TNM-Based Head-to-Head Comparison of Urachal Carcinoma and Urothelial Bladder Cancer: Stage-Matched Analysis of a Large Multicenter National Cohort / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Outcome analysis of urachal cancer (UraC) is limited due to the scarcity of cases and different staging methods compared to urothelial bladder cancer (UroBC). We attempted to assess survival outcomes of UraC and compare to UroBC after stage-matched analyses. @*Materials and Methods@#Total 203 UraC patients from a multicenter database and 373 UroBC patients in single institution from 2000 to 2018 were enrolled (median follow-up, 32 months). Sheldon stage conversion to corresponding TNM staging for UraC was conducted for head-to-head comparison to UroBC. Perioperative clinical variables and pathological results were recorded. Stage-matched analyses for survival by stage were conducted. @*Results@#UraC patients were younger (mean age, 54 vs. 67 years; p < 0.001), with 163 patients (80.3%) receiving partial cystectomy and 23 patients (11.3%) radical cystectomy. UraC was more likely to harbor ≥ pT3a tumors (78.8% vs. 41.8%). While 5-year recurrence-free survival, cancer-specific survival (CSS) and overall survival were comparable between two groups (63.4%, 67%, and 62.1% in UraC and 61.5%, 75.9%, and 67.8% in UroBC, respectively), generally favorable prognosis for UraC in lower stages (pT1-2) but unfavorable outcomes in higher stages (pT4) compared to UroBC was observed, although only 5-year CSS in ≥ pT4 showed statistical significance (p=0.028). Body mass index (hazard ratio [HR], 0.929), diabetes mellitus (HR, 1.921), pathologic T category (HR, 3.846), and lymphovascular invasion (HR, 1.993) were predictors of CSS for all patients. @*Conclusion@#Despite differing histology, UraC has comparable prognosis to UroBC with relatively favorable outcome in low stages but worse prognosis in higher stages. The presented system may be useful for future grading and risk stratification of UraC.

Expression of neurotransmitter receptors in oral keratinocytes and their response to agonists

This study aimed to investigate whether neurotransmitter receptors in the nervous system were also expressed in oral keratinocytes. Expressions of various neurotransmitter receptor genes in immortalized mouse oral keratinocyte (IMOK) cells were examined by reverse transcriptase polymerase chain reaction. IMOK cells expressed calcitonin gene-related peptide (CGRP) receptor subunit genes Ramp1 and Ramp3 and glutamate receptor subunit genes Grina , Gria3 , Grin1 , Grin2a , and Grin2d . Moreover, IMOK cells expressed Adrb2 and Chrna5 that encode beta 2 adrenergic receptor and cholinergic receptor nicotinic alpha 5 for sympathetic and parasympathetic neurotransmitters, respectively. The expression of Bdkrb1 and Ptger4 , which encode receptors for bradykinin and prostaglandin E2 involved in inflammatory responses, was also observed at low levels. Expressions of Ramp1 and Grina in the mouse gingival epithelium were also confirmed by immunohistochemistry. When the function of neurotransmitter receptors expressed on IMOK cells was tested by intracellular calcium response, CGRP, glutamate, and cholinergic receptors did not respond to their agonists, but the bradykinin receptor responded to bradykinin. Collectively, oral keratinocytes express several neurotransmitter receptors, suggesting the potential regulation of oral epithelial homeostasis by the nervous system.

Expression of neurotransmitter receptors in oral keratinocytes and their response to agonists

This study aimed to investigate whether neurotransmitter receptors in the nervous system were also expressed in oral keratinocytes. Expressions of various neurotransmitter receptor genes in immortalized mouse oral keratinocyte (IMOK) cells were examined by reverse transcriptase polymerase chain reaction. IMOK cells expressed calcitonin gene-related peptide (CGRP) receptor subunit genes Ramp1 and Ramp3 and glutamate receptor subunit genes Grina , Gria3 , Grin1 , Grin2a , and Grin2d . Moreover, IMOK cells expressed Adrb2 and Chrna5 that encode beta 2 adrenergic receptor and cholinergic receptor nicotinic alpha 5 for sympathetic and parasympathetic neurotransmitters, respectively. The expression of Bdkrb1 and Ptger4 , which encode receptors for bradykinin and prostaglandin E2 involved in inflammatory responses, was also observed at low levels. Expressions of Ramp1 and Grina in the mouse gingival epithelium were also confirmed by immunohistochemistry. When the function of neurotransmitter receptors expressed on IMOK cells was tested by intracellular calcium response, CGRP, glutamate, and cholinergic receptors did not respond to their agonists, but the bradykinin receptor responded to bradykinin. Collectively, oral keratinocytes express several neurotransmitter receptors, suggesting the potential regulation of oral epithelial homeostasis by the nervous system.

