Safety and quality of cystectomy and pelvic lymph node dissection after neoadjuvant durvalumab and cisplatin/gemcitabine.

OBJECTIVE: To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle-invasive bladder cancer (MIBC) after neoadjuvant chemo-immunotherapy. PATIENTS AND METHODS: The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open-label single-arm phase II trial including 61 cisplatin-fit patients with clinical stage (c)T2-T4a cN0-1 operable urothelial MIBC or upper urinary tract cancer. Patients received neoadjuvant cisplatin/gemcitabine and durvalumab followed by surgery. Prospective quality assessment of surgeries was performed via central review of intraoperative photographs. Postoperative complications were assessed using the Clavien-Dindo Classification. Data were analysed descriptively. RESULTS: A total of 50 patients received RC and PLND. All patients received neoadjuvant chemo-immunotherapy. The median (interquartile range) number of lymph nodes removed was 29 (23-38). No intraoperative complications were registered. Grade ≥III postoperative complications were reported in 12 patients (24%). Complete nodal dissection (100%) was performed at the level of the obturator fossa (bilaterally) and of the left external iliac region; in 49 patients (98%) at the internal iliac region and at the right external iliac region; in 39 (78%) and 38 (76%) patients at the right and left presacral level, respectively. CONCLUSION: This study supports the surgical safety of RC and PLND following neoadjuvant chemo-immunotherapy in patients with MIBC. The extent and completeness of protocol-defined PLND varies between patients, highlighting the need to communicate and monitor the surgical template.

Prostatic Artery Embolisation Versus Transurethral Resection of the Prostate for Benign Prostatic Obstruction: 5-year Outcomes of a Randomised, Open-label, Noninferiority Trial.

BACKGROUND AND OBJECTIVE: Prostatic artery embolisation (PAE) and transurethral resection of the prostate (TURP) are two of the surgical options for treatment of lower urinary tract symptoms/benign prostatic obstruction (LUTS/BPO). Our aim was to compare the efficacy and safety of PAE and TURP for LUTS/BPO treatment at long-term follow-up. METHODS: We conducted a randomised, open-label, single-centre trial at a Swiss tertiary care centre. The main outcome was the change in International Prostate Symptom Score (IPSS) after PAE versus TURP. Secondary outcomes included patient-reported outcomes, functional measures, and adverse events assessed at baseline and at 3, 6, 12, 24, and 60 mo. Between-group differences in the change from baseline to 5 yr were tested using two-sided Mann-Whitney and t tests. KEY FINDINGS AND LIMITATIONS: Of the 103 patients with refractory LUTS/BPO who were randomised between 2014 and 2017, 18/48 who underwent PAE and 38/51 who underwent TURP reached the 60-mo follow-up visit. The mean reduction in IPSS from baseline to 5 yr was -7.78 points after PAE and -11.57 points after TURP (difference 3.79 points, 95% confidence interval [CI] -0.66 to 8.24; p = 0.092). TURP was superior for most patient-reported secondary outcomes except for erectile function. At 5 yr, PAE was less effective than TURP regarding objective parameters, such as the improvement in maximum urinary flow rate (3.59 vs 9.30 ml/s, difference -5.71, 95% CI -10.72 to -0.70; p = 0. 027) and reduction in postvoid residual volume (27.81 vs 219.97 ml; difference 192.15, 95% CI 83.79-300.51; p = 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: The improvement in LUTS/BPO at 5 yr after PAE was inferior to that achieved with TURP. The limitations of PAE should be considered during patient selection and counselling. PATIENT SUMMARY: In this study, we show the long-term results of prostate artery embolisation (PAE) in comparison to transurethral resection of the prostate (TURP) for the treatment of benign prostate enlargement causing urinary symptoms. PAE shows good long-term results in properly selected patients, although the improvements are less pronounced than with TURP. This trial is registered on ClinicalTrials.gov as NCT02054013.

Prostatic Artery Embolization in Patients with Advanced Prostate Cancer: A Prospective Single Center Pilot Study.

