Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.

Comparison of Oncological Outcomes of Pembrolizumab as Second-line Therapy and Maintenance Avelumab Therapy in Advanced Urothelial Carcinoma After Platinum-based Chemotherapy.

BACKGROUND/AIM: Sequential therapy using chemotherapy and subsequent immune checkpoint inhibitor (ICI) treatment prolongs the survival of patients with advanced urothelial carcinoma (UC). However, no comparison data for oncological outcome between pembrolizumab and avelumab has been reported. Thus, we compared oncological outcomes between pembrolizumab as second-line therapy and maintenance avelumab therapy in patients with advanced UC. PATIENTS AND METHODS: We retrospectively evaluated patients with advanced UC treated with pembrolizumab or avelumab between January 2018 and February 2023. We compared oncological outcomes after adjusting for patient characteristics. Immune-related adverse events (AEs) in each group were evaluated using the Common Terminology Criteria for Adverse Events. RESULTS: There were 186 and 44 patients in the pembrolizumab- and avelumab-treated cohorts, respectively. After propensity score matching, 43 patients from each group were selected and analyzed. Median progression-free survival from the initiation of pembrolizumab and avelumab treatments was 126 and 139 days, respectively (log-rank test, p=0.625). Median overall survival in the pembrolizumab and avelumab cohorts were 658 days and not reached, respectively (log-rank test, p=0.249). Thirty-eight (20.4%) and 14 (31.8%) all-grade immune-related AEs were observed in 186 pembrolizumab- and 44 avelumab-treated patients, respectively (chi-squared test, p=0.112). Regarding endocrine-related AEs, 12 (6.5%) and none (0%) were observed in pembrolizumab- and avelumab-treated patients, respectively (Fisher's exact probability test, p=0.129). CONCLUSION: Pembrolizumab and maintenance avelumab therapy provide equivalent oncological outcomes in patients with advanced UC. Although no significant difference was observed, there might be a potential risk of higher endocrine-related AEs due to pembrolizumab compared to avelumab maintenance therapy.

Prevention of local symptoms in muscle invasive bladder cancer patients: clinical significance of local radiation therapy.

PURPOSE: To evaluate the significance of local radiation therapy (LRT) for prevention of local symptoms (LSs) caused by muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively reviewed the clinical records of 133 patients from 13 hospitals. MIBC patients with or without metastases who were treated with LRT alone from January 2015 through December 2020 were enrolled. Exclusion criteria were urinary diversion (UD) prior to LRT, non-MIBC, or lack of clinical information. LSs were defined as hematuria requiring invasive treatment or transfusion, UD after LRT, bladder tamponade, and opioid use for bladder pain. RESULTS: One hundred fourteen patients were finally enrolled in the study. During the median follow-up period of 13.5 months, 30 patients (26.3%) had LSs. Risk factors of LSs in multivariate analysis were a prior history of non-MIBC (NMIBC) (hazard ratio [HR] 2.99; 95% confidence interval [CI], 1.36 to 6.56; P < 0.01), radiation dose of less than 50 Gray (Gy) (HR 3.99; 95% CI, 1.80 to 8.82; P < 0.01), and tumor stage 3 or more (HR 2.43; 95% CI, 1.14 to 5.21; P = 0.02). Risk factors of overall survival (OS) in multivariate analysis were being female (HR 3.32; 95% CI, 1.68 to 6.58; P < 0.01), an age-adjusted Charlson Comorbidity index of 6 or more (HR 2.19; 95% CI, 1.18 to 4.10; P = 0.01), distant metastases (HR 3.20; 95% CI, 1.39 to 6.58; P < 0.01), and tumor size of 40 mm or more (HR 2.38; 95% CI, 1.34 to 4.52; P < 0.01). Toxicity (all grades) occurred in 40.4% of the patients, 4.8% with grade 3 or more and 95.2% with lower grades. CONCLUSIONS: We determined the risk factors for LSs in MIBC patients treated with LRT alone. An escalated-dose of 50 Gy or more may contribute to prevention of LSs caused by MIBC. Thus, dose-escalated LRT for MIBC patients who can expect favorable survival may be a good option to avoid future annoying LSs.

[THE USEFULNESS OF POSITRON EMISSION TOMOGRAPHY / COMPUTED TOMOGRAPHY IN THE DIAGNOSIS OF METASTASIS IN PATIENTS WITH UROTHELIAL CARCINOMA].

