The impact of body mass index on survival endpoints among patients with metastatic urothelial carcinoma undergoing treatment with immune checkpoint inhibitors: A real-world multicenter analysis.

BACKGROUND: Studies on the correlation between high body mass index (BMI) and extended survival among patients receiving immune checkpoint inhibitors (ICIs) have been made, although findings have shown variability. Our research explored the phenomenon of the "obesity paradox" in patients with metastatic urothelial carcinoma (mUC) undergoing treatment with ICIs. MATERIALS AND METHODS: We conducted a retrospective analysis of patients diagnosed with mUC who received a minimum of one cycle of ICI treatment at two medical centers in Taiwan from September 2015 to January 2023. Features of patients' clinicopathologic factors, including age, sex, primary or metastatic location, treatment line, and BMI were examined. The primary outcome were overall survival (OS) and progression-free survival (PFS), which were assessed utilizing the Kaplan-Meier method. We employed the Cox-regression model to adjust for multiple covariates. RESULTS: A total of 215 patients were included, with 128 (59.5%) being male, and the median age was 70 years. In the obese group (BMI ≥25 kg/m2 ), patients demonstrated significantly better median OS compared to the non-obese group (BMI <25 kg/m2 ) (21.9 vs. 8.3 months; p = 0.021). However, there was no significant difference in median PFS between the high and low BMI groups (4.7 vs. 2.8 months; p = 0.16). Post-hoc subgroup revealed a survival benefit from ICI treatment in male patients within the BMI ≥25 kg/m2 group (HR 0.49, 95% CI 0.30-0.81, p = 0.005). CONCLUSION: Based on real-world data from the Asia-Pacific region, there appears to be a correlation between obesity and prolonged OS in patients receiving ICI treatment for mUC.

The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy.

BACKGROUND: While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. METHOD: We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. RESULT: A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). CONCLUSION: The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.

Combination of 180-W GreenLight XPS laser and bipolar transurethral resection of prostate for the treatment of large prostates beyond 100 ml: a novel hybrid technique.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of the 180-W GreenLight laser (GL) XPS™ plus bipolar transurethral resection of the prostate (TURP) for the treatment of a prostate volume (PV) beyond 100 ml. STUDY DESIGN/MATERIALS AND METHODS: From January 2014 to December 2022, 79 patients with PV > 100 ml who underwent GL-XPS plus bipolar TURP were enrolled. The median follow-up time was 13.7 months. The International Prostate Symptom Score (IPSS), PV, uroflow study, post-void residual (PVR) volume, and prostate-specific antigen (PSA) before and after the operation were recorded. Subgroup analysis was performed to compare the outcomes between the patients with follow-up times of < 36 months and > 36 months. RESULTS: Statistically significant improvements in all the postoperative parameters were observed in both < 36 months and > 36 months groups. There was no blood transfusion or transurethral resection (TUR) syndrome in this series. Most of all, a second TURP was unnecessary during the follow-up. Only one (1.3%) Clavien-Dindo grade 3b complication was noted. CONCLUSIONS: The hybrid technique of 180-W XPS™ GreenLight laser plus bipolar TURP can be safely and efficiently performed on patients with a prostate volume of > 100 ml.

Laparoendoscopic Single-Site Inguinal Herniorrhaphy: Experience of a Single Institute.

Background: Minimally invasive techniques for inguinal herniorrhaphy have focused on developing the laparoendoscopic single-site (LESS) procedure to improve cosmesis. Outcomes of total extraperitoneal (TEP) herniorrhaphy vary considerably because of being performed by different surgeons. We aimed to evaluate the perioperative characteristics and outcomes of patients undergoing the LESS-TEP approach for inguinal herniorrhaphy and to determine its overall safety and effectiveness. Methods: Data of 233 patients who underwent 288 laparoendoscopic single-site total extraperitoneal approach (LESS-TEP) herniorrhaphies at Kaohsiung Chang Gung Memorial Hospital between January 2014 and July 2021 were reviewed retrospectively. We reviewed the experiences and results of LESS-TEP herniorrhaphy performed by a single surgeon (CHC) using homemade glove access and standard laparoscopic instruments with a 50 cm long 30° telescope. Results: Among 233 patients, 178 patients had unilateral hernias and 55 patients had bilateral hernias. About 32% (n = 57) of patients in the unilateral group and 29% (n = 16) of patients in the bilateral group were obese (body mass index ≥ 25). The mean operative time was 66 min for the unilateral group and 100 min for the bilateral group. Postoperative complications occurred in 27 (11%) cases, which were minor morbidities except for one mesh infection. Three (1.2%) cases were converted to open surgery. Comparison of the variables between obese and non-obese patients found no significant differences in operative times or postoperative complications. Conclusion: LESS-TEP herniorrhaphy is a safe and feasible operation with excellent cosmetic results and a low rate of complication, even in obese patients. Further large-scale prospective controlled studies and long-term analyses are needed to confirm these results.

