[Treatment of osteoporosis in hypogonadal men].

About 3million men have been reported to have osteoporosis in Japan. One of known causes of osteoporosis in men is late-onset-hypogonadism. Androgen replacement therapy has been reporte to be effective in seveal literatures, however, patitiets should be excluded if prostate cancer is suspected. Addition of bisphosphpnate and active vitain D derivatives are recommended.

[Prospective survey of erectile dysfunction after external beam radiotherapy for prostate cancer].

OBJECTIVE: We prospectively evaluated the effect of external beam radiotherapy on erectile function in patients with localized or locally advanced prostate cancer using the Japanese version of the International Index of Erectile Function (IIEF) survey. PATIENTS AND METHODS: From 2000 to 2007, we identified 55 patients who underwent external beam radiotherapy at our institution for localized or locally advanced prostate cancer and could respond to the IIEF survey. The patients did not receive neo- and/or adjuvant hormone therapy and they were followed-up for at least 12 months after radiotherapy. Mean patient age was 69 years and the mean PSA level before radiotherapy was 24.9 ng/ml. RESULTS: First we evaluated the change of the erectile function domain score over time before and after radiotherapy. The population of severe erectile dysfunction (ED) increased while those with no or mild ED decreased after radiotherapy. The erectile function and intercourse satisfaction domain score of the IIEF declined significantly after radiotherapy, however, the orgasmic function, sexual desire, and overall satisfaction domain scores did not change after external beam radiation. Of the 34 patients who had erectile function at baseline, 10 patients could maintain erectile function 12 months after radiotherapy. Though there were no significant differences in clinical features between patients who could maintain erectile function and those who had worsening erectile function 12 months after radiotherapy, the sexual desire domain score before radiotherapy was significantly higher in patients who could maintain erectile function than their counterparts. CONCLUSION: Using the IIEF survey, external beam radiation was found to affect erectile function in patients with localized or locally advanced prostate cancer.

[Adenocarcinoma of the rete testis. A case report].

Adenocarcinoma of the rete testis is a rare malignant tumor with a poor prognosis. About 60 cases of this adenocarcinoma have been reported in the literature. The diagnosis is often difficult and made incidentally. Herein, we report a case of adenocarcinoma of the rete testis and review the literature. Our patient was an 80-year-old man who presented with painless scrotal swelling for 2 years. Physical examination revealed an enlarged, hard mass of the left scrotum. The serum markers alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-HCG), and carcinoembryonic antigen (CEA) were negative. Magnetic resonance imaging (MRI) showed a left hydrocele with central necrosis of the testis. After 4 months, the patient presented with appetite loss, general fatigue, and pain in the left scrotum. Positron emission tomography (PET) was performed in another hospital, and the patient was referred for a left testicular tumor, multiple lung metastases, and para-aorta lymph node metastasis. The patient underwent left high inguinal orchiectomy. Pathological examination revealed a hard whitish mass around the testis involving the epididymis and tunica vaginalis and spreading under the subcutaneous tissue. Histological examination revealed adenocarcinoma in the hilum of the testis, which extended to the subcutaneous tissue but not to the surface of the scrotum. The tunica albuginea was intact, and no invasion of carcinoma in the testis was seen. After the histological diagnosis of adenocarcinoma of the rete testis was confirmed, computed tomography (CT) was performed and showed multiple pulmonary nodules and para-aortica lymph node swelling of 3 cm diameter. Because the patient did not wish to receive chemotherapy or other aggressive treatment, he has been followed-up with palliative care since his diagnosis. Although local recurrence has occurred 4 months later, he is still alive for 8 months since his diagnosis.

Sex among Asian men and women: the Global Better Sex Survey in Asia.

OBJECTIVES: To explore by a pooled subanalysis of the Global Better Sex Survey sexual aspirations and unmet needs of men and women from Hong Kong, Indonesia, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. METHODS: To qualify, respondents must have had sexual intercourse at least once in the past 12 months. Women must have had heterosexual intercourse. Data were weighted by population size between countries. RESULTS: Of 3538 Asian respondents (1776 men and 1762 women), 52% were aged <40 years, 40% were aged 40-59 years, and 8% were aged >or=60 years. The majority were married or in a relationship. Men and women reported having sexual intercourse 5.1 and 4.0 times monthly, respectively. Attraction to partner, foreplay, intercourse, and achieving orgasm were important to most men and women. Two thirds were less than very satisfied with their sex life, and 36% of men were interested in improving sex. For a good sexual experience, the man's ability to get and maintain an erection and erection hardness were important to the majority of Asian men and women. Few respondents reported using a prescription erectile dysfunction medication, but many showed interest in using these medications to improve their sex lives. A comparison between individual countries suggests that attitudes about sex differ from country to country, and between men and women in each country. CONCLUSIONS: Sex is very important to Asian men and women, but many of them are not fully satisfied with their sex lives and want to improve them.

