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Abstract Real-world data on health-related quality of life (HRQoL) in advanced urothelial carcinoma (aUC) receiving immune checkpoint inhibitors (ICIs) are limited. This study included 42 patients with aUC who received second-line or later pembrolizumab (n = 19), maintenance avelumab followed by first-line chemotherapy (n = 13), or adjuvant nivolumab after radical surgery (n = 10). Time-course changes in the domains and scales related to HRQoL were evaluated using the EORTC QLQ-C30, FACT-G, and SF-8 questionnaires during ICI therapy. Anchor-based approaches for minimally important differences were determined as ‘improved’, ‘stable’, and ‘deteriorated’. We found significant improvements after the start of pembrolizumab treatment on many scales. Almost none of the scales changed significantly in the avelumab and nivolumab groups. Approximately 80% of the pembrolizumab group had deteriorated social/family well-being in FACT-G. Approximately 60% of the patients in the avelumab group had deteriorated general health and vitality in SF-8. In the nivolumab group, none of the scales deteriorated in > 50% of the patients. Deterioration of physical function in the SF-8 was associated with occurrence of treatment-related adverse events ≥ grade 2 during ICI therapy (P = 0.013). Our findings demonstrated that majority of patients with aUC who received ICI therapy had a stable HRQoL, which was consistent with evidence from clinical trials.

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.

Abstract. Background. Radical cystectomy (RC) is the standard surgical treatment for patients with muscle-invasive bladder cancer, but the prognosis is not favorable, and new prognostic factors need to be discovered. We investigated the potential of depth of invasion (DOI) as a prognostic factor in patients with muscle-invasive bladder cancer who underwent RC. Furthermore, we examined the association between preoperative levels of circulating cell-free DNA and DOI. Materials and methods. We retrospectively reviewed patients who underwent RC between January 2007 and December 2017; those who received neoadjuvant chemotherapy were excluded. Depth of invasion was measured using hematoxylin-eosin–stained RC specimens. Results. Of the 121 patients selected, 41 (33.9%) were eligible for analysis. The median follow-up period was 14 months and mean DOI was 17 mm (range, 2–75 mm). Long DOI (>17 mm) was significantly associated with shorter progression-free survival (hazard ratio, 14.5; 95% confidence interval, 3.9–53.97, p < 0.0001) and cancer-specific survival (hazard ratio, 18.97; 95% confidence interval, 4.04–88.99, p = 0.0002) compared with short DOI. Multivariate analysis revealed that DOI was an independent risk factor for cancer-specific survival. The levels of circulating cell-free DNA were significantly higher in patients with a longer DOI than in those with short DOI (65 vs. 20 ng/mL, respectively; p = 0.028). Conclusions. Depth of invasion predicted with levels of circulating cell-free DNA and thus could be a useful prognostic factor.

Abstract 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.

Unresectable, metastatic, advanced urothelial carcinoma (aUC) is an aggressive disease and is treated with platinum-containing first-line chemotherapy, followed by immune checkpoint inhibitors and antibody–drug conjugates. Response to first-line chemotherapy is a vital priority in sequential treatment strategies because a better response to first-line chemotherapy is associated with a better response to subsequent therapies. Gemcitabine plus carboplatin chemotherapy is conventionally recommended for cisplatin-ineligible patients. This multicenter, single-arm prospective trial will investigate whether dose-dense methotrexate, vinblastine, doxorubicin, and carboplatin (DD-MVACarbo) chemotherapy is superior to gemcitabine plus carboplatin chemotherapy in terms of efficacy in platinum-naïve, cisplatin-ineligible patients with aUC. After screening and registration, a total of 46 patients will be treated with this novel chemotherapy regimen. The primary endpoint is the objective response rate. The secondary endpoints include disease control rate, patient-reported outcomes, and adverse events. No evidence of this novel intervention is available as of July 2024. The results are expected to change the standard of care and improve the management of patients with aUC.

Background. Photodynamic diagnosis-assisted transurethral resection of bladder tumors (PDD-TURBT) enhances detection of elusive lesions compared to standard white light-transurethral resection of bladder tumors (WL-TURBT). If minimal light exposure during PDD-TURBT induces the accumulation of reactive oxygen species (ROS), potentially resulting in phototoxicity in small lesions, apoptosis may be triggered in residual small tumors, allowing them to escape resection. We investigated the hypothesis of a potential photodynamic therapeutic effect during PDD-TURBT. Methods and Materials. Our study, conducted between January 2016 and December 2020 at Nara Medical University Hospital, focused on a specific emphasis on ROS production. Immunohistochemical analysis for thymidine glycol and Nε-hexanoyl-lysine was performed on 69 patients who underwent 5-aminolevulinic acid-mediated PDD-TURBT and 28 patients who underwent WL-TURBT. Additionally, we incrementally applied the minimal irradiation energy to T24 and UM-UC-3 cells treated with 5-aminolevulinic acid using instruments similar to those used in PDD-TURBT and evaluated intracellular ROS production and phototoxicity. Results. Immunohistochemical analysis revealed a significant increase in production of thymidine glycol and Nε-hexanoyl-lysine within the PDD-TURBT group. In T24 and UM-UC-3 cells treated with 5-aminolevulinic acid and light exposure, immunofluorescent staining demonstrated a dose-dependent increase in intracellular ROS production. In addition, higher irradiation energy levels were associated with a greater increase in ROS production and phototoxicity, as well as more significant decrease in mitochondrial membrane potential. Conclusion. Although the irradiation energy used in PDD-TURBT did not reach the levels commonly used in photodynamic therapy, our findings support the presence of a potential cytotoxic effect on bladder lesions during PDD-TURBT.

