Association of preoperative sarcopenia with the long-term prognosis of patients with bladder cancer undergoing radical cystectomy.

PURPOSE: This retrospective study aimed to assess the correlation between preoperative sarcopenia and long-term oncologic outcomes in patients undergoing radical cystectomy for bladder cancer. METHODS: We included 528 patients who underwent radical cystectomy for bladder cancer between 2000 and 2010 at Asan Medical Center, Seoul, Korea. Preoperative skeletal muscle mass was quantified by analyzing computed tomography images at the third lumbar vertebra. Sarcopenia was defined based on the skeletal muscle index. We evaluated various clinical and pathological factors to analyze the association between sarcopenia and long-term oncologic outcomes. RESULTS: The median follow-up time was 104 months. Sarcopenia was identified in 37.9% of the patients. Although no significant differences were observed in traditional pathological factors between the sarcopenic and non-sarcopenic groups, sarcopenia was significantly associated with worse oncologic outcomes. Compared to the non-sarcopenic groups, the sarcopenic group had lower overall survival rates (52.0% vs. 67.1% at 5 years, 35.5% vs. 52.7% at 10 years) and higher cancer-specific mortality (63.3% vs. 74.3% at 5 years, 50.7% vs. 67.4% at 10 years). Multivariable Cox regression analysis demonstrated that sarcopenia was an independent predictor of cancer-specific survival (hazard ratio: 1.49, 95% confidence interval: 1.11-2.01, p = 0.008), alongside body mass index, tumor stage, lymph node metastasis, and lymphovascular invasion. CONCLUSION: Sarcopenia was significantly associated with poor cancer-specific survival in patients undergoing radical cystectomy for bladder cancer. Detecting sarcopenia may assist in preoperative risk stratification and long-term management after radical cystectomy.

Effectiveness of Adjuvant Chemotherapy in Variant Histology Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy: Stabilized Inverse Probability Treatment Weighting Analysis of Single Center Experience.

PURPOSE: The study aimed to investigate the impact of adjuvant chemotherapy on time to recurrence (TTR) and overall survival (OS) in patients with histologic variants of upper tract urothelial carcinoma (VUTUC) following radical nephroureterectomy (RNU). MATERIALS AND METHODS: A retrospective review of 131 VUTUC patients' medical records, from a pool of 368 non-metastatic localized or locally advanced UTUC cases, treated at a single tertiary referral center between January 2011 and January 2021. The intervention was adjuvant chemotherapy administration post-RNU. TTR and OS were evaluated using Kaplan-Meier and Cox proportional hazard regression, covariates adjusted for age, postoperative GFR, history of neoadjuvant chemotherapy, T and N stage with stabilized inverse probability of treatment weighting (sIPTW). RESULTS: The application of adjuvant chemotherapy showed a significant extension in TTR (P = .01), but no substantial impact on OS (P = .19) after sIPTW adjustment for covariates. Multivariate analysis revealed adjuvant chemotherapy, tumor size, and lymphovascular invasion as significant prognostic factors for TTR. In contrast, only tumor size and perineural invasion were significant for OS. Adjuvant chemotherapy reduced the progression risk in certain VUTUC subtypes (squamous or glandular/micropapillary), but not in sarcomatoid variants. CONCLUSIONS: Adjuvant chemotherapy appears to improve TTR, albeit without a significant effect on OS, in nonmetastatic localized and locally advanced VUTUC patients post-RNU. While beneficial to some VUTUC subtypes, it did not yield significant advantages for sarcomatoid variants. Despite adjustments for known confounders, the study's findings may be subject to potential selection bias and unmeasured confounding factors.

2023 Korean sexually transmitted infections guidelines for non-gonococcal bacterial infection (chlamydia, syphilis, etc.) by the Korean Association of Urogenital Tract Infection and Inflammation.

