Effects of resection volume on postoperative micturition symptoms and retreatment after transurethral resection of the prostate.

PURPOSE: Despite advances in technology, such as advent of laser enucleation and minimally invasive surgical therapies, transurethral resection of the prostate (TURP) remains the most widely performed surgical technique for benign prostatic hyperplasia (BPH). We evaluated resection volume (RV)-derived parameters and analyzed the effect of RV on post-TURP outcomes. METHODS: This observational study used data from patients who underwent TURP at two institutions between January 2011 and December 2021 Data from patients with previous BPH surgical treatment, incomplete data, and underlying disease affecting voiding function were excluded. The collected data included age, prostate-specific antigen, transrectal ultrasound (TRUS)- and uroflowmetry-derived parameters, RV, perioperative laboratory values, perioperative International Prostatic Symptom Score (IPSS), follow-up period, retreatment requirements and interval between the first TURP and retreatment. RESULTS: In 268 patients without prior BPH medication, there were no differences in prostate volume (PV), transitional zone volume (TZV), or RV according to IPSS. A total of 60 patients started retreatment, including medical or surgical treatment, within the follow-up period. There was a significant difference in RV/PV between the groups without and with retreatment respectively (0.56 and 0.37; p = 0.008). However, preoperative TRUS- and uroflowmetry-derived parameters did not differ between the two groups. Multiple linear regression analysis showed that RV (p = 0.003) and RV/TZV (p = 0.006) were significantly associated with differences in perioperative IPSS. In the multivariate logistic regression analysis, only RV/PV was correlated with retreatment (p = 0.010). CONCLUSION: Maximal TURP leads to improved postoperative outcomes and reduced retreatment rate, it may gradually become a requirement rather than an option.

Omics-based biomarkers for diagnosis and prediction of kidney allograft rejection.

Kidney transplantation is the preferred treatment for patients with end-stage kidney disease, because it prolongs survival and improves quality of life. Allograft biopsy is the gold standard for diagnosing allograft rejection. However, it is invasive and reactive, and continuous monitoring is unrealistic. Various biomarkers for diagnosing allograft rejection have been developed over the last two decades based on omics technologies to overcome these limitations. Omics technologies are based on a holistic view of the molecules that constitute an individual. They include genomics, transcriptomics, proteomics, and metabolomics. The omics approach has dramatically accelerated biomarker discovery and enhanced our understanding of multifactorial biological processes in the field of transplantation. However, clinical application of omics-based biomarkers is limited by several issues. First, no large-scale prospective randomized controlled trial has been conducted to compare omics-based biomarkers with traditional biomarkers for rejection. Second, given the variety and complexity of injuries that a kidney allograft may experience, it is likely that no single omics approach will suffice to predict rejection or outcome. Therefore, integrated methods using multiomics technologies are needed. Herein, we introduce omics technologies and review the latest literature on omics biomarkers predictive of allograft rejection in kidney transplant recipients.

Newly diagnosed metastatic pulmonary calcification in a kidney transplantation recipient: a case report.

Metastatic pulmonary calcification (MPC) is defined as calcium deposition in lung tissues. It is commonly seen in end-stage renal disease patients. However, MPC occurring in kidney transplant recipients (KTRs) is rare. We report a case of MPC in a 55-year-old female patient after successful kidney transplantation (KT). One year after KT, bisphosphonate and vitamin D were prescribed for osteoporosis. Then, 4.5 years after KT, we incidentally found multiple nodular lesions on chest X-ray (CXR) without any symptoms. Chest computed tomography showed multiple high-density nodules. A bone scan confirmed MPC in the right middle lobe and right lower lobe. A retrospective review of pretransplant blood chemistry revealed the following: serum calcium level, 11.2 mg/dL; phosphorus level, 3.2 mg/dL; intact parathyroid hormone level, lower than 2.5 pg/mL; and 24-hour urine calcium level, within normal limits (WNL). After KT, all of these parameters remained WNL. Therefore, hidden adynamic bone disease might have been aggravated by bisphosphonate and vitamin D supplementation, causing MPC. Both were discontinued. She was monitored by routine CXR, and MPC did not progress. Since MPC is commonly asymptomatic and difficult to diagnose in KTRs, caution is required when administering such medications. Patient should be followed up with routine CXR.

Effects of intravenous iron therapy on mortality and hospitalization of hemodialysis patients: A prospective cohort study in Korea.

