Adjuvant Low-dose Statin Use after Radical Prostatectomy: The PRO-STAT Randomized Clinical Trial.

PURPOSE: Statin use is reportedly associated with the risk of prostate cancer, outcomes after treatment, and prostate cancer-specific mortality. We sought to determine the efficacy of adjuvant atorvastatin in prostate cancer after radical prostatectomy. PATIENTS AND METHODS: In this randomized, double-blind trial, we assigned patients with pathologic high-risk prostate cancer to receive either low-dose atorvastatin (20 mg/day, n = 183) or placebo (n = 181) for 1 year after radical prostatectomy. The primary endpoint was the 1-year biochemical recurrence rate. The secondary endpoints included the 5-year biochemical recurrence-free survival and changes in lipid, testosterone, and sex hormone binding globulin levels. RESULTS: From October 2012 through January 2019, a total of 364 patients underwent randomization. Among 59 total primary end points, 30 (16.4%) and 29 (16.0%) occurred in the atorvastatin and placebo groups, respectively. Atorvastatin did not significantly reduce the primary endpoint of 1-year biochemical recurrence [HR, 0.96; 95% confidence interval (CI), 0.58-1.60]. During a median follow-up of 24 months, 131 patients experienced biochemical recurrence (68 in the atorvastatin group and 63 in the placebo group), representing Kaplan-Meier estimated event rates of 24.0% and 25.4% in the atorvastatin and placebo groups, respectively, at 24 months (HR, 1.00; 95% CI, 0.71-1.41). We observed no significant between-group differences in the testosterone and sex hormone binding globulin levels. CONCLUSIONS: Among patients with high-risk pathologic features after radical prostatectomy for prostate cancer, 1-year adjuvant use of atorvastatin was not associated with a lower risk of disease recurrence compared with that for placebo. (ClinicalTrials.gov number, NCT01759836).See related commentary by Murtola and Siltari, p. 4947.

A randomized controlled comparison between periprostatic nerve block and pelvic plexus block at the base and apex of 14-core prostate biopsies.

PURPOSE: To compare the pain control efficacies of the pelvic plexus block (PPB), periprostatic nerve block (PNB), and controls during a 14-core basal and apical core prostate biopsy. METHODS: This randomized controlled study, performed between January 2015 and January 2016, included patients with an abnormal serum prostate-specific antigen (PSA > 3 ng/mL) level or a palpable nodule on digital rectal examination. The enrolled patients were randomized into three groups: Group 1, intrarectal local anesthesia (IRLA, 10 mL of 2% lidocaine jelly) and PPB with 3.0 mL of 2% lidocaine injected at the bilateral pelvic plexus; Group 2, IRLA and PNB with 3.0 mL of 2% lidocaine injected at both periprostatic nerves; and Group 3, only IRLA. Patients answered the visual analog scale (VAS) questionnaire at 6 time points. RESULTS: This study consisted of 163 patients (Group 1 = 55, Group 2 = 55, and Group 3 = 53). Pain at the apical biopsy location was less in Groups 1 and 2 than in Group 3 (p < 0.001, p < 0.001) and between the two local anesthetic groups (PNB + IRLA vs PPB + IRLA). Group 2 patients reported less pain than Group 1 patients (p = 0.022). Pain during the basal core biopsy was significantly less in Groups 1 and 2 than in Group 3 (p = 0.002, p < 0.001), but there were no significant differences in pain control between the two methods (PNB + IRLA vs PPB + IRLA, p = 0.054) during basal core biopsy. CONCLUSIONS: PNB + IRLA is an effective local anesthetic method for reducing pain when performing apical biopsies compared with PPB + IRLA or IRLA alone.

Loss of Aquaporin-3 in Placenta and Fetal Membranes Induces Growth Restriction in Mice.

Aquaporin (AQP) 3, a facilitated transporter of water and glycerol, expresses in placenta and fetal membranes, but the detailed localization and function of AQP3 in placenta remain unclear. To elucidate a role of AQP3 in placenta, we defined the expression and cellular localization of AQP3 in placenta and fetal membranes, and investigated the structural and functional differences between wild-type and AQP3 null mice. Gestational sacs were removed during mid-gestational period and amniotic fluid was aspirated for measurements of volume and composition. Fetuses with attached placenta and fetal membranes were weighed and processed for histological assessment. AQP3 strongly expressed in basolateral membrane of visceral yolk sac cells of fetal membrane, the syncytiotrophoblasts of the labyrinthine placenta and fetal nucleated red blood cell membrane. Mice lacking AQP3 did not exhibit a significant defect in differentiation of trophoblast stem cells and normal placentation. However, AQP3 null fetuses were smaller than their control litter mates in spite of a decrease in litter size. The total amniotic fluid volume per gestational sac was reduced, but the amniotic fluid-to-fetal weight ratio was increased in AQP3 null mice compared with wild-type mice. Glycerol, free fatty acid and triglyceride levels in amniotic fluid of AQP3 null mice were significantly reduced, whereas lactate level increased when compared to those of wild-type mice. These results suggest a role for AQP3 in supplying nutrients from yolk sac and maternal blood to developing fetus by facilitating transport of glycerol in addition to water, and its implication for the fetal growth in utero.

