Nivolumab in patients with unresectable locally advanced or metastatic urothelial carcinoma: CheckMate 275 2-year global and Japanese patient population analyses.

BACKGROUND: Nivolumab has demonstrated antitumor activity and manageable safety in the single-arm, phase II CheckMate 275 study in patients with unresectable locally advanced or metastatic platinum-resistant urothelial carcinoma. We report updated results of the global population and a subanalysis of Japanese patients from this study. METHODS: Patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) confirmed by blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS) by BIRC and overall survival (OS). Safety was also reported. The minimum follow-up was 21 months. RESULTS: Overall, 270 patients were treated with nivolumab globally; 23 patients were Japanese. In the global and Japanese populations, respectively, ORR per BIRC was 20.4% and 21.7%; median PFS was 1.9 (95% confidence interval [CI] 1.9-2.3) and 3.8 months (95% CI 1.9-7.2); and median OS was 8.6 (95% CI 6.1-11.3) and 21.0 months (95% CI 7.2-not reached). The most common any grade treatment-related adverse events were fatigue (18.1%) and diarrhea (12.2%) in the global population; the most common in the Japanese population were diarrhea (26.1%) and pyrexia (13.0%). Grade 3 or 4 treatment-related adverse events occurred in 61 (22.6%) and seven (30.4%) of the global and Japanese patients, respectively. CONCLUSIONS: Nivolumab continues to show antitumor activity and survival in the global population of CheckMate 275. Meaningful clinical benefit was also observed in Japanese patients. No new safety signals were identified.

[Histologic Evaluation of Prolonged Ischemic Priapism Using Winter Procedure with Percutaneous Distal Shunt Construction-Report of Two Cases].

We present 2 cases of prolonged ischemic priapism in which corpus cavernosum tissue was obtained using the Winter procedure with an automatic biopsy needle for construction of a percutaneous distal shunt and the relationship with erectile recovery was evaluated. A 24-year-old male was referred to our hospital at 72 hours after onset of priapism. Conservative procedures failed to achieve detumescence. Thus, a Winter procedure, which creates a fistula between the glans penis and corpora cavernosa, was attempted and the patient was successfully treated. Corpus cavernosa biopsy findings showed a nearly normal cavernosal tissue structure. Improvement of erectile function sufficient for sexual intercourse was noted 3 months after the surgery. The second case was in a 51-year-old man suffering from painful priapism that occurred following percutaneous coronary intervention. He was referred to our hospital at 48 hours after onset. Conservative treatment was insufficient, whereas detumescence was obtained with a Winter shunt procedure. Corpora cavernosa biopsy findings revealed extensive fibrosis and erectile function was not improved at 6 months after surgery. Histological evaluation of the corpus cavernosum utilizing the Winter method was found useful for determining post-operative erection recovery in these cases of ischemic priapism.

Hereditary leiomyomatosis and renal cell cancer without cutaneous manifestations in two Japanese siblings.

Hereditary leiomyomatosis and renal cell cancer is a rare genetic disorder characterized by cutaneous and uterine leiomyomatosis, and an aggressive type 2 papillary renal cell carcinoma. The disease is caused by a germline mutation in the fumarate hydratase gene. We report a familial hereditary leiomyomatosis and renal cell cancer in two siblings. A 34-year-old woman underwent nephrectomy for treatment of a renal cell carcinoma. The patient's sister had been diagnosed with renal cell carcinoma at 28 years-of-age and died of the disease. Neither sister had apparent skin tumors. Histopathology of the renal cell carcinomas of the siblings showed tubulocystic and papillary architectures with high nuclear grades. Immunostaining showed no fumarate hydratase expression in either tumor. Genomic DNA sequencing of the patient showed a germline mutation in the fumarate hydratase gene (c.675delT). Although there is no epidemiological information on Asian hereditary leiomyomatosis and renal cell cancer, physicians should be aware that typical cutaneous leiomyomatosis might not always be present in patients with hereditary leiomyomatosis and renal cell cancer.

Impact of aging and comorbidity on the efficacy of low-intensity shock wave therapy for erectile dysfunction.

