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Background The incidence and risk factors of severe anaphylaxis by intravenous anti‐cancer drugs are unclear, whereas those of milder reactions have been reported. Study Design Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non‐epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). Results Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person‐day anti‐cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person‐based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%–0.67%) and the administration‐based incidence was 0.031% (27/88,200, 95% CI 0.019%–0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin‐induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%–13.1%). Carboplatin caused severe anaphylaxis after at least 9‐min interval since the drip started. Thirteen out of 14 patients experienced carboplatin‐induced severe anaphylaxis within a 75‐day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life‐long incidence of 0.93% (9/968, 95% CI 0.27%–1.59%). Conclusion We elucidated the high‐risk settings of chemotherapy‐induced severe anaphylaxis., 88,200 person‐days of chemotherapy provided for 5584 patients were reviewed. They induced 27 severe anaphylaxes defined by Brown’s criteria. Most were caused by carboplatin (14 cases) or paclitaxel (9 cases).

Objectives To assess the correlation of urine loss rate after catheter removal with long-term continence after robot-assisted radical prostatectomy. Methods We enrolled 163 patients on whom robot-assisted radical prostatectomy was carried out and whose urine loss rate we were able to evaluate after catheter removal. Urinary incontinence was evaluated from immediately after removal of the catheter to the date of discharge, and at 1, 3, 6 and 12 months after surgery. Urine loss rate was defined as the urine loss volume divided by the total urine volume. Results The continence rates of patients with ≤1% urine loss rate on the day of catheter removal were 100% at 6 and 12 months after surgery. A multivariate analysis proved that ≤10% urine loss rate on the day of catheter removal was a significant predictor of continence at 3 months after surgery. Furthermore, the continence rate at 12 months of patients who did not achieve ≤10% urine loss rate on the day of catheter removal was 79.5%. Among them, the continence rate at 12 months of patients who achieved ≥15% urine loss rate improvement from the day of catheter removal to the next day was 95.2%; the factor differed significantly between the continence and incontinence groups at 12 months after surgery. Conclusions The urine loss rate on the day of catheter removal is significantly related to the acquisition of urinary continence. Furthermore, our findings suggest that long-term urinary continence can be expected, even in the event of poor urine loss rate on the day of catheter removal, if it improves on the next day.

The objective of this study was to evaluate automated bone scan index (aBSI) as a prognostic biomarker for overall survival (OS) in bone-metastatic, castration-resistant prostate cancer (mCRPC) patients treated with radium-223 (Ra-223).We identified 42 men treated with Ra-223 for mCRPC. We investigated aBSI as an independent prognostic factor by multivariate analysis. Moreover, we evaluated the prognostic value of the aBSI after 12 weeks after the first cycle of Ra-223 administration and aBSI change from baseline to after 12 weeks (ΔBSI).Median baseline PSA and aBSI were 42.8 ng/mL and 1.5%, respectively. Median OS was 20.7 months. Multivariate analysis showed that baseline aBSI was a significant prognostic factor for OS. The aBSI at 12 weeks after first Ra-223 administration also exhibited significant prognostic value for OS, while we found no evidence of prognostic value for ΔBSI.Baseline aBSI may be a significant prognostic factor for OS in bone-metastatic CRPC patients treated with Ra-223.

Background The number of facilities adapting intracorporeal urinary diversion (ICUD) using robots instead of extracorporeal urinary diversion (ECUD) is increasing, but the clinical evidence is limited. Methods We retrospectively analyzed 26 consecutive patients who underwent ICUD with an ileal conduit following robot-assisted radical cystectomy (RARC) between 2018 and 2020 (RARC + ICUD group), and compared them with 26 consecutive patients who underwent ECUD with an ileal conduit following laparoscopic radical cystectomy (LRC) between 2012 and 2019 (LRC + ECUD group) at Yokohama City University. Results In both groups, the patient background was similar except for age and neoadjuvant chemotherapy. In the RARC + ICUD group vs. the LRC + ECUD group, the median total operation time was 516 min vs. 532.5 min (p = 0.217), the time to cystectomy was 163 min vs. 194.5 min (p = 0.007), and the time of urinary diversion with an ileal conduit was 161 min vs. 201.5 min (p

This open‐label, phase I dose‐finding study evaluated the gonadotropin‐releasing hormone antagonist, TAK‐385, in Japanese patients with nonmetastatic prostate cancer. In a two‐part design, patients received daily oral TAK‐385 at doses of 320 (loading, day 1)/80 (maintenance, day 2 and thereafter), 320/120, 320/160, or 360/120 mg for 28 days in a dose‐escalation phase (part A, n = 13), and at 320/80 or 320/120 mg for up to 96 weeks in a randomized expansion phase (part B, n = 30). Primary endpoint in both parts was safety, including dose‐limiting toxicity in part A. Secondary endpoints included pharmacokinetics, pharmacodynamics, and prostate‐specific antigen concentration. Ten (77%) patients in part A and all patients in part B experienced an adverse event; hot flush (part A, n = 4; part B, n = 15), viral upper respiratory tract infection (part A, n = 1; part B, n = 10), and diarrhea (part B, n = 8) were most frequent. No dose‐limiting toxicities were observed (part A). In 12 evaluable patients (part A), TAK‐385 was rapidly absorbed after a single loading dose; on day 28 (maintenance dose), median steady‐state T max was ~1‐2 hours and mean t 1/2z was 67‐79 hours. All doses rapidly reduced testosterone concentrations to castration levels within 1 week. Durable reductions in prostate‐specific antigen of >90% from baseline were observed through 96 weeks. TAK‐385 appeared tolerable and resulted in sustained reductions in testosterone to castration levels at all doses. The lowest loading/maintenance dose required for a clinical effect was 320/80 mg. http://ClinicalTrials.gov: NCT02141659., TAK‐385 is an orally active gonadotropin‐releasing hormone (GnRH) antagonist with rapid testosterone‐lowering effects in clinical studies, achieving effective and sustained castration in patients with prostate cancer without the initial testosterone surge observed with GnRH agonists. To date, clinical trials of TAK‐385 for the treatment of prostate cancer have been conducted in a predominantly Western patient population. Building on these data, the current study establishes an appropriate dose range for TAK‐385 in Japanese patients with non‐metastatic prostate cancer, and evaluates safety, pharmacokinetics, pharmacodynamics and preliminary efficacy in this population.

