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Background: This study aimed to investigate factors, including the degree of hydronephrosis, that may be associated with decreased renal function after radical nephroureterectomy (RNU). Methods: This study included 252 patients who underwent laparoscopic RNU with an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 in three institutions. We assessed the association between hydronephrosis grade and perioperative renal function and performed a stepwise multivariate linear regression analysis to identify factors associated with postoperative eGFR. Patients with preoperative eGFR ≥ 50 ml/min/1.73 m2 were divided into a training set and an independent external validation set to develop a predictive model for postoperative renal function. Results: The median preoperative and postoperative eGFR were 61.1 and 46.4 ml/min/1.73 m2, respectively. The eGFR preservation rates were 66.9%, 66.6%, 88.1%, and 100.0% in groups without, with mild, moderate, and severe hydronephrosis, respectively, and this difference was statistically significant (p < 0.001). Multivariate analysis revealed that factors predictive of postoperative eGFR included sex, preoperative eGFR, clinical T stage (cT3–4), and the presence of moderate or severe hydronephrosis. Our predictive model, based on these factors, positively correlated with actual postoperative renal function, and the similarity in categories with or without renal function insufficiency between predicted and actual postoperative renal functions was 78% in both training and validation sets. Conclusion: Moderate or severe hydronephrosis is associated with a modest postoperative decline in renal function, while mild hydronephrosis is not. Our predictive model may be useful in predicting postoperative renal function insufficiency and guiding decision-making for perioperative medical treatment. [ABSTRACT FROM AUTHOR]

Abstract We experienced an 82-year-old man with transitional cell carcinoma in an ectopic ureter draining into the prostatic urethra. Carcinoma arising from an ectopic ureter is very rare and a differential diagnosis is difficult. To our knowledge, our case is the third male case reported in the literature. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to identify preoperative risk factors and create a risk classification for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy in a multi‐institutional cohort. Methods: We retrospectively analyzed 283 patients who had undergone laparoscopic radical nephroureterectomy for nonmetastatic upper tract urothelial cancer between March 2002 and March 2020. The cumulative incidence of intravesical recurrence for 224 patients without previous or concomitant bladder cancer was examined using multivariate Fine‐Gray competing risks proportional hazards models. A risk stratification model was created to predict subsequent patient outcomes based on the results. Results: The median follow‐up duration was 33.3 months, and 71 (31.7%) patients experienced intravesical recurrence. The estimated cumulative incidence of intravesical recurrence at one and 5 years was 23.5% and 36.4%, respectively. In multivariate analysis, the presence of ureter tumors and multiple tumors were shown to be independently significant predictive factors for intravesical recurrence. Based on the results, we classified patients into three risk groups. The cumulative incidence rates of intravesical recurrence within 5 years after surgery were 24.4%, 42.5%, and 66.7% in the low‐, intermediate‐, and high‐risk groups, respectively. Conclusions: We identified risk factors and created a risk classification model for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy. Based on this model, an individualized surveillance protocol or adjuvant therapy could be provided. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the recurrence patterns and the atypical oncologic failure (AOF) defined as the presence of atypical recurrences, such as retroperitoneal carcinomatosis or port-site recurrence, after laparoscopic radical nephroureterectomy (LRNU). Methods: LRNU performed at three institutions were included in this retrospective study. The primary endpoints were the first recurrence site and recurrence-free survival. The recurrence sites were classified as atypical recurrences, such as retroperitoneal carcinomatosis or port-site recurrence, as well as distant, local, and intravesical. The Kaplan–Meier curves were obtained to elucidate the time until recurrence and survival. Results: A total of 283 patients were included in the final analysis. Postoperative pathology was T3 or higher in 112 (40%) patients. The median follow-up period was 31 months, and the 3-year recurrence-free, cancer-specific, and overall survival rates were 69.6%, 78.1%, and 72.0%, respectively. The first recurrence sites involved distant, local, atypical, and intravesical recurrences in 51 (18%), 36 (13%), 14 (5%), and 94 (33%) patients, respectively. Of the 14 patients with AOF, 12 had pathologically locally advanced tumors, but seven patients had a preoperative diagnosis of clinical stage T2 or less. Conclusion: A small number of AOF cases were found after LRNU for patients with upper tract urothelial carcinoma. Careful patient selection is critical for AOF prevention. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the incidence of postoperative complications occurring within 30 days of surgery between octogenarians and younger patients and identify preoperative risk factors for the incidence of postoperative complications. Moreover, we also compared the oncological outcomes between octogenarians and younger patients. Methods: This retrospective study included 283 patients who underwent laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma from 2002 to 2020. The patients were divided into octogenarians and younger patients (age: < 80 years), and their clinical characteristics, perioperative parameters, and postoperative complications were evaluated. The predictors of postoperative complications were evaluated using logistic regression models. Recurrence-free survival, cancer-specific survival, and overall survival were measured using the Kaplan–Meier method. Results: Twelve (17.1%) octogenarians and 40 (18.7%) younger patients had postoperative complications. No significant difference in the incidence of postoperative complications was observed between octogenarians and younger patients (p = 0.14). A high body mass index was a significant risk factor for complications (p = 0.03). The 5-year recurrence-free survival, cancer-specific survival, and overall survival rates for octogenarians and younger patients were 72% and 64% (p = 0.31), 76% and 63% (p = 0.63), and 43% and 63% (p = 0.06), respectively. Conclusion: Laparoscopic radical nephroureterectomy can be performed in octogenarians with complication rates similar to those in younger patients. Similarly, the outcomes of laparoscopic radical nephroureterectomy for oncological control do not differ significantly between octogenarians and younger patients. This procedure is safe and effective for selected octogenarians. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the oncological outcomes and recurrence patterns in clinically node-negative patients with renal pelvic and/or upper or middle ureteral tumors after template-based retroperitoneal lymph node dissection (RPLND) in conjunction with retroperitoneal laparoscopic radical nephroureterectomy (LRNU). Materials and Methods: A total of 283 patients who received LRNU with and without RPLND at three Japanese institutions were enrolled. The template for RPLND included the renal hilar and para-aortic lymph nodes (LNs) (left side) and renal hilar, paracaval, retrocaval, and intra-aortocaval LNs (right side). The LNs and kidneys were removed en bloc. The primary endpoint was set as recurrence-free survival. All RPLND cases were matched one-to-one with no-RPLND cases using a propensity score matching approach, and 47 matched pairs were included in analyses. Results: Compared with the control group, significant differences were not observed in the RPLND group in terms of operation time, blood loss, postoperative complication rate, and pathological findings. The estimated 5-year recurrence-free survival was significantly higher in the RPLND group (86.8%) compared with the group without RPLND (64.2%) (p = 0.014). The estimated 5-year cancer-specific survival showed a similar tendency; however, it did not reach a statistically significant difference (87.5% vs 71.3%, respectively; p = 0.168). As for the first recurrence site, the RPLND group showed a lower incidence of distant recurrence, while no significant difference was observed in the rate of regional LN recurrence. Conclusions: This study suggests that template-based RPLND in conjunction with retroperitoneal LRNU efficiently improves recurrence-free survival by reducing distant recurrences. [ABSTRACT FROM AUTHOR]