PURPOSE: To assess efficacy and safety of prostatic artery embolization (PAE) in patients with advanced prostate cancer (PCa). MATERIALS AND METHODS: In this prospective single-center, single-arm, pilot study, 9 men with advanced PCa underwent PAE. PAE was performed with the use of 250-400 µm Embozene microspheres (Boston Scientific, Natick, Massachusetts, USA). International Prostate Symptoms Score (IPSS), urinary peak flow (Qmax) and post-void residual urine volume (PVR) was assessed at 12 weeks and up to 12 months. Changes in total prostate volume (TPV) and tumor responses by PSA, changes in tumor volume and evaluation of tumor regression by multiparametric magnetic resonance imaging were assessed at 12 weeks after PAE. RESULTS: IPSS reduction in median 6 points (0-19) and a significant decrease in PVR from median 70 (20-600) mL to 10 (0-280) mL could be achieved within 12 weeks after PAE. Median TPV and tumor volumes (TV) increased slightly from 19.7 (6.4-110.8) mL to 23.4 (2.4-66.3) mL and 6.4 (4.6-18.3) mL to 8.1 (2.4-25.6) mL at a median of 12 weeks after the procedure. Significant tumor necrosis (≥ 50%) was found in one patient. Eight patients showed > 50% of viable tumor on post-PAE MRI according to MRI. Only one Clavien-Dindo Grade 1 adverse event related to PAE occurred. CONCLUSIONS: PAE with the use of 250-400 µm microspheres is feasible, safe and effective in some patients with advanced PCa regarding functional outcomes. A cytoreductive effect might be achieved in individual patients but must be further assessed. TRIALS REGISTRATION: NCT03457805.

Carfilzomib, thalidomide, and dexamethasone is safe and effective in relapsed and/or refractory multiple myeloma: final report of the single arm, multicenter phase II ALLG MM018/AMN002 study.

This multicentre, phase II study of the Australian Lymphoma and Leukaemia Group (ALLG) and the Asian Myeloma Network (AMN) investigated fixed-duration (18-month) treatment with carfilzomib (K), thalidomide (T), and dexamethasone (d; KTd) in patients with relapsed and/or refractory multiple myeloma and 1-3 prior lines of therapy. Patients received induction with up to twelve 28-day cycles of K [20mg/m2 IV cycle 1 day 1 and 2, 56mg/m2 (36mg/m2 for patients ≥75 years) from day 8 onwards), T 100mg PO nocte and weekly dexamethasone 40mg (20mg for patients ≥75 years). During maintenance T was omitted, while K continued on days 1,2,15,16 with fortnightly dexamethasone. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall response rate, overall survival (OS), duration of response, safety, and tolerability. Ninety-three patients (median age 66.3 years (41.9 - 84.5)) were enrolled with a median follow-up of 26.4 (1.6 - 54.6) months. The median PFS was 22.3 months (95% CI 15.7 - 25.6) with a 46.3% (95% CI 35.1 - 52.8) 2-year PFS. Median OS was not reached and was 73.8% (95% CI 62.9 - 81.9) at 2 years. The overall response rate was 88% (≥ VGPR 73%). There was no difference in the depth of response, PFS or OS comparing Asian and Non-Asian cohorts (p=0.61). The safety profile for KTd was consistent with each individual drug. KTd is well tolerated and effective in patients with RRMM irrespective of Asian or non-Asian ethnicity and provides an alternative option particularly where use of KRd is limited by access, cost, or renal impairment.

Latest insights into the pathophysiology of bladder pain syndrome/interstitial cystitis.

