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The TITAN study is a randomized, double-blind, placebo-controlled, multinational trial that evaluated apalutamide with androgen deprivation therapy in patients with metastatic castration-sensitive prostate cancer. At the first interim analysis in the Japanese subpopulation (median follow-up 25.7 months), there was an improvement in overall survival and radiological progression-free survival with apalutamide versus placebo. Here, we report the final analysis results for the Japanese subpopulation.Patients were randomized 1:1 to receive apalutamide 240 mg or placebo. After the first interim analysis, protocol treatment was unblinded, and crossover was allowed. Efficacy and safety were evaluated in the preplanned, event-driven final analysis.Fifty-one patients were Japanese (apalutamide n = 28; placebo n = 23). After a median follow-up of 46.0 months, the median overall survival was not reached neither in the apalutamide nor the placebo group; the hazard ratio was 0.45, favoring apalutamide, which was consistent with the overall population. Hazard ratios for time to cytotoxic chemotherapy (0.39), time to pain progression (0.87), and time to chronic opioid use (0.82) also favored apalutamide and were comparable with those of the overall population. Time to prostate-specific antigen progression and progression-free survival 2, respectively, was favored in the apalutamide group (0.21 and 0.44). Apalutamide was associated with higher incidences of rash and fracture in the Japanese subpopulation compared with the overall population.The efficacy of apalutamide with androgen deprivation therapy in Japanese patients was consistent with efficacy demonstrated in the overall population. No new safety concerns emerged with long-term follow-up.

Summary Background PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. Methods KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m2] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m2] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study is completed and is no longer enrolling patients, and is registered at ClinicalTrials.gov , number NCT02853305 . Findings Between Oct 19, 2016 and June 29, 2018, 1010 patients were enrolled and allocated to receive pembrolizumab plus chemotherapy (n=351), pembrolizumab monotherapy (n=307), or chemotherapy alone (n=352). Median follow-up was 31·7 months (IQR 27·7–36·0). Pembrolizumab plus chemotherapy versus chemotherapy did not significantly improve progression-free survival, with a median progression-free survival of 8·3 months (95% CI 7·5–8·5) in the pembrolizumab plus chemotherapy group versus 7·1 months (6·4–7·9) in the chemotherapy group (hazard ratio [HR] 0·78, 95% CI 0·65–0·93; p=0·0033), or overall survival, with a median overall survival of 17·0 months (14·5–19·5) in the pembrolizumab plus chemotherapy group versus 14·3 months (12·3–16·7) in the chemotherapy group (0·86, 0·72–1·02; p=0·0407). No further formal statistical hypothesis testing was done. In analyses of overall survival with pembrolizumab versus chemotherapy (now exploratory based on hierarchical statistical testing), overall survival was similar between these treatment groups, both in the total population (15·6 months [95% CI 12·1–17·9] with pembrolizumab vs 14·3 months [12·3–16·7] with chemotherapy; HR 0·92, 95% CI 0·77–1·11) and the population with CPS of at least 10 (16·1 months [13·6–19·9] with pembrolizumab vs 15·2 months [11·6–23·3] with chemotherapy; 1·01, 0·77–1·32). The most common grade 3 or 4 adverse event attributed to study treatment was anaemia with pembrolizumab plus chemotherapy (104 [30%] of 349 patients) or chemotherapy alone (112 [33%] of 342 patients), and diarrhoea, fatigue, and hyponatraemia (each affecting four [1%] of 302 patients) with pembrolizumab alone. Six (1%) of 1010 patients died due to an adverse event attributed to study treatment; two patients in each treatment group. One each occurred due to cardiac arrest and device-related sepsis in the pembrolizumab plus chemotherapy group, one each due to cardiac failure and malignant neoplasm progression in the pembrolizumab group, and one each due to myocardial infarction and ischaemic colitis in the chemotherapy group. Interpretation The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma. Funding Merck Sharp and Dohme, a subsidiary of Merck, Kenilworth, NJ, USA.

Background We evaluated patient‐reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca). Methods A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT‐P questionnaires and EPIC urinary, bowel, and sexual bother subscales. Results The FACT‐P total scores were significantly better (p, The quality of life was significantly favorable in intermittent androgen deprivation therapy (ADT) on FACT‐P total score, physical well‐being and functional score than those is continuous ADT in adjuvant hormone therapy for locally advanced prostate cancer.

Background/aim Curcumin is a natural compound of turmeric, which inhibits prostate cancer cell proliferation. This study examined whether treatment of LNCaP prostate cancer cells with the combination of curcumin and dutasteride, a 5-alpha reductase inhibitor, affect proliferation and the amount of testosterone and dihydrotestosterone. Materials and methods LNCaP Cells were incubated with curcumin or the combination of curcumin and dutasteride and cell proliferation was measured at 72 h. LC-MS/MS was used to determine testosterone and dihydrotestosterone concentrations in prostate cancer cells. Results Curcumin combined with dutasteride suppressed proliferation and affected apoptosis of LNCaP cells. The combination of curcumin and dutasteride also reduced the amount of testosterone and dihydrotestosterone in LNCaP cells. The secretion of prostate-specific antigen was inhibited by the combination treatment in a dose-dependent manner. Conclusion Treatment with the combination of curcumin and dutasteride may interfere with the intra-tumoral androgen activity.

Aim The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. Methods Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (, This study investigated efficacy and safety of abiraterone acetate plus prednisolone in chemotherapy-naive early metastatic castration-resistant prostate cancer patients. Abiraterone acetate plus prednisolone proved to be a beneficial treatment option with regards to its higher response rate.

