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The clinical implications of postoperative detection of circulating tumor cells in prostate cancer are largely unknown. We investigated the association between postoperative circulating tumor cell detection after radical prostatectomy and disease recurrence in prospectively enrolled patients with prostate cancer.A total of 203 patients with an undetectable prostate specific antigen who had undergone radical prostatectomy for prostate cancer were prospectively enrolled. Circulating tumor cell sampling was performed at a median of 4.5 months after surgery. The primary end point was biochemical recurrence-free survival. Detection of circulating tumor cells in the blood of patients was performed using a novel approach with a replication-competent adenovirus controlled by prostate specific antigen/prostate specific membrane antigen transcription regulatory elements (Ad5/35E1aPSESE4).Circulating tumor cells were detected in 73 (36.0%) patients with undetectable prostate specific antigen concentrations after surgery. The 3-year biochemical recurrence-free survival rate from the time of surgery was significantly higher in circulating tumor cell-negative than in circulating tumor cell-positive cases (81.6% vs 48.9%, log rank p0.001). Multivariable analysis showed that postoperative circulating tumor cell detection was independently associated with an increased risk of biochemical recurrence (HR 5.42, 95% CI 3.24-9.06, p0.001). C-index was increased in combinations of multivariable model and postoperative circulating tumor cell detection compared with the multivariable model alone.Circulating tumor cells in the blood were frequently detected in patients with undetectable prostate specific antigen levels after radical prostatectomy for localized prostate cancer. Furthermore, circulating tumor cell detection was associated with an increased risk of biochemical recurrence, suggesting that circulating tumor cell detection precedes prostate specific antigen rise after surgery in cases of prostate cancer recurrence. Large-scale validation is needed in the future.

The formation of hyperphosphorylated intracellular Tau tangles in the brain is a hallmark of Alzheimer's disease (AD). Tau hyperphosphorylation destabilizes microtubules, promoting neurodegeneration in AD patients. To identify suppressors of tau-mediated AD, we perform a screen using a microRNA (miR) library in Drosophila and identify the miR-9 family as suppressors of human tau overexpression phenotypes. CG11070, a miR-9a target gene, and its mammalian orthologue UBE4B, an E3/E4 ubiquitin ligase, alleviate eye neurodegeneration, synaptic bouton defects, and crawling phenotypes in Drosophila human tau overexpression models. Total and phosphorylated Tau levels also decrease upon CG11070 or UBE4B overexpression. In mammalian neuroblastoma cells, overexpression of UBE4B and STUB1, which encodes the E3 ligase CHIP, increases the ubiquitination and degradation of Tau. In the Tau-BiFC mouse model, UBE4B and STUB1 overexpression also increase oligomeric Tau degradation. Inhibitor assays of the autophagy and proteasome systems reveal that the autophagy-lysosome system is the major pathway for Tau degradation in this context. These results demonstrate that UBE4B, a miR-9 target gene, promotes autophagy-mediated Tau degradation together with STUB1, and is thus an innovative therapeutic approach for AD.

To investigate and compare surgical outcomes in totally tubeless percutaneous nephrolithotomy (ttPCNL) patients according to the type of sealant during nephrostomy tract closure, the records of 158 patients who underwent ttPCNL were retrospectively reviewed. Fibrin sealant [Tisseel®; n = 107, fibrin-only sealant (FS)] or gelatin matrix hemostatic sealant [FloSeal®; n = 51, gelatin matrix sealant (GS)] was applied during tract closure according to surgeon’s preference. On the first postoperative day, computed tomography (CT) was scanned for all patients. Unsatisfactory radiological outcome (URO) was defined as any postoperative hematoma or urinoma (≥ 2 cm) on the CT. Unsatisfactory clinical outcome (UCO) was defined as any adverse event requiring additional intervention. Both UROs and UCOs were sub-classified as either hemorrhage or drainage related. 2:1 propensity score matching was applied according to clinical parameters. Median age was 58 (19–78) years and a mean stone size was 2.1 ± 1.1 cm. The treatment success rate (stone free or

// Yoon Seok Suh 1, * , Jae Young Joung 1, * , Sung Han Kim 1 , Jeong Eun Kim 1 , Moon Kyung Choi 2 , Weon Seo Park 2 , Sang-Jin Lee 3 , Ho Kyung Seo 1 , Jinsoo Chung 1 and Kang Hyun Lee 1 1 Department of Urology, Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Korea 2 Department of Pathology, Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Korea 3 Immunotherapeutics Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Korea * These authors contributed equally to this work Correspondence to: Kang Hyun Lee, email: uroonco@ncc.re.kr Keywords: prostate stem cell antigen; prostate cancer; biochemical recurrence; survival Received: September 04, 2017 Accepted: March 13, 2018 Published: May 29, 2018 ABSTRACT Objectives: To investigate whether the preoperative detection of prostate stem cell antigen (PSCA) mRNA in blood has predictive value for biochemical recurrence, overall survival, and cancer-specific survival after radical prostatectomy in patients with high-risk prostate cancer. Results: Median age was 67 years (interquartile range: 63-71), and median follow-up was 41 months (interquartile range: 25–65). PSCA mRNA was detected in 151 patients (51.1%). Biochemical recurrence was developed in 101 patients (34.2%), and all-cause mortality and prostate cancer-specific mortality occurred in 17 (5.7%) and 8 (2.7%) patients, respectively. Kaplan–Meier analysis revealed significant differences in biochemical recurrence, overall survival, and cancer-specific survival according to PSCA mRNA positivity. Cox regression hazards model analysis showed that PSCA mRNA positivity was an independent predictor of biochemical recurrence, overall survival, and cancer-specific survival. Conclusions: PSCA mRNA in the peripheral blood was related to poor prognosis. Detection of PSCA mRNA by polymerase chain reaction in peripheral blood can be used to predict survival after radical prostatectomy in patients with high-risk prostate cancer. Future study with larger cohort and long-term follow-up is required to confirm this finding. Materials and methods: A total of 295 patients with high-risk prostate cancer scheduled to undergo radical prostatectomy were prospectively enrolled from 2008 to 2016. Nested reverse transcription polymerase chain reaction was used to detect cells with PSCA mRNA in peripheral blood. The predicting ability of PSCA mRNA positivity for biochemical recurrence, overall survival, and cancer-specific survival after radical prostatectomy was evaluated.