The effect of AQP3 deficiency on fuel selection during a single bout of exhausting exercise.

Aquaporin-3 (AQP3) is an integral membrane protein that facilitates the transport of water and glycerol across cell membranes. However, the precise localization and function of AQP3 in skeletal muscles is currently unknown. In this study, we investigated the capacity of AQP3 knockout mice to perform a single bout of exhausting exercise and analyzed the parameters related to skeletal muscle energy metabolism during exhausting exercise. Mice were exposed to a single bout of treadmill running at a speed of 12 m/min with 10° inclination until exhaustion, and sacrificed immediately, 24 h and 48 h after exercise. Both immunohistochemistry and double immunofluorescence staining revealed that AQP3 is expressed at the cell surface with no evidence of colocalization with either AQP1 or AQP4 in hamstring skeletal muscles. When exposed to a single bout of exhaustive exercise, AQP3 knockout mice fatigued more easily with the average time to exhaustion shorter than the wild-type mice. After exhausting exercise, plasma glucose, muscle glycogen, muscle triglyceride, and muscle free fatty acid levels decreased compared with the values before exercise in both AQP3 knockout and wild-type mice. However, muscle glycerol concentration after exercise decreased in the wild-type mice, but rather increased in AQP3 knockout mice. These findings suggest that decreased glycerol efflux from the skeletal muscles in AQP3 knockout mice may result in low exercise capacity, presumably due to the limitations in the constant energy supply through hepatic gluconeogenesis from glycerol during the prolonged endurance exercise.

Prognostic impact of preoperative statin use after radical nephroureterectomy for upper urinary tract urothelial carcinoma.

PURPOSE: The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC. CONCLUSIONS: Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC.

Comparison of perioperative outcomes between running versus interrupted vesicourethral anastomosis in open radical prostatectomy: A single-surgeon experience.

PURPOSE: To compare perioperative outcomes between running and interrupted vesicourethral anastomosis in open radical prostatectomy (RP). MATERIALS AND METHODS: The medical records of 112 patients who underwent open RP for prostate cancer at our institution from 2006 to 2008 by a single surgeon were retrospectively reviewed. Preoperative, intraoperative, and postoperative parameters were measured. RESULTS: Of 112 consecutive patients, 62 patients underwent vesicourethral anastomosis by use of the running technique, whereas 50 patients underwent anastomosis with the interrupted technique. The groups did not differ significantly in age, body mass index, prostate-specific antigen, prostate volume, or pathologic findings. The intraoperative extravasation rate was significantly lower in the running group (8.1% vs. 24.0%, p=0.01). The mean anastomosis time was 15.1±5.3 and 19.3±4.6 minutes in the running and interrupted groups, respectively (p=0.04). The rates of postoperative extravasation were similar for both groups (6.4% vs. 10.0%, p=0.12). The duration of catheterization was significantly shorter in the running group (9.0±3.0 days vs. 12.9±6.4 days, p<0.01). The rate of urinary retention after catheter removal and the rate of bladder neck contracture were not significantly different between the two groups. The rate of urinary continence at 3, 6, 9, and 12 months after RP was also similar in both groups. CONCLUSIONS: Both anastomosis techniques provided similar functional results and a similar rate of postoperative urine extravasation. However, running vesicourethral anastomosis decreased the rate of intraoperative extravasation and time for anastomosis, without increasing the risk of urinary retention or bladder neck contracture.

A novel simple one-step air jet spinning approach for deposition of poly(vinyl acetate)/hydroxyapatite composite nanofibers on Ti implants.

