Robot-assisted radical prostatectomy with the Hugo™ robot-assisted surgery system: A single-center initial experience in Japan.

BACKGROUND: Recently, various novel robotic systems have been put into clinical use. The aim of the present study was to assess the perioperative outcomes of robot-assisted radical prostatectomy (RARP) using the Hugo™ RAS system, one of brand-new robot-assisted surgical platforms. METHODS: We performed RARP with the Hugo™ RAS system in 13 cases of localized prostate cancer (PCa) between August 2023 and February 2024 at our hospital. The perioperative outcomes of these 13 patients were assessed. RESULTS: The median operative and console times were 197 (interquartile range [IQR], 187-228) and 134 min (IQR, 125-157), respectively. The median docking time was 7 min (IQR, 6-10), and the median estimated blood loss was 150 mL (IQR, 80-250). The vesical catheter was removed on postoperative day 6 in all cases. A positive surgical margin was observed in one patient (7.7%), and none experienced major perioperative complications, defined as Clavien-Dindo classification ≥3. The median postoperative length of stay was 8 days (IQR, 8-8.5). CONCLUSIONS: This was the first study to focus on RARP using the Hugo™ RAS system in Japan. Although further investigations should be conducted to assess the long-term oncological and functional outcomes, the Hugo™ RAS system could provide safe and favorable perioperative outcomes for patients with localized PCa undergoing RARP.

A case of Legionella pneumonia after robot-assisted radical prostatectomy.

Introduction: Postoperative Legionella pneumonia is very rare. Case presentation: A 71-year-old male patient with prostate cancer (cT2bN0M0) underwent a robotic-assisted radical prostatectomy. On the 5th postoperative day, the patient developed chills and a fever of 39.2°C. Chest radiography revealed decreased permeability in the right middle lung field, leading to the diagnosis of postoperative pneumonia. Antimicrobial therapy was initiated immediately. Blood tests on postoperative day 10 revealed mild liver function abnormalities, electrolyte abnormalities, and a markedly elevated inflammatory response. Legionella pneumonia was suspected based on blood sample results and systemic symptoms, such as diarrhea and nausea. Furthermore, Legionella antigens were detected in the patient's urine, prompting further administration of levofloxacin. The patient's subsequent clinical course was favorable. Conclusion: When bacterial pneumonia fails to respond to antimicrobial therapy and systemic symptoms develop, atypical pneumonia, caused by pathogens such as Legionella pneumophila, should be considered even in cases of postoperative pneumonia.

Impact of an enhanced recovery protocol in frail patients after intracorporeal urinary diversion.

OBJECTIVE: To determine whether an enhanced recovery after surgery (ERAS) protocol enhances bowel recovery and reduces postoperative ileus (POI) in both non-frail and frail patients after robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: This retrospective cohort study included 186 patients (104 with and 82 without ERAS) who underwent iRARC between 2012 and 2023. 'Frail' patients was defined as those with a low Geriatric-8 questionnaire score (≤13). The primary outcomes were postoperative bowel recovery and the incidence of POI. Secondary outcomes included length of stay (LOS), 30- and 90-day complications, 90-day readmission rate, and POI predictors. RESULTS: The ERAS group exhibited a significantly shorter LOS, early bowel recovery, a lower POI rate, fewer 90-day high-grade complications, and fewer 90-day readmissions than the non-ERAS group in the entire cohort. Non-frail patients in the ERAS group had a lower rate of POI (7.1% vs. 22.1%; P = 0.008), whereas ERAS did not reduce POI in frail patients (44.1% vs. 36.6%; P = 0.50). In the multivariate analysis, ERAS was associated with a reduced risk of POI in both the entire cohort (odds ratio [OR] 0.39, P = 0.01) and in non-frail patients (OR 0.24, P = 0.01), whereas ERAS was not likely to reduce POI (OR 1.14, P = 0.70) in frail patients. Prehabilitation was identified as a favourable predictor of POI. CONCLUSIONS: The ERAS protocol did not reduce POI in frail patients after iRARC, although it enhanced bowel recovery and reduced POI in non-frail patients. Prehabilitation for frail patients might reduce POI.