The Effects of Recombinant Bacillus Calmette-Guérin Resistant to Antimicrobial Peptides on Orthotopic Bladder Cancer Mouse Model

Purpose@#Although Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure. Here, we developed genetically modified recombinant BCG (rBCG) strains which escape AMPs and evaluate the efficacy and effects of rBCG. @*Materials and Methods@#We constructed rBCG strains expressing Streptococcal inhibitor of complement (Sic), which confers resistance to human α-defensin-1 and cathelicidin, and d-alanyl carrier protein ligase (dltA), which confers resistance to cationic AMPs. Sic and dltA were separately cloned into the pMV306 plasmid and introduced into BCG via electroporation. The efficacy of the Sic and dltA gene electroporation into BCG was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The internalization rates and anticancer effects of the rBCG strains containing Sic (rBCG-Sic) and dltA (rBCG-dltA) was evaluated by the orthotopic bladder cancer mouse model. @*Results@#The cycle quantification (Cq) values of rBCG-Sic (y=-4.8823x+13.645, R2=0.9996) and rBCG-dltA (y=-5.438x+11.641, R2=0.9995) were inverse correlations to the amount of Sic and dltA genes dose dependently. The mean introduction proportions of Sic and dltA genes into BCG by electroporation were 22.2%, 27.5% and showed constant efficacy. In the orthotopic bladder cancer mouse model, the relative internalization number of rBCG-Sic, and rBCG-dltA into bladder cell in mouse bladder were higher than that of BCG and the tumor volume at rBCG-Sic were lower than at BCG and rBCG-dltA at 11, 14 and 18 days. @*Conclusions@#Our results showed that constructed rBCG-Sic and rBCG-dltA by electroporation and the rBCG-Sic and rBCG-dltA can effectively escape BCG-stimulated AMPs, and significantly improved immunotherapeutic tools to treat bladder cancer in orthotopic bladder cancer mouse model.

Does intraoperative frozen section really predict significant positive surgical margins after robot-assisted laparoscopic prostatectomy? A retrospective study / 亚洲男科学杂志(英文版)

We investigated the relationship between positive surgical margin (PSM)-related factors and biochemical recurrence (BCR) and the ability of intraoperative frozen sections to predict significant PSM in patients with prostate cancer. The study included 271 patients who underwent robot-assisted laparoscopic prostatectomy with bilateral nerve sparing and maximal urethral preservation. Intraoperative frozen sections of the periurethra, dorsal vein, and bladder neck were analyzed. The ability of PSM-related factors to predict BCR and significant PSM was assessed by logistic regression. Of 271 patients, 108 (39.9%) had PSM and 163 (60.1%) had negative margins. Pathologic Gleason score ≥8 (18.9% vs 7.5%, P = 0.015) and T stage ≥T3a (51.9%vs 24.6%, P < 0.001) were significantly more frequent in the PSM group. Multivariate analysis showed that Gleason pattern ≥4 (vs <4; hazard ratio: 4.386; P = 0.0004) was the only significant predictor of BCR in the PSM cohort. Periurethral frozen sections had a sensitivity of 83.3% and a specificity of 84.2% in detecting PSM with Gleason pattern ≥4. Multivariate analysis showed that membranous urethra length (odds ratio [OR]: 0.79, P = 0.0376) and extracapsular extension of the apex (OR: 4.58, P = 0.0226) on magnetic resonance imaging (MRI) and positive periurethral tissue (OR: 17.85, P < 0.0001) were associated with PSM of the apex. PSM with Gleason pattern ≥4 is significantly predictive of BCR. Intraoperative frozen sections of periurethral tissue can independently predict PSM, whereas sections of the bladder neck and dorsal vein could not. Pathologic examination of these samples may help predict significant PSM in patients undergoing robot-assisted laparoscopic prostatectomy with preservation of functional outcomes.