A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-naïve patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined with docetaxel and dexamethasone (n = 25) or placebo with docetaxel and dexamethasone (n = 26). The primary endpoint was the difference in prostate-specific antigen (PSA) decline between each treatment. The rates of > 50% PSA decline in the two arms were similar (56.5% versus 53.8%; P = 0.851). Human leukocyte antigen (HLA)-matched peptide-specific immunoglobulin G (P = 0.018) and CTL (P = 0.007) responses in the KRM-20 arm significantly increased after treatment. The addition of KRM-20 did not increase toxicity. There were no between-group differences in progression-free or overall survival (OS). The addition of KRM-20 was safe, and similar PSA decline and HLA-matched peptide-specific CTL and IgG responses increased in combination with docetaxel and dexamethasone in CRPC patients. Subgroup analysis suggested that this treatment is favorable for CRPC patients with ≥ 26% lymphocytes or PSA levels of

ObjectivesWith novel antiandrogen treatments of varying clinical benefits and risks becoming available, this study investigates how patients with castration-resistant prostate cancer (CRPC) value differences in treatment characteristics.DesignCross-sectional observational study.SettingA discrete choice experiment was conducted. Patients chose between two hypothetical non-metastatic CRPC (nmCRPC) treatments defined by six attributes: risk of fatigue, falls or fracture, cognitive impairment, hypertension, rashes as side effects to treatment and extension of time until cancer-related pain occurs.ParticipantsA total of 137 adult male patients with CRPC with no prior experience with chemotherapy and with Eastern Cooperative Oncology Group status 0–1 were recruited. Patients were excluded if they participated in an investigational programme outside of routine clinical practice, had a clinically relevant medical or psychiatric condition, or diagnosis of visceral/other metastases not related to the prostate, or were otherwise deemed ineligible by the referring physician.Primary outcome measuresRelative preference weights and relative importance of the attributes was estimated by hierarchical Bayesian logistic regression.ResultsAmong the treatment attributes, ‘risk of cognitive impairment as a side effect of treatment’ was the most important attribute (relative importance (RI) (95% CI): 27.47% (24.80% to 30.14%)), followed by ‘extension of time until cancer-related pain occurs’ (RI (95% CI): 17.87% (15.49% to 20.25%)) and the ‘risk of falls or fracture’ (RI (95% CI): 15.99% (14.73% to 17.25%)). The ‘risk of hypertension as a side effect of treatment’ (RI (95% CI): 13.77% (12.73% to 14.81%)) had similar RI as ‘risk of rashes as a side effect of treatment’ (RI (95% CI): 13.17% (12.15% to 14.19%)), followed by the ‘risk of fatigue as a side effect of treatment’ (RI (95% CI): 11.74% (10.75% to 12.73%)).ConclusionsPatients consider the risk of cognitive impairment as a side effect of treatment as the most important attribute in nmCRPC, followed by the extension of time until cancer-related pain occurs, and the risk of falls and fracture. These features should be considered in treatment decision making for nmCRPC in Japan.

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma.Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24.Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted.Funding: AstraZeneca.

First‑line chemotherapy for men with metastatic castration‑resistant prostate cancer (mCRPC) has been employed to improve overall survival (OS) and progression‑free survival (PFS). However, several new agents for CRPC after first‑line chemotherapy prolonged survival by only a few months. To develop a new treatment modality, we conducted a phase III randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)‑A24‑positive patients with castration‑resistant prostate cancer (CRPC) for whom docetaxel chemotherapy failed. This randomized, double‑blind, placebo‑controlled, phase III trial was carried out at 68 medical centers in Japan. Patients were randomly assigned at a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on pre‑existing peptide‑specific immunoglobulin G levels or the corresponding placebo were subcutaneously injected in 6 doses weekly and then bi‑weekly following the maximum of 30 doses until disease progression. The primary end‑point was overall survival (OS). Efficacy analyses were performed by the full analysis set. Between August 2013 and April 2016, 310 patients were randomly assigned, and 306 patients were analyzed. Baseline characteristics were balanced between groups. The estimated median OS was 16.1 months [95% confidence interval (CI), 13‑18.2] with PPV and 16.9 months (95% CI, 13.1‑20.4) with placebo [hazard ratio (HR), 1.04, 95% CI, 0.80‑1.37; P=0.77]. Grade ≥3 adverse events were observed in 41% of both groups. The analysis of treatment arm effects among subgroups revealed lower HRs for OS in favor of the PPV arm in patients with

Objective To evaluate the efficacy and safety of apalutamide + androgen deprivation therapy versus androgen deprivation therapy alone in Japanese patients with metastatic castration-sensitive prostate cancer from the phase 3, randomized, global TITAN study. Methods Men with metastatic castration-sensitive prostate cancer randomly (1:1) received 240 mg apalutamide + androgen deprivation therapy or matching placebo + androgen deprivation therapy. The primary efficacy endpoints were radiographic progression-free survival and overall survival. Secondary efficacy endpoints were time to cytotoxic chemotherapy, pain progression, chronic opioid use, and skeletal-related events. Safety was also assessed. Results Of the 1052 patients included in the TITAN study, 51 (4.85%) were Japanese (apalutamide group, n = 28; placebo group, n = 23). In all, 81.8% of patients in the apalutamide and 71.8% in the placebo group did not experience radiographic progression or death, and the hazard ratio for radiographic progression-free survival favored treatment with apalutamide (hazard ratio 0.712, 95% confidence interval 0.205-2.466; P = 0.59). At 24 months, 85.7% of patients in the apalutamide group and 81.5% in the placebo group were alive, and the hazard ratio for overall survival favored apalutamide (hazard ratio 0.840, 95% confidence interval 0.210-3.361; P = 0.805). In the interim analysis, the median radiographic progression-free survival and overall survival were not reached in the apalutamide group and time to cytotoxic chemotherapy was delayed following apalutamide treatment. The safety profile of apalutamide in the Japanese subpopulation was comparable with that of the global population, except for skin rash. Conclusions The results of the present analyses suggest that apalutamide + androgen deprivation therapy in Japanese patients had favorable efficacy compared with androgen deprivation therapy alone, and these findings are comparable to those in the overall population. Apalutamide + androgen deprivation therapy can be considered as one of the therapeutic options for a broad spectrum of metastatic castration-sensitive prostate cancer regardless of prior treatment and disease extent in Japanese patients.

