Therapy decisions after diagnosis of prostate cancer in men with negative prostate MRI.

BACKGROUND: To investigate the clinical implications of magnetic resonance imaging (MRI) negative prostate cancer (PCa) in a cohort of men undergoing transperineal prostate biopsy. METHODS: We included all men without prior diagnosis of PCa undergoing transperineal template saturation ± fusion-guided targeted biopsy of the prostate between November 2014 and March 2018. Before biopsy, all patients underwent MRI and biopsies were performed irrespective of imaging results. Baseline characteristics, imaging, biopsy results, and follow-up information were retrieved from the patient charts. Patients were classified as either MRI negative (Prostate Imaging Reporting and Data System [PIRADS] ≤ 2) or positive (PIRADS ≥ 3). ISUP grade group 1 was defined as clinically nonsignificant (nsPCa) and ≥2 as clinically significant PCa (csPCa). Primary outcome was the individual therapeutic decision after diagnosis of PCa stratified according to MRI visibility. Secondary outcomes were the sensitivity and specificity of MRI, and the urooncological outcomes after radical prostatectomy (RP). RESULTS: From 515 patients undergoing prostate biopsy, 171 (33.2%) patients had a negative and 344 (66.8%) a positive MRI. Pathology review stratified for MRI negative and positive cases revealed nsPCa in 27 (15.8%) and 32 (9.3%) and csPCa in 26 (15.2%) and 194 (56.4%) of the patients, respectively. The rate of active treatment in the MRI negative was lower compared with the MRI positive cohort (12.3% vs. 53.2%; odd ratio [OR] = 0.12; p < 0.001). While men with negative MRI were more likely to undergo active surveillance (AS) than MRI positive patients (18.1% vs. 10.8%; OR = 1.84; p = 0.027), they rarely underwent RP (6.4% vs. 40.7%, OR = 0.10; p < 0.001). Logistic regression revealed that a negative MRI was independently protective for active treatment (OR = 0.32, p = 0.014). The specificity, sensitivity, negative, and positive predictive value of MRI for detection of csPCa were 49.2%, 88.2%, 56.4%, and 84.8%, respectively. The rate of adverse clinicopathological outcome features (pT3/4, ISUP ≥4, or prostate-specific antigen [PSA]-persistence) following RP was 4.7% for men with MRI negative compared to 17.4% for men with MRI positive PCa (OR = 3.1, p = 0.19). CONCLUSION: Only few men with MRI negative PCa need active cancer treatment at the time of diagnosis, while the majority opts for AS. Omitting prostate biopsies and performing a follow-up MRI may be a safe alternative to reduce the number of unnecessary interventions.

Diagnostic accuracy of ultrasonography, computed tomography, cystoscopy and cytology to detect urinary tract malignancies in patients with asymptomatic hematuria.

PURPOSE: To report the incidence of urinary tract malignancies (UTM) and to compare the diagnostic accuracy of cytology with cystoscopy, renal ultrasound (US) and computed tomography (CT) in patients with hematuria. METHODS: A retrospective analysis was conducted of patients who underwent cystoscopy, cytology, US and CT for hematuria between 2011 and 2017. Age, gender, BMI, smoking status, and results of further diagnostic interventions including transurethral resection of the bladder (TURB), ureterorenoscopy (URS), renal biopsy and imaging were extracted from medical charts. Logistic regression to identify risk factors for UTM was performed. Discriminatory accuracy of US, CT and cytology was assessed by 2 × 2 tables. RESULTS: Of 847 patients, 432 (51%) presented with non-visible hematuria (NVH) and 415 (49%) with visible hematuria (VH). Of all patients with NVH, seven (1.6%) had bladder cancer (BCA), three (< 1%) had renal cell cancer (RCC) and no single patient had upper tract urothelial cancer (UTUC). Of the patients with VH, 62 (14.9%) were diagnosed with BCA, 7 (1.6%) with RCC and 4 (< 1%) with UTUC. In multivariable analysis VH, higher age, smoking and lower BMI were associated with an increased risk for UTM. The specificity/negative predictive value of US for the detection of RCC or UTUC in patients with NVH and VH were 96%/100% and 95%/99%, respectively. CONCLUSION: Due to the low incidence of UTM, the necessity of further diagnostics should be questioned in patients with NVH. In contrast, patients with VH are at considerable risk for BCA, and cystoscopy and upper tract imaging is justified.