Nanodiamonds Doped with Manganese for Applications in Magnetic Resonance Imaging.

Nanodiamonds (NDs) are emerging with great potential in biomedical applications like biomarking through fluorescence and magnetic resonance imaging (MRI), targeted drug delivery, and cancer therapy. The magnetic and optical properties of NDs could be tuned by selective doping. Therefore, we report multifunctional manganese-incorporated NDs (Mn-NDs) fabricated by Mn ion implantation. The fluorescent properties of Mn-NDs were tuned by inducing the defects by ion implantation and enhancing the residual nitrogen vacancy density achieved by a two-step annealing process. The cytotoxicity of Mn-NDs was investigated using NCTC clone 929 cells, and the results revealed no cytotoxicity effect. Mn-NDs have demonstrated dual mode contrast enhancement for both T 1- and T 2-weighted in vitro MR imaging. Furthermore, Mn-NDs have illustrated a significant increase in longitudinal relaxivity (fivefold) and transversal relaxivity (17-fold) compared to the as-received NDs. Mn-NDs are employed to investigate their ability for in vivo MR imaging by intraperitoneal (ip) injection of Mn-NDs into mice with liver tumors. After 2.5 h of ip injection, the enhancement of contrast in T 1- and T 2-weighted images has been observed via the accumulation of Mn-NDs in liver tumors of mice. Therefore, Mn-NDs have great potential for in vivo imaging by MR imaging in cancer therapy.

Treatment outcomes with radium-223 in docetaxel-naïve versus docetaxel-treated metastatic castration-resistant prostate cancer patients: Real-world evidence from Taiwan.

While radium (Ra)-223 is among the multiple, known life-prolonging treatments in bone-predominant metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequencing has not been determined, particularly in the Asia-Pacific context. Hence, we aimed to compare treatment outcomes of docetaxel-naïve and post-docetaxel mCRPC patients undergoing Ra-223 therapy in Taiwan. Using a single-center retrospective cohort design, we reviewed records of adult patients receiving Ra-223 for bone-metastatic mCRPC from 2018 to 2021. Patients were categorized into docetaxel-naïve or post-docetaxel groups based on history of docetaxel use preceding Ra-223. We compared the 2 groups in terms of all-cause death, 6-cycle treatment completion, and the following secondary outcomes: pain control, change in biochemical parameters (prostate-specific antigen, lactate dehydrogenase, alkaline phosphatase), biochemical response, and treatment-emergent adverse events. We performed total population sampling and a complete case analysis. We included 48 patients (25 docetaxel-naïve, 23 post-docetaxel) in the study. The mean follow-up duration was 12.4 months for the entire cohort. The docetaxel-naïve group exhibited a significantly lower all-cause mortality rate versus the post-docetaxel group (40.0% vs 78.3%, P = .02), as well as a significantly higher treatment completion rate (72.0% vs 26.1%, P < .01). We did not find significant differences in pain control, change in biochemical parameters, biochemical response, or hematologic treatment-emergent adverse events between the 2 groups. However, the docetaxel-naïve group had a numerically higher pain control rate, numerically greater improvements in alkaline phosphatase and prostate-specific antigen, and numerically lower rates of grade ≥ 3 neutropenia and grade ≥ 3 thrombocytopenia than the post-docetaxel group. Use of Ra-223 in docetaxel-naïve patients with mCRPC led to lower mortality and higher treatment completion than post-docetaxel use. Our study adds preliminary real-world evidence that Ra-223 may be used safely and effectively in earlier lines of treatment for bone-predominant mCRPC. Further large-scale, longer-term, and controlled studies are recommended.