Background. Although routine surveillance imaging to examine upper urinary tract urothelial cancer recurrence during follow-up of nonmuscle invasive bladder cancer is recommended, its necessity remains invalidated. A single-institute long-term follow-up cohort study to evaluate the clinical impact of routine surveillance imaging and identify risk factors for upper urinary tract urothelial cancer recurrence after nonmuscle invasive bladder cancer treatment was conducted. Methods and Materials. A retrospective chart review of 864 patients with primary nonmuscle invasive bladder cancer who underwent initial transurethral resection of bladder tumor between 1980 and 2020 was conducted. The opportunities to diagnose its recurrence were examined. Moreover, oncological outcomes included upper urinary tract urothelial cancer recurrence-free survival and overall survival. Results. Of 864 patients, 19 (2.2%) experienced upper urinary tract urothelial cancer recurrence. Among 19 patients, recurrence was detected through routine imaging in 12 (63.2%), cystoscopy in 2 (10.5%), urine cytology in 2 (10.5%), and presence of gross hematuria in 1 (5.3%). All patients had high- or highest-risk NMIBC at diagnosis of primary nonmuscle invasive bladder cancer. On multivariate Fine-Gray proportional regression analyses, a tumor size of ≥30 mm and carcinoma in situ were independently associated with short upper urinary tract urothelial cancer recurrence-free survival (P=0.040 and 0.0089, respectively). Conclusion. Most patients experiencing upper urinary tract urothelial cancer recurrence were diagnosed by routine surveillance imaging, suggesting its clinical importance, especially for patients with nonmuscle invasive bladder cancer accompanied by a tumor size of ≥30 mm and carcinoma in situ.

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.

Abstract Objective To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil in Japanese men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with dutasteride. Results Twenty-four patients were enrolled. The participants had a median age of 71.0 (64.8–73.0) years and a median prostate volume of 37.3 (29.7–41.8) mL as measured using transabdominal sonography. The efficacy indicators, such as International Prostate Symptom Score (IPSS), quality of life (QOL) score, night-time urinary frequency, and night-time maximum voided volume, improved significantly at 4 weeks, and the effects lasted until 24 weeks (IPSS: 9.5 vs. 17.0, QOL: 2.0 vs. 4.0, nocturia: 2.0 vs. 2.0, night-time maximum voided volume: 290.0 vs. 240.0 mL). Overactive bladder symptom score (OABSS) and sexual health inventory for men (SHIM) significantly improved at 12 weeks, and the effects lasted until 24 weeks (OABSS: 3.0 vs. 5.0, SHIM: 11.0 vs. 7.5). However, maximum urine flow and residual urine volume showed no improvement at any point. Adverse events occurred in two cases. Taken together, add-on therapy with tadalafil was effective for patients with LUTS/BPH resistant to dutasteride monotherapy. In addition, this therapy was not associated with severe adverse events.

Enfortumab vedotin (EV), a nectin-4-directed antibody conjugated to monomethyl auristatin E (MMAE), has been approved for patients with advanced urothelial carcinoma (aUC) previously treated with platinum-based chemotherapy and immune inhibitors. Taxane agents and MMAE share antitumor mechanisms through microtubule disruption, thus raising a notable concern regarding cross-resistance between these drugs. This case report describes two patients with taxane-based chemotherapy-refractory aUC who responded well to EV. A 71-year-old man (case 1) with pT3N0M0 renal pelvic UC showed a partial response to EV in metastatic lesions of the bilateral lungs and right pelvic lymph nodes after three cycles of paclitaxel plus gemcitabine chemotherapy. A 53-year-old man (case 2) with cT3bN2M0 bladder UC underwent platinum-based neoadjuvant chemotherapy and the following radial cystectomy (ypTis ypN0). He developed bilateral lung metastases and showed a complete response to EV in the metastatic lesions after 20 cycles of paclitaxel plus nedaplatin chemotherapy. Our experience of two cases demonstrated that tumor response to EV can be expected in patients with taxane-refractory aUC.

Background: Latest guidelines recommend kidney-sparing management as the primary treatment option for selected patients with upper urinary tract urothelial carcinoma (UTUC). One of the biggest issues of ureteroscopic laser ablation (ULA) is a high rate of surgical site recurrence, which is largely attributed to residual lesions at the initial ULA. Another clinical issue is a significant lack of non-invasive reliable detection tools of urinary recurrent tumors in this treatment setting. Methods: The FLUAM trial is a prospective, single-center, single-arm pilot trial to investigate the efficacy of 5-aminolevulinic acid-mediated photodynamic diagnosis (ALA-PDD)-assisted ULA for localized UTUC and the usefulness of the UroVysion® assay (multiprobe fluorescence in situ hybridization) as a monitoring test after the kidney-sparing treatment. After the screening and registration, a total of 20 patients with localized UTUC will undergo the initial ALA-PDD-assisted ULA followed by the second look ALA-PDD-assisted ureteroscopic examination. The primary endpoint is progression-free survival. Secondary endpoints include patient reported outcomes, diagnostic accuracy of UroVysion assay to detect tumor recurrence, adverse events, and safety of the intervention. Conclusion: The goal of this trial is to determine the potential benefit of ALA-PDD assistance in patients who undergo the ULA. The evidence of this novel technique is still limited. The results are expected to change the standard of care and lead to better management of localized UTUC. Trial registration: This clinical trial was prospectively registered with the Japan Registry of Clinical Trials on 23 June 2021. The reference number is jRCTs051210042, nara0023 (Certified Review Board of Nara Medical University).