OBJECTIVE To investigate the efficacy of endoscopic ablation of Hunner lesions (HLs) in patients with interstitial cystitis (IC) and to find predictors of early recurrence of HLs. PATIENTS AND METHODS A prospective study was performed of patients with Hunner type IC who underwent transurethral ablation. We repeated endoscopic ablation when symptoms and HLs recurred during the follow-up period. The primary endpoint was recurrence-free time. Secondary endpoints were a change in frequency, nocturia, and urgency episodes, and changes in visual analogue scale (VAS) pain scores and other symptom indices at follow-up visits. RESULTS A total of 72 patients were analysed. The median (range) follow-up period was 29.5 (12.0-50.0) months. After primary ablation treatment, HLs recurred in 75.0% (54/72) of patients, and the median (sd) recurrence-free time was 12.0 (1.6) months. Amongst the 54 patients with recurrence, 50 underwent a second ablation treatment. HLs occurred in 44.0% (22/50) of individuals after the second operation, and the median (sd) recurrence-free time was 18.0 (5.1) months. Lower maximal cystometric capacity (odds ratio 1.01, 95% confidence interval 1.001-1.013) was the predictive factor for early recurrence. There were significant improvements in the VAS pain scores, O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index, Pelvic Pain and Urgency/Frequency Patient Symptom Scale after treatment (all, P < 0.05). CONCLUSIONS Endoscopic ablation is an effective treatment option for HLs and significantly reduces pain and improves voiding symptoms. Repeat ablation upon recurrence could help symptom control and bladder preservation only if the bladder capacity is maintained.

Purpose The aim of this study was to investigate urinary nerve growth factor (NGF) as a biomarker of treatment efficacy and recurrence in overactive bladder (OAB) patients. Methods We enrolled 189 OAB subjects who visited our outpatient clinic from February 2010 to February 2015. All subjects with OAB received antimuscarinic treatment. A 3-day voiding diary and questionnaire were collected from each patient. Urinary levels of NGF were evaluated at baseline, the beginning of antimuscarinic treatment, and the end of antimuscarinic treatment. Urinary NGF was normalized to urine creatinine (Cr). Between-group comparisons of baseline characteristics were made using the Mann-Whitney U-test. Multivariate logistic regression analyses were used to predict responses to anticholinergic treatment and recurrence. The Wilcoxon signed-rank test with the Bonferroni correction was used for intragroup comparisons. A receiver operating characteristic curve was used to analyze the utility of this biomarker. Results Urinary levels of NGF/Cr tended to decrease in patients who responded to treatment (n=62), but this was not significant (P=0.260). Urinary NGF levels were higher at baseline in patients who did not experience recurrence than in those who did (P=0.047). In those who did not experience recurrence (n=29), urinary NGF/Cr decreased at the end of treatment compared to baseline, and this reduction was maintained at 12 weeks after the end of treatment (P

PURPOSE This study aimed to investigate potential biomarkers for the diagnosis of overactive bladder (OAB). METHODS A total of 219 subjects were enrolled and divided into 2 groups: OAB subjects (n=189) and controls without OAB symptoms (n=30). Three-day voiding diaries and questionnaires were collected, and urinary levels of nerve growth factor (NGF), prostaglandin E2, and adenosine triphosphate were measured and normalized to urine creatinine (Cr). Baseline characteristics and urinary levels of markers were analyzed. A receiver-operator characteristic (ROC) curve was used to analyze the diagnostic performance of urinary markers. Urinary levels of markers according to subgroup and pathogenesis of OAB were evaluated. Correlation analyses were used to analyze the relationship between urinary levels of markers and voiding diary parameters and questionnaires. RESULTS There was no difference between the 2 groups with regards to age, sex ratio, or urine Cr (P>0.05). The urinary levels of NGF/Cr were higher in OAB subjects than in controls (P

To evaluate the surgical outcomes of female urethral diverticulectomy.We retrospectively analyzed the medical records of 68 patients with symptomatic urethral diverticula (UD) with at least 1 year of follow-up data following transvaginal urethral diverticulectomy conducted by a single surgeon. The presence of UD was confirmed by a preoperative magnetic resonance imaging (MRI). According to MRI findings, the UDs were classified as simple, U-shaped, or circumferential. Cure was defined as the absence of residual diverticulum on a postoperative MRI with a resolution of symptoms.There were 27 cases (39.7%) of simple, 16 cases (23.5%) of U-shaped, and 25 cases (36.8%) of circumferential diverticula. The initial cure rate for UD was 77.9%. According to configuration, the cure rates for simple, U-shaped, and circumferential diverticula were 100%, 75.0%, and 64.0%, respectively (P = .043). Of the 15 patients with UD recurrence, 4 did not require reoperation because of symptom resolution. Of the 11 cases that underwent a second operation, 8 patients were cured: 7 via a Martius labial fat pad interposition (MLFI) procedure and 1 via simple excision without MLFI. The overall cure rate was 92.6%. The circumferential configuration was an independent factor for a lower cure rate (odds ratio, 7.97; 95% confidence interval, 1.14-55.69).Transvaginal diverticulectomy is an effective treatment for female UD. The success rate of an initial surgery was significantly lower for UDs with circumferential configurations than for simple or U-shaped UDs. Regardless of the initial configuration, MLFI is a good treatment option for recurrent or persistent diverticula.

