Won Ik Seo

Korean Prostate Cancer Patients Have Worse Disease Characteristics than their American Counterparts

BACKGROUND Although the PSA test has been used in Korea for over 20 years, the incidence of prostate cancer has risen, and the associated mortality has increased about 13-fold over the 20-year period. Also, several investigators have suggested that Asians in America are more likely to present with more advanced prostate cancer than Caucasians. We compared the characteristics of native Koreans and Americans (Caucasians and African- Americans) undergoing radical prostatectomies in Korea and the US. MATERIALS AND METHODS Study subjects comprised patients at Korean and US hospitals from 2004 to 2012 who had undergone radical prostatectomies. We compared the characteristics of the subjects, including age, preoperative prostate-specific antigen (PSA) levels, body mass index (BMI), Gleason score, and pathological T stage. RESULTS In total, 1,159 males (502 Koreans, 657 Americans) were included. The Korean and American patients had mean ages of 67.1 ± 6.6 and 59.2 ± 6.7 years, respectively. The mean preoperative PSAs were 15.4 ± 17.9 and 6.2 ± 4.6 ng/mL (p=0.0001) and the mean BMIs were 23.6 ± 2.6 and 28.7 ± 4.4 kg/m2 (p=0.0001), respectively. Pathological localized prostate cancer represented 71.7% of cases for Koreans and 77.6% for Americans (p=0.07). According to age, Koreans had higher T stages than Americans in their 50s (p=0.021) and higher Gleason scores than Americans in all age groups. According to PSA, Koreans had higher Gleason scores than Americans for PSA >10 ng/mL (p<0.05). According to prostate size and Gleason scores, Koreans had higher PSA values than Americans (p<0.01). CONCLUSIONS These results show that Korean patients have elevated risk of malignant prostate cancers, as indicated by the significantly higher Gleason scores and PSAs, suggesting a need for novel prostate cancer treatment strategies in Korea.

Incidental abnormal FDG uptake in the prostate on 18-fluoro-2-deoxyglucose positron emission tomography-computed tomography scans.

18-fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scans are commonly used for the staging and restaging of various malignancies, such as head and neck, breast, colorectal and gynecological cancers. However, the value of FDG PET/CT for detecting prostate cancer is unknown. The aim of this study was to evaluate the clinical value of incidental prostate 18F-FDG uptake on PET/CT scans. We reviewed 18F-FDG PET/CT scan reports from September 2009 to September 2013, and selected cases that reported focal/diffuse FDG uptake in the prostate. We analyzed the correlation between 18F-FDG PET/CT scan findings and data collected during evaluations such as serum prostate-specific antigen (PSA) levels, digital rectal examination (DRE), transrectal ultrasound (TRUS), and/or biopsy to confirm prostate cancer. Of a total of 18,393 cases, 106 (0.6%) exhibited abnormal hypermetabolism in the prostate. Additional evaluations were performed in 66 patients. Serum PSA levels were not significantly correlated with maximum standardized uptake values (SUVmax) in all patients (rho 0.483, p=0.132). Prostate biopsies were performed in 15 patients, and prostate cancer was confirmed in 11. The median serum PSA level was 4.8 (0.55-7.06) ng/mL and 127.4 (1.06-495) ng/mL in the benign and prostate cancer groups, respectively. The median SUVmax was higher in the prostate cancer group (mean 10.1, range 3.8-24.5) than in the benign group (mean 4.3, range 3.1-8.8), but the difference was not statistically significant (p=0.078). There was no significant correlation between SUVmax and serum PSA, prostatic volume, or Gleason score. 18F-FDG PET/CT scans did not reliably differentiate malignant or benign from abnormal uptake lesions in the prostate, and routine prostate biopsy was not usually recommended in patients with abnormal FDG uptake. Nevertheless, patients with incidental prostate uptake on 18F-FDG PET/ CT scans should not be ignored and should be undergo further clinical evaluations, such as PSA and DRE.

Cancer of the Prostate Risk Assessment (CAPRA) Preoperative Score Versus Postoperative Score (CAPRA-S): Ability to Predict Cancer Progression and Decision-Making Regarding Adjuvant Therapy after Radical Prostatectomy

The University of California, San Francisco, announced in 2011 Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score which included pathologic data, but there were no results for comparing preoperative predictors with the CAPRA-S score. We evaluated the validation of the CAPRA-S score in our institution and compare the result with the preoperative progression predictor, CAPRA score. Data of 130 patients were reviewed who underwent radical prostatectomy for localized prostate cancer from 2008 to 2013. Performance of CAPRA-S score in predicting progression free probabilities was assessed through Kaplan Meier analysis and Cox proportional hazards regression test. Additionally, prediction probability was compared with preoperative CAPRA score by logistic regression analysis. Comparing CAPRA score, the CAPRA-S score showed improved prediction ability for 5 yr progression free survival (concordance index 0.80, P = 0.04). After risk group stratification, 3 group model of CAPRA-S was superior than 3 group model of CAPRA for 3-yr progression free survival and 5-yr progression free survival (concordance index 0.74 vs. 0.70, 0.77 vs. 0.71, P < 0.001). Finally the CAPRA-S score was the more ideal predictor concerned with adjuvant therapy than the CAPRA score through decision curve analysis. The CPARA-S score is a useful predictor for disease progression after radical prostatectomy. Graphical Abstract

Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP

Aberrant up-regulation of Wnt/β-catenin signaling is associated with the development and progression of prostate cancer, but the underlying mechanism is unclear. Here we show that in the absence of androgens, the Wnt/β-catenin pathway activates AR-mediated transcription through up-regulation of the Hippo pathway effector Yes-associated protein (YAP). Wnt3a-conditioned medium (Wnt3a-CM) promotes the growth of LNCaP cells and increases AR and YAP protein levels. Moreover, Wnt3a-CM induces the nuclear translocation of YAP and the AR, but not β-catenin, thereby activating the expression of AR- and YAP-dependent genes, in an androgen-independent manner. In addition, depletion of YAP with small interfering RNA (siRNA) prevented Wnt3a-CM-mediated up-regulation of AR-dependent gene expression. Thus, our findings provide mechanistic insight into the proposed cross-talk between the Wnt/β-catenin and Hippo pathways in androgen-independent prostate cancer development.

Predictive Value of the Cancer of the Prostate Risk Assessment Score for Recurrence-Free Survival After Radical Prostatectomy in Korea: A Single-Surgeon Series

Purpose To evaluate the validity of the cancer of the prostate risk assessment (CAPRA) score, a newly developed nomogram for preoperative prediction of recurrence after radical prostatectomy, in a single institution in Korea. Materials and Methods We retrospectively studied 115 men who had undergone radical prostatectomy as the first treatment for localized prostate cancer. The validity of the CAPRA score for the prediction of recurrence-free survival (RFS) and pathologic outcome was evaluated by using Kaplan-Meier analysis and a proportional hazards regression model. A seven-group model and a three-group model were used for the results. Results None of the variables of the CAPRA score was favorable compared with the previously reported data. The three-group model was significantly related with 3- and 5-year RFS (p<0.05), but the seven-group model was not. The concordance indices of the CAPRA score were 0.74 and 0.77. Of four components excluding the clinical T stage, three independently predicted RFS (age, Gleason sum, and percentage of positive biopsies). The CAPRA score was significantly related to the margin status, extracapsular extension, and seminal vesicle invasion in both the seven- and three-group models. In the three-group model, pathologic outcomes were more strongly related, especially a higher risk of seminal vesicle invasion. Conclusions The CAPRA score showed high accuracy for predicting RFS. In particular, the three-group model was more useful for predicting RFS and pathologic outcomes. Therefore, the CAPRA score may be a useful prediction model for risk stratification and may help clinicians to develop localized prostate cancer treatment.

Thulium laser (RevoLix) vaporesection versus vapoenucleation with morcellator (Piranha) for the treatment of benign prostatic obstruction: a propensity-matched multicenter analysis.

To compare the efficacy and safety of vaporesection without a morcellator, and vapoenucleation with a morcellator in thulium laser prostatectomy for the treatment of benign prostatic obstruction.

Correlation between postoperative prostate-specific antigen and biochemical recurrence in positive surgical margin patients: Single surgeon series

Background To evaluate the relationship between postoperative prostate-specific antigen (PSA) levels and biochemical recurrence (BCR) after radical prostatectomy, especially in patients with positive surgical margins (PSMs). Materials and methods A total of 144 patients who underwent radical prostatectomies performed by a single surgeon without any neoadjuvant or adjuvant treatment were analyzed. Differences in clinicopathological factors were compared by surgical margin status, and the relationship between postoperative PSA level and BCR in patients with PSMs was evaluated. Results Fifty of the 144 patients (34.7%) had PSMs. Of these, 74% experienced BCR. The negative surgical margins and PSMs groups differed significantly in terms of PSA level at diagnosis, clinical T stage, and risk group by the cancer of the prostate risk assessment score (P = 0.002, P = 0.002, and P = 0.004, respectively). Also, the nadir PSA level, tumor volume, and BCR rate differed between the two groups (P = 0.007, P = 0.015, and P = 0.005, respectively) On Kaplan–Meier analysis, BCR-free survival was better in the negative surgical margins than the PSMs group (64.1 vs. 55.4 months, log-rank test, P = 0.011). BCR-free survival did not differ significantly in PSMs patients according to whether PSA level was or was not detectable at 1 month postoperatively. However, BCR-free survival improved when the nadir PSA level was undetectable (compared to detectable) in PSMs patients (64.3 vs. 26.1 months, log-rank test, P < 0.001). In PSMs patients belonging to the high risk group by cancer of the prostate risk assessment score, BCR-free survival was significantly better when the PSA level attained the nadir within 3 months, compared to > 6 months, postoperatively (64.2 vs. 29.5 months, log-rank test, P = 0.022). Conclusion If PSA is detectable in PSMs patients until 1 month after operation, cautious observation may be possible. If the nadir is attained within 3 months postoperatively in high-risk patients with PSMs, better BCR-free survival may be expected.

