DIAGNOSIS AND TREATMENT OF UROTHELIAL CARCINOMA OF THE BLADDER

Chapter 1 is a general introduction. Chapter 2 describes currently known methylation markers in urine for diagnosis of bladder cancer and their diagnostic accuracy. In Chapter 3 several methylation markers in urine are evaluated to use for diagnosis of bladder cancer and an optimal two gene panel is proposed. In chapter 4 several additives are tested to preserve urinary DNA prior to the analysis of methylation markers in urine. A protocol for preservation is proposed. In chapter 5 the two systems used for grading bladder cancer are tested to determine their reproducibility, both are poorly reproducible. In chapter 6, several measurents are used to determine whether a more objective method to determine bladder cancer grade is possible. In chapter 7 the value of an immediate instillation of mitomycin C after transurethral resection of a bladder tumor is evaluated in a randomised controlled trial. The study shows that an immediate instillation reduces the risk of recurrent bladder cancer. In chapter 8, we evaluate whether the value of an immediate instillation is different in several subgroups of patients. We found that an immediate instillation is effective in all risk groups. In Chapter 9, the timing of an immediate instillation of mitomycin C is investigated. We found that, altough it is recommended to administer an immediate instillation as soon a possible after transurethral resection of a bladder tumour, patients may still benefit from an instillation 1 day after transurethral resection. In chapter 10, interleukin-2 instillations are tested in patients with bladder cancer with and without a marker lesion. The study was closed prematurely so no soli conclusions can be made. However no clear benefit of a marker lesion was detected. In part 3 bladder preservation using brachytherapiy in high risk non muscle invasive bladder cancer, and muscle invasive bladder cancer is evaluatied. We found that brachytherapy is a good alternative to cystectomy in selected patients, without compromising survival. Additionally, the implantaion of the brachytherapey cathethers can safely be conducted using a robot-assisted laparoscopic approach

Bladder necrosis: 'A man without a bladder'

Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function

Kidney Blow Out Due to Inguinal Herniation of the Ureter in an Infant

Ureteroinguinal herniation is a rare event, usually diagnosed during the surgical repair of inguinal hernias. Here, we describe the first case of a kidney blow out due to this condition in a male infant

Trial-based Cost-effectiveness Analysis of an Immediate Postoperative Mitomycin C Instillation in Patients with Non-muscle-invasive Bladder Cancer

BACKGROUND: Bladder cancer imposes a significant public health burden on the European Union. There is a need for cost-effective treatment and follow-up regimens. OBJECTIVE: To assess the cost-effectiveness of immediate mitomycin C (MMC) instillation within 1 d after surgery compared to delayed MMC instillation within 2 wk after surgery with further adjuvant treatment, depending on the patient's risk group. DESIGN SETTING AND PARTICIPANTS: This economic evaluation was based on a randomized controlled trial among 2243 Dutch patients with non-muscle-invasive bladder cancer (NMIBC) patients from a health care perspective over a 3-yr time period. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The treatment effect was measured as time to recurrence and recurrence-free survival. Missing effect data were imputed with multiple imputation. Health care utilization and related costs were estimated on the basis of treatment protocols for NMIBC patients in the Netherlands. Statistical uncertainty was estimated using bootstrapping and is graphically presented using cost-effectiveness planes and cost-effectiveness acceptability curves. RESULTS AND LIMITATIONS: Time to recurrence was significantly longer for immediate MMC instillation (27.31 mo) than for delayed MMC instillation (24.97 mo), with an adjusted mean difference of 2.21 mo (95% confidence interval [CI] 1.58-2.84). The proportion of patients with recurrence-free survival was significantly higher after immediate MMC instillation (0.65) than after delayed MMC instillation (0.56), with an adjusted mean difference of 0.08 (95% CI 0.06-0.11). Total mean health care costs per patient were significantly lower for immediate MMC instillation (€22 959) than for delayed MMC instillation (€24 624), with an adjusted mean difference of -€1350 (95% CI -€1799 to -€900). The study is limited by the retrospective estimation of costs. CONCLUSIONS: This trial-based cost-effectiveness analysis shows that from a health care perspective, immediate MMC instillation is more effective and less expensive compared to delayed MMC instillation. PATIENT SUMMARY: We assessed the cost-effectiveness of immediate bladder instillation of mitomycin C after surgery to reduce the risk of recurrence after removal of the bladder tumor as compared to delayed instillation in a large Dutch population of patients with non-muscle-invasive bladder cancer. We found that immediate instillation was more effective and less expensive than delayed instillation. We conclude that immediate mitomycin C instillation is a cost-effective treatment for non-muscle-invasive bladder cancer

Value of an Immediate Intravesical Instillation of Mitomycin C in Patients with Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Randomised Study in 2243 patients