Purpose Many surgeons worry about postoperative voiding problems in patients with stress urinary incontinence (SUI) and detrusor underactivity (DU). This study hypothesized that adjusting the tension after surgery would benefit patients with DU, and therefore researchers evaluated the outcomes and quality of life of women with SUI and DU who underwent the readjustable sling procedure (Remeex). Methods The medical records of 27 patients who were treated with the Remeex system for SUI and DU between 2007 and 2013 were retrospectively analyzed. The incontinence visual analogue scale (I-VAS), incontinence quality of life questionnaire (I-QOL) and the Sandvik incontinence severity index (ISI) were used to evaluate the efficacy of the Remeex system both prior to surgery and at the last visit after surgery. The treatment was considered successful if there was no urine leakage based on the Sandvik questionnaire. Results The mean follow-up period was 38.0 months (range, 1-75 months), and the treatment success rate was 81.5%. Despite no urine leakage, 7 patients wanted the Remeex system to be removed due to persistent postoperative urinary retention within a year of surgery. One patient underwent a long-term adjustment under local anesthesia 6 years after the initial surgery. The I-VAS, ISI and all domains of the I-QOL scores improved significantly postoperatively and the maximum flow rate decreased significantly after the procedure. However, the postvoid residual did not change significantly. Conclusions The Remeex system provided a good cure rate and improved the quality of life of women with SUI and DU. Therefore, the Remeex system should be considered as a treatment option for female patients with concomitant SUI and DU.

Objective To investigate the efficacy of Holmium laser transurethral incision of the prostate (Ho-TUIP) with preoperative characteristics based on urodynamic parameters. Methods The medical records of 40 consecutive cases of Ho-TUIP in patients unresponsive to medical treatment were retrospectively reviewed. The efficacy of Ho-TUIP was analyzed according to preoperative factors, including urodynamic parameters. Treatment success was confirmed if overall efficacy demonstrated an improvement that was “good or greater” according to the criteria developed by Homma et al. Predictive factors of treatment success were analyzed using logistic regression analysis with demographics, symptom questionnaires, prostate size, and urodynamic parameters. Postoperative complications and Global Response Assessment (GRA) were investigated. Results Mean age was 60.9 years (range 37–84), mean follow-up period was 36.6 months (range 6.3–114.8), and mean prostate size was 23.5 mL (range 12.7–39.5). All patients underwent medical treatment before Ho-TUIP, and mean medication duration was 50.5 months (range 3.4–140.0). The treatment success rate was 60.0%. Treatment success rates were higher in the bladder outlet obstruction index (BOOI) ≥20 group (n = 26) than in the BOOI

Drosophila melanogaster expressing amyloid-β42 (Aβ42) transgenes have been used as models to study Alzheimer's disease. Various Aβ42 transgenes with different structures induce different phenotypes, which make it difficult to compare data among studies which use different transgenic lines. In this study, we compared the phenotypes of four frequently used Aβ42 transgenic lines, UAS-Aβ422X , UAS-Aβ42BL33770 , UAS-Aβ4211C39 , and UAS-Aβ42H29.3 . Among the four transgenic lines, only UAS-Aβ422X has two copies of the upstream activation sequence-amyloid-β42 (UAS-Aβ42) transgene, while remaining three have one copy. UAS-Aβ42BL33770 has the 3' untranslated region of Drosophila α-tubulin, while the others have that of SV40. UAS-Aβ4211C39 and UAS-Aβ42H29.3 have the rat pre-proenkephalin signal peptide, while UAS-Aβ422X and UAS-Aβ42BL33770 have that of the fly argos protein. When the transgenes were expressed ectopically in the developing eyes of the flies, UAS-Aβ422X transgene resulted in a strongly reduced and rough eye phenotype, while UAS-Aβ42BL33770 only showed a strong rough eye phenotype; UAS-Aβ42H29.3 and UAS-Aβ4211C39 had mild rough eyes. The levels of cell death and reactive oxygen species (ROS) in the eye imaginal discs were consistently the highest in UAS-Aβ422X , followed by UAS-Aβ42BL33770 , UAS-Aβ4211C39 , and UAS-Aβ42H29.3 . Surprisingly, the reduction in survival during the development of these lines did not correlate with cell death or ROS levels. The flies which expressed UAS-Aβ4211C39 or UAS-Aβ42H29.3 experienced greatly reduced survival rates, although low levels of ROS or cell death were detected. Collectively, our results demonstrated that different Drosophila AD models show different phenotypic severity, and suggested that different transgenes may have different modes of cytotoxicity. Abbreviations: Aβ42: amyloid-β42; AD: Alzheimer's disease; UAS: upstream activation sequence.

Methionyl-tRNA synthetase (MRS) is essential for translation. MRS mutants reduce global translation, which usually increases lifespan in various genetic models. However, we found that MRS inhibited Drosophila reduced lifespan despite of the reduced protein synthesis. Microarray analysis with MRS inhibited Drosophila revealed significant changes in inflammatory and immune response genes. Especially, the expression of anti-microbial peptides (AMPs) genes was reduced. When we measured the expression levels of AMP genes during aging, those were getting increased in the control flies but reduced in MRS inhibition flies age-dependently. Interestingly, in the germ-free condition, the maximum lifespan was increased in MRS inhibition flies compared with that of the conventional condition. These findings suggest that the lifespan of MRS inhibition flies is reduced due to the down-regulated AMPs expression in Drosophila.

