[Promotion of Diversity in the Academic Field of Urology : Analysis of 10,000 Articles Published in Acta Urologica Japonica during a 65-Year Period].

Gender equality is one of the most important issues in the promotion of diversity. The participation status of female urologists in academic activities has not been clarified. In the present study, we analyzed a total of 10,288 articles published by 58,914 authors in Acta Urologica Japonica since the first issue in 1955 to the present. The author's gender was determined by an application program interface for gender estimation in combination with independent manual confirmation by two researchers. The increasing rate (⊿person/⊿year) of female authors was as low as 0.067 in 1955-79, but increased to 0.400 in 1980-2000 and 0.814 in 2001-20. Over the time periods, the annual total numbers of female authors (person/year) showed an increasing trend from 3.2 in 1955-79 to 16.3 in 1980-2000 and 26.0 in 2001-20. The numbers of female author individuals, the ratio of female authors to all authors and the ratio of publications by female first author to all publications also showed similar trends. These results suggest that gender equality is becoming more prevalent in the academic field of urology. The methods and data of this study are considered to be useful for the promotion of gender equality in the academic field of urology for the future.

Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial.

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 (<1%) patient in the chemotherapy group (acute kidney injury). 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.

[The Safety of Laparoscopic Radical Cystectomy during Initial Phases in a Japanese Multicenter Cohort].

We evaluated the safety of laparoscopic radical cystectomy (LRC) during initial phases and its learning curve in a Japanese multicenter cohort by studying 436 patients who underwent LRC with no robot assistance at 10 institutions in Japan. We divided the patients into three groups according to cumulative surgical volume at each institution (first 10 cases, 11-30 cases, after 31 cases in each institution), and compared perioperative and pathologic variables among the three groups. The first, second, and third groups included 100, 166, 170 patients, respectively. The preoperative variables were similar in the three groups except for the rate of neoadjuvant chemotherapy. The methods of LRC procedure, such as urinary diversion, the extent of lymph node dissection, and concomitant urethrectomy or nephroureterectomy, were similar in the three groups. Mean operative time was 629, 562 and 531 minutes, respectively, and mean blood loss was 755, 650 and 435 ml, respectively. Both values decreased over time with the institution's experience. There was no significant difference among the three groups in the rate of positive surgical margin, the number of retrieved lymph nodes, and the rate of intra- and postoperative complications. LRC was safely performed during initial phases with an acceptable complication rate and without compromising oncological results, although operative time was longer and blood loss increased.

The efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration: JMTO Pca 10-01 phase II trial.

OBJECTIVES: Previously, one randomized control trial (TAX327) revealed the efficacy of docetaxel-based chemotherapy combined with prednisone. On the other hand, several studies showed a high prostate specific antigen (PSA) response with low-dose dexamethasone in castration-resistant prostate cancer (CRPC) patients. The objective of this study was to evaluate the efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone in CRPC patients. MATERIALS AND METHODS: This study was a single-arm multi-institutional phase II trial. Patients received 75 mg/m2 of docetaxel, and 0.5 mg of dexamethasone orally twice a day continuing throughout the treatment period. Treatment was planned for 10 cycles, and continued for at least four cycles depending on the observation of PSA flare. The primary endpoint was PSA response defined as a reduction from baseline of at least 50% that continued for at least 3 weeks. Secondary endpoints were safety, PSA flare, time to PSA failure and adherence rate to protocol treatment (10 cycles). RESULTS: Between January 2011 and February 2014, a total of 76 chemotherapy-naïve CRPC patients were enrolled. Seventy-five patients received docetaxel-based chemotherapy combined with dexamethasone. The median age and PSA level at enrollment were 71 years (53-85) and 23.2 ng/mL (2.9-852), respectively. PSA response rate was 76.8% (90% confidence interval (CI): 66.9-84.9). Of all patients, 30 patients completed 10 cycles of chemotherapy (40%). The incidence rate of PSA flare was 10.7% (eight patients). The median time to PSA failure was 369 days (95% CI: 245-369). The most frequently observed adverse event was hematotoxicity (neutropenia of G2 or greater: 100%). CONCLUSIONS: The present study showed a significantly high PSA response compared with previous reports. Most patients tolerated the protocol treatment well, whereas hematotoxicity was often observed.