Purpose The aim of this analysis was to compare acute and late toxicities between low-dose-rate brachytherapy (LDR-BT) (110 Gy) in combination with 45 Gy in 25 fractions external beam radiation therapy (EBRT) and LDR-BT (160 Gy) alone for localized prostate cancer. Material and methods One hundred five consecutive patients with localized prostate cancer treated from May 2014 to May 2017 were included in this retrospective analysis. Sixty patients received combination therapy and 45 patients received BT monotherapy. The LDR-BT procedure was performed using 125I seeds. Results The median follow-up time was 28 months in both groups. Three-year effect rates were overall survival: 100% in both groups. The biochemical failure rate was 2.3% in the combination group and 0% in the monotherapy group (p = 0.373). No patients died during the study period. In both groups, almost all the patients experienced acute urethritis. There was a significant difference between the combination therapy group (8.3%) and BT monotherapy group (11.1%) in late genitourinary (GU) toxicities ≥ grade 2 (p = 0.035). Only 2 patients (3.3%) in the combination therapy group developed late ≥ grade 2 rectal hemorrhage. There were no significant differences between two groups in hematuria ≥ grade 2 (p = 0.068) or rectal hemorrhage ≥ grade 2 (p = 0.206). Conclusions To our knowledge, this is the first report to compare the GU and gastrointestinal toxicities between the combination therapy and BT monotherapy (160 Gy) for localized prostate cancer. Unexpectedly, there were more late GU toxicities (except for hematuria) in the BT monotherapy group.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant disorder that results from a germline mutation in the fumarate hydratase gene (FH). Individuals with FH mutations are at risk of developing renal cell carcinoma (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is as yet no standardized therapy for advanced HLRCC-RCC. We report an aggressive RCC case in a 49-year-old man. Nine weeks after undergoing a total nephroureterectomy of the right kidney, he had a metastasectomy at port site. Within 14 weeks of the initial surgery, multiple recurrent tumors developed in the right retroperitoneal space. The pathological diagnosis was FH-deficient RCC. Genetic testing identified a heterozygous germline mutation of FH (c.641_642delTA), which confirmed the diagnosis of HLRCC-RCC. He received combination therapy with the immune checkpoint inhibitors (ICIs) nivolumab and ipilimumab as the first-line therapy. After 31 weeks of ICI treatment, a complete response was achieved. The disease-free condition has been prolonged for 24 months since the initial surgical treatment. This is the first case report of successful treatment of HLRCC-RCC with nivolumab plus ipilimumab. This combination immunotherapy is expected to be an effective approach to treat patients with advanced-stage HLRCC-RCC.

We investigated prospectively whether 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) can predict the overall survival (OS) of patients with advanced renal cell carcinoma (RCC) previously treated by molecular targeted therapies. Between 2009 and 2016, 81 patients who had received single molecular targeted therapies (43 sorafenib, 27 sunitinib, 8 temsirolimus and others) and were scheduled for second line molecular targeted therapies for advanced RCC were enrolled in this prospective study. FDG PET/CT was performed after first line molecular targeted therapies, the max SUVmax (highest standardized uptake value for each patient) recorded, and its association with OS compared with those of known risk factors. The median follow-up was 15.4 months (range 0.9–97.4 months). The max SUVmax of the 81 subjects ranged from undetectable to 23.0 (median 7.1). Patients with high max SUVmax had a poor prognosis and multivariate analysis with established risk factors showed that it was an independent predictor of survival (p

A 45-year-old woman with dyspnea and appetite and weight loss was admitted to our hospital. Computed tomography (CT) revealed a right hypovascular renal tumor with tumor thrombus in the inferior vena cava and metastases in the liver, stomach, and left kidney. The renal tumor was diagnosed as a mucinous tubular and spindle cell carcinoma (MTSCC) by pathological examination of a percutaneous needle biopsy specimen. She was treated with temsirolimus (25 mg per week). Five weeks after initiation of this treatment, her liver metastases had clearly decreased in size and her appetite had been restored. However, progressive disease was diagnosed by CT scan revealing expansion of tumor thrombus after 7 weeks, prompting a switch in treatment to axitinib. Approximately 6 months after the diagnosis, she died of cancer. MTSCC is considered to have relative good prognosis, however, many cases with poor prognoses have been reported recently. Our experience with this patient suggests that temsirolimus may be effective treatment for metastatic MTSCC.

More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer.The subjects were 50 consecutive men with a PSA level of 2.0-10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer.In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%).PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer.

We evaluated 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) results as outcome predictors for patients with metastatic renal cell carcinoma (RCC) treated by everolimus (EVL), an inhibitor of mammalian target of rapamycin. We retrospectively reviewed 30 patients who were treated with EVL for metastatic RCC between May 2010 and March 2015, by evaluating their FDG PET/CT result before and 1 month after starting EVL treatment. We examined the relationships between each patient’s maximum standardized uptake value (max SUVmax) assessed by FDG PET/CT on progression-free survival (PFS) and overall survival (OS). Median PFS for all 30 patients was 3.77 months (range 0.72–24.56 months) and median OS after EVL treatment of all 30 patients was 11.67 months (range 1.0–62.98 months). Enrolled patients were divided into two groups by max SUVmax prior to EVL (median = 7.6) and at 1 month after EVL treatment (median = 5.7). PFS were significantly shorter in higher max SUVmax prior to EVL (