This study aimed to compare the oncologic outcomes between retroperitoneal radical nephroureterectomy (rRNU) and transperitoneal radical nephroureterectomy (tRNU) for the treatment of patients with upper urinary tract urothelial carcinoma (UTUC). Medical records of 743 eligible patients who underwent rRNU or tRNU between 1995 and 2015 were reviewed retrospectively. Progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were compared according to the surgical approach using the Kaplan–Meier method. Predictors of PFS, CSS, and OS were analyzed with a multivariable Cox regression model. Overall, 620 (83.4%) and 123 (16.6%) patients were treated with rRNU and tRNU, respectively. Five-year CSS and OS rates were equivalent between rRNU and tRNU groups, but 5-year PFS was lower in the tRNU group than the rRNU group (P = 0.005). When patients were stratified by pathological T stage, PFS was significantly different between the two groups in favor of the rRNU group for both organ-confined disease (pTis/pTa/pT1/T2) (P = 0.022) and locally advanced disease (pT3/pT4) (P = 0.039). However, no significant differences in CSS or OS was observed when comparing the two surgical types in patients with organ-confined disease (P = 0.336 and P = 0.851) or patients with locally advanced disease (P = 0.499 and P = 0.278). tRNU was a significant predictor of PFS (hazard ratio = 1.54; P = 0.023), but not CSS or OS. Our findings indicate that the rRNU approach resulted in better PFS than the tRNU approach in patients with UTUC.

Extra-transitional zone density (ETzD), a novel parameter is proposed to stratify the deviation of prostate specific antigen (PSA) due to structural change according to stromal hyperplasia of prostate. ETzD was conducted on a concept to estimate the PSA density (PSAD) after hypothetical enucleation of the transitional zone of an enlarged prostate by a non-linear regression prediction model with intrinsic linearity, from the retrospective analysis of PSA change observed actual enucleation by laser. The performance to predict the presence and severity of malignancy was validated by two cohorts of 3,440 prostate biopsies and 2,783 radical prostatectomy specimens. The performance of ETzD was compared with conventional parameters. The receiver operative curve of area under curve (AUC) of ETzD to predict the presence of malignacy was 0.862 (95% CI; 0.843~0.881), better than PSA, PSAD or transitional zone PSAD (TzPSAD). The AUC of ETzD to predict an unfavorable cancer among prostate cancer patients was 0.736 (95% CI; 0.705~0.768), which performs better than PSA and comparable to PSAD or TzPSAD. In summary, the performance of ETzD as a universal parameter to quantify the oncological hazard of a prostate was validated and the superiority to conventional parameters was verified.

The Down syndrome critical region 1 (DSCR1), a Down syndrome-associated protein, is an endogenous inhibitor of the Ca2+-dependent phosphatase calcineurin. It has been also suggested to be associated with Alzheimer’s disease (AD) but the role of DSCR1 in the pathogenesis of AD still remains controversial. In this paper, we investigated the effects of knockdown of sarah (sra), a Drosophila DSCR1 ortholog, on the Aβ42-induced developmental phenotypes of Drosophila. Knockdown of sra showed detrimental effects on the rough eye phenotype and survival of Aβ42-expressing flies without altering the Aβ42 accumulation. Furthermore, the knockdown of sra increased glial cell numbers in the larval brains and its susceptibility to oxidative stress. Overexpression of an active form of calcineurin produced similar results to sra knockdown as they both exacerbated the Aβ42-induced rough eye phenotype. However, sra knockdown did not alter apoptosis or c-Jun N-terminal kinase activation in Aβ42-expressing flies. In conclusion, our results suggest that sra does play an important role in Aβ42-induced developmental defects in Drosophila without affecting its stress responses.

Prostate cancer (PC) is the second most common cause of cancer-related mortality in US men, and 180,890 of new PC cases occurred in 2016 [1]. At the time of diagnosis, approximately 12% of patients had locally advanced PC, and about 4% of patients had PC with metastasis [2]. Cure for localized PC that is newly diagnosed is available with definitive therapy. However, almost 30% of patients with PC experience recurrence of PC and castration-resistant PC (CRPC) [2]. Many new drugs have been approved by the US Food and Drug Administration (FDA) as a therapeutic option for CRPC. Various pathways and targets have demonstrated major advances in understanding the mechanisms of acquiring castration resistance and showing progression of PC. In this chapter, the clinical trials in CRPC will be elaborated. A large number of new agents for CRPC that is based on various mechanisms are currently being studied worldwide. Clinical trials of CRPC are summarized in Table 24.1.

Abnormal aggregation of β-amyloid (Aβ) peptides is a major hallmark of Alzheimer’s disease (AD). In spite of numerous attempts to prevent the β-amyloidosis, no effective drugs for treating AD have been developed to date. Among many candidate chemicals, methylene blue (MB) has proved its therapeutic potential for AD in a number of in vitro and in vivo studies; but the result of recent clinical trials performed with MB and its derivative was negative. Here, with the aid of multiple photochemical analyses, we first report that photoexcited MB molecules can block Aβ42 aggregation in vitro. Furthermore, our in vivo study using Drosophila AD model demonstrates that photoexcited MB is highly effective in suppressing synaptic toxicity, resulting in a reduced damage to the neuromuscular junction (NMJ), an enhanced locomotion, and decreased vacuole in the brain. The hindrance effect is attributed to Aβ42 oxidation by singlet oxygen (1O2) generated from photoexcited MB. Finally, we show that photoexcited MB possess a capability to disaggregate the pre-existing Aβ42 aggregates and reduce Aβ-induced cytotoxicity. Our work suggests that light illumination can provide an opportunity to boost the efficacies of MB toward photodynamic therapy of AD in future.

