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Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is expected to be useful in preventing oversight of non-muscle-invasive bladder cancer (NMIBC) and in reducing the intravesical recurrence rate after transurethral resection of bladder tumor (TURBT). We report our initial experience with28 cases of PDD-assisted TURBT (122 samples) performed at our hospital from February 2018 to April 2019. The median age of the patients was 74.5 years, and 18 of the 28 were primary cases. Each patient underwent TURBT with oral administration of 5-ALA 20 mg/kg 3 hours before endoscopic examination. The sensitivity was 89.8% when both white light and blue light were used, which was superior to the sensitivity of 67.8% when using only white light (p＜0.01, McNemar's test). Among the first several cases, we experienced high false positivity, which suggested that some experience may be required to discriminate tumors from inflammatory lesions. In fact, the specificity and the positive likelihood ratio improved with experience. No grade 2 or higher adverse events were observed among our cases. The median follow-up period was 738 days, and 9 of 28 patients (32. 1%) had recurrence within the follow-up period. In conclusion, our initial experience with PDD-assisted TURBT demonstrated its excellent diagnostic sensitivity and safety, as previously reported.

Prostate cancer (PCa) cells frequently invade the surrounding stroma, leading to heterogeneous formation of structural atypia. The surrounding stroma contains multiple functionally diverse populations of fibroblasts that trigger numerous changes in PCa cells including motility. Thus, we hypothesized that direct or indirect contact of PCa cells with fibroblasts determines an invasive phenotype in PCa cells. We investigated the effects of 10 different patient-derived fibroblast lines on the three-dimensional (3D) morphogenesis of PCa cells growing on a viscous substrate in vitro. When grown alone, all 10 patient-derived fibroblast lines clumped on the viscous substrate, whereas the human androgen-sensitive PCa cell line LNCaP did not. Cocultures of LNCaP cells with seven of the patient-derived fibroblast lines (PrSC, pcPrF-M5, pcPrF-M7, pcPrF-M23, pcPrF-M24, pcPrF-M28, and pcPrF-M31) formed a thick fibroblast layer that resembled human prostate stromal structures. In contrast, cocultures of LNCaP cells with the remaining three fibroblast lines (NPF-M13, pcPrF-M10, and pcPrF-M26) did not form a thick fibroblast layer. Of the seven fibroblast lines that caused thick layer formation, four patient-derived fibroblast lines (PrSC, pcPrF-M5, pcPrF-M28, and pcPrF-M31) induced an invasive phenotype in LNCaP cells with a cord-like infiltrating growth pattern, whereas the other three fibroblast lines (pcPrF-M7, pcPrF-M23, and pcPrF-M24) induced no or a very weak invasive phenotype. Using cell culture inserts, none of the four patient-derived fibroblast lines that induced an invasive phenotype (PrSC, pcPrF-M5, pcPrF-M28, and pcPrF-M31) affected CDH1 mRNA expression in LNCaP cells; yet, two patient-derived fibroblast lines (pcPrF-M5 and pcPrF-M28) increased CDH2 mRNA expression in LNCaP cells, whereas the other two fibroblast lines (PrSC and pcPrF-M31) did not. These results suggest that the existence of multiple functionally diverse populations of fibroblasts in PCa tissue may be responsible for the diversity in PCa cell invasion, leading to heterogeneous formation of structural atypia., (© 2021 Wiley Periodicals LLC.)

Background: Radical prostatectomy (RP) is the standard treatment in patients with high-risk prostate cancer (PCa). However, there is a high rate of recurrence, and new approaches are required to improve surgical efficacy. Here, we evaluated the feasibility and safety of neoadjuvant chemohormonal therapy (NCHT) before RP for Japanese patients with high-risk localized prostate cancer (PCa)., Methods: From February 2009 to April 2016, 21 high-risk patients were enrolled in this prospective study. Patients were treated with docetaxel (70 mg/m 2 ) every four weeks for three cycles and luteinizing hormone-releasing hormone agonist. Patients with grade 3-4 toxicities had 25% dose reductions for the following course., Results: Median follow-up was 88.6 months. The dose of docetaxel was reduced in 13 patients. The estimated five-year biochemical progression-free survival (bPFS) rate was 57.1%. National Comprehensive Cancer Network criteria (high-risk, but not very high-risk (nVHR) versus VHR) was associated with bPFS ( p = 0.03). Five-year bPFS rates in the nVHR and VHR groups were 76.9% and 25.0%, respectively. There was a significant difference in bPFS between the nVHR and VHR groups ( p = 0.023) by Kaplan-Meier analysis., Conclusions: Although our study included a small number of cases, at least in our exploration, NCHT was safe and feasible. However, more extensive treatment modalities are needed to improve outcomes, especially in VHR patients.

Tacrolimus is important for immunosuppression in kidney transplantation. In this historical cohort and in vitro study, we evaluated the changes in tacrolimus pharmacokinetics early after living donor kidney transplantation and the effects of interleukin (IL)-6 on cytochrome P450 3A4 (CYP3A4) and cytochrome P450 3A5 (CYP3A5) expression. In the historical cohort study, 22 patients who met the inclusion criteria were classified into CYP3A5 expressors and non-expressors (n = 16 and 6, respectively). The blood tacrolimus concentration per dose ratio (C/D) temporarily increased post-kidney transplantation on days 3-4 only in CYP3A5 non-expressors. The effects of IL-6 on CYP3A4 and CYP3A5 expression were also investigated in vitro using HepG2 and Caco-2 cells. IL-6 induced a significant concentration- and time-dependent decrease in CYP3A4 and CYP3A5 expression in both cells. The mean CYP3A4 expression level at 12 hours after IL-6 exposure (% of 0 hour) was 44.0 and 62.6 in HepG2 and Caco-2 cells, respectively, whereas the CYP3A5 expression level was 30.7 and 52.4, respectively. We hypothesize that CYP3A5 non-expressors might exhibit a temporary decrease in the oral clearance of tacrolimus via an increase in serum IL-6 concentrations early after kidney transplantation. These results may help develop strategies to improve kidney transplant outcome., (© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

A 21-year-old man with chief complaints of left hypochondriac and chest pain was shown to have multiple masses in the lung, a pleural effusion in the right cavum thoracis, a mediastinal mass, and lymphadenopathy detected by computed tomographic scan. He was diagnosed with an extragonadal germ cell tumor based on pathologic findings from lung biopsies and elevation of the serum total human chorionic gonadotropin. He underwent a reduced chemotherapy regimen consisting of bleomycin, cisplatin, and etoposide (reduced BEP) to lower the risk of acute respiratory distress syndrome (ARDS), a manifestation of choriocarcinoma syndrome, which occurs at induction chemotherapy with the full-dose BEP regimen. Choriocarcinoma syndrome did not develop during chemotherapy, and he has been disease-free since salvage chemotherapy and subsequent retroperitoneal lymph node dissection.

