RESUMEN
Formalin-fixed paraffin-embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer-related gene mutations including driver genes in PDAC, using next-generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for KRAS, 62% for TP53, 32% for SMAD4, and 18% for CDKN2A. There were no cases of single SMAD4 mutations; its rate of coincidence with KRAS or TP53 mutations was 30% and 2%, respectively. The combination of KRAS and SMAD4 mutations resulted in significantly shorter relapse-free survival (RFS; median survival time [MST], 12.3 vs. 28.9 months, P = .014) and overall survival (OS; MST, 22.3 months vs. not reached, P = .048). On multivariate analysis, the combination of KRAS and SMAD4 mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77-10.08; P = .001) and OS (HR 6.730; 95% CI, 1.93-23.43; P = .003). The combination of KRAS and SMAD4 mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína Smad4/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/mortalidad , Análisis Mutacional de ADN/métodos , Femenino , Formaldehído , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Pancreáticas/mortalidad , Adhesión en Parafina , Pronóstico , Fijación del TejidoRESUMEN
To clarify how students' awareness is linked to their understanding of Kampo medicine, we carried out a questionnaire and test for 94 fourth-year medical students (MS) following all the lectures at Yamaguchi University School of Medicine.Gender was not associated with performance in the test.MS having been admitted to an undergraduate program had a significantly better performance record in the test than did MS who had passed the usual university entrance examinations (P < 0.0001).MS who had experienced the efficacy of Kampo medicine had a significantly better performance record in the test than did MS who had not.Understanding of both the merits and demerits of Kampo medicine, a desire to see bedside teaching of Kampo medicine currently or in the future, and a desire to integrate Kampo medicine with primary care in the future were associated with a better performance record in the test.Multiple logistic regression analysis showed that admission to an undergraduate program (odds ratio (OR) = 6.9) and having experienced the efficacy of Kampo medicine (OR = 4.5) were independently contributing factors to a good performance record in the test.Taken together, these results suggest that experiencing efficacy and bedside teaching are needed to increase understanding of Kampo medicine for MS.