OBJECTIVES: To evaluate the efficacy of low-intensity shock wave therapy and to identify the predictive factors of its efficacy in Japanese patients with erectile dysfunction. METHODS: The present study included 57 patients with erectile dysfunction who satisfied all the following conditions: more than 6-months history of erectile dysfunction, sexual health inventory for men score of ≤ 12 without phosphodiesterase type-5 inhibitor, erection hardness score grade 1 or 2, mean penile circumferential change by erectometer assessing sleep related erection of < 25 mm and non-neurological pathology. Patients were treated by a low-energy shock waves generator (ED1000; Medispec, Gaithersburg, MD, USA). A total of 12 shock wave treatments were applied. Sexual health inventory for men score, erection hardness score with or without phosphodiesterase type-5 inhibitor, and mean penile circumferential change were assessed at baseline, 1, 3 and 6 months after the termination of low-intensity shock wave therapy. RESULTS: Of 57 patients who were assigned for the low-intensity shock wave therapy trial, 56 patients were analyzed. Patients had a median age of 64 years. The sexual health inventory for men and erection hardness score (with and without phosphodiesterase type-5 inhibitor) were significantly increased (P < 0.001) at each time-point. The mean penile circumferential change was also increased from 13.1 to 20.2 mm after low-intensity shock wave therapy (P < 0.001). In the multivariate analysis, age and the number of concomitant comorbidities were statistically significant predictors for the efficacy. CONCLUSIONS: Low-intensity shock wave therapy seems to be an effective physical therapy for erectile dysfunction. Age and comorbidities are negative predictive factors of therapeutic response.

Novel prediction model of renal function after nephrectomy from automated renal volumetry with preoperative multidetector computed tomography (MDCT).

BACKGROUND AND PURPOSE: The predictive model of postoperative renal function may impact on planning nephrectomy. To develop the novel predictive model using combination of clinical indices with computer volumetry to measure the preserved renal cortex volume (RCV) using multidetector computed tomography (MDCT), and to prospectively validate performance of the model. PATIENTS AND METHODS: Total 60 patients undergoing radical nephrectomy from 2011 to 2013 participated, including a development cohort of 39 patients and an external validation cohort of 21 patients. RCV was calculated by voxel count using software (Vincent, FUJIFILM). Renal function before and after radical nephrectomy was assessed via the estimated glomerular filtration rate (eGFR). Factors affecting postoperative eGFR were examined by regression analysis to develop the novel model for predicting postoperative eGFR with a backward elimination method. The predictive model was externally validated and the performance of the model was compared with that of the previously reported models. RESULTS: The postoperative eGFR value was associated with age, preoperative eGFR, preserved renal parenchymal volume (RPV), preserved RCV, % of RPV alteration, and % of RCV alteration (p < 0.01). The significant correlated variables for %eGFR alteration were %RCV preservation (r = 0.58, p < 0.01) and %RPV preservation (r = 0.54, p < 0.01). We developed our regression model as follows: postoperative eGFR = 57.87 - 0.55(age) - 15.01(body surface area) + 0.30(preoperative eGFR) + 52.92(%RCV preservation). Strong correlation was seen between postoperative eGFR and the calculated estimation model (r = 0.83; p < 0.001). The external validation cohort (n = 21) showed our model outperformed previously reported models. CONCLUSIONS: Combining MDCT renal volumetry and clinical indices might yield an important tool for predicting postoperative renal function.

Autoimmune hemolytic anemia associated with renal urothelial cancer: A case report and literature review.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is hemolytic anemia characterized by autoantibodies directed against red blood cells. AIHA can be induced by hematological neoplasms such as malignant lymphoma, but is rarely observed in the urological field. We report a case of renal urothelial cancer inducing Coombs-positive warm AIHA and severe thrombocytopenia that was responsive to nephroureterectomy. CASE PRESENTATION: A 52-year-old man presented with a 1-month history of general weakness and dizziness. Hemoglobin level was 4.2 g/dL, and direct and indirect Coombs tests both yielded positive results. Abdominal computed tomography revealed huge left hydronephrosis due to a renal pelvic tumor measuring 4.0 x 4.0 x 3.0 cm, and renal regional lymph-node involvement was also observed and suspected as metastasis. Corticosteroid therapy was administered, and nephroureterectomy was performed. After surgical resection, the hemoglobin level gradually normalized, and direct and indirect Coombs tests yielded negative results. We thus diagnosed warm AIHA associated with renal urothelial cancer. CONCLUSION: To the best of our knowledge, this represents the first report of AIHA associated with renal urothelial cancer and severe thrombocytopenia responsive to nephroureterectomy. Renal urothelial cancer needs to be included in the differential diagnoses for warm AIHA, and nephroureterectomy represents a treatment option for AIHA.

