Six-year outcomes of robot-assisted radical prostatectomy versus volumetric modulated arc therapy for localized prostate cancer: A propensity score-matched analysis.

BACKGROUND: Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes. METHODS: We compared 6­year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, a rotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy. RESULTS: The median follow-up duration was 79 months (> 6 years). PSM generated a matched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6­year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6 and 68.8% of the patients achieved ≤ 1 pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and a very low rate (4.4%) of grade ≥ 2 gastrointestinal complications. CONCLUSION: On the basis of PSM after a 6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles.

Robotic versus open and laparoscopic pelvic exenterations for pelvic cancer: a multicenter propensity-matched analysis in Japan.

BACKGROUND: Pelvic exenteration (PE) is the last resort for achieving a complete cure for pelvic cancer; however, it is burdensome for patients. Minimally invasive surgeries, including robot-assisted surgery, have been widely used to treat malignant tumors and have also recently been used in PE. This study aimed to evaluate the safety and efficacy of robot-assisted PE (RPE) by comparing the outcomes of open PE (OPE) with those of conventional laparoscopic PE (LPE) for treating pelvic tumors. METHODS: Following the ethics committee approval, a multicenter retrospective analysis of patients who underwent pelvic exenteration between January 2012 and October 2022 was conducted. Data on patient demographics, tumor characteristics, and perioperative outcomes were collected. A 1:1 propensity score-matched analysis was performed to minimize group selection bias. RESULTS: In total, 261 patients met the study criteria, of whom 61 underwent RPE, 90 underwent OPE, and 110 underwent LPE. After propensity score matching, 50 pairs were created for RPE and OPE and 59 for RPE and LPE. RPE was associated with significantly less blood loss (RPE vs. OPE: 408 mL vs. 2385 ml, p < 0.001), lower transfusion rate (RPE vs. OPE: 32% vs. 82%, p < 0.001), and lower rate of complications over Clavien-Dindo grade II (RPE vs. OPE: 48% vs. 74%, p = 0.013; RPE vs. LPE: 48% vs. 76%, p = 0.002). CONCLUSION: This multicenter study suggests that RPE reduces blood loss and transfusion compared with OPE and has a lower rate of complications compared with OPE and LPE in patients with locally advanced and recurrent pelvic tumors.

Fourth national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from patients with complicated urinary tract infections.

INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.

A Safer Method for Disinfection of Bacillus Calmette-Guerin-Containing Urine: A Prospective, Randomized Study.

INTRODUCTION: The aim of the study was to examine whether disinfection of bacillus Calmette-Guerin-containing urine with etaprocohol® (ethanol 76.9-81.4 vol % and isopropanol as an additive) is safer than disinfection with sodium hypochlorite. METHOD: In prospective research, safety and efficacy was analyzed in 5 patients in the etaprocohol® disinfection group and 5 patients in the sodium hypochlorite disinfection group. The primary endpoint was the temperature change after disinfection and the secondary endpoint was the unpleasantness of the odor caused by disinfection. Additionally, concentration of gas produced was also examined. Sensory tests were taken from staff who performed urine disinfection and the odor generated by disinfection was evaluated. As a safety protocol, post-BCG-treated urine is cultured to verify the negativity for mycobacteria. RESULTS: Mycobacteria were disinfected in all cases. The temperature rise following disinfection was significantly higher in the sodium hypochlorite group. The sensory test outcomes were significantly worse in the group disinfected with sodium hypochlorite. The concentration of gas generated immediately after disinfection in both groups reached the maximum value and declined quickly. CONCLUSIONS: Disinfection of bacillus Calmette-Guerin-containing urine with etaprocohol® was safer than disinfection with sodium hypochlorite, and an equivalent disinfection effect was achieved.

Lower bleeding volume contributes to decreasing surgical site infection in radical cystectomy: A propensity score-matched comparison of open versus robot-assisted radical cystectomy.

