The incidence of occult cancer in patients with deep venous thrombosis: a prospective study (original) (raw)
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Vascular endothelial growth factor and endoglin expression in colorectal cancer
Journal of Cancer Research and Clinical Oncology, 2009
Background. Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. Additionally, CD-105 (endoglin) was proposed as a marker of neovascularization in solid malignancies. The aim of the present study was to (1) evaluate the VEGF and CD-105 expression in gastric carcinoma, (2) determine the role of VEGF gene sequence variations in VEGF expression in gastric carcinoma, and (3) correlate the results of VEGF and CD-105 expression with other standard prognostic parameters, such as size, grade, stage of the disease, metastases, and patient survival. Methods. VEGF and CD-105 expression were evaluated in 100 unrelated gastric cancer patients using immunohistochemistry. For the genotyping, DNA was isolated from the blood of the gastric cancer patients and from 100 healthy individuals. The genotyping was performed by polymerase chainrestriction fragment length polymorphism analysis. Results. VEGF protein was strongly expressed in the cytoplasm of 36% of the gastric carcinoma samples tested. In all cases, high VEGF expression was accompanied with high endoglin expression. Our results revealed no statistical significant association of any VEGF gene polymorphism with the VEGF and endoglin expression. The correlation of VEGF/ CD-105 expression with the clinicopathological parameters of gastric cancer showed that the high expression of VEGF/ CD015 was correlated only with lymph node metastasis (P = 0.028). The Kaplan-Meier survival curves have shown a clear association of overall survival after diagnosis of gastric cancer with high VEGF, as well as high CD-105 expression. Conclusion. Our results support that VEGF and CD-105 are closely relevant to lymph node metastasis and act as two valuable indicators of prognosis.
Blood, 2012
Cancer patients often have an activated clotting system and are at increased risk for venous thrombosis. In the present study, we analyzed tissue factor (TF) expression in 4 different human pancreatic tumor cell lines for the purpose of producing derivative tumors in vivo. We found that 2 of the lines expressed TF and released TF-positive microparticles (MPs) into the culture medium. The majority of TF protein in the culture medium was associated with MPs. Only TF-positive cell lines activated coagulation in nude mice, and this activation was abolished by an anti-human TF Ab. Of the 2 TFpositive lines, only one produced detectable levels of human MP TF activity in the plasma when grown orthotopically in nude mice. Surprisingly, < 5% of human TF protein in plasma from tumor-bearing mice was associated with MPs. Mice with TF-positive tumors and elevated levels of circulating TF-positive MPs had increased thrombosis in a saphenous vein model. In contrast, we observed no difference in thrombus weight between tumor-bearing and control mice in an inferior vena cava stenosis model. The results of the present study using a xenograft mouse model suggest that tumor TF activates coagulation, whereas TF on circulating MPs may trigger venous thrombosis. (Blood. 2012; 119(23):5543-5552) Methods Cell lines Human pancreatic (MIAPaCa-2 [CRL-1420], PANC-1 [CRL-146]), Capan-2 [HTB 80], HPAF-II [CRL-1997] and HPAC [CRL-2119]) and colorectal
Relationship between β -catenin expression and prognostic parameters of colorectal carcinomas
Turkish Journal of Pathology, 2013
Objective: Colorectal carcinomas are the most frequent tumors of the gastrointestinal tract. β-catenin, which is related to cadherins, is a cytoplasmic protein responsible for intercellular adhesion. It is also an important component in the Wnt signal pathway. Recent studies have shown structural alterations in the APC gene and axin in patients with colorectal carcinoma, along with β-catenin. We aimed to compare β-catenin expression, which is a prognostic factor itself, with other prognostic parameters. Material and Method: A total of 70 patients who had surgical intervention for colorectal malignancies between January 1994 and December 2003 were included in the study. Fift y-nine of the patients (84.3%) were male, 11 of the patients (15.7%) were female; their ages varied between 24 and 82 (mean 60.3 ±15.2) years. Paraff in blocks were immunohistochemically stained for β-catenin. Th e number of stained cell nuclei was assessed according to the stage of disease using the TNM classification, histological grade, lymphatic invasion, vascular invasion and tumor's local invasion. Results: When groups constituted according to tumor histologic grade were compared for prognostic parameters in terms of stain density for β-catenin and number of stained cell nuclei, stain density was mild (+) and the number of stained nuclei was smaller in well-diff erentiated groups while stain density was strong (+++) and the number of stained nuclei was higher in poorly diff erentiated groups. Th ere was a relation between β-catenin expression and diff erentiation grade, lymph node metastasis, stage and tumor size but not with vascular invasion. Conclusion : Th ese data indicate that β-catenin, with functions in cell homeostasis and relations with the APC gene, has a substantial role in colorectal carcinogenesis.
