Association between Postoperative Detection of Circulating Tumor Cells and Recurrence in Patients with Prostate Cancer.

PURPOSE: 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. MATERIALS AND METHODS: 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). RESULTS: 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 p <0.001). 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, p <0.001). C-index was increased in combinations of multivariable model and postoperative circulating tumor cell detection compared with the multivariable model alone. CONCLUSIONS: 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.

Therapeutic effects of endoscopic ablation in patients with Hunner type interstitial cystitis.

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.

Long-term outcomes of primary implantation and revisions of artificial urinary sphincter in men with stress urinary incontinence.

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.

Diagnosing bladder outlet obstruction using the penile cuff test in men with lower urinary tract symptoms.

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 < 0.0001). The mean procedure time for PCT (6.3 ± 0.6 min) was shorter than that of PFS (23.3 ± 2.2 min) (P < 0.0001). There were no adverse events reported during PCT. CONCLUSIONS: Given its high NPV, PCT may be an efficient screening test for BOO in men. In addition, PCT is advantageous over PFS with regard to its short procedure time and acceptable tolerability.

Tailoring pharmacotherapy for male lower urinary tract symptoms: A prospective, multicenter, observational trial.

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.

Comparison of the efficacy and safety of tolterodine 2 mg and 4 mg combined with an α-blocker in men with lower urinary tract symptoms (LUTS) and overactive bladder: a randomized controlled trial.

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.

Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO.

DJ-1, a Parkinson's disease (PD)-associated gene, has been shown to protect against oxidative stress in Drosophila. However, the molecular mechanism underlying oxidative stress-induced phenotypes, including apoptosis, locomotive defects, and lethality, in DJ-1-deficient flies is not fully understood. Here we showed that Daxx-like protein (DLP), a Drosophila homologue of the mammalian Death domain-associated protein (Daxx), was upregulated under oxidative stress conditions in the loss-of-function mutants of Drosophila DJ-1ß, a Drosophila homologue of DJ-1. DLP overexpression induced apoptosis via the c-Jun N-terminal kinase (JNK)/Drosophila forkhead box subgroup O (dFOXO) pathway, whereas loss of DLP increased resistance to oxidative stress and UV irradiation. Moreover, the oxidative stress-induced phenotypes of DJ-1ß mutants were dramatically rescued by DLP deficiency, suggesting that enhanced expression of DLP contributes to the DJ-1ß mutant phenotypes. Interestingly, we found that dFOXO was required for the increase in DLP expression in DJ-1ß mutants and that dFOXO activity was increased in the heads of DJ-1ß mutants. In addition, subcellular localization of DLP appeared to be influenced by DJ-1 expression so that cytosolic DLP was increased in DJ-1ß mutants. Similarly, in mammalian cells, Daxx translocation from the nucleus to the cytosol was suppressed by overexpressed DJ-1ß under oxidative stress conditions; and, furthermore, targeted expression of DJ-1ß to mitochondria efficiently inhibited the Daxx translocation. Taken together, our findings demonstrate that DJ-1ß protects flies against oxidative stress- and UV-induced apoptosis by regulating the subcellular localization and gene expression of DLP, thus implying that Daxx-induced apoptosis is involved in the pathogenesis of DJ-1-associated PD.

Photoexcited Porphyrins as a Strong Suppressor of ß-Amyloid Aggregation and Synaptic Toxicity.

The abnormal assembly of ß-amyloid (Aß) peptides into neurotoxic, ß-sheet-rich amyloid aggregates is a major pathological hallmark of Alzheimer's disease (AD). Light-induced photosensitizing molecules can regulate Aß 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 Aß aggregation in vitro. Furthermore, Aß 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 Aß overexpression, were also rescued by blue light-excited TPPS.

UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation.

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.

Comparison of outcomes in totally tubeless percutaneous nephrolithotomy according to nephrostomy tract sealing with fibrin versus gelatin matrix: a propensity score matching study.

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 < 4 mm residual) among all patients was 91.1% (144/158). UROs and UCOs occurred in 35.4% (86/158) and 11.4% (18/158) of all cases, respectively. Neither of the frequency of URO nor hemorrhage-related UCO was different according to sealant type. However, drainage-related UCOs were more prevalent among the GS group, mainly due to the higher postoperative ureter stenting rate. The postoperative pain severity and the length of hospitalization were comparable between groups. In summary, using GS rather than FS during tract closure did not worsen hemorrhage-related outcomes. However, the clinical risk of ureter occlusion requiring additional temporary ureteral stenting was increased.

