Heterogeneous induction of an invasive phenotype in prostate cancer cells by coculturing with patient-derived fibroblasts.

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.

[Initial Experience of Photodynamic Diagnosis-Assisted Transurethral Resection of Bladder Tumor (PDD-TURBT)].

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.

Castration-induced stromal remodeling disrupts the reconstituted prostate epithelial structure.

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-ß1 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-ß 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-ß signaling. The alteration of prostate stromal structure may be responsible for loss of the BM and epithelial cell polarity.

First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors.

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.

[Neoajuvant Chemotherapy with Gemcitabine and Cisplatin Plus S-1 for Primary Female Urethral Adenocarcinoma].

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.

[A Case of Extragonadal Germ Cell Tumor Treated by Induction Therapy with A Reduced Bep Regimen].

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.

Tyrosine kinase inhibitor therapy prescribed for non-urologic diseases can modify PSA titers in urology patients.

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.

Interleukin-6 induces VEGF secretion from prostate cancer cells in a manner independent of androgen receptor activation.

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.

Ablation therapy for renal cell cancer of elderly patients.

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.

Fibroblasts prolong serum prostate-specific antigen decline after androgen deprivation therapy in prostate cancer.

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.

Low serum dehydroepiandrosterone examined by liquid chromatography-tandem mass spectrometry correlates with poor prognosis in hormone-naïve prostate cancer.

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.

Evaluation of predictors of unfavorable pathological features in men eligible for active surveillance using radical prostatectomy specimens: a multi-institutional study.

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/ml2. CONCLUSIONS: Prostate-specific antigen density is the most important predictor of unfavorable pathological features in active surveillance candidates.

[A Case of Emphysematous Cystitis with Bladder Diverticulum].

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.

Unresectable Adrenal Metastases: Clinical Outcomes of Radiofrequency Ablation.

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.

CT-Guided Percutaneous Cryoablation in Renal Cell Carcinoma: Factors Affecting Local Tumor Control.

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.

Radiofrequency ablation versus radical nephrectomy: clinical outcomes for stage T1b renal cell carcinoma.

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.

High testosterone levels in prostate tissue obtained by needle biopsy correlate with poor-prognosis factors in prostate cancer patients.

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.

Radiofrequency ablation for the treatment of recurrent bone and soft-tissue sarcomas in non-surgical candidates.

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.

A case of IgG4-positive plasma cell-rich tubulointerstitial nephritis in a kidney allograft mimicking IgG4-related kidney disease.

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.

[Urinary schistosomiasis: report of a case].

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.