Peritoneal Flap Following Lymph Node Dissection in Robotic Radical Prostatectomy: A Novel "Bunching" Technique.

BACKGROUND: Pelvic lymph node dissection (PLND) is recommended while performing robot-assisted radical prostatectomy (RARP) for patients with localized intermediate or high-risk prostate cancer. However, symptomatic lymphoceles can occur after surgery, adding significant morbidity to patients. Our objective is to describe a novel Peritoneal Bladder Flap Bunching technique (PBFB) to reduce the risk of clinically significant lymphoceles in patients undergoing RARP and PLND. METHODS: We evaluated 2267 patients who underwent RARP with PLND, dividing them into two groups: Group 1, comprising 567 patients who had the peritoneal flap (PBFB), and Group 2, comprising 1700 patients without the flap; propensity score matching carried out at a 1:3 ratio. Variables analyzed included estimated blood loss (EBL), operative time, postoperative complications, lymphocele formation, and the development of symptomatic lymphocele. RESULTS: The two groups exhibited similar preoperative characteristics after matching. There was no statistically significant difference in the occurrence of lymphoceles between the flap group and the non-flap group, with rates of 24% and 20.9%, respectively (p = 0.14). However, none of the patients in the flap group (0%) developed symptomatic lymphoceles, whereas 2.2% of patients in the non-flap group experienced symptomatic lymphoceles (p = 0.01). CONCLUSION: We have demonstrated a modified technique for a peritoneal flap (PBFB) with the initial elimination of postoperative symptomatic lymphoceles and promising short-term outcomes.

Oncologic outcomes with and without amniotic membranes in robotic-assisted radical prostatectomy: A propensity score matched analysis.

Objective: Placement of human placenta derived grafts during robotic-assisted radical prostatectomy (RARP) hastens the return of continence and potency. The long-term impact on the oncologic outcomes remains to be investigated. Our objective was to determine the oncologic outcomes of patients with dehydrated human amnion chorion membrane (dHACM) at RARP compared to a matched cohort. Methods: In a referral centre, from August 2013 to October 2019, 599 patients used dHACM in bilateral nerve-sparing RARP. We excluded patients with less than 12 months follow-up, simple prostatectomy, and unilateral nerve-sparing. Patients with dHACM (amnio group) were 529, and were propensity score matched 1:1 to 2465 patients without dHACM (non-amnio group) and a minimum follow-up of 36 months. At the time of RARP, dHACM was placed around the neurovascular bundle in the amnio group. Continuous and categorical variables in matched groups was tested by two-sample Kolmogorov-Smirnov test and Fisher's exact test respectively. Outcomes measured were biochemical recurrence (BCR), adjuvant and salvage therapy rates. Results: Propensity score matching resulted in two groups of 444 patients. Cumulative incidence functions for BCR did not show a difference between the groups (p=0.3). Patients in the non-amnio group required salvage therapy more frequently than the amnio group, particularly after partial nerve-sparing RARP (6.3% vs. 2.3%, p=0.001). Limitations are the absence of prospective randomization. Conclusion: The data suggest that using dHACM does not have a negative impact on BCR in patients. Outcomes of cancer specific and overall survival will require follow-up study to increase our understanding of these grafts' impact on prostate cancer biology.

Impacts on functional and oncological outcomes of Robotic-assisted Radical Prostatectomy 10 years after the US Preventive Service Taskforce recommendations against PSA screening.

OBJECTIVE: In the following years after the United States Preventive Service Task Force (USPSTF) recommendation against prostate cancer screening with PSA in 2012, several authors worldwide described an increase in higher grades and aggressive prostate tumors. In this scenario, we aim to evaluate the potential impacts of USPSTF recommendations on the functional and oncological outcomes in patients undergoing robotic-assisted radical prostatectomy (RARP) in a referral center. MATERIAL AND METHODS: We included 11396 patients who underwent RARP between 2008 and 2021. Each patient had at least a 12-month follow-up. The cohort was divided into two groups based on an inflection point in the outcomes at the end of 2012 and the beginning of 2013. The inflection point period was detected by Bayesian regression with multiple change points and regression with unknown breakpoints. We reported continuous variables as median and interquartile range (IQR) and categorical variables as absolute and relative percent frequencies. RESULTS: Group 1 had 4760 patients, and Group 2 had 6636 patients, with a median follow-up of 109 and 38 months, respectively. In the final pathology, Group 2 had 9.5% increase in tumor volume, 24% increase on Gleason ≥ 4+3 (ISUP 3) , and 18% increase on ≥ pT3. This translated to a 6% increase in positive surgical margins and 24% reduction in full nerve sparing in response to the worsening pathology. There was a significant decline in post-operative outcomes in Group 2, including a 12-month continence reduction of 9%, reduction in potency by 27%, and reduction of trifecta by 22%. CONCLUSIONS: The increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. Among some historical changes in prostate cancer diagnosis and management in the period of our study, the USPSTF recommendation coincided with worse outcomes of prostate cancer treatment in a population who could benefit from PSA screening at the appropriate time.

