A Proposal for Standardization of Early Outcomes Following Robot-Assisted Radical Cystectomy (RARC): RARC Tetrafecta.

BACKGROUND: Currently, there is no dedicated tool to record the early outcomes of robot-assisted radical cystectomy (RARC), and existing criteria for longer-term outcomes require a minimum of 3 months for assessment. However, early evaluation is essential to prevent future morbidity and mortality, especially in surgeries with a high risk of complications in the short term. We propose a comprehensive approach to report early RARC outcomes and investigate the influence of surgeon experience on these results. PATIENTS AND METHODS: We retrospectively analyzed the outcomes of patients who underwent RARC for bladder cancer between April 2009 and April 2020. The cohort was divided chronologically into three groups: patients 1-60 in group 1, 61-120 in group 2, and 121-192 in group 3. Patients with yields of ≥ 16 lymph nodes (LN), negative soft tissue surgical margins, absence of transfusion, and absence of major complications at 30 days were regarded as attaining the RARC tetrafecta. RESULTS: Of the 192 included patients, 93 (48.4%) achieved RARC tetrafecta, with the proportion increasing with surgical experience from 41.7% in group 1 to 55.6% in group 3. Age [odds ratio (OR) 0.947; 95% confidence interval (CI) 0.924-0.970; P = 0.021], LN yield (OR 1.432; 95% CI 1.139-1.867; P = 0.001), and greater surgical experience with RARC (> 120 patients; OR 2.740; 95% CI 1.231-6.100; P = 0.014) were significantly associated with the achievement of RARC tetrafecta. CONCLUSIONS: RARC tetrafecta could be a comprehensive method for reporting early outcomes in patients undergoing RARC, with improvements aligned with the surgeon's experience.

Sextant Systematic Biopsy Versus Extended 12-Core Systematic Biopsy in Combined Biopsy for Prostate Cancer.

BACKGROUND: This study assessed the comparative effectiveness of sextant and extended 12-core systematic biopsy within combined biopsy for the detection of prostate cancer. METHODS: Patients who underwent combined biopsy targeting lesions with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3-5 were assessed. Two specialists performed all combined cognitive biopsies. Both specialists performed target biopsies with five or more cores. One performed sextant systematic biopsies, and the other performed extended 12-core systematic biopsies. A total of 550 patients were analyzed. RESULTS: Cases requiring systematic biopsy in combined biopsy exhibited a significant association with age ≥ 65 years (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.25-4.32; P = 0.008), PI-RADS score (OR, 2.32; 95% CI, 1.25-4.32; P = 0.008), and the number of systematic biopsy cores (OR, 3.69; 95% CI, 2.11-6.44; P < 0.001). In patients with an index lesion of PI-RADS 4, an extended 12-core systematic biopsy was required (target-negative/systematic-positive or a greater Gleason score in the systematic biopsy than in the targeted biopsy) (P < 0.001). CONCLUSION: During combined biopsy for prostate cancer in patients with PI-RADS 3 or 5, sextant systematic biopsy should be recommended over extended 12-core systematic biopsy when an effective targeted biopsy is performed.

Potential Role of Macrophage Polarization in the Progression of Hunner-Type Interstitial Cystitis.

BACKGROUND: Hunner-type interstitial cystitis (HIC) is a chronic inflammatory condition of the bladder. However, it remains unclear whether there is a causal relationship between the presence of Hunner lesions and seemingly normal-appearing areas in the bladder (non-Hunner lesions). This study aimed to investigate the fundamental aspects of HIC by examining potential genetic differences between Hunner and non-Hunner lesions and elucidate their role as potential markers in the progression and suppression of the disease. METHODS: This cross-sectional study enrolled patients with HIC (n = 10) who underwent supratrigonal cystectomy along with augmentation cystoplasty. Full-thickness bladder tissue was collected from Hunner and non-Hunner lesions in the same patient. Normal bladder tissue biopsies were also obtained as controls. Whole transcriptome analysis was performed to analyze the gene expression patterns and immune cell populations. RESULTS: The mucosal layers of patients exhibited similar pathway dysregulation across Hunner and non-Hunner lesions, with immunerelated pathways being prominently affected. In the mucosal layer, genes related to anti-inflammatory and immune suppression were downregulated in Hunner lesions compared to non-Hunner lesions. Moreover, in Hunner lesions, genes related to macrophage differentiation and polarization, such as VSIG4, CD68, MAFB, and LIRB4, were downregulated. The cell fraction of M2 macrophages was found to decrease in Hunner lesions. Immunohistochemical staining revealed an elevated fraction of M1 macrophages and a reduced fraction of M2 macrophages in Hunner lesions compared to those in non-Hunner lesions. In the muscular layer, transcriptomic evidence of muscle thickness was observed in both Hunner and non-Hunner lesions; however, the difference was not significant. CONCLUSION: Hunner lesions showed a reduced expression of anti-inflammatory and immunosuppressive factors compared to non-Hunner lesions, along with alterations in immune cell populations. This study suggests the possibility that macrophage polarization is related to the progression from non-Hunner lesions to Hunner lesions, suggesting its relevance to the characteristics of autoimmune diseases.