OBJECTIVES: To compare the incidence of surgical site infections (SSI) between robot-assisted and open radical cystectomies and investigate the risk factors for SSI after radical cystectomies. METHODS: Consecutive patients who underwent radical cystectomy between July 2008 and December 2022 were retrospectively reviewed. The prevalence and characteristics of SSI after open and robot-assisted radical cystectomies were compared, and the risk factors for SSI were investigated using propensity score matching. RESULTS: This study enrolled 231 patients (open: 145, robot-assisted: 86). In the robot-assisted group, urinary diversion was performed using an intracorporeal approach. SSI occurred in 34 (open: 28, robot-assisted: 6) patients, and the incidence was significantly lower in the robot-assisted group (19.3% vs. 7.0%, p = 0.007). After propensity score matching cohort (open: 34, robot-assisted: 34), increased bleeding volume, blood transfusion, and delayed postoperative oral feeding were significantly associated with SSI. Only increased bleeding volume remained a significant risk factor in the multivariate regression analysis (odds ratio, 1.13 [per 100 mL increase]; 95% confidence interval: 1.02-1.25; p = 0.001). The cutoff bleeding volume for predicting SSI was 1630 mL with an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.773, 0.73, and 0.75, respectively. CONCLUSIONS: The incidence of SSI after robot-assisted radical cystectomy was significantly lower than that after the open procedure. However, decreased bleeding volume, which was significantly associated with robot-assisted procedures, was an independent and more significant factor for reducing SSI after radical cystectomy than the differences of the surgical procedure even after propensity score matching.

Early recovery of urinary continence after robot-assisted radical prostatectomy is associated with membranous urethra and neurovascular bundle preservation.

OBJECTIVES: We investigated the correlation between surgical outcomes and postoperative urinary continence recovery in robot-assisted radical prostatectomy (RARP). METHODS: Patients who underwent RARP in our institution (n = 195) were included in this study. Preserved urethral length (PUL) was assessed during the procedure. Other outcomes of the surgical procedure were collected from operative records. Kaplan-Meier analysis with log-rank test was used to compare urinary continence recovery rate with the PUL, sparing of the neurovascular bundle (NVB), and other surgical procedures. Univariate and multivariate analyses were performed using Cox proportional hazards model, and p-values of <0.05 were considered significant. RESULTS: Patients with a PUL ≥26 mm had 10.0%, 24.7%, 36.6%, and 89.0% continence recovery rates at 30, 60, 90, and 365 days after surgery, respectively, while patients with a PUL <26 mm had 0%, 17.8%, 26.1%, and 80.9% recovery rates, respectively. Kaplan-Meier curves showed significantly better postoperative urinary continence recovery at 30 days after RARP in patients with a PUL ≥26 mm than those with a PUL <26 mm (p = 0.0028) and in patients with NVB preservation than those with no NVB preservation (p = 0.014). Urinary continence recovery within 30, 60, and 90 days after surgery was 90.6% for patients with a PUL of ≥26 mm and NVB preservation, while only 82.3% for patients with a PUL of <26 mm or no NVB preservation. CONCLUSION: Our results suggest that a PUL ≥26 mm and NVB preservation after RARP correlate with a significantly higher postoperative rate of recovery of urinary continence.

Impact of early ureteral drainage on mortality in obstructive pyelonephritis with urolithiasis: an analysis of the Japanese National Database.

BACKGROUND: The impact of early drainage on mortality in patients with obstructive pyelonephritis with urolithiasis was evaluated. METHODS: We identified 34,924 patients in the Japanese Diagnosis Procedure Combination database with obstructive pyelonephritis with urolithiasis receiving ureteral drainage. The effects of early drainage (1-2 days) compared to those of delayed drainage (on 3-4 and ≥ 5 hospital days) on mortality were evaluated among 31,696 patients hospitalized for ≥ 5 days. Multivariate analysis was performed to identify independent factors for mortality. RESULTS: The mortality rates for overall cases and those hospitalized for ≥ 5 days were 2.0% and 1.6%, respectively. Those receiving drainage on 1-2, 3-4, and ≥ 5 days had mortality rates of 1.5%, 2.0%, and 2.5%, respectively (p < 0.001). Multivariate analysis revealed that delayed drainage was an independent factor for higher mortality (odds ratio [OR] on days 3-4 and ≥ 5; 1.44, p = 0.018; and 1.69, p < 0.001). Increasing age (OR for 60 s, 70 s, and ≥ 80 years; 2.02, 3.85, and 7.77), Charlson comorbidity index score (OR, 1.41 by 1-point increase), disseminated intravascular coagulation (OR, 2.40), ambulance use (OR, 1.22), impaired consciousness at admission (disoriented, arousable with stimulation, and unarousable; OR 1.58, 2.84, and 5.50), and nephrostomy (OR, 1.65) were associated with higher mortality. In contrast, female sex (OR, 0.76) and high hospital volume (OR on 9-16, and ≥ 17 cases/year; 0.80, and 0.75) were associated with lower mortality. CONCLUSION: Ureteral drainage within 2 hospital days was an independent factor for low mortality in obstructive pyelonephritis with urolithiasis. Delayed drainage could increase mortality in a time-dependent manner.

