Hormone concentration, metabolic disorders and immunoexpression of androgen and estrogen-alpha receptors in men with benign prostatic hyperplasia and testosterone deficiency syndrome

Introduction. A slight decrease in blood testosterone level in men is a physiological state associated with the aging. The aim of our study was to evaluate the occurrence of hormone and metabolic disorders, as well as the immunolocalization and immunoexpression of androgen receptors (AR) and estrogen-alpha receptors (ERa) in the prostates of men with benign prostatic hyperplasia (BPH) and coexisting testosterone deficiency syndrome (TDS). Material and methods. The study involved 150 men, diagnosed with and receiving pharmacological treatment for BPH. Concentrations of glucose, total cholesterol (TCh), high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides (TG) were determined in blood serum. Serum concentrations of total testosterone (TT), free testosterone (FT), estradiol (E2), luteinizing hormone (LH), insulin (I), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF-1) were measured by ELISA. The number of AR-positive cells and ERa-positive cells were measured in prostate sections of men with BPH. Results. Patients eligible for transurethral resection of the prostate and TDS were significantly more likely to have higher abdominal circumference and higher serum levels of insulin and IGF-1 as well as lower levels of FT and SHBG than control subjects with BPH and no TDS. Quantitative analysis revealed 35.8% AR-positive colum­nar epithelial cells and 24.3% AR-positive stromal cells in prostates of BPH patients with TDS and 30.5% and 23.0%, respectively, in BPH patients without TDS. However, the differences between the study and the control groups were statistically not significant. In prostates of BPH patients with TDS the immunoexpression of ERa was observed in 2.88% of the columnar epithelial cells and 0.39% of stromal cells. In BPH patients without TDS ERa-positive cells were only found in 0.04% of columnar epithelial cells and 0.62% of prostatic stromal cells. Conclusions. Considering the statistically significantly higher levels of I and IGF-1 and larger abdominal circumference of men with BPH and TT deficiency, it can be supposed that visceral obesity and carbohydrate disorders may contribute to the reduction of testosterone concentration. The results of our study indicate a relationship between TT concentration in the plasma of patients with BPH and the percentage of AR-positive cells in the prostate.

Changing patterns of urologic emergency visits and admissions during the COVID-19 pandemic : a retrospective, multicenter, nationwide study

INTRODUCTION: We aimed to examine the change in the number and severity of visits to the emergency departments (EDs) and subsequent admissions for urgent urologic conditions in the early stage of the coronavirus disease 2019 (COVID-19) pandemic in Poland. MATERIAL AND METHODS: We evaluated data from 13 urologic centers in Poland and compared the number of visits to the EDs and subsequent admissions before and after the advent of COVID-19 in 2020, and before and after the escalating national restrictions. Furthermore, data on types of urologic complaints, crucial laboratory parameters, and post-admission procedures were analyzed. RESULTS: In total 1,696 and 2,187 urologic visits (22.45% decrease) and 387 and 439 urologic urgent admissions (11.85% decrease) were reported in given periods in 2020 and 2019, respectively. The year-over-year difference in daily mean visits was clear (36.1 vs. 46.5; p < 0.001). Declines were seen in all complaints but device malfunction. In 2020 daily mean visits and admissions decreased from 40.9 and 9.6 before lockdowns to 30.9 (p < 0.001) and 6.9 (p = 0.001) after severe restrictions, respectively. There was a trend towards more negative laboratory parameter profiles in 2020, with patients who visited the EDs after severe restrictions having twice as high median levels of C-reactive protein (15.39 vs. 7.84, p = 0.03). CONCLUSIONS: The observed declines in ED visits and admissions were apparent with the significant effect of national lockdowns. Our results indicate that some of the patients requiring urgent medical help did not appear at the ED or came later than they would have done before the pandemic, presenting with more severe complaints

Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (<1%) patient in the chemotherapy group (acute kidney injury). Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted. Funding: AstraZeneca