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Introduction: To evaluate the clinical effectiveness and quality of life (QOL) of outpatient mid-urethral tissue fixation system sling (TFS) procedures for urodynamic stress urinary incontinence (SUI) at 3-year follow-up. Methods: We analyzed 50 mid-urethral TFS sling operations between 2007 and 2012 at Yokohama Motomachi Women's Clinic LUNA. The primary outcome was success defined as a negative 24-h pad test, negative cough and Valsalva stress test, and no re-treatment for SUI. Secondary outcome was improvement in quality of life, which was assessed using the Incontinence Questionnaire-Short Form (ICIQ-SF) and the Incontinence Impact Questionnaire Short Form (IIQ-7). The 3-year postoperative scores were compared with baseline scores using the Wilcoxon signed rank test. A 5% two-sided significance level was used for all statistical testing. Results: All operations were carried out on an outpatient basis with no intraoperative complications. The primary cure rate result at 3-year follow-up was 90%. Median total ICIQ-SF score changed from 12 (6-20) to 0 (0-14) and median total IIQ-7 score changed from 156 (0-300) to 0 (0.00-16.7) at 3-year follow-up. Conclusions: Results show that the TFS mid-urethral sling operation is a simple, safe, effective procedure that may be done without difficulty at a freestanding clinic on an outpatient basis and favorably improves subjective QOL of the patient. [ABSTRACT FROM AUTHOR]

Objectives To assess the outcomes of the tissue fixation system midurethral sling for the treatment of intrinsic sphincter deficiency. Methods We retrospectively studied a total of 96 intrinsic sphincter deficiency patients treated with the tissue fixation system midurethral sling at Yokohama Motomachi Women's Clinic from 2006 to 2015. We evaluated intraoperative and 1-year postoperative results. Regarding the cure rate, we divided patients into three groups: (i) patients with maximum urethral closure pressure <20 and Valsalva leak point pressure <65 combined ( n = 17); (ii) patients with maximum urethral closure pressure <20 ( n = 55); and (iii) patients with Valsalva leak point pressure <65 ( n = 47). Results The median age was 63 years (range 38-89 years). The median operating time including local anesthesia was 24 min (range 12-55 min) and median blood loss was 5.0 mL (range 3-69 mL). All operations were day surgery under local anesthesia. Postoperative pain was minimal. All patients were discharged the same day. There were no intraoperative complications except one bladder perforation. There were no tape rejections. The 1-year postoperative cure rates were: 88.2% among patients with maximum urethral closure pressure <20 and Valsalva leak point pressure <65, 90.9% for patients with maximum urethral closure pressure <20, and 85.1% among patients with Valsalva leak point pressure <65. Conclusions The tissue fixation system midurethral sling operation is a simple, safe and effective operation for older women with intrinsic sphincter deficiency, and it can be carried out under local anesthesia. [ABSTRACT FROM AUTHOR]

Birt-Hogg-Dubé syndrome ( BHD) is a rare genetic disorder characterized by fibrofolliculomas, pulmonary cysts and renal cell carcinomas ( RCCs). The affected individuals inherit germline mutations in the folliculin gene ( FLCN). We investigated the mutation spectrum and clinicopathologic findings of 312 patients from 120 different families (119 Japanese and 1 Taiwanese). A total of 31 different FLCN sequence variants were identified. The majority were c. 1285dupC ( n = 34), c.1533_1536delGATG ( n = 25), and c.1347_1353dupCCACCCT ( n = 19). Almost all patients presented with pulmonary cysts. The incidence of RCCs in FLCN mutation carriers over the age of 40 was 34.8% (40/115). Fifty-five RCC lesions were surgically resected; most were either chromophobe RCC ( n = 24; 43.6%) or hybrid oncocytic/chromophobe tumors (19; 34.5%). Seventy-six of 156 FLCN mutation carriers (120 probands and 36 sibs, 48.7%) had skin papules; however, cutaneous manifestations were so subtle that only one patient voluntarily consulted dermatologists. Japanese Asian BHD families have three FLCN mutational hotspots. Recurrent episodes of pneumothoraces are the major symptoms suggestive of a BHD diagnosis in our cohort. Characteristic features of lung and kidney lesions may be more informative than fibrofolliculomas as diagnostic criteria for BHD in the Japanese Asian population. [ABSTRACT FROM AUTHOR]

High serum calcium ( Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone ( PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma ( RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization ( WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset ( n = 683) and/or as of recurrence ( n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival ( OS) and disease-free survival ( DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs. [ABSTRACT FROM AUTHOR]

The article presents views of several authors on the treatment of advanced metastatic renal cell carninoma (RCC), a cytokine based immunotherapy. As stated, a significant improvement in progression free survival compared with cytokine-based immunotherapy is made possible from targeted molecules. It mentions that race plays a vital role in the inherent incidence rate and age for the survival of RCC. The hepatocyte growth factor signaling pathway is considered as a prime target for papillary RCC.

Background: Somatic alteration of the von Hippel-Lindau disease tumor suppressor gene (VHL) is one of the most common genetic changes observed in the sporadic, clear-cell subtype of renal cell carcinoma (RCC). However, the prognostic utility of VHL mutations has not been examined. The purpose of this study was to explore the association between VHL mutations and the risk of death from sporadic clear-cell RCC.Methods: A total of 187 Japanese patients with clear-cell RCC who underwent nephrectomy from October 1986 through December 1995 were examined for somatic VHL gene alteration. Clinicopathologic and survival data were also collected. Kaplan-Meier analyses and Cox proportional hazards models were used to explore associations. All statistical tests were two-sided.Results: A VHL alteration (mutation or hypermethylation) was detected in 108 RCC tumor samples: intragenic mutations in 98 (52%) and hypermethylation in 10 (5.3%). VHL alterations were strongly associated with better cancer-free survival and cancer-specific survival for the 134 patients with stage I-III clear-cell RCC treated by radical nephrectomy (log-rank P =.024 and.023, respectively). These associations were more statistically significant among patients with relatively advanced disease (stage III [P =.014 and.010, respectively] or stage II + III [P =.002 and.009]) or higher grade tumors (G3 or higher [P =.013 and.032] or G2 or higher [P =.013 and.018]) and among patients who presented with symptoms (P =.005 and.012). VHL alterations remained an independent prognostic factor for patients with stage I-III tumors after adjustment for sex, age, stage, grading, and symptomatic presentation. VHL alterations were not associated with cancer-specific survival for the 53 patients with stage IV tumors treated with palliative or adjunctive nephrectomy (log-rank P =.760).Conclusion: The VHL alteration status may provide useful prognostic information, as a biomolecular marker, for patients with stage I-III clear-cell RCC who have undergone nephrectomy. [ABSTRACT FROM AUTHOR]

