Chronic kidney disease and Charlson comorbidity index predict complications after robot-assisted radical cystectomy: A single-center study in Japan.

OBJECTIVES: To investigate preoperative patient factors that may predict the occurrence of perioperative complications following robot-assisted radical cystectomy at a single center in Japan. METHODS: From 2013 to 2022, 103 patients underwent RARC at our institution. Complications within 90 days after surgery were assessed using the Clavien-Dindo classification. Preoperative characteristics and surgical outcomes were compared between cohorts with and without complications ≥grade 3. Logistic regression analysis was used to identify the risk factors associated with perioperative complications. RESULTS: Overall, 27% of patients (27/103) experienced grade 3 or higher complications. The cohort that developed complications ≥grade 3 exhibited significantly higher Charlson comorbidity index (p = 0.046) and significantly lower estimated glomerular filtration rate (p = 0.048). Charlson comorbidity index ≥2 (p = 0.037) and estimated glomerular filtration rate <53 (p = 0.008) were independent predictors for the occurrence of complications ≥grade 3. The incidence of complications ≥grade 3 was 61.5% in the group possessing both factors, which was significantly higher than those in the groups possessing neither factor nor only one of the two factors. CONCLUSIONS: Our results suggest that the Charlson comorbidity index and preoperative estimated glomerular filtration rate may be predictors of perioperative complications. It is important to evaluate the patient's preoperative characteristics and choose the surgical procedure accordingly.

[Robotic-Assisted Surgery for Renal Cancer and Cancer of the Renal Pelvis and Ureter].

Recently, minimally invasive urological surgery has become increasingly common as years pass, with the rapid development of laparoscopic, minimal wound, mono-sectional, and robot-assisted surgeries. Robot-assisted surgery's indication for renal, renal pelvis, and ureter cancers has been expanded, and in Japan, robot-assisted partial nephrectomy(RAPN)has been covered by insurances since 2016. Additionally, robot-assisted radical nephrectomy(RARN)and robot-assisted nephroureterectomy(RANU)were covered by insurances in 2022. Compared to that of conventional laparoscopic surgery, robot-assisted surgery offers many advantages, such as 3-dimensional magnified vision, highly flexible forceps manipulation with anti-shake function, and improved dexterity. RARN and RANU are widely used mainly in Western countries, and their effectiveness is being reported. Since RARN and RANU require precise vascular manipulation and often, accurate lymph node dissection, we believe that the surgical robot's characteristics will be extremely useful in these procedures. Therefore, it is expected that RAPN will become similarly popular as RAPN in Japan. In this study, we will review the current status, surgical results, indications, and future prospects of RARN and RANU, which are newly covered by insurances in Japan.

Effect of Adjuvant Systemic Chemotherapy on Intravesical Recurrence After Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma.

BACKGROUND/AIM: There are few reports confirming the relationship between the therapeutic effects of adjuvant systemic chemotherapy and intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. We aimed to evaluate the benefits of adjuvant systemic chemotherapy on intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 133 patients with pathological T stage ≥3 upper urinary tract urothelial carcinoma or lymph node metastasis who underwent radical nephroureterectomy between January 2010 and September 2020 at our hospital and other satellite hospitals. In total, 60 patients received adjuvant systemic chemotherapy, and 73 did not. The Student's t-test and chi-square (χ2) test were used to compare between-group differences. The log-rank test was utilized to compare differences in intravesical recurrence between patients with or without adjuvant systemic chemotherapy. Cox proportional hazards regression analysis was performed to identify the predictive factors of intravesical recurrence. RESULTS: The median follow-up period was 25 months. Forty (30.1%) patients presented with intravesical recurrence. The 1-year intravesical recurrence-free survival rates of patients with and without adjuvant systemic chemotherapy were 86.0% and 70.2%, respectively (p=0.046). Multivariate analysis showed that adjuvant systemic chemotherapy was significantly associated with a lower risk of intravesical recurrence (p=0.032). CONCLUSION: Patients with pathological T stage ≥3 upper urinary tract urothelial carcinoma or lymph node metastasis can have a satisfactory intravesical recurrence-free survival rate with adjuvant systemic chemotherapy.