Prospective, Randomized, Double-blind, Placebo-controlled, Pilot Study of Extracorporeal Shock Wave Therapy for Detrusor Underactivity/Underactive Bladder.

BACKGROUND: Detrusor underactivity/underactive bladder (DU/UAB) is a disease with great unmet needs and no current approved drug treatment. Extracorporeal shock wave therapy (ESWT) has been shown to improve regeneration of tissue and increase detrusor contractility in preclinical studies of DU/UAB. OBJECTIVE: To assess ESWT as a treatment of DU/UAB. DESIGN, SETTING, AND PARTICIPANTS: Patients with DU/UAB were enrolled in this phase 2 randomized, double-blind, placebo-controlled, physician-initiated study. INTERVENTION: The patients were assigned to ESWT (N = 6, 2500 shocks, frequency of four pulses per second, and maximum total energy flow density of 0.25 mJ/mm2) once a week for 6 wk at the suprapubic bladder area or to placebo (N = 5, shock wave setting without energy transmission). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the average changes in postvoid residual urine (PVR) from baseline to 4 wk after treatment. Other endpoints included the average changes in 3-d voiding diary, global response assessment of patient satisfaction, Underactive Bladder Questionnaire (UAB-Q) score, and urodynamic evaluation. RESULTS AND LIMITATIONS: The difference in improvement in PVR was -157.8 ml (95% confidence interval [CI]: -380.1, 64.4) versus -6.6 ml (95% CI: -178.1, 164.9) and -77.5 ml (95% CI: -242.1, 87.1) versus 81.8 ml (95% CI: -137.2, 300.7) for ESWT versus placebo (p = 0.116 and 0.056) at 4 and 12 wk, respectively. The ESWT group exhibited a significant reduction in the UAB-Q score (-4.3; 95% CI: -9.1, 0.4) compared with the placebo group (-0.4; 95% CI: -1.8, 1.0) at 4 wk after treatment (p = 0.025), and the effects were decreased at 12 wk (p = 0.091). This study was limited by small sample size. CONCLUSIONS: ESWT was well tolerated with a statistically significant decrease of DU/UAB symptoms and a trend to decrease PVR versus placebo. These results indicate that ESWT may be a promising treatment for DU/UAB and multicenter studies are needed. PATIENT SUMMARY: Bladder shock wave therapy was studied in this randomized, double-blind, placebo-controlled study in patients with inadequate bladder emptying (underactive bladder). Bladder shock wave therapy was found to be well tolerated with an improvement in bladder emptying. These results indicate that bladder shock wave therapy may be a promising treatment for patients who cannot empty their bladder adequately.

Totally X-ray-Free Ultrasound-Guided Mini-Percutaneous Nephrolithotomy in Galdakao-Modified Supine Valdivia Position: A Novel Combined Surgery.

We introduced a novel surgery that combines ultrasound guidance, miniaturization and Galdakao-modified supine Valdivia (GMSV) position in percutaneous nephrolithotomy (PCNL) and evaluated the safety and efficacy. This retrospective, single-center study retrospectively reviewed 150 patients who underwent ultrasound-guided mini-PCNL in the GMSV position from November 2019 to March 2022. All perioperative parameters were collected. Stone-free status was defined as no residual stones or clinically insignificant residual fragments (CIRF) <0.4 cm on postoperative day one. Among the 150 patients, the mean age was 56.96 years. The mean stone size was 3.19 cm (427 mm2). The mean S.T.O.N.E. score was 7.61, including 36 patients (24%) with scores ≥9. The mean operative time was 66.22 min, and the success rate of renal access creation in the first attempt was 88.7%. One hundred and forty (93.3%) patients were stone free. The mean decrease in Hemoglobin was 1.04 g/dL, and no patient needed a blood transfusion. Complications included transient hematuria (n = 13, 8.7%), bladder blood clot retention (n = 2, 1.3%), fever (n = 15, 10%) and sepsis (n = 2, 1.3%). Totally X-ray-free ultrasound-guided mini-PCNL in the GMSV position is feasible, safe and effective for patients with upper urinary tract stones, indicating the synergistic and complementary effects of the three novel techniques.

First-line Immune Checkpoint Inhibitor Versus Immune Checkpoint Inhibitor With Chemotherapy for Cisplatin-ineligible Metastatic Urothelial Carcinoma: Evidence From a Real-world, Multicenter Analysis.