Background To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). Methods A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. Results The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). Conclusions Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

The PROPHET (Prostate Cancer: Prostate Health Index Trial) is a prospective study to clarify the diagnostic impact of laboratory based and prostate volume adjusted p2PSA ([-2] proenzyme prostate specific antigen) related indexes on prostate cancer and clinically significant prostate cancer with prostate specific antigen less than 10 ng/ml.Between April 2015 and March 2017, 421 men 50 to 79 years old in the prostate specific antigen range above age specific cutoffs and below 10 ng/ml were registered in the PROPHET. We investigated the diagnostic impacts of various clinical laboratory based free prostate specific antigen related and p2PSA related indexes on any grade and high Gleason grade group prostate cancer.Of the 363 eligible participants 179, 141 and 80 were diagnosed with any grade, and Gleason Grade Group 2-5 and 3-5 prostate cancer, respectively. The AUC-ROCs distinguishing nonprostate cancer vs prostate cancer, nonprostate cancer plus low Gleason Grade Group and low volume vs remaining prostate cancer with a higher Gleason Grade group or a higher volume on the PHI (Prostate Health Index) were significantly superior to the AUC-ROCs of prostate specific antigen and free-to-total prostate specific antigen. At 90% sensitivity in all investigated p2PSA related indexes the false-positive rate was superior to that of prostate specific antigen and free-to-total prostate specific antigen in any group comparison in terms of the Gleason Grade Group and positive biopsy cores. In 35% to 42% of men without prostate cancer and/or those with less aggressive prostate cancer the PHI would avoid unnecessary biopsy.Laboratory based p2PSA related indexes were significantly superior for detecting clinically significant prostate cancer compared to free-to-total prostate specific antigen. The indexes those would avoid up to 42% of prostate biopsies in men without aggressive cancer while maintaining 90% sensitivity.

We describe the first case of a 25-year-old patient with gender identity disorder (GID) who underwent cryopreservation of sperm prior to male-to-female (MTF) sex reassignment surgery in Japan. The patient wanted to freeze sperm to keep open the option of conceiving a child in the future. The ethics committee of our institution discussed the case and officially approved cryopreservation of sperm before sex reassignment surgery. Compared with foreign countries, sperm cryopreservation of GID is not recognized and guidelines have yet been published in Japan. Here, we report sperm cryopreservation for MTF before sex reassignment surgery.

Purpose: The prognosis of platinum-based chemotherapy–resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity. Experimental Design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity. Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4–1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34–0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5–12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8–6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions. Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results. Clin Cancer Res; 22(1); 54–60. ©2015 AACR.

The heterogeneity expression of tumor-associated antigens (TAA) and variability of human T cell repertoire suggest that effective cancer vaccine requires induction of a wide breadth of cytotoxic T lymphocyte (CTL) specificities. This can be achieved with vaccines targeting multiple TAA. We evaluated the safety and immune dynamics of a cancer vaccine consisting of 20 mixed peptides (KRM-20) designed to induce CTLs against 12 different TAA in patients with castration-resistant prostate cancer (CRPC). Patients received each of three different randomly assigned doses of KRM-20 (6, 20, or 60 mg) once a week for 6 weeks. KRM-20 was applicable for patients with positive human leukocyte antigen (HLA) A2, A3, A11, A24, A26, A31 or A33 alleles, which cover the majority of the global population. To evaluate the minimum immunological effective dose (MIED), peptide-specific CTL and immunoglobulin G (IgG) responses, and immune suppressive subsets were evaluated during the vaccination. Total of 17 patients was enrolled. No serious adverse drug reactions were encountered. The MIED of KRM-20 in CTL or IgG response calculated by logistic regression model was set as 16 or 1.6 mg, respectively. The frequency of immune suppressive subsets was fewer in the 20 mg cohort than that in 6 or 60 mg cohort. Clinical responses determined by prostate-specific antigen levels were two partial responses (from the 20 mg cohort), five no changes and ten progressive diseases. Twenty milligrams of KRM-20 could be recommended for further studies because of the safety and ability to augment CTL activity.

A 71-year-old man was referred to our department due to inflammation in the right scrotum. A tumor in the right spermatic cord was suspected on palpation, and abdominal computed tomography revealed a 4-cm mass in the tail of the pancreas and a low-density lesion in the liver segment 6. In addition, the patient's serum level of CA19-9 was high, at 135.7 U/mi. We referred the patient to our institution's Department of Gastroenterology, where he was diagnosed as having a liver metastasis from pancreatic cancer. Despite three courses of gemcitabine and erlotinib combination therapy for pancreatic cancer, his serum level of CA19-9 increased to 744.0 U/m, indicating no response to chemotherapy. Because uncontrollable pain developed in the right scrotum and right inguinal area during the course of treatment, inguinal orchiectomy was performed for pain management and pathological diagnosis. Careful examination revealed a hard, whitish tumor occupying the right spermatic cord and extending from the epididymis to the internal inguinal ring. Because a palpable mass in the peritoneum near the internal inguinal ring was detected, part of the peritoneum was resected concurrently. Pathological findings were remarkable with spermatic cord metastasis and peritoneal dissemination from pancreatic cancer. Pain subsided postoperatively and no analgesics were needed. Pancreatic cancer accompanied by spermatic cord metastasis and peritoneal dissemination is extremely rare. Surgical resection in the present case provided effective treatment of the intractable pain due to spermatic cord metastasis. To the best of our knowledge, this is only the 14th case reported in Japan of spermatic cord metastasis from pancreatic cancer as a primary cancer.

