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We aimed to compare the outcomes of high-dose-rate brachytherapy (HDR-BT) boost and external beam radiation therapy (EBRT) alone for high-risk prostate cancer. This was a single-center, retrospective and observational study. Consecutive patients who underwent initial radical treatment by HDR-BT boost or EBRT alone from June 2009 to May 2016 at the Niigata University Medical and Dental Hospital, Japan were included. A total of 96 patients underwent HDR-BT boost, and 61 underwent EBRT alone. The prescription dose of HDR-BT boost was set to 18 Gy twice a day with EBRT 39 Gy/13 fractions. The dose for EBRT alone was mostly 70 Gy/28 fractions. The high-risk group received >6 months of prior androgen deprivation therapy. Overall survival, biochemical-free survival, local control and distant metastasis-free survival rates at 5 years were analyzed. The incidence of urological and gastrointestinal late adverse events of Grade 2 and above was also summarized. In the National Comprehensive Cancer Network (NCCN) high-risk calssification, HDR-BT boost had a significantly higher biochemical-free survival rate at 5 years (98.9% versus 90.7%, P = 0.04). Urethral strictures were more common in the HDR-BT boost group. We will continuously observe the progress of the study patients and determine the longer term results.

DOI： 10.1093/jrr/rrab006

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PURPOSE: This study aims to investigate the utility of prostate-specific antigen (PSA) screening by conducting an all-case survey of newly diagnosed prostate cancer patients at Niigata Prefecture, Japan. PATIENTS AND METHODS: Depending on whether patients were subjected to screening, information was prospectively collected on all prostate cancer patients newly diagnosed between October 1, 2019, and September 30, 2020, at all institutions in Niigata Prefecture where urologists performing prostate biopsy routinely work and differences in clinical parameters were investigated. RESULTS: PSA was measured in 478 out of 1332 patients (35.8%) as part of a community health screening. The rate of metastatic carcinoma (M1) in all patients was 14.9%. When patients were divided into three categories of population-based screening (community health screening and workplace health screening), opportunistic screening (PSA measurements at complete medical check-ups or on patient request), and testing triggered by clinical symptoms or findings, the proportion of metastatic cancer was 4.5%, 3.7%, and 30.6%, respectively, demonstrating that the number of distant metastases was significantly lesser in all patients who underwent screening. CONCLUSION: The one-year all-case survey of newly diagnosed prostate cancer patients demonstrated that PSA screening significantly contributed to the early diagnosis of current prostate cancer in Japan.

DOI： 10.2147/RRU.S341347

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Objective To estimate the outcomes of high-dose-rate brachytherapy combined with hypofractionated external beam radiotherapy in prostate cancer patients classified as very high risk by the National Comprehensive Cancer Network. Methods Between June 2009 and September 2015, 66 patients meeting the criteria for very high-risk disease received high-dose-rate brachytherapy (2 fractions of 9 Gy) as a boost of external beam radiotherapy (13 fractions of 3 Gy). Androgen deprivation therapy was administered for approximately 3 years. Biochemical failure was assessed using the Phoenix definition. Results The median follow-up period was 53 months from the completion of radiotherapy. The 5-year biochemical failure-free, distant metastasis-free, prostate cancer-specific and overall survival rates were 88.7, 89.2, 98.5 and 97.0%, respectively. The independent contribution of each component of the very high-risk criteria was assessed in multivariable models. Primary Gleason pattern 5 was associated with increased risks of biochemical failure (P = 0.017) and distant metastasis (P = 0.049), whereas clinical stage >= T3b or >4 biopsy cores with Gleason score 8-10 had no significant impact on the two outcomes. Grade 3 genitourinary toxicities were observed in two (3.0%) patients, whereas no grade >= 3 gastrointestinal toxicities occurred. Conclusions The present study shows that this multimodal approach provides potentially excellent cancer control and acceptable associated morbidity for very high-risk disease. Patients with primary Gleason pattern 5 are at a higher risk of poor outcomes, indicating the need for more aggressive approaches in these cases.

