Beyond 2D: A scalable and highly sensitive method for a comprehensive 3D analysis of kidney biopsy tissue.

The spatial organization of various cell populations is critical for the major physiological and pathological processes in the kidneys. Most evaluation of these processes typically comes from a conventional 2D tissue cross-section, visualizing a limited amount of cell organization. Therefore, the 2D analysis of kidney biopsy introduces selection bias. The 2D analysis potentially omits key pathological findings outside a 1- to 10-µm thin-sectioned area and lacks information on tissue organization, especially in a particular irregular structure such as crescentic glomeruli. In this study, we introduce an easy-to-use and scalable method for obtaining high-quality images of molecules of interest in a large tissue volume, enabling a comprehensive evaluation of the 3D organization and cellular composition of kidney tissue, especially the glomerular structure. We show that CUBIC and ScaleS clearing protocols could allow a 3D analysis of the kidney tissues in human and animal models of kidney disease. We also demonstrate that the paraffin-embedded human biopsy specimens previously examined via 2D evaluation could be applicable to 3D analysis, showing a potential utilization of this method in kidney biopsy tissue collected in the past. In summary, the 3D analysis of kidney biopsy provides a more comprehensive analysis and a minimized selection bias than 2D tissue analysis. Additionally, this method enables a quantitative evaluation of particular kidney structures and their surrounding tissues, with the potential utilization from basic science investigation to applied diagnostics in nephrology.

Seasonal Serum 25(OH) Vitamin D Level and Reproductive or Immune Markers in Reproductive-Aged Women with Infertility: A Cross-Sectional Observational Study in East Japan.

Several studies have reported that vitamin D may modify human reproductive functions; however, the results are conflicting. We aimed to comprehensively evaluate serum vitamin D levels and examine the relationship between serum vitamin D levels and ovarian reserve markers, and immune markers of implantation, in reproductive-aged Japanese women with infertility.in reproductive-aged women with infertility. This cross-sectional, single-center study included reproductive-aged women who underwent preconception screening for fertility. Serum vitamin D levels and reproductive and immune markers were measured. Standard and advanced statistical techniques were used. We observed a statistically significant difference in the seasonal and monthly 25(OH) vitamin D levels; the 25(OH) vitamin D level during winter was the lowest among all seasons. However, there was no linear correlation between 25(OH) vitamin D levels and ovarian reserve markers, such as follicle-stimulating hormone and anti-Müllerian hormone, or the Th1/Th2 cell ratio, which is used as an implantation-related immunological marker. In this large-scale study, we evaluated the serum 25(OH) vitamin D concentration in reproductive-aged women with infertility in Japan; however, there was no association between reproductive function and vitamin D levels.

Results of lifestyle modification promotion and reproductive/general health check for male partners of couples seeking conception.

Purpose: Male infertility is partially caused by an inappropriate lifestyle and comorbidities. In this study, we analyzed the prevalence of these factors and the effects of lifestyle modifications as part of male preconception care. Methods: Four hundred and two male partners of couples seeking conception with abnormal parameters upon the first semen analysis were enrolled. They were advised to modify their inappropriate lifestyle as male preconception care. Afterward, their general and male reproductive health was examined. Semen quality was compared before and after the promotion. Results: Smoking, chronic alcohol use, and genital heat stress were found in 22.6%, 47.0%, and 75.1% of patients, respectively. Palpable varicoceles, hypogonadism, obesity (body mass index ≧30 kg/m2), hypertension, zinc deficiency, hyperlipidemia, liver dysfunction, and diabetes mellitus were found in 25.9%, 17.0%, 7.0%, 14.9%, 16.2%, 37.0%, 26.9% and 3.4% of the participants, respectively; 98.8% of the patients had at least one factor. After the promotion, semen parameters and sperm DNA fragmentation were improved significantly. Improvement was found in those with palpable varicocele or hypogonadism but not in those with night work shift, abstinence (>3 days), erectile dysfunction, hypertension, obesity, zinc deficiency, or diabetes mellitus. Conclusions: Comorbidities and inappropriate lifestyle choices were common among men with infertility. The promotion of lifestyle modifications as part of male preconception care could improve semen quality without urologic intervention.