Urinary tract infection in patients with lower urinary tract dysfunction.

Lower urinary tract dysfunction (LUTD) is becoming more common in aging societies worldwide. In patients with LUTD, the risk of urinary tract infection (UTI) rises due to several distinct mechanisms, including easy bacterial access to the urinary tract, impaired bacterial washout, and an impaired innate defense system. The pathophysiology of LUTD varies depending on whether it is neurogenic or non-neurogenic, as well as by gender; therefore, the etiology and characteristics of UTI differ according to the type of LUTD. Patients with neurogenic LUTD, especially those with spinal cord injury, have a high risk of febrile UTI, and strict bladder management is required to prevent UTI. Clean intermittent catheterization with or without appropriate pharmacological therapy is also strongly recommended for patients with neurogenic LUTD at risk of febrile UTI, unable to void, or with high post-void residual volume. In contrast, both male and female patients with non-neurogenic LUTD have a lower risk of symptomatic UTI. There is insufficient evidence for non-neurogenic LUTD regarding the association between symptomatic UTI but not asymptomatic bacteriuria and LUTD severity, including the presence of post-void residual volume, or whether therapeutic intervention for LUTS reduces the incidence of UTI, particularly in male patients. In this narrative review, we aimed to highlight the pathogenesis, epidemiology, and management of UTI in patients with LUTD.

Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study.

OBJECTIVE: Enfortumab vedotin (EV) was approved for advanced urothelial carcinoma (UC) in 2021 after the EV-301 trial showed its superiority to non-platinum-based chemotherapy as later-line treatment after platinum-based chemotherapy and immune checkpoint inhibitors including pembrolizumab. However, no study has compared EV with rechallenging platinum-based chemotherapy (i.e., "platinum rechallenge") in that setting. METHODS: In total, 283 patients received pembrolizumab for advanced UC after platinum-based chemotherapy between 2018 and 2023. Of them, 41 and 25 patients received EV and platinum rechallenge, respectively, as later-line treatment after pembrolizumab. After excluding two patients with EV without imaging evaluation, we compared oncological outcomes, including progression-free survival (PFS) and overall survival (OS), between the EV (n = 39) and platinum rechallenge groups (n = 25) using propensity score matching (PSM). RESULTS: Analyses on crude data (n = 64) showed no significant differences between the two groups regarding patients' baseline characteristics. PFS (5 months) and OS (11 months) in the EV group were comparable to those (8 and 12 months, respectively) in the platinum rechallenge group. After PSM (n = 36), the baseline characteristics between the two groups became more balanced, and PFS (not reached) and OS (not reached) in the EV group were comparable to those (8 and 11 months, respectively) in the platinum rechallenge group. CONCLUSIONS: EV and platinum rechallenge showed equivalent oncological outcomes, even after PSM, and both treatments should therefore be effective treatment options for post-platinum, post-pembrolizumab advanced UC.

Creatinine reduction ratio on postoperative day 2 predicts long-term outcomes after living donor kidney transplantation.

