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.

Benefits and Harms of Electrical Neuromodulation for Chronic Pelvic Pain: A Systematic Review.

CONTEXT: Patients with chronic pelvic pain (CPP) may have pain refractory to conventional pain management strategies. Neuromodulation could provide relief of pain. OBJECTIVE: To evaluate the benefits and harms of neuromodulation for CPP. EVIDENCE ACQUISITION: A comprehensive search of EMBASE, PUBMED, and SCOPUS was performed for the entire database to January 2018. Studies were selected, data were extracted, and quality was assessed by two independent reviewers. A meta-analysis was used to combine randomized controlled trials (RCTs); otherwise, a narrative analysis was used. EVIDENCE SYNTHESIS: After screening 1311 abstracts, 36 studies including eight RCTs were identified, enrolling 1099 patients. Studies covered a broad range in terms of phenotypes of CPP and methods of neuromodulation. A meta-analysis was possible for percutaneous tibial nerve stimulation and transcutaneous electrical nerve stimulation, which showed improvement in pain. Only narrative synthesis was possible for other modalities (sacral nerve stimulation, spinal cord stimulation, intravaginal electrical stimulation, and pudendal nerve stimulation) which appeared to reduce pain in patients with CPP. Treatments generally improved quality of life but with variable reporting of adverse events. Many studies showed high risks of bias and confounding. CONCLUSIONS: While electrical neuromodulation may improve symptoms in CPP, further work is needed with high-quality studies to confirm it. PATIENT SUMMARY: Neuromodulation may be useful in reducing pain and improving quality of life in patients with chronic pelvic pain, but more research is needed.

The prevalence and natural history of urinary symptoms among recreational ketamine users.

UNLABELLED: Study Type--Symptom prevalence (prospective cohort) Level of Evidence 1b. What's known on the subject? and What does the study add? Case series have described lower urinary tract symptoms associated with ketamine use including severe pain, frequency, haematuria and dysuria. Little is known regarding the frequency of symptoms, relationship of symptoms with dose and frequency of use and natural history of symptoms once the ketamine user has stopped. This study describes the prevalence of ketamine use in a population of recreational drug users in a dance music setting. It shows a dose-frequency relationship with ketamine use. It shows that urinary symptoms associated with recreational ketamine use may lead to a considerable demand on health resources in the primary-, secondary- and emergency-care settings. It shows that symptoms may improve once ketamine use is decreased. OBJECTIVE: • To investigate the prevalence and natural history of urinary symptoms in a cohort of recreational ketamine users. PATIENTS AND METHODS: • A purposeful sampling technique was used. • Between November 2009 and January 2010 participants were invited to undertake an on-line questionnaire promoted by a national dance music magazine and website. • Data regarding demographics and illicit drug-use were collected. • Among respondents reporting recent ketamine use, additional information detailing their ketamine use, experience of urinary symptoms and use of related healthcare services was obtained. RESULTS: • In all, 3806 surveys were completed, of which 1285 (33.8%) participants reported ketamine use within the last year. • Of the ketamine users, 17% were found to be dependent on the drug; 26.6% (340) of recent ketamine users reported experiencing urinary symptoms. • Urinary symptoms were significantly related to both dose of ketamine used and frequency of ketamine use. • Of 251 users reporting their experience of symptoms over time in relationship to their use of ketamine, 51% reported improvement in urinary symptoms upon cessation of use with only eight (3.8%) reporting deterioration after stopping use. CONCLUSIONS: • Urinary tract symptoms are reported in over a quarter of regular ketamine users. • A dose and frequency response relationship has been shown between ketamine use and urinary symptoms. • Both users and primary-care providers need to be educated about urinary symptoms that may arise in ketamine users. A multi-disciplinary approach promoting harm reduction, cessation and early referral is needed to manage individuals with ketamine-associated urinary tract symptoms to avoid progression to severe and irreversible urological pathologies.

Recreational ketamine: from pleasure to pain.

Ketamine has become increasingly recognized as a drug of recreational use. Individuals using significant amounts have developed symptoms including a small painful bladder, ureteric obstruction, papillary necrosis and hepatic dysfunction. The present paper examines the current literature on the relationship between ketamine use and these symptoms. Our own clinical experience and the data available clarify the causal relationship, and further data help to elucidate the mechanism of damage. On the basis of continued work and development with patients who are ketamine users we suggest an assessment and treatment regime that includes cessation of ketamine use and adequate analgesia to overcome symptoms. In conclusion, it is important for medical practitioners who encounter patients with these symptoms to ask about recreational drug use. Ketamine remains a safe and effective drug to use under appropriate medical supervision. Patients identified as suffering from this syndrome will need to be referred to a urological unit with an interest in the treatment of the condition.

Ketamine cystitis as a mimic of carcinoma in situ.

AIMS: To describe the histopathological features of a series of patients with ketamine-related cystitis. METHODS AND RESULTS: Seventeen patients with ketamine-related cystitis, who had undergone biopsy, were identified and reviewed. Twelve showed ulceration with significant urothelial atypia. In 10 of these, immunohistochemistry was performed; 9/10 had high p53 immunoreactivity and 7/10 had moderate to high levels of Ki67 reactivity, but all were negative for cytokeratin 20. CONCLUSIONS: Ketamine can lead to reactive urothelial changes that can mimic carcinoma in situ, but the long-term cancer risk remains unknown.