Intracrine androgen biosynthesis in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression. METHODS: Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume. RESULTS: We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01). CONCLUSIONS: Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.

Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective, Multi-Institutional Study.

PURPOSE: To identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data were collected and analyzed for 2412 NMIBC patients from 15 centers who were initially diagnosed after transurethral resection of bladder tumor (TURBT) from January 2006 to December 2010. Using univariable and multivariable Cox proportional hazards models, the prognostic value of each variable was evaluated for the time to first recurrence and progression. RESULTS: With a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy. CONCLUSION: A preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.

Malignant renal cysts: diagnostic performance and strong predictors at MDCT.

BACKGROUND: Utilization of multidetector-row CT (MDCT) is anticipated to improve the diagnostic accuracy and reliability for determining malignant cysts. PURPOSE: To assess the diagnostic accuracy, interobserver agreement, benefit of consensus reading, and strong predictors of malignancy in determining malignant cystic renal masses at MDCT. MATERIAL AND METHODS: Two radiologists independently rated the probability of malignancy at MDCT in 72 benign and 53 malignant cysts. The accuracy and interobserver agreement for determining malignant cysts were evaluated. The strong predictors of malignancy were determined, and in patients with interobserver disagreement for determining malignant cysts, consensus readings were performed. RESULTS: Az value of the two readers was 0.905-0.936 and the sensitivity and specificity were 85-89% and 83-93%, respectively. The overall interobserver agreement for determining the malignant cyst was good as the kappa value was 0.696 (% agreement, 61% (76/125)). Thickened irregular wall, thickened irregular septa, and enhancing soft tissue component were strong predictors for malignancy with both readers. In the 17 patients with interobserver disagreement for determining malignant cysts, the sensitivity was improved from 38-63% to 89% by the consensus reading. CONCLUSION: At MDCT, some false negative decisions for determining malignant cysts can be corrected by consensus reading, and thickened irregular septa, thickened irregular wall, and enhancing soft tissue component are the strong predictors of malignant cysts.

Histologic type, staging, and distribution of germ cell tumors in Korean adults.

OBJECTIVES: To investigate the presentation of germ cell tumors (GCT) in terms of histology and stage, to better clarify the epidemiology of this disease in eastern Asia. METHODS: Six hundred ninety-eight patients diagnosed with GCT between 1995 and 2004 were analyzed. Clinical parameters at the time of initial diagnosis were classified in terms of the American Joint Committee on Cancer (AJCC) tumor, nodes, metastasis staging (TNMS) system, the International Germ Cell Cancer Collaborative Classification (IGCCC), for high-risk stage I nonseminomatous GCT (NSGCT) of testis. RESULTS: The anatomic distributions for the primary sites of the observed tumors were as follows: testis 471 cases (67%); central nervous system (CNS) 137 cases (20%); mediastinum 78 cases (11%), and retroperitoneum 12 cases (2%); 239 (51%) of 471 tumors with testicular primary were seminoma. High risk vs. non-high risk stage I NSGCT cases were 62 vs. 58. Of NSGCT of testis, 129 (58%), 73 (33%), and 21 (9%) of tumors presented with good, intermediate, and poor prognosis, respectively, based on IGCCC, whereas 231 (99%) patients were classified with a good prognosis and 3 (1%) with an intermediate prognosis amongst seminomas of testis; 193 (82%) cases presented as stage I testicular seminoma whereas 120 (54%) cases presented as stage I NSGCT. CONCLUSIONS: Extragonadal primary GCTs are very common in Korean. Incidence of high risk NSGCT of testis with stage I disease was lower than in the Western report. NSGCT presents itself as a more aggressive form whereas seminoma is a very indolent tumor when compared with cases in Western countries.