PURPOSE OF REVIEW: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a common medical problem in both sexes affecting people of all ages. Patients might report overactive bladder symptoms with additional bladder pain at maximum bladder filling, during and after micturition. This review aims to highlight pathophysiological mechanisms associated with this disease. RECENT FINDINGS: Latest literature exposes different pathophysiological mechanisms such as impaired urothelial barrier function, alteration of urothelial factors and cytokines, chronic inflammation, vascular lesions, neurogenic inflammation and processes in the central nervous system leading to central sensitization. According to the involved mechanisms, BPS/IC may be arranged in clusters according to the clinical phenotype thus helping in clinical decision-making and treatment. Moreover, patients with BPS/IC suffer from other comorbidities such as fibromyalgia, irritable bowel syndrome, chronic pain and functional syndromes and psychosomatic diseases making the management challenging for medical professionals. SUMMARY: Bladder pain syndrome/interstitial cystitis is a complex heterogeneous medical condition involving different pathomechanisms leading to bladder pain and dysfunction, consequently, impairing quality-of-life in affected individuals. However, these mechanisms are still not fully understood, so that patient treatments often remain unsatisfactory. For this reason, continuing research is important to understand the underlying pathomechanisms to discover biomarkers and treatment targets eventually improving diagnostic and therapeutic measures of BPS/IC.

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.

Interdisciplinary Swiss consensus recommendations on staging and treatment of advanced prostate cancer.

The management of prostate cancer is undergoing rapid changes in all disease settings. Novel imaging tools for diagnosis have been introduced, and the treatment of high-risk localized, locally advanced and metastatic disease has changed considerably in recent years. From clinical and health-economic perspectives, a rational and optimal use of the available options is of the utmost importance. While international guidelines list relevant pivotal trials and give recommendations for a variety of clinical scenarios, there is much room for interpretation, and several important questions remain highly debated. The goal of developing a national consensus on the use of these novel diagnostic and therapeutic strategies in order to improve disease management and eventually patient outcomes has prompted a Swiss consensus meeting. Experts from several specialties, including urology, medical oncology, radiation oncology, pathology and nuclear medicine, discussed and voted on questions of the current most important areas of uncertainty, including the staging and treatment of high-risk localized disease, treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and use of new options to treat metastatic castration-resistant prostate cancer (mCRPC).

bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction.

OBJECTIVE: To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS: bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS: A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end.

Ventral-inlay buccal mucosal graft urethroplasty in a 44-year old female patient with recurrent urethral stricture.

Female urethral stricture is a rare manifestation of bladder outlet obstruction in women. According to the current guidelines of the European Association of Urology, urethral dilatation should be offered as first line treatment. Intermittent self-dilatation (ISD) in case of recurrence is recommended. However, if patients wish definitive surgical treatment or are not able to perform ISD, urethroplasty can be considered. So far, there are little data available on urethroplasty in female patients. We present a case of a 44-year old female patient with a postoperative urethral stricture who underwent ventral-inlay buccal mucosal graft urethroplasty due to inability to perform ISD.

Comparison of traditional outcome measures and self-assessed goal achievement in patients treated surgically for benign prostatic hyperplasia.

PURPOSE: To determine self-assessed goal achievement (SAGA) outcomes in men treated surgically for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) and compare them to the traditional outcome measures. METHODS: Single-center analysis of prospective database of men undergoing surgical treatment of LUTS/BPO at a single institution between July 2019 and March 2021. We assessed individual goals, traditional questionnaires, and functional outcomes prior to treatment, and at first follow-up after 6-12 weeks. We compared SAGA outcomes 'overall goal achievement' and 'satisfaction with treatment' to subjective and objective outcomes using Spearman's rank correlations (rho). RESULTS: A total of sixty-eight patients completed the individual goal formulation prior to surgery. Preoperative goals varied between different treatments and individuals. IPSS correlated with 'overall goal achievement' (rho = - 0.78, p < 0.001) and 'satisfaction with treatment' (rho = - 0.59, p < 0.001). Similarly, the IPSS-QoL was correlated with overall goal achievement (rho = - 0.79, p < 0.001) and satisfaction with treatment (rho = - 0.65, p < 0.001). No correlation was seen between SAGA outcomes and functional outcomes Qmax and PVR. CONCLUSIONS: SAGA represents a uniquely patient-specific outcome measure. Our study is, to our knowledge, the first to assess patient-specific goals prior to surgery and examine SAGA outcomes following treatment in men suffering from LUTS/BPO. The correlation of SAGA outcomes with IPSS and IPSS-QoL highlight the importance of this well-established questionnaire. Functional outcomes do not necessarily reflect patient's goals and may rather be considered physician-directed outcomes.

