Search

Objectives: During the past 2 decades, in order to improve perioperative and ontological outcomes, a minimally invasive approach, neoadjuvant chemotherapy (NAC), and an enhanced postoperative recovery program after surgery have been introduced into routine clinical practice of radical cystectomy (RC). Our aim was to examine the differences in clinical practice and postoperative complications after RC by comparing our previous and current cohorts. Materials and methods: A retrospective multi-institutional study. We collected all complications within 90 days after surgery between 2011 and 2017 (current cohort), and categorized them according to a standardized methodology. Then, we compared the outcomes with those in our previous study (previous cohort, 1997-2010). A multivariate logistic regression model was utilized to determine predictors of complications in the current cohort. Results: A total of 838 patients were newly collected (current cohort), and 919 from the previous cohort were included in the subsequent analyses. In the current cohort, the rate of performing NAC was significantly higher (13% vs. 4%, respectively, P < 0.0001), and 26% (222/ 838) underwent laparoscopic RC (LRC, without robotic assistance: n = 210, with robotic assistance: n = 12). There was no significant difference in the overall complication [69% (580/838) vs. 68% (629/919), respectively, P = 0.7284] or major complication (Grades 3-5) [25% (211/838) vs. 22% (201/919), respectively, P = 0.1022] rates between the 2 cohorts. In both cohorts, the most frequent categories were infectious, gastrointestinal, wound-related, and genitourinary. In the current cohort, the performance status (odds ratio, OR = 2.11, P = 0.0013) and operative time (OR = 1.003, P = 0.0016) remained significant predictors of major complications. NAC was not associated with any or major complications. Conclusions: Surgical complications related to RC still remain significant problems, despite the recent improvements in s

Objectives We examined the outcomes of eight weekly bacillus Calmette-Guerin induction therapy after second transurethral resection, and investigated risk factors for intravesical recurrence or disease progression in high-risk non-muscle-invasive bladder cancer patients. Methods This retrospective study included 146 high-risk non-muscle-invasive bladder cancer patients who received eight weekly bacillus Calmette-Guerin instillations without a maintenance schedule between 2000 and 2019. Intravesical recurrence-free and progression-free survival rates were evaluated using the Kaplan-Meier method. The Cox proportional hazards model was used to identify risk factors. Results Pathological T staging in the first transurethral resection was pTa in 56 patients (38.4%), pT1 in 75 (51.4%) and primary carcinoma in situ in 15 (10.2%). A total of 109 (83.2%) with pTa-1 disease underwent second transurethral resection before bacillus Calmette-Guerin induction therapy, and residual disease was detected in 54 (49.5%). The completion rate of eight instillations was 82.2%. The 2- and 5-year intravesical recurrence-free survival rates were 80.7% and 75.2%, whereas the 2- and 5-year progression-free survival rates were 85.7% and 82.0%. Recurrent tumors (hazard ratio 6.5830, P = 0.0007) and residual tumors at the second transurethral resection (hazard ratio 4.0337, P = 0.0021) were risk factors for intravesical recurrence. Multiple tumors (hazard ratio 5.8056, P = 0.0302), pT1 disease (hazard ratio 3.7351, P = 0.0447) and residual tumors at second transurethral resection (hazard ratio 3.2552, P = 0.0448) were associated with disease progression. Conclusions Accurate disease staging and disease elimination by second transurethral resection followed by eight weekly bacillus Calmette-Guerin instillations achieved good disease control. Our protocol (without a maintenance schedule) after thorough surgical resection has potential as a treatment option in the current bacillus Calmette-Guerin s

Background Our aim was to build a skill assessment system, providing objective feedback to trainees based on the motion metrics of laparoscopic surgical instruments. Methods Participants performed tissue dissection around the aorta (tissue dissection task) and renal parenchymal closure (parenchymal-suturing task), using swine organs in a box trainer under a motion capture (Mocap) system. Two experts assessed the recorded movies, according to the formula of global operative assessment of laparoscopic skills (GOALS: score range, 5-25), and the mean scores were utilized as objective variables in the regression analyses. The correlations between mean GOALS scores and Mocap metrics were evaluated, and potential Mocap metrics with a Spearman's rank correlation coefficient value exceeding 0.4 were selected for each GOALS item estimation. Four regression algorithms, support vector regression (SVR), principal component analysis (PCA)-SVR, ridge regression, and partial least squares regression, were utilized for automatic GOALS estimation. Model validation was conducted by nested and repeated k-fold cross validation, and the mean absolute error (MAE) was calculated to evaluate the accuracy of each regression model. Results Forty-five urologic, 9 gastroenterological, and 3 gynecologic surgeons, 4 junior residents, and 9 medical students participated in the training. In both tasks, a positive correlation was observed between the speed-related parameters (e.g., velocity, velocity range, acceleration, jerk) and mean GOALS scores, with a negative correlation between the efficiencyrelated parameters (e.g., task time, path length, number of opening/closing operations) and mean GOALS scores. Among the 4 algorithms, SVR showed the highest accuracy in the tissue dissection task (MAE(median) = 2.2352), and PCA-SVR in the parenchymal-suturing task (MAE(median) = 1.2714), based on 100 iterations of the validation process of automatic GOALS estimation. Conclusion We developed a machine lea

