Intravesical Injection of OnabotulinumtoxinA (Botulinum Toxin Type A) in Japanese Patients With Refractory Overactive Bladder.

BACKGROUND/AIM: Botulinum toxin intravesical injection therapy (hereafter, botulinum therapy) is approved in Japan for treating urinary urgency, frequency, and urinary incontinence due to refractory overactive bladder or neurogenic bladder. Although botulinum therapy is classified as urinary incontinence surgery, it is minimally invasive, effective, and safe. However, there are few reports on the actual use of botulinum therapy and examination of its effects and side-effects. Herein, we report real-world data on botulinum therapy. PATIENTS AND METHODS: Patients who received botulinum therapy for refractory overactive bladder at the Nara Medical University and affiliated facilities from May 2020 to May 2022 were enrolled. The patient background, treatment efficacy, and safety were retrospectively reviewed. RESULTS: Twenty-three cases of refractory overactive bladder (age: 68.4±14.1 years; 7 males, 16 females; 17 outpatient, 6 hospitalized) were enrolled. Pretreatment, the overactive bladder symptom score (OABSS) was 10.1±2.7, and post-void residual urine volume was 27.1±31.6 ml. Botulinum was administered once, twice, thrice, and four times in 11, eight, three, and one cases, respectively. OABSS decreased to 6.1±3.2 2 weeks after botulinum therapy (p<0.0001), and the effect persisted at 6.6±3.2 after 12 weeks (p<0.0001). Post-void residual urine volume increased to 74.6±79.2 ml after 2 weeks (p=0.0010), but subsequently improved to 33.9±42.0 ml after 12 weeks (p=0.0002). Adverse events included post-void residual urine volume of 200 ml or more in three patients (7.5%) and urinary retention grade 2 in two (5.0%). CONCLUSION: Botulinum therapy is effective and relatively safe for refractory overactive bladders.

Trisomy 13 with retroiliac ureter diagnosed by assessment for recurrent febrile urinary tract infections.

Introduction: Patients with trisomy 13 have multiple malformations, including urological anomalies, and severe cognitive and psychomotor disabilities. We conducted a ureteroureterostomy for a mid-ureteral stricture due to a retroiliac ureter in a patient with trisomy 13. Case presentation: A 6-month-old girl with trisomy 13 developed a urinary tract infection. Computed tomography for assessing recurrent urinary tract infection revealed a left mid-ureteral stricture due to the retroiliac ureter. At the age of 2, a ureteroureterostomy was performed. Two years after surgery, the urinary tract infection did not recur. Conclusion: Ureteroureterostomy is a safe procedure for children with trisomy 13 and multiple comorbidities. Surgical treatment should be considered for patients with trisomy 13 when agreed upon by the family and comorbidities are well-controlled.

Factors associated with patient satisfaction with antiretroviral therapy in Japan: A cross-sectional, multicenter study.

BACKGROUND: Current antiretroviral therapy (ART) regimens are highly effective; therefore, to differentiate between various regimens, considering patient-reported outcomes is essential. This study aimed to assess patient satisfaction with their current ART regimens and investigate factors associated with the Human Immunodeficiency Virus Treatment Satisfaction Questionnaire: Status (HIVTSQs) score. METHODS: This cross-sectional, multicenter study was conducted in Japan between April and December 2021. Patient-reported satisfaction with ART was assessed using the Japanese version of the HIVTSQs. Binary logistic regression was used to identify factors associated with a low total HIVTSQs score. RESULTS: A total of 679 patients completed the questionnaire. The median total HIVTSQs score was 58 (interquartile range: 52.5-64). In the multivariable logistic regression analyses, a total HIVTSQs score in the lowest quartile (indicating low satisfaction) was independently associated with twice- or thrice-daily regimens compared with single-tablet, once-daily regimens (adjusted odds ratio: 2.80, 95% confidence interval: 1.29-6.06, p = 0.009) and depression (adjusted odds ratio: 2.30, 95% confidence interval: 1.32-4.01, p = 0.003). CONCLUSIONS: Satisfaction with the current ART regimen was high. Depression and twice- or thrice-daily ART regimen were associated with low HIVTSQ. Switching to a single-tablet, once-daily regimen may improve patient satisfaction in patients receiving twice- or thrice-daily regimens.