Abstract Background Selecting the treatment procedure for cancer patients is a challenging task. We report our initial experience of complete laparoscopic radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC). Methods A total of four patients with UTUC underwent complete laparoscopic RNU combined with transvesical laparoscopic excision of the distal ureter using three 5-mm ports. Transvaginal specimen extraction was applied in female patients to reduce incisional pain and improve cosmesis. Peri-operative complications were evaluated using the Clavien-Dindo classification system. Postoperative pain was evaluated during hospitalization using a numeric pain rating scale (scales of 1 to 10). Patients who underwent retroperitoneal laparoscopic surgery combined with open excision of the distal ureter during the same period were included as a control group (conventional RNU, consisting of laparoscopic nephrectomy combined with open bladder cuff excision) for pain scale evaluation. Results The novel surgery was successfully completed for all four patients (two males and two females). The mean pneumoperitoneum time for retroperitoneoscopic nephroureterectomy and specimen extraction was 174 min, while the mean pneumovesicum time for the ureteral orifice excision was 88 min. One male patient had bladder leakage at the suture site of the bladder wall, which lasted for 2 weeks. No patient experienced recurrent disease during the follow-up period (median, 10 months). Mild to moderate pain lasted for 5 or 6 days after RNU. A couple of days after surgery, the numeric pain rating scale of complete laparoscopic RNU and conventional RNU group reached its peak level at 3.0 ± 1.8 and 5.3 ± 2.8, respectively. There was no statistical difference in the degree of postoperative pain (P = 0.31). Conclusions We described our initial experience and outcome of complete laparoscopic RNU for UTUC. Further experience and research are required to determine whether this advanced laparoscopic technique yields better outcomes and has true clinical value.

Abstract Background Transplant renal artery dissection is a rare and serious event that can cause allograft dysfunction and activation of the renin–mediated renovascular hypertension. Most cases are induced by percutaneous transluminal angioplasty, arteriosclerotic disease, or fibromuscular dysplasia. We observed a case of transplant renal artery dissection induced by unusual causes during kidney transplantation. Case presentation A 35-year-old woman, whose mother donated a kidney to her, underwent ABO-incompatible living kidney transplantation. The allograft had one renal artery and vein that were anastomosed to the internal iliac artery and external iliac vein, respectively. Although careful handling was performed in all procedures including vascular clamping, Doppler ultrasonography (US) immediately after reperfusion showed an increase in the systolic blood velocity and urine output was not observed. Arterial anastomotic stenosis was suspected, but upon exploration, a renal artery dissection was detected in the middle portion of the donor artery. The part of the transplant renal artery was resected, and cold reflux was started again. At the resected part of transplant renal artery, dissection was identified. After re-anastomosis, Doppler US revealed that the blood flow of the renal artery was adequate without an increase in the systolic blood velocity, and sufficient blood flow was observed throughout the allograft. Urine output was also observed as soon as blood flow returned, and serum creatinine level decreased to 0.95 mg/dL after surgery. The cause of injury might have been vascular clamping in order to drain the air and check bleeding at the anastomosis. Conclusions Our case reaffirmed that careful handling is needed in all procedures, including donor nephrectomy, cannulation for transplant perfusion, vascular clamping, and anastomosis, even without any evidence of arteriosclerosis. Kidney transplant recipients commonly have atherosclerosis and hypertension, which are risk factors for arterial dissection. Early diagnosis and intervention can lead to the prevention of allograft dysfunction. Therefore, close monitoring of allograft blood flow by Doppler US during surgery should be considered.

Introduction Spina bifida is a congenital anomaly caused by a neural tube closure defect that may result in sexual dysfunction. Sexual dysfunction and infertility are prevalent in spina bifida patients but have been scarcely reported. Case presentation We report the case of a 36‐year‐old man with spina bifida and mild‐moderate erectile dysfunction. He could experience erection and ejaculation. He got married at the age of 28 years, but his wife was unable to conceive for 2 years thereafter. Semen analyses revealed that semen volume, sperm density, and sperm motility rate were below normal levels. It was concluded that natural conception would be difficult, and assisted reproductive strategies were planned. After 4 years, his wife conceived through intracytoplasmic sperm injection and gave birth to a healthy baby. Conclusion Fertility treatment, including intracytoplasmic sperm injection, is a useful therapeutic method for male patients with spina bifida who desire to father a child.

Purpose: The clinical management and follow-up of patients with recurrent prostate cancer after salvage radiotherapy (SRT) has not yet been established, and no standardized definition of biochemical recurrence (BCR) after SRT exists. We compared the impact of applying three different definitions of BCR following SRT on patient outcomes and prognostication. Subjects: Patients who received salvage androgen-deprivation therapy before the completion of SRT were excluded. The data of 118 men who had undergone salvage radiation as monotherapy for BCR after radical prostatectomy were reviewed. In all patients, SRT comprised irradiation to the prostatic bed (70 Gy) using three-dimensional conformal radiotherapy techniques. Treatment outcomes, including BCR-free survival and prognostic factors, were analyzed and compared among three definitions: The Nara, Radiation Therapy Oncology Group (RTOG) 9601, and GETUG-AFU 16 definitions. Results: The BCR rate differed significantly among the applied definitions. Multivariate analyses identified the same four independent prognostic factors, including primary Gleason pattern 4 or 5, negative resection margin, prostate-specific antigen (PSA) level before SRT 0.5 or more, and PSA doubling time before SRT

Abstract Background Retroperitoneal tumors are an uncommon disease known to consist of a diverse group of benign and malignant neoplasms. Treatment of unresectable retroperitoneal lesions requires pathological diagnosis. Here, we report the utility and safety of retroperitoneoscopic biopsy for unresectable retroperitoneal lesions excluding urogenital cancers. Methods We analyzed 47 patients consisting of 23 (49%) and 24 (51%) cases that underwent retroperitoneoscopic tissue biopsy and open biopsy, respectively. The clinicopathological features, including postoperative complications, were compared between the two groups. Results Tumor pathology was diagnosed successfully with a single operation in all patients. Malignant pathology (68%) was more common than benign pathology (32%). The most common pathology was malignant lymphoma, which accounted for about 50% of all cases. There was no significant difference with respect to the age, sex, tumor size, presence of tumor-related symptom, histopathology, operative time, and complications. Three (13%) of 23 patients in the retroperitoneoscopic biopsy group received percutaneous needle biopsy before laparoscopic excisional biopsy because the evaluation of needle cores failed to confirm subclasses of diagnosed pathologies. One patient was converted to open surgery just after the initiation of operation due to severe adhesion of adjacent structures. We had two cases with iatrogenic urinoma due to ureteral injury after retroperitoneoscopic biopsy. Conclusions We conclude that retroperitoneoscopic biopsy is a safe and useful tool for benign and malignant retroperitoneal lesions, in comparison to open biopsy. It is critical to carefully examine the preoperative imaging for the location of tumors, especially those close to the renal pelvis and ureter.