Background Our aim was to build a skill assessment system, providing objective feedback to trainees based on the motion metrics of laparoscopic surgical instruments. Methods Participants performed tissue dissection around the aorta (tissue dissection task) and renal parenchymal closure (parenchymal-suturing task), using swine organs in a box trainer under a motion capture (Mocap) system. Two experts assessed the recorded movies, according to the formula of global operative assessment of laparoscopic skills (GOALS: score range, 5-25), and the mean scores were utilized as objective variables in the regression analyses. The correlations between mean GOALS scores and Mocap metrics were evaluated, and potential Mocap metrics with a Spearman's rank correlation coefficient value exceeding 0.4 were selected for each GOALS item estimation. Four regression algorithms, support vector regression (SVR), principal component analysis (PCA)-SVR, ridge regression, and partial least squares regression, were utilized for automatic GOALS estimation. Model validation was conducted by nested and repeated k-fold cross validation, and the mean absolute error (MAE) was calculated to evaluate the accuracy of each regression model. Results Forty-five urologic, 9 gastroenterological, and 3 gynecologic surgeons, 4 junior residents, and 9 medical students participated in the training. In both tasks, a positive correlation was observed between the speed-related parameters (e.g., velocity, velocity range, acceleration, jerk) and mean GOALS scores, with a negative correlation between the efficiencyrelated parameters (e.g., task time, path length, number of opening/closing operations) and mean GOALS scores. Among the 4 algorithms, SVR showed the highest accuracy in the tissue dissection task (MAE(median) = 2.2352), and PCA-SVR in the parenchymal-suturing task (MAE(median) = 1.2714), based on 100 iterations of the validation process of automatic GOALS estimation. Conclusion We developed a machine lea

Background Our aim was to characterize the motions of multiple laparoscopic surgical instruments among participants with different levels of surgical experience in a series of wet-lab training drills, in which participants need to perform a range of surgical procedures including grasping tissue, tissue traction and dissection, applying a Hem-o-lok clip, and suturing/knotting, and digitize the level of surgical competency. Methods Participants performed tissue dissection around the aorta, dividing encountered vessels after applying a Hem-o-lok (Task 1), and renal parenchymal closure (Task 2: suturing, Task 3: suturing and knot-tying), using swine cadaveric organs placed in a box trainer under a motion capture (Mocap) system. Motion-related metrics were compared according to participants' level of surgical experience (experts: 50 <= laparoscopic surgeries, intermediates: 10-49, novices: 0-9), using the Kruskal-Wallis test, and significant metrics were subjected to principal component analysis (PCA). Results A total of 15 experts, 12 intermediates, and 18 novices participated in the training. In Task 1, a shorter path length and faster velocity/acceleration/jerk were observed using both scissors and a Hem-o-lok applier in the experts, and Hem-o-lok-related metrics markedly contributed to the 1st principal component on PCA analysis, followed by scissors-related metrics. Higher-level skills including a shorter path length and faster velocity were observed in both hands of the experts also in tasks 2 and 3. Sub-analysis showed that, in experts with 100 <= cases, scissors moved more frequently in the "close zone (0 <= to < 2.0 cm from aorta)" than those with 50-99 cases. Conclusion Our novel Mocap system recognized significant differences in several metrics in multiple instruments according to the level of surgical experience. "Applying a Hem-o-lok clip on a pedicle" strongly reflected the level of surgical experience, and zone-metrics may be a promising tool t