Penoscrotal defect reconstruction using loco-regional flaps in treatment of extramammary Paget's disease: Experience and suggestion of a simplified algorithm.

BACKGROUND: Reconstruction of penoscrotal defects resulted from margin-controlled excision of extramammary Paget's disease (EMPD) remains challenging, due to its unpredictably varying extents. The present study aimed to investigate outcomes of reconstruction of penoscrotal defects following radical excision of EMPD and to introduce a simplified algorithm for selecting reconstruction strategies. METHODS: Patients with penoscrotal EMPD who were treated with wide excision and subsequent reconstruction from 2009 to 2020 were reviewed. Their demographics, operation-related characteristics, and postoperative outcomes were evaluated. RESULTS: In total, 46 patients with a mean age of 64.9 years (range, 44-85 years) were analyzed. An average size of defects was 129.6 cm2 (range, 8-900 cm2 ). The most frequently involving anatomical subunit was scrotum, followed by suprapubic area and penile shaft. Twenty-six patients had defects spanning multiple subunits. The most commonly used reconstruction methods for each anatomical subunit were internal pudendal artery perforator (IPAP) flaps and/or scrotal flaps for scrotal defects, superficial external pudendal artery perforator (SEPAP) flaps for suprapubic defects, and skin grafts for penile defects. In all but four cases, successful reconstruction was achieved with combination of those reconstruction options. No major complications developed except for one case of marginal flap necrosis. All patients were satisfied with their aesthetic and functional results. CONCLUSIONS: Diverse penoscrotal defects following excision of EMPD could be solidly reconstructed with combination of several loco-regional options. A simplified algorithm using in combination of IPAP flap, SEPAP flap, scrotal flap, and skin graft may enable efficient and reliable reconstruction of penoscrotal EMPD defects.

Fat Loss in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors.

The purpose of this study was to determine the prognostic impact of fat loss after immune checkpoint inhibitor (ICI) treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). Data from 60 patients treated with ICI therapy for metastatic ccRCC were retrospectively analyzed. Changes in cross-sectional areas of subcutaneous fat (SF) between the pre-treatment and post-treatment abdominal computed tomography (CT) images were expressed as percentages and were divided by the interval between the CT scans to calculate ΔSF (%/month). SF loss was defined as ΔSF < -5%/month. Survival analyses for overall survival (OS) and progression-free survival (PFS) were performed. Patients with SF loss had shorter OS (median, 9.5 months vs. not reached; p < 0.001) and PFS (median, 2.6 months vs. 33.5 months; p < 0.001) than patients without SF loss. ΔSF was independently associated with OS (adjusted hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.07-2.07; p = 0.020) and PFS (adjusted HR, 1.57; 95% CI, 1.17-2.12; p = 0.003), with a 5%/month decrease in SF increasing the risk of death and progression by 49% and 57%, respectively. In conclusion, Loss of SF after treatment initiation is a significant and independent poor prognostic factor for OS and PFS in patients with metastatic ccRCC who receive ICI therapy.

Characterization and functional roles of KCNQ-encoded voltage-gated potassium (Kv7) channels in human corpus cavernosum smooth muscle.