Iron replacement therapy is necessary for anemia treatment in patients with advanced chronic kidney disease. Intravenous (IV) iron therapy is an efficient method for iron replacement. However, there are concerns regarding its considerable side effects, including increased risks of infection or major adverse cardiovascular events (MACE). This is a longitudinal study from a multicenter prospective cohort study conducted in the Korean end-stage renal disease population. All-cause mortality, death due to infection or MACE, hospitalization due to infection or MACE, and all adverse event of death or hospitalization due to infection or MACE were compared according to the iron replacement methods during the first 3 months of enrollment. Among 1,680 hemodialysis patients, 29.3% of patients received IV iron therapy, and 38% of patients received oral iron therapy. During the median 632 days follow-up, all-cause mortality, mortality or hospitalization due to infection or MACE, and all adverse events did not differ among iron replacement groups. There were significant differences related to the risk of all adverse events among iron replacement therapies in the log-rank test and univariate Cox regression analysis only in the prevalent dialysis patients; however, the significance was lost in multivariate Cox regression analysis. Similar results were observed in the 1-year short-term outcome analysis. High-dose IV iron did not increase adverse outcomes. All-cause mortality or all adverse events due to infection or MACE were not higher with the current clinical regimen of IV iron replacement therapy than with oral or no iron therapy in Korean hemodialysis patients.

Development of End Stage Renal Disease after Long-Term Ingestion of Chaga Mushroom: Case Report and Review of Literature.

Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.

Assessment of nephrotoxicity of herbal medicine containing aristolochic acid in mice.

BACKGROUND/AIMS: It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. METHODS: We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. RESULTS: The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2'-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. CONCLUSION: The nephrotoxic potential of HM containing AA was similar to that of AA itself.

Coenzyme Q10 alleviates tacrolimus-induced mitochondrial dysfunction in kidney.

The major side effect of tacrolimus (Tac) is nephrotoxicity. We studied whether supplementation of coenzyme Q10, (CoQ10) a potent antioxidant, can reduce Tac-induced nephrotoxicity via improving mitochondrial function. In an in vitro study, CoQ10 reduced the production of Tac-induced mitochondrial reactive oxygen species and abolished the loss of mitochondrial membrane potential in proximal tubular cell line. Assessment of mitochondrial function revealed that CoQ10 decreased oxygen consumption and mitochondrial respiration rate increased by Tac, suggesting improvement of mitochondrial function to synthesize ATP with CoQ10 treatment. The effect of the CoQ10in vitro study was observed in an experimental model of chronic Tac-induced nephropathy. CoQ10 attenuated Tac-induced oxidative stress and was accompanied by function and histologic improvement. On electron microscopy, addition of CoQ10 increased not only the number but also the volume of mitochondria compared with Tac treatment only. Our data indicate that CoQ10 improves Tac-induced mitochondrial dysfunction in kidney. Supplementary CoQ10 treatment may be a promising approach to reduce Tac-induced nephrotoxicity.-Yu, J. H., Lim, S. W., Luo, K., Cui, S., Quan, Y., Shin, Y. J., Lee, K. E., Kim, H. L., Ko, E. J., Chung, B. H., Kim, J. H., Chung, S. J., Yang, C. W. Coenzyme Q10 alleviates tacrolimus-induced mitochondrial dysfunction in kidney.

Ginseng increases Klotho expression by FoxO3-mediated manganese superoxide dismutase in a mouse model of tacrolimus-induced renal injury.

The antioxidant function of Klotho is well-documented as a regulatory factor implicated in countering the aging process. This study investigated whether ginseng upregulates Klotho and its antiaging signaling in a setting of calcineurin inhibitor-induced oxidative stress. Although tacrolimus treatment reduced Klotho level in the serum and kidney, ginseng treatment was found to reverse the levels. Tacrolimus-induced oxidative stress was reduced by ginseng treatment, with functional and histological improvements. Effect of ginseng on Klotho-induced manganese superoxide dismutase signaling pathway during tacrolimus treatment in mice revealed that ginseng suppressed phosphatidylinositol 3-kinase/serine-threonine kinase Akt-mediated phosphorylation of forkhead box protein O3a and promoted the binding of forkhead box protein O3a to manganese superoxide dismutase promoter. In the mitochondria, ginseng reduced mitochondrial reactive oxygen species production, mitochondrial membrane potential, and oxygen consumption rate, whereas blocking phosphatidylinositol 3-kinase activity with LY294002 enhanced them. These findings together suggested that ginseng attenuated tacrolimus-induced oxidative stress via signaling between Klotho and the phosphatidylinositol 3-kinase/serine-threonine kinase Akt/forkhead box protein O3a-related antioxidant pathway.

