Gender-specific outcomes in immune checkpoint inhibitor therapy for advanced or metastatic urothelial cancer: a systematic review and meta-analysis.

PURPOSE: To analyze gender-specific differences in survival parameters in advanced or metastatic urothelial cancer patients undergoing immune checkpoint inhibition. METHODS: The primary aim of this systematic review and meta-analysis was to evaluate gender-specific differences in disease-free (DFS), progression-free (PFS), cancer-specific survival (CSS), event-free survival (EFS), overall survival (OS) and objective response rate (ORR). The sources MEDLINE, Embase and Cochrane Library were systematically searched from January 2010 to June 2022. No restrictions were made concerning language, study region or publication type. A comparison of gender-specific differences in survival parameters was performed using a random-effects meta-analysis. A risk of bias assessment was done using the ROBINS-I tool. RESULTS: Five studies were included. In a random-effect meta-analysis of the studies, PCD4989g and IMvigor 211 with both using atezolizumab, females were more likely to have better objective response rate (ORR) than men (OR 2.24; 95% CI 1.20-4.16; p = 0.0110). In addition, females had a comparable median OS to men (MD 1.16; 95% CI - 3.15-5.46; p = 0.598). In summary, comparing all results, a tendency was seen toward better response rates and survival parameters in female patients. The risk of bias assessment yielded an overall low risk of bias. CONCLUSIONS: There is a tendency toward better outcomes in women for immunotherapy in advanced or metastatic urothelial cancer, but only for the antibody atezolizumab women have a significantly better ORR. Unfortunately, many studies fail to report gender-specific outcomes. Therefore, further research is essential when aiming for individualized medicine. This research should address immunological confounders.

[What is the proportion of infectiology in the specialization urology? : A pilot study to underline the significance of Antibiotic Stewardship in urology]. / Welchen Anteil hat die Infektiologie am Fachgebiet Urologie? : Ein Pilotprojekt, zur Hervorhebung der Antibiotic-Stewardship-Bedeutung.

BACKGROUND: Urinary tract infections account for one of the most bacterial infectious diseases worldwide. OBJECTIVES: The primary aim of this pilot project was to identify the relative percentage of antibiotic use in comparison to all patients in a university medical center for the better establishment of antibiotic stewardship (ABS) programs. MATERIAL AND METHODS: This is an epidemiological pilot project. In the time period of three months it was evaluated which relative percentage of the patients was treated with antibiotics for bacterial urinary tract infection in comparison to all patients. RESULTS: In summary, about 40% of all urological patients received an antibiotic treatment against urinary tract infections or as perioperative prophylaxis against bacterial infection in the operating room (OR). The antibiotic use at the urological ward is highest in comparison to ambulance or OR. CONCLUSION: Infectious diseases, especially bacterial infections, account for a significant part of urology. This knowledge is essential to establish ABS programs and to tackle the progression of antibiotic resistance. Detailed studies are necessary to understand antibiotic prescription practice in urology to develop targeted ABS interventions.

Reduction of Perioperative Antibiotic Prophylaxis in Open Radical Cystectomy with Ileal Conduit Is Feasible: Results of a Prospective Clinical Trial.

