Ureteroenteric strictures after cystectomy: Side-specific risk factors and radiological assessment.

Objective: To evaluate risk factors contributing to side-specific benign ureteroenteric strictures following radical cystectomy with an ileal conduit. Materials and Methods: Data obtained from patients with bladder cancer who underwent radical cystectomy with ileal conduit surgery between 2015 and 2018 were retrospectively analysed. Imaging prior to surgery was analysed, regarding calcifications in the aorta, sarcopenia and postoperatively for length of remaining left ureter. Descriptive analyses were performed on preoperative and perioperative data, comparing patients who developed unilateral left- or right-sided strictures, bilateral strictures, to those who remained free of strictures. COX regression analysis was employed to calculate crude and adjusted hazard ratio for side-specific strictures. Results: The study included 395 patients. Strictures developed in 19% (75/395) of the patients, within a median period of 9 months: 57% (43/75) unilateral left sided, 20% (15/75) unilateral right sided and 23% (17/75) bilateral. Unilateral left-sided stricture was associated with higher body mass index (p = 0.077) and hypercholesterolemia (p = 0.007). Right-sided stricture was associated with a history of prior abdominal surgery (p = 0.029) and postoperative leakage (p = 0.004). Bilateral stricture was associated with smoking (p = 0.006) and high BMI (p = 0.015). The adjusted HR comparing patients with and without previous abdominal surgery was only significantly higher for right-sided ureteroenteric strictures (HR 3.18 [95% CI: 1.11; 9.05]) compared with patients without strictures. No association was identified between strictures and preoperative aortic calcification of the abdominal aorta or sarcopenia as estimated from imaging. Conclusion: The aetiology of ureteroenteric strictures appears multifactorial. Our findings suggest that development of left-sided stricture is influenced by factors associated with metabolic syndrome, indicating a potential role of distal ureteric ischemia. On the other hand, right-sided stricture was more frequent in patients with previous abdominal surgery and postoperative leakage.

Perioperative management of upper tract urothelial carcinoma in the Nordic countries.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare malignancy, with typically only few new cases annually per urological department. Adherence to European association of urology (EAU) guidelines on UTUC in the Nordic countries is unknown. The objective of this survey was to examine the implementation of EAU guidelines, the perioperative management and organization of the treatment of UTUC in the Nordic countries. METHODS: The electronic survey was distributed to 93 hospitals in the Nordic countries performing radical nephroureterectomy (NU). The survey consisted of 57 main questions and data was collected between December 1st, 2021 and April 23rd, 2022. RESULTS: Overall response rate was 47/93 (67%) with a completion rate of 98%. Five out of the 6 examined subjects on diagnostic practice are applied by ≥ 72% of the participating centers. NU as treatment for high-risk UTUC is performed by 37/47 (79%), and 91% include a bladder cuff excision. CONCLUSIONS: Adherence to EAU guidelines is high on diagnostic practice in the Nordic countries, whereas disease management is less coherent.

Definition of Benign Ureteroenteric Anastomotic Strictures in Ileal Conduits After Radical Cystectomy: Experience From a Single Center and Previously Published Literature.

OBJECTIVE: To evaluate a cohort of patients diagnosed with benign ureteroenteric stricture (UES) after radical cystectomy with ileal conduits using a strict predefined definition of strictures. Additionally, we want to illustrate the UES debut, regarding symptoms and clinical findings. UES is a well-known long-term complication after radical cystectomy, affecting up to 20% of all patients. In the literature, different incidence rates are reported. However, these are based on various definitions of strictures. METHODS: We used strict predefined criteria to evaluate UES incidence including symptoms, timing, diagnostic methods, treatment, and outcome in all patients who underwent radical cystectomy with an ileal conduit between 2012 and 2018 at a single high-volume center. RESULTS: Of a total of 693 patients who underwent radical cystectomy with ileal conduit, we found 109 patients with 135 UES in total, corresponding to 15.7% of patients (CI: 13.2-18.6) and 10% of all included ureteroenteric anastomosis (CI: 8.5-11.6) after radical cystectomy. Median follow-up was 24months (interquartile range (IQR): 12-31), and postoperatively UES was diagnosed after a median of 6months (IQR: 3-16). A total of 56% was diagnosed with elevated creatinine. Every UES underwent a median of two (IQR: 1-2) treatment attempts and 122 UES were treated successfully. CONCLUSION: Benign UES is a significant cause of morbidity following radical cystectomy. Our findings contribute to the knowledge of timing, incidence, and recommended treatment of strictures. We argue the importance of establishing a clear gold standard when defining UES to ensure accurate reporting in future research.