Objective To investigate the rates and predictive factors associated with the development of de novo overactive bladder (OAB) and to assess the effects of de novo OAB on surgical outcomes after an artificial urinary sphincter (AUS). Materials and Methods We performed a retrospective review of 132 patients with postprostatectomy incontinence who underwent AUS surgery. Urodynamic studies were performed during preoperative visits in all patients, and patients with OAB or neurogenic bladder were excluded. We assessed the development of de novo OAB based on patient symptoms. Treatment success was defined as no need for pads, and social continence was defined as the need for ≤1pad per day at the end of the follow-up. A multivariate analysis was performed using a logistic regression model to assess predictors of de novo OAB. Results The rate of development of de novo OAB after surgery was 37.5%. The treatment success rate was significantly higher in the no-OAB group (72.4%) than in the de novo OAB group (55.4%) ( P = .038). A low preoperative cystometric capacity of less than 300 mL (odds ratio 5.27, confidence interval 1.02-27.28; P = .048) and pelvic irradiation (odds ratio 3.18, confidence interval 1.01-10.03; P = .049) were predictive factors of de novo OAB after AUS surgery. Conclusion De novo OAB occurs commonly after AUS surgery, and the presence of de novo OAB adversely impacts treatment success. Low preoperative cystometric capacity of less than 300 mL and pelvic irradiation predict the occurrence of de novo OAB after AUS implantation.

// Sung Han Kim 1 , Yoon Seok Suh 1 , Jung Kwon Kim 1 , Jae Young Joung 1 , Ho Kyung Seo 1 , Kang Hyun Lee 1 and Jinsoo Chung 1 1 Center for Prostate Cancer, Research Institute and Hospital of National Cancer Center, Goyang, Korea Correspondence to: Jinsoo Chung, email: cjs5225@ncc.re.kr Keywords: renal cell carcinoma; metastasis; sequential; targeted therapy; survival Received: May 19, 2017 Accepted: August 26, 2017 Published: October 19, 2017 ABSTRACT Objective: To evaluate the progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with double- and triple-sequence targeted therapy (TT) using tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORi). Materials and Methods: Records of 292 patients with mRCC, treated with TT between January 2005 and July 2015, were analyzed retrospectively. Kaplan-Meier and log-rank analyses were used to calculate and compare the total PFS (tPFS) and OS when patients underwent double- or triple-TT using TKIs or mTORi. Results: Eighty-one (27.7%) patients who underwent second-line TT were enrolled; 30 (10.3%) of whom underwent third-line TT. The tPFS and OS of double-TT using TKI-mTORi (5.4 and 30 months, respectively) were significantly better compared with TKI-TKI (0.3 and 2 months) or mTORi-TKI (2 and 6 months) (p

// Sung Han Kim 1, * , Yoon Seok Suh 1, * , Dong-Eun Lee 2 , Boram Park 2 , Jungnam Joo 2 , Jae Young Joung 1 , Ho Kyung Seo 1 , Kang Hyun Lee 1 and Jinsoo Chung 1 1 Department of Urology, Center for Prostate Cancer, Research Institute and Hospital of National Cancer Center, Goyang, Korea 2 Biometric Research Branch, Division of Cancer Epidemiology and Prevention, Research Institute and Hospital of National Cancer Center, Goyang, Korea * These authors have contributed equally to this work Correspondence to: Jinsoo Chung, email: cjs5225@ncc.re.kr Keywords: renal cell carcinoma, metastasis, synchronous, metachronous, prognosis Received: February 07, 2017 Accepted: July 18, 2017 Published: September 06, 2017 ABSTRACT Introduction: The aim of this study was to compare progression-free survival (PFS) and overall survival (OS) between metachronous and synchronous metastatic renal cell carcinomas treated with VEGF-targeted therapy. Methods: Between 2005 and 2014, 93 (78.8%) intermediate- and 25 (21.2%) poor-Heng-risk patients, including 32 (27.1%) patients with metachronous and 86 (72.9%) patients with synchronous renal cell carcinoma, were enrolled retrospectively. PFS and OS values were compared according to the number of risk factors and treatment-free interval using the Kaplan-Meier method and log-rank test. The prognostic risk factors were also evaluated using a Cox proportional hazard model, with a p-value 0.05). There was a significant difference in PFS (hazard ratio: 1.81) and OS (hazard ratio: 2.19) with increasing number of Heng risk factors among patients with synchronous renal cell carcinoma and a treatment-free interval

// Sung Han Kim 1, * , Jae Young Joung 1, * , Yoon Seok Suh 1 , Young Ae Kim 2 , Jin Hyuk Hong 2 , Tong Sun Kuark 3 , Eun Sook Lee 4 and Kang Hyun Lee 1 1 Department of Urology, Center for Prostate Cancer, Research Institute and Hospital of National Cancer Center, Goyang, Korea 2 Cancer Policy Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea 3 Health Insurance Policy Research Institute, National Health Insurance Service, Seoul, Korea 4 Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea * These authors have contributed equally to this work Correspondence to: Kang Hyun Lee, email: uroonco@ncc.re.kr Keywords: prostate cancer, end-stage renal disease, transplantation, prostate-specific antigen, prognosis Received: January 25, 2017 Accepted: May 10, 2017 Published: July 22, 2017 ABSTRACT Objective: The study was aimed to evaluate the prevalence and prognosis of prostate cancer (PC) and end-stage renal disease (ESRD), determine the risk factors for overall survival (OS) and PC-specific survival (CSS), and evaluate differences in PC-related clinical therapeutic patterns between patients with and without PC-ESRD. Methods: This observational population study, performed at the National Cancer Center and Cancer Research Institute in Korea, included patients with PC and ESRD from the nationwide Korean Health Insurance System and Korean Central Cancer Registry data. Five-year overall and cancer-specific survival. A joinpoint regression analysis was performed to predict incidence and mortality of PC. Survival was analyzed using Kaplan-Meir curves with log rank tests of patients with dialysis or transplantation. Results: Of 3945 patients with PC-ESRD, 3.9% were on dialysis (N=152), 0.2% had kidney transplantation (N=10, D-TPL group); 3783 (95.9%) had neither dialysis nor transplantation (non-D-TPL ESRD group). There were 697 PC-specific deaths. The median respective OS, PC-specific survival, and 5-year survival rates in the non-ESRD, non-D-TPL ESRD, dialysis ESRD, and transplantation ESRD groups were significantly different (p