Background We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab. Methods Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study. All patients underwent FDG-PET/CT at baseline and 1 month as a first response assessment, and contrast-enhanced or non-contrast-enhanced CT scan at 4 month as a second response assessment. Logistic regression analysis was performed to assess the association of potential predictors, including age, gender, baseline diameter, baseline maximum standardized uptake value (SUVmax), lung or not lung metastasis, elevation of SUVmax at 1st assessment, and decrease in diameter at 1st assessment with the response at 2nd assessment (decrease in the diameter ≥ 30% or not). Results There were 9 patients and 30 lesions. Mean days of first assessment with FDG-PET/CT and second assessment by CT scan from initiation of treatment were 32.3 ± 6.4, 115.5 ± 14.9, respectively. Lesions whose diameter decreased ≥30% at second assessment were defined as responding, and lesions whose diameter did not decrease ≥30% were defined as non-responding. There were 18 responding lesions, and 12 non-responding lesions. We compared change in diameter and SUVmax at first assessment with FDG-PET/CT, respectively. All lesions with decreased diameter and elevated SUVmax at first assessment with FDG-PET/CT showed responding at second assessment by CT scan, while most lesions with increased diameter and declined SUVmax at first assessment showed non-responding at second assessment. The multivariate logistic regression analyses revealed that only the elevation of SUVmax at 1 month was an independent predictor (P = 0.025, OR: 13.087, 95%CI: 1.373–124.716). Conclusion Our findings suggest that the early assessment using FDG-PET/CT can be effective to predict the response of RCC to nivolumab. However, larger prospective studies are needed to confirm these preliminary results. Trial registration Registered in University Hospital Medical Information Network in JAPAN [UMIN0000008141], registration date: 11 Jun 2012.

Introduction and Objectives. The neutrophil-to-lymphocyte ratio (NLR) has been suggested as a simple marker of the systemic inflammatory response in critical care patients. The NLR can be easily calculated from routine complete blood counts in the peripheral blood. This parameter has been reported to be an independent prognosticator for some solid malignancies. In the present study, we examined the importance of the NLR as a prognostic marker for castration-resistant prostate cancer (CRPC) patients who received docetaxel- (DOC-) based chemotherapy. Methods. We analyzed a total of 73 patients who received DOC chemotherapy for CRPC in Yokohama City University Medical Center and affiliated hospitals. Complete blood cell counts were performed, and the NLR was calculated using the neutrophil and lymphocyte counts obtained on the same day or a few days before the initiation of DOC chemotherapy. We determined the NLR cutoff value based on the sensitivity and specificity levels derived from area under the receiver operator characteristic curves for death. Results. The median overall survival (OS) after DOC was 21.0 months (range: 2.0–51.0). The median OS was shorter in patients with a high NLR (≥2.59) than in those with a low NLR (p=0.001). In the multivariate analysis, the NLR and lymph node (LN) metastasis were independent predictors of the OS (hazard ratio 3.643, p=0.001; hazard ratio 2.184, p=0.038, respectively). Conclusions. The higher NLR group showed a significantly poorer OS than the lower NLR group. Pre-DOC NLR might be a new marker for predicting the prognosis of patients who receive DOC chemotherapy.

Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduced incidence of febrile neutropenia in Japanese metastatic castration-resistant prostate cancer patients. Cabazitaxel+G-CSF therapy was a safe and effective treatment option., Background Cabazitaxel is an efficacious treatment for patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel, but febrile neutropenia during the first cycle is a frequent complication. Asian patients are at increased risk of febrile neutropenia. Although primary prophylaxis with granulocyte colony-stimulating factor can reduce the incidence, its efficacy has not been prospectively demonstrated in Japanese patients with cabazitaxel treatment. Methods PEGAZUS, a prospective, single-arm study conducted at eight clinical sites in Japan, enrolled 21 heavily pretreated patients with metastatic castration-resistant prostate cancer. Patients received cabazitaxel 25 mg/m2 every 3 weeks, up to 10 cycles. Oral prednisolone 10 mg was taken daily. Pegfilgrastim 3.6 mg was administered at least 24 h after the cabazitaxel infusion. The primary endpoint was the incidence of febrile neutropenia in the first cycle. Results The median number of treatment cycles was seven. The relative dose intensity of cabazitaxel was 67.4% (range, 53.2–91.3%). Two of 21 patients (9.5%) experienced febrile neutropenia in the first cycle. This rate was lower than the rate (43%) previously observed without prophylactic granulocyte colony-stimulating factor in a similar patient population. Six patients showed a prostate-specific antigen response (28.6%). Three of four patients evaluable for tumor response had stable disease and one had progressive disease. Grade ≥3 diarrhea was not observed. Primary prophylaxis with granulocyte colony-stimulating factor significantly reduced the incidence of febrile neutropenia in this study. Conclusions Cabazitaxel plus granulocyte colony-stimulating factor is safe and effective for Japanese patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel. Clinical trial registration: ClinicalTrials.gov (NCT02441894).

To compare the outcomes of radical prostatectomy (RP), intensity-modulated radiation therapy (IMRT), and low-dose-rate brachytherapy (BT) using propensity score matching analysis in patients with clinically localized prostate cancer. A group of 2273 patients with clinically localized prostate cancer between January 2004 and December 2015 at the Yokohama City University hospital were identified. The records of 1817 of these patients, who were followed up for a minimum of 2 years, were reviewed; 462 were treated with RP, 319 with IMRT, and 1036 with BT. The patients were categorized according to the National Comprehensive Cancer Network risk classification criteria, and biochemical outcomes and overall survival rates were examined. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for IMRT and BT as nadir PSA level + 2 ng/ml. Propensity scores were calculated using multivariable logistic regression based on covariates, including the patient's age, preoperative PSA, Gleason score, number of positive cores, and clinical T stage. Median follow-up was 77 months for the RP, 54 months for IMRT, and 66 months for BT patients. After the propensity scores were adjusted, a total of 372 (186 each) and 598 (299 each) patients were categorized into RP vs IMRT and RP vs BT groups, respectively. Kaplan–Meier analysis did not show any statistically significant differences in terms of overall survival rate between these groups (RP vs IMRT: p = 0.220; RP vs BT: p = 0.429). IMRT was associated with improved biochemical failure-free survival compared to RP in all risk groups (high-risk: p

Xanthogranulomatous pyelonephritis (XGP) is a type of chronic suppurative renal inflammation. We present an extremely rare case of XGP concomitant with chromophobe renal cell carcinoma (RCC). A-39-year-old woman presented with transient fever and left lower abdominal pain during steroid pulse therapy for thyroid eye disease. Imaging studies including contrast-enhanced computed tomography, magnetic resonance imaging, and doppler ultrasonography, showed a 40 mm unusual mass lesion in the upper pole of the left kidney, and we could not rule out the possibility of malignancy.A left open partial nephrectomy for the renal mass was performed. Pathological examination revealed a 5 mm chromophobe RCC located beside a 30 mm XGP. The patient presented a favorable course without inflammatory episodes or tumor recurrence during the 9-month follow-up. This is the first case report of the coexistent XGP and chromophobe RCC.