The normal prostate epithelial structure is maintained by homeostatic interactions with smooth muscle cells. However, structural alterations of the stroma are commonly observed in prostatic proliferative diseases, leading to the abnormalities of prostate epithelial structure. A decrease in the androgen level experimentally induces stromal remodeling, i.e., replacement of smooth muscle cells with fibroblasts or myofibroblasts. In this study, we investigated the effects of castration-induced stromal remodeling and subsequent aberrant activation of epithelial-stromal interactions on the reconstituted human prostate-like epithelial structure. We performed in vivo experiments using the human prostate epithelial cell line BPH-1 and fetal rat urogenital sinus mesenchyme to generate heterotypic tissue recombinants that form human prostate-like epithelial structure (i.e., solid- and canalized-epithelial cords). Host mice were castrated at 12 weeks post transplantation (castration) and implanted with a dihydrotestosterone pellet at 14 days post castration (androgen replacement treatment; ART). In the castration group, the percentages of fibrotic area and disrupted prostate epithelial structure without the basement membrane (BM) increased proportionally in a time-dependent manner, but were suppressed by ART. In the castration group, tenascin-C (TNC)-positive fibroblasts were abundant in the stroma surrounding disrupted prostate epithelial structure without the BM. TGF-β1 secretion from BPH-1 cells was increased by co-culturing with human primary cultured prostate fibroblasts. TNC mRNA expression was increased in fibroblasts co-culturing with BPH-1 cells and was suppressed by treatment with a TGF-β RI kinase inhibitor. Moreover, in the castration group, the percentage of p-Smad2-positive cells was significantly higher in the stroma surrounding disrupted prostate epithelial structure without the BM. Our results demonstrate that castration-induced stromal remodeling disrupted the reconstituted human prostate-like epithelial structure and induced the appearance of TNC-positive fibroblasts accompanied by activation of TGF-β signaling. The alteration of prostate stromal structure may be responsible for loss of the BM and epithelial cell polarity.

A 67-year-old female presented for evaluation of a left inguinal mass. Contrast-enhanced computed tomography revealed a tumor surrounding the urethra. Magnetic resonance imaging showed that the tumor had invaded the bladder neck on the anterior aspect of the urethra. The serum carbohydrate antigen 19-9 level was elevated. The clinical diagnosis was a primary adenocarcinoma of the female urethra (cT4N2M0). The initial treatment consisted of gemcitabine plus cisplatin (GC) and oral fluoropyrimidine (S-1). A total cysto-urethrectomy with anterior vaginal wall resection, pelvic and inguinal lymphadenectomy, and urinary diversion with ileal conduit formation were performed. The final diagnosis was urethral adenocarcinoma (ypT4ypN2, stage IV). Twelve months post-operatively, there was no evidence of recurrence or distant metastases.

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (μg/μg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4-5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8 + T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.

Computed tomography (CT) attenuation value of ureteral stones is one of the predictors of shockwave lithotripsy (SWL) outcome. It is common to use the mean Hounsfield units (HU) to describe the CT attenuation value. However, an observer bias can occur when measuring the mean HU in the conventional method. On the other hand, our way to obtain only the maximum HU is simpler and less biased. We retrospectively evaluated 464 patients with ureteral stones who underwent SWL and compared predictive accuracy of various factors including maximum and mean HU. Results were determined after a single SWL. Predictors of SWL success were examined by the statistical analysis of successful and failed groups. 324 of the 464 patients who underwent SWL were stone-free after a single SWL. Significant differences were found in factors related to CT attenuation value and stone size. As a result of receiver operating characteristic analysis, it was found that maximum HU and mean HU, major diameter and volume have equivalent prediction accuracy, respectively. Multivariate analysis revealed that maximum HU and major diameter were included in independent predictors. We also examined the new original indicators using maximum HU and major diameter. Stone-resistant probability obtained from the logistic model and Maximum HU and Major diameter Index obtained by multiplying maximum HU by major diameter were useful for predicting SWL success, respectively. In conclusion, maximum HU and mean HU have equivalent predictive accuracy, and maximum HU is easier to measure and less biased than mean HU.

Loss of androgen receptor (AR) dependency in prostate cancer (PCa) cells is associated with progression to castration-resistant prostate cancer (CRPC). The tumor stroma is enriched in fibroblasts that secrete AR-activating factors. To investigate the roles of fibroblasts in AR activation under androgen deprivation, we used three sublines of androgen-sensitive LNCaP cells (E9 and F10 cells: low androgen sensitivity; and AIDL cells: androgen insensitivity) and original fibroblasts derived from patients with PCa. We performed in vivo experiments using three sublines of LNCaP cells and original fibroblasts to form homotypic tumors. The volume of tumors derived from E9 cells plus fibroblasts was reduced following androgen deprivation therapy (ADT), whereas that of F10 or AIDL cells plus fibroblasts was increased even after ADT. In tumors derived from E9 cells plus fibroblasts, serum prostate-specific antigen (PSA) decreased rapidly after ADT, but was still detectable. In contrast, serum PSA was increased even in F10 cells inoculated alone. In indirect cocultures with fibroblasts, PSA production was increased in E9 cells. Epidermal growth factor treatment stimulated Akt and p44/42 mitogen-activated protein kinase phosphorylation in E9 cells. Notably, AR splice variant 7 was detected in F10 cells. Overall, we found that fibroblast-secreted AR-activating factors modulated AR signaling in E9 cells after ADT and loss of fibroblast-dependent AR activation in F10 cells may be responsible for CRPC progression.

Background: The tyrosine kinase inhibitors (TKI), imatinib and nilotinib, are used to treat chronic myelogenous leukemia (CML). In three CML patients being monitored for urologic diseases, we observed that switching of TKI therapy affected prostate-specific antigen (PSA) titers. Urologists and other medical professionals need to be aware of the potential side-effects of drugs that patients may be receiving for other indications to modify this important prostate diseases indicator. TKIs may affect PSA titers independent of prostate growth or volume., Materials and Methods: We followed PSA levels in urology patients who were also undergoing TKI treatment for CML. We determined the effects of nilotinib and imatinib on proliferation, AR and PSA expression in the LNCaP and 22Rv1 prostate cancer (PCa) cell lines using real-time PCR and Western blotting., Results: Clinically, nilotinib and dasatinib reversibly reduced PSA titers compared to imatinib. At high doses nilotinib and imatinib both demonstrated antiproliferative effects in the PCa cells. At low doses expression of AR and PSA was decreased by both drugs, at mRNA and protein levels. Nilotinib exerted greater effects at lower doses than imatinib., Conclusions: Nilotinib down-regulates serum PSA in patients being treated for non-urological indications, potentially masking a clinical useful marker, we cannot exclude a similar but smaller effect of imatinib. Nilotinib and imatinib both decreased AR and PSA expression in PCa cell lines with the nilotinib effect evident at lower doses. Urologists must appreciate the effects of drugs provided for other diseases on PSA titers and be aware that sudden changes may not reflect underlying prostatic disease., (© 2018 Wiley Periodicals, Inc.)

Pirfenidone (PFD) is an anti-fibrotic drug used to treat idiopathic pulmonary fibrosis by inducing G₁ cell cycle arrest in fibroblasts. We hypothesize that PFD can induce G₁ cell cycle arrest in different types of cells, including cancer cells. To investigate the effects of PFD treatment on the growth of human prostate cancer (PCa) cells, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines (androgen-low-sensitive E9 and F10 cells and androgen-insensitive AIDL cells), as well as an androgen-insensitive human PCa cell line (PC-3). PFD treatment suppressed the growth of all PCa cells. Transforming growth factor β1 secretion was significantly increased in PFD-treated PCa cells. In both LNCaP and PC-3 cells, PFD treatment increased the population of cells in the G₀/G₁ phase, which was accompanied by a decrease in the S/G₂ cell population. CDK2 protein expression was clearly decreased in PFD-treated LNCaP and PC-3 cells, whereas p21 protein expression was increased in only PFD-treated LNCaP cells. In conclusion, PFD may serve as a novel therapeutic drug that induces G₁ cell cycle arrest in human PCa cells independently of androgen sensitivity. Thus, in the tumor microenvironment, PFD might target not only fibroblasts, but also heterogeneous PCa cells of varying androgen-sensitivity levels.