A 45-year-old previously healthy woman presented to our hospital with a right abdominal mass. Abdominal computed tomography (CT), magnetic resonance imaging, and bone scanning revealed a 15-×10-×14-cm, welldelineated, retroperitoneal tumor originating from the right kidney. No metastases detected. The patient underwent successful extirpation of the renal tumor. The tumor showed 50% necrosis without perirenal fat infiltration, and it was diagnosed as a high-grade (grade 3) myxofibrosarcoma without nodal positivity, according to the French Federation of Cancer Centers Sarcoma (FNCLCC) grading system. Tumor immunohistochemical staining revealed positive staining for CD34, Ki67, smooth muscle actin (SMA), and cluster of differentiation 68 (CD68), and negative staining for S100 protein, desmin, mast/stem cell growth factor receptor (c-kit), and melanoma marker antibody (HMB45). Three months post-surgery, follow-up CT revealed no new abdominal metastasis, and the patient is currently receiving routine follow-up without any additional systemic therapy. Myxofibrosarcoma of the kidney is an uncommon soft tissue tumor, and radical surgery is the treatment of choice. Long-term follow-up is recommended because of the tumor’s aggressive invasiveness and potential for distant metastasis.

Purpose: To analyze the location of the positive surgical margin (PSM) and its association with the biochemical recurrence (BCR) rate in cases of radical prostatectomy (RP) according to the type of surgery. Materials and Methods: We retrospectively analyzed 1,880 cases of RP. Baseline characteristics were analyzed. Locations of the PSM were recorded in the four surgery groups as apex, anterior, posterolateral, and base and were analyzed by using chi-square test. The association of the location of the PSM with the BCR rate was analyzed by using Kaplan-Meier survival analysis according to the type of surgery, which included radical perineal prostatectomy (RPP, n=633), radical retroperitoneal prostatectomy (RRP, n=309), laparoscopic radical prostatectomy (LRP, n=164), and robot-assisted laparoscopic radical prostatectomy (RALRP, n=774). Results: A PSM was found in a total of 336 cases (18%): 122 cases of RPP (18%), 67 cases of RRP (17%), 29 cases of LRP (17%), and 119 cases of RALRP (15%). The PSM rate did not differ significantly by surgical type (p=0.142). The location of the PSM was the apex in 136 cases (7.2%), anterior in 67 cases (3.5%), posterolateral in 139 cases (7.3%), and base in 95 cases (5.0%), and showed no significant difference according to surgical type (p=0.536, p=0.557, p=0.062, and p=0.109, respectively). The BCR rate according to the location of the PSM did not differ significantly for the four types of surgery (p= 0.694, p=0.301, p=0.445, and p=0.309 for RPP, RRP, LRP, and RALRP, respectively). Conclusions: The location of the PSM seemed to be unrelated to type of RP. There was no significant correlation between the BCR rate and the location of the PSM for any of the RP types.

To investigate the efficacy of Holmium laser transurethral incision of the prostate (Ho-TUIP) with preoperative characteristics based on urodynamic parameters.The medical records of 40 consecutive cases of Ho-TUIP in patients unresponsive to medical treatment were retrospectively reviewed. The efficacy of Ho-TUIP was analyzed according to preoperative factors, including urodynamic parameters. Treatment success was confirmed if overall efficacy demonstrated an improvement that was "good or greater" according to the criteria developed by Homma et al. Predictive factors of treatment success were analyzed using logistic regression analysis with demographics, symptom questionnaires, prostate size, and urodynamic parameters. Postoperative complications and Global Response Assessment (GRA) were investigated.Mean age was 60.9 years (range 37-84), mean follow-up period was 36.6 months (range 6.3-114.8), and mean prostate size was 23.5 mL (range 12.7-39.5). All patients underwent medical treatment before Ho-TUIP, and mean medication duration was 50.5 months (range 3.4-140.0). The treatment success rate was 60.0%. Treatment success rates were higher in the bladder outlet obstruction index (BOOI) ≥20 group (n = 26) than in the BOOI20 group (n = 14) (p = 0.003). In logistic regression analysis, BOOI ≥20 was a predictor of treatment success (OR 7.60, 95% CI 1.60-35.90, P = 0.010). Among patients who maintained an active sex life, 77.8% (14/18) reported retrograde ejaculation. In terms of GRA, 81.5% (31/38, two patients expired) of patients improved at the final follow-up.Ho-TUIP is an effective procedure with tolerable complications for the treatment of symptomatic mild-to-moderate BPE in patients with BOOI ≥20 that are unresponsive to medical treatment.

Aims To evaluate long-term outcomes of primary implantation and revisions of artificial urinary sphincter (AUS) in men with stress urinary incontinence (SUI). Methods The medical records of 155 consecutive patients who underwent AMS 800™ implantation from 2003 to 2015 were reviewed. Treatment success (TS) was defined as no need for pads, and social continence (SC) was defined as a need for pad ≤1/day at last follow-up. The efficacy, complication rates, and associated risk factors with reoperation and durability of primary AUS implantation, as well as treatment outcomes following AUS revision were evaluated. Results The median age was 69.0 years (range 27-85), and median follow-up was 45.1 months (range 9-126). The rates of TS and SC were 63.2% and 84.5%, respectively. The reoperation rate of AUS was 26.4%. Non-mechanical failure (70.7%) was a dominant etiology of reoperation. The 5-year device survival rate without reoperation was 67.0%. The immediate TS rates of primary AUS without reoperation (pAUS) and AUS revision without secondary reoperation (rAUS) groups were 88.6% and 79.2% (P = 0.352), respectively. At last follow-up, the SC rate was higher in patients with pAUS (92.1%) than with rAUS (62.5%) (P = 0.001). Conclusions Although there are appreciable rates of reoperation, the AMS 800™ offers high rates of continence in men with SUI. The immediate TS rate was comparable in patients with pAUS and rAUS. At the final follow-up, however, the SC rate was significantly higher in patients with pAUS than with rAUS.