DOI： 10.1111/iju.14305

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Introduction:We aimed to assess the outcome of free tube graft urethroplasty for single-stage repair of hypospadias with chordee in children.Materials and Methods:We retrospectively evaluated a series of 56 patients (16 months to 9 years old, median 24 months) who underwent free graft urethroplasty for repair of hypospadias with chordee between May 2005 and November 2017. The median follow-up was 7 years (range 1-11).Results:After releasing the chordee, the hypospadiac orifice was retracted to become penile in 32 patients (57%), penoscrotal in 18 patients (32%), and scrotal in 6 patients (11%). Single-stage repair was achieved without complications in 42 patients (75%). Of the remaining 14 patients with postoperative complications requiring surgical intervention, 2 had meatal stenosis, 9 had urethrocutaneous fistula, 1 had urethral diverticulum without meatal stenosis, and 1 had meatal regression. One patient who complained the urine stream went upwards in an arc underwent cutback meatoplasty to correct the stream. In all patients, a neomeatus with a vertically oriented slit-like appearance was eventually achieved at the tip of the glans.Conclusion:A free graft is an appropriate choice for repairing hypospadias with chordee. Our procedure achieved favorable functional and cosmetic outcomes with a low postoperative morbidity rate.

DOI： 10.1159/000504146

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We herein report an unusual case of brain metastasis from prostate cancer during androgen deprivation therapy and post-docetaxel and definitive local therapy. The brain metastasis was surgically resected followed by Whole-brain radiation therapy. Postoperatively, his PSA again decreased to an undetectable level and remained undetectable with no evidence of new or recurrent disease.

DOI： 10.1016/j.eucr.2019.100879

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BACKGROUND: Brachytherapy is one of the standard treatments for localized prostate cancer (CaP). However, the feasibility of brachytherapy for renal transplant recipients (RTRs) is still uncertain. MATERIALS AND METHODS: Between August 2007 and March 2018, all patients who had undergone low-dose-rate (LDR) brachytherapy or high-dose-rate (HDR) brachytherapy for clinically localized CaP at our institution were retrospectively identified (n = 394). Of these patients, 3 had a history of renal transplantation. We reviewed all available clinical data retrospectively. RESULTS: All of the RTRs received ABO-incompatible renal grafts from their spouses and had stable renal graft function before the diagnosis of CaP. The median age at diagnosis of CaP was 65 years (range, 60-67 years). The median time between transplantation and brachytherapy was 7 years (range, 4-10 years). In all of the patients, clinical stage was cT1cN0M0. Two patients received 125I LDR-brachytherapy (dose, 145 Gy) and 1 patient was treated by 192Ir HDR brachytherapy (dose, 19 Gy in 2 fractions) combined with external beam radiation therapy of 39 Gy in 13 fractions. The median follow-up period after brachytherapy was 44 months (range, 34-50 months). During the follow-up period, none of the patients developed disease progression including biochemical recurrence or clinically significant adverse events associated with radiation therapy. CONCLUSIONS: LDR brachytherapy and HDR brachytherapy are safe and technically feasible in RTRs with CaP, and oncological outcomes in RTRs do not appear to be inferior to those of patients who did not receive renal transplant.

DOI： 10.1016/j.transproceed.2018.10.027

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Pheochromocytomas are catecholamine-producing neuroendocrine tumors that arise from the adrenal medulla. The clinical presentation includes headache, palpitation, and hypertension, but pheochromocytomas are sometimes clinically silent. The present case highlights the importance of biochemical testing for pheochromocytoma in patients with adrenal incidentaloma, even if they are completely normotensive and asymptomatic.

DOI： 10.1002/ccr3.1772

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Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by heterozygous germline mutations in the tumor suppressor gene MEN1, which encodes a nuclear protein, menin. MEN1 is characterized by the combined occurrence of tumors involving the pituitary gland, pancreatic islets, and parathyroid glands. Additionally, patients with MEN1 often exhibit adrenal tumors. Although most MEN1-associated tumors are benign, malignant lesions arising in these endocrine organs have been reported. Additionally, malignant diseases of non-endocrine organs concomitant with MEN1 have also been reported. Here, we report a rare case of a MEN1 patient who exhibited adrenocortical carcinoma (ACC) and lung adenocarcinoma (LAC).A 53-year-old Japanese woman was diagnosed with genetically proven MEN1 that initially manifested as parathyroid, pancreatic, and adrenal tumors. During the course of the disease, she developed LAC harboring the epidermal growth factor receptor gene mutations and cortisol-secreting ACC. Both tumors were surgically resected. The tumor cells were immunohistochemically negative for menin.Studies have suggested a causative link between MEN1 gene mutations and ACC, and menin expression may decrease in MEN1-related ACCs. In contrast, there are few reports suggesting a specific role of MEN1 gene mutations in LAC. Menin is often inactivated in the LACs of patients without MEN1. Thus, our patient's ACC probably occurred as part of MEN1, whereas the latter had no evident etiological association with her LAC. This case demonstrates the need for physicians to consider the potential development of malignant diseases originating from both endocrine and non-endocrine organs in MEN1 patients. (C) 2016 The Authors. Published by Elsevier Ltd.