Abstract Objective Urine production is regulated throughout the night to ensure that it remains within functional bladder capacity. Increasing bladder capacity may thus play an important role in urine production. We investigated arginine vasopressin (AVP) secretion in female rats anesthetized with urethane in the daytime and nighttime under distended/empty bladder conditions. Chronological serum AVP was measured by enzyme immunoassay in rats with distended or empty bladders. Results The mean baseline AVP level was significantly higher in the nighttime than in the daytime (17.21 ± 5.29 vs 11.68 ± 3.16 pg/mL, p = 0.0019). However, serum AVP levels did not change with time in the daytime or nighttime, regardless of an empty or distended bladder. We therefore concluded that AVP secretion was unaffected by bladder filling.

Abstract Objectives Several studies have shown the relationship between lower urinary tract symptoms and autonomic imbalance. We investigated the relationship between detrusor overactivity (DO) or urgency, and transient increase in blood pressure as a type of hypertension related to sympathetic hyperactivity. Study 1: we enrolled 14 male patients with DO and 10 without DO. We measured the overactive bladder symptom score (OABSS) and blood pressure during cystometry. Study 2: we enrolled 14 men patients with overactive bladder (OAB) and 8 without OAB. We measured OABSS and blood pressure using a 24-h ambulatory device. Results Study 1: the mean systolic pressure was significantly higher at urgency or SDV than at the other measurement points in the DO group (161.3 ± 23.2 vs. 134.5 ± 16.3, 137.8 ± 15.3, or 139.5 ± 14.8 mmHg). Study 2: the mean systolic pressure was significantly higher at the measurement points before micturition than at the points unrelated to micturition in the OAB group (159.7 ± 24.9 vs. 124.9 ± 13.8 mmHg). In conclusion, DO or urgency induces a transient increase of blood pressure, suggesting that OAB induces a type of hypertension before micturition.

Abstract Background Page kidney phenomenon is caused by strong renal parenchymal compression and leads to renal hypoperfusion and microvascular ischemia, resulting in renal dysfunction and hypertension. Although the development of Page kidney phenomenon in allograft is rare, most of its cases are induced by allograft biopsy or trauma. We observed a case of Page kidney phenomenon that was induced by unusual causes immediately after kidney transplantation. Case presentation A 66-year-old man, whose wife donated a kidney, underwent ABO-compatible living kidney transplantation. The allograft had three renal arteries that were trimmed and formed into one piece on the back table, and subsequently, it was anastomosed to the internal iliac artery. Intraoperative Doppler ultrasonography (US) revealed adequate blood flow of each renal artery. Urine output was also observed as soon as allograft blood flow was reperfused. After the surgery, the urine output decreased, and serum creatinine level increased to 6.0 mg/dL. Doppler US did not show evidence of acute rejection, ureteral obstruction, or anastomotic stenosis of the renal arteries. On postoperative day 7, surgical exploration was performed and revealed that the blood flow of each renal artery was adequate but subcapsular hematoma was detected at the upper pole of the allograft. Capsulotomy and hematoma evacuation were performed. Subsequently, urine output increased and serum creatinine level decreased up to 1.7 mg/dL. Allograft sample was obtained 1 h after the transplantation from the lower pole of the allograft. Although the cause of subcapsular bleeding was unclear in this case, a small cyst of the allograft, which might have ruptured during donor nephrectomy, was located in the middle of the hematoma, and oozing around the cyst was observed. Conclusions Our case indicated that the small ruptured cyst of the allograft could be the cause of subcapsular hematoma and Page kidney phenomenon. Subcapsular hematoma caused by oozing over time could be difficult to diagnose using Doppler US, and thus, other imaging modalities, such as computed tomography, should be considered. Knowledge of the Page kidney phenomenon in the allograft can lead to early diagnosis and intervention, resulting in better outcomes for recipients with allograft dysfunction.

Abstract Background The aim of this study was to evaluate the combined use of the overactive bladder symptom score (OABSS) and International Prostate Symptom Score (IPSS) as an assessment tool for urinary symptom flare after iodine-125 (125I) implant brachytherapy. The association between urinary symptom flare and prostate-specific antigen (PSA) bounce was investigated. Methods Changes in the IPSS and OABSS were prospectively recorded in 355 patients who underwent seed implantation. The percentage distribution of patients according to the difference between the flare peak and post-implant nadir was plotted to define significant increases in the scores. The clinicopathologic characteristics, treatment parameters, and post-implant dosimetric parameters were compared between the non-flare and flare groups. PSA bounce was defined as an elevation of ≥0.1 ng/mL or ≥0.4 ng/mL compared to the previous lowest value, followed by a decrease to a level at or below the pre-bounce value. Results A clinically significant increase required an IPSS increase of at least 12 points and an OABSS increase of at least 6 points based on a time-course analysis of total scores and the QOL index. Assessment only by IPSS failed to detect 40 patients (11%) who had urinary symptom flare according to the OABSS. Univariate and multivariate analyses revealed that patients treated with higher biologically effective doses and those without diabetes mellitus had higher risks of urinary flare. There was no statistical correlation between the incidence and time of urinary symptom flare onset and that of a PSA bounce. Conclusions To our knowledge, this is the first report to prove the clinical potential of the OABSS as an assessment tool for urinary symptom flare after seed implantation. Our findings showed that persistent lower urinary tract symptoms after seed implantation were attributed to storage rather than to voiding issues. We believe that assessment with the OABSS combined with the IPSS would aid in decision-making in terms of timing, selection of a treatment intervention, and assessment of the outcome.