Patient-Specific Tumor Microenvironment Models

The heterogeneity of cancer makes it difficult to predict the prognosis of treatment. There is still a lack of preclinical model systems that reflect the clinical characteristics of patients who have heterogenetic tumors. Advances in 3-dimentional (3D) cell culture are leading to discoveries that occur in the development and progression of cancer that has not been known. There are many models including patient-derived xenograft, patient-derived organoid and spheroid, patient-derived explant, scaffold-based model, and system-based model. Each 3D model has its strengths and limitations. One model cannot answer every question, so it seems most reasonable to approach multiple models when studying cancer heterogeneity. Hopefully, 3D tumor modeling will make tremendous progress on this path by fusion of innovative biomaterials and advanced modeling techniques that can partially mimic the heterogeneous environment of real tumors.

Construction of a Retrospective Cohort to Observe 10-Year Urologic Cancer Treatment Trends at the Biggest Medical Center of South Korea

Purpose@#To construct a urologic cancer database using a standardized, reproducible method, and to assess preliminary characteristics of this cohort. @*Materials and Methods@#Patients with prostate, bladder, and kidney cancers who were enrolled with diagnostic codes in the electronic medical record (EMR) at Asan Medical Center from 2007–2016 were included. Research Electronic Data Capture (REDCap) was used to design the Asan Medical Center-Urologic Cancer Database (AMC-UCD). The process included developing a data dictionary, applying branching logic, mapping clinical data warehouse structures, alpha testing, clinical record summary testing, creating “standards of procedure,” importing data, and entering data. Descriptive statistics were used to identify rates of surgeries and numbers of patients. @*Results@#Clinical variables (n=407) were selected to develop a data dictionary from REDCap. In total, 20,198 urologic cancer patients visited our institution from 2007–2016 (bladder cancer, 4,616; kidney cancer, 5,750; prostate cancer, 10,330). The overall numbers of patients and surgeries increased over time, with robotic surgeries rapidly growing over a decade. The most common treatment for urologic cancer was surgery, followed by chemotherapy and radiation therapy. @*Conclusions@#Using a standardized method, the AMC-UCD fosters multidisciplinary research. This constructed database provides access to clinical statistics to effectively assist research. Preliminary data should be refined through EMR chart review. The successful organization of data from 2007–2016 provides a framework for future periods of investigation and prospective models.

Malignant transformation of oral lichen planus and related genetic factors

Oral lichen planus (OLP) is a chronic inflammatory disease observed in approximately 0.5–2.2% of the population, and it is recognized as a premalignant lesion that can progress into oral squamous cell carcinoma (OSCC). The rate of malignant transformation is approximately 1.09–2.3%, and the risk factors for malignant transformation are age, female, erosive type, and tongue site location. Malignant transformation of OLP is likely related to the low frequency of apoptotic phenomena. Therefore, apoptosis-related genetic factors, like p53, BCL-2, and BAX are reviewed. Increased p53 expression and altered expression of BCL-2 and BAX were observed in OLP patients, and the malignant transformation rate in these patients was relatively higher. The involvement of microRNA (miRNA) in the malignant transformation of OLP is also reviewed. Because autophagy is involved in cell survival and death through the regulation of various cellular processes, autophagy-related genetic factors may function as factors for malignant transformation. In OLP, decreased levels of ATG9B mRNA and a higher expression of IGF1 were observed, suggesting a reduction in cell death and autophagic response. Activated IGF1-PI3K/AKT/mTor cascade may play an important role in a signaling pathway related to the malignant transformation of OLP to OSCC. Recent research has shown that miRNAs, such as miR-199 and miR-122, activate the cascade, increasing the prosurvival and proproliferative signals.

