Takashi Fukagai

Detection of circulating urothelial cancer cells in the blood using the CellSearch System

Circulating tumor cells (CTCs) have been shown to aid in the therapeutic management of patients. But, only a few attempts have been made at the detection of urothelial cancer cells in the blood. The purpose of this study was to test the hypothesis that CTCs are detected in patients with urothelial cancers using newly developed CellSearch Assay.

Discrepancies between Gleason scores of needle biopsy and radical prostatectomy specimens.

The purpose of this study was to determine the accuracy of Gleason scores in prostate needle biopsy diagnosis and to investigate factors affecting the accuracy of the tumor grade. A single pathologist reviewed 116 sets of prostate cancer biopsies and radical prostatectomy specimens. The following factors were examined to determine their effect on the accuracy of the biopsy Gleason scores: (i) relative tumor differentiation; (ii) pathological stage; (iii) amount of tissue in the biopsy specimen; (iv) amount of cancer tissue in the biopsy specimen; (v) tumor heterogeneity; (vi) clinical findings (prostate specific antigen value and digital rectal examination); and (vii) interobserver variability. In 53 cases the Gleason score of biopsy specimens was identical to the score of prostatectomy specimens (45.7%). Fifty‐four cases (46.6%) of biopsy specimens were undergraded. The most common discrepancy was diagnosis of well‐differentiated carcinoma in the biopsy but diagnosis of moderately differentiated tumor in the corresponding prostatectomy specimen. This discrepancy occurred when the amount of tumor in the biopsy was 3 mm or less. Biopsy and prostatectomy results showed less agreement when the original biopsy tumor grade rendered by nine different pathologists was used, suggesting that interobserver variability can adversely affect the accuracy of tumor grade. Clarifying the histologic criteria for distinguishing each grade, especially between Gleason grades 2 and 3, is important for accurate grading.

Prostate Cancer Working Group report.

The incidence of prostate cancer, while still lower than in Western nations, is increasing rapidly in Asian countries due to a more westernized lifestyle. Prostate cancer mortality is declining in the USA, where most prostate cancers are diagnosed in the early stage. In contrast, the mortality rates of prostate cancer in Asian countries are expected to continue to increase, because the percentage of advanced-stage prostate cancers remains high. Therefore, early detection by prostate-specific antigen screening and a comprehensive strategy for cancer prevention are essential for Asian people. The exposure rate of prostate-specific antigen screening is very low in Asian countries. Increased prostate-specific antigen screening may reduce the mortality rate. The stances regarding population screening differ among countries. Urological associations should promote population screening. Reliable data from Asian countries are needed. The prostate cancer incidence is low in Asian countries, perhaps due to high soy consumption. Isoflavones may prevent prostate cancer in Asian countries, but that is not yet clear. A large, multinational study in Asia is needed to clarify whether or not isoflavone consumption shows efficacy in preventing prostate cancer. Clinical data suggest that hormonal therapy is more effective in Asians than in Westerners. Clinical guidelines should consider including hormonal therapy as one of the options for the treatment of localized prostate cancer. At the same time, effort should be made to decrease the adverse effects of each treatment. Collaborative studies on the treatment of prostate cancer should be carried out among Asian countries.

Efficacy of primary hormonal therapy for patients with localized and locally advanced prostate cancer: A retrospective multicenter study

Aim: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long‐term prognosis in these patients.

Zoledronate Stimulates γδ T Cells in Prostate Cancer Patients

Androgen deprivation therapy is the mainstay of treatment for prostate cancer. Given its frequent failure, new therapy that reduces prostate cancer progression would be a breakthrough in treating this disease. Bisphosphonates are well-established agents for treating skeletal-related events (SREs) in prostate cancer patients with bone metastases. Exposure to bisphosphonates may not only reduce the incidence of SREs, but also have anticancer effects by modulating a patients immunity. The purpose of this study was to examine the effect of zoledronate (ZOL) on γδ T cells, serum prostate-specific antigen (PSA) levels, and velocities. The effect of ZOL, with and without IL-2, on γδ T cell activation was examined in vitro. Furthermore, the activated state and the number of γδ T cells and changes in serum PSA levels were examined for patients who received ZOL infusion for the prevention of SREs. We found that ZOL activated γδ T cells, and the number of γδ T cell was increased when IL-2 was administered with ZOL in vitro. Comparisons before and after the first ZOL infusion revealed that γδ T cells in peripheral blood were activated by ZOL. Moreover, after the first ZOL treatment, reduction in serum PSA was observed in 3 of 11 patients, and reduction in PSA velocity was observed in 5 of 10 patients. Our findings indicate that ZOL stimulates γδ T cells in vivo and in vitro. This study provides further insight into the ability of γδ T cells to induce an antitumor immune response.