Grafts in Peyronie's surgery without the use of prostheses: a systematic review and meta-analysis.

Peyronie's disease (PD) is characterized by abnormal penile curvature, and various surgical methods have been developed using different graft materials. However, there is currently no universal agreement on which type of graft is the best. The objective of this review was to evaluate the available literature and identify the most effective graft material for penile curvature correction in PD. A literature search was conducted using electronic databases, including PubMed, Scopus, and the Cochrane Library. The patients, intervention, comparison, and outcome (PICO) approach was used to define the eligibility of studies. Two authors independently selected studies, evaluated them, and extracted data. Random-effect models using the DerSimonian-Laird method were used. Most studies were single-arm studies and had a high risk of bias. Buccal mucosa grafts (BMG) were found to result in the highest penile straightening rates and were associated with the least de novo erectile dysfunction. TachoSil grafts demonstrated a high success rate in straightening despite a higher mean preoperative curvature, while Tutoplast grafts had a higher incidence of postoperative erectile dysfunction. BMG had the highest percentage of postoperative penile straightening. Overall, the TachoSil graft showed the best performance when preoperative curvature is taken into account. Based on the available literature, BMG appear to be the most effective for penile curvature correction in PD, but this is offset by the requirement for low preoperative curvature. The TachoSil graft shows the best overall performance when preoperative curvature is considered. Comparative randomized clinical trials are still needed to determine graft superiority.

Mitochondrial hyperpolarization in pulmonary vascular remodeling. Mitochondrial uncoupling protein deficiency as disease model.

Alterations of mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial respiration are possible triggers of pulmonary vascular remodeling in pulmonary hypertension (PH). We investigated the role of MMP in PH and hypothesized that deletion of the mitochondrial uncoupling protein 2 (UCP2) increases MMP, thus promoting pulmonary vascular remodeling and PH. MMP was measured by JC-1 in isolated pulmonary arterial smooth muscle cells (PASMCs) of patients with PH and animals with PH induced by exposure to monocrotaline (MCT) or chronic hypoxia. PH was quantified in vivo in UCP2-deficient (UCP2(-/-)) mice by hemodynamics, morphometry, and echocardiography. ROS were measured by electron spin resonance spectroscopy and proliferation by thymidine incorporation. Mitochondrial respiration was investigated by high-resolution respirometry. MMP was increased in PASMCs of patients and in animal models of PH. UCP2(-/-) mice exhibited pulmonary vascular remodeling and mild PH compared with wild-type (WT) mice. PASMCs of UCP2(-/-) mice showed increased proliferation, MMP, and ROS release. Increased proliferation of UCP2(-/-) PASMCs could be attenuated by ROS inhibitors and inhibited by carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, which decreased MMP to the level of WT mice. Mitochondrial respiration was altered in PASMCs from MCT rats and PASMCs exposed to hypoxia but not in isolated pulmonary mitochondria of UCP2(-/-) mice or PASMCs after treatment with small interfering RNA for UCP2. Our data suggest that increased MMP causes vascular remodeling in UCP2(-/-) mice partially via increased ROS. In chronic hypoxia and MCT-induced PH, additional pathomechanisms such as decreased respiration may play a role.

Do Swiss urologists and Swiss internists screen themselves and their relatives for prostate cancer? A questionnaire study.