Therapeutic potential of coenzyme Q10 in mitochondrial dysfunction during tacrolimus-induced beta cell injury.

We previously reported that oxidative stress induced by long-term tacrolimus treatment impairs mitochondrial function in pancreatic beta cells. In this study, we aimed to investigate the therapeutic potential of coenzyme Q10, which is known to be a powerful antioxidant, in mitochondrial dysfunction in tacrolimus-induced diabetic rats. In a rat model of tacrolimus-induced diabetes mellitus, coenzyme Q10 treatment improved pancreatic beta cell function. The administration of coenzyme Q10 improved insulin immunoreactivity within islets, which was accompanied by reductions in oxidative stress and apoptosis. Assessment of the mitochondrial ultrastructure by electron microscopy revealed that coenzyme Q10 treatment increased the size, number, and volume of mitochondria, as well as the number of insulin granules compared with that induced by tacrolimus treatment alone. An in vitro study using a pancreatic beta cell line showed that tacrolimus treatment increased apoptosis and the production of mitochondrial reactive oxygen species, while cotreatment with coenzyme Q10 effectively attenuated these alterations. At the subcellular level, tacrolimus-induced impairment of mitochondrial respiration was significantly improved by coenzyme Q10, as evidenced by the increased mitochondrial oxygen consumption and ATP production. Our data indicate that coenzyme Q10 plays an important role in reducing tacrolimus-induced oxidative stress and protects the mitochondria in pancreatic beta cells. These findings suggest that supplementation with coenzyme Q10 has beneficial effects in tacrolimus-induced diabetes mellitus.

Effects of resveratrol on Th17 cell-related immune responses under tacrolimus-based immunosuppression.

BACKGROUND: We previously reported that tacrolimus (Tac) does not decrease T helper 17 cells (Th17) response in kidney transplantation. In this study, we evaluated whether Resveratrol (Resv) has immunosuppressive effects by decreasing Th17 responses in Tac-based immunosuppression. METHODS: We investigated the effects of Resv under Tac-treatment conditions, on CD4+ T cell differentiation to Th17 cells in peripheral blood mononuclear cells (PBMCs), and proliferation of CD4+ T cells co-cultured with human renal proximal tubular epithelial cells (HRPTEpiCs). The effects of Resv on Th17 cells were tested in the murine skin transplant model. RESULTS: In PBMCs, Tac did not but combination of Tac and Resv further suppressed Th17 immune response. In the co-culture study, combination of Resv to Tac significantly decreased HRPTEpiC-induced T cell proliferation compared to Tac alone. Resv treatment in the Jurkat cell induced the expression of AMP-activated protein kinase and suppressed the expression of mammalian target of rapamycin (mTOR), suggesting blocking Th17 pathway by Resv. In the murine skin transplant model, combination of Resv to Tac significantly prolonged skin graft survival accompanied by the suppression of Th17 cells, compared to either the Tac-alone or control groups. CONCLUSION: The results of our study suggest that Resv provides additional immunosuppressive effects to Tac by suppressing effector CD4+ T cells, especially Th17 cells, in the transplantation setting.

What is the most effective local anesthesia for transrectal ultrasonography-guided biopsy of the prostate? A systematic review and network meta-analysis of 47 randomized clinical trials.

We aimed to compare the effectiveness of various local anesthetic methods for controlling prostate biopsy (PBx) related pain using network meta-analysis. Literature searches were performed on PubMed/Medline, Embase, and Cochrane Library up to March 2018. Forty-seven randomized controlled trials, in which the effectiveness of PBx-related pain was investigated using a visual analogue scale after various local anesthetic methods, were included. The local anesthetic methods included intraprostatic local anesthesia (IPLA), intrarectal local anesthesia (IRLA), intravenous sedation (IVS), periprostatic nerve block (PNB), pelvic plexus block (PPB), and spinal anesthesia (SPA). Eight pairwise meta-analyses and network meta-analyses with 21 comparisons were performed. All modalities, except single use of IPLA and IRLA, were more effective than placebo. Our results demonstrate that PNB + IVS (rank 1) and SPA (rank 2) were the most effective methods for pain control. The followings are in order of PPB + IRLA, PNB + IPLA, PPB, PNB + IRLA, IVS, and PNB. In conclusion, the most effective way to alleviate PBx-related pain appears to be PNB + IVS and SPA. However, a potential increase in medical cost and additional risk of morbidities should be considered. In the current outpatient setting, PPB + IRLA, PNB + IPLA, PPB, PNB + IRLA, and PNB methods are potentially more acceptable options.