I-131-meta-iodobenzylguanidine (I-131-MIBG) radiotherapy has shown some survival benefits in metastatic neuroendocrine tumors (NETs). European Association of Nuclear Medicine clinical guidelines for I-131-MIBG radiotherapy suggest a repeated treatment protocol, although none currently exists. The existing single-high-dose I-131-MIBG radiotherapy (444 MBq/kg) has been shown to have some benefits for patients with metastatic NETs. However, this protocol increases adverse effects and requires alternative therapeutic approaches. Therefore, the aim of this study was to evaluate the effects of repeated I-131-MIBG therapy on tumor size and tumor metabolic response in patients with metastatic NETs. Methods: Eleven patients with metastatic NETs (aged 49.2 +/- 16.3 y) prospectively received repeated 5,550-MBq doses of I-131-MIBG therapy at 6-mo intervals. In total, 31 treatments were performed. The mean number of treatments was 2.8 0.4, and the cumulative I-131-MIBG dose was 15,640.9 + 2,245.1 MBq (286.01 MBq/kg). Tumor response was observed by CT and 18F-FDG PET or by F-18-FDG PET/CT before and 3-6 mo after the final I-131-MIBG treatment. Results: On the basis of the CT findings with RECIST, 3 pa tients showed a partial response and 6 patients showed stable disease. The remaining 2 patients showed progressive disease. Al though there were 2 progressive-disease patients, analysis of all patients showed no increase in summed length diameter (median, 228.7 mm [interquartile range (10R), 37.0-336.0 mm] to 171.0 mm [IQR, 38.0-270.0 mm]; P = 0.563). In tumor region-based analysis with par tial-response and stable-disease patients (n = 9), I-131-MIBG therapy significantly reduced tumor diameter (79 lesions; median, 16 mm [IQR, 12-22 mm] to 11 mm [10R, 6-16 mm]; P < 0.001). Among 5 patients with hypertension, there was a strong trend toward systolic blood pressure reduction (P = 0.058), and diastolic blood pressure was significantly reduced (P = 0.006). Conclusion: Eighty-two per

A 66-year-old man was referred to our hospital for an incidentally detected 40-mm mass located at the inter-aortocaval area around the renal hilum. Positron emission tomography CT revealed high accumulation (SUVmax 12.382) without distant metastasis. Bilateral testes were normal by ultrasonography and physical examination, but the serum AFP level was increased to 1161 ng/mL. The pathology based on trans-duodenal needle biopsy demonstrated a yolk sac tumor; therefore, we diagnosed him with retroperitoneal primary germ cell tumor. Due to old age, the potential toxicity of systemic chemotherapy, and no significant signs of invasion to adjacent organs, we performed surgical resection. Although the AFP level decreased to 13.2 ng/mL postoperatively, it increased to 553 ng/mL 2 months after surgery without clinical recurrence on imaging studies. Four cycles of a VIP regimen (VP-16, ifosfamide, and CDDP) were performed, and the AFP level normalized to 2.4 ng/mL. The patient is now disease-free 1 year and 6 months after surgery.

Objectives: This study investigated the relapse pattern and oncologic outcomes after laparoscopic nephroureterectomy with template-based lymph node dissection (LND) in patients with clinically node-negative (cN0) upper urinary tract urothelial carcinoma. The frequency of lymph node metastasis, including micrometastases, was also evaluated. Methods and materials: A total of 105 patients with cTa-3N0M0 upper urinary tract urothelial carcinoma were analyzed, all of whom underwent regional LND during laparoscopic nephroureterectomy. Of those patients, 96 (91%) underwent complete LND in accordance with an anatomical template-based rule. We collected patient characteristics, pathological data, and follow-up data from medical charts. Micrometastases were assessed by pan-cytokeratin immunohistochemistry. Nonurothelial recurrence-free survival and cancer-specific survival were estimated using the Kaplan-Meier method. Results: The median number of lymph nodes removed was 12 (range, 1-59). Lymph node metastasis was identified by routine pathological examination in 7 (7/105, 6.7%) patients. Pan-cytokeratin immunohistochemistry revealed micrometastases in 5 additional patients (pNmicro +: 5/105, 4.8%). Nonurothelial disease recurrence was observed in 21 (20%) patients at a median of 10 months (range: 1- 33) after surgery. Distant metastasis was dominant (15/105, 14.3%), followed by locoregional recurrence (5/105, 4.8%) and both (1/105, 0.95%). The 5-year nonurothelial recurrence-free survival rates were 84.8% for pN0, 53.3% for pNmicro+, and 19.1% for pN+ (3-sample log-rank test, P < 0.0001). The 5-year cancer-specific survival rates were 95.0% for pN0, 53.3% for pNmicro+, and 23.8% for pN+ (P < 0.0001). Conclusions: Our observation showed that template-based LND could contribute to precise disease staging and better local disease control probably by eliminating nodal disease, compared with previous studies. The survival impact and ideal management of pNmicro+ disease shou