Immune checkpoint inhibitors (ICIs) are widely used for first-line cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC). However, whether to use ICIs as monotherapy or in combination with chemotherapy is still uncertain. We retrospectively analyzed cisplatin-ineligible patients with mUC who underwent first-line ICI monotherapy or ICI plus chemotherapy at 2 medical centers in Taiwan from 2016 to 2021. We calculated the objective response rate, progression-free survival, and overall survival (OS) using the Kaplan-Meier method and Cox regression model for multivariable analysis. In total, 130 patients were enrolled and categorized into 2 groups: an ICI monotherapy group [immunotherapy (IO), n=101] and an ICI plus noncisplatin chemotherapy group [immunotherapy and chemotherapy (IC), n=29]. The median OS of patients in the IO and IC groups was 19.5 and 9.7 months ( P =0.33). Among patients with high programmed cell death ligand-1-expressing tumors, the median OS was significantly prolonged in the IO group compared with the IC group (not reached vs. 6.3 mo, P =0.02). First-line ICI monotherapy demonstrated robust antitumor activity in cisplatin-ineligible patients with mUC. Combining noncisplatin chemotherapy with ICI did not improve clinical outcomes.

The Prognostic Impact of Tumor Location in pT3N0M0 Upper Urinary Tract Urothelial Carcinoma: A Retrospective Cohort Study.

Background: We aimed to evaluate the impact of tumor location on cancer outcomes in patients with pT3N0M0 upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU) with bladder cuff excision. Materials and Methods: We retrospectively reviewed 302 patients with pT3N0M0 UTUC who underwent RNU with bladder cuff excision at our institution between 2005 and 2019, including 191 renal pelvis tumors and 111 ureteral tumors. Clinicopathologic characteristics were compared between renal pelvis and ureter urothelial carcinomas. Multivariate Cox proportional hazard regression was used to assess the association between outcomes and clinical factors. Outcomes of interest included intravesical recurrence-free survival (IVRFS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS), which were measured using the Kaplan-Meier curve with a log-rank test. Results: A total of 302 patients underwent RNU with bladder cuff excision. During the median follow-up of 42.7 months, 70 (23.2%), 95 (31.5%), and 99 (32.8%) patients experienced intravesical recurrence, local recurrence, and distant metastasis, respectively. Seventy (23.2%) patients died from UTUC. Multivariate Cox regression analysis showed that tumor location was an independent predictor of local recurrence (HR = 2.05, p = 0.001), with borderline independent significance in intravesical recurrence (HR = 1.54, p = 0.074) and distant metastasis (HR = 1.45, p = 0.08). Kaplan-Meier analysis showed that ureter tumors had a worse 5-year local recurrence (log-rank p < 0.001) and borderline worse 5-year intravesical recurrence (log-rank p = 0.055) and 5-year distant metastasis (log-rank p = 0.073). Conclusion: Ureter tumors seem to be associated with worse oncological outcomes, especially with local recurrence in UTUC. Further large and long-term studies are warranted for investigating biological differences based on tumor location.

Comparison of the Prognostic Value of Ki-67 and Programmed Cell Death Ligand-1 in Patients with Upper Tract Urothelial Carcinoma.

We retrospectively enrolled 102 patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy to examine the prognostic value of Ki-67 and programmed cell death ligand-1 (PD-L1). Then, we performed PD-L1 and Ki-67 immunohistochemical staining on whole tissue sections. The cut-off value of PD-L1 positivity was a combined positive score (CPS) ≥10 and the Ki-67 overexpression was 20%. Among the 102 patients, 16.7% and 48.0% showed positive PD-L1 expression and Ki-67 overexpression, respectively. A CPS ≥10 was significantly associated with a higher pathological T stage (p = 0.049). In addition, Ki-67 overexpression was significantly associated with a pathological T stage ≥ 2 (p = 0.027) and tumour necrosis (p = 0.016). In the multivariable analysis, a positive PD-L1 expression was significantly correlated with worse cancer-specific survival (HR = 3.66, 95% CI =1.37-9.77, p = 0.01). However, there was no predictive value using a combination of PD-L1 expression and Ki-67 overexpression as a prognostic predictor. Compared with Ki-67 overexpression, a positive PD-L1 expression with CPS ≥ 10 was a stronger independent prognostic factor for CSS in patients with UTUC.

