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Background: To identify the real high-risk group among Japanese de novo metastatic prostate cancer patients who fit CHAARTED or LATITUDE criteria. Methods: We retrospectively studied patients who fitted CHAARTED (292 patients) and LATITUDE (294 patients) criteria from Japanese multi-institutions. All patients received androgen deprivation therapy with bicalutamide as an initial treatment. Factors related to overall survival (OS) and progression-free survival were statistically analyzed. Results: The median OS was 55.5 months and 60.0 months in patients who met the CHAARTED and the LATITUDE criteria, respectively. In patients who met CHAARTED criteria, lactate dehydrogenase (LDH) (hazard ratio (HR) 2.63, P

Introduction The advent of pembrolizumab has contributed to improved treatment outcomes for metastatic urothelial carcinoma, but the outcomes of treatments after second-line treatment have not been established. Case presentation A 72-year-old man was referred to our hospital with gross hematuria and diagnosed with suspicion of bladder cancer cT1N0M0. Transurethral resection of the bladder tumor was performed, but local recurrence and multiple lung metastases appeared 5 months after surgery. Although gemcitabine-cisplatin was performed as first-line chemotherapy, the local lesion increased, and pembrolizumab was used as a second-line treatment. Pembrolizumab was also ineffective; however, re-challenge with gemcitabine-cisplatin as third-line treatment produced a good therapeutic effect. Conclusion We report a successful case in which gemcitabine-cisplatin re-challenge after pembrolizumab therapy was effective in metastatic bladder cancer. Re-administration of chemotherapy after immune checkpoint inhibitors may be a broadly effective treatment option.

Objectives To investigate whether the result of the 1-mg dexamethasone suppression test can predict the improvement of comorbidities after adrenalectomy in patients with subclinical Cushing syndrome. Methods This retrospective study included 117 subclinical Cushing syndrome patients who underwent adrenalectomy. The numbers of prescribed drugs for metabolic comorbidities and the clinical variables at diagnosis were compared with those at the follow up. Patients were classified into subgroups according to the result of the 1-mg dexamethasone suppression test. Results Significant improvements in blood pressure, serum cholesterol and body mass index were observed. Furthermore, a significant improvement in glycated hemoglobin was observed in patients with diabetes mellitus. These improvements led to a discontinuation or reduction of prescribed drugs after surgery. In addition, the greatest reduction of prescribed drugs was observed in patients whose serum cortisol levels were between 1.8 and 3.0 µg/dL after the 1-mg dexamethasone suppression test. Conclusions The result of the 1-mg dexamethasone suppression test can be a useful factor predicting the improvement of comorbidities after adrenalectomy. Current data might give us a new insight into the decision-making for the treatment of subclinical Cushing syndrome.

BACKGROUND Oligometastatic cancer has been suggested as an intermediate state between localized disease and wide-ranging metastases. The clinical significance of local treatment in oligometastatic prostate cancer (PCa) has been a recent topic of interest. However, standard definitions of oligometastasis are lacking. Here we studied risk factors among Japanese de novo oligometastatic patients with PCa. METHODS We retrospectively assessed clinical data from 264 patients, including locally advanced (T3 or T4N0M0) cancer, lymph-node-positive cancer (Tany N1M0), and cancer with ≤10 bone metastases. All patients received androgen deprivation therapy only. The number of bone metastases and clinical factors were evaluated in association with overall survival (OS) and progression-free survival (PFS). The Mann-Whitney U test, Cox proportional hazard models, and Kaplan-Meier methods were used as statistical analyses. RESULTS Median age, PSA at baseline and OS were 74 years, 55.2 ng/mL, and 129.0 months, respectively. The cutoff for the number of bone metastases having the greatest impact on OS was ≥3 (hazard ratio [HR]: 2.67; P = .0001). In multivariate analysis, non-regional lymph node (LN) metastases (HR: 2.15; P = .0222), ISUP grade group (GG) 5 (HR: 2.04; P = .0186) and ≥3 bone metastases (HR: 1.82; P = .0390) were independent predictors of OS. In risk classification based on these factors, OS and PFS were significantly classifiable into poor (2-3 factors), intermediate (1 factor), and good (no factors) risk groups (P

BACKGROUND The role of testosterone as a prognostic factor for castration-resistant prostate cancer treated with docetaxel in Japan was investigated. METHODS A total of 164 patients with castration-resistant prostate cancer who received docetaxel treatment at Chiba University Hospital and an affiliated hospital were retrospectively analyzed. Testosterone and other clinical factors at the start of docetaxel treatment were evaluated with respect to overall survival and progression-free survival. RESULTS Of the 164 patients, 69 had high-volume tumors. The median prostatic-specific antigen was 27.0 ng/mL. The median testosterone was 13.0 ng/dL. The rates of bone and visceral metastases were 80.1% and 8.8%, respectively. For progression-free survival, testosterone ≥13 ng/dL was an independent prognostic factor only on univariate analysis (hazard ratio, 1.81; P = .0108). For overall survival, testosterone ≥ 1.3 ng/dL (hazard ratio, 3.37; P

Objective To examine the impact of post-void residual urine volume on the risk of postoperative recurrence of intravesical carcinoma in patients with upper urinary tract urothelial carcinoma undergoing nephroureterectomy. Methods We retrospectively reviewed the data of 81 patients who were admitted to Chiba University Graduate School of Medicine Hospital and underwent nephroureterectomy for upper urinary tract urothelial carcinoma without bladder carcinoma. We assessed the predictive factors for intravesical recurrence after nephroureterectomy in all patients. Next, we compared patients with and without a residual urine volume using propensity score-matching analysis. The presence of a residual urine volume was defined as ≥30 mL. Results The median follow-up period among all patients was 48 months. The presence of pyuria and a residual urine volume were associated with bladder recurrence in the multivariate analysis. A total of 19 patients each were selected after matching, and we confirmed a significant difference between the presence and absence of a residual urine volume (P = 0.0291). The 2-year postoperative recurrence-free rate of patients with and without a residual urine volume was 32% and 82%, respectively. Conclusions This is the first study to evaluate the post-void residual urine volume and intravesical recurrence rate after nephroureterectomy for upper urinary tract urothelial carcinoma. The presence of residual urine might be a risk factor for postoperative recurrence of intravesical carcinoma.