[Deceased Donor Kidney Transplantation from a Liver Transplantation Recipient].

We report a 40-year-old man with end-stage renal disease due to IgA nephropathy who underwent deceased donor kidney transplantation. The donor was diagnosed to be brain-dead due to cerebral hemorrhage after her second liver transplantation for non-viral liver cirrhosis. Intraoperative 1-hour biopsy of the graft kidney revealed moderate global glomerular sclerosis (22%) and interstitial fibrosis (40%) consistent with underlying nephrosclerosis or calcineurin inhibitor nephrotoxicity. Although hemodialysis was needed until the graft began functioning several days after the kidney transplantation, the postoperative clinical course thereafter was uneventful and the graft functioned well with stable serum creatinine levels around 2.4 mg/dl at 6 monthspos toperatively.

[Experience of transobturator sling for iatrogenic male stress urinary incontinence].

We performed transobturator sling (TOS) surgery for iatrogenic stress urinary incontinence (SUI) in 7 men. Assessment with the International Consultation Society Incontinence Questionnaire Short Form revealed that complete continence, significant improvement, and no change of incontinent status were observed in two, three, and two patients, respectively, at one year after surgery. Of the three patients with significant improvement, two patients obtained a pad-free status. Both of the two patients without improvement had a past history of salvage radiation therapy for biochemical recurrence after radical prostatectomy before TOS surgery. The severity of SUI seems not to be associated with the outcome of TOS surgery. TOS surgery can be one of the surgical options for iatrogenic male SUI.

[A case of prostate carcinosarcoma successfully treated with combined modality therapy].

A 58-year-old man was referred to our hospital with dysuria and elevation of prostate specific antigen (38.0 ng/ml). Prostate surface was smooth and elastic hard on digital rectal examination. Transrectal ultrasound (TRUS) indicated irregular boundary and low echoic area of the prostate. Prostate biopsy specimen included the components of adenocarcinoma (Gleason score 9) and sarcoma. The tumor had extended to the rectum and metastasized to bilateral obturator lymph nodes and right ischial bone (cT4N1M1b). We started hormone therapy for the adenocarcinoma component followed by total pelvic exenteration with colostomy and ileal conduit diversion for the sarcoma component. In addition, pelvic cavity and the bone metastasis were irradiated. The patient was free of recurrence at four and a half years after surgery.

Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes.

To investigate the effect of highly purified eicosapentaenoic acid (EPA) on the progression of diabetic macroangiopathy, we performed an open-label randomized prospective trial. A total of 81 Japanese type 2 diabetes were randomly assigned to the EPA (1800 mg/day) treated group or the control group. Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were evaluated before and after treatment in both groups. Sixty patients (EPA group, n=30; control group, n=30) completed this study. During the study period of 2.1+/-0.2 years, the mean IMT and max IMT of the EPA treated group showed a significant annual decrease compared with that of the control group (mean IMT, -0.029+/-0.112 mm versus 0.016+/-0.109 mm, respectively, P=0.029; max IMT, -0.084+/-0.113 mm versus -0.005+/-0.108 mm, respectively, P=0.0008). The baPWV was also improved significantly in the EPA treated group compared with the control group (-22.1+/-127.9 cm/s versus 62.3+/-223 cm/s, respectively, P=0.021). Multiple regression analysis showed that the administration of EPA was a significant and independent factor associated with an annual improvement of mean IMT (R2=0.067). In summary, this is the first demonstration that administration of purified EPA improves the carotid IMT and the baPWV in patients with type 2 diabetes.

Urine CXCL1 as a biomarker for tumor detection and outcome prediction in bladder cancer.

