This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism.
RWPE-2 cells were ...randomly divided into three groups: (a) RWPE-2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE-2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague-Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 β-estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA.
ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX-2) through inhibiting TLR4-NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2-COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate.
ESWT improved CP/CPPS and reduced inflammation by degrading COX-2 in microenvironment through TLR4-NFκB-inhibiting pathway. TRAF2 regulator in ERK1/2-COX-2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.
We aimed to identify the association between Hounsfield Unit(HU)-related variables and percutaneous nephrolithotomy (PCNL) outcomes. We enrolled patients with single renal stones (1-3 cm) who ...underwent single-tract PCNL between January 2014 and October 2019. Demographics and stone characteristics were retrospectively reviewed. Preoperative computerized tomography (CT) and follow-up CT within at least 3 months after PCNL were included in this analysis. Stone-free status was defined as residual stone measuring ≤ 2 mm within 3 months postoperatively. HU and cross-sectional area (CSA) were measured using the free-draw technique. We analyzed HU-related variables using logistic regression model for outcomes. Altogether, 188 out of 683 patients met the inclusion criteria. The stone-free rate (SFR) was 79.2%. There were no significant differences in age, sex, BMI, ASA class, laterality, pre-op shockwave lithotripsy, stone size, stone burden, skin-to-stone distance, and HU between the stone-free and remnant groups. CSA and HU/CSA in the stone-free and remnant groups were 94.5 ± 46.1 and 128.3 ± 98.5 (p = 0.043) and 10.1 ± 5.6 and 7.3 ± 3.4 (p = 0.001), respectively. Multivariate logistic regression analysis revealed that pelvis, ureteropelvic junction stones, and HU/CSA were independent predictors of SFR. HU did not affect PCNL outcomes. We believe that HU/CSA could be used for determining stone treatment plans and predicting outcomes.
The authors intend to compare the effects of each targeted therapy (TT) in the treatment of patients with metastatic renal cell carcinoma (mRCC) using big data based on the Korean National Health ...Insurance System (NHIS) and determine the optimal treatment sequence.
Data on the medical use of patients with kidney cancer were obtained from the NHIS database from January 1, 2002, to December 31, 2020. Patient variables included age, sex, income level, place of residence, prescribing department, and duration from diagnosis to the prescription date. The primary outcome was overall survival (OS) for each drug and sequencing. We performed propensity score matching (PSM) according to age, sex, and Charlson Comorbidity Index based on the primary TTs.
After 1:1 PSM, the sunitinib (SUN) (n = 1,214) and pazopanib (PAZ) (n = 1,214) groups showed a well-matched distribution across the entire cohort. In the primary treatment group, PAZ had lower OS than SUN (HR, 1.167; p = 0.0015). In the secondary treatment group, axitinib (AXI) had more favorable OS than cabozantinib (CAB) (HR, 0.735; p = 0.0118), and everolimus had more adverse outcomes than CAB (HR, 1.544; p < 0.0001). In the first to second TT sequencing, SUN-AXI had the highest OS; however, there was no statistically significant difference when compared with PAZ-AXI, which was the second highest (HR, 0.876; p = 0.3312). The 5-year survival rate was calculated in the following order: SUN-AXI (51.44%), PAZ-AXI (47.12%), SUN-CAB (43.59%), and PAZ-CAB (34.28%). When the four sequencing methods were compared, only SUN-AXI versus PAZ-CAB (p = 0.003) and PAZ-AXI versus PAZ-CAB (p = 0.017) were statistically significant.
In a population-based RWD analysis of Korean patients with mRCC, SUN-AXI sequencing was shown to be the most effective among the first to second TT sequencing methods in treatment, with a relative survival advantage over other sequencing combinations. To further support the results of this study, risk-stratified analysis is needed.