Purpose: We evaluated our experience with low-dose-rate salvage brachytherapy for local recurrence after primary prostate radiotherapy, and described the changes in lower urinary tract symptoms and health-related quality of life. Material and methods: Between 2011 and 2016, eight men with local recurrence after primary prostate radiotherapy underwent iodine-125 salvage brachytherapy with a prescribed dose of 110 or 145 Gy. Recurrence-free survival was evaluated with a post-treatment prostate-specific antigen profile. The toxicity and changes in lower urinary tract symptoms and health-related quality of life during the follow-up were evaluated on the Common Terminology Criteria for Adverse Events version 4.0, International Prostate Symptom Score, Short Form-8, and Expanded Prostate Cancer Index Composite, respectively. Results: The median follow-up was 12.2 months (range, 8.3-71.9) after salvage brachytherapy. Of all eight patients, two (25%) experienced treatment failure, one of whom developed left seminal vesicle recurrence 36 months after salvage brachytherapy for the right seminal vesicle recurrence, while the other developed bone metastases after 6 months. The International Prostate Symptom Scores peaked at 3 months, and returned to baseline by 6 months. The scores of all domains of health-related quality of life remained unchanged during the 12-month follow-up after salvage brachytherapy. Early grade ≤ 2 genitourinary toxicity was observed in five patients (63%), and late grade 2 gastrointestinal toxicity in one patient (13%) having persistent diarrhea. No patient required intermittent catheterization and no grade 3 or greater toxicity occurred during follow-up. Conclusions: The present study is our experiment of eight patients undergoing salvage brachytherapy, suggesting that this modality is noninvasive, safe, and an effective salvage local treatment in selected patients. To our knowledge, this is the first study to evaluate lower urinary tract symptoms and health-related quality of life in the post-treatment period in prostate cancer patients.

Abstract Background We evaluated the cancer detection rate of prostate cancer using transperineal template-guided saturation biopsy aimed at sampling one core for each milliliter of prostate volume for patients requiring repeated prostate biopsies. Methods In total, 103 consecutive patients with repeated prostate biopsies were enrolled in this retrospective study. The number of biopsy cores was defined by prostate volume. In principle, one biopsy core covered 1 mL of prostate volume. We used a prostate brachytherapy template with a 5-mm grid and adopted a transperineal needle biopsy. Results The median age, prostate-specific antigen level, and prostate volume were 69 (range, 37–83) years, 9.2 (range, 1.9–107) ng/mL, and 34.7 (range, 18–76.7) mL, respectively. The median number of biopsy cores was 37 (range, 18–75 cores). Fifty-three patients (51.5%) were diagnosed with prostate cancer. The Gleason score was 6, 7, and 8–10 in 24.5, 64.2 and 11.3% patients, respectively. Forty-two patients (79.2%) were diagnosed with clinically significant PCa. Acute urinary retention was detected in 2 patients (1.9%). Conclusions Transperineal template-guided saturation biopsy with one core per milliliter of prostate volume helped achieve a high cancer detection rate and high significant cancer detection rate with acceptable biopsy-associated adverse events.

Abstract Background Although the significance of preoperative nutritional status has been investigated, there is no report regarding the relationship of their postoperative changes on outcomes in patients who underwent radical cystectomy for bladder cancer. Here, we report the clinical impact of the change, from baseline, in nutritional status and volume of abdominal skeletal muscle mass and adipose tissue after radical cystetomy. Methods A retrospective analysis of 89 patients with bladder cancer, who underwent curative radical cystectomy, was conducted to assess the time course of change, from baseline, in body composition and nutritional status at 1, 3, 6, 12, and 24 months, after surgery. Skeletal muscle mass and abdominal adipose tissue mass were quantified by unenhanced computed tomography images. Two different nutritional indices, the Prognostic Nutritional Index and the Controlling Nutritional Status score were calculated from laboratory blood tests. We evaluated the prognostic value of the rate of change in the body composition and nutritional status after radical cystectomy. Results The cross-sectional area at the level of the third lumbar vertebra of the psoas major muscle and nutritional indices showed a transient deterioration at 1 and 3 months after radical cystectomy, with a return to baseline values from 6 to 24 months. A ≤ −10% loss in the area of the psoas muscle was associated with a shorter overall survival, compared to those with a > −10 change [hazard ratio (HR) 2.2, P = 0.02]. Multivariate analyzes identified sarcopenia status at baseline (HR 2.2, P = 0.03) and a ≤ −10% loss in the psoas muscle (HR 2.4, P = 0.02) were identified as independent prognostic factors for overall survival. A subanalysis of patients without sarcopenia identified a worse survival outcome for patients with a ≤ −10% loss in the psoas muscle (HR 2.6, P = 0.03) and ≤ − 5 change in the Prognostic Nutritional Index (HR 3.6, P = 0.01). Conclusion Further research is required to establish appropriate rehabilitation protocols and nutritional interventions after radical cystectomy for maintaining skeletal muscle mass and nutrition status which could counteract physical deterioration and improve outcomes.