The group of KCNQ-encoded voltage-gated potassium (Kv7) channels includes five family members (Kv7.1-7.5). We examined the molecular expression and functional roles of Kv7 channels in corporal smooth muscle (CSM). Isolated rabbit CSM strips were mounted in an organ bath system to characterize Kv7 channels during CSM relaxation. Intracellular Ca2+ levels were measured in the CSM using the Ca2+ dye Fluo-4 AM. The expression of the KCNQ1-5 (the encoding genes for Kv7.1-7.5) and KCNE1-5 subtypes was determined by quantitative real-time PCR. Electrophysiological recordings and an in situ proximity ligation assay (PLA) were also performed. ML213 (a Kv7.2/7.4/7.5 activator) exhibited the most potent relaxation effect. XE911 (a Kv7.1-7.5 blocker) significantly inhibited the relaxation caused by ML213. Removal of the endothelium from the CSM did not affect the relaxation effect of ML213. H-89 (a protein kinase A inhibitor) and ESI-09 (an exchange protein directly activated by cAMP inhibitor) significantly inhibited ML213-induced relaxation (H-89: 31.3%; ESI-09: 52.7%). XE991 significantly increased basal [Ca2+]i in hCSM cells. KCNQ4 (the Kv7.4-encoding gene) and KCNE4 in CSM were the most abundantly expressed subtypes in humans and rats, respectively. KCNQ4 and KCNE4 expression was significantly decreased in diabetes mellitus rats. ML213 significantly increased the outward current amplitude. XE991 inhibited the ML213-induced outward currents. ML213 hyperpolarized the hCSM cell membrane potential. Subsequent addition of XE991 completely reversed the ML213-induced hyperpolarizing effects. A combination of Kv7.4 and Kv7.5 antibodies generated a strong PLA signal. We found that the Kv7.4 channel is a potential target for ED treatment.

Utility of lymphadenectomy in bladder cancer: where do we stand?

PURPOSE OF REVIEW: The aim of this review is to provide insight into the current state of lymph node dissection (LND) during radical cystectomy in patients with bladder cancer (BCa). RECENT FINDINGS: The first prospective, multicenter, randomized, phase III trial to assess the therapeutic benefit of extended versus limited LND at the time of radical cystectomy failed to demonstrate relevant improvement with extended LND, but showed that this approach does not increase overall complications. Although contemporary rate of LND during radical cystectomy has increased, it remains suboptimal. Minimally invasive radical cystectomy with LND is feasible in most patients and has similar lymph node yields and complication rates compared with open procedures when performed by experienced surgeons. Overall major complication, readmission and mortality rates do not significantly differ according to extent of LND. SUMMARY: Meticulous LND provides both diagnostic and potentially therapeutic benefits in patients with bladder cancer. Results of ongoing trials will provide additional insights regarding the anatomic extent and therapeutic benefit of extended versus standard true pelvic-only LND.

Strategy for Prostate Cancer Patients with Low Prostate Specific Antigen Level (2.5 to 4.0 ng/mL).

BACKGROUND: To evaluate the strategy for detection of prostate cancer (PCa) with low prostate specific antigen (PSA) level (2.5-4.0 ng/mL), prostate biopsy patients with low PSA were assessed. We evaluated the risk of low PSA PCa and the strategy for screening low-PSA patients. METHODS: We retrospectively analyzed the patients who underwent prostate biopsy with low PSA level. Baseline characteristics, PSA level before prostate biopsy, prostate volume, prostate specific antigen density (PSAD), and pathological data were assessed. RESULTS: Among the 1986 patients, 24.97% were diagnosed with PCa. The PSAD was 0.12 ± 0.04 ng/mL² in the PCa-diagnosed group and 0.10 ± 0.04 ng/mL² in non-cancer-diagnosed group (P < 0.001). Of the 496 patients diagnosed with PCa, 302 (60.89%) were in the intermediate- or high-risk group. PSAD was 0.13 ± 0.04 ng/mL² in the intermediate- or high-risk group and 0.11 ± 0.03 ng/mL² in the very low- and low-risk group (P < 0.001). Of 330 patients who underwent radical prostatectomy, 85.15% were diagnosed as having significant cancer. There was significant correlation between PSAD and PCa (r = 0.294, P < 0.001). PSAD with a specificity of 80.00% of a clinically significant cancer diagnosis was assessed at 0.1226 ng/mL². CONCLUSION: The PCa detection rate in the low-PSA group was not lower than that of previous studies of patients with PSA from 4.0 to 10.0 ng/mL. Further, it may be helpful to define a strategy for PCa detection using PSAD in the low-PSA group.