DaBlaCa-17: nationwide observational study in Denmark on survival before and after implementation of neoadjuvant chemotherapy prior to cystectomy for muscle-invasive bladder cancer.

OBJECTIVE: To investigate the impact of neoadjuvant chemotherapy implementation with gemcitabine-cisplatin on survival outcomes for patients with muscle-invasive bladder cancer in Denmark. MATERIALS AND METHODS: Data were collected on all patients in Denmark undergoing radical cystectomy who were potential candidates for neoadjuvant chemotherapy from 2010 to 2015 (n = 851). A cohort before the implementation of neoadjuvant chemotherapy (Cohort 2010-12) was compared with a cohort after implementation (Cohort 2013-15). Patients in Cohort 2013-15 receiving neoadjuvant chemotherapy (+NAC, n = 213) were compared with patients in Cohort 2013-15 not receiving neoadjuvant chemotherapy (-NAC, n = 139). Pathological results after radical cystectomy and oncological outcomes were compared between the study cohorts. Overall survival, disease-free survival, and disease-specific survival were compared with Kaplan-Meier plots and with univariable and multivariable Cox regression. Kaplan-Meier estimates of overall survival were also performed separately for treating hospital and for pathological stage. RESULTS: Pathological T0 (pT0) was more frequent in patients who received neoadjuvant chemotherapy: 34% versus 18% when comparing Cohort 2013-15 with Cohort 2010-12 (p < 0.001), and 46% versus 16% in +NAC compared with -NAC (p < 0.001). Overall survival, disease-free survival, and disease-specific survival at 5 years after cystectomy were not improved in Cohort 2013-15 compared with Cohort 2010-12 with adjusted hazard ratios of 1.11 (95% confidence interval [CI]: 0.87-1.43), 1.02 (95% CI: 0.81-1.29), and 1.06 (95% CI: 0.80-1.41), respectively. CONCLUSIONS: This observational study found no improved survival in a national cohort of patients with muscle-invasive bladder cancer undergoing radical cystectomy after implementation of NAC. However, reservations should be made regarding the study design and the true effect of NAC on survival outcomes.

DaBlaCa-16: Retrosigmoid Versus Conventional Ileal Conduit in Robot-assisted Radical Cystectomy, the MOSAIC Randomized Controlled Trial-Feasibility and 90-day Postoperative Complications.

Background: Approximately 15% of patients undergoing radical cystectomy (RC) develop benign ureteroenteric strictures. Of these strictures, the majority are located in the left ureter. To lower the rate of strictures, a retrosigmoid ileal conduit has been suggested. Objective: To investigate the feasibility and safety of a retrosigmoid ileal conduit during robot-assisted RC in bladder cancer patients. Design setting and participants: This randomized controlled trial included 303 patients from all five cystectomy centers in Denmark from May 2020 to August 2022. Participants were diagnosed with bladder cancer and scheduled for robot-assisted RC with an ileal conduit. Intervention: Intervention group: a retrosigmoid ileal conduit was constructed using approximately 25 cm of the terminal ileum and tunneled behind the sigmoid where the left ureter was anastomosed from end to side. Control group: the conventional ileal conduit ad modum Bricker with individual end-to-side anastomoses. Outcome measurements and statistical analysis: Patients were analyzed by the intention-to-treat approach. Complications within 90 d were categorized using the Clavien-Dindo grading system and compared using Fisher's exact test. Wilcoxon's test was used for pre- and postoperative renal function. Results and limitations: Of the 149 patients randomized for the retrosigmoid ileal conduit (MOSAIC), a total of 137 (92%) patients received the allocated conduit. Postoperative complications were distributed equally between the two groups. The relative risk of Clavien-Dindo complications of grade ≥III was 1.12 (95% confidence interval: 0.96-1.31) in the intervention group compared with the control group. Conclusions: The retrosigmoid ileal conduit with robot-assisted RC was technically feasible. Early postoperative complications were not significantly different when comparing the two groups. Further investigation of long-term complications, including strictures, is needed. Patient summary: We compared a conventional urinary diversion with a longer conduit to prevent constriction from developing in the ureters. The new conduit is feasible and safe within the first 90 d, with no differences in postoperative complications from those of the conventional diversion.

