The purpose of the present study was to evaluate the prognostic significance and relationship between tumor volume and microvessel density in squamous cell carcinoma of the uterine cervix. The estimated tumor volume (TV) in 57 patients (22 stage Ib, 18 stage IIa, and 17 stage IIb) had radical hysterectomy was calculated on the assumption that the tumor mass was spheroid. The micro-vessel density (MVD) was evaluated as the ratio of endothelial area immunoreactive to factor-VIII related antigen (von Willebrand factor) to whole image area measured by computer-aided image analysis system. Tumor volume ranged from 0.1 to 41.0 cm³ (median 3.6 cm³) and MVD from 0.33 to 2.95 % (median 0.85 %). A significantly larger median TV was noted in women with positive pelvic node metastasis (6.3 vs 2.6 cm³, P=0.0228), parametrial invasion (8.9 vs 0.8 cm³, P<0.0001), and postoperative irradiation (5.4 vs 0.6 cm³, P=0.0007). In contrast, these clinical parameters had no effect on MVD. There was no correlation between TV and MVD. The overall survival rate at 5 years was 93.1% and 60.7% (P=0.0037) between women with a TV of ≤4 cm³ and >4 cm³, respectively; and 96.2% and 61.3% (P=0.0022) between tissue specimens with a MVD of ≤0.8% and >0.8%, respectively. A combined TV of >4 cm³ and MVD >0.8% further deteriorated 5 year survival rate (42.1% vs 94.7%, P<0.0001). Multivariate analysis indicated TV and MVD as independent risk factor in this series (P=0.041, P=0.03, respectively). Our current findings suggested that TV and MVD are independent prognostic factors in women with cervical carcinoma who underwent radical hysterectomy. These prognostic factors may be clinically useful for the selection of high-risk patients who need extensive adjuvant therapy.

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AIM: The aim of this study was to investigate the role for vascular endothelial growth factor (VEGF) and its receptors, VEGFR-1 and -2, in the hyperplastic polyp (HP)- serrated adenoma (SA)-adenocarcinoma (AC) sequence of the colorectum.Methods: Thirty-six HPs, 33 SAs and 7 ACs (which contained HP and/or SA) were immunohistochemically examined for the expression of VEGF, VEGFR-1, and VEGFR-2.Results: VEGF protein was expressed in the cytoplasm of SA and AC tumor cells, and VEGFR-1 and VEGFR-2 were expressed both in the cytoplasm and on the membrane of these tumors, while there was faint or no expression of VEGF, VEGFR-1 and VEGFR-2 in HPs. Immunohistochemical staining revealed that 8.3% (3 of 36) HPs, 87.9% (29 of 33) SAs and 100% (7 of 7) ACs were positive for VEGF; 2.8% (1 of 36) HPs, 97.0% (32 of 33) SAs and 100% (7 of 7) ACs were positive for VEGFR-1; 16.7% (6 of 36) HPs, 100% (33 of 33) SAs and 100% (7 of 7) ACs were positive for VEGFR-2. The expression of VEGF, VEGFR-1 or VEGFR-2 was statistically correlated with the sequence of HP, SA and AC (P < 0.0001, respectively) Conclusion: Our results suggest that the VEGF pathway may play an important role in the HP-SA-AC sequence.

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Extrahepatic bile duct cancer is a high mortal malignancy. Angiopoietin (Ang) and its receptor Tie, which are known to contribute to angiogenesis, have recently been reported to participate in the proliferation and differentiation of malignant tumor cells. The aim of this study is to investigate the expression and the significance of Ang-1, 2 and Tie-2 in extrahepatic bile duct carcinoma cells. We used immunohistochemistry to study 119 cases of surgically resected human extrahepatic bile duct carcinoma, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) to confirm the expression of Ang-1, 2 and Tie-2 mRNA. Among these 119 cases, 52 (43.7%), 50 (42.0%) and 89 (74.8%) cases showed positive staining for Ang-1, 2 and Tie-2, respectively, in bile duct carcinoma cells. In 38 cases of normal mucosa, 6 (15.8%), 10 (26.3%) and 9 (23.7%) cases were positive for Ang-1, 2 and Tie-2, respectively. The positivity for Ang-1 and Tie-2 in normal mucosa was significantly different from all carcinomas (p<0.01 and p<0.001, respectively). We found no significant correlation between Ang-1 and Ang-2 expression and other clinicopathological factors such as histological differentiation, grade of tumor invasion or survival rate after surgery. In contrast, Tie-2 expression correlated significantly with degree of desmoplasia, cancer stage and survival of patients. RT-PCR analyses of five surgically resected tumor samples and three human bile duct cancer cell lines all showed positive expression of Ang-1, 2 and Tie-2 mRNAs. High expressions of Ang-1, 2 and Tie-2 in human extrahepatic bile duct carcinoma cells suggested that Ang-Tie system may be involved in the progression of human bile duct cancer.

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Background: Hepatocellular carcinoma (HCC) commonly develops in patients with chronic hepatitis. This situation is one of the reasons why intrahepatic recurrence frequently occurs even after curative resection. There are two different components of such recurrences, which occurs within 12 months (the early recurrence group) and at more than 12 months after resection (the late recurrence group). The present study was conducted to clarify the factors contributing to these different types of HCC recurrence. Methods: Ninety seven patients who underwent curative resection for HCCs were followed for initial recurrence, and predictive factors of recurrence were examined. Results: Early and late intrahepatic recurrences developed in 30 and 42 patients, respectively. In the former group, univariate analyses showed the serum AFP level (>100ng/ml, P=0.045), higher inflammatory activity (Grading) (p=0.048) and status of fibrosis (Staging) (p=0.027) in non-cancerous liver tissues to be significant risk factors, while the serum AFP level (>100ng/ml) was the only independent risk factor based on a multivariate analysis (RR: 2.78). In the latter group, only the presence of hyperplastic foci (HPF) was found to be a significant risk factor (p=0.005). Higher Grading tended to be linked to shorter disease-free survival time, although not significant. In the non-cancerous liver tissues with HPF, the level of Grading, Staging, and PCNA labeling index was significantly higher (p=0.033, 0.003, 0.040, respectively).Conclusion: Not only the tumor factors but also the underlying hepatic status including HPF, Grading, and Staging were significant risk factors for intrahepatic recurrence after curative resection for HCC.

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Total knee arthroplasty (TKA) without a tourniquet can reduce the risk of large venous emboli, but is associated with increased blood loss. To provide an accurate estimate of this blood loss, we divided 136 patients who underwent primary TKA into four groups based on the type of operation: 1) bilateral TKA with tourniquet; 2) bilateral TKA without tourniquet; 3) unilateral TKA with tourniquet; and 4) unilateral TKA without tourniquet. Blood loss was estimated by calculating the fall in hemoglobin and total blood volume corrected for Japanese. A small difference in intraoperative blood loss was seen between unilateral TKA without tourniquet (308 ml) and bilateral TKA without tourniquet (411 ml). Total blood loss was 879 ml in unilateral TKA with tourniquet, 1165 ml in unilateral TKA without tourniquet, 1458 ml in bilateral TKA with tourniquet and 1823 ml in bilateral TKA without tourniquet. Uni- and bilateral TKAs without a tourniquet were thus associated with an increased blood loss. Performing TKA without a tourniquet should thus be reconsidered to avoid venous thromboembolism.

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