Synergistic Effects of Combination Therapy with AKT and mTOR Inhibitors on Bladder Cancer Cells.

Despite comprehensive genomic analyses, no targeted therapies are approved for bladder cancer. Here, we investigate whether a single and combination therapy with targeted agents exert antitumor effects on bladder cancer cells through genomic alterations using a three-dimensional (3D) high-throughput screening (HTS) platform. Seven human bladder cancer cell lines were used to screen 24 targeted agents. The effects of 24 targeted agents were dramatically different according to the genomic alterations of bladder cancer cells. BEZ235 (dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor) showed antitumor effects against most cell lines, while AZD2014 (mTOR inhibitor) had an IC50 value lower than 2 µM in 5637, J82, and RT4 cell lines. AZD5363 (protein kinase B (AKT) inhibitor) exerted antitumor effects on 5637, J82, and 253J-BV cells. J82 cells (PI3KCA and mTOR mutations) were sensitive to AZD5363, AZD2014, and BEZ235 alone or in AZD5363/AZD2014 and AZD5363/BEZ235 combinations. Although all single drugs suppressed cell proliferation, the combination of drugs exhibited synergistic effects on cell viability and colony formation. The synergistic effects of the combination therapy on the PI3K/Akt/mTOR pathway, apoptosis, and EMT were evident in Western blotting. Thus, the 3D culture-based HTS platform could serve as a useful preclinical tool to evaluate various drug combinations.

A randomized, double-blind, placebo-controlled trial to evaluate the role of curcumin in prostate cancer patients with intermittent androgen deprivation.

BACKGROUND: The anti-cancer activities of curcumin are well-documented from preclinical studies using prostate cancer models. Our objective was to evaluate the anti-cancer activity of oral curcumin in patients with prostate cancer. METHODS: This randomized, double-blind, placebo-controlled trial was performed on patients with prostate cancer who received intermittent androgen deprivation (IAD). Participants who finished the first on-treatment period of IAD were randomized into a curcumin or placebo group. The patients took oral curcumin (1440 mg/day) or placebo for six months and were followed up until the beginning of the second on-treatment. The primary end-point was duration of the first off-treatment. The secondary end-points were change in PSA and testosterone levels during 6 months, PSA progression rate, and health-related quality of life (HRQOL) scores at 6 months. Safety assessments included adverse event, adverse drug reaction, and serious adverse event. RESULTS: A total of 97 participants were randomized 1:1 to curcumin (n = 49) and placebo (n = 48) groups. Among them, 82 patients (84.5%) were evaluable for the analysis (39 and 43 patients in the curcumin and placebo groups, respectively). The median off-treatment duration was 16.3 months (95% confidence interval [CI] 12.3-20.3 months) and 18.5 months (95% CI 12.5-23.0 months) in the curcumin and placebo groups, respectively. There was no significant difference in the curve of off-treatment duration between the two groups (P = 0.4816). The proportion of patients with PSA progression during the active curcumin treatment period (6 months) was significantly lower in the curcumin group than the placebo group (10.3% vs 30.2%, P = 0.0259). The change of PSA, testosterone levels during 6 months, and HRQOL scores at 6 months were not different between curcumin and placebo groups. Adverse events were higher in the placebo group (16 of 46 vs 7 of 45 patients, P = 0.0349). No significant differences in the adverse drug reaction were found between the two groups. CONCLUSIONS: Six months' intake of oral curcumin did not significantly affect the overall off-treatment duration of IAD. However, PSA elevation was suppressed with curcumin intake during the curcumin administration period. Curcumin at this dose was well tolerated and safe.

Combination of multiparametric magnetic resonance imaging and transrectal ultrasound-guided prostate biopsies is not enough for identifying patients eligible for hemiablative focal therapy for prostate cancer.