PURPOSE: Prostate-specific antigen (PSA) screening for men at risk of prostate cancer is controversial. The current recommendation is to raise awareness of prostate cancer and offer PSA screening in accordance with shared decision- making. Whether the possibility of a PSA screen is discussed with the patient depends on the treating physician, but data on physicians' attitudes towards PSA screening are scarce. This study aimed to examine internists' and urologists' personal PSA screening activity as an indicator of their attitude towards PSA screening. MATERIALS AND METHODS: Members of the Swiss Society of Urology and the Swiss Society of General Internal Medicine were asked in 08/2020 to anonymously complete an online survey about personal PSA screening behaviour for themselves, their fathers, brothers and partners. Categorical and continuous variables were compared by chi-squared tests and t-tests, respectively. RESULTS: In total, 190/295 (response rate: 64%) urologists and 893/7400 (response rate: 12%) internists participated in the survey. Of the participants, 297/1083 (27.4%) were female. Male urologists >50 years of age screened themselves more often than male internists >50 years of age (89% vs 70%, p <0.05). Furthermore, urologists reported recommending screening statistically significantly more often than internists to their brother, father or partner regardless of their sex (men: 38.1% vs 18.5%; p <0.05; women: 81.8% vs 32.2%; p <0.05).   CONCLUSIONS: Most participating male physicians >50 years of age have screened themselves for prostate cancer. Furthermore, PSA screening of relatives was significantly associated with the urology specialty. The reasons physicians screen themselves substantially more often than the public and why male and female urologists as well as male internists perform PSA screening more frequently in their private environment than female internists should be further examined.

Assessment of Diagnostic Yield of Cystoscopy and Computed Tomographic Urography for Urinary Tract Cancers in Patients Evaluated for Microhematuria: A Systematic Review and Meta-analysis.

Importance: Microhematuria (MH) is a common finding that often leads to further evaluation for urinary tract cancers. There is ongoing debate about the extent to which patients with MH should be evaluated for cancer. Objective: To assess the diagnostic yield for detection of urinary tract cancers, specifically bladder cancer, upper tract urothelial carcinoma (UTUC), and kidney cell carcinoma, among patients evaluated for MH using cystoscopy and computed tomographic (CT) urography. Data Sources: MEDLINE, Scopus, and Embase were systematically searched for eligible studies published between January 1, 2009, and December 31, 2019. Study Selection: Original prospective and retrospective studies reporting the prevalence of cancer among patients evaluated for MH were eligible. Two authors independently screened the titles and abstracts to select studies that met the eligibility criteria and reached consensus about which studies to include. Among 5802 records identified, 5802 articles were screened using titles and abstracts. After exclusions, 55 full-text articles were assessed for eligibility, with 39 studies selected for systematic review. Data Extraction and Synthesis: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Studies were quantitatively synthesized using a random-intercept logistic regression model. Main Outcomes and Measures: The primary outcome was diagnostic yield, defined as the proportion of patients with a diagnosis of urinary tract cancer (bladder cancer, UTUC, or kidney cell carcinoma) after presentation with MH. Studies were stratified by the percentage of cystoscopy and CT urography use and by high-risk cohorts. The diagnostic yields of CT urography and cystoscopy were calculated for each cancer type. Results: A total of 30 studies comprising 24 366 patients evaluated for MH were included in the meta-analysis. The pooled diagnostic yield among all patients was 2.00% (95% CI, 1.30%-3.09%) for bladder cancer, 0.02% (95% CI, 0.0%-0.15%) for UTUC, and 0.18% (95% CI, 0.09%-0.36%) for kidney cell carcinoma. Stratification of studies that used cystoscopy and/or CT urography for 95% or more of the cohort produced diagnostic yields of 2.74% (95% CI, 1.81%-4.12%) for bladder cancer, 0.09% (95% CI, 0.01%-0.75%) for UTUC, and 0.10% (95% CI, 0.04%-0.23%) for kidney cell carcinoma. In high-risk cohorts, the diagnostic yields increased to 4.61% (95% CI, 2.34%-8.90%) for bladder cancer and 0.45% (95% CI, 0.22%-0.95%) for UTUC. Conclusions and Relevance: This study's findings suggest that, given the low diagnostic yield of CT urography and the associated risks and costs, limiting its use to high-risk patients older than 50 years is warranted. Risk stratification, as recommended by the recent American Urology Association guidelines on MH, may be a better approach to tailor further evaluation.