Non-gonococcal sexually transmitted infections (STIs) include chlamydia, syphilis, and chancroids. Chlamydia is the most common STI caused by Chlamydia trachomatis and is mainly transmitted through sexual intercourse or vertical transmission at birth. Although symptoms are mostly absent or mild, untreated chlamydial infections in females can lead to pelvic inflammatory disease, chronic pelvic pain, and infertility due to the narrowing of fallopian tubes. Syphilis is caused by Treponema pallidum and is divided into phase I, phase II, latent syphilis, and phase III. The incidence of syphilis, including congenital syphilis, has significantly increased in the United States in recent years. The chronic status of this disease can significantly increase morbidity and potentially affect almost all body organs, which, in rare cases, can lead to death. Additionally, untreated maternal syphilis can lead to fetal death and fatal congenital infections in newborns. Chancroid is an STI caused by Haemophilus ducreyi, and its prevalence is gradually decreasing in Korea and worldwide. The symptoms include shallow genital ulcers with suppurative granulomatous inflammation and tender inguinal lymphadenopathy. Chancroids can be differentiated from syphilitic chancres based on their appearance. In contrast to painless chancres, chancroids are painful. Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis are considered symbiotic bacteria. Infections caused by these bacteria are usually not considered STIs and do not require treatment unless they are suspected of being associated with infertility. This article presents the 2023 Korean STI guidelines for non-gonococcal bacterial infections.

Therapeutic potential of BMSC-conditioned medium in an in vitro model of renal fibrosis using the RPTEC/TERT1 cell line.

We investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell-conditioned medium (BMSC-CM) on immortalized renal proximal tubule epithelial cells (RPTEC/ TERT1) in a fibrotic environment. To replicate the increased stiffness characteristic of kidneys in chronic kidney disease, we utilized polyacrylamide gel platforms. A stiff matrix was shown to increase α-smooth muscle actin (α-SMA) levels, indicating fibrogenic activation in RPTEC/TERT1 cells. Interestingly, treatment with BMSC-CM resulted in significant reductions in the levels of fibrotic markers (α-SMA and vimentin) and increases in the levels of the epithelial marker E-cadherin and aquaporin 7, particularly under stiff conditions. Furthermore, BMSC-CM modified microRNA (miRNA) expression and reduced oxidative stress levels in these cells. Our findings suggest that BMSC-CM can modulate cellular morphology, miRNA expression, and oxidative stress in RPTEC/TERT1 cells, highlighting its therapeutic potential in fibrotic kidney disease. [BMB Reports 2024; 57(2): 116-121].

Preoperative C-reactive protein to albumin ratio as a novel prognostic biomarker for the oncological outcomes of radical nephroureterectomy.

PURPOSE: This study aimed to evaluate the prognostic impact of the preoperative C-reactive protein to albumin ratio (CAR) on progression-free survival (PFS) and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). METHODS: A retrospective analysis was conducted using data from a single-center nephroureterectomy registry between January 2011 and December 2017. Participants were categorized into high and low CAR groups based on the optimal CAR cut-off value determined using the Youden index. The primary endpoint was PFS, the time from RNU to metastasis or disease recurrence. The secondary endpoint was CSS, the time from RNU to UTUC-related death. Median PFS and CSS were compared between the high and low CAR groups using Kaplan-Meier analysis and log-rank test. Multivariable Cox proportional hazard regression analysis was performed to assess the prognostic significance of CAR, adjusting for known prognostic factors. RESULTS: We included 491 patients with UTUC in the analysis. The optimal CAR cut-off value was determined to be 0.036, which resulted in classifying 49.3% (242/491) of patients into the high CAR group. The high CAR group had older patients (69.8 vs. 67.4, p-value = 0.01), advanced T and N stages (p-value<0.001), high-grade tumor (p-value = 0.03), and a higher incidence of preoperative hydronephrosis (p-value < 0.01) than the low CAR group. The high CAR group demonstrated significantly inferior median PFS (78.3 vs. 100.3 months, p-value < 0.01) and CSS (73.2 vs. 96.1 months, p-value < 0.01) than the low CAR group. Moreover, high CAR independently increased the risk of disease progression (hazard ratio [HR]: 1.80, 95% confidence interval [CI]: 1.23-2.64, p < 0.01) and UTUC-related mortality (HR: 1.79, 95% CI: 1.15, p < 0.01). CONCLUSION: Pre-operative CAR is independently associated with poor PFS and CSS in patients with UTUC undergoing RNU. Moreover, CAR may be an independent UTUC prognostic factor, offering a cost-effective and minimally invasive marker. However, further validation through large-scale, multi-center studies is necessary to confirm these findings and determine the optimal CAR cut-off value.