Contemporary perspective and management of testosterone deficiency: Modifiable factors and variable management.

Testosterone deficiency can occur in males of all ages. In adult males, it is induced by endogenous testosterone decline through aging and other modifiable factors. Recent publications suggested the importance of the magnitude of longitudinal decline of testosterone from baseline. The baseline level and the longitudinal decline have individual variability influenced by individual factors including digit ratio, CAG repeat of the androgen receptor and sirtuin activity. Regarding treatment for testosterone deficiency, testosterone replacement therapy is the gold standard for the management of testosterone-deficient patients, and it improves three domains of testosterone deficiency symptoms, such as the physical, psychological and sexual domain. Recent reports suggested the importance of modifiable factors in the testosterone decline in addition to aging. Therefore, it might be responsible for the prevention of testosterone deficiency symptoms to maintain testosterone secretion taking account of the modifiable factors. The present article reviews the literature, and introduces contemporary perspectives and management of testosterone deficiency.

Novel insight for midline cyst formation in prostate: The involvement of decreased prenatal testosterone suggested by second-to-fourth digit ratio study.

OBJECTIVES: To clarify the relationship between midline cyst formation and second to fourth finger length ratio. METHODS: The present study included 95 benign prostatic hyperplasia patients and 61 healthy male college students. All midline cysts were identified by transrectal ultrasonography. In the benign prostatic hyperplasia group, 45 midline cyst (+) men (M(age) = 67.2 years) and age-matched 50 midline cyst (-) men (M(age) = 67.1 years) were included. In the university student group, 12 midline cyst (+) men (M(age) = 21.7 years) and age-matched 49 midline cyst (-) men (Mage = 21.1 years) were included. We took photocopies of the participants' bilateral hands, and measured the second and fourth finger length was measured by one examiner in a blind manner. RESULTS: Second to fourth finger length ratios in the benign prostatic hyperplasia group (right/left mean ± SD) were higher bilaterally in midline cyst (+) (0.95 ± 0.03/0.95 ± 0.03) than those in midline cyst (-) (0.92 ± 0.03/0.92 ± 0.03; P < 0.0001/P = 0.0010). Second to fourth finger length ratios in students were higher only in the right hand in midline cyst (+) (0.96 ± 0.03/0.94 ± 0.03) than those in midline cyst (-) (0.93 ± 0.03/0.94 ± 0.03; P = 0.0018/P = 0.9968). The second to fourth finger length ratio of midline cyst (+) men was significantly higher than that in midline cyst (-) men. CONCLUSIONS: The second to fourth finger length ratio is higher in subjects with midline cyst of the prostate. It can be speculated that the prostatic utricle dilates in cases less exposed to male hormones during fetal development.

Feasibility and accuracy of computational robot-assisted partial nephrectomy planning by virtual partial nephrectomy analysis.