Background Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. Methods We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. Results There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p

Key Clinical Message Renal lymphoma as an initial lesion is relatively rare. Bilateral renal lymphoma frequently presents as acute kidney injury. With systematic chemotherapy for the lymphoma, patients usually recover their kidney function. However, in the case we describe here, the patient's kidney function recovered greatly after an open renal biopsy. Here, we review and discuss this unique case.

Purpose To report 10-year outcomes of patients treated with I125 low-dose-rate brachytherapy (BT) for clinically localized prostate cancer.

Introduction: We evaluated bone scan index (BSI) as a predictive biomarker for time to castration-resistant prostate cancer (CRPC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Materials and Methods: We identified 85 consecutive mHSPC patients treated with first-line androgen deprivation therapy. We analyzed the correlations between time to CRPC and clinicopathological characteristics, including age, prostate-specific antigen (PSA) level, Gleason score, clinical TNM stage, hemoglobin, lactate dehydrogenase, C-reactive protein, and BSI. Results: The median BSI was 2.7%. Progression to CRPC occurred in 55 (64.7%) patients and the median time to CRPC was 12.9 months. In multivariate analysis, 3 significant risk factors for time to CRPC were identified: age (>73 vs. ≤73 years; hazard ratio [HR] 0.53), p = 0.038, PSA level (>270 vs. ≤270 ng/mL; HR 0.53, p = 0.038), and BSI (>2.7 vs. ≤2.7%; HR 2.97, p < 0.001). Conclusion: Age, PSA level, and BSI were found to be significant predictive factors for time to CRPC in patients with mHSPC.

e17030Background: It was reported that GnRH antagonist could extend progression free survival for prostate cancer patients significantly longer than GnRH agonist in a first line hormonal therapy. H...

216 Background: The objective of this study was to evaluate the bone scan index (BSI) as a prognostic biomarker for overall survival (OS) among patients treated with radium-223 (Ra-223) for bone metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively identified 42 men who had been treated with Ra-223 for bone metastatic CRPC between 2012 and 2017 and investigated correlations between the baseline clinical factors of age, time to CRPC, previous use of docetaxel, PSA, Gleason score, alkaline phosphatase (ALP), and BSI and OS by multivariate analysis using the Cox proportional hazard model. We also analyzed the correlations between OS and absolute BSI value or BSI change from baseline after 12 weeks of treatment. Continuous variables were classified as dichotomous. Results: The median age, PSA, and time to CRPC were 75.5 years, 42.8 ng/mL, and 11.2 months, respectively. The median observation period was 11.7 months. Twenty-five (59.5 %) of the 42 patients had completed six cycles of Ra-223 treatment. Twenty-two patients (52.4 %) had died, including 20 (47.6 %) of cancer, by the time of analysis. The median OS in the entire cohort was 20.7 months. Multivariate analysis also showed that only BSI (≥1.5 vs. < 1.5, HR 3.72, 95% CI 1.17–11.79, p = 0.026) was significantly correlated with OS. The BSI had decreased in 16 (51.6%) of the 31 patients who had undergone bone scans after 12 weeks of treatment . Multivariate analysis showed that absolute BSI value after 12 weeks treatment was significantly correlated with OS (BSI (≥2.0 vs. < 2.0%, HR 13.07, 95% CI 2.61–65.53, p = 0.002). No correlation was found between BSI change from baseline after 12 weeks and OS. Conclusions: According to multivariate analysis, both baseline BSI and PSA were significant prognostic factors for OS among men treated with Ra-223. Absolute BSI value after 12 weeks of Ra-223 treatment was also found to be an independent prognostic factor for OS.

317 Background: The olfactory receptor gene (OR) superfamily is the largest in the human genome. ORs are expressed not only in the neurons of the olfactory epithelium, but also in various other tissues in which their functions are largely unknown. We here investigated OR51T1 expression as a potential biomarker for predicting primary hormone therapy efficacy among men with metastatic hormone-naïve prostate cancer (mHNPC). Methods: Sixty-nine men with bone metastatic HNPC diagnosed from 2006 to 2015 were enrolled in this retrospective study. All patients had received hormone therapy as first-line treatment. Prostate cancer tissue obtained by needle biopsies before treatment were immunohistochemically stained for OR51T1. Correlations between the baseline clinical factors of age, PSA, Gleason score, T stage, N stage, extent of disease on bone scan (EOD), OR51T1 expression and primary hormone therapy efficacy (time to castration-resistant prostate cancer [CRPC]) were investigated by multivariate analysis using the Cox proportional hazard model. Continuous variables were classified as dichotomous. Results: Median age and PSA were 73.7 years and 263 ng/mL, respectively. Distribution of Gleason score of 9–10/6–8, T4/≤3, N1/0, and EOD 3–4/1–2 were 30 (43.5%)/39 (56.5%), 12 (17.4%)/57 (82.6%), 28 (40.6%)/41 (59.4%), and 26 (37.7%)/43 (62.3%), respectively. Median time to CRPC was 13.6 months. Patients with high OR51T1 expression had significantly shorter time to CRPC than those with low expression. Multivariate analysis showed that EOD (3–4 vs. 1–2, HR 3.1, 95% CI 1.6–6.2, p = 0.001) and OR51T1 expression (high vs. low; HR 2.3, 95%CI 1.2–4.4, p = 0.014) were significant biomarkers for predicting time to CRPC. Conclusions: OR51T1 expression could be a potential biomarker for predicting primary hormone therapy efficacy among men with mHNPC.