Older versus younger patients in robot-assisted radical cystectomy with intracorporeal ileal conduit comparing safety and clinical outcomes.

OBJECTIVE: To evaluate the safety and efficacy of robot-assisted radical cystectomy using an intracorporeal ileal conduit in older compared to younger patients. METHODS: We retrospectively analyzed 122 patients who underwent robot-assisted radical cystectomy with an intracorporeal ileal conduit at Fujita Health University Hospital and Fujita Health University Okazaki Medical Center between 2012 and 2022. Patients were categorized into two groups: older (age ≥ 75 years; n = 53) and younger (age < 75 years; n = 69). Perioperative outcomes, complications, recurrence-free survival, cancer-specific survival, and overall survival were compared between the cohorts. RESULTS: The groups had no significant differences in perioperative outcomes, such as estimated blood loss, operative time, and blood transfusion rate. However, hospital stay was longer in the older patients than in the younger group (19 vs. 16 days; p < 0.001). The 30-day minor and major complication rates were 33.3% and 13.0%, respectively, for the younger group and 50.9% and 9.4% for the older group (p = 0.11). Urinary tract infection and bowel ileus were the most common complications in both groups. No significant differences were observed in recurrence-free survival, cancer-specific survival, and overall survival between the groups (p = 0.58, p = 0.75, and p = 0.78), and subgroup analysis in ≥cT3 revealed the older group tended to have poorer cancer-specific survival and overall survival (p = 0.07 and p = 0.01). Multivariate analysis indicated that older age was not associated with high-grade complications and cancer-specific survival. CONCLUSIONS: Robot-assisted radical cystectomy with an intracorporeal ileal conduit is a safe and effective treatment option for older patients.

The Role of Lymph Node Dissection in Patients With Muscle-Invasive Bladder Cancer Who Underwent Radical Cystectomy Following Neoadjuvant Chemotherapy.

BACKGROUND: The interaction between lymph node dissection (LND) during radical cystectomy (RC) and neoadjuvant chemotherapy (NAC) remains unclear. This study aimed to evaluate the role of LND in patients undergoing RC after NAC. PATIENTS AND METHODS: We retrospectively analyzed 259 patients with muscle-invasive bladder cancer (MIBC) who underwent RC following NAC at Fujita Health University Hospital and Fujita Health University Okazaki Medical Center between 2010 and 2022. Baseline characteristics, pathological outcomes, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between propensity score (PS)-matched cohorts. RESULTS: PS matching analysis resulted in 94 matched pairs from the adequate (standard or extended template) and inadequate (limited template or unilateral- or no-LND) LND groups. The median number of dissected nodes was significantly higher in the adequate LND group than in the inadequate LND group (19 vs. 5, P < .001). Similarly, a higher pathological node-positive rate (ypN+) was observed in the adequate group than in the inadequate group (18.1% vs. 7.4%, P = .03). The adequate LND group identified more ypN+ with ≤ ypT1 cases than the inadequate group (4 vs. 1). There were no statistically significant differences between the adequate and inadequate groups in RFS (P = .94), CSS (P = .54), and OS (P = .65). Subgroup analysis also showed comparable survival rates, even in patients with ≥ pT3 or cN+ disease. ypN+ was an independent predictor of OS in the Cox regression analysis, while adequate LND and the number of lymph nodes removed (≥10 or ≥15) were not associated with survival. CONCLUSIONS: Although adequate LND did not show a significant therapeutic effect in RC after NAC, adequate LND may have an important diagnostic role in detecting ypN+, which is a robust predictor, and is a useful biomarker to perform appropriate adjuvant immunotherapy especially in ≤ ypT1 cases.

Robot-assisted retroperitoneal lymph node dissection: Initial experience in Japan.