Melatonin inhibits nicotinic acetylcholine receptor functions in bovine chromaffin cells

Melatonin is a neurotransmitter that modulates various physiological phenomena including regulation and maintenance of the circadian rhythm. Nicotinic acetylcholine receptors (nAChRs) play an important role in oral functions including orofacial muscle contraction, salivary secretion, and tooth development. However, knowledge regarding physiological crosstalk between melatonin and nAChRs is limited. In the present study, the melatonin-mediated modulation of nAChR functions using bovine adrenal chromaffin cells, a representative model for the study of nAChRs, was investigated. Melatonin inhibited the nicotinic agonist dimethylphenylpiperazinium (DMPP) iodide-induced cytosolic free Ca²⁺ concentration ([Ca²⁺](i)) increase and norepinephrine secretion in a concentration-dependent manner. The inhibitory effect of melatonin on the DMPP-induced [Ca²⁺](i) increase was observed when the melatonin treatment was performed simultaneously with DMPP. The results indicate that melatonin inhibits nAChR functions in both peripheral and central nervous systems.

The Systematic Review of the Efficacy and Safety of Immune Checkpoint Inhibitor in Urological Cancers

To systematically review relevant literature on efficacy and safety of immune checkpoint inhibitors (ICIs) in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer. In platinum pretreated UCC, efficacy of pembrolizumab was superior to chemotherapy, with longer median overall survival (OS; 10.3 months vs. 7.4 months), a higher objective response rate (ORR; 21.1% vs. 11.4%, p=0.001), and a lower adverse event rate (60.9% vs. 90.2%). Three randomized controlled trials (RCTs) assessed the safety and efficacy of nivolumab in advanced RCC. The median OS (25.0 months vs. 19.6 months) and the ORR (25% vs. 5%) were higher in patients treated with nivolumab compared with second-line everolimus. In patients with metastatic castration-resistant prostate cancer, 2 RCTs were identified, which did not show significant benefits for ipilimumab over placebo. In UCC and RCC, there was no conclusive association between programmed cell death receptor ligand 1 (PD-L1) expression in tumor tissue and clinical outcome during pembrolizumab and nivolumab treatment, respectively. Therefore, in metastatic UCC and RCC, pembrolizumab and nivolumab have superior efficacy and safety to second-line chemotherapy and everolimus, respectively. No beneficial effect of ipilimumab was observed in prostate cancer patients. PD-L1 expression status is currently not suitable as a predictive marker for treatment outcome.

Comparison of Prognosis in Types 1 and 2 Papillary Renal Cell Carcinoma and Clear Cell Renal Cell Carcinoma in T1 Stage

PURPOSE: We compared subtypes of papillary renal cell carcinoma (pRCC; types 1 and 2) and clear cell renal cell carcinoma (ccRCC) in patients with T1-stage RCC to analyze the impact of the subtype on oncological outcomes. MATERIALS AND METHODS: This paper reviewed 75 patients with pRCC and 252 patients with ccRCC at T1-stage from 1998–2012. Thus, we assessed the impact of subtype on oncologic outcomes among patients with T1-stage RCC. We used Kaplan-Meier analysis to estimate the overall survival and recurrence-free survival The median follow-up duration was 95 months (interquartile range, 75.4–119.3 months). RESULTS: The 5-year recurrence-free survivals of pRCC and ccRCC were 95.4% and 97.6%, respectively. pRCC is worse than ccRCC in terms of recurrence-free survival (p=0.008) and there was no significant difference in the overall survival between pRCC and ccRCC (p=0.32). In addition, there was no significant statistical difference between type 1 pRCC and type 2 pRCC in terms of either recurrence-free survival (p=0.526) or overall survival (p=0.701). Age (hazard ratio [HR], 1.069; p < 0.001) and recurrence (HR, 4.93; p < 0.001) were predictors of overall survival. Only tumor size (HR, 1.071; p=0.004) was predictors in the case of cancer specific survival in the multivariate analysis. CONCLUSIONS: Among patients with T1-stage RCC, recurrence after surgery was more common in pRCC than ccRCC. The subtype of pRCC (types 1 and 2) had no impact on the recurrence-free survival or overall survival.