Objective: Overproduction of reactive oxygen species results in oxidative stress, a deleterious process that damages cell structure as well as lipids, proteins, and DNA. Oxidative stress plays a major role in various human diseases, such as oligoasthenozoospermia syndrome. Materials and methods: We evaluated the effectiveness of antioxidant co-supplementation therapy using vitamin C, vitamin E, and coenzyme Q10 in men with oligoasthenozoospermia. Overall, 169 infertile men with oligoasthenozoospermia received antioxidant therapy with 80 mg/day vitamin C, 40 mg/day vitamin E, and 120 mg/day coenzyme Q10. We evaluated spermiogram parameters at baseline and at 3 and 6 months of follow-up. Results: Significant improvements were evident in sperm concentration and motility following coenzyme Q10 therapy. Treatment resulted in 48 (28.4%) partner pregnancies, of which 16 (9.5%) were spontaneous. Significant improvements in sperm cell concentration and sperm motility were observed after 3 and 6 months of treatment. Conclusions: Vitamin C, vitamin E, and coenzyme Q10 supplementation resulted in a significant improvement in certain semen parameters. However, further studies are needed to empirically determine the effect of supplementation on pregnancy rate.

When sperm cannot be retrieved from the testes of patients with azoospermia due to spermatogenic dysfunction (ASD), there is no rational way for the patient to become a biological father. We investigated the possibility of inducing spermatogenesis in such patients by hormonal therapy with recombinant human follicle-stimulating hormone (rhFSH) alone. Twenty-six ASD patients who could not obtain spermatozoa by microdissection testicular sperm extraction (micro-TESE) were confirmed to have arrested spermatogenesis at the late stage of maturation arrest. They were subsequently treated with 75-150 IU two times/week rhFSH alone for 12 months. The primary endpoint was the appearance of sperm in ejaculate, and we followed the patients to determine the outcome of inseminating their partners. After rhFSH treatment, mature spermatozoa were found in the ejaculate in five of 26 (19.2%) patients, all of whom showed histology of non-uniform type maturation arrest. Intracytoplasmic sperm injection of the mature spermatozoa resulted in two ongoing clinical pregnancies (insemination success rate, 40.0%). Recombinant human follicle-stimulating hormone treatment can be used as an advanced assisted reproductive technology to improve spermatogenesis in some azoospermic patients with maturation arrest of spermatogenesis and is a potential treatment option after unsuccessful micro-TESE.

Estrogen exposure has been linked to a risk of testicular germ cell cancers, although predominantly in animal studies. In the human testis, estrogen receptor beta (ER-β) mediates the physiological action of estrogen. We describe a case of a 30-year-old transgender woman (male-to-female [MtF]) with gender dysphoria who developed a mature testicular teratoma with positive estrogen receptor beta expression while receiving cross-sex hormonal therapy with estradiol and progesterone. Although the presence of hormone receptors does not always imply that hormones have played a role in the development of the tumor, a contribution of exposure to exogenous estrogen in this case cannot be ruled out.

Advances in multimodal treatment have led to dramatic improvement in cancer treatment outcomes. It is now necessary to consider cancer patients' holistic quality of life. Fertility preservation is the top concern for cancer survivors of reproductive age. Sperm cryopreservation before treatment is recommended for postpubescent men, but many patients lose fertility without having been informed about options for fertility preservation. To determine how sperm cryopreservation is perceived and practiced in Japan, we surveyed hematologists who often treat young males. A questionnaire about sperm cryopreservation was sent to 45 major hematology institutions. A total of 22 institutions responded before the deadline. All institutions but one responded that they felt sperm cryopreservation is necessary. Only 15 institutions responded that they inform patients about sperm cryopreservation, and 12 institutions responded that they perform sperm cryopreservation before chemotherapy. A total of 213 young males started their first course of chemotherapy during the survey period, of whom 61 (28.6%) had their sperm cryopreserved. Although almost all hematologists stated that sperm cryopreservation is necessary for fertility preservation, not all institutions informed patients about it. Our findings indicate that, to promote fertility preservation in Japan, it will be necessary to systematize sperm cryopreservation and build inter-hospital networks.

Objectives Recently the incidence of intravaginal ejaculatory dysfunction is increasing among infertile couples in Japan. Some unusual ways of masturbation and psychogenic issues were reported to cause this disorder. Patients, who had done masturbation in an unusual way for long time since their adolescence, were difficult to gain normal intravaginal ejaculation by the behavior therapy which was used for erectile dysfunction. We, therefore, used a masturbation aid (TENGA) for rehabilitation of ejaculation to overcome this condition. Patients and methods From January, 2010 through March, 2011, a total of 16 patients with intravaginal ejaculatory dysfunction underwent rehabilitation of ejaculation using TENGA. Patients' satisfaction and achievement of intravaginal ejaculation were evaluated by the questionnaire. Results Twelve patients (75%) could ejaculate in the masturbation aid (TENGA). Five patients (31%) succeeded to ejaculate in the partner's vagina after rehabilitation. Conclusions A masturbation aid (TENGA) was a useful tool to correct the way of masturbation and achieve normal intravaginal ejaculation. This masturbation aid can be one of the effective options for the treatment of intravaginal ejaculatory dysfunction.