Loss of expression of bone morphogenetic protein receptor type II in human prostate cancer cells.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily and signal through a number of membrane receptors. We have previously demonstrated that the loss of expression of BMP receptors (BMPRs) type IA, -IB, and -II (BMP-RIA, -RIB, and -RII) correlates with Gleason score in prostate cancer patients. To evaluate the prognostic value of this observation, we used immunohistochemistry to investigate the expression of BMPRs in association with disease progression in 60 patients. The results demonstrated a significant association between the loss of expression of the three BMPRs and Gleason score and clinical stage. However, only the loss of expression of BMP-RII showed a statistically significant association with 5-year survival rate (P<0.05) and biochemical recurrence-free rate following radical prostatectomy (P<0.005). To elucidate the effect of an abnormal BMP signaling in prostate cancer cells, we transfected dominant-negative BMP-RII (BMP-RIIDN) into the human prostate cancer cell line, PC3M. When a stable clone overexpressing BMP-RIIDN was inoculated subcutaneously into nude mice, the tumor growth rate was approximately 10 times that of control and parental cell line. These observations, taken together, indicate that the loss of BMP-RII expression as measured by immunohistochemistry may be a prognostic marker in prostate cancer patients, and that the loss of BMP-RII function may result in increased tumorigenicity in human prostate cancer cells.

Bladder cancer: analysis of multi-detector row helical CT enhancement pattern and accuracy in tumor detection and perivesical staging.

PURPOSE: To evaluate the enhancement pattern of bladder cancer and the accuracy of multi-detector row helical computed tomography (CT) in the detection and staging of bladder cancer. MATERIALS AND METHODS: In 20 patients, the attenuation value of bladder cancer was measured on dynamic contrast material-enhanced multiphasic CT images obtained with scanning delays of 40, 60, 80, and 100 seconds. In 67 patients, CT data were obtained with a 60-second scanning delay that covered the bladder (section thickness, 2.5 mm; beam pitch, 1.5) and a 180-second scanning delay that covered the abdomen (section thickness, 5 mm; beam pitch, 1.5). We prospectively evaluated CT images and compared findings at CT with findings at histologic examination. We evaluated cancer detection rate, positive predictive value of cancer detection, and sensitivity and specificity in the diagnosis of perivesical invasion. RESULTS: The attenuation value of bladder cancers was significantly higher on 60- (105 HU +/- 16) and 80-second (97 HU +/- 15) delayed CT images than on the other images (P <.05). The cancer detection rate and positive predictive value for cancer detection were 97% and 95%, respectively, in 67 patients and increased to 100% and 100%, respectively, in 44 patients with a time interval of 7 or more days between transurethral resection of the bladder (TURB) and CT examination. Sensitivity and specificity in the diagnosis of perivesical invasion were 89% and 95%, respectively, in 67 patients and increased to 92% and 98%, respectively, in 44 patients with a time interval of 7 or more days between TURB and CT examination. CONCLUSION: Bladder cancer tends to show peak enhancement with the 60-second scanning delay. Multi-detector row helical CT is useful in the detection and staging of bladder cancer.

Living donor kidneys: usefulness of multi-detector row CT for comprehensive evaluation.

PURPOSE: To evaluate in living renal donors the usefulness of multi-detector row computed tomography (CT) in the assessment of renal vasculature and the upper urinary tract. MATERIALS AND METHODS: Four-channel multi-detector row CT scans were obtained in 77 patients. Vascular phase scans were used for CT angiography; excretory phase scans, for CT urography. At CT angiography, two independent observers evaluated the number of arteries and veins and the presence of early-branching arteries. CT urographic images were evaluated with regard to the opacification of the urinary tract and for abnormalities. Findings of CT angiography and urography were compared with surgical findings. Interobserver agreement between CT angiographic and surgical findings was quantified with weighted kappa statistics. Sensitivity and specificity of CT angiography in identifying supernumerary vessels and early-branching arteries were also evaluated. To evaluate the radiation dose to patients, weighted CT dose index (DI) was assessed for each scan. RESULTS: Agreement between CT angiographic and surgical findings was excellent for the number of renal arteries (kappa = 0.896) and veins (kappa = 0.843). Detection rate of CT angiography was 98% (89 of 91) for arteries and 98% (83 of 85) for veins. The respective sensitivity and specificity of CT angiography were 86% (12 of 14) and 100% (65 of 65) for supernumerary arteries, 100% (11 of 11) and 100% (66 of 66) for early-branching arteries, and 75% (six of eight) and 100% (69 of 69) for supernumerary veins. At CT urography, collecting systems and proximal ureters were well opacified in all patients; two patients had underrotated kidneys without obstruction. The weighted CT DI was 10.19 mGy for unenhanced and excretory phase scans and 12.88 mGy for the vascular phase scan. CONCLUSION: Multi-detector row CT can help assess well the renal vasculature and the urinary tract of living renal donors.