Summary of the clinical practice manual for late-onset hypogonadism.

Testosterone plays an important role in maintaining both physical and mental function. Age-related testosterone depletion contributes to the development of angina, arteriosclerosis, obesity, metabolic syndrome, dementia, frailty, and a range of other conditions. A condition involving age-related testosterone depletion and the associated clinical symptoms is defined as late-onset hypogonadism (LOH). LOH is treated by testosterone replacement therapy. Indications for testosterone replacement therapy are determined by evaluating symptoms and signs.

Detection of intraductal carcinoma in prostate cancer patients with small tumor volume.

OBJECTIVES: The purpose of this study was to investigate intraductal carcinoma of the prostate (intraductal carcinoma) and significant cancer (SC) in patients with small tumor volume (<0.5 cm3 ) in prostatectomy specimens. METHODS: Data from 639 patients undergoing radical prostatectomy between April 2006 and December 2017 at Chiba University Hospital and 2 affiliated institutions were retrospectively reviewed. Tumor volume in prostatectomy specimens was measured, and with a tumor volume of less than 0.5 cm3 , the presence of intraductal carcinoma and SC was examined. SC was defined as one that did not meet the definition of pathological insignificant cancer (organ-confined cancer, Grade Group 1, tumor volume < 0.5 cm3 ). The number of patients who met four active surveillance (AS) protocols was also examined. RESULTS: A total of 83 patients with tumor volume < 0.5 cm3 were identified in this study population (SC: 43 patients [52%], intraductal carcinoma: 5 patients [6%]). The median follow-up was 34.6 months (range: 18-57 months). Four (5%) developed biochemical recurrence. The number of positive biopsy cores ≥ 2 was an independent predictor of SC in patients with tumor volume < 0.5 cm3 (hazard ratio: 4.39; 95% confidence interval: 1.67-11.56; p = 0.003). In tumor volume < 0.5 cm3 , tumor volume was significantly correlated with the International Society of Urological Pathology Grade Group (1 vs. 4-5, p = 0.002) and the presence of intraductal carcinoma (p = 0.004). In intraductal carcinoma-positive cases, four of five patients (80%) had the predictor of SC, which was two or more positive biopsy cores. Of the four AS protocols, the criteria for Prostate Cancer Research International: Active Surveillance were met most frequently in 46 cases (55%) of tumor volume less than 0.5 cm3 if targeted biopsy by magnetic resonance imaging was available. CONCLUSION: The results of the present study suggest that intraductal carcinoma was present even in cases with small tumor volumes. Grade Group and intraductal carcinoma showed a positive correlation with tumor volume.

A clinical investigation of recurrence and lost follow-up after renal cell carcinoma surgery: a single-center, long-term, large cohort, retrospective study.

BACKGROUND: Late recurrence of renal cell carcinoma (RCC) is observed in some postoperative patients. In addition, some of these patients are lost to long-term postoperative follow-up. We reviewed the treatment results and prognosis of postoperative patients with RCC at Chiba University Hospital, with the aim of clarifying the proportion and background of patients lost to follow-up. METHODS: This retrospective study included 1176 RCC patients who underwent radical or/and partial nephrectomy. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and lost follow-up free survival (LFFS) were evaluated and the risk factors for LFFS identified. RESULTS: The median RFS for stage II and II cases was 188.3 and 104.0 months, respectively. Even in stage I, recurrence was observed in about 20% of patients 20 years after surgery. The Kaplan-Meier curve for LFFS showed a linear descent over time, with 50% of patients lost to follow-up within 25 years. Older age (≥ 62 years), histological type (clear cell RCC), and no recurrence were significant risk factors for lost follow-up. CONCLUSIONS: Long-term follow-up is necessary after RCC surgery because late recurrence cases are not uncommon. We believe that lifelong follow-up with imaging studies is recommended for postoperative RCC patients. Early detection of recurrence in postoperative patients is a very important issue, and it may be worthwhile for improving the prognosis of postoperative patients to focus on patients lost to follow-up who may have been overlooked.