OBJECTIVES To analyze incidents related to Foley catheter insertion and maintenance, and to compare the rate of incidents before and after a medical staff education program. METHODS Data regarding Foley catheter insertion incidents and maintenance were collected at Toyama University Hospital, Toyama, Japan. The degree of harm for each incident was assessed. In the middle of the study period, a medical staff education program by urologists was implemented to help understand basic urological anatomy, urethral catheter insertion techniques and catheter safety. The incidents before and after the intervention were then compared. RESULTS During the study period, Foley catheter insertion was carried out in 12 476 patients. Related incidents were reported in 66 (0.53%), including 22 (0.18%) occurring during catheter insertion and 44 (0.35%) occurring during catheter maintenance. A total of 13 (0.10%) cases of urethral injury were reported. The degree of harm associated with catheter insertion incidents was moderate in 13. Nine of these incidents occurred before the education program (9/6799, 0.13%), and four were reported after the end of the program (4/5677, 0.07%, P = 0.4303). Transient suprapubic cystostomy was required in two due to urethral injury reported before the program. Among 44 incidents occurring during catheter maintenance, 37 catheters were removed or cut by the patient. Such incidents occurred regardless of the education program. CONCLUSIONS The rate of incidents related to Foley catheter use at our institution is low. A specific medical staff education program might prevent iatrogenic catheter-related urethral injury requiring cystostomy.

Objectives To evaluate the relationship between residual urine volume, pyuria and bladder carcinoma recurrence. Methods The clinical data of 305 patients who had post-void residual urine volume measured and preoperative pyuria were retrospectively collected. The patients were classified into three risk groups based on the presence of residual urine and pyuria: good (negative residual urine and pyuria), intermediate (positive residual urine or pyuria) and poor (positive residual urine and pyuria). Predictive factors for intravesical recurrence-free survival were statistically analyzed using Cox proportional hazard models and Kaplan-Meier methods. The propensity score matching method was used to adjust the patients' backgrounds. Results The median follow-up period for all patients was 44 months. The presence of residual urine (P = 0.0164) and pyuria (P = 0.0233) were two independent prognostic factors for recurrence. After patients were classified into risk groups, the poor-risk group showed significantly shorter recurrence-free survival compared with that of the good- (P = 0.0002) and intermediate-risk groups (P = 0.0090). Even after matching, the presence of residual urine was related to short recurrence-free survival in male patients (P = 0.0012). When stratified by European Organization for Research and Treatment of Cancer risk groups, the presence of pyuria was related to short recurrence-free survival, especially for intermediate-risk patients without bacillus Calmette-Guerin treatment. Conclusions Post-void residual urine and preoperative pyuria are two risks for recurrence-free survival in non-muscle-invasive bladder cancer.

A husband and his wife, both 34 years old, consulted our clinic because of primary infertility. Sperm analysis revealed that the sperm concentration, motility, and progressive motility were (42.8±22.8)×10(6)/mL, 23.3%±12.2%, and 12.9%±6.1%, respectively. Based on Krugar strict morphology criteria, 100% of the sperm were teratozoospermic, with 7.9% DNA fragmentation index. Observation of the sperm under a transmission electron microscope revealed that most parts of the fibrous sheath (FS) surrounding the tails of the sperm were missing from midway through the principal piece to the end piece, although the sperm’s heads, necks and midpieces were morphologically normal. To collect oocytes, the gonadotropin-releasing hormone antagonist protocol was carried out, and 7 oocytes were retrieved. Intracytoplasmic sperm injection (ICSI) was performed for all the teratozoospermic sperm. Of the 7 oocytes, 3 were fertilized, and one 8-cell embryo and 2 expanded blastocysts were vitrified. Although repeated transfers of expanded blastocysts resulted in no implantation, one 8-cell embryo transfer in a hormone replacement therapy cycle led to pregnancy. The pregnancy using an 8-cell vitrified embryo resulted in the delivery of a healthy female baby at 38 weeks of gestation. No congenital malformations were found until 28 days after birth. Our results demonstrated that healthy birth could be achieved following the transfer of an embryo derived from ICSI using teratozoospermic sperm exhibiting the dysplasia of the fibrous sheath (DFS). Furthermore, while the previous reports on DFS have not investigated male infertility, we evaluated sperms from various aspects such as Kruger sperm function test, chromatin dispersion test, electron microscopy findings, time-lapse images of the obtained embryos, and concluded that ICSI could be desirable as a treatment policy for DFS.

BACKGROUND The inflammatory process has been reported to be involved in the formation and progression of various types of cancer. Recently, a peripheral inflammatory index, combining the derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and the lactate dehydrogenase (LDH) level, was proposed as a useful prognostic marker in advanced nonsmall cell lung cancer. The prognostic value of inflammatory markers in prostate cancer has not been established. We aimed to validate the prognostic significance of this peripheral inflammatory index in metastatic castration-resistant prostate cancer (mCRPC). METHODS Clinical data of 196 mCRPC patients were retrospectively collected from multiple institutions. Clinical factors and inflammatory markers at the development of CRPC, including white blood cell count, absolute neutrophil count, dNLR, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, C-reactive protein (CRP), and LDH levels, were evaluated. The patients were classified into three groups based on the inflammatory index: Good (low dNLR and LDH), Intermediate (high dNLR or LDH), and Poor (high dNLR and LDH). Overall survival (OS) and cancer-specific survival after CRPC were analyzed using Cox proportional hazard models and Kaplan-Meier methods. RESULTS The median age and baseline prostate-specific antigen level were 75 years and 397.15 ng/mL, respectively. On multivariate analysis, dNLR (≥1.51; hazard ratio [HR] = 1.624; P = .0173), LDH (≥upper limit of normal; HR = 2.065; P = .0004), alkaline phosphatase (≥310 U/L; HR = 2.546; P

