EffectiveNess of a multimodal preHAbilitation program in patieNts with bladder canCEr undergoing radical cystectomy: protocol of the ENHANCE multicentre randomised controlled trial.

INTRODUCTION: Radical cystectomy (RC) is the standard treatment for patients with non-metastatic muscle-invasive bladder cancer, as well as for patients with therapy refractory high-risk non-muscle invasive bladder cancer. However, 50-65% of patients undergoing RC experience perioperative complications. The risk, severity and impact of these complications is associated with a patient's preoperative cardiorespiratory fitness, nutritional and smoking status and presence of anxiety and depression. There is emerging evidence supporting multimodal prehabilitation as a strategy to reduce the risk of complications and improve functional recovery after major cancer surgery. However, for bladder cancer the evidence is still limited. The aim of this study is to investigate the superiority of a multimodal prehabilitation programme versus standard-of-care in terms of reducing perioperative complications in patients with bladder cancer undergoing RC. METHODS AND ANALYSIS: This multicentre, open label, prospective, randomised controlled trial, will include 154 patients with bladder cancer undergoing RC. Patients are recruited from eight hospitals in The Netherlands and will be randomly (1:1) allocated to the intervention group receiving a structured multimodal prehabilitation programme of approximately 3-6 weeks, or to the control group receiving standard-of-care. The primary outcome is the proportion of patients who develop one or more grade ≥2 complications (according to the Clavien-Dindo classification) within 90 days of surgery. Secondary outcomes include cardiorespiratory fitness, length of hospital stay, health-related quality of life, tumour tissue biomarkers of hypoxia, immune cell infiltration and cost-effectiveness. Data collection will take place at baseline, before surgery and 4 and 12 weeks after surgery. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Medical Ethics Committee NedMec (Amsterdam, The Netherlands) under reference number 22-595/NL78792.031.22. Results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05480735.

Quality appraisal of clinical guidelines for recurrent urinary tract infections using AGREE II: a systematic review.

INTRODUCTION AND HYPOTHESIS: Recommendations for preventing and diagnosing recurrent urinary tract infection (UTI) tend to vary between clinical practice guidelines (CPGs) because of low-quality scientific evidence, potentially leading to practice variation and suboptimal care. We assessed the quality of existing CPGs for recurrent UTI. METHODS: A systematic search was performed from January 2000 to June 2021 in PubMed and EMBASE for CPGs on recurrent UTI prevention or hospital diagnostics in Dutch, English, and Spanish. Each CPG was assessed by four appraisers in a multidisciplinary review team, using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) instrument. RESULTS: We identified and assessed eight CPGs published between 2013 and 2021. The scope and purpose (mean and standard deviation: 67.3 ± 21.8) and clarity of presentation (74.8 ± 17.6) domains scored highly. However, issues with methods, patient participation, conflict of interests, and facilitators and barriers were common and resulted in lower scores for the rigour of development (56.9 ± 25.9), applicability (19.6 ± 23.4), stakeholder involvement (50.4 ± 24.6), and editorial independence (62.1 ± 23.1) domains. Overall, two CPGs were recommended, three were recommended with modifications, and three were not recommended. CONCLUSIONS: Significant room for improvement exists in the quality of CPGs for recurrent UTI, with most displaying serious limitations in the stakeholder involvement, rigour of development, and applicability domains. These aspects must be improved to decrease diagnostic and therapeutic uncertainty. Developers could benefit from using checklists and following guidelines when developing de novo CPGs.

Comparison of the diagnostic yield of routine versus indicated flowmetry, ultrasound and cystoscopy in women with recurrent urinary tract infections.

INTRODUCTION AND HYPOTHESIS: To quantify and compare the outcomes of routine vs. urologist-requested diagnostic testing for recurrent urinary tract infections (rUTI). METHODS: A retrospective cohort study of patients with rUTI referred to a large non-academic teaching hospital between 2016 and 2018 (Hospital A) and a university hospital between 2014 and 2016 (Hospital B). Electronic medical records were reviewed for baseline and diagnostic data. Women underwent the following assessments routinely: urinalysis, voiding diary, flowmetry in Hospital A and urinalysis, voiding diary, flowmetry, ultrasound, abdominal x-ray and cystoscopy in Hospital B. All other diagnostics were performed by indication in each hospital. RESULTS: We included 295 women from Hospital A and 298 from Hospital B, among whom the mean age (57.6 years) and mean UTI frequency (5.6/year) were comparable, though more were postmenopausal in Hospital A. We identified abnormalities by flowmetry or post-void residual volumes in 134 patients (Hospital A: 79; Hospital B: 55), cystoscopy in 14 patients (Hospital A: 6; Hospital B: 8) and ultrasound in 42 patients (Hospital A: 16; Hospital B: 26), but these differences were not significant. Diagnostics altered treatment in 117 patients (e.g., pelvic floor muscle training, referral to another specialist, surgical intervention), mostly due to flowmetry and post-void residual volume measurement. The retrospective design and absence of follow-up data limit these results. CONCLUSIONS: The routine use of cystoscopy and ultrasound in female patients with rUTIs should not be recommended as they yield few abnormalities and lead to additional costs.

