[A Case of Metastatic Renal Cancer Responding to Sunitinib as the Eighth Line Therapy].

A 62-year-old male presenting with gross hematuria and right renal mass was referred to our Urology Department. Computed tomography revealed a right renal mass, with multiple pulmonary lesions. He underwent right nephrectomy for highly suspected renal cell carcinoma with pulmonary metastases (cT3aN0M1). The pathological diagnosis was clear cell renal cell carcinoma, pT1b. Following surgery, he was treated with multiple regimens of chemotherapy, ranging from interferon alpha, multiple tyrosine kinase inhibitors such as sorafenib, axitinib, pazopanib and cabozantinib, everolimus, and nivolumab, all of which were discontinued after its induction, either due to adverse events or progressive disease. He was finally administered Sunitinib as the 8th line "last-ditch" treatment, which resulted in significant tumor shrinkage. No disease progression has been observed 25 months after initiating sunitinib administration.

Sterile versus non-sterile gloves during cystoscopy: A randomized prospective single-blind study.

Objective: The objective of this study is to evaluate the need for sterile gloves during cystoscopy by comparing the incidence of UTI symptoms between patients in whom the procedure is performed with non-sterile gloves with those performed with non-sterile gloves. Patients and Methods: This study had a randomized, prospective, single-blind design and included patients aged >20 years who underwent cystoscopy in either of two outpatient clinics between September 2015 and November 2021. The patients were allocated to a sterile group or a non-sterile group. Only the urologists were aware of whether or not the gloves were sterile. The patients were instructed to report any symptoms suggestive of UTI after cystoscopy. Results: A total of 1258 patients were enrolled in the sterile group and 1376 in the non-sterile group. Symptoms of UTI were reported by six patients (0.48%) in the sterile group and six (0.44%) in the non-sterile group. The between-group difference was not statistically significant (p = 0.88). Conclusion: It is not necessary to use sterile gloves during routine cystoscopy.

Efficacy and safety of axitinib for metastatic renal cell carcinoma: Real-world data on patients with renal impairment.

OBJECTIVES: Limited information is currently available on the efficacy and safety of axitinib for metastatic renal cell carcinoma (mRCC) patients with renal impairment. Therefore, the present study investigated the efficacy and toxicity of axitinib in patients with chronic kidney disease. METHODS: Post-hoc analyses were performed on a Japanese multicenter cohort study of 477 mRCC patients who received axitinib followed by 1 or 2 regimens of systemic antiangiogenic therapy between January 2012 and December 2016. Differences in clinical characteristics and the efficacy and safety of axitinib were assessed based on pretreatment renal function. RESULTS: Patients were categorized into the following 5 renal function groups according to baseline renal function: estimated glomerular filtration rate (eGFR) ≥60 ml/min (n = 133), 45 ml/min ≤eGFR <60 ml/min (n = 153), 30 ml/min ≤eGFR< 45 ml/min (n = 130), eGFR <30 ml/min (n = 45), and dialysis (n = 16). Median progression-free survival (PFS) (95% confidence interval [CI]) in the 5 groups was 11 (8-16), 14 (11-19), 14 (10-19), 12 (8-24), and 6 (3-NR) months, respectively (p = 0.781). After adjustments for treatment-related confounders, the renal function group was not a significant prognostic factor for PFS. Objective response rates in the 5 groups were 22%, 23%, 23%, 18%, 20%, and 38%, respectively (p = 0.468). Regarding adverse events of all grades, hypertension (p = 0.0006) and renal and urinary disorders (p < 0.0001) were more frequently observed in the eGFR <30 ml/min group than in the other groups. CONCLUSIONS: Since renal function at the initiation of treatment with axitinib does not adversely affect the efficacy of VEGF-TKI therapy, clinicians do not need to avoid its administration to mRCC patients with impaired renal function in consideration of the risk of progression to end-stage renal disease.

[The Effect of Naldemedine Tosylate on the Postoperative Course of Robot-Assisted Radical Cystectomy].

