Purpose: Lymph vessel density (LVD) and microvessel density (MVD) correlate with the malignant potential of tumors and patient survival. Vascular endothelial growth factors (VEGF)-A, VEGF-C, and VEGF-D could modulate LVD and MVD. We investigated the clinical and prognostic significance of LVD and MVD on lymphangiogenic and angiogenic function of VEGF-A,VEGF-C, and VEGF-D in human bladder cancer. Experimental Design: We reviewed tissue samples from patients with nonmetastatic bladder cancer who had undergone transurethral resections (n = 126). The densities of D2-40-positive vessels (LVD) and CD34-positive vessels (MVD) were measured by a computer-aided image analysis system. Expression of VEGF-A, VEGF-C, and VEGF-D was examined by immunohistochemistry; survival analyses and their independent roles were investigated using multivariate analysis models. Results: LVD was associated with tumor grade but not with pTstage. LVD was associated with metastasis-free survival (log rank P = 0.039), but was not an independent prognostic factor. Although MVD affected survival, the combination of high LVD and high MVD in tumors was an independent predictor of metastasis-free survival. Although VEGF-C expression was positively associated with both LVD and MVD,VEGF-D was associated only with LVD.VEGF-A expression was associated with MVD in univariate analysis, however, it was not an independent factor. Conclusions: Lymphangiogenesis and angiogenesis influence metastasis-free survival, and are regulated by VEGF-C and/or VEGF-D. Our results suggest that LVD and MVD are useful tools for the selection of postoperative management and treatment strategies in patients with bladder cancer.Metastatic dissemination of the primary tumor is an important factor that negatively affects the prognosis in most malignancies and neovascularization (angiogenesis) plays a critical role in tumor growth and systemic dissemination of cancer cells (1). As such, much attention has been focused on the pathologic significance and detailed mechanism of the vascular system and angiogenesis in cancers. In addition to dissemination of cancer cells via the bloodstream, the lymphatic system is also thought to play an important role in tumor cell dissemination.Indeed, metastatic spread to regional lymph nodes is an early step in the systemic dissemination of tumors, and lymph node metastasis is generally associated with poor survival (2, 3). However, the clinical significance of the de novo formation of lymphatic capillaries (lymphangiogenesis) and its regulation in cancer remains unclear, largely because specific endothelial markers for lymphatic vessels are unknown and lymphatic vessels cannot be detected in human cancer tissues (4). In recent years, several new specific antibodies for lymphatic endothelial cells have been developed and used to investigate the clinical and pathologic significance of lymphangiogenesis in various cancers (5).Bladder cancer is the second most common malignant tumor of the urogenital region. This tumor is associated with fr...

ObjectivesTo provide information of semen quality among normal young Japanese men and indicate the frequency of reduced semen quality.DesignCross-sectional, coordinated studies of Japanese young men included from university areas. The men had to be 18–24 years, and both the man and his mother had to be born in Japan. Background information was obtained from questionnaires. Standardised and quality-controlled semen analyses were performed, reproductive hormones analysed centrally and results adjusted for confounding factors.SettingFour study centres in Japan (Kawasaki, Osaka, Kanazawa and Nagasaki).Participants1559 men, median age 21.1 years, included during 1999–2003.Outcome measuresSemen volume, sperm concentration, total sperm count, sperm motility, sperm morphology and reproductive hormone levels.ResultsMedian sperm concentration was 59 (95% CI 52 to 68) million/ml, and 9% and 31.9% had less than 15 and 40 million/ml, respectively. Median percentage of morphologically normal spermatozoa was 9.6 (8.8 to 10.3)%. Small, but statistically significant, differences were detected for both semen and reproductive hormone variables between men from the four cities. Overall, the semen values were lower than those of a reference population of 792 fertile Japanese men.ConclusionsAssuming that the investigated men were representative for young Japanese men, a significant proportion of the population had suboptimal semen quality with reduced fertility potential, and as a group they had lower semen quality than fertile men. However, the definitive role—if any—of low semen quality for subfertility and low fertility rates remain to be investigated.

Lymphangiogenesis may have important roles in tumor metastasis and survival in patients with transitional cell carcinoma of the upper urinary tract. Quantification of lymphatic vessels, especially peritumor lymphatic vascular area and intratumor lymphatic vessels, was useful for predicting metastasis-free survival. In addition, the presence of intratumor lymphatic vessels was an independent predictor of cause specific survival.

Co-expression of COX-2 and EP4R is a potentially useful marker for tumor progression and survival in patients with nonmetastatic TCC-UUT.

The present study revealed significant differences in the results of estimation of testicular volume among the ten investigators, but intra-investigator variation was not considerable. Improved training and proper standardization of the measurement will be necessary before starting a multi-center study based on an andrological examination.