Longitudinal tumor sequencing of recurrent bladder cancer (BC) can facilitate the investigation of BC progression-associated genomic and transcriptomic alterations. In this study, we analyzed 18 ...tumor specimens including distant and locoregional metastases obtained during tumor progression for five BC patients using whole-exome and transcriptome sequencing. Along with the substantial level of intratumoral mutational heterogeneity across the cases, we observed that clonal mutations were enriched with known BC driver genes and apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC)-associated mutation signatures compared with subclonal mutations, suggesting the genetic makeup for BC tumorigenesis associated with APOBEC deaminase activity was accomplished early in the cancer evolution. Mutation-based phylogenetic analyses also revealed temporal dynamics of mutational clonal architectures in which the number of mutational clones varied along the BC progression and notably was often punctuated by clonal sweeps associated with chemotherapy. The bulk-level transcriptome sequencing revealed frequent subtype switching in which transcriptionally defined BC subtypes may vary during tumor progression. Longitudinal whole-exome and transcriptome sequencing of recurrent BC may advance our understanding into the BC heterogeneity in terms of somatic mutations, cell clones and transcriptome-based tumor subtypes during disease progression.
Urinary tract infections (UTIs) are infectious diseases that commonly occur in communities. Although several international guidelines for the management of UTIs have been available, clinical ...characteristics, etiology and antimicrobial susceptibility patterns may differ from country to country. This work represents an update of the 2011 Korean guideline for UTIs. The current guideline was developed by the update and adaptation method. This clinical practice guideline provides recommendations for the diagnosis and management of UTIs, including asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, complicated pyelonephritis related to urinary tract obstruction, and acute bacterial prostatitis. This guideline targets community-acquired UTIs occurring among adult patients. Healthcare-associated UTIs, catheter-associated UTIs, and infections in immunocompromised patients were not included in this guideline.
Background. Mesenchymal stem cell therapy (MSCT) and defocused low-energy shock wave therapy (ESWT) has been shown to ameliorate erectile dysfunction (ED). However, the interactions and effects of ...action between MSCT and ESWT remain poorly understood. In this study, we investigated the mechanisms of combination therapy with MSCT and ESWT in a rat model of diabetic ED. Materials and Methods. Eight-week-old male Sprague-Dawley rats were randomly divided into 2 parts. Diabetic rats induced by streptozotocin (65 mg/kg) were randomly divided into 4 groups: (1) DM control group, (2) DM + ESWT group, (3) DM + MSCT group, and (4) DM + ESWT + MSCT group. The sham group was a normal control group (without streptozotocin). MSCT and (or) ESWT were, respectively, administered to each group according to the proposal for 8 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA, and Western blotting. Results. The ratio of ICP/MAP was significantly higher in the DM + ESWT + MSCT group than in ESWT or MSCT treated group (P<0.05). Also, the treatment stimulated angiogenesis and vasodilatation in the corpus cavernosum (P<0.05). ESWT increased the quantity of MSCs in the corpus cavernosum and also induced MSCs to express more VEGF in vitro and vivo (P<0.05) which activated the PI3K/AKT/mTOR and NO/cGMP signaling pathways in the corpus cavernosum. The combination approach stimulated autophagy and decreased apoptosis in the corpus cavernosum. NGF and BDNF expressions were higher in the DM + ESWT + MSCT group than in the DM control group (P<0.01). Furthermore, the treatment promoted the MSC recruitment by inducing penile tissues to express more PECAM and SDF-1. Conclusions. Combination of LI-ESWT and MSCT can get a better result than a single treatment by expressing more VEGF which can take part in autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative therapy would provide a new research direction in ED treatment for the future.
Many studies have demonstrated the mechanisms of progression to castration-resistant prostate cancer (CRPC) and novel strategies for its treatment. Despite these advances, the molecular mechanisms ...underlying the progression to CRPC remain unclear, and currently, no effective treatments for CRPC are available. Here, we characterized the key genes involved in CRPC progression to gain insight into potential therapeutic targets. Bicalutamide-resistant prostate cancer cells derived from LNCaP were generated and named Bical R. RNA sequencing was used to identify differentially expressed genes (DEGs) between LNCaP and Bical R. In total, 631 DEGs (302 upregulated genes and 329 downregulated genes) were identified. The Cytohubba plug-in in Cytoscape was used to identify seven hub genes (
,
,
,
,
,
, and
) associated with CRPC progression. Among these hub genes,
and
were markedly upregulated in CRPC cell lines and CRPC patient samples. The patients with high expression of
and
showed worse disease-free survival in patients with The Cancer Genome Atlas (TCGA)-prostate adenocarcinoma (PRAD) datasets. Our study revealed a potential association between
and
and the progression to CRPC. These results may contribute to the development of potential therapeutic targets and mechanisms underlying CRPC progression, aiming to improve clinical efficacy in CRPC treatment.