Clinical Significance of Radical Prostatectomy in Clinical Lymph Node Metastasis in Prostate Cancer.

BACKGROUND: This study aimed to investigate the role of radical prostatectomy (RP) among clinical nodal metastasis prostate cancer and whether histological confirmation of lymph node metastasis through surgery can help with treatment. PATIENTS AND METHODS: After excluding patients with distant metastatic prostate cancer or neoadjuvant androgen deprivation therapy, 42 patients with clinical nodal metastasis who underwent RP at our institution were included in the study. We classified them as having or not having pathological lymph node metastasis. Clinicopathologic data were analyzed in this retrospective chart review. Kaplan-Meier analysis was used to calculate the estimated castration-resistant prostate cancer (CRPC)-free survival, biochemical recurrence (BCR)-free survival, and cancer-specific survival (CSS). RESULTS: There is no significant difference in age, presence of diabetes mellitus, hypertension, BCR time, CRPC time, overall survival, salvage RT rate, and initial prostate-specific antigen level between the two groups. However, there is a significant difference in the pathology N1 group in terms of pathological T stage, pathologic Gleason score, BCR rate, CRPC rate, and CSS. A multivariate Cox proportional hazard regression analysis was used to identify predictors of CRPC-free survival. Patients with pathological lymph node metastasis had a shorter CRPC-free survival [hazard ratio (HR) 4.87; 95% confidence interval (CI) 1.25-19.00, p = 0.02]. CONCLUSION: Radical prostatectomy can confirm lymph node metastasis. Although pathologic diagnosis has no effect on time to BCR and CPRC, because it affects BCR rate, CRPC rate, and CSS, an accurate pathological diagnosis obtained through surgery is beneficial in the treatment of clinical lymph node metastasis prostate cancer.

Kidney sparing surgery in upper tract urothelial carcinoma: paradigm change in surgical treatment for ureter cancer.

PURPOSE: To extend the indications of kidney-sparing surgery (KSS) for ureter cancer by comparing the oncological outcomes between patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU) or KSS. METHODS: We retrospectively reviewed 708 patients with UTUC who underwent RNU (N = 646) or KSS (N = 62) between 2011 and 2019 to analyze the oncologic outcomes and prognostic factors. Subgroup analyses were performed for patients with unifocal ureteral urothelial carcinoma (UC). RESULTS: No significant difference was observed in the overall survival (OS) or cancer-specific survival (CSS) between RNU and KSS (distal ureterectomy with reimplantation (N = 33), ureterectomy with ileal ureter (N = 14), ureteroscopic tumor resection (N = 10), and ureterectomy with ureteroureterostomy (N = 5)). Among 269 (38.0%) patients with unifocal ureteral UC, 219 and 50 patients underwent RNU and KSS, respectively. OS and CSS were not significantly different between these two groups. Pathologic stage was a significant risk factor in multivariate analysis (hazard ratio = 2.621; p = 0.000). Among 646 RNU patients, 219 (33.9%) had unifocal ureteral UC, 40 (18.3%) with low-grade tumors. Among these, 13 (5.9%) patients with unifocal, low-grade and small (< 2 cm) tumors received nephroureterectomy. CONCLUSION: Kidney-sparing surgery should be regarded as an important alternative to RNU for patients with unifocal ureteral UC thought to have noninvasive disease to preserve renal function and reduce overtreatment.

