Does bilateral seminal vesicle invasion at radical prostatectomy predict worse prognosis than unilateral invasion among patients with pT3b prostate cancers?

OBJECTIVES: To determine whether bilateral seminal vesicle invasion is associated with worse biochemical recurrence-free survival than unilateral seminal vesicle invasion after radical prostatectomy. METHODS: We reviewed the clinicopathological data of 598 men who underwent radical prostatectomy between 2008 and 2015. Among them, 107 (17.9%) had seminal vesicle invasion. After excluding cases with neo-/adjuvant hormone treatment or radiotherapy, 93 were included in the analysis. We compared biochemical recurrence-free survival rates in subgroups with or without bilateral seminal vesicle invasion using Kaplan-Meier estimates. Cox proportional hazard regression models were used to determine the predictors of biochemical recurrence-free survival. RESULTS: Bilateral prostatic lobes and bilateral seminal vesicles were involved by prostate cancers in 85 (91.4%) and 35 patients (37.6%), respectively. Actuarial 3-year and 5-year biochemical recurrence-free survival rates in patients with pT3b tumors with/without bilateral seminal vesicle invasion were 13.0%/34.3%, and 4.3%/19.8%, respectively. On multivariable analysis, preoperative prostate-specific antigen (hazard ratio 1.01, 95% confidence interval 1.00-1.02, P = 0.034), lymph node metastasis (hazard ratio 2.88, 95% confidence interval 1.43-5.81, P = 0.003) and bilateral seminal vesicle invasion (hazard ratio 1.75, 95% confidence interval 1.01-3.05, P = 0.047) were independent predictors of biochemical recurrence-free survival. After excluding cases with lymph node metastasis, preoperative prostate-specific antigen, surgical margin status and bilateral seminal vesicle invasion were independent predictors of biochemical recurrence-free survival. CONCLUSIONS: Although most men with seminal vesicle invasion experience biochemical recurrences after radical prostatectomy, their survival outcome is not uniform. Bilateral seminal vesicle invasion seems to represent an independent prognostic factor for pT3b patients, together with the preoperative prostate-specific antigen and lymph node status.

Nomogram for prediction of prostate cancer with serum prostate specific antigen less than 10 ng/mL.

Although prostate-specific antigen (PSA) is a very useful screening tool, prostate biopsy is still necessary to confirm prostate cancer (PCA). However, it is reported that PSA is associated with a high false-positive rate and prostate biopsy also has various procedure-related complications. Therefore, the authors have devised a nomogram, which can be used to estimate the risk of PCA, using available clinical data for men with a serum PSA less than 10 ng/mL. Prostate biopsies were obtained from 2,139 patients from January 1998 to March 2011. Of them, 1,171 patients with a serum PSA less than 10 ng/mL were only included in this study. Patient age, PSA, free PSA, prostate volume, PSA density and percent free PSA ratio were analyzed. Among 1,171 patients, 255 patients (21.8%) were diagnosed as PCA. Multivariate analyses showed that patient age, prostate volume, PSA and percent free PSA had statistically significant relationships with PCA (P < 0.05) and were used as nomogram predictor variables. The area under the (ROC) curve for all factors in a model predicting PCA was 0.759 (95% CI, 0.716-0.803).

Clinical significance of a large difference (≥ 2 points) between biopsy and post-prostatectomy pathological Gleason scores in patients with prostate cancer.

We investigated the clinical significance of large difference (≥ 2 points) between biopsy-derived (bGS) and post-prostatectomy Gleason scores (pGS). At 14 medical centers in Korea, 1,582 men who underwent radical prostatectomy for prostate cancer were included. According to the difference between bGS and pGS, the patients were divided into three groups: A (decreased in pGS ≥ 2, n = 30), B (changed in pGS ≤ 1, n = 1,361; control group), and C (increased in pGS ≥ 2, n = 55). We evaluated various clinicopathological factors of prostate cancer and hazards for biochemical failure. Group A showed significantly higher mean maximal percentage of cancer in the positive cores (max%) and pathological T stage than control. In group C, the number of biopsy core was significantly smaller, however, tumor volume and max% were significantly higher and more positive biopsy cores were presented than control. Worse pathological stage and more margin-positive were observed in group A and C than in control. Hazard ratio for biochemical failure was also higher in group A and C (P = 0.001). However, the groups were not independent factors in multivariate analysis. In conclusion, large difference between bGS and pGS shows poor prognosis even in the decreased group. However it is not an independent prognostic factor for biochemical failure.