Impact of Prostate Size on the Functional and Oncological Outcomes of Robot-assisted Radical Prostatectomy.

BACKGROUND AND OBJECTIVE: Robot-assisted radical prostatectomy (RARP) is the main surgical approach for treatment of prostate cancer in the USA. Prostate size is always depicted as a factor affecting the outcomes of RARP as shown by many studies, but these studies are limited to a small number of patients. Our aim was to evaluate functional and oncologic outcomes of RARP across varying prostate size measured as prostate specimen weight. METHODS: A cohort of 14 481 patients who underwent RARP in a single center was divided into four groups according to prostate specimen weight: group 1, <50 g; group 2, 50-100 g; group 3, 100-150 g; and group 4, >150 g. Perioperative and postoperative variables and pathological and functional outcomes were compared among the four groups. Cumulative incidence functions were plotted to visualize the distribution of event-time variables among the groups, and differences were evaluated using the log-rank test. KEY FINDINGS AND LIMITATIONS: Patients with larger prostates (groups 3 and 4) were more likely to have higher prostate-specific antigen (PSA), lower biopsy grade group, and worse baseline urinary and sexual characteristics. Group 4 had lower rates of full nerve-sparing surgery (13.7% vs 38.3%) and lymph node dissection (51.3% vs 71.4%), more pT2 disease (69.8% vs 60.3%), less pT3 disease (30.2% vs 39.7%), and lower rates of positive surgical margins (12.8% vs 19.3%) and biochemical recurrence (5.9% vs 7.5%) than group 1. Finally, we observed differences in functional outcomes among the groups for greater prostate size, and patients in group 4 had worse rates of urinary continence (77.8% vs 89.5%) and recovery of sexual function (70.0% vs 84.1%) than group 1. Our study is limited by its retrospective design. CONCLUSIONS AND CLINICAL IMPLICATIONS: The results demonstrate that in this large cohort of patients, greater prostate size affects multiple outcomes, including the rate of nerve-sparing surgery, potency and continence recovery, and oncological and pathological outcomes. These data will be valuable when counseling patients regarding possible RARP outcomes and the timeline for recovery. PATIENT SUMMARY: Our study shows that prostate size can affect the outcomes of robot-assisted removal of the prostate for patients with prostate cancer. Larger prostate size can be associated with worse functional outcomes after surgery.

FK506 bypasses the effect of erythroferrone in cancer cachexia skeletal muscle atrophy.

Skeletal muscle atrophy is a hallmark of cachexia, a wasting condition typical of chronic pathologies, that still represents an unmet medical need. Bone morphogenetic protein (BMP)-Smad1/5/8 signaling alterations are emerging drivers of muscle catabolism, hence, characterizing these perturbations is pivotal to develop therapeutic approaches. We identified two promoters of "BMP resistance" in cancer cachexia, specifically the BMP scavenger erythroferrone (ERFE) and the intracellular inhibitor FKBP12. ERFE is upregulated in cachectic cancer patients' muscle biopsies and in murine cachexia models, where its expression is driven by STAT3. Moreover, the knock down of Erfe or Fkbp12 reduces muscle wasting in cachectic mice. To bypass the BMP resistance mediated by ERFE and release the brake on the signaling, we targeted FKBP12 with low-dose FK506. FK506 restores BMP-Smad1/5/8 signaling, rescuing myotube atrophy by inducing protein synthesis. In cachectic tumor-bearing mice, FK506 prevents muscle and body weight loss and protects from neuromuscular junction alteration, suggesting therapeutic potential for targeting the ERFE-FKBP12 axis.

PHAF1/MYTHO is a novel autophagy regulator that controls muscle integrity.

Skeletal muscles play key roles in movement, posture, thermogenesis, and whole-body metabolism. Autophagy plays essential roles in the regulation of muscle mass, function and integrity. However, the molecular machinery that regulates autophagy is still incompletely understood. In our recent study, we identified and characterized a novel Forkhead Box O (FoxO)-dependent gene, PHAF1/MYTHO (phagophore assembly factor 1/macro-autophagy and youth optimizer), as a novel autophagy regulator that controls muscle integrity. MYTHO/PHAF1 is upregulated in multiple conditions leading to muscle atrophy, and downