Comparison of Oncologic Outcomes Between Two Alternative Sequences with Abiraterone Acetate and Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Sequential treatment of androgen receptor axis targeted agents (ARAT), abiraterone acetate (ABI) and enzalutamide (ENZA), in metastatic castration-resistant prostate cancer (mCRPC) demonstrated some positive effects, but cross-resistances between ABI and ENZA that reduce activity have been suggested. Therefore, we conducted a meta-analysis to compare oncologic outcomes between the treatment sequences of ABI-ENZA and ENZA-ABI in patients with mCRPC. The primary endpoint was a combined progression-free survival (PFS), and the secondary endpoint was overall survival (OS). A total of five trials on 553 patients were included in this study. Each of the included studies was retrospective. In two studies including both chemo-naïve and post-chemotherapy mCRPC patients, for ABI-ENZA compared with ENZA-ABI, pooled hazard ratios (HRs) for PFS and OS were 0.37 (p < 0.0001; 95% confidence intervals (CIs), 0.23-0.60) and 0.64 (p = 0.10; 95% CIs, 0.37-1.10), respectively. In three studies with chemo-naïve mCRPC patients only, for ABI-ENZA compared with ENZA-ABI, pooled HRs for PFS and OS were 0.57 (p = 0.02; 95% CIs, 0.35-0.92) and 0.86 (p = 0.39; 95% CIs, 0.61-1.21), respectively. The current meta-analysis revealed that ABI-ENZA had a significantly more favorable oncological outcome, but the level of evidence was low. Therefore, large-scale randomized trials may be needed.ope

Does an Alternative Sunitinib Dosing Schedule Really Improve Survival Outcomes over a Conventional Dosing Schedule in Patients with Metastatic Renal Cell Carcinoma? An Updated Systematic Review and Meta-Analysis

Treatment-related adverse events (AEs) can obfuscate the maintenance of a conventional schedule of sunitinib in patients with metastatic renal cell carcinoma. Accordingly, alternative schedules seeking to improve the safety profile of sunitinib have been tested. Recently, two meta-analyses similarly described improved safety profiles favoring a two weeks on and one week off (2/1) schedule, but with conflicting results for survival outcomes. Therefore, we conducted an updated systematic review and meta-analysis, including all recently published studies and using complementary statistical methods. Endpoints included progression-free survival, overall survival, and AEs of 15 types. Eleven articles were included in this meta-analysis. Using adjusted findings, we noted statistically better results in progression-free survival (hazard ratio, 0.58; 95% confidence interval, 0.39-0.84; p = 0.005), but no difference in overall survival (hazard ratio, 0.66; 95% confidence interval, 0.42-1.04; p = 0.08). Moreover, the 2/1 schedule was beneficial for reducing the incidence of several AEs. Conclusively, our meta-analysis suggests that the 2/1 schedule holds promise as an alternative means of reducing AEs and maintaining patient quality of life. While the survival outcomes of the 2/1 schedule seem also to be favorable, the level of evidence for this was low, and the interpretation of these findings should warrant caution. Large scale randomized trials are needed to support these results.ope

Effectiveness of Percutaneous Nephrolithotomy, Retrograde Intrarenal Surgery, and Extracorporeal Shock Wave Lithotripsy for Treatment of Renal Stones: A Systematic Review and Meta-Analysis

Background and objectives: To perform a updated systematic review and meta-analysis comparing effectiveness of percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and extracorporeal shock wave lithotripsy (ESWL) for treatment of renal stones (RS). Materials and Methods: A total of 37 studies were included in this systematic review and meta-analysis about effectiveness to treat RS. Endpoints were stone-free rates (SFR), incidence of auxiliary procedure, retreatment, and complications. We also conducted a sub-analysis of ≥2 cm stones. Results: First, PCNL had the highest SFR than others regardless of stone sizes and RIRS showed a higher SFR than ESWL in <2 cm stones. Second, auxiliary procedures were higher in ESWL than others, and it did not differ between PCNL and RIRS. Finally, in <2 cm stones, the retreatment rate of ESWL was higher than others. RIRS required significantly more retreatment procedures than PCNL in ≥2 cm stones. Complication was higher in PCNL than others, but there was no statistically significant difference in complications between RIRS and PCNL in ≥2 cm stones. For ≥2 cm stones, PCNL had the highest SFR, and auxiliary procedures and retreatment rates were significantly lower than others. Conclusions: We suggest that PCNL is a safe and effective treatment, especially for large RS.ope