PURPOSE: To evaluate focal therapy (hemiablation) eligibility in men undergoing prostate biopsy and multiparametric magnetic resonance imaging (mpMRI) with reference to histopathology from radical prostatectomy (RP) specimens. METHODS: Subjects were selected among 810 men who underwent prostate biopsy, mpMRI, and RP from January 2016 to December 2017. Hemiablation eligibility criteria were biopsy-proven unilateral cancer, prostate-specific antigen ≤ 15 ng/ml, and Gleason score (GS) ≤ 3 + 4. Evidence of non-organ-confined disease or Prostate Imaging Reporting and Data System score ≥ 4 on the contralateral lobe on mpMRI was classified as ineligible for hemiablation. Of the 810, data for 185 who met the screening criteria were compared to final pathology findings. Significant cancer at RP was defined as any of the following: (1) GS 6 with tumor volume ≥ 0.5 ml; (2) GS ≥ 3 + 4; or (3) the presence of advanced stage (≥ pT3). RESULTS: Among the 185 candidates for hemiablation, 62 (33.5%) had unilateral cancer on final RP histopathology. Among the 123 bilateral cancers, 50 (27%) were organ confined and had GS ≤ 3 + 4 = 7 and bilateral multifocal tumor in which the index tumor was confined to one lobe and the secondary tumor in the contralateral lobe had tumor volume < 0.5 ml and GS ≤ 6. A total of 112 (60.5%) patients in this series were considered suitable for hemiablation. Significant cancer on biopsy and mpMRI-negative lobes were found in 72 (38.9%) of 185 lobes, including 1 (0.5%) with advanced stage. CONCLUSIONS: The combination of standard prostate biopsy and mpMRI did not accurately identify lobes that could be considered as non-treated regions.

A retrospective feasibility study of biweekly docetaxel in patients with high-risk metastatic castration-naïve prostate cancer.

BACKGROUND: Results from randomized phase III trials have shown that thrice-weekly docetaxel added to androgen-deprivation therapy (ADT) has a significant impact on the survival of patients with metastatic castration-naïve prostate cancer (mCNPC) and established early chemotherapy as part of the standard of care for high-risk disease. Controversy remains, however, because some patients experience critical toxicities related to docetaxel. The purpose of the current study was to evaluate the feasibility and adverse events of biweekly-administered docetaxel in patients with previously-untreated, high-risk mCNPC. METHODS: The study included 35 consecutive patients with high-risk mCNPC who received ADT plus docetaxel 40 mg/m2. Oral prednisone 5 mg twice daily was also given. Treatment was repeated every two weeks for up to 12 cycles or until disease progression or unacceptable toxicity occurred. High-risk was defined as bone metastases beyond axial skeleton and/or visceral disease. RESULTS: The included patients' median age was 68 years (range: 31-86 years) and 17 (49%) had visceral metastases. Biweekly docetaxel was generally well-tolerated; the most commonly observed adverse events, considering those of all grades, included alopecia (74%), nail changes (42%), and constipation (31%). Hematologic adverse events were infrequent, and no patient received hematopoietic growth factors. One patient died after the fourth cycle due to respiratory failure, which occurred as a complication of pneumonia. Among the 35 patients, 28 completed the planned 12 cycles of biweekly docetaxel. Prostate-specific antigen response (> 50% decrease from baseline) was recorded in 33 patients (94%), and the radiologic response rate was 49%. Median progression-free survival was 13.6 months (95% confidence interval: 6.7-20.4). CONCLUSION: ADT plus biweekly-administered docetaxel appeared to be tolerated and effective in patients with high-risk mCNPC.

Cancer Location in Upgrading and Detection after Transperineal Template-Guided Mapping Biopsy for Patients in Active Surveillance and Negative Transrectal Ultrasonography-Guided Prostate Biopsy.