Objective To clarify the prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients treated by systemic chemotherapy. Methods Of the 228 metastatic urothelial carcinoma patients treated with systemic chemotherapy, 97 received radiotherapy mainly to metastatic sites. In patients for whom the purpose of radiotherapy was not specified, more than 50 Gy irradiation was considered to be for disease consolidation for survival analysis, while less than 50 Gy was categorized as palliation. According to the Kaplan-Meier method, we analysed overall survival from the initiation of treatment for metastatic urothelial carcinoma until death or the last follow-up, using the log-rank test to assess the significance of differences. The Cox model was applied for prognostic factor analysis. Results Overall, there was no significant difference in survival between patients with and those without radiotherapy (P = 0.1532). When analysing the patients undergoing consolidative radiotherapy separately, these 25 patients showed significantly longer survival than the 72 patients with palliative radiotherapy (P = 0.0047), with a 3-year overall survival of 43.3%. Of the present cohort, 22 underwent metastasectomy for disease consolidation, and there was no overlapping case between the metastasectomy cohort and cohort receiving consolidative radiotherapy. After controlling for four independent prognostic factors (sex, performance status, haemoglobin level and number of organs with metastasis) in our previous study, radiotherapy for disease consolidation showed a marginal value (hazard ratio = 0.666, P = 0.0966), while metastasectomy remained significant (hazard ratio = 0.358, P = 0.0006). Conclusions In the selected patients, long-term disease control could be achieved after consolidative radiotherapy for metastatic urothelial carcinoma disease. Our observations suggest that local ablative therapy (surgery or radiotherapy) could facilitate long-term disease control. Howev

Objectives To develop a wet laboratory training model for learning core laparoscopic surgical skills and evaluating learners' competency level outside the operating room. Methods Participants completed three tasks (task 1: tissue dissection around the aorta; task 2: tissue dissection and division of the renal artery; task 3: renal parenchymal closure). Each performance was video recorded and subsequently evaluated by two experts, according to the Global Operative Assessment of Laparoscopic Skills and task-specific metrics that we developed (Assessment Sheet of Laparoscopic Skills in Wet Lab score). Mean scores were used for analyses. The subjective mental workload was also assessed (NASA Task Load Index). Results The 54 participants included 32 urologists, eight young trainees and 14 medical students. A total of 13 participants were categorized as experts (>= 50 laparoscopic surgeries), eight as intermediates (10-49) and 33 as novices (0-9). There were significant differences in the Global Operative Assessment of Laparoscopic Skills and Assessment Sheet of Laparoscopic Skills in Wet Lab scores among the three groups in all three tasks. Higher NASA Task Load Index scores were observed in novices, and there were significant differences in tasks 1 (Kruskal-Wallis test,P = 0.0004) and 2 (P = 0.0002), and marginal differences in task 3 (P = 0.0745) among the three groups. Conclusions Our training model has good construct validity, and differences in the NASA Task Load Index score reflect previous laparoscopic surgical experiences. Our findings show the ability to assess both laparoscopic surgical skills and mental workloads, which could help educators comprehend trainees' level outside the operating room. Given the decreasing opportunity to carry out pure laparoscopic surgeries because of the dissemination of robotic surgery, especially in urology, our model can offer practical training opportunities.

Objective: Bladder-preserving trimodal therapy is recognized as a promising alternative treatment for muscle-invasive bladder cancer. We report the updated outcomes of muscle-invasive bladder cancer patients that were treated using our treatment protocol, which involves radiotherapy delivered with a real-time tumor-tracking radiotherapy system. Methods: Thirty-eight patients who were diagnosed with T2-T4N0M0 bladder cancer between 1998 and 2016 and had clinically inoperable disease or refused to undergo surgery were enrolled. The treatment protocol included maximal transurethral resection followed by whole-bladder radiotherapy (40 Gy). Concurrent nedaplatin-based chemotherapy was administered to patients with adequate renal function. At the time of the first evaluation (via transurethral resection of the tumor bed), fiducial markers were endoscopically inserted into the bladder wall around the tumor. A boost of 25 Gy was administered using the real-time tumor-tracking radiotherapy system. The second evaluation (via transurethral resection of the tumor bed) was performed 6 months after the start of treatment. The Kaplan-Meier method and Cox hazards analysis were used to analyze overall survival and cancer-specific survival. Results: The median duration of the follow-up period was 28 months (range: 3-161 months). The 5- and 10-year overall survival rates were 54.9 and 41.2%, respectively. Twenty-five (65.8%) and twenty (74.1%) patients had achieved complete responses to chemoradiation at the first and second evaluations, respectively. In univariate and multivariate analyses, performance status was found to be significantly associated with overall survival [P = 0.03, hazard ratio: 3.48, 95% confidence interval: 1.15-10.6] and cancer-specific survival [P = 0.02, hazard ratio: 4.57, 95% confidence interval: 1.32-16.9], and sex was shown to be significantly associated with cancer-specific survival [P = 0.03, hazard ratio: 3.07, 95% confidence interval: 1.09-8.30]. Conclus