For patients with testicular tumors who need the surgical management, open retroperitoneal lymph node dissection (O-RPLND) is considered the gold standard treatment. However, recently, robot-assisted RPLND (R-RPLND) has gained popularity as a minimally invasive therapy alternative to O-RPLND and laparoscopic RPLND. Here, we report the case of a 32-year-old man presenting with a left testicular teratoma with several enlarged left para-aortic lymph nodes. After the orchiectomy, the patient underwent R-RPLND with an operation time of 279 min, console time of 189 min, bleeding volume of 59 mL, and no significant complications, resulting in a successful outcome. To the best of our knowledge, this is the first reported case of R-RPLND in Japan. Based on our experience, R-RPLND may provide safe and effective outcomes; however, further research is required before the widespread implementation of this technique.

Comparison of perioperative outcomes and complications between intracorporeal, extracorporeal, and hybrid ileal conduit urinary diversion during robot-assisted radical cystectomy: a comparative propensity score-matched analysis from nationwide multi-institutional study in Japan.

BACKGROUND: To investigate the impact of different urinary diversion (UD) techniques on the peri- and postoperative complications of robot-assisted radical cystectomy (RARC) with ileal conduit. METHODS: We retrospectively analyzed 373 patients undergoing RARC with ileal conduit at 11 institutions in Japan between April 2018 and December 2021. Propensity score weighting was performed to adjust for confounding factors such as age, sex, body mass index, performance status, American Society of Anesthesiologists score, previous abdominal surgery, neoadjuvant chemotherapy, and preoperative high T stage (≥ cT3) and high N stage (≥ cN1). Perioperative complications were then compared among three groups: extracorporeal, intracorporeal, and hybrid urinary diversion (ECUD, ICUD, and HUD, respectively). RESULTS: A total of 150, 68, and 155 patients received ECUD, HUD, and ICUD, respectively. Bowel reconstruction time and UD time were significantly shorter in the ECUD group (p < 0.001), and console time was significantly longer and blood loss was significantly higher in the ICUD group (p < 0.001). For postoperative complications (Clavien-Dindo Classification grade ≥ 3), surgical site infection (p = 0.004), pelvic abscess (p = 0.013), anastomotic urine leak (p = 0.007), and pelvic organ prolapse (p = 0.011) significantly occurred in the ECUD group. For all grades, ileus was more common in the HUD group, whereas anastomotic stricture was more common in the ECUD group compared with the other groups (p < 0.05). CONCLUSIONS: Severe complications did not increase after HUD and ICUD compared with ECUD; however, console time tended to be longer and blood loss was slightly higher during RARC.

Comparing pentafecta outcomes between nerve sparing and non nerve sparing robot-assisted radical prostatectomy in a propensity score-matched study.

Pentafecta (continence, potency, cancer control, free surgical margins, and no complications) is an important outcome of prostatectomy. Our objective was to assess the pentafecta achievement between nerve-spring and non-nerve-sparing robot-assisted radical prostatectomy (RARP) in a large single-center cohort. The study included 1674 patients treated with RARP between August 2009 and November 2022 to assess the clinical outcomes. Cox regression analyses were performed to evaluate the prognostic significance of RARP for pentafecta achievement, and 1:1 propensity score matching (PSM) was performed between the nerve-sparing and non-nerve-sparing to test the validity of the results. Pentafecta definition included continence, which was defined as the use of zero pads; potency, which was defined as the ability to achieve and maintain satisfactory erections or ones firm enough for sexual activity and sexual intercourse. The biochemical recurrence rate was defined as two consecutive PSA levels > 0.2 ng/mL after RARP; 90-day Clavien-Dindo complications ≤ 3a; and a negative surgical pathologic margin. The median follow-up period was 61.3 months (IQR 6-159 months). A multivariate Cox regression analysis demonstrated that pentafecta achievement was significantly associated with nerve-sparing (NS) approach (1188 patients) (OR 4.16; 95% CI 2.51-6.9), p < 0.001), unilateral nerve preservation (983 patients) (OR 3.83; 95% CI 2.31-6.37, p < 0.001) and bilateral nerve preservation (205 patients) (OR 7.43; 95% CI 4.14-13.36, p < 0.001). After propensity matching, pentafecta achievement rates in the NS (476 patients) and non-NS (476 patients) groups were 72 (15.1%) and 19 (4%), respectively. (p < 0.001). NS in RARP offers a superior advantage in pentafecta achievement compared with non-NS RARP. This validation study provides the pentafecta outcome after RARP associated with nerve-sparing in clinical practice.