Risk factors for ipsilateral adrenal involvement in renal cell carcinoma.

OBJECTIVES: We retrospectively review patients treated for renal cell carcinoma at 19 institutes in collaboration with the Japanese Society of Renal Cancer, to clarify the risk factors for ipsilateral adrenal involvement (IADI). METHODS: The clinicopathologic factors of the 30 patients with IADI were compared with those of the 926 control patients without IADI, and independent predictors for IADI were identified by multivariate analysis. RESULTS: Preoperative computed tomography (CT) could detect 83.3% of the instances of synchronous ipsilateral adrenal metastasis. Patients with IADI had significantly larger primary tumors, higher pT stages and histologic grades, and higher percentages of upper pole involvement, microvascular invasion, spindle-cell-type tumors, lymph node metastasis (LNM), and distant metastasis (DM) outside the ipsilateral adrenal gland (IAd) than in control patients. Multivariate logistic regression analysis of clinical factors revealed that tumor size greater than 5.5 cm, pT stage of 3 or higher, LNM, and DM outside IAd, but not upper pole involvement, were significant predictors of IADI. CONCLUSIONS: Tumor size greater than 5.5 cm, clinical T stage of 3 or higher (tumor for which pT stage of 3 or higher is suspected), LNM, and DM outside IAd seemed to be important preoperative indicators of IADI. These factors and CT findings would be useful preoperative indicators for ipsilateral adrenalectomy. Moreover, patients with renal cell carcinoma who have normal adrenal on CT, have a T1 tumor extending less than 5.5 cm, and have neither LNM nor DM are good candidates for adrenal-sparing nephrectomy.

Prevalence and correlates of erectile dysfunction (ED) and treatment seeking for ED in Asian Men: the Asian Men's Attitudes to Life Events and Sexuality (MALES) study.

INTRODUCTION: There have been limited multiregional studies in Asia examining the parameters of men's general and sexual health and quality of life in the general population vs. those in clinical cohorts of patients with erectile dysfunction (ED). AIMS: The aims of the Asian Men's Attitudes to Life Events and Sexuality (Asian MALES) study were to investigate the prevalence of ED, associated health conditions, and ED treatment-seeking patterns in the general male population in five regions of Asia (China, Japan, Korea, Malaysia, and Taiwan). MAIN OUTCOME MEASURE: Standardized questionnaire previously used in a similar multiregional study and modified to ensure culturally appropriate content for Asia. METHODS: Phase I of the study involved 10,934 adult men, aged 20-75 years, who were interviewed using the standardized questionnaire. Phase II of the study involved men with self-reported ED recruited from Phase I and via physician referral, invitations in general practitioner offices, and street interception (total Phase II sample, N = 1,209). RESULTS: The overall prevalence of self-reported ED in the Phase I study population was 6.4%. ED prevalence varied by region and significantly increased with age (P < 0.01). Men with ED reported significantly greater rates of comorbid illness (P < 0.0001) and a reduced quality of life (P = 0.0001), compared with men without ED. Phase II of the study revealed that fewer than half of men with self-reported ED had sought treatment for their problem. Men were more likely to seek help for erection difficulties from Western doctors than from traditional medicine practitioners (P = 0.0001). A man's partner/spouse was the most common influencer of treatment seeking in all regions except Malaysia. CONCLUSION: The findings confirm those of existing research on ED in both Asian and non-Asian males: ED is a prevalent condition; the prevalence of ED increases with age and is strongly associated with comorbid conditions; and the majority of men have never sought treatment for their condition. This study highlights a substantial need for the evaluation and treatment of ED in Asian men.

Prevalence of renal cell carcinoma: a nation-wide survey in Japan, 2002.

OBJECTIVE: To investigate the incidence of renal cell carcinoma, classified by sex, age group and region in Japan, following a 5-year interval after a previous survey performed in 1997. METHODS: The survey was conducted between the beginning of January 2002 and the end of December 2002. A total of 1288 institutions in all 47 prefectures throughout Japan were requested to register cases. RESULTS: There were 7405 persons with renal cell carcinoma, consisting of 5063 males and 2342 females. Crude incidence rates were 8.2 and 3.6 per 100 000 population for men and women, respectively. Incidence rates in the Hokkaido region were highest followed by the Shikoku region. CONCLUSIONS: Despite incidence of renal cell carcinoma increasing to 7405 from the 6358 persons in 1997, statistical data reported by the Ministry of Health, Labor and Welfare indicate that rising age-adjusted death rate for this tumor reached a ceiling in the past decade. Early detection may have contributed to this current trend; however, further epidemiological research is required to fully elucidate this.