DOI： 10.1016/j.rmcr.2016.12.002

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Intratumoural dihydrotestosterone (DHT) synthesis could be an explanation for castration resistance in prostate cancer (PC). By using liquid chromatography-mass spectrometry, we evaluated the intratumoral DHT synthesis from 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol), which is inactive androgen metabolized from DHT. 3 beta-diol had biochemical potential to be converted to DHT via three metabolic pathways and could stimulate PC cell growth. Especially, 3 beta-diol was not only converted back to upstream androgens such as dehydroepiandrosterone (DHEA) or Delta 5-androstenediol but also converted directly to DHT which is the main pathway from 3 beta-diol to DHT. Abiraterone had a significant influence on the metabolism of DHEA, epiandrosterone and 3 beta-diol, by the inhibition of the intratumoural 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activities which is one of key catalysts in androgen metabolic pathway. The direct-conversion of 3 beta-diol to DHT was catalysed by 3 beta-HSD and abiraterone could inhibit this activity of 3 beta-HSD. These results suggest that PC had a mechanism of intratumoural androgen metabolism to return inactive androgen to active androgen and intratumoural DHT synthesis from 3 beta-diol is important as one of the mechanisms of castration resistance in PC. Additionally, the inhibition of intratumoural 3 beta-HSD activity could be a new approach to castration-resistant prostate cancer treatment.

DOI： 10.1038/srep32198

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Background: Recruitment of cofactors in the interaction of the androgen receptor (AR) and AR ligands plays a critical role in determining androgenic/antiandrogenic effects of the AR ligand on signaling, but the functions of key cofactors, including nuclear receptor coactivator (NCOA), remain poorly understood in prostate cancer cells treated with AR ligands.Methods: We examined prostate cancer cell lines LNCaP and VCaP expressing mutated and wild-type ARs, respectively, to clarify the significance of NCOAs in the effect of antiandrogens. Hydroxyflutamide showed antagonistic activity against VCaP and an agonistic effect on LNCaP. Bicalutamide served as an antagonist for both. We analyzed mRNA transcription and protein expression of NCOAs in these cells pretreated with dihydrotestosterone and thereafter treated with the mentioned antiandrogens. Transcriptional silencing of candidate NCOAs and AR was performed using small interfering RNA (siRNA). Cell proliferation was evaluated with MTT assay.Results: LNCaP treated with bicalutamide showed an about four-fold increase in the expression of NCOA2 mRNA compared to those pretreated with dihydrotestosterone alone (P < 0.01). In VCaP pretreated with dihydrotestosterone, transcriptions of NCOA2 and NCOA7 were slightly increased with bicalutamide (1.96- and 2. 42-fold, respectively) and hydroxyflutamide (1.33-fold in both). With Western blotting, the expression of NCOA2 protein also increased in LNCaP cells treated with bicalutamide compared with that in control cells pretreated with dihydrotestosterone alone. Following silencing with siRNA for NCOA2, PSA levels in media with LNCaP receiving bicalutamide were elevated compared with those in non-silencing controls (101.6 +/- 4.2 vs. 87.8 +/- 1.4 ng/mL, respectively, P = 0.0495). In LNCaP cells treated with dihydrotestosterone and bicalutamide, NCOA2-silencing was associated with a higher proliferation activity compared with non-silencing control and AR-silencing.Conclusion: NCOA2, which has been thought to be recruited as a coactivator, possibly plays a corepressive role in AR of prostate cancer cells when treated with antiandrogens, suggesting its potential as a therapeutic target.

DOI： 10.1186/s12885-016-2378-y

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Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.juro.2015.02.2059

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DOI： 10.1016/j.juro.2015.02.1362

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DOI： 10.1016/j.juro.2013.02.1836

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Intratumoral synthesis of dihydrotestosterone (DHT) from precursors cannot completely explain the castration resistance of prostate cancer. We showed that DHT was intratumorally synthesized from the inactive androgen metabolites 5α-androstane-3α/β,17β-diol (3α/β-diol) in prostate cancer cells via different pathways in a concentration-dependent manner. Additionally, long-term culture in androgen-deprived media increased transcriptomic expression of 17β-hydroxysteroid dehydrogenase type 6 (HSD17B6), a key enzyme of oxidative 3α-HSD that catalyzes the conversion of 3α-diol to DHT in prostate cancer cells. Correspondingly, the score for HSD17B6 in tissues of 42 prostate cancer patients undergoing androgen deprivation therapy (ADT) was about 2-fold higher than that in tissues of 100 untreated individuals. In men receiving ADT, patients showing biochemical progression had a higher HSD17B6 score than those without progression. These results suggested that 3α/β-diol also represent potential precursors of DHT, and the back conversion of DHT from androgen derivatives can be a promising target for combination hormone therapy.