PURPOSE I observed bladder and urethral morphology and lumen by making a virtual endoscopy (VE) of the bladder and a urethra for patients with lower urinary tract symptoms. I have herein reported the procedures to use this model to evaluate the condition of patients more precisely. PATIENTS AND METHODS Of those referred for investigation of lower urinary tract symptoms, subjects were 22 boys (5-13 years old, mean 9) in whom voiding cystourethrography (VCUG) was suspected for urethral obstruction between March, 2009 and October, 2010. Eleven of these 22 cases were extracted at random and underwent voiding computed tomography (VCT). Except one dropped out, the 21 cases were assigned to a VCT/VCUG combination group or a VCUG-single group. We confirmed the two groups, the rate of agreement of imaging views and cystourethroscopy (CS) views, and the effectiveness of endoscopic operation. RESULT I made the following imaging diagnoses in the VCT/VCUG combination group: congenital obstructive posterior urethral membrane (COPUM), n = 7; Cobb's collar, n = 1; and COPUM and Cobb's collar combined, n = 3. In contrast, in the VCUG-single group, I diagnosed COPUM, n = 5; bulbar region urethral stricture, n = 2; posterior urethral expansion, n = 2; and bladder form abnormality, n = 1. The rate of agreement between preoperative diagnosis and CS views on imaging was 72.7% in the VCT/VCUG combination group, and 33.3% in the VCUG-single group. All patients underwent transurethral incision (TUI) of the urethral obstruction. In the VCT/VCUG combination group, effectiveness of the TUI was assessed as good in 2 cases and moderate in 6 cases giving an overall effectiveness rate (good + moderate) of 72.7%. In the VCUG-single group, effectiveness was rated as moderate in 5 cases (overall effectiveness rate = 50%). CONCLUSION I developed a method of VE for lower urinary tract obstruction of children and examined the effectiveness. This method was found to be more effective than conventional urinary tract imaging. With the developments in the equipment, this method may in future be useful as an adjunct to CS and urodynamic studies.

Objectives To explore an optimal combination of sampling sites to detect prostate cancer in a repeat biopsy setting. Methods A transrectal ultrasound-guided systematic three-dimensional 26-core biopsy (3D26PBx), a combination of transrectal 12 and transperineal 14 core biopsies, was performed in 235 Japanese men with prior negative biopsy. Using recursive partitioning, we evaluated cancer detection of all possible combinations of sampling sites and selected the combination that provides the highest cancer detection rate at a given number of biopsy cores. Results Prostate cancer was detected in 87 of the 235 (37%) men. The 3D26PBx improved cancer detection by 89% relative to the conventional transrectal sextant biopsy. Neither Gleason score nor percentage of Gleason 4/5 cancers differed between cancers with and without positive cores within the transrectal sextant-sampling sites. A three-dimensional combination of transrectal and transperineal approaches outperformed either transrectal or transperineal approach alone. Recursive partitioning revealed that a three-dimensional 16-core (transrectal eight cores plus transperineal eight cores) biopsy could detect all the cancers with the minimum number of cores. Conclusions We propose a three-dimensional combination of transrectal eight cores taken from the far lateral peripheral zone and the parasagittal base, and transperineal eight cores taken from the anterior and posterior apex and the transition zone as an optimal set of sampling sites for repeat biopsy.

We evaluated the effectiveness of antioxidant co-supplementation therapy using Larginine and Pycnogenol® in Japanese men with oligoasthenozoospermia and mild erectile dysfunction (ED). A total of forty-seven adult males with oligoasthenoteratozoospermia syndrome (OAT) were eligible for enrollment. The effectiveness of supplementation with a combination of L-arginine 690 mg and French maritime pine bark extract (Pycnogenol®) 60mg for OAT and ED was investigated. The sperm concentration was enhanced significantly after treatment 2 and 4 months (11.79 ± 9.86 to 21.22 ± 28.17 and 20.15 ± 23.99 × 106/ml). Significant improvements in the International Index of Erectile Function (IIEF) were observed in the total score of IIEF (57.69 ± 11.04 to 59.43 ± 12.57) and domain of Orgasmic Function (9.01 ± 1.92 to 9.34 ± 1.66) after 4 months of treatment. L-arginine acts to increase the production of nitric oxide and Pycnogenol® activates the endothelial nitric oxide synthase and it is a potent antioxidant and inhibitor of inducible nitric oxide synthase. This study suggests that the combination of Pycnogenol® and L-arginine (Edicare®) is helpful for infertile men to ameliorate simultaneously quality of sperms as well as erectile functions.

Testicular cancer(TC)is the most common and curable cancer affecting men of reproductive age. Successful treatment approaches have resulted in longer life expectancy in TC survivors. The most frequently used treatment for TC is a combination of inguinal orchiectomy, and either radiotherapy or cisplatin-based chemotherapy. In many TC patients, sperm quality is already abnormal and there may even be a lack of viable spermatozoa at the time of diagnosis. Therefore, the effect of cancer treatment on fertility is a potentially significant issue. Fertility preservation in these men has become essential and needs to be discussed prior to the start of cancer treatment. The only currently established fertility preservation method is the cryopreservation of sperm before therapy. For most patients seeking cryopreservation, the semen sample is collected via masturbation. If the patient is unable to ejaculate for any reason, other techniques such as vibratory stimulation and electroejaculation can be performed. In azoospermic or severely oligozoospermic patients, testicular sperm extraction at the time of the inguinal orchiectomy is a useful technique for obtaining spermatozoa before cytotoxic therapy. We herein present an overview of the current topics on fertility in TC patients, including the effects of surgery, chemotherapy, and radiation therapy. We also describe the strategy for fertility preservation in these patients.

Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34-45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

OBJECTIVES To examine the possibility of nerve grafting to repair the sympathetic pathway projecting to the prostate, as contraction of the prostate is known to be controlled by the sympathetic pathway via the hypogastric nerve (HGN), and injuries to the pathway cause significant disturbances in prostatic secretion. MATERIALS AND METHODS In six dogs both of the HGNs were partly removed and immediately repaired with an autologous nerve graft. The left HGN was repaired with a colonic (autonomic) nerve graft and the right with a genitofemoral (somatic) nerve graft. Twenty months after surgery the reconstruction of the sympathetic pathway was assessed by measuring contraction of the prostate after stimulating the lumbar splanchnic nerves (LSNs). RESULTS Nine of the 17 right LSNs stimulated elicited prostatic contractions. After transecting the left HGN five of these nine responses were restored. Seven of the 11 left LSNs stimulated elicited prostatic contractions; after transection of the left HGN four of these seven responses were preserved. CONCLUSION The sympathetic pathways via the HGN to the canine prostate can be reconstructed by nerve grafting, regardless of the use of autonomic or somatic nerve grafts, and the cross-innervation mechanism from the LSN to the prostate can also be repaired.

