Complete retroperitoneal cutaneous ureterostomy with robot-assisted radical cystectomy.

Introduction: Cutaneous ureterostomy is beneficial for older patients in a hypoalimentation state, providing less invasive options than intestinal tract reconstruction techniques. However, complications such as ileus and stoma site hernia still pose risks owing to the anatomical location of the ureter. We introduce a novel method, complete retroperitoneal cutaneous ureterostomy, performed simultaneously with robot-assisted radical cystectomy. Case presentation: Our technique involves extending the retroperitoneal space to minimize complications and achieve stent-free outcomes. The median procedure time for complete retroperitoneal cutaneous ureterostomy was approximately 30 min. The stent-free rates at 1 and 4 months postoperatively were 66.7% and 100%, respectively; no case of stent reinsertion after stent removal was reported. Conclusion: Our approach is promising for avoiding postoperative intestinal tract complications.

Postoperative complications and determinant of selecting non intracorporeal urinary diversion in patients undergoing robot-assisted radical cystectomy: an initial experience.

Background: Robot-assisted radical cystectomy (RARC) with urinary diversion has become a standard surgical procedure because of its three-dimensional high-definition surgical field of view, flexibility, and stability. However, because of the highly complex steps of surgery, postoperative complications cannot be ignored. Methods: This retrospective, single-center, observational cohort study investigated the postoperative complications following RARC at a non-high-volume center in Japan. From August 2019 to March 2023, 50 consecutive patients who underwent RARC for histologically proven muscle-invasive bladder cancer (MIBC) or high-risk non-MIBC with an indication for radical cystectomy according to the Japanese Urological Association Guideline 2019 were included. Factors correlated with the selection of extracorporeal urinary diversion (ECUD) or cutaneous ureterostomy rather than intracorporeal urinary diversion (ICUD) for urinary diversion were also investigated. Results: In total, 33 (66%) and 31 (62%) patients experienced complications during the first 90 and 30 days after RARC, respectively. Among them, 19 (38%) and 18 (36%) patients developed Clavien-Dindo classification G2 complications, and 12 (24%) and 11 (22%) developed G3 or higher (major) complications during the first 90 and 30 days after RARC, respectively. The most common complications were gastrointestinal complications (26%) and urinary tract infections (22%). Nine patients (18%) underwent surgical intervention within 90 days of undergoing RARC. Higher infusion volume during the operations was significantly correlated with the occurrence of major complications within 90 days (P=0.025) and 30 days (P=0.0158) after RARC. Nineteen patients (38%) underwent non-ICUD. Twelve patients received ECUD as an ileal conduit or neobladder, and among them, three patients received ECUD due to intraabdominal adhesion for previous abdominal surgery or radiation, while four patients received ECUD ileal conduit due to comorbidities and advanced cases (palliative surgery) to shorten the surgery time. Conclusions: Surgical complications related to the initial experience with RARC at a non-high-volume center in Japan cannot be ignored. Although this complicated surgical procedure requires a learning curve to achieve a stable rate of much fewer major complications after RARC, careful assessment of patients' status before surgery and critical postoperative management may reduce complication rates more quickly, even at non-high-volume centers.

Prognostication in Lymph Node-Positive Prostate Cancer with No PSA Persistence After Radical Prostatectomy.

BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.

Female pelvic organ-preserving robot-assisted simple cystectomy and intracorporeal ileal neobladder reconstruction on a young woman with Hunner-type interstitial cystitis.

Introduction: Cystectomy is the last treatment option for Hunner-type interstitial cystitis. However, consensus regarding optimal patient selection or treatment approaches is lacking. Case presentation: A 27-year-old woman presented to a regional hospital with bladder pain and frequent urination. Antimicrobial therapy was administered; however, her symptoms persisted and she was finally diagnosed with HIC. Multiple endoscopic fulgurations of Hunner's lesions with bladder hydrodistension or intravesical therapy were performed; however, the symptoms persisted. A urethral catheter was inserted 1 month before she visited our clinic because of a severely contracted bladder. We performed female pelvic organ-preserving robot-assisted simple cystectomy and intracorporeal ileal neobladder reconstruction. The patient's postoperative course was uneventful and her symptoms resolved. Conclusion: This is the first report of pelvic organ-preserving robot-assisted simple cystectomy and intracorporeal ileal neobladder reconstruction in a young woman with HIC.

Clinical Efficacy and Openness to New Challenges of Low Dose Rate Brachytherapy for Prostate Cancer.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachytherapy has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision making regarding radiological parameters by radiation oncologists. The combined use of LDR brachytherapy with other therapeutic modalities, such as external beam radiation and androgen deprivation therapy, for the clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology departments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

[Idiopathic Thrombocytopenia Purpura After Pembrolizumab Treatment Against Locally Recurrent Bladder Cancer : A Case Report].