(Purpose) This study examined the usefulness of positron emission tomography (PET) / computed tomography (CT) in the diagnosis of metastasis in patients with urothelial carcinoma. (Materials and methods) The subjects were patients who were newly diagnosed with urothelial carcinoma in our department on whom we performed CT and PET/CT to search for metastasis. (Results) The median age of the 92 subjects was 71 years, and bladder and upper tract urotherial cancer were underlying diseases in 41 (46%) and 51 (54%) patients, respectively. In 66 (72%) of the 92 cases, no metastasis was observed by CT, while PET/CT revealed metastasis in 9 (14%). The 57 (86%) patients in whom both CT and PET/CT showed no metastasis underwent radical surgery, while 2 patients (4%) exhibited pathological lymph node metastasis.Of the 26 patients in whom CT revealed metastasis, PET/CT showed no metastasis in 3 (12%), and the absence of pathological metastasis was confirmed in all patients. Of the 23 patients found to have metastasis in both CT and PET/CT, metastasis that could not be identified by CT was discovered by performing PET/CT in 10 (43%) patients.PET/CT showed significantly higher diagnostic accuracy than CT alone (p< 0.01), with sensitivities of 94.1% and 67.6%, specificities of 100% and 94.8%, and positive diagnosis rates of 97.8% and 84.7%, respectively. (Conclusions) PET/CT in patients with urothelial cancer revealed that metastases that cannot be diagnosed by CT alone are found at a significant frequency. Since these metastases can affect treatment choices in patients with urothelial cancer, PET/CT is considered to be useful in diagnosing patients with urothelial cancer.

[A Case of Diagnosed Lynch Syndrome in a Patient with Ureteral Cancer].

Lynch syndrome (LS) is an autosomal dominant genetic disorder in which tumors are known to develop at an early age. Upper tract urothelial carcinoma is one of the tumors related to Lynch syndrome. A 49-year-old woman visited a urologic clinic due to left abdominal pain. She had a history of ovarian cancer. Her mother had a history of colorectal cancer and renal pelvic cancer, and her grandmother had had colorectal cancer. After detailed examination, she received laparoscopic left nephroureterectomy and she was pathologically diagnosed with left ureteral cancer. LS was suspected based on her past history, family history, and age. A microsatellite instability (MSI) test gave a positive result, and genetic analysis confirmed a mutation in the MSH2 gene, leading to the diagnosis of Lynch syndrome. Although LS has a high frequency of carcinogenesis, it is thought that an improved prognosis can be achieved by early discovery and treatment of cancer in LS patients. From our case report, we recommend screening of LS in patients with a past/family history, who have had an upper tract urothelial carcinoma. Once LS is diagnosed, the patient should be followed by a planned surveillance of cancer development.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in urological malignancies: a multi-center retrospective study.

INTRODUCTION: We evaluated the incidence and risk factors for antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate and kidney cancer patients. MATERIALS AND METHODS: We retrospectively reviewed the clinical data of 547 patients from 13 hospitals. Prostate and kidney cancer patients with bone metastases who were treated with a bone-modifying agent (BMA) between January 2012 and February 2019 were enrolled. Exclusion criteria were BMA use for hypercalcemia, a lack of clinical data, a follow-up period of less than 28 days and a lack of evaluation by dentists before BMA administration. The diagnosis and staging of ARONJ were done by dentists. RESULTS: Two-hundred eighteen patients were finally enrolled in the study, including 168 prostate cancer patients and 50 kidney cancer patients. Of them, 49 (29%) prostate cancer patients and 18 (36%) kidney cancer patients needed tooth extraction prior to BMA initiation. The mean follow-up period after BMA initiation was 552.9 ± 424.7 days (mean ± SD). In the cohort, 23% of the patients were diagnosed with ARONJ in the follow-up period. The 1-year cumulative incidences of ARONJ were 9.4% and 15.4% in prostate and kidney cancer patients, respectively. Multivariate analysis indicated that kidney cancer, tooth extraction before BMA and a body mass index (BMI) ≥ 25 kg/m2 were significant predictors for ARONJ. CONCLUSION: ARONJ is not a rare adverse event in urological malignancies. Especially, kidney cancer, high BMI patients and who needed tooth extraction before BMA were high risk for developing ARONJ.

Which Happens Earlier, Lower Urinary Tract Symptoms or Erectile Dysfunction?