Comparison of Robot-Assisted Laparoscopic Partial Nephrectomy with Laparoscopic Cryoablation in the Treatment of Localised Renal Tumours: A Propensity Score-Matched Comparison of Long-Term Outcomes.

Preserving renal function and controlling oncological outcomes are pertinent when managing renal neoplasms. Cryoablation is the recommended treatment only for clinical T1a stage renal tumour. Here, we compared the outcomes of robot-assisted laparoscopic partial nephrectomy (RaPN) and laparoscopic cryoablation (LCA) in the treatment of patients with localised T1-T2 renal tumours. Overall, 86 patients who received RaPN and 78 patients underwent LCA were included in this study. The intraoperative, postoperative, and oncological outcomes in the LCA group were non-inferior to the RaPN group. Moreover, LCA demonstrated shorter operative time (267.45 ± 104.53 min vs. 138.56 ± 45.28 min, p < 0.001), lower blood loss (300.56 ± 360.73 mL vs. 30.73 ± 50.31 mL, p < 0.001), and slight renal function deterioration because of the reduced invasiveness, without compromising on the oncological outcomes.

Prognostic value of PD-L1 combined positive score in patients with upper tract urothelial carcinoma.

PURPOSE: Upper tract urothelial carcinoma (UTUC) is relatively rare in Western countries. The impact of programmed death-ligand 1 (PD-L1) expression on UTUC remains unclear because previous studies have focused on bladder UC. We investigated the association of PD-L1 expression with clinicopathological features and prognosis in patients with UTUC. METHODS: We retrospectively reviewed the patients with UTUC that we treated at our institute from 2013 to 2018. In total, 105 patients with UTUC undergoing radical nephroureterectomy were analyzed to evaluate the PD-L1 expression on representative whole-tissue sections using the Combined Positive Score (CPS; Dako 22C3 pharmDx assay). A PD-L1 CPS ≥ 10 was considered positive. RESULTS: Among the 105 UTUC cases, 17.1% exhibited positive PD-L1 expression. A CPS ≥ 10 was significantly associated with higher tumor stage (≥ T2, p = 0.034) and lymph node invasion at diagnosis (p = 0.021). A multivariable analysis indicated that a CPS ≥ 10 was an independent prognostic predictor of shorter cancer-specific survival (hazard ratio [HR] = 4.59, 95% confidence interval [CI] = 1.66 - 12.7, p = 0.003) and overall survival (HR = 2.51, 95% CI = 1.19 - 5.27, p = 0.015). CONCLUSIONS: A PD-L1 CPS ≥ 10 in UTUC was associated with adverse pathological features and independently predicted worse cancer-specific and overall survival.

Promise and the Pharmacological Mechanism of Botulinum Toxin A in Chronic Prostatitis Syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) has a negative impact on the quality of life, and its etiology still remains unknown. Although many treatment protocols have been evaluated in CP/CPPS, the outcomes have usually been disappointing. Botulinum neurotoxin A (BoNT-A), produced from Clostridium botulinum, has been widely used to lower urinary tract dysfunctions such as detrusor sphincter dyssynergia, refractory overactive bladder, interstitial cystitis/bladder pain syndromes, benign prostatic hyperplasia, and CP/ CPPS in urology. Here, we review the published evidence from animal models to clinical studies for inferring the mechanism of action underlying the therapeutic efficacy of BoNT in CP/CPPS. Animal studies demonstrated that BoNT-A, a potent inhibitor of neuroexocytosis, impacts the release of sensory neurotransmitters and inflammatory mediators. This pharmacological action of BoNT-A showed promise of relieving the pain of CP/CPPS in placebo-controlled and open-label BoNT-A and has the potential to serve as an adjunct treatment for achieving better treatment outcomes in CP/CPPS patients.

Modest dose anti-thymocyte globulin administered intraoperatively is safe and effective in kidney transplantations: a retrospective study.