Surgical outcomes of partial nephrectomy for renal cell carcinoma: a joint study by the Japanese Society of Renal Cancer.

OBJECTIVE: A joint study was undertaken by the Japanese Society of Renal Cancer to investigate the present status of partial nephrectomy in Japan and to speculate about what may be the indications for partial nephrectomy in patients with renal cell carcinoma. METHODS: Data were tabulated for 469 patients from participating medical institutions and various clinical factors were investigated with regard to disease progression (local recurrence and distant metastasis). RESULTS: Disease progression was observed in 21 patients (4.5%). No significant relation to disease progression was observed for sex, laterality, tumor histology, grade and tumor size. Although patients with solitary tumors displayed excellent prognosis irrespective of tumor diameter, patients with multiple tumors displayed a high likelihood of disease progression. Patients older than 77 years old and patients with imperative indication were found to have a poorer prognosis. CONCLUSION: In patients with solitary tumors, partial nephrectomy can be actively performed, even if the patient displays elective indications and the tumor is >4 cm in diameter. In patients displaying multiple tumors with imperative indications, the decision whether to perform partial nephrectomy should be made by the patients and their physicians after considering the impact on curability and the quality of life.

The effect of patient age and other factors on the maintenance of permanent hemodialysis vascular access.

The objective of the present study was to investigate whether patient age is associated with vascular access failure during maintenance hemodialysis. Thus, patients who had a successful permanent hemodialysis vascular access installed (Group N: 314 cases), and those who required vascular access revision (Group R: 108 patients) were studied. To assess the association between patient age and the risk of vascular access failure, Cox proportional hazards regression was used to determine hazard ratios (HR) and 95% confidence intervals (CI). We found that in Group N, the significant risk factors were age, gender, and diabetes mellitus (95% CI: 1.004-1.013, 0.380-0.827, 1.279-2.859). Using a univariate analysis model, significant hazard ratios (HR) were found with ages of 60 (CI: 1.062-2.302), 65 (CI: 1.052-2.280), and 70 (CI: 1.082-2.537) years, with the largest HR at 70 years of age (HR: 1.657). In contrast, in Group R, multivariate analysis using Cox proportional hazards identified only one prognostic variable, the location of the vascular access. In Group R, univariate analysis models showed that age was not a significant factor. We conclude that our data show that age is a risk factor for the successful maintenance of initial permanent hemodialysis vascular access. Other risk factors include gender and diabetes mellitus. However, these factors were not related to the successful maintenance of revised vascular access.

A comparison of the efficacy and tolerability of tadalafil 10 mg and 20 mg in Japanese patients with severe erectile dysfunction.

INTRODUCTION: Tadalafil is a phosphodiesterase type 5 inhibitor with documented efficacy in the treatment of erectile dysfunction (ED). AIM: To compare the efficacy and tolerability of tadalafil 10 mg and 20 mg in men with severe ED. METHODS: A prespecified subgroup analysis was conducted to compare the efficacy of tadalafil 10 and 20 mg measured by the International Index of Erectile Function (IIEF) erectile function (EF) domain and Sexual Encounter Profile (SEP) among patients with severe ED (EF domain score = 1-10) in a Japanese placebo-controlled study (PCT). We also analyzed the efficacy of the two doses in men with severe ED post hoc by pooling data from three tadalafil clinical trials that evaluated these doses using a similar study design (three placebo-controlled trials), and evaluated (post hoc) the presence of organic comorbidities in patients with different levels of response to tadalafil 10 or 20 mg. MAIN OUTCOME MEASURES: Mean change in the IIEF-EF domain and mean per-patient changes in percent "yes" responses to SEP Question 2 (SEP2) and Question 3 (SEP3). RESULTS: Patients with severe ED in the Japanese study experienced numerically greater increases (improvements) when taking tadalafil 20 mg compared with 10 mg in the IIEF-EF domain (14.3 vs. 12.4; P = 0.355), SEP2 (60% vs. 57%; P = 0.781), and SEP3 (61% vs. 49%, P = 0.196). When sufficiently powered, these observations reached statistical significance in the three PCTs: patients with severe ED experienced greater increases when taking tadalafil 20 mg compared with 10 mg in the IIEF-EF domain (13.6 vs. 10.4; P = 0.014) and SEP3 (56% vs. 43%, P = 0.019). Both doses were well tolerated. CONCLUSIONS: Patients with severe ED, and especially those with an organic comorbidity, may derive greater clinical benefits from tadalafil 20 mg compared with 10 mg.

