Effectiveness of onabotulinumtoxin A for refractory overactive bladder with cough-associated detrusor overactivity.

Introduction: We report a case of refractory overactive bladder with cough-associated detrusor overactivity treated by onabotulinumtoxin A. Case presentation: A 79-year-old woman who underwent mid-urethral sling surgery 8 years ago complained mainly of urinary incontinence following abdominal pressure. Various medicines to treat overactive bladder symptoms were ineffective. Cystometry revealed cough-associated detrusor overactivity. Onabotulinumtoxin A injections in her bladder improved subjective symptoms, and cough-associated detrusor overactivity disappeared on cystometry. Conclusions: Onabotulinumtoxin A injection effectively resolved refractory overactive bladder with urgency urinary incontinence due to cough-associated detrusor overactivity.

Utility and safety of robot-assisted radical cystectomy in older patients with bladder cancer.

Introduction: This study aimed to investigate the efficacy and safety of robot-assisted radical cystectomy (RARC) in older patients with bladder cancer (BCa).Material and methods: We reviewed the clinical and pathological records of 110 patients with BCa who underwent RARC at Gifu University Hospital between February 2019 and January 2023. Older patients were defined as those with BCa aged ≥ 75 years. The enrolled patients were divided into two groups: those aged < 75 years (Group I) and those aged ≥ 75 years (Group II). Oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS), were the primary endpoints of the study; the secondary endpoints were the surgical and pathological outcomes.Results: A shorter console time, less blood loss, and reduced time to postoperative fluid and food intake in Group II may be attributed to the fact that more patients opted for ureterocutaneostomy in Group II than in Group I. In all patients, the three-year OS and RFS rates were 84.7% and 88.5%, respectively. There were no significant differences in OS or RFS between the two groups. (p = .403, p = .963, respectively).Conclusions: RARC appears to be a safe and useful treatment option for older patients with BCa.

[A Case Report of a Patient with Metastatic Adrenocortical Carcinoma who Received the Combination Etoposide, Doxorubicin, Cisplatin, and Mitotane Therapy and Achieved Remission].

A 40-year-old Japanese female was referred to our institution with a high serum lactate dehydrogenase level. Computed tomography (CT) showed a large right adrenal tumor, 14 cm in size without distant metastases. The patient was clinically diagnosed with T2N0M0 adrenocortical carcinoma and underwent right adrenalectomy. The pathological diagnosis was adrenocortical carcinoma with negative surgical margin. The patient was administered mitotane for 2 years as adjuvant therapy. Subsequently, CT revealed asynchronous multiple metastases, including liver, lung, left kidney, and right acetabulum. The patient received 15 courses of EDP (a combination of etoposide, doxorubicin, and cisplatin) plus mitotane therapy, and had stable disease without new lesions.

Validation of standardized training system for robot-assisted radical prostatectomy: comparison of perioperative and surgical outcomes between experienced surgeons and novice surgeons at a low-volume institute in Japan.

INTRODUCTION: Although robot-assisted radical prostatectomy (RARP) has become a standard treatment modality in patients with prostate cancer (PCa), RARP is a complicated and difficult surgical procedure due to the risk of serious surgery-related complications. This study aimed to evaluate the validation of a standardized training system for RARP in patients with PCa at a single institute. MATERIAL AND METHODS: We retrospectively reviewed the clinical and pathological records of 155 patients with PCa who underwent RARP at Gifu University between August 2018 and April 2021. We developed an institutional program for new surgeons based on the separation of the RARP procedure into six checkpoints. The primary endpoints were surgical outcomes and perioperative complications among three groups (expert, trainer, and novice surgeon groups). RESULTS: The console time was significantly longer in the novice surgeon group than in the other groups. Regarding bladder neck dissection, ligation of lateral pedicles, and vesicourethral anastomosis, the operative time was significantly shorter in the expert group than in the other groups. Surgery-related complications occurred in 15 patients (9.7%). CONCLUSIONS: Our training system for RARP might help reduce the influence of the learning curve on surgical outcomes and ensure that the surgeries performed at low-volume institutions are safe and effective.

Utility of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immune Inflammation Index as Prognostic, Predictive Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab and Ipilimumab.