대한내과학회 추계학술발표논문집, 2011
Abnormal hemostasis in cancer patients has prev iously been studied. The primary objective of the present study was to evaluate the association between preoperative hemostasis markers and clinicopathological parameters, and to identify a hemostasis marker affecting survival in patients following curative resection for colorectal cancer. A total of 170 patients who underwent curative surgery for colorectal carcinoma were evaluated. Preoperative coagulation tests included platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer and fibrinogen degradation product (FDP). The clinicopathological variables, including age, gender, tumor location (rectum/colon), tumor size (≥5 cm vs. <5 cm), depth of tumor invasion, lymph node metastasis, stage, lymphovascular invasion, margin involvement and histological differentiation were analyzed. The median age of analyzed patients was 63 years (range, 28-84). The male to female ratio was 62:38. Increased levels of plasma fibrinogen, PT and platelet count (PLT) were associated with larger tumor size (P<0.001, P=0.015 and P=0.002, respectively). Increased plasma fibrinogen levels were significantly associated with depth of tumor invasion and stage (P=0.014 and P=0.048, respectively). Increased plasma D-dimer and FDP levels were significantly associated with tumor node metastasis stage (P=0.031 and P=0.002, respectively). Prolonged PT level (≥11.7 sec), hyper-fibrinogenemia (≥327 mg/dl), high D-dimer level (≥1.3 µg/ml) and increased FDP level (≥2.7 µg/ml) were the prognostic factors associated with shorter survival. Preoperative plasma fibrinogen level was significantly associated with tumor size and depth of tumor invasion. Preoperative plasma prolonged PT level, hyperfibrinogenemia, high D-dimer level and increased FDP level may function as hemostasis markers that predict overall survival in operable patients with colorectal cancer.
Changes in PDGF concentration in surgically treated colorectal carcinoma
Advances in Medical Sciences, 2008
The aim of the present study was to asses the effect of tumor advancement, differentiation grade and surgery treatment on PDGF-AB level and platelet (PLT) count depending on the site of blood collection. Material and methods: The study included 38 patients submitted to surgical treatment due to diagnosis of colorectal cancer (CRC) without remote metastasis: G2-20 patients and group G3-18 patients. The control group consisted of 24 healthy subjects. In CRC patients the blood samples was collected three times: 1) before surgery, 2) intrasurgically and 3) 90 days after surgery. Serum PDGF-AB concentration was determined by ELISA-Kit reagents. Results: PDGF concentration in all the patients was several times higher than in the control group, irrespective of tumor differentiation grade and the site of blood collection. However the level of PDGF-AB in intraoperatively collected arterial blood and venous blood in group G3 (arterial blood-379.9±12.1ng/ml; venous blood-398.4±13.2 ng/ml) was significantly higher than in group G2 (arterial blood-169.4 ±88.6 ng/ml; venous blood-194.2±84.0 ng/ml). No significant differences were observed between venous and arterial blood. No correlation was found between the PLT count and PDGF-AB concentration. Conclusion: High blood PDGF-AB concentration in CRC patients but no significant positive correlation observed between the PLT count and PDGF-AB suggest its neoplastic origin beside PLT. Determination of this factor in blood serum may have an important implication in early diagnosis of CRC, which is the second most common malignant neoplasm with high recurrence rates.
European Journal of Surgical Oncology (EJSO), 2001
Introduction: Neo-angiogenesis, of great importance for tumour growth and nutrition, is preferentially mediated by the cytokine vascular endothelial growth factor (VEGF), which has a direct effect on vascular endothelial cell proliferation and migration. This study was designed to clarify whether VEGF is a suitable tumour marker in sera of patients with a colorectal cancer, and whether VEGF concentrations in sera and tumour tissues are correlated with tumour extension (pTNM) and especially with tumour volume or size. Furthermore, the influence of VEGF levels on patients' prognosis was examined. Methods: VEGF serum concentrations of 122 patients with colorectal cancer and 65 controls were determined with an ELISA kit. Additionally, VEGF concentrations of tumour and normal tissue were measured in 38 patients using the same ELISA. Results: Our results demonstrate that VEGF is not a suitable diagnostic tumour marker in patients with colorectal cancer due to its low sensitivity (36%). However, a combination of the serum tumour markers CEA and VEGF can significantly increase the pre-operative diagnostic sensitivity to 62%. VEGF serum levels differed significantly between patients (mean 438 pg/ml) and controls (mean 203 pg/ml), and also between tumour and normal tissue (984 vs 89 pg/ mg protein). Serum concentration showed a significant correlation to tumour volume and size. Patients with VEGF serum levels greater than cutoff had a poorer prognosis than those less than or equal to cutoff. For this reason VEGF could be used as a predictor of patients' outcome.