To investigate the feasibility of preoperative low-dose chemoradiotherapy, 50 patients with localized muscle-invasive bladder cancer (T2-T4) were treated with concurrent cisplatin (100 mg/body x 2 courses) and pelvic irradiation (40 Gy). Among 20 patients (40%) who achieved clinical complete regression, 11 with solitary tumor underwent partial cystectomy because of advanced age, poor condition of the patients, or a reluctance to have radical surgery. Radical cystectomy was carried out in the remaining 39 cases (complete regression 9, partial regression 30). Pathologic T0 response (no residual tumor) was achieved in 18 (36%) of all the cases. Median follow-up was 19 months (range 2-59 months). Estimated 3-year disease-free survival was 75% for all patients and 100% for T0 responders. Local recurrence (2 patients) or distant metastasis (6 patients) developed in 8 of 32 patients with pathologic persistent tumor. All of the 11 patients (9 with T0 response and 2 with a small residual tumor nest) who underwent partial cystectomy were recurrence free for observation periods up to 59 months. Low-dose chemoradiotherapy is as effective as other neoadjuvant protocols and is applicable to high-risk patients. The bladder can be preserved by partial cystectomy in selected cases with clinical complete regression.

BACKGROUND For small, incidentally discovered renal cell carcinoma, partial nephrectomy is becoming more widely accepted as an alternative to radical nephrectomy and the need for minimally invasive approach is increasing. METHODS We carried out endoscopic minilaparotomy partial nephrectomy in seven cases of solitary renal cell carcinoma smaller than 4 cm. Five of them were without renal pedicle clamping. All procedures were done through single skin incision (5-8 cm) using a 30 degrees telescope. Hemostasis was achieved with a harmonic scalpel, a microwave tissue coagulator, an argon beam coagulator and autologous fibrin glue. RESULTS There were no perioperative complications. All patients had negative surgical margins. The operating time was 157-275 min (average 209 min). The blood loss was 20-1200 ml (average 525 ml). Postoperatively, renal function as assessed by serum creatinine was within normal limits. Neither local recurrences nor metastases were observed during a follow-up of 6-15 months. The postoperative course was markedly improved over that expected from standard open surgery. CONCLUSIONS With minimal morbidity and complications, endoscopic minilaparotomy partial nephrectomy is feasible for small renal cell carcinoma.

To investigate factors influencing the degree of difficulty in finding and maintaining an appropriate plane on the surgical capsule of the prostate during holmium laser enucleation of the prostate.A total of 116 men undergoing holmium laser enucleation of the prostate for benign prostate hyperplasia between January 2010 and September 2013 at our hospital were included in this analysis. The degree of difficulty in finding and maintaining the plane of the surgical capsule of the prostate was retrospectively evaluated and graded by using video-based analysis according to newly defined criteria (grade I, least difficult; grade IV, most difficult). Factors influencing the degree of difficulty were investigated.Video analysis was possible in 99 of 116 patients. Decapsulation difficulty in decapsulation was deemed as being grade I in 32 patients, grade II in 31 patients, grade III in 20 patients and grade IV in 16 patients. Preoperative dutasteride therapy was the only factor associated with an increasing level of difficulty in decapsulation during holmium laser enucleation of the prostate.Although preoperative dutasteride therapy effectively reduces intraoperative blood loss, surgeons with limited experience should be careful with the use of dutasteride, because its administration might increase surgical difficulty during holmium laser enucleation of the prostate.

Zoledronic acid (ZA) reduces the risk of skeletal-related events (SREs) in castration-resistant prostate cancer (CRPC) with bone metastasis and improves quality of life. It remains unclear when clinicians should initiate ZA treatment.Hormone-naïve patients were randomized to a combined androgen blockade (CAB) group or CAB with ZA group (CAB-ZA) based on Gleason score (GS) or extent of disease. The primary end-point of the study was progression-free survival (PFS) and the secondary end-point was incidence of SREs and bone pain.Thirty-one and 29 patients among 60 enrolled patients were assigned to the CAB group and the CAB-ZA group, respectively. There was no significant difference in PFS between the two groups. Subgroup analyses revealed better PFS in the CAB-ZA group with GS ≥8 (p=0.021). Moreover, incidence of SREs, including bone pain, was lower in the CAB-ZA group (p=0.019).CAB-ZA treatment was found to improve PFS for patients with prostate cancer with high GS. CAB-ZA treatment could be recommended for treatment of patients with prostate cancer.

We followed 135 primary bladder carcinoma patients for at least 3 years. Subsequent carcinomas of the upper urinary tract were found in 5 patients (3.7 per cent) an average of 67 months after an initial treatment of the bladder tumors. Two patients underwent radical cystectomy and the remaining 3 patients received transurethral resections or partial cystectomy five to seven times for bladder lesions. Primary bladder tumor was multiple in all and one of them was accompanied by carcinoma in situ in the bladder and urethra. Except for one patient who presented with gross hematuria, four patients had no symptoms referable to the upper urinary tract tumor. However two of them had high stage disease. Positive urinary cytology was observed in only one patient. All patients underwent nephroureterectomy and the four got well but one died of acute heart failure. Regular urinary cytology and IVP should be done for an extended period of time for early detection of renal pelvic and ureter cancers in patients who had multiple and recurrent bladder cancers.