Racial Differences in Sexuality Profiles among American, Japanese, and Japanese American Men with Localized Prostate Cancer

INTRODUCTION Although there were marked racial differences in the clinical outcomes among Japanese men (JP), Caucasian men (CA), and Japanese American (JA) men with localized prostate cancer, the effect of race/ethnicity on sexual profiles remains unclear. AIM To determine differences of sexual profiles in JP, CA, and JA with localized prostate cancer. METHODS A total of 412 JP, 352 CA, and 54 JA with clinically localized prostate cancer were enrolled in separate studies of health-related quality of life outcomes. We developed a collaborative study in each database. MAIN OUTCOME MEASURE Sexual function and bother were estimated before treatment with validated English and Japanese versions of the University of California in Los Angeles Prostate Cancer Index (UCLA PCI). RESULTS The CA reported the highest sexual function score of all. Even after controlling for age, prostate specific antigen, clinical T stage, Gleason score and comorbidity, the JP were more likely than the CA to report poor sexual desire, poor erection ability, poor overall ability to function sexually, and poor ability to attain orgasm. With regard to sexual bother, however, no differences were reported between CA and JP. The JA reported sexual function closely approximate that of the JP, and they were less likely than the CA to report erection ability and intercourse. The JA were more likely to feel distress from their sexual function than the CA. When the JA were divided into two groups according to the ethnicity of their partners, UCLA PCI sexual function scores were equivalent between JA-partnered men and men partnered with other races. On the other hand, JA-partnered men were significantly less likely to report sexual bother scores than men partnered with other races. CONCLUSION We found significant interethnic variations among CA, JP, and JA with prostate cancer in terms of their sexual profiles. Ethnicity and/or country appear to modify some of these variables.

Papillary cystadenocarcinoma of the prostate

A giant cystic formation was found behind the prostate of a 69‐year‐old man who presented with urinary retention. Ultrasonography, computed tomography scans and magnetic resonance imaging revealed a large cystic intrapelvic mass and biopsy of the cyst wall diagnosed papillary cyst adenocarcinoma. Immunohistochemically, the tumor originated from the prostate.

Effectiveness and adverse effects of hormonal therapy for prostate cancer: Japanese experience and perspective.

Recently, novel anti-androgens and inhibitors of androgen biosynthesis have been developed through the elucidation of mechanisms of castration resistance of prostate cancer. We believe that these new developments will improve hormonal therapy. On the other hand, there has been an increase in criticism of hormonal therapy, because hormonal therapy is supposed to induce adverse effects such as cardiovascular disease. In this review, we have introduced the Japanese experience of hormonal therapy, because we believe that there may be ethnic differences between Caucasians and Asian people in the efficacy and adverse effects of hormonal therapy. First, we showed that primary hormonal therapy can achieve long-term control of localized prostate cancer in some cases and that quality of life of patients receiving hormonal therapy is rather better than previously thought. Neoadjuvant and adjuvant hormonal therapy in cases undergoing radical prostatectomy or radiotherapy are very useful for high-risk or locally advanced prostate cancer. Further clinical trials are required to confirm the efficacy of neoadjuvant or adjuvant hormonal therapy. We showed that the death from cardiovascular diseases in Japanese patients receiving hormonal therapy was not higher than that in the general population. However, efforts should be made to decrease the adverse effects of hormonal therapy, because life-style change may increase the susceptibility to adverse effects by hormonal therapy even in Japan. Managements of endocrine and metabolic dysfunction, such as diabetes mellitus, are essential. New hormonal compounds such as selective androgen receptor modulators capable of specifically targeting prostate cancer are expected to be developed.

Enzalutamide in Japanese patients with chemotherapy‐naïve, metastatic castration‐resistant prostate cancer: A post‐hoc analysis of the placebo‐controlled PREVAIL trial

To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients.

Practice patterns regarding prostate cancer and benign prostatic hyperplasia in Japanese primary care practitioners.

Objective:  Although primary care practitioners (PCP) take an active role in diagnosis of prostate disorders in Western countries, how PCP take part in management of prostate disease still differs worldwide by country. We investigated practice and referral patterns concerning prostate disease among Japanese PCP and compared these with reported patterns in the West.