They found that intratumoral heterogeneity contributes to non-seminomatous germ cell tumor chemoresistance, and primary lesion site yolk sac tumors and teratomas are associated with a greater risk of viable cells. Treatment with silodosin and the higher dose of tadalafil improved the urodynamic parameters, bladder blood flow, and bladder tissue levels of malondialdehyde in the rat model without affecting the blood pressure and bladder tissue levels of interleukin-6 and tumor necrosis factor-alpha. Photodynamic diagnosis and transurethral resection of bladder tumor using oral 5-aminolevulinic acid is one of the standard treatment strategies for bladder tumor. [Extracted from the article]

B (Bologna, Italy) b prospectively evaluated the clinical impact of 68 Ga-prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT) on the planned management of prostate cancer patients with biochemical recurrence after surgery. 68 Ga-prostate-specific membrane antigen PET/CT allows clinicians to radically change the intended treatment approach before imaging evaluation, in roughly two out three individuals. SP 18 sp F-fluorodeoxyglucose PET/CT might aid in patient counseling and treatment decisions. [Extracted from the article]

An editorial is presented on the contribution of the readers and the members of Japanese Urological Association (JUA), International Journal of Urology(IJU) and Urological Association of Asia (UAA). It talks about IJU celebrating it's 25th anniversary with it's readers and it's members. It tells about IJU trying to improve the quality of the manuscripts submitted by the members.

An introduction is presented to editorial policy including impact factor of the periodical, maintaining good relationship with reviewers, and collaboration with professor Jian Huang.

Objective: To examine the correlation between smoking habit and lower urinary tract symptoms in women. Methods: We first screened 10 000 female patients to examine their smoking habit. A total of 7004 samples were successfully collected for further analysis through a urinary continence survey. The ratio of current smoking to non‐smoking participants was set as 1:3 to allow thorough assessment of the impact of cigarette smoking on lower urinary tract symptoms. Results: A total of 4756 complete responses were obtained for the Overactive Bladder Symptom Score and International Consultation on Incontinence Questionnaire‐Short Form questionnaire. The current smokers (2.54 ± 2.91, 2.48 ± 4.01) and ex‐smokers (2.27 ± 2.50, 2.25 ± 3.50) showed significantly higher Overactive Bladder Symptom Score and International Consultation on Incontinence Questionnaire‐Short Form scores than the non‐smokers (1.70 ± 2.05, 1.49 ± 2.73) (P < 0.0001, P < 0.0001 and P < 0.0001, P < 0.0001, respectively). The prevalence of urgency was affected by the smoking status. Younger participants (aged 20–39 years) showed a stronger influence of their smoking habit than older participants (aged ≥40 years). Urgency urinary incontinence was also affected by the smoking status. Conclusions: The prevalence of urgency and urgency urinary incontinence is correlated with age and smoking habit, and both current and ex‐smokers show an increased prevalence of urgency and urgency urinary incontinence compared with non‐smokers, especially younger women. [ABSTRACT FROM AUTHOR]

While the overall survival of patients with castration-resistant prostate cancer (CRPC) has been prolonged by enzalutamide, a considerable number of patients suffer from enzalutamide-induced nausea and fatigue. An 86-year-old male patient who started enzalutamide (160 mg) for CRPC treatment, experienced nausea and vomiting approximately 2 weeks after the start of treatment. Enzalutamide treatment was stopped for two weeks, then restarted enzalutamide at a half-dose (80 mg); the dose was then increased to 120 mg. He remained free from any adverse events and showed good CRPC control for 53 months. We herein report the case of a patient with enzalutamide-induced nausea and vomiting, whose symptoms were overcome and in whom long-term CRPC control was achieved following a temporary drug holiday. [ABSTRACT FROM AUTHOR]

Dysgeusia is an adverse effect caused by enzalutamide said to affect 1–5% of patients. The reported management strategies include a temporary drug holiday, the prescription of herbal medicine, and changing the timing of enzalutamide intake from morning to before sleep at night. Case 1: A 72-year-old man developed castration-resistant prostate cancer (CRPC) and was administered enzalutamide. After six weeks of enzalutamide installation, he showed taste alternation, and consequently his dysgeusia increased to grade 2; we therefore changed the medicine intake time from morning to night just before sleep without dose reduction. Four weeks after changing the timing, his dysgeusia had improved. Case 2: A 63-year-old man had developed bone metastatic CRPC, so the combination of Ra-223 and enzalutamide (160 mg/body) was introduced. His serum PSA level had gradually decreased, but dysgeusia appeared, so we changed the timing of enzalutamide intake from morning to night just before sleep without dose reduction. One month after changing the timing, his dysgeusia had improved. We herein report two cases of enzalutamide-induced dysgeusia successfully treated by changing the timing of drug intake from morning intake to just before sleep. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for advanced renal cell carcinoma (RCC), but it has been unclear whether the antitumor effect of TKIs depends on the organ where the RCC metastasis is located. We previously reported that the FDG accumulation assessed by FDG PET/CT, was a powerful index for evaluating the biological response to TKI. In this study we investigated the differences in FDG accumulation and the response to TKI as assessed by FDG PET/CT among various organs where RCC were located.Methods: A total of 48 patients with advanced RCC treated with a TKI (25 with sunitinib and 23 with sorafenib) were evaluated by FDG PET/CT before and at 1 month after a TKI treatment initiation. The maximum standardized uptake value (SUVmax) of all RCC lesions were measured and analyzed.Results: We evaluated 190 RCC lesions. The pretreatment SUVmax values (mean ± SD) were as follows: in the 49 lung metastases, 4.1 ± 3.3; in the 40 bone metastases, 5.4 ± 1.6; in the 37 lymph node metastases, 6.7 ± 2.7; in the 29 abdominal parenchymal organ metastases, 6.6 ± 2.7; in the 26 muscle or soft tissue metastases, 4.4 ± 2.6; and in the nine primary lesions, 8.9 ± 3.9. Significant differences in the SUVmax were revealed between metastases and primary lesions (p = 0.006) and between lung metastases and non-lung metastases (p < 0.001). The SUVmax change ratios at 1 month after TKI treatment started were -14.2 ± 48.4% in the lung metastases, -10.4 ± 23.3% in the bone metastases, -9.3 ± 47.4% in the lymph node metastases, -24.5 ± 41.7% in the abdominal parenchymal organ metastases, -10.6 ± 47.4% in the muscle or soft tissue metastases, and -24.2 ± 18.3% in the primary lesions. There was no significant difference among the organs (p = 0.531).Conclusions: The decrease ratio of FDG accumulation of RCC lesions evaluated by PET/CT at 1 month after TKI treatment initiation was not influenced by the organs where the RCC metastasis was located. This result suggests that TKIs can be used to treat patients with advanced RCC regardless of the metastatic site. [ABSTRACT FROM AUTHOR]