INTRODUCTION: The aim of this study is to perform a prospective clinical trial in antibiotic prophylaxis, infectious complication, and colonization of ileal conduit (IC) following radical cystectomy (RC) since urinary tract infections (UTIs) and surgical site infections (SSIs) contribute significantly to the morbidity associated with RC and IC. Moreover, an optimal regimen of antibiotic prophylaxis has not been established, yet. MATERIAL AND METHODS: After a positive vote of ethical review committee and the registration at the German Clinical Trials Register (DKRS 00020406), we started a prospective clinical unicentric not interventional study. The urine samples were collected by sterile catheterization of the IC. All patients received an antibiotic prophylaxis with 3 × 500 mg metronidazole and 3 × 1.5 g cefuroxime intravenously for 3 days starting on the day before RC. Ureteral stents got removed on days 9 and 10 after surgery without prior antibiotic administration. The student t test and the χ2 test or the Fisher exact test were used. For risk factor assessment, the univariate Cox regression method was applied. RESULTS: Nineteen male (63.3%) and 11 female patients (36.7%) with a median age of 70.5 years were included. Three patients developed complicated UTI (10%) on day 12 after RC with E. faecium and needed antibiotic treatment with meropenem (Clavien-Dindo II). Two patients (6.7%) developed SSI with E. faecium and needed surgery (Clavien-Dindo IIIb). Palliative RC (p < 0.0001), prior radiation therapy (p < 0.0001), and timeframe >3 months from diagnosis to RC (p = 0.036) are significantly associated with the development of complicated UTI. Interestingly, the IC got colonized with Staph. haemolyticus at day 12 after RC (n = 12; 40.0%). We must assume that our data have some limitations like a unicentric study population. CONCLUSION: Further evaluation of reduction to single-shot antibiotic prophylaxis in nonpalliative RC with IC could be feasible.

Significance of BK Polyomavirus in Long-Term Survivors after Adult Allogeneic Stem Cell Transplantation.

BACKGROUND: Allogeneic stem cell transplantation (aSCT) is a common treatment for a variety of hematological diseases. Advances in transplantation practices have led to an increasing number of long-term aSCT survivors, but data about health status and late complications are sparse. This analysis focusses on kidney function and urological complications in this population. METHODS: This study is a prospective unicentric non-interventional trial. Before starting the study, we obtained the approval of the local ethics review board. Furthermore, the study was registered at WHO Clinical Trial Registry. The study protocol is available via UTN. RESULTS: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). The median survival time following allogeneic stem cell transplantation was 9.0 years (IQR 8.5-13.0). Five patients (15.2%) had BKPyV viruria with mean 218.3 (SD 674.2) copies/mL. BKPyV viruria was significantly linked to pre-existing chronic kidney failure (p = 0.019), creatine > 100 µmol/L (p < 0.001), and cystatin c > 1.11 mg/L (p = 0.021), respectively. We were not able to identify a single risk factor for BKPyV viruria in univariate or multivariate Cox regression. CONCLUSIONS: BKPyV-associated nephropathy might be one reason for impaired kidney function in long-term survivors of aSCT.

[New aspects in Fournier's gangrene - a rapid review]. / Neue Aspekte zur Fournierschen Gangrän ­ Ein Rapid Review.

Fournier's gangrene (FG) is a sporadic, life-threatening, necrotising infection affecting the perineum, perineal region and genitals. Published literature provides hints that the outcome of this disease has failed to improve in recent years. We have therefore performed a rapid evidence synthesis by searching the database MEDLINE. The literature from 2020 was studied to identify new aspects to improve the care of FG patients and plan further therapeutic research. 18 publications were chosen for this review, 15 of these were original research and three systematic reviews. 12 were retrospective case series, 2 epidemiological studies, with one prospective clinical study, one systematic review and 2 systematic reviews, together with a meta-analysis. Most of the authors of the studies concluded that FG is still a severe disease with unacceptable mortality rates, so that there is urgent need for therapy improvement. New risk factors for higher mortality in FG have been identified in these studies, namely dyslipoproteinemia, diabetes mellitus, heart disease, as well as both acute and chronic kidney failure. Furthermore, 4 of the included studies investigated the association of SGLT2- and DDP4-inhibitors, which are drugs used in diabetes mellitus, and the incidence of FG. No studies reported a significant association between these drugs and FG, especially not a meta-analysis with 84 included studies. New promising concepts for wound conditioning are hyperbaric oxygenation (HBO), vacuum-assisted wound closure (VAC) and Maggot therapy (blowfly larvae). In summary, FG is still a severe disease, the prognosis has not improved in recent years and so there is an urgent need for improved therapy. This could only be achieved with further research in FG. In our opinion and due to the rarity of FG, this would be possible with a national registry study. For example, it might be possible to calculate risk stratification from this registry to identify patients who would benefit from treatment in a centre or with special wound conditioning.

