ABSTRACT
PURPOSE: To analyze the prognostic value of variables of the primary tumor in patients with synchronous liver metastases in colorectal cancer (CLRMs) treated with neoadjuvant chemotherapy and surgery. METHODS/PATIENTS: From a prospective database, we retrospectively identified all patients with synchronous CLRMs who were treated with neoadjuvant chemotherapy and liver resection. Using univariate and multivariate analyses, we identified the variables associated with tumor recurrence. Overall survival and disease-free survival were calculated using the Kaplan-Meier method with differences determined by the Cox multiple hazards model. Results were compared using the log-rank test. RESULTS: Ninety-eight patients with synchronous CLRMs were identified. With a median follow-up of 39.8 months, overall survival and disease-free survival at 5 and 10 years were 53%, 41.7%, 29% and 29%, respectively. Univariate analysis identified three variables associated with tumor recurrence: location in the colon (p = 0.025), lymphovascular invasion (p = 0.011) and perineural invasion (p = 0.005). Multivariate analysis identified two variables associated with worse overall survival: perineural invasion (HR 2.36, 95% CI 1.162-4.818, p = 0.018) and performing frontline colectomy (HR 3.286, 95% CI 1.256-8.597, p = 0.015). Perineural invasion remained as the only variable associated with lower disease-free survival (HR 1.867, 95% CI 1.013-3.441, p = 0.045). Overall survival at 5 and 10 years in patients with and without perineural invasion was 68.2%, 54.4% and 29.9% and 21.3%, respectively (HR 5.920, 95% CI 2.241-15.630, p < 0.001). CONCLUSIONS: Perineural invasion in the primary tumor is the variable with most impact on survival in patients with synchronous CLRMs treated with neoadjuvant chemotherapy and surgery.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Neoadjuvant Therapy , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Colorectal Neoplasms/pathologyABSTRACT
Las plaquetas implicadas en la angiogénesis tumoral secretan factor de crecimiento endotelial vascular (VEGF). Los niveles de inhibidor del activador de plasminógeno tipo 1 (PAI-1) podrían regular la degradación de la matriz extracelular durante la angiogénesis. Durante este proceso tiene lugar la activación del sistema de la coagulación-fibrinólisis, que representa un evento clínico desfavorable. El factor de Von Willebrand (vWf), el dímero D (DD) y el fibrinógeno son marcadores sensibles de estos procesos. El recuento de plaquetas y los niveles de VEGF, PAI-1, vWf, DD y fibrinógeno podrían predecir la evolución clínica en pacientes con cáncer. En este estudio correlacionamos los niveles de VEGF, PAI-1, vWf, DD y fibrinógeno en pacientes con carcinoma colorrectal (CCR) en estadios I a IV sometidos a cirugía, a quimioterapia o a ambos métodos, con el análisis patológico/inmunohistoquímico en pacientes en estadios I-III y con la respuesta al tratamiento, y el riesgo de muerte en pacientes en estadio IV. Treinta y dos pacientes con CCR localizado o localmente avanzado y 32 con CCR metastático fueron evaluados. Las muestras sanguíneas se extrajeron antes de la cirugía y antes y después de la quimioterapia basada en fluoropirimidinas. Los enfermos en estadio IV recibieron una mediana de 3 ciclos de quimioterapia, entre muestras. En los pacientes en estadio I a III, los niveles basales de VEGF, recuento de plaquetas, fibrinógeno y PAI-1 se correlacionaron con el estadio tumoral. Además, la expresión tumoral de p21 y c-myc se asoció con niveles más elevados de vWf e inferiores de DD, respectivamente. En tumores metastásicos, los niveles prequimioterapia y posquimioterapia de VEGF, PAI-1 y CA19.9 se encontraron relacionados con las tasas de progresión.
Subject(s)
Humans , Male , Female , Angiogenesis Inducing Agents , Coagulation Agents , Fibrinolysis , Colorectal Neoplasms/complications , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/therapyABSTRACT
INTRODUCTION: von Willebrand factor (vWf) is thought to mediate binding of tumour cells to platelets and to favour their systemic spreading capacity. Platelets involved in tumour angiogenesis are capable of releasing vascular endothelial growth factor (VEGF). Hence, levels of vWf and VEGF may correlate with cancer stage. The objectives are determine the impact of surgery and chemotherapy on vWf and VEGF in colorectal cancer (CRC) patients. MATERIAL AND METHODS: Twenty healthy volunteers (group 1), 14 patients with locally advanced CRC (group 2) and 12 patients with metastatic CRC (group 3) were enrolled. Blood samples were taken at recruitment in group 1, and before and after surgery and chemotherapy in groups 2 and 3, respectively. Blood levels of vWf, VEGF, platelet count, C-reactive protein (CRP), ceruloplasmin and carcinoembrionary antigen (CEA) were measured. RESULTS: At baseline, group 3 showed higher concentrations of vWf than the other groups (p<0.05). In group 2, vWf became elevated 40% post-surgery (p=0.016), independently of changes in CRP or ceruloplasmin. In group 3, chemotherapy caused a 42% reduction in VEGF (p=0.015). CONCLUSIONS: There was a strong correlation between higher vWf levels and more advanced CRC stage at diagnosis. These levels were elevated post-surgery in patients with locally advanced CRC. Chemotherapy significantly decreased VEGF in metastatic CRC patients before CEA showed any significant change.