Comparison of Ultra-Mini Percutaneous Nephrolithotomy and Retrograde Intrarenal Surgery for Renal Stones: A Systematic Review and Meta-Analysis from the KSER Update Series

Miniaturized percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) for renal stones have been developed to overcome the invasive disadvantages of PCNL. We aimed to compare the therapeutic effect and safety of ultra-mini percutaneous nephrolithotomy (UMPCNL) and RIRS for renal stones using an updated systematic review and meta-analysis. We searched clinical trials comparing UMPCNL and RIRS for renal stones using the PubMed, EMBASE, Cochrane Library, and Google Scholar databases up to October 2021. Seven studies were included in the current study. The renal stone size was 10-20 mm in three studies, 10-25 mm in one study, 10-35 mm in two studies, and not specified in one study. The stone-free rate of UMPCNL was higher than that of RIRS (p = 0.02; odds ratio (OR) = 2.01; 95% confidence interval (CI) = 1.12, 3.61). The complication rate showed no significant difference between UMPCNL and RIRS (p = 0.48; OR = 1.20; 95% CI = 0.73, 1.98). Regarding the operative time, UMPCNL was shorter than RIRS (p = 0.005; weighted mean difference (WMD) = -15.63; 95% CI = -26.60, -4.67). The hospital stay of UMPCNL was longer than that of RIRS (p = 0.0004; WMD = 1.48; 95% CI = 0.66, 2.31). UMPCNL showed higher efficacy than RIRS and similar safety to RIRS. UMPCNL may be a useful therapeutic option for moderate-sized renal stones.ope

Effect of Bladder Neck Preservation on Long-Term Urinary Continence after Robot-Assisted Laparoscopic Prostatectomy: A Systematic Review and Meta-Analysis

This study aimed to evaluate the effect of bladder neck preservation (BNP) on long-term urinary continence after robot-assisted laparoscopic prostatectomy (RALP). We systematically searched the PubMed, Embase, and Cochrane Library databases to identify studies that assessed the difference in urinary continence and oncologic outcomes between patients who underwent RALP with BNP and those who underwent RALP without BNP. Four trials (1880 cases with BNP, 727 controls without BNP) were considered suitable for meta-analysis. BNP was associated with significantly better urinary continence outcomes at 3-4 months (odds ratio (OR), 2.88; 95% confidence interval (CI), 1.52-5.48; p = 0.001), 12 months (OR, 2.03; 95% CI, 1.10-3.74; p = 0.02), and 24 months (OR, 3.23; 95% CI, 1.13-9.20; p = 0.03) after RALP. There was no difference in the rate of overall positive surgical margin (PSM) (OR, 1.00; 95% CI, 0.72-1.39; p = 0.99) and that of PSM at the prostate base (OR, 0.49; 95% CI, 0.21-1.13; p = 0.09) between the two groups. The BNP technique during RALP leads to early return of urinary continence and long-term urinary continence without compromising the oncologic outcomes.ope

A role of phospholipase C isozymes in H2O2-induced oxidative stress of rat aortic smooth muscle cells

Dept. of Medical Science/석사Backgroung Intracellular calcium ions ([Ca2+]i) have an important function in modulating the contractility of all kinds of muscle, including vascular smooth muscle cells. Reactive oxygen species (ROS) can induce Ca2+-overload by directly affecting the Ca2+ handling proteins. Little is known that phospholipase C (PLC) isozymes are involved in the Ca2+-overload induced by ROS in smooth muscle cells. Methods and Results [Ca2+]i response to exogenous H2O2 and ionopore A23187 was measured using the fluorescent probe, fura2-AM, in rat aortic smooth muscle cells(RASMCs). The differential expression levels of PLC isozymes were measured in cells exposed actually with H2O2 and ionopore. The subsequent signaling cascades related with PLC isozymes were also investigated in RASMCs. H2O2 (1 mM) inhibited the proliferation of RASMCs in DMEM containing 0.1% FBS and increased the [Ca2+]i by a 50%. In H2O2-stimulated RASMCs, the expression of PLC-1 was suppressed within 1 hour, but the other PLC isozymes, -, and -form were not affected. In contrast, the expression of PLC-1 and PLC-1 were suppressed by ionophore, A23187 (10M), for 3 hr. The activity of protein kinase C (PKC) was also suppressed in same trend of PLC-1, not PLC-1. Conclusions The H2O2-induced Ca2+ overload may differentially suppress the expression of PLC isozymes in RASMCs and the decreased expression of PLC-1 subsequently inhibited the PKC activity. These results suggest that the PLC/PKC-regulated Ca2+ homeostasis is the crucial targets of exogenous ROS in H2O2-stimulated RASMC.ope