Alzheimer’s disease (AD), the most common neurodegenerative disease, has a complex and widespread pathology that is characterized by the accumulation of amyloid [Formula: see text]-peptide (A[Formula: see text]) in the brain and various cellular abnormalities, including increased oxidative damage, an amplified inflammatory response, and altered mitogen-activated protein kinase signaling. Based on the complex etiology of AD, traditional medicinal plants with multiple effective components are alternative treatments for patients with AD. In the present study, we investigated the neuroprotective effects of an ethanol extract of Coriandrum sativum (C. sativum) leaves on A[Formula: see text] cytotoxicity and examined the molecular mechanisms underlying the beneficial effects. Although recent studies have shown the benefits of the inhalation of C. sativum oil in an animal model of AD, the detailed molecular mechanisms by which C. sativum exerts its neuroprotective effects are unclear. Here, we found that treatment with C. sativum extract increased the survival of both A[Formula: see text]-treated mammalian cells and [Formula: see text]42-expressing flies. Moreover, C. sativum extract intake suppressed [Formula: see text]-induced cell death in the larval imaginal disc and brain without affecting A[Formula: see text]42 expression and accumulation. Interestingly, the increases in reactive oxygen species levels and glial cell number in AD model flies were reduced by C. sativum extract intake. Additionally, C. sativum extract inhibited the epidermal growth factor receptor- and A[Formula: see text]-induced phosphorylation of extracellular signal-regulated kinase (ERK). The constitutively active form of ERK abolished the protective function of C. sativum extract against the [Formula: see text]-induced eye defect phenotype in Drosophila. Taken together, these results suggest that C. sativum leaves have antioxidant, anti-inflammatory, and ERK signaling inhibitory properties that are beneficial for patients with AD.

Objectives The aim of this study was to evaluate the pattern of tailoring and efficacy of several types of pharmacotherapy in male LUTS. Methods Prospectively 404 male subjects were included who were over 40 years old, had at least 3 months symptom duration, and 12 or higher international prostate symptom score (IPSS). Subjects were treated with several types of pharmacotherapy for 6 months and were evaluated with IPSS/QoL at every follow-up. Subjects were subdivided into storage (44%), nocturia (18.5%), and voiding symptom (37.5%) groups according to the most bothersome symptom. Results At 6 months, 188 subjects (46.5%) completed the study. The mean age was 64.2±8.5 years, and symptom duration was 30.6±32.6 months. PSA was 2.98±7.96 ng/mL, and prostate size was 32.8±14.2 cc. IPSS continually decreased from baseline (18.7) to last follow-up (10.8). Combination therapy increased from 33.0% to 52.7% at last follow-up (P=.006). However, there was no difference of IPSS changes between combination and monotherapy groups (P>.05). Only antimuscarinic prescription significantly increased from 15.4% to 28.2% (P=.004). Mean number of visits to the clinic was 3.6±1.3 and the number of treatment changes was 0.31±0.47. The nocturia (0.47±0.51) group changed treatment more than voiding group (0.21±0.41, P=.003). However, the voiding group (−9.4) had significantly more improvement than e storage (−6.4) and nocturia (−7.8) groups (P=.011). Conclusions Male LUTS continually improved over 6 months with customised treatment. Pharmacotherapy for male LUTS should be tailored by symptom type and alteration of symptoms during treatment.

Aim The current standard diagnostic test to evaluate bladder outlet obstruction (BOO) is pressure-flow study (PFS). The penile cuff test (PCT) was introduced as a non-invasive alternative to PFS to determine the isovolumetric bladder pressure and also flow rate. The aim of the study was to evaluate the diagnostic accuracy and acceptability of the PCT, compared to those of PFS, in the assessment of BOO in men. Methods A total of 146 consecutive men with an International Prostate Symptom Score (IPSS) >12 and lower urinary tract symptoms (LUTS) for >6 months were included in this single-institution, prospective, diagnostic study. The primary outcome was to evaluate the diagnostic accuracy of PCT. Secondary outcomes included pain severity measured on a visual analog scale (VAS), procedure time, and adverse events. In addition, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated. Results Based on the PFS results, the sensitivity of PCT was 89.7%, the PPV 54.2%, the specificity 71.8%, and the NPV 94.9%. The mean pain VAS for the PFS and PCT were 5.04 ± 2.17 and 1.83 ± 1.98, respectively (P

INTRODUCTION AND OBJECTIVES: Metabolic syndrome (MetS) is a common disease in the United States, with more than 20% prevalence.MetShasbeenshown tohavedetrimental effectson thebladder, including significant lower urinary tract symptoms (LUTS), decreased quality of life, and detrusor underactivity (DU). However, the progression and mechanism of disease are poorly understood. A large animal model for diabetic bladder dysfunction was developed with Ossabaw pigs. It is hypothesized thatMetSaffects thebladder in theOssabawmetabolicpigandpossibly humans by causing DU over time, contributing to LUTS. METHODS: A group of 11 Ossabaw pigs underwent dietary modification consisting of a hypercaloric, atherogenic diet for 10months to induce MetS. This cohort was compared to a group of 5 lean pigs. Urodynamic studies were performed at 7 and 10 months after randomization. Bladder pressure and compliance were used to define detrusor underactivity. RESULTS: MetS was confirmed between the two groups by demonstrating increased body weight in the MetS animals, increased systolic and diastolic blood pressure, fasting serum glucose, total cholesterol, but not triglycerides (Table 1). Eleven Metabolic pigs demonstrated decreased bladder pressure at maximum capacity (28.2 4.6 vs. 63.8 6.5 cmH2O, p1⁄40.001) and increased compliance (67.1 7.9 vs. 22.2 3.2 cc/cmH2O, p