INTRODUCTION: Although an association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) has been suggested, it was not clarified whether LUTS developed before ED or vice versa. AIM: To clarify whether LUTS develop before ED or vice versa and which symptoms predicted the onset of the other condition in a longitudinal community-based study. METHODS: We conducted a longitudinal community-based study on LUTS and ED in aged Japanese men. A follow-up study was conducted to determine their longitudinal changes of LUTS and ED after 15 years. Erectile function was evaluated using a validated questionnaire. LUTS were evaluated based on the International Prostate Symptom Score, quality of life index, and prostate volume. MAIN OUTCOME MEASURE: We evaluated the baseline symptoms among the participants who had LUTS and ED in the follow-up survey and what prior symptoms could predict the onset of the other condition using the data from a long-term longitudinal survey. RESULTS: A total of 108 men were enrolled in this study. Of the 47 men having both LUTS and ED in the follow-up study, men having only LUTS (n = 16) were more frequent than those having only ED (n = 6) in the initial study. Likewise, of the 38 men having both nocturia and ED at the time of the follow-up study, those having only nocturia (n = 12) were more frequent than those having only ED (n = 5) in the initial study. In multivariable analysis, age 60 years or older (odds ratio: 7.10, 95% CI: 2.09-24.13) and nocturia (odds ratio: 15.83, 95% CI: 3.05-82.15) were independent predictors for the onset of ED. CONCLUSION: There were more men with prior onset of LUTS, especially nocturia, than men with prior onset of ED among those with both ED and LUTS in this long-term longitudinal study. Nocturia may be a predictor of subsequent ED. Matsuda Y, Kobayashi K, Fukuta F, et al. Which Happens Earlier, Lower Urinary Tract Symptoms or Erectile Dysfunction?. J Sex Med 2021;9:100275.

[RENAL CELL CARCINOMA METASTASIS TO BLADDER DURING MOLECULAR TARGETED THERAPY WITH PAZOPANIB: REPORT OF TWO CASES].

Renal cell carcinoma (RCC) metastasis to the bladder is rare. We report two cases that occurred metachronously during pazopanib treatment for other metastases. To our knowledge, this is the first report to demonstrate bladder metastasis from RCC during molecular targeted therapy with pazopanib. (Case 1) A woman in her 60s was referred to our department for evaluation of an incidental right renal tumor. Dynamic CT showed a 6 cm renal cell carcinoma. In February 201X she underwent laparoscopic right radical nephrectomy, revealing clear cell carcinoma (grade 1>2), stage pT3aN0M0. In February 201X+1 she complained of left pelvic pain. She was found to have metastasis to two iliac bones and an occipital bone. She received pazopanib, in addition to a bone modifying agent and radiotherapy for the iliac bones. After 8 months, she complained of asymptomatic gross hematuria in spite of having stable disease for bone metastasis. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor on the posterior wall. She underwent transurethral resection of bladder tumor (TUR-BT). Histological examination showed metastatic RCC. Thereafter she received sequential therapies (axitinib, sunitinib, nivolumab). She remains alive without recurrence in the bladder 51 months after TUR-BT. (Case 2) A woman in her 60s presented to our department with a complaint of painless gross hematuria. A dynamic CT showed an 8.5 cm renal cell carcinoma and multiple lung metastases. In March 201Y she underwent right radical nephrectomy, revealing clear cell carcinoma (grade 2>3), stage pT2aN0M1. In June 201Y she started pazopanib. After 9 months CT showed a bladder tumor in addition to progression of lung metastases. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor at dome. She underwent TUR-BT. Histological examination showed metastatic RCC. She had no recurrence in the bladder during follow-up although she died of RCC.

[Predictive Factor of Urinary Continence after Robot-Assisted Laparoscopic Radical Prostatectomy].

We examined the postoperative urinary continence rate, and preoperative and postoperative factors predicting postoperative urinary continence for patients who underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our hospital. In all, 122 patients who received RARP were retrospectively analyzed. All patients answered a questionnaire to evaluate the urinary condition and also had a follow-up period of 6 months or longer after surgery. We defined urinary continence to be the use of 1 pad per day or less, including a safety pad. Membranous urethral length (MUL) was measured using sagittal sections of T1-weighted MRI. Postoperative urinary incontinence rates were 48.7, 72.4, 82.6 and 86.8% at 3, 6, 12 and 24 months after surgery, respectively. MUL was a significant predictive factor of urinary continence at 6 months after surgery (p<0.01). We examined the factors predicting the urinary continence recovery at 6 months after surgery, including only patients who did not obtain urinary continence at 1 month after surgery. Two factors, MUL of 11 mm or longer and two pads per day at 1 month after surgery, were significant predictive factors of urinary continence recovery at 6 months after surgery (P=0.02, P=0.04). Patients who had a long MUL could easily obtain urinary continence after RARP compared to those with a short MUL. Most patients with a long MUL and with use of 2 pads per day at 1 month after surgery could obtain urinary continence at 6 months after surgery, even if they had urinary incontinence at 1 month after surgery.