Background: Virtual reality simulators allow trainees to perform repeated practice and provide objective dexterity metrics regarding their performance, which means that virtual reality-based surgical training is becoming a vital part of initial learning of basic laparoscopic surgical skills. However, its educational role in learning advanced procedures remains undetermined. We evaluated the validity of the laparoscopic radical nephrectomy module of the LapVision virtual reality simulator. Methods: Urologists, medical students, and a junior resident voluntarily participated in the present study, and they performed training with a laparoscopic left radical nephrectomy module. For construct validation, dexterity metrics calculated in the simulator and the mean score of Global Operative Assessment of Laparoscopic Skills evaluated by 2 experts' video review were compared according to the certification of Japanese Endoscopic Surgical Skill Qualification or previous surgical experience. Results: Ten experts (>= 50 laparoscopic surgeries), 9 intermediates (11-49), and 14 novices (0-10) voluntarily participated in the present study. Regarding the construct validity, there was a significant difference in the total number of errors, blood loss, and Global Operative Assessment of Laparoscopic Skills score among the groups for both the Endoscopic Surgical Skill Qualification status and previous surgical experience. Conclusion: The present study demonstrated good construct validity for the LapVision nephrectomy module. Furthermore, global skill assessment was possible by experts' reviews, which indicates the usefulness of the virtual reality procedural module as a skill assessment tool. Virtual reality-based procedural simulation has marked potential to become a vital part of integrated laparoscopic training programs. (C) 2019 The Authors. Published by Elsevier Inc.

Background Difficult surgical procedures may result in a higher mental workload, leading to increased fatigue and subsequent errors. This study was aimed to investigate the effect of repeated simulation training in ureterorenoscopy in a high-fidelity setting on the performance and mental workload of novice operators. Methods Medical students voluntarily participated in the present simulation study. After a didactic and video-based lecture, they underwent simulation training involving a renal stone case, including a rigid cystoscope component (task 1, performing a WHO checklist, assembling a scope, and insertion of a guide-wire and an access sheath after examining the bladder) and a flexible ureterorenoscope component (task 2, retrieving a stone located in the upper calyx using a basket after inspecting the upper, middle, and lower calyx). Training was performed in a mock operating theater. Technical skills were assessed by one author (an experienced urologist) onsite using an Objective Structured Assessment of Technical Skills (OSATS) score at each training session. The mental workload was subjectively evaluated by the National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire after each training session. Results Seventeen students completed a minimum of 6 training sessions (male: female = 10: 7, median age of 22) over a median of 21 days (range, 10-32). In both tasks 1 and 2, the OSATS score improved over the 6 sessions with evidence of plateauing (MANOVA model, task 1: p < 0.0001, task 2: p < 0.0001). In contrast, the NASA-TLX score persistently decreased without plateauing (task 1: p = 0.0005, task 2: p = 0.0028). Conclusions Under repeated simulation training in ureterorenoscopy in a high-fidelity setting, participants showed a continual decrease of the mental workload, while the improvement of technical skills reached a plateau over the 6 sessions. Our study showed the important benefit of simulation training to reduce the ment

Objective: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). Methods: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. Results: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. Conclusions: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

Objectives: The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Methods: Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. Results: The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. Conclusions: The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