Background Recent landmark randomized trials (CHAARTED and LATITUDE studies) have highlighted potent upfront therapy for "high-volume" and "high-risk" metastatic castration-naive prostate cancer (mCNPC). However, treatment response shows racial differences. We aimed to propose a novel definition for "high-volume" prostate cancer in Asians. Methods We retrospectively pursued 426 patients with de novo mCNPC from multiple institutions between 1999 and 2017. All patients received androgen deprivation therapy alone as initial treatment. We evaluated the number of bone metastases at diagnosis to clarify the clinical significance for progression-free survival and overall survival (OS). Statistical analyses were conducted using the Mann-Whitney U test, Cox proportional hazard models, and Kaplan-Meier methods. Results Median age and prostate-specific antigen level were 73 years and 266.2 ng/ml, respectively. Median OS was 55.5 months in patients who met the CHAARTED high criteria (vs 33.1 months in the trial). We evaluated 5 thresholds in the number of bone metastases (≥4, ≥6, ≥11, ≥16, and ≥21) to investigate the prognostic values. Patients with ≥11 bone metastases showed the highest HR for OS (2.766). Patients with 11 to 20 bone metastases had a significantly shorter OS than those with ≤10 metastases (P = .0001). We, therefore, proposed modified CHAARTED and LATITUDE high criteria (extending bone metastases ≥11). In multivariate analysis, the modified criteria were the only independent prognostic factors for OS (P = .0272 and P = .042, respectively). Conversely, no significant differences in OS were seen between patients with 1 to 3 bone metastases and 4 to 10 (P = .7513). Conclusion Our exploratory study suggested ≥11 bone metastases as a suitable definition for "high-volume" prostate cancer in Asians. A larger, prospective study is warranted to verify our findings.

OBJECTIVES To identify pre-treatment factors affecting the duration of post-surgical steroid replacement in patients undergoing adrenalectomy for subclinical Cushing syndrome. METHODS The present retrospective analysis included 64 patients who underwent unilateral laparoscopic adrenalectomy for subclinical Cushing syndrome. Adrenal tumor and contralateral adrenal sizes together with various clinical factors were studied in association with the duration of post-surgical steroid replacement. Adrenal tumor and contralateral adrenal size were measured at the level of the maximum transverse plane of the adrenal glands using computed tomography scan or magnetic resonance imaging. Cox's proportional hazards model was used for the statistical analysis. RESULTS All 64 patients were treated with post-surgical steroid replacement after adrenalectomy. The median duration of the steroid treatment was 6 months. When assessing the duration of post-surgical steroid replacement, contralateral adrenal volume 2.65 μg/dL were significant predictors of prolonged post-surgical steroid treatment on univariate analysis. On multivariate analysis, contralateral adrenal width

OBJECTIVES To determine the predictors of testosterone recovery after termination of androgen deprivation therapy in high/intermediate-risk prostate cancer patients receiving external beam radiation therapy with neoadjuvant and adjuvant androgen deprivation therapy. METHODS A total of 82 patients who underwent external beam radiation therapy with androgen deprivation therapy for prostate cancer were retrospectively analyzed. Serum testosterone levels after androgen deprivation therapy terminations were studied. Cox proportional hazard models and the Kaplan-Meier method were used for statistical analysis. RESULTS Median age, baseline testosterone, nadir testosterone and duration of androgen deprivation therapy were 73 years, 456 ng/dL, 16 ng/dL and 26 months, respectively. Androgen deprivation therapy duration of 33 months (hazard ratio 0.13; P = 0.0018), nadir testosterone of 20 ng/dL (hazard ratio 0.35; P = 0.0112) and testosterone >50 ng/dL at 6 months after androgen deprivation therapy termination (hazard ratio 0.21; P = 0.0075) were significantly associated with testosterone recovery to normal levels (200 ng/dL) on multivariate analysis. Androgen deprivation therapy duration of 33 months (hazard ratio 0.31; P = 0.0023) and nadir testosterone of 20 ng/dL (hazard ratio 0.38; P = 0.0012) were significantly associated with testosterone recovery to the supracastrate level (50 ng/dL) on multivariate analysis. After dividing patients into three risk groups, the rate of testosterone recovery to the normal level after 2 years of androgen deprivation therapy termination was 100% in the low-risk group versus 20.8% in the high-risk group (P < 0.0001); the rate of testosterone recovery to the supracastrate level was 100% in the low-risk group versus 51.5% in the high-risk group (P < 0.0001). CONCLUSIONS Duration of androgen deprivation therapy and achievement of nadir testosterone 20 ng/dL both predict testosterone recovery to the supracastrate level in prostate cancer patients undergoing external beam radiation therapy with androgen deprivation therapy.

