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BACKGROUND/AIMS: We investigated whether the serum Thymidine phosphorylase (TP) levels in venous blood drainage specimens were associated with the prognosis and risk of liver metastasis in patients with resectable colorectal cancer. METHODOLOGY: From 88 patients with colorectal cancer, specimens of venous blood drainage were obtained during operation. The serum TP levels were measured by a highly sensitive Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULTS: Subsequently, 88 patients were divided into two groups based on the levels of TP. The dividing line was determined to be 55ng/mL. The TP-high group (> 55ng/mL) had a significantly shorter overall survival than the TP-low group (< 55ng/mL). A multivariate analysis indicated that the serum TP level in venous blood drainage specimens to be a better prognostic factor independent of the traditional pathologic parameters. The serum TP levels of 3 patients with metachronous liver metastasis were high (> 55ng/mL). CONCLUSIONS: These findings suggest that the serum TP levels in venous blood drainage specimens reflect the prognosis of patients with colorectal cancer undergoing curative resection, particularly the risk of liver metastasis.

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An eighty-year-old female was transferred to the hospital after experiencing abdominal pain and nausea. She had had a history of total gastrectomy for gastric cancer 14 years previously. Abdominal X-ray revealed a localized expansion of the small bowel. Computed tomography revealed a mass with a lamellar structure in a concentric circle. With a tentative diagnosis of small bowel obstruction due to intussusception, she underwent emergency operation. Laparotomy revealed a retrograde jejuno-jejunal intussusception. Bowel resection was performed due to the severe ischemic damage. All reported intussusception cases after total gastrectomy displayed retrograde characteristics and could occur both during the early and late period after surgery. It is important to consider the possibility of intussusception for patients presenting with acute abdomen who have previously undergone gastric resection.

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PURPOSE: The clinical value of carcinoembryonic antigen messenger ribonucleic acid in the draining venous blood has been controversial because of short observation period. The authors prospectively investigated the clinical significance of detection of carcinoembryonic antigen messenger ribonucleic acid in the draining venous blood to predict hepatic metastases in patients with resectable colorectal cancer. METHODS: Drainage venous blood from 80 patients who underwent curative resections for colorectal cancer were obtained immediately before surgery to determine the presence of cancer cells by means of reverse transcription polymerase chain reaction. RESULTS: After an average follow-up period of 52.1 months, 7 of the 35 patients (20 percent) with positive carcinoembryonic antigen messenger ribonucleic acid had hepatic metastases, whereas 2 of the 45 patients (4.5 percent) with negative carcinoembryonic antigen messenger ribonucleic acid had hepatic metastases. The cumulative probability of hepatic metastatic recurrence rate differed significantly between two patient groups with positive or negative carcinoembryonic antigen messenger ribonucleic acid expression in the drainage vein (log-rank, 4.900; P = 0.0269). However, 28 of the 35 patients (80 percent) with positive carcinoembryonic antigen messenger ribonucleic acid did not have hepatic metastases. Additionally, Cox proportional hazards models identified the presence of lymph node metastases as the only independent predictor of hepatic metastatic recurrence. CONCLUSIONS: This study failed to demonstrate the high predictive value of carcinoembryonic antigen messenger ribonucleic acid detection in the draining venous blood for the development of hepatic metastases. However, the authors demonstrated that the presence of cancer cells in the draining venous blood was the essential and initial step to the development of hepatic metastasis.

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Thymidine phosphorylase (dThdPase) is known to promote the development of new blood vessels. Increased dThdPase expression in solid tumors has been shown to correlate with tumor growth, invasion and metastasis. In the present study, we measured dThdPase levels in the tumor tissue and in the serum from the tumor drainage and peripheral venous blood obtained from patients with resectable colorectal cancer. Serum dThdPase levels, measured by a modified ELISA method, were significantly higher in patients with hematogenous metastasis. In the tumor tissue specimens, no significant difference was observed between patients with or without hematogenous metastasis. These results suggest that the serum dThdPase levels are a novel marker to predict occurrence of hematogenous metastasis in patients with resectable colorectal cancer.

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To investigate the relationship between tumor angiogenesis and hematogenous metastasis in colorectal cancer, an immunohistochemical analysis using antibody against factor VIII was carried out on archival specimens of 35 primary tumors. In addition, we also evaluated the levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), by an enzyme-linked immunosorbent assay (ELISA), in tumor specimens and the serum in the drainage venous blood. The levels of VEGF showed no correlation with the microvessel density and also did not increase significantly in patients with hepatic metastasis. On the other hand, the IL-8 levels in the tumor tissue (r=0.45) and the serum IL-8 levels (r=0.49) showed a significant correlation with the microvessel density. The serum IL-8 levels in patients with Dukes' C colorectal cancer and hepatic metastasis were significantly higher than in those without hepatic metastasis (p<0.05). In addition, the serum levels of IL-8 in patients with Dukes' C cancer without hepatic metastasis and those with Dukes' A and B cancer were also closely similar. These results suggest that IL-8 is associated with the microvessel density in primary tumors and thus play an important role in the occurrence of hepatic metastasis in patients with colorectal cancer. As a result, elevated levels of IL-8 in the drainage vein are considered to be a useful predictor for developing hepatic metastasis in patients with resectable colorectal cancer.

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