Successful treatment of metastatic bladder cancer by gemcitabine-cisplatin re-challenge after pembrolizumab.

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.

Prognostic Value of High-Sensitivity Modified Glasgow Prognostic Score in Castration-Resistant Prostate Cancer Patients Who Received Docetaxel.

The Glasgow prognostic score, a marker of systemic inflammation, is associated with clinical outcomes in different cancers including prostate cancer. However, there is no evidence for the relationship between the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in prostate cancer and its prognosis. This study aimed to investigate the prognostic significance of Hs-mGPS in castration-resistant prostate cancer (CRPC) treated with docetaxel. We retrospectively analyzed clinical datasets from 131 CRPC patients who received docetaxel treatment at Chiba University Hospital and a related hospital. Clinical factors including Hs-mGPS before docetaxel treatment were evaluated according to overall survival. The numbers of patients with Hs-mGPS of 0, 1, and 2 were 88, 30, and 13, respectively. The median prostate-specific antigen (PSA) level was 28.9 ng/mL. The median testosterone level was 13.0 ng/dL. The percentages of bone and visceral metastases were 80.8% and 10.2%, respectively. For overall survival, Hs-mGPS ≥ 1 (hazard ratio of 2.41; p = 0.0048), testosterone ≥ 13.0 ng/dL (hazard ratio of 2.23; p = 0.0117), and PSA ≥ 28.9 ng/mL (hazard ratio of 2.36; p = 0.0097) were significant poor prognostic factors in the multivariate analysis. The results of the two-group analysis showed that a higher Hs-mGPS was associated with high PSA, alkaline phosphatase, and testosterone levels. The median testosterone levels for Hs-mGPS of 0, 1, and 2 were 9.0, 16.5, and 23.0, respectively. Based on the multivariate analysis, we created a combined score with three prognostic factors: Hs-mGPS, testosterone, and PSA. The low-risk group (score of 0-1) showed a significantly longer overall survival compared to the intermediate-risk (score of 2-3) and high-risk (score of 4) groups (p < 0.0001). Our results demonstrated that an elevated Hs-mGPS was an independent prognostic factor in CRPC patients treated with docetaxel therapy. Risk classification based on Hs-mGPS, testosterone, and PSA may be useful in predicting the prognosis of CRPC patients.

Efficacy of an educational program for medical staff in preventing incidents related to Foley catheter insertion and maintenance: A single-institution retrospective study.

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.

Revision of CHAARTED and LATITUDE criteria among Japanese de novo metastatic prostate cancer patients.

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 < 0.0001) and C-reactive protein (CRP) (HR 1.65, P = 0.042) were independent risk factors for OS. In patients who met the LATITUDE criteria, Gleason score (GS) ≥9 (HR 1.77, P = 0.0326) and LDH (HR 2.62, P < 0.0001) were independent risk factors for OS. Modified CHAARTED criteria by adding LDH and CRP showed a significant difference in OS (HR 2.55, P < 0.0001) with a comparative median OS (31.8 months) to placebo of CHAARTED trial (32.2 months). Modified LATITUDE criteria by adding GS ≥9 and LDH showed a significant difference in OS (HR 2.66, P < 0.0001) with a comparative median OS (32.7 months) to placebo of LATITUDE trial (34.7 months). CONCLUSION: Modified criteria may potentially elucidate the true "high volume" and "high risk" patients in the Japanese cohort who require early intensive therapy.

Adrenalectomy in Japanese patients with subclinical Cushing syndrome: 1-mg dexamethasone suppression test to predict the surgical benefit.

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.

Identification of AR-V7 downstream genes commonly targeted by AR/AR-V7 and specifically targeted by AR-V7 in castration resistant prostate cancer.

Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) under androgen deprivation therapy, by mechanisms e.g. expression of androgen receptor (AR) splice variant-7 (AR-V7). Here we conducted comprehensive epigenome and transcriptome analyses comparing LNCaP, primary PC cells, and LNCaP95, AR-V7-expressing CRPC cells derived from LNCaP. Of 399 AR-V7 target regions identified through ChIP-seq analysis, 377 could be commonly targeted by hormone-stimulated AR, and 22 were specifically targeted by AR-V7. Among genes neighboring to these AR-V7 target regions, 78 genes were highly expressed in LNCaP95, while AR-V7 knockdown led to significant repression of these genes and suppression of growth of LNCaP95. Of the 78 AR-V7 target genes, 74 were common AR/AR-V7 target genes and 4 were specific AR-V7 target genes; their most suppressed genes by AR-V7 knockdown were NUP210 and SLC3A2, respectively, and underwent subsequent analyses. NUP210 and SLC3A2 were significantly upregulated in clinical CRPC tissues, and their knockdown resulted in significant suppression of cellular growth of LNCaP95 through apoptosis and growth arrest. Collectively, AR-V7 contributes to CRPC proliferation by activating both common AR/AR-V7 target and specific AR-V7 target, e.g. NUP210 and SLC3A2.

Relationship between post-void residual urine volume, preoperative pyuria and intravesical recurrence after transurethral resection of bladder carcinoma.

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-Guérin treatment. CONCLUSIONS: Post-void residual urine and preoperative pyuria are two risks for recurrence-free survival in non-muscle-invasive bladder cancer.

Prognostic factors influencing overall survival in de novo oligometastatic prostate cancer patients.

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 < .0001). CONCLUSION: Not only the number of bone metastases, but also non-regional LN metastases predict OS in patients with de novo oligometastatic PCa.

Successful pregnancy and delivery achieved following intracytoplasmic sperm injection using teratozoospermic sperm exhibiting marked dysplasia of the fibrous sheath: a case report.

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)×106/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.

Prognostic value of an inflammatory index for patients with metastatic castration-resistant prostate cancer.

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 < .0001), and positive N stage (HR = 1.621; P = .048) were associated with poor OS after CRPC, whereas other inflammatory markers including the NLR were not. The Good inflammatory index group showed significantly longer OS after CRPC compared to the Intermediate and Poor groups, with median survivals of 46.2, 28.9, and 16.6 months, respectively. CONCLUSIONS: The novel inflammatory index combining dNLR and LDH was a useful prognostic parameter in patients with mCRPC. Our analysis suggested that dNLR emerged as a more valuable prognostic marker than NLR.

How many bone metastases may be defined as high-volume metastatic prostate cancer in Asians: A retrospective multicenter cohort study.

BACKGROUND: Recent landmark randomized trials (CHAARTED and LATITUDE studies) have highlighted potent upfront therapy for "high-volume" and "high-risk" metastatic castration-naïve 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.

Higher serum testosterone levels predict poor prognosis in castration-resistant prostate cancer patients treated with docetaxel.

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 < .0001), high volume (hazard ratio, 3.06; P = .0009), and prostate-specific antigen ≥ 27.0 ng/mL (hazard ratio, 2.75; P = .0013) were independent prognostic factors on multivariate analysis. When assessing related clinical factors, higher serum testosterone was associated with visceral metastasis, high volume, and prostate-specific antigen. Based on three prognostic factors (testosterone, high volume, prostate-specific antigen), a risk classification was developed. The high-risk group (3 risk factors) showed a significantly shorter overall survival compared to the moderate-risk (2 risk factors) and low-risk (0-1 risk factor) groups (P < .0001). CONCLUSIONS: The present study identified higher serum testosterone (≥13 ng/dL) as a significant prognostic factor in castration-resistant prostate cancer patients treated with docetaxel therapy.

Impact of post-void residual urine volume on intravesical recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma.

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.