Background To investigate prognostic difference between Gleason Score (GS) 8 and 9–10, as the 2014 International Society of Urological Pathology Gleason Grading Systems proposed, in patients with prostate cancer (PCa) with bone metastasis. Materials and methods We retrospectively reviewed data on 106 patients with GS 8–10 between 2006 and 2016. All patients received androgen deprivation therapy immediately. We validated biochemical recurrence, PCa-specific survival, and overall survival, and analyzed the predictive value for overall survival. Results Patients with GS 9–10 had significantly lower PCa-specific survival (50.5% vs. 83.4%, P = 0.01) and overall survival (38.8% vs. 66.3%, P = 0.04) at 5 years than those with GS 8, while biochemical recurrence rate was not significantly different (P = 0.26). Furthermore, these significant differences between GS 8 and 9–10 were also observed among high-risk groups proposed in Japan Cancer of the Prostate Risk Assessment Stratification (prostate cancer-specific survival: P = 0.03, overall survival: P = 0.04, respectively). Pathological GS 9–10 was an independent prognostic factor for overall survival (hazard ratio = 1.97, P = 0.04) in multivariable cox proportional hazard regression analysis. Among patients with GS 9–10, albumin level was an only prognostic factor for overall survival (hazard ratio = 0.33, P

Reductions in testosterone concentration play a significant role in the treatment of prostate cancer. We studied the role of testosterone as a prognostic marker for advanced prostate cancer (stage C or higher) treated with primary androgen-deprivation therapy (ADT).A total of 348 patients were treated using ADT as first-line therapy for prostate cancer at Chiba University Hospital between 1999 and 2016. Of these, 222 patients with advanced prostate cancer (stage C or higher) were enrolled onto this study. The prognostic values of serum testosterone level and other clinical factors were evaluated in association with prostate-specific antigen (PSA), progression-free survival during first-line therapy, and overall survival.Median age was 73 years. PSA at baseline was 86 ng/mL. Gleason scores of ≤ 6, 7, 8, and ≥ 9 were seen in 2.3%, 19.4%, 21.2%, and 41.9%, respectively. Mean follow-up was 60.5 months. Median testosterone at baseline was 482 ng/dL and nadir testosterone was 13 ng/dL. No variable associated with testosterone predicted progression-free survival. With regard to overall survival, multivariate analysis identified nadir testosterone ≤ 20 ng/dL (hazard ratio = 0.44, P = .026) and testosterone reduction ≥ 480 ng/dL (hazard ratio = 0.35, P = .030) as independent prognostic factors. With regard to progression-free survival, multivariate analysis identified nadir PSA ≤ 0.1 ng/mL (hazard ratio = 3.07, P .001), presence of lymph node metastasis (hazard ratio = 1.67, P = .017), and time to nadir PSA (hazard ratio = 0.30, P .001) as independent prognostic factors.Our data suggested both nadir testosterone (20 ng/dL; P = .026) and testosterone reduction (≥ 480 ng/dL; P = .030) to be key prognostic factors for primary ADT in advanced prostate cancer in Japanese men.

(Purpose) Targeted therapy has been standard therapeutic approach for advanced renal cell carcinoma (RCC). General fatigue is frequently observed in patients who receive targeted therapies for advanced RCC. General fatigue makes it difficult to continue a standard schedule of treatment in many cases. In this preliminary report, we explored the effect of Koujin powder (red ginseng powder) with Ninjin-youeito for general fatigue induced by targeted therapies for advanced RCC. (Material and method) The patients who complained of general fatigue during the treatment of Tyrosine Kinase Inhibitors (TKIs) as targeted therapies for advanced RCC were included in this retrospective analysis. Thirty patients with advanced RCC were enrolled from January 2016 to December 2016 at Chiba University Hospital. Twelve patients were given 3 g of Koujin powder with 9 g of Ninjin-youeito orally for two to four weeks (ginseng combination group). Eighteen patients who were not orally administered were compared as a control group (ginseng non-combination group). General fatigue was assessed with the Cancer Fatigue Scale (CFS), which divides quality of fatigue into three subgroups by using a "physical subscale", an "affective subscale", and a "cognitive subscale". We compared CFS scores at baseline and 2-8 weeks after administration. (Results) There was no statistical difference in the clinical variables between the two groups. The total CFS score was significantly decreased after treatment in the ginseng combination group (average score, 21.8 points at baseline vs 18.5 points after treatment; p=0.041). On subgroup analyses, the physical subscale score was significantly reduced after treatment in the ginseng combination group (average score, 9.7 points at baseline vs 7 points after treatment; p=0.0042). In the ginseng non-combination group, the total CFS score was significantly increased during the course (average score, 16.2 points at baseline vs 20.6 points during the course; p=0.047). On subgroup analyses, the physical subscale score was significantly increased during the course (average score, 4.4 points at baseline vs 7.3 points during the course; p=0.0042). (Conclusions) Koujin powder with Ninjin-youeito can be a therapeutic approach for general fatigue induced by targeted therapies. The precise management for general fatigue can keep patients on therapy, consequently provides a survival benefit.

INTRODUCTION AND OBJECTIVES:Cancer cells take up massive amounts of amino acids for survival. L-type amino acid transporter 1(LAT1) transports essential amino acids, including leucine, which trigge...

Saturation prostate biopsy protocols have been developed to improve the prostate cancer (PCa) detection rate, particularly in the setting of repeat biopsies. The present study attempted to clarify the association between PCa detection and various risk factors in repeat saturation biopsies. A retrospective analysis was conducted on 78 Japanese patients for whom findings had caused suspicion of PCa despite previous negative prostate biopsies, and who consecutively underwent a 24-core transperineal repeat biopsy at Toyama University Hospital (Toyama, Japan). PCa was confirmed histologically in 16 of the 78 patients (20.5%). A univariate analysis revealed that the prostate-specific antigen (PSA) level at repeat biopsy was higher (P

454 Background: The bladder carcinoma recurrence rate after nephroureterectomy is known to be high. Here we studied the clinical benefit of Intravesical irrigation during laparoscopic radical nephroureterectomy in upper urinary tract cancer (UUTUC) patients. Methods: This study enrolled 197 UUTUC patients who receive laparoscopic radical nephroureterectomy at Chiba University Hospital and Yokohama Rosai Hospital between 2001 and 2019. Association between the various clinical factors and postoperative recurrence rates within two years were statistically analyzed. Intravesical irrigation was carried out only during surgery and by using distilled water or saline. Results: Bladder recurrence was confirmed for 79 of the 197 patients. Irrigation was carried out in 75 cases (distilled water, 49 cases; saline, 26 cases). Tumor grade (G1-2 vs G3; p=0.0029) and irrigation (with vs. without; p