Virtual cystoscopy of the contrast material-filled bladder in patients with gross hematuria.

OBJECTIVE: The objective of this study was to evaluate the usefulness of virtual cystoscopy of the contrast material-filled bladder in evaluating patients with gross hematuria. SUBJECTS AND METHODS: Seventy-three consecutive patients who had gross hematuria and whose upper urinary tracts had a normal appearance on single-detector helical CT scans were prospectively evaluated with virtual cystoscopy. Source CT data for virtual cystoscopy were obtained on a multidetector CT scanner with 1.25-mm slice thickness and transferred to a workstation for interactive navigation using volume rendering. Two radiologists independently interpreted the virtual cystoscopic images, and discrepancies were resolved by consensus. All patients also underwent conventional cystoscopy. We assessed the agreement between the findings on virtual and conventional cystoscopy. Using conventional cystoscopy as the gold standard, we evaluated the usefulness of virtual cystoscopy as an aid in identifying bladder lesions and detecting abnormal bladders. RESULTS: Virtual cystoscopy depicted 60 lesions in the bladders of 43 patients. Fifty-six lesions (in 41 bladders) revealed on virtual cystoscopy were true-positive findings. Four lesions in two bladders with abnormal findings were false-positive. On virtual cystoscopy, the radiologists missed three lesions in two abnormal bladders that were identified on conventional cystoscopy. On virtual cystoscopy, 15 (88%) of 17 lesions smaller than 0.5 cm were identified. The agreement between the findings of virtual and conventional cystoscopy was excellent in the reviewers' identification of bladder lesions (kappa = 0.83) and detection of abnormal bladders (kappa = 0.89). The sensitivity and specificity of virtual cystoscopy were 95% and 87% for identifying bladder lesions and 95% and 93% for detecting abnormal bladders. CONCLUSION: Virtual cystoscopy of the contrast material-filled bladder is useful for the evaluation of the bladder in patients with gross hematuria.

Differentiation of subtypes of renal cell carcinoma on helical CT scans.

OBJECTIVE: The purpose of our study was to differentiate subtypes of renal cell carcinoma on helical CT scans. MATERIALS AND METHODS: We reviewed CT scans of four subtypes of renal cell carcinoma: 76 conventional (clear cell), 19 papillary, 13 chromophobe, and two collecting duct. Biphasic CT scans (unenhanced, corticomedullary, and excretory phase scans) were obtained in 61 patients, and monophasic CT scans (unenhanced and excretory phase scans) in 49. We compared patient age and sex; tumor size; degree and pattern (homogeneous, heterogeneous, predominantly peripheral) of enhancement; presence or absence of calcification; and tumor-spreading patterns including perinephric change, venous invasion, and lymphadenopathy in four subtypes. RESULTS: Conventional renal carcinoma showed stronger enhancement than the other subtypes (p < 0.05): 106 +/- 48 H (mean +/- SD) in the corticomedullary phase and 62 +/- 25 H in the excretory phase. The sensitivity and specificity for differentiating conventional renal carcinoma from the other subtypes were 74% and 100% when 84 H was used as the cutoff value in the corticomedullary phase and 84% and 91% when 44 H was used as the cutoff value in the excretory phase. Conventional (84%), papillary (74%), and collecting duct (100%) renal carcinomas tended to show heterogeneous or predominantly peripheral enhancement, whereas chromophobe renal carcinoma (69%) usually showed homogeneous enhancement. Calcification was more common in papillary (32%) and chromophobe (38%) renal carcinomas than in conventional renal carcinoma (11%) (p < 0.05). Perinephric change and venous invasion were not noted in chromophobe renal carcinoma, whereas both were common in collecting duct renal carcinoma. CONCLUSION: For the differentiation of the subtypes of renal cell carcinoma, degree of enhancement is the most valuable parameter; enhancement pattern, the presence or absence of calcification, and tumor-spreading patterns can serve supplemental roles in the identification of the subtype of renal cell carcinoma.