OBJECTIVES: To evaluate the feasibility and accuracy of virtual partial nephrectomy analysis, including a color-coded three-dimensional virtual surgical planning and a quantitative functional analysis, in predicting the surgical outcomes of robot-assisted partial nephrectomy. METHODS: Between 2012 and 2014, 20 patients underwent virtual partial nephrectomy analysis before undergoing robot-assisted partial nephrectomy. Virtual partial nephrectomy analysis was carried out with the following steps: (i) evaluation of the arterial branch for selective clamping by showing the vascular-supplied area; (ii) simulation of the optimal surgical margin in precise segmented three-dimensional model for prediction of collecting system opening; and (iii) detailed volumetric analyses and estimates of postoperative renal function based on volumetric change. At operation, the surgeon identified the targeted artery and determined the surgical margin according to the virtual partial nephrectomy analysis. The surgical outcomes between the virtual partial nephrectomy analysis and the actual robot-assisted partial nephrectomy were compared. RESULTS: All 20 patients had negative cancer surgical margins and no urological complications. The tumor-specific renal arterial supply areas were shown in color-coded three-dimensional model visualization in all cases. The prediction value of collecting system opening was 85.7% for sensitivity and 100% for specificity. The predicted renal resection volume was significantly correlated with actual resected specimen volume (r(2) = 0.745, P < 0.001). The predicted estimated glomerular filtration rate was significantly correlated with actual postoperative estimated glomerular filtration rate (r(2) = 0.736, P < 0.001). CONCLUSIONS: Virtual partial nephrectomy analysis is able to provide the identification of tumor-specific renal arterial supply, prediction of collecting system opening and prediction of postoperative renal function. This technique might allow urologists to compare various arterial clamping methods and resection margins with surgical outcomes in a non-invasive manner.

Correlation between erection hardness score and nocturnal penile tumescence measurement.

INTRODUCTION: The Erection Hardness Score (EHS) and the Sexual Health Inventory for men (SHIM) are patient-reported outcome scoring systems for erectile function. It is unclear which is more reliable for predicting the objective erectile function. AIM: The aim of this study was to evaluate whether the EHS could predict objective erectile function by measuring the maximal penile circumferential change (MPCC) with an erectometer. METHODS: The study included 98 patients who visited our clinic from 2005 to 2010. The erectile function was evaluated using the SHIM, EHS, and MPCC. The MPCC was measured with the largest circumferential change of three consecutive occurrences of nocturnal penile tumescence (NPT) determined using the erectometer. MAIN OUTCOME MEASURES: We defined erectile dysfunction (ED) as MPCC < 20 mm and carried out multivariate analysis using logistic regression analysis to clarify the predictors for ED, with the variables including age, the SHIM score, and the EHS. We compared the tendency for MPCC ≥ 20 mm when EHS was 3 or more with that when EHS was 2 or less. RESULTS: The median age of the patients was 59.5 years (range 18-83). In logistic regression analysis, the EHS was the only predictor for ED with MPCC < 20 mm. The mean EHS in the MPCC < 20 mm group was 1.64 ± 0.20 (mean ± SEM) and that in the MPCC ≥ 20 mm group was 2.46 ± 0.13 (P = 0.0018). There was a correlation between the EHS and the MPCC (correlation coefficient = 0.33). In comparison with the group having an EHS of 2 or less, that with an EHS of 3 or more tended to have MPCC ≥ 20 mm (P = 0.013). CONCLUSIONS: The EHS was correlated with the MPCC. The EHS represents the objective erectile function shown by the measurement of NPT.

Correlation between the Japanese Aging Male Questionnaire (JAMQ) and Aging Male's Symptom (AMS) scale in Japanese male.

OBJECTIVES: To clarify the correlation between the Japanese Aging Male Questionnaire (JAMQ) and the Aging Males' Symptoms (AMS) scale through the factor analysis in Japanese male. MATERIALS AND METHODS: In 61 male patients who visited the LOH outpatient clinic of Teikyo University Hospital, subjective symptoms featuring LOH were evaluated using the JAMQ and AMS. Factor analysis was performed on each questionnaire to clarify the LOH-related factors. Correlational analysis between the subscale scores representing such factors and the serum hormone profiles was also performed. RESULTS: Factor analysis of the JAMQ revealed an internal structure consisting of three subgroups: somatic, psychological and sexual factors with good categorization of the indicators to the appropriate subgroup. In contrast, the indicators of the AMS showed incomplete conformity to the subgroups of the JAMQ. Correlational analysis showed that each score on the JAMQ subgroups had the highest coefficient of correlation with the corresponding AMS subgroup (p < 0.001). There was no significant association between total and free serum testosterone levels and the total and subscale scores on either AMS or JAMQ. CONCLUSIONS: The results of factor analysis suggest that the sexual perceptions of Japanese populations might differ from those of Caucasian populations. JAMQ would be useful to separately assess individual aspects of somatic, psychological and sexual symptoms related to LOH among Japanese males.