Combination of deep learning and ensemble machine learning using intraoperative video images strongly predicts recovery of urinary continence after robot-assisted radical prostatectomy.

BACKGROUND: We recently reported the importance of deep learning (DL) of pelvic magnetic resonance imaging in predicting the degree of urinary incontinence (UI) following robot-assisted radical prostatectomy (RARP). However, our results were limited because the prediction accuracy was approximately 70%. AIM: To develop a more precise prediction model that can inform patients about UI recovery post-RARP surgery using a DL model based on intraoperative video images. METHODS AND RESULTS: The study cohort comprised of 101 patients with localized prostate cancer undergoing RARP. Three snapshots from intraoperative video recordings showing the pelvic cavity (prior to bladder neck incision, immediately following prostate removal, and after vesicourethral anastomosis) were evaluated, including pre- and intraoperative parameters. We evaluated the DL model plus simple or ensemble machine learning (ML), and the area under the receiver operating characteristic curve (AUC) was analyzed through sensitivity and specificity. Of 101, 64 and 37 patients demonstrated "early continence (using 0 or 1 safety pad at 3 months post-RARP)" and "late continence (others)," respectively, at 3 months postoperatively. The combination of DL and simple ML using intraoperative video snapshots with clinicopathological parameters had a notably high performance (AUC, 0.683-0.749) to predict early recovery from UI after surgery. Furthermore, combining DL with ensemble artificial neural network using intraoperative video snapshots had the highest performance (AUC, 0.882; sensitivity, 92.2%; specificity, 78.4%; overall accuracy, 85.3%) to predict early recovery from post-RARP incontinence, with similar results by internal validation. The addition of clinicopathological parameters showed no additive effects for each analysis using DL, EL and simple ML. CONCLUSION: Our findings suggest that the DL algorithm with intraoperative video imaging is a reliable method for informing patients about the severity of their recovery from UI after RARP, although it is not clear if our methods are reproducible for predicting long-term UI and pad-free continence.

Estimating copy number to determine BRCA2 deletion status and to expect prognosis in localized prostate cancer.

BACKGROUND: The significance of BRCA alterations has been implicated in the development of metastatic castration-resistant prostate cancer (PC). The details of the frequency and significance of BRCA alterations in localized PC remain unknown. In this study, we investigated the frequency and clinical significance of BRCA alterations in localized PCs using an in-house next-generation sequencer (NGS) system. METHODS: DNA was extracted from formalin-fixed paraffin-embedded tissues of surgical specimens from 126 patients with clinically localized PC who underwent radical prostatectomy. The mutation information of 164 cancer genes was analyzed using the PleSSision-Rapid test. Both copy number (CN) variation and loss of heterozygosity of various genes, such as BRCA1 and BRCA2, were estimated and reported. RESULTS: Next-generation sequencer analyses revealed that the BRCA2 CN was decreased in 17 patients (13.5%) and the BRCA1 CN in six (4.8%) patients. NGS-based CN values were shown to be highly correlated with droplet digital PCR-based CN values. Tissue-specific BRCA expression investigated using the Human Protein Atlas showed that the decreased CN of BRCA2, but not BRCA1, is responsible for the decreased BRCA activity in PC. Ten of the 22 patients with decreased BRCA2 CN were presumed to have somatic heterozygous deletion. There were no observed associations between the heterozygous deletion of BRCA2 and various clinicopathological parameters. Furthermore, three of 10 patients developed biochemical recurrence within 3 months after surgery. Multivariate analyses revealed that the initial prostate-specific antigen levels and BRCA2 CN were independent factors for biochemical recurrence. CONCLUSION: Our results suggest that a decrease in BRCA2 CN may be used as a biomarker for predicting recurrence after surgery in localized PC. Early screening for somatic alterations in BRCA2 using NGS may help to broadly predict the risk of PC progression.