Efficacy and safety of tadalafil 5, 10, and 20 mg in Japanese men with erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVES: To investigate the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in Japanese men with erectile dysfunction (ED). METHODS: This multicenter, randomized, double-blind, placebo-controlled, 12-week study enrolled 343 Japanese men with ED. The men were stratified into those with mild, moderate, or severe ED and then randomly assigned 1:1:1:1 to placebo and 5 mg, 10 mg, and 20 mg tadalafil. Co-primary outcomes were the International Index of Erectile Function erectile function domain score, the percentage of "yes" responses to the Sexual Encounter Profile Diary Questions 2 and 3, and tolerability. Secondary outcomes included the International Index of Erectile Function intercourse satisfaction and overall satisfaction domain scores and the percentage of "yes" responses to a global assessment question. RESULTS: The least square mean change from baseline was 7.5, 9.1, and 9.4 for 5, 10, and 20 mg tadalafil versus 2.1 for placebo for the International Index of Erectile Function erectile function domain; 28.5, 36.0, and 36.5 for 5, 10, and 20 mg tadalafil versus 8.6 for placebo for Sexual Encounter Profile question 2; and 34.3, 47.3, and 50.8 for 5, 10, and 20 mg tadalafil versus 12.3 for placebo for Sexual Encounter Profile question 3, respectively (P <0.001 for all doses and all measures). Patients taking tadalafil had significantly greater changes from baseline for the intercourse satisfaction and overall satisfaction domains compared with patients taking placebo (P <0.001). Also, 76.5%, 81.4%, and 83.7% of patients taking 5, 10, and 20 mg tadalafil, respectively, reported improved erections (global assessment question) versus 31.4% of patients taking placebo (P <0.001). Most (98%) treatment-emergent adverse events were mild or moderate in severity. One patient (tadalafil 5 mg) discontinued because of an adverse event (ureteral calculus). Of the 343 patients, 302 (88%) completed the study. No deaths were reported. CONCLUSIONS: All doses of tadalafil studied were efficacious and well tolerated in Japanese men with ED.

Maximum tumor diameter is a simple and valuable index associated with the local extent of disease in clinically localized prostate cancer.

BACKGROUND: The present study was undertaken to investigate the association of pathological features, including the total tumor volume (TTV), maximum tumor area (MTA), and maximum tumor diameter (MTD), with the local extent of disease in clinically localized prostate cancer. METHODS: Serial whole sections of the prostate from 164 patients who underwent radical prostatectomy for localized prostate cancer were investigated. The correlations between the indicators of tumor size, including the TTV, MTA, and MTD, and other pathological parameters were evaluated. RESULTS: The MTD, MTA, and TTV were significantly correlated with each other. Multivariate stepwise logistic regression analysis indicated that the Gleason score, perineural invasion, microvascular invasion, and MTD were significant independent parameters associated with extraprostatic disease. CONCLUSION: The histological tumor grade, perineural invasion, microvascular invasion, and tumor size were correlated with the local extent of disease. The MTD, a simple, easy, and inexpensive parameter, is a more significant pathological feature associated with the local extent of disease than the MTA or TTV.

Clinicopathological features predicting nodal metastasis of testicular seminoma: results from 100 cases in a single institute.

BACKGROUND/AIMS: To investigate the clinical and pathological features which predict nodal metastasis and/or the prognosis of testicular seminoma and to evaluate the current treatment strategy in a single institute. METHODS: We retrospectively analyzed 100 patients who had been pathologically diagnosed as having testicular seminoma in our institute. Ninety-one patients (91%) had stage I disease, 9 patients (9%) were stage II and none stage III. The median follow-up was 63.2 months (range 0.5-249). RESULTS: The duration between the tumor recognition and the first outpatient visit ranged from 0 to 144 weeks, with a median of 5 weeks, which did not influence the clinical stage. The tumor diameter and the preoperative serum lactate dehydrogenase (LDH) level were the significant predictors of stage II disease. Following orchiectomy, 68 patients (74.7%) with stage I disease received radiotherapy. Only 1 patient who had not received adjuvant radiotherapy died from the recurrent disease. The 5-year survival was 100% for the irradiation group but 95% for the surveillance group, although the difference was not statistically significant. All the stage II patients were successfully treated with chemotherapy following orchiectomy. CONCLUSION: The maximum tumor diameter and the preoperative serum LDH level were the significant predictors of nodal metastasis. Adjuvant radiotherapy in patients with stage I seminoma did not influence the survival. Systemic chemotherapy promised good survival for the seminoma, even with nodal metastasis, in this series. Our results support the good prognosis of testicular seminoma with the current treatment strategy.