Objectives: To describe the detailed perioperative complications and their management after retroperitoneal lymph node dissection with retroperitoneal laparoscopic radical nephroureterectomy for patients with upper tract urothelial carcinoma at three institutions. Methods: Retroperitoneal lymph node dissection was performed on patients with upper tract urothelial carcinoma located at the pelvis and/or upper or middle ureter, and its template included the renal hilar and para‐aortic lymph nodes (left side) and the renal hilar, paracaval, retrocaval, and intra‐aortocaval lymph nodes (right side). The lymph nodes and kidneys were removed en bloc. The primary endpoint was postoperative complication rates, and the secondary endpoints were intraoperative findings and chylous leakage management. The associations of retroperitoneal lymph node dissection with postoperative complications were examined using logistic regression with propensity score techniques. Results: Eighty‐eight (31%) and 195 (69%) patients underwent and did not undergo retroperitoneal lymph node dissection, respectively. There was no significant difference in postoperative complications and other perioperative findings in the entire cohort, except for prolonged operation time. Retroperitoneal lymph node dissection was not statistically significantly associated with total and serious complications in propensity score analyses. Postoperative chylous leakage could be conservatively managed even though it is common in patients with retroperitoneal lymph node dissection (14/88 (16%)). The incidence of chylous leakage was significantly lower in patients whose lymphatic vessels were meticulously clipped completely during retroperitoneal lymph node dissection (5.3% vs 24%; P = 0.017). Conclusion: There was no association between retroperitoneal lymph node dissection with laparoscopic radical nephroureterectomy and postoperative complications. However, chylous leakage is often observed after retroperitoneal lymph node dissection and careful management is highly required. The use of clips during retroperitoneal lymph node dissection is recommended to minimize chylous leakage risk. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effect of optimal neoadjuvant chemotherapy of at least three cycles of cisplatin‐based regimen on oncological outcomes of clinical stage T3 or higher bladder cancer treated with laparoscopic radical cystectomy. Methods: Laparoscopic radical cystectomies carried out at 10 institutions were included in this retrospective study. The outcomes of patients who received optimal neoadjuvant chemotherapy and those who did not receive neoadjuvant chemotherapy were compared using propensity score matching in clinical stage T3–4 or T2 cohorts, separately. Results: Of the 455 patients screened, matched pairs of 54 patients in the clinical T3–4 cohort and 68 patients in the clinical T2 cohort were finally analyzed. In the cT3–4 cohort, the 5‐year overall survival (78% vs 41%; P = 0.014), cancer‐specific survival (81% vs 44%; P = 0.008) and recurrence‐free survival (71% vs 53%; P = 0.049) were significantly higher in the optimal neoadjuvant chemotherapy group than in the no neoadjuvant chemotherapy group; no significant survival difference was shown between the two groups in the cT2 cohort. In the cT3–4 cohort, the incidence of local recurrence (4% vs 26%; P = 0.025) and abdominal or intrapelvic recurrence, including peritoneal carcinomatosis (7% vs 30%; P = 0.038), was significantly lower in the optimal neoadjuvant chemotherapy group. Conclusions: Administration of optimal neoadjuvant chemotherapy has a significant survival benefit. It decreases the incidence of local and atypical recurrence patterns in patients with clinical stage T3 or higher locally advanced bladder cancer undergoing laparoscopic radical cystectomy. [ABSTRACT FROM AUTHOR]