A biocompatible coating consists of a poly(vinyl acetate)/hydroxyapatite (PVAc/HA) composite nanofiber mat was applied to NaOH-treated titanium metal by means of a novel, facile and efficient air jet spinning (AJS) approach. Results showed that HA nanoparticles (NPs) strongly embedded onto the AJS single fiber surface resulting in a strong chemical interfacial bonding between the two phases due to the difference in kinetic energies. It was proven that AJS membrane coatings can provide significant improvement in the corrosion resistance of titanium substrate. Interestingly, the biocompatibility using MC3T3-E1 osteoblast to the PVAc/HA fiber composite layer coated on Ti was significantly higher than pure titanium-substrates.

Effect of Gleason scores of lymph node metastases on prognosis of patients with prostate cancer.

The long-term mortality risk from prostate cancer increases in lymph node (LN) positive patients. This study was done to assess the effect of lymph node Gleason score (LNGS) on prognosis in patients with LN-positive prostate cancer. Among the 1,415 patients who received pelvic lymph node dissection (PLND), 117 (8.4%) patients had a positive LN. The PGS of the prostate specimens and the LNGS of the positive LNs were assessed by uropathologists. The median age of patients at surgery was 67 years (interquartile range [IQR], 62-71 years) and the median follow-up duration was 44.3 months (IQR, 27.0-78.5 months). Pathologic Gleason scores (PGS) of 6-9 included one (0.9%), 53 (49.5%), 22 (20.6%), and 31 (29.0%) patients. The median total number of retrieved LNs was 9.0 (IQR, 5.3-12.8). The median number of positive LNs was one (IQR, 1-2). Cancer architecture with a Gleason pattern and score were observed in LNs as in ordinary prostate specimens. LNGS 6-9 included nine (8.1%), 57 (51.4%), 31 (27.9%), and 14 (12.6%) patients. The speaman's analysis showed the meaningful correlation between PGS and LNGS (P = 0.249, P = 0.011). The univariate analysis showed that the number of positive LNs and LNGS were significantly associated with prostate cancer-specific survival (P = 0.028; P = 0.005). The same architecture that is seen in the prostate was seen in positive LNs, and LNGS may be a significant prognostic factor in patients with LN-positive prostate cancer.

Prognosis of prostate cancer with other primary malignancies.

PURPOSE: The objective was to investigate the clinicopathological characteristics and the prognosis of prostate cancer patients affected by other primary malignancies. MATERIALS AND METHODS: From 1990 to 2008, we retrospectively reviewed the medical records of 1,317 patients who underwent radical prostatectomy (RP) for prostate cancer. We assessed the effect of other primary malignancies on clinicopathological features, biochemical recurrence (BCR)-free survival, cancer-specific survival (CSS), and overall survival (OS). RESULTS: Of 1,317 patients, at least one additional other primary malignancy was detected in 187 patients (14.2%). A comparison of patient groups according to the presence or absence of other primary malignancies showed no significant differences in preoperative serum prostate-specific antigen concentrations, pathological Gleason scores, or pathological staging. Prostate cancer patients with other primary malignancies were older than patients without other primary malignancies (p<0.001). No significant differences in 5-year BCR-free survival (80.2% compared with 77.7%; p=0.656) or CSS (98.9% compared with 98.5%; p=0.733) were found between these groups, respectively. Five-year OS was significantly lower in prostate cancer patients with than in those without other primary malignancies (89.3% compared with 95.4%; p<0.001). Multivariate analysis showed that other primary malignancies diagnosed after RP for prostate cancer were independent predictors of OS (hazard ratio, 4.10; p<0.001) but not of BCR-free survival or CSS. Conversely, other primary malignancies diagnosed before RP for prostate cancer did not independently predict BCR-free survival, OS, or CSS. CONCLUSIONS: Prostate cancer prognosis after RP is not dependent on the presence or absence of other primary malignancies. However, other primary malignancies diagnosed after RP for prostate cancer negatively affect OS.

Impact of tamsulosin on urinary retention following early catheter removal after robot-assisted laparoscopic radical prostatectomy: a prospective randomized controlled trial.