Impact of visceral fat ratio on sleep-related erection: a retrospective study of elderly patients.

OBJECTIVES: To investigate the impact of visceral fat accumulation on the preoperative erectile function of elderly patients undergoing radical prostatectomy. METHODS: A total of 83 patients who underwent radical prostatectomy from August 2005 through August 2013 were included in the present study. Findings at preoperative computed tomography scanning and sleep-related erection were used to determine the objective erectile function. Sleep-related erection was measured with an erectometer during at least three nights, and we assessed the maximum penile circumferential change. The visceral fat ratio was calculated as the ratio of the visceral fat area to the total subcutaneous fat area on computed tomography images, and the influence of these parameters on preoperative erectile function was assessed. RESULTS: In simple linear regression analysis there was a strong correlation between the waist circumference and visceral fat ratio (P < 0.01). A visceral fat ratio of 55% was equivalent to a waist circumference of 85 cm, which is the standard value for central obesity in Japan. Furthermore, the factor that most negatively affected maximum penile circumferential change was the visceral fat ratio. In addition, only a visceral fat ratio of 55% or greater was a significant independent risk factor for declining maximum penile circumferential change in both univariate and multivariate analyses (P = 0.04 and 0.02, respectively). CONCLUSIONS: The present study is the first to show the utility of the visceral fat ratio as an index of central obesity and the relationship with sleep-related erection in elderly men.

Successful treatment with low-dose oral steroids for contracted bladder after intravesical instillation of Bacillus Calmette-Guérin.

Introduction: Contracted bladder is a rare adverse effect of intravesical Bacillus Calmette-Guérin instillation, with an incidence of 0.2-3.3%. This report aimed to present a case of contracted bladder successfully treated with a low-dose oral steroid. Case presentation: A 78-year-old man underwent a third transurethral resection of a bladder tumor. The pathological diagnosis was urothelial carcinoma in situ. After the fifth instillation of the second-line induction therapy of Bacillus Calmette-Guérin, the patient discontinued treatment because of increased urinary frequency and a continuous mean voiding volume of 80 mL. The patient was diagnosed with a contracted bladder based on computed tomography findings and a urination chart. After initiating oral prednisolone (20 mg/day), the patient experienced significant recovery within 2 weeks for both urinary frequency and mean voiding volume of 226 mL. Conclusion: A patient with a contracted bladder after Bacillus Calmette-Guérin instillation was successfully treated with low-dose oral steroid therapy.

Maintenance therapy with intravesical bacillus Calmette-Guerin in patients with intermediate- or high-risk non-muscle-invasive bladder cancer.

OBJECTIVE: We investigated the efficacy, safety and an optimal schedule of maintenance therapy with intravesical instillation of Bacillus-Calmette Guérin in patients with non-muscle-invasive bladder cancer. METHODS: We compared the oncological outcome and adverse events of maintenance Bacillus-Calmette Guérin therapy (n = 40) with control subjects (n = 64) of Bacillus-Calmette Guérin induction therapy. Maintenance therapy was scheduled to be administered in 3-week cycles at 6, 12, 18, 24 and 36 months after the induction therapy. RESULTS: There was a significant difference in the 5-year recurrence-free survival rate between the maintenance and induction groups in all patients (72.4 vs. 62.0%; P = 0.019) and in patients with high recurrence risk (100.0 vs. 17.9%; P = 0.009). There was a significant difference in the 5-year progression-free survival rate between the maintenance and induction groups in patients with high progression risk (100.0 vs. 69.3%; P = 0.047). Maintenance Bacillus-Calmette Guérin instillations for a total of four times or more (recurrence-free survival: hazard ratio: 0.2, P = 0.039) or with a total dosage of >243 mg (recurrence-free survival: hazard ratio: 0.2, P = 0.041) after 6 months of induction therapy significantly improve tumor recurrence-free survival and progression-free survival. There were no significant differences between induction therapy and maintenance therapy in the frequency of all adverse drug reactions. CONCLUSIONS: Bacillus-Calmette Guérin maintenance therapy was effective in preventing the recurrence and progression of high-risk non-muscle-invasive bladder cancer. Maintenance Bacillus-Calmette Guérin instillations for a total of four times or more or with a total dosage of >243 mg after 6 months of induction therapy are necessary to obtain the optimal effect as maintenance therapy.