Development of a Management Algorithm for Acute and Chronic Radiation Urethritis and Cystitis.

OBJECTIVE: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based management algorithm. MATERIAL AND METHODS: The PubMed/MEDLINE database was searched by a multidisciplinary group of experts in January 2021. RESULTS: In total, 48 publications were identified. Three different types of RUC can be observed in clinical practice: inflammation-predominant, bleeding-predominant, and the combination of inflammation- and bleeding-RUC. There is no consensus on the optimal treatment of RUC. Inflammation-predominant RUC should be treated symptomatically based on the existence of bothersome storage or voiding lower urinary tract symptom as well as on pain. When bleeding-predominant RUC has occurred, hydration and hyperbaric oxygen therapy (HOT) should be used first and, if HOT is not available, oral drugs instead (sodium pentosane polysulfate, aminocaproic acid, immunokine WF 10, conjugated estrogene, or pentoxifylline + vitamin E). If local bleeding persists, focal therapy of bleeding vessels with a laser or electrocoagulation is indicated. In case of generalized bleeding, intravesical installation should be initiated (formalin, aluminium salts, and hyaluronic acid/chondroitin). Vessel embolization is a less invasive treatment with potentially less complications and good clinical outcomes. Open- or robot-assisted surgery is indicated in patients with permanent, life-threatening bleeding, or fistulae. CONCLUSIONS: Treatment of RUC, if not self-limiting, should be done according to the type of RUC and in a stepwise approach. Conservative/medical treatment (oral and topic agents) should primarily be used before invasive (transurethral) treatments.

Exhaled-breath Testing for Prostate Cancer Based on Volatile Organic Compound Profiling Using an Electronic Nose Device (Aeonose™): A Preliminary Report.

BACKGROUND: Prostate biopsy, an invasive examination, is the gold standard for diagnosing prostate cancer (PCa). There is a need for a novel noninvasive diagnostic tool that achieves a significantly high pretest probability for PCa, reducing unnecessary biopsy numbers. Recent studies have shown that volatile organic compounds (VOCs) in exhaled breath can be used to detect different types of cancers via training of an artificial neural network (ANN). OBJECTIVE: To determine whether exhaled-breath analysis using a handheld electronic nose device can be used to discriminate between VOC patterns between PCa patients and healthy individuals. DESIGN, SETTING, AND PARTICIPANTS: This prospective pilot study was conducted in the outpatient urology clinic of the Maastricht University Medical Center, the Netherlands. Patients with histologically proven PCa were already included before initial biopsy or during follow-up, with no prior treatment for their PCa. Urological patients with negative biopsies in the past year or patients with prostate enlargement (PE) with low or stable serum prostate-specific antigen were used as controls. Exhaled breath was probed from 85 patients: 32 with PCa and 53 controls (30 having negative biopsies and 23 PE). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient characteristics were statistically analyzed using independent sample t test and Pearson's chi-square test. Data analysis was performed by Aethena software after data compression using the TUCKER3 algorithm. ANN models were trained and evaluated using the leave-10%-out cross-validation method. RESULTS AND LIMITATIONS: Our trained ANN showed an accuracy of 0.75, with an area under the curve of 0.79 with sensitivity and specificity of 0.84 (95% confidence interval [CI] 0.66-0.94) and 0.70 (95% CI 0.55-0.81) respectively, comparing PCa with control individuals. The negative predictive value was found to be 0.88. The main limitation is the relatively small sample size. CONCLUSIONS: Our findings imply that the Aeonose allows us to discriminate between patients with untreated, histologically proven primary PCa and control patients based on exhaled-breath analysis. PATIENT SUMMARY: We explored the possibility of exhaled-breath analysis using an electronic nose, to be used as a noninvasive tool in clinical practice, as a pretest for diagnosing prostate cancer. We found that the electronic nose was able to discriminate between prostate cancer patients and control individuals.

Long-term compliance and results of intravesical botulinum toxin A injections in male patients.