[A Case of Refractory Hemorrhagic Cystitis in which Bleeding Control was Finally Achieved by Cystectomy].

A 60-year-old man presented at our hospital with gross hematuria. He had been treated for nephrotic syndrome with cyclophosphamide and steroids since he was in his 20s. We detected diffuse hemorrhagic cystitis on cystoscopy and diagnosed him with cyclophosphamide-induced hemorrhagic cystitis. He was hospitalized due to clot retention. We treated him with blood transfusion for severe anemia and conducted continuous bladder irrigation. We performed hyperbaric oxygen therapy and transurethral electric coagulation, and increased the steroid dose. However, we could not control the hematuria. Finally, we performed cystectomy, and he is now well without hematuria. Although cystectomy is the final option, it is important to decide it in a timely manner because a delay decreases the quality of life.

Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats.

INTRODUCTION: Intravenous preload (delivered before cavernous nerve [CN] injury) of bone marrow-derived mesenchymal stem cells (MSCs) can prevent or decrease postoperative erectile dysfunction (J Sex Med 2015;12:1713-1721). In the present study, the potential therapeutic effects of intravenously administered MSCs on postoperative erectile dysfunction were evaluated in a rat model of CN injury. METHODS: Male Sprague-Dawley rats were randomized into 2 groups after electric CN injury. Intravenous infusion of bone marrow-derived MSCs (1.0 × 106 cells in Dulbecco's modified Eagle's medium 1 mL) or vehicle (Dulbecco's modified Eagle's medium 1 mL) was performed 3 hours after electrocautery-induced CN injury. MAIN OUTCOME MEASURES: To assess erectile function, we measured intracavernous pressure at 4 weeks after MSC or vehicle infusion. Histologic examinations were performed to investigate neuronal innervation and inhibition of smooth muscle atrophy. Green fluorescent protein-positive bone marrow-derived MSCs were used for cell tracking. To investigate mRNA expression levels of neurotrophins in the major pelvic ganglia (MPGs), quantitative real-time polymerase chain reaction was performed. RESULTS: The decrease of intracavernous pressure corrected for arterial pressure and area under the curve of intracavernous pressure in the bone marrow-derived MSC group was significantly lower than that in the vehicle group at 4 weeks after infusion (P < .05). Retrograde neuronal tracing indicated that the MSC group had a larger number of FluoroGold-positive neurons in the MPGs compared with the vehicle group. The ratio of smooth muscle to collagen in the MSC group was significantly higher than in the vehicle group. Green fluorescent protein-positive bone marrow-derived MSCs were detected in the MPGs and injured CNs using confocal microscopy, indicating homing of cells to the MPGs and injured CNs. Brain-derived neurotrophic factor and glial cell-derived neurotrophic factor expression levels in the MPGs were significantly higher in the MSC group than in the vehicle group (P < .01). CONCLUSION: Intravenous infusion of bone marrow-derived MSCs after CN injury might have therapeutic efficacy in experimental erectile dysfunction. Matsuda Y, Sasaki M, Kataoka-Sasaki Y, et al. Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats. Sex Med 2018;6:49-57.

[LONGITUDINAL CHANGES OF FREE TESTOSTERONE LEVELS AND SEXUAL FUNCTION IN JAPANESE MEN EVALUATING TWO CROSS-SECTIONAL COMMUNITY-BASED STUDIES].