Impact of Complete Surgical Resection of Metastatic Lesions in Patients with Advanced Renal Cell Carcinoma in the Era of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.

Complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) has demonstrated efficacy in the cytokine era, but its effectiveness in the era of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) remains unclear. A multi-institutional database included clinicopathological data of 367 patients with mRCC. Patients were divided into two groups: the CM group and the non-CM group. These two groups were compared before and after propensity score matching (PSM). Cox proportional hazard models were used to detect factors associated with disease-free survival (DFS) and overall survival (OS) from mRCC diagnosis. The CM group showed a significant association with longer overall survival compared to the non-CM group in the PSM-unadjusted cohorts (p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35-0.69), but no superiority was noted in the adjusted cohorts. The median DFS after CM was 24 months, with no significant differences based on relapse timing. Notably, the international metastatic RCC database consortium risk categories and metastatic burden were associated with DFS. This study supports the potential of CM in mRCC management during the TKI/ICI era, although limitations including sample size and selection bias need to be considered.

Long-term follow-up of congenital hydronephrosis in a single-center study.

OBJECTIVES: Many congenital hydronephroses spontaneously resolve. This study evaluated a long-term follow-up of more than 4 years of patients with congenital hydronephrosis at a single center. METHODS: In total, 215 patients (286 kidneys) with congenital hydronephrosis were included. Hydronephrosis outcomes (resolution, improvement, and persistence) and time-to-outcome were evaluated. RESULTS: Fourteen patients underwent early surgical intervention until the age of 2 years. A total of 189 congenital hydronephrosis cases (66%) showed resolution at a median of 16 months (interquartile range: 7-21 months) and 169 (80%) of 210 kidneys with grade I to II hydronephrosis showed resolution at a median of 14 months (interquartile range: 6-23 months). Of 76 kidneys with grade III to IV hydronephrosis, 24 (32%) showed resolution at a median of 29 months (interquartile range: 24-41 months), and 56 (74%) showed improvement to grade II or less at a median of 12 months (interquartile range: 5-23 months). Of the 76 kidneys with grade III to IV hydronephrosis, five required delayed pyeloplasty at a median of 66 months (interquartile range: 42-89 months). One patient was asymptomatic, with a marked worsening of hydronephrosis and decreased renal function 6 years after the resolution of hydronephrosis. CONCLUSIONS: None of the patients with grade I to II hydronephrosis required surgical treatment, and a shorter follow-up may be sufficient. Grade III to IV severe hydronephrosis should be considered for a longer and more careful follow-up, given the possibility of asymptomatic exacerbation of hydronephrosis.

Quality of life after non-nerve-sparing, robot-assisted radical prostatectomy.

OBJECTIVE: To evaluate quality of life (QOL) after non-nerve-sparing, robot-assisted radical prostatectomy (RARP) and factors associated with worsened QOL. METHODS: Patients who underwent non-nerve-sparing RARP (n = 115) were enrolled. The Expanded Prostate Cancer Index Composite and 8-item Short Form Health Survey were used to evaluate QOL at baseline and postoperative 1, 3, 6, 12, and 24 months. Preoperative factors were evaluated by multivariate analysis for worsened QOL. RESULTS: Postoperative 24-month urinary QOL worsened in 68 of 115 (59%) patients. In multivariate analysis, membranous urethral length ≥10.8 mm [odds ratio (OR): .26, 95% confidence interval (CI): .07-.96] and intravesical prostatic protrusion ≥12 mm (OR: .14, 95% CI .06-.35) were significantly associated with maintaining postoperative 24-month urinary QOL. Significantly more patients with intravesical prostatic protrusion ≥12 mm than < 12 mm had improved urinary QOL. At postoperative 24 months, 43 of 115 (38%) patients had worsened sexual QOL. In multivariate analysis, higher Sexual Health Inventory for Men score (OR: 8.39, 95% CI 2.28-30.9), sexual activity (OR: 6.94, 95% CI: 2.27-21.2), and intercourse activity (OR: 6.81, 95% CI: 1.64-28.3) preoperatively were significantly associated with worsened postoperative 24-month sexual QOL. More patients with high preoperative intercourse activity (12/23,53%) had significantly worsened (p = .009) QOL regarding sexual bother than those who had no preoperative intercourse activity (21/92, 23%). CONCLUSION: After non-nerve-sparing RARP, patients with long membranous urethral length and/or intravesical prostatic protrusion maintain urinary QOL. Patients with high intercourse activity presented with impairment of sexual QOL after non-nerve-sparing RARP.