OBJECTIVES: To examine the impact of tamsulosin on the rate of acute urinary retention following early catheter removal after robot-assisted laparoscopic radical prostatectomy. METHODS: A total of 236 patients who underwent robot-assisted laparoscopic radical prostatectomy for prostate cancer carried out by a single surgeon were enrolled in this randomized study. Patients were randomly divided into two groups: treatment with tamsulosin (0.4 mg) from 1 day before to 14 days after surgery (tamsulosin group), or no tamsulosin treatment (control group). The urethral catheter was removed on the fifth postoperative day. The primary end-point was the acute urinary retention rate. Changes in each domain of the International Continence Society male short-form questionnaire and uroflowmetry parameters were secondary end-points. RESULTS: The primary end-point was assessed in 218 patients (92.4%; n = 109 in each group). It was not assessed in 18 patients because of cystographic leak from the vesicourethral anastomosis. The acute urinary retention rate was lower in the tamsulosin group (7.3%) than in the control group (17.4%, P = 0.018). Multivariate logistic regression analysis identified tamsulosin treatment and the operative experience of the surgeon as independent risk factors for acute urinary retention. Tamsulosin-treated patients had a 0.30-fold lower risk of developing acute urinary retention compared with control patients (95% confidence interval 0.12-0.76; P = 0.011). None of the International Continence Society male questionnaire domain scores showed significant changes between the groups. CONCLUSIONS: Perioperative treatment with tamsulosin in patients undergoing robot-assisted laparoscopic radical prostatectomy reduces the rate of acute urinary retention after early catheter removal, without aggravating urinary incontinence.

Nomogram using transrectal ultrasound-derived information predicting the detection of high grade prostate cancer on initial biopsy.

PURPOSE: To develop a nomogram using transrectal ultrasound (TRUS)-derived information for predicting high grade (HG) prostate cancer (PCa) on initial biopsy. METHODS: Data were collected on 1,048 men with serum prostate-specific antigen (PSA) levels 4.0 to 9.9 ng/mL who underwent an initial prostate biopsy. Two logistic regression-based nomograms were constructed to predict the detection of PCa. Nomogram-1 incorporated age, digital rectal examination, PSA and percent free PSA data, whereas nomogram-2 incorporated those factors plus TRUS-derived information (i.e., prostate volume and the presence of hypoechoic lesions). The prediction of any PCa and HGPCa (Gleason score≥7) were determined. Twenty percent of the data were randomly reserved for study validation, and the predictive accuracies of the two nomograms were directly compared. RESULTS: Of the 1,048 men who underwent biopsy, 216 (20.6%) were found to have any PCa, and 97 (9.3%) were found to have HGPCa. All six risk factors were found to be independent predictors for both any PCa and HGPCa. The area under curve (AUC) for nomogram-2 was 0.76 (95% confidence interval [CI], 0.72 to 0.81) for predicting any PCa, and 0.83 (95% CI, 0.79 to 0.88) for predicting HGPCa. These AUCs were greater than those for nomogram-1 (0.72 [95% CI, 0.68 to 0.76 for any PCa; P<0.001], 0.78 [95% CI, 0.72 to 0.83 for HGPCa; P<0.001]). Removing the TRUS-derived information from nomogram-2 resulted in an incremental AUC decrease of 0.052 for any PCa and 0.063 for HGPCa. CONCLUSIONS: The nomogram using TRUS-derived information had a high predictive accuracy for HGPCa on initial prostate biopsy.

External validation of the cancer of the prostate risk assessment-s score in koreans undergoing radical prostatectomy.

PURPOSE: To evaluate the validity of the University of California San Francisco Cancer of the Prostate Risk Assessment-S score (CAPRA-S score), a biochemical indicator of recurrent prostate cancer that uses histopathologic data, in Korean prostate cancer patients. MATERIALS AND METHODS: A total of 203 prostate cancer patients who underwent radical prostatectomy between February 1997 and November 2010 were observed for longer than 6 months. The CAPRA-S score of 134 patients for whom records were available for preoperative prostate-specific antigen (PSA), pathologic specimen Gleason score, surgical margin, seminal vesicle invasion, extracapsular extension, and lymph node invasion were calculated. Biochemical recurrence was defined as repetitive measurement of PSA ≥0.2 ng/mL at least 6 months after surgery with at least a 4-week interval. The Cox proportional hazard model and Kaplan-Meier analysis were used for the statistical testing. RESULTS: The CAPRA-S scores were divided into nine groups. The 5-year disease-free survival rate was reduced as the CAPRA-S score increased compared with the group with a CAPRA-S score of 0-1. The CAPRA-S score in this study was more sensitive to biochemical recurrence than was the CAPRA score conducted at this institution (CAPRA-S concordance index, 0.776; CAPRA concordance index, 0.728). CONCLUSIONS: The CAPRA-S score is judged to be a useful tool for predicting the disease-free survival rate of Korean prostate cancer patients and is thought to assist in establishing postoperative management.

Incremental value of magnetic resonance imaging for clinically high risk prostate cancer in 922 radical prostatectomies.

