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Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P P

Objective To evaluate the predictors of the total laser energy (TLE) required during ureteroscopic lithotripsy (URS) using the holmium:yttrium-aluminum-garnet (Ho:YAG) laser for a single ureteral stone. Materials and Methods We retrospectively analyzed the data of 93 URS procedures performed for a single ureteral stone in our institution from November 2011 to September 2015. We evaluated the association between TLE and preoperative clinical data, such as age, sex, body mass index, and noncontrast computed tomographic findings, including stone laterality, location, maximum diameter, volume, stone attenuation values measured using average Hounsfield units (HUs), and presence of secondary signs (severe hydronephrosis, tissue rim sign, and perinephric stranding). Results The mean maximum stone diameter, volume, and average HUs were 9.2 ± 3.8 mm, 283.2 ± 341.4 mm 3 , and 863 ± 297, respectively. The mean TLE and operative time were 2.93 ± 3.27 kJ and 59.1 ± 28.1 minutes, respectively. Maximum stone diameter, volume, average HUs, severe hydronephrosis, and tissue rim sign were significantly correlated with TLE (Spearman's rho analysis). Stepwise multiple linear regression analysis defining stone volume, average HUs, severe hydronephrosis, and tissue rim sign as explanatory variables showed that stone volume and average HUs were significant predictors of TLE (standardized coefficients of 0.565 and 0.320, respectively; adjusted R 2 = 0.55, F = 54.7, P .001). Conclusion Stone attenuation values measured by average HUs and stone volume were strong predictors of TLE during URS using Ho:YAG laser procedures.

A 36-year-old male was referred to our hospital with left scrotal swelling. Computed tomography revealed a massive tumor in his left scrotum. The tumor extended along the gonadal vein extraperitoneally forming a massive tumor. Pathological examination showed a mixed-type germ cell tumor. Despite several chemotherapeutic treatments, the tumor continued to grow, and the patient died 28 months later after his first presentation at our institution. Autopsy revealed that the tumor comprised rhabdomyosarcoma and mature teratoma. We could not find useful tumor markers to facilitate the diagnosis of rhabdomyosarcoma. However, we recommend rebiopsy or palliative operation as options for re-diagnosis in case of resistant germ cell tumor. Here, we present a case of testicular tumor that exhibited different pathological examination results before and after treatment.

Purpose To assess the efficacy of a combined regimen of levofloxacin (LVFX) plus isepamicin (ISP) as prophylaxis for transrectal ultrasound-guided needle biopsy of the prostate (TRUSP-Bx). Materials and methods Overall, 562 patients undergoing TRUSP-Bx were included in the present study. All patients were administered a single-dose of oral LVFX (500 mg) in the morning and intravenous ISP (400 mg) 60 min before biopsy. All biopsies were performed via TRUSP-Bx with an 18-gauge needle, and 12-core specimens were routinely obtained. Before initiating antibiotic treatment, urine and blood bacterial cultures were tested to determine the causative microorganisms in the patients with acute bacterial prostatitis. Results Acute bacterial prostatitis developed in three (0.53%) participants. The incidence rates of acute bacterial prostatitis in the low- and high-risk groups were 0.79% and 0.46%, respectively. These patients showed clinical symptoms of acute bacterial prostatitis 12–24 h after their biopsy. Escherichia coli (E. coli) was isolated in the urine or bladder cultures of all of patients. All three isolates were determined to be LVFX-resistant E. coli, although they had good sensitivity to aminoglycosides, cephalosporins, and carbapenems. All patients were administered antibiotic treatment (cephalosporin or carbapenem) immediately and were treated successfully with no evidence of further disease progression. Conclusion Antibiotic prophylaxis with LVFX plus ISP was effective, resulting in a lower incidence of acute bacterial prostatitis after TRUSP-Bx in both low- and high-risk patients.