(Purpose) We conducted cross-sectional studies two times, in 1992 and 2007 and investigated the longitudinal changes of fT levels and sexual function by comparing the results. (Methods) In 1992 and 2007, we conducted cross-sectional surveys about lower urinary tract symptoms and sexual function in male inhabitants aged 40 to 79 years in Shimakaki village, Hokkaido. Comparing the results of these surveys, we analyzed longitudinal changes in fT levels and sexual function. FT levels were measured by radioimmunoassay and sexual function was evaluated using a validated questionnaire. (Results) A total of 123 inhabitants participated in the both surveys. The average age at the initial survey was 57.2 years.Complications causing sexual dysfunction were observed in 43 participants (35%) and 75 participants (61%) in the first and second surveys, respectively. Average fT levels were 12.9 pg/ml and 4.4 pg/ml in the first and second surveys, respectively. Linear approximations of fT (Y) using age (X) were Y = -0.12 X+19.6 and Y = -0.10 X+11.6, for the first and second surveys, respectively. Although decreased fT levels with aging were comparable in both surveys, fT levels were lower in the second survey than in the first survey. There was no significant association between fT levels and sexual function. (Conclusions) The fT levels at the time of the second surey were lower than those in the first survey. The fT level has no significant association with sexual function.

Natural history of hematospermia in 189 Japanese men.

OBJECTIVES: To prospectively investigate the natural history of hematospermia. METHODS: This study included 189 patients with hematospermia. All the patients underwent watchful waiting without any empirical treatment. RESULTS: The median observation period was 52 months. Hematospermia resolved spontaneously in 168 (88.9%) of the 189 patients, and the median disease duration was 1.5 months. Kaplan-Meier analysis showed that the persistence rates of hematospermia were 57.7% at 1 month, 34.2% at 3 months, 23.3% at 6 months, 12.5% at 1 year and 7.6% at 2 years. Hematospermia reoccurred in 20 (13.5%) of the 148 patients who had adequate follow up. The recurrence-free rates were 96.6% at 3 months, 89.0% at 1 year, 84.8% at 5 years and 78.2% at 10 years. Multivariate analysis showed that seminal vesicle hemorrhage and a midline cyst of the prostate were significant factors to predict the duration of hematospermia until spontaneous resolution. The nine patients with persisting hematospermia for more than 1 year were treated with transurethral endoscopic surgery (unroofing of the midline cyst in six, and transurethral resection of the ejaculatory duct in three), and hematospermia resolved postoperatively in all these patients. CONCLUSIONS: In patients with hematospermia without inflammation, infection or malignancy, it is important to provide information on the possibility that symptoms will resolve spontaneously and to implement measures to relieve their anxiety. Detection of seminal vesicle hemorrhage and a midline cyst of the prostate is important for prediction of the duration of hematospermia.

Changes of sexual function and perception in Japanese men: A 15-year cross-sectional community-based study.

OBJECTIVES: To investigate the longitudinal changes of sexual function of Japanese men. METHODS: From 1992 to 1993, we carried out a cross-sectional community-based study on sexual function in Japanese men aged 40-79 years. After 15 years, a follow-up study was carried out to determine longitudinal changes of their sexual function. Of the 319 participants in the initial study, 135 participated again in the follow-up study. Sexual function was assessed using the same validated questionnaire in the two studies. RESULTS: Erectile rigidity declined in men of each age decade at baseline (40s, 50s, 60s and 70s) of the initial study (P < 0.01, <0.01, <0.01 and <0.05). The frequency of sexual drive was significantly decreased in men aged in their 40s, 50s and 60s (P < 0.05, <0.01 and <0.01). Men aged in their 40s were dissatisfied with their decreased sexual function (P < 0.05). In contrast, men aged in their 70s were satisfied with their sexual life (P < 0.01). CONCLUSIONS: Over a 15-year period, the sexual function of Japanese men declined in each age decade. However, the perception of this decline differed among different age group. Most elderly Japanese men did not worry about their impaired sexual function.

Relationship of serum levels and dietary intake of isoflavone, and the novel bacterium Slackia sp. strain NATTS with the risk of prostate cancer: a case-control study among Japanese men.