Robot-assisted radical cystectomy with intracorporeal urinary diversion: a Danish 11-year series.

OBJECTIVES: To evaluate the oncological and perioperative outcomes from a large, single-centre, robot-assisted radical cystectomy (RARC) cohort performed with intracorporeal urinary diversion (ICUD). PATIENTS AND METHODS: Patients who underwent RARC because of bladder cancer or recurrent carcinoma in situ from June 2009 until August 2020 at Herlev and Gentofte Hospital were prospectively and consecutively included. Kaplan-Meier survival analysis was used to estimate recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). A Cox proportional hazards model was used to identify individual predictors of outcomes. Multiple logistic regression analysis was used to identify predictors of high-grade complications (Clavien-Dindo Grade ≥III). RESULTS: A total of 542 patients were included. The median (interquartile range) follow-up was 5.3 (2.73-8.06) years. In all, 78 patients (14%) were converted to open surgery; 15 (3%) during cystectomy and 63 patients (12%) were converted from ICUD to extracorporeal urinary diversion. The 5-year RFS, CSS and OS rates were 63% (95% confidence interval [CI] 59%-68%), 75% (95% CI 72%-80%) and 67% (95% CI 63%-72%), respectively. Pathological non-organ-confined disease (tumour stage >T2 or positive lymph nodes) predicted poorer RFS, CSS and OS. Reconstruction with a neobladder (20% of cases) compared to an ileal conduit was the only predictor of high-grade complications (odds ratio 2.54, 95% CI 1.46-4.43; P < 0.001). CONCLUSION: A RARC with ICUD is feasible as a standard surgical procedure for bladder cancer with only a few patients converted to open surgery. In our hands reconstruction with a neobladder was a strong predictor for high-grade complications.

Can maneuverability in the robot assisted laparoscopic stapler during ileoileal anastomosis compensate for shorter stapler length? - A randomized experimental porcine study.

BACKGROUND: Ileal anastomosis is imperative in patients given a urinary diversion during radical cystectomy. Proper handling and staplers with a certain length are important to prevent stenosis of the bowel. The study aim was to compare the circumference and diameter of ileoileal anastomoses using the Endo GIA tri-stapler 45 mm and 60 mm iDrive systems compared to the RAL Endowrist DaVinci 45 mm. This was to investigate if the better maneuverability of the robotic stapler would compensate for the shorter stapler length in the RAL Endowrist DaVinci 45. MATERIALS AND METHODS: Twenty ileoileal anastomoses were performed in a total of three pigs after randomization according to the type of anastomosis technique used (depending on stapler and robotic system) allocated to four groups (each with five anastomoses): (1) iDrive 45 mm, (2) iDrive 60 mm, (3) RAL DaVinci 45 mm (Si-system), and (4) RAL DaVinci 45 mm (Xi-system). Diameter (mm) and circumference (mm) were measured and compared. RESULTS: Diameters and circumferences in Group 1 were significantly smaller compared to all the other groups, which did not differ from each other, except in Group 2 where anastomoses had a significantly higher circumference than Group 4. CONCLUSION: The iDrive 60 mm makes the anastomoses with the widest diameter and highest circumference compared to the iDrive 45 mm. With the RAL DaVinci 45 mm, the diameter and circumference were comparable to the iDrive 60 mm and significantly better than the iDrive 45 mm. An explanation may be the better maneuverability and surgeon control of the RAL DaVinci stapler.