Background: Despite the broad global use of antibiotics, there is no established definition of early antibiotic treatment failure (EATF) to aid clinical evaluation of treatment, which leads to inconsistent assessments of drug effectiveness. Aim: This scoping review aims to identify common components of EATF definitions by synthesizing studies mentioning EATF and its relevant thesaurus matches. Design: Scoping review Methods: This scoping review was conducted following the PRISMA Scoping review guidelines. A systematic literature search was conducted using MEDLINE (PubMed), CENTRAL, CINAHL, and Web of Science, as well as a manual Google search. Search terms were EATF and its thesaurus matches. After removing duplications, candidate studies were screened by title and abstract prior to full text searches, and quality analysis was performed on eligible studies using the Critical Appraisal Skills Programme. From each eligible study, the timing of evaluation, basic components, and detailed information for each definition of EATF were collected. The components of each definition for EATF were then summarized and counted, and finally the most common essential components were identified. Results: Our systematic literature search found 2,472 candidate studies. After title and abstract screening, full text search and quality assessment, 61 studies, including 56 original studies and five reviews, were eligible for our analysis. Of these 56 original studies, 43 mentioned the timing of EATF evaluation 72 hours after the start of treatment with antibiotics. From these 43 studies, the most common indicators of EATF were extracted, among which a set of essential components for a definition of EATF were identified: mortality, vital signs, fever, symptoms, and additional treatment. Conclusions: Our scoping review uncovered five essential factors for EATF. Further study is needed to evaluate the validity of our findings. [ABSTRACT FROM AUTHOR]

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta‐analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow‐up, and quality of life‐related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition. [ABSTRACT FROM AUTHOR]

Introduction: To determine whether training laparoscopic nephrectomy (LN) with a virtual reality (VR) simulator improves the performance of porcine LN. Methods: Twelve urological residents were assigned to two groups: a training and a non‐training group. All participants performed baseline assessments of LN skills and time on the LapPASS® simulator. The training group received preoperative LapPASS® training. Both groups then performed LN using a porcine model. The operations were videotaped and evaluated using the Global Operative Assessment of Laparoscopic Skills (GOALS) system. After porcine LN, the training group performed a final LN with the LapPASS® simulator. Results: There was no significant difference in the operation time required for porcine LN. There were no significant differences in the total A (autonomy), B (bimanual dexterity), D (depth perception), or T (tissue handling) GOALS scores. However, the total E (efficiency) score in the training group was higher than that in the non‐training group (P =.030). The final LN score with LapPASS® was significantly higher than the baseline (P =.004). Conclusions: The results of this study demonstrated that VR LN training improved performance in an actual operation. VR‐based procedural simulation could become a vital part of the laparoscopic training program for residents. [ABSTRACT FROM AUTHOR]

Objectives To review the imaging findings of renal epithelioid angiomyolipomas. Methods Eight patients treated at two institutions were pathologically diagnosed as having epithelioid angiomyolipoma. All of them underwent computed tomography, and four underwent magnetic resonance imaging. The tumor size, existence of fat, heterogeneity, computed tomography attenuation, degree of enhancement, enhancement pattern and magnetic resonance imaging signal intensity were evaluated. Results Intratumoral fat was not detected in any of the cases. On unenhanced computed tomography, the intratumoral attenuation was hyperattenuating in six of the seven patients who were examined using this modality. On T2-weighted images, the signal intensity of the solid component, cyst wall or septum was low in three of the four cases. Four of the eight cases were heterogeneous solid-type accompanied by hemorrhage, necrosis or hyalinization. One homogeneous solid-type lesion was large in size and was pathologically accompanied by neither hemorrhage nor necrosis. All three multilocular cystic types were pathologically accompanied by massive hemorrhage in the cystic component. One was accompanied by spontaneous perirenal hematoma. Conclusions The radiological appearance of most epithelioid angiomyolipomas has a tendency to be hyperattenuating on unenhanced computed tomography images, with low intensities on T2-weighted images. They can be heterogeneously solid, homogeneously solid or a multilocular cystic lesion with massive hemorrhage. [ABSTRACT FROM AUTHOR]

Background: In this era of molecular targeting therapy when various systematic treatments can be selected, prognostic biomarkers are required for the purpose of risk-directed therapy selection. Numerous reports of various malignancies have revealed that 18-Fluoro-2-deoxy-D-glucose (18F-FDG) accumulation, as evaluated by positron emission tomography, can be used to predict the prognosis of patients. The purpose of this study was to evaluate the impact of the maximum standardized uptake value (SUVmax) from 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) on survival for patients with advanced renal cell carcinoma (RCC). Methods: A total of 26 patients with advanced or metastatic RCC were enrolled in this study. The FDG uptake of all RCC lesions diagnosed by conventional CT was evaluated by 18F-FDG PET/CT. The impact of SUVmax on patient survival was analyzed prospectively. Results: FDG uptake was detected in 230 of 243 lesions (94.7%) excluding lung or liver metastases with diameters of less than 1 cm. The SUVmax of 26 patients ranged between 1.4 and 16.6 (mean 8.8 ± 4.0). The patients with RCC tumors showing high SUVmax demonstrated poor prognosis (P = 0.005 hazard ratio 1.326, 95% CI 1.089-1.614). The survival between patients with SUVmax equal to the mean of SUVmax, 8.8 or more and patients with SUVmax less than 8.8 were statistically different (P = 0.0012). This is the first report to evaluate the impact of SUVmax on advanced RCC patient survival. However, the number of patients and the follow-up period were still not extensive enough to settle this important question conclusively. Conclusions: The survival of patients with advanced RCC can be predicted by evaluating their SUVmax using 18F-FDG- PET/CT. 18F-FDG-PET/CT has potency as an "imaging biomarker" to provide helpful information for the clinical decision-making. [ABSTRACT FROM AUTHOR]

Introduction: In laparoscopic surgery, surgical instruments are inserted from a trocar to the target organ in a blind fashion, which carries a risk of organ injury. To clarify the risks associated with surgical instrument insertion, we measured grip strength and pushing/pressing force during surgical instrument insertion in laparoscopic surgery. Methods: Using forceps with sensors inside a trocar, 10 urologists performed a laparoscopic procedure in pigs, in which they were asked to touch the abdominal wall. The surgeons closed their eyes during the procedure and stopped moving the forceps when they felt them come into contact with the abdominal wall. They were ordered to grip the forceps strongly or softly and to move them rapidly or slowly during the procedure. Grip strength and the pushing/pressing force when the forceps hit the abdominal wall were measured and analyzed. Results: The mean pushing/pressing force when the surgeons gripped the forceps strongly and moved them rapidly (strong/rapid), strongly/slowly, softly/rapidly, and softly/slowly were 2.8, 2.0, 1.7, and 1.1 N, respectively. The pushing/pressing force was significantly greater when the surgeons gripped the forceps strongly, regardless of the forceps speed (P <.001). The pushing/pressing force was significantly greater when the surgeons moved the forceps rapidly, regardless of grip strength (P <.001). Conclusions: When surgeons insert laparoscopic instruments through trocars, the instruments should be gripped softly and moved slowly to avoid organ injuries. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effect of our new classification on surgical outcomes after flexible ureteroscopy (fURS) for kidney stones. Methods: We retrospectively examined 128 patients after single renal fURS procedures performed using ureteral access sheaths (UASs) with the fragmentation technique. Based on the gap (calculated by subtracting the ureteroscope diameter from the UAS diameter), enrolled patients were divided into three groups: small (< 0.6 mm), medium (0.6 to < 1.2 mm), and large space groups (≥ 1.2 mm). Stone-free (SF) status was defined as either complete absence of stones (SF) or the presence of stones < 4 mm in diameter on non-contrast computed tomography (NCCT). Results: The SF rate was significantly lower in the small space group (50% in small, 97.9% in medium, 89.2% in large; p = 0.001). Perioperative complications over Clavien–Dindo Grade I were observed in 16.7%, 4.2%, and 8.1% of patients, respectively (p = 0.452). The ratio of stone volume and operative time (efficiency of stone removal) was significantly higher in the large space group compared to the small and medium space groups (0.009 ± 0.003 ml/min, 0.013 ± 0.005 ml/min, 0.027 ± 0.012 ml/min, respectively; p < 0.001). Conclusion: Our findings that gaps > 0.6 mm (1.8 Fr), including the combination of a 9.5-Fr UAS and a small caliber ureteroscope, improve SF rates, and larger gaps facilitate stone removal efficiency providing the basis for future development of clinical protocols aimed at improving outcomes. [ABSTRACT FROM AUTHOR]