Segmental ureterectomy (SU) represents a promising alternative for the treatment of upper tract urothelial carcinomas (UTUCs) as it is a less invasive procedure and guarantees the preservation of renal units. The present study evaluated oncological outcomes and renal functions following SU when compared with radical nephroureterectomy (RNU). A total of 26 patients with UTUCs who underwent SU (n=12) or RNU (n=14) were retrospectively evaluated. SU was performed in patients with clinically unifocal disease. In the SU group, the following surgeries were carried out: 7 direct ureterocystoneostomy, 1 reimplantation on psoas hitch bladder, 1 reimplantation on Boari flap bladder, 2 ureteral end-to-end anastomosis and 1 subtotal ureterectomy. In the SU group, tumors were low grade urothelial carcinoma (UC) in 6 patients, high grade UC in 5 patients and high grade UC with squamous cell differentiation in 1 patient, as well as ≤pT1 in 5, ≥pT2 in 6 and pTis in 1 patient; ‘p’ refers to the pathological state. The 5-year overall, cancer-specific, recurrence free and metastasis free survival in the SU group were 77.8, 87.5, 34.4 and 80.8%, respectively, which all exhibited no significant differences when compared with those of the RNU group. With regard to renal function, postoperative estimated glomerular filtration rates were preserved in the SU group. The present study demonstrated that SU does not result in poorer cancer control when compared with RNU. Thus, SU is an acceptable alternative to RNU in selected cases, as it is less invasive and preserves renal functions.

A 69-year-old man presented initially with back pain and incomplete bilateral lower limb paralysis. The level of prostate-specific antigen (PSA) in the patient was elevated to 167.0 ng/ml, and multiple bone metastases were detected. Thoracic laminectomy was performed in an emergency due to spinal decompression. Subsequently, the patient was diagnosed with prostate cancer from an examination of resected bone specimens. Combined androgen blockade with degarelix and bicalutamide was initiated in October 2013. Consequently, the serum PSA level decreased to

We retrospectively assessed the clinical significance of the Prostate Imaging Reporting and Data System (PI-RADS), version 2, criteria based on biparametric magnetic resonance imaging (bp-MRI), together with the International Society of Urological Pathology (ISUP) grade, for predicting biochemical recurrence (BCR) after radical prostatectomy.The data from 126 patients who had undergone radical prostatectomy were retrospectively analyzed. The prognostic significance of the PI-RADS v2 score based on bp-MRI was assessed with other clinical factors, including the ISUP grade. We defined a positive PI-RADS and ISUP score as ≥ 4 and ≥ 3, respectively. Statistical analysis was performed using Cox proportional hazard models, logistic regression analysis, and the Kaplan-Meier method.The median age and median prostate-specific antigen level were 66 years and 7.96 ng/mL, respectively. The number of positive PI-RADS scores was 106 (84.1%) and the number of positive ISUP grade scores was 71 (56.3%). PI-RADS ≥ 4 (P = .0031) and ISUP ≥ 3 (P = .070) were the 2 independent prognostic factors predictive of BCR. A positive PI-RADS score was related to tumor volume (P = .014), and a positive ISUP score was related to prostate-specific antigen level (P = .043), extraprostatic extension (P = .029), and Gleason upgrading (P .0001). After stratifying patients into risk groups according to PI-RADS and ISUP positivity, the poor-risk group (PI-RADS and ISUP grade positive) showed significantly worse BCR-free survival compared with that of the favorable- and intermediate-risk groups (P .0001), with a median survival difference of 21 months.Biparametric PI-RADS v2 and ISUP grade criteria predicted for BCR after radical prostatectomy. PI-RADS v2 combined with the ISUP grade might be helpful in choosing the treatment modality of patients with localized prostate cancer.

A 72-year-old man initially presented with lumbar and right chest pain, but was later found out to also have an elevated prostate-specific antigen (PSA) level at 2,000.0 ng/ml. Further evaluation disclosed metastatic prostate cancer involving the bones and lymph nodes. The patient was initially treated with combined androgen blockade (CAB) with leuprolide acetate and bicalutamide. After 6 months of CAB, the patient's PSA level began to rise from the nadir (85.1 ng/ml) to 113.3 ng/ml. Bicalutamide was withdrawn in anticipation of anti-androgen withdrawal syndrome and the PSA level declined temporally. However, it increased up to 517.0 ng/ml thereafter. Consequently, a year after CAB, abiraterone acetate (AA) was initiated at a standard dose of 1,000 mg daily in combination with 10 mg of prednisolone. PSA rapidly decreased to the nadir of 20.1 ng/ml thereafter. The PSA level remained stable until 2 years after AA administration. However, he decided to reduce the dose of AA to half of the standard dose (500 mg daily). Contrary to our expectations, the serum PSA level promptly decreased to a nadir of 8.1 ng/ml. Thereafter, the PSA level remained stable until 3 years and 9 months after AA administration. Subsequently, the patient stopped taking AA and prednisolone. However, to our surprise, the patient's serum PSA level decreased further to