PURPOSE: Isoflavones may play a role in the prevention of hormone-related cancers. Equol is an isoflavone metabolized from daidzein in the presence of certain intestinal bacteria. Slackia sp. strain NATTS, a newly identified equol-producing bacterium, was recently isolated from human feces in Japan. We investigated the association of serum levels and dietary intake of isoflavones and Slackia sp. strain NATTS with the risk of prostate cancer in a case-control study among Japanese men. METHODS: Fifty-six patients with newly diagnosed prostate cancer and 56 hospital controls were enrolled in this study. Isoflavones were assessed by measurement of serum levels and administration of a food frequency questionnaire. Slackia sp. strain NATTS in feces was also measured. The odds ratios (ORs) and 95 % confidence intervals (CIs) for prostate cancer were then determined using a logistic regression model. RESULTS: The adjusted ORs for prostate cancer in comparison with the highest to lowest categories were 0.06 (95 % CI 0.02-0.24) for serum genistein, 0.18 (95 % CI 0.06-0.52) for daidzein, 0.16 (95 % CI 0.06-0.46) for glycitein, 0.52 (95 % CI 0.22-1.22) for equol, 0.86 (95 % CI 0.30-2.48) for dietary genistein, and 0.80 (95 % CI 0.28-2.28) for dietary daidzein. The adjusted OR for prostate cancer in comparison with values above versus below the median was 0.95 (95 % CI 0.42-2.16) for Slackia sp. strain NATTS. CONCLUSION: Our study findings suggest that high serum levels of genistein, daidzein, and glycitein are significantly associated with a decreased risk of prostate cancer among Japanese men.

Who needs further evaluations to diagnose upper urinary tract urothelial cancers among patients with abnormal findings by enhanced CT?

OBJECTIVE: We evaluated who would need further evaluations such as retrograde pyelography (RP) and/or ureteroscopy to diagnose upper urinary tract urothelial cancers (UUTUCs) when abnormal findings for the upper urinary tract (UUT) were detected by enhanced computed tomography (CT). METHODS: We retrospectively analyzed 125 patients who underwent enhanced CT for various reasons and had abnormal findings for the UUT. Patients whose tumors were suspected to be of extraureteral origin were excluded. All patients received RP and/or ureteroscopy to evaluate the UUTUCs. RESULTS: The median age of the 125 patients was 70 years and gross hematuria (26.4%) was the most frequently observed symptoms. RP, ureteroscopy and both were performed for 121, 59 and 55 patients, respectively. CT revealed tumor-like lesions in 58 patients and the other patients had non-tumor-like lesions. UUTUCs were found in 43 (34.4%) of the 125 patients. All of them had tumor-like lesions on CT. In 58 patients who had tumor-like lesions on CT, univariate and multivariate analyses revealed that tumor diameter and tumor enhancement were significant predictive factors for UUTUCs. ROC curve analysis of enhanced CT to diagnose UUTUCs revealed that a tumor diameter of 18 mm was the best cutoff point. The sensitivity, specificity and accuracy were 90.0%, 98.8% and 92.7% for RP and 95.5%, 100% and 97.1% for ureteroscopy, respectively. Both of them had high sensitivity, specificity and accuracy. CONCLUSION: We should decide to evaluate the UUT according to the tumor diameter on enhanced CT. When we evaluate the UUT in patients with tumor diameters of less than 20 mm, ureteroscopy is recommended.

Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat Model of Cavernous Nerve Injury.

INTRODUCTION: We evaluated the potential preventive effects and mechanisms of intravenously preloaded mesenchymal stem cells (MSCs) for erectile dysfunction (ED) in a cavernous nerve (CN) injury model. METHODS: Male Sprague-Dawley (SD) rats were used for this study. Rats were randomized into two groups. One group was intravenously preloaded with MSCs (1.0 × 10(6) cells in 1 mL total fluid volume) and the other was infused with medium alone (1 mL Dulbecco's modified Eagle's medium [DMEM]) for sham control, respectively. Crushed CN injury was induced immediately after infusion. The surgeon was blind to the experimental conditions (MSC or medium). MAIN OUTCOME MEASURES: To assess erectile function, we measured the intracavernous pressure (ICP) and arterial pressure (AP) at 1 hour and 2 weeks after CN injury. After measuring the initial ICP/AP of pre-injury (normal) male SD rats, they were randomized into the two groups and infused with MSCs or medium. PKH26-labelled MSCs were used for tracking. To investigate the mRNA expression levels of neurotrophins in the major pelvic ganglia (MPG), we performed real-time quantitative real-time polymerase chain reaction. RESULTS: The reduction of ICP/AP and area under the curve of ICP (ICP-AUC) in the MSC group was significantly lower than in the DMEM group (P < 0.05; P < 0.05) at 1 hour. The ICP/AP and ICP-AUC at 2 weeks post-injury in the MSC group was significantly higher than in the DMEM group (P < 0.01; P < 0.05). The preloaded PKH26-labelled MSCs were detected in the MPG and CN using confocal microscopy indicating homing of the cells to the injured nerve and ganglia. Glia cell-derived neurotrophic factor (GDNF) and neurturin, which are important neurotrophic factors for erection, had expression levels in MPG significantly higher in the MSC group than in the DMEM group (P < 0.01, 0.05). CONCLUSION: Intravenous preload of MSCs before a CN injury may prevent or reduce experimental ED.