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

Objectives: To compare the outcomes of radical prostatectomy (RP), intensity-modulated radiation therapy (IMRT), and low-dose-rate brachytherapy (BT) using propensity score matching analysis in patients with clinically localized prostate cancer. Methods: A group of 2273 patients with clinically localized prostate cancer between January 2004 and December 2015 at the Yokohama City University hospital were identified. The records of 1817 of these patients, who were followed up for a minimum of 2 years, were reviewed; 462 were treated with RP, 319 with IMRT, and 1036 with BT. The patients were categorized according to the National Comprehensive Cancer Network risk classification criteria, and biochemical outcomes and overall survival rates were examined. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for IMRT and BT as nadir PSA level + 2 ng/ml. Propensity scores were calculated using multivariable logistic regression based on covariates, including the patient's age, preoperative PSA, Gleason score, number of positive cores, and clinical T stage. Results: Median follow-up was 77 months for the RP, 54 months for IMRT, and 66 months for BT patients. After the propensity scores were adjusted, a total of 372 (186 each) and 598 (299 each) patients were categorized into RP vs IMRT and RP vs BT groups, respectively. Kaplan–Meier analysis did not show any statistically significant differences in terms of overall survival rate between these groups (RP vs IMRT: p = 0.220; RP vs BT: p = 0.429). IMRT was associated with improved biochemical failure-free survival compared to RP in all risk groups (high-risk: p < 0.001; intermediate-risk: p = 0.009; low-risk: p = 0.001), whereas significant differences were observed only in the intermediate-risk group (p = 0.003) within the RP vs BT group. Conclusion: The results of our propensity score analysis of mid-term localized prostate cancer treatment outcomes demonstrated no significant differences in the overall survival rate. Despite the difference in biochemical failure definition between surgery and radiotherapeutic approaches, the results of this study demonstrate improved biochemical control favoring IMRT and BT as compared to RP. [ABSTRACT FROM AUTHOR]

Purpose: To identify risk factors by developing and internally validating a nomogram for preventing perioperative complications in overnight ureteral catheterization cases after fURS for kidney stones. Methods: We retrospectively examined 309 patients with overnight ureteral catheterization after single fURS procedures for renal stones. fURS procedures were performed based on the fragmentation technique. The ureteral catheter was removed on postoperative day 1. Within this group, patients who experienced perioperative complications (complication group) were compared with those who did not experience complications (non-complication group). The complication group included 77 patients whose Clavien–Dindo classification score was I, II, III, or IV and/or those whose body temperature during hospitalization was over 37.5 °C. Results: The overall stone volume, stone-free rate, incidence of perioperative complications, and procedure duration were 1.39 mL, 94.8%, 24.9%, and 62 min, respectively. Severe complications of a Clavien–Dindo level III or IV were observed in only four cases (1.3%). Multivariate assessment revealed five independent predictors of perioperative complications after fURS with overnight catheterization: age (p = 0.11), sex (p = 0.067), stone volume (p = 0.33), Hounsfield units (p = 0.16), and narrow ureter (p = 0.018). We developed a nomogram to predict perioperative complications after fURS using these parameters. Conclusions: We developed a predictive model for perioperative complications of patients with overnight catheterization after fURS for renal stones. This model could select patients who were at a low risk of complications. [ABSTRACT FROM AUTHOR]

In vitro mouse spermatogenesis using a classical organ culture method became possible by supplementing basal culture medium with only the product of bovine serum albumin purified by chromatography (AlbuMAX), which indicated that AlbuMAX contained every chemical factor necessary for mouse spermatogenesis. However, since the identity of these factors was unclear, improvements in culture media and our understanding of the nutritional and signal substances required for spermatogenesis were hindered. In the present study, chemically defined media (CDM) without AlbuMAX was used to evaluate each supplementary factor and their combinations for the induction of spermatogenesis. Similar to in vivo conditions, retinoic acid, triiodothyronine (T3), and testosterone (T) were needed. Based on differences in spermatogenic competence between AlbuMAX, fetal bovine serum, and adult bovine serum, we identified α‐tocopherol, which strongly promoted spermatogenesis when combined with ascorbic acid and glutathione. Differences were also observed in the abilities of lipids extracted from AlbuMAX using two different methods to induce spermatogenesis. This led to the identification of lysophospholipids, particularly lysophosphatidylcholine, lysophosphatidic acid, and lysophosphatidylserine, as important molecules for spermatogenesis. New CDM formulated based on these results induced and promoted spermatogenesis as efficiently as AlbuMAX‐containing medium. In vitro spermatogenesis with CDM may provide a unique experimental system for research on spermatogenesis that cannot be performed in in vivo experiments. [ABSTRACT FROM AUTHOR]