Objective: To assess the number of lymph nodes removed as a surrogate marker of the extent of lymph node dissection, and compare survival outcomes between laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) in patients undergoing standardized lymph node dissection. Methods: We retrospectively analyzed the data of 214 cTanyN0M0 patients undergoing radical NU with regional lymph node dissection according to the tumor location. The Kaplan-Meier method and Cox hazards model were utilized for survival analyses, including recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Results: A total of 114 patients underwent LRNU and 100 underwent ORNU. There was no significant difference in the pT stage, pN stage, or tumor grade, but distal ureteral tumors were more frequent in the LRNU group. The number of lymph nodes removed did not differ between the two groups [LRNU: 12 (median), ORNU: 11.5, P = 0.3852]. Lymph node metastasis was pathologically identified in 19 patients (8.9%). The 5-year RFS (ORNU: 71.7%, LRNU: 74%, P = 0.7829), CSS (77.8 and, 80%, P = 0.8441) and OS (72.8, and 75.9%, P = 0.3456) did not differ between the two groups. In the sub-analysis of pT3/4 patients (n = 83), there were no significant differences in RFS, CSS, or OS between the two groups, although Kaplan-Meier survival curves were slightly better for those receiving ORNU. In the multivariate model, LRNU was not significantly correlated with a poorer RFS, CSS or OS. Conclusion: Our data support the feasibility of lymph node dissection with a laparoscopic approach and the equivalent oncological outcome of LRNU compared with ORNU when regional lymph node dissection is performed. However, LRNU should be performed after careful patient selection for advanced disease.

Background: Current adaptive and dose escalating radiotherapy for muscle invasive bladder cancer requires knowledge of both inter-fractional and intra-fractional motion of the bladder wall involved. The purpose of this study is to characterize inter- and intra-fractional movement of the partial bladder wall using implanted fiducial markers and a real-time tumor-tracking radiotherapy system. Methods: Two hundred fifty one sessions with 29 patients were analysed. After maximal transurethral bladder tumor resection and 40 Gy of whole bladder irradiation, up to six gold markers were implanted transurethrally into the bladder wall around the tumor bed and used for positional registration. We compared the systematic and random uncertainty of positions between cranial vs. caudal, left vs. right, and anterior vs. posterior tumor groups. The variance in intrafractional movement and the percentage of sessions where 3 mm and 5 mm or more of intrafractional wall movement occurring at 2, 4, 6, 8, 10, and at more than 10 min until the end of a session were determined. Results: The cranial and anterior tumor group showed larger interfractional uncertainties in the position than the opposite side tumor group in the CC and AP directions respectively, but these differences did not reach significance. Among the intrafractional uncertainty of position, the cranial and anterior tumor group showed significantly larger systematic uncertainty of position than the groups on the opposite side in the CC direction. The variance of intrafractional movement increased over time; the percentage of sessions where intrafractional wall movement was larger than 3 mm within 2 min of the start of a radiation session or larger than 5 mm within 10 min was less than 5%, but this percentage was increasing further during the session, especially in the cranial and anterior tumor group. Conclusions: More attention for intrafractional uncertainty of position is required in the treatment of cranial and anterior

Objectives: Pressure flow studies are regarded as the gold standard for evaluating both bladder outlet obstruction and detrusor contractility, but none of the current methods for evaluating bladder contraction patterns are well validated. Impaired bladder contraction results in a lower peak Watts factor and poorly sustained detrusor contractions. From this viewpoint, the maximum Watts factor and its pattern should be considered separately. To examine detrusor contraction pattern in patients after radical prostatectomy by using multiple parameters. Methods: A total of 37 patients with clinically localized prostate cancer underwent both pre- and post-radical prostatectomy urodynamic evaluations. The examined urodynamic parameters included the maximum flow rate, post-void residual volume, detrusor pressure at maximum flow, maximum Watts factor and relative volume (maximum Watts factor). Some parameters were defined from the Watts factor curve throughout micturition. Relative volume (maximum Watts factor) was the relative bladder volume at the maximum Watts factor. A normal detrusor contractility pattern involves an increase in Watts factor at the initiation followed by further gradual increases until the end of micturition. Results: Maximum flow rate increased significantly after radical prostatectomy (pre: 13.0 ± 6.5, post: 17.3 ± 7.7 mL/min; P < 0.01), whereas detrusor pressure at maximum flow and post-void residual volume decreased significantly (pre: 49.6 ± 21.6 and 31.4 ± 18.2 cmH2O; post: 48.6 ± 66.1 and 10.1 ± 28.5 mL; P < 0.05). Maximum Watts factor did not change significantly after radical prostatectomy (pre: 10.5 ± 3.1 W/m2, post: 11.0 ± 3.2 W/m2), but relative volume (maximum Watts factor) decreased significantly (pre: 0.48 ± 0.3, post: 0.20 ± 0.20; P < 0.001). Maximum Watts factor represents the maximum power of bladder contraction at a particular point in time, whereas relative volume (maximum Watts factor) can be used to detect changes in detrus