183 Background: It was reported that GnRH antagonist could extend progression free survival for prostate cancer patients significantly longer than GnRH agonist in a first line hormonal therapy. However, the usefulness of switching from GnRH agonist to GnRH antagonist as a second hormonal therapy remains obscure. We performed a multicentral prospective study to investigate whether the switching from GnRH agonist to GnRH antagonist (degalerix) for patients with castration resistant prostate cancer (CRPC) as the 2nd line hormonal therapy was effective. Methods: 37 patients who were pathologically diagnosed as prostatic adenocarcinoma and developed CRPC after 1st line hormonal therapy with GnRH agonist plus anti-androgens were enrolled. After confirming anti-androgen withdrawal syndrome, they were treated with switching from GnRH agonists to degalerix. The primary endpoint was PSA response (PSA decline or up to 10% over baseline PSA). Secondary endpoints were the time to 25% PSA increase from the baseline (PSA response time), PSA progression free survival (PPFS), the time to treatment failure, cancer specific survival, radiographic PFS (rPFS), and safety. Results: Mean age was 76 years old, super high risk; 20 cases (54.1%), high risk; 11 cases (29.7%), intermediate risk; 5 cases (13.5%), low risk; one case (2.7%). PSA responder rate was 24.3% (9 cases). In responders, the median PSA response time was 5.75 months, the median PPFS was 1.77 months, and rPFS rate at 3 months was 96%. Regarding safety, only 2 cases (5.4%) showed G3 of AE. The PSA response had no relationship with the change of serum testosterone, LH nor FSH. Conclusions: The effectiveness of switching from GnRH agonist to GnRH antagonist showed to be limited. Although no predictive factor of the switching was recognized, some long-term responders were seen. We expect the possibility of switching to GnRH antagonist for patients in the early stage of CRPC, especially non-metastatic status. Clinical trial information: UNKNOWN.

316 Background: Protein tyrosine phosphorylation is an important event associated with the processes of cellular metabolism and is regulated by protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Recent studies showed that low-molecular-weight protein tyrosine phosphatase (LMW-PTP) could be a biomarker for predicting overall survival among men with metastatic hormone-naïve prostate cancer (mHNPC). In this study, we evaluated the value of LMW-PTP expression for predicting primary hormone therapy efficacy among men with mHNPC. Methods: A total of 45 men with mHNPC diagnosed from 2003 to 2009 were enrolled in this retrospective study. All patients had received androgen ablation therapy as first-line treatment. Prostate cancer tissues obtained by needle biopsies before treatment were immunohistochemically stained for LMW-PTP. Correlations between the baseline clinical factors of age, PSA, Gleason scores, T stage, N stage, extent of disease on bone scan (EOD), LMW-PTP expression and primary hormone therapy efficacy (time to castration-resistant prostate cancer [CRPC]) were investigated by multivariate analysis using the Cox proportional hazard model. Continuous variables were classified as dichotomous. Results: Median age and PSA were 70.0 years and 87.8 ng/mL, respectively. Distribution number of Gleason score 8-10/6-7, T4/≤3, N1/0, and EOD 3-4/0-2 were 30 (66.7%)/15 (33.3%), 13 (28.9%)/32 (71.1%), 25 (55.6%)/20 (44.4%), and 7 (15.5%)/38 (84.5%). Median time to CRPC was 40.2 months. Patients with high LMW-PTP expression had significantly shorter time to CRPC than those with low expression (p = 0.005). Multivariate analysis showed that age (≥70 vs < 70, HR 2.5, 95%CI 0.96-6.32, p = 0.060) and LMW-PTP expression (high vs low; HR 3.3, 95%CI 1.2-8.6, p = 0.02) were significant prognostic biomarkers for predicting time to CRPC. Conclusions: LMW-PTP expression could be a potential biomarker for predicting primary hormone therapy efficacy among men with mHNPC.

OBJECTIVES This study is to elucidate the advantage of laparoscopic radical cystectomy (LRC) over open radical cystectomy (ORC) in an early perioperative period. MATERIALS AND METHODS We investigated the perioperative outcome of the consecutive patients who underwent radical cystectomy at Yokohama City University Hospital. The data of 11 patients who underwent LRC from February 2008 to May 2009 was compared with that of 11 patients who had ORC from October 2006 to April 2009. RESULTS The operative time was significantly longer in LRC (p = 0.00794); the mean operative time for LRC and ORC was 521 and 428 minutes respectively. The blood loss was significantly smaller in LRC (p = 0.0014); the mean volume of bleeding by LRC and ORC was 801 and 2,156 ml respectively. The date of the diet resumption after the operation comes significantly earlier in the case of LRC (p = 0.0142); the mean number of days to the resumption after LRC and ORC were 4.6 and 9.3 respectively. The top C-reactive protein (CRP) figure was significantly lower in LRC (p = 0.0124); the mean of peak CRP after LRC and ORC was 10.8 and 16.6 mg/dl respectively. As for postoperative complications, there were no significant differences between two groups (p = 0.375); the rate of complications occurred after LRC and ORC was 27 and 45% respectively. Also no significant differences were observed as to the number of dissected lymph nodes among these two groups (p = 0.262); the mean number in LRC and ORC was 10.9 and 13.7 respectively. CONCLUSIONS From our investigations it is appropriate to conclude that in an early perioperative period LRC has advantages over ORC: a smaller amount of blooding, an earlier date of the diet resumption, and a lower peak of CRP. LRC is less invasive than ORC, though the former takes longer time for an operation than the latter.

A 73-year-old female was operated with radical nephrectomy and cholecystectomy for renal cell carcinoma and suspected gallstones after 9 courses of sunitinib treatment. Gallbladder specimen showed gallbladder metastasis originating from the renal cell carcinoma. Gallbladder metastasis from renal cell carcinoma is rare. Here, we discuss a case of gallbladder metastasis from renal cell carcinoma.

