Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors.

Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy. However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses. Therefore, there is an unmet need for novel therapeutic agents with improved efficacy and minimal long-term side effects. Recent advances in the development of immunotherapeutic agents, particularly immune checkpoint inhibitors (ICIs), have offered an opportunity to test their activity in various tumor types, including GCTs. This review aims to analyze the immune microenvironment of these tumors and present the most recently available data from studies that have tested immunotherapeutic agents against GCTs. The majority of the available knowledge derives from case reports or small cohort studies, particularly those involving ICIs of the PD-1/PD-L1 axis alone or in combination with anti-CTLA-4 monoclonal antibodies. Other immunotherapeutic targeted approaches, including antibody-drug conjugates, antibody prodrugs, vaccines, tyrosine kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapy, have biological rationales and have shown preliminary activity or are currently being tested. Growing evidence on these and other approaches will assist in broadening the currently limited treatment armamentarium against platinum-refractory TGCTs.

The Impact of Enhanced Recovery after Surgery Protocol Implementation on Postoperative Pain Management in the Era of Opioid Crisis: The Postchemotherapy Open RPLND Experience.

AIM: Enhanced Recovery After Surgery (ERAS) protocols have been proven to optimize postoperative outcomes; however, misuse of opioid analgesics can still hinder postoperative recovery due to related side effects and potential complications. INTRODUCTION: To determine if the implementation of ERAS protocol in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) patients could help with reducing postoperative pain and opioid use. METHODS: A case-control study of consecutive testicular cancer patients with indications for PCRLPND, who were offered Conventional Post-operative Management (CPM) or ERAS protocol. Outcomes of interest included Visual Analogue Scale (VAS)-assessed pain level at postoperative days 3, 7, and 30, and Morphine-Equivalent Doses (MEDs)/postoperative day. Intraoperative parameters and postoperative complications were recorded. Parametric and non-parametric tests were used for statistical analysis. RESULTS: In total, 100 opioid-naïve PC-RPLND patients were studied. CPM and ERAS groups (36 and 64 patients, respectively) had similar demographic and baseline clinical characteristics). ERAS group patients had significantly lower blood loss (p = 0.005), blood transfusion rate (p < 0.001), and duration of the procedure (p < 0.001). Post-operative complications were comparable between groups. Nausea and bowel disorders were numerically but not statistically more frequent in the CPM group. ERAS patients had shorter mean hospital stay (5.3 ± 1.4 vs. 7.4 ± 1.6 days, p < 0.001), lower daily MEDs (4.73 ± 2.63 vs. 7.04 ± 2.29, p < 0.001), and lower VAS scores on post-operative day 7 (3.89 ± 1.07 vs. 4.67 ± 1.17, p = 0.001). Post-operative pain was similar between groups on post-operative days 3 and 30. CONCLUSION: Systematic implementation of ERAS protocol after PC-RPLND improves pain management, optimizes patient recovery, and prevents over-prescription of opioid analgesics.

Is a Course of Intermittent Self-dilatation with Topical Corticosteroids Superior at Stabilising Urethral Stricture Disease in Men and Improving Functional Outcomes over a Course of Intermittent Self-dilatation Alone? A Systematic Review and Meta-analysis.

Context: Intermittent self-dilatation (ISD) is a therapeutic strategy used to stabilise a urethral stricture and postpone or avoid further treatment. Adding corticosteroids to this mode of management might further enhance its outcomes by downregulation of collagen deposition and excessive scar tissue formation. Objective: To explore whether a course of ISD with topical corticosteroids is superior at stabilising urethral stricture disease in men and improving functional outcomes over a course of ISD alone. Evidence acquisition: This systematic review and meta-analysis was undertaken by the European Association of Urology Urethral Strictures Guideline Panel according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (CRD42021256744). The primary benefit outcome was successful stabilisation of the urethral stricture. Treatment-related complications were the primary harm outcome. Evidence synthesis: In total, 978 records were screened for eligibility, ultimately leading to five included studies, all randomised controlled trials, comprising 250 patients, of whom 124 underwent a course of ISD with corticosteroids and 126 underwent a course of ISD alone, all after direct vision internal urethrotomy (DVIU). Successful stabilisation of the stricture was achieved in 77% and 64% of patients in the group with and without corticosteroids, respectively (p = 0.04). No extra complications related to the addition of corticosteroids to the ISD regimen were reported. The risk of bias of the included studies was generally unclear to high. Conclusions: Based on the currently available data, a course of ISD with topical corticosteroids appears to be safe and superior at stabilising a urethral stricture after DVIU in the short term to a course of ISD alone. However, given the unclear to high risk of bias in the included studies, further high-quality studies are needed to fully underpin this. Patient summary: This study shows that addition of topical corticosteroids to intermittent self-dilatation after direct vision internal urethrotomy can better stabilise the stricture in the short term.