Fate of abstracts presented at the annual meeting of the korean urological association.

PURPOSE: The acceptance rate for journal publication of the abstracts presented at the annual Korean Urological Association (KUA) meeting, the time to publication, and the effect of abstract characteristics on the publication pattern were analyzed and compared with data for abstracts from other major urological meetings. MATERIALS AND METHODS: A total of 1,005 abstracts listed in the abstract books of the 2006 (58th) and 2007 (59th) annual KUA meetings were analyzed, and their subsequent publication as listed in PubMed or KoreaMed between August 2006 and August 2011 was evaluated. RESULTS: A total of 41.59% of abstracts were published as full-length reports. Abstracts on sexual dysfunction, neurourology, prostate cancer, basic research, and benign prostatic hyperplasia showed the highest publication rates (54%, 52.27%, 48%, 47.56%, and 45%, respectively). It took 19.01±12.83 months on average for abstracts to be published in a journal, whereas it took 25.24±14.64 months and 17.51±11.89 months for publication in foreign and Korean journals, respectively (p<0.001). CONCLUSIONS: Approximately 40% of studies presented as abstracts at the KUA meeting are subsequently published as full-length articles. The KJU is the most targeted journal. The mean time to publication is 1.5 years, and publication seems to be influenced by the study subject.ope

Optimal sequencing of the first- and second-line target therapies in metastatic renal cell carcinoma: based on nationally representative data analysis from the Korean National Health Insurance System

Background: 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. Methods: 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. Results: 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. Conclusions: 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. © 2023, The Author(s).ope