BACKGROUND: Anti-thymocyte globulin (ATG) as induction therapy in renal transplantation is facing the dilemma of reducing the incidence of acute rejection (AR) and delayed graft function (DGF) or increasing risks of infection and malignancy. The purpose of this study was to delineate the safety and efficiency of the optimal ATG dosage. METHODS: We retrospectively evaluated 91 deceased donor kidney transplant recipients (KTRs) in our institution between March 2011 and January 2019. The patients were classified into three groups based on induction therapy: (1) Group 1: modest-dose ATG (three mg/kg) intraoperatively (N = 21); (2) Group 2: low-dose ATG (1-1.5 mg/kg) intraoperatively (N = 23); (3) Group 3: basiliximab 20 mg both on day 0 and 4 (N = 47). In Groups 1 and 2, all patients received a daily low-dose program (1-1.5 mg/kg each day) with target dosage of six mg/kg. Induction therapy was combined with standard immunosuppressive regimen consisting of calcineurin inhibitors, mycophenolate/the mammalian target of rapamycin inhibitors and corticosteroids. RESULTS: There was no significant difference in patient characteristics among groups. The outcomes of infection rate, biopsy-proven acute rejection, post-transplant diabetes mellitus, graft survival, and patient survival were similar among groups. Compared to the daily low-dose ATG regimen, the intraoperative modest-dose regimen did not cause more dose interruption and hence was more likely to reach the target ATG dosage. The intraoperative modest-dose regimen also seemed to reduce the rate of DGF. DISCUSSION: In recent years, a trend of using a "lower" dose of ATG has seemed to emerge. Our results suggest intraoperative modest-dose ATG followed by daily low-dose ATG regimen was safe and effective in cadaveric renal transplantations for preventing DGF, AR, and graft loss.

The extracellular domain of epithelial cell adhesion molecule (EpCAM) enhances multipotency of mesenchymal stem cells through EGFR-LIN28-LET7 signaling.

Mesenchymal stem cells (MSCs) are widely considered to be an attractive cell source for regenerative therapies, but maintaining multipotency and self-renewal in cultured MSCs is especially challenging. Hence, the development and mechanistic description of strategies that help promote multipotency in MSCs will be vital to future clinical use. Here, using an array of techniques and approaches, including cell biology, RT-quantitative PCR, immunoblotting, immunofluorescence, flow cytometry, and ChIP assays, we show that the extracellular domain of epithelial cell adhesion molecule (EpCAM) (EpEX) significantly increases the levels of pluripotency factors through a signaling cascade that includes epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), and Lin-28 homolog A (LIN28) and enhances the proliferation of human bone marrow MSCs. Moreover, we found that EpEX-induced LIN28 expression reduces the expression of the microRNA LET7 and up-regulates that of the transcription factor high-mobility group AT-hook 2 (HMGA2), which activates the transcription of pluripotency factors. Surprisingly, we found that EpEX treatment also enhances osteogenesis of MSCs under differentiation conditions, as evidenced by increases in osteogenic markers, including Runt-related transcription factor 2 (RUNX2). Taken together, our results indicate that EpEX stimulates EGFR signaling and thereby context-dependently controls MSC states and activities, promoting cell proliferation and multipotency under maintenance conditions and osteogenesis under differentiation conditions.

Prognostic impact of tumor infiltrating lymphocytes on patients with metastatic urothelial carcinoma receiving platinum based chemotherapy.

The impact of tumor infiltrating lymphocytes (TILs) on survival was confirmed in various cancer types. Our study aims to investigate the prognostic role of TILs on survival in patients with metastatic urothelial carcinoma (mUC) receiving platinum based chemotherapy. Patients who were diagnosed to have pathologically proved mUC between 1997 and 2016 and received palliative chemotherapy with platinum based regimen were recruited into our study. Kaplan-Meier curves and Cox regression analysis were constructed for overall survival (OS). A total of 259 mUC patients were enrolled into our study with median age 63 years and median follow-up visit 13.5 months. Of these patients, 179 (69%) had intense TILs and 80 (31%) had non-intense TILs. The median OS were 15.7 vs. 6.7 months (P = < 0.001) for patients with intense TILs and non-intense TILs, respectively. Subgroup analysis showed that TILs was both prognostically significant no matter for urothelial carcinoma of bladder and upper tract urothelial carcinoma. Multivariate analysis showed that TILs were strongly prognostic factors related to OS. Our study suggested mUC patients with intense TILs were independently associated with survival. Based on our study, TILs is clinically useful for outcomes anticipation and risk stratification, as well as patients counseling.

Outcome of GreenLight HPS laser therapy in surgically high-risk patients.