Diagnostic value of probe-based confocal laser endomicroscopy versus conventional endoscopic biopsies of non-muscle invasive bladder tumors: a pilot study.

PURPOSE: The standard procedure for diagnostics and follow-up for non-muscle invasive bladder cancer (NMIBC) is cystoscopy in the outpatient clinic. Suspicious lesions are biopsied for histopathological assessment. This pilot study aimed to evaluate the ability of Confocal Laser Endomicroscopy (CLE) to rule out High Grade Urothelial Carcinoma (HGUC) to select patients for in-office fulguration. MATERIALS AND METHODS: We performed a prospective non-randomized, single surgeon study. Intraoperative CLE was performed independently by the surgeon and a blinded on-site uropathologist. Following the procedure, a CLE evaluation was performed by another blinded urologist. Lesions were classified as normal/inflammatory, Low Grade Urothelial Carcinoma (LGUC) or HGUC. With the histological evaluations as the gold standard we calculated sensitivity, specificity, PPV and NPV for HGUC and the accuracy for each CLE assessor. The primary outcome was the NPV for HGUC for the surgeon. RESULTS: Twelve patients with a total of 34 lesions were included. Six lesions were flat and 28 were exophytic. On histopathology, 25 lesions were classified as normal/inflammatory or LGUC, while nine were classified as HGUC. For the surgeon, the uropathologist and the second urologist, the sensitivity was 44%, 78% and 22%, respectively. Specificities for the three observers were 84%, 68% and 96%. This corresponded to PPVs for HGUC of 50%, 47% and 67% and NPV for HGUC of 81%, 89% and 77%. CONCLUSIONS: In our hands the NPV of CLE is not high enough for it to be considered an alternative to histopathological assessment of bladder lesions.

DaBlaCa-11: Photodynamic Diagnosis in Flexible Cystoscopy-A Randomized Study With Focus on Recurrence.

OBJECTIVE: To examine whether photodynamic diagnosis (PDD) in addition to flexible cystoscopy in the outpatient clinic can reduce risk of tumor recurrence in patients with previous nonmuscle invasive bladder cancer. PDD is an optical technique that enhances the visibility of pathologic tissue and helps guidance tumor resection. METHODS: From February 2016 to December 2017, 699 patients from 3 urologic departments in Denmark were enrolled in a randomized controlled trial. Four months after transurethral resection of bladder tumor patients were randomized 1:1 to either an intervention group (hexaminolevulinate was instilled in the bladder before flexible cystoscopy with PDD video cystoscope) or a control group (white light flexible cystoscope), only. Primary endpoint was tumor recurrence within 8 months from the randomization. Secondary outcomes were numbers of procedures in general anesthesia, time to the first recurrence, differences in tumor size, risk of tumor progression, and identification of carcinoma in situ. RESULTS: A total of 351 patients were allocated to the intervention group (flexible PDD), and 348 to the control group (flexible white light). Throughout the following 8 months after randomization, only 117 patients in the intervention group had at least 1 tumor recurrence compared to 143 patients in the control group (P = .049). Odds ratio of 0.67 (P = .02, 95% CI: 0.48-0.95) correlates with a tumor reduction of 33% in favor of the intervention group. CONCLUSION: Use of PDD in a routine surveillance cystoscopy first time after transurethral resection of bladder tumor for nonmuscle invasive bladder cancer reduces subsequent risk of tumor recurrence compared to WL cystoscopy alone.

Reasons why not all Danish patients with muscle invasive bladder cancer receive neoadjuvant chemotherapy before radical cystectomy.