OBJECTIVES: To evaluate the relationship between the creatinine reduction ratio between postoperative days 1 and 2 and post-transplantation clinical outcomes after living donor kidney transplantation. METHODS: Clinical data of patients who underwent living donor kidney transplantation at Jichi Medical University Hospital, Tochigi, Japan, between 2006 and 2019 were retrieved. The creatinine reduction ratio between postoperative days 1 and 2 was calculated based on the formula: (Cre1 - Cre2) × 100/Cre1; patients were then classified into either the slow graft function (creatinine reduction ratio between postoperative days 1 and 2 ≤30%) or immediate graft function (creatinine reduction ratio between postoperative days 1 and 2 >30%) group. We carried out the log-rank test and multivariate Cox proportional hazards regression analyses to assess graft survival and rejection-free survival, and the unpaired t-test and multivariate linear regression to assess post-transplantation estimated glomerular filtration rates. Multivariate analyses used age, sex, dialysis duration, ABO compatibility, donor-specific antibody positivity and medically complex living donors as explanatory variables. RESULTS: Of the 272 patients, 30 and 242 were in the slow graft function and immediate graft function groups, respectively. Multivariate Cox proportional hazards regression analyses showed a significantly higher incidence of overall and death-censored graft loss in the slow graft function group than the immediate graft function group. The frequency of rejection after 1 week post-transplantation did not differ within the groups. Post-transplantation estimated glomerular filtration rates tended to decline earlier in the slow graft function group than in the immediate graft function group; however, the difference was not statistically significant. CONCLUSIONS: The creatinine reduction ratio between postoperative days 1 and 2 could potentially predict long-term outcomes after living donor kidney transplantation. Using the creatinine reduction ratio between postoperative days 1 and 2 and other conventional indicators might allow accurate risk classification and appropriate therapeutic interventions.

Improved survival in real-world patients with advanced urothelial carcinoma: A multicenter propensity score-matched cohort study comparing a period before the introduction of pembrolizumab (2003-2011) and a more recent period (2016-2020).

OBJECTIVES: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.

Clinical significance and risk factors of International Society of Urological Pathology (ISUP) grade upgrading in prostate cancer patients undergoing robot-assisted radical prostatectomy.

BACKGROUND: The objective of this study is to investigate the clinical significance and risk factors of upgrading in the International Society of Urological Pathology (ISUP) Grade Group System in men undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer. METHODS: A total of 583 patients diagnosed with prostate cancer by systematic biopsy were treated with RARP without neoadjuvant therapy from November 2011 to December 2018. Clinicopathological data were obtained from our clinical records. ISUP grade upgrading (IGU) was defined as 'ISUP grade in prostatectomy specimen determined to be higher than that in the biopsy specimen'. Clinicopathological factors, including age, PSA, prostate volume at biopsy (PV), PSA density, clinical stage, body mass index (BMI), interval from biopsy to prostatectomy, maximum percentage of cancer involvement per core (%CI), total number of biopsy cores, percentage of cancer positive biopsy cores (%PC), and sampling density were analyzed to detect potential risk factors of IGU. Biochemical recurrence (BCR) rates were calculated to analyze the effect of IGU on cancer prognosis. RESULTS: In univariate analysis, BMI was a positive predictor of IGU, while %CI, %PC, and sampling density were negative predictors of IGU. BMI and %PC were statistically significant predictors of IGU in multivariate analysis. For cases diagnosed as ISUP grade group 2 or higher at biopsy, there was a significant difference in BCR rates between cases with and without IGU. CONCLUSIONS: The results from our cohort showed that elements of both high-grade cancer risk (such as BMI) and sampling efficiency (such as %PC) contribute to IGU. Excluding cases diagnosed as ISUP grade group 1 at biopsy, BCR-free rates were significantly worse in cases with IGU, highlighting the need for more accurate pathological diagnosis at biopsy.

Predictive factors and management of urinary tract infections after kidney transplantation: a retrospective cohort study.