BACKGROUND Docetaxel-based chemotherapy (DBC) showed limited clinical efficacy for castration-resistant prostate cancer (CRPC) patients. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for DBC-resistant CRPC patients. METHODS Twenty DBC-resistant CRPC patients and 22 patients with no prior DBC, as a control, were treated with PPV using peptides chosen from 31 peptides in patients, respectively. Cytokines, inflammatory markers, and immune responses were measured as candidate biomarkers. DBC-resistant CRPC patients without PPV was set as a historical control for evaluation of clinical benefit of PPV. RESULTS Median overall survival (OS) time from the first vaccination was 14.8 months or not reached in DBC-resistant CRPC patients and patients with no prior DBC (log-rank; P = 0.07), respectively. Median OS time from the first day of progression disease was 17.8 and 10.5 months in DBC-resistant CRPC patients receiving PPV and those with no PPV (P = 0.1656), respectively. Elevated IL-6 levels before vaccination was an unfavorable factor for OS of DBC-resistant CRPC patients (P = 0.0161, hazard ratio (HR): 0.024, 95% CI:0.001–0.499) as well as all 42 patients with PPV(P = 0.0011, HR: 0.212, 95% CI:0.068–0.661) by multivariable analysis. CONCLUSIONS Further clinical study of PPV is recommended for DBC-resistant CRPC patients, because of the safety and possible prolongation of MST. Control of elevated IL-6 by combined therapy may provide much better clinical outcome. Prostate 72:834–845, 2012. © 2011 Wiley Periodicals, Inc.

We report a rare case of primary signet-ring cell carcinoma of the prostate in an advanced stage. A 62-year-old man with serum level of prostate-specific antigen at 364.70 ng/ml was diagnosed as having cT4N1M1c prostatic signet-ring cell carcinoma of Gleason score 5 + 4 = 9. Immunohistochemical examination demonstrated cytoplasmic immunoreactivity to prostate-specific antigen in signet-ring cancer cells. The intracytoplasmic vacuoles in the signet-ring cells showed mucin production with a positive staining with periodic acid-Schiff. Although the patient received hormonal therapy, the disease progressed and lead to death 15 months after the diagnosis. The clinical and immunohistochemical characteristics of this malignancy are also reviewed.

An 86-year-old man with a serum prostate-specific antigen level of 93.33 ng/ml was diagnosed as having cT3aN0M0 prostatic adenocarcinoma of Gleason score 9. Although the serum prostate-specific antigen responded well to combined androgen blockade, the cancer spread and lead to death 6 months after diagnosis. The patient had leukocytosis during the clinical course with no sign of localized infection, especially after manipulation of the prostate. Enzyme immunoassay demonstrated elevated serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor. To our knowledge, this is the first case of prostate cancer with G-CSF production, which was confirmed immunohistochemically.

In a case of renal cell carcinoma extending into the vena cava, a temporary intracaval filter was applied before surgery to prevent pulmonary artery thrombosis. Two days later, the filter accidentally migrated into the right ventricle during defecation. Fortunately, it was successfully removed without damaging cardiac musculature under fluoroscopy.

We report a case of invasive renal pelvic tumor with high serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9). An 86-year-old man presented with macrohematuria. Retrograde pyelography demonstrated a filling defect in right upper calyx, suspected of renal pelvic tumor. The levels of serum CEA and CA 19-9 were elevated to 28.0 ng/ml and 122 U/ml, respectively. No abnormalities were found in the gastrointestinal tract. Right nephroureterectomy was performed, and histopathological diagnosis was transitional cell carcinoma, grade 2grade 3, accompanied with adenocarcinoma immuno-stained for CEA and CA19-9. A part of the tumor showed a tubular growth pattern. Both serum levels of CEA and CA 19-9 immediately decreased to the normal range after the operation, but increased again with lung and hepatic metastases.

We investigated the clinical risk factors and bacteriological examination for surgical site infection (SSI) in 144 portless endoscopic surgeries consisting of 66 clean and 78 clean-contaminated surgeries in urological diseases from April 2000 to December 2001. There were no cases of SSI in the clean surgeries. SSI occurred in 5 cases (3.5%) of clean-contaminated surgeries including total cystectomy and ileal conduit in 4 cases and total prostatectomy in 1 case. Multivariate statistical studies revealed that usage of ileum during operation and preoperative hypo-albuminemia were significant risk factors for SSI. Gram-negative rods and anaerobic bacteria were isolated from the operative wound in the total cystectomy and ileal conduit, suggesting that SSI in the operation with usage of the ileum was partially derived from contamination with endogenous bacteria, while, normal flora of the skin in the wound did not cause any post-operative SSI.

OBJECTIVE To assess the roles of RhoA small GTPase (RhoA) in upper urinary tract cancer by analysing the mRNA and protein levels of RhoA. PATIENTS AND METHODS The mRNA and protein levels of RhoA in matched sets of tumour, non-tumour and metastatic lymph node tissues of surgical specimens were analysed in 47 consecutive patients with renal pelvic/ureteric cancer, using the polymerase chain reaction after reverse transcription and Western blotting. The relationship between mRNA and protein levels of RhoA in tumour tissues and the clinicopathological features of the patients was also assessed. RESULTS The mRNA levels of RhoA and RhoA protein were greater in tumour and metastatic lymph node tissues than in non-tumour tissues (all P

Background: To assess the feasibility of laparoscope-guided minilaparotomy (endoscopic minilaparotomy) for renal cell carcinoma in patients on chronic dialysis. Methods: Endoscopic retroperitoneal minilaparotomy using a 30° telescope was carried out through single skin incision (5–8 cm) in eight patients with renal cell carcinoma who were on chronic dialysis. Outcomes of the operations were compared to those in eight patients on chronic dialysis with renal cell carcinoma who underwent standard translumbar radical nephrectomy. Results: Resection of the tumor was successfully completed without complication and the postoperative course was uneventful in both of the treatment groups. No significant difference in mean operative time or mean blood loss was observed between the treatment groups. Wound pain was minimal and analgesics were generally not required in the minilaparotomy group. The endoscopic laparotomy group resumed full diet and began walking earlier than the group that underwent standard radical nephrectomy. Conclusions: Endoscopic minilaparotomy seems to be a valuable alternative treatment for renal cell carcinoma in patients on chronic dialysis.