Robot-assisted radical nephrectomy with inferior vena cava thrombectomy: a case report.

Background: Recently, robot-assisted surgery has been widely used to treat several urological cancers. Robot-assisted radical nephrectomy (RARN) was approved by the health insurance system in April 2022; however, RARN with inferior vena cava tumor thrombectomy (IVCTT) is still challenging. Also, its safety and feasibility have not yet been established owing to lack of literature, especially in Japan. Case Description: We performed RARN with IVCTT in four patients between April 2022 and March 2023 at Fujita Health University Hospital. To reduce the risk of tumor embolism and major hemorrhage, an "IVC-first, kidney-last" robotic technique was developed. The safety and feasibility of RARN with IVCTT were evaluated by assessing the perioperative outcomes. Three women and one man were enrolled in this study. The median age was 72 years, and the tumor was on the right side in all cases. According to the Mayo Clinic thrombus classification, two patients were classified as level I, and the others were classified as level II. The two patients at level I did not undergo presurgical treatments, whereas the others at level II underwent presurgical treatments, which were combinations of tyrosine kinase inhibitors and immune-checkpoint inhibitors. The median operation and console times were 341 and 247 min, respectively. The median bleeding volume was 577 mL, and no complications beyond grade III of the Clavien-Dindo classification were observed. The median length of postoperative hospital stay was 10 days. Conclusions: Although the sample size was relatively small, we demonstrated the safety and feasibility of RARN with IVCTT in the Japanese population.

Robotic surgery for pelvic organ prolapse with complete bladder eversion.

Introduction: Pelvic organ prolapse with complete bladder eversion is extremely rare. Case presentation: An 82-year-old woman was diagnosed with uterine prolapse 3 years ago and underwent occasional urethral catheter placement for difficulty in micturition. She presented with vulvar bleeding and prolapsed uterus from the vagina. Pelvic examination revealed uterine prolapse and a 65 × 65-mm red mass ventrally with urinary outflow. Contrast medium leakage from the vulvar mass and guidewire observed on antegrade pyeloureterography indicated pelvic organ prolapse with complete bladder eversion. Manual reduction of the everted bladder, robotic sacrocolpopexy, and bladder neck reconstruction was performed. However, eversion recurred 10 months postoperatively. Subsequently, robotic Burch colposuspension, cystopexy to the rectus fascia, bladder neck reconstruction, colpoclesis, and cystostomy were performed. There was no recurrence postoperatively. Conclusion: Robotic Burch colposuspension, cystopexy to the rectus fascia, bladder neck reconstruction, colpoclesis, and cystostomy were performed for complete bladder eversion.

Alanine-Serine-Cysteine Transporter 2 Inhibition Suppresses Prostate Cancer Cell Growth In Vitro.

Alanine-serine-cysteine transporter 2 (ASCT2) has been associated with increased levels of metabolism in various malignant tumors. However, its biological significance in the proliferation of prostate cancer (PCa) cells remains under investigation. We used the cBioPortal database to assess the effect of ASCT2 expression on the oncological outcomes of 108 PCa patients. To evaluate the function of ASCT2 in castration-sensitive PCa (CSPC) and castration-resistant PCa (CRPC), LNCaP cells and the ARV7-positive PCa cell line, 22Rv1, were assessed using cell proliferation assays and Western blot analyses. The ASCT2 expression level was associated with biochemical recurrence-free survival after prostatectomy in patients with a Gleason score ≥ 7. In vitro experiments indicated that the growth of LNCaP cells after combination therapy of ASCT2 siRNA and enzalutamide treatment was significantly reduced, compared to that following treatment with enzalutamide alone or ASCT2 siRNA transfection alone (p < 0.01, 0.01, respectively). After ASCT2 inhibition by siRNA transfection, the growth of 22Rv1 cells was significantly suppressed as compared with negative control siRNA via downregulation of ARV7 both in fetal bovine serum and androgen-deprivation conditions (p < 0.01, 0.01, respectively). We demonstrated that ASCT2 inhibition significantly reduced the proliferation rates of both CSPC and CRPC cells in vitro.