Purpose: Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Here, we investigate C-reactive protein (CRP) at 1 month after treatment of nivolumab as a target to predict the response of patients with metastatic renal cell carcinoma (mRCC) to nivolumab.Methods: After approval of the study by our institutional review board, 64 patients with mRCC who underwent nivolumab treatment at Kanagawa Cancer Center and Yokohama City University Hospital were enrolled. The patient characteristics, blood examination data at start of nivolumab treatment and 1 month after treatment, response to treatment and progression-free survival (PFS) were evaluated. Tumour responses were assessed according to both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the immune RECIST (iRECIST) criteria. Moreover, in 12 patients who agreed to an additional blood examination, several serum inflammatory factors were investigated and their correlation with CRP level was examined.Results: The median follow-up was 8.3 months (range 0.2-29.8 months). The median PFS period was 4.5 months and the median immune-PFS (iPFS) period was 5.3 months. RECIST 1.1 criteria underestimated the benefits of nivolumab in four (6.4%) cases. Multivariate analyses showed that an Eastern Cooperative Oncology Group performance status (≥ 2) at start of treatment and CRP level at 1 month after treatment (≥ 1.5 mg/dL) were independent risk factors for a poor iPFS of nivolumab. The CRP level at baseline was not an independent prognostic factor for iPFS. When compared with the responder group (iCR + iPR + iSD), the non-responder group (iPD) had a significantly higher CRP levels at 1 month after treatment (p < 0.001). In the responder group, there was significant decrease in the CRP level after nivolumab treatment when compared with the baseline (p = 0.002), whereas there was a significant increase in the non-responder group (p = 0.019). Even patients with high baseline CRP (≥ 1.5 mg/dL) obtained good iPFS if CRP was decreased (< 1.5 mg/dL) 1 month after treatment. In addition, the classification of Glasgow prognostic score (GPS), which is a cumulative prognostic score based on CRP and albumin, was a significant predictor for iPFS. A strong correlation (|r| > 0.7) with CRP level at 1 month after treatment was seen for sCD163, IL-34, MMP-1, MMP-2, osteopontin, sTNF-R1 and sTNF-R2. Of these, MMP-1 and MMP-2 were not correlated at baseline.Conclusion: Our results indicated that the CRP level at 1 month after treatment with nivolumab appears to be a promising predictive biomarker for response to nivolumab treatment in patients with mRCC. It is clinically useful to be able to predict the effect within a short period. Further prospective trials are needed to prove these preliminary findings. [ABSTRACT FROM AUTHOR]

Introduction and Objectives. The neutrophil-to-lymphocyte ratio (NLR) has been suggested as a simple marker of the systemic inflammatory response in critical care patients. The NLR can be easily calculated from routine complete blood counts in the peripheral blood. This parameter has been reported to be an independent prognosticator for some solid malignancies. In the present study, we examined the importance of the NLR as a prognostic marker for castration-resistant prostate cancer (CRPC) patients who received docetaxel- (DOC-) based chemotherapy. Methods. We analyzed a total of 73 patients who received DOC chemotherapy for CRPC in Yokohama City University Medical Center and affiliated hospitals. Complete blood cell counts were performed, and the NLR was calculated using the neutrophil and lymphocyte counts obtained on the same day or a few days before the initiation of DOC chemotherapy. We determined the NLR cutoff value based on the sensitivity and specificity levels derived from area under the receiver operator characteristic curves for death. Results. The median overall survival (OS) after DOC was 21.0 months (range: 2.0–51.0). The median OS was shorter in patients with a high NLR (≥2.59) than in those with a low NLR (<2.59) (12.0 versus 31.6 months, p=0.001). In the multivariate analysis, the NLR and lymph node (LN) metastasis were independent predictors of the OS (hazard ratio 3.643, p=0.001; hazard ratio 2.184, p=0.038, respectively). Conclusions. The higher NLR group showed a significantly poorer OS than the lower NLR group. Pre-DOC NLR might be a new marker for predicting the prognosis of patients who receive DOC chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Mouse in vitro spermatogenesis is possible with classical organ culture methods, by placing the testis tissue at the interphase between culture medium and air. In this condition, however, a tissue piece tends to round up to be compact, whose central region suffers from shortage of nutrients and oxygen. In this study, the authors improved the culture condition by spreading each tissue thin and flat, by which they were able to get better access to the oxygen and nutrients. Methods: Immature mouse testis tissues placed on agarose gel block were forced to spread flat by covering with a polydimethylsiloxane (PDMS) ceiling chip (PC chip). They were then cultured for weeks and evaluated by the transgene expression of Acr‐Gfp, which reflects the progression of spermatogenesis. Results: Testis tissues covered with PC chip initiated and maintained spermatogenesis in its wider region than those without PC chip covering. Flow cytometric analysis demonstrated that the PC method yielded more numerous meiotic germ cells than those without PC. Immunohistochemical examination confirmed the authentic histological figure of spermatogenesis from spermatogonia up to round or elongating spermatids. Conclusions: The PC chip method is simple and effective to improve the efficiency of in vitro spermatogenesis in the organ culture system. [ABSTRACT FROM AUTHOR]

GnRH antagonist and GnRH agonist are widely used as androgen deprivation therapy for metastatic prostate cancer. A previous report demonstrated that patients with PSA levels of >20 ng/mL using GnRH antagonists showed favorable outcomes in comparison to those using GnRH agonists. An 82-year old male patient with edema, a stony hard nodule on his prostate, and an initial PSA level of 6,717 ng/mL was referred to our hospital due to suspected prostate cancer. He received prostate needle biopsy and was diagnosed with prostate cancer with bone metastasis, with a Gleason Score of 4 + 4 = 8. He was then treated with a GnRH agonist (leuprorelin acetate) and bicalutamide from July 2015. Although his PSA level decreased to 582.0 ng/mL in December 2015, his PSA level gradually increased and CRPC developed. He indicated that he did not wish to take 2nd generation anti-androgen drugs or receive systemic chemotherapy. We introduced a GnRH antagonist (degarelix) in February 2015; his PSA level did not change and his CRPC was controlled. We herein report a case in which changing a GnRH agonist to a GnRH antagonist contributed to CRPC control. [ABSTRACT FROM AUTHOR]

Introduction: Nivolumab has been introduced for metastatic renal cell carcinoma (mRCC) as a second-line therapy for years. However, despite widespread evidence of its utility, few reports have described the efficacy of nivolumab for mRCC patients on hemodialysis. Case Presentation: A 68-year-old man with a 20-year history of dialysis due to chronic glomerulotubular nephritis was referred to our department for bilateral renal tumors in 2015. In February 2015, contrast-enhanced CT revealed findings suggestive of RCC, so we performed right nephrectomy. The pathological diagnosis was clear cell carcinoma and papillary renal cell carcinoma. In July 2015, we consequently performed left nephrectomy, and the pathological diagnosis was metastatic RCC. In February 2016, because follow-up CT revealed a right adrenal tumor with time-dependent growth, sunitinib (25 mg/body) was introduced. In January 2017, although sunitinib had controlled the adrenal metastasis for 9 courses (11 months), liver metastasis was observed, so nivolumab was introduced as a second-line chemotherapy in March 2017. Nivolumab was able to control the mRCC for 15 months (32 courses). While CT showed no metastatic sites except for the liver and adrenal glands, his general condition gradually decreased, and he died in October 2018. Conclusion: We herein report a patient with RCC on hemodialysis with long-term cancer control by nivolumab. [ABSTRACT FROM AUTHOR]

For the treatment of internal ureteral orifice invasion of bladder cancer, percutaneous nephrostomy is usually attempted initially. However, percutaneous nephrostomy reduces patients' quality of day life. A 65-year-old man showed bilateral hydronephrosis due to locally advanced bladder cancer, and right percutaneous nephrostomy was created. After dilating the percutaneous nephrostomy, we inserted a metallic ureteral stent via an antegrade approach. We herein report a case of metallic ureteral stent insertion via an antegrade approach after initial creation of a nephrostomy, thus freeing the patient from nephrostomy. [ABSTRACT FROM AUTHOR]