We analyzed the inter-examination differences in sperm nuclear vacuoles among male patients with infertility. We enrolled 56 male patients with infertility who underwent multiple semen analyses and high-magnification observation of the sperm head. A total of 162 ejaculates were evaluated. The average patient age was 34.5 years. Following the conventional semen analysis, the nuclear vacuoles in motile spermatozoa were evaluated at 3700-6150 × magnification on an inverted microscope equipped with differential interference contrast optics. A large sperm nuclear vacuole (LNV) was defined as one or more vacuoles with a maximum diameter exhibiting50% width of the sperm head. We compared the differences in the proportion of spermatozoa with LNVs between two consecutive semen samples before treatment. Treatment-related differences in the number of LNVs were also analyzed. Student's t-test was used to perform the statistical analyses. No differences were observed in any semen parameters between the first and second ejaculates. On high-magnification microscopy, the proportion of spermatozoa with LNVs was 23.5% and 29.4% (p = 0.0220) in the first and second ejaculates, respectively in 33 patients. Among the 18 patients who underwent varicocele repair using a microsurgical subinguinal approach, the proportion of spermatozoa with LNVs at baseline, three, and six months after surgery was 27.7%, 12.0% (p = 0.0132 versus baseline), and 10.3% (p = 0.0226 versus baseline), respectively. After three months of medical treatment for male infertility in 28 patients, the proportion of spermatozoa with LNVs slightly decreased from 33.3% to 28.6% (p = 0.1276); however, it was not statistically significant. In conclusion, when multiple ejaculates were obtained, in the subset of male patients with infertility, the proportion of spermatozoa with LNVs could be different. The number of LNVs decreased following varicocele repair.

Background: We investigated how urinary, sexual, and testicular functions and generic health-related quality of life (HR-QOL) affect each other in aged men. Methods: Ninety patients who were negative for cancer on prostate biopsies were enrolled in this study. The mean patient age was 66±7 years (mean±s.d.). The mean prostate volume was 44.3±21.9 mL, and the mean serum total testosterone (TT) level was 3.63±1.18 ng/mL. Before conducting the prostate biopsies, the patients were asked to complete questionnaires, including the International Prostate Symptom Score (I-PSS), UCLA Prostate Cancer Index (UCLA-PCI), and the Rand Medical Outcome Study 36-Item Short Form (SF-36), to evaluate urinary symptoms, sexual function, and generic HR-QOL. The relationships between these parameters were analyzed. Other objective variables, such as the prostate volume, maximal urinary flow (Qmax), postvoid residual urine volume, and age, were also evaluated. Results: The TT level was found to be related to the I-PSS Q6...

This study compared the sperm nuclear vacuoles and semen quality in the evaluation of male infertility. One hundred and forty-two semen samples were obtained from patients who visited the Male Infertility Clinic at Toyama University Hospital. Semen samples were evaluated by conventional semen analyses and the Sperm Motility Analysis System (SMAS). In addition, spermatozoa were analyzed at 3,700-6,150x magnification on an inverted microscope equipped with DIC/Nomarski differential interference contrast optics. A large nuclear vacuole (LNV) was defined as one or more vacuoles with the maximum diameter showing 50% width of the sperm head. The percentage of spermatozoa with LNV (% LNV) was calculated for each sample. Correlations between the % LNV and parameters in SMAS and conventional semen analyses were analyzed. Processed motile spermatozoa from each sample were evaluated. The mean age of patients was 35 years old. Semen volume was 2.9 ± 1.6mL (0.1-11.0; mean ± standard deviation, minimum-maximum), sperm count was 39.3 ± 54.9 (x10(6)/mL, 0.01-262.0), sperm motility was 25.1 ± 17.8% (0-76.0), and normal sperm morphology was 10.3 ± 10.1% (0-49.0). After motile spermatozoa selection, we could evaluate % LNV in 125 ejaculates (88.0%) and at least one spermatozoon with LNV was observed in 118 ejaculates (94.4%). The percentage of spermatozoa with LNV was 28.0 ± 22.4% (0-100) and % LNV increased significantly when semen quality decreased. The correlation between the % LNV and the semen parameters was weak to moderate; correlation coefficients were -0.3577 in sperm count (p 0.0001), -0.2368 in sperm motility (p = 0.0084), -0.2769 in motile sperm count (p = 0.019), -0.2419 in total motile sperm count (p = 0.0070), and -0.1676 in normal sperm morphology (p = 0.0639). The % LNV did not show a significant correlation with the SMAS parameters except for weak correlation to beat/cross frequency (r = -0.2414, p = 0.0071). The percentage of spermatozoa with LNV did not have a strong correlation with parameters in conventional semen analysis and SMAS in the patients with male infertility; however, a certain level of negative influence of LNV to sperm quality cannot be excluded.

Background and Purpose: When percutaneous image-guided biopsies are not possible for retroperitoneal tumor of unknown origin (RTUO), surgical tissue diagnosis becomes necessary. Laparotomy and laparoscopic surgery are current standard treatments; however, the laparoendoscopic single-site (LESS) approach offers many potential benefits. We describe our technique for LESS biopsy of RTUO. Patients and Methods: Five patients underwent LESS biopsy for diagnosis of RTUO. A multichannel port was inserted into the peritoneal or retroperitoneal space through a 3-cm skin incision, which adequately exposed the retroperitoneal tumor. The specimen was grasped and isolated circumferentially from the surrounding tissue. Results: LESS surgery was performed successfully without any complications such as open conversion. Mean operative time was 183 min and estimated blood loss was negligible. The diagnoses were IgG4-related retroperitoneal fibrosis (n = 4) and lymphoma (n = 1). Sufficient specimens were safely obtained not only for pathological diagnosis but also for further examinations such as immunophenotyping or DNA analysis. Convalescence was satisfactory. All patients were treated appropriately according to the resulting diagnosis. Conclusions: LESS biopsy for RTUO is a safe and effective alternative to open surgical and standard laparoscopic biopsies. Further studies of clinical experiences are needed to confirm the benefits of this new technique.