A 47-year-old female presented to a clinic complaining of right back pain. A CT scan revealed a right retroperitoneal mass and she was referred to our department for further evaluation. Contrast-enhanced CT and MRI revealed a right retroperitoneal mass (6 cm) in the hilum of the right kidney that invaded the right renal vein and inferior vena cava (IVC). Suspecting a tumor arising from retroperitoneal tissues involving the right renal vein and IVC, the decision was made to excise the tumor with the right kidney, renal vein, and a portion of the IVC. The histologic findings indicated that the tumor was a leiomyosarcoma originating from the renal vein wall. The tumor cells were spindle-shaped and stained positive for desmin, caldesmon and HHF35. The post-operative course was uneventful and she was recurrence-free 20 months after surgery. In addition to presenting a case of a leiomyosarcoma of the renal vein, a short review of the literature is provided.

Prostate-specific antigen (PSA) is currently the most useful biomarker for detection of prostate cancer (PCa). The ability to measure serum PSA levels has affected all aspects of PCa management over the past two decades. The standard initial systemic therapy for advanced PCa is androgen-deprivation therapy (ADT). Although PCa patients with metastatic disease initially respond well to ADT, they often progress to castration-resistant prostate cancer (CRPC), which has a high mortality rate. We have demonstrated that time to PSA nadir (TTN) after primary ADT is an important early predictor of overall survival and progression-free survival for advanced PCa patients. In in vivo experiments, we demonstrated that the presence of fibroblasts in the PCa tumor microenvironment can prolong the period for serum PSA decline after ADT, and enhance the efficacy of ADT. Clarification of the mechanisms that affect TTN after ADT could be useful to guide selection of optimal PCa treatment strategies. In this review, we discuss recent in vitro and in vivo findings concerning the involvement of stromal⁻epithelial interactions in the biological mechanism of TTN after ADT to support the novel concept of "tumor regulating fibroblasts".

Background: In nonmuscle invasive bladder cancer patients, prediction of pTa and pT1 bladder cancer recurrence and progression must be established. Micropapillary structures have been defined as small clusters of invasive cancer cells having features of the epithelial-mesenchymal transition. Since the stromal microenvironment helps to induce the epithelial-mesenchymal transition, interactions between cancer cells and stroma should be closely examined to predict the tumorigenic phenotype of human bladder cancer cells., Materials and Methods: To investigate differences in the responsiveness of cancer cells to stroma, we combined 3 established human bladder cancer cell lines (high-grade T24 and UM-UC-3 cells, and low-grade papillary RT4 cells) with fetal rat mesenchyme., Results: Among 3 bladder cancer cell lines, the expression profiles of p63 isoforms were distinct, i.e., p63γ in T24 cells, p63β in UM-UC-3 cells, and p63α in RT4 cells. Tumors formed by T24 cells combined with fetal mesenchyme formed micropapillary-like structures, whereas those formed by T24 cells alone did not. T24 cells combined with fetal mesenchyme showed poor differentiation, e.g., innumerable chromatic atypia in the nuclei, higher levels of chromatic condensation, and increased nucleoli. In contrast, both UM-UC-3 and RT4 cells combined with fetal mesenchyme did not form micropapillary-like structures. Ki-67 and p63 labeling indices were significantly elevated by combining fetal mesenchyme with T24 cells but not with the others., Conclusions: By mixing cancer cells with fetal mesenchyme, our data demonstrated that formation of micropapillary-like structures may predict the tumorigenic phenotype of invasive bladder cancer cells. Taken together, distinct expression profiles of p63 isoforms may predict poor outcomes in invasive bladder cancer., (Copyright © 2018. Published by Elsevier Inc.)

Background: The reduced androgen-sensitivity of prostate cancer (PCa) cells is an important clinical development because of its association with the cells' progression to castration-resistant prostate cancer (CRPC). During androgen deprivation therapy (ADT), stroma-derived growth factors and cytokines can activate the androgen receptor (AR). For example, IL-6 is a multifunctional cytokine that is involved in the malignancy of PCa cells through AR activation. In the present study, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines to investigate the relationship between the responsiveness of PCa cells to IL-6 treatment and the cellular AR signaling pathway., Methods: The androgen-low-sensitive F10 and E9 cells were obtained from LNCaP cells by limiting dilution method in regular culture condition. In contrast, the androgen-insensitive AIDL cells were established from LNCaP cells by continuous passaging in hormone-depleted condition. Original carcinoma-associated fibroblasts (CAFs) PCaSC-8 and PCaSC-9 cells were isolated from needle biopsy samples of PCa patients., Results: In fibroblasts derived from PCa patients, IL-6 secretion was generally higher than that observed with normal fibroblasts. In contrast, IL-6 secretion was not detected in LNCaP and its sublines. The soluble IL-6 receptor was detected in PCa cells but not in fibroblasts. IL-6 treatment suppressed cell growth of LNCaP, F10, and E9 cells but not AIDL cells and it was accompanied with neuroendocrine-like differentiation. Induction of PSA secretion was observed in IL-6-treated LNCaP and F10 cells. VEGF secretion was strongly induced in IL-6-treated LNCaP and AIDL cells. IL-6-induced VEGF secretion was significantly suppressed by a PI3K inhibitor (LY294002) and it was accompanied by inhibited phosphorylation of Akt., Conclusions: Our results suggest that IL-6 might induce VEGF secretion from PCa cells in a manner independent of AR activation. To prevent IL-6-induced VEGF secretion, inhibition of the PI3K/AKT signaling pathway could be an important pharmacological goal regardless of ADT., (© 2018 Wiley Periodicals, Inc.)

Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial-stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers., Competing Interests: The authors declare no conflicts of interest.

Purpose: Docetaxel (DTX) is a standard chemotherapeutic drug for castration-resistant prostate cancer (CRPC), although adverse events are common. To overcome this problem, researchers have evaluated the efficacy of DTX treatment in combination with other drugs. Naftopidil is a tubulin-binding drug with fewer adverse events, implying the usefulness of this drug in clinical applications when combined with DTX. Here, we investigated the efficacy of additive naftopidil treatment in combination with DTX on prostate cancer (PCa) cells., Methods: The effects of combination treatment with DTX plus naftopidil were analyzed using two animal models of LNCaP cells plus PrSC xenografts (sub-renal capsule grafting) and PC-3 xenografts (intratibial injection)., Results: Combination treatment with DTX plus naftopidil significantly inhibited cell growth in LNCaP cells compared with DTX alone. Analysis of the cooperativity index (CI) showed that combination treatment exhibited additive effects on DTX-induced growth inhibition in LNCaP cells. In contrast, combination treatment showed more than an additive (synergistic) effect on DTX-induced apoptosis in LNCaP and PC-3 cells. In LNCaP cells plus PrSC xenografts, combination treatment showed synergistic effects on DTX-induced apoptosis. The synergistic effects of naftopidil on DTX-induced apoptosis were also observed in PC-3 xenografts., Conclusions: Our results demonstrated that additive naftopidil treatment in combination with DTX increased the efficacy of DTX for the treatment of LNCaP and PC-3 tumors in vivo. Thus, additive naftopidil treatment showed a synergistic effect on DTX-induced apoptosis in PCa cells in vitro and in vivo, suggesting that this treatment approach may yield improved clinical benefits compared with DTX alone.