OBJECTIVES: We investigated the efficacy of transperineal template-guided mapping biopsy (TTMB) for patients on active surveillance (AS) or those with previous negative transrectal ultrasound-guided biopsy (TRUS-Bx). METHODS: We retrospectively analyzed 99 patients on AS and 60 patients with previous negative TRUS-Bx, which is a total of 159 patients who underwent TTMB from May 2017 to January 2019. Cancer location was analyzed with focus on the anterior and apex lesions of the prostate after TTMB. Multiparametric magnetic resonance imaging was performed before TTMB. Cancer location after TTMB in 138 patients, excluding 21 patients who were not eligible for analysis (4 patients on AS and 17 patients with previous negative TRUS-Bx) was compared with Prostate Imaging-Reporting and Data System version 2 (PI-RADSTM v2) score. Factors that may affect detecting cancer after TTMB with previous negative TRUS-Bx was analyzed using a logistic regression model. RESULTS: In AS patients, 29 patients (29.3%) exhibited an upgrade in Gleason score (GS) after TTMB. Among them, 22 patients (75.9%) showed at the anterior or apex lesions. In patients with previous negative TRUS-Bx, 18 patients (30.0%) were diagnosed with prostate cancer. Among them, 13 patients (72.2%) exhibited cancer at the anterior or apex lesion. Among the 25 AS patients with PI-RADSTM score 1-2, 5 patients (20.0%) showed an upgrade in GS. Among the 26 patients with previous negative TRUS-Bx and PI-RADSTM score 1-2, 6 patients (23.1%) had cancer. In multivariate regression model, prostate volume (OR 0.951) was identified as the predictor for a positive biopsy result after TTMB with previous negative TRUS-Bx. CONCLUSIONS: TTMB is efficient for patients on AS in the detection of upgraded cancer located in anterior or apex or those with previous negative TRUS-Bx in the detection of anterior or apex cancer. In PI-RADSTM score 1-2, a substantial proportion of patients after experienced upgrade in GS on AS patients or cancer detection on previous negative TRUS-Bx. Moreover, we identified prostate volume is the independent predictor for a positive biopsy result after TTMB with previous negative TRUS-Bx.

Changeable Conditional Survival Rates and Associated Prognosticators in Patients with Metastatic Renal Cell Carcinoma Receiving First Line Targeted Therapy.

PURPOSE: In this study we evaluated conditional survival probabilities in patients with metastatic renal cell carcinoma who underwent first line tyrosine kinase inhibitor therapy. We also identified predictors of conditional survival with time. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 1,659 individuals with metastatic renal cell carcinoma in the Korean Renal Cancer Study Group database, of whom the records of 1,131 were finally analyzed. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities using the formula, conditional survival (α│ß) = S(α + ß)/S(ß), indicating the likelihood of additional α years survivorship in person who has already survived for ß years after initial therapy. S(χ) represents the actual survival rate. Multivariate Cox regression model was used to identify predictors of conditional survival with time. RESULTS: Six, 12, 18, 24 and 36-month conditional overall survival gradually increased in patients at all additional survival times after initial treatment compared to patient baseline survival estimations. While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment. Furthermore, predictors of conditional overall survival changed with time. Only previous metastasectomy remained a key prognosticator of conditional overall survival until 36 months of survival following initial tyrosine kinase inhibitor treatment. CONCLUSIONS: Conditional survival improved with time after initial tyrosine kinase inhibitor treatment in patients with metastatic renal cell carcinoma. Our study offers valuable information for practical survival estimations and relevant prognosticators in patients with metastatic renal cell carcinoma who receive first line tyrosine kinase inhibitor.

RFA versus robotic partial nephrectomy for T1a renal cell carcinoma: a propensity score-matched comparison of mid-term outcome.

OBJECTIVE: To compare oncological and functional mid-term outcomes following robotic partial nephrectomy (RPN) and radiofrequency ablation (RFA) for treating T1a renal cell carcinoma (RCC) using propensity score-matching. METHODS: Between December 2008-April 2016, 63 patients from each treatment group were propensity score-matched for age, sex, American Society of Anesthesiologists score, tumour size, tumour laterality, tumour histology, R.E.N.A.L. nephrometry score and preoperative estimated glomerular filtration rate (eGFR). Post-treatment follow-up periods for RPN and RFA ranged from 1-90 months (median, 24.6) and 1-65 months (21), respectively. Tumour location, percentage of eGFR preservation and 2-year recurrence-free survival rate were compared between groups. RESULTS: Exophytic and endophytic RCC occurred in 73.0 % (46/63) and 27.0 % (17/63) of the RPN group, and 52.4 % (33/63) and 47.6 % (30/63) of the RFA group, respectively (p=0.017). There was 91.7 % preservation of eGFR in the RPN group and 86.8 % in the RFA group (p=0.088). Two-year recurrence-free survival rate was 100 % in the RPN and 95.2 % in the RFA group (p=0.029). CONCLUSIONS: RPN provides a higher recurrence-free survival rate than RFA. However, RFA is a better treatment option for an endophytic or recurrent RCC that is difficult to treat with RPN. KEY POINTS: • RPN provides a higher recurrence-free survival rate than RFA. • Unlike RPN, repeat RFA is easy to perform for recurrent RCC. • Endophytic RCC could be better treated with RFA.

