Long-term treatment and prognostic factors of alpha 1-blockers for lower urinary tract symptoms associated with benign prostatic hyperplasia: a pilot study comparing naftopidil and tamsulosin hydrochloride.

OBJECTIVE: This study evaluated the 5-year failure rate of naftopidil (NAF) or tamsulosin hydrochloride (TAM) in lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH/LUTS) and compared the prognostic factor of two alpha(1)-blockers. MATERIAL AND METHODS: A total of 131 patients with International Prostate Symptom Score (IPSS) >or= 8 or IPSS quality of life (IPSS-QOL) >or= 3 with BPH/LUTS receiving treatment with alpha(1)-blockers had been administered NAF or TAM, and failure rates were calculated for 5 years. Age, prostate volume (PV), acute urinary retention (AUR), overactive bladder (OAB), IPSS, IPSS-QOL and postvoiding residual volume (PVR) were evaluated as prognostic factors. RESULTS: No significant differences in failure rate were observed between the drugs. The failure rate was significantly high for patients with a PV >or= 35 ml, PVR >or= 30 ml, a history of AUR or complications of OAB symptoms. The failure rate for patients with a history of AUR was significantly higher than in those without AUR in the NAF group. By contrast, in the TAM group, it was significantly higher in patients who had OAB symptoms than in those without OAB. CONCLUSIONS: No significant differences were observed between the drugs for the failure rate. Each treatment had a unique factor for prognosis, such as history of AUR for NAF and complications of OAB for TAM. Therefore, it will be necessary to use the two alpha(1)-blockers properly, considering the patient's background.

Factors associated with variation in utility scores among patients with prostate cancer.

OBJECTIVE: We aimed to assess the effects of age, comorbidity, and disease-specific functions on utility scores derived from three methods on prostate cancer. METHODS: A total of 330 Japanese prostate cancer patients were asked to answer self-administered questionnaires. Community-weighted utility scores were derived from the EuroQoL-5D (EQ-5D) and the Short Form-36 (SF-36), while the patient's directly elicited utility score was derived from time trade-off technique. Univariate and multivariate analyses were performed to examine the relation between covariates and utility scores. We assigned age, the Index of Co-existent Disease, and disease-specific functions including sexual, urinary, bowel, and hormonal function as covariates. RESULTS: Bowel and hormonal function were related to utility scores, while age and sexual function were not. Comorbidities were more closely related to utility scores derived from EQ-5D and SF-36. CONCLUSIONS: These results contribute to an understanding of which factor has an impact on utility scores in patients with prostate cancer.

Decision analyses in consideration of treatment strategies for patients with biochemical failure after curative therapy on clinically localized prostate cancer in the prostate-specific antigen era.

BACKGROUND: The introduction of prostate-specific antigen (PSA) testing has not only shortened the time required to make diagnosis but changed the treatment strategies of localized prostate cancer. We conducted the decision analysis on its treatment focusing on patients with biochemical failure. METHODS: We developed a Markov model to calculate life expectancy (LE) and quality-adjusted life expectancy (QALE) stratified by age, comorbidity and tumor characteristics in patients with newly diagnosed prostate cancer or biochemical failure after curative therapy. For newly diagnosed patients, three treatment strategies were considered as primary managements: radial prostatectomy (RP), external beam radiotherapy (EBRT) and watchful waiting (WW). Managements considered for biochemical failure were: after RP, salvage radiotherapy (SRT), salvage hormonal therapy (SHT) and WW; and after EBRT, SHT and WW. Transition probabilities in the Markov model were derived from published studies. Quality of life (QOL) data to estimate QALE score were derived from 323 patients with prostate cancer. RESULTS: For patients with Gleason 2-6 cancer at diagnosis, WW yielded the greatest number of QALE. For patients with Gleason 7 cancer, it was controversial whether curative therapy was the preferred strategy. For patients with Gleason 8-10 cancer, curative therapy yielded the greatest number of QALE in younger patients without severe comorbidity. Patients' benefit from salvage therapy for biochemical failure after curative therapy depended on age, comorbidities, tumor characteristics and QOL effect. CONCLUSIONS: Our findings support the need for various treatment options, taking into consideration the patient's age, comorbidity and the QOL effect in the aging society.