Radical cystectomy is an invasive procedure frequently followed by postoperative complications. Although the protocol of enhanced recovery after surgery (ERAS) is used in the postoperative course, several components of the ERAS protocol may increase the workload of medical workers. In this study, we added naldemedine tosylate only to routine postoperative management instead of using the ERAS protocol and evaluated the effect on the postoperative course of robot-assisted radical cystectomy (RARC). We retrospectively investigated 58 patients who underwent RARC from May 2015 to February 2022 at our hospital and evaluated the postoperative complications, such as ileus and urinary tract infections, and, length of hospital stay (LOS). We used naldemedine tosylate for the patients who underwent RARC after November 2019. As a result, naldemedine tosylate reduced 26.8% of postoperative complications within 30 days after the operation (p＝0.041) and shortened LOS 8 days (p＝0.018). Naldemesine tosylate improved the postoperative course of RARC.

[Risk Factors of Antiresorptive Agent-Related Osteonecrosis of the Jaw in Prostate Cancer Patients with Bone Metastases].

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a severe adverse event associated with use of bone resorption inhibitors (BRIs), such as zoledronic acid and denosumab. Based on the results of phase 3 clinical trials for BRIs, the frequency of ARONJ is reported to be 1 to 2%, but the actual frequency could be higher. We investigated 173 patients with prostate cancer with bone metastases who were treated either with zoledronic acid or denosumab at our hospital between July 2006 and June 2020. ARONJ occurred in 13 patients (8%); i.e., ten out of 159 patients (6%) who were treated with zoledronic acid, and three out of 14 patients (21%) who were treated with denosumab. Multivariate analysis showed that longer duration of BRI exposure and dental treatment before the initiation of BRI are associated with risk of ARONJ. ARONJ is associated with decreased mortality but the association is not significant. Generally, the occurrence of ARONJ may be underestimated; therefore, further studies are warranted to determine the actual frequency of ARONJ.

[Intraoperative Evaluation of Ureteral Blood Flow Using Indocyanine Green Fluorescence imaging on Living-Donor Kidney Transplantation].

Ureteral stenosis occurs in 2-10% after kidney transplantation. Most are caused by ischemia of the distal ureter and are difficult to manage. There is no standard method for evaluating ureteral blood flow during surgery, and it is left to the judgement of the operator. Indocyanine green (ICG) is used not only for a liver or cardiac function test but also for an assessment of tissue perfusion. We evaluated the intraoperative ureteral blood flow under a surgical light and by ICG fluorescence imaging in 10 living-donor kidney transplant patients between April 2021 and March 2022. No ureteral ischemia was detected under the surgical light, but ICG fluorescence imaging revealed/decreased blood flow in 4 of the 10 patients (40%). Further resection was performed in these 4 patients to increase the blood flow, and the median resection length was 1.0cm (0.3-2.0). The postoperative course was uneventful in all 10 patients, and no ureter-related complications were observed. ICG fluorescence imaging is a useful method for evaluating ureteral blood flow and is expected to help reduce complications caused by ureteral ischemia.

[Challenging Case of Primary Renal Castleman's Disease Accompanied with Bacterial Pyelonephritis].

Castleman's disease is a rare lymphoproliferative disease, mostly found in the mediastinum. The number of Castleman's disease cases involving the kidneys is still limited. We report a case of primary renal Castleman's disease sporadically detected during a regular health check-up as pyelonephritis with ureteral stones. In addition, computed tomography showed renal pelvic and ureteral wall thickening with paraaortic lymphadenopathy. A lymph node biopsy was performed, but it did not confirm either malignancy or Castleman's disease. The patient underwent open nephroureterectomy for diagnostic and therapeutic purposes. The pathological diagnosis was renal and retroperitoneal lymph node Castleman's disease with pyelonephritis.

Evaluation of sexual function after dutasteride treatment in patients with once-negative prostate biopsy and benign prostate hyperplasia.