Objective To evaluate the efficacy and safety of low-dose (2 mg) tolterodine extended release (ER) with an α-blocker compared with standard-dose (4 mg) tolterodine ER with an α-blocker for the treatment of men with residual storage symptoms after α-blocker monotherapy. Patients and Methods The study was a 12-week, single-blind, randomized, parallel-group, non-inferiority trial that included men with residual storage symptoms despite receiving at least 4 weeks of α-blocker treatment. Inclusion criteria were total International Prostate Symptom Score (IPSS) ≥12, IPSS quality-of-life item score ≥3, and ≥8 micturitions and ≥2 urgency episodes per 24 h. The primary outcome was change in the total IPSS score from baseline. Bladder diary variables, patient-reported outcomes and safety were also assessed. Results Patients were randomly assigned to addition of either 2 mg tolterodine ER (n = 47) or 4 mg tolterodine ER (n = 48) to α-blocker therapy for 12 weeks. Patients in both treatment groups had a significant improvement in total IPSS score (−5.5 and −6.3, respectively), micturition per 24 h (−1.3 and −1.7, respectively) and nocturia per night (−0.4 and −0.4, respectively). Changes in IPSS, bladder diary variables, and patient-reported outcomes were not significantly different between the treatment groups. All interventions were well tolerated by patients. Conclusions These results suggest that 12 weeks of low-dose tolterodine ER add-on therapy is similar to standard-dose tolterodine ER add-on therapy in terms of efficacy and safety for patients experiencing residual storage symptoms after receiving α-blocker monotherapy.

The abnormal assembly of β-amyloid (Aβ) peptides into neurotoxic, β-sheet-rich amyloid aggregates is a major pathological hallmark of Alzheimer's disease (AD). Light-induced photosensitizing molecules can regulate Aβ amyloidogenesis. Multiple photochemical analyses using circular dichroism, atomic force microscopy, dot blot, and native gel electrophoresis verified that photoactivated meso-tetra(4-sulfonatophenyl)porphyrin (TPPS with M = 2H(+), Zn(2+), Cu(2+), Mn(2+)) successfully inhibits Aβ aggregation in vitro. Furthermore, Aβ toxicity was relieved in the photoexcited-TPPS-treated Drosophila AD model. TPPS suppresses neural cell death, synaptic toxicity, and behavioral defects in the Drosophila AD model under blue light illumination. Behavioral phenotypes, including larval locomotion defect and short lifespan caused by Aβ overexpression, were also rescued by blue light-excited TPPS.

MicroRNAs (miRNAs) regulate many physiological processes including body growth. Insulin/IGF signalling is the primary regulator of animal body growth, but the extent to which miRNAs act in insulin-producing cells (IPCs) is unclear. Here we generate a UAS-miRNA library of Drosophila stocks and perform a genetic screen to identify miRNAs whose overexpression in the IPCs inhibits body growth in Drosophila. Through this screen, we identify miR-9a as an evolutionarily conserved regulator of insulin signalling and body growth. IPC-specific miR-9a overexpression reduces insulin signalling and body size. Of the predicted targets of miR-9a, we find that loss of miR-9a enhances the level of sNPFR1. We show via an in vitro binding assay that miR-9a binds to sNPFR1 mRNA in insect cells and to the mammalian orthologue NPY2R in rat insulinoma cells. These findings indicate that the conserved miR-9a regulates body growth by controlling sNPFR1/NPYR-mediated modulation of insulin signalling., Insulin signaling governs many physiological processes but the molecular and neural mechanisms of its regulation are largely unknown. Here the authors describe a novel molecular pathway controlling sNPF regulation of insulin signalling in the fruit fly, which is mediated by the evolutionary conserved miR-9a.

Purpose To evaluate the oncologic outcomes and postoperative complications of high-intensity focused ultrasound (HIFU) as a salvage therapy after external-beam radiotherapy (EBRT) failure in patients with prostate cancer. Materials and Methods Between February 2002 and August 2010, we retrospectively reviewed the medical records of all patients who underwent salvage HIFU for transrectal ultrasound-guided, biopsy-proven locally recurred prostate cancer after EBRT failure (by ASTRO definition: prostate-specific antigen [PSA] failure after three consecutive PSA increases after a nadir, with the date of failure as the point halfway between the nadir date and the first increase or any increase great enough to provoke initiation of therapy). All patients underwent prostate magnetic resonance imaging and bone scintigraphy and had no evidence of distant metastasis. Biochemical recurrence (BCR) was defined according to the Stuttgart definition (PSA nadir plus 1.2 ng/mL). Results A total of 13 patients with a median age of 68 years (range, 60-76 years) were included. The median pre-EBRT PSA was 21.12 ng/mL, the pre-HIFU PSA was 4.63 ng/mL, and the period of salvage HIFU after EBRT was 32.7 months. The median follow-up after salvage HIFU was 44.5 months. The overall BCR-free rate was 53.8%. In the univariate analysis, predictive factors for BCR after salvage HIFU were higher pre-EBRT PSA (p=0.037), pre-HIFU PSA (p=0.015), and short time to nadir (p=0.036). In the multivariate analysis, there were no significant predictive factors for BCR. The complication rate requiring intervention was 38.5%. Conclusions Salvage HIFU for prostate cancer provides effective oncologic outcomes for local recurrence after EBRT failure. However, salvage HIFU had a relatively high rate of complications.