Background: Danish guidelines on muscle invasive bladder cancer (MIBC) recommend neoadjuvant chemotherapy (NAC) for non-metastatic patients fit for cisplatin-based chemotherapy. The current indication is urothelial MIBC in patients less than 75 years old with no metastasis on imaging and normal renal function (GFR ≥ 60 ml/min). Data from the Danish Bladder Cancer Database (DaBlaCa-Data) reveals that only 40-50% of MIBC patients below 75 years of age receive NAC prior to cystectomy. The aim of this study was to clarify the reasons why the remaining patients do not receive NAC.Methods: Individual patient data were collected retrospectively from all five Danish urologic departments performing cystectomies. Patients fulfilling the inclusion criteria: MIBC at TURBT, age less than 75 years old and subsequent cystectomy were included and registered by the specific reason why NAC was not given. In total, 449 patients met the age- and T-stage criteria for NAC in the period September 2014 through August 2017.Results: In total, 274 patients (61.0%) received chemotherapy. Of the 175 patients who did not receive NAC, 140 patients (80%) were not fit for cisplatin and 35 patients did not receive NAC and had no specific contraindication. This ranged from 0-18% of included patients in the different centres. The main reason was patient refusal (97%). Interestingly, this ranged from 0-50% of patients not receiving NAC when comparing the five centres.Conclusion: These findings underline the need for proper patient information in order to get a uniform treatment strategy between centres.

Perioperative management of radical cystectomy in the Nordic countries.

Objective: Radical cystectomy is performed in all of the Nordic countries, but the current practice patterns remain unclear. This study explored current perioperative care and adherence to the Early Recovery After Cystectomy (ERAC) protocol and EAU guidelines by cystectomy surgeons in the Nordic countries. Materials and methods: The study was performed as a survey including 47 centers performing cystectomies in Norway, Sweden, Finland, Iceland and Denmark. The survey addressed surgical volume, complications, preoperative imaging, use of chemotherapy, multidisciplinary conferences and current practice for perioperative and postoperative care. The survey was dispersed electronically and data was collected between November 2016 and October 2017. Results: The response rate was 55%, with a 78% completion rate of the 58 main questions. Most centers performed 10-50 cystectomies annually. Of responding centers, 96% had preoperative multidisciplinary conferences. Bowel preparation was avoided in 95% of centers and 92% did not use nasogastric tubes. All centers offered neoadjuvant chemotherapy, prescribed prophylactic antibiotics, used urinary drainage and did in-department follow-up. None of the responders waited for proof of bowel function before restarting oral diet and 96% had a standard plan for early mobilization. Conclusion: This study found a high degree of implementation of ERAC and EAU guidelines and similar practice patterns regarding perioperative management of Radical cystectomy among Nordic countries.

Human papillomavirus and squamous cell carcinoma of the urinary bladder: DaBlaCa-10 study.

OBJECTIVE: To evaluate a potential association between Human Papillomavirus (H.P.V.) and squamous cell carcinoma (S.C.C.) urinary bladder cancer (B.C.). Furthermore, the relation between p16INK4a, H.P.V. and B.C. was examined. PATIENTS AND METHODS: Patients were included and divided into three groups based on the histological diagnosis of B.C. SPECIMENS: An extensive exclusion was performed, including accepted casual risk factors for S.C.C. B.C., such as long-term use of catheters, cystolithiasis and Schistosoma hematobium infection. A total of 100 patients were included: 50 with pure S.C.C., 25 with urothelial carcinomas (U.C.) and 25 with squamous differentiation of U.C. (Sq.D.). The patients were operated at one of four major Danish hospitals in the period January 2005 to December 2016. Clinical information was collected from the medical records. Presence of H.P.V. was analyzed using the INNO-LiPA H.P.V. Genotyping Extra II. p16INK4a was analyzed using immunohistochemical (I.H.C.) staining. A p-value <0.05 was considered statistically significant. RESULTS: An overall H.P.V. prevalence of 12/100 (12%) was observed. H.P.V. was demonstrated in 9/50 (18%) of the S.C.C. PATIENTS: Overall, p16INK4a over-expression was observed in 52/100 (52%) patients. However, concomitant H.P.V. positivity and p16INK4a over-expression were observed in only 4/100 (4%) patients. CONCLUSION: The presence of H.P.V. in one fifth of patients with S.C.C. B.C. was demonstrated. H.P.V. infection could have a significant association with S.C.C. B.C. without other known casual risk factors for S.C.C. B.C.