당뇨병성 하지 혈관 질환 모델에서의 골수 줄기 세포 치료

Dept. of medicine/박사[한글]당뇨병은 심장 혈관 질환의 가장 중요한 위험 요소 중에 하나이며 최근 그 유병율과 발병율이 증가하여 중요한 보건학적 사회문제로 부각되고 있다. 당뇨병 환자에서 상처 회복이 느리고 조직 손상 시 회복이 느린 것은 경험적으로 알려져 있다. 본 연구의 목적은 쥐를 이용하여 당뇨병에서 하지 허혈 시 재생이 느린 이유를 밝히고 혈관 전구세포나 간엽 줄기 세포와 같은 골수에서 유래한 줄기 세포의 기능을 평가하며 골수 줄기세포를 당뇨병이 유발된 쥐의 급성 하지 허혈 모델에 사용 했을 때의 치료 효과를 보기 위함이다.당뇨병에서 하지 혈관 손상 후 정상으로 회복이 지연되는 것은 골격근 내에 VEGF-A가 적고, 말초 혈액 내에 있는 혈관 전구세포의 수가 적으며 골수에서 유래하는 혈관 전구세포 그리고 간엽 줄기 세포의 혈관 재생에 관여하는 세포 기능이 떨어진 것 때문인 것으로 사료된다. 또한 당뇨병 쥐에서 얻은 골수 유래 전구세포는 VEGF-A등의 중요한 혈관 재생에 필요한 cytokine의 mRNA 양이 정상 쥐에서 얻은 세포에 비해 적었다. 정상 쥐에서 채취한 혈관 전구 세포와 간엽 줄기 세포를 당뇨병 쥐의 하지 허혈 수술 후 주사 한 결과 대조군에 비해 현저한 혈류 개선 효과를 보여 주었다. 주사한 세포는 2주 관찰 하는 동안 조직 내에서 살아 있었으며 골격근 내에서 미세 혈관 및 증식 중인 세포의 개수가 증가된 것을 보여주었다. 이는 투여한 세포에서 분비되는 VEGF-A, FGF-2, PlGF등의 혈관 조성에 관여하는 단백질의 증가 효과와 줄기 세포가 미세 혈관을 구성하는 일부 세포로 분화되었기 때문으로 본 연구 결과 추론할 수 있었다.결론적으로 당뇨병에서 하지 허혈에 대한 회복이 느린 것은 당뇨병에 의한 하지 조직 자체의 변화와 골수 및 말초 혈액에서 줄기 세포의 기능이 떨어진 것에 기인한 것으로 사료되며 정상 골수 줄기 세포를 이용하면 허혈 손상 시 치료 효과를 얻을 수 있을 것으로 사료 된다. [영문]Diabetes mellitus (DM) is one of the greatest risk factors for the cardiovascular disease. Diabetes patients have delayed wound healing and recovery from vascular injury. Coronary and peripheral occlusive disease and its complication such as acute myocardial infarction and peripheral artery disease have been an important issue among in cardiovascular medicine. The purpose of these experiments is to show the mechanism of the delayed recovery from the ischemic injury in DM and to reveal the molecular functional assessment of the bone marrow derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) as well as to study their therapeutic application with the murine hindlimb ischemia model.Blood flow recovery from the hindlimb ischemia was delayed in the diabetic mice. This study showed the possible mechanisms for the delay : decrease vascular endothelial growth factor (VEGF)-A level in the diabetic skeletal muscle; decreased circulating EPCs number in DM; decreased the important angiogenic cytokines such as VEGF-A, insulin-like growth factor-1, angiopoietin-1 in the diabetic bone marrow derived mononuclear cells (BM-MNC) with RT-PCR; decreased VEGF-A in diabetic EPCs, and MSCs; reduced multiple angiogenesis related cytokines in diabetic BM-MNCs, EPCs and MSCs with Microarray, functional derangements of EPCs and MSCs for angiogenesis confirmed by migration, adhesion, tube formation assay. Transplantation of EPCs and MSCs cultured from normal BM-MNCs to the diabetic hindlimb ischemia showed significantly better recovery compared to the saline injection. The mechanism of these favorable effects was proposed of increased capillary density, long engraftment of the injected stem cells up to 2 weeks in vivo, increased cytokines such as VEGF-A, HIF-1α, FGF-2, and PlGF in the cell transplanted hindlimb, and partly transdifferentiation to the newly forming vascular structures of the injected stem cells documented by co-localization of injected cells to vessels. In conclusion, DM induced delayed blood flow recovery after ischemia and showed dysfunction of bone marrow derived stem cells such as EPCs and MSCs. Normal EPCs or MSCs transplantation in to diabetic hindlimb ischemia showed significant improvement in their recovery from ischemia.ope

The natural course of incidental ureteral polyp during ureteroscopic surgery: KSER research

Background: The natural course of polypoid lesions in the ureter during ureteroscopic stone surgery was not yet clarified. Methods: Patient data were collected prospectively from six teaching hospitals between 2019 and 2021. Patients with polypoid lesions in the ureter distal to ureteral stones were included during ureteroscopy. Computed tomography was performed on all enrolled patients three months after the procedure. Follow-up ureteroscopy was performed only if the patient consented, due to the need for general anesthesia and ethical considerations. Results: Among the 35 patients who were followed up, 14 had fibroepithelial polyps and 21 had inflammatory polyps. Twenty of the followed-up patients underwent ureteroscopy, and nine of them had fibroepithelial polyps. Although fibroepithelial polyps did not disappear in the follow-up ureteroscopy (p = 0.002), the rate of postoperative hydronephrosis was not higher in the fibroepithelial group than in the inflammatory group. Postoperative ureteral stricture and moderate-to-severe hydronephrosis were found to be closely related to the number of resected polyps, regardless of the type of polyp (p = 0.014 and 0.006, respectively). Conclusion: Fibroepithelial polyps in the ureter may persist after treatment of adjacent ureter stones. However, conservative management may be preferable to active removal of ureteral polyps because fibroepithelial polyps may not contribute to clinically significant hydronephrosis after surgery, and inflammatory polyps disappear spontaneously. Hasty resections of polyps may increase the risk of ureteral stricture.ope