Objectives: To compare the perioperative and oncological outcomes of pure laparoscopic intracorporeal ileal conduit urinary diversion versus extracorporeal ileal conduit urinary diversion after laparoscopic radical cystectomy for bladder cancer in a multicenter cohort in Japan. Method: A total of 455 patients who underwent laparoscopic radical cystectomy carried out at 10 institutions were included in this retrospective study. The perioperative data of the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups were compared using the propensity score matching method. The Kaplan–Meier curves were obtained to elucidate time to ureteroenteric stricture, reoperation, recurrence and survival. Results: In total, 72 matched pairs were evaluated for the final analysis. The median follow‐up period was 28 and 23 months in the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups, respectively. The operative time in the intracorporeal ileal conduit urinary diversion group was approximately 1 h longer than that in the extracorporeal ileal conduit urinary diversion group. The early and late postoperative complication rates were similar in both groups, except for the reduced wound‐related complication rates in the intracorporeal ileal conduit urinary diversion group. The median days to regular oral food intake were 4 and 5 days in the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups, respectively (P = 0.014). No significant difference was noted in the occurrence of ureteroenteric strictures and reoperation rate. Furthermore, recurrence‐free, cancer‐specific, and overall survival rates and recurrence patterns did not significantly differ. Conclusions: Laparoscopic intracorporeal ileal conduit urinary diversion is a safe, feasible and reproducible procedure with similar postoperative complication rates, ureteroenteric stricture rate and oncological outcomes when compared with extracorporeal ileal conduit urinary diversion, but faster postoperative bowel recovery and decreased wound‐related complication rates. [ABSTRACT FROM AUTHOR]

Objective: To investigate oncological outcomes and recurrence patterns after laparoscopic radical cystectomy for bladder cancer in a Japanese multicenter cohort, and to explore the risk factors associated with recurrences due to tumor dissemination. Method: Laparoscopic radical cystectomies carried out at 10 institutions were included in this retrospective study. Multivariate analyses were carried out to identify the clinical parameters associated with overall recurrences together with specific recurrence types. Kaplan–Meier curves were created to elucidate time to recurrence and survival. Results: A total of 411 patients were included after the final analysis. Postoperative pathology was T2 or higher in 196 patients (48%), and lymph node metastasis was present in 46 patients (11%). The median follow‐up period was 23 months, and the 2‐year recurrence‐free and cancer‐specific survival rates were 71.0% and 84.7%, respectively. The recurrence sites involved distant metastasis in 75 patients (18%), local recurrence in 52 patients (13%) and urinary tract recurrence in eight patients (2%). When local recurrence at the cystectomy bed (28 patients; 7%) and abdominal recurrence including peritoneal carcinomatosis or port site recurrence (17 patients; 4%), which might be caused by tumor dissemination, were combined into a single group, prolonged surgical time was a significant risk factor, in addition to high pathological stage (T3–4 and/or positive lymph nodes), positive surgical margins, and variant histology by both univariate and multivariate analyses. Conclusions: Our study findings suggest that recurrences after laparoscopic radical cystectomy might be caused by tumor dissemination, and attention should be paid to avoid prolonged surgical time in laparoscopic radical cystectomy. [ABSTRACT FROM AUTHOR]

The article discusses modified technique to facilitate ureteroenteric anastomosis during pure laparoscopic intracorporeal ileal conduit (IC) after laparoscopic radical cystectomy (LRC). It is noted that pure laparoscopic intracorporeal IC is a safe and feasible procedure to decrease technical difficulty of ureteroenteric anastomosis.