A man in his 70s visited our hospital for gross hematuria. He was diagnosed with invasive urothelial carcinoma (cT3N2M0) and underwent total cystectomy and ileum conduit construction after three courses of neoadjuvant chemotherapy. Eight months after the operation, the disease reoccurred in the pelvic lesion. He received pembrolizumab therapy but developed idiopathic thrombocytopenic purpura (ITP) immediately before the ninth course of administration; and, treatment was discontinued. Recovery of symptoms and normalization of blood test data were achieved 3.5months after starting steroid treatment. Reduction of recurrent disease has been maintained for 2 years.

Pre-operative Plasma Fibrinogen Level as a Potential Predictor of Pathological T3 Upstaging in Clinically Localized Renal Cell Carcinoma.

BACKGROUND/AIM: We investigated pre-operative factors for predicting pathological T3 (pT3) upstaging in clinical T1 renal cell carcinoma (RCC). PATIENTS AND METHODS: We evaluated 181 patients with renal tumors suspected to be clinical T1 RCC. All patients had undergone a partial or radical nephrectomy. Pre-operative parameters, including patient characteristics, RENAL nephrometry score and blood tests were analyzed to determine factors predicting pT3 upstaging. RESULTS: Eight (4.4%) tumors were diagnosed as pT3. Large tumor diameter, less than 4 mm distance between the tumor and the renal collecting system and a high level of preoperative plasma fibrinogen were associated with pT3 stage. Multivariate analysis showed that a preoperative plasma fibrinogen level >330 mg/dl was a significant independent factor predicting upstage (p=0.041). Furthermore, among patients diagnosed with RCC (n=162), a preoperative plasma fibrinogen level >330 mg/dl was related to poor overall survival (p<0.001) and poor recurrence-free survival (p=0.002). CONCLUSION: A high preoperative plasma fibrinogen level may be a predictor of pT3 upstaging and may suggest the need for radical nephrectomy rather than partial nephrectomy because of the associated poor oncological outcomes.

Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells.

BACKGROUND: Androgen receptor splice variant (AR-V) expression has been associated with prostate cancer (PCa) progression to castration-resistant PCa during androgen deprivation therapy, which reduces androgen production and inhibits androgen action in PCa cells. However, the mechanisms whereby aberrant AR-V expression is increased in PCa are still largely unknown. Fibroblasts in tumor stroma influence PCa initiation and aggressiveness, and which may play a crucial role in eliciting genetic changes during malignant transformation in human prostate epithelium. Here, our aim was to determine whether prostate fibroblasts in tumor stroma induce aberrant AR-V7 expression in PCa cells under low androgen concentration. METHODS: We performed in vitro experiments using androgen-sensitive, AR-positive PCa cell lines (LNCaP and 22Rv1 cells), commercially available prostate stromal cells (PrSC), and primary cultured prostate fibroblasts (pcPrF) from PCa specimens collected from biopsies of patients with advanced PCa. PCa cells were cocultured with each of the three fibroblast lines (PrSC, pcPrF-M37, and pcPrF-M48). RESULTS: The proliferation under low androgen concentration of LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 was significantly increased compared to that of PCa cells cultured alone. Androgen receptor-full length (AR-FL) protein expression was increased in LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. AR-V7 protein expression was increased in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. Under low androgen concentration, AR-V7 protein expression was slightly detected in LNCaP cells cocultured with PrSC or pcPrF-M37. Cytokine array analysis revealed that monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) levels in the conditioned medium of 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 were increased under low androgen concentration. High IL-8 concentration (30 ng/ml) resulted in significantly increased protein expression of AR-FL, AR-V7, and phospho-NF-κB p65 in 22Rv1 cells. In contrast, IL-8 antibody (1 µg/ml) decreased AR-V7 protein expression in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. CONCLUSIONS: pcPrF from PCa specimens increase the expression of aberrant AR-V7 in PCa cells. IL-8 may be a target for preventing the expression of aberrant AR-Vs in PCa.

Impact of family history on clinicopathological variables and disease progression in Japanese prostate cancer patients undergoing robotic-assisted radical prostatectomy.

OBJECTIVE: We evaluated whether a first-degree family history (FH) of prostate cancer (PCa) in Japanese patients undergoing robotic-assisted radical prostatectomy (RP) is correlated with clinicopathological variables and disease progression. METHODS: We reviewed consecutive 392 localized PCa patients undergoing robotic-assisted RP at our institution between 2015 and 2020. Information on FH was obtained via a self-administered questionnaire. A positive FH was defined as having a first-degree FH: a father and/or one or more brothers with PCa prior to diagnosis. All patients had clinically localized PCa treated by robotic-assisted RP. We evaluated the relationship between clinical characteristics, pathological findings, and biochemical progression-free survival (bPFS) according to first-degree FH status. RESULTS: Median follow-up was 20.8 months. FH was identified in 42 (10.7%) patients. Patients in the FH group (median, 64.8 years) were diagnosed at a significantly younger age than patients in the non-FH (NFH) group (patients without FH) (median, 67.7 years) (p = 0.003). The 5-year bPFS in the FH and NFH groups was 72.0% and 78.1%, respectively (p = 0.90). A subgroup analysis revealed a significant difference in prostate-specific antigen (PSA) density between the FH group (median, 0.51 ng/ml/cm3 ) and the NFH group (median, 0.29 ng/ml/cm3 ) in patients younger than 60 years (p = 0.033). CONCLUSIONS: In this RP population, FH of PCa was not associated with worse clinical characteristics, pathological findings, or disease progression. Patients with a FH underwent surgery at a significantly younger age, and among patients <60 years, patients with a FH had significantly higher PSA density compared with patients without a FH.