Prostatic Artery Embolization in Patients with Prostate Cancer: A Systematic Review.

CONTEXT: Prostatic artery embolization (PAE) is increasingly performed worldwide for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). In contrast, the role of PAE in patients with prostate cancer (PCa) is unclear. OBJECTIVE: This systematic review summarizes the current available literature on PAE in patients with PCa regarding oncological and functional outcome. EVIDENCE ACQUISITION: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. A structured search for the relevant literature from 1985 to 2022 was performed in Medline, Embase, and York CRD. Risk of bias and confounding assessments were performed using the ROBINS tool. EVIDENCE SYNTHESIS: Thirteen trials (12 case series and one animal study using a canine model) were included in this systematic review. Four studies had a prospective study design. The risk of bias was rated moderate to serious in all the studies. CONCLUSIONS: PAE in patients with PCa seems to be a safe procedure and effective regarding the improvement of LUTS. Despite PAE having been shown to be feasible in different treatment scenarios of localized or advanced PCa, the oncological benefits are debatable due to an unreliable tumor response and a lack of controlled trials including long-term follow-up. PATIENT SUMMARY: We investigated the literature to determine the role of prostatic artery embolization (PAE) in patients with prostate cancer regarding oncological and functional outcomes. The results suggest a similar safety profile and efficacy in terms of functional outcomes to those reported earlier for PAE in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. The role of PAE regarding oncological outcomes has to be assessed further.

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.

Incidence and outcome of patients with renal cell carcinoma treated with partial or radical nephrectomy in the Cantons St Gallen and Appenzell 2009-2018.

BACKGROUND: Over recent years, the incidence of renal cell carcinoma (RCC) has remained unchanged in Switzerland and is low compared with other European countries. Partial or radical nephrectomy is the mainstay of treatment in patients with localised disease. METHODS: We conducted an analysis of data from the cancer registry of Eastern Switzerland on patients with surgery for RCC from 2009 to 2018, focusing on a comparison of surgical technique and outcome in tertiary and non-tertiary hospitals. RESULTS: 492 nephrectomies were performed. Out of 441 curative procedures, 226 were radical and 195 partial nephrectomies (20 unknown). At the tertiary hospital, statistically significantly more partial nephrectomies were performed in non-metastatic patients than at non-tertiary hospitals. We demonstrate a trend towards better disease-free survival after partial compared with radical nephrectomy. The 5-year overall survival for patients diagnosed between 2009 and 2013 was 85%, 83%, and 70% in stage I, II, and III, respectively, compared with 96%, 78%, and 72% for patients diagnosed between 2014 and 2018. CONCLUSION: RCC incidence in Switzerland has been stable during the past decade in contrast to other European countries, and no stage migration occurred. We demonstrated that patients with localised renal cancer at our tertiary centre were more likely to be treated with renal preserving surgery compared with non-tertiary hospitals. This analysis underlines the importance of local cancer registries in the comparison of treatment and outcome over time.

A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non-muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14.

BACKGROUND: VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. OBJECTIVE: To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. DESIGN, SETTING, AND PARTICIPANTS: We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. INTERVENTION: Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that ≥30% of the patients would be without recurrence at 60 wk after registration. RESULTS AND LIMITATIONS: After exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients and metastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade ≥4 AEs occurred. Two of the 42 patients did not tolerate five or more instillations during induction. Limitations include the single-arm trial design and the low number of patients for subgroup analysis. CONCLUSIONS: At 1 yr after treatment start, almost half of the patients remained recurrence-free after therapy with VPM100BC. The primary endpoint of the study was met and the therapy is safe and well tolerated. PATIENT SUMMARY: We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC.

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.

Sacral Neuromodulation for Neurogenic Lower Urinary Tract Dysfunction.

SNM for Urinary Tract DysfunctionThis study evaluated SNM for neurogenic lower urinary tract dysfunction. A neurostimulator was implanted for permanent stimulation and optimized using subsensory stimulation. It remained on or was switched off, with patients masked to the condition. After 2 months, the SNM ON group had significantly different success compared with the SNM OFF group (76% vs. 42%).