We investigated whether the European Organization for Research and Treatment of Cancer (EORTC) scoring system can be used for the selection of adjuvant intravesical therapies for individual patients who undergo transurethral resection (TURB) for non-muscle-invasive bladder cancer (NMIBC). We retrospectively analyzed the data of 469 TURB cases for NMIBC. Clinical and pathological variables were compared using univariate and multivariate Cox proportional hazards regression analyses. The recurrence-free survival (RFS) rate was estimated by the Kaplan–Meier method, and the log-rank test was used to compare groups divided according to EORTC score or type of adjuvant therapy. The overall RFS rate at 1 and 3 years was 59.1 and 40.3 %, respectively. Of the total, 424 TURB cases (90.4 %) had an EORTC score of 1–9. Tumor number, size, and grade were significant predictors of time to recurrence. The EORTC score was a significant predictor of RFS according to multivariate analysis, and the hazard ratios increased according to each EORTC score in multivariate analysis of a combination of EORTC score and adjuvant therapies. In groups with intermediate recurrence risk as defined by the European Association of Urology guidelines, the recurrence prevention effects in patients with an EORTC score of ≥5 were significantly greater with intravesical Bacillus Calmette-Guerin therapy than with weekly intravesical chemotherapy. The EORTC scoring system provides useful information for the selection of adjuvant therapies for patients at intermediate risk of NMIBC recurrence.

Objective To evaluate continence status and mechanism of urinary incontinence immediately after robot-assisted radical prostatectomy (RARP) by performing urodynamic evaluation. Methods A total of 87 patients with localized prostate cancer who underwent RARP were included. Filling cystometry, urethral pressure profilometry, and abdominal leak point pressure (ALPP) tests were performed before and immediately after RARP. Results The mean urine loss ratio (ULR), calculated by dividing the total urine volume by the weight of urine loss after RARP, was 17.8%. Nerve-sparing (NS) surgery significantly affected ULR compared with non-NS surgery. In the comparison between preoperative and postoperative results, the mean maximal cystometric capacity (MCC) and maximal closure urethral pressure (MUCP) decreased from 341 mL and 84.6 cm H 2O to 250 mL and 35.6 cm H2O, respectively. No urine leakage was observed in ALPP test preoperatively; however, urine leakage was observed postoperatively in 75 patients (86%), with a mean ALPP of 47.7 cm H2O. Multivariate analysis revealed that MCC, MUCP, and ALPP after RARP were predictive factors for ULR. Linear correlations were found between ULR and MUCP and between ULR and ALPP after RARP. NS status and MUCP after RARP (r = 0.247; P =.021) and the ALPP (r = 0.254; P =.018) were significantly correlated. Conclusion In urodynamic evaluation immediately after RARP, MCC, MUCP, and ALPP were found to predictive factors for urinary incontinence. The NS procedure contributed to continence status after RARP. © 2014 Elsevier Inc.

金沢大学医薬保健研究域医学系, To clarify the recent trends in prostate-specific antigen (PSA) distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54-69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng ml⁻¹ in 2000, and gradually decreased to approximately 1.30 ng ml⁻¹ in 2006. That of participants excluding prostate cancer patients was 1.46 ng ml⁻¹ in 2000, and there was no remarkable change during the study period. The 95 th percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54-59, 60-64, and 65-69 years old were 2.90, 3.60, and 4.50 ng ml⁻¹, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.

BACKGROUND The matricellular protein secreted protein acidic and rich in cysteine (SPARC) plays an important role on tumor metastasis and progression in several cancers. However, the roles of SPARC in prostate cancer (PCa) remain unclear. METHODS To identify SPARC protein in prostate tissue, immunohistochemical analysis of SPARC was conducted using human prostate tissue microarray. To detect SPARC expression in prostate cancer (LNCaP, DU145, and PC-3) and stromal cells, RT-PCR, western blot analysis, and ELISA was conducted. To reveal the function of exogenous SPARC in PCa cells, AKT phosphorylation was confirmed by western blot analysis after coculture with stromal cells. Proliferation and migration of PCa cells were examined by addition of SPARC. The interaction between SPARC and integrin β1 was confirmed by western blot analysis after immunoprecipitation. RESULTS SPARC protein was expressed well in normal tissue compared with PCa tissue. ELISA showed high secreted SPARC protein in normal prostate-derived stromal cell (PrSC) compared with PCa-derived stromal cell (PCaSC) and PCa. PCa cells cocultured with PrSC showed reduced AKT phosphorylation more than with PCaSC. PCa cells cocultured with PrSC whose SPARC was knocked-down restored AKT phosphorylation. Moreover, PCa cells treated with SPARC led to reduced AKT phosphorylation. Immunoprecipitation with SPARC revealed interaction of SPARC and integrin β1 in PCa cells. Inhibited proliferation and migration of PCa cells by SPARC was restored by integrin β1 neutralizing antibody. CONCLUSIONS Reduced SPARC secretion from stromal cells might affect PCa progression mediating through limiting AKT phosphorylation after interaction with integrin β1. Prostate 73: 1159–1170, 2013. © 2013 Wiley Periodicals, Inc.