Impact of nutrition and inflammation indicators on peritoneal dialysis initiation and management.

BACKGROUND: The clinical significance of nutrition and inflammation in dialysis patients is well established. This study aimed to evaluate the association between prognosis and indicators of nutrition and inflammation. METHODS: A total of 253 consecutive patients who underwent peritoneal dialysis (PD) as primary renal replacement therapy at our institute between 2006 and 2021 were included. We retrospectively reviewed the patient's medical charts and obtained their clinical information. Nine nutritional and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored. RESULTS: The median age and follow-up period were 65 years and 54 months, respectively. Most nutritional indicators and C-reactive protein (CRP) levels showed a significant correlation with residual renal function. Multivariate analysis revealed that the survival index, nutritional risk index for Japanese hemodialysis patients, and CRP levels were independent indicators of patient survival (P < 0.001, P = 0.034, and P = 0.005, respectively) and cardiovascular disease-free survival (P = 0.009, P = 0.04, and P = 0.017, respectively). Patients with a survival index < 19 and CRP ≥ 0.5 had a high risk of mortality and cardiovascular death (P < 0.0001 and P = 0.0002, respectively). CONCLUSIONS: Our findings suggest that indicators of nutrition and inflammation play important roles in predicting patient outcomes. Further research is warranted to establish optimal management strategies for patients on PD.

Assessment of diagnostic accuracy for cryptorchidism and risk factors for delayed orchidopexy.

OBJECTIVES: Cryptorchidism (CO) diagnosis by palpation is challenging. Patients with suspected CO are primarily referred to pediatric urologists by general pediatricians and urologists. Currently, surgical treatment for CO is recommended earlier than in previous guidelines. In this study, we evaluated factors that lead to diagnosis discordance and delayed orchidopexy in patients referred with suspected CO in addition to timing of initial screening. METHODS: In total, 731 patients (1052 testes) with suspected CO were included. Risk factors for diagnostic discrepancy in CO diagnosis by pediatric urologists and risk of delayed orchiopexy were evaluated. RESULTS: Herein, 659 (90%) patients were diagnosed during routine public health checkups for infants and young children, and 419 (57%) patients were referred by pediatric practitioners. Of 1052 testes, 374 (36%) were diagnosed with CO by pediatric urologists. In multivariate analysis, risk factors of diagnostic discrepancy for CO diagnosis by pediatric urologists were bilateral testis (odds ratio [OR] = 9.17, p < 0.0001), >6 months old at initial diagnosis (OR = 1.036, p < 0.0001), and pediatric referral (OR = 4.60, p < 0.0001). In total, 296 patients underwent orchiopexy for CO. In multivariate analysis, risk factors for delayed orchiopexy were presence of comorbidities (OR = 3.43, p = 0.003) and >10 months old at referral (OR = 12.62, p < 0.0001). CONCLUSIONS: Pediatric referral is a risk factor for discordant CO diagnostics, and late age at referral brings a risk of delayed orchiopexy. It is necessary to enlighten pediatricians, who are mainly responsible for routine health checkups, in teaching CO diagnostic techniques to ensure early referral.

[The Relationship Between Prognosis and Duration of Drug Holidays after Docetaxel Therapy for Castration-Resistant Prostate Cancer].

The next treatment strategy after drug holidays following docetaxel (DTX) therapy for patients with castration-resistant prostate cancer (CRPC) is unclear. This study investigated the relationship between the duration of drug holidays and prognosis after DTX therapy. This study retrospectively assessed 26 patients treated with DTX in our hospital. Overall survival duration was significantly longer in the long-term withdrawal group (duration of drug holidays ≥6 months) than in the short-term withdrawal group (duration of drug holidays ＜6 months) (P＝0.015). Similarly, progression-free survival duration was significantly longer in the long-term withdrawal group than in the short-term withdrawal group (P＝0.008). The short-term withdrawal group had a significantly lower body mass index (P＝0.009) and higher prostate-specific antigen (PSA) (P＝0.017) at the initiation of DTX therapy, higher PSA nadir during DTX therapy (P＝0.009), and higher PSA at the end of DTX therapy (P＝0.022), compared to the long-term withdrawal group. This study suggests that the optimal opportunity to introduce DXT therapy is when the patients with CRPC are physically able to tolerate chemotherapy and their tumor volume remains a lower burden. This may provide a clinical benefit, longer drug holidays, and a better prognosis.

