Novel therapeutics in metastatic bladder cancer.

BACKGROUND: Albeit transitional cell carcinoma of the urinary bladder is a chemosensitive neoplasm, metastatic disease is related with poor prognosis and short-term survival data. OBJECTIVE: Cisplatin-based combination chemotherapy is recognised as the golden standard therapy for patients with inoperable locally advanced or metastatic bladder cancer. However, owing to treatment-related toxicities and short-response durations, novel treatment options or agents, with both enhanced efficacy and tolerability, have been sought. METHODS: Reviewing the current status and addressing the future of novel anticancer therapeutics in metastatic urinary bladder cancer. RESULTS/CONCLUSION: Non-platinum, single agents, such as gemcitabine and taxanes, as well as multidrug regimens in doublet or triplet chemotherapeutic combinations are regarded as promising alternatives. Dose intensification of conventional regimens, dose-dense sequential administration of new agents, the use of molecular markers for predicting chemosensitivity and the integration of biologically targeted agents to enhance chemotherapeutic efficacy are promising approaches.

Upper urinary tract transitional cell carcinoma. A 10-year experience.

OBJECTIVE: To present our 10-year experience with patients surgically treated for upper urinary tract transitional cell carcinoma. PATIENTS AND METHODS: We reviewed the medical records of 264 patients (218 males and 46 females), aged 37-93 years (mean, 69.5), treated surgically for upper tract transitional cell carcinoma during the period January 1996 to December 2005. RESULTS: During the mean follow-up of 58 months (range, 12-120), local relapse was diagnosed in 14% of the patients. The mean time to recurrence was 13 months (range, 1-102). The overall mortality was 14%, and the mean survival was 109 months. Survival was significantly influenced by the following parameters: male gender (P = 0.0151), age over 80 years (P = 0.0012), location in both the pelviocaliceal system and the ureter (P = 0.051), a two incision operation (P = 0.0075), grade III (P = 0.0314), stage T3 and T4 (P < 0.0001). CONCLUSIONS: Tumor stage was identified as the most important determinant in predicting recurrence and survival. Other predictors of survival included male gender, age over 80 years, location in the pelviocaliceal system and the ureter, a two incision operation, and high grade.

Pseudosarcomatous myofibroblastic lesion of the urinary bladder: a rare entity posing a diagnostic challenge and therapeutic dilemma.

BACKGROUND: Pseudosarcomatous myofibroblastic lesions of the urinary bladder are relatively rare entities of an uncertain pathogenesis and benign indolent nature. CASE PRESENTATION: We present an extremely rare case of an ALK-1-positive pseudosarcomatous myofibroblastic lesion of the urinary bladder, which was initially misinterpreted as a low-grade leiomyosarcoma of myxoid subtype on histologic examination owing to prominent atypia, high mitotic activity, abnormal mitotic figures and infiltration of the bladder wall. Although the histologic features were suggestive of a sarcoma, the correct diagnosis was finally established and radical surgical treatment was subsequently avoided. The patient is currently free of disease without any evidence of tumor recurrence or metastasis at 3 years post-operatively. CONCLUSION: The key differentiating point rests in distinguishing the aforementioned mass forming lesion from the myxoid subtype of low-grade leiomyosarcoma in order to avoid unnecessary radical therapy.

The expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and angiogenesis markers in hyperplastic and malignant prostate tissue.

BACKGROUND: The process of ingrowth of new blood vessels is stimulated by the action of vascular endothelial growth factor (VEGF), while it may be simultaneously related to the degree of tissue hypoxia. Hypoxia-inducible factor 1alpha (HIF-1alpha) is a protein of cellular response to hypoxia. The relationship between hypoxia and angiogenesis in patients with benign prostate hyperplasia (BPH) and prostate cancer (PCa) was examined. MATERIALS AND METHODS: One hundred and seventy (170) prostatic tissue samples were immunohistochemically evaluated. The microvessel density (MVD) was calculated by CD34 immunostaining; the angiogenetic profile was further assessed using a monoclonal antibody against VEGF. HIF-1alpha immunoreaction was recognized through nuclear staining of positive cells. RESULTS: CD34, VEGF and HIF-1alpha staining reactions were significantly higher in the PCa group than in the BPH group. In both groups, an interrelationship between the immunoexpression of CD34 and HIF-1alpha, VEGF and HIF-1alpha, as well as VEGF and CD34 was detected. CONCLUSION: MVD, VEGF cytoplasmic immunoreactivity and HIF-1alpha immunoreaction were more prominent in PCa than in BPH and were also significantly associated with high-grade carcinomas.

Finasteride effects on hypoxia and angiogenetic markers in benign prostatic hyperplasia.

OBJECTIVES: To assess the effects of finasteride on angiogenetic and hypoxia markers in benign prostatic hyperplasia. METHODS: A total of 178 patients aged 51 to 85 years (mean 68.7) with benign prostatic hyperplasia and awaiting transurethral prostate resection were prospectively randomized into a group of patients receiving finasteride (group 1; 88 patients) and a group of patients who received no medication until transurethral prostate resection (group 2; 90 patients). Tissue specimens were immunohistochemically stained with monoclonal antibodies against CD34 for microvessel density (MVD), vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1alpha (HIF-1alpha). RESULTS: Blood loss during transurethral prostate resection was significantly higher in group 2 compared with group 1 (P <0.001). The distribution of CD34 immunostaining was mainly at the suburethral prostate. MVD, VEGF, and HIF-1alpha values were significantly lower statistically (P <0.001) in group 1 compared with group 2. In the finasteride group (group 1), the positive correlation of the immunoreactivity of CD34 and HIF-1alpha, VEGF and HIF-1alpha, and VEGF and CD34 was statistically significant (P <0.001). In the same group, MVD and VEGF and HIF-1alpha expression correlated statistically with the treatment duration. CONCLUSIONS: Finasteride administration in benign prostatic hyperplasia results in statistically significant suppression of MVD, VEGF, and HIF-1alpha in a time-dependent manner.