RESUMEN
BACKGROUND: E2F target genes are essential for the cell cycle. A score that quantifies its activity is expected to reflect the aggressiveness and prognosis of hepatocellular carcinoma. METHODS: Cohorts of hepatocellular carcinoma patients (total n = 655) from The Cancer Genome Atlas, GSE89377, GSE76427, and GSE6764 were analyzed. The cohorts were divided into high versus low by the median. RESULTS: All the Hallmark cell proliferation-related gene sets were consistently enriched in hepatocellular carcinoma with high E2F targets score, and E2F score was associated with grade, tumor size, American Joint Committee on Cancer staging, proliferation score, and MKI67 expression, as well as with less abundance of hepatocytes and stromal cells. E2F targets enriched DNA repair, mTORC1 signaling, glycolysis, and unfolded protein response gene sets and were significantly associated with the higher intratumoral genomic heterogeneity, homologous recombination deficiency, and progression of hepatocellular carcinoma. On the other hand, there was no relationship between E2F targets and mutation rates or neoantigens. High E2F hepatocellular carcinoma did not enrich any of the immune-response-related gene sets but was associated with high infiltration of Th1, Th2 cells, and M2 macrophage; however, there was no difference in cytolytic activity. In both early (I and II) and late (III and IV) stages of hepatocellular carcinoma, a high E2F score was associated with worse survival and was an independent prognostic factor for overall and disease-specific survival in patients with hepatocellular carcinoma. CONCLUSION: The E2F target score, associated with cancer aggressiveness and worse survival, could be used as a prognostic biomarker in patients with hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Pronóstico , Proliferación CelularRESUMEN
A small number of cases of small bowel obstruction caused by foods without the formation of phytobezoars have been reported. Repeated small bowel obstruction due to the ingestion of the same food is extremely rare. We present the case of 63-year-old woman who developed small bowel obstruction twice due to the ingestion of chestnuts without the formation of phytobezoars. This is the first reported case of repeated small bowel obstruction caused by chestnut ingestion. Careful interviews are necessary to determine the meal history of elderly patients and psychiatric patients.
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Aesculus , Cuerpos Extraños/complicaciones , Obstrucción Intestinal/etiología , Enfermedades del Yeyuno/etiología , Yeyuno/diagnóstico por imagen , Bezoares/etiología , Ingestión de Alimentos , Femenino , Cuerpos Extraños/diagnóstico , Humanos , Obstrucción Intestinal/diagnóstico por imagen , Enfermedades del Yeyuno/diagnóstico por imagen , Persona de Mediana Edad , Recurrencia , Tomografía Computarizada por Rayos XRESUMEN
UNLABELLED: The aim of this study was to clarify the risk factors associated with recurrence in patients with stage II colorectal cancer. METHOD: We performed a retrospective analysis of 316 patients with stage II colorectal cancer who underwent gross radical colectomy between 1994 and 2003. RESULTS: The overall recurrence rate was 10.8%. Univariate analysis identified 5 risk factors associated with recurrence: depth of tumor invasion (tumor penetration of the serosa[SE]-tumor invasion of adjacent structure[s SI]), lymphatic invasion( ly2-3), venous invasion( v2-3), budding( grade 2-3), and perineural invasion (PN1). Multivariate analysis identified 3 risk factors associated with recurrence: budding (grade 2-3; p=0.008), depth of tumor invasion( SE-SI; p=0.008), and venous invasion( v2-3; p=0.034). CONCLUSION: The results of this study suggest that active postoperative adjuvant chemotherapy should be considered for the treatment of patients with stage II colorectal cancer with budding( grade 2-3), venous invasion( v2-3), or tumor depth of SE or SI.
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Neoplasias Colorrectales/diagnóstico , Colectomía , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Metástasis Linfática , Masculino , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Recurrencia , Factores de RiesgoRESUMEN
We evaluated the predictive relevance of several biomarkers on the survival of patients with stage III colorectal cancer treated with adjuvant chemotherapy of oral fluoropyrimidines. This was a multicenter phase II trial on adult patients with histologically confirmed resected stage III (Dukes' C) colorectal cancer. Patients received oral doxifluridine (800 mg/m2/day) in 3 divided doses, or oral uracil/tegafur (UFT) (400 mg/m2/day) in 2 divided doses for 5 days, every 7 days for 12 months with a 5-year follow-up. Outcome measures were disease-free survival and tissue markers [thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) protein levels and TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyltransferase (OPRT) mRNA levels in tumor samples and TS tandem-repeat type in blood samples]. There was a significant association between the intratumoral TP/DPD enzyme ratio and disease-free survival when the model included the drug, the parameter and the interactions between them [hazard ratio (HR)=2.76; P=0.00469]. The 5-year disease-free survival rate was statistically significantly higher in patients with high TP/DPD ratios [median ≥2.63: 71.9%; 95% confidence interval (CI) 61.4-80.0] compared to patients with low TP/DPD ratios (<2.63: 57.0%; 95% CI 46.3-66.3) (log-rank P=0.0277) following adjuvant therapy with oral fluoropyrimidines. No significant association was observed between the intratumoral TP/DPD enzyme ratio (cut-off value 2.0) and the disease-free survival rate in the doxifluridine group; primary endpoint (log-rank P=0.6850). The magnitude of the intratumoral TP/DPD enzyme ratio may be a potential indicator for the individualization of postoperative adjuvant chemotherapy with oral fluoropyrimidines for stage III colorectal cancer.
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Antimetabolitos Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/enzimología , Floxuridina/uso terapéutico , Tegafur/uso terapéutico , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Intervalos de Confianza , Dihidrouracilo Deshidrogenasa (NADP)/genética , Dihidrouracilo Deshidrogenasa (NADP)/metabolismo , Supervivencia sin Enfermedad , Femenino , Floxuridina/efectos adversos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Orotato Fosforribosiltransferasa/genética , Modelos de Riesgos Proporcionales , ARN Mensajero/metabolismo , Tegafur/efectos adversos , Timidina Fosforilasa/genética , Timidina Fosforilasa/metabolismo , Timidilato Sintasa/genéticaRESUMEN
Two cases of recurrent gastric cancer are described. Recurrence at anastomosis was detected following total gastrectomy in both patients. They declined surgery but wanted medical treatment. Therefore, 100 mg/kg of TS-1 was administered with informed consent. Symptoms related to stenosis were relieved after the first course, and complete responses were confirmed by endoscopic and pathological studies after completion of 4 courses in both patients. Palliative surgery remains a major option of treatments for patients with recurrence at anastomosis after total gastrectomy. TS-1, however, should be considered a treatment for such cases with satisfactory QOL, especially for outpatients who do not want surgery.