Effect of decreased renal function on poor oncological outcome after radical cystectomy.

PURPOSE: To evaluate the impact of preoperative renal impairment on the oncological outcomes of patients with urothelial carcinoma who underwent radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with urothelial carcinoma who underwent radical cystectomy from 2004 to 2017. All patients who underwent preoperative 99mTc-diethylenetriaminepentaacetic acid renal scintigraphy (DTPA) were identified. We divided the patients into two groups according to their glomerular filtration rates (GFRs): GFR group 1, GFR≥90 mL/min/1.73 m²; GFR group 2, 60≤GFR<90 mL/min/1.73 m². We included 89 patients in GFR group 1 and 246 patients in GFR group 2 and compared the clinicopathological characteristics and oncological outcomes between the two groups. RESULTS: The mean time required for recurrence was 125.5±8.0 months in GFR group 1 and 85.7±7.4 months in GFR group 2 (p=0.030). The mean cancer-specific survival was 131.7±7.8 months in GFR group 1 and 95.5±6.9 months in GFR group 2 (p=0.051). The mean overall survival was 123.3±8.1 months in GFR group 1 and 79.5±6.6 months in GFR group 2 (p=0.004). CONCLUSIONS: Preoperative GFR values in the range of 60≤GFR<90 mL/min/1.73 m² are independent prognostic factors for poor recurrence-free survival, cancer-specific survival, and overall survival in patients after radical cystectomy compared with GFR values of ≥90 mL/min/1.73 m².

A novel biguanide derivative, IM176, induces prostate cancer cell death by modulating the AMPK-mTOR and androgen receptor signaling pathways.

Background: Metformin and phenformin, biguanide derivatives that are widely used to treat type 2 diabetes mellitus, have recently been shown to exert potential anticancer effects in prostate cancer. This study compared the antiprostate cancer effects of the novel biguanide derivative IM176 with those of metformin and phenformin. Methods: Prostate cancer cell lines and patient-derived castration-resistant prostate cancer (CRPC) cells were treated with IMI76, metformin, and phenformin. The effects of these agents on cell viability, annexin V-FITC apoptosis, mammalian target of rapamycin inhibition, protein expression and phosphorylation, and gene expression were evaluated. Results: IM176 dose dependently reduced the viability of all prostate cancer cell lines tested, with IC50s (LNCaP: 18.5 µM; 22Rv1: 36.8 µM) lower than those of metformin and phenformin. IM176 activated AMP-activated protein kinase, inhibiting mammalian target of rapamycin and reducing the phosphorylation of p70S6K1 and S6. IM176 inhibited the expression of androgen receptor, the androgen receptor splice variant 7, and prostate-specific antigen in LNCaP and 22Rv1 cells. IM176 increased caspase-3 cleavage and annexin V-positive/propidium iodide-positive cells, which indicated apoptosis. Moreover, IM176 reduced viability, with low IC50, in cultured cells derived from two patients with CRPC. Conclusion: The antitumor effects of IM176 were comparable with those of other biguanides. IM176 may therefore be a novel candidate for the treatment of patients with prostate cancer, including those with CRPC.

The association between serum lipid profile and the prostate cancer risk and aggressiveness.