INTRODUCTION: Intravesical injections with botulinum toxin A (BoNT-A) is an established treatment for patients with overactive bladder (OAB) symptoms. However, most studies have evaluated the efficacy of this treatment in women and report short-term results. In this study, we evaluated the long-term compliance of BoNT-A in a heterogeneous group of male patients. MATERIALS AND METHODS: This is a retrospective, single-centre study. We evaluated all male patients who have been treated with BoNT-A from 2004 until 2010 in a large teaching hospital. Patients received 100-300 U of onabotulinum toxin-A in 20 intravescial injections. Some patients received dose adjustment with repeated injections. RESULTS: In total, 88 male patients were included. The mean follow-up was almost 6 years (69 months). Of all patients, 22 (25%) continued BoNT-A treatment at last follow-up (success). Of the patients who discontinued treatment, 35 had insufficient effect and 27 had tolerability issues (eg, urinary retention, self-catheterisation, voiding LUTS). Four patients abandoned treatment due to other reasons that were not related to BoNT-A. Of all patients, 24% had to use intermittent catheterisation (de novo) or indwelling catheters at some point during the follow-up. DISCUSSION: In this real-life, heterogeneous cohort of men, the long-term compliance with BoNT-A was 25%. Patients with neurogenic OAB symptoms appear to have the best results in our study with 36% of patients who were still on active treatment during last follow-up. Intravesical BoNT-A can be an effective treatment for men with OAB symptoms. In our study, only 25% of patients continued treatment during long-term follow-up. Larger, prospective trials are needed to confirm these results.

Incidence of Iatrogenic Ureteral Injury During Open and Laparoscopic Colorectal Surgery: A Single Center Experience and Review of the Literature.

INTRODUCTION: Iatrogenic ureteral injury is a rare but potentially devastating complication of colorectal surgery. We evaluated the incidence and management of iatrogenic ureteral injuries in colorectal surgery during the transition phase from open to laparoscopic surgery. MATERIALS AND METHODS: We conducted a retrospective single center study. All patients who underwent colorectal surgery between 2004 and 2014 were evaluated by collecting data of electronic patient charts. Both acute and elective procedures were included. RESULTS: A total of 3302 colorectal procedures were performed in the study period. Of these, 2817 operations were performed open and 484 laparoscopically. A total of 23 iatrogenic ureteral injuries were identified, of which 5 were found during laparoscopic surgery. The cumulative incidence of ureteral injuries was 0.6% for open procedures and 1.0% for laparoscopic procedures. CONCLUSIONS: Ureteral injury is a rare complication of colorectal surgery. The incidence might rise with the increasing use of laparoscopy.

[A man with pelvic pain]. / Een man met pijn in het bekken.

A 29-year-old male patient was involved in a crush injury of the right pelvis. Trauma screening showed a right-sided fracture of the pubic bone. CT imaging of the abdomen showed an urethral rupture with cranial displacement of the bladder, the so-called 'pie in the sky' sign.

Sacral neuromodulation in patients with idiopathic overactive bladder after initial botulinum toxin therapy.

PURPOSE: We evaluated whether patients with overactive bladder and incontinence who discontinued intravesical botulinum toxin therapy can be successfully treated with sacral neuromodulation. MATERIALS AND METHODS: All patients who were referred to our center after discontinuation of botulinum toxin-A between 2005 and 2010 were included in this observational study. All patients underwent test stimulation with sacral neuromodulation and were evaluated with voiding diaries. Success was defined as more than 50% improvement in leakage episodes. Successful test stimulation was subsequently followed by a definitive implant. Patient satisfaction with sacral neuromodulation therapy was evaluated 1 year after the definitive implant. RESULTS: A total of 20 patients were included in the study. Of these patients 17 (85%) had discontinued botulinum toxin-A because of lack of efficacy and 3 had been treated successfully with botulinum toxin-A but requested a more permanent solution. The mean interval between the botulinum toxin-A and the sacral neuromodulation test stimulation was 23 months. In 14 patients (70%) the test stimulation was successful and they received a definitive implant. Of the 14 patients 5 even showed a decrease of greater than 90% in leakage episodes. One year after implantation 11 patients (79%) were satisfied with the sacral neuromodulation treatment. CONCLUSIONS: Despite the small sample size, this study indicates that patients who are dissatisfied with or in whom botulinum toxin-A treatment fails can respond successfully to sacral neuromodulation. The success rate of the test stimulation was comparable to that of patients who have never been treated with botulinum toxin-A. The 1-year satisfaction rate was comparable that of patients without a history of botulinum toxin-A treatment.

[A woman with urinary tract infections and flank pain]. / Een vrouw met urineweginfecties en flankpijn.