DOI： 10.1016/j.juro.2013.02.1716

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Intratumoral synthesis of dihydrotestosterone(DHT) from precursors cannot completely explain the castration resistance of prostate cancer. We showed that DHT was intratumorally synthesized from the inactive androgen metabolites 5 alpha-androstane-3 alpha/beta, 17 beta-diol(3 alpha/beta-diol) in prostate cancer cells via different pathways in a concentration-dependent manner. Additionally, long-term culture in androgen-deprived media increased transcriptomic expression of 17 beta-hydroxysteroid dehydrogenase type 6(HSD17B6), a key enzyme of oxidative 3 alpha-HSD that catalyzes the conversion of 3 alpha-diol to DHT in prostate cancer cells. Correspondingly, the score for HSD17B6 in tissues of 42 prostate cancer patients undergoing androgen deprivation therapy(ADT) was about 2-fold higher than that in tissues of 100 untreated individuals. In men receiving ADT, patients showing biochemical progression had a higher HSD17B6 score than those without progression. These results suggested that 3 alpha/beta-diol also represent potential precursors of DHT, and the back conversion of DHT from androgen derivatives can be a promising target for combination hormone therapy.

DOI： 10.1038/srep01528

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OBJECTIVE To elucidate the mechanism of the androgen deprivation therapy (ADT)-related decrease in lean body mass (LBM).MATERIALS AND METHODS The LBM and blood samples were studied before and after 6 months of ADT in 72 patients with localized prostate cancer. The LBM was assessed using a foot-to-foot bioelectrical impedance analyzer.RESULTS Before ADT, the LBM correlated with none of the serum sex steroid levels; however, it correlated closely with serum 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (Spearman's rank correlation coefficient = 0.409, P = .001) and insulin-like growth factor-1 (IGF-I, Spearman's rank correlation coefficient = 0.329, P = .005). After ADT, the LBM decreased by 0.9% (P = .036), and the serum testosterone and dihydrotestosterone had decreased by 96.8% and 94.3%, respectively (P < .001 for both), and the IGF-I had increased by 11.6% (from 19.9 to 22.2 nmol/L, P = .001). The serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels decreased after ADT by 9.8% (from 66.2 to 59.7 pg/mL, P = .008), and the post-treatment LBM correlated inversely with 1,25(OH) 2D (Spearman's rank correlation coefficient = -0.343, P = .003). The post-treatment LBM was dissociated with 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide and IGF-I. The pretreatment and post-treatment LBMs both correlated inversely with serum sex hormone-binding globulin (P = .024 and P = .016, respectively).CONCLUSION The deficiency in androgen levels was suggested to be a link to the ADT-related decrease in LBM; the androgen metabolite 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide has a potential value for assessing the LBM in untreated men. IGF-I also promotes muscle building and is positively regulated during ADT. Sex hormone-binding globulin possibly accelerates the ADT-related decrease in LBM. Although the mechanism for the decrease in 1,25(OH) 2D and its inverse correlation with LBM during ADT is unclear, 1,25(OH) 2D might be a biomarker reflecting the ADT-related decrease in LBM. UROLOGY 81: 376-380, 2013. (C) 2013 Elsevier Inc.

DOI： 10.1016/j.urology.2012.10.050

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Language：English   Publisher：MARY ANN LIEBERT INC  