Utility of a penile compression device for the quality of life in male patients with urinary incontinence after prostatectomy (the MORE study): a randomized prospective study.

OBJECTIVES: To verify the effects of penile clamping on the degree of stress urinary incontinence and quality of life in post-radical prostatectomy patients. RESULTS: Thirty-seven patients suffering from stress urinary incontinence after undergoing radical prostatectomy were enrolled. A total of 19 and 18 patients were analyzed in the non-clamp and clamp groups, respectively. The mean ages of the patients in non-clamp and clamp groups were 68.3 ± 7.1 years and 71.2 ± 4.8 years, respectively; the mean time after radical prostatectomy was 28.9 ± 44.0 months and 26.2 ± 39.0 months, respectively. The penile clamp used was the CLAMPMED® (URINE CONTROL CLAMP) size M (MURANAKA MEDICAL INSTRUMENTS Co., Ltd.). Specific urinary care pads (Sawayaka Pad for Men, Small Quantity®, Unicharm Corporation), were provided; the average daily usage was monitored for four weeks. The quality of life was evaluated using the King's Health Questionnaire. The average daily use of urinary care pads was significantly reduced in the clamp group than in the non-clamp group (-0.83 ± 1.51 vs. -0.16 ± 0.69, P = 0.0071). King's Health Questionnaire scores did not change significantly in either group. Wearing the CLAMPMED® reduced the amount of urinary incontinence but did not improve the quality of life. TRIAL REGISTRATION: The Japan Registry of Clinical Trials (jRCT1052230083). Registered 2 August, 2023.

Chronological Changes in Emotional Status and Vaccine Implementation Rate Among Patients on the Waiting List for Deceased-Donor Kidney Transplantation During the Prolonged COVID-19 Pandemic.

BACKGROUND: To investigate the emotional attributes and vaccine implementation rate of patients waiting for kidney transplants during the prolonged COVID-19 pandemic. METHODS: We included 145 patients who were on the waiting list at our institution. Clinical information was obtained from medical charts, and emotional changes were assessed using a telephone questionnaire comprising 13 questions, including vaccine implementation. We also investigated factors affecting the decision to accept or decline deceased-donor kidney transplantation during the COVID-19 pandemic. RESULTS: Of the 145 patients, 121 (83.4%) provided informed consent and completed the questionnaire. The median age at registration on the waiting list for deceased-donor kidney transplantation and the median waiting period was 45.5 years and 103 months, respectively. This cohort comprised 84 males and 37 females. Twenty patients (16.5%) were diagnosed with COVID-19, and 15 (12.4%) were more curious about deceased-donor kidney transplantation. One hundred patients (82.6%) were vaccinated against COVID-19 more than thrice. Thirty patients (24.8%) declined, and 91 patients (75.2%) accepted an organ transplant offer during the COVID-19 pandemic. Multivariate analysis revealed that the long-term waiting period (P = .038) and anxiety about COVID-19, such as visiting the transplant facility (P < .0001) and prudence over time (P < .0001), were independent factors influencing the decline of a kidney transplant offer. CONCLUSIONS: Our findings suggest that some patients hesitated to undergo deceased-donor kidney transplantation during the pandemic. There is a need to develop an appropriate system to ensure safe and secure kidney transplantation during prolonged pandemics.

Impaired nitric oxide mechanisms underlying lower urinary tract dysfunction in aging rats.