Clinical evidence regarding risk reduction of repeated bladder recurrence after initial photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) is still limited in patients with non-muscle-invasive bladder cancer (NMIBC). We analyzed patients with primary NMIBC undergoing TURBT without any adjuvant treatment to compare the risk of cumulative recurrence between the conventional white-light (WL)-TURBT and PDD-TURBT. Out of 430 patients diagnosed with primary NMIBC from 2010 to 2019, 40 undergoing WL-TURBT and 60 undergoing PDD-TURBT were eligible. Multivariate Cox regression analysis for time to the first recurrence demonstrated that PDD assistance was an independent prognostic factor with better outcome (p = 0.038, hazard ratio = 0.39, and 95% confidence interval 0.16–0.95). While no patient experienced more than one recurrence within 1000 postoperative days in the PDD-TURBT group, five out of 40 patients treated by WL-TURBT experienced repeated recurrence. The comparison of cumulative incidence per 10,000 person-days between the two groups revealed that PDD assistance decreased by 6.6 recurrences per 10,000 person-days (exact p = 0.011; incidence rate ratio 0.37, Clopper–Pearson confidence interval 0.15–0.82). This is the first study addressing PDD assistance-induced risk reduction of repeated bladder recurrence using the person-time method. Our findings could support clinical decision making, especially on adjuvant therapy after TURBT.

Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are reported to be associated with poor prognosis, depending on their pro-tumoral roles. Current knowledge of TAMs and CAFs in the tumor microenvironment of urothelial cancer of the bladder (UCB) is limited. Therefore, we investigated the paracrine effect induced by TAMs and CAFs in the tumor microenvironment of human UCB. For this, we first carried out immunohistochemical analysis for CXCL1, CD204 (TAM marker), αSMA (CAF marker), E-cadherin, and MMP2 using 155 UBC tissue samples. Next, CXCL1-overexpressing clones of THP-1-derived TAMs and NIH3T3-derived CAFs were developed by lentiviral vector infection. The immunohistochemical study showed high CXCL1 levels in UCB cells to be associated with enhanced recruitment of TAMs/CAFs, higher metastatic potential, and poor prognosis. Three-dimensional (3D) co-culture of UCB cells and TAMs/CAFs suggested that CXCL1 production in TAMs/CAFs play an important role in cell-to-cell adhesion and interaction among cancer cells and these stromal cells. CXCL1-expressing TAMs/CAFs enhanced tumor growth of subcutaneous UCB tumors in nude mice when injected together. In addition, an experiment using the orthotopic bladder cancer model revealed that CXCL1 production in TAMs/CAFs supported tumor implantation into the murine bladder wall and UCB growth when injected together, which was confirmed by clinical data of patients with bladder cancer. Thus, CXCL1 signaling in the tumor microenvironment is highly responsible for repeated intravesical recurrence, disease progression, and drug resistance through enhanced invasion ability. In conclusion, disrupting CXCL1 signaling to dysregulate this chemokine is a promising therapeutic approach for human UCB.

Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model. Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly divided into six groups and treated with chemotherapeutic agents once a week for four weeks. After last treatment, bladder and serum samples were analyzed for cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1) using immunohistochemistry staining. Serum and urine cytokine levels were evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties similar to those of BCG. These included changes in immune cells that resulted in fewer M2 macrophages and regulatory T cells around tumors. This result was compatible with those in human samples. Intravesical chemotherapy also induced systemic changes in cytokines, especially urinary interleukin (IL)-17A and granulocyte colony stimulating factor (G-CSF), as well as in the distribution of blood neutrophils, lymphocytes, and monocytes. Our findings suggest that intravesical treatment with mitomycin C and adriamycin suppresses protumoral immunity while enhancing anti-tumor immunity, possibly through the action of specific cytokines. A better understanding of the immunoreaction induced by chemotherapeutic agents can lead to improved outcomes and fewer side effects in intravesical chemotherapy against NMIBC.

The detection of carcinoma in situ (CIS) is essential for the management of high-risk non-muscle invasive bladder cancers. Here, we focused on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with photodynamic diagnosis (PDD) for the detection of CIS. A total of 45 patients undergoing pre-surgical DCE-MRI and PDD-assisted endoscopic surgery accompanied by biopsies of the eight segmentations were analyzed. Immunohistochemical analysis of the biopsies revealed hypervascularity of CIS lesions, a cause of strong submucosal contrast-enhancement. It was found that 56 (16.2%) of 344 biopsies had pathologically proven CIS. In the DCE-MRI, the overall sensitivity and specificity for detecting CIS were 48.2% and 81.9%, respectively. We set out two different combinations of PDD and DCE-MRI for detecting CIS. Combination 1 was positive when either the PDD or DCE-MRI were test-positive. Combination 2 was positive only when both PDD and DCE-MRI were test-positive. The overall sensitivity of combinations 1 and 2 were 75.0% and 37.5%, respectively (McNemar test, vs PDD alone; p = 0.041 and p < 0.001, respectively). However, the specificity was 74.0% and 91.7%, respectively (vs PDD alone; both p < 0.001). Our future goal is to establish ‘MRI-PDD fusion transurethral resction of the bladder tumor (TURBT), which could be an effective therapeutic and diagnostic approach in the clinical management of high-risk disease.

We aimed to determine the oncological outcomes of patients with clinical T1 renal cell carcinoma (RCC) upstaged to pathological T3a and to identify the preoperative predictive factors for upstaging. We retrospectively reviewed 272 patients with clinical T1 RCC who underwent surgical treatment. Thirty-three patients (12%) were upstaged to pathological T3a. These patients had a significantly larger tumor size on computed tomography (p < 0.0001), a higher aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (p = 0.037), and an elevated c-reactive protein (CRP) level (p = 0.014) preoperatively compared with those with pathological T1 RCC. On multivariate analysis, tumor diameter was the only significant preoperative predictive factor for upstaging [hazard ratio (HR), 3.61; 95% confidence interval (CI), 1.32−9.84; p = 0.01]. The AST/ALT ratio tended to be a preoperative predictive factor for upstaging, although it was not significant (HR, 2.14; 95% CI, 0.97−4.73; p = 0.06). Pathological T3a upstaging occurred in 25% of those with a tumor diameter ≥30 mm and a preoperative AST/ALT ratio ≥1.1. There was a significant correlation between pathological T3a upstaging and the number of preoperative risk factors (p = 0.0002). The preoperative tumor diameter and serum AST/ALT ratio can be predictive factors for pathological T3a upstaging in patients with clinical T1 RCC.