COMPARZ study revealed no marked differences in terms of the progression free survival and overall survival between sunitinib and pazopanib treatment. Regarding the quality of life and early tumor shrinkage, pazopanib showed more favorable results than sunitinib treatment. A 70-year-old man underwent right nephrectomy in 2015. In 2017, iliac bone metastasis was found and consequently lung metastasis was developed. Pazopanib (200 mg × 4 tablets) was introduced. He showed no abnormal liver function markers during pazopanib treatment for more than two years and the size and number of lung metastases decreased. We herein report a case of successful control of metastatic renal cell carcinoma for more than two years using pazopanib treatment. [ABSTRACT FROM AUTHOR]

Pembrolizumab has been used as a second-line systemic therapy for urothelial carcinoma. We herein report a case of cisplatin-resistant renal-pelvic urothelial carcinoma that was successfully resected after pembrolizumab treatment. A 74-year-old woman was referred to our hospital for further examination for gross hematuria and a renal-pelvis tumor. Retrograde pyelography showed a defect lesion in her renal pelvis and urinary cytology of the renal pelvis showed class V. Because staging CT could not deny lung metastasis, we planned to perform nephro-ureterectomy after evaluating the response to neoadjuvant chemotherapy. After three courses of gemcitabine and cisplatin chemotherapy, the original site showed progression; thus, nephro-ureterectomy was cancelled. We introduced pembrolizumab as a second-line therapy. After four courses of pembrolizumab treatment, the size of the original lesion was significantly decreased. During these therapies the lung tumor size was unchanged; thus, we determined that the lung tumor was not metastatic and performed nephro-ureterectomy. A pathological examination demonstrated that the tumor was completely resected with a negative surgical margin. We described the first case in which cisplatin-resistant renal pelvic tumor was successfully resected after pembrolizumab treatment. [ABSTRACT FROM AUTHOR]

Background: Non-muscular invasive bladder cancer (NMIBC) has a high risk of recurrence. As androgen receptor (AR) reportedly affects bladder cancer, we assessed the correlation between NMIBC recurrence and tumor AR expression in Japanese patients.Methods: We retrospectively reviewed 53 specimens of non-metastatic NMIBC, with recurrence-free survival (RFS) as the primary endpoint. We used real-time quantitative polymerase chain reaction to quantify AR mRNA expression. Kaplan-Meier product-limit estimators were used to assess RFS distribution, log-rank tests to analyze differences in RFS between high- and low-risk groups; and multivariate analyses of AR mRNA expression and other clinicopathological factors to predict independent factors for RFS.Results: The high AR mRNA-expressing group (n = 43) tended to have a longer median RFS (not reached) than did the low-AR group (n = 10; 9.04 months; P = 0.112). Multivariate analysis showed female sex (hazard ratio [HR]: 7.360, 95% CI: 1.649-32.856, P = 0.009), tumor size ≥3 cm (HR: 23.697, 95% CI: 4.383-128.117, P < 0.001) and low AR mRNA expression (HR: 0.202, 95% CI: 0.048-0.841, P = 0.028) to be independent predictors of shorter RFS.Conclusion: Our study showed that low AR mRNA expression level is an independent risk factor for RFS in Japanese patients with NMIBC. Further studies are necessary but AR expression might be a new indicator of recurrence of NMIBC. [ABSTRACT FROM AUTHOR]

Objective: Urethral stenosis is a disease in which the lumen of the urethra becomes constricted by fibrosis. Such stenoses have been treated by urethral dilation using a bougie and optical internal urethrotomy (OIU). Recently, high‐pressure balloon dilation (BD) has been developed as a new treatment method for urethral stenosis. The present study compared the effectiveness of urethral dilation by BD and OIU. Methods: Twenty‐two patients of urethral stenosis were treated at Yokohama City University Medical Center between 2005 and 2015. Of these, 13 underwent BD, whereas OIU was performed in 9. BD was performed at 30 atm twice for 5 min each time. In OIU, an endoscopic knife was used to cut out the stenotic lesion in 3 directions. The endpoint was set as restenosis, which required additional surgical treatment, including BD, OIU, and the use of a urethral bougie. Results: The causes of urethral stricture were endoscopic surgery (n = 7; 31.8%), development after total prostatectomy (n = 4; 18.2%), iatrogenic reasons associated with catheter insertion (n = 5; 22.7%), development after a prostate needle biopsy (n = 3; 13.6%), and unknown (n = 3; 13.6%). The site of the stenotic lesion site was the anastomosis (n = 3; 13.6%), bladder neck (n = 6; 27.3%), prostatic urethra (n = 4; 18.2%), anterior urethra (n = 7; 31.8%), and membranous urethra (n = 2; 9.1%). The stenosis‐free rate was 84% for those undergoing BD and 22% for those receiving OIU. The median stenosis‐free time was significantly longer after BD than OIU (1675 vs. 244 days, respectively; P < .01). Conclusion: The stenosis‐free time was significantly longer after BD than OIU. [ABSTRACT FROM AUTHOR]

Introduction: Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression affects carcinogenesis in various cancers and has been associated with determining the overall survival among men with metastatic hormone-naïve prostate cancer (mHNPC). In this study, we analyzed the value of LMWPTP for prediction of time to castration-resistant prostate cancer (CRPC) for men with mHNPC. Materials and Methods: We retrospectively enrolled 45 men with mHNPC who were diagnosed from 2003 to 2009. All patients had received androgen deprivation therapy as first-line treatment. Prostate cancer tissues (pre-treatment needle biopsies) were immunohistochemically stained for LMW-PTP. Multivariate analyses (Cox proportional hazard model) were used to correlate baseline clinical factors of age, prostate-specific antigen (PSA), Gleason scores, T stage, N stage, extent of disease on bone scan (EOD), LMW-PTP expression and time to CRPC. Continuous variables were classified as dichotomous. Results: Median age and PSA were 70.0 years and 87.8 ng/mL respectively. Median time to CRPC was 40.2 months. Median time to CRPC was significantly shorter in the high LMW-PTP group (14.8 months) than that in the low LMW-PTP group (86.3 months, p < 0.01). In multivariate analysis, age ≥70 years and high LMW-PTP expression were significant predictors of time to CRPC. [ABSTRACT FROM AUTHOR]

Clinical use of a patient-specific simulator for patients who were scheduled for robot-assisted laparoscopic partial nephrectomy Abbreviations & Acronyms CT computed tomography PN partial nephrectomy RAPN robot-assisted laparoscopic partial nephrectomy VR virtual reality Commercially available training systems that simulate surgical processes are useful for basic training, but do not correspond to the specific characteristics of each patient. Patient-specific simulations of RAPN using silicone models were previously reported.5 A surgeon carried out a pre-surgical simulation with a robot using patient-specific models created by a 3-D printer. [Extracted from the article]