The intracavitary injection of OK-432 (a streptococcal preparation) with subcutaneous priming has been shown to be an effective immunotherapy for patients with malignant effusion. We applied this treatment in a case of advanced renal cell carcinoma with massive ascites. The patient received 0.2 Klinishe Einheit (KE) OK-432 in the subcutaneous injection twice (day 1 and day 7) followed by 10KE OK-432 intra-abdominal administration (day 9). The treatment was performed safely without major side-effects except for transient pyrexia. A significant reduction of ascites was noted 1 month after the treatment without subsequent re-accumulation. Intracavitary injection of OK-432 with subcutaneous priming seems to be a simple, safe and effective treatment for ascites in advanced renal cell carcinoma.

We compared the efficacy of naftopidil with that of tamsulosin hydrochloride for benign prostatic hyperplasia patients. Eighty-five patients without improvement of quality of life (QOL) score by the administration of 50-75 mg naftopidil for more than four weeks were assigned to receive doses of 0.1-0.2 mg tamsulosin hydrochloride and 89 patients without improvement of QOL score by the administration of 0.1-0.2 mg tamsulosin hydrochloride for more than four weeks were assigned to receive doses of 50-75 mg naftopidil once a day for 8 weeks. International prostate symptom score, maximum flow rate, residual urine volume and side effect profile were determined before the administration of the first medicine, before the administration of the second medicine and after 8 weeks of treatment with the second medicine. In the group without improvement of QOL score by naftopidil, significant improvements in symptoms of urgency, weak stream and straining were observed after 8 weeks of treatment with tamsulosin hydrochloride. In the group without improvement of QOL score by tamsulosin hydrochloride, significant improvements in symptoms of incomplete emptying, intermittency and nocturia were observed after 8 weeks of treatment with naftopidil. In conclusion, improvement of symptoms by each alpha 1-blocker differs symptom by symptom. Tamsulosin hydrochloride was superior to naftopidil for the symptoms of urine flow and naftopidil was superior to tamsulosin hydrochloride for the symptom of nocturia.

Objectives. The pathologic complexity of the testicular tumor makes it difficult to demonstrate exactly the relationship between the impaired spermatogenesis in patients with a testicular tumor and the serum level of the human chorionic gonadotropin beta subunit (beta-hCG). Therefore, we performed quantitative evaluation of spermatogenesis in ipsilateral and contralateral testicular tissues of seminoma to simplify the relation pathologically and endocrinologically and to demonstrate the exact correlation between spermatogenesis and serum beta-hCG levels. Methods. Fifty-three biopsy specimens from ipsilateral and contralateral testicular tissues of seminoma were analyzed histologically. The quantitative evaluation of spermatogenesis was performed by the mean Johnsen’s score count (MJSC). Beta-hCG expression in seminoma was examined immunohistochemically. Serum beta-hCG, testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were analyzed before orchiectomy. Results. A significant linear relationship (r = −0.82; P

BACKGROUND Good local control has been reported in cases of muscle-invasive bladder cancer treated by chemoradiotherapy and transurethral resection (TUR). However, definitive irradiation or extensive chemotherapy is often intolerable for elderly or poor-risk patients. We report here benefits of partial cystectomy after concurrent low-dose chemoradiotherapy for high-risk patients. METHODS Thirty-seven patients with localized muscle-invasive bladder cancer (T2-T4) were treated with concurrent cisplatin (50-100 mg/body x 2 courses) and pelvic irradiation (40 Gy) preoperatively. Among 17 patients (46%) who achieved complete response (CR), 10 were not suitable for radical cystectomy and underwent partial cystectomy. Radical cystectomy was performed in 24 cases [CR = 6, partial response (PR) = 18]. Two patients (one CR and one PR) rejected open surgery and were treated by TUR of the primary site. One no change (NC) patient received no further treatment because of mental disorder. RESULTS Median follow-up was 12 months (range 2-37 months). Fifteen of 36 evaluable cases (42%) achieved a pathological T0 response (no residual tumor). Estimated 3-year disease-free survival was 56% for all patients and 100% for T0 responders. Seven of 21 patients with pathological persistent tumor developed local recurrence (three patients) or distant metastasis (four patients). All of the 10 patients (eight with T0 response and two with a small residual tumor nest) who underwent partial cystectomy were recurrence-free for an observation period of up to 3 years. CONCLUSIONS Bladder preservation by partial cystectomy may be a choice for patients who show a good response to preoperative chemoradiotherapy and are not suitable for radical cystectomy.

A 83-year-old-man underwent radical cystectomy with bilateral pelvic lymphadenectomy and conduit urinary diversion for invasive bladder tumor in May 1997. Pathological diagnosis of the surgical specimen was grade 3, pT2apNOMO transitional cell carcinoma. The patient presented with a palpable solid mass in the right pelvic space in November. Imaging studies showed that the tumor was invading the iliac bone but no distant metastases were seen. Histological diagnosis of the pelvic tumor specimen acquired by needle biopsy was transitional cell carcinoma. Although radiotherapy and systemic chemotherapy were attempted, the patient became gradually worse. In April 1998 as the recurrent tumor progressed leukocytosis (37,10O/mrn?, normal 4,000 to 8,000, more than 90% mature granulocytes) and hypercalcemia (serum calcium 13.8 mg./dl., normal 8.5 to 10.5) occurred with no signs of inflammatory disease or bone metastasis. Serum analysis for granulocyte colony-stimulating factor and parathyroid hormone related protein by enzyme-linked immunosorbent assay demonstrated a n elevated value of 52 pg./ml. (normal less than 6.3) and 7.1 pmo1.A. (normal less than 1.1), respectively. In contrast serum level of intact parathyroid hormone measured by enzyme linked immunosorbent assay was decreased at 8 pg./ml. (normal 14 to 66). Although we could not acquire antihuman parathyroid hormone related protein antibody, cancer cells of the radical cystectomy specimen stained positive with antihuman granulocyte colony-stimulating factor antibody (see figure). The patient died of carcinoma in May 1998, and autopsy was not performed.