Counts of Slackia sp. strain NATTS in intestinal flora are correlated to serum concentrations of equol both in prostate cancer cases and controls in Japanese men.

BACKGROUND: Isoflavones, which are included in soybeans, have been suggested to protect against prostate cancer. Equol, one of isoflavones, is an intestinally derived bacterial metabolite of daidzein. A newly identified equol-producing bacterium, Slackia sp. strain NATTS, with a high equol-producing activity was isolated from human feces in Japanese adults. Counts of Slackia sp. strain NATTS in intestinal flora have not been assessed with regard to prostate cancer risk. In this study, we investigated the association of serum isoflavones and counts of Slackia sp. strain NATTS with prostate cancer risk in a case-control study. MATERIALS AND METHODS: Concentrations of isoflavones and counts of Slackia sp. strain NATTS in feces were measured from 44 patients with prostate cancer and 28 hospital controls. The risk of prostate cancer was evaluated in terms of odds ratios (ORs) and 95% confidence intervals (CIs) by the logistic regression analysis. RESULTS: The detection proportions of Slackia sp. strain NATTS in cases and controls were 34.1% and 25.0%, respectively. Counts of Slackia sp. strain NATTS were significantly correlated with serum concentrations of equol both in cases and controls (Spearman correlation coefficients, rs=0.639 and rs=0.572, p<0.01, respectively). Serum concentrations of genistein, daidzein, glycitein, and equol were not significantly associated with risk of prostate cancer. CONCLUSIONS: This study found that counts of Slackia sp. strain NATTS correlated with serum concentrations of equol both in prostate cancer cases and controls, but serum isoflavone concentrations were not associated with risk of prostate cancer in our patients.

[Pathological complete response to gemcitabine and cisplatin chemotherapy for advanced upper tract urothelial carcinoma: a case report].

A 61-year-old man was referred to our hospital with the chief complaint of right leg weakness. Abdominal magnetic resonance imaging (MRI) and computed tomography (CT) demonstrated a ureteral tumor and a neighboring massive retroperitoneal tumor in addition to retroperitoneal lymph node and right renal metastases. The tumor was diagnosed as upper tract urothelial carcinoma (cT4N1M1) by percutaneous tumor biopsy. As the patient achieved a partial response after three courses of combination chemotherapy with gemcitabine and cisplatin, he received total nephroureterectomy and lymph node dissection. The pathology showed no viable cancer cells, demonstrating a pathological complete response. He remains alive after 26 months with no evidence of disease.

Upper urinary tract recurrence after radical cystectomy for bladder cancer: incidence and risk factors.

OBJECTIVES: To examine the incidence of and the risk factors for upper urinary tract recurrence in patients undergoing a radical cystectomy for bladder cancer, and to examine the clinical course of patients harboring upper urinary tract recurrence. METHODS: This retrospective study included 362 patients who underwent radical cystectomy for bladder cancer. Patients with a history of upper urinary tract recurrence and concomitant upper urinary tract recurrence at cystectomy were excluded. RESULTS: After a median follow up of 48 months (range 0-214) after radical cystectomy, 11 patients (3.0%) developed upper urinary tract recurrence. The median time to upper urinary tract recurrence was 48.4 months (range 11.6-78.6). The overall probability of upper urinary tract recurrence was 3.3% at 5 years. The median overall survival period after upper urinary tract recurrence was 23.5 months (range 4.3-53.9), with a better overall survival for patients who received a radical operation than for those who did not (38.6 months vs 11.9 months, respectively; P=0.03). At multivariable analysis, the presence of carcinoma in situ (P < 0.01) and invasion of the urethra (P = 0.02) were independent risk factors for upper urinary tract recurrence. The 5-year upper urinary tract recurrence was significantly higher for patients positive for either of these risk factors than for those without risk factors (12.0% vs 0.9%, respectively; P < 0.001). CONCLUSIONS: This study shows that the presence of carcinoma in situ and cancer invading the urethra are risk factors for upper urinary tract recurrence. Close follow up is needed for early detection of upper urinary tract recurrence in patients at higher risk.