Succinate dehydrogenase B-deficient renal cell carcinoma with a germline variant in a Japanese patient: a case report.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare renal cancer. A 75-year-old Japanese female presented with gross hematuria. Computed tomography revealed two tumors in the left kidney, which were resected. Immunohistochemistry indicated negative staining for the B subunit of SDH (SDHB) in the resected specimen, leading to a final diagnosis of SDHB-deficient RCC. Genetic testing for SDHB showed a RCC germline variant in exon 6 (NM_003000.3:c.642 G > C) that was previously reported but associated with a novel phenotype (i.e., RCC). Twenty-six years prior, her daughter, who was 25 years old at the time, had undergone radical nephrectomy for a pathologic diagnosis of renal oncocytoma of the right kidney; SDHB immunostaining of her daughter's tumor was also negative retrospectively. We confirmed that her daughter carried the germline variant in SDHB exon 6, similar to the patient. The patient had no evidence of disease progression at 15 months after surgery.

Species differences between rats and primates (humans and monkeys) in complex cleavage pathways of DS-8500a characterized by 14C-ADME studies in humans and monkeys after administration of two radiolabeled compounds and in vitro studies.

Our previous study in rats demonstrated that the metabolic pathways of DS-8500a, a novel GPR119 agonist, include cleavage pathways: reductive cleavage of the oxadiazole ring in the liver and hydrolysis of the amide side chain. In the present study, in vivo metabolic profiling in humans and monkeys after the oral administration of two 14C-labeled compounds was performed to investigate species differences of the cleavage pathways. In monkeys, the oxadiazole ring-cleaved metabolites were mainly detected in feces, but not observed in bile, unlike in rats, suggesting that the reductive ring-opening metabolism occurs in the gastrointestinal tract. In vitro incubation with enterobacterial culture media demonstrated that the reductive cleavage of the oxadiazole ring in humans and monkeys was considerably faster than that in rats. The other cleavage metabolite (M20), produced via hydrolysis of the amide side chain, was detected as the major plasma metabolite in humans and monkeys, and its subsequent metabolite (M21) was excreted in feces, whereas M21 was not a major component in rats, indicating a notable species difference in the amide hydrolysis. In conclusion, this study comprehensively revealed the pronounced species difference of the cleavage pathways: reductive ring-opening by intestinal microflora and liver, and amide hydrolysis.

Radiotherapy plus androgen deprivation therapy for prostate-specific antigen persistence in lymph node-positive prostate cancer.

The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis-free survival (MFS) was the primary outcome. Patients were stratified by prostate-specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan-Meier method and log-rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15-0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.

Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer.

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of "frailty" has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm2) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.

[Presurgical Treatment with Axitinib and Pembrolizumab Reduced Operation Risk by Downsizing the Vena Cava Tumor Thrombus in Clear Cell Renal Cell Carcinoma : A Case Report].

A woman in her seventies complained of chest pain during exertion and visited a local hospital. Computed tomographic scan showed right renal cell carcinoma with inferior vena cava (IVC) tumor thrombus extending above the diaphragm, and the patient was referred to our hospital. She was diagnosed with right renal cell carcinoma cT3cN0M0, with level IV IVC thrombus by Mayo classification. Axitinib and pembrolizumab were administered against intractable advanced renal cell carcinoma. The dose of axitinib was reduced due to grade 3 liver dysfunction. Right nephrectomy together with IVC thrombectomy was performed because the primary lesion had shrunk, and the level of IVC thrombus had become level III. The pathological results were clear cell carcinoma, pT3c, G3, Fuhrman grade3, INFA, v1, and ly0. Axitinib and pembrolizumab might be a presurgical option against an intractable renal cell carcinoma with an IVC thrombus.

A case of adenocarcinoma of the rete testis with durable response to cisplatin-based chemotherapy.

INTRODUCTION: Adenocarcinoma of the rete testis is a rare malignancy with a poor prognosis. We report a case of adenocarcinoma of the rete testis with a durable response to cisplatin-based chemotherapy. CASE PRESENTATION: A 48-year-old man with Down syndrome (trisomy 21) presented with a 1-month history of painless swelling of the left scrotum. The physical examination revealed a left testis with a hydrocele associated with a tumor and enlarged pelvic and para-aortic lymph nodes. He underwent a radical orchiectomy. The specimen was diagnosed as adenocarcinoma of the rete testis. The patient received 7 cycles of chemotherapy (1 cycle of BEP and 6 cycles of EP) postoperatively. The metastatic lymph nodes were reduced in size for at least 12 months. Our patient with adenocarcinoma of the rete testis obtained an acceptable response to cisplatin-based chemotherapy. CONCLUSION: We treated a patient with an adenocarcinoma of the rete testis who had an acceptable response to platinum-based chemotherapy.