Purpose To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy 3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

Objectives: To evaluate the early quality of life outcomes in prostate cancer patients managed by high-dose-rate brachytherapy as monotherapy. Methods: A total of 51 patients with cT1c–T3aN0M0 prostate cancer treated between July 2007 and January 2010 were included in this study. The average age was 69 years, and the average initial serum prostate-specific antigen was 10.98 ng/mL. A total of 25, 18 and eight patients were considered to be low, intermediate and high risk, respectively. All patients received one implant of Ir-192 and seven fractions of 6.5 Gy within 3.5 days for a total prescribed dose of 45.5 Gy. For high-risk prostate cancer, neoadjuvant androgen deprivation therapy was carried out for at least 6 months, and continued after high-dose-rate brachytherapy. Quality of life outcomes were measured by using the International Prostate Symptom Score, the Functional Assessment of Cancer Therapy-Prostate and the International Index of Erectile Function Questionnaire. The oncological outcome was assessed by serum prostate-specific antigen and diagnostic imaging. Adverse events were also recorded. Results: The Functional Assessment of Cancer Therapy-Prostate scores decreased for a few months after high-dose-rate brachytherapy, and recovered to pretreatment condition thereafter. The International Prostate Symptom Score significantly increased 2 weeks after treatment for each of its items and their sum, and it returned to baseline after 12 weeks. Sexual function decreased at 2 and 4 weeks, and recovered after 12 weeks. Severe complications were rare. Within a median follow up of 17.2 months, two patients showed a prostate-specific antigen recurrence. Conclusions: High-dose-rate brachytherapy for prostate cancer is a feasible treatment modality with acceptable toxicity and only a limited impact on the quality of life.

We retrospectively reviewed infertile Japanese males for testicular volume discrepancies (D) and semen parameters to evaluate whether left grade II-III varicoceles (V) cause testicular damage.Seventy-seven patients who had idiopathic male infertility and 88 who had V without other causes of infertility were examined. We excluded cases of azoospermia. Testicular volume was measured using a punched-out orchidometer. D was defined as a size difference of at least 3 ml. The frequency of D was compared between the patients with and without V. The semen parameters were reviewed in association with D and V.The mean left and right testicular volumes were 19.4 and 20.1 ml, respectively (In the patients with V, D was more common than in those without V. The semen parameters were worse if D was present in the patients with V. These results indicated that V could induce testicular atrophy and negatively affect semen quality. Therefore, the ipsilateral reduced testicular volume is considered to be a sign of persisting testicular damage by V.

Japanese traditional medicines, Kampo medicines (KMs), are usually herbal medicine based on traditional Chinese herbal medicine but developed into a unique form in Japan. At present, 148 kinds of KMs have been approved and are enlisted on the “National Health Insurance Drug Tariff.” About 72% of Japanese physicians prescribe some KMs to their patients. Based on patients' symptoms, KMs are given alone or in combination with contemporary western medicines. KMs can manage urological problems including erectile dysfunction, male infertility, lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia, overactive bladder (OAB), urolithiasis as well as late-onset hypogonadism (LOH) in Japan. In men's health clinic, a number of patients is eugonadal with suspicious LOH-related symptoms. Some are not eligible for androgen replacement therapy (ART) while others have no response to ART. To manage these patients, KMs can be used to improve indefinite complaints, or LOH-related symptoms. F...

Objectives: To investigate the benefit of α1-adrenoceptor antagonist naftopidil on the quality of life (QOL) of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS). Methods: A total of 99 men with BPH/LUTS were prospectively recruited. The Short Form-8 (SF-8) was used for generic QOL assessment and each parameter was compared with the norm in these patients. Longitudinal changes were evaluated using the SF-8 and the International Prostatic Symptoms Score (I-PSS) at baseline, 4 and 8 weeks after naftopidil administration. The relationship between SF-8 and I-PSS was analyzed. Results: Five of eight components in the SF-8 were significantly lower than the Japanese national norm at baseline. SF-8 score was improved by naftopidil at 4 and 8 weeks in general health (GH) and physical component summary (PCS) in the patients in their 70s. Mental health (MH) and mental component summary (MCS) were improved at 8 weeks in patients in their 60s. When analyzing the whole cohort, SF-8 GH, role emotional (RE) and MH had improved at 8 weeks, which was similar to the norm, and bodily pain (BP) results were better. Compared with the baseline, total I-PSS, storage/voiding symptoms and QOL index scores improved significantly under naftopidil. Each component of I-PSS (except for hesitancy) correlated with SF-8 sub-scales (except for BP) to some extent. Conclusions: BPH/LUTS impairs generic QOL, which is improved by naftopidil treatment. SF-8 can be a useful instrument to assess the efficacy of BPH/LUTS treatment because its simplicity to complete and analyze, and its meaningful relationship to I-PSS.

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (

Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients' sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points: point A, pre-treatment; point B, at the nadir of the prostate-specific antigen (PSA) level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients' sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC-I). Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-I protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.

BACKGROUND Hepatocyte growth factor (HGF) is secreted as an inactive single-chain precursor called pro-HGF. Pro-HGF is converted to an active two-chain form by HGF activator and matriptase. We attempted to clarify whether serum levels of active HGF (AHGF) could be used as a marker of prostate cancer. METHODS Serum levels of AHGF and total HGF (THGF; pro-HGF + AHGF) were measured by enzyme-linked immunosorbent assay in 38 patients with benign prostatic disease and 160 patients with prostate cancer. RESULTS Serum levels of AHGF in patients with untreated prostate cancer (0.37 ± 0.12 ng/ml) were significantly higher than those in patients with benign prostatic disease (0.28 ± 0.08 ng/ml) (P = 0.0001). Serum AHGF levels were increased in patients with stage D or D3 compared with stage B. In addition, there were significant differences in serum AHGF levels between patients with well-differentiated and poorly differentiated adenocarcinoma. Furthermore, the mean serum AHGF/THGF ratio in patients with stage D3 prostate cancer was significantly higher than that in patients with stage B. CONCLUSIONS AHGF may be a potential tumor marker for prostate cancer. Further studies in large groups of patients are needed to define the clinical value of AHGF. Prostate 69:346–351, 2009. © 2008 Wiley-Liss, Inc.