The aim of this study was to assess the utility of neutrophil-to-lymphocyte ratio (NLR), plate-let-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) as predictive biomarkers with oncological outcomes for metastatic renal cell carcinoma (mRCC) patients treated with nivolumab and ipilimumab (NIVO + IPI). We conducted a retrospective multicenter cohort study assessing patients with mRCC treated with NIVO + IPI at eight institutions in Japan. In this study, the follow-up period was median 14 months. The 1-year overall- and progression-free survival (PFS) rates were 89.1% and 63.1, respectively. The objective response rate (ORR) and disease control rate (DCR) were 41.9% and 81.4%, respectively. The 1-year PFS rates were 85.7% and 49.1% for NLR ≤ 2.8 and >2.8, respectively (p = 0.005), and 75.5% and 49.7% for PLR ≤ 215.6 and >215.6, respectively (p = 0.034). Regarding SII, the 1-year PFS rates were 90.0% and 54.8% when SII was ≤561.7 and >561.7, respectively (p = 0.023). Therefore, NLR, PLR, and SII levels in mRCC patients treated with NIVO + IPI may be useful in predicting oncological outcomes.

A Case of Localized Prostate Cancer Associated with Polymyalgia Rheumatica with Marked Symptomatic Improvement after Robot-Assisted Radical Prostatectomy.

A 73-year-old man visited our hospital with chief complaints of fever of unknown origin and bilateral shoulder and hip joint pain. He was initially diagnosed with polymyalgia rheumatica (PMR). Although the patient was treated with prednisolone 15 mg/day, his PMR-related symptoms did not improve. Further examination was performed as the patient was suspected of having paraneoplastic syndrome. Assessment results showed prostate cancer without metastases. After undergoing robot-assisted radical prostatectomy, the patient's PMR-related symptoms dramatically improved. Hence, the prednisolone dose was decreased to 4 mg/day. PCa may have triggered the development of PMR through the activation of immune-mediated systemic inflammatory responses.

[Paraurethral Leiomyoma in a Female Patient who Had Clinical Symptoms with Increase of Tumor Volume: A Case Report].

A 34-year-old woman underwent total hysterectomy for management of uterine leiomyoma. At the same time, a paraurethral tumor (2 cm in size) was diagnosed based on magnetic resonance imaging (MRI). However, the patient was not treated for the tumor considering its small size. Eight years later, the patient was referred to our institution with a chief complaint of urethral bleeding. Computed tomography revealed a paraurethral mass at the same location, which was 13 cm in size. A percutaneous needle biopsy was performed and the tumor was diagnosed as leiomyoma. Tumor extirpation was performed and immunohistochemical analysis of the specimen demonstrated positive estrogen and progesterone receptors. Recurrence was not observed on MRI taken 6 months after the surgery. Paraurethral leiomyoma is rare, but relatively common in young women.

[Renal Cell Carcinoma in the Left Pelvic Kidney : A Case Report].

We report the case of a 61-year-old man who was incidentally diagnosed with a left pelvic ectopic kidney with renal tumor. Computed tomography showed a hypervascular tumor at the posterior surface of the ectopic kidney with five arterial and two venous supply vessels. On preoperative examination, this patient had respiratory dysfunction. For these reasons, an open radical nephrectomy was performed. Histological examination revealed a clear cell renal cell carcinoma, pT1aN0M0, G1, and a Fuhrman nuclear grading system grade of G2. No evidence of disease was observed 15 months after surgery.

Ghrelin after chemotherapy as a prognostic predictor of progression-free survival in patients with muscle-invasive bladder cancer.