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Background: Luteinizing hormone (LH) during androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone analogues (GnRHa) has been thought to be biologically inactive, and the regulation of LH during ADT with GnRHa is thus unknown. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and differentiation, and IGF-1 production in the liver is dependent on growth hormone (GH) secretion from the anterior pituitary. Despite the presence of IGF-1 receptors in the gonadotroph, associations between the GH/IGF-1 and pituitary-gonadal axes, e.g., whether IGF-1 elicits the LH secretion, remain unclear.Methods: Seventy-one patients with localized prostate cancer, who received ADT with GnRHa, were prospectively studied based on their blood samples before treatment and after ADT for 6 months. We employed highly sensitive assays for measurement of serum testosterone (electrochemiluminescence immunoassay), GH/IGF-1 (radioimmunoassay), adrenocorticotropic hormone (ACTH: immunoradiometric assay), LH (chemiluminescent immunoassay), and dehydroepiandrosterone sulfate (DHEA-S: chemiluminescent enzyme immunoassay).Results: No correlation was noted between the pretreatment LH and IGF-1 levels; after ADT, the serum LH level was closely correlated with the IGF-1 concentration [Spearman's correlation coefficient (rs) = 0.370, P = 0.001]. The serum levels of androgens and gonadotropins reduced following ADT (P < 0.001 in all). The serum IGF-1 level increased (22 +/- 6 nmol/L) compared with that at the baseline (19 +/- 5 nmol/L) (P < 0.001), but no change was observed in the serum GH concentration between before and after ADT (1.4 +/- 2.3 vs. 0.9 +/- 0.9 mu g/L, respectively, P = 0.691). The serum testosterone level was not correlated with the LH level either before or after ADT. The testosterone and DHEA-S levels after ADT were correlated with ACTH concentration (rs = 0.367, P = 0.002 and rs = 0.354, P = 0.002, respectively). We did not identify any correlations between the serum IGF-1 concentration and Gleason score, PSA value, or androgen levels.Conclusions: During ADT with GnRHa, IGF-1 possibly promotes LH production, although its role is unclear. Associations among pituitary-gonadal, pituitary-adrenal, and GH/IGF-1 axes represented by IGF-1-mediated LH secretion and ACTH-mediated androgen synthesis are of interest, since both prostate epithelium proliferation and male anabolic activity are involved in these 3 axes. Assessment of oncologic outcomes is warranted for their significance in patients with prostate cancer. (C) 2012 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.urolonc.2010.11.001

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BACKGROUND Interleukin-6 produced in adipose tissue plays a role in lipid metabolism, and also interacts with sex steroids. This study was performed to elucidate the mechanism of lipid metabolism disorder during androgen deprivation therapy (ADT) in terms of the association of interleukin-6 with sex steroids. METHODS Seventy-two patients with localized prostate cancer were prospectively studied based on their body-composition and blood samples before and after ADT for 6 months. RESULTS Before ADT, serum interleukin-6 levels were inversely correlated with serum total-testosterone (rs?=?-0.305, P?=?0.009) and dihydrotestosterone (rs?=?-0.380, P?=?0.006) concentrations, but not correlated with adrenal androgen or estradiol levels. Pretreatment interleukin-6 levels were positively correlated with %body fat (rs?=?0.349, P?=?0.003) and %visceral fat (rs?=?0.384, P?=?0.001). After ADT, %body fat increased (P?<?0.001) and lean body mass decreased (P?=?0.036). After ADT, in contrast to the pretreatment relationship, interleukin-6 levels were positively correlated with total-testosterone concentrations (rs?=?0.343, P?=?0.003), and were positively correlated also with levels of androstenedione (rs?=?0.351, P?=?0.002) and estoradiol (rs?=?0.335, P?=?0.004). Interleukin-6 levels were equivalent between before and after ADT (2.02 vs. 2.16?pg/ml, P?=?0.205), but the positive correlation between interleukin-6 levels and %body or %visceral fat noted before ADT disappeared after ADT. CONCLUSIONS Posttreatment interleukin-6 levels had a strong positive correlation with total-testosterone, androstenedione, and estradiol levels, suggesting that a regulation loop may emerge between these sex steroids and interleukin-6 during ADT. The altered association between interleukin-6 and sex steroids is possibly involved in ADT-related lipid metabolism disorder with unchanged interleukin-6 levels despite increased %body fat. Prostate 72:12071213, 2012. (C) 2011 Wiley Periodicals, Inc.