Leflunomide in the treatment of BK polyomavirus associated nephropathy in kidney transplanted patients - A systematic review.

BK polyomavirus (BKPyV) associated nephropathy (BKVAN) is seen in about 5% of renal transplant patients and can lead to chronic graft failure or graft loss. No effective therapy is available. Leflunomide has shown promising results in BKVAN. We performed a systematic review about the use of leflunomide for the treatment of BKVAN. The recommendations of the Cochrane Handbook of systematic Reviews were followed. Due to different study designs and endpoints no meta-analysis was performed. The literature search for primary studies yielded 274 results. Finally, twelve studies were included with a total of 267 patients. Clearance of BKPyV viremia was reported in 33.3% to 92.3% of cases and 27 graft losses (10.1%). The included studies were very heterogeneous, especially in terms of leflunomide dosing. Pharmacokinetics seem to have an important impact on the efficacy of leflunomide in BKVAN. There was no correlation between leflunomide serum levels and virus reduction. New adverse events of leflunomide have been described, e.g. haemolytic anaemia and thrombotic microangiopathy. Overall, the risk of bias in the studies was assessed as high and the quality of evidence was rated low. The role of leflunomide in BKVAN remains unclear, but further studies seem reasonable and should address pharmacokinetic aspects.

[18F]FDG PET/CT for assessing inguinal lymph nodes in patients with penile cancer - correlation with histopathology after inguinal lymphadenectomy.

AIM: Accurate staging of penile cancer requires invasive methods such as sentinel node biopsy or lymphadenectomy (LAD). We assessed the value of [18F]FDG PET/CT for non-invasive nodal staging in penile cancer (PC) patients before inguinal LAD. PATIENTS AND METHODS: 41 consecutive patients with PC (stage pT1 or higher, cN0) received [18F]FDG PET/CT before undergoing bilateral modified or radical inguinal staging LAD. Lymph nodes with a visually increased [18F]FDG uptake were classified as suspicious of lymph node metastases (LNM). Standardized uptake value (SUV) of suspicious inguinal lymph nodes was determined. Results of [18F]FDG PET/CT were correlated with histopathology. RESULTS: In total 623 lymph nodes were resected, in 10 patients LNM were histologically confirmed (14/623 lymph nodes). In patient-based analysis [18F]FDG PET/CT showed a sensitivity and specificity of 80% and 68 %, respectively, a positive predictive value (PPV) of 44 % and a negative predictive value (NPV) of 91 %. In the groin-based analysis, [18F]FDG PET/CT had a sensitivity of 69 %, a specificity of 77 %, a PPV of 36 % and a NPV of 93 %. There was no significant difference in SUVmean and SUVmax between true positive and false positive lymph nodes (p = 0.093 and 0.069, respectively). CONCLUSION: [18F]FDG PET/ CT shows a high NPV in penile cancer patients without clinically evident LNM. However, due to its limited sensitivity (especially with respect to LNM of small size) and specificity (i. e. in the differentiation between (post)inflammatory and metastatic lymph nodes) [18F]FDG PET/CT cannot replace invasive nodal staging.

Urinary Retention Due to Severe Pseudocystic Mucoid Degeneration of the Prostatic Matrix: A Rare Urologic Manifestation of Cystic Fibrosis.

Cystic fibrosis (CF) is an autosomal recessive genetic disease, which is characterized by the production of thick mucus in exocrine glands. The main cause for morbidity and mortality in CF patients is respiratory failure. The gastrointestinal system is also commonly affected. Urologic manifestations of CF include infertility and azoospermia, nephrolithiasis, and stress urinary incontinence. In this report, we describe a 33-year-old male, who presented with recurrent urinary retention due to prostatic enlargement despite his young age. After transurethral resection, the voiding problems resolved. Histopathological examination, however, revealed a severe pseudocystic mucoid degeneration of the prostatic matrix as a cause of his subvesical obstruction. Although these structural changes are most probably due to his underlying disease, detailed histologic features have not been described in the literature.