The study aimed to investigate the bladder and urethral activity and nitric oxide (NO)-related molecular changes in aging rats. Rats were divided into two groups: Group Y (young rats; 12 wk) and Group A (aging rats; 15 mo). A 24-h voiding assay was performed, and the urodynamic parameters were evaluated using awake cystometry (CMG) and urethral perfusion pressure (UPP) recordings under urethane anesthesia. The mRNA expression levels of NO-, ischemia-, and inflammation-related markers in urethra and bladder tissues and cGMP levels in the urethra were assessed. Body weight was significantly higher in Group A than in Group Y. Voiding assay results (24 h) were insignificant. In the CMG, the number of non-voiding contractions per voiding cycle and post-void residual volume were significantly higher in Group A than in Group Y; voiding efficiency was significantly lower in Group A than in Group Y. In the UPP recordings, the urethral pressure reduction and high-frequency oscillation (HFO) amplitude were significantly lower in Group A than in Group Y. The mRNA expression levels of Hif-1α, Vegf-a, and Tgf-ß1 in the bladder were significantly higher in Group A than in Group Y. The mRNA expression levels of Nos1 and Prkg1 and the cGMP concentrations in the urethra were significantly lower in Group A than in Group Y. Aging rats can be useful models for studying the natural progression of age-related lower urinary tract dysfunctions, for which impaired NO-mediated transmitter function is likely to be an important mechanism.NEW & NOTEWORTHY Aging rats can be useful models for studying the natural progression of age-related lower urinary tract dysfunctions, for which impaired nitric oxide-mediated transmitter function is likely to be an important mechanism.

Serum anandamide and lipids associated with linoleic acid can distinguish interstitial cystitis/bladder pain syndrome from overactive bladder: An exploratory study.

OBJECTIVES: Diagnosing interstitial cystitis/bladder pain syndrome presents a major challenge because it relies on subjective symptoms and empirical cystoscopic findings. A practical biomarker should discriminate diseases that cause increased urinary frequency, particularly overactive bladder. Therefore, we aimed to identify blood biomarkers that can discriminate between interstitial cystitis/bladder pain syndrome and overactive bladder. METHODS: We enrolled patients with Hunner-type interstitial cystitis (n = 20), bladder pain syndrome (n = 20), and overactive bladder (n = 20) and without lower urinary tract symptoms (controls, n = 15) at Ueda Clinic and Nara Medical University Hospital from February 2020 to August 2021. The degree of interstitial cystitis/bladder pain syndrome symptoms was evaluated using the interstitial cystitis symptom and problem indices. Metabolomics analysis was performed on 323 serum metabolites using liquid chromatography time-of-flight mass spectrometry. RESULTS: In the Hunner-type interstitial cystitis or bladder pain syndrome group, we observed smaller relative areas, including anandamide, acylcarnitine (18:2), linoleoyl ethanolamide, and arachidonic acid, compared to those in the overactive bladder or control group. Notably, the differences in the relative areas of anandamide were statistically significant (median: 3.950e-005 and 4.150e-005 vs. 8.300e-005 and 9.800e-005), with an area under the curve of 0.9321, demonstrating its ability to discriminate interstitial cystitis/bladder pain syndrome. CONCLUSIONS: Serum anandamide may be a feasible diagnostic biomarker for interstitial cystitis/bladder pain syndrome. Reduced serum anandamide levels may be associated with pain and inflammation initiation, reflecting the pathology of interstitial cystitis/bladder pain syndrome. Furthermore, our findings suggest that abnormal linoleic acid metabolism may be involved in the pathogenesis of interstitial cystitis/bladder pain syndrome.

Assessment of satisfaction with antiretroviral drugs and the need for long-acting injectable medicines among people living with HIV in Japan and its associated factors: a prospective multicenter cross-sectional observational study.

BACKGROUND: Long-acting injectable formulations for HIV infection have been approved and are now available in Japan. Although not currently recommended as first-line drugs in Japanese or overseas guidelines, use of such formulations may increase, in accordance with patient conditions and preference. We determine the level of satisfaction with current anti-HIV drugs and analyzed the preferences of patients who favor long-acting injectable drugs based on their satisfaction level with the present anti-HIV drugs. METHODS: People living with HIV (PLWH) who had received antiretroviral therapy (ART) for at least one month and consented to the study between 1 April and 31 December 2021 were included in a survey conducted using a self-administered questionnaire. The content of the survey included satisfaction with seven items (tablet size, ease and feeling when taking the medicine, color, taste, portability, daily oral therapy, and co-payment) related to the anti-HIV drugs they were taking and their need for future drugs (dosage form, frequency of dosing, long-acting injectable, etc.). In addition, factors related to the need for long-acting injectable medications were analyzed with regard to the relationship with satisfaction with anti-HIV drugs. RESULTS: Overall, 667 patients available for analysis were included in this study. Satisfaction with anti-HIV drugs was highest with regard to "co-payment" and lowest with "daily oral therapy". Regarding the need for long-acting injectable medications, logistic regression analysis indicated that tablet size and daily oral therapy were significant predictors of patient preference for a once-every-eight-weeks intramuscular formulation in terms of their requirement for long-acting injectable medications (tablet size, OR = 2.14, 95%CI 1.030-4.430, p = 0.042; and daily oral therapy, OR = 1.75, 95%CI 1.010-3.030, p = 0.044). CONCLUSIONS: Patients currently receiving anti-HIV drugs who express dissatisfaction with tablet size and daily oral therapy may prefer a long-acting injectable formulation, taking into consideration patient age, employment status, ART history, frequency of daily dosage and concomitant medications other than ART.

