Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the stemness marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Recent Advances In The Surgical Treatment Of Benign Prostatic Hyperplasia

TURP for many years has been considered the gold standard for surgical treatment of BPH. Symptoms relief, improvement in Maximum flow rate and reduction of post void residual urine have been reported in several experiences. Notwithstanding a satisfactory efficacy, concerns have been reported in terms of safety outcomes:intracapsular perforation, TUR syndrome, bleeding with a higher risk of transfusion particularly in larger prostates have been extensivelyreported in the literature. In the recent years the use of new forms of energy and devices suchas bipolar resector, Ho: YAG and potassium-titanyl-phosphate laserare challenging the role of traditional TURP for BPH surgical treatment. In 1999 TURP represented the 81% of surgical treatment for BPHversus 39% of 2005. Is this a marketing driven change or is there areal advantage in new technologies? We analyzed guidelines and higher evidence studies to evaluate therole of the most relevant new surgical approaches compared to TURPfor the treatment of BPH. In case of prostates of very large size the challenge is ongoing, withminimally invasive laparoscopic approach and most recently roboticapproach. We will evaluate the most recent literature on thisemerging field. © 2011, SAGE Publications. All rights reserved

Psa Mass Screening: Is There Enough Evidence?

Prostate cancer plays an important role in widely understood aspects of men\u27s health, and is becoming a growing problem in terms of public life. Prostate cancer is one of the most common neoplasms among men. Male patients can live with prostate cancer for a long time so it is important to offer appropriate males adequate diagnostic tools and treatments. Prostate cancer and PSA potentially represent a pair of a disease and an appropriate indicator to be used in mass screening, but regardless of that there is still active debate about it. Extensive use of PSA screening has modified epidemiology of the diseases. Randomized controlled studies provided sufficient results regarding a reduction in mortality through PSA mass screening, while all agreed on risks of overdiagnosis and overtreatment. New and accurate screening tools are necessary, along with adequate counseling and risk stratification

Current Knowledge on Genomic Profiling of Upper Tract Urothelial Carcinoma

Recent research in next-generation sequencing characterized the genomic landscape of urothelial cancer. However, the majority of the studies focused on bladder cancer (BC). Upper urinary tract urothelial carcinomas (UTUC) and BC share some histological characteristics, but, considering the differences in terms of embryologic precursors, epidemiology, genetics, medical and surgical management and response to therapy, UTUC and BC should be considered as two distinct diseases. Our objective is to analyze through a literature search the latest updates and the current knowledge about the genomics of UTUC. We also evaluate genetic differences between BC and UTUC and the potential implications for systemic therapy. Molecular subtyping and variant histology and their correlation with response to chemotherapy were also explored. In summary, the most frequent genomic variations in UTUC included FGFR3, chromatin remodeling genes, TP53/MDM2 and other tumor suppressors/oncogenes. The genomics of UTUC, integrated with clinical data, could drive the selection of patients who could benefit from targeted therapy or off-label treatment. Routine implementation of tumor genomic characterization in UTUC patients should therefore be contemplated and evaluated prospectively

Extended versus standard pelvic lymphadenectomy during robot-assisted radical prostatectomy: the role of extended template as an independent predictor of lymph node invasion with comparable morbidity burden

To assess oncologic and surgical outcomes in patients subjected to standard (S) versus extended (E) pelvic lymph node dissection (PLND) during robot-assisted radical prostatectomy (RARP)

DOES ROBOTIC SURGERY AFFECT KATTAN'S POSTOPERATIVE 5-YEAR CANCER-FREE SURVIVAL FORECAST MORE THAN OPEN SURGERY

DOES ROBOTIC SURGERY AFFECT KATTAN'S POSTOPERATIVE 5-YEAR CANCER-FREE SURVIVAL FORECAST MORE THAN OPEN SURGER

Role of Bed Assistant During Robot-assisted Radical Prostatectomy: The Effect of Learning Curve on Perioperative Variables

Background: A remote interaction between a console surgeon (CS) and a bedside surgeon (BS) makes the role of the latter critical. No conclusive data are reported about the length of the learning curve of a BS. Objective: To highlight the role of a BS during robot-assisted radical prostatectomy (RARP) and to analyze the effect of the learning curve of a BS on intra- and postoperative outcomes. Design, setting, and participants: From June 2013 to September 2016, 129 RARPs were performed by one expert CS (>1000 RARPs) and two BSs (residents). According to the learning curve of the BS, the patients were divided into three groups: group 1 (first 20 procedures), group 2 (21–40 procedures), and group 3 (>40 procedures). Outcome measurements and statistical analysis: Preoperative variables, pathological data, operating time (OT), blood loss (BL), number of lymph nodes excised (LE), length of hospital stay (LHS), and time to catheter removal (CR) were analyzed. Linear/logistic regression analyses tested the impact of BS experience on surgical outcomes. T test and chi-square test compared the outcomes of the two BSs. Results and limitations: Perfect interaction between CSs and BSs are requested to obtain the optimal exposure and avoid any conflict. On the linear regression model, BS learning curve was not related to OT, BL, LHS, and CR, but was related to LE (r2= 0.09; p = 0.03). On multivariate analyses, no correlation between BS experience and OT, BL, LHS, CR, LE, margin status, and complications (all p > 0.05) was found. Comparing the two BSs, no difference was found for the abovementioned outcomes in the first 40 surgeries (all p > 0.05). Study limitations include the limited cohort of patients and its retrospective nature. Conclusions: In this study, BS learning curve does not appear to influence the surgical outcomes; good experience of the CS was probably the explanation. Patient summary: In our experience, it is the primary surgeon who dictates the perioperative outcomes during robot-assisted radical prostatectomy. In this study, bedside surgeon learning curve does not appear to influence the surgical outcomes; good experience of the console surgeon was probably the explanation. In our experience, it is the primary surgeon who dictates the perioperative outcomes during robot-assisted radical prostatectomy

Human epididymal and prostatic tracts of vas deferens: different contraction response to noradrenaline stimulation in isolated organ bath assay

In the present study epididymal and prostatic portions of human vas deferens were separately isolated and stimulated with exogenous noradrenaline to study their contractile properties. The results displayed that the epididymal tract produced a phasic-tonic response, while the prostatic strip produced only a phasic response suggesting a different functional role of each vas deferens segment. Moreover, it has been verified if alpha(1)-adrenoceptor antagonists doxazosin, alphuzosin and terazosin could differently block the noradrenaline response in each segment. Doxazosin, the most potent antagonist, displayed similar potency in epididymal and prostatic tract (pA(2)=8.51 and 8.42, respectively). Analogously, alphuzosin, although less potent than doxazosin, displayed in the same tracts a superimposed potency (pA(2)=7.25 and 7.30, respectively). In contrast with doxazosin and alphuzosin, terazosin displayed higher potency in blocking the contractile response in prostatic tract (pA(2)=7.67) than in epididymal segment (pA(2)=6.43). These results showed that alpha(1)-adrenoceptor antagonists doxazosin and alphuzosin, although with a different potency, did not discriminate between epididymal and prostatic segment while terazosin showed high potency in prostatic tract and only a moderate activity in epididymal section. Moreover, the biological model employed in our experiments could be a valid screening method to test the potential interferences of drugs indicated for bladder outlet obstruction with the peristaltic activity or the global tone of the human vas deferens