Unanswered questions in prostate cancer - findings of an international multi-stakeholder consensus by the PIONEER consortium.

PIONEER is a European network of excellence for big data in prostate cancer consisting of 37 private and public stakeholders from 9 countries across Europe. Many progresses have been done in prostate cancer management, but unanswered questions in the field still exist, and big data could help to answer these questions. The PIONEER consortium conducted a two-round modified Delphi survey aiming at building consensus between two stakeholder groups - health-care professionals and patients with prostate cancer - about the most important questions in the field of prostate cancer to be answered using big data. Respondents were asked to consider what would be the effect of answering the proposed questions on improving diagnosis and treatment outcomes for patients with prostate cancer and to score these questions on a scale of 1 (not important) to 9 (critically important). The mean percentage of participants who scored each of the proposed questions as critically important was calculated across the two stakeholder groups and used to rank the questions and identify the highest scoring questions in the critically important category. The identification of questions in prostate cancer that are important to various stakeholders will help the PIONEER consortium to provide answers to these questions to improve the clinical care of patients with prostate cancer.

First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility.

OBJECTIVES: To gain insights into the technical feasibility of maternal spindle transfer (MST) applied in the context of repeated in vitro fertilization (IVF) failures for the treatment of idiopathic infertility. DESIGN: A prospective pilot study. SETTING: IVF center. PATIENT(S): Twenty-five infertile couples with multiple previous unsuccessful IVF cycles (range, 3-11), no previous pregnancy, and no history of mitochondrial DNA (mtDNA) disease participated. The study focused on women <40 years, with previous IVF attempts characterized by a pattern of low fertilization rates and/or impaired embryo development. Couples with severe male-factor infertility were not eligible. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice. INTERVENTION(S): We performed MST by transferring metaphase II spindles from the patients' oocytes into the previously enucleated donor oocytes, followed by intracytoplasmic sperm injection, in vitro embryo culture, blastocyst biopsy, and vitrification. Only euploid blastocysts were considered for embryo transfer. MAIN OUTCOME MEASURE(S): Outcome measures included oocyte fertilization, blastocyst development, clinical pregnancy and live birth, incidence of mitochondrial carryover and potential mtDNA reversal, as well as general health of the children born. RESULT(S): Twenty-eight MST cycles produced 6 children (19 embryo transfers, 7 clinical pregnancies). Pediatric follow-up of the children, performed at intervals from birth to 12-24 months of age, revealed their development to be unremarkable. DNA fingerprinting confirmed that the nuclear DNA of MST children was inherited from both parents, without any contribution from the oocyte donor. For 5 of the children, mtDNA was derived almost exclusively (>99%) from the donor. However, 1 child, who had similarly low mtDNA carryover (0.8%) at the blastocyst stage, showed an increase in the maternal mtDNA haplotype, accounting for 30% to 60% of the total at birth. CONCLUSION(S): This pilot study provides the first insights into the feasibility of applying MST for patients with idiopathic infertility and repeated IVF failures. Reconstructed oocytes produced embryos capable of implanting, developing to term and producing apparently healthy newborns/children. However, claims concerning the efficacy of MST with respect to infertility treatment would be premature considering the limitations of this study. Importantly, mtDNA reversal was detected in one child born after MST, a finding with possible implications for mitochondrial replacement therapies. CLINICAL TRIAL REGISTRATION NUMBER: Pilot trial registry number, ISRCTN11455145. The date of registration: 20/02/2018. The date of enrolment of the first patients: 18/03/2018.

Radiological features characterising indeterminate testes masses: a systematic review and meta-analysis.