Total intravenous anaesthesia versus inhalational anaesthesia for adults undergoing transabdominal robotic assisted laparoscopic surgery.

BACKGROUND: Rapid implementation of robotic transabdominal surgery has resulted in the need for re-evaluation of the most suitable form of anaesthesia. The overall objective of anaesthesia is to minimize perioperative risk and discomfort for patients both during and after surgery. Anaesthesia for patients undergoing robotic assisted surgery is different from anaesthesia for patients undergoing open or laparoscopic surgery; new anaesthetic concerns accompany robotic assisted surgery. OBJECTIVES: To assess outcomes related to the choice of total intravenous anaesthesia (TIVA) or inhalational anaesthesia for adults undergoing transabdominal robotic assisted laparoscopic gynaecological, urological or gastroenterological surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016 Issue 5), Ovid MEDLINE (1946 to May 2016), Embase via OvidSP (1982 to May 2016), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCOhost (1982 to May 2016) and the Institute for Scientific Information (ISI) Web of Science (1956 to May 2016). We also searched the International Standard Randomized Controlled Trial Number (ISRCTN) Registry and Clinical trials gov for ongoing trials (May 2016). SELECTION CRITERIA: We searched for randomized controlled trials (RCTs) including adults, aged 18 years and older, of both genders, treated with transabdominal robotic assisted laparoscopic gynaecological, urological or gastroenterological surgery and focusing on outcomes of TIVA or inhalational anaesthesia. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures of Cochrane. Study findings were not suitable for meta-analysis. MAIN RESULTS: We included three single-centre, two-arm RCTs involving 170 participants. We found one ongoing trial. All included participants were male and were undergoing radical robotic assisted laparoscopic radical prostatectomy (RALRP). The men were between 50 and 75 years of age and met criteria for American Society of Anesthesiologists physical classification scores (ASA) I, ll and III.We found evidence showing no clinically meaningful differences in postoperative pain between the two types of anaesthetics (mean difference (MD) in visual analogue scale (VAS) scores at one to six hours was -2.20 (95% confidence interval (CI) -10.62 to 6.22; P = 0.61) in a sample of 62 participants from one study. Low-quality evidence suggests that propofol reduces postoperative nausea and vomiting (PONV) over the short term (one to six hours after surgery) after RALRP compared with inhalational anaesthesia (sevoflurane, desflurane) (MD -1.70, 95% CI -2.59 to -0.81; P = 0.0002).We found low-quality evidence suggesting that propofol may prevent an increase in intraocular pressure (IOP) after pneumoperitoneum and steep Trendelenburg positioning compared with sevoflurane (MD -3.90, 95% CI -6.34 to -1.46; P = 0.002) with increased IOP from baseline to 30 minutes in steep Trendelenburg. However, it is unclear whether this surrogate outcome translates directly to clinical avoidance of ocular complications during surgery. No studies addressed the secondary outcomes of adverse effects, all-cause mortality, respiratory or circulatory complications, cognitive dysfunction, length of stay or costs. Overall the quality of evidence was low to very low, as all studies were small, single-centre trials providing unclear descriptions of methods. AUTHORS' CONCLUSIONS: It is unclear which anaesthetic technique is superior - TIVA or inhalational - for transabdominal robotic assisted surgery in urology, gynaecology and gastroenterology, as existing evidence is scarce, is of low quality and has been generated from exclusively male patients undergoing robotic radical prostatectomy.An ongoing trial, which includes participants of both genders with a focus on quality of recovery, might have an impact on future evidence related to this topic.

Clinical relevance of narrow-band imaging in flexible cystoscopy: the DaBlaCa-7 study.