INTRODUCTION: Patients with benign prostatic hyperplasia are usually treated with 5α-reduced inhibitors (5ARIs) such as finasteride and dutasteride. However, studies on the influence of 5ARIs on sexual function have been controversial. In this study, we evaluated the impact of dutasteride treatment for erectile function in patients with once-negative prostate biopsy and benign prostate hyperplasia. PATIENTS AND METHODS: 81 patients with benign prostate hyperplasia were enrolled in a one-armed prospective study. They were administrated 0.5 mg/day of dutasteride for 12 months. Patient characteristics and changes of International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF)-15 scores at baseline and 12 months after dutasteride administration were examined. RESULTS: The mean ± standard deviation (SD) age of the patients was 69.4 ± 4.9 years and the prostate volume was 56.6 ± 21.3 mL, respectively. The mean ± SD prostate volume and PSA levels were decreased 25.0 and 50.9%, respectively, after 12 months of dutasteride administration. IPSS total, voiding subscore, storage subscore, and quality of life score significantly improved after 12 months of dutasteride administration. No statistically significant change in IIEF-total score from 16.3 ± 13.5 to 18.8 ± 16.0 (p = 0.14), IIEF-EF score from 5.1 ± 6.9 to 6.4 ± 8.3 (p = 0.13) were observed. There was no decrease in erectile function severity. CONCLUSION: Twelve months administration of dutasteride for patients with BPH improved urinary function and did not increase the risk of sexual dysfunction.

Prostate cancer recurring as small-cell carcinoma with a BRCA2 somatic mutation.

Introduction: Small-cell carcinoma of the prostate has a poor prognosis, and treatment options for the refractory disease are unclear. Case presentation: A 68-year-old man with prostate cancer was referred to our hospital. He was treated with combined androgen blockade (bicalutamide and degarelix acetate). The disease progressed to castration-resistant prostate cancer, but with additional treatment, prostate-specific antigen levels remained below 0.02 ng/mL. However, computed tomography revealed enlarged right inguinal lymph nodes; moreover, his neuron-specific enolase levels were elevated. Histopathologic analysis of a biopsied lymph node confirmed small-cell carcinoma. After administering cytotoxic chemotherapy (etoposide plus cisplatin and amrubicin), the patient temporarily improved before relapsing. After genetic testing of the biopsy specimen revealed a BRCA2 deletion, we administered the oral PARP-2 inhibitor olaparib, which has achieved partial remission for 8 months. Conclusion: PARP-2 inhibition may improve the survival of patients with BRCA2-positive small-cell carcinoma of the prostate.

Triple combination therapy for clinically nonmetastatic super-high-risk prostate cancer.

Introduction: Patients with nonmetastatic but exceptionally high-risk prostate cancer are liable to have biochemical failure and may even die. Triple combination therapy, which consists of surgery, radiotherapy, and androgen-deprivation therapy, as first-line treatment, may control the disease for a long period. Case presentation: We treated a patient with super-high-risk, nonmetastatic prostate cancer, with triple combination therapy. He was biochemical relapse free at 60 months after the initiation of treatment. Conclusion: Triple combination therapy may be an option for super-high-risk, nonmetastatic prostate cancer.

[Efficacy of Combination Chemotherapy of Gemcitabine and Nedaplatin for Squamous Cell Carcinoma of the Urinary Tract : Experience of Four Cases].

We report the use of combination chemotherapy of gemcitabine (800 mg/m² on day1 and 8) and nedaplatin (60 mg/m² on day 1), including neoadjuvant therapy in four cases of squamous cell carcinoma of the urinary tract. In each case, the dose was reduced after assessing the performance status and renal function of the patient. Among the four cases, the best overall outcome was complete response in one case, partial response in two cases, and stable disease in one case. The main adverse event observed was thrombocytopenia; however, no serious adverse events were observed, and this regimen was safely administered. Therefore, we believe that this regimen could be an effective treatment option for progressive squamous cell carcinoma originating from the urinary tract.

Clinical Impact of Detecting Low-Frequency Variants in Cell-Free DNA on Treatment of Castration-Resistant Prostate Cancer.

PURPOSE: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. EXPERIMENTAL DESIGN: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. RESULTS: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [HR, 2.52; 95% confidence interval (CI), 1.24-5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60-8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. CONCLUSIONS: Detecting low-frequency ctDNA variants with a VAF <1% is important to identify clinically informative genomic alterations in CRPC.

Prostate-specific antigen density during dutasteride treatment for 1 year predicts the presence of prostate cancer in benign prostatic hyperplasia after the first negative biopsy (PREDICT study).

OBJECTIVES: To prospectively evaluate the detection rate of prostate cancer, and to identify the risk factors of prostate cancer detection after a 1-year administration of dutasteride and first negative prostate biopsy. METHODS: Patients with benign prostatic hyperplasia who presented high prostate-specific antigen levels after the first negative prostate biopsy were administered 0.5 mg dutasteride daily for 1 year. They underwent a repeat prostate biopsy after 1 year. The primary end-point was the detection rate of prostate cancer. The secondary end-point was the ability of prostate-specific antigen kinetics to predict prostate cancer detection. Prostate-specific antigen was measured before the initial prostate biopsy and at 6, 9 and 12 months after starting dutasteride. Patients were classified into a prostate cancer and a non-prostate cancer group. RESULTS: Prostate cancer was detected in 15 of 149 participants (10.1%). The total prostate-specific antigen change between the prostate cancer and non-prostate cancer group at 1 year was significantly different (P = 0.002). Although prostate-specific antigen levels at baseline did not significantly differ between study groups (P = 0.102), prostate-specific antigen levels at 6, 9 and 12 months were significantly different (P = 0.002, P = 0.001 and P < 0.001, respectively). The mean reduction rate of prostate-specific antigen density between the prostate cancer and non-prostate cancer group at 1 year was significantly different (-4.25 ± 76.5% vs -38.0 ± 28.7%, P = 0.001). Using a multivariate analysis, a >10% increase of prostate-specific antigen density at 1 year post-dutasteride treatment was the only predictive risk factor for prostate cancer after the first negative prostate biopsy (odds ratio 11.238, 95% confidence interval 3.112-40.577, P < 0.001). CONCLUSION: In the present study cohort, >10% increase in prostate-specific antigen density represented the only significant predictive risk factor for prostate cancer diagnosis in patients with elevated prostate-specific antigen after the first negative prostate biopsy.

Medical history of nocturnal enuresis during school age is an independent risk factor for nocturia in adults: The Nagahama study.

AIM: To evaluate the relationship between nocturia and medical history of nocturnal enuresis: two conditions where diurnal urination rhythm is disturbed. METHODS: The Nagahama study is a longitudinal population-based health survey involving people aged 30-75 years in Nagahama city, Japan. Our analysis included 5,402 participants who completed enuresis and International Prostate Symptom Score questionnaires. Associations between nocturnal enuresis and nocturia were evaluated cross-sectionally and longitudinally with three models: (1) univariate analysis; (2) adjusted for basic characteristics (e.g., age, sex, body mass index, activity, alcohol, and smoking); and (3) adjusted for basic and clinical variables (e.g., hyperglycemia, hyperlipidemia, hypertension, renal insufficiency, insomnia, obstructive sleep apnea, and mental health). RESULTS: In total, 1,613 participants (29.9%) had a medical history of enuresis. The mean night-time frequency was 0.73 at baseline and 0.85 at the 5-year follow-up. The cross-sectional analysis showed participants with a medical history of enuresis had night-time frequency more often than those without this history (0.84 vs. 0.68, p < .0001). Significant differences were observed in Models 2 (p < .0001) and 3 (p < .0001). The longitudinal analysis showed nocturia progression was significantly related to a history of enuresis, with odds ratios of 1.32 (p < .0001) in Model 1, 1.21 (p < .01) in Model 2, and 1.22 (p < .01) in Model 3. CONCLUSIONS: Medical history of enuresis during school age was significantly related to nocturia in adulthood in the cross-sectional analysis, and to progression to nocturia in the longitudinal analysis. These two conditions may possess a common causative association.