A 52-year-old woman presented with recurrent urinary tract infections and flank pain. Both an abdominal CT-scan and a plain abdominal X-ray showed bilateral nephrocalcinosis and a kidney stone in the left ureter. These findings are suggestive of medullary sponge kidneys.

[Neuromodulation as a treatment for overactive bladder syndrome]. / Neuromodulatie voor overactieve-blaasklachten.

Neuromodulation is used as a treatment for overactive bladder syndrome, if conservative management is ineffective or only partially effective. Sacral neuromodulation is now a minimally invasive treatment as a result of improvements in surgical technique, and it has good long-term results. Nevertheless the risk of complications such as pain and decreasing effect is still present. Developments in alternative neuromodulation treatments, such as posterior tibial nerve stimulation, pudendal nerve stimulation and intravesical injection therapy with botulinum neurotoxin, have extended the role of neuromodulation. Intravesical injection therapy with botulinum toxin, along with sacral neuromodulation, has been included in the treatment algorithm of overactive bladder syndrome if this does not respond to conservative therapy. When choosing for a neuromodulation therapy, the side-effects and complications of the treatments should be considered alongside the specific patient situation and evidence for effectiveness and long-term effectiveness.

Sacral neuromodulation for lower urinary tract dysfunction.

OBJECTIVES: To review the technique, indications, results and working mechanisms of sacral neuromodulation (SNM) for lower urinary tract dysfunction. METHODS: The available literature on SNM for lower urinary tract dysfunction was searched. Based on the information available in the literature and also based on personal experience, the urological indications, technique, mechanisms of action and results of SNM are presented and discussed. RESULTS: SNM for lower urinary tract dysfunction involves stimulation of the 3rd sacral nerve with an electrode implanted in the sacral foramen and connected to a pulse generator. The technique is accepted by the FDA since 1997. Currently, SNM for lower urinary tract dysfunction has been successfully used in about 26,000 patients with various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. The actual procedure of SNM consists of a minimal invasive technique and is effective in about 70% of the patients who have been implanted with a permanent system. Also, in pelvic pain, interesting results have been described. SNM modulates the micturition reflexes at different levels in the central nervous system. CONCLUSIONS: Sacral neuromodulation is a safe and effective therapy for various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. It should be the first choice after failure of maximal conservative therapy.

Psychological and psychiatric factors as predictors for success in sacral neuromodulation treatment.

UNLABELLED: What's known on the subject? and What does the study add? Sacral neuromodulation (SNM) is a well-established treatment for patients with chronic LUTS. The selection of eligible candidates could be improved by identifying factors that can predict a successful response. In the present study, we evaluated the role of various psychological and psychiatric factors in relation to SNM treatment. OBJECTIVE: • To evaluate if psychological and psychiatric factors can predict the outcome of test stimulation or permanent treatment with sacral neuromodulation (SNM). PATIENTS AND METHODS: • Between 2006 and 2009, patients with overactive bladder syndrome or non-obstructive urinary retention who were eligible for test stimulation were included. • All patients completed the Amsterdam Biographic Questionnaire (ABQ), which measures the personality traits of the patient, and the Symptom Check-List-90-Revised (SCL-90-R), which is a screening instrument for neuroticism, and for current level of complaints. • The results of the questionnaires were compared with the outcomes of test stimulation and permanent treatment. • In addition to the questionnaires, we also included the psychiatric history as a potential predictive factor. RESULTS: • On univariate analysis there was no relationship between the psychological characteristics and the outcome of test stimulation or the occurrence of adverse events (AEs) with permanent treatment. • A history of psychiatric disease was not related to the outcome of test stimulation, but was shown to be a positive predictor for the occurrence of AEs with permanent SNM treatment. CONCLUSIONS: • In the present study there was no evidence that psychological screening with the ABQ or SCL-90-R can predict the outcome of SNM treatment. • Patients with a medical history of psychiatric disease appear to be more likely to encounter AEs with permanent SNM treatment.

The effect of pulse rate changes on the clinical outcome of sacral neuromodulation.

PURPOSE: We evaluated the effect of pulse rate changes on the clinical response to and stimulation related pain symptoms of sacral neuromodulation treatment. MATERIALS AND METHODS: In this pilot study we evaluated the effect of 4 pulse rates, including 5.2, 10, 21 and 40 Hz, in patients with a suboptimal response to sacral neuromodulation. The effect of each frequency was evaluated during a 6-day test period. To avoid the carryover effect stimulation was discontinued for 24 hours between consecutive test periods. On the last 3 days of each test period a voiding diary and questionnaire were completed. Changes in the clinical response and pain symptoms were compared between the 4 pulse rates using multivariate analysis. RESULTS: Of the 50 patients included in the study 40 (80%) were female. Mean ± SD age was 55.5 ± 12.3 years. Of the patients 41 (82%) had overactive bladder symptoms and 9 (18%) were in chronic nonobstructive urinary retention. No significant difference was found in clinical outcome on the voiding diary and questionnaire between the pulse rates and none of the 4 rates was significantly related to sacral neuromodulation associated pain. However, individuals appeared to benefit from changing the pulse rate in terms of treatment efficacy and stimulation related pain. CONCLUSIONS: On the group level none of the 4 pulse rates appeared to have a significantly different effect on clinical outcome or sacral neuromodulation related pain. However, an individualized approach to optimize treatment efficacy by changing the pulse rate appears to be useful.