Correlation between 5-α reductase type 2 protein expression and methylation of 5-α reductase type 2 promotor gene of benign prostatic hyperplasia

PurposeThe enzyme 5-α reductase type 2 (5-AR 2) plays a key role in the development and maintenance of the prostate gland. We evaluated the level 5-AR 2 protein expression and the relationship between methylation of the 5-AR 2 gene-promoter and 5-AR 2 protein expression of benign prostatic hyperplasia (BPH).Materials and methodsA total of 37 prostate samples were evaluated. These included 22 samples from men undergoing transurethral prostate resections and 15 non-cancerous transition-zone human prostate tissue samples taken following radical prostatectomy. We quantified 5-AR 2 protein expression and gene-promoter methylation status using common assay procedures. Clinical variables included age, body mass index (BMI), prostate-specific antigen (PSA) levels, lipid profiles, and prostate volumes. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling.ResultsWe were able to extract DNA from 36 of the 37 tissue samples and 10 of these (28%) did not express the 5-AR 2 protein. In total, 26 patients (72%) had methylated 5-AR 2 promoter-regions. There was a strong correlation between methylation of the 5-AR 2 promoter-regions and low-absent 5-AR 2 protein expression (p = 0.0003). Increasing age significantly predicted methylation status and protein expression level (p = 0.013).ConclusionsThe level of 5-AR 2 protein expression varies among prostate tissue samples. Methylation of the 5-AR 2 gene-promoter may account for low or absent expression of 5-AR 2 in adult human prostate tissues. Increased age correlates with increased 5-AR 2 gene-promoter methylation and decreased protein expression in men with BPH.

Laparoscopic -2port Varicocelectomy with Scarless Periumblical Mini-Incision: Initial Experience in Approach and Outcomes

PURPOSE As with other areas, there have been many efforts for minimally invasive surgery in varicocelectomy. We present our initial experience with laparoscopic varicocelectomy with a two-port scarless periumbilical mini-incision. MATERIALS AND METHODS The study enrolled 18 patients who underwent laparoscopic varicocelectomy with a twoportscarless periumbilical mini-incision from February 2012 to April 2013. The laparoscopic varicocelectomy was performed using two 5-mm ports at periumbilical sites in skin creases. Here, the surgical procedure is introduced and the outcomes of the case series are summarized. We reviewed other laparoscopic techniques and compared them with our technique. RESULTS The mean patient age was 34.8 years. Of the 18 patients, 15 had grade 3 varicoceles. The mean operatingtime was 62.5 minutes. Postoperatively, the scrotal pain level decreased immediately from a mean VAS score of 6.3 to 4.4 and then to 1.7 by 24 hours postoperatively. The mean hospital stay was 2.8 days. Complications included one hydrocele and two recurrent varicoceles. The operating time decreased as the surgeons experience increased. CONCLUSION Laparoscopic varicocelectomy with a two-port scarless periumbilical mini-incision is a feasible technique that can be mastered relatively easily. Prospective and comparative studies are required to validate this new technique.

AB144. Histological structures of female genital tissues from angle of the entry of topical drugs

Objective Genital skin is composed of three tissue layers including epidermis, dermis and hypodermis. There are limited histologic and morphologic data concerning the skin of female genital erectile tissues. Knowledge of the histology of female genital erectile tissue is important to the development of safe and effective drug delivery system with topical vasoactive agents for management of female sexual arousal disorder. The aim of this study was to determine the structural and morphological components of various aspects of the external female genital erectile tissue to evaluate the entry of topical drugs for treatment of female sexual arousal disorder. Methods Female genital erectile tissues including glans clitoris, labia minora and labia majora were sampled from 20 female cadavers by punch-biopsy (2-3 mm diameter, 5-8 mm long). The tissues were fixed in formalin to be embedded in paraffin, and cut as 12 mm transverse sections, which were stained with haematoxylin and eosin. Thickness of epidermis and dermis, keratin-layer in epidermis, skin appendage in dermis and adipose tissue density in dermis and hypodermis was evaluated. Results Epidermis of the glans clitoris was thin compared to general skin area but thicker than other genital tissues. Thickness of the Rete ridge of glans clitoris was also thicker than other genital tissues. However, thickness of dermis and hypodermis was much thinner than other genital tissues. Skin appendages such as hair, sebaceous gland and sweat gland and adipose tissue were observed in labia minora and majora but not in glans clitoris. Blood vessels were abundant in all three genital tissues. Hypodermis in labia minora and majora was fatty but not in glans clitoris. In the glans clitoris, no tunica separating hypodermis from the corpus spongiosum (labia) was observed. Also skin of glans clitoris with thin epithelium was easily connected to erectile tissue through loose connective tissue in hypodermis. Conclusions Topical delivery of vasoactive drugs of low molecular weight to the glans clitoris might reach the labia but not likely the clitoral cavernous tissue. Further research in the vascular system of the female genitals will be required.