The molecular mechanisms underlying stress urinary incontinence (SUI) at the tissue level are poorly understood.To study genetic and molecular alterations in the urethras of animals with experimentally induced SUI.Cohort analysis of primiparous 2-month-old female Sprague-Dawley rats with experimentally induced SUI versus those who did not develop SUI in a university research laboratory setting.Rats underwent intravaginal balloon dilation within 24 hours of parturition followed by bilateral ovariectomy one week later. Transvesical cystometry was performed 12 weeks after parturition. Rats were classified as continent (C) or incontinent (I) according to the results of cystometry.The expression of over 22,000 genes in urethral tissue from the two groups was assessed with the use of an oligo microarray. The expression of relevant genes was confirmed by real-time polymerase chain reaction. Protein expression of small mothers against decapentaplegic 2 (Smad2), one of the differentially expressed genes, was extensively studied by immunohistochemistry and Western blot analysis. Regulation of Smad2 activity by transforming growth factor-beta (TGF-beta) was assessed in cultured urethral smooth muscle cells (USMCs).After intervention, 14 (58.3%) rats remained continent and 10 (41.7%) became incontinent. There were significant differences in the expression of 42 urethral genes between continent and incontinent rats. The expression of genes involved in the TGF cellular signaling pathway (Smad2), collagen breakdown (matrix metalloproteinase 13 [Mmp13]), and smooth muscle inhibition (regulator of G-protein signaling 2 [Rgs2]) was significantly increased in the incontinent group. SMAD2 protein expression was significantly upregulated in the incontinent rats. In cultured USMCs, SMAD2 phosphorylation and nuclear translocation increased after Tgf-beta treatment.Genes important in inflammation, collagen breakdown, and smooth muscle inhibition are upregulated in the urethras of female rats with parturition-associated incontinence.

The case was a 40-year-old female. She visited a local doctor with a chief complaint of right side abdominal pain. A right kidney tumor measuring 10 cm in diameter was observed in an abdominal Computed Tomography (CT) scan. Based on the CT image, the possibility of angiomiolipoma (AML) could not be ruled out, but a high maximum standardized uptake value (SUVmax) of 7.8 was observed in a Positron Emission Tomography CT (PET-CT) scan and there was a possibility of malignancy. We therefore performed a transperitoneal right radial nephrectomy. Although adhesion of the tumor to the duodenum and the inferior vena cava was observed, it was possible to perform an excision. The tumor accounted for a large proportion of the excised kidney; the surrounding areas had taken on a cyst-like structure, and the interior comprised grayish brittle tissue exhibiting solid growth. Histologically, gland-like and cyst-like structures composed of cylindrical cuboidal cells and mainly characterized by the solid growth of short fusiform-shaped and oval-shaped basophilic cells were observed, and we believed it was a synovial sarcoma. There were no malignant findings in the adrenal gland. There have been approximately 30 reported cases around the world of synovial sarcoma that developed in the kidney, and we herein report this case with bibliographic considerations.

CMV infection is uncommon in our practice except kidney transplantation. We report a case of cytomegalovirus enterocolitis during standard chemotherapy for testicular cancer. A 31-year-old male presented to his local urologist in January, 2006 with left scrotal swelling. He was diagnosed as left testicular tumor and underwent radical orchiectomy. Pathological examination showed Mixed germ cell tumor (seminoma, yolk sac, embryonal). Four months later, follow-up CT scan revealed multiple metastasis in lung and para aortic lymph nodes. The patient was referred to our institution for further consultation. During 3rd cycle of standard BEP chemotherapy, laboratory data showed severe bone marrow suppression and he subsequently presented prolonged spike fever with watery diarrhea. Despite intensive diagnostic examination including colon fiberscopy, those symptoms remained undiagnosed. One month later, the patient recovered with conservative treatment and serological data showed slightly elevated anti-CMV Ig-M, Ig-G antibody. Immunohistological examination demonstrated CMV positive inclusion bodies in colorectal mucosa. Accordingly the patient's complication was finally diagnosed as CMV enterocolitis. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy. It is necessary to screen for CMV infection in patients with prolonged fever with diarrhea during chemotherapy.

A 45-year-old man complained of a palpable mass in his left abdomen. Computed tomography showed a horseshoe kidney with a Bosniak type II complicated cyst from a left segment. Three years after his initial examination, due to the growing cystic lesion and the compression imposed on the urinary collecting system and surrounding organs, we performed a left heminephrectomy. The diagnosis was mucinous cystadenoma of the kidney. No recurrence was observed 6 months after surgery. The histopathology was unique since the inner surface of the cyst was covered by a mucin-positive columnar epithelium connected to a urothelium, with continuous transition between the two. This suggests that the mucinous tumour may have originated from a sequestered segment of the renal pelvic epithelium in the renal parenchyma.

Background Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for advanced renal cell carcinoma (RCC), but it has been unclear whether the antitumor effect of TKIs depends on the organ where the RCC metastasis is located. We previously reported that the FDG accumulation assessed by FDG PET/CT, was a powerful index for evaluating the biological response to TKI. In this study we investigated the differences in FDG accumulation and the response to TKI as assessed by FDG PET/CT among various organs where RCC were located. Methods A total of 48 patients with advanced RCC treated with a TKI (25 with sunitinib and 23 with sorafenib) were evaluated by FDG PET/CT before and at 1 month after a TKI treatment initiation. The maximum standardized uptake value (SUVmax) of all RCC lesions were measured and analyzed. Results We evaluated 190 RCC lesions. The pretreatment SUVmax values (mean ± SD) were as follows: in the 49 lung metastases, 4.1 ± 3.3; in the 40 bone metastases, 5.4 ± 1.6; in the 37 lymph node metastases, 6.7 ± 2.7; in the 29 abdominal parenchymal organ metastases, 6.6 ± 2.7; in the 26 muscle or soft tissue metastases, 4.4 ± 2.6; and in the nine primary lesions, 8.9 ± 3.9. Significant differences in the SUVmax were revealed between metastases and primary lesions (p = 0.006) and between lung metastases and non-lung metastases (p

We reported a case of primary seminal vesicle cancer, detected by FDG-PET/CT. A 65-year-old man with constipation and appetite loss was admitted to our hospital. An ultrasound examination revealed evidence of bilateral hydronephrosis. He was diagnosed as acute post renal failure, and nephrostomy was done. CT and MRI showed a solid mass in the area of seminal vesicle. He underwent transrectal core biopsy, which histologically showed poorly differentiated adenocarcinoma. Immunohistochemistry showed the tumor to be CA125 positive, CEA positive and CK7 positive but PSA negative. FDG-PET/CT revealed an increased uptake of FDG only in the area of seminal vesicle. Serum CA125 was elevated and PSA stayed within normal limit. Primaly rectal carcinoma was ruled out by colonoscopy. The result of transperineal prostate biopsy was negative. We diagnosed him as suffering from primary seminal vesicle carcinoma. Anti-androgen blockade and radiotherapy to whole pelvis were performed, and serum CA125 level was improved. But, 6 months later serum CA125 re-elevated and 19 months later multiple liver metastases were noted. The patient received two cycles of docetaxel and cisplatin chemotherapy, however he developed pulmonaly embolism and rectal bleeding by tumor invasion and he died of his disease 22 months after the diagnosis.