Although the intravesical instillation of Bacillus Calmette-Guerin (BCG) is widely used as adjuvant treatment for nonmuscle-invasive bladder cancers, the clinical benefit is variable across patients, ...and the molecular mechanisms underlying the sensitivity to BCG administration and disease progression are poorly understood. To establish the molecular signatures that predict the responsiveness and disease progression of bladder cancers treated with BCG, we performed transcriptome sequencing (RNA-seq) for 13 treatment-naïve and 22 post-treatment specimens obtained from 14 bladder cancer patients. To overcome disease heterogeneity, we used non-negative matrix factorization to identify the latent molecular features associated with drug responsiveness and disease progression. At least 12 molecular features were present, among which the immune-related feature was associated with drug responsiveness, indicating that pre-treatment anti-cancer immunity might dictate BCG responsiveness. We also identified disease progression-associated molecular features indicative of elevated cellular proliferation in post-treatment specimens. The progression-associated molecular features were validated in an extended cohort of BCG-treated bladder cancers. Our study advances understanding of the molecular mechanisms of BCG activity in bladder cancers and provides clinically relevant gene markers for evaluating and monitoring patients.
We examined the association between obesity and prostate cancer based on both body mass index (BMI) and waist circumference (WC) using the National Health Insurance System (NHIS) database for the ...entire male population of Korea.
A total of 1,917,430 men who underwent at least one health examination in 2009 without a previous diagnosis of any other cancer were tracked through December 2015. The hazard ratio (HR) and 95% confidence interval (CI) value for the association between prostate cancer and obesity were analyzed using multiple Cox regression model. Since there was a statistically significant interaction between WC and BMI, a multiple HR for prostate cancer was estimated with stratifying both WC and BMI to control the interaction between WC and BMI.
Without considering WC as an adjustment factor, very weak association between BMI and prostate cancer development risk was observed. When WC was considered as an adjustment factor, no significant change in the HRs for prostate cancer development beyond the reference BMI was observed in the group with WC < 85 cm in the multivariable-adjusted models. However, in the group with WC ≥ 85 cm, the HRs for prostate cancer increased as the BMI increased beyond the reference BMI. In addition, there was a discrepancy in the trend of prostate cancer development according to BMI among the groups with different categories for WC.
In groups with abdominal obesity, a significant linear relationship was observed between increasing BMI and prostate cancer risk. Higher the WC category, the stronger was the association with BMI, signifying that the association of BMI with risk of prostate cancer development depends on abdominal obesity.
To investigate the efficacy and safety of single-port (SP) robotic transperitoneal (TP) and retroperitoneal (RP) partial nephrectomy.
We sequentially analyzed 30 partial nephrectomy performed after ...the SP robot was introduced to the hospital in September 2021 to June 2022. All patients were found to have T1 renal cell carcinoma (RCCs) and were operated by a single expert in conventional robot with da Vinci SP platform.
Total of 30 patients underwent SP robotic partial nephrectomy with 16 (53.33%) by TP approach and 14 (47.67%) by RP. Body mass index was slightly higher in TP group (25.37
23.53,
-value = 0.040). The other demographic information was not significantly different. There was no statistical difference in ischemic time (727.41 ± 561.18 seconds for TP and 698.56 ± 299.23 seconds for RP,
-value = 0.812), and console time (67.97 ± 24.06 minutes for TP and 69.71 ± 28.66 minutes for RP,
-value = 0.724). There was no statistical difference in perioperative and pathologic outcomes either. Postoperative renal function calculated from diethylenetriaminepentacetate was 103.33 mL/min/1.73 m
for TP and 101.33 mL/min/1.73 m
for RP (
-value = 0.214). And 90.36 mL/min/1.73 m
for TP and 87.74 mL/min/1.73 m
for RP at 90 days after surgery (
-value = 0.592).
SP robot partial nephrectomy can be performed effectively and safely regardless of the approach. TP and RP approach offers similar perioperative and postoperative outcomes for T1 RCC. The Clinical Trial Registration number KC22WISI0431.
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