Effects of Conditioned Medium of Adipose-Derived Stem Cells Exposed to Platelet-Rich Plasma on the Expression of Endothelial Nitric Oxide Synthase and Angiogenesis by Endothelial Cells.

ABSTRACT: Platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) are known to secrete angiogenic factors that contribute to the treatment of intractable ulcers. The combination of PRP and ADSCs may enhance their angiogenic effects. However, it remains unclear whether treatment of ADSCs with PRP influences angiogenesis. We studied whether the conditioned medium from PRP-treated ADSCs under hypoxic conditions exerts angiogenic effects. Although PRP stimulated the proliferation of ADSCs obtained from rats, it decreased the mRNA levels of vascular endothelial growth factor, hepatocyte growth factor, and TGF-ß1, but not of basic fibroblast growth factor, under hypoxia. The conditioned medium of PRP-treated ADSCs inhibited endothelial nitric oxide synthase phosphorylation, decreased NO production, and suppressed tube formation in human umbilical vein endothelial cells. Transplantation of ADSCs alone increased both blood flow and capillary density of the ischemic limb; however, its combination with PRP did not further improve blood flow or capillary density. This suggests that both conditioned medium of ADSCs treated with PRP and combination of PRP with ADSCs transplantation may attenuate the phosphorylation of endothelial nitric oxide synthase and angiogenesis.

Advanced Reconstruction of Vesicourethral Support May Improve Urinary Continence and Quality of Life After Non-nerve-sparing Robot-assisted Radical Prostatectomy.

BACKGROUND/AIM: Postoperative urinary incontinence (UI) after robot-assisted radical prostatectomy (RARP) has a significant impact on patients' quality of life (QOL). Several surgical techniques have been reported to improve postoperative UI. The aim of the study was to investigate the impact of advanced reconstruction of vesicourethral support (ARVUS) on urinary symptoms and QOL after non-nerve-sparing robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Patients who underwent non-nerve-sparing RARP from October 2010 to October 2020 at the Division of Urology, Department of Surgery, Tottori University Faculty of Medicine were reviewed. Patients were divided into the ARVUS and non-ARVUS groups, and propensity score matching was performed. Patients were evaluated by the International Prostate Symptom Score (IPSS), Incontinence Modular Questionnaire Short Form (ICIQ-SF), QOL index, and number of pads used before and 1, 3, 6, and 12 months after RARP. RESULTS: The number of patients in the ARVUS and non-ARVUS group were 41 and 41, respectively. On cystography, the distance of the symphysis pubis to the bladder neck was significantly shorter (p<0.001) and the posterior urethrovesical angle was significantly smaller in the AUVUS group (p<0.001). In the ICIQ-SF, the ARVUS group was significantly better at 6 and 12 months postoperatively. In the IPSS, the ARVUS group was significantly better than the non-ARVUS group at 3 months postoperatively. In a multivariable analysis, membranous urethral length [odds ratio (OR)=3.44, p=0.015] and ARVUS (OR=2.72, p=0.046) were significant factors in achieving 0 pads and total ICIQ-SF Question 1 and 2 scores of ≤2 at 12 months postoperatively. CONCLUSION: ARVUS improved urinary symptoms and QOL. ARVUS seems to be a useful surgical procedure for non- nerve-sparing RARP.

C-reactive protein as a prognostic predictor for non-muscle invasive bladder cancer after intravesical bacillus Calmette-Guérin therapy: A Japan Urological Oncology Group study analysis.

