The Benefits and Harms of Pharmacological Treatment for Postradiation Pelvic Pain: A Systematic Review by the European Association of Urology Chronic Pelvic Pain Panel with Recommendations for Clinical Practice.

Context: Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are acknowledged complications. Objective: The primary objective is to assess the clinical effectiveness and safety of pharmacological therapies on postradiation pelvic pain. Evidence acquisition: A systematic review of the use of different pharmacological treatments in the management of post-radiation pelvic pain was conducted (PROSPERO-ID: CRD42021249026). Comprehensive searches of EMBASE, Medline, and Cochrane library were performed for publications between January 1980 and April 2021. The primary outcomes were improvement in pain and adverse events following treatment. The secondary outcomes included quality of life, bowel function, and urinary function. Evidence synthesis: After screening 1514 abstracts, four randomised controlled trials were identified, enrolling 355 patients with bladder and anorectal subtypes of postradiotherapy chronic pelvic pain (CPP). A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis. A single study reported a significant reduction in pain after 6 mo in patients with bladder pain syndrome treated with hyaluronic acid or hyperbaric oxygen. Anorectal pain was reported to be reduced by the application of 4% formalin, but the use of hyperbaric oxygen in postradiotherapy anorectal pain remains controversial. Adverse event reporting was generally poor. Studies looking at medications used routinely in guidelines for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, and duloxetine, were absent or of poor quality when it came to postradiation pelvic pain. Conclusions: Beneficial effects of hyperbaric oxygen or formalin on pain, quality of life, and functional symptoms were seen in patients with certain CPP subtypes, but the current evidence level is too weak to allow recommendations about the use of any pharmacological treatment for postradiation pelvic pain. Patient summary: Different pharmacological treatments are used to treat pain after radiotherapy, but current studies are of insufficient quality to determine whether these should be recommended and many chronic pelvic pain subtypes are not covered. Further research is needed.

Myofascial Pelvic Pain: Best Orientation and Clinical Practice. Position of the European Association of Urology Guidelines Panel on Chronic Pelvic Pain.

CONTEXT: Despite the high prevalence of a myofascial pain component in chronic pelvic pain (CPP) syndromes, awareness and management of this component are lacking among health care providers. OBJECTIVE: To summarize the current state of the art for the management of myofascial pain in chronic primary pelvic pain syndromes (CPPPS) according to scientific research and input from experts from the European Association of Urology (EAU) guidelines panel on CPP. EVIDENCE ACQUISITION: A narrative review was undertaken using three sources: (1) information in the EAU guidelines on CPP; (2) information retrieved from the literature on research published in the past 3 yr on myofascial pelvic pain; and (3) expert opinion from panel members. EVIDENCE SYNTHESIS: Studies confirm a high prevalence of a myofascial pain component in CPPPS. Examination of the pelvic floor muscles should follow published recommendations to standardize findings and disseminate the procedure. Treatment of pelvic floor muscle dysfunction and pain in the context of CPP was found to contribute to CPP control and is feasible via different physiotherapy techniques. A multidisciplinary approach is the most effective. CONCLUSIONS: Despite its high prevalence, the myofascial component of CPP has been underevaluated and undertreated to date. Myofascial pain must be assessed in all patients with CPPPS. Treatment of the myofascial pain component is relevant for global treatment success. Further studies are imperative to reinforce and better define the role of each physiotherapy technique in CPPPS. PATIENT SUMMARY: Pain and inflammation of the body's muscle and soft tissues (myofascial pain) frequently occurs in pelvic pain syndromes. Its presence must be evaluated to optimize management for each patient. If diagnosed, myofascial pain should be treated.

The Benefits and Harms of Botulinum Toxin-A in the Treatment of Chronic Pelvic Pain Syndromes: A Systematic Review by the European Association of Urology Chronic Pelvic Pain Panel.