DOI： 10.1002/pros.22471

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

Objective: This study was performed to elucidate the mechanism of high bone turnover during androgen deprivation therapy (ADT) in terms of osteogenic endocrine activity by testosterone, adrenal androgens, and insulin-like growth factor-1 (IGF-I), and to identify markers reflecting the bone mineral density (BMD) during ADT.Design: BMD and samples of blood and urine were studied before and after 6 months of ADT in 70 patients with localized prostate cancer.Results: Before ADT, serum free-testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and IGF-I levels were correlated with BMD (rs = 0.344, p = 0.004; rs = 0.264, p = 0.027; rs = 0.329, p = 0.005; rs = 0.300, p = 0.012, respectively). The serum IGF-I level was independently correlated with the pretreatment BMD (Multivariate p = 0.001). These relationships disappeared after ADT (p = 0.519, 0.316, 0.116, and 0.597, respectively). After ADT, serum levels of free-testosterone decreased (7.9 to 0.2 pg/mL), and DHEA-S and androstenedione were also reduced (3.6 to 2.3 mu mol/L and 5.6 to 2.9 nmol/L, respectively) (p<0.001 in all). In contrast, IGF-I levels were elevated after ADT by 11.6% (19.9 to 22.3 nmol/L, p<0.001). Delta-values of IGF-I (post- minus pretreatment levels, mean: +2.2, ranged between -7.1 and +15.3) were inversely correlated with the pretreatment (rs = -0.333 p = 0.005) and post-treatment (rs = -0.408, p = 0.001) BMD. After ADT, the serum IGF-I level was closely correlated with the serum level of the bone formation marker bone-specific alkaline phosphatase (BAP) (rs = 0.328, p = 0.006), and delta-IGF-I and delta-BAP showed a close positive correlation.(rs = 0.388, p = 0.001). The post-treatment BMD was correlated only with the urine deoxypyridinoline (DPD) concentration (rs = -0.302, p = 0.024) among the bone formation/resorption markers including serum/urine N-telopeptide.Conclusions: Serum IGF-I levels increased during ADT in men with a low BMD. Coupled with reduced androgen levels, elevated IGF-I levels, which were positively correlated with BAP during ADT, possibly explain the mechanism of ADT-related high bone turnover. The increase of IGF-I is more prominent in men whose BMD is already low at the baseline, and urine DPD might be a marker that reflects BMD during ADT. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ghir.2012.04.003

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Background: The prediction of pathological outcomes prior to surgery remains a challenging problem for the appropriate surgical indication of prostate cancer. This study was performed to identify preoperative values predictive of pathological and oncological outcomes based on standardized extended prostate biopsies with core histological results diagrammed/mapped in patients receiving radical prostatectomy for prostate cancer clinically diagnosed as localized or locally advanced disease.Methods: In 124 patients with clinically localized or locally advanced prostate cancer (cT1c-cT3a) without prior treatment, pathological outcomes on the surgical specimen including seminal vesicle involvement (SVI), positive surgical margin (PSM), and perineural invasion (PNI) were studied in comparison with clinical parameters based on the results of 14-core prostate biopsies comprising sextant, laterally-directed sextant, and bilateral transition zone (TZ) sampling.Results: Concerning the association of pathological outcomes with oncological outcomes, patients with PSM and PNI on surgical specimens had poorer biochemical-progression-free survival than those without PSM (logrank p = 0.002) and PNI (p = 0.003); it was also poorer concerning SVI, although the difference was not significant (p = 0.120). Concerning the impact of clinical parameters on these pathological outcomes, positive TZ and multiple positive biopsy cores in the prostatic middle were independent values predictive of SVI with multivariate analyses (p = 0.020 and p = 0.025, respectively); both positive TZ and multiple positive prostatic middle biopsies were associated with larger tumor volume (p<0.001 in both). The percentage of positive biopsy cores (%positive cores) and biopsy Gleason score were independent values predictive of PSM (p=0.001) and PNI (p=0.001), respectively. Multiple positive cores in the prostatic base were associated with proximal/bladder-side PSM (p<0.001), and also linked to poorer biochemical-progression-free survival (p=0.004). Clinical T stage had no association with these pathological outcomes.Conclusions: %positive cores and Gleason score in extended biopsies were independent values predictive of PSM and PNI in prostate cancer clinically diagnosed as localized or locally advanced disease, respectively, which were associated with poorer oncological outcomes. When diagramming biopsy-core results, extended biopsy may provide additional information for predicting oncological and pathological outcomes including SVI in patients clinically diagnosed as having localized or locally advanced disease.

DOI： 10.1186/1746-1596-7-68

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DOI： 10.1016/j.juro.2012.02.846

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DOI： 10.1158/1538-7445.AM2012-960

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DOI： 10.1016/j.juro.2012.02.553

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Objective: In 2005, the University of California, San Francisco developed the Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score as a new risk stratification tool. The UCSF-CAPRA, which ranges from 0 to 10 points, consists of five clinical variables, prostate-specific antigen, Gleason score, T stage, percent of positive biopsies and age. The aim of this study was to validate the UCSF-CAPRA score for Japanese prostate cancer patients receiving radical prostatectomy using the contemporary Gleason grading.Methods: From 1999 to 2010, 211 men who underwent radical prostatectomy were used for validation. Biochemical progression-free survival was calculated using the Kaplan-Meier method and the UCSF-CAPRA and D'Amico risk categories were compared using the log-rank method. The concordance index (c-index) for the UCSF-CAPRA and D'Amico risk classification was calculated.Results: Using the UCSF-CAPRA score, 85 (40.3%), 106 (50.2%) and 20 (9.5%) subjects were stratified as 0-2 points (low risk), 3-5 points (intermediate risk) and 6-10 points (high risk). Using the D'Amico risk criteria, 66 (31.3%), 89 (42.2%) and 56 (26.5%) were stratified as low-, intermediate- and high-risk groups, respectively. The Kaplan-Meier analysis showed that the UCSF-CAPRA divided the patients significantly into each risk category. There was no significant difference between low and intermediate in the D'Amico risk classification. The c-index of the UCSF-CAPRA and D'Amico classification was 0.755 and 0.713, respectively.Conclusion: The UCSF-CAPRA is an acceptable risk category tool comparable to that of the D'Amico risk classification for Japanese prostate cancer patients receiving radical prostatectomy in the contemporary Gleason grading era.