Naftopidil monotherapy vs naftopidil and an anticholinergic agent combined therapy for storage symptoms associated with benign prostatic hyperplasia: A prospective randomized controlled study.

AIM: The aim of this study was to compare the efficacy and safety of alpha1-adrenoceptor (alpha1-AR) antagonist monotherapy with combination therapy using alpha1-AR antagonist and anticholinergic agent for benign prostatic hyperplasia (BPH) with storage symptoms as the chief complaint. METHODS: In this prospective comparative study, either 25-75 mg/day of naftopidil monotherapy (monotherapy group) or combination therapy using 25-75 mg/day of naftopidil and an anticholinergic agent (10-20 mg/day of propiverine hydrochloride or 2-6 mg/day of oxybutynin hydrochloride; cotherapy group) were administered for 12 weeks to 101 BPH patients with storage symptoms. RESULTS: International prostate symptom score (IPSS) and quality of life (QOL) index improved significantly in both groups, with no marked differences between groups. Maximum flow rate (Qmax) and residual urine volume (RUV) tended to improve in both groups, again with no marked differences between groups. However, median post-therapeutic RUV was significantly worse for the cotherapy group (45.0 mL) than for the monotherapy group (13.5 mL; P = 0.0210). Ratio of patients with increased RUV was also significantly worse for cotherapy (22.9%) than for monotherapy (5.0%; P = 0.038). CONCLUSIONS: Although the anticholinergic dosage was low, the present results suggest that naftopidil monotherapy was as useful as combination therapy of naftopidil and an anticholinergic agent. Therefore, naftopidil is a useful agent as the first choice in BPH patients with storage symptoms.

Hypoxia-inducible protein 2 (HIG2), a novel diagnostic marker for renal cell carcinoma and potential target for molecular therapy.

To identify molecules to serve as diagnostic markers for renal cell carcinoma (RCC) and as targets for novel therapeutic drugs, we investigated genome-wide expression profiles of RCCs using a cDNA microarray. We subsequently confirmed that hypoxia-inducible protein-2 (HIG2) was expressed exclusively in RCCs and fetal kidney. Induction of HIG2 cDNA into COS7 cells led to secretion of the gene product into culture medium and resulted in enhancement of cell growth. Small interfering RNA effectively inhibited expression of HIG2 in human RCC cells that endogenously expressed high levels of the protein and significantly suppressed cell growth. Moreover, addition of polyclonal anti-HIG2 antibody into culture medium induced apoptosis in RCC-derived cell lines. By binding to an extracellular domain of frizzled homologue 10 (FZD10), HIG2 protein enhanced oncogenic Wnt signaling and its own transcription, suggesting that this product is likely to function as an autocrine growth factor. ELISA analysis of clinical samples identified secretion of HIG2 protein into the plasma of RCC patients even at an early stage of tumor development, whereas it was detected at significantly lower levels in healthy volunteers or patients with chronic glomerulonephritis. The combined evidence suggests that this molecule represents a promising candidate for development of molecular-targeting therapy and could serve as a prominent diagnostic tumor marker for patients with renal carcinomas.

Small cell carcinoma of the prostate with hypercalcemia.

We present a case of small cell prostate carcinoma with hypercalcemia in a 75-year-old man. He was diagnosed as having stage T3bN1M0 adenocarcinoma of the prostate. His serum prostate-specific antigen level was reduced to below the normal range after a combination treatment of a luteinizing hormone-releasing hormone agonist and flutamide for prostate carcinoma. He subsequently experienced increasing fatigue, poor appetite, short time loss of consciousness and pain in his lower abdomen. His serum calcium level and carcinoembryonic antigen were increased. He died 5 months from the start of treatment. The autopsy revealed small cell carcinoma of the prostate and multiple metastasis of the lung, liver, pancreas, lymph nodes and spine.

Sarcomatoid carcinoma and carcinosarcoma of the urinary bladder.

Two cases, sarcomatoid carcinoma and carcinosarcoma, of the urinary bladder are reported. A 68-year-old man with sarcomatoid carcinoma underwent total cystectomy and was alive and had had no recurrence after 21 months. A 78-year-old woman with carcinosarcoma underwent total cystectomy, but she died from increasing multiple lung metastases 4 months after surgery. The histopathological characteristics of both neoplasms are reported and discussed.