Purpose: This study aims to evaluate the association of serum lipid profile on prostate cancer (PC) risk and aggressiveness. Methods: Men who underwent prostate biopsy between January 2005 and December 2015 were retrospectively analyzed. The association between lipid profile and the risk, stage, and Gleason grade group (GG) of the PC were investigated. Sensitivity analysis was conducted using univariate and multivariate quantile analysis for lipide profile on the risk and stage of PC. Results: Of the 1740 study populations, 720 men (41.4%) were diagnosed as PC. From multivariate logistic regression analysis, age, prostate specific antigen, triglyceride (odds ratio (OR):1.05, confidence interval (CI):1.03-1.07, p-value<0.001) significantly increased PC risk, while total cholesterol (OR:0.96, CI:0.92-0.99, p-value=0.011) significantly decreased the PC risk. The increase of serum triglyceride increased the risk of both of locally advanced (OR:1.03, CI:1.00-1.07, p-value=0.025) and metastatic PC (OR:1.14, CI:1.04-1.25, p-value=0.004). The increase of serum triglyceride increased the risk of GG2-3 (OR:1.03, CI:1.00-1.06, p-value=0.027) and GG4-5 (OR:1.04, CI:1.01-1.08, p-value=0.027). Univariate quartile analysis founded serum triglyceride increasing risk of locally advanced disease than organ confined disease. (OR: 1.00, 1.25, 2.04, 4.57 for 1st, 2nd, 3rd and 4th quartile, p-value<0.001). Adjusted multivariate quartile analysis confirmed statistically significant increasing PC risk of triglyceride (OR: 1.00, 1.25, 2.04, 4.57 for 1st, 2nd, 3rd and 4th quartile, p-value<0.001). Conclusions: This study findings suggested increased in triglyceride level increased the risk PC. Increased in triglyceride level also associated with aggressive presentation of PC, with higher stage and GG.

Laparoscopic renal surgery using multi degree-of-freedom articulating laparoscopic instruments in a porcine model.

PURPOSE: We evaluated the performance of a new multi-degree-of-freedom articulating laparoscopic instrument, ArtiSential, and compared it with that of a straight-shaped instrument and the da Vinci surgical system, in renal surgery using porcine model. MATERIALS AND METHODS: Nine female Yorkshire pigs were equally divided into three groups. The three groups were compared at each surgical step in terms of objective and subjective parameters. RESULTS: The median operative times for renal pedicle clamping and ureter dissection were significantly shorter in ArtiSential group than robotic group (1.3 min vs. 4.7 min, p=0.002; 8.1 min vs. 11.1 min, p=0.015). The median operative time for bladder repair was significantly longer in ArtiSential group than robotic and straight-shaped groups (17.9 min vs. 5.5 min, p=0.002; 17.9 min vs. 9.3 min, p=0.026). There were no significant differences among groups in terms of blood loss or intraoperative complications. ArtiSential device was less useable for renorrhaphy (p=0.009) and bladder repair (p=0.002) compared to the robotic system. ArtiSential group was less accurate than robotic group in terms of tumor resection, renorrhaphy, and bladder repair. During ureter dissection, bladder cuff excision, and bladder repair, the surgeon experienced greater wrist discomfort but lesser back discomfort in ArtiSential group than robotic group. CONCLUSIONS: For most steps, ArtiSential performed as well as robotic and straight-shaped instruments. The development of specialized surgical techniques for ArtiSential will maximize the advantages of these instruments.

Efficacy and Safety of Human Bone Marrow-Derived Mesenchymal Stem Cells according to Injection Route and Dose in a Chronic Kidney Disease Rat Model.

Background and Objectives: We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease. Methods and Results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×106 cells), renal artery moderate dose (RA-MD) (1.0×106 cells), renal artery high dose (RA-HD) (2.0×106 cells), tail vein low dose (TV-LD) (0.5×106 cells), tail vein moderate dose (TV-MD) (1.0×106 cells), and tail vein high dose (TV-HD) (2.0×106 cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p<0.01), 16 weeks (p<0.05), and 24 weeks (p<0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p<0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p<0.01, p<0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups. Conclusions: Our findings confirm the efficacy and safety of high dose (2×106 cells) injection of hBMSC via the tail vein.

Therapeutic Effect of Three-Dimensional Cultured Adipose-Derived Stem Cell-Conditioned Medium in Renal Ischemia-Reperfusion Injury.

Background and Objectives: We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury. Methods and Results: Forty male Sprague-Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla. Conclusions: The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.

Comparison of Stromal Vascular Fraction and Adipose-Derived Stem Cells for Protection of Renal Function in a Rodent Model of Ischemic Acute Kidney Injury.