CONTEXT: Patients with chronic pelvic pain syndrome (CPPS) may have pain refractory to conventional management strategies. Botulinum toxin A (BTX-A) is a potential therapeutic option. OBJECTIVE: To evaluate the benefits and harms of BTX-A injections in the treatment of CPPS. EVIDENCE ACQUISITION: A systematic review of the use of BTX-A in the treatment of CPPS was conducted (PROSPERO-ID: 162416). Comprehensive searches of EMBASE, PUBMED, Medline, and SCOPUS were performed for publications between January 1996 and May 2020. Identified studies were screened and selected studies assessed for quality prior to data extraction. The primary outcomes were improvement in pain and adverse events following treatment. Secondary outcomes included quality of life, global response assessment, sexual function, bowel function, and bladder function. EVIDENCE SYNTHESIS: After screening 1001 abstracts, 16 studies including 11 randomised controlled trials were identified, enrolling 858 patients and covering a range of CPPS subtypes. Most studies showed high risks of bias and confounding across all domains. A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis and calculation of pooled effect estimates of measured outcomes. BTX-A reduced pain significantly in patients with bladder pain syndrome in two studies and in patients with prostate pain syndrome in one study, but no included studies showed benefit for patients with gynaecological pelvic pain. Adverse event reporting was variable and generally poor, but no serious adverse events were described. CONCLUSIONS: Beneficial effects of BTX-A on pain, quality of life, and functional symptoms were seen in patients with certain CPPS subtypes, but the current evidence level is too weak to allow recommendations about BTX-A use for treating CPPS. PATIENT SUMMARY: Botulinum toxin A is used to treat different pain disorders, but current studies are of insufficient quality to determine whether it reduces pain and improves quality of life in patients with chronic pelvic pain. Further research is needed.

Management of chronic primary pelvic pain syndromes.

Management of chronic pelvic pain (CPP) remains a huge challenge for care providers and a major burden for healthcare systems. Treating chronic pain that has no obvious cause warrants an understanding of the difficulties in managing these conditions. Chronic pain has recently been accepted as a disease in its own right by the World Health Organization, with chronic pain without obvious cause being classified as chronic primary pain. Despite innumerable treatments that have been proposed and tried to date for CPP, unimodal therapeutic options are mostly unsuccessful, especially in unselected individuals. In contrast, individualised multimodal management of CPP seems the most promising approach and may lead to an acceptable situation for a large proportion of patients. In the present review, the interdisciplinary and interprofessional European Association of Urology Chronic Pelvic Pain Guideline Group gives a contemporary overview of the most important concepts to successfully diagnose and treat this challenging disease.

TRPM8 agonists modulate contraction of the pig urinary bladder.

The transient receptor potential melastin-8 (TRPM8) channel is activated by the "cooling" compounds menthol and icilin. Pathophysiologically, it is implicated in the overactive bladder and bladder cooling reflex, but the activity of TRPM8 in normal bladder physiology is poorly understood. We investigated the distribution of TRPM8 channels and the effect of TRPM8 agonists on the contractile function of pig bladder (n = 35) strips and whole bladders. The distribution of TRPM8 was examined by immunohistochemistry. The effect of vesical or intravascular menthol (0.1-0.3 mmol/L) or icilin (50 µmol/L) on carbachol-induced isolated whole bladder contractions was monitored by recording vesical pressure. Strips of denuded detrusor or mucosa were mounted in organ baths to study the effect of TRPM8 agonists on the contractile responses to 10 µmol/L carbachol. TRPM8-like immunoreactivity was detected on pig urothelium. Intravascular menthol (0.3 mmol/L) and icilin (50 µmol/L) significantly decreased the magnitude of carbachol-induced whole bladder contraction, whereas vesical administration significantly increased the response. In detrusor and mucosal strips, both menthol (0.3 mmol/L) and icilin (50 µmol/L) inhibited carbachol-induced contractions. We conclude that the TRPM8 channel is expressed on the urothelium of pig bladder. In the whole organ, exposure of the urothelium to menthol or icilin increases the contractile response to carbachol. Where detrusor muscle is exposed directly to these compounds, the contractile response to carbachol is reduced.

The penile tourniquet.

Tourniquets are commonly used in penile surgery to achieve a bloodless operating field or produce artificial erections intraoperatively. Several techniques have been described, but there is a paucity of data and a lack of guidelines to direct their safe use. In penile surgery, it is the local rather than systemic effects of tourniquet use that are the main concern. Tourniquet time should be kept to a minimum, as the limited data available suggests that reperfusion injury can occur even after short periods of ischaemia. High risk groups such as diabetics and arteriopaths are at particular risk. Further studies are needed to determine safe tourniquet times and pressures.

The validation of a functional, isolated pig bladder model for physiological experimentation.

Characterizing the integrative physiology of the bladder requires whole organ preparations. The purpose of this study was to validate an isolated large animal (pig) bladder preparation, through arterial and intravesical drug administration, intravesical pressure recording, and filming of surface micromotions. Female pig bladders were obtained from the local abattoir and arterially perfused in vitro. Arterial and intravesical pressures were recorded at varying volumes. Bladder viability was assessed histologically and by monitoring inflow and outflow pH. Arterial drug administration employed boluses introduced into the perfusate. Intravesical administration involved slow instillation and a prolonged dwell-time. Surface micromotions were recorded by filming the separation of surface markers concurrently with intravesical pressure measurement. Adequate perfusion to all bladder layers was achieved for up to 8 h; there was no structural deterioration nor alteration in inflow and effluent perfusate pH. Arterial drug administration (carbachol and potassium chloride) showed consistent dose-dependent responses. Localized movements (micromotions) occurred over the bladder surface, with variable correlation with fluctuations of intravesical pressure. The isolated pig bladder is a valid approach to study integrative bladder physiology. It remains viable when perfused in vitro, responds to different routes of drug administration and provides a model to correlate movements of the bladder wall directly to variation of intravesical pressure.

Success rates for learning intermittent self-catheterisation according to age and gender.

PURPOSE: Voiding dysfunction becomes increasingly prevalent with ageing. Clean intermittent self-catheterisation (ISC) is associated with a lower morbidity than indwelling transurethral or suprapubic catheterisation. However, doctors and patients sometimes fail to consider ISC as an option because of a perception it will be unmanageable or poorly tolerated. This study aimed to determine how age and gender affect the success rates of patients being taught ISC. METHODS: Six years retrospective study (January 2004-January 2010) of non-neurogenic patients referred to be taught ISC by urology specialist nurses in a tertiary referral hospital. Patients were sent information about ISC in advance of their appointment, were given additional information at the appointment, received training under supervision and had access to follow-on support. Successful patients were those who continued to perform the technique independently at 6-week follow-up. RESULTS: Three hundred and nine patients (209 men, 100 women) with a mean age of 63 years (range 17-95 years) were taught ISC during the study period and had documented follow-up. The main reasons for needing ISC were incomplete bladder emptying (46%), urethral stricture disease (20%) and inability to void (18%). The overall ISC success rate was 84% for all age groups, 86% for patients under the age of 65 and 82% for those aged 65 years and over. Men had a higher success rate than women (88 and 76%, respectively). CONCLUSIONS: Older patients can successfully be taught ISC in a high proportion, and it can be offered as an alternative to an indwelling catheter irrespective of age.

Increased patient information does not reduce patient anxiety regarding urodynamic studies.

OBJECTIVE: To establish if patient anxiety pre-urodynamic investigation can be reduced by providing more information within the patient information sheet (PIS). PATIENTS AND METHODS: Two prospective cohorts of consecutive patients (round 1, n = 98 and round 2, n = 94) were asked to complete a visual analogue scale (VAS) quantifying their anxiety prior to urodynamics (UDS) and again after UDS quantifying their anxiety of potentially repeating UDS. Patients in round 1 received the standard hospital PIS. Concurrently with round 1, a parallel group of patients (n = 95) completed a questionnaire regarding their experience of UDS and their post-UDS complications. This information was incorporated into a revised PIS used in round 2. RESULTS: In both rounds, the VAS reduced post-UDS (Wilcoxon matched-pairs test p < 0.001). In females, pre-UDS VAS was significantly higher in round 2 than round 1 (Mann-Whitney U test p = 0.037). In males, pre-UDS VAS was lower in round 2 than round 1, but this difference was not statistically significant (Mann-Whitney U test p = 0.112). Post-UDS VAS was remarkably similar between round 1 and 2. CONCLUSIONS: Patients are less anxious about having repeat UDS regardless of the depth of information provided. However, more detailed information before UDS failed to significantly reduce patient anxiety.