BACKGROUND: Urinary tract infection (UTI) is one of the most common infectious complications in kidney transplant recipients. The aims of our study were to identify possible predictive factors for UTI and advocate for the management of UTI after kidney transplantation (KT). METHODS: Between January 2013 and December 2018, 182 adult patients with end-stage kidney disease who underwent KT were retrospectively analyzed. Patients who had urinary symptoms and positive urine culture were diagnosed with UTI. The types of urinary bacteria causing UTIs were also examined. RESULTS: UTIs occurred in forty-one patients (25.1%), and the median time to UTI onset (UTI-free survival) after KT was 189 days. The Cox hazard regression analysis showed that the predictive factors for UTI onset were as follows: posttransplant urinary catheterization, including indwelling urinary catheterization and clean intermittent catheterization; a maximum bladder capacity before KT of less than 150 ml; and a low serum albumin level at 1 month after KT. The most common causative agent was Escherichia coli (56.6%), followed by Enterococcus spp. (15.6%) and Klebsiella spp. CONCLUSIONS: Kidney transplant recipients with prolonged postoperative malnutrition, posttransplant voiding dysfunction and/or urinary storage disorder had an increased risk of UTI. Bladder function tests, such as uroflowmetry, postvoid residual urine tests, and urodynamic tests, were needed to predict UTI. For patients with malnutrition, care should be taken to ensure sufficient calorie intake. Kidney transplant recipients who develop UTI should be treated as complicated UTI patients.

Clinical significance and risk factors of urethrovesical anastomotic urinary leakage following robot-assisted radical prostatectomy: a multi-institutional study.

BACKGROUND: There has been a limited number of reports on the significance and risk factors of urethrovesical anastomotic urinary leakage (AUL) following robot-assisted radical prostatectomy (RARP). We aimed to analyze the clinical significance of AUL and evaluated its risk factors. METHODS: We conducted a multi-institutional study to review patients with prostate cancer undergoing RARP in three centers (The University of Tokyo Hospital, Mitsui Memorial Hospital, and Chiba Tokushukai Hospital). "Positive AUL" was defined as urinary extravasation at the anastomosis detected by post-operative cystogram and was further categorized into minor or major AUL. Univariate and multivariate analyses were performed to identify predictors of AUL. Postoperative continence rates and time to achieve continence were also analyzed. RESULTS: A total of 942 patients underwent RARP for prostate cancer in 3 centers. Of these patients, a cystogram after the RARP procedure was not performed in 26 patients leaving 916 patients for the final analysis. AUL was observed in 56 patients (6.1%); 34 patients (3.7%) with minor AUL and 22 patients (2.4%) with major AUL. Patients with major AUL exhibited a significantly longer time to achieve continence than those without major AUL. Multivariate analysis demonstrated that longer console time (≥ 184 min) was significantly associated with overall AUL, and higher body mass index (≥ 25 g/kg2) was a significant predictor of both major and overall AUL. CONCLUSIONS: The presence of major AUL was associated with the achievement of urinary continence, suggesting clinical relevance of its diagnosis by postoperative cystogram. A selective cystogram has been proposed for high-risk cases. Furthermore, identification of the risk factors of AUL will lead to optimal application.

COBLL1 modulates cell morphology and facilitates androgen receptor genomic binding in advanced prostate cancer.

Androgen receptor (AR) signaling is essential for prostate cancer progression and acquiring resistance to hormone therapy. However, the molecular pathogenesis through AR activation has not been fully understood. We performed integrative transcriptomic analysis to compare the AR program in a castration-resistant prostate cancer (CRPC) model with that in their parental hormone-sensitive cells. We found that the gene cordon-bleu-like 1 (COBLL1) is highly induced by AR in CRPC model cells. The expression of COBLL1 that possesses an actin-binding domain is up-regulated in clinical prostate cancer tissues and is associated with a poor prognosis for prostate cancer patients. COBLL1 is involved in the cancer cell morphogenesis to a neuron-like cell shape observed in the CRPC model cells, promoting cell growth and migration. Moreover, nuclear COBLL1 interacts with AR to enhance complex formation with CDK1 and facilitates AR phosphorylation for genomic binding in CRPC model cells. Thus, our findings showed the mechanistic relevance of cordon-bleu proteins during the AR-mediated progression to CRPC.

Lacking transient receptor potential melastatin 2 attenuates lipopolysaccharide-induced bladder inflammation and its associated hypersensitivity in mice.