OBJECTIVE: To investigate the involvement of pretreatment C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in the prognosis of patients who underwent intravesical bacillus Calmette-Guérin (BCG) therapy for non-muscle invasive bladder cancer (NMIBC). METHODS: The clinicopathological data of 1709 patients with NMIBC who underwent initial intravesical BCG therapy after transurethral resection of bladder tumor were retrospectively analyzed to evaluate the outcome of intravesical BCG therapy in a multicenter study conducted by the Japan Urological Oncology Group. The prognoses of these patients were analyzed to determine whether the biomarkers (CRP and NLR) could predict the efficacy of intravesical BCG therapy. Patients were divided into two groups according to the pretreatment CRP and NLR, with cutoff values defined as CRP ≥ 0.5 mg/dl and NLR ≥ 2.5, based on several previous reports. RESULTS: In the univariable analysis, CRP ≥ 0.5 mg/dl was significantly associated with intravesical recurrence, cancer-specific survival, and bladder cancer (BC) progression, while NLR ≥ 2.5 was not significantly associated with patient prognosis. In the multivariable analysis, CRP ≥ 0.5 mg/dl was significantly associated with intravesical recurrence and BC progression. The concordance index was used to examine the accuracy in predicting recurrence and progression events. While CRP was slightly, though not statistically significant, inferior to the European Association of Urology risk classification, the combination of them showed improved predictive accuracy. CONCLUSION: This study suggests that CRP can be a prognostic factor after intravesical BCG therapy and may provide useful data for determining treatment and follow-up strategies for patients with NMIBC.

Efficacy of Combination Treatment with Tadalafil and Mirabegron in Patients with Benign Prostatic Hyperplasia Who Presented with Persistent Storage Symptoms After Tadalafil Monotreatment: A Prospective, Multicenter, Open-Labeled Study.

Background: The aim of this study is to evaluate the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, plus mirabegron, a ß3-adrenoreceptor agonist, in patients with benign prostatic hyperplasia who presented with persistent storage symptoms after tadalafil monotreatment. Methods: The registration of this study started in August 2016 and ended in July 2019. The inclusion criteria included patients aged ≥ 50 years who were diagnosed with benign prostatic hyperplasia and who presented with overactive bladder symptoms. Patients were treated with oral tadalafil 5 mg once daily for 4 weeks. Then, its efficacy was evaluated. Patients who responded to the treatment received oral tadalafil 5 mg once daily for 4 more weeks (monotreatment group). Meanwhile, those who did not respond received oral tadalafil 5 mg and mirabegron 50 mg, which is an add-on treatment, once daily for 4 more weeks (combination therapy group). Results: After 8 weeks, the monotreatment group (n = 19) and the combination group (n = 56) had significantly better total Overactive Bladder Symptom Score and International Prostate Symptom Score and International Prostate Symptom Score voiding and storage subscale scores. Moreover, the two groups experienced significant improvements in the total Overactive Bladder Questionnaire and Nocturia Quality of Life Questionnaire scores, and Nocturia Quality of Life Questionnaire Bother/Concern subscale score after 8 weeks. However, there were no cases of urinary retention or serious adverse events. Conclusion: Combination treatment with tadalafil and mirabegron is effective and safe for patients with benign prostatic hyperplasia who presented with persistent storage symptoms after tadalafil monotreatment. Hence, tadalafil plus mirabegron is a promising therapeutic option, and it can improve overactive bladder related-quality of life.

Incidence and predictive factors of orgasmic dysfunction after robot-assisted radical prostatectomy: A cross-sectional, questionnaire-based study.

OBJECTIVE: We sought to evaluate the incidence and extent of orgasmic dysfunction in patients after robot-assisted radical prostatectomy and to identify factors that could predict patients at risk. METHODS: A single-center, questionnaire-based, cross-sectional study was conducted on patients who underwent robot-assisted radical prostatectomy (n = 523) between October 2010 and November 2019. In addition to six questions about sexual activity, orgasmic function, altered perception of orgasms, dysorgasmia, and climacturia, the International Consultation on Incontinence Questionnaire Short Form was administered. In February 2020, a letter was mailed inviting patients to participate in the survey. The primary outcome measure was the rate of orgasmic dysfunction. Logistic regression analyses were used to identify predictors of orgasmic dysfunction. RESULTS: Overall, 259 questionnaires were used for analysis. Among sexually active patients (n = 145), 33 (22.8%) reported anorgasmia, and 83 (57.2%) reported decreased orgasm intensity. Twenty-two (15.1%) patients reported dysorgasmia; among these patients, the pain was experienced almost always or always in 13.6%, sometimes in 13.6%, and a few times in 72.8% of cases. Climacturia was reported by 44 patients (30.3%). Nerve-sparing procedures decreased the risk of anorgasmia (odds ratio 0.37, 95% confidence interval 0.15-0.88) and urinary incontinence increased the risk of climacturia (odds ratio 3.13, 95% confidence interval 1.20-8.15). CONCLUSIONS: These results indicate that orgasmic dysfunction after robot-assisted radical prostatectomy is relatively common.

