sobre todo en el cáncer de mama y ovario, ya que aunque solo el 10% se van a relacionar con una mutación hereditaria, actualmente se dispone de la posibilidad de realizar estudio genético. Por motivos éticos y efectivos, dicho estudio no está indicado en toda la población, sino que se ha de reservar para aquellas pacientes con un mayor riesgo de cáncer hereditario, en base a antecedentes familiares y personales. Sin embargo, aún no se han establecido unos criterios claros para el estudio genético, seguimiento y medidas preventivas a adoptar en dichas pacientes. La presente revisión tiene como finalidad aclarar cuáles son los criterios a partir de los cuales podemos identificar a aquellas pacientes con un mayor riesgo de presentar cáncer hereditario, y con ello poder ofrecerles información sobre la posibilidad de estudio genético, así como de las diferentes opciones de seguimiento y medidas profilácticas disponibles (AU)

Most gynecologic cancers are sporadic rather than inherited. While only 10% of these cancers are related to an inherited mutation, the role of heredity should be considered–especially in breast and ovarian cancer–because the possibility of genetic study has become available. For ethical and psychological reasons, genetic study is not indicated in everyone but should be reserved to those patients with an increased risk of hereditary cancer, based on the familial and personal history. There is still a lack of clear criteria for the monitoring and preventive measures to be adopted in these patients. This review aims to clarify the criteria that can be used to identify those patients at increased risk of hereditary cancer, who could then be provided with information on the possibility of genetic study, as well as on the various options available for monitoring and preventive measures (AU)

Survival after lung metastasectomy for colorectal cancer: importance of previous liver metastasis as a prognostic factor.

AIMS: To analyse patient survival after the resection of lung metastases from colorectal carcinoma and specifically to verify whether presence of liver metastasis prior to lung metastasectomy affects survival. METHODS: All patients who, between 1998 and 2008, underwent lung metastasectomy due to colorectal cancer were included in the study. Kaplan-Meier survival analysis was performed with the log-rank test and Cox regression multivariate analysis. RESULTS: During this period, 101 metastasectomies were performed on 84 patients. The median age of patients was 65.4 years, and 60% of patients were male. The 30-day mortality rate was 2%, and incidence of complications was 7%. The overall survival was 72 months, with 3-and 5-year survival rates of 70% and 54%, respectively. A total of 17 patients (20%) had previously undergone resection of liver metastasis. No significant differences were found in the distribution of what were supposed to be the main variables between patients with and without previous hepatic metastases. Multivariate analysis identified the following statistically significant factors affecting survival: previous liver metastasectomy (p = 0.03), tumour-infiltrated pulmonary lymph nodes (p = 0.04), disease-free interval ≥ 48 months (p = 0.03), and presence of more than one lung metastasis (p < 0.01). In patients with previous liver metastasis, the shorter the time between primary colorectal surgery and the hepatectomy, the lower the survival rate after pulmonary metastasectomy (p = 0.048). CONCLUSIONS: A previous history of liver metastasis shortens survival after lung metastasectomy. The time between hepatic resection and lung metastasectomy does not affect survival; however, patients with synchronous liver metastasis and colorectal neoplasia have poorer survival rates than those with metachronous disease.

Urinary excretion of 6-hydroxychlorzoxazone as an index of CYP2E1 activity.

OBJECTIVE: To determine whether the urinary excretion of 6-hydroxychlorzoxazone is an index of CYP2E1 activity in vivo. METHODS: Male volunteers (n = 27; age range, 17 to 36 years) who were abstinent from alcohol were studied. Chlorzoxazone, 500 mg, was given orally and plasma was collected at 31/2, 41/2, 51/2, and 61/2 hours after dosing. Urine was collected for 8 hours. Ten volunteers participated in full kinetic studies to define the absorption phase and plasma area under the concentration-time curve of chlorzoxazone and the urinary kinetics of the 6-hydroxy metabolite. Chlorzoxazone and the 6-hydroxy metabolite were measured by high-performance liquid chromatography. CYP2E1 activity was expressed as a hydroxylation index (HI = mmole oral chlorzoxazone dose/mmole 6-hydroxychlorzoxazone in 8-hour urine). RESULTS: There was a significant positive correlation between plasma elimination rate constant for chlorzoxazone (Ke) and urinary excretion of the metabolite (n = 27, r = 0.42, p < 0.03) and a significant negative correlation between plasma Ke and HI (n = 27, r = -0.41, p < 0.04). The mean absorption rate constant for chlorzoxazone of 3.11 +/- 4.67 hr-1 was fivefold greater than the plasma Ke of 0.57 +/- 0.17 hr-1 for the full kinetic studies. The formation clearance of the 6-hydroxy metabolite was negative between plasma Ke of the parent compound and disposition rate constant for urinary excretion of the 6-hydroxy metabolite (n = 15, r = 0.85, p < 0.0001). CONCLUSIONS: The urinary excretion of 6-hydroxychlorzoxazone is limited by formation rate and may be useful as an in vivo probe of CYP2E1 activity.