Purpose: To evaluate the influence of overnight ureteral catheterization and determine if routine long-term post-stenting can be avoided in flexible ureterorenoscopy (fURS) procedure for kidney stone.Methods: Three hundred ninety-three patients who underwent single fURS for kidney stone between January 2013 and June 2016 at a single institute were retrospectively analyzed. The stone-free (SF) and perioperative complication rates in patients with routine long-term post-stenting after fURS (long-term stent group) were compared with those of patients with overnight ureteral catheterization (short-term stent group). Propensity score-matching analysis was used to adjust the difference in baseline preoperative parameters between the two groups. All preoperative parameters were chosen to develop the propensity score, and 74 patients in the short-term stent group were retrospectively matched with the patients in the long-term stent group at a 1:1 ratio.Results: Patient characteristics included age, sex, side of involvement, height, body weight, body mass index, number of stone(s), stone volume, Hounsfield units of stone, preoperative white blood cell count, preoperative C-reactive protein, preoperative creatinine, pretreatment, pre-stenting, stenosis of the ureter, and procedure duration. The SF rates were 91.9 and 93.2% in the short-term and long-term stent groups, respectively. Perioperative complications were 14.9 and 12.2%. No difference was noted between the two groups in terms of SF and perioperative complication rates.Conclusions: Short-term post-stenting using overnight ureteral catheterization in uncomplicated cases after fURS for kidney stone was as effective as conventional long-term post-stenting in reducing postoperative complications. These preliminary data suggest the possibility that routine long-term post-stenting was unnecessary. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

A 59-year-old man was referred to our hospital complaining of asymptomatic gross hematuria. Cystoscopy revealed a papillary tumor 8 cm in diameter filling the bladder. The patient underwent transurethral resection of the bladder tumor. The pathological findings revealed the sarcomatoid variant of urothelial carcinoma with a heterologous osteosarcomatous element. He had no metastasis according to our imaging analyses; thus, we planned radical cystectomy after two courses of neoadjuvant chemotherapy (gemcitabine and cisplatin). Following chemotherapy, enlarged pelvic lymph nodes were noted, and extremely aggressive local progression of the bladder tumor was confirmed. The patient ultimately died 6 months after his initial visit to our hospital. [ABSTRACT FROM AUTHOR]

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic disorder characterized by cutaneous and uterine leiomyomatosis with RCC. This disorder is caused by a germline mutation in the fumarate hydratase (FH) gene, which encodes an important enzyme of the tricarboxylic acid (TCA) cycle. This mutation distinguishes HLRCC from sporadic RCCs. Herein, we investigated a case of HLRCC in a 32-year-old man who underwent nephrectomy for treatment of a solid-cystic tumor in the left kidney. Histopathology demonstrated a variegated architecture of papillary, tubulocystic and cribriform patterns composed of high-grade tumor cells with enlarged nuclei and eosinophilic nucleoli. Immunostaining and western blotting revealed no FH expression in the tumor. Genomic DNA sequencing identified a heterozygous mutation involving deletion of the 3' end of exon 2 and intron 2 of the FH gene (c.251_267+7delTGACAGAACGCATGC CAGTAAGTG), and RT-PCR confirmed exon 2 skipping in FH mRNA. The somatic FH gene status of the tumor showed only the mutated allele, indicating loss of heterozygosity as the "second hit" of tumor suppressor gene inactivation. These data support that an FH mutation involving the splice site causes exon skipping, changing the conformation of the protein and accelerating carcinogenic cascades under impaired FH functioning in the TCA cycle. [ABSTRACT FROM AUTHOR]

In our previous study, we produced a microfluidic device (MFD) which successfully maintained spermatogenesis for over 6 months in mouse testis tissues loaded in the device. In the present study, we developed a new MFD, a monolayer device (ML-D) with a barrier structure consisting of pillars and slits, which is simpler in design and easier to make. This ML-D was also effective for inducing mouse spermatogenesis and maintained it for a longer period than the conventional culture method. In addition, we devised a way of introducing sample tissue into the device during its production, just before bonding the upper layer of polydimethylsiloxane (PDMS) and bottom glass slide. The tissue can obtain nutrients horizontally from the medium running beside it and oxygen vertically from above through PDMS. In addition, the glass slide set at the bottom improved the visibility of the sample tissue with an inverted microscope. When we took photos of cultured tissue of the Acr-Gfp transgenic mouse testis in ML-D sequentially every day, morphological changes of the acrosome during spermiogenesis were successfully recorded. The ML-D is simple in design and useful for culturing testis tissue for inducing and maintaining spermatogenesis with clearer visibility. Due to the new method of sample loading, tissues other than testis should also be applicable. [ABSTRACT FROM AUTHOR]

Primary penile cancer is a rare disease. Higher incidence rates occur in underdeveloped countries. Many studies have suggested an association between human papillomavirus (HPV) infection and penile cancer. Although HPV can affect the squamous epithelium of the male genitalia similarly to the female genital tract, the association between penile cancer and HPV remains unclear. In the present study, the HPV gene expression was examined in penile cancer tissue using in situ hybridization (ISH). The present study included 41 cases in which penectomy was performed and 3 cases in which tumor resection was performed to treat pathologically-diagnosed penile cancer at Yokohama City University Medical Center, and its 7 affiliated hospitals between April 1990 and March 2010. The penile cancer tissue was subjected to an ISH analysis, and the clinicopathological features and prognosis were investigated. A total of 5/44 cases (11.4%) showed the expression of high-risk HPV. None of the patients showed the expression of low-risk HPV. The associations between the expression of high-risk HPV, and age, tumor location, tumor size, T stage, pathological differentiation, nuclear grade, Broder's classification, pattern of invasion, Y-K grade, vascular invasion, lymphoid invasion, koilocytosis and lymph-node metastasis were then examined. Patients with a well-differentiated status (P=0.044) and Broder's Grade 1 (P=0.019) showed a signifi- cantly lower rate of HPV positivity. The HPV expression was not significantly associated with cancer specific survival (P=0.932). ISH using INFORM HPV III does not detect the HPV genotype, this method is easy to employ and may be useful for the diagnosis of penile cancer tissue, similarly to cervical cancer. [ABSTRACT FROM AUTHOR]

Background: A computer-assisted diagnostic system for analyzing bone scans (BONENAVI) calculates the automated bone scan index (aBSI). Here we evaluated the aBSI as a prognostic imaging biomarker for men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel.Methods: We retrospectively analyzed 48 patients who received cabazitaxel for mCRPC and evaluated the ability of the aBSI to predict overall survival (OS). The Cox proportional hazards model was used to investigate the associations between baseline aBSI at cabazitaxel treatment and OS with the clinical variables as follows: age, number of cycles of docetaxel, serum prostate-specific antigen, hemoglobin (Hb), lactate dehydrogenase (LDH), and alkaline phosphatase. We determined the C-index to evaluate the discriminatory ability of our models when we included or excluded the aBSI from the analyses.Results: The median OS after cabazitaxel treatment was 10.0 months, and patients with aBSI ≤1% achieved significantly longer OS compared with patients with aBSI ≥1%. Multivariate analysis showed that age, Hb, LDH, and aBSI were independent prognostic factors of OS. Adding aBSI to the base model increased the C-index from 0.78 to 0.80.Conclusions: The aBSI may serve as a useful imaging biomarker for predicting OS among men with mCRPC treated with cabazitaxel. Prospective studies are required to establish the value of aBSI as prognostic imaging biomarker. [ABSTRACT FROM AUTHOR]