Neuroendocrine (NE) cells originally exist in the normal prostate acini and duct, regulating prostatic growth, differentiation and secretion. Clusters of malignant NE cells are found in most prostate cancer (PCa) cases. NE differentiation (NED) is the basic character of the prostate, either benign or malignant. NE cells hold certain peptide hormones or pro-hormones, which affect the target cells by endocrine, paracrine, autocrine and neuroendocrine transmission in an androgen-independent fashion due to the lack of androgen receptor. NED is accessed by immunohistochemical staining or measurement of serum levels of NE markers. The extent of NED is associated with progression and prognosis of PCa. Chromogranin A (CGA) is the most important NE marker. In metastatic PCa, pretreatment serum CGA levels can be a predictor for progression and survival after endocrine therapy. It is recommended to measure longitudinal change in serum CGA. The NE pathway can also be a therapeutic target.

The relationships between serum level of testosterone (T) and prostate cancer (PCa) are complex. The present study evaluated whether presence of PCa alters serum T levels. Subjects were 125 patients with clinically localized PCa treated using radical prostatectomy (RP), for whom pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment prostate-specific antigen, Gleason score and pathological stage. Serum T and human luteinizing hormone (LH) levels before and after RP were then compared in 118 of the 125 patients. Mean pretreatment T level was significantly higher in patients with organ-confined PCa (pT2; 4.03+/-1.50 ng ml(-1)) than in patients with nonorgan-confined cancer (pT3; 3.42+/-1.06 ng ml(-1); P=0.0438). No association existed between pretreatment serum T level and pathological Gleason score. After RP, serum T level (5.60+/-1.90 ng ml(-1)) was significantly elevated compared to preoperative level (3.89+/-1.43 ng ml(-1); P0.0001). In parallel, significant increases were seen in postoperative serum LH level (6.86+/-3.64 ng ml(-1)) compared to preoperative level (5.11+/-2.47 ng ml(-1); P=0.0001). In contrast, differences in serum T levels according to pathological stage disappeared postoperatively (P=0.5513). Significant increases in serum T and LH levels were seen after RP, compared to preoperative levels in parallel. This study suggests that serum T levels are altered by the presence of PCa, supporting the possibility that PCa may inhibit serum T levels with negative feedback in the hypothalamic-pituitary axis.

Relationships between androgenic hormones and prostatic tissue growth are complex. It is certainly true that the prostate will not develop without androgens and the gland will atrophy if androgen support is withdrawn. The hormonal hypothesis remains one of the most important hypotheses in the etiology of prostate cancer (PCa), and efforts are continuing to improve the understanding of androgen actions in PCa. Although evidence from epidemiological studies of associations between circulating levels of androgens and PCa risk has been inconsistent, the traditional view that higher testosterone (T) levels represent a risk factor for PCa appears to have little evidentiary support. Reinvestigation of the relationship between T and PCa seems important and necessary if a new, clinically and scientifically rewarding concept is to be constructed. The present review considers the metabolism and intraprostatic action of T, epidemiological evidence, and the association between T and PCa risk.

Prostate-specific antigen (PSA) screening has led to a remarkable increase in prostate cancer cases undergoing operative therapy. Over half of patients with locally advanced cancer (>or=pT3) develop rising PSA levels (biochemical failure) within 10 years. It is very difficult to predict which patients will progress rapidly to advanced disease following biochemical failure (BF). Therefore, a more useful prognostic factor is needed to suggest the most appropriate therapies for each patient. To determine chromosomal aberrations, we examined 30 patients with stage pT2 or pT3 primary prostate adenocarcinomas and no metastases (pN0M0) by comparative genomic hybridization (CGH). Laser capture microdissection (LCM) was used to gather cancer cells from frozen prostate specimens. Common chromosomal alterations included losses on 2q23-24, 4q26-28, 6q14-22, 8p12-22 and 13q21-31, as well as gains on 1p32-36, 6p21 and 17q21-22. Losses at 8p12-22 and 13q21-31 were observed more frequently in pT3 than pT2 tumors (P

Objective: We evaluated health-related quality of life (HRQOL) in Japanese men receiving androgen deprivation therapy (ADT) for prostate cancer. Methods: Fifty-six men were enrolled in this study. HRQOL was prospectively measured before ADT, and at 3, 6 and 12 months after treatment began, using a general (36-item Short-Form Health Survey) and disease-specific (the University of California, Los Angeles Prostate Cancer Index) HRQOL questionnaire. Results: In the general HRQOL questionnaire, patients with stage B (n = 22) or C (n = 17) disease showed a decline in vitality at 6 and 12 months (P

The high incidence of tumor recurrence following transurethral resection (TUR) represents a major problem encountered in the management of bladder cancer. This study examined the efficacy of intravesical chemotherapy in superficial bladder cancer. We retrospectively analyzed 90 Japanese cases with low-grade superficial transitional cell carcinoma (stage T1, grades 1 and 2) who were rendered tumor-free by TURBT (TUR of bladder tumor) and who thereafter were treated with or without intravesical chemotherapy. Among them, instillation was terminated in 2 patients due to adverse effects (severe but reversible chemical cystitis). Remaining 88 patients were divided into 2 groups according to therapy: the TURBT-only group(n=46), defined as patients treated with TURBT alone, and the Instillation group(n=42), defined as patients treated with weekly intravesical instillation therapies using epirubicin plus Ara-C. Recurrence-free rate was significantly higher in the Instillation group than in the TURBT-only group (p=0.02, HR = 0.457). The 5-year recurrence-free rate was 58.5% for the Instillation group and 38.6% for the TURBT-only group. Our instillation schedule represents the most intensive regimen among previously reported therapies and resulted in a 54.3% decrease in incidence of tumor recurrence. We believe that the results of this study could provide useful information on management of bladder cancer.