Novel Intraoperative Navigation Using Ultra-High-Resolution CT in Robot-Assisted Partial Nephrectomy.

To assess the perioperative and short-term functional outcomes of robot-assisted partial nephrectomy (RAPN) with intraoperative navigation using an ultra-high-resolution computed tomography (UHR-CT) scanner, we retrospectively analyzed 323 patients who underwent RAPN using an UHR-CT or area-detector CT (ADCT). Perioperative outcomes and the postoperative preservation ratio of estimated glomerular filtration rate (eGFR) were compared. After the propensity score matching, we evaluated 99 patients in each group. Although the median warm ischemia time (WIT) was less than 25 min in both groups, it was significantly shorter in the UHR-CT group than in the ADCT group (15 min vs. 17 min, p = 0.032). Moreover, the estimated blood loss (EBL) was significantly lower in the UHR-CT group than in the ADCT group (33 mL vs. 50 mL, p = 0.028). However, there were no significant intergroup differences in the postoperative preservation ratio of eGFR at 3 or 6 months of follow-up (ADCT 91.8% vs. UHR-CT 93.5%, p = 0.195; and ADCT 91.7% vs. UHR-CT 94.0%, p = 0.160, respectively). Although no differences in short-term renal function were observed in intraoperative navigation for RAPN in this propensity score-matched cohort, this study is the first to demonstrate that UHR-CT resulted in a shorter WIT and lower EBL than ADCT.

Perioperative and long-term functional outcomes of robot-assisted versus open partial nephrectomy: A single-center retrospective study of a Japanese cohort.

Objective: This study aimed to compare the perioperative and long-term functional outcomes between robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN) in Japanese patients. Methods: We retrospectively analyzed 242 patients who underwent either RAPN or OPN between 2007 and 2017 at our hospital. Propensity score matching was carried out between the two groups at a ratio of 1:1. Perioperative outcomes and postoperative estimated glomerular filtration rates (eGFR) were compared at one and three years of follow-up. Results: After propensity score matching, we evaluated 39 patients from each group. The ischemia duration of the RAPN group was significantly shorter than that of the OPN group (18 vs. 24, p < 0.001). Moreover, the estimated blood loss (EBL) was significantly lower in the RAPN group than in the OPN group (50 vs. 174, p < 0.001). However, there were no significant differences in the postoperative eGFR between the two groups at one or three years of follow-up (OPN 54.8 vs. RAPN 61.2, p = 0.109, and OPN 54.8 vs. RAPN 55.5, p = 0.262, respectively). Conclusion: RAPN resulted in shorter ischemia durations and lower rates of EBL than did OPN; however, no differences in long-term renal function were observed between RAPN and OPN in our propensity-score matched Japanese cohort.

Risk factors for postoperative ileus after robot-assisted radical cystectomy with intracorporeal urinary diversion.