Impact of Histologic Variants of Bladder Cancer on Oncology Outcome After Radical Cystectomy

PURPOSE: To evaluate the oncological outcome of histologic variants in bladder cancer patients who underwent radical cystectomy. MATERIALS AND METHODS: We identified 393 bladder cancer patients who underwent radical cystectomy at single center between January 2007 and August 2014. Patients were divided into 4 groups according to histologic types: pure urothelial cell carcinoma (UC) and squamous, micropapillary, and other variants. Kaplan-Meier analysis was performed to assess recurrence-free (RFS) and overall survivals (OS). The patients were divided into those with pathologic stage and nodal status. RESULTS: Among 393 bladder cancer patients, squamous, micropapillary histologic variants were observed in 38 (9.7%), 26 (6.6%), respectively, whereas 39 had other variant types. Stage T3 cancer occurred in more patients with histologic variant compared with those with pure UC. Pathologic positive nodal status was also frequently found in the histologic variant groups. Subgroup analysis according to T stage and nodal status showed no significant difference in RFS and OS. On multivariate analysis, pathologic T stage (stage T2: hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.34–5.63; p=0.005; stage ≥T3: HR, 3.20; 95% CI, 1.62–6.30; p=0.001) and nodal status (HR, 1.85; 95% CI, 1.05–2.56; p=0.028) were prognostic factors for RFS. CONCLUSIONS: In patients who underwent radical cystectomy, histologic variants were detected more often at advanced pathologic stage. Although histologic variants have been identified in the radical cystectomy specimen, treatment should be performed according to the pathologic stage.

Daily Mean Temperature and Urolithiasis Presentation in Six Cities in Korea: Time-Series Analysis

Seasonal variation in urinary stone presentation is well described in the literature. However, previous studies have some limitations. To explore overall cumulative exposure-response and the heterogeneity in the relationships between daily meteorological factors and urolithiasis incidence in 6 major Korean cities, we analyzed data on 687,833 urolithiasis patients from 2009 to 2013 for 6 large cities in Korea: Seoul, Incheon, Daejeon, Gwangju, Daegu, and Busan. Using a time-series design and distributing lag nonlinear methods, we estimated the relative risk (RR) of mean daily urolithiasis incidence (MDUI) associated with mean daily meteorological factors, including the cumulative RR for a 20-day period. The estimated location-specific associations were then pooled using multivariate meta-regression models. A positive association was confirmed between MDUI and mean daily temperature (MDT), and a negative association was shown between MDUI and mean daily relative humidity (MDRH) in all cities. The lag effect was within 5 days. The multivariate Cochran Q test for heterogeneity at MDT was 12.35 (P = 0.136), and the related I2 statistic accounted for 35.2% of the variability. Additionally, the Cochran Q test for heterogeneity and I2 statistic at MDHR were 26.73 (P value = 0.148) and 24.7% of variability in the total group. Association was confirmed between daily temperature, relative humidity and urolithiasis incidence, and the differences in urolithiasis incidence might have been partially attributable to the different frequencies and the ranges in temperature and humidity between cities in Korea.

Urologic Diseases in Korean Military Population: a 6-year Epidemiological Review of Medical Records

We sought to describe the incidence rate of the urologic disease in the Korean military by reviewing diagnoses made in active duty soldiers from 2008 to 2013. A total of 72,248 first visits were generated in the Defense Medical Statistics Information System (DMSIS) with its gradually increasing trend over 6 years. A sharp increase of first visit was observed after implementation of the regular health check-up for all conscripted soldiers since 2013. Urolithiasis, prostatitis, epididymoorchitis, urethritis, and varicocele were prevalent. Prostatitis was the highest diagnosis made in the outpatient service, while varicocele was ranked the highest in the inpatient service. The incidence rates of urologic disease varied from 12.3 to 34.2 cases per 1,000 person-years. The urologic disease in conscripted men showed different distribution when we separated the population into conscripted and professional soldiers. Epididymoorchitis was the highest disease followed by urolithiasis, dysuresia, and balanoposthitis in 2013. This study underscores that the urologic disease has spent significant amount of health care resources in the Korean military. This calls for further study to find any significant difference and contributing factors of the urologic disease in the military and the civilian population.