BACKGROUND. Conversion into androgen-hypersensitive state and adaptation to the low concentration of androgen during ADT cause relapse of prostate cancer (PCa). It is important to identify differentially expressed genes between PCa and normal prostate tissues and to reveal the function of these genes that are involved in progression of PCa. METHODS. We performed cDNA microarray analysis to identify differentially expressed genes, calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2). Immunohistochemical analysis was conducted to investigate the relationship between the CAMKK2 expression level and prognosis. The function of CAMKK2 was assessed by generating CAMKK2 overexpressed LNCaP cells and by knockdown of CAMKK2. RESULTS. We identified CAMKK2 overexpressed six times in PCa more than normal prostate by cDNA microarray analysis. Immunohistochemical analysis of CAMKK2 protein showed that CAMKK2 protein was expressed more in PCa than normal tissue. However, the expression in the high-grade PCa diminished. Moreover, the narrowness of CAMKK2positive area before ADT was a poor prognostic factor. Androgen-deprivation treatment from the medium in which LNCaP cells were cultured in the presence of 10 nM DHT repressed CAMKK2 expression. CAMKK2 overexpressed LNCaP cells (LNCaP/GFPCAMKK2) attenuated androgen-sensitivity. Tumorigenesis of LNCaP/GFP-CAMKK2 cells in male SCID mice was decreased compared with control cells irrespective of castration. Finally, knockdown of CAMKK2 mRNA in LNCaP cells induced androgen-hypersensitivity and stimulated LNCaP cell proliferation. CONCLUSIONS. Induction of androgen-hypersensitivity after ADT may be involved in down-regulation of CAMKK2. This result may provide new therapeutic approach to keep androgen-sensitivity of PCa after ADT. Prostate 72: 1789–1801, 2012. # 2012 Wiley Periodicals, Inc.

We investigated the relationship between a new index considering the estimated working space and difficulty of robot-assisted radical prostatectomy (RARP) using our database.Working height was calculated by the obstetric conjugate diameter minus the bladder and rectal wall thicknesses minus the thickness of postvesical fat minus the rectal fat thicknesses measured using preoperative magnetic resonance imaging (MRI). The proportion of working height was calculated by dividing the working height by the obstetric conjugate diameter.A total of 112 RARP cases were enrolled. The mean obstetric conjugate was 105 mm and the mean proportion of working height was 72.5%. Multivariate linear regression analysis indicated that the proportion of working height was an independent predictive factor for both console time and estimated blood loss.The difficulty of RARP can be predicted by measuring the fat thicknesses around the rectum and bladder by MRI before surgery.

Although laparoscopic radical nephroureterectomy is the standard treatment for localized upper urinary tract urothelial carcinoma, open radical nephroureterectomy has been reported to have a different rate of intravesical recurrence.Intravesical recurrence-free, progression-free, and overall survival rates among patients undergoing open and laparoscopic radical nephroureterectomy from 2002 to 2013 were analyzed.Although no single factor predicted intravesical recurrence-free survival, a past history of bladder cancer or grade 3 was related to poorer intravesical recurrence-free survival rate in patients treated with laparoscopic radical nephroureterectomy. Moreover, the novel proposed risk classification based on our data clearly showed better progression-free survival and overall survival, as well as intravesical recurrence-free survival, in patients treated with laparoscopic radical nephroureterectomy.The findings reported here may help urologists predict oncological outcomes and to plan follow-up schedules after laparoscopic radical nephroureterectomy.