OBJECTIVES: To evaluate the risk factors for postoperative ileus in patients who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion. METHODS: We retrospectively analyzed 78 patients with bladder cancer who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion at Fujita Health University between 2011 and 2021. Baseline characteristics and perioperative outcomes were compared between the cohorts with and without ileus. Logistic regression analysis was used to identify the risk factors for postoperative ileus. RESULTS: Out of the 78 patients included in this study, 20 (25.6%) developed postoperative ileus. The ileus cohort was associated with a significantly lower Geriatric-8 score (P = 0.003) and a higher rate of previous abdominal/pelvic surgery (P = 0.04) compared with those of the nonileus cohort. Significantly longer intestinal tract reconstruction time, hospital stay, time to mobilization, fluid intake, solid intake, flatus, and stool were observed in the ileus cohort. According to the results of the logistic regression analysis, the Geriatric-8 sum (P = 0.009), time to mobilization (P = 0.03), and time to fluid intake (P = 0.004) were independent predictors of postoperative ileus. In the model predicting postoperative ileus, the area under the receiver operating characteristic curve was 0.716, and the cutoff value of the Geriatric-8 sum was 13. CONCLUSIONS: Early mobilization and fluid intake and low Geriatric-8 scores were significant risk factors for postoperative ileus. Preoperative Geriatric-8 evaluation is a useful tool for predicting postoperative ileus. Comprehensive enhanced recovery after surgery, including key components, may help bowel recovery and prevent subsequent ileus.

Predictors of Secondary Bladder Cancer in Patients with Prostate Cancer Treated with Brachytherapy: A Single-institution Study of a Japanese Cohort.

PURPOSE: The incidence of secondary bladder cancer after treatment for localized prostate cancer (PCa) remains unclear. In this study, PCa cases treated with brachytherapy (BT) were evaluated to assess the incidence of a second malignancy of bladder cancer in a Japanese cohort. MATERIALS AND METHODS: Overall, 969 patients treated with BT at our hospital between July 2006 and January 2019 were included in the study cohort. The incidence and predictors of secondary bladder cancer were also assessed. RESULTS: The incidence of secondary bladder cancer was 1.5% (n = 14). Of the seven factors (age, pretreatment PSA, Gleason score, cTNM stage, prostate volume, total activity, and combined external beam), prostate volume and total activity showed significant differences between the cohorts with and without secondary bladder cancer (P = .03 and P = .001, respectively). Upon comparison of the seven parameters for the 969 patients treated with BT, we found that only the total activity factor was affected by the incidence of secondary bladder cancer in the multivariate analysis (P = .007). CONCLUSION: The incidence of secondary bladder cancer was evaluated after BT for PCa. Total activity was associated with the incidence of secondary bladder cancer in Japanese patients who received BT.

Longitudinal measurement of subcutaneous and intratibial human prostate cancer xenograft growth and response to ionizing radiation by plasma Alu and LINE-1 ctDNA: A comparison to standard methods.

BACKGROUND: Current preclinical models of metastatic prostate cancer (PCa) require sophisticated technologies and/or genetically engineered cells for the noninvasive monitoring of tumors in remote sites, such as bone. Recent developments in circulating tumor DNA (ctDNA) analysis provide an alternative method for noninvasive tumor monitoring at a low cost. Here, we sought to evaluate human Alu and LINE-1 ctDNA for the longitudinal measurement of subcutaneous and intratibial human PCa xenograft growth and response to ionizing radiation (IR) through comparison with standard slide caliper and bioluminescence measurements. MATERIAL AND METHODS: Intratibial and subcutaneous xenografts were established in male athymic nude mice using LNCaP cells that stably express firefly luciferase. A subset of tumors was treated with a single dose of IR (CT-guided focal IR, 6 Gy). Tumor measurements were simultaneously taken by slide caliper (subcutaneous only), in vivo bioluminescence imaging, and quantitative real-time PCR (qPCR) of human-specific Alu and LINE-1 ctDNA for several weeks. RESULTS: Levels of ctDNA and bioluminescence increased concordantly with subcutaneous and intratibial tumor growth. A statistically significant correlation (Spearman) was observed between ctDNA and subcutaneous tumor volume (LINE-1, r = .94 and Alu, r = .95, p < .0001), ctDNA and bioluminescence (LINE-1, r = .66 and Alu, r = .60, p < .002), and bioluminescence and tumor volume (r = .66, p = .0003). Bioluminescence and ctDNA were also significantly correlated in intratibial tumors (LINE-1, r = .82 and Alu, r = .81, p < .0001). Following external beam IR, the tumor responses varied briefly by method of measurement, but followed a similar trend. Statistically significant correlations were maintained between ctDNA and slide caliper measurement in irradiated subcutaneous tumors (LINE-1, r = .64 and Alu, r = .44, p < .02), and ctDNA and bioluminescence in intratibial tumors (LINE-1, r = .55, p = .018). CONCLUSIONS: Real-time qPCR of circulating human Alu and LINE-1 DNA provides an accurate measurement of subcutaneous and intratibial xenograft burden that is comparable with conventional bioluminescence imaging and slide caliper measurement. Transient differences in measurements were observed following tumor-targeted IR, but overall all measurements mirrored tumor growth and response.