Background: The optimal dose of mycophenolate mofetil (MMF) in renal transplant patients has been recommended to be decided on the basis of area under the concentration-time curve (AUC 0-12 ) of mycophenolic acid (MPA). Although meta-analysis has revealed that postoperative day (POD) is an influencing factor in MPA pharmacokinetics, there are no reports regarding a limited sampling strategy (LSS) for MPA AUC in consideration of POD. The aim of this study was to construct of an LSS considering POD that appropriately expresses the MPA AUC following renal transplantation and evaluation of the usefulness., Methods: Serum concentration-time profiles (measured AUC 0-12 ) comprising nine sampling points over 12 h were analyzed in 36 living-donor renal transplant recipients after MMF administration with concomitant once-daily prolonged-release tacrolimus. Two LSSs were developed by stepwise multiple regression analysis (Method A: not classified by PODs; Method B: classified by PODs into POD < 31 and POD ≥ 31). Each LSS comprised four blood-sampling points within 6 h after MMF administration. Precision and reliability were verified by using root-mean-square error (RMSE), correlation coefficient (R 2 ), and coefficient of determination (q 2 ) by using leave-one-out cross-validation. The absolute values of the difference between measured and estimated AUCs (delta AUC) were compared for both estimating equations., Results: One-hundred samples obtained from 36 recipients for AUC 0-12 comprised POD < 31 ( n  = 39) and POD ≥ 31 ( n  = 61). Estimation of AUC 0-12 by Method B resulted in better accuracy and reliability (Method A: RMSE = 5.5, R 2  = 0.85, q 2  = 0.83; Method B: POD < 31: RMSE = 5.5, R 2  = 0.86, q 2  = 0.83; POD ≥ 31: RMSE = 3.9, R 2  = 0.92, q 2  = 0.89) and significantly lower median delta AUC compared with that by Method A (delta AUC: 2.6 (0.0-11.6) v.s. 3.9 (0.1-18.1), p  = 0.032)., Conclusion: These results suggest that LSS, classified as POD < 31 or POD > 31, would provide more accurate and reliable estimation of MPA AUC 0-12 in Japanese living-donor renal transplant patients.

Purpose: Clinically, radiotherapy (RT) often leads to the development of prostate cancer (PCa) resistance because of protective responses in cancer cells. One of the mechanisms includes the upregulation of RT-induced antioxidant enzymes. Thus, combination therapy with RT and certain pharmaceutical drugs targeting antioxidant enzymes may be ideal for increasing the efficacy of RT with minimum side effects. Naftopidil is a subtype-selective α 1D -adrenoceptor antagonist used for the treatment of benign prostatic hyperplasia (BPH). In our drug repositioning study, naftopidil showed not only unique growth-inhibitory effects but also AKT phosphorylation-inhibitory effects in PC-3 human PCa cells. Here, we examined the efficacy of additive naftopidil treatment in combination with RT in PC-3 cells., Methods: The effects of combination therapy with RT plus naftopidil were analyzed using an animal model of PC-3 xenografts in BALB/c nude mice. The expression of the antioxidant enzyme manganese superoxide dismutase (MnSOD) was evaluated by western blotting., Results: Combination therapy with RT plus naftopidil induced a more efficacious delay in PC-3 xenograft tumor growth as compared with monotherapy with naftopidil or RT. In PC-3 tumors, combination therapy with RT plus naftopidil suppressed the upregulation of RT-induced MnSOD expression. In vitro, neither AKT inhibitor IV nor naftopidil directly altered MnSOD expression. Upregulation of RT-induced MnSOD expression was markedly suppressed by combination treatment with RT plus AKT inhibitor IV or naftopidil., Conclusions: These results suggest that additive naftopidil treatment in combination with RT may increase the efficacy of RT for the treatment of PCa.

Japanese Urological Association reported that 3,648 patients of renal cell carcinoma were diagnosed in 2007 from 340 institutions and 70 years old or more accounted for 35.5% of pa- tients and 8.3% were more than 80 years old. If the elderly patients are frail and have severe comorbidity, surveillance might be taken for small renal cancer. However, relatively large tu- mor or rapid tumor growth rate lead to disease progression. Because percutaneous ablation to renal cell carcinoma is less invasive treatment than surgery and is superior in quality of life maintenance, it will be suitable treatment for small renal carcinoma of elderly patients. We showed results of the radiofrequency ablation of renal cell carcinoma of elderly patients 80 years or older. Among 17 patients, four patients were dead of other causes and the death due to renal carcinoma was absent. Only one patient had local tumor progression and needed re- ablation. Renal function preservation after treatment was good.

Purpose: To evaluate the long-term outcomes and safety photoselective vaporization of the prostate (PVP)., Patients and Methods: From April 2005 to December 2015, a total of 1154 patients with benign prostatic hyperplasia underwent PVP. The type of Green Light laser was an 80 W potassium-titanyl-phosphate laser and later a 120 W lithium triborate laser. Before and after surgery, the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), post-voiding volume of residual urine (PVR), prostate-specific antigen (PSA) level, and prostate volume were assessed regularly. After surgery, events such as second PVP, transurethral incision, and permanent urethral catheterization were defined as retreatment., Results: The mean and median periods of follow-up after PVP were 35.4 and 24.0 months, respectively. The maximum duration of follow-up was 125 months. Compared with before surgery, the IPSS, quality of life score, and PSA concentration improved significantly, even at 10 years after PVP; however, Qmax and PVR were not improved at 10 years. The retreatment-free survival rate was 93.9% at 5 years and 79.0% at 10 years. Prostate cancer was found in 27 cases after PVP, and all patients who were found to have prostate cancer remained alive. Prostate cancer-free survival after PVP was 96.7% at 5 years and 89.4% at 10 years., Conclusion: Our data suggest that the efficacy of PVP was maintained for 10 years; however, it may decrease after more than 10 years. PVP also did not promote the progression of or worsen the prognosis of prostate cancer.

Objective: Active surveillance has emerged as an alternative to immediate treatment in men with favorable-risk prostate cancer; however, consensus about defining the appropriate candidates is still lacking. To examine the factors predicting unfavorable pathology among active surveillance candidates, we assessed low-risk radical prostatectomy specimens., Methods: This retrospective study included 1753 men who had undergone radical prostatectomy at six independent institutions in Japan from 2005 to 2011. Patients who met the active surveillance criteria were categorized depending on the pathological features of the radical prostatectomy specimens. 'Reclassification' was defined as upstaging (≥pT3) or upgrading (radical prostatectomy Gleason score ≥7), and 'adverse pathology' was defined as pathological stage ≥pT3 or radical prostatectomy Gleason score ≥4 + 3. Multivariate analysis was used to analyze the preoperative factors for reclassification and adverse pathology. The rates of reclassification and adverse pathology were evaluated by classifying patients according to biopsy core numbers., Results: The active surveillance criteria were met by 284 cases. Reclassification was identified in 154 (54.2%) cases, while adverse pathology in 60 (21.1%) cases. Prostate-specific antigen density and percentage of positive cores were independently associated with reclassification and adverse pathology. The rates of reclassification and adverse pathology were significantly higher among patients with <10 biopsy cores than among others. Thus, focusing on 149 patients with ≥10 biopsy cores, prostate-specific antigen density was the only independent predictor of unfavorable pathological features. The receiver operating characteristic curve analysis determines an optimal cut-off value of prostate-specific antigen density as 0.15 ng/ml 2 ., Conclusions: Prostate-specific antigen density is the most important predictor of unfavorable pathological features in active surveillance candidates., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Emphysematous cystitis (EC) is a rare form of acute complicated urinary tract infection (UTI). We report a case of EC with bladder diverticulum. A 77-year-old man who had a medical history of diabetes mellitus was admitted to our hospital with the chief complaint of macrohematuria and pneumaturia. Based on the findings of an abdominal computed tomography and cystoscopy, the diagnosis of EC and bladder diverticulum was made with its characteristic feature being gas within the bladder wall and lumen and a cystic lesion from the bladder. His condition improved immediately with a combination of bladder drainage and appropriate antibiotics. The cystography revealed a very large diverticulum causing incomplete bladder emptying and stagnation of urine. We considered diabetes mellitus and a large amount of residual urine after urination due to bladder diverticulum and neurogenic bladder as the possible causal factors of EC in this case.

