Platelet-Rich Plasma-Embedded Porous Polycaprolactone Film with a Large Surface Area for Effective Hemostasis.

BACKGROUND: Uncontrollable and widespread bleeding caused by surgery or sudden accidents can lead to death if not treated with appropriate hemostasis. To prevent excessive life-threatening bleeding, various hemostatic agents based on polymeric biomaterials with various additives for accelerated blood coagulation have been adopted in clinical fields. In particular, platelet-rich plasma (PRP), which contains many blood coagulation factors that can accelerate blood clot formation, is considered as one of the most effective hemostatic additives. METHODS: We investigated a PRP-embedded porous film using discarded (expired) PRP and a film with a leaf-stacked structure (FLSS), as a hemostatic agent to induce rapid hemostasis. The film, which contained an LSS on one side (PCL-FLSS), was fabricated by a simple heating-cooling technique using tetraglycol and polycaprolactone (PCL) film. Activated PRP was obtained by the thawing of frozen PRP at the end of its expiration date (the platelet cell membrane is disrupted during the freezing and thawing of PRP, thus releasing various coagulation factors) and embedded in the PCL-FLSS (PRP-FLSS). RESULTS: From in vitro and in vivo experiments using a rat hepatic bleeding model, it was recognized that PRP-FLSS is not only biocompatible but also significantly accelerates blood clotting and thus prevents rapid bleeding, probably due to a synergistic effect of the sufficient supply of various blood coagulants from activated PRP embedded in the LSS layer and the large surface area of the LSS itself. CONCLUSION: The study suggests that PRP-FLSS, a combination of a porous polymer matrix with a unique morphology and discarded biofunctional resources, can be an advanced hemostatic agent as well as an upcycling platform to avoid the waste of biofunctional resources.

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

Progression-directed therapy in patients with oligoprogressive castration-resistant prostate cancer.

PURPOSE: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. MATERIALS AND METHODS: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan-Meier method was used to assess treatment outcomes. RESULTS: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. CONCLUSIONS: PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.

Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease.

INTRODUCTION: With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging. OBJECTIVES: To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds. METHODS: Hybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold. RESULTS: With functionalities of Mg(OH)2 and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD. CONCLUSION: Our study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.

Comparison of Short-Term Outcomes and Safety Profiles between Androgen Deprivation Therapy+Abiraterone/Prednisone and Androgen Deprivation Therapy+Docetaxel in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups. RESULTS: No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups. CONCLUSIONS: ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.

The epidemiology of male lower urinary tract symptoms associated with benign prostatic hyperplasia: Results of 20 years of Korean community care and surveys.

PURPOSE: To investigate the prevalence of lower urinary tract symptoms/benign prostatic hyperplasia in a Korean population. MATERIALS AND METHODS: The Korean Prostate & Voiding Health Association provided free prostate-related community health care and conducted surveys in all regions of Korea from 2001 to 2022 with the cooperation of local government public health centers. A total of 72,068 males older than 50 were surveyed and analyzed. History taking, International Prostate Symptom Score (IPSS), transrectal ultrasonography, prostate-specific antigen (PSA) testing, uroflowmetry, and urine volume testing were performed. RESULTS: The mean prostate volumes in males in their 50s, 60s, 70s, and 80s or above were 24.7 g, 27.7 g, 31 g, and 33.7 g, respectively. The proportion of males with high PSA greater than 3 ng/mL was 3.8% among males in their 50s, 7.7% among males in their 60s, 13.1% among males in their 70s, and 17.9% among males 80 years of age or older. The mean IPSS total scores in males in their 50s, 60s, 70s, and 80s or above were 10.7, 12.7, 14.5, and 16, respectively. Severe symptoms were reported by 27.3% of males, whereas 51.7% reported moderate symptoms. The mean Qmax in males in their 50s, 60s, 70s, and 80s or above were 20 mL/s, 17.4 mL/s, 15.4 mL/s, and 13.8 mL/s, respectively. CONCLUSIONS: In this population-based study, mean prostate volume, IPSS, PSA, and Qmax were 30.6±15.1 g, 14.8±8.2, 1.9±4.7 ng/mL, and 15.6±6.5 mL/s, respectively. Aging was significantly associated with increased prostate volume, PSA levels, and IPSS scores, and with decreased Qmax and urine volume.