CONTEXT: The use of scrotal ultrasonography (SUS) has increased the detection rate of indeterminate testicular masses. Defining radiological characteristics that identify malignancy may reduce the number of men undergoing unnecessary radical orchidectomy. OBJECTIVE: To define which SUS or scrotal magnetic resonance imaging (MRI) characteristics can predict benign or malignant disease in pre- or post-pubertal males with indeterminate testicular masses. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with Cochrane Collaboration guidance. Medline, Embase, Cochrane controlled trials and systematic reviews databases were searched from (1970 to 26 March 2021). Benign and malignant masses were classified using the reported reference test: i.e., histopathology, or 12 months progression-free radiological surveillance. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). EVIDENCE SYNTHESIS: A total of 32 studies were identified, including 1692 masses of which 28 studies and 1550 masses reported SUS features, four studies and 142 masses reported MRI features. Meta-analysis of different SUS (B-mode) values in post-pubertal men demonstrated that a size of ≤0.5 cm had a significantly lower odds ratio (OR) of malignancy compared to masses of >0.5 cm (P < 0.001). Comparison of masses of 0.6-1.0 cm and masses of >1.5 cm also demonstrated a significantly lower OR of malignancy (P = 0.04). There was no significant difference between masses of 0.6-1.0 and 1.1-1.5 cm. SUS in post-pubertal men also had a statistically significantly lower OR of malignancy for heterogenous masses vs homogenous masses (P = 0.04), hyperechogenic vs hypoechogenic masses (P < 0.01), normal vs increased enhancement (P < 0.01), and peripheral vs central vascularity (P < 0.01), respectively. There were limited data on pre-pubertal SUS, pre-pubertal MRI and post-pubertal MRI. CONCLUSIONS: This meta-analysis identifies radiological characteristics that have a lower OR of malignancy and may be of value in the management of the indeterminate testis mass.

The impact of low-pressure pneumoperitoneum on robotic-assisted radical cystectomy and intracorporeal ileal conduit urinary diversion: a case-control study.

PURPOSE: To evaluate the role of low intra-abdominal pressure (IAP) in improving postoperative recovery in Robotic-assisted radical cystectomy (RARC) and intracorporeal ileal conduit urinary diversion (ICUD). METHODS: A retrospective case-control study of 49 bladder cancer patients offered RARC/ICUD with standard (12 mmHg, n = 24) or low IAP (8 mmHg, n = 25). Outcomes of interest included length of procedure (LoP), estimated blood loss (EBL), blood transfusion, margin positivity rates, time to first flatus (TtFF), time to first bowel movement (TtFBM), ileus and small bowel obstruction (SBO) rates, time to safe discharge (TtSD), postoperative hospital stay (PHS) and pain levels on a postoperative day (POD) 1 and 3. Perioperative complications were recorded using the Clavien-Dindo system. RESULTS: Demographic and baseline clinical characteristics, LoP, EBL and margin positivity rates were similar between groups. No transfusions were recorded. Median (IQR) TtFF, TtFBM and TtSD were significantly longer in Group 1 vs Group 2 (4 (1) vs 2 (1), 7 (3) vs 6 (2) and 8.5 (5.75) vs 5.0 (1), respectively). PHS and rates of postoperative ileus and SBO were lower in Group 2, however not statistically significant. Severe pain was uncommon in both groups but moderate/severe pain was significantly higher in Group 1 (95.8% vs 48% on POD1 and 62.5% vs 16% on POD3). No significant intraoperative complications were recorded and ≥ Grade 3 postoperative complications at 30 and 90 days were similar. CONCLUSION: With limitations, Low-IAP RARC can be safely offered to RARC/ICUD patients and leads to faster bowel recovery, and shorter time to safe discharge compared to standard pneumoperitoneum.

Randomised controlled trial comparing the clinical and cost-effectiveness of various washout policies versus no washout policy in preventing catheter associated complications in adults living with long-term catheters: study protocol for the CATHETER II study.