Prognostic impact of the pretreatment aspartate transaminase/alanine transaminase ratio in patients treated with first-line systemic tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma.

OBJECTIVES: To examine the prognostic role of the pretreatment aspartate transaminase/alanine transaminase or De Ritis ratio in patients with metastatic renal cell carcinoma receiving first-line systemic tyrosine kinase inhibitor therapy. METHODS: We retrospectively searched the medical records of 579 patients with metastatic renal cell carcinoma who visited Samsung Medical Center, Seoul, Korea, from January 2001 through August 2016. After excluding 210 patients, we analyzed 360 patients who received first-line tyrosine kinase inhibitor therapy. Cancer-specific survival and overall survival were defined as the primary and secondary end-points, respectively. A multivariate Cox proportional hazards regression model was used to identify independent prognosticators of survival outcomes. RESULTS: The overall population was divided into two groups according to the pretreatment De Ritis ratio as an optimal cut-off value of 1.2, which was determined by a time-dependent receiver operating characteristic curve analysis. Patients with a higher pretreatment De Ritis ratio (≥1.2) had worse cancer-specific survival and overall survival outcomes, compared with those with a lower De Ritis ratio (<1.2). Notably, a higher De Ritis ratio (≥1.2) was found to be an independent predictor of both cancer-specific survival (hazard ratio 1.61, 95% confidence interval 1.13-2.30) and overall survival outcomes (hazard ratio 1.69, 95% confidence interval 1.19-2.39), along with male sex, multiple metastasis (≥2), non-clear cell histology, advanced pT stage (≥3), previous metastasectomy and the Memorial Sloan Kettering Cancer Center risk classification. CONCLUSION: Our findings show that the pretreatment De Ritis ratio can provide valuable information about the survival outcomes of metastatic renal cell carcinoma patients receiving first-line tyrosine kinase inhibitor therapy.

Prognostic Significance of Pre- to Postoperative Dynamics of the Prognostic Nutritional Index for Patients with Renal Cell Carcinoma Who Underwent Radical Nephrectomy.

BACKGROUND: This study aimed to examine the prognostic role of Prognostic Nutritional Index (PNI) dynamics in the pre- and postoperative periods for patients with renal cell carcinoma (RCC) who undergo radical nephrectomy (RN). METHODS: The study analyzed 324 patients with RCC who underwent RN. The overall population was classified into four groups according to four types of pre- to postoperative PNI dynamics as follows: group 1 (low â†’ low PNI), group 2 (low â†’ high PNI), group 3 (high â†’ low PNI), and group 4 (high â†’ high PNI). The level of PNI was calculated using the following formula: 10 × serum albumin level (g/dL) + 0.005 × absolute lymphocyte counts in blood (/mm3). The primary end point was cancer-specific survival (CSS), and the secondary end point was overall survival (OS). RESULTS: The patients with higher pre- and postoperative PNI (>45) had better survival outcomes than those with lower pre- and postoperative PNI (≤45). Notably, the patients in group 4 showed the best CSS and OS rates, whereas the patients in group 1 had the worst survival outcomes. Furthermore, PNI dynamics were identified as an independent predictor of CSS and OS outcomes, in addition to pre- and postoperative PNI, tumor size, and pathologic T (pT) stage. The patients with localized RCC (≤pT2) showed significant differences in both CSS and OS estimates, whereas the patients with advanced pT stage (≥pT3) demonstrated a difference only in OS outcomes, according to PNI dynamics. CONCLUSIONS: This study is the first to provide the independent prognostic importance of dynamics of nutritional status for patients with RCC.

Effect of BKCa Channel Opener LDD175 on Erectile Function in an In Vivo Diabetic Rat Model.