Objective: To determine the characteristics of 90-day morbidity and mortality after radical cystectomy in Japanese octogenarians. Methods: A retrospective multi-institutional study. We reviewed the records of 834 patients treated by open radical cystectomy between 1997 and 2010. All complications within 90 days after surgery were sorted into the 11 categories proposed by the Memorial Sloan-Kettering Cancer Center and graded according to the modified Clavien-Dindo system. We compared the characteristics of complications between >= 80-year (n = 86) and < 80-year (n = 748) groups. Multivariate regression models were used to determine the predictors of complications. Results: American Society of Anesthesiologists score III-IV was more frequent (14% vs. 6%, respectively, P < 0.0001), and ureterocutaneostomy was more frequently performed (30% vs. 21%, respectively, P = 0.0148) in the >= 80-year group compared with < 80-year group. There were no significant differences in the rates of any complication, major (Grade 3-5) complication, or 90-day mortality between the two groups (>= 80-year group: 70%, 21%, 3.5%, respectively, < 80-year group: 68%, 22%, 2%, respectively). The >= 80-year group had fewer genitourinary complications (7% vs. 16%, respectively, P = 0.0131). Multivariate regression analyses revealed that bowel-using urinary diversion (P = 0.0031) and the operative time (P = 0.0269) were significant predictors of any grade of complications, and a male sex (P = 0.0167), annual cystectomy volume (P = 0.0284) and prior cardiovascular comorbidity (P = 0.0034) were significant predictors of major complications. Conclusions: In our experience, radical cystectomy in Japanese octogenarians caused similar perioperative comorbidities. Old age as a single criterion should not be used to abandon radical cystectomy; careful preoperative assessment is mandatory.

Background: Due to variations in location and size, laparoscopic surgery for paraaortic or paracaval neurogenic tumors is challenging. We evaluated the surgical outcomes, as well as surgical tips and tricks. Methods: Between 2000 and 2015, 25 procedures were performed in 24 patients. One patient underwent second surgery due to the recurrence of paraganglioma. Data were collected on the tumor diameter, tumor location, perioperative outcomes, pathology, and last known disease status. Regarding the operative procedures, we reviewed the operative charts or videos to identify surgical tips and tricks. Results: The median tumor diameter was 5.0 cm (range, 1.5-10). The tumor location was suprahilar in 10, hilar in 6, and infrahilar in 9. Regarding the approach, a transperitoneal approach was selected in 24 cases and retroperitoneal approach in 1. The median operative time and blood loss were 208 minutes (range, 73-513) and 10 mL (range, 0-1,020), respectively. No patient required blood transfusion or conversion to open surgery. Pathological examination revealed paraganglioma in 12, ganglioneuroma in 7, and schwannoma in 6. At the last follow-up, 23 patients were free of disease, while one patient developed metastatic multiple recurrence of paraganglioma 54 months after the second laparoscopic surgery. A review of the surgical records revealed several tips and tricks, including taping the vena cava/ renal vein (n=2) being helpful for detaching a retrocaval tumor from these great vessels, or rotating the kidney to provide a favorable operative view of tumors behind the renal hilum (n=2). In recent cases, 3D-CT was helpful for preoperative planning. Conclusion: Laparoscopic resection of paraaortic or paracaval neurogenic tumors is feasible in experienced hands. Surgeons should be familiar with detaching maneuvers around great vessels and the mobilization of adjacent organs. Careful preoperative planning is mandatory.

A multicenter cooperative study was conducted to clarify the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular-targeted therapy and the clinical usefulness of the Japanese metastatic renal cancer (JMRC) prognostic classification. Of 389 consecutive patients for whom treatment was started between 2008 and 2010 at 23 hospitals in Japan, 357 patients who received vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) or cytokine as initial systemic therapy were the subject of the present study. Patients were classified into three prognostic groups according to the JMRC prognostic classification. The endpoints were progression-free survival (PFS) and overall survival (OS) after the start of the initial treatment. The median PFS and OS for the entire cohort of 357 patients were 9.1 and 27.2months, respectively. VEGFR-TKI were selected for patients with multiple organ metastases, those with liver metastasis, and those with bone metastasis. The median PFS and OS were 11.0 and 23.2months and 5.4 and 38.2months in the VEGFR-TKI group and the cytokines group, respectively. The JMRC prognostic classification was useful as a prognostic model for PFS and OS (c-indexes: 0.613 and 0.630 in patients who initially received VEGFR-TKI and 0.647 and 0.642 in patients who received cytokines, respectively). The present study showed for the first time the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular-targeted therapy. The JMRC prognostic classification may be clinically useful as a prognostic model.