BACKGROUND: Although the patients with muscle-invasive bladder cancer (MIBC) generally have poor prognosis, the utility of these biomarkers for the prediction of oncological outcomes in MIBC has not been completely explored. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, and angiogenesis. Thus, we aimed to evaluate the impact of serum ghrelin levels on survival in MIBC. METHODS: In this study, we reviewed the clinical and pathological records of 56 patients who were diagnosed with MIBC between November 2015 and November 2019 at Gifu and Hirosaki University Hospitals. We focused on 27 patients who had received chemotherapy and collected blood samples before and after chemotherapy. Blood samples were collected before chemotherapy and after completing two cycles of chemotherapy. Serum acyl (AG) and desacyl ghrelin (DG) were measured using AG and DG enzyme-linked immunosorbent assay kits (SCETI, Tokyo, Japan), respectively. RESULTS: The 3-year overall and progression-free survival (PFS) rates were 82.9% and 68.3%, respectively. According to the AG level after chemotherapy, the 3-year PFS rates were 77.5% and 53.0% in patients with AG levels ≥1.34 and <1.34 pg/mL, respectively (P=0.038). With regard to DG levels after chemotherapy, the 3-year PFS rates were 90.9% and 43.3% in patients with DG levels <92.3 and ≥92.3 pg/mL, respectively (P=0.039). On multivariate analysis, serum AG levels were significantly associated with PFS. CONCLUSIONS: This study suggested the usefulness of the ghrelin as a prognostic predictor of PFS in patients with MIBC.

The Utility of Combined Target and Systematic Prostate Biopsies in the Diagnosis of Clinically Significant Prostate Cancer Using Prostate Imaging Reporting and Data System Version 2 Based on Biparametric Magnetic Resonance Imaging.

This study aimed to determine the predictive value of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) based on biparametric magnetic resonance imaging (bpMRI) with combined target biopsy (TBx) and systematic biopsy (SBx) in patients with suspicion of having clinically significant prostate cancer (csPCa). In this retrospective study, we reviewed the clinical and pathological records of 184 consecutive patients who underwent bpMRI before prostate biopsy. We focused on patients with PI-RADS v2 scores ≥ 3. MRI was performed using a 3-Tesla clinical scanner with a 32-channel phased-array receiver coil. PI-RADS v2 was used to describe bpMRI findings based on T2-weighted imaging and diffusion-weighted imaging scores. The primary endpoint was the diagnostic accuracy rate of PI-RADS v2 based on bpMRI for patients with prostate cancer (PCa) who underwent combined TBx and SBx. A total of 104 patients were enrolled in this study. Combined TBx and SBx was significantly superior to either method alone for PCa detection in patients with suspicious lesions according to PI-RADS v2. TBx and SBx detected concordant csPCa in only 24.1% of the patients. In addition, the rate of increase in the Gleason score was similar between SBx (41.5%) and TBx (34.1%). The diagnostic accuracy of bpMRI is comparable to that of standard multiparametric MRI for the detection of csPCa. Moreover, combined TBx and SBx may be optimal for the accurate determination of csPCa diagnosis, the International Society of Urological Pathology grade, and risk classification.

Efficacy and Safety of Nivolumab and Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study.

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

The utility of laparoscopic partial nephrectomy with renal function preservation, regardless of warm ischemia time, compared with laparoscopic radical nephrectomy.

INTRODUCTION: This study aimed to evaluate the chronologic changes in renal function after laparoscopic partial (LPN) or radical nephrectomy (LRN) in patients with clinical T1 renal cell carcinoma. METHODS: In this retrospective study, patients with clinical stage T1 renal cell carcinoma who underwent LPN or LRN were divided into three groups, namely, LPN-A group including LPN patients with WIT ≤25 minutes, LPN-B group including LPN patients with WIT >25 minutes, and LRN group. Perioperative complications that occurred within 30 days after surgery were retrieved. All patients were followed-up every 3 months to evaluate the estimated glomerular filtration rate. The primary endpoint of this study was to assess the chronological changes in renal function after surgery. RESULTS: A total of 153 patients were enrolled in this study. The change in estimated glomerular filtration rate between day 1 and 2 weeks after surgery was significantly lower in the LPN-B group than in the LPN-A group (p<0.005). Both LPN-A and -B groups achieved eGFR ≥90% 2 weeks after surgery. In addition, the estimated glomerular filtration rate decline from post-operative day 1 through 24 months in the LPN-A group or the LPN-B group was significantly smaller than that in the LRN group (P < 0.001, P < 0.001, respectively). CONCLUSION: Our results demonstrate the efficacy and safety of LPN in patients with T1 renal cell carcinoma. Although complication rates were similar in both groups, post-operative renal function was not different between the LPN-A and -B groups.

[Well Leg Compartment Syndrome after Cystectomy in the Lithotomy Position: A Case Report].