Percutaneous radiofrequency ablation (RFA) for small renal tumors has been reported to be effective in patients with poor surgical status. We retrospectively analyzed clinical outcomes, including renal function, after RFA.We retrospectively analyzed data of 24 patients with small renal tumors treated by RFA in our institution from January 2007 to November 2012.A total of 36 tumors (35 renal cell carcinomas and one colon cancer metastasis) with a mean diameter of 21.1 mm (10-45 mm) in 24 patients were treated. Complete ablation was achieved in 22 patients (91.7%). There were two recurrences in other sites of the kidney (8.3%) and two distant metastases (8.3%) during the mean follow-up period of 21 months (1-57 months). No severe perioperative complications were observed. No significant difference in serum creatinine levels before and after RFA procedures in the 22 evaluable patients, nor in seven patients with a solitary kidney.RFA for small renal tumors is a safe treatment with sufficient preservation of renal function, even in patients with a solitary kidney.

Prevention of the development of castration-resistant from hormone-naïve prostate cancer is an important issue in maintaining the quality of life of the patients. We explored the effect of 2'-hydroxyflavanone on proliferation and androgen responsiveness using prostate cancer cell lines.To investigate the effect of 2'-hydroxyflavanone on proliferation, prostate cancer cells were treated with 2'-hydroxyflavanone. Androgen-responsiveness in LNCaP cells was confirmed by luciferase assay after transfection of luciferase reporter driven by prostate specific antigen promoter. To detect androgen receptor (AR) expression, reverse transcriptase polymerase chain reaction and western blot analysis were conducted.2'-Hydroxyflavanone inhibited the proliferation of PC-3 and DU145 cells by induction of apoptosis. 2'-Hydroxyflavanone inhibited the proliferation of LNCaP cells stimulated by androgens and attenuated androgen-responsiveness through down-regulation of AR protein.2'-Hydroxyflavanone not only inhibited proliferation of prostate cancer cells, but also repressed androgen-responsiveness, suggesting that it might be a useful agent in preventing recurrence of prostate cancer.

The matricellular protein secreted protein acidic and rich in cysteine (SPARC) plays an important role on tumor metastasis and progression in several cancers. However, the roles of SPARC in prostate cancer (PCa) remain unclear.To identify SPARC protein in prostate tissue, immunohistochemical analysis of SPARC was conducted using human prostate tissue microarray. To detect SPARC expression in prostate cancer (LNCaP, DU145, and PC-3) and stromal cells, RT-PCR, western blot analysis, and ELISA was conducted. To reveal the function of exogenous SPARC in PCa cells, AKT phosphorylation was confirmed by western blot analysis after coculture with stromal cells. Proliferation and migration of PCa cells were examined by addition of SPARC. The interaction between SPARC and integrin β1 was confirmed by western blot analysis after immunoprecipitation.SPARC protein was expressed well in normal tissue compared with PCa tissue. ELISA showed high secreted SPARC protein in normal prostate-derived stromal cell (PrSC) compared with PCa-derived stromal cell (PCaSC) and PCa. PCa cells cocultured with PrSC showed reduced AKT phosphorylation more than with PCaSC. PCa cells cocultured with PrSC whose SPARC was knocked-down restored AKT phosphorylation. Moreover, PCa cells treated with SPARC led to reduced AKT phosphorylation. Immunoprecipitation with SPARC revealed interaction of SPARC and integrin β1 in PCa cells. Inhibited proliferation and migration of PCa cells by SPARC was restored by integrin β1 neutralizing antibody.Reduced SPARC secretion from stromal cells might affect PCa progression mediating through limiting AKT phosphorylation after interaction with integrin β1.