[SURGEON QUESTIONNAIRE FOR ESTABLISHING A SURGEON EDUCATION SYSTEM FOR TRANSURETHRAL LASER RESECTION OF THE PROSTATE (HoLEP)].

(Introduction)HoLEP's role in the surgical management of benign prostatic hyperplasia (BPH) is steadily growing. In this study, a questionnaire containing questions about perioperative management was submitted to HoLEP surgeons to help establish standard surgical training procedures. (Methods)We sent a comprehensive 17 questionnaires on HoLEP procedures to 18 surgeons. The questionnaire asked, "Which method are you using, the 1-LOBE or 3-LOBE method?", "What educational methods are being used for surgeons?", "How long is the catheter insertion period after HoLEP?", and "What is the most difficult problem encountered in surgical HoLEP education and what aspect of training is the most emphasized?" (Results)Sixteen (88.9%) surgeons answered these questionnaires. Five surgeons reported using the one lobe method, five surgeons reported using the three lobe method, and four surgeons answered that it depends on the case. Regarding educational methods, the main answer was that it is important to evaluate pre-HoLEP imaging tests such as MRI and cystoscopy and to simulate surgery for education. Regarding the postoperative catheter insertion period, 1 day: 1 surgeon, 2 days: 9 surgeons, 3 days: 3 surgeons, 4 days or more: 1 surgeon. The most important thing reported for surgical education was to help beginners understand the characteristics of lasers, including direction, distance to prostate tissue, and adenoma removal. (Conclusions)The surgeons' responses clearly indicated some differences in practices between institutions. More detailed data from these results will provide a step towards designing standardized surgical and educational protocols for HoLEP.

[A Case of Bladder Cancer Treated with Arterial Stent-Grafting to Prevent Uretero-Arterial Fistula Due to Radiation Therapy for Metastasis].

A 66-year-old male with bladder cancer underwent radical cystectomy and ileal conduit construction. The pathological diagnosis was urothelial carcinoma with squamous differentiation (pT3b). Computed tomography (CT) 18 months postoperatively revealed a right external iliac lymph node metastasis. He was treated with systemic chemotherapy after placement of bilateral ureteral stents, but CT following chemotherapy revealed an increase in the size of the metastasis, and the patient was diagnosed with progressive disease. Radiotherapy to the metastasis was selected as local therapy, but the patient was at risk of an uretero-arterial fistula because the right external iliac artery and the right ureter adjacent to the metastasis were involved in the irradiated field. The right external iliac lymph node metastasis was irradiated with a dose of 50 Gy after stent grafting for the right external iliac artery to prevent an ureteroarterial fistula. He had no adverse events, including hematuria after radiotherapy, but died of cancer cachexia 12 months after radiotherapy.

Eosinophilic airway inflammation and eosinophilic chronic rhinosinusitis during nivolumab and ipilimumab.

Immune-related adverse events (irAEs) are induced by immune checkpoint inhibitors (ICIs) which are administered for many cancers. There are many irAEs such as endocrine abnormalities, interstitial lung disease, and colitis. However, irAEs associated with type 2 (T2) inflammation are less known. We herein report a 71-year-old woman who developed eosinophilic airway inflammation and eosinophilic chronic rhinosinusitis (ECRS) simultaneously during combination therapy with nivolumab and ipilimumab for renal cell carcinoma. After two cycles of therapy, she developed cough and nasal congestion with high level of fractioned exhaled nitric oxide and blood eosinophil count, and nasal polyps with eosinophil infiltration in bilateral nasal cavities. She was diagnosed with eosinophilic airway inflammation and ECRS, and treated with corticosteroid inhalation, steroid nasal spray, and nasal irrigation, resulting in symptom reduction. Although they are relatively rare irAEs of ICIs, clinicians should consider these diseases associated with T2 inflammation and treat appropriately.

A comparison of laparoendoscopic single-site surgery versus conventional procedures for laparoscopic donor nephrectomy: a Japanese multi-institutional retrospective study.