Endoscopic Ablation of Upper Tract Urothelial Carcinoma: A Report of Two Cases with Long Disease Recurrence-Free Periods.

Upper tract urothelial carcinoma (UTUC) is a relatively rare disease that accounts for 5% to 10% of all urothelial carcinomas (UCs). Radical nephroureterectomy (RNU) with a bladder cuff is the current gold standard for the management of UTUC; however, endoscopic ablation is also an option for low-risk UTUC to preserve kidney function. Herein, we present two cases of solitary kidney with a right lower ureteral tumor. Both patients underwent left RNU in the past. An 82-year-old man with a right ureteral tumor whose histopathological examination revealed low-grade UC. Laser ablation was performed with ureteroscopy, and there was no recurrence for 7 years after treatment. A 67-year-old woman with a right lower ureteral tumor whose histopathological examination also revealed low-grade UC. Laser ablation was performed, and there was no recurrence for 5 years after the treatment. We closely followed-up our two patients after RNU. This allowed for early detection of tumor recurrence, after which we could perform laser ablation therapy.

A Comparison Between Laparoscopic and Robot-Assisted Laparoscopic Pyeloplasty in Patients with Ureteropelvic Junction Obstruction.

Background: The aim of this study is to compare the results of laparoscopic pyeloplasty and robot-assisted laparoscopic pyeloplasty in patients with ureteropelvic junction obstruction. Methods: Between March 2008 and May 2019, the patients who underwent retroperitoneal laparoscopic or robotic-assisted laparoscopic pyeloplasty in our institution were retrospectively reviewed. Results: Thirteen patients underwent laparoscopically, and 12 patients underwent robotic surgery. The significant difference was found in median operative time between laparoscopic group (296 minutes) and robotic group (199 minutes) (P = 0.001). The median time for drain removal in laparoscopic group was longer than robotic group (3 vs. 2 days, respectively, P = 0.029). Conclusion: Laparoscopic and robot-assisted laparoscopic pyeloplasty is safe and excellent success rates in patients with ureteropelvic junction obstruction. However, our experience study suggested that robotic surgery improves a total operative time, decreases drain removal time and less intraoperative blood loss than laparoscopic approach.

Initial Experience of Robot-Assisted Adrenalectomy in Japan: What is the Optimal Selection of Robotic Forceps for Adrenalectomy?

Minimally invasive adrenalectomy is the preferred technique for managing adrenal tumors. Laparoscopic adrenalectomy is widely performed and covered by insurance in Japan, but robot-assisted adrenalectomy is not. To investigate the best forceps combinations for performing robot-assisted adrenalectomy safely, we performed robot-assisted adrenalectomy for two left and two right adrenal adenomas using different robotic forceps combinations (bipolar forceps, monopolar curved scissors, Vessel Sealer Extend, and SynchroSeal) for each case. Although we evaluated a small number of RAs, lower blood loss was observed in patients where the vessel sealing devices were used. The extent of dissection is small for adrenalectomy, and robotic bipolar vessel sealing tools may not be necessary, especially for the small adrenal tumors. However, considering the risk benefits, the combination of forceps with Vessel Sealer Extend (by the left arm) and monopolar curved scissors (by the right arm) will become one of the best forceps combinations for performing robot-assisted adrenalectomy safely.

Early effects of adipose-derived stem cell sheets against detrusor underactivity in a rat cryo-injury model.

