RESUMEN
Detection of circulating tumor DNA (ctDNA) from plasma cell free DNA (cfDNA) has shown promise for diagnosis, therapeutic targeting, and prognosis. This study explores ctDNA detection by next generation sequencing (NGS) and associated clinicopathologic factors in patients with pancreatic adenocarcinoma (PDAC). Patients undergoing surgical exploration or resection of pancreatic lesions were enrolled with informed consent. Plasma samples (4-6 ml) were collected prior to surgery and cfDNA was recovered from 95 plasma samples. Adequate cfDNA for NGS (20 ng) was obtained from 81 patients. NGS was performed using the Oncomine Lung cfDNA assay on the Ion Torrent S5 sequencing platform. Twenty-five patients (30.9%) had detectable mutations in KRAS and/or TP53 with allele frequencies ranging from 0.05 to 8.5%, while mutations in other genes were detected less frequently and always along with KRAS or TP53. Detectable ctDNA mutations were more frequent in patients with poorly differentiated tumors, and patients without detectable ctDNA mutations showed longer survival (medians of 10.5 months vs. 18 months, p = 0.019). The detection of circulating tumor DNA in pancreatic adenocarcinomas is correlated with worse survival outcomes.
Asunto(s)
Adenocarcinoma , ADN Tumoral Circulante , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/sangre , Anciano de 80 o más Años , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/sangreRESUMEN
BACKGROUND: We evaluated the incidence of chronic pancreatitis and chronic bile duct inflammation in patients undergoing pancreaticoduodenectomy (PD) for suspected periampullary cancer. METHODS: Differences between clinical presentation, surgical management, and outcomes were compared between patients with malignancy and benign inflammatory disease. RESULTS: The incidence of chronic inflammatory disease was 12.9% (21/162). Patients with chronic inflammatory disease were associated with a higher incidence of smoking (75.0% versus 64.7%) and chronic alcohol use (66.7% versus 46.2%). Jaundice was significantly more frequent in patients with malignant disease (83.6% versus 42.9%, P < .05). Surgery for chronic inflammatory disease was associated with significantly more intraoperative bleeding (P < .05). CONCLUSIONS: The finding of chronic inflammatory disease after PD for suspected carcinoma is justifiable because (1) none of the available diagnostic modalities are infallible, (2) early treatment of pancreatic cancer is crucial for achieving cure, and (3) PD may relieve clinical symptoms in patients with chronic pancreatitis or pancreatic cancer.