Introduction. Adrenal hemangioma is a rare disease, with only some 60 cases reported previously. Due to the difficulty of the preoperative diagnosis of adrenal hemangioma, almost all of the cases were diagnosed by a histopathological analysis of surgical specimens. Case Presentation. A 52-year-old man was referred to our department for further examination of his left retroperitoneal tumor. He had received hemodialysis due to chronic renal failure resulting from membranous nephropathy. Computed tomography revealed a mass around his left hilum. Magnetic resonance imaging (MRI) and positron-emission tomography (PET)-CT were unable to confirm or deny malignancy, and tumor markers, including CEA and CA19-9, showed slight elevation. His tumor grew from 38 mm to 54 mm in diameter in 7 months of follow-up. We therefore planned retroperitoneal tumor resection with left nephrectomy. Histopathologically, hyperplastic small vessels with hemorrhaging and denaturation were seen. The endothelial cells showed no variants or division of the nucleus. Based on this diagnosis, no further therapy was performed. He has had no recurrence in the eight months since the surgery. Conclusion. We herein report a rare case of adrenal hemangioma. [ABSTRACT FROM AUTHOR]

This study aimed to develop a prediction model for the operative time of flexible ureteroscopy (fURS) for renal stones. We retrospectively evaluated patients with renal stones who had been treated successfully and had stone-free status determined by non-contrast computed tomography (NCCT) 3 months after fURS and holmium laser lithotripsy between December 2009 and September 2014 at a single institute. Correlations between possible factors and the operative time were analyzed using Spearman’s correlation coefficients and a multivariate linear regression model. The P value < 0.1 was used for entry of variables into the model and for keeping the variables in the model. Internal validation was performed using 10,000 bootstrap resamples. Flexible URS was performed in 472 patients, and 316 patients were considered to have stone-free status and were enrolled in this study. Spearman’s correlation coefficients showed a significant positive relationship between the operation time and stone volume (ρ = 0.417, p < 0.001), and between the operation time and maximum Hounsfield units (ρ = 0.323, p < 0.001). A multivariate assessment with forced entry and stepwise selection revealed six factors to predict the operative time of fURS: preoperative stenting, stone volume, maximum Hounsfield unit, surgeon experience, sex, and sheath diameter. Based on this finding, we developed a model to predict operative time of fURS. The coefficient of determination (R2) in this model was 0.319; the mean R2 value for the prediction model was 0.320 ± 0.049. To our knowledge, this is the first report of a model for predicting the operative time of fURS treatment of renal stones. The model may be used to reliably predict operative time preoperatively based on patient characteristics and the surgeons’ experience, plan staged URS, and avoid surgical complications. [ABSTRACT FROM AUTHOR]

We previously reported the successful induction and completion of mouse spermatogenesis by culturing neonatal testis tissues. The culture medium consisted of α-minimum essential medium (α-MEM), supplemented with Knockout serum replacement (KSR) or AlbuMAX, neither of which were defined chemically. In this study, we formulated a chemically defined medium (CDM) that can induce mouse spermatogenesis under organ culture conditions. It was found that bovine serum albumin (BSA) purified through three different procedures had different effects on spermatogenesis. We also confirmed that retinoic acid (RA) played crucial roles in the onset of spermatogonial differentiation and meiotic initiation. The added lipids exhibited weak promoting effects on spermatogenesis. Lastly, luteinizing hormone (LH), follicle stimulating hormone (FSH), triiodothyronine (T3), and testosterone (T) combined together promoted spermatogenesis until round spermatid production. The CDM, however, was not able to produce elongated spermatids. It was also unable to induce spermatogenesis from the very early neonatal period, before 2 days postpartum, leaving certain factors necessary for spermatogenic induction in mice unidentified. Nonetheless, the present study provided important basic information on testis organ culture and spermatogenesis in vitro. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Lenalidomide has been developed as the derivative of thalidomide that has fewer side effects. We herein report a rare case of castration‐resistant prostate cancer successfully maintained using lenalidomide for multiple myeloma. [ABSTRACT FROM AUTHOR]

Succinate dehydrogenase-deficient renal cell carcinoma (SDH-deficient RCC) is a newly introduced histological type of RCC, which is caused by loss of subunit genes of SDH. It is known to frequently demonstrate familial occurrence and be frequently associated with gastrointestinal stromal tumors and paraganglioma. To date, only 53 cases have been reported. Here, we present an additional case of SDH-deficient RCC occurring in a 40-year-old female. The tumor was histologically biphasic, consisting of tubular and solid architectures. The tumor cells possessed oval nuclei with small nucleoli, and an eosinophilic granular cytoplasm with occasional vacuoles. These cells completely lost the immunohistochemical expression of B subunit of SDH (SDHB). Consequently, the tumor was diagnosed as SDHB-deficient RCC. We identified a novel germ line mutation of the SDHB gene, and also confirmed a hemizygous deletion of the wild-type allele in the tumor cells. To define the pathological characteristics of SDH-deficient RCC, precise diagnosis and accumulation of more cases are required. [ABSTRACT FROM AUTHOR]

Background: Primary large cell neuroendocrine carcinoma of the kidney is a rare and generally very aggressive disease. We present a case of a patient with primary large cell neuroendocrine carcinoma of the kidney with cardiac metastasis.Case Presentation: A 59-year-old Japanese man presented to his previous physician with hematuria. Computed tomography revealed masses in the heart and right kidney, and fluorodeoxyglucose-positron emission tomography showed abnormal uptake in the heart. A cardiac biopsy under transesophageal echocardiographic guidance revealed a metastatic tumor. Subsequently, multiple lung lesions were detected, and a right nephrectomy was performed after these metastases were suspected to have originated from renal carcinoma. Large cell neuroendocrine carcinoma of the kidney was ultimately diagnosed. Pancreatic metastasis was detected on computed tomography postoperatively. Three courses of chemotherapy with carboplatin and irinotecan were administered, and were temporarily effective against the metastatic lesions in the lungs and pancreas. However, our patient's general condition deteriorated with the progression of the lesions, and he died 9 months after his initial examination.Conclusions: Multi-agent chemotherapy, including platinum-based drugs was effective against large cell neuroendocrine carcinoma metastases, albeit only temporarily. This is the first reported case of large cell neuroendocrine carcinoma with cardiac metastasis. [ABSTRACT FROM AUTHOR]