RESUMEN
OBJECTIVE: The aim of this study was to analyze the profile of tumor recurrence for patients operated on for cancer of oesophagogastric junction or oesophagus by Ivor-Lewis oesophagectomy. METHODS: Patients undergoing potentially curative Ivor-Lewis oesophageal resection between January 1999 to December 2008 at a single center institution were retrospectively analyzed. Their clinical records, details of surgical procedure, postoperative course, pathological findings, recurrence and long term survival were reviewed retrospectively. Univariate and multivariate survival analyses were performed. RESULTS: One hundred and twenty patients were analyzed. Fifty three patients (44%) presented recurrence during median follow-up of 58 months. Five-year relapse free survival (RFS) rate was 51% (95%CI = [46; 65%]). On multivariate analysis, pT stage > 2 (HR = 2.42, 95%CI = [1.22; 4.79] p = 0.011), positive lymph node status (HR = 3.69; 95% CI = [1.53; 8.96] p = 0.004) and lymph node ratio > 0.2 (HR = 2.57; 95%CI = [1.38; 4.76] p = 0.003) were associated with a poorer RFS and their combination was correlated to relapse risk. Moreover, preoperative tumor stenosis was associated with an increased risk of local recurrence (HR = 3.46; 95% CI = [1.38; 8.70] p = 0.008) whereas poor or undifferentiated tumor was associated with an increased risk of distant recurrence (HR = 3.32; 95% CI = [1.03; 10.04] p = 0.044). CONCLUSION: pT stage > 2, positive lymph node status and lymph node ratio > 0.2 are independent prognostic factors of recurrence after Ivor-Lewis surgery for cancer. Their combination is correlated with an increasing risk of recurrence that may argue favorably, in addition with preoperative tumor stenosis assessment, for adjuvant treatment or reinforced follow-up.
Asunto(s)
Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Unión Esofagogástrica/patología , Adulto , Anciano , Análisis de Varianza , Supervivencia sin Enfermedad , Neoplasias Esofágicas/patología , Unión Esofagogástrica/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estudios RetrospectivosRESUMEN
Tumor protein p53-induced nuclear protein 1 (TP53INP1) is involved in cell stress response. Its expression is lost at the pancreatic intraepithelial neoplasia 1b (PanIN1b)/PanIN2 stage of pancreatic carcinogenesis. Our objective was to determine whether TP53INP1 loss of expression contributes to pancreatic cancer formation in a conditional KrasG12D mouse model. We generated Kras-INP1KO mice using LSL-Kras(G12D/+);Pdx1-Cre(+/-) mice (Kras mice) and TP53INP1(-/-) mice. Analysis of pancreases during ageing shows that in the presence of activated Kras, TP53INP1 loss of expression accelerated PanIN formation and increased pancreatic injury and the number of high-grade lesions as compared with what occurs in Kras mice. Moreover, cystic lesions resembling intraductal papillary mucinous neoplasm (IPMN) were observed as early as 2 months of age. Remarkably, TP53INP1 is down-regulated in human IPMN. Activation of the small GTPase Rac1 shows that more oxidative stress is generated in Kras-INP1KO than in Kras mice pancreas despite elevated levels of the Nrf2 antioxidant regulator. We firmly establish the link between Kras-INP1KO pancreatic phenotype and oxidative stress with rescue of the phenotype by the antioxidant action of N-acetylcysteine. Our data provide in vivo functional demonstration that TP53INP1 deficiency accelerates progression of pancreatic cancer, underlining its role in the occurrence of IPMN and highlighting the importance of TP53INP1 in the control of oxidative status during development of pancreatic cancer.