To prospectively compare the prevention of tumour recurrence by four intravesical adjuvant administration protocols, and thus elucidate the efficacy of early and high total dose instillations of epirubicin to prevent superficial bladder tumour recurrence after transurethral resection of bladder tumour (TURBT). In all, 69 patients with Ta/T1 bladder cancer were randomly assigned to four intravesical administration protocols: A, delayed instillation (first instillation 7 days after TURBT) and low-dose (30 mg once every 2 weeks, six times): B, early instillation (three instillations before 7 days after TURBT) and low-dose; C, delayed and high-dose (30 mg once weekly 12 times) instillation; D, early and high-dose. The influence of the instillation protocols and tumour characteristics on the probability of recurrence-free survival was examined using Kaplan-Meier analysis and a Cox regression hazard model. The early-instillation and high-dose groups had relatively lower recurrence rates after 6 months (A, 30%; B, 25%; C, one of 12; and D, none) and 1 year (50%, 35%, four of nine and one of eight, respectively). Patients who received 360 mg epirubicin (C and D) had a significantly better recurrence-free survival than those receiving 180 mg (A and B; P = 0.012). Preoperative urine cytology and tumour multiplicity were significantly associated with recurrence. However, multivariate analysis of the risk of recurrence using a Cox proportional hazard model showed that urine cytology (hazard ratio 3.11, 95% confidence interval 1.08–8.94, P = 0.04) and total dose (0.32, 0.11–0.92, P = 0.03) were independent prognostic factors for recurrence. Patients who received a high-dose epirubicin instillation had a significantly lower recurrence rate but the benefit of early instillation was not confirmed, as the study group was too small. [ABSTRACT FROM AUTHOR]

Abstract Background: The circadian variation of clinical pharmacokinetics of tacrolimus in kidney transplant recipients receiving continuous intravenous administration has not been clarified. The aim of this study was to evaluate the circadian variation of this drug in continuous intravenous administration, with regard to the dosing scheme for conversion from intravenous to oral therapy. Methods: The blood concentration–time curve was studied in 10 living-related kidney transplant recipients, aged 18–51 years (mean, 36.5 years), 1 day before operation for preoperative oral administration, the third postoperative day for continuous intravenous administration and the sixth postoperative day at the conversion from intravenous to oral therapy. Results: Although the total body clearance of daytime was slightly higher than that of night-time, the intravenous tacrolimus infusion maintained an adequate therapeutic blood concentration for 24 h. There were significant differences between the preoperative and the postoperative state in the area under the curve, total body clearance and bioavailability for the oral administration. The mean absolute bioavailability was 17.7% in preoperative and 11.1% in postoperative state, respectively and a large interindividual variation was confirmed in this parameter, which was 7.0–27.2% for preoperative and 6.4–22.0% for postoperative area under the curve, respectively. Conclusion: This study proposes that intravenous administration is a safe and appropriate method to achieve the required blood concentration in patients with various tacrolimus metabolism in the early post-transplant period. As the oral tacrolimus absorption was found to be variable between preoperative and postoperative states in identical patients, the conversion dosage cannot be calculated from preoperative oral or postoperative intravenous pharmacokinetics. Frequent blood concentration monitoring is needed to ensure safe treatment. [ABSTRACT FROM AUTHOR]

Transcriptional silencing by CpG island hypermethylation of gene regulatory regions is one mechanism for inactivation of tumour suppressor genes. Chromosome 9q deletion is frequently found in transitional cell carcinoma (TCC) of the bladder and upper urinary tract and one of the putative tumour suppressor loci has been mapped to 9q32-33. A gene designated as DBCCR1 was identified in the candidate region and its mRNA expression is thought to be suppressed by hypermethylation. To understand the role of hypermethylation in TCC, we evaluated the methylation status of 20 CpG sites of the DBCCR1 5′-CpG island region in a total of 69 tumours from 45 patients, 21 normal urothelial specimens, and six bladder cancer cell lines. Aberrant hypermethylation levels were found in 36 (52%) of 69 tumours without any association with tumour grade or stage. Methylation was weakly detected in the normal urothelium in association with ageing. Although recurrent tumours tended to have higher methylation levels than the initial tumours, the methylation pattern was mostly maintained between multifocal TCCs in individual patients. The results suggest that hypermethylation of the DBCCR1 region is one of the earliest alterations in the development of TCCs and there may be an age-related hypermethylation-based field defect in normal urothelium. Methylator or methylation-resistant phenotype seems to be maintained during multifocal development or recurrence of most TCCs. Oncogene (2001) 20, 531–537. [ABSTRACT FROM AUTHOR]