Aims: Few studies have compared the use of different cell types derived from adipose tissue or the optimal route for efficient and safe cell delivery in ischemic acute kidney injury (AKI). We compared the abilities of stromal vascular fraction (SVF) and adipose-derived stem cells (ADSC), injected via three different routes, to protect renal function in a rodent model of ischemic AKI. Methods: Ninety male Sprague-Dawley rats were randomly divided into 9 groups: sham, nephrectomy control, AKI control, transaortic renal arterial SVF injection, renal parenchymal SVF injection, tail venous SVF injection, transaortic renal arterial ADSC injection, renal parenchymal ADSC injection, and tail venous ADSC injection groups. Their renal function was assessed 4 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures to induce ischemic AKI. The histomorphometric studies were performed 14 days after surgical procedures. Results: Renal parenchymal injection of SVF notably reduced the level of serum blood urea nitrogen and creatinine elevation compared to the AKI control group. Renal parenchymal injection of SVF notably reduced the level of creatinine clearance decrease. In addition, collagen content was lower in the renal parenchymal SVF injection group, and fibrosis was reduced. Apoptosis was reduced in the renal parenchymal SVF injection group, and proliferation was increased. The expression levels of antioxidative markers such as glutathione reductase and peroxidase were higher in the renal parenchymal SVF injection group. Conclusions: Our findings suggest that renal function is protected from ischemic AKI through renal parenchymal injection of SVF, which has enhanced antifibrotic, antiapoptotic, and antioxidative effects.

Solo-surgeon pure laparoscopic donor nephrectomy using passive camera holder: IDEAL stage 2a study.

BACKGROUND: Solo-surgery can be defined as a practice of a surgeon operating alone using a camera holder, without other surgical members except for a scrub nurse. This study was designed to evaluate the feasibility and safety of solo-surgeon pure laparoscopic donor nephrectomy. METHODS: The study protocol was approved by the Institutional Review Board of Asan Medical Center, Seoul, Korea. The brief study protocol was registered on the Clinical Research Information Service site of the Korea Centers for Disease Control and Prevention. Candidates fulfilling all inclusion and exclusion criteria were enrolled in the clinical trial and underwent solo-surgeon pure laparoscopic donor nephrectomy. The feasibility was assessed by the proportion of subjects who could undergo solo-surgeon pure laparoscopic donor nephrectomy without difficulty. The perioperative complications were identified to assess the safety of solo-surgeon pure laparoscopic donor nephrectomy. RESULTS: Of the 47 potential candidates from November 2018 to August 2019, 40 were enrolled in the clinical trial and seven excluded due to declining participation. The feasibility of solo-surgeon pure laparoscopic donor nephrectomy was 100%, without an occasion of any difficulty requiring conversion to the human assisted pure laparoscopic donor nephrectomy. Fourteen intraoperative complications occurred in 10 patients. The most common intraoperative complication was spleen injury. Two of three cases classified as the Satava classification grade II were due to the incomplete stapling of endoscopic stapler. Seventy-eight postoperative complications occurred in 34 patients. The most common postoperative complication was nausea/vomiting and followed by aspartate aminotransferase/alanine aminotransferase elevation. Most postoperative complication was independent of the solo-surgery itself. CONCLUSIONS: Solo-surgeon pure laparoscopic donor nephrectomy using passive camera holder is technically feasible. In terms of safety, it is necessary to adjust the scope of surgery performed alone. Trial Registration CRIS, KCT0003458. Registered 30/01/2019, Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/15868 .

miR-96-5p targets PTEN to mediate sunitinib resistance in clear cell renal cell carcinoma.

