RESUMEN
BACKGROUND AND OBJECTIVES: Approximately 30-50% of patients with colorectal cancer develop liver metastasis for which liver resection is the only hope for potential cure. However, hepatic resection is associated with considerable morbidity. The aim was to detect early complications by utilising the neutrophil: lymphocyte ratio (NLR). METHODS: We performed a retrospective cohort study of patients undergoing hepatic resection at a single institution between 2008 and 2016. Baseline demographics and complications within 30 days following surgery were recorded, with blood tests measured until day 7. Statistical analysis was performed using Mann Whitney and ROC analysis. RESULTS: One hundred eighty-eight operations were included. 47.3% had an associated complication, of which 31.46% were major. The median NLR was 6.31 across the cohort, 5.44 for uncomplicated procedures, 7.0 for complications and 10.65 in major complications. Median NLR was the best parameter for detecting major complications versus minor complications (AUC 0.74) as opposed to lymphocytes (AUC 0.65), neutrophils (AUC 0.60), and CRP (AUC 0.60). The diagnostic ability of NLR increased further when predicting major complications versus an uncomplicated recovery (AUC 0.78), and it was the only significant parameter in the early post-operative period on days 2, 3, and 4 (AUC 0.70, 0.72, and 0.75). CONCLUSIONS: The NLR may have a role in predicting complications following hepatic resection for CLM, and with earlier detection, potentially improving outcomes.
Asunto(s)
Neoplasias Colorrectales/patología , Hepatectomía/efectos adversos , Neoplasias Hepáticas/secundario , Linfocitos/patología , Neutrófilos/patología , Complicaciones Posoperatorias/diagnóstico , Anciano , Neoplasias Colorrectales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
The activating E17K mutation in the AKT1 gene has been detected in several tumor entities. Currently several clinical studies with specific AKT1 inhibitors are under way. To determine whether AKT1 mutations are involved in human tumors of the nervous system, we examined a series of 1,437 tumors including 391 primary intracranial brain tumors and 1,046 tumors of the coverings of the central and peripheral nervous system. AKT1E17K mutations were exclusively seen in meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was seen in the variant of meningothelial meningioma WHO grade I of basal and spinal localization. In contrast, AKT1E17K mutations were rare in WHO grade II and absent in WHO grade III meningiomas. In order to more effectively detect this mutation, we tested for immunohistochemical markers associated with this alteration. We observed strong up-regulation of SFRP1 expression in all meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation.
Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas de la Membrana/metabolismo , Neoplasias Meníngeas/genética , Meningioma/genética , Mutación , Proteínas Proto-Oncogénicas c-akt/genética , Biomarcadores de Tumor/análisis , Análisis Mutacional de ADN , Células HEK293 , Humanos , Immunoblotting , Inmunohistoquímica , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patología , Meningioma/metabolismo , Meningioma/patología , Clasificación del Tumor , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TransfecciónRESUMEN
BACKGROUND: Colorectal cancer is one of the most common malignancies worldwide; whilst approximately 20% of patients have hepatic disease at presentation. Hepatic resection remains the gold standard of care; however, it is associated with significant morbidity. We sought to establish whether the lymphocyte-to-monocyte ratio (LMR) could help predict post-operative complications, thus improving patient outcomes. METHODS: We performed a retrospective cohort study of patients undergoing hepatic resection at a single centre. Baseline demographics and complications within 30 days following surgery were recorded. White blood cell counts and C-reactive protein (CRP) were recorded pre-operatively, and until post-operative day 7. RESULTS: A total of 188 operations were included. About 47.3% of resections had a complicated recovery, of which 31.46% were major. The median LMR was 1.29 across the cohort, 1.60 for uncomplicated procedures, 1.14 for those with complications and 0.85 in major complications. For detecting major complications versus an uncomplicated recovery, median LMR was the best parameter (area under the curve 0.78), whilst it was the only parameter to accurately predict such complications within 48 hours of surgery (area under the curve 0.72 on day 1). It was consistently the most accurate parameter at detecting uncomplicated versus complicated recovery, minor versus major complications, and major complications versus an uncomplicated recovery, at numerous timepoints over the post-operative period. CONCLUSION: The LMR appears better at predicting complications following hepatic resection for colorectal liver metastases, as opposed to conventionally measured parameters.
Asunto(s)
Adenocarcinoma/secundario , Neoplasias Colorrectales/patología , Técnicas de Apoyo para la Decisión , Hepatectomía , Leucocitos/metabolismo , Neoplasias Hepáticas/secundario , Complicaciones Posoperatorias/etiología , Adenocarcinoma/cirugía , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Recuento de Leucocitos , Neoplasias Hepáticas/cirugía , Linfocitos/metabolismo , Masculino , Monocitos/metabolismo , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico , Curva ROC , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
The World Health Organization (WHO) classification and grading system attempts to predict the clinical course of meningiomas based on morphological parameters. However, because of high interobserver variation of some criteria, more reliable prognostic markers are required. Here, we assessed the TERT promoter for mutations in the hotspot regions C228T and C250T in meningioma samples from 252 patients. Mutations were detected in 16 samples (6.4% across the cohort, 1.7%, 5.7%, and 20.0% of WHO grade I, II, and III cases, respectively). Data were analyzed by t test, Fisher's exact test, log-rank test, and Cox proportional hazard model. All statistical tests were two-sided. Within a mean follow-up time in surviving patients of 68.1 months, TERT promoter mutations were statistically significantly associated with shorter time to progression (P < .001). Median time to progression among mutant cases was 10.1 months compared with 179.0 months among wild-type cases. Our results indicate that the inclusion of molecular data (ie, analysis of TERT promoter status) into a histologically and genetically integrated classification and grading system for meningiomas increases prognostic power. Consequently, we propose to incorporate the assessment of TERT promoter status in upcoming grading schemes for meningioma.