The effects of addition of coenzyme Q10 to metformin on sirolimus-induced diabetes mellitus.

BACKGROUND/AIMS: This study was performed to determine whether adding coenzyme Q10 (CoQ10) to metformin (MET) has a beneficial effect as a treatment for sirolimus (SRL)-induced diabetes mellitus (DM). METHODS: DM was induced in rats by daily treatment with SRL (0.3 mg/kg, subcutaneous) for 28 days, and animals were treated with CoQ10 (20 mg/kg, oral) and MET (250 mg/kg, oral) alone or in combination for the latter 14 days of SRL treatment. The effects of CoQ10 and MET on SRL-induced DM were assessed with the intraperitoneal glucose tolerance test (IPGTT) and by determining plasma insulin concentration and the homeostatic model assessment of insulin resistance (HOMA-R) index. We also evaluated the effect of CoQ10 on pancreatic islet size, apoptosis, oxidative stress, and mitochondria morphology. RESULTS: IPGTT revealed overt DM in SRL-treated rats. The addition of CoQ10 to MET further improved hyperglycemia, decreased HOMA-R index, and increased plasma insulin concentration compared with the SRL group than MET alone therapy. While SRL treatment induced smaller islets with decreased insulin staining intensity, the combination of CoQ10 and MET significantly improved insulin staining intensity, which was accompanied by a reduction in oxidative stress and apoptosis. In addition, co-treatment of CoQ10 and MET significantly increased the levels of antiperoxidative enzymes in the pancreas islet cells compared with MET. At the subcellular level, addition of CoQ10 to MET improved the average mitochondrial area and insulin granule number. CONCLUSION: Addition of CoQ10 to MET has a beneficial effect on SRL-induced DM compared to MET alone.

Effects of age and comorbidity on survival vary according to risk grouping among patients with prostate cancer treated using radical prostatectomy: A retrospective competing-risk analysis from the K-CaP registry.

A multicenter Korean Prostate Cancer Database (K-CaP) has been established to provide information regarding Korean patients with prostate cancer (PCa). We used the K-CaP registry to investigate the value of age and comorbidity for predicting cancer-specific mortality (CSM) and other-cause mortality (OCM) according to risk grouping.The K-CaP registry includes 2253 patients who underwent radical prostatectomy (RP) between May 2001 and April 2013 at 5 institutions. Preoperative clinicopathologic data were collected and stratified according to the National Comprehensive Cancer Network risk criteria. Survival was evaluated using Gray's modified log-rank test according to risk category, age (<70 years vs ≥70 years), and Charlson comorbidity index (CCI) (0 vs ≥1).The median follow-up was 55.0 months (interquartile range: 42.0-70.0 months). Competing-risk regression analysis revealed that, independent of CCI, ≥70-year-old high-risk patients had significantly greater CSM than <70-year-old high-risk patients (P = .019). However, <70-year-old high-risk patients with a CCI of ≥1 had similar CSM relative to ≥70-year-old patients. Survival was not affected by age or CCI among low-risk or intermediate-risk patients. Multivariate analysis revealed that a CCI of ≥1 was independently associated with a higher risk of CSM (P = .003), while an age of ≥70 years was independently associated with a higher risk of OCM (P = .005).Age and comorbidity were associated with survival after RP among patients with high-risk PCa, although these associations were not observed among low-risk or intermediate-risk patients. Therefore, older patients with high-risk diseases and greater comorbidity may require alternative multidisciplinary treatment.

Update of aristolochic acid nephropathy in Korea.

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSION: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.

Cancer-Specific Mortality Among Korean Men with Localized or Locally Advanced Prostate Cancer Treated with Radical Prostatectomy Versus Radiotherapy: A Multi-Center Study Using Propensity Scoring and Competing Risk Regression Analyses.