INTRODUCTION: The development of novel therapeutic options is imperative in patients with erectile dysfunction, especially those non-responsive to phosphodiesterase type 5 inhibitors. LDD175, a potent BKCa channel opener, has a relaxation effect on the in vitro cavernosal smooth muscle strip. AIM: To investigate the effect of LDD175 on erectile function using in vivo animal disease model. METHODS: Male Sprague-Dawley rats were assigned to a normal control group and seven diabetic groups: diabetic control, sildenafil (1 and 5 mg/kg), LDD175 (5 and 10 mg/kg), LDD175 5 mg/kg plus sildenafil 1 mg/kg, and LDD175 10 mg/kg plus tetraethylammonium. MAIN OUTCOME MEASURES: Intracavernosal pressure (ICP), ratio of ICP to mean arterial pressure (MAP), and the area under curve of ICP/MAP of eight groups were compared using in vivo pelvic nerve stimulation. RESULTS: The ICP, ICP/MAP ratio, and area under curve of the ICP/MAP ratio of the normal control rats increased with an increase in electrical field stimulation voltage. All parameters in the diabetic control group were significantly lower than those in the normal control rats, with an electrical field stimulation ranging from 1 to 5 V (P < .05). LDD175 improved the erectile response in diabetic rats in a dose-dependent manner. The combination of sildenafil (1 mg/kg) and LDD175 (5 mg/kg) showed a significant additive effect (P < .05) on the improvement of erectile function compared with sildenafil (1 mg/kg) alone. The enhancement of erectile function by LDD175 was completely blocked by tetraethylammonium. CONCLUSION: The results showed that the BKCa channel opener LDD175 improved erectile function in an in vivo diabetic rat model. Furthermore, combination therapy of LDD175 and sildenafil had an additive effect on the improvement of erectile function in diabetic rats. LDD175 could be a new candidate for the treatment of erectile dysfunction.

Accuracy of preoperative multiparametric magnetic resonance imaging for prediction of unfavorable pathology in patients with localized prostate cancer undergoing radical prostatectomy.

INTRODUCTION: We investigated the accuracy of multiparametric MRI (mpMRI) for preoperative staging and its influence on the determination of neurovascular bundle sparing and disease prognosis in patients with localized prostate cancer. METHODS: We reviewed 1045 patients who underwent radical prostatectomy with preoperative mpMRI at a single institution. Clinical local stages determined from mpMRI were correlated with preoperative and postoperative pathological outcomes. RESULTS: The sensitivity and specificity to diagnose seminal vesicle invasion (SVI) on mpMRI were 43.8 and 95.4 %, respectively. The negative predictive value was 78.9 %. The sensitivity and specificity to diagnose extracapsular extension (ECE) were 54.5 and 80.5 %, respectively. The overall sensitivity and specificity of diagnosing pathological T3 or higher were 52.6 and 82.1 %, respectively. Non-organ-confined disease determined by mpMRI was significantly associated with positive surgical margin and pathological T3 disease on multivariate analysis. Preoperative adverse findings on mpMRI were significantly associated with performance of the non-nerve-sparing technique. CONCLUSION: mpMRI did not show outstanding diagnostic accuracy relative to our expectations in predicting SVI or ECE preoperatively. However, adverse findings on preoperative mpMRI were significantly related to worse postoperative pathological outcomes as well as postoperative biochemical recurrence.

Diagnosing bladder outlet obstruction using the penile cuff test in men with lower urinary tract symptoms.

AIM: The current standard diagnostic test to evaluate bladder outlet obstruction (BOO) is pressure-flow study (PFS). The penile cuff test (PCT) was introduced as a non-invasive alternative to PFS to determine the isovolumetric bladder pressure and also flow rate. The aim of the study was to evaluate the diagnostic accuracy and acceptability of the PCT, compared to those of PFS, in the assessment of BOO in men. METHODS: A total of 146 consecutive men with an International Prostate Symptom Score (IPSS) >12 and lower urinary tract symptoms (LUTS) for >6 months were included in this single-institution, prospective, diagnostic study. The primary outcome was to evaluate the diagnostic accuracy of PCT. Secondary outcomes included pain severity measured on a visual analog scale (VAS), procedure time, and adverse events. In addition, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated. RESULTS: Based on the PFS results, the sensitivity of PCT was 89.7%, the PPV 54.2%, the specificity 71.8%, and the NPV 94.9%. The mean pain VAS for the PFS and PCT were 5.04 ± 2.17 and 1.83 ± 1.98, respectively (P < 0.0001). The mean procedure time for PCT (6.3 ± 0.6 min) was shorter than that of PFS (23.3 ± 2.2 min) (P < 0.0001). There were no adverse events reported during PCT. CONCLUSIONS: Given its high NPV, PCT may be an efficient screening test for BOO in men. In addition, PCT is advantageous over PFS with regard to its short procedure time and acceptable tolerability.