AIMS: This study investigated the effects of adipose-derived stem cell sheets on a rat model of detrusor underactivity. MAIN METHODS: Adipose-derived stem cell sheets were prepared from the subcutaneous adipose tissue of male Lewis rats. Female Lewis rats were assigned into four groups: control, sham operation, cryo-injury, and cryo-injury+sheet (n = 8 per group). Rats in the cryo-injury+sheet group were implanted with ASC sheets 3 days after cryo-injury induction and underwent cystometry 7 days later. Subsequently, reverse transcription-polymerase chain reaction (RT-PCR) and histopathological examinations were performed. Cell sheets expressing the green fluorescent protein were prepared and transplanted to confirm the viability and differentiation of the sheets. Fluorescence was confirmed using a fluorescence stereomicroscope on days 3, 7, 14, 21, and 28 after sheet implantation, and tissue immunostaining was performed. KEY FINDINGS: Cystometry showed that sheet implantation improved the maximum intravesical pressure (P = 0.009) and the residual urine volume (P = 0.011). Furthermore, RT-PCR indicated that the mRNA levels of the angiogenic factors vascular endothelial growth factor and hepatocyte growth factor were significantly higher in the cryo-injury+sheet group than in the cryo-injury group (P = 0.045, P = 0.037, respectively). Histologically, sheet implantation resulted in an improvement in inflammation and increased the number of blood vessels. Green fluorescent protein-positive cells fused with von Willebrand factor-positive cells and differentiated into blood vessels 7 days after sheet implantation. SIGNIFICANCE: Adipose-derived stem cell sheets transplanted into the bladder of cryo-injured rats differentiated into blood vessels and restored bladder contractile function 7 days after transplantation.

Extent of pelvic lymph node dissection improves early oncological outcomes for patients with high-risk prostate cancer without lymph node involvement after robot-assisted radical prostatectomy.

BACKGROUND: We investigated the effect of the extent of pelvic lymph node dissection (LND) on biochemical recurrence (BCR) in patients with prostate cancer (PCa) without lymph node involvement (LNI) treated with robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively analyzed data from 378 patients who underwent RARP with LND at our hospital between October 2010 and June 2019. The BCR-free survival rate was determined using Kaplan-Meier analysis, and Cox regression analysis was used to investigate BCR prognostic factors. The total score calculated from the D'Amico risk classification and the percentage of positive biopsy cores were used for analysis. Patients were classified into 3 BCR risk groups (low risk: 0-3 points, intermediate risk: 4-5 points, and high risk: 6-8 points). RESULTS: Limited LND was performed in 161 patients (42.6%), extended LND in 217 patients (57.4%), and BCR was confirmed in 66 patients (17.5%) after RARP. Both univariate and multivariate analyses showed no significant difference in the association between the extent of LND and BCR. The Kaplan-Meier curve for BCR generated using our risk classification for patients with PCa without LNI showed no significant association between the extent of LND and BCR in the low-risk group (p = 0.790). A significantly improved BCR-free survival was observed in the extended LND group among patients with PCa at intermediate risk or higher (p < 0.05). CONCLUSION: According to our risk classification, BCR may be less likely to occur when extended LND is performed during RARP for patients with localized PCa at intermediate risk or higher.

Sarcopenia is associated with survival in patients with urothelial carcinoma treated with systemic chemotherapy.

BACKGROUND: Sarcopenia impacts perioperative outcomes and prognosis in various carcinomas. We aimed to investigate whether sarcopenia at the time of chemotherapy induction in patients with urothelial carcinoma is associated with prognosis. METHODS: We evaluated patients treated with chemotherapy for urothelial carcinoma between April 2013 and February 2018 at our institution and affiliated centers. Skeletal muscle mass (total psoas muscle, paraspinal muscle, and total skeletal muscle areas) were used to calculate the total psoas muscle index, paraspinal muscle index, and skeletal muscle index. All participants were grouped as per cutoff points set at the median value for each sex. Overall survival was evaluated using Cox regression analysis. RESULTS: Of the 240 patients, 171 were men and 69 were women; mean age during chemotherapy was 71 years (range: 43-88); and 36, 56, and 148 patients were at stages II, III, and IV, respectively. Paraspinal muscle index was most associated with the prognosis; groups with lower paraspinal muscle index were defined as sarcopenic (men: ≤ 20.9 cm2/m2, women: ≤ 16.8 cm2/m2). The overall survival was significantly longer in the non-sarcopenia group including all stages (p = 0.001), and in stage III (p = 0.048) and IV (p = 0.005) patients. There was no significant difference among stage II patients (p = 0.648). After propensity score matching, survival was still significantly longer in the non-sarcopenia group (p = 0.004). CONCLUSIONS: Paraspinal muscle index measurements obtained during chemotherapy induction for urothelial carcinoma were independent prognostic factors. The absence of sarcopenia may lead to long-term survival in patients undergoing chemotherapy for urothelial carcinoma.