Prostate Cancer Working Group report.

The incidence of prostate cancer, while still lower than in Western nations, is increasing rapidly in Asian countries due to a more westernized lifestyle. Prostate cancer mortality is declining in the USA, where most prostate cancers are diagnosed in the early stage. In contrast, the mortality rates of prostate cancer in Asian countries are expected to continue to increase, because the percentage of advanced-stage prostate cancers remains high. Therefore, early detection by prostate-specific antigen screening and a comprehensive strategy for cancer prevention are essential for Asian people. The exposure rate of prostate-specific antigen screening is very low in Asian countries. Increased prostate-specific antigen screening may reduce the mortality rate. The stances regarding population screening differ among countries. Urological associations should promote population screening. Reliable data from Asian countries are needed. The prostate cancer incidence is low in Asian countries, perhaps due to high soy consumption. Isoflavones may prevent prostate cancer in Asian countries, but that is not yet clear. A large, multinational study in Asia is needed to clarify whether or not isoflavone consumption shows efficacy in preventing prostate cancer. Clinical data suggest that hormonal therapy is more effective in Asians than in Westerners. Clinical guidelines should consider including hormonal therapy as one of the options for the treatment of localized prostate cancer. At the same time, effort should be made to decrease the adverse effects of each treatment. Collaborative studies on the treatment of prostate cancer should be carried out among Asian countries.

Preoperative nomograms for predicting extracapsular extension in Korean men with localized prostate cancer: a multi-institutional clinicopathologic study.

We developed a nomogram to predict the probability of extracapsular extension (ECE) in localized prostate cancer and to determine when the neurovascular bundle (NVB) may be spared. Total 1,471 Korean men who underwent radical prostatectomy for prostate cancer between 1995 and 2008 were included. We drew nonrandom samples of 1,031 for nomogram development, leaving 440 samples for nomogram validation. With multivariate logistic regression analyses, we made a nomogram to predicts the ECE probability at radical prostatectomy. Receiver operating characteristic (ROC) analyses were also performed to assess the predictive value of each variable alone and in combination. The internal validation was performed from 200 bootstrap re-samples and the external validation was also performed from the another cohort. Overall, 314 patients (30.5%) had ECE. Age, Prostate specific antigen (PSA), biopsy Gleason score, positive core ratio, and maximum percentage of biopsy tumor were independent predictors of the presence of ECE (all P values <0.05). The nomogram predicted ECE with good discrimination (an area under the ROC curve of 0.777). Our nomogram allows for the preoperative identification of patients with an ECE and may prove useful in selecting patients to receive nerve sparing radical prostatectomy.

Changes in renal function after nephron-sparing surgery in patients with a normal contralateral kidney.

OBJECTIVES: To evaluate the pattern of the recovery of the overall and isolated renal function in patients with a normal contralateral kidney undergoing nephron-sparing surgery (NSS). METHODS: Between 2003 and 2006, 62 patients underwent open NSS at our institution. Among them, 35 having unilateral renal tumors smaller than 7 cm and a normally functioning contralateral kidney were included in the analysis. The estimated glomerular filtration rate (eGFR) was checked preoperatively, and 2 weeks, 6 months and 1 year postoperatively, and annually thereafter. Renal scintigraphy was carried out before the procedure, at 6 months and 1 year postoperatively to measure individual renal uptake. RESULTS: eGFR was 80.9, 70.8, 76.7, 76.9, 75.8, 76.9, 78.6 and 78.2 mL/min/1.73 m(2) preoperatively, and postoperatively at 2 weeks, 6 months, 1, 2, 3, 4 and 5 years, respectively. Average isolated differential function of the operated kidney decreased 11.6% and 5.6% at 6 months and 1 year after surgery, respectively. CONCLUSIONS: Within 6 months after NSS, the overall renal function recovered up to 95% by a compensatory increase of contralateral renal function. Thereafter, isolated function of the operated kidney recovered slowly.

The Association of Phosphodiesterase 5 Inhibitor on Ischemia-Reperfusion Induced Kidney Injury in Rats.