PURPOSE: We investigated the incremental value of magnetic resonance imaging in addition to clinical variables for predicting pathological outcomes and disease recurrence in patients with clinically high risk prostate cancer. MATERIALS AND METHODS: A total of 922 consecutive patients with clinically high risk prostate cancer underwent magnetic resonance imaging before radical prostatectomy. We created multivariate logistic regression and Cox proportional hazards models with clinical variables only or combined with magnetic resonance imaging data to predict pathological outcomes and biochemical recurrence. The models were compared using ROC curves and the Harrell concordance index. RESULTS: The proportion of patients with pathological extracapsular extension, seminal vesicle invasion and lymph node metastasis was 57.5%, 12.7% and 6.3%, respectively. The sensitivity and specificity of extracapsular extension, seminal vesicle invasion and lymph node metastasis detection were 43% and 84.2%, 34.9% and 93.8%, and 14.0% and 96.9%, respectively. The area under the ROC curve of the model with clinical variable and magnetic resonance imaging data was greater than that of the model with clinical variables alone to predict extracapsular extension and seminal vesicle invasion (0.734 vs 0.697, p=0.001 and 0.750 vs 0.698, p<0.001, respectively). The 5-year biochemical recurrence-free survival rate was 56.1%. To predict biochemical recurrence the concordance index of the multivariate model with clinical variables only and with clinical variables plus magnetic resonance imaging data was 0.563 and 0.599, respectively (p=0.003). CONCLUSIONS: Magnetic resonance imaging findings have incremental value in addition to clinical variables for predicting pathological outcomes and disease recurrence.

Time-dependent expression patterns of cardiac aquaporins following myocardial infarction.

Aquaporins (AQPs) are expressed in myocardium and the implication of AQPs in myocardial water balance has been suggested. We investigated the expression patterns of AQP subtypes in normal myocardium and their changes in the process of edema formation and cardiac dysfunction following myocardial infarction (MI). Immunostaining demonstrated abundant expression of AQP1, AQP4, and AQP6 in normal mouse heart; AQP1 in blood vessels and cardiac myocytes, AQP4 exclusively on the intercalated discs between cardiac myocytes and AQP6 inside the myocytes. However, neither AQP7 nor AQP9 proteins were expressed in CD1 mouse myocardium. Echocardiography revealed that cardiac function was reduced at 1 week and recovered at 4 weeks after MI, whereas myocardial water content determined by wet-to-dry weight ratio increased at 1 week and rather reduced below the normal at 4 weeks. The expression of cardiac AQPs was up-regulated in MI-induced groups compared with sham-operated control group, but their time-dependent patterns were different. The time course of AQP4 expression coincided with that of myocardial edema and cardiac dysfunction following MI. However, expression of both AQP1 and AQP6 increased persistently up to 4 weeks. Our findings suggest a different role for cardiac AQPs in the formation and reabsorption of myocardial edema after MI.

Cystoscopic injection of N-butyl-2-cyanoacrylate followed by fibrin glue for the treatment of persistent or massive vesicourethral anastomotic urine leak after radical prostatectomy.

OBJECTIVES: Vesicourethral anastomotic urine leak is a common postoperative complication of radical prostatectomy. Herein we describe a novel method for the treatment of this complication. METHODS: Intervention for a prolonged or massive anastomotic urine leak was required in 10 out of 1828 patients (0.5%) submitted to radical prostatectomy between 2007 and 2011. N-butyl-2-cyanoacrylate (Histoacryl) followed by fibrin glue (Greenplast) were injected under local anesthesia into vesicourethral anastomotic gaps under fluoroscopic guidance using a 20-Fr rigid cystoscope. Cystograms were taken in all patients to confirm complete urine leak resolution before the removal of the urethral catheter. RESULTS: Cystoscopic injection of Histoacryl followed by fibrin glue was technically successful and well tolerated in all patients. The mean time from radical prostatectomy to glue injection was 16.0 days (range 12-27 days). Urethral catheterization was required for an average of 7.7 days after cystoscopic injection of fibrin glue (range 3-13 days). These measures ultimately enabled complete resolution of the urine leak in all cases. At a mean follow up of 23.3 months, all 10 patients were fully continent. The mean time to recovery of urinary continence was 20.4 weeks (range 3.9-60.0 weeks). CONCLUSIONS: Cystoscopic injection of N-butyl-2-cyanoacrylate followed by fibrin glue into the anastomotic gap is both a feasible and effective solution in patients with a persistent or massive vesicourethral anastomotic urine leak after radical prostatectomy.