BACKGROUND: Various washout policies are widely used in adults living with long-term catheters (LTC). There is currently insufficient evidence on the benefits and potential harms of prophylactic LTC washout policies in the prevention of blockages and other LTC-related adverse events, such as urinary tract infections. CATHETER II tests the hypothesis that weekly prophylactic LTC washouts (normal saline or citric acid) in addition to standard LTC care reduce the incidence of catheter blockage requiring intervention compared to standard LTC care only in adults living with LTC. METHODS: CATHETER II is a pragmatic three-arm open multi-centre superiority randomised controlled trial with an internal pilot, economic analysis, and embedded qualitative study. Eligible participants are adults aged ≥ 18 years, who have had a LTC in use for ≥ 28 days, have no plans to discontinue the use of the catheter, are able to undertake the catheter washouts, and complete trial documentation or have a carer able to help them. Participants are identified from general practitioner practices, secondary/tertiary care, community healthcare, care homes, and via public advertising strategies. Participants are randomised 1:1:1 to receive a weekly saline (0.9%) washout in addition to standard LTC care, a weekly citric acid (3.23%) washout in addition to standard LTC care or standard LTC care only. Participants and/or carers will receive training to administer the washouts. Patient-reported outcomes are collected at baseline and for 24 months post-randomisation. The primary clinical outcome is catheter blockage requiring intervention up to 24 months post-randomisation expressed per 1000 catheter days. Secondary outcomes include symptomatic catheter-associated urinary tract infection requiring antibiotics, catheter change, adverse events, NHS/ healthcare use, and impact on quality of life. DISCUSSION: This study will guide treatment decision-making and clinical practice guidelines regarding the effectiveness of various prophylactic catheter washout policies in men and women living with LTC. This research has received ethical approval from Wales Research Ethics Committee 6 (19/WA/0015). TRIAL REGISTRATION: ISRCTN ISRCTN17116445 . Registered prospectively on 06 November 2019.

What is the role of single-stage oral mucosa graft urethroplasty in the surgical management of lichen sclerosus-related stricture disease in men? A systematic review.

PURPOSE: The benefits and harms of the available types of surgical management for lichen sclerosus-related (LS) strictures remain unclear and, thus, clear and robust clinical practice recommendations cannot be given. MATERIALS AND METHODS: To assess the role of single-stage OMGU in the management of LS strictures and explore how its benefits and harms compare with the alternative management options. Medline, Embase and Cochrane controlled trial databases (CENTRAL, CDSR) were systematically searched. Randomized (RCTs) and nonrandomized studies (NRCSs) comparing single-stage OMGU with other surgical management options for LS strictures and single-arm studies on single-stage OMGU were included. Risk of bias (RoB) was assessed. RESULTS: Of the 1912 abstracts identified, 15 studies (1 NRCS and 14 single-arm studies) were included, recruiting in total 649 patients. All studies were at high RoB. In the only NRCS available, stricture-free rate (SFR) for single-stage and staged OMGU was 88% vs 60%, respectively (p = 0.05), at a mean follow-up of 66.5 months. SFR range for single-stage OMGU in single-arm studies was 65-100% (mean/median follow-up, 12-59 months). Single-stage OMGU had low complication rates and beneficial impact on LUTS and QoL. CONCLUSIONS: The present SR highlights the methodological limitations of the available literature. In the absence of adverse local tissue conditions, and taking into consideration benefit-harm balance and surgeon's skills and expertise, single-stage OMGU can be justified in patients with LS strictures.

European Association of Urology Guidelines on Urethral Stricture Disease Part 3: Management of Strictures in Females and Transgender Patients.