DOI： 10.1093/jjco/hyr136

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DOI： 10.1016/j.juro.2011.02.2627

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DOI： 10.1016/j.juro.2011.02.378

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

The intracellular androgen metabolism and cell activity in prostate cancer cells with mutated (LNCaP-FGC) or wild-type (VCaP) androgen receptors in the presence of trilostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, were examined. Trilostane suppressed the intracellular production of androstenedione, testosterone, and dihydrotestosterone from dehydroepiandrosterone in LNCaP-FGC cells. In both LNCaP-FGC and VCaP cell types, the prostate-specific antigen (PSA) levels in media were increased by trilostane alone in a concentration-dependent manner. Both cells pretreated with trilostane showed a dose-dependent decrease in PSA production with bicalutamide (P<0.001). Trilostane should be used with particular concern when treating prostate cancer. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.canlet.2010.05.015

Web of Science

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Two men with inverted papilloma of the prostatic urethra are reported. Case 1 was a 67-year-old man with complaints of gross hematuria and urinary retention. Urethroscopy revealed a smooth-surface tumor with a stalk at the prostatic urethra. Case 2 was a 76-year-old man with complaints of gross hematuria and urinary retention. In these cases, the tumors were resected transurethrally and were consistent with inverted papilloma histopathologically.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

The effects of androgen deprivation therapy (ADT) include not only suppression of tumor growth, but also adverse effects on various bodily functions. The aim of this study was to determine the metabolic effects of ADT in patients with nonmetastatic prostate cancer. Forty-nine men with prostate cancer were treated with ADT before beginning radical therapy for 6 months. Body weight, peripheral red blood cell counts, hemoglobin, hematocrit, fasting blood sugar, serum total cholesterol, blood urea nitrogen, uric acid, compensated calcium, inorganic phosphorus, bone-specific alkaline phosphatase, urinary deoxypyridinoline, and radial bone density determined using dual energy x-ray absorptiometry were examined before and 6 months after ADT treatment. Body weight (P = 0.037) and the levels of fasting blood sugar (P = 0.014), serum total cholesterol (P = 0.017), blood urea nitrogen (P = 0.030), compensated calcium (P < 0.001), inorganic phosphorus (P < 0.001), bone-specific alkaline phosphatase (P < 0.001), and compensated urinary deoxypyridinoline (P < 0.001) increased significantly. Peripheral red blood cell counts (P < 0.001), hemoglobin level (P < 0.001), hematocrit (P < 0.001), uric acid (P < 0.001), and radial bone density (P = 0.023) decreased significantly. These effects of ADT on various bodily functions warrant systematic study in clinical trials. We should be aware of the far-reaching consequences of ADT and incorporate strategies for preventing and managing adverse effects into routine practice.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

The basal layer of the epithelium is usually thought to contain stem or progenitor cell populations. In order to analyze its biological characteristics, we attempted to produce novel monoclonal antibodies recognizing basal cells of the human esophageal epithelium. Hybridomas were generated from fusions between spleen cells of ddY mice immunized with esophageal epithelial cells (EECs) cultured at low calcium concentrations. A clone, NJ-E-H10, producing a monoclonal antibody (moAb) reacting with basal cells of human esophageal epithelia, was selected for its staining pattern on frozen sections of the epithelia. The immunoreactivities of NJ-E-H10 were detected in the cytoplasm of basal cells predominantly located in the interpapillary zones of the epithelia. In the primary culture of EECs, immunoreactive cells were present at the marginal area of the growing colonies, where EECs extend their cytoplasm and migrate out of the colonies. Immunoelectron microscopy demonstrated the immunoreactivities of the moAb NJ-E-H10 around the intermediate filaments of basal cells, but not on the filaments themselves. In the human skin, NJ-E-H10 positive cells were also observed in the basal layer of the epidermis as well as in keratinocytes in the outer layer of the outer root sheath in hair follicles and myoepitheial cells in the sweat glands. Since the distribution of NJ-E-H10 immunoreactivities differs from that reported by hitherto-known antibodies, the MoAb NJ-E-H10 is considered a new marker for clarifing the biological properties of the basal cell compartment in stratified epithelia.