A multiple receptor tyrosine kinase inhibitor, sunitinib, is a first-line therapy for clear cell renal cell carcinoma (CCRCC). Unfortunately, it has the major challenges of low initial response rate and resistance after about one year of treatment. Here we evaluated a microRNA (miRNA) and its target responsible for sunitinib resistance. Using miRNA profiling, we identified miR-96-5p upregulation in tumors from sunitinib-resistant CCRCC patients. By bioinformatic analysis, PTEN was selected as a potential target of miR-96-5p, which showed low levels in tumors from sunitinib-resistant CCRCC patients. Furthermore, PTEN and miR-96-5p levels were negatively correlated in a large The Cancer Genome Atlas kidney renal clear cell carcinoma cohort and high miR-96 and low PTEN represented poor prognosis in this cohort. Additionally, four-week sunitinib treatment increased miR-96-5p and decreased PTEN only in tumors from a sunitinib-resistant patient-derived xenograft model. We found a novel miR-96-5p binding site in the PTEN 3' UTR and confirmed direct repression by luciferase reporter assay. Furthermore, we demonstrated that repression of PTEN by miR-96-5p increased cell proliferation and migration in sunitinib-treated cell lines. These results highlight the direct suppression of PTEN by miR-96-5p and that high miR-96-5p and low PTEN are partially responsible for sunitinib resistance and poor prognosis in CCRCC.

Therapeutic Effect of Human Mesenchymal Stem Cell-Conditioned Medium on Erectile Dysfunction.

PURPOSE: Owing to the safety and cost effectiveness of conditioned medium (CM), its therapeutic effects have attracted significant attention from many researchers. To date, numerous studies have been conducted on CM; however, little has been done with regard to erectile dysfunction (ED). In this research, the potential of human mesenchymal stem cell-derived CM (MSC-CM) for the treatment of ED was investigated. MATERIALS AND METHODS: A high concentration of MSC-CM was prepared through 3D spheroid culturing with bone marrow-derived MSCs and cut-off filtering. The composition of CM was analyzed using biochemical assays, and the effect of the preparation process on the quality of CM was investigated. The therapeutic effects of MSC-CM were evaluated through animal studies using a cavernous nerve (CN) injury rat model. RESULTS: 3D spheroid culturing afforded a 278-fold increase in the total protein content of CM, as compared to that from 2D cultures; the protein concentration increased by 19 times on increasing the centrifugation time for cut-off filtering. Biochemical assays indicated that the CM contains various types of angiogenic, neurotrophic, and anti-inflammatory factors. Histological assay results showed that MSC-CM has angio- and neuro-trophic effect in a CN injury rat model in vivo, and these therapeutic effects appear in a dose-dependent manner. CONCLUSIONS: The experimental results confirmed the therapeutic effect of MSC-CM in healing damaged cavernosal tissue and restoring erectile function. These results successfully demonstrated that MSC-CM has significant potential for the treatment of ED.

Biopsy-detected Gleason grade 5 tumor is an additional prognostic factor in metastatic hormone-sensitive prostate cancer.

PURPOSE: A Gleason score ≥ 8, metastatic tumor burden, and visceral metastasis are known prognostic factors for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Notably, however, these indicators have not been fully validated internationally. We aimed in this present study to further analyze the factors that influence the prognosis of mHSPC. METHODS: In this retrospective study, we identified 201 patients with newly diagnosed mHSPC between 2008 and 2014 and collected their clinical information. Cox proportional hazard regression models were used to identify prognostic factors in mHSPC. RESULTS: The mean age of the patients at presentation was 70 years (interquartile range (IQR), 64-76 years). The prostate-specific antigen level was 141 ng/mL (IQR, 58.8-464.5 ng/mL). Of the 201 study patients, 191 (94.5%) and 131 (65.2%) cases had a biopsy Gleason score ≥ 8 and grade 5, respectively. More than 4 metastases were detected in 134 patients. Castration-resistant prostate cancer (CRPC) was evident in 160 cases after a mean follow-up period of 46.6 months. By multivariable analysis, a Gleason grade of 5 and bone metastasis lesion count ≥ 4 were found to be significantly associated with CRPC-free survival (hazard ratio (HR), 1.45; 95% confidence interval (CI), 1.01-2.07) and (HR 2.02; 95% CI 1.39-2.92) and overall survival (HR 1.67 95%; CI 1.16-2.42) and (HR 1.67 95%; CI 1.16-2.41). CONCLUSIONS: Bone metastases ≥ 4 and a Gleason grade 5 are independent prognostic factors for CRPC-free and overall survival in mHSPC. A Gleason grade 5 is therefore a new prognostic indicator in mHSPC.