Clinical impact of catheter insertion for peritoneal dialysis on patient survival and catheter-related complications.

OBJECTIVES: The stepwise initiation of peritoneal dialysis (PD) using Moncrief and Popovich's technique (SMAP) for catheter insertion is recommended for the systemic introduction of PD and prevention of catheter-related infections. In this study, we investigated patient outcomes in patients who underwent insertion of a PD catheter with a direct method versus the SMAP method. METHODS: We enrolled 295 consecutive patients who underwent PD as a primary renal replacement therapy and underwent insertion of a PD catheter at our institute between 2006 and 2021. We retrospectively reviewed their data and investigated patient outcomes, including mortality and PD catheter-related complications. RESULTS: Median age at PD induction was 65 years in the direct insertion group and 65 years in the SMAP group (P = 0.80). The rate of PD introduction after emergency hemodialysis was significantly higher in the direct insertion group than in the SMAP group (P < 0.001). There was no significant difference in survival between the direct insertion and SMAP groups during the median follow-up period of 54 months (P = 0.12). Additionally, patients who transitioned to hemodialysis or kidney transplantation after PD showed significantly longer survival (P < 0.001). The incidence of PD catheter-related complications was not significantly different between the two groups. A body mass index ≥ 23 kg/m2 was an independent risk factor for peritonitis and exit-site infection (P = 0.006 and P = 0.011, respectively). CONCLUSIONS: Planned sequential renal replacement therapy including hybrid hemodialysis, complete hemodialysis, and kidney transplantation after PD is important for improving patient outcomes. PD catheter insertion by SMAP may not be mandatory in our clinical practice.

Validation of the risk stratification newly defined in the Japanese Urological Association guidelines 2019 for non-muscle invasive bladder cancer: A multi-institutional collaborative study.

OBJECTIVES: To validate the risk stratification newly defined in the Japanese Urological Association guidelines 2019 for non-muscle invasive bladder cancer and provide a more accurate stratification model for a heterogeneous intermediate-risk group. METHODS: A total of 1610 patients, who underwent transurethral resection, diagnosed with non-muscle invasive bladder cancer in nine collaborating hospitals were retrospectively reviewed. They were classified into low-risk, intermediate-risk, high-risk, and highest-risk groups, and recurrence-free survival, progression-free survival, cancer-specific survival, and overall survival were compared among the groups. The intermediate-risk group was subdivided into two groups based on the multivariable Cox regression model of recurrence and progression risk factors, and a revised risk model was created. RESULTS: The progression-free survival, cancer-specific survival, and overall survival were well stratified, while the recurrence-free survival of the intermediate-risk group was the shortest among the four groups (p < 0.001). The independent risk factors for recurrence and progression-free survival in the intermediate-risk group were as follows: age ≥ 70 years, sex, multiple tumors, tumor size ≥3 cm, and recurrent cases. The intermediate-risk group was subdivided into two groups: favorable intermediate-risk group and unfavorable intermediate-risk group. The revised risk model showed significant differences. CONCLUSION: We validated the Japanese Urological Association guidelines 2019 stratification model. The revised risk model provided a more accurate treatment selection for this disease subset.

Perioperative outcomes of open and robot-assisted partial nephrectomy in patients with renal tumors of moderate to high complexity.