PURPOSE: Ischemia-reperfusion (IR) causes various damage in renal tissues. The aim of the present study was to evaluate the renoprotective effect of phosphodiesterase 5 inhibitor (PDE5I) on IR induced renal injury in a rat model. MATERIALS AND METHODS: Thirty adult male, 12-week-old, Sprague-Dawley rats were divided into three groups. Renal IR injury was induced by occlusion of the bilateral renal pedicle for 45 min followed by reperfusion for 24 h. The rats were sacrificed for collecting blood and tissue specimens. IR rats were administered daily oral Tadalafil (group I) or no pills (group II), while sham-operated animals were treated with no pills (sham group). The pill was diluted with distilled water and administered to rats for 15 days, orally. Renal histopathology, function, pro-inflammatory and inflammatory cytokines and mediators were assessed by serum creatinine, western blot assay and immunohistochemistry. RESULTS: Compared with sham group, rats that underwent renal IR operation exhibited a significant increase in concentration in serum creatinine (p< .01) and tissue pro-inflammatory and inflammatory mediators. In group I, however, tadalafil significantly suppressed elevation of the serum creatinine and increased the levels of endothelial nitric oxide synthase and decreased the level of intercellular adhesion molecule-1 (ICAM-1) than group II (p< .05). Moreover, tadalafil prevented IR-induced expression of pro-inflammatory mediators such as monocyte chemotactic protein-1 (MCP-1) (p< .05). CONCLUSION: Tadalafil significantly promotes functional recovery after renal IR injury and effectively inhibits the induction of pro-inflammatory and inflammatory mediators. The results substantiate Tadalafil as a protective agent against IR-induced renal injury.

Conditional biochemical recurrence-free survival after radical prostatectomy in patients with high-risk prostate cancer.

BACKGROUND: Conditional survival is defined as the likelihood of subsequent survival given the precondition of having already survived a certain length of time. Most analyses of conditional survival in prostate cancer are not clinically applicable because they do not analyze outcomes conditioned on the durability of cure after treatment. We evaluated the conditional probability of biochemical recurrence (BCR)-free survival (C-BCRFS) after radical prostatectomy (RP) for prostate cancer according to the National Comprehensive Cancer Network risk classification and prognostic factors in patients who survived several years without BCR. METHODS: Between January 2009 and December 2018, 877 patients with complete clinicopathologic and follow-up data were included. Using the Kaplan-Meier estimation, the probabilities of C-BCRFS after RP were estimated in patients who did not experience BCR at 0-4 years. C-BCRFS was analyzed according to the National Comprehensive Cancer Network risk classification and compared using the log-rank test. Prognostic factors at each year without BCR were evaluated using multivariable Cox regression analysis. RESULTS: The median follow-up duration and patient age were 48 months and 67 years, respectively. As the BCR-free interval increased (baseline, 1, 2, 3, and 4 years after RP), the 5-year C-BCRFS rates improved marginally (74.8%, 83.2%, 89.1%, 93.6%, and 98.5%, respectively). However, the 5-year C-BCRFS rates in the high/very high-risk group rose from 54.0% at baseline to 67.6%, 80.3%, 88.6, and 97.8% after 1-4 years free of BCR, respectively. In patients with a BCR-free duration more than 1 year, only seminal vesicle invasion and pathological Gleason score were significant predictive factors of BCR thereafter. CONCLUSION: In the high/very high-risk group, the C-BCRFS markedly improved as the interval without BCR increased. In patients who were BCR-free for several years, seminal vesicle invasion and pathological Gleason score were prognostic factors of continued BCRFS. This is useful not only for patient counseling but also to optimize postoperative follow-up strategies.

Effectiveness of hyaluronic acid/carboxymethylcellulose in preventing adhesive bowel obstruction after laparoscopic radical cystectomy.

BACKGROUND/OBJECTIVE: Adhesive bowel obstruction is one of the most frequent complications after radical cystectomy, prolonging hospital stay and fasting period and increasing medical expenses. This study evaluated the effectiveness of hyaluronic acid/carboxymethylcellulose (HA/CMC) in preventing adhesive bowel obstruction after laparoscopic radical cystectomy. METHODS: Randomized, controlled, single-blinded study was performed. Of 76 patients who underwent laparoscopic radical cystectomy for bladder cancer, 38 received HA/CMC instillation and 38 did not. The primary endpoint was the rate of postoperative adhesive bowel obstruction. The secondary endpoint was the rate of other postoperative outcomes. RESULTS: None of the patients who received HA/CMC instillation experienced postoperative adhesive bowel obstructions, compared with six (15.79%) patients in the control group (p = 0.025). Of the six patients with ileus, two underwent adhesiolysis. There were no significant differences between the two groups in other postoperative outcomes. CONCLUSION: HA/CMC instillation during laparoscopic radical cystectomy may reduce the incidence of postoperative adhesive bowel obstruction without adverse effects.