Methionyl-tRNA Synthetase Regulates Lifespan in Drosophila.

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 agedependently. 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.

Transperitoneal radical nephroureterectomy is associated with worse disease progression than retroperitoneal radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

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.

Establishment and Validation of Extra-transitional Zone Prostate Specific Antigen Density (ETzD), a Novel Structure-based Parameter for Quantifying the Oncological Hazard of Prostates with Enlarged Stroma.

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.

Predictive Factors of De Novo Overactive Bladder After Artificial Urinary Sphincter Implantation in Men With Postprostatectomy Incontinence.

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.

Efficacy of Holmium Laser Transurethral Incision of the Prostate in Symptomatic Mild-to-Moderate Benign Prostate Enlargement Based on Preoperative Characteristics.

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 <20 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. CONCLUSIONS: 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.

Prostate stem cell antigen mRNA in blood is a predictor of survival after radical prostatectomy in patients with high-risk prostate cancer.

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.

Assessing the Readjustable Sling Procedure (Remeex System) for Female Stress Urinary Incontinence With Detrusor Underactivity.

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.

Surgical Outcomes and Safety of Robotic Sacrocolpopexy in Women With Apical Pelvic Organ Prolapse.

PURPOSE: This study aimed to investigate the surgical outcomes and safety of robotic sacrocolpopexy (RSC) in patients with uterine/vaginal vault prolapse. METHODS: Between January 2009 and June 2015, 16 women with apical prolapse underwent RSC. Pelvic organ prolapse quantification (POP-Q) examination was performed, and treatment success was defined as the presence of grade 0 or I apical prolapse upon POP-Q examination at the final follow-up. Pelvic floor distress inventory-short form 20 (PFDI-SF 20) was administered at every follow-up. A treatment satisfaction questionnaire was administered by telephone to evaluate patient satisfaction with the operation. RESULTS: Median age was 65 years (interquartile range [IQR], 56-68 years), and follow-up duration was 25.3 months (IQR, 5.4-34.0 months). Thirteen women (81.3%) had ≥grade III apical prolapse. Operation time was 251 minutes (IQR, 236-288 minutes), and blood loss was 75 mL (IQR, 50-150 mL). Median hospital stay was 4 days (IQR, 3-5 days). At the final follow-up, treatment success was reported in all patients, who presented grade 0 (n=8, 57.1%) and grade I (n=6, 42.9%) apical prolapse. Dramatic improvements in PFDI-SF 20 scores were noted after RSC (from 39 to 4; P=0.001). Most patients (12 of 13) were satisfied with RSC. An intraoperative complication (sacral venous plexus injury) was reported in 1 patient, and there was no conversion to open surgery. Mesh erosion was not reported. CONCLUSIONS: RSC is an efficient and safe surgical option for apical prolapse repair. Most patients were satisfied with RSC. Thus, RSC might be one of the best treatment options for apical prolapse in women.

Shedding Light on Alzheimer's ß-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of ß-Amyloid Peptides and Disintegrates Their Aggregates.

Abnormal aggregation of ß-amyloid (Aß) peptides is a major hallmark of Alzheimer's disease (AD). In spite of numerous attempts to prevent the ß-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 Aß42 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 Aß42 oxidation by singlet oxygen (1O2) generated from photoexcited MB. Finally, we show that photoexcited MB possess a capability to disaggregate the pre-existing Aß42 aggregates and reduce Aß-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.

Establishment and Application of Prostate Cancer Circulating Tumor Cells in the Era of Precision Medicine.

Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths worldwide. Additionally, there is concern for overdiagnosis and overtreatment of PC. Thus, selection of an appropriate candidate for active surveillance as well as more accurate and less invasive tools for monitoring advanced PC is required. Circulating tumor cells (CTCs) have emerged as a liquid biopsy tool; there have been several reports on its role, technologies, and applications to various cancers, including PC. Liquid biopsy using CTCs has been gaining attention as a minimal invasive tool for investigation of biomarkers and for prognosis and assessment of response to therapies in patients with PC. Because of the lower invasiveness of liquid biopsy using CTCs, it can be performed more frequently; accordingly, personalized disease status can be successively determined at serial time points. CTC analysis enables detection of genomic alterations, which is drug-targetable, and it is a potential tool for monitoring response to therapeutic agents in patients with PC. This review focuses on the characteristics, technologies for analysis, and advantages and disadvantages of CTCs as a liquid biopsy tool and their application in PC. Finally, we propose future directions of CTCs.