PURPOSE: Studies comparing radical prostatectomy (RP) outcomes with those of radiotherapy with or without androgen deprivation therapy (RT±ADT) for prostate cancer (PCa) have yielded conflicting results. Therefore, we used propensity score-matched analysis and competing risk regression analysis to compare cancer-specific mortality (CSM) and other-cause mortality (OCM) between these two treatments. MATERIALS AND METHODS: The multi-center, Severance Urological Oncology Group registry was utilized to identify 3,028 patients with clinically localized or locally advanced PCa treated by RP (n=2,521) or RT±ADT (n=507) between 2000 and 2016. RT±ADT cases (n=339) were matched with an equal number of RP cases by propensity scoring based on age, preoperative prostate-specific antigen, clinical tumor stage, biopsy Gleason score, and Charlson Comorbidity Index (CCI). CSM and OCM were co-primary endpoints. RESULTS: Median follow-up was 65.0 months. Five-year overall survival rates for patients treated with RP and RT±ADT were 94.7% and 92.0%, respectively (p=0.105). Cumulative incidence estimates revealed comparable CSM rates following both treatments within all National Comprehensive Cancer Network risk groups. Gleason score ≥ 8 was associated with higher risk of CSM (p=0.009). OCM rates were comparable between both groups in the low- and intermediate-risk categories (p=0.354 and p=0.643, respectively). For high-risk patients, RT±ADT resulted in higher OCM rates than RP (p=0.011). Predictors of OCM were age ≥ 75 years (p=0.002) and CCI ≥ 2 (p < 0.001). CONCLUSION: RP and RT±ADT provide comparable CSM outcomes in patients with localized or locally advanced PCa. The risk of OCM may be higher for older high-risk patients with significant comorbidities.

Re-stratification of Patients with High-Risk Prostate Cancer According to the NCCN Guidelines among Patients Who Underwent Radical Prostatectomy: An Analysis Based on the K-CaP Registry.

PURPOSE: The present study aimed to re-stratify patients with high-risk prostate cancer according to the National Comprehensive Cancer Network guidelines among patients who underwent radical prostatectomy (RP). MATERIALS AND METHODS: This study used the Korean Prostate Cancer Database registry and identified 1,060 patients with high-risk prostate cancer who underwent RP between May 2001 and April 2013. All patients were categorized into risk groups, and subgroups were identified according to the type and number of high-risk factors. RESULTS: Of the 1,060 high-risk patients, 599 (56.5%), 408 (38.5%), and 53 (5.0%) had 1, 2, and 3 risk factors, respectively. In multivariate analysis, the Gleason score, percentage of positive biopsy cores, and number of risk factors present were identified as independent predictors of biochemical recurrence. There were significant differences in the 5-year postoperative biochemical failure-free survival (BCFFS) rate among the different high-risk factor subgroups (log-rank p < 0.001). There were no significant differences in the BCFFS rate between the subgroup of high-risk patients with a prostate-specific antigen level > 20 ng/mL alone and the intermediate-risk group with all factors (log-rank p=0.919 and p=0.781, respectively). Additionally, no significant difference was noted in the BCFFS rate between high-risk patients having all factors and those in the very-high-risk group (p=0.566). CONCLUSION: We successfully re-stratified patients with high-risk prostate cancer and identified the combinations of high-risk criteria that will help in the selection of patients for RP.

Urologic cancers in Korea.

The incidence and prevalence of prostate and kidney cancers have been increasing in Korea during the last decade, and a marked improvement in survival rates has been noted. With a substantial proportion of the cancers diagnosed at an earlier stage of the disease, the landscape of urologic cancer treatment in Korea has been characterized by an exponential increase in the number of patients receiving surgical treatment. Throughout the last decade, an increasing proportion of surgeries have been performed using minimally invasive methods, with a notable increase in robot-assisted surgery.The evaluation and management strategies of urologic cancer in Korea are primarily based on an existing evidence-based framework provided by international guidelines. The adoption and clinical application of novel surgical techniques and systemic agents targeted at advanced stage cancer are promptly adopted; accordingly, multidisciplinary treatment options are often available for various cancers at different stages. At the same time, treatment decisions are greatly influenced by the availability of healthcare resources, which may be limited due to the National Health Insurance reimbursement policy.A racial disparity in cancer features appears to exist for certain urologic cancers among Korean patients, and the optimal management strategy specific for the Korean population has yet to be confirmed. A national comprehensive cancer database is needed for better insight into risk factors, selection of sequential strategies, tumor biology and survival outcome of Korean urologic cancer patients.

