RESUMEN
BACKGROUND AND AIMS: Germline mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer (HDGC). These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance. We describe the clinical presentation of three sibling cases with advanced gastric cancer, the way of confirming the suspicion of underlying HDGC and the clinical management of the other healthy family members. METHODS: Screening for CDH1 germline mutation was carried out by denaturing high-performance liquid chromatography and automated DNA sequencing. The clinical suspicion of HDGC has been confirmed by identifying a frameshift mutation in exon 9 (1302_1303insA, 1306_1307delTT) of the E-cadherin gene. RESULTS: Eight of nine tested family members were positive for the CDH1 germline mutation. Prophylactic laparoscopic gastrectomies were performed in five mutation carriers. After pathological examination, we could identify intramucosal malignant signet-ring cell carcinoma in all resected stomachs. CONCLUSION: This report underlines that prophylactic gastrectomy remains the only option to eliminate the high risk for gastric cancer in CDH1 mutation carriers.
Asunto(s)
Cadherinas/genética , Carcinoma de Células en Anillo de Sello/genética , Mutación de Línea Germinal , Neoplasias Gástricas/genética , Antígenos CD , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células en Anillo de Sello/prevención & control , Carcinoma de Células en Anillo de Sello/cirugía , Quimioterapia Adyuvante , Cromatografía Líquida de Alta Presión , Análisis Mutacional de ADN , Exones , Resultado Fatal , Femenino , Gastrectomía/métodos , Predisposición Genética a la Enfermedad , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Linaje , Fenotipo , Medición de Riesgo , Factores de Riesgo , Neoplasias Gástricas/patología , Neoplasias Gástricas/prevención & control , Neoplasias Gástricas/cirugía , Insuficiencia del TratamientoRESUMEN
We report a 53-year-old man with lymphoid blast crisis of Ph+ chronic myeloid leukaemia who was treated with STI571, a selective inhibitor of the enzymatic activity of BCR-ABL. He responded excellently to STI571 (600 mg/d), obtaining a complete cytogenetic remission after 3 months of therapy. Although remission in the bone marrow was sustained, the patient developed an isolated central nervous system relapse. Subsequent analyses of STI571 concentrations in the cerebrospinal fluid (CSF) revealed 2-log lower CSF levels of STI571 than corresponding plasma levels. These are the first data demonstrating a low penetration of orally administered STI571 into the CSF in humans.