Objective: To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy., Methods: The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0g/50mL) was performed 180-240min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source., Results: Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20mg/kg/body., Conclusions: ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20mg/kg/body in the present study., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In patients with prostate cancer (PCa), serum prostate-specific antigen (PSA) is a useful marker for evaluating the effects of androgen deprivation therapy (ADT). Intuitively, most urologists expect that a more rapid PSA decline in response to ADT would be positively associated with extended survival. Recently, we have reported that prolonged gradual serum PSA decline after ADT is strongly associated with favorable prognosis in PCa patients, however, the mechanism remains unknown. We investigated the role of fibroblasts in serum PSA decline after ADT. We performed in vitro experiments using androgen-sensitive, androgen receptor (AR)-positive prostate epithelial cell lines (LNCaP, 22Rv1, and RWPE-1 cells), commercially available prostate stromal cells (PrSC), and primary cultures of prostate fibroblasts (pcPrFs). In LNCaP and 22Rv1 cells, PSA production was increased by co-culture with fibroblasts under androgen-deprived conditions. In an in vivo model using LNCaP cells, serum PSA declined rapidly after ADT becoming undetectable within 14 days in mice inoculated with LNCaP cells alone. In contrast, when LNCaP cells were co-inoculated with fibroblasts, serum PSA levels were still high on 14 days post ADT and did not drop to undetectable levels until 21 days post ADT. Tumor volumes and Ki67 labeling indices were not altered between days 14 and 21 post ADT in mice inoculated with LNCaP cells; however, those in mice inoculated with LNCaP cells plus fibroblasts decreased gradually. PSA protein was detected in all tumors on 21 days post ADT by immunohistochemical staining. Microvessel densities were higher on 14 days post ADT for tumors from mice inoculated with LNCaP cells plus fibroblasts as compared with LNCaP cells alone. In summary, co-inoculation of fibroblasts with LNCaP cells prolonged serum PSA decline after ADT and enhanced the efficacy of ADT. Prolonged serum PSA decline may indicate the presence of protective fibroblasts that preserve the AR dependence of PCa cells, improving treatment efficacy.

Background: There is no consensus on blood adrenal androgen concentrations in men with different stages and pathological grades of prostate cancer. In this study, dehydroepiandrosterone (DHEA) concentrations in blood were examined by ultrasensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS). We analyzed the correlation between DHEA concentrations in blood and clinicopathological findings of prostate cancer., Methods: We analyzed 196 men (mean age 70 years) with prostate cancer. The patients underwent systematic needle biopsy, and peripheral blood sampling was conducted for measurement of DHEA. DHEA concentrations in blood were determined using LC-MS/MS method. Patient age, serum prostate-specific antigen, prostate volume measured by ultrasound, and DHEA levels in blood were compared with Gleason score and clinical stage by multivariate analyses., Results: Median value of PSA and prostate volume were 11.5 ng/ml and 27.7 ml, respectively. Median concentration of DHEA in blood was 1,506.4 pg/ml. There was no correlation between serum DHEA and clinical variables such as age, serum PSA, and prostate volume. In multivariate analysis, low serum DHEA levels in prostate cancer patients were significantly related to high Gleason score and advanced clinical stage. Serum PSA levels in prostate cancer patients were also significantly associated with high Gleason score and advanced clinical stage. High serum PSA and low serum DHEA levels were significantly associated with poor prognosis factors in men with hormone-naïve prostate cancer., Conclusions: DHEA concentrations in blood were examined by newly developed ultrasensitive LC-MS/MS. We confirmed that low serum DHEA levels in prostate cancer patients were related to high Gleason score and advanced clinical stage. These results suggest that serum DHEA level may be a useful prognostic factor in prostate cancer patients., (© 2015 Wiley Periodicals, Inc.)

Purpose: To retrospectively evaluate the clinical outcomes of radiofrequency (RF) ablation for the treatment of unresectable adrenal metastasis., Materials and Methods: The institutional review board approved this retrospective study, and informed consent to perform adrenal RF ablation was obtained from all patients. From February 2005 through May 2014, 35 patients (25 men and 10 women; mean age, 64.7 years ± 9.6; age range, 39-82 years) underwent RF ablation to treat 41 metastatic adrenal tumors from lung cancer (n = 15), renal cell carcinoma (n = 9), colorectal cancer (n = 5), hepatocellular carcinoma (n = 4), and other tumors (n = 2). Tumors ranged in size from 1.2 to 8.2 cm (mean, 3.3 cm ± 1.6). The diagnosis was established mainly on the basis of radiologic findings. Adrenal arterial embolization was combined with RF ablation in 12 of the 35 patients (34%). Technical success, safety, local tumor progression, and survival were evaluated. The Kaplan-Meier method and Cox proportional hazard model were used to evaluate prognostic factors., Results: There were 48 completed sessions with planned procedures and treatment protocols with no mortality and a major complication rate of 8.3% (four of 48 sessions). Tumor enhancement disappeared after initial adrenal RF ablation in 33 of the 35 patients (94%). Local tumor progression developed in eight of the 35 patients (23%); two patients received repeated RF ablation, resulting in adrenal tumor control in 27 of the 35 patients (77%) at the last follow-up (mean, 30.1 months ± 27.5; range 1.2-96.8 months). The 1-, 3-, and 5-year overall survival rates were 75% (95% confidence interval [CI], 61%, 90%), 34% (95% CI: 17%, 52%), and 30% (95% CI: 13%, 48%), respectively, with a median survival time of 26.0 months. Existence of extra-adrenal tumors (P = .005) and age of 65 years or older (P = .04) were significant indicators of a poor prognosis., Conclusion: Adrenal RF ablation is a feasible and useful method for controlling adrenal metastases and offers patients opportunities for improved survival., (© RSNA, 2015)

Purpose: To retrospectively evaluate factors affecting local tumor control in cryoablation of renal cell carcinomas (RCCs)., Materials and Methods: This study examined 61 patients (43 men, 18 women) with a mean age of 69.1 years ± 10.8 (range 38-87 y) who underwent computed tomography (CT)-guided percutaneous cryoablation for a single RCC and were followed for 6 months or longer. Maximum tumor diameter was 0.8-4.8 cm (mean ± standard deviation, 2.4 ± 0.9 cm). Factors affecting local tumor control were evaluated. Deep tumor location was defined as the center side of the body perpendicular to the kidney midline., Results: Median follow-up was 12.7 months. Residual unablated tumors and local tumor progression were observed after initial cryoablation in 4 patients each (13%, 8 of 61). All uncontrolled tumors were located in the deep side of the kidney (100%, 8 of 8), and were covered by an ice-ball margin of 5 mm or less. Deep tumor location (P = .005) and ice-ball margin (P = .002) were detected as significant factors affecting local tumor control on univariate analysis, and ice-ball margin remained significant in a stepwise logistic regression model (P = .006; odds ratio, 0.57; 95% confidence interval, 0.38-0.83). Complete tumor control rates were 42.9% (3 of 7), 92.6% (50 of 54), and 100% (20 of 20) with ice-ball margins of less than 3 mm, 3 mm or larger, and 6 mm or larger, respectively., Conclusions: Deep tumor location and ice-ball margins less than 6 mm were associated with incomplete local control following CT-guided percutaneous cryoablation for RCC., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