INTRODUCTION AND OBJECTIVES: Both radical prostatectomy(RP) and brachytherapy(BT) are widely accepted treatments for clinically localized prostate cancer. In the recent literature, a few studies have demonstrated that RP was associated with statistically significant improvement in overall survival. Propensity score matching analysis in nonrandomized studies is to balance the treatment and comparison groups on observed preintervention characteristics. Though it may not be considered an equivalent to randomized trial, it reduces to a minimum the inherent treatment selection bias associated with retrospective data. We analyzed the results of two treatment modalities in Japan. METHODS: From March 2004 to February 2012, a group of 1152 patients with clinically localized prostate cancer treated with I125 BT(789pts) and radical RP(363pts) were identified in our institution. The records of 490 (BT) and 250 (RP) patients with a minimum of 2 years of follow-up were reviewed. Propensity scores were calculated using multivariable logistic regression based on the covariates including patient age, preoperative PSA, biopsy Gleason score, positive cores and clinical T stage. Each cohorts were categorized according to NCCN risk classification and biochemical outcomes plus overall survival were examined. Biochemical failure was defined as nadir PSA level 2ng/ml for BT and PSA 0.2ng/ml for RP. RESULTS: Median follow-up was 51.5 months for BT patients and 59.2 months for RP patients. Overall biochemical failure free survival was 93.8% for BT patients and 64.8% for RP patients. After adjustment of propensity scores, a total of 314 patients (157each) were matched in this study. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival between two cohorts (p 0.159). Regarding biochemical failure free survival, there was statistically significant differences in low risk group (BT:98.2% vs RP:72.3%) between two cohorts (p 0.0011), while no significant differences were observed in intermediate (p 0.1093) and high (p 0.2432) risk group. CONCLUSIONS: Contrary to the reports from U.S. and Europe, our study using propensity score analysis demonstrated no statistically significant difference in overall survival. Despite the difference of biochemical failure definition, BT improved biochemical free survival compared to RP with excellent tumor-control outcomes in Japanese people. These results may arise from the difference of tumor malignancy among races and/or matured brachytherapy procedure.

purpose When retroperitoneoscopic radical nephrectomy for renal cell carcinoma was introduced into our institution, we performed a combined small skin incision method. In this method, a small incision was made to approach the retroperitoneal space prior to setting trockers and thereafter a LAPDISC was placed in the incision to start the retroperitoneoscopic procedure. In this study, we compared the outcomes between the combined small skin incision method ("A method" hereinafter) and the conventional method ("B method" hereinafter). material and methods Among the cases of T1N0M0 suspicious renal cell carcinoma treated at Yokohama City University between May 2003 and June 2009, the A method was performed in 51 cases and the B method was performed in 33 cases. The factors in the outcomes compared between the A and B methods were the duration of procedure, volume of bleeding, volume of transfusion, weight of the specimen, incidence of peritoneal injury, rate of conversion to open surgery, and perioperative complications. results The duration of the procedure was 214.4 ± 46.9 minutes in the A method group and 208.1 ± 36.4 minutes in the B method group (p = 0.518). The volume of bleeding and the weight of the specimen were 105.5 ± 283.2 ml and 335.1 ± 137.4 g in the A method group and 44.8 ± 116 ml (p = 0.247) and 309.2 ± 126 g (p = 0.385) in the B method group. There was no significant difference in all factors analyzed. conclusion The A method would be highly possible to produce stable results, even during the introduction period when the staff and the institution are still unfamiliar with the retroperitoneoscopic surgery.

Introduction: We tested the hypothesis that extended-term (5-week) estrogentherapy would negatively impact voiding function in a postpartum, ovariectomizedrat model.Methods: Immediately after delivery, 30 primiparous Sprague–Dawley rats underwentintravaginal balloon dilation, followed by ovariectomy 1 week later. Cystometry at postpartum week 2 determined normal or abnormal voiding patterns.After randomization, one-half the normal and abnormal voiding ratsreceived 5 weeks of estrogen therapy, while the remainder received placebo. Estrogen effect was determined by repeat cystometry and immunohistochemical analysis of the urethra and vagina.Results: Abnormal voiding increased from 60.0% to 73.3% in the estrogen treated group and declined from 60% to 33% for the placebo group. Rats were then divided into 4 groups for comparison: normal voiding versus placebo(group 1), abnormal voiding versus placebo (group 2), normal voiding versus estrogen (group 3) and abnormal voiding versus estrogen (group 4). Bladdercapacity, leak point pressure and maximum voiding pressure were mostdepressed in group 4. Estrogen treatment was associated with a significant downregulationof α1A and α1D-adrenoceptors in the urethral submucosa but an upregulationof nNOS in the urethral smooth muscle.Conclusion: Extended-term estrogen therapy in a rat model of simulated birth trauma and ovariectomy resulted in a higher rate of incontinence. Immunohistochemical examination demonstrated significant downregulationof urethral α1A- and α1D-adrenoceptors and upregulation of neuronal nitric oxidesynthase (nNOS) in the urethra of estrogen-treated groups. These studies question the use of hormone replacement therapy in the treatment of postmenopausalincontinence.