We have previously reported that an adaptor protein CRK, including CRK-I and CRK-II, plays essential roles in the malignant potential of various aggressive human cancers, suggesting the validity of targeting CRK in molecular targeted therapy of a wide range of cancers. Nevertheless, the role of CRK in human bladder cancer with marked invasion, characterized by distant metastasis and poor prognosis, remains obscure. In the present study, immunohistochemistry indicated a striking enhancement of CRK-I/-II, but not CRK-like, in human bladder cancer tissues compared to normal urothelium. We established CRK-knockdown bladder cancer cells using 5637 and UM-UC-3, which showed a significant decline in cell migration, invasion, and proliferation. It is noteworthy that an elimination of CRK conferred suppressed phosphorylation of c-Met and the downstream scaffold protein Gab1 in a hepatocyte growth factor-dependent and -independent manner. In epithelial-mesenchymal transition-related molecules, E-cadherin was upregulated by CRK elimination, whereas N-cadherin, vimentin, and Zeb1 were downregulated. A similar effect was observed following treatment with c-Met inhibitor SU11274. Depletion of CRK significantly decreased cell proliferation of 5637 and UM-UC-3, consistent with reduced activity of ERK. An orthotopic xenograft model with bioluminescent imaging revealed that CRK knockdown significantly attenuated not only tumor volume but also the number of circulating tumor cells, resulted in a complete abrogation of metastasis. Taken together, this evidence uncovered essential roles of CRK in invasive bladder cancer through the hepatocyte growth factor/c-Met/CRK feedback loop for epithelial-mesenchymal transition induction. Thus, CRK might be a potent molecular target in bladder cancer, particularly for preventing metastasis, leading to the resolution of clinically longstanding critical issues.

Objective: The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time.We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique. Methods: Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than +2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated. Results: Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65%. Conclusions: Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients’ quality of life.

Background: We prospectively assessed the utility of intensity-modulated radiation therapy (IMRT) with urethral dose reduction and a small margin between the clinical target volume (CTV) and the planning target volume (PTV) for patients with localized prostate cancer. Methods: The study population was 110 patients in low- (14.5%), intermediate- (41.8%), and high-risk (43.6%) categories. Three gold fiducial markers were inserted into the prostate. A soft guide-wire was used to identify the urethra when computed tomography (CT) scan for treatment planning was performed. A dose constraint of V70 < 10% was applied to the urethral region. Margins between the CTV-PTV were set at 3 mm in all directions. Patients were treated with 70 Gy IMRT in 30 fractions (D95 of PTV) over 7.5 weeks. The patient couch was adjusted to keep the gold markers within 2.0 mm from their planned positions with the use of frequent on-line verification. Results: The median follow-up period was 31.3 (3.2 to 82.1) months. The biochemical relapse-free survival (bRFS) rates at 3 years were 100%, 93.8% and 89.5% for the low-, intermediate-, and high-risk patients, respectively. The incidences of acute adverse events (AEs) were 45.5% and 0.9% for grades 1 and 2, respectively. The late AEs were grade 1 cystitis in 10.0% of the patients, rectal bleeding in 7.3%, and urinary urgency in 6.4%. Only three patients (2.7%) developed grade 2 late AEs. Conclusions: On-line image guidance with precise correction of the table position during radiotherapy achieved one of the lowest AEs rates with a bRFS equal to the highest in the literature.

Purpose: We determined prognostic factors associated with prolonged survival after metastasectomy for urothelial carcinoma. Materials and Methods: A total of 42 patients who underwent resection of urothelial carcinoma metastases with curative intent at 4 Japanese university hospitals were included in analysis. Of the patients 41 of 42 underwent systemic chemotherapy before and/or after metastasectomy. Overall survival was analyzed using the Kaplan-Meier method. The relationship between clinical characteristics and survival was analyzed using the log rank test. Results: Metastasectomy included lymph node dissection in 20 cases, pulmonary resection in 12, pelvic exenteration in 3, resection of local recurrence in 2, resection of subcutaneous metastasis in 2, liver resection in 1 and other in 2. Median overall survival was 29 months (IQR 19-80) from the initiation of treatment for metastases and 26 months (IQR 11-90) from metastasectomy. The overall 5-year survival rate after metastasectomy was 31%. On univariate analysis patients treated with metastasectomy for a solitary lung or solitary lymph node metastasis had significantly longer survival than the others who underwent metastasectomy (81 vs 19 months, log rank test p = 0.0296). Conclusions: Long-term cancer control could be achieved in a subgroup of patients who undergo metastasectomy, especially those with a solitary lung or solitary lymph node metastasis.