Intra-corporeal robot-assisted versus open radical cystectomy: a propensity score-matched analysis comparing perioperative and long-term survival outcomes and recurrence patterns.

BACKGROUND: To compare perioperative and long-term oncological outcomes and recurrence patterns between robot-assisted radical cystectomy with intra-corporeal urinary diversion (iRARC) and open radical cystectomy (ORC). METHODS: We retrospectively analyzed 177 bladder cancer patients who received iRARC or ORC at Fujita Health University between 2008 and 2020. Our primary endpoint was long-term oncological outcomes. As a secondary endpoint, we examined perioperative outcomes, complications, and recurrence patterns. These outcome measures were compared between the propensity score (PS)-matched cohorts. RESULTS: PS-matched analysis resulted in 60 matched pairs from iRARC and ORC groups. The iRARC cohort was associated with significantly longer operative time (p = 0.02), lower estimated blood loss (p < 0.001), lower blood transfusion rate (p < 0.001), shorter length of hospital stay (p < 0.001), fewer overall complications (p = 0.03), and lower rate of postoperative ileus (p = 0.02). There was no statistically significant difference between iRARC and ORC in 5-year RFS (p = 0.46), CSS (p = 0.63), and OS (p = 0.71). RFS and CSS were also comparable, even in locally advanced (≥ cT3) disease. Multivariate analysis identified lymphovascular invasion as a robust predictor of RFS, CSS, and OS. The number of recurrence was similar between the groups, while extra-pelvic lymph nodes were more frequent in iRARC than that in ORC (22.7% vs. 7.7%). CONCLUSIONS: iRARC has favorable perioperative outcomes, fewer complications, and comparable long-term survival outcomes, including locally advanced (≥ cT3) disease, compared to that in ORC. Our results need to be validated in prospective randomized clinical trials.

Combined α-methylacyl-CoA racemase inhibition and docetaxel treatment reduce cell proliferation and decrease expression of heat shock protein 27 in androgen receptor-variant-7-positive prostate cancer cells.

BACKGROUND: Disease progression in castrate-resistant prostate cancer (PCa) is most commonly driven by the reactivation of androgen receptor (AR) signaling and involves AR splice variants including ARV7. MATERIALS AND METHODS: We used the ARV7-positive PCa cell line, 22Rv1, to study the relationship of the PCa marker α-methylacyl-CoA racemase (AMACR), AR, and ARV7 in PCa. RESULTS: Docetaxel addition but not AMACR inhibition decreased the proliferation of 22Rv1 cells. The combination of AMACR inhibition and docetaxel treatment resulted in a maximum reduction of cell proliferation. The Western blotting analysis revealed that both AR and ARV7 expression were significantly decreased with the use of charcoal-stripped serum following AMACR inhibition and docetaxel treatment. AMACR inhibition and docetaxel treatment in the charcoal-stripped serum condition reduced the proliferation of 22Rv1, possibly via the downregulation of the heat shock protein 27. CONCLUSION: Using cell proliferation and Western blot analysis, we demonstrated that AMACR inhibition and docetaxel treatment, under androgen deprivation conditions, significantly reduced the proliferation of ARV7 positive cancer cells and decreased the levels of AR and ARV7 expression, possibly via downregulation of heat shock protein 27.