Transurethral resection of the prostate for patients with Gleason score 6 prostate cancer and symptomatic prostatic enlargement: a risk-adaptive strategy for the era of active surveillance.

OBJECTIVE: To investigate whether transurethral resection of the prostate can be used as both (i) treatment for symptomatic prostatic enlargement in patients with prostate cancer and (ii) a risk-adaptive strategy for reducing prostate-specific antigen levels and broadening the indications of active surveillance. METHODS: We retrospectively reviewed data of 3680 patients who underwent prostate biopsies at a single institution (March 2006 to January 2012). Of 529 men who had Gleason score 6 prostate cancer and were ineligible for active surveillance, 86 (16.3%) underwent transurethral resection of the prostate for symptomatic prostatic enlargement. We assessed how changes in prostate-specific antigen and prostate-specific antigen density influenced the eligibility for active surveillance and the outcome of subsequent therapy. The following active surveillance criteria were used: prostate-specific antigen ≤ 10 ng/ml, prostate-specific antigen density ≤ 0.15, positive cores ≤ 3 and single core involvement ≤ 50%. RESULTS: The median age, pre-operative prostate-specific antigen and prostate volume were 71 years, 6.95 ng/ml, and 45.8 g, respectively. In 82.6% (71/86) of analyzed cases, ineligibility for active surveillance had resulted from elevated prostate-specific antigen level or prostate-specific antigen density. With a median resection of 16.5 g, transurethral resection of the prostate reduced the percentage of prostate-specific antigen and the percentage of prostate-specific antigen density by 34.5 and 50.0%, respectively, making 81.7% (58/71) of the patients eligible for active surveillance. Prostate-specific antigen level remained stabilized in all (21/21) patients maintained on active surveillance without disease progression during the median follow-up of 50.6 months. Among patients who underwent radical prostatectomy, 96.7% (29/30) exhibited localized disease. CONCLUSIONS: Risk-adaptive transurethral resection of the prostate may prevent overtreatment and allay prostate-specific antigen-associated anxiety in patients with biopsy-proven low-grade prostate cancer and elevated prostate-specific antigen. Additional benefits include voiding symptom improvement and the avoidance of curative therapy's immediate side effects.

Ginseng treatment attenuates autophagic cell death in chronic cyclosporine nephropathy.

AIMS: Chronic cyclosporine (CsA) treatment induces autophagic cell death characterized by excessive autophagosome formation and decreased autophagic clearance. In this study, we evaluated the influence of ginseng treatment on autophagy in chronic CsA nephropathy. METHODS: Mice were treated with CsA (30 mg/kg) with or without Korean red ginseng (KRG) extract (0.2, 0.4 g/kg) for 4 weeks. The effect of KRG on CsA-induced autophagosome formation was measured using phospholipid-conjugated form of LC3-II, beclin-1, and autophagic vacuoles were visualized with electron microscopy. Autophagic clearance was evaluated by accumulation of p62/sequestosome 1 (p62) and ubiquitin, then double immunolabeling for p62 and either LC3-II or ubiquitin. To demonstrate the association between the effects of KRG treatment on autophagy and apoptosis, double immunolabelling for LC3-II and active caspase-3 was performed. Multiple autophagy pathways were also examined. RESULTS: KRG co-treatment significantly decreased the expression of LC3-II, beclin-1, and the number of autophagic vacuoles compared with the CsA group, and these changes were accompanied by improvements in renal dysfunction and fibrosis. CsA-induced accumulation of p62 and ubiquitin was also decreased by KRG treatment, and these proteins were colocalized with LC3-II and with each other. KRG treatment simultaneously reduced the expression of both active caspase-3 and LC3-II in the injured area. KRG treatment during chronic CsA nephropathy induced the expression of AKT/mTOR, which is a pathway that inhibits autophagy, and reduced AMPK expression. CONCLUSION: Ginseng treatment attenuated CsA-induced excessive autophagosome formation and autophagic aggregates. These findings suggest that ginseng has a renoprotective effect against CsA-induced autophagic cell death.