Preoperative thrombocytosis is associated with survival after surgery for colorectal cancer.
ABSTRACT OBJECTIVE: To evaluate the influence of preoperative thrombocytosis on survival after surgery in patients with colorectal cancer (CRC). METHODS: Four hundred fifty-three patients who had undergone CRC surgery were retrospectively identified from institutional database. On the basis of receiver operating characteristic (ROC) curve analysis, they were classified into two groups: Group A, with a preoperative platelet count of ≤300 (×10(9) /L), and Group B, with a preoperative platelet count of >300 (×10(9) /L). Uni- and multivariate analyses were performed to evaluate the relationship to overall survival. Kaplan-Meier analysis and log rank test were used to compare the survival curves between groups A and B. RESULTS: There was a significant difference in overall survival between the two groups (P = 0.007). Multivariate analysis of selected preoperative clinicolaboratory characteristics showed that overall survival was associated with the platelet count (Group A/B) (odds ratio, 1.642; 95% CI, 1.025-2.629; P = 0.039) as well as the number of tumors (1/≥2), and the serum levels of C-reactive protein (CRP) and carcinoembryonic antigen (CEA). CONCLUSION: Preoperative thrombocytosis is associated with survival after surgery in CRC patients, and is able to divide such patients into two independent groups before surgery. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.
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ABSTRACT: Tumor angiogenesis is associated with metastasis in several types of solid tumors, including melanoma, breast, prostate, lung, bladder, and oral-cavity tumors. The purpose of this study was to determine whether tumor angiogenesis could predict recurrence following curative surgery for colorectal cancer. Thirty-five patients were studied, including 13 patients with recurrent tumor and 22 without. Representative formalin-fixed, paraffin-embedded sections of invasive colorectal cancers from these patients were sectioned. The endothelial cells of microvessels within the tumors were highlighted by immunohistochemical staining for CD31. The most active areas were identified and the microvessels counted in a x 400 field (0.152 mm2) by two observers in a blinded fashion. Tumor microvessel count (p = 0.0062). Dukes' staging (p = 0.0004), vascular invasion (p = 0.0280), and tumor grade (p = 0.0559) were all significantly associated with tumor recurrence. Tumor microvessel counts > or = 65 per x 400 field were associated with tumor recurrence (p = 0.0035, relative risk [RR] = 11.3). Controlling for Dukes' stage, a multivariate logistic regression model revealed that a tumor microvessel count > or = 65 is an important predictor of tumor recurrence (p = 0.0783, RR = 6.0). A backwards elimination proportional hazards model revealed that a microvessel count > or = 65 shows a trend toward independent prediction of time to tumor recurrence (p = 0.1203, RR = 2.967) when controlled for Dukes' staging (p = 0.0029, RR = 9.089). Despite the small number of patients studied, these results suggest that the number of microvessels in sections of invasive colorectal adenocarcinoma immunohistochemically stained with CD31 may be an important independent predictor of tumor recurrence and time to recurrence.American Journal of Surgical Pathology 11/1996; 20(10):1260-5. · 4.87 Impact Factor
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ABSTRACT: In patients with malignancies, thrombocytosis has previously been related to disease stage, histological type, and survival. In the present study, the prevalence of thrombocytosis and the prognostic information provided by platelet counts were analysed in a large cohort of patients with primary lung cancer. At the time of diagnosis, pretreatment platelet counts were retrospectively recorded in 1,115 consecutive patients with histologically proven primary lung cancer. All patients were reviewed regarding histological type, tumour, node, metastasis (TNM) classification stage and survival. The prevalence of thrombocytosis in patients with lung cancer was compared with that in a series of 550 consecutive out-patients with benign lung disorders. In 269 surgically resected patients, postoperative platelet counts were recorded 1-3 months after resection of the tumour. In the follow-up period, thromboembolic episodes diagnosed either clinically or at autopsy were recorded. The overall prevalence of thrombocytosis (> 400 x 10(9) platelets.L-1) in the patients with lung cancer was 32%. The frequency of thrombocytosis was significantly higher compared with the control subjects (32 vs 6%; p < 0.0001). Platelet counts differed significantly among subgroups defined by the TNM classification, with the proportion of patients with > 400 x 10(9) platelets.L-1 greatest in the more advanced TNM stages (stage I and II 23% vs stage III and IV 37%; p < 0.0001). Patients with thrombocytosis had a significantly poorer survival than patients with normal platelet counts (p < 0.0001). In a multivariate survival analysis (Cox model), thrombocytosis continued to correlate strongly with poor survival even when adjusted for histological type, sex, age, and TNM stage (p < 0.001). In surgically resected patients, the frequency of preoperative and postoperative thrombocytosis differed significantly (23.0 vs 8.9%; p < 0.0001). Survival rate was significantly reduced in patients with preoperative thrombocytosis (p = 0.005). Thrombocytosis was not associated with an increased incidence of thromboembolism. In conclusion, thrombocytosis is an independent prognostic factor of survival in patients with primary lung cancer. We suggest that platelet counts should be included in future multivariate analyses of survival in patients with lung cancer.European Respiratory Journal 10/1996; 9(9):1826-30. · 6.36 Impact Factor
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ABSTRACT: We have shown that coculture of bone marrow microvascular endothelial cells with hematopoietic progenitor cells results in proliferation and differentiation of megakaryocytes. In these long-term cultures, bone marrow microvascular endothelial cell monolayers maintain their cellular integrity in the absence of exogenous endothelial growth factors. Because this interaction may involve paracrine secretion of cytokines, we evaluated megakaryocytic cells for secretion of cytokines, we evaluated megakaryocytic cells for secretion of vascular endothelial growth factor (VEGF). Megakaryocytes (CD41a+) were generated by ex vivo expansion of hematopoietic progenitor cells with kit-ligand and thrombopoietin for 10 days and further purified with immunomagnetic microbeads. Using reverse transcription-PCR, we showed that megakaryocytic cell lines (Dami, HEL) and purified megakaryocytes expressed mRNA of the three VEGF isoforms (121, 165, and 189 amino acids). Large quantities of VEGF (> 1 ng/10(6) cells/3 days) were detected in the supernatant of Dami cells, ex vivo-generated megakaryocytes, and CD41a+ cells isolated from bone marrow. The constitutive secretion of VEGF by CD41a+ cells was stimulated by growth factors of the megakaryocytic lineage (interleukin 3, thrombopoietin). Western blotting of heparin-Sepharose-enriched supernatant mainly detected the isoform VEGF165. In addition, immunohistochemistry showed intracytoplasmic VEGF in polyploid megakaryocytes. Thrombin stimulation of megakaryocytes and platelets resulted in rapid release of VEGF within 30 min. We conclude that human megakaryocytes produce and secrete VEGF in an inducible manner. Within the bone marrow microenvironment, VEGF secreted by megakaryocytes may contribute to the proliferation of endothelial cells. VEGF delivered to sites of vascular injury by activated platelets may initiate angiogenesis.Proceedings of the National Academy of Sciences 01/1997; 94(2):663-8. · 9.74 Impact Factor