PURPOSE: Laparoendoscopic single-site donor nephrectomy (LESSDN) is a feasible and effective procedure because of its non-invasiveness and better cosmetic outcomes. However, there have been few multi-institutional studies conducted by multiple surgeons on LESSDN. We retrospectively compared the clinical data and outcomes between LESSDN and conventional laparoscopic donor nephrectomy (LDN) at multiple institutes in Japan. MATERIALS AND METHODS: From 2009 to 2015, the clinical data of 223 donors who underwent LESSDN and 151 donors who underwent LDN were collected from 10 institutes. All LESSDNs were performed transperitoneally, whereas LDNs were performed transperitoneally (P-LDN) in 75 patients and retroperitoneally (R-LDN) in 76 patients. RESULTS: In the LESSDN group, the single-incision site was pararectal in 155 (69.5%) patients and umbilical in 65 (29.1%) patients. Multiple surgeons (one to eight per institute) performed the LESSDN. No significant differences were observed between the three groups regarding estimated blood loss and warm ischemic time. The operative time was significantly shorter in the LESSDN group than in the R-LDN group (p = 0.018). No significant differences were observed regarding the rates of blood transfusion, open conversion, visceral injuries, and postoperative complications. Furthermore, no significant differences were observed regarding the dose of analgesic and the rate of delayed graft function. One patient required open conversion due to injury to the renal artery. Selection of LESS procedure was not an independent risk factor for the median serum creatinine level of above 1.27 mg/dL in recipients at 1 year after kidney transplantation. CONCLUSION: The results showed the technical feasibility of LESSDN compared with the standard LDNs in a multi-institutional and multi-surgeon setting. A few observed non-negligible complications and the significantly higher levels of serum creatinine in patients who underwent LESSDN indicate that this procedure should be employed cautiously when performed by surgeons without ample experience in performing LESS procedures.

[Repair of Iatrogenic Recto-Urethral Fistulas : Experience of 6 Cases].

I repaired iatrogenic recto-urethral fistulas (RUF) in 6 patients. All the fistulas had developed after surgery, 5 for prostate cancer (prostatectomy) and the remaining one for pelvic solitary fibrous tumor. All of them were"simple"fistulas. I performed repair using the transperineal approach with gracilis muscle flap interposition in 4 cases, and using the transsphincteric approach (modified York-Mason method) in 2, with the cooperation of general surgeons and/or plastic surgeons. All fistulas were successfully repaired. The operation time ranged from 414 to 464 minutes for transperineal repair and 246 and 253 minutes for transsphincteric repair. The blood loss ranged from 100 to 533 ml for transperineal repair and 30 and 60 ml for transsphincteric repair. Transsphincteric approach was less invasive and may be the first choice for simple RUF repair.

[A Case of Advanced Right Renal Pelvic Cancer with Left Supraclavicular Lymph Node Metastasis that Attained Long-Term Survival by Multidisciplinary Treatments].

A man in his 70s was referred to our hospital for further examination of a positive occult blood finding. Imaging studies showed that the patient had right renal pelvic cancer with interaortocaval, multiple paracaval and left supraclavicular lymph node metastases (cT3N2Ml). Induction chemotherapy was performed with 5 cycles of MEC (methotrexate/epirubicin/cisplatin) followed by 2 cycles of GT (gemcitabine/paclitaxel). After the combined chemotherapies, the residual lesions were the primary tumor in the right renal pelvis and the left supraclavicular lymph node. Right total nephroureterectomy combined with lymph node dissection of paraaortic, paracaval, and interaortocaval area and left cervical area were performed. Histopathologically the postoperative T stage of the primary tumor was determined as ypT3. As for lymph nodes dissected, an interaortocaval lymph node alone, but not the other nodes, contained viable cancer cells. Adjuvant chemotherapy was performed with 7 courses of GT therapy. The patient had intravesical recurrence once and received transurethral resection of bladder tumor followed by intravesical instillations of Bacillus Calmette-Guerin (BCG). Finally, the patient has been free from recurrence for 10 years after the final treatment.