Influence of the time interval between biopsy and surgery on the biochemical recurrence after robot-assisted radical prostatectomy in Japanese patients.

OBJECTIVE: We evaluated the impact of the duration between the biopsy and surgery on the biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively evaluated 302 patients who underwent RARP in our institution from April 2010 to December 2017. Patients were categorized into 2 groups, an interval between biopsy and surgery of 180 days or less (Group A) and longer than 180 days (Group B). Factors retrospectively analyzed for the BCR for the interval between the biopsy and RARP included patient's characteristics, intraoperative and postoperative results. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the predictors of BCR. RESULTS: The median follow-up was 42 months, with 24 patients developing BCR at a mean of 13.5 months after RARP. There was no difference in the rate of BCR in Group A and Group B. Multivariate analysis showed that BMI (<23.5 kg/m2, p = 0.034), worst GS of the biopsy (≥8, p = 0.007), and without lymph node dissection (p = 0.034) were significant predictors of BCR. Analysis of the interval from the biopsy showed that there was no significant difference between Group A and Group B, when tested according to the NCCN risk stratification (low risk: p = 0.871, intermediate risk: p = 0.205, high risk: p = 0.287). CONCLUSION: The preoperative predictors of BCR included BMI (<23.5 kg/m2) and worst GS of the biopsy, and without lymph node dissection. A long duration from biopsy to RARP did not influence the probability of BCR, even in patients considered to be at a high risk.

Longitudinal, 5-year long-term outcomes for urinary continence and quality of life after robot-assisted radical prostatectomy in Japanese patients.

OBJECTIVES: The aim of this study was to investigate the longitudinal 5-year long-term outcomes for urinary continence and quality of life (QOL) after robot-assisted radical prostatectomy (RARP), particularly nerve-sparing. METHODS: Among patients who underwent RARP between October 2010 and October 2015, postoperative urinary symptoms were retrospectively examined using the International Prostate Symptom Score (IPSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), QOL index, and number of pads used. Patients were divided into nerve-sparing and non-nerve-sparing groups, and all data were evaluated before and at 1, 3, 6, 12, 24, 36, 48, and 60 months after surgery. RESULTS: After propensity score matching, 47 patients each were included in the two groups. No significant difference in the IPSS or QOL index was seen between groups. The IPSS and QOL index showed an increase in the first month after RARP, but at 6 months, values were lower than preoperative levels and then slowly improved. Pad-free rates at 5 years after surgery were 93.6% and 80.1% in the nerve-sparing and non-nerve-sparing groups, respectively (P = .029). ICIQ-SF scores were significantly improved in the nerve-sparing compared with the non-nerve-sparing group at 1, 3, and 6 months after surgery. After 12 months, no significant changes were identified until 60 months. CONCLUSIONS: In this study, nerve-sparing had a strong impact on urinary continence in the early postoperative period. After 12 months, urinary continence remained stable until 60 months.

Response to Platinum-based Chemotherapy Rechallenge for Patients With Pembrolizumab-refractory Urothelial Carcinoma.

BACKGROUND: This study aimed to investigate the response to platinum-based chemotherapy rechallenge in patients with pembrolizumab-refractory urothelial carcinoma. PATIENTS AND METHODS: We retrospectively reviewed 14 patients with pembrolizumab-refractory urothelial carcinoma. Each patient received a regimen that they had not previously received (paclitaxel plus carboplatin in 10, gemcitabine plus docetaxel and carboplatin in four). Tumor response and adverse events were assessed. We evaluated overall survival from the chemotherapy rechallenge start date until death. RESULTS: The median overall survival was 11.2 months. The disease-control rate was 85.7%. Partial responses occurred in the metastases in lymph nodes in three (37.5%) patients, lung in one (25%), peritoneal in three (75%), and liver in three (100%). Neutropenia of grade ≥3 occurred in 13 (92.9%) patients. CONCLUSION: The activity of platinum-based chemotherapy rechallenge after pembrolizumab was maintained. Neutropenia was observed in most patients.