Conversion into androgen-hypersensitive state and adaptation to the low concentration of androgen during ADT cause relapse of prostate cancer (PCa). It is important to identify differentially expressed genes between PCa and normal prostate tissues and to reveal the function of these genes that are involved in progression of PCa.We performed cDNA microarray analysis to identify differentially expressed genes, calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2). Immunohistochemical analysis was conducted to investigate the relationship between the CAMKK2 expression level and prognosis. The function of CAMKK2 was assessed by generating CAMKK2 overexpressed LNCaP cells and by knockdown of CAMKK2.We identified CAMKK2 overexpressed six times in PCa more than normal prostate by cDNA microarray analysis. Immunohistochemical analysis of CAMKK2 protein showed that CAMKK2 protein was expressed more in PCa than normal tissue. However, the expression in the high-grade PCa diminished. Moreover, the narrowness of CAMKK2-positive area before ADT was a poor prognostic factor. Androgen-deprivation treatment from the medium in which LNCaP cells were cultured in the presence of 10 nM DHT repressed CAMKK2 expression. CAMKK2 overexpressed LNCaP cells (LNCaP/GFP-CAMKK2) attenuated androgen-sensitivity. Tumorigenesis of LNCaP/GFP-CAMKK2 cells in male SCID mice was decreased compared with control cells irrespective of castration. Finally, knockdown of CAMKK2 mRNA in LNCaP cells induced androgen-hypersensitivity and stimulated LNCaP cell proliferation.Induction of androgen-hypersensitivity after ADT may be involved in down-regulation of CAMKK2. This result may provide new therapeutic approach to keep androgen-sensitivity of PCa after ADT.

We report a case of a pyogenous vesical abscess resulting from an ingested fish bone embedded in the bladder wall that was treated endoscopically in an asymptomatic man. Computed tomography of the abdomen showed a linear radiopaque structure in the thickened left anterolateral wall of the bladder. Cystoscopy revealed a protruding mass, covered with normal-appearing mucosa, with outflow of pus from a shallow recess. Histopathological findings indicated that the transurethrally removed linear structure, located in the submucosa, was compatible with fish bone. A high index of suspicion should be maintained for the correct diagnosis to be made.

Background: Since androgen-androgen receptor (AR) axis is the main stream for development and progression of prostate cancer, androgen-deprivation therapy (ADT) is conducted as a first line hormonal therapy using medical castration, such as LH-RH agonists, LH-RH antagonist, and antiandrogen for advanced PCa. After an initial response to ADT, however, PCa eventually loses responsiveness to ADT and progresses into castration-resistant prostate cancer (CRPC). Prevention of the development of castration-resistant from hormone-naïve prostate cancer is an important issue in maintaining the quality of life of the patients. We explored the effect of 2’-hydroxyflavanone on proliferation and androgen responsiveness using prostate cancer cell lines. Materials and Methods: To investigate the effect of 2’ -hydroxyflavanone on proliferation, prostate cancer cells were treated with 2’-hydroxyflavanone. Androgen-responsiveness in LNCaP cells was confirmed by luciferase assay after transfection of luciferase reporter driven by prostate specific antigen promoter. To detect androgen receptor (AR) expression, reverse transcriptase polymerase chain reaction and western blot analysis were conducted. Results: 2’ -Hydroxyflavanone inhibited the proliferation of PC-3 and DU145 cells by induction of apoptosis. 2’ -Hydroxyflavanone inhibited the proliferation of LNCaP cells stimulated by androgens and attenuated androgen-responsiveness through down-regulation of AR protein. Conclusion: 2’ -Hydroxyflavanone not only inhibited proliferation of prostate cancer cells, but also repressed androgen-responsiveness, suggesting that it might be an useful agent in preventing recurrence of prostate cancer. Citation Format: Atsushi Mizokami, Mitsuo Ofude, Misako Kumaki, Kouji Izumi, Hiroyuki Konaka, Yoshifumi Kadono, Minkyoung Shin, Jian Zhang, Evan T. Keller, Mikio Namiki. Repression of cell proliferation and androgen receptor activity by 2’-hydroxyflavanone in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 617. doi:10.1158/1538-7445.AM2014-617