The aims of this study are to present our experience with GreenLight HPS laser in the treatment of benign prostatic hyperplasia (BPH) and evaluate the outcomes of laser therapy in surgically high-risk patients. This study included a total of 132 patients who were treated for BPH by using GreenLight HPS laser between August 2008 and December 2010 by the same operator. These patients were further divided into five subgroups: group A (age ≧ 80 years), group B (prostate volume ≧ 80 ml), group C (American Society of Anesthesiologists score = 3), group D (anticoagulant use), and group E (non-A, non-B, non-C, and non-D patients). Data on International Prostate Symptom Score, maximum flow rate (Q max), post-void residual urine, and quality-of-life score were evaluated at baseline and at 1, 12, and 24 months after surgery. The result showed that group B patients required a longer lasing time during surgery. In addition, longer post-operative catheterization time and hospital stay were noted in groups B, C, and D patients. Statistically significant improvements were noted post-operatively for all functional parameters in all groups. The proportion of secondary surgery was significantly higher in group B patients. No major complication was observed in all groups. This suggested that GreenLight HPS laser is safe and effective in the treatment of surgically high-risk patients.

High-intensity diode laser in combination with bipolar transurethral resection of the prostate: a new strategy for the treatment of large prostates (>80 ml).

BACKGROUND AND OBJECTIVE: The ideal treatment of large prostates with symptomatic benign prostatic hyperplasia (BPH) remains controversial. We compare the efficacy and safety of monopolar transurethral resection of the prostate (TURP) with high-intensity diode laser in combination with bipolar TURP (DL + b-TURP) in the treatment of large prostates. MATERIALS AND METHODS: We retrospectively analyzed all patients with lower urinary tract symptoms (LUTS) secondary to BPH with prostates larger than 80 ml, undergoing monopolar TURP (n = 36) or DL + b-TURP (n = 37) between January 2008 and March 2010. The preoperative and follow-up functional parameters including International Prostate Symptom Score (IPSS), post-void residual urine (PVR), maximum flow rate (Q(max) ), quality of life score (QoLs), prostate size, and prostate-specific antigen (PSA) were assessed. The operative data, peri- and post-operative complications were also recorded. RESULTS: The demographic data were comparable between the two groups. Preoperative prostate volume was 110.8 ± 28.9 ml in the DL + b-TURP group and 103.7 ± 31.2 ml in the TURP group. TURP group had significantly shorter operative time; however, the catheterization time and hospital stay were in favor of the DL + b-TURP group (P < 0.001). The decrease in hemoglobin was statistically significantly greater in the TURP group. Late complications were also comparable. Both groups could achieve significant improvements in functional outcomes during the follow-up of 24 months. CONCLUSIONS: With regard to the operative safety and functional results, high-intensity diode laser combined with bipolar TURP is feasible for BPH treatment with large prostates.

Rutin, a Flavonoid That Is a Main Component of Saussurea involucrata, Attenuates the Senescence Effect in D-Galactose Aging Mouse Model.

Saussurea involucrata (Kar. et Kir.), known as the snow lotus, grows in the Tian Shan and A'er Tai areas of China. It has recently been reported that the ethyl acetate extract of S. involucrata (SI-2) can inhibit proliferation and induce apoptosis in PC-3 human prostate cancer cells. This study investigated the protective effect of ethyl acetate extract of S. involucrata (SI-2) or rutin, a flavonoid extracted from ethyl acetate extract of S. involucrata (SI-2), on D-galactose- (D-gal-) induced brain injury in mice. Administering SI-2 or rutin (30 mg/kg/d and 30 mg/kg/d) for 6 weeks, concomitant with D-gal injection, significantly increased superoxide dismutase and glutathione peroxidase activities and decreased the MDA level in plasma. Furthermore, the result showed that the percentages of cleaved caspase-3 and PARP in the D-gal-treated mice were much higher than those in the control. Pretreatment using SI-2 or rutin decreased the expression of cyclooxygenase-2 via downregulation of NF-kappaB, resulting in a decrease in lipid peroxidation. Furthermore, our results also showed that oral administration of rutin to these mice significantly improved behavioral performance in a step-through passive avoidance task and these results suggest that SI-2 or rutin exerts potent antiaging effects on D-gal in mice via antioxidative mechanisms.