Clinical experience with limited lymph node dissection for prostate cancer in Korea: single center comparison of 247 open and 354 robot-assisted laparoscopic radical prostatectomy series.

PURPOSE: There are limited data on the role of limited pelvic lymph node dissection (PLND) in patients with prostate cancer in Korea. The objective of this study was to demonstrate our clinical experience with limited PLND and the difference in its yield between open retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer patients in Korea. MATERIALS AND METHODS: We retrospectively analyzed 601 consecutive patients undergoing radical prostatectomy and bilateral limited PLND by either RRP (n=247) or RALP (n=354) in Asan Medical Center. All patients were divided into three groups according to the D'Amico's risk stratification method. Clinicopathologic data, including the yield of lymph nodes, were thoroughly reviewed and compared among the three risk groups or between the RRP and RALP subjects. RESULTS: The mean patient age was 64.9 years and the mean preoperative prostate-specific antigen was 9.8 ng/ml. The median number of removed lymph nodes per patient was 5 (range, 0 to 20). The numbers of patients of each risk group were 167, 199, and 238, and the numbers of patients with tumor-positive lymph nodes were 1 (0.6%), 4 (2.0%), and 17 (7.1%) in the low-, intermediate-, and high-risk groups, respectively. In the high-risk group, the lymph node-positive ratio was higher in RRP (14.9%) than in RALP subjects (2.4%). CONCLUSIONS: We speculate that limited PLND may help in prostate cancer staging in intermediate- and high-risk prostate cancer groups. RRP is a more effective surgical modality for PLND than is RALP, especially in high-risk prostate cancer groups.

Changes in Prostate Cancer Aggressiveness over a 12-Year Period in Korea.

PURPOSE: To investigate whether tumor aggressiveness in patients with prostate cancer has changed in Korea since the introduction of prostate-specific antigen (PSA) testing. MATERIALS AND METHODS: The data from 2,508 patients with pathologically confirmed prostate cancer who underwent radical prostatectomy at Asan Medical Center between 2000 and 2011 were reviewed. The patients were divided into four 3-year time series, and the changes between the groups in terms of serum PSA levels, pathological Gleason score (GS), and pathological stage were assessed. The change in GS over time in organ-confined disease and in patients whose PSA was below 10 ng/ml was also analyzed. RESULTS: The mean PSA levels dropped significantly over the 12-year period (p<0.001). The frequency of organ-confined disease increased (55.7% vs. 64.7% vs. 62.9% vs. 63.5%, p=0.043). The frequency of patients with a GS of 8 or more decreased (38.9% vs. 25.7% vs. 18.2% vs. 19.7%) and the frequency of patients with a GS of 6 or less increased (15.0% vs. 18.9% vs. 26.7% vs. 18.2%, p=0.003). However, the vast majority (more than 70%) of all cases had a high GS (7 or greater) at all time points. The GS distribution did not change over time in patients whose PSA levels were below 10 ng/ml or in those who had organ-confined disease. CONCLUSIONS: In 2000 to 2011, the preoperative PSA, pathological stage, and pathological GS dropped. However, the majority of the prostate cancers in Korean men were poorly differentiated, even when the patients had organ-confined disease or their PSA levels were less than 10 ng/ml.

Preferential effects of leptin on CD4 T cells in central and peripheral immune system are critically linked to the expression of leptin receptor.

Leptin can enhance thymopoiesis and modulate the T-cell immune response. However, it remains controversial whether these effects correlate with the expression of leptin receptor, ObR. We herein addressed this issue by using in vivo animal models and in vitro culture systems. Leptin treatment in both ob/ob mice and normal young mice induced increases of CD4 SP thymocytes in thymus and CD4 T cells in the periphery. Interestingly, expression of the long form ObR was significantly restricted to DN, DP and CD4 SP, but not CD8 SP thymocytes. Moreover, in the reaggregated DP thymocyte cultures with leptin plus TSCs, leptin profoundly induced differentiation of CD4 SP but not CD8 SP thymocytes, suggesting that the effects of leptin on thymocyte differentiation might be closely related to the expression of leptin receptor in developing thymocytes. Surprisingly, ObR expression was markedly higher in peripheral CD4 T cells than that in CD8 T cells. Furthermore, leptin treatment with or without IL-2 and PHA had preferential effects on cell proliferation of CD4 T cells compared to that of CD8 T cells. Collectively, these data provide evidence that the effects of leptin on differentiation and proliferation of CD4 T cells might be closely related to the expression of leptin receptor.