OBJECTIVE: To study the role of transient receptor potential melastatin 2 in bladder function and inflammation-associated hypersensitivity. METHODS: We evaluated physiological function of the bladder and intravesical lipopolysaccharide-induced inflammatory nociceptive responses in female wild-type and transient receptor potential melastatin 2-knockout mice. In vivo frequency/volume and decerebrated unanesthetized cystometry measurements, as well as in vitro detrusor strip functional studies, were carried out to evaluate bladder function. Mice received intravesical lipopolysaccharide (2.0 mg/mL) or saline instillation to evaluate responses to bladder inflammation. Voiding and bladder pain-like behaviors, cystometry measurements and histological evaluation were carried out before and after intravesical lipopolysaccharide instillation. RESULTS: Few phenotypic differences in in vivo and in vitro physiological function were found between the two genotypes. Comparison of measurements taken before and 24-48 h after intravesical lipopolysaccharide instillation showed that voiding parameters did not change in transient receptor potential melastatin 2-knockout mice, whereas an increased voiding frequency was observed in wild-type mice. At 24 h after intravesical lipopolysaccharide instillation, the numbers of bladder pain-like behaviors and of infiltrated inflammatory cells in the bladder submucosal layer were significantly increased, and the voided volume and the intercontraction interval were significantly decreased on cystometry measurements in wild-type mice compared with those in both transient receptor potential melastatin 2-knockout mice and in wild-type mice treated with saline instillation. CONCLUSIONS: Although the physiological roles of transient receptor potential melastatin 2 channels in the bladder might be limited, inflammation and associated hypersensitivity of the bladder caused by intravesical lipopolysaccharide instillation are attenuated in transient receptor potential melastatin 2-knockout mice, suggesting pathophysiological roles of transient receptor potential melastatin 2 channels in these processes.

Mechanism of hypertensive crisis during energy device ablation of the adrenal gland: An experimental animal study.

OBJECTIVE: To elucidate the mechanism of hypertensive crisis during energy device ablation of the adrenal gland. METHODS: Electrocoagulation on the adrenal glands of six pigs was carried out with the same energy device (VIO300D) using four methods: (i) monopolar coagulation; (ii) monopolar soft coagulation using IO-advanced ball-type electrodes; (iii) bipolar soft coagulation by pinching; and (iv) bipolar soft coagulation by non-pinching (surface contact) using Bipolar forceps Premium. After electrocoagulation for 5 s, blood pressure and pulse changes were monitored, and adrenal hormones were measured from a central vein. The adrenal glands were removed, and the degree of tissue damage was scored histologically. RESULTS: Hypertensive crisis occurred with electrocoagulation of the adrenal gland by the monopolar coagulation, monopolar soft coagulation and bipolar soft coagulation pinching methods. Blood pressure did not change with the bipolar soft coagulation non-pinching method. Pathologically, tissue damage to the adrenal medulla was associated with elevated blood pressure and adrenaline and noradrenaline release. CONCLUSIONS: Hypertensive crisis caused by energy device ablation to the adrenal gland is caused by the release of catecholamines due to heat damage to the adrenal medulla rather than the type of energy device. Proper use of an energy device that does not cause thermal degeneration of the medulla is required to prevent hypertensive crisis.

Histological and radiological evaluation of thermal denaturation depth using soft coagulation during partial nephrectomy in living pigs.

OBJECTIVES: To evaluate thermal denaturation depth using soft coagulation in kidneys in vivo. METHODS: In experiment 1, nine kidneys from five pigs were cauterized using five soft-coagulation settings at 80 W with effect 7 by VIO300D and one monopolar-coagulation setting. The surface of the kidney was cauterized over a period of 2, 5 and 10 s. The temperature change was measured at depths of 5 and 10 mm. In experiment 2, three kidneys from two pigs were excised in a semicircular shape with a diameter of 5, 10 and 20 mm without clamping the renal artery. Cauterization was carried out until hemostasis was confirmed by soft coagulation at 80 W with effect 7. After completion of the experiments, pathology examinations of the kidneys were carried out. RESULTS: Experiment 1 showed that with proper saline dripping, denaturation spread with increased cauterization time, reaching a depth of 4 mm at 10 s with or without clamps. The depth remained at 2-3 mm at 10 s in the absence or excess of saline. The temperature increased by 15.6°C at a depth of 5 mm and 8.8°C at 10 mm. In experiment 2, the depth was 4.6 mm from the incision surface regardless of the cauterization time or excision size. CONCLUSIONS: These findings suggest that soft coagulation can be useful for preserving renal function and reducing complications in partial nephrectomy.