Background: The aim of this study is to evaluate the clinical impact of intravesical Bacillus Calmette-Guérin (BCG)-induced changes in blood/urinary immune markers. Methods: Time-course changes in blood/urinary clinical parameters and mRNA expression of 13 genes in urine sediment taken eight times during the treatment course of intravesical BCG (before, every 2 weeks for 8 weeks, and after) in 24 patients with non-muscle invasive bladder cancer. The genes examined include cellular markers of four immune checkpoint proteins (PD-L1, PD-L2, PD-1, and CTLA-4), immunosuppressive cells (regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells), pan-T lymphocytes, B lymphocytes, and neutrophils. Results: Significant transient increase in gene expression was observed for PD-L1, PD-1, FOXP3, and CD204 at 6−8 doses of BCG. The patients were stratified into two groups depending on the number of genes with increased mRNA expression. Fourteen (58%) had 0−1 genes upregulated, while 10 (42%) had 2−4 genes with increased expression. No patient in the 0−1 group experienced recurrence, while 70% of patients in the 2−4 group experienced recurrence (p value = 0.037, hazard ratio = 5.93). Conclusions: Our findings suggested that increases in more than one of PD-L1, PD-1, FOXP3, and CD204, expression in the urine sediments was associated with resistance to BCG treatment.

The evidence of association between sexually transmitted infection and prostatic inflammation in human prostate cancer (PCa) is limited. Here, we sought to examine the potential association of prostatic infection with the inflammatory environment and prostate carcinogenesis. We screened surgical and biopsy specimens from 45 patients with PCa against a panel of sexually transmitted infection-related organisms using polymerase chain reaction and examined the severity of intraprostatic inflammation by pathologic examination. Among tested organisms, the rate of Mycoplasma genitalium (Mg) infection was significantly different between the prostate cancer cohort and benign prostate hyperplasia (BPH) cohort (P = 0.03). Mg infection in the surgical specimens was associated with younger patients. The rate of extensive disease (pT2c–3b) was higher in Mg-positive patients than in Mg-negative patients (P = 0.027). No significant correlation was observed between Mg infection status and the grade of intraprostatic inflammation. The detection sensitivity of biopsy specimens was 61% for Mg and 60% for human papillomavirus (HPV)18, indicating possible clinical application of this material. A comprehensive understanding of the correlation between the urogenital microbiome and inflammation would facilitate the development of strategies for PCa prevention. Further studies are required to explore its clinical utility in recommendations of early re-biopsy, close follow-up, and treatment by antibiotics.

Methylmercury (MeHg) is a well known environmental pollutant that induces serious neuronal damage. Although MeHg readily crosses the blood-brain barrier, and should affect both neurons and glial cells, how it affects glia or neuron-to-glia interactions has received only limited attention. Here, we report that MeHg triggers ATP/P2Y1 receptor signals in astrocytes, thereby protecting neurons against MeHg via interleukin-6 (IL-6)-mediated pathways. MeHg increased several mRNAs in astrocytes, among which IL-6 was the highest. For this, ATP/P2Y1 receptor-mediated mechanisms were required because the IL-6 production was (i) inhibited by a P2Y1 receptor antagonist, MRS2179, (ii) abolished in astrocytes obtained from P2Y1 receptor-knockout mice, and (iii) mimicked by exogenously applied ATP. In addition, (iv) MeHg released ATP by exocytosis from astrocytes. As for the intracellular mechanisms responsible for IL-6 production, p38 MAP kinase was involved. MeHg-treated astrocyte-conditioned medium (ACM) showed neuro-protective effects against MeHg, which was blocked by anti-IL-6 antibody and was mimicked by the application of recombinant IL-6. As for the mechanism of neuro-protection by IL-6, an adenosine A1 receptor-mediated pathway in neurons seems to be involved. Taken together, when astrocytes sense MeHg, they release ATP that autostimulates P2Y1 receptors to upregulate IL-6, thereby leading to A1 receptor-mediated neuro-protection against MeHg.

Background/Aim: To evaluate the difficulty of laparoscopic adrenalectomy by investigating the usefulness of the Mayo Adhesive Probability (MAP) score for assessing adherent perinephric fat and its correlation with histological reality. Patients and Methods: We retrospectively evaluated 103 patients who underwent laparoscopic adrenalectomies. Based on preoperative computed tomography images, the patients were categorized into two groups: high (3-5 points) and low MAP (0-2 points). Clinical characteristics and perioperative data were compared between the two groups. Additionally, we analyzed the pathological tissue of the tumor and surrounding fat using hematoxylin-eosin-saffron staining. Results: Compared with the low MAP group, the high MAP group had younger patients (59 vs. 62 years, p=0.097), more male patients (93.3% vs. 44.3%, p<0.001), and higher body mass indices (26.4 vs. 23.8, kg/m², p=0.029). The MAP group experienced a significantly higher estimated blood loss compared to the low MAP group (10 vs. 52.3, ml, p=0.047). Tumor and adhering perirenal fat tissues of pheochromocytoma, adrenal carcinoma, and metastatic adrenal tumors exhibited significantly higher expression of vascular endothelial growth factor and cluster of differentiation 204 compared to the low MAP group (p<0.001). Additionally, both proteins were highly expressed in the adhering perirenal fat in the high MAP group (p=0.020, p=0.015). Conclusion: Patients with a preoperative MAP score ≥3, pheochromocytoma, or malignant tumor had a high risk of increased intraoperative blood loss. Strict perioperative management should be performed in such cases. [ABSTRACT FROM AUTHOR]