Aim: We assessed the effect of adding diffusion-weighted magnetic resonance imaging (DW-MRI) to conventional MRI for T staging and the correlation between apparent diffusion coefficient (ADC) values and clinicopathological parameters for patients with bladder cancer., Materials and Methods: We retrospectively reviewed the records of 160 patients with bladder cancer who underwent MRI at our institute. All patients were routinely assessed with conventional MR imaging. Since January 2008, we added DW-MRI., Results: In these 160 patients, 127 (79.4%) tumors were detectable by MRI. In all patients with detectable tumors, on a stage-by-stage basis, 96 (75.6%) of 127 patients received the correct diagnosis. With DW-MRI, accurate diagnosis was obtained in 80 (80.0%) of 100 cases; without DWI in only 16 (59.3%) of 27 cases (P=0.026). For T staging, the accuracy for distinguishing muscle invasion (T≦1 vs T≧2) with DW-MRI (83.0%) was superior to that without DW-MRI (66.7%). The accuracy for distinguishing perivesical fat invasion (T≦2 vs T≧3) with DW-MRI (98.0%) was also superior to that without DW-MRI (92.6%). The ADC values were significantly related with tumor diameter (<3 cm vs ≧3 cm, P<0.001), histopathological grade (low grade vs high grade, P<0.001), T stage (≦T1 vs ≧T2, P<0.001), and operative method (transurethral resection vs total cystectomy, P<0.001)., Conclusions: We demonstrated that DW-MRI is not only useful for bladder cancer T staging, but also a prognostic factor for patients with bladder cancer.

Aims: The aim of this study was to evaluate the safety and clinical utility of radiofrequency ablation (RFA) retrospectively in non-surgical candidates with recurrent bone and soft-tissue sarcomas., Methods: Percutaneous RFA was used in 52 patients (21 female, 31 male; mean age, 52.2 ± 21.1 years; range 10-87 years) with recurrent bone and soft-tissue sarcomas. The number of tumors was 3 or fewer in 23 patients (44.2 %) and 4 or more in the others, with a mean maximum tumor diameter of 3.0 ± 3.7 cm (range 0.5-18 cm). Safety, tumor control, and prognosis were evaluated., Results: All tumors were ablated after RFA in 21 patients (40.4 %, 21/52), although 14 experienced re-recurrence. Tumors were controlled in 8 cases of recurrence by repeat RFA (n = 7) and surgical intervention (n = 1). Therefore, 15 patients (28.8 %, 15/52) were tumor-free at the end of follow-up (mean follow-up 25.5 ± 24.2 months; range 3.9-117 months). Residual tumors were found after RFA in the other 31 patients (59.6 %, 31/52). Overall survival rates were 73.4 % (95 % CI 61.0-85.9 %) at 1 year, 39.3 % (95 % CI 23.6-54.9 %) at 3 years, and 34.3 % (95 % CI 18.0-50.7 %) at 5 years in all patients. Recurrence-free interval (p = 0.040), tumor number (p = 0.0094), and complete tumor ablation (p < 0.0001) were detected as significant prognostic factors in univariate analysis. The latter two factors were significant in multivariate analysis. The rate of major complications was 0.9 %., Conclusions: RFA is a safe and useful therapeutic option for treatment of recurrent bone and soft-tissue sarcomas. Prognostic factors found in this study will help to identify those patients who would benefit from RFA.

Background: There is currently no consensus on the correlations between androgen concentrations in prostate tissue and blood and stage and pathological grade of prostate cancer. In this study, we used a newly-developed ultra-sensitive liquid-chromatography tandem mass spectrometry method to measure testosterone (T) and dihydrotestosterone (DHT) concentrations in blood and needle biopsy prostate specimens from patients with prostate cancer., Methods: We analyzed androgen levels in 196 men diagnosed with prostate cancer. All patients had undergone systematic needle biopsy, and an additional needle biopsy from the peripheral zone was conducted for the simultaneous determination of T and DHT. We analyzed the relationships between T and DHT levels in tissue and blood and Gleason score, clinical stage, and percentage of positive biopsy cores, using multivariate analysis., Results: The median T and DHT levels in blood were 3551.0 pg/mL and 330.5 pg/mL, respectively. There was a strong correlation between serum T and DHT. The median T and DHT levels in prostate tissue were 0.5667 pg/mg and 7.0625 pg/mg, respectively. In multivariate analysis, serum prostate-specific antigen and tissue T levels were significantly associated with poor prognosis; high T levels in prostate tissue were significantly related to high Gleason score (p = 0.041), advanced clinical stage (p = 0.002), and a high percentage of positive biopsy cores (p = 0.001)., Conclusions: The results of this study indicate that high T levels in prostate tissue are related to high Gleason score, advanced clinical stage, and a high percentage of positive biopsy cores in patients with prostate cancer. T level in needle biopsy specimens may therefore be a useful prognostic factor in prostate cancer patients.

The phenylpiperazine derivative naftopidil is an α1-adrenoceptor (AR) antagonist that has been used clinically to treat benign prostatic hyperplasia. In our drug repositioning research, naftopidil shows the unique growth-inhibitory effects. Naftopidil inhibits cell cycle progression not only in cancer cells, but also in fibroblasts and vascular endothelial cells. Naftopidil-inhibited cell cycle progression is independent of α1-AR expression in cells. Therefore, the antiproliferative effects of naftopidil may be due to the off-target effects of the drug. In this study, we attempted to identify the off-target molecules of naftopidil using the magnetic nanobeads, ferrite glycidyl metharcrylate (FG) beads. Similar to naftopidil, its derivatives TG09-01 and TG09-02, which were introduced with amino groups for immobilizing to FG beads, inhibited cell growth in human HT29 colon adenocarcinoma cells. Both derivatives were associated with inhibition of cell cycle progression in HT29 cells. This observation is consistent with that seen with naftopidil. Using TG09-02-immobilized FG beads, α- and β-tubulins were identified as the specific binding proteins of naftopidil. The tubulin polymerization assay clearly indicated that naftopidil bound directly to tubulin and inhibited the polymerization of tubulin. Other phenylpiperazine derivatives, such as RS100329, BMY7378, and KN-62, also inhibited the polymerization of tubulin. These results suggest that phenylpiperazine derivatives including naftopidil may have broad spectrum of cellular cytotoxicity in various types of cells. In addition, the tubulin polymerization-inhibiting activity of phenylpiperazine derivatives may be a specific feature of the phenylpiperazine-based structure. These findings can allow us to design and synthesize new tubulin-binding drugs derived from naftopidil as a lead compound.