CONTEXT: Urethral stricture management guidelines are an important tool for guiding evidence-based clinical practice. OBJECTIVE: To present a summary of the 2021 version of the European Association of Urology (EAU) guidelines on management of urethral strictures in females and transgender patients. EVIDENCE ACQUISITION: The panel performed a literature review on these topics covering a time frame between 2008 and 2018 and used predefined inclusion and exclusion criteria for study selection. Key papers beyond this time period could be included as per panel consensus. A strength rating for each recommendation was added based on the review of the available literature and after panel discussion. EVIDENCE SYNTHESIS: Management of urethral strictures in females and transgender patients has been described in a few case series in the literature. Endoluminal treatments can be used for short, nonobliterative strictures in the first line. Repetitive endoluminal treatments are not curative. Urethroplasty encompasses a multitude of techniques and adaptation of the technique to the local conditions of the stricture is crucial to obtain durable patency rates. CONCLUSIONS: Management of urethral strictures in females and transgender patients is complex and a multitude of techniques are available. Selection of the appropriate technique is crucial and these guidelines provide relevant recommendations. PATIENT SUMMARY: Although different techniques are available to manage narrowing of the urethra (called a stricture), not every technique is appropriate for every type of stricture. These guidelines, developed on the basis of an extensive literature review, aim to guide physicians in selecting the appropriate technique(s) to treat a specific type of urethral stricture in females and transgender patients. TAKE HOME MESSAGE: Although different techniques are available to manage urethral strictures, not every technique is appropriate for every type of stricture. Management of urethral strictures in females and transgender patients is complex and a multitude of techniques are available. Selection of the appropriate technique is crucial and these guidelines provide relevant recommendations.

European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility.

CONTEXT: The European Association of Urology (EAU) has updated its guidelines on sexual and reproductive health for 2021. OBJECTIVE: To present a summary of the 2021 version of the EAU guidelines on sexual and reproductive health, including advances and areas of controversy in male infertility. EVIDENCE ACQUISITION: The panel performed a comprehensive literature review of novel data up to January 2021. The guidelines were updated and a strength rating for each recommendation was included that was based either on a systematic review of the literature or consensus opinion from the expert panel, where applicable. EVIDENCE SYNTHESIS: The male partner in infertile couples should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors causing fertility impairment. Infertile men are at a higher risk of harbouring and developing other diseases including malignancy and cardiovascular disease and should be screened for potential modifiable risk factors, such as hypogonadism. Sperm DNA fragmentation testing has emerged as a novel biomarker that can identify infertile men and provide information on the outcomes from assisted reproductive techniques. The role of hormone stimulation therapy in hypergonadotropic hypogonadal or eugonadal patients is controversial and is not recommended outside of clinical trials. Furthermore, there is insufficient evidence to support the widespread use of other empirical treatments and surgical interventions in clinical practice (such as antioxidants and surgical sperm retrieval in men without azoospermia). There is low-quality evidence to support the routine use of testicular fine-needle mapping as an alternative diagnostic and predictive tool before testicular sperm extraction (TESE) in men with nonobstructive azoospermia (NOA), and either conventional or microdissection TESE remains the surgical modality of choice for men with NOA. CONCLUSIONS: All infertile men should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors. Increasing data indicate that infertile men are at higher risk of cardiovascular mortality and of developing cancers and should be screened and counselled accordingly. There is low-quality evidence supporting the use of empirical treatments and interventions currently used in clinical practice; the efficacy of these therapies needs to be validated in large-scale randomised controlled trials. PATIENT SUMMARY: Approximately 50% of infertility will be due to problems with the male partner. Therefore, all infertile men should be assessed by a specialist with the expertise to not only help optimise their fertility but also because they are at higher risk of developing cardiovascular disease and cancer long term and therefore require appropriate counselling and management. There are many treatments and interventions for male infertility that have not been validated in high-quality studies and caution should be applied to their use in routine clinical practice.

European Association of Urology Guidelines on Urethral Stricture Disease (Part 1): Management of Male Urethral Stricture Disease.

OBJECTIVE: To present a summary of the 2021 version of the European Association of Urology (EAU) guidelines on management of male urethral stricture disease. EVIDENCE ACQUISITION: The panel performed a literature review on these topics covering a time frame between 2008 and 2018, and used predefined inclusion and exclusion criteria for the literature to be selected. Key papers beyond this time period could be included as per panel consensus. A strength rating for each recommendation was added based on a review of the available literature and after panel discussion. EVIDENCE SYNTHESIS: Management of male urethral strictures has extensively been described in literature. Nevertheless, few well-designed studies providing high level of evidence are available. In well-resourced countries, iatrogenic injury to the urethra is one of the most common causes of strictures. Asymptomatic strictures do not always need active treatment. Endoluminal treatments can be used for short, nonobliterative strictures at the bulbar and posterior urethra as first-line treatment. Repetitive endoluminal treatments are not curative. Urethroplasty encompasses a multitude of techniques, and adaptation of the technique to the local conditions of the stricture is crucial to obtain durable patency rates. CONCLUSIONS: Management of male urethral strictures is complex, and a multitude of techniques are available. Selection of the appropriate technique is crucial, and these guidelines provide relevant recommendations. PATIENT SUMMARY: Injury to the urethra by medical interventions is one of the most common reasons of male urethral stricture disease in well-resourced countries. Although different techniques are available to manage urethral strictures, not every technique is appropriate for every type of stricture. These guidelines, developed based on an extensive literature review, aim to guide physicians in the selection of the appropriate technique(s) to treat a specific type of urethral stricture.