[Role of androgen in the elderly. What is LOH syndrome?].

Late-onset Hypogonadism (LOH) syndrome has been established for a few years. It was formally called as "ADAM (Androgen deficiency in aging male) " or "PADAM (Partial androgen deficiency in aging male) " , and the international guideline has been developed. LOH is defined by reduced serum testosterone levels (either total testosterone or free testosterone). Considering "Men's health" , LOH is an important issue for the quality of life of elderly males.

A case of 18 F-FDG- PET positive chronic expanding hematoma in the retroperitoneum.

Chronic expanding hematomas (CEHs) in the retroperitoneal space are rare disease. Since CEHs often develop huge masses, it is difficult to differentiated from malignant tumor. Here, we present a case of CEH in the retroperitoneal space. The lesion exhibited increased activity on 18F-fluordeoxyglucose positron emission tomography (FDG-PET). In the present case, the increased FDG uptake was showed only in the peripheral rim of the mass, and no other abnormal uptake was observed. The findings of our case and previously reported cases suggest that FDG uptake observed only in peripheral rim of the mass might be characteristic findings of CEHs.

The relationship between second-to-fourth digit ratio and female gender identity.

INTRODUCTION: Gender identity and the second-to-fourth finger length ratio (2D : 4D) are discriminative between the sexes. However, the relationship between 2D : 4D and gender identity disorder (GID) is still controversial. AIM: The aim of this study is to investigate the relationship between 2D : 4D and score on the Gender Identity Scale (GIS) in female-to-male (FtM) GID subjects. METHODS: Thirty-seven GID-FtM with testosterone replacement therapy from our clinic were included in this study. As controls, 20 male and 20 female volunteers participated from our institution (medical doctors and nurses). We photocopied left and right hands of the participants and measured the second and fourth finger lengths. Gender identity was measured with the GIS. MAIN OUTCOME MEASURES: 2D : 4D digit ratio and GIS in male, female, and GID-FtM subjects. RESULTS: The 2D : 4D (mean ± standard deviation) in male, female, and GID-FtM were 0.945 ± 0.029, 0.999 ± 0.035, and 0.955 ± 0.029 in right hand and 0.941 ± 0.024, 0.979 ± 0.040, and 0.954 ± 0.036 in left hand, respectively. The 2D : 4D was significantly lower in male controls in both hands and GID-FtM in the right hand than in female controls (P < 0.05, analysis of variance). Multiple linear regression analysis revealed that "consistent gender identity" score in the higher domain in GIS and "persistent gender identity" score in the lower domain are statistically significant variables correlating with 2D : 4D in the right hands among biological females. CONCLUSIONS: The finger length ratio 2D : 4D in GID-FtM was significantly lower than in female controls in the right hand in this study. 2D : 4D showed a positive correlation with GIS score. Because 2D : 4D influences are assumed to be established in early life and to reflect testosterone exposure, our results suggest a relationship between GID-FtM and perinatal testosterone.

The potential influence of interferon-α on the growth of the growing teratoma: A case report.

Growing teratoma syndrome (GTS) is rare. It is fatal if the teratoma is unresectable. A standard systemic therapy is not established. The efficacy of interferon-alpha (IFN-α) for GTS was described but the treatment periods were relatively short. A 23-year-old Japanese male with bulky retroperitoneal lymph node and multiple lung metastases that progressed to GTS was administered 6 × 106 units of natural IFN-α 2 × /week. Since the IFN-α treatment suppressed both lesions' growth, it was continued for >10 years. The patient is well with controlled metastases (135 months since the IFN-α's initiation). This is apparently the longest follow-up of INF-α treatment for GTS.