OBJECTIVE: This multicenter study investigated whether the use of narrow-band imaging (NBI) in flexible cystoscopy could improve diagnostics to a degree where clinical management was relevantly changed. MATERIALS AND METHODS: From May 2014 to June 2015, 955 patients were enrolled at three Danish urological departments. Patients had either hematuria (n = 483) or known recurrent non-muscle-invasive bladder cancer (NMIBC) (n = 472). High-definition (HD) cystoscopy was performed in white light (WL) and a preliminary clinical decision was made. Then, a second cystoscopy was performed in NBI and a conclusive clinical decision was made. A difference between the two decisions that had a clinical impact on the patient was considered clinically relevant. RESULTS: Pathology was found in 216 WL cystoscopies, and additional pathology in 15 NBI cystoscopies (6.9%). Based on NBI, pathology was suspected in 23 patients (3.1%) in whom a WL cystoscopy revealed no tumor. In total, NBI changed the clinical decision relevantly in 1.9% of the patients. In hematuria patients, the calculated sensitivities of both NBI and WL were identically high, whereas sensitivity in patients with known NMIBC was significantly higher in NBI compared to WL (NBI: 100.0% vs WL: 83.2%, p < .05). NBI had a lower specificity compared to WL, especially in follow-up cystoscopies (NBI: 86.5% vs WL: 92.1, p < .05). CONCLUSION: NBI can be a useful tool in clinical decision making as a supplement to WL because it yields a significantly higher detection rate than WL cystoscopy alone. This is particularly relevant in patients with known recurrent NMIBC.

Comparison of White Light, Photodynamic Diagnosis, and Narrow-band Imaging in Detection of Carcinoma In Situ or Flat Dysplasia at Transurethral Resection of the Bladder: the DaBlaCa-8 Study.

OBJECTIVE: To compare findings in NBI to findings in WL and PDD in a high-risk patient population. MATERIALS AND METHODS: A total of 171 patients were included in the study from 4 different urology departments in Denmark and Norway. Patients were scheduled for a PDD-guided transurethral tumor resection or cystoscopy-guided biopsy in accordance with Danish guidelines, on the suspicion of primary or concomitant CIS. All patients were examined with WL cystoscopy followed by both NBI and PDD before biopsy. RESULTS: A total of 136 patients were biopsied due to findings with suspicion of CIS in at least 1 modality (482 biopsies with a mean of 3.5 biopsies per patient). Analysis at patient level showed that NBI and PDD had a significantly higher sensitivity regarding identification of CIS and dysplasia compared with WL (NBI: 95.7%, PDD: 95.7% vs WL: 65.2%, P < .05). Specificity was not significantly different between the 3 methods (NBI: 52.0%, PDD: 48.0%, and WL: 56.8%). When analyzed per biopsy, NBI and PDD had a significantly higher sensitivity than WL (NBI: 72.7% and PDD: 78.2% vs WL: 52.7%, P < .05), whereas the positive predictive values were not significantly different (NBI: 23.7%, PDD: 22.2%, and WL: 19.0%). CONCLUSION: NBI was found to be a valid alternative to PDD regarding diagnosis of CIS and flat dysplasia.

Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events.

The bladder cancer genome harbors numerous oncogenic mutations and aberrantly methylated gene promoters. The aim of our study was to generate a profile of these alterations and investigate their use as biomarkers in urine sediments for noninvasive detection of bladder cancer. We systematically screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4, SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine samples (N = 113) from 118 bladder tumor patients. We also analyzed urine samples from 33 patients with noncancerous urinary lesions. A total of 95 oncogenic mutations and 189 hypermethylation events were detected in the 105 tumor biopsies. The total panel of markers provided a sensitivity of 93%, whereas mutation and methylation markers alone provided sensitivities of 72% and 70%, respectively. In urine samples, the sensitivity was 70% for all markers, 50% for mutation markers and 52% for methylation markers. FGFR3 mutations occurred more frequently in tumors with no methylation events than in tumors with one or more methylation events (78% vs. 33%; p < 0.0001). FGFR3 mutation in combination with three methylation markers (APC, RASSF1A and SFRP2) provided a sensitivity of 90% in tumors and 62% in urine with 100% specificity. These results suggest an inverse correlation between FGFR3 mutations and hypermethylation events, which may be used to improve noninvasive, DNA-based detection of bladder cancer.