Pathologic fractures of the humerus during adjuvant pembrolizumab in patients with renal cell carcinoma after radical nephrectomy: A case report.

INTRODUCTION AND IMPORTANCE: Immune checkpoint inhibitors (ICIs) have noticeably enhanced oncologic outcomes associated with patient survival in different subtypes of metastatic cancer by enhancing cytotoxic T-cell activity. ICI-associated toxicities are often referred to as immune-related adverse events (irAEs) and occur in nearly every organ system. However, the effect of ICIs on the skeleton is poorly examined, and only a few case series have been published. CASE PRESENTATION: A 37-year-old man who presented with pathologic fractures of the right proximal humerus during adjuvant pembrolizumab therapy following laparoscopic radical nephrectomy for right renal cell carcinoma. CLINICAL DISCUSSION: ICIs are associated with various irAEs virtually affecting all host tissues, most of which have been described well by pharmacovigilance analyses. However, to date, very few studies have examined the effects of ICI on the skeleton. CONCLUSION: Urologic oncologists and urologists should be aware of the rare but potentially fatal bone side effects of ICIs.

Kidney tissue regeneration using bioactive scaffolds incorporated with differentiating extracellular vesicles and intermediate mesoderm cells.

BACKGROUND: To overcome the limitations of current alternative therapies for chronic kidney disease (CKD), tissue engineering-mediated regeneration strategies have demonstrated the possibilities for complete kidney tissue regeneration. Given the challenges associated with the reproducibility of renal basal cells, the incorporation of intermediate mesoderm (IM) cells and bioactive materials to control bioactivities of cells with supported scaffolds should be considered as a viable approach to enable the regeneration of the complex kidney structure via renal differentiation. METHODS: We developed PMEZ scaffolds by combining crucial bioactive components, such as ricinoleic acid-grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) integrated into biodegradable porous PLGA (P) platform. Additionally, we utilized differentiating extracellular vesicles (dEV) isolated during intermediate mesoderm differentiation into kidney progenitor cells, and IM cells were serially incorporated to facilitate kidney tissue regeneration through their differentiation into kidney progenitor cells in the 3/4 nephrectomy mouse model. RESULTS: The use of differentiating extracellular vesicles facilitated IM differentiation into kidney progenitor cells without additional differentiation factors. This led to improvements in various regeneration-related bioactivities including tubule and podocyte regeneration, anti-fibrosis, angiogenesis, and anti-inflammation. Finally, implanting PMEZ/dEV/IM scaffolds in mouse injury model resulted in the restoration of kidney function. CONCLUSIONS: Our study has demonstrated that utilizing biodegradable PLGA-based scaffolds, which include multipotent cells capable of differentiating into various kidney progenitor cells along with supporting components, can facilitate kidney tissue regeneration in the mouse model that simulates CKD through 3/4 nephrectomy.

Expired Platelet Concentrate Up-Cycling: Growth Factor-Rich Bioproduct Preparation for FBS Substitute.