European Association of Urology Guidelines on Urethral Stricture Disease (Part 2): Diagnosis, Perioperative Management, and Follow-up in Males.

CONTEXT: Urethral stricture management guidelines are an important tool for guiding evidence-based clinical practice. OBJECTIVE: To present a summary of the 2021 European Association of Urology (EAU) guidelines on diagnosis, classification, perioperative management, and follow-up of male urethral stricture disease. EVIDENCE ACQUISITION: The panel performed a literature review on the topics covering a time frame between 2008 and 2018, and using predefined inclusion and exclusion criteria for the literature. Key papers beyond this time period could be included if panel consensus was reached. A strength rating for each recommendation was added based on a review of the available literature after panel discussion. EVIDENCE SYNTHESIS: Routine diagnostic evaluation encompasses history, patient-reported outcome measures, examination, uroflowmetry, postvoid residual measurement, endoscopy, and urethrography. Ancillary techniques that provide a three-dimensional assessment and may demonstrate associated abnormalities include sonourethrography and magnetic resonance urethrogram, although these are not utilised routinely. The classification of strictures should include stricture location and calibre. Urethral rest after urethral manipulations is advised prior to offering urethroplasty. An assessment for urinary extravasation after urethroplasty is beneficial before catheter removal. The optimal time of catheterisation after urethrotomy is <72 h, but is unclear following urethroplasty and depends on various factors. Patients undergoing urethroplasty should be followed up for at least 1 yr. Objective and subjective outcomes should be assessed after urethral surgeries, including patient satisfaction and sexual function. CONCLUSIONS: Accurate diagnosis and categorisation is important in determining management. Adequate perioperative care and follow-up is essential for achieving successful outcomes. The EAU guidelines provide relevant evidence-based recommendations to optimise patient work-up and follow-up. PATIENT SUMMARY: Urethral strictures have to be assessed adequately before planning treatment. Before surgery, urethral rest and infection prevention are advised. After urethral surgery, x-ray dye tests are advised before removing catheters to ensure that healing has occurred. Routine follow-up is required, including patient-reported outcomes. These guidelines aim to guide doctors in the diagnosis, care, and follow-up of patients with urethral stricture.

Free Graft Augmentation Urethroplasty for Bulbar Urethral Strictures: Which Technique Is Best? A Systematic Review.

CONTEXT: Four techniques for graft placement in one-stage bulbar urethroplasty have been reported: dorsal onlay (DO), ventral onlay (VO), dorsolateral onlay (DLO), and dorsal inlay (DI). There is currently no systematic review in the literature comparing these techniques. OBJECTIVE: To assess if stricture recurrence and secondary outcomes vary between the four techniques and to assess if one technique is superior to any other. EVIDENCE ACQUISITION: The EMBASE, MEDLINE, and Cochrane Systematic Reviews-Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane HTA, DARE, HEED) databases and ClinicalTrials.gov were searched for publications in English from 1996 onwards. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), observational studies (cohort, case-control/comparative, single-arm), and case series with ≥20 adult male participants were included. EVIDENCE SYNTHESIS: A total of 41 studies were included involving 3683 patients from one RCT, four NRCSs, and 36 case series. Owing to the overall low quality of the evidence, a narrative synthesis was performed. CONCLUSIONS: No single technique appears to be superior to another for bulbar free graft urethroplasty. Both DO and VO are suitable for bulbar augmentation urethroplasty, with a ≤20% recurrence rate over medium-term follow-up. No recommendations can be made regarding DI or DLO techniques owing to the paucity of evidence. Secondary outcomes including sexual function, and complications are infrequently reported. Recurrence rates deteriorate in the long term for both DO and VO procedures. PATIENT SUMMARY: We reviewed the evidence for four different skin-graft techniques used to repair narrowing of a section of the urethra (bulbar urethra, under the scrotum and perineum) in men. Two of the techniques seem to give consistent results, with recurrence rates lower than 20%. Recurrence rates increase over time, so patients should continue to monitor their symptoms. There is poorer reporting of other outcomes such as sexual function, urinary symptoms, and complications, and it is possible that these occur more frequently than the current data suggest.