Background: The efficacy of an immediate single chemotherapy instillation after transurethral resection of a bladder tumour (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC) remains a topic of debate. Evidence is even more scarce when an immediate instillation is followed by adjuvant instillations. Objective: To compare the effect of a mitomycin C (MMC) instillation within 24. h to an instillation 2 wk after TURBT in patients with NMIBC with or without adjuvant instillations. Design, Setting, and participants: Between 1998 and 2003, 2844 NMIBC patients were randomised for immediate versus delayed MMC instillation after TURBT. Patients were categorised in low-risk (LOR), intermediate-risk (IMR), and high-risk (HIR) groups. Total numbers of instillations in these groups were 1, 9, and 15, respectively. Outcome measurements and statistical analysis: Primary end point was 3-yr recurrence risk for the IMR and HIR groups and 5-yr risk for the LOR group. Secondary outcomes were time to recurrence and incidence of adverse events. Analyses were performed with the log-rank test, Cox-regression, and χ2 test in SPSS. Results and limitations: A total of 2243 patients were eligible on an intention-to-treat basis. Recurrence risks were 43% and 46% in the LOR group (5-yr follow-up, p = 0.11), 20% and 32% in the IMR group (3-yr follow-up, p = 0.037), and 28% and 35% in the HIR group (3-yr follow-up, p = 0.007), for an immediate and a delayed instillation, respectively. For all patients, the recurrence risk was 27% (95% confidence interval [CI], 24-30) in the immediate and 36% (95% CI, 33-39) in the delayed instillation group (p <. 0.001) with a 27% reduction in relative recurrence risk (hazard ratio: 0.73, 95% CI, 0.63-0.85, p <. 0.001). The incidence of adverse events did not differ significantly between treatment groups (immediate instillation 25%, delayed instillation 22%, p = 0.08). The risk groups in our study differ slightly from the current guidelines, which is a limitation of our study. Conclusions: An immediate, single instillation after TURBT reduces the recurrence risk in NMIBC patients, independent of the number of adjuvant installations. Patient summary: A single instillation of chemotherapy after the resection of non-muscle-invasive bladder cancer reduces the recurrence risk, even if patients are treated with an adjuvant schedule of instillations. An intravesical instillation with mitomycin C within 24. h after transurethral resection of a bladder tumour reduces the risk of recurrence in non-muscle-invasive bladder cancer patients, independent of the number of adjuvant installations

The effect of timing of an immediate instillation of mitomycin C after transurethral resection in 941 patients with non-muscle-invasive bladder cancer

Objective: To investigate whether the timing of an immediate instillation of mitomycin C (on the day of transurethral resection of bladder tumour [TURBT] or 1 day later) has an impact on time to recurrence of non-muscle-invasive bladder cancer (NMIBC). Patients and Methods: All patients with NMIBC who were enrolled in a prospective trial between 1998 and 2003, and treated with an early mitomycin C instillation (on the day of TURBT or 1 day later), were selected. Statistical analysis was performed with Kaplan-Meier curves and multivariable Cox regression. Results: Administering an instillation of mitomycin C on the day of TURBT or 1 day later did not show a statistically significant difference in time to recurrence in a univariable model (log-rank P = 0.99). After correcting for the number of scheduled adjuvant instillations, no statistically significant difference could be detected either: hazard ratio 1.05 (95% confidence interval 0.81-1.35, P = 0.74). Conclusion: These data do not support the hypothesis that a very early instillation (on the day of TURBT) of mitomycin C decreases the risk of recurrence as compared with an early instillation (1 day after TURBT)

Exploring the impact of urogenital organ displacement after abdominoperineal resection on urinary and sexual function

Purpose This study aimed to establish the functional impact of displacement of urogenital organs after abdominoperineal resection (APR) using validated questionnaires. Methods Patients who underwent APR for primary or recurrent rectal cancer (2001-2018) with evaluable pre- and postoperative radiological imaging and completed urinary (UDI-6, IIQ-7) and sexual questionnaires (male, IIEF; female, FSFI, FSDS-R) were included from 16 centers. Absolute displacement of the internal urethral orifice, posterior bladder wall, distal end of the prostatic urethra, and cervix were correlated to urogenital function by calculating Spearman's Rho (rho). Median function scores were compared between minimal or substantial displacement using median split. Results There were 89 male and 36 female patients included, of whom 45 and 19 were sexually active after surgery. Absolute displacement of the internal urethral orifice and posterior bladder wall was not correlated with UDI-6 in men (rho = 0.119 and rho = 0.022) nor in women (rho = - 0.098 and rho = - 0.154). In men with minimal and substantial displacement of the internal urethral orifice, median UDI-6 scores were 10 (IQR 0-22) and 17 (IQR 5-21), respectively, with corresponding scores of 25 (IQR 10-46) and 21 (IQR 16-36) in women. Displacement of the cervix and FSDS-R were correlated (rho = 0.433) in sexually active patients. Conclusion This first analysis on functional impact of urogenital organ displacement after APR suggests that more displacement of the cervix might be associated with worse sexual function, while the data does not indicate any potential functional impact of bladder displacement. Studies are needed to further explore this underexposed topic

Exploring the impact of urogenital organ displacement after abdominoperineal resection on urinary and sexual function

Purpose: This study aimed to establish the functional impact of displacement of urogenital organs after abdominoperineal resection (APR) using validated questionnaires. Methods: Patients who underwent APR for primary or recurrent rectal cancer (2001–2018) with evaluable pre- and postoperative radiological imaging and completed urinary (UDI-6, IIQ-7) and sexual questionnaires (male, IIEF; female, FSFI, FSDS-R) were included from 16 centers. Absolute displacement of the internal urethral orifice, posterior bladder wall, distal end of the prostatic urethra, and cervix were correlated to urogenital function by calculating Spearman’s Rho (ρ). Median function scores were compared between minimal or substantial displacement using median split. Results: There were 89 male and 36 female patients included, of whom 45 and 19 were sexually active after surgery. Absolute displacement of the internal urethral orifice and posterior bladder wall was not correlated with UDI-6 in men (ρ = 0.119 and ρ = 0.022) nor in women (ρ = − 0.098 and ρ = − 0.154). In men with minimal and substantial displacement of the internal urethral orifice, median UDI-6 scores were 10 (IQR 0–22) and 17 (IQR 5–21), respectively, with corresponding scores of 25 (IQR 10–46) and 21 (IQR 16–36) in women. Displacement of the cervix and FSDS-R were correlated (ρ = 0.433) in sexually active patients. Conclusion: This first analysis on functional impact of urogenital organ displacement after APR suggests that more displacement of the cervix might be associated with worse sexual function, while the data does not indicate any potential functional impact of bladder displacement. Studies are needed to further explore this underexposed topic