Prostate is a male sex-accessory organ. The prostatic epithelia consist primarily of basal and luminal cells that differentiate from embryonic urogenital sinus epithelia. Prostate tumors are believed to originate in the basal and luminal cells. However, factors that promote normal epithelial differentiation have not been well elucidated, particularly for bone morphogenetic protein (Bmp) signaling. This study shows that Bmp signaling prominently increases during prostatic differentiation in the luminal epithelia, which is monitored by the expression of phosphorylated Smad1/5/8. To elucidate the mechanism of epithelial differentiation and the function of Bmp signaling during prostatic development, conditional male mutant mouse analysis for the epithelial-specific Bmp receptor 1a (Bmpr1a) was performed. We demonstrate that Bmp signaling is indispensable for luminal cell maturation, which regulates basal cell proliferation. Expression of the prostatic epithelial regulatory gene Nkx3.1 was significantly reduced in the Bmpr1a mutants. These results indicate that Bmp signaling is a key factor for prostatic epithelial differentiation, possibly by controlling the prostatic regulatory gene Nkx3.1.

A 51-year-old woman received an ABO blood type-incompatible renal transplant. She was administered rituximab and basiliximab and underwent plasma exchanges for induction therapy, followed by administration of tacrolimus, mycophenolate mofetil and methylprednisolone as maintenance immunosupression therapy. A planned renal biopsy 2 years after transplantation revealed infiltration of plasma cells in the renal interstitium, although there was no 'storiform' fibrosis surrounding these cells. There were also no findings of rejection, BK virus nephropathy, or atypical plasma cells. Immunohistochemical stainings showed a large number of IgG4-positive plasma cells, most of which expressed kappa-type light chains. A CT scan showed a mass at the renal hilum. The serum IgG4 level was high. Based on these findings, the patient was suspected of having IgG4-related kidney disease. Nine months after the biopsy, her serum creatinine level increase to 1.56 mg/dL and the dose of methylprednisolone was therefore increased to 16 mg/day. Three months after this increase in steroid, a CT scan showed the hilum mass had disappeared. A follow-up biopsy 5 months later showed that infiltration of plasma cells in the renal interstitium had decreased markedly, although focal and segmental severely fibrotic lesions with IgG4-positive plasma cells were observed. Serum IgG4 levels decreased immediately after the increase in steroid dose and remained <100 mg/dL despite a reduction in methylprednisolone to 6 mg/day. Serum creatinine levels also remained stable at around 1.6 mg/dL. To our knowledge, this is the first report of IgG4-positive plasma cell-rich tubulointerstitial nephritis mimicking IgG4-related kidney disease after kidney transplantation., (© 2014 Asian Pacific Society of Nephrology.)

A 20-year-old unmarried Ghanaian man complaining of macroscopic hematuria and cystitis symptom was admitted to our institute. Abdominal ultrasound revealed a hyper echoic lesion in the entire bladder wall. Computed tomography showed a calcification of the whole bladder wall and of the left lower ureter. Flexible cystoscopy revealed many nodular masses, so-called 'bilharzial tubercles', at the trigone and posterior wall of the urinary bladder, and there was partial bleeding. Pathological examination revealed granuloma with many calcified eggs of schistosome haematobium. He was diagnosed with Bilharzial schistosomiasis and was treated with 1,500 mg of praziquantel for two days. However the therapeutic effect was insufficient. Therefore, he was treated with 2,400 mg of praziquantel for two days, and the symptoms disappeared.

Purpose: To compare clinical outcomes of radiofrequency (RF) ablation retrospectively with those after radical nephrectomy in patients with stage T1b renal cell carcinoma (RCC)., Materials and Methods: This retrospective study was approved by the institutional review board, and the requirement to obtain written informed consent was waived. From June 2002 to March 2012, 60 patients (mean age, 65.2 years; age range, 39-86 years) with a single RCC measuring 4.1-7.0 cm (stage T1b) underwent RF ablation (n = 21) or radical nephrectomy (n = 39). Selective renal artery embolization was performed before RF ablation in eight patients. The overall, RCC-related, and disease-free survival rates, the percentage decrease in the glomerular filtration rate (GFR), and safety were compared by using the log-rank (survival), paired and Student t (GFR), and Fisher exact (safety) tests., Results: The overall survival rate was significantly lower in the RF ablation group than in the radical nephrectomy group (48% vs 97% at 10 years, respectively; 95% confidence interval [CI]: 12.4%, 76.7% vs 78.2%, 99.5%; P < .009). The RCC-related survival rate (94% [95% CI: 62.6%, 99.1%] with RF ablation vs 100% with radical nephrectomy at 10 years) and the disease-free survival rate (88% [95% CI: 59.2%, 96.9%] with RF ablation vs 84% [95% CI: 60.6%, 94.3%] with radical nephrectomy at 10 years, P = .99) were comparable between the two groups. No treatment-related deaths occurred. Although major complication rates were similar between the two patient groups (8.0% [two of 25 patients] vs 5.1% [two of 39 patients], P = .61), the percentage decrease in the GFR was significantly lower in the RF ablation group than in the radical nephrectomy group at the last follow-up (12.5% ± 23.4 vs 32.3% ± 20.8, respectively; P < .003)., Conclusion: RF ablation is a safe procedure for patients at substantial surgical risk for radical nephrectomy, providing comparable RCC-related and disease-free survival and preserving renal function., (© RSNA, 2013.)

The prostate gland is unique in that it undergoes rapid regression following castration but regenerates completely once androgens are replaced. Residual ductal components play an important role in the regeneration of a fully functional prostate. In this study, to examine how androgen status affects prostate structure and components, we conducted histopathological studies of the involuted and regenerated mouse dorsolateral prostate (DLP). In the castrated mouse DLP, the number of luminal epithelial cells decreased in a time-dependent manner. On Day 14 postandrogen replacement, the number of luminal epithelial cells was completely restored to the baseline level. In contrast, the number of basal epithelial cells gradually increased in the castrated mouse prostate. The Ki67-labeling index of prostate basal epithelial cells was significantly increased after castration. The number of basal epithelial cells decreased to baseline after androgen replacement. After castration, mRNA expression levels of specific growth factors, such as Fgf2, Fgf7, Hgf, Tgfa, and Tgfb, were relatively abundant in whole mouse DLPs. In organ culture experiments, basal epithelial proliferation was recapitulated in the absence of dihydrotestosterone (DHT). The proliferation of basal epithelial cells in the absence of DHT was suppressed by treatment with an FGF receptor inhibitor (PD173074). Moreover, FGF2 treatment directly stimulated the proliferation of basal epithelial cells. Taken together, these data indicated that the FGF2-FGF receptor signal cascade in the prostate gland may be one of the pathways stimulating the proliferation of basal epithelial cells in the absence of androgens.

A 48-year-old married woman complaining of macroscopic hematuria and cystitis symptom was admitted to our institute. Flexible cystoscopy revealed many yellowish, nodular masses at the paries posterior of the urinary bladder, and cold-punch biopsy proved it to be amyloidosis. Serum amyloid protein A (SAA) was high, and suggested systemic amyloidosis. Renal biopsy and colon fiberscopy did not reveal any abnormalities. We therefore diagnosed a primary localized amyloidosis of the urinary bladder. Transurethral resection and dimethyl sulfoxide (DMSO) infusion therapy are used to treat amyloidosis of the urinary bladder. However there is no definite cure for amyloidosis of the urinary bladder. Therefore we selected DMSO occlusive dressing technique therapy. After 5 years of therapy, there was no evidence of a recurrence of amyloidosis.