Therapeutic Equivalence of a New Preparation of Liquid Levothyroxine with Tablets in Patients with Overt Primary Hypothyroidism.

BACKGROUND: A new liquid levothyroxine (LT4) dissolved in glycerol and water has recently been developed by a Greek pharmaceutical company (Uni-Pharma, Athens, Greece). OBJECTIVES: To evaluate the therapeutic equivalence of this new liquid LT4 preparation versus the already existing tablet formulation of the same manufacturer, in order to obtain approval by the Greek National Organization for Medicines. METHODS: This was a prospective, randomized, cross-over phase III study. The study included 50 patients (9 men and 41 non-pregnant women, with a mean age of 42.5 ± 12.5 years), with documented overt primary hypothyroidism. All subjects were well controlled on substitution therapy with various LT4 formulations. None of the patients had known LT4 malabsorption. The patients were randomized into 2 groups (A and B). The individuals of group A initially received T4® tablets for 10 ± 2 weeks and subsequently switched to T4® drops (100 µg/mL solution) at the same dose for another 10 ± 2 weeks. In group B, the reverse procedure was followed. Total T3 (T3), free T4 (fT4), and TSH were measured in all participants at enrollment and at the end of each 10 ± 2-week trial period. RESULTS: Out of the 50 recruited patients, 6 were lost to follow-up and 5 were excluded due to non-compliance with the study protocol. In the 39 patients who completed the study, the serum TSH levels after 10 ± 2 weeks of treatment either with T4® tablets or with T4® drops did not differ (1.759 ± 1.104 vs. 2.076 ± 1.334 mIU/L, mean ± SD). CONCLUSIONS: In hypothyroid patients, the new liquid LT4 preparation (T4® drops) is therapeutically equivalent to the tablet form (T4® tablets).

What influences adherence to guidance for postoperative instillation of intravesical chemotherapy to patients with bladder cancer?

OBJECTIVE: To understand the barriers and facilitators to single instillation of intravesical chemotherapy (SI-IVC) use after resection of non-muscle-invasive bladder cancer (NMIBC) in Scotland and England using a behavioural theory-informed approach. SUBJECTS AND METHODS: In a cross-sectional descriptive study of practices at seven hospitals, we investigated care pathways, policies, and interviewed 30 urology staff responsible for SI-IVC. We used the Theoretical Domains Framework (TDF) to organise our investigation and conducted deductive thematic analyses, while inductively coding emergent beliefs. RESULTS: Barriers to SI-IVC were present at different organisational levels and professional roles. In four hospitals, there was a policy to not instil SI-IVC in theatre. Six hospitals' staff reported delays in mitomycin C (MMC) ordering and/or local storage. Lack of training, skills and perceived workload affected motivation. Facilitators included access to modern instilling devices (four hospitals) and incorporating reminders in operation proforma (four hospitals). Performance targets (with audit and feedback) within a national governance framework were present in Scotland but not England. Differences in coordinated leadership, sharing best practices, and disliking being perceived as underperforming, were evident in Scotland. CONCLUSIONS: High-certainty evidence shows that SI-IVC, such as MMC, after NMIBC resection reduces recurrences. This evidence underpins international guidance. The number of eligible patients receiving SI-IVC is variable indicating suboptimal practice. Improving SI-IVC adherence requires modifications to theatre instilling policies, delivery and storage of MMC, staff training, and documentation. Centralising care, with bladder cancer expert leadership and best practices sharing with performance targets, likely led to improvements in Scotland. National quality improvement, incorporating audit and feedback, with additional implementation strategies targeted to professional role could improve adherence and patient outcomes elsewhere. This process should be controlled to clarify implementation intervention effectiveness.