Potential role of ghrelin on the micturition reflex in rats.

INTRODUCTION: The aim of this study was to investigate the effects of intravenous ghrelin administration on the micturition reflex in rats. MATERIAL AND METHODS: Continuous cystometrograms were performed with female Sparague-Dawley rats under urethane anesthesia. Stable micturition cycles were established, and ghrelin was then administered intravenously to evaluate changes in bladder activity. In this experiment investigating the role of opioid systems, ghrelin was administered intravenously at the time of first observed bladder contraction after intravenous administration of naloxone methiodide, an opioid receptor antagonist. RESULTS: Intravenous administration of ghrelin increased intercontraction interval that was dose-dependent. These inhibitory effects returned to pre-controls level within 80 minutes of administration. Similarly, intravenous administration of ghrelin increased threshold pressure in a dose-dependent fashion. These inhibitory effects of ghrelin were antagonized by intravenous naloxone methiodide administration. CONCLUSIONS: These results show that ghrelin inhibits the micturition reflex through an opioid-dependent mechanism in rats under urethane anesthesia.

Optimal Number of Systematic Biopsy Cores Used in Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Targeted Prostate Biopsy.

BACKGROUND: In recent years, the effectiveness of magnetic resonance imaging (MRI)-ultrasound fusion targeted biopsy (MRF-TB) has been widely reported. In this study, we assessed the effect of reduction of the number of systematic biopsy (SB) cores on the cancer detection rate (CDR). METHODS: Patients with a high prostate-specific antigen (PSA) level underwent prostate MRI. The Prostate Imaging-Reporting and Data System version 2 (PI-RADS) was then used to rate the lesions. The inclusion criteria were as follows: (1) PSA level between 4.0 and 30.0 ng/mL and (2) patients with one or more lesions on MRI and a PI-RADS score of 3 or more. All enrolled patients were SB naïve or had a history of one or more prior negative SBs. A total of 104 Japanese met this selection criterion. We have traditionally performed 14-core SB following the MRF-TB. In this study, the CDRs of 10-core SB methods, excluding biopsy results at the center of the base and mid-level on both sides, were compared with those of the conventional biopsy method. RESULTS: We compared CDRs of the 14-core and 10-core SBs used in combination. The overall CDR was 55.8% for the former and 55.8% for the latter, thereby indicating that there was no significant difference (P = 1.00) between the two. In addition, the CDRs of csPCa were 51.9% for the former and 51.1% for the latter, which indicated that there was no significant difference (P = 0.317). CONCLUSION: There was no significant difference in the CDR when the number of SB cores to be used in combination was 14 and 10.

Intravesical Bacillus Calmette-Guérin Treatment for T1 High-Grade Non-Muscle Invasive Bladder Cancer with Divergent Differentiation or Variant Morphologies.

The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette-Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), and UC with VMs (UC-VM) are limited. We evaluated 1490 patients with T1 high-grade bladder UC who received intravesical BCG during 2000-2019. They were classified into three groups: 93.6% with pUC, 4.4% with UC-DD, and 2.0% with UC-VM. Recurrence-free, progression-free, and cancer-specific survival following intravesical BCG were compared among the groups using multivariate Cox regression analysis, also used to estimate inverse probability of treatment weighting-adjusted hazard ratio and 95% confidence interval for the outcomes. Glandular differentiation and micropapillary variant were the most common forms in the UC-DD and UC-VM groups, respectively. Of 1490 patients, 31% and 13% experienced recurrence and progression, respectively, and 5.0% died of bladder cancer. Survival analyses revealed the impact of concomitant VMs was significant for cancer-specific survival, but not recurrence-free and progression-free survival compared with that of pUC. Our analysis clearly demonstrated that concomitant VMs were associated with aggressive behavior in contrast to concomitant DD in patients treated with intravesical BCG.