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.

Does T1- and diffusion-weighted magnetic resonance imaging give value-added than bone scintigraphy in the follow-up of vertebral metastasis of prostate cancer?

PURPOSE: To evaluate the effectiveness of limited Magnetic Resonance (MR) images including T1- and diffusion-weighted image (DWI) for monitoring vertebral metastasis in patients with prostate cancer. MATERIALS AND METHODS: From July 2014 to November 2016, patients diagnosed with spinal metastasis from prostate cancer using 99mTc bone scintigraphy were enrolled. Regardless of the primary local therapy, the changes in spinal metastasis were followed up using bone scan and biparametric MR (T1+DWI). All tests were followed up for more than 3 months. RESULTS: Among the 14 follow-ups of 10 patients, 6 and 10 (including all progressed cases on bone scan) follow-ups were determined to show progressive disease using bone scan and biparametric MR, respectively. Otherwise, we could have predicted neurologic sequela earlier using biparametric MR. Examination time for biparametric MR was 15 minutes, and it was 4 hours for bone scan, respectively. CONCLUSIONS: Although bone scan has been considered the standard test for bony metastasis in men with prostate cancer, limited MR including T1 and DWI has an additional benefit in monitoring spinal metastasis in patients who are already diagnosed as having spinal metastasis. The limited MR is more sensitive in detecting progressive disease. In addition, it can reduce neurologic complications caused by spinal metastasis.

Growth kinetics of small renal mass: Initial analysis of active surveillance registry.

Purpose: To evaluate the clinical safety and natural history of active surveillance (AS) for incidentally diagnosed small renal mass (SRM). Materials and Methods: We analyzed prospective data for patients who underwent AS for SRM. From 2010 to 2016, 37 SRMs of less than 3 cm were registered. Computed tomography (CT) and magnetic resonance imaging were used for initial diagnosis and CT, ultrasonography, and chest CT were performed at 6-month intervals. If there was no change in size during 2 years, follow-ups were performed annually. If the growth rate was more than 0.5 cm/y, if the diameter was more than 4 cm, or if clinical progression was observed, we regarded it as progression of SRM and recommended active treatment. We compared the growth rate and clinical course of SRM between patients who remained on surveillance and those who had progressed disease. Results: The mean age was 63 years (range, 30-86 years) and the mean diameter was 1.8 cm (range, 0.6-2.8 cm) at diagnosis. The mean follow-up period was 27.3 months (range, 6-80 months) and the average growth rate was 0.2 cm/y (range, 0-1.9 cm/y). Six patients (16.2%) showed progression of SRM. Three patients wanted continuous observation, and partial nephrectomy was performed on 3 other patients. None of the patients had clinical progression, including metastasis. Conclusions: We could delay active treatment for patients with an SRM with scheduled surveillance if the SRM grew relatively slowly. If more long-term AS results are documented for more patients, AS could be an alternative treatment modality for SRM.

Comparison of Multiparametric and Biparametric MRI in First Round Cognitive Targeted Prostate Biopsy in Patients with PSA Levels under 10 ng/mL.

PURPOSE: To determine the efficacy of cognitive targeted prostate biopsy using biparametric magnetic resonance imaging (b-MRI) for patients with prostate-specific antigen levels under 10 ng/mL. MATERIALS AND METHODS: We reviewed data from 123 consecutive patients who underwent cognitive targeted prostate biopsy using prostate MRI. Of these patients, the first 55 underwent prostate biopsy using multiparametric MRI (mp-MRI), and the remaining 68 underwent prostate biopsy using b-MRI. For b-MRI, we generated T2 weighted axial imaging and diffusion-weighted imaging sequences. We found that 62 of the 123 men had suspicious lesions on MRI (32 of the 55 men in the mp-MRI group and 30 of the 68 men in the b-MRI group). We compared the prostate cancer detection rates and the proportions of clinically significant prostate cancer between the different MRI sequences. RESULTS: Between the two MRI groups, there were no statistically significant differences in prostate cancer detection rate and proportions of clinically significant prostate cancer (41.8% vs. 30.9%, p=0.208 and 82.6% vs. 76.2%, p=0.598). Among the 62 men who had suspicious lesions on MRI, the prostate cancer detection rates were 62.5% and 63.3% (p=0.709) in the mp-MRI and b-MRI groups, respectively, and the proportions of clinically significant prostate cancer were 95.0% and 84.2% (p=0.267). CONCLUSION: Prostate biopsy using b-MRI showed similar performance to that using mp-MRI for detecting prostate cancer and clinically significant prostate cancer. Considering the satisfactory performance and cost effectiveness of b-MRI, this technique could be a good option for obtaining intraprostatic information for first round prostate biopsy.

Visually Estimated MRI Targeted Prostate Biopsy Could Improve the Detection of Significant Prostate Cancer in Patients with a PSA Level <10 ng/mL.

PURPOSE: To compare prostate cancer detection rates between 12 cores transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and visually estimated multiparametric magnetic resonance imaging (mp-MRI)-targeted prostate biopsy (MRI-visual-Bx) for patients with prostate specific antigen (PSA) level less than 10 ng/mL. MATERIALS AND METHODS: In total, 76 patients with PSA levels below 10 ng/mL underwent 3.0 Tesla mp-MRI and TRUS-Bx prospectively in 2014. In patients with abnormal lesions on mp-MRI, we performed additional MRI-visual-Bx. We compared pathologic results, including the rate of clinically significant prostate cancer cores (cancer length greater than 5 mm and/or any Gleason grade greater than 3 in the biopsy core). RESULTS: The mean PSA was 6.43 ng/mL. In total, 48 of 76 (63.2%) patients had abnormal lesions on mp-MRI, and 116 targeted biopsy cores, an average of 2.42 per patient, were taken. The overall detection rates of prostate cancer using TRUS-Bx and MRI-visual-Bx were 26/76 (34.2%) and 23/48 (47.9%), respectively. In comparing the pathologic results of TRUS-Bx and MRI-visual-Bx cores, the positive rates were 8.4% (77 of 912 cores) and 46.6% (54 of 116 cores), respectively (p<0.001). Mean cancer core lengths and mean cancer core percentages were 3.2 mm and 24.5%, respectively, in TRUS-Bx and 6.3 mm and 45.4% in MRI-visual-Bx (p<0.001). In addition, Gleason score ≥7 was noted more frequently using MRI-visual-Bx (p=0.028). The detection rate of clinically significant prostate cancer was 27/77 (35.1%) and 40/54 (74.1%) for TRUS-Bx and MRI-visual-Bx, respectively (p<0.001). CONCLUSION: MRI-visual-Bx showed better performance in the detection of clinically significant prostate cancer, compared to TRUS-Bx among patients with a PSA level less than 10 ng/mL.

Prognostic value of sex-hormone receptor expression in non-muscle-invasive bladder cancer.

PURPOSE: We investigated sex-hormone receptor expression as predicting factor of recurrence and progression in patients with non-muscle invasive bladder cancer. MATERIALS AND METHODS: We retrospectively evaluated tumor specimens from patients treated for transitional cell carcinoma of the bladder at our institution between January 2006 and January 2011. Performing immunohistochemistry using a monoclonal androgen receptor antibody and monoclonal estrogen receptor-beta antibody on paraffin-embedded tissue sections, we assessed the relationship of immunohistochemistry results and prognostic factors such as recurrence and progression. RESULTS: A total of 169 patients with bladder cancer were evaluated in this study. Sixty-threepatients had expressed androgen receptors and 52 patients had estrogen receptor beta. On univariable analysis, androgen receptor expression was significant lower in recurrence rates (p=0.001), and estrogen receptor beta expression was significant higher in progression rates (p=0.004). On multivariable analysis, significant association was found between androgen receptor expression and lower recurrence rates (hazard ratio=0.500; 95% confidence interval, 0.294 to 0.852; p=0.011), but estrogen receptor beta expression was not significantly associated with progression rates. CONCLUSION: We concluded that the possibility of recurrence was low when the androgen receptor was expressed in the bladder cancer specimen and it could be the predicting factor of the stage, number of tumors, carcinoma in situ lesion and recurrence.

A milk protein, casein, as a proliferation promoting factor in prostate cancer cells.

PURPOSE: Despite most epidemiologic studies reporting that an increase in milk intake affects the growth of prostate cancer, the results of experimental studies are not consistent. In this study, we investigated the proliferation of prostate cancer cells treated with casein, the main protein in milk. MATERIALS AND METHODS: Prostate cancer cells (LNCaP and PC3), lung cancer cells (A459), stomach cancer cells (SNU484), breast cancer cells (MCF7), immortalized human embryonic kidney cells (HEK293), and immortalized normal prostate cells (RWPE1) were treated with either 0.1 or 1 mg/mL of α-casein and total casein extracted from bovine milk. Treatments were carried out in serum-free media for 72 hours. The proliferation of each cell line was evaluated by an 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: α-Casein and total casein did not affect the proliferations of RWPE1, HEK293, A459, SNU484, MCF7, HEK293, or RWPE1 cells. However, PC3 cells treated with 1 mg/mL of α-casein and casein showed increased proliferation (228% and 166%, respectively), and the proliferation of LNCaP cells was also enhanced by 134% and 142%, respectively. The proliferation mechanism of α-casein in PC3 and LNCaP cells did not appear to be related to the induction of Insulin-like growth factor-1 (IGF-1), since the level of IGF-1 did not change upon the supplementation of casein. CONCLUSIONS: The milk protein, casein, promotes the proliferation of prostate cancer cells such as PC3 and LNCaP.

Reasons for prescription change of α1-blockers in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: To investigate the reasons for prescription change of α1-blockers in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. METHODS: The ratio and interval of prescription change were assessed in 3200 patients who were eligible for the study and took 1 of 4 different α1-blockers (doxazosin, alfuzosin, tamsulosin, or silodosin). The reasons for prescription change and evaluation of efficacy were analyzed in 444 patients whose medical records were complete. RESULTS: Prescription change to another α1-blocker occurred in 694 of 3200 patients (21.7%), and the mean duration of taking their first α1-blocker was 10.8 ± 8.2 weeks. Lack of efficacy (52.7%) was the main reason for changing α1-blockers, followed by adverse events (33.1%), relatively high cost compared with other α1-blockers (7.0%), inconvenience of taking drugs (4.1%), and cardiovascular comorbidity (3.2%). The mean duration of treatment according to each reason is as follows: increased adverse events: 6.3 ± 5.2 weeks, relatively high cost compared with other α1-blockers: 8.7 ± 4.5 weeks, cardiovascular comorbidity: 10.5 ± 6.8 weeks, inconvenience of taking drugs: 10.8 ± 3.9 weeks, and lack of efficacy: 14.8 ± 6.8 weeks. The proportion of prescription change (16.3%) and prescription change because of hemodynamic adverse events (2.4%) in the silodosin group were low compared with those in the other groups (P <.05 and P <.006, respectively), but prescription change because of a ejaculation disorder was high in the silodosin group (30.1%, P <.001). CONCLUSION: Major reasons for prescription change in patients taking α1-blockers were lack of efficacy and adverse events. In the silodosin group, the proportion of prescription change was significantly low compared with that in the other 3 groups.

Expression analysis and clinical significance of CXCL16/CXCR6 in patients with bladder cancer.

The interactions between chemokines and their receptors are closely involved in the progression and metastasis of cancer. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in bladder cancer progression. To evaluate this hypothesis, the expression levels of CXCL16 and CXCR6 were evaluated in 160 patients, including 155 patients with bladder cancer and 5 patients with benign bladder disease. The tissues were analyzed by immunohistochemical (IHC) staining and real-time reverse-transcription polymerase chain reaction. We compared the expression of CXCL16/CXCR6 in bladder cancer and benign bladder disease. The expression of CXCR6 was increased in patients with bladder cancer compared with benign bladder disease in RT-PCR. The mRNA expression levels of CXCL16 and CXCR6 were 1.75×10(-2) and 1.99×10(-2) in benign bladder tissue and 1.39×10(-2) and 2.32×10(-2) in bladder cancer tissue, respectively. In IHC staining, the expression of CXCL16/CXCR6 in bladder cancer tissues was higher compared with benign bladder tissues. On multivariate analysis, the IHC staining of CXCL16 was correlated with the 2004 WHO grade and lymphovascular invasion (P=0.021 and P=0.011, respectively). CXCR6 was correlated with the 1973 WHO grade (P=0.001), 2004 WHO grade (P<0.001), pathological T stage (P=0.002) and perineural invasion (P=0.031). However, Cox regression analysis revealed that the expression of CXCL16 and CXCR6 was not correlated with cancer recurrence and cancer-specific survival (P=0.142 and P=0.324, respectively). The expression of CXCL16/CXCR6 was higher in bladder cancer compared to benign disease and correlated with aggressive cancer behavior. Based on our results, the CXCL16/CXCR6 axis appears to be important in the progression of bladder cancer. Thus, CXCL16 and CXCR6 serve as potential therapeutic targets.

The Studer orthotopic neobladder: long-term (more than 10 years) functional outcomes, urodynamic features, and complications.

PURPOSE: Radical cystectomy and urinary diversion are the standard treatment for invasive bladder cancer. We analyzed the long-term (>10 years postoperatively) functional outcomes, complications, and urodynamic findings in a single center series of patients who underwent cystectomy and a Studer ileal neobladder substitution. MATERIALS AND METHODS: A retrospective chart review of 108 Studer pouches constructed during 1990 and 2011 was performed. Data were analyzed in terms of long-term (>10 years) outcomes. Complications, incontinence, voiding difficulties, upper urinary tract changes, overall satisfaction, and urodynamic findings of the reservoir were obtained. RESULTS: We evaluated 19 out of 50 patients who had lived for over 10 years postoperatively. Another 31 patients were not traced: 7 patients died following recurrence, 15 died due to exacerbation of a comorbidity, and 9 patients were lost to follow-up. Concerning complications, 6 patients had an atrophied kidney, 5 patients had moderate hydronephrosis, 5 patients had chronic recurrence of pylelonephritis, and 2 patients had voiding difficulty because of bladder neck stricture due to clean intermittent catheterization. One patient underwent an operation due to intestinal obstruction. Seven patients had incontinence; all 7 patients showed intermittently at night and 2 patients even in waking hours. Maximum bladder capacity was 484.1±119.2 mL, maximum flow rate was 13.6±9.7 mL/sec, and post-void residual urine volume was 146.8±82.7 mL. CONCLUSION: Long-term outcomes with the Studer orthotopic ileal neobladder have an acceptable complication rate and good functional results. However, potential adverse outcomes such as renal deterioration, dysfunctional voiding should also be considered.

Development of an immunotherapeutic adenovirus targeting hormone-independent prostate cancer.

BACKGROUND: To develop a targeting therapy for hormone-independent prostate cancer, we constructed and characterized conditionally replicating oncolytic adenovirus (Ad) equipped with mRFP (monomeric red fluorescence protein)/ttk (modified herpes simplex virus thymidine kinase). This construct was then further modified to express both mRFP/ttk and a soluble form of cytokine FLT3L (fms-related tyrosine kinase 3 ligand) simultaneously. METHODS: To construct the recombinant oncolytic adenovirus, E1a and E4 genes, which are necessary for adenovirus replication, were controlled by the prostate-specific enhancer sequence (PSES) targeting prostate cancer cells expressing prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA). Simultaneously, it expressed the mRFP/ttk fusion protein in order to be able to elicit the cytotoxic effect. RESULTS: The Ad5/35PSES.mRFP/ttk chimeric recombinant adenovirus was generated successfully. When replication of Ad5/35PSES.mRFP/ttk was evaluated in prostate cancer cell lines under fluorescence microscopy, red fluorescence intensity increased more in LNCaP cells, suggesting that the mRFP/ttk fusion protein was folded functionally. In addition, the replication assay including wild-type adenovirus as a positive control showed that PSES-positive cells (LNCaP and CWR22rv) permitted virus replication but not PSES-negative cells (DU145 and PC3). Next, we evaluated the killing activity of this recombinant adenovirus. The Ad5/35PSES. mRFP/ttk killed LNCaP and CWR22rv more effectively. Unlike PSES-positive cells, DU145 and PC3 were resistant to killing by this recombinant adenovirus. Finally, in order to potentiate therapeutic efficacy, we developed a recombinant adenovirus expressing multiexogenous genes, mRFP/ttk and sFLT3L. CONCLUSION: In the present study, a replication-competent adenovirus was successfully designed to replicate conditionally in PSA-positive and PSMA-positive prostate cancer cells. This recombinant adenovirus is equipped with the fusion protein of suicidal and red-fluorescence fusion protein together with sFLT3L. This construct would be expected to have potent antitumor effects and deserves more extensive investigation.