Background/Aim: This study investigated the follow-up rate of living kidney donors and explored the factors related to continuous follow-up and remnant renal function, enabling the optimal management of living kidney donors. Patients and Methods: We retrospectively evaluated 180 living kidney donors who underwent donor nephrectomies at our institute. Clinical information was obtained from medical charts, and remnant renal function was defined as the estimated glomerular filtration rate 12 months after donor nephrectomy. Results: Overall, 6/180 donors (3.3%) were lost to follow-up within a year, and the follow-up rate gradually declined yearly. Independent risk factors for loss to follow-up included a follow-up period <60 months and graft survival of the recipient (p=0.002 and p=0.043, respectively). Recipient survival was correlated with loss to follow-up; however, this was not significant (p=0.051). Regarding remnant renal function, age ≥60 years, preoperative estimated glomerular filtration rate <74 ml/min/1.73 m², and a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73m² were independent risk factors for poorly preserved remnant renal function (p=0.036, p<0.0001, and p<0.0001, respectively). Using propensity score matching to adjust for preoperative factors, a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73 m2 was the only significant postoperative factor for poorly preserved remnant renal function (p=0.023). Conclusion: An increased 5-year follow-up rate could lead to an increase in long-term follow-up, and recipient prognosis may be correlated with the living kidney donor follow-up status. Furthermore, Δsingle-kidney estimated glomerular filtration rate was identified as a factor for establishing the optimal precision follow-up management of living kidney donors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-β1 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. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the effects of a soluble guanylate cyclase (sGC) activator, BAY 60-2770, on neurogenic lower urinary tract dysfunction in mice with spinal cord injury (SCI). Mice were divided into the following three groups: spinal cord intact (group A), SCI + vehicle (group B), and SCI + BAY 60-2770 (group C). SCI mice underwent Th8-Th9 spinal cord transection and treatment with BAY 60-2770 (10 mg/kg/day) once daily for 2-4 wk after SCI. We evaluated urodynamic parameters using awake cystometry and external urethral sphincter electromyograms (EMG); mRNA levels of mechanosensory channels, nitric oxide (NO)-, ischemia-, and inflammation-related markers in L6-S1 dorsal root ganglia, the urethra, and bladder tissues; and protein levels of cGMP in the urethra at 4 wk after SCI. With awake cystometry, nonvoiding contractions, postvoid residual, and bladder capacity were significantly larger in group B than in group C. Voiding efficiency (VE) was significantly higher in group C than in group B. In external urethral sphincter EMGs, the duration of notch-like reductions in intravesical pressure and reduced EMG activity time were significantly longer in group C than in group B. mRNA expression levels of transient receptor potential ankyrin 1, transient receptor potential vanilloid 1, acid-sensing ion channel (ASIC)1, ASIC2, ASIC3, and Piezo2 in the dorsal root ganglia, and hypoxiainducible factor-1α, VEGF, and transforming growth factor-β1 in the bladder were significantly higher in group B than in groups A and C. mRNA levels of neuronal NO synthase, endothelial NO synthase, and sGCα1 and protein levels of cGMP in the urethra were significantly lower in group B than in groups A and C. sGC modulation might be useful for the treatment of SCI-related neurogenic lower urinary tract dysfunction. [ABSTRACT FROM AUTHOR]

The optimal first-line chemotherapy regimen and dose adjustment for cisplatin-unfit patients with advanced urothelial carcinoma remains unclear in the era of immune checkpoint inhibitors. We investigated the association between response to first-line chemotherapy and response to subsequent pembrolizumab treatment, suggesting that the response to pembrolizumab after dose-reduced cisplatin plus gemcitabine chemotherapy was inferior to that after carboplatin plus gemcitabine chemotherapy. Introduction: Response to pembrolizumab after first-line chemotherapy is vital to prolonged survival in advanced, unresectable, and/or metastatic urothelial carcinoma (aUC). However, there are sparse clinical data on host-tumor immune modification by first-line platinum-based chemotherapy. This study investigated the association between response to firstline gemcitabine plus cisplatin (GC) or carboplatin (GCarbo) chemotherapy and response to subsequent pembrolizumab treatment. Patients and Methods: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 108 patients who received first-line GC or GCarbo followed by second-line or later pembrolizumab were eligible for investigation and were classified into 3 groups: 48 receiving full-dose GC, 21 receiving dose-reduced GC, and 39 receiving GCarbo. Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. Possible factors associated with the response to pembrolizumab were evaluated using binary logistic regression methods. Results: The rate of patients undergoing surgical removal of the primary organ was higher and creatinine clearance was lower in the dose-reduced GC and GCarbo groups than in the full-dose GC groups. Pembrolizumab responders had significantly better survival benefits than nonresponders. The rate of pembrolizumab responders was much higher in first-line chemotherapy responders than in first-line chemotherapy nonresponders. In contrast to the full-dose GC and GCarbo groups, the pembrolizumab responder rate was lower, and no association was observed between response to first-line chemotherapy and response to pembrolizumab in the dose-reduced GC group. Conclusion: Cisplatin and carboplatin may play an important role in the antitumor immune response, which could impact the outcome of subsequent pembrolizumab treatment. Given that the rate of response to pembrolizumab after dose-reduced GC chemotherapy was relatively low, this regimen is not recommended for cis-unfit patients with aUC. Further studies are required to understand the mechanisms responsible for the cross-reactivity of platinum and immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]