OBJECTIVE: To compare the perioperative outcomes of patients with complex renal tumors treated with open versus robot-assisted partial nephrectomy. METHODS: This retrospective study included 273 patients diagnosed with localized renal tumors at our institution between January 2007 and October 2020. Patients with moderate to high complexity tumors based on the RENAL nephrometry score were included. Perioperative outcomes were compared between open and robot-assisted partial nephrectomy patients. Remnant renal function was defined as the estimated glomerular filtration rate at 12 months after surgery. RESULTS: Open and robot-assisted partial nephrectomy were performed in 43 and 77 patients, respectively. There was no significant difference in overall, cancer-specific, recurrence-free, and metastasis-free survival between the two groups. Remnant renal function was significantly better preserved in the open group, and body mass index was identified as an independent predictive factor (odds ratio 3.05, P = 0.017). Ischemia or type of surgery were not related to remnant renal function. The trifecta achievement rate was 51.2% in the open group and 71.4% in the robot-assisted group (P = 0.031), and the incidence of complications was significantly higher in the open partial nephrectomy group (P = 0.0030). Multivariate analysis revealed that open partial nephrectomy was an independent predictive factor for the incidence of complications (odds ratio 3.92, P = 0.0020). CONCLUSION: Robot-assisted partial nephrectomy can provide good and acceptable oncological and functional outcomes with fewer complications in patients with more complex renal tumors. Further research is needed to establish appropriate treatment strategies and guidelines in current clinical practice.

Anesthetic Management Using Remimazolam for Transcatheter Edge-to-Edge Repair of the Mitral Valve in Patients With Reduced Ejection Fraction: A Case Report of Two Cases.

Remimazolam is an ultrashort-acting benzodiazepine that causes minimal hemodynamic changes. We present two patients, with reduced ejection fraction, who underwent remimazolam anesthesia for transcatheter edge-to-edge repair of the mitral valve with the MitraClip system. In case 1, the patient's vitals were stable throughout the surgery. However, in case 2, which had a lower cardiac output, the patient's blood pressure decreased remarkably after anesthesia induction. Though remimazolam does not alter the cardiac output, it reportedly has vasodilatory effects. Since remimazolam can reduce blood pressure in patients where the reduction in cardiac output is compensated for by high peripheral vascular resistance, caution should be exercised.

5­Aminolevurinic acid inhibits the proliferation of bladder cancer cells by activating heme synthesis.

Iron is an essential nutrient that facilitates cell proliferation and growth, and it can contribute to tumor growth. Although iron chelators have shown great potential in preclinical cancer models, they can cause adverse side­effects. The aim of the present study was to determine whether treatment with 5­aminolevurinic acid (5­ALA) has antitumor effects in bladder cancer, by reduction of mitochondrial iron without using an iron chelator, through activation of heme synthesis. T24 and MGH­U3 cells were treated with 5­ALA. Ferrochelatase uses iron to convert protoporphyrin IX into heme, thus additional groups of T24 and MGH­U3 cells were transfected with synthesized ferrochelatase small interfering RNA (siRNA) either to silence ferrochelatase or to provide a negative siRNA control group, and then cell viability, apoptosis, mitochondrial Fe2+, the cell cycle, and ferritin expression were analyzed in all groups and compared. As an in vivo assessment, mice with orthotopic bladder cancer induced using N­butyl­N­(4­hydro­oxybutyl) were treated with 5­ALA. Bladder weight and pathological findings were evaluated, and immunohistochemical analysis was performed for ferritin and proliferating cell nuclear antigen (PCNA). In the cells treated with 5­ALA, proliferation was decreased compared with the controls, and apoptosis was not detected. In addition, the expression of Fe2+ in mitochondria was decreased by 5­ALA, expression of ferritin was also reduced by 5­ALA, and the percentage of cells in the S phase of the cell cycle was significantly increased by 5­ALA. In T24 and MGH­U3 cells with silenced ferrochelatase, the inhibition of cell proliferation, decreased expression of Fe2+ in mitochondria, reduced expression of ferritin, and increased percentage of cells in the S phase by treatment with 5­ALA were weakened. In vivo, no mouse treated with 5­ALA developed muscle­invasive bladder cancer. The expression of ferritin was weaker in mice treated with 5­ALA and that of PCNA was higher than that in mice treated without 5­ALA. It was concluded that 5­ALA inhibited proliferation of bladder cancer cells by activating heme synthesis.