Introduction Advances in neurobiology have led to a surge of clinical interest in the development of protective and regenerative neuromodulatory strategies, as surgical therapies for prostate cancer often result in neuronal damage and debilitating loss of sexual function. Aim To investigate the dose-dependent efficacy of FK1706, a nonimmunosuppressant immunophilin ligand, for the recovery of erectile function following bilateral cavernous nerve crush injury in the rat. Main Outcome Measures Recovery of erectile function was assessed by cavernous nerve electrostimulation and reported as maximal increase of intracavernous pressure (ICP) and area under the curve (AUC). Changes in animal weights, percentage completion of treatment course, and survival were compared between groups. Methods Thirty-five Sprague–Dawley male rats were randomly divided into five equal groups: seven animals received a sham operation, whereas 28 animals underwent bilateral cavernous nerve crush injury, followed by subcutaneous injection of vehicle alone (1.0 mL/kg), or low (0.1 mg/kg), medium (0.32 mg/kg), or high dose (1.0 mg/kg) FK1706 5 days per week for 8 weeks. Results Erectile dysfunction did not occur in the sham group (mean maximal ICP increase of 100.8 ± 6.3 cmH 2 O), whereas nerve injury and vehicle treatment produced a significant reduction in ICP response to 34.4 ± 12.8 cmH 2 O. The mean ICP increase for high-dose FK106 treatment was 73.9 ± 6.3 cmH 2 O ( P 2 O and 56.9 ± 8.3 for low and medium doses ( P > 0.05). Similar stepwise findings were observed using AUC data. No significant maximal aortic blood pressure or weight differences occurred between groups and all animals completed treatment. Conclusion High-dose subcutaneous FK1706 therapy promoted recovery of erectile function following bilateral cavernous nerve crush injury in the rat. No significant differences between groups were observed for changes in weight, and the 8-week treatment course was completed for all animals. Bella AJ, Hayashi N, Carrion RE, Price R, and Lue TF. FK1706 enhances the recovery of erectile function following bilateral cavernous nerve crush injury in the rat.

We investigated the neurotrophic effect of FK1706 on erectile recovery following bilateral cavernous nerve crush injury in a rat model.A total of 28 male Sprague-Dawley rats were randomly divided into 4 equal groups. Seven animals underwent sham operation and subcutaneous vehicle injection, whereas 21 underwent bilateral cavernous nerve crush injury followed by vehicle injection alone, or by low (0.1 mg/kg) or high (1.0 mg/kg) dose FK1706 treatment. Injections were continued 5 days weekly for 8 weeks. Erectile function was then assessed by cavernous nerve electrostimulation and penile tissue was evaluated immunohistochemically.No erectile dysfunction was identified in the sham treated group (mean maximal intracavernous pressure +/- SEM 106.8 +/- 6.4 cm H(2)O), whereas nerve injury significantly decreased ICP to 17.9 +/- 7.0 cm H(2)O. FK1706 facilitated neural and erectile recovery in a concentration dependent manner with a mean ICP in the high dose FK treatment group of 80.1 +/- 7.8 cm H(2)O compared with 44.1 +/- 12.9 cm H(2)O in the low dose group. Similar stepwise findings were observed using mean area under the curve data. Sham treated animals showed regular axon sizes and shapes with homogenous GAP-43 and neurofilament staining, whereas injured axons showed irregular shapes, sizes and staining patterns. FK1706 treatment restored axon shape and staining patterns. Injury significantly decreased nicotinamide adenine dinucleotide phosphate staining and FK1706 treatment showed a nonsignificant trend toward increased staining.Bilateral cavernous nerve crush causes reproducible erectile dysfunction, consistent with prior experiments. High dose subcutaneous FK1706 therapy promotes significant neuroregeneration and erectile function recovery.

e16078 Background: Our previous report indicated that angiotensin II receptor blockers (ARB) have the potential to decrease or stabilize PSA level of patients with CRPC and inhibit the occurrence o...

e16098 Background: For patients with advanced prostate cancer, long-term treatment of androgen deprivation has been conventionally performed. Among the adverse events such as hormonal therapy, bone fracture due to osteoporosis or metastatsis is one of indispensable events. We assessed the frequency of bone fractures in Japanese patients received hormonal therapy. Methods: Between 2000 and 2010, 1,108 Japanese patients were treated with hormonal therapy including GnRH agonist plus anti-androgens or GnRH agonist alone at Yokohama City University Hospital. Of those patients, 48 patients (4.3%) had bone fractures during their treatment. In this retrospective study, we examined the association of bone fracture with the long-term hormonal therapy by investigating the duration of hormonal therapy, fracture sites, and the occurrence of fracture in castration resistant prostate cancer (CRPC) patients. Results: The median age of the patients with fracture was 77 (60-85) years; the median duration from the start of hormonal therapy to fracture was 29.4 (5.4-110.4) months. Eight patients with CRPC had pathological fractures at bone metastases. With respect of fracture sites, 22 patients (46%) had spinal fractures and 10 patients (21%) had fracture of lower legs. Of 8 CRPC patients, 7 patients had spinal fracture after long-term hormonal therapy (median: 38.6 months, range: 15.7-99.1 months). Conclusions: Japanese patients with prostate cancer treated with hormonal therapy have lower risk for bone fracture compared with those in western countries and USA, and interestingly, it is recognized that vertebral body is vulnerable to fracture in Japanese, especially in CRPC patients treated for long-term hormonal therapy. Because bone fracture in patients with prostate cancer endanger their prognosis, the bone management how to prevent bone fracture is very important during hormonal therapy. For the purpose of it, more detailed analysis in this retrospective study should be required.

PURPOSE: For patients with metastatic castration-resistant prostatic cancer (mCRPC), docetaxel plus prednisone leads to superior survival and a higher response rate compared with mitoxantrone plus prednisone. We analyzed the efficacy of long-term treatment with ≥10 cycles of docetaxel, and validated the risk group classification in predicting overall survival (OS) in Japanese patients with mCRPC. PATIENTS AND METHODS: Fifty-two patients with mCRPC were administered 55 mg/m(2) docetaxel and 8 mg dexamethasone, every 3 or 4 weeks, simultaneously with hormonal therapy and daily oral dexamethasone. They were divided into two groups, short-term (9 or fewer cycles) and long-term (10 or more cycles). Four risk factors including the presence of anemia, bone metastases, significant pain and visceral metastases were utilized for the risk group classification. RESULTS: Fourteen patients (27%) had an elevation of PSA in spite of docetaxel treatment, while 23 patients (44%) had a decline in PSA level, including 9 patients (17%) whose PSA level declined by ≥50%. The median duration of OS after the initiation of this therapy was 11.2 months in the short-term group and 28.5 months in the long-term group. The good risk group showed a significant difference in OS compared with the intermediate and poor risk groups (P