Stay cool! Special underwear for cyclic cooling significantly decreases scrotal skin temperature.

INTRODUCTION: Male reproductive health is rapidly declining during the past decades and it is well known that scrotal temperature is linked to male infertility. MATERIAL AND METHODS: We performed a prospective data evaluation within a counterfactual analysis study design. Scrotal cooling was performed using Snowballs™ underwear, scrotal temperature was monitored using a wireless temperature sensor (SensorPush, Brooklyn, NY, 11215). RESULTS: Overall, scrotal skin temperatures were monitored for 1008 hours. Median scrotal skin temperature was 34.6°C (IQR 33.1 to 35.3) and 35.3°C (IQR 34.4 to 35.9) in the experimental (SnowWedge™) period and control period, respectively, which was significantly different (P <0.001). CONCLUSIONS: Cyclic scrotal skin cooling using specialized underwear is feasible and efficacious without impairing the activities of daily living and reduces median scrotal skin temperature significantly by 0.7°C. Given the proven association of scrotal skin temperature and semen quality, cyclic scrotal skin cooling by a device such as Snowballs™ underwear may eventually increase semen quality and fertility.

Investigating the response scale of the EORTC QLQ-C30 in German cancer patients and a population survey.

BACKGROUND: The European Organization for research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) scales are scored on a 4-point response scale, ranging from not at all to very much. Previous studies have shown that the German translation of the response option quite a bit as mäßig violates interval scale assumptions, and that ziemlich is a more appropriate translation. The present studies investigated differences between the two questionnaire versions. METHODS: The first study employed a balanced cross-over design and included 450 patients with different types of cancer from three German-speaking countries. The second study was a representative survey in Germany including 2033 respondents. The main analyses included compared the ziemlich and mäßig version of the questionnaire using analyses of covariance adjusted for sex, age, and health burden. RESULTS: In accordance with our hypothesis, the adjusted summary score was lower in the mäßig than in the ziemlich version; Study 1: - 4.5 (95% CI - 7.8 to - 1.3), p = 0.006, Study 2: - 3.1 (95% CI - 4.6 to - 1.5), p < 0.001. In both studies, this effect was pronounced in respondents with a higher health burden; Study 1: - 6.8 (95% CI - 12.2 to - 1.4), p = 0.013; Study 2: - 4.5 (95% CI - 7.3 to - 1.7), p = 0.002. CONCLUSIONS: We found subtle but consistent differences between the two questionnaire versions. We recommend to use the optimized response option for the EORTC QLQ-C30 as well as for all other German modules. TRIAL REGISTRATION: The study was retrospectively registered on the German Registry for Clinical Studies (reference number DRKS00012759, 04th August 2017, https://www.drks.de/DRKS00012759 ).

Adenovirus vector vaccination reprograms pulmonary fibroblastic niches to support protective inflating memory CD8+ T cells.

Pathogens and vaccines that produce persisting antigens can generate expanded pools of effector memory CD8+ T cells, described as memory inflation. While properties of inflating memory CD8+ T cells have been characterized, the specific cell types and tissue factors responsible for their maintenance remain elusive. Here, we show that clinically applied adenovirus vectors preferentially target fibroblastic stromal cells in cultured human tissues. Moreover, we used cell-type-specific antigen targeting to define critical cells and molecules that sustain long-term antigen presentation and T cell activity after adenovirus vector immunization in mice. While antigen targeting to myeloid cells was insufficient to activate antigen-specific CD8+ T cells, genetic activation of antigen expression in Ccl19-cre-expressing fibroblastic stromal cells induced inflating CD8+ T cells. Local ablation of vector-targeted cells revealed that lung fibroblasts support the protective function and metabolic fitness of inflating memory CD8+ T cells in an interleukin (IL)-33-dependent manner. Collectively, these data define a critical fibroblastic niche that underpins robust protective immunity operating in a clinically important vaccine platform.