Modulation of bcl-2 family proteins in MAPK independent apoptosis induced by a cdc25 phosphatase inhibitor Cpd 5 in renal cancer cells.

Protein phosphatases have been classified into two basic types, namely protein serine/threonine phosphatase (PP), and protein tyrosine phosphatase (PTP). Cpd 5 is a selective inhibitor of cdc25 phosphatases, which belong to members of PTPs and regulate cell proliferation by controlling cyclin-dependent kinases (cdks). The present study was undertaken to investigate the potential utility of Cpd 5 as an anti-neoplastic agent for renal cell carcinomas (RCCs). Three renal cancer cell lines, 769P, Sw839, and A498 were used. The effects of Cpd 5 on the viability of renal cancer cell lines was analyzed using an Alamar Blue assay. Apoptosis was determined by flow cytometric TUNEL analysis. Changes in the expression of cdc25 phosphatases, mitogen-activated protein kinases (MAPKs), and bcl-2 family proteins were detected using Western blot analysis. The apoptosis-inducing effect of Cpd 5 on human RCC tissue was analyzed through TUNEL staining of organ cultures from RCCs. Cpd 5 showed a strong cytotoxicity against all renal cancer cell lines with an apoptosis-inducing effect. All cell lines treated with Cpd 5 resulted in a down-regulation of cdc25A, cdc25B, and cdc25C, however, the MAPK pathways were not affected. In addition, the up-regulation of bax, and the down-regulation of bcl-2 and bcl-xL, was observed. In organ cultures from RCCs, TUNEL-positive apoptotic nuclei were observed when treated with Cpd 5. Cpd 5 was thus found to effectively inhibit the proliferation of human renal cancer cells while also inducing apoptosis by inhibiting cdc25 phosphatases and modulating bcl-2 family proteins. The administration of Cpd 5 may thus be an effective therapeutic approach for RCCs.

Repeated regression of pulmonary metastases from renal cell carcinoma after treatment using different interferon-alpha preparations.

A 49-year-old man with pulmonary metastasis from renal cell carcinoma (RCC) was treated with recombinant IFN-alpha2b (Intron A). A complete response was achieved within 4 months and thereafter persisted for 5 years until he developed another lung lesion. Interleukin-2 (Imunace) was administered without any response. Finally, he was treated by natural IFN-alpha (OIF). The pulmonary lesion achieved a partial response after 11 months of treatment. Because IFN-alpha preparations include different subtypes, changing the use of IFN-alpha preparations may thus be a potentially useful option for the successful immunotherapy of RCC.

C-jun activation in acquired cystic kidney disease and renal cell carcinoma.

PURPOSE: Activator protein-1 has a central role in transducing cytokine signals. Activator protein-1 is composed of 2 proto-oncogene families, namely Jun and Fos. Of them c-Jun has been suggested to have a role in cell cycle progression and neoplastic transformation. We examined the impact of c-Jun protein activation on pathological parameters in renal cell carcinoma (RCC). MATERIALS AND METHODS: The expression of total c-Jun protein and phosphorylated c-Jun protein was determined by immunohistochemistry in 72 patients with RCC, including 10 with tumor arising from acquired cystic kidney disease (ACKD) of end stage kidneys. RESULTS: c-Jun expression was observed in the distal but not the proximal tubules. Atypical hyperplastic cells in ACKD were positive for phosphorylated c-Jun. RCC arising in end stage kidneys was pT1 and 5 of these cases showed increased c-Jun activation. Of 62 cases arising from normally functioning kidneys 21 showed an increased degree of c-Jun activation. In localized small cell cases (pT1a) 55.5% (10 of 18) showed enhanced activation, whereas such enhanced activation was only observed in 25% (11 of 44) of more advanced cases (pT1b or greater). Therefore, c-Jun activation was considered to be related to the early carcinogenesis of RCC. CONCLUSIONS: This study emphasizes the role that c-Jun activation has in early RCC carcinogenesis. Thus, chronic stimulation of cytokines inducing c-Jun activation may have a role in the aberrant proliferation of hyperplastic atypical cells in ACKD and RCC.