Custom-designed MLPA using multiple short synthetic probes: application to methylation analysis of five promoter CpG islands in tumor and urine specimens from patients with bladder cancer.

Ligation of two oligonucleotide probes hybridized adjacently to a DNA template has been widely used for detection of genome alterations. The multiplex ligation-dependent probe amplification (MLPA) technique allows simultaneous screening of multiple target sequences in a single reaction by using pairs of probes that carry tails for binding of common amplification primers. Resolution of the various targets is achieved by electrophoresis on the basis of predefined differences in amplicon length. In the conventional MLPA approach, one of the two target probes is generated by cloning in a single-stranded bacteriophage vector to introduce a sequence of defined length between the primer binding site and the specific target sequence. Here we demonstrate that differences in amplicon length can be achieved by using multiple short synthetic probes for each target sequence. When joined by a DNA ligase, these probes will form a single amplifiable template whose length is defined by the number and lengths of the individual probes. We have used this principle to establish a methylation-specific MLPA (MS-MLPA) assay that simultaneously determines the methylation status of five promoter CpG islands, and we have used this assay to analyze DNA from tumor tissue and corresponding urine samples from patients with bladder cancer. Our data show that the use of multiple short synthetic probes provides a simple means for custom-designed MS-MLPA analysis.

Predicting recurrence and progression of noninvasive papillary bladder cancer at initial presentation based on quantitative gene expression profiles.

BACKGROUND: Currently, tumor grade is the best predictor of outcome at first presentation of noninvasive papillary (Ta) bladder cancer. However, reliable predictors of Ta tumor recurrence and progression for individual patients, which could optimize treatment and follow-up schedules based on specific tumor biology, are yet to be identified. OBJECTIVE: To identify genes predictive for recurrence and progression in Ta bladder cancer at first presentation using a quantitative, pathway-specific approach. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of patients with Ta G2/3 bladder tumors at initial presentation with three distinct clinical outcomes: absence of recurrence (n=16), recurrence without progression (n=16), and progression to carcinoma in situ or invasive disease (n=16). MEASUREMENTS: Expressions of 24 genes that feature in relevant pathways that are deregulated in bladder cancer were quantified by real-time polymerase chain reaction on tumor biopsies from the patients at initial presentation. RESULTS AND LIMITATIONS: CCND3 (p=0.003) and HRAS (p=0.01) were predictive for recurrence by univariate analysis. In a multivariable model based on CCND3 expression, sensitivity and specificity for recurrence were 97% and 63%, respectively. HRAS (p<0.001), E2F1 (p=0.017), BIRC5/Survivin (p=0.038), and VEGFR2 (p=0.047) were predictive for progression by univariate analysis. Multivariable analysis based on HRAS, VEGFR2, and VEGF identified progression with 81% sensitivity and 94% specificity. Since this is a small retrospective study using medium-throughput profiling, larger confirmatory studies are needed. CONCLUSIONS: Gene expression profiling across relevant cancer pathways appears to be a promising approach for Ta bladder tumor outcome prediction at initial diagnosis. These results could help differentiate between patients who need aggressive versus expectant management.

[Urological training in the county of Roskilde]. / Den urologiske uddannelse i Roskilde Amt.

INTRODUCTION: Training in surgical skills and the importance of function-bearing units are the subject of much debate at the moment. An exposition is given of the quality of the urological training in the County of Roskilde, which corresponds to a function-bearing unit as to size. MATERIAL AND METHODS: The exposition is based on charts of specific oncological diagnoses during one year and the list of operations performed by phase III interns during a period of six months. RESULTS: The number of operations performed by phase III interns during the two periods in compared with the informal claims of The Danish Urological Society. DISCUSSION: As regards open surgery, the number of operations performed by phase III interns fully lives up to the informal requirements of the Danish Urological Society and the number of operations per intern exceeds what has previously been calculated at branch-specialized departments. The number of endoscopic operations was a little lower than expected and did not quite live up to the requirements. It is concluded that the urological training at a county urological department meets the requirements of the Danish Urological Society.