Due to the short storage period, large quantities of platelet concentrate (PC) are expiring. The expired PC cannot be injected into a blood vessel, but the activity of bioactive molecules, especially growth factors, is still preserved. In this paper, we organized a process to obtain a growth factor-rich bioproduct for use as a supplement in human cell culture by optimizing freezing, thawing, and sterilization conditions. Each unit of PC displayed visual differences, diverse biochemical values, and growth factor concentrations. To minimize lot-to-lot variation, we pooled a minimum of 10 PC units. The concentrations of growth factors were maximized through five freeze-thaw cycles for 12 h at -80 °C for freezing and for 5 min at 36 °C for thawing. We used a cell strainer with 40 µm pores, followed by a 0.45 µm filter and a 0.22 µm filter sequentially to sterilize the bioproduct with minimizing loss. The obtained growth factors remained stable for 4-6 h at room temperature (23 °C), 24 h at 4 °C, and 12 months at -80 °C. Cellular responses to the growth factor-rich bioproduct were tested with primary human renal proximal tubule epithelial cells. The cells exhibited a significantly increased growth rate, compared to the fetal bovine serum (FBS)-treated control group. The cells maintained their characteristic cuboidal shape, and stem cells and renal progenitor cells also preserved their genetic characteristics during culture. Therefore, the growth factor-rich bioproduct isolated from expired PC through our process can be used as a medium supplement to replace FBS in human cell culture for clinical application.

Using Comparative Proteomics to Identify Protein Signatures in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Renal cell carcinoma (RCC) is one of the most commonly diagnosed cancers in the world. Approximately 25-30% of patients identified with initial kidney cancer will have metastasized tumors, thus 5-year survival rates for these patients are poor. Therefore, biomarker research is required to identify and predict molecular signatures in RCC. MATERIALS AND METHODS: To address this, we used a mass spectrometry (MS)-based proteomics approach to identify proteins related to clear cell RCC (ccRCC) tissues from patients with T1G2, T1G3, T3G2, T3G3, and metastatic RCC (mRCC) stages. RESULTS: We identified and quantified 2,608 and 2,463 proteins, respectively, in ccRCC tissue and identified 1,449 differentially expressed proteins (DEPs). Bioinformatics analysis revealed that serpin family A member 3 (SERPINA3) qualified as biomarker for ccRCC progression. Using indirect enzyme-linked immunosorbent assay (ELISA), immunoblotting, and immunohistochemistry assays it was found that SERPINA3 expression levels in ccRCC tissues were much higher in stages before metastasis. CONCLUSION: Comparative proteomics analysis of ccRCC tissues provided new evidence of SERPINA3 association with ccRCC progression.

Single omental metastasis of renal cell carcinoma after radical nephrectomy: A case report.

BACKGROUND: Renal cell carcinoma (RCC) is the third most common malignancy in the genitourinary tract. The lungs, bone, lymph nodes, liver, and brain are common metastatic sites of RCC. However, there is limited literature on single omental metastasis of RCC. CASE SUMMARY: We present the case of a 44-year-old man with single omental metastasis of RCC after laparoscopic radical nephrectomy. Pathological diagnosis of the resected left kidney revealed pT3a clear cell RCC (Fuhrman grade III). At 6 mo postoperatively, abdominal computed tomography revealed a 12-mm enhancing nodule in the left lower peritoneum. At 7 mo after initial operation, laparoscopic removal of the left omental nodule was performed. The pathological results indicated metastatic clear cell RCC. Currently, the patient is being treated with adjuvant pembrolizumab. CONCLUSION: Omental metastasis of RCC owing to laparoscopic radical nephrectomy is rare. Urologists should be aware of the diverse nature of RCC.

A prospective, multicenter study on the clinical effectiveness of abiraterone in metastatic castration-resistant prostate cancer in Korea: Pre- vs. post-chemotherapy.

PURPOSE: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data. MATERIALS AND METHODS: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded. RESULTS: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups. CONCLUSIONS: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions.

Protaetia Brevitarsis-Derived Protein Hydrolysate Reduces Obesity-Related Colitis Induced by High-Fat Diet in Mice through Anti-Inflammatory Pathways.