Well leg compartment syndrome (WLCS) is an uncommon and severe complication that occurs after prolonged surgery in the lithotomy position. A 67-year-old male with bladder cancer who underwent cystectomy including ileal conduit construction in the lithotomy position developed severe, gradually worsening cramping pain in the right leg on the day after surgery. The posterior compartmental pressure of the right leg was high (40 mmHg), and WLCS was diagnosed. Emergency fasciotomy was followed by rehabilitation for one month and he recovered from motor or sensory deficits, but the pain continued. We considered that important factors associated with the development of WLCS in this patient were arteriosclerosis obliterans and the length of time during which he remained in the lithotomy position during the ileal conduit procedure. We consider thatlengthy surgical procedures for cystectomy with patients in the lithotomy position have high potential for inducing WLCS.

[Tadalafil Ameliorates Symptoms of Patients with Benign Prostatic Hyperplasia Complicated by Chronic Pelvic Pain Syndrome].

To examine the efficacy and safety of tadalafil in the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia with chronic pelvic pain syndrome, we treated 23 Japanese men with tadalafil 5 mg once daily for 4 weeks. The mean age of the participantswas58.7 yearsand the prostate volume was25. 2 ml. Significant improvementsin total International Prostatic Symptom Score, International Prostatic Symptom Score Quality of Life Index, total National Institutes of Health Chronic Prostatitis Symptom Index score, pain subscore, urinary symptom subscore, and quality of life impact subscore, were observed for tadalafil versus before treatment. These findings confirm that tadalafil is a valuable new treatment option for patients with benign prostatic hyperplasia complicated by chronic pelvic pain syndrome.

Capsaicin-induced increase of intestinal cefazolin absorption in rats.

The effect of capsaicin on intestinal cefazolin absorption was examined by means of an in situ closed loop method in rats to clarify whether the vanilloid receptor (TRPV1) is involved in drug absorption driven by passive diffusion. In control experiments with 1 mg/mL cefazolin, the amount of cefazolin absorbed from the closed loop was 15.3+/-1.5 microg/cm in the rat jejunum. The absorption amount was increased to 22.8+/-0.9 and 23.4+/-2.4 microg/cm when capsaicin was applied with cefazolin at concentrations of 10 and 400 microM, respectively. The enhancing effect of capsaicin on cefazolin absorption was suppressed when ruthenium red, a non-selective inhibitor of transient receptor potential (TRP) cation channels, was intravenously infused into the rat during the experiment. Cefazolin accumulation in the intestinal tissue was not altered in the presence of capsaicin. Collectively, the mechanism accounting for the capsaicin-induced increase in the intestinal cefazolin absorption is probably that capsaicin associating with TRPV1 increases the intrinsic permeability of cefazolin in intestine.

Effects of capsaicin on intestinal cephalexin absorption in rats.

The effects of capsaicin on intestinal cephalexin absorption were investigated by means of in situ single pass perfusion in rats to clarify whether this pungent compound present in spice is a potential factor altering the intestinal drug absorption processes. Under the control condition, cephalexin was absorbed at a rate of 1.16+/-0.08 and 0.90+/-0.06 nmol/min/cm in the jejunum and ileum, respectively. The intestinal cephalexin absorption rate was decreased when capsaicin was dissolved in the perfusate at a concentration of 400 microM, being 0.54+/-0.07 and 0.46+/-0.10 nmol/min/cm in the jejunum and ileum, respectively. The inhibitive effect of capsaicin on intestinal cephalexin absorption was diminished when ruthenium red, a non-selective inhibitor of the transient receptor potential (TRP) cation channels, was intravenously infused into the rat during the experiment. Moreover, when we evaluated the paracellular permeability of cephalexin by utilizing a competitive inhibitor, glycylsarcosine, it was demonstrated that glycylsarcosine-insensitive intestinal cephalexin absorption in the jejunum was increased by 4.5 times in the presence of 400 microM capsaicin. These findings indicate that capsaicin affects both transcellular and paracellular pathways of intestinal cephalexin absorption by interacting with the TRP cation channels in intestinal tissues, in which capsaicin seems to change the transport activity of H+/peptide co-transporter 1 (PEPT1), and to a lesser degree, it seems to alter the paracellular permeability of the intestinal epithelia.