Purpose: We examined the safety and efficacy of photo-selective vaporization of the prostate (PVP) using a 120-W high-performance system (HPS) for benign prostatic hyperplasia (BPH)., Patients and Methods: We prospectively reviewed the records of 25 patients who had undergone PVP using a 120-W HPS in our institution. Patients were evaluated pre-operatively, and at 2 weeks and 1, 3, and 6 months postoperatively., Result: The mean age was 73.6 years, and the mean estimated preoperative prostate volume was 51.5 ml. Laser vaporization was performed successfully in all 25 patients. The operating time was 104 +/- 29 minutes. The mean decrease in hemoglobin was 0.6 g/dl on post-operative day 1. The International Prostate Symptom Score (IPSS), QOL score, maximum flow rate, and residual urine volume were significantly improved 2 weeks after the procedure. There were no serious complications during the peri-operative period, and no patients were transfused., Conclusion: PVP using a 120-W HPS was shown to be an effective, safe procedure for patients with BPH and lower urinary tract symptoms.

Renal cell carcinoma (RCC) is an angiogenesis-dependent and hypoxia-driven malignancy. As a result, several targeting agents are being investigated. However, the efficacy of current regimens is generally insufficient for their toxicity and poor overall response rates. We have recently reported that naftopidil exerts growth-inhibitory effects on human prostate cancer cells. In this study, we investigated the biochemical mechanisms by which naftopidil produces growth-inhibitory and antiangiogenic effects on RCC. We first tested the effects of naftopidil on the proliferation of ACHN and Caki-2 RCC cells. Next, we set up a model simulating the tumor microenvironment, in which ACHN cells were grafted onto the renal capsule of mice. We then tested the effects of naftopidil on human umbilical vein endothelial cells' cell proliferation and Matrigel plug vascularization. Finally, to establish the antitumor activity of naftopidil on RCC, we tested the antitumor effects of naftopidil on excised tumor specimens from 20 patients with RCC that were grafted beneath the renal capsule of mice. Naftopidil showed similar in vitro growth-inhibitory effects on all cell lines. Fluorescence-activated cell sorting analysis revealed an increase in G1 cell-cycle arrest in all naftopidil-treated cell lines. In vivo tumorigenic studies showed a significant reduction of ACHN tumor weight, Ki-67 index, and microvessel density (MVD) in naftopidil-treated mice. Naftopidil attenuated neovascularization in an in vivo Matrigel plug assay. Studies in mouse xenograft models also showed a significant MVD reduction in naftopidil-treated excised human RCC. The growth-inhibitory effects of naftopidil suggest it may be a novel anticancer agent and a potential preventive option for RCC.

We prospectively reviewed the records of 62 patients who had sought evaluation at our hospital with a chief complaint of male climacteric symptoms. Late-onset hypogonadism (LOH)-related symptoms were evaluated during the initial visit based on the Aging Males' Symptoms (AMS) score, International Index of Erectile Function (IIEF) -5 score, and Center for Epidemiologic Studies Depression Scale (CES-D). Laboratory and endocrinologic testing, including the free testosterone (FT) level, was performed with blood samples collected before 10 : 00 am. The AMS psychological and CES-D scores in patients with a FT ＞8.5 pg/ml were significantly higher than those in patients with a FT ≦8.5 pg/ml. The study included 32 patients who were diagnosed with LOH (FT ≦8.5 pg/ml) and treated with androgen replacement therapy (ART). The total, somatic, psychological, and sexual scores of the AMS were significantly decreased after the third intramuscular administration of testosterone enanthate; there were no serious complications. Because a significant proportion of depressed patients may be amongst the patients with aging male's symptoms, it is important to consider depression in the exclusion diagnosis during a clinical examination for LOH.

Objectives: To investigate the presence of manserin in human prostate cancers and to correlate manserin expression with pathologic outcomes and progression-free survival., Methods: Eighty-seven patients with recent prostate cancer were classified into 4 groups based on Gleason score, and manserin immunohistochemistry was correlated with Gleason sum grade. To investigate the validity of manserin as a prognostic factor, the Cox proportional hazards regression model was performed on 48 patients in our cohort with T3 or T4 prostate cancer who were initially treated with androgen deprivation therapy., Results: The manserin-positive rates of patients with Gleason sums of 6, 7, 8, and ≥9 were 0%, 20.0%, 35.0%, and 48.1%, respectively. Manserin-positive rates were positively correlated with Gleason sums (P = 0.0001). Median times to cancer progression in groups with (n = 8) and without (n = 40) manserin expression were 8 months and 28 months, respectively (P = 0.01). Univariate Cox analysis revealed that manserin expression, clinical stage T4, and high Gleason sum were significantly associated with progression. Multivariate analysis revealed that only 2 factors, manserin expression (hazard ratio (HR) 4.99, P = 0.01) and clinical stage T4 (HR 4.77, P = 0.03), were independent risk factors for progression., Conclusions: This is the first report of manserin expression in human prostate cancers. Manserin may serve as a marker of prostate cancer progression., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Here, we report a case of malignant lymphoma (ML) of the prostate. A 77-year-old man was referred to our hospital with the chief complaint of left lumbago. Computed tomography imaging showed a large mass below the bladder, as well as left hydronephrosis resulting from infiltration of the mass. Magnetic resonance imaging (MRI) revealed enlargement and high-intensity of the whole prostate with diffusionweighted image. An enlarged, stony, hard prostate was palpable on digital rectal examination, but the prostate-specific antigen (PSA) level was 4.65 ng/ml. Since the patient developed urinary retention and macrohematuria, transurethral hemostasis and biopsy were performed. Histological findings and immunohistochemical studies revealed diffuse large B-cell non-Hodgkin's lymphoma (DLBCL). MRI is thought to play a critical role in localization diagnosis of Non-Hodgkin's lymphoma (NHL) since NHL demonstrates characteristic signs. Although the frequency of primary ML of the prostate is low, by paying careful attention to the characteristic signs on MRI and examination findings, we should consider a differential diagnosis of ML of the prostate, which is not a typical manifestation of prostatic cancer.

Purpose: To prospectively evaluate the safety and effectiveness of radiofrequency ablation with a multiple-electrode switching system for the treatment of renal cell carcinoma (RCC)., Materials and Methods: From November 2009 to December 2010, 33 patients (mean age, 70.7 years; range, 44-86 years) with histologically proved RCCs--including 24 men (mean age, 69.5 years [range, 44-86 years]) and nine women (mean age, 74.1 years [range, 64-83 years])--were enrolled in this phase II study. The institutional review board approved the study after patients provided written informed consent. The mean maximum tumor diameter was 2.9 cm ± 1.0 (standard deviation) (range, 1.5-5.0 cm). Radiofrequency ablation was conducted with a multiple-electrode switching system. The primary endpoint was evaluated with the Common Terminology Criteria for Adverse Events. Secondary endpoints were changes in renal function, technique effectiveness, local tumor progression, and survival. Changes in renal function were evaluated by using the Mann-Whitney U test., Results: No severe adverse events occurred, but three of 33 patients (9%) had grade 2 adverse events. Although the mean glomerular filtration rate at 1 year after radiofrequency ablation was similar to the baseline value in 26 patients with bilateral kidneys (P = .14), it was decreased significantly in six patients with a single kidney (P = .03). Tumor enhancement disappeared after a single radiofrequency session in 31 patients and after two radiofrequency sessions in the other two patients (rates of primary and secondary technique effectiveness, 94% [31 of 33] and 100% [33 of 33], respectively). No local tumor progression was found during the mean follow-up of 20.0 months (range, 11.6-27.6 months). The respective 1-year overall and RCC-related survival rates were 97% (95% confidence interval: 91%, 100%) and 100%., Conclusion: Radiofrequency ablation with a multiple-electrode switching system is safe and effective for treatment of RCCs. However, further study is warranted to determine whether this technology is superior to other previously described methods., (RSNA, 2013)