BACKGROUND AND OBJECTIVE: To clarify the clinical usefulness and diagnostic accuracy of urine chemokine (C-X-C motif) ligand 1 (CXCL1) as a biomarker for tumor detection and outcome prediction in patients with bladder cancer (BCa). METHODS: We measured urine CXCL1 levels in 175 patients with BCa and 30 healthy controls. The value of urine CXCL1 concentration normalized by urine creatinine (CXCL1/Cre) was analyzed in terms of detecting bladder tumors and predicting intravesical recurrence after transurethral resection (TUR). RESULTS: CXCL1/Cre was significantly higher (3-fold) in BCa patients than in healthy participants and the difference from control samples was greater in patients with advanced BCa. Although the urine cytology test generally lost diagnostic power in patients with low-grade superficial tumors, the sensitivity of CXCL1/Cre was not compromised in this patient population. Patients with higher CXCL1/Cre were significantly more likely to develop intravesical recurrence after TUR and multivariate analysis identified CXCL1/Cre as an independent predictor of post-TUR intravesical recurrence. Importantly, CXCL1/Cre could successfully classify the probabilities of post-TUR recurrence among patients with intermediate-risk according to EORTC risk criteria into two groups equivalent to its high- and low-risk groups. CONCLUSIONS: Urine CXCL1 is a promising, non-invasive molecular marker for tumor detection and outcome prediction in patients with BCa.

Retroperitoneoscopic treatment of caliceal diverticular calculi: report of two cases and review of the literature.

Two women with symptomatic stone-filled caliceal diverticula were treated by a retroperitoneoscopic approach. With a three-port technique, the diverticulum was marsupialized, the calculi removed, the cavity fulgurated, and perirenal fat inserted. The patients had no morbidity and remain stone and symptom free. They represent the 17th and 18th reported cases of this condition. We also review the clinical results in the literature.

[Clinical results of immunosuppressive triple therapies in living-related renal transplantation--a single center experience].

We reviewed the outcome of three methods employed for living-related renal transplantation (RTx) in our institution to assess triple immunosuppressive regimens. Between January 1989 and July 2003, a total of 35 living-related RTxs were performed at our institution. The immunosuppressive regimen given to 16 patients (group A) was cyclosporine (CsA), steroid and azathoprine (AZ) that given to 9 patients (group B) was tacrolimus (TAC), steroid and AZ and that given 9 patients (group C) was TAC, steroid and mycophenolate mofetil (MMF). Graft survival rate, serum creatinine, proteinuria, acute rejection, chronic allograft nephropathy (CAN), cytomegalovirus (CMV) infection and drug-induced nephropathy were investigated. There was no significant difference in graft survival rate among the three groups. Although serum creatinine levels (mg/dl) at 3 months post-transplant were 1.22+/-0.37 in group A, 1.43+/-0.14 in group B, 1.30+/-0.34 in group C, respectively (p<0.05; A vs. B), there was no significant difference at 1 year post-transplant. Frequency of proteinuria in groups A, B and C was 75.0, 50.0, 25.0%, respectively (p<0.05; A vs. C). The incidences of acute rejection and CAN within 1 year post-transplant were, respectively, 56.3% and 43.8% in group A, 37.5% and 37.5% in group B; and, 25.0% and 12.5% in group C (NS). The incidence of drug-induced nephrotoxicity was 12.5, 50.0% and 37.5% in groups A, B and C, respectively (p<0.05; A vs. B). The triple immunosuppressive therapy including calcineurin inhibitors, especially the regime of TAC, MMF, and steroids decreased the frequencies of proteinuria and rejections, which deteriorated the long-term outcome in living-related RTxs.

Preoperative diagnosis of congenital segmental giant megaureter presenting as a fetal abdominal mass.

We describe a case of congenital segmental giant megaureter in a boy that presented as a fetal abdominal mass. He also had bilateral undescended testes, bilateral vesicoureteral reflux, and segmental aniridia. He presented with hypoglycemia in the neonatal period that resolved. Postnatal magnetic resonance imaging, voiding cystourethrography and radionuclide imaging established the diagnosis, and a ureteroureterostomy was performed at 12 months.

Living related renal transplantation for end-stage renal disease after liver transplantation from a brain-dead donor.

We report a case in which a living related renal transplantation was successfully performed for end-stage renal disease that had progressed after a liver transplantation from a brain-dead donor for liver cirrhosis associated with type C hepatitis. Because the transplanted liver function had been excellent with the use of tacrolimus and mycophenolate mofetil, the same immunosuppressive agents with prednisolone were employed for the renal transplantation. Both grafts are functioning well without recurrence of hepatitis at 10 months after the renal transplantation. From our experience, renal transplantation should not be contraindicated even if the patient has undergone liver transplantation or has hepatitis C viral infection.