The association of 5-alpha reductase type 2 (SRD5A2) gene polymorphisms with prostate cancer in a Korean population

PURPOSE: Steroid 5-alpha reductase type 2 (SRD5A2) modifies testosterone to dihydrotestosterone (DHT) in the prostate. Single-nucleotide polymorphisms (SNPs) of the SRD5A2 gene might affect DHT. We sought to understand the relationship of SRD5A2 SNPs to prostate cancer in the Korean population. MATERIALS AND METHODS: Twenty-six common SNPs in the SRD5A2 gene were assessed in 272 prostate cancer cases and 173 controls. Single-locus analyses were conducted by using conditional logistic regression. Additionally, we performed a haplotype analysis for the SRD5A2 SNPs tested. RESULTS: Among the 20 SNPs and 4 haplotypes, there were no statistically significant results in the prostate cancer patients and the controls. In the logistic analysis of SRD5A2 polymorphisms with prostate-specific antigen (PSA) criteria, two SNPs (rs508562, rs11675297) and haplotype 1 displayed significant results (odds ratio [OR], 1.76; p=0.05; OR, 1.88-2.02; p=0.01-0.04; OR, 0.59; p=0.02, respectively). rs508562, rs11675297, rs2208532, and haplotype 1 (OR, 1.49; p=0.05; OR, 2.02; p=0.05; OR, 2.01; p=0.04; OR, 0.56-0.64, p=0.03-0.04, respectively) had significant associations with Gleason score. rs508562, rs11675297, and haplotype 1 (OR, 1.41-2.34; p=0.004-0.05; OR, 1.74-1.82; p=0.03-0.05; OR, 0.42-0.67; p=0.0005-0.03, respectively) were significantly associated with clinical stage. CONCLUSIONS: We conclude that there was no significant association between SRD5A2 SNPs and the risk of prostate cancer in the Korean population. However, we found that some SNPs and 1 haplotype influenced PSA level, Gleason score, and clinical stage.

Predicting Recurrence and Progession of Non Muscle Invasive Urothelial Cell Carcinoma of Bladder by Clinical and Pathological Prognostic Factors

About 80% of Bladder cancer is non muscle invasive bladder cancer (NMIBC). Despite of appropriate therapy, a lot of NMIBC recur as a superficial tumor or progress to muscle invasive disease. Several studies about prognostic factors of recurrence and progression have reported a single risk factor variously according to each study. These efforts were developed to predict the risk by scoring system and large-scale studies had been conducted. These studies had limitations that their patients did not receive BCG (bacillus Calmette-Guerin) immunotherapy, immediate intravesical chemotherapy, second-look TUR (transurethral resection) in high-risk group. Through studies to date, patients with NMIBC have showed heterogenous prognosis and a more sophisticated scoring system can give personalized treatment and exact prediction.

Predicting Recurrence and Progression of Non-Muscle-Invasive Bladder Cancer in Korean Patients: A Comparison of the EORTC and CUETO Models

PURPOSE: This study aimed to confirm the utility of the European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) scoring systems and to determine which model is preferred as a prognostic model in Korean patients with non-muscle-invasive bladder cancer. MATERIALS AND METHODS: Between 1985 and 2011, 531 patients who were treated by transurethral resection of bladder cancer were retrospectively analyzed by use of the EORTC and CUETO models. Statistically, we performed Kaplan-Meier survival analysis; calculated Harrell's concordance index, receiver operating characteristic (ROC) curve, and cutoff values; and performed univariate and multivariate Cox proportional hazards regression analyses. RESULTS: For risk of recurrence, with the use of the EORTC model, all groups had statistically significant differences except between the group with a score of 0 and the group with a score of 1-4. With the use of the CUETO model, all groups differed significantly. For risk of progression, with the use of the EORTC model, significant differences were observed between all groups except between the group with a score of 2-6 and the group with a score of 7-13. With the use of the CUETO model, a significant difference was observed between the group with a score of 0 and the other groups. The concordance index of the EORTC and CUETO models was 0.759 and 0.836 for recurrence and 0.704 and 0.745 for progression, respectively. The area under the ROC curve for the EORTC and CUETO models was 0.832 and 0.894 for recurrence and 0.722 and 0.724 for progression, respectively. CONCLUSIONS: Both scoring systems, especially the CUETO model, showed value in predicting recurrence and progression in Korean patients, which will help in individualizing treatment and follow-up schedules.