Ulcerative colitis is an inflammatory bowel disease characterized by inflammation in the mucosal and submucosal layers of the colon. Obesity is closely related to the occurrence and progression of colitis. The most plausible mechanism linking obesity and colitis is an excessive adipogenesis-related inflammatory response, which causes mucosal dysfunction. Obesity and colitis are linked by several etiologic mechanisms, including excessive adipogenesis, lipotoxicity, pro-inflammatory adipokines/cytokines, macrophage polarization, oxidative stress, endoplasmic reticulum (ER) stress, and gut microbiota. These low-grade enteric inflammations cause mucosal layer damage, especially goblet cell dysfunction through mucin 2 (MUC2) misfolding, ultimately leading to colitis. Inhibiting the inflammatory response can be the most effective approach for treating obesity-related colitis. We focused on the anti-inflammatory effects of polyphenols in Protaectia brevitas larvae. The P. brevitas was prepared as a low molecular protein hydrolysate (PHPB) to increase the concentration of anti-inflammatory molecules. In the current study, we investigated the anti-inflammatory effect of PHPB in an obesity-induced colitis mouse model. Compared with the high-fat diet (HFD) group, the group treated with PHPB exhibited reduced body/organ/fat weight, appetite/food intake inhibition, hypolipidemic effect on ectopic fat, and anti-adipogenic mechanism through the AMPK signaling pathway. Furthermore, we observed attenuated expression of PPARγ and C/EBPα, inhibition of pro-inflammatory molecules, stimulation of anti-inflammatory molecules, probiotic-like effect against obesogenic gut microbiota, inhibition of macrophage polarization into M1, suppression of oxidative/ER stress, and reduction of Muc2 protein misfolding in colon. These diverse anti-inflammatory responses caused histological and functional recovery of goblet cells, eventually improving colitis. Therefore, our findings suggest that the protein hydrolysate of Protaetia brevitarsis can improve obesity-related colitis through its anti-inflammatory activities.

Machine learning based prediction for oncologic outcomes of renal cell carcinoma after surgery using Korean Renal Cell Carcinoma (KORCC) database.

We developed a novel prediction model for recurrence and survival in patients with localized renal cell carcinoma (RCC) after surgery and a novel statistical method of machine learning (ML) to improve accuracy in predicting outcomes using a large Asian nationwide dataset, updated KOrean Renal Cell Carcinoma (KORCC) database that covered data for a total of 10,068 patients who had received surgery for RCC. After data pre-processing, feature selection was performed with an elastic net. Nine variables for recurrence and 13 variables for survival were extracted from 206 variables. Synthetic minority oversampling technique (SMOTE) was used for the training data set to solve the imbalance problem. We applied the most of existing ML algorithms introduced so far to evaluate the performance. We also performed subgroup analysis according to the histologic type. Diagnostic performances of all prediction models achieved high accuracy (range, 0.77-0.94) and F1-score (range, 0.77-0.97) in all tested metrics. In an external validation set, high accuracy and F1-score were well maintained in both recurrence and survival. In subgroup analysis of both clear and non-clear cell type RCC group, we also found a good prediction performance.

Current treatment patterns within 1 year after prostate cancer diagnosis in Korean patients over 75 years old: a retrospective multicenter study.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

Optimal management of renal cell carcinoma in octogenarians: Retrospective analysis using updated Korean Renal Cell Carcinoma (KORCC) database.

BACKGROUND: There is few of optimal management guideline in elderly patients with renal cell carcinoma (RCC). To compare the survival outcomes of octogenarian RCC group and younger RCC group after surgery using nationwide multi-institutional database. METHODS: A total of 10,068 patients who underwent surgery for RCC were included in the current retrospective, multi-institutional study. A propensity score matching (PSM) analysis was conducted to control other confounding factors in analyzing survival outcomes of octogenarian and younger group RCCs. Kaplan-Meier curve analysis to calculate the survival estimates for cancer-specific survival (CSS) and overall survival (OS), and multivariate Cox-proportional hazard regression analyses to evaluate the significant variables associated with the survival outcomes were also performed. RESULTS: Both groups were well-balanced in all baseline characteristics. In a total cohort, Kaplan-Meier survival analysis showed a significantly decreased 5-year and 8-year CSS and OS in the octogenarian group compared with the younger group. However, in a PSM cohort, no significant differences were evident between the two groups in terms of CSS (5-year, 87.3% vs. 87.0%; 8-year, 82.2% vs. 78.9%, respectively, log-rank test, p = 0.964). In addition, age ≥ 80 years (HR, 1.199; 95% CI, 0.497-2.896, p = 0.686) was not a significant prognostic factor of CSS in a PSM cohort. CONCLUSIONS: The octogenarian RCC group after surgery had comparable survival outcomes compared with younger group after PSM analysis. For the life expectancy of octogenarian is getting longer, active treatment is considerable in patients with good performance status.