TRIM44 promotes cell proliferation and migration by inhibiting FRK in renal cell carcinoma.

TRIM44 has oncogenic roles in various cancers. However, TRIM44 expression and its function in renal cell carcinoma (RCC) are still unknown. Here in this study, we investigated the clinical significance of TRIM44 and its biological function in RCC. TRIM44 overexpression was significantly associated with clinical M stage, histologic type (clear cell) and presence of lymphatic invasion (P = .047, P = .005, and P = .028, respectively). Moreover, TRIM44 overexpression was significantly associated with poor prognosis in terms of cancer-specific survival (P = .019). Gain-of-function and loss-of-function studies using TRIM44 and siTRIM44 transfection showed that TRIM44 promotes cell proliferation and cell migration in two RCC cell lines, Caki1 and 769P. To further investigate the role of TRIM44 in RCC, we performed integrated microarray analysis in Caki1 and 769P cells and explored the data in the Oncomine database. Interestingly, FRK was identified as a promising candidate target gene of TRIM44, which was downregulated in RCC compared with normal renal tissues. We found that cell proliferation was inhibited by TRIM44 knockdown and then recovered by siFRK treatment. Taken together, the present study revealed the association between high expression of TRIM44 and poor prognosis in RCC patients and that TRIM44 promotes cell proliferation by regulating FRK.

Quantification of the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy: development of the modified Gleason grade grouping (mGGG) model.

BACKGROUND: While the new Gleason grade grouping (GGG), which started in 2016, has been widely validated in prostate cancer, it does not incorporate the concept of tertiary Gleason pattern 5. Furthermore, no study has "quantified" the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy. METHODS: We reviewed 1022 men with adjuvant-treatment-naïve prostate cancer who underwent radical prostatectomy between 2005 and 2017. The primary endpoint was biochemical recurrence-free survival, defined as two consecutive prostate-specific antigen measurements ≥0.2 ng/ml after surgery. The individual quantitative risk score (IQRS) of each amount (primary/secondary/tertiary) of each Gleason pattern (3/4/5) was calculated using the Cox regression model. On the basis of the IQRS, the modified Gleason grade grouping (mGGG) model was developed. As a robustness analysis of the mGGG model, salvage treatment-free survival was also assessed. RESULTS: During a median follow-up of 45 months, 229 of 1022 (22.4%) patients developed biochemical recurrence. The IQRS of each Gleason pattern was as follows: primary 5, 1.81 points (hazard ratio [HR] 6.13); secondary 5, 1.37 points (HR 3.92); tertiary 5, 0.87 points (HR 2.39); primary 4, 1.07 points (HR 2.91); secondary 4, 0.79 points (HR 2.21); and any Gleason pattern 3, 0 points (HR 1). Based on the IQRS, the mGGG model was developed, which classified patients into the following five groups: I (3 + 3 or less); II (3 + 4); III (4 + 3); IV (3 + 4 + t5, 4 + 3 + t5, 3 + 5, 5 + 3, and 4 + 4); V (4 + 4 + t5, 4 + 5, 5 + 4, and 5 + 5). The c-index for biochemical recurrence-free survival was significantly improved from 0.655 of the original GGG model to 0.672 of the mGGG model (P < 0.05). In the robustness analysis, the c-index for salvage treatment-free survival was also significantly improved from 0.619 of the original GGG model to 0.638 of the mGGG model (P < 0.05). CONCLUSIONS: The quantitative risk of tertiary (< 5%) Gleason pattern 5 is slightly higher than that of secondary (5-50%) Gleason pattern 4. Our newly developed mGGG model more accurately predicts outcomes after radical prostatectomy than the original GGG model.