PubMed

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本癌治療学会  

J-GLOBAL

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

J-GLOBAL

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Language：English   Publisher：(一社)日本癌治療学会  

J-GLOBAL

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Language：English   Publisher：(一社)日本癌治療学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

J-GLOBAL

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：日本小児泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(株)医学出版  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J00990&link_issn=&doc_id=20140317220017&doc_link_id=%2Fdg3nigta%2F2013%2Fs12711%2F010%2F0638-0638%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2013%2Fs12711%2F010%2F0638-0638%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J00990&link_issn=&doc_id=20130222020024&doc_link_id=%2Fdg3nigta%2F2012%2Fs12609%2F015%2F0508-0508%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2012%2Fs12609%2F015%2F0508-0508%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本排尿機能学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)新潟県臨床検査技師会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J01175&link_issn=&doc_id=20110328480463&doc_link_id=10.5980%2Fjpnjurol.102.359_3&url=https%3A%2F%2Fdoi.org%2F10.5980%2Fjpnjurol.102.359_3&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J01175&link_issn=&doc_id=20110328481228&doc_link_id=10.5980%2Fjpnjurol.102.493_6&url=https%3A%2F%2Fdoi.org%2F10.5980%2Fjpnjurol.102.493_6&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J01175&link_issn=&doc_id=20110328480504&doc_link_id=10.5980%2Fjpnjurol.102.366_2&url=https%3A%2F%2Fdoi.org%2F10.5980%2Fjpnjurol.102.366_2&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J01175&link_issn=&doc_id=20110328480974&doc_link_id=10.5980%2Fjpnjurol.102.451_2&url=https%3A%2F%2Fdoi.org%2F10.5980%2Fjpnjurol.102.451_2&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J01175&link_issn=&doc_id=20100323480489&doc_link_id=10.5980%2Fjpnjurol.101.286_2&url=https%3A%2F%2Fdoi.org%2F10.5980%2Fjpnjurol.101.286_2&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：医学図書出版(株)  

当院にて1996年4月から2006年9月までに前立腺癌脊椎転移に対し手術・放射線療法を行った18例について検討を行った。手術単独群が2例、手術+放射線治療群が4例、放射線単独群が12例であった。7例で麻痺を呈し、3例に麻痺の改善を認めた。疼痛を主訴とした7例では全例で改善が認められた。脊椎転移に対する放射線・手術治療はQOLの改善につながると考えられた。(著者抄録)

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Language：Japanese   Publisher：泌尿器科紀要刊行会  

症例1(67歳男性)。肉眼的血尿を主訴とした。1999年から尿閉で救急外来を3回受診した。症例2(75歳男性)。肉眼的血尿、尿閉を主訴とした。いずれも血液検査、生化学検査に異常はなく、PSA は前者が1.6ng/ml、後者が3.0ng/mlであった。症例1は、尿道鏡で前立腺部尿道に約1.5cmの有茎性で表面平滑な腫瘍が認められ、症例2は術中に前立腺部尿道に有茎性乳頭状腫瘍を認めた。両症例とも尿道腫瘍切除、TURPが施行され、病理組織学的に上皮の逆転構成、正常な移行上皮による被覆、上皮に異型性を認めないこと、核分裂がほとんど認めないこと、微小嚢胞の形成を認めたことから、前立腺尿道部に発生した内反性乳頭腫(IP)と診断された。尚、検索した限り、我が国の前立腺部尿道発生のIP例は本症例を含め34例の報告があるにすぎなかった。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J01269&link_issn=&doc_id=20080227380013&doc_link_id=120001177994&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F120001177994&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J01175&link_issn=&doc_id=20080305220496&doc_link_id=10.5980%2Fjpnjurol.99.312_3&url=https%3A%2F%2Fdoi.org%2F10.5980%2Fjpnjurol.99.312_3&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本農村医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J01169&link_issn=&doc_id=20070926320248&doc_link_id=%2Fcv2jjrme%2F2007%2F005603%2F253%2F0434-0434%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv2jjrme%2F2007%2F005603%2F253%2F0434-0434%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本農村医学会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2006&ichushi_jid=J00990&link_issn=&doc_id=20060828250060&doc_link_id=%2Fdg3nigta%2F2006%2F012006%2F061%2F0363-0363%26dl%3D2&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2006%2F012006%2F061%2F0363-0363%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本研究皮膚科学会  

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Language：Japanese   Publisher：(一社)日本解剖学会  

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