The Efficacy and Safety of a Human Perirenal Adipose Tissue-Derived Stromal Vascular Fraction in an Interstitial Cystitis Rat Model.

BACKGROUND: Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients' quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model. METHODS: From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 µg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation. RESULTS: The mean pain scores in the SVF 20 µl group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group. In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group. CONCLUSION: This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.

LDHA Desuccinylase Sirtuin 5 as A Novel Cancer Metastatic Stimulator in Aggressive Prostate Cancer.

Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men worldwide. Around 80% of the patients who developed advanced PCa suffered from bone metastasis, with a sharp drop in the survival rate. Despite great efforts, the detailed mechanisms underlying castration-resistant PCa (CRPC) remain unclear. Sirtuin 5 (SIRT5), an NAD+-dependent desuccinylase, is hypothesized to be a key regulator of various cancers. However, compared to other SIRTs, the role of SIRT5 in cancer has not been extensively studied. Here, we revealed significantly decreased SIRT5 levels in aggressive PCa cells relative to the PCa stages. The correlation between the decrease in the SIRT5 level and the patient's reduced survival rate was also confirmed. Using quantitative global succinylome analysis, we characterized a significant increase in the succinylation at lysine 118 (K118su) of lactate dehydrogenase A (LDHA), which plays a role in increasing LDH activity. As a substrate of SIRT5, LDHA-K118su significantly increased the migration and invasion of PCa cells and LDH activity in PCa patients. This study reveals the reduction of SIRT5 protein expression and LDHA-K118su as a novel mechanism involved in PCa progression, which could serve as a new target to prevent CPRC progression for PCa treatment.

Comparison of the efficacy of the early LI-SWT plus daily tadalafil with daily tadalafil only as penile rehabilitation for postprostatectomy erectile dysfunction.

This study compares the efficacy of the early low-intensity shock wave therapy (LI-SWT) plus daily tadalafil with daily tadalafil only therapy as penile rehabilitation for postprostatectomy erectile dysfunction in patients with prostate cancer who underwent bilateral interfascial nerve-sparing radical prostatectomy (robotic or open). From April 2019 to March 2021, 165 patients were enrolled, and 80 of them successfully completed this prospective study. Daily tadalafil were administered to all the patients. LI-SWT consisted of a total of six sessions. Each session was performed on days 4, 5, 6, and 7, and on the second and fourth weeks after surgery. Each LI-SWT session consisted of 300 shocks at an energy density of 0.09 mJ/mm2 and a frequency of 120 shocks per minute that were delivered at each of the five treatment points for 15 min. Thirty-nine patients were treated with tadalafil-only (group A) while 41 were treated with tadalafil and LI-SWT simultaneously (group B). At postoperative 6 months, the proportion of patients with erection hardness scores (EHS) ≥ 3 (4/39 vs. 12/41) was significantly higher in group B (p = 0.034), and LI-SWT was the only independent factor for predicting EHS ≥ 3 (OR, 3.621; 95% CI, 1.054-12.437; p = 0.041). There were no serious side effects related to early LI-SWT. Early LI-SWT plus daily tadalafil therapy as penile rehabilitation for postprostatectomy erectile dysfunction is thought to be more efficacious than tadalafil only. Further large-scaled randomized controlled trials will be needed to validate these findings.