Emerging treatment options for benign prostatic obstruction.

Benign prostatic obstruction (BPO) affects an increasing number of men with age. It can cause troublesome lower urinary tract symptoms, can have a negative impact on quality of life, and may be associated with significant morbidity. Currently available medication and surgical treatments are limited by adverse events, invasiveness, and patient compliance. This has driven research into the pathogenesis of benign prostatic hyperplasia and led to the development of novel pharmacological agents and minimally invasive therapeutic interventions. This review highlights emerging treatment options for BPO.

Animal models in overactive bladder research.

Overactive bladder syndrome (OAB) is a symptom-based diagnosis characterised by the presence of urinary urgency. It is highly prevalent and overlaps with the presence of bladder contractions during urine storage, which characterises the urodynamic diagnosis of detrusor overactivity. Animal models are needed to understand the pathophysiology of OAB, but the subjective nature of the symptom complex means that interpretation of the findings in animals requires caution. Because urinary urgency cannot be ascertained in animals, surrogate markers such as frequency, altered toileting areas, and non-micturition contractions have to be used instead. No model can recapitulate the subjective, objective, and related factors seen in the clinical setting. Models used include partial bladder outlet obstruction, the spontaneous hypertensive rat, the hyperlipidaemic rat, various neurological insults and some gene knock-outs. Strengths and weaknesses of these models are discussed in the context of the inherent difficulties of extrapolating subjective symptoms in animals.

The role of invasive and non-invasive urodynamics in male voiding lower urinary tract symptoms.

INTRODUCTION: Troublesome voiding lower urinary tract symptoms (LUTS) are a common problem in men, particularly with ageing. Implicitly, management of voiding LUTS can be guided by accurate determination of underlying mechanisms, distinguishing men with voiding symptoms caused by outlet obstruction from those with reduced bladder contractility. METHODS: A PubMed search of the published literature on invasive and non-invasive methods used to assess lower urinary tract function was carried out. RESULTS: A multitude of methods have been applied to assess LUTS. Multichannel pressure flow studies (PFS) are the standard for diagnosing bladder outlet obstruction and underlying mechanisms of LUTS, though their invasive nature can be difficult to tolerate, and improved prediction of treatment outcome is disputed. Uroflowmetry and post void residual measurement are insufficient to make a definitive diagnosis. Ultrasound-derived measurements of bladder wall thickness and estimated bladder weight offer a potential non-invasive alternative to PFS, but their diagnostic parameters are still under evaluation. Non-invasive methods that measure isovolumetric bladder pressure by interrupting the urinary stream can reproducibly measure pressure and urinary flow, but are unable to determine the effects of abdominal straining during voiding and give no insight into urine storage symptoms. Doppler ultrasound during urethral flow is informative, but it is an expensive approach whose clinical utility has yet to be established. CONCLUSION: A variety of non-invasive urodynamic and non-urodynamic techniques have been used to evaluate LUTS and some show great promise. However, there is as yet, insufficient evidence to justify replacement of invasive voiding cystometry by these investigational approaches.

Prostate cancer and urinary incontinence.

Prostate cancer is the third most common cancer worldwide and an increasing proportion of men are being diagnosed with localised disease. Urinary incontinence is uncommon in healthy men, but may develop as a result of curative treatment for prostate cancer. The optimal therapy remains undefined so the treatment associated morbidity is an important determinant in patient choice. Urinary incontinence may also develop from tumour progression during deferred treatment, sphincter involvement in advanced disease or surgery for symptomatic malignant bladder outlet obstruction. As urinary incontinence is known to have a significant impact on health related quality of life, we have reviewed the literature on incontinence related to prostate cancer and its treatment.