Impact of Changing Trends in Medical Therapy on Surgery for Benign Prostatic Hyperplasia Over Two Decades

PURPOSE: Following the introduction of medical therapy for benign prostatic hyperplasia (BPH), we determined the effect of the change in trends in medical therapy on the indication and outcome of surgical intervention for BPH. MATERIALS AND METHODS: We compared the basic characteristics of, weight of resected tissue of, transfusions in, and postoperative complications of patients who underwent surgery between 1985 and 1989 (before the advent of medical therapy for BPH), between 1995 and 1999 (when medical therapy was developed and became widely used as alternative treatment), and between 2005 and 2009 (when medical therapy superseded surgical intervention to become first-line treatment and when combination therapy became widely adopted). RESULTS: At our institution, the mean age and BMI of patients increased over the past two decades (p<0.001). Hypertension, operation history, and other comorbidities also increased significantly (p<0.001, p=0.005, and p<0.001, respectively). The indications for surgery in 1985 to 1989, 1995 to 1999, and 2005 to 2009 were as follows: acute urinary retention in 34.7%, 20.2%, and 15.1% of patients and symptomatic deterioration in 61.1%, 72.3%, and 73.0% of patients, respectively. Prostate volume and the weight of resected tissue increased from 34.4+/-14.5 ml to 61.3+/-32.4 ml and from 7.2+/-6.4 g to 10.8+/-7.6 g, respectively, over two decades. Patients who underwent surgery in 2005 to 2009 had their catheters removed earlier (p<0.001). Secondary hemorrhage within four postoperative weeks and repeat transurethral resection of the prostate within 1 year decreased significantly (p=0.03 and p=0.003, respectively). No statistically significant change in impaired detrusor contractility was found (p=0.523). CONCLUSIONS: Although patients who underwent surgery were older after widespread use of medical therapy for BPH, advancements in surgical techniques have benefitted these patients.

Effects of Saccharin Intake on Hippocampal and Cortical Plasticity in Juvenile and Adolescent Rats

The sensory system is developed and optimized by experiences given in the early phase of life in association with other regions of the nervous system. To date, many studies have revealed that deprivation of specific sensory experiences can modify the structure and function of the central nervous system; however, the effects of sensory overload remains unclear. Here we studied the effect of overloading the taste sense in the early period of life on the synaptic plasticity of rat hippocampus and somatosensory cortex. We prepared male and female Sprague Dawley rats with ad libitum access to a 0.1% saccharin solution for 2 hrs per day for three weeks after weaning on postnatal day 22. Saccharin consumption was slightly increased in males compared with females; however, saccharin intake did not affect chow intake or weight gain either in male or in female rats. We examined the effect of saccharin-intake on long term potentiation (LTP) formation in hippocampal Schaffer collateral pathway and somatosensory cortex layer IV - II/III pathways in the 6-week old saccharin-fed rats. There was no significant difference in LTP formation in the hippocampus between the control group and saccharin-treated group in both male and female rats. Also in the somatosensory cortex, we did not see a significant difference in LTP among the groups. Therefore, we conclude that saccharin-intake during 3~6 weeks may not affect the development of physiological function of the cortical and hippocampal synapses in rats.

P2X7 Receptor-mediated Membrane Blebbing in Salivary Epithelial Cells

High concentrations of ATP induce membrane blebbing. However, the underlying mechanism involved in epithelial cells remains unclear. In this study, we investigated the role of the P2X7 receptor (P2X7R) in membrane blebbing using Par C5 cells. We stimulated the cells with 5 mM of ATP for 1~2 hrs and found the characteristics of membrane blebbing, a hallmark of apoptotic cell death. In addition, 500 micrometer Bz-ATP, a specific P2X7R agonist, induced membrane blebbing. However, 300 micrometer of Ox-ATP, a P2X7R antagonist, inhibited ATP-induced membrane blebbing, suggesting that ATP-induced membrane blebbing is mediated by P2X7R. We found that ATP-induced membrane blebbing was mediated by ROCK I activation and MLC phosphorylation, but not by caspase-3. Five mM of ATP evoked a biphasic [Ca2+]i response; a transient [Ca2+]i peak and sustained [Ca2+]i increase secondary to ATP-stimulated Ca2+ influx. These results suggest that P2X7R plays a role in membrane blebbing of the salivary gland epithelial cells.