The use of bilateral sacral nerve stimulation in patients with loss of unilateral treatment efficacy.

PURPOSE: We evaluated whether bilateral sacral nerve stimulation can be effective to restore treatment efficacy in patients in whom unilateral sacral neuromodulation fails. MATERIALS AND METHODS: Patients in whom unilateral sacral neuromodulation failed were included in analysis. The percutaneous nerve evaluation test was used to evaluate the effect of contralateral and bilateral stimulation. The stimulation electrode was placed in the contralateral S3 foramen and symptoms were self-recorded using a 3-day voiding diary. Clinical success was defined as more than 50% improvement in at least 1 relevant voiding diary parameter vs baseline. RESULTS: The 15 study patients underwent test stimulation with percutaneous nerve evaluation. In 3 patients lead migration was suspected and, thus, they were not included in analysis. Four of the remaining 12 patients had a successful response to percutaneous nerve evaluation, of whom 3 were eventually implanted with a contralateral lead. After 12 months of treatment 2 of the 3 patients had a successful outcome. CONCLUSIONS: In this pilot study only a select group of patients appeared to benefit from bilateral stimulation after unilateral therapy failure. Further investigation is needed to determine the predictive factors and cost-effectiveness of this treatment.

Satisfaction and patient experience with sacral neuromodulation: results of a single center sample survey.

PURPOSE: We systematically assessed long-term satisfaction and patient experience with sacral nerve modulation therapy. MATERIALS AND METHODS: All patients who received sacral neuromodulation between 1990 and 2007 at our center and who still had the implant were included in the survey. All received a postal questionnaire regarding satisfaction and experiences with the system, such as side effects, complications, burden, impact on sexuality and defecation changes. RESULTS: Of the 275 questionnaires sent 207 were returned for a 75% response rate. The population was 83% female. Overall treatment was done for overactive bladder syndrome, nonobstructive urinary retention, combined overactive bladder and retention, and pelvic pain in 55%, 24%, 20% and 1% of patients, respectively. Overall satisfaction with sacral neuromodulation was high at 90%. No correlations were found between the satisfaction rate, and pretreatment age, gender, complaint type, sexual dysfunction or therapy duration. However, 56% of patients reported side effects, such as pain at the internal nerve stimulator site and due to stimulation. However, 89% of these patients did not seek further therapy. Of patients with additional defecation problems 47% experienced relief of complaints. CONCLUSIONS: This study shows a high satisfaction rate in patients with sacral neuromodulation. There was no relation between patient age, complaint type, therapy duration or side effects and the satisfaction rate. The number of side effects was limited but further analysis in prospective cohorts should identify patients who are likely to have side effects or stop sacral neuromodulation treatment.

Long-term results of sacral neuromodulation with the tined lead procedure.

PURPOSE: We present long-term followup data on the outcome of sacral neuromodulation using the tined lead procedure. MATERIALS AND METHODS: We conducted a single center study including all patients who received an implantable neurostimulator between 2002 and 2005 using the tined lead technique. Treatment efficacy was evaluated by comparing the data of a 3-day voiding diary filled out in May 2009 to the data before the onset of sacral neuromodulation treatment (baseline). Clinical success was defined as more than 50% improvement in at least 1 of the relevant voiding diary parameters. RESULTS: A total of 64 patients underwent implantation with an implantable neurostimulator using the tined lead procedure. Mean followup was 53 months (range 35 to 77). Five patients died of causes unrelated to sacral neuromodulation and they were not included in analysis. The implantable neurostimulator was removed from 7 patients and 3 stopped using the neurostimulator. Voiding diary analysis showed that 38 of 59 patients (64%) were successfully treated. There were 21 patients (33%) who underwent a surgical revision due to an adverse event and 1 (1.6%) who underwent lead revision because of suspected lead migration. CONCLUSIONS: Sacral neuromodulation with the tined lead procedure is a safe and effective treatment for patients with overactive bladder symptoms or urinary retention.