Association Between Sarcopenia and Survival of Patients with Organ-Confined Renal Cell Carcinoma after Radical Nephrectomy.

BACKGROUND: We aimed to describe the effect of preoperative sarcopenia on oncologic outcomes of organ-confined renal cell carcinoma (RCC) after radical nephrectomy. PATIENTS AND METHODS: A total of 632 patients with pT1-2 RCC who underwent radical nephrectomy between 2004 and 2014 were retrospectively analyzed. From preoperative computerized tomography (CT) scans, skeletal muscle index (SMI) was measured and gender-specific cutoff values at third lumbar vertebra of 52.4 cm2/m2 for men and 38.5 cm2/m2 for women were used to define sarcopenia. Survivals were compared and associations with sarcopenia were analyzed using Kaplan-Meier log rank tests and Cox proportional hazard regression models. Median follow-up was 83 months. RESULTS: Of 632 patients, 268 (42.4%) were classified as sarcopenic. The sarcopenic group was more advanced in age (57 versus 53 years) and more predominantly male (71.3% versus 59.9%). Sarcopenic patients had lower body mass index (BMI, 23.0 versus 25.9 kg/m2), but there was no difference in tumor size, stage, or nuclear grade. Sarcopenia was associated with poorer overall survival (OS) and cancer-specific survival (CSS; OS 94.0% versus 82.1%; p < 0.001 and CSS 97.5% versus 91.8%; p < 0.001). On multivariate analysis, sarcopenia was an independent risk factor for all-cause mortality [hazard ratio (HR) 2.58; 95% CI 1.02-6.54] and cancer-specific mortality (HR 3.07; 95% CI 1.38-6.83). CONCLUSIONS: Sarcopenia at diagnosis was an independent risk factor for all-cause and cancer-specific mortality after radical nephrectomy for pT1-2 RCC. These findings underscore the importance of assessing presence of sarcopenia for risk stratification even among surgical candidates.

Width of spared neurovascular bundle after robot-assisted laparoscopic prostatectomy in patients with prostate cancer: is it a reliable factor for predicting postoperative sexual outcome?

PURPOSE: To investigate the relationship between the width of spared neurovascular bundle (NVB) measured during robot-assisted laparoscopic prostatectomy and postoperative sexual outcomes. METHODS: Patients with localized prostate cancer with erectile hardness score ≥2 (N = 105) who underwent NVB-sparing robot-assisted laparoscopic prostatectomy were included. Patients were divided into three groups [first (Q1) vs. second and third (Q2-3) vs. fourth (Q4) quartile] according to width of spared NVB measured with a flexible ruler after prostate removal. Preoperative and postoperative sexual function was evaluated according to erectile hardness score and Expanded Prostate Cancer Index Composite questionnaires. RESULTS: The proportion of patients with postoperative erectile hardness score ≥2 at postoperative 6 months was as follows: 38.9% (Q1), 48.6% (Q2-3), and 83.3% (Q4) (P = 0.016). The preoperative/postoperative 6-month sexual function score was 40.7/16.9 (Q1), 48.1/19.0 (Q2-3), and 51.2/28.1 (Q4). Postoperative sexual function was significantly associated with preoperative sexual function in Q4 (P = 0.006) and Q2-3 (P = 0.030) but not in Q1. On multivariate analysis, the width of spared NVB was a significant predictor for postoperative 6-month erectile hardness score ≥2. Limitation includes selection bias and short follow-up duration. CONCLUSIONS: Not only the performance but also the degree and quality of NVB sparing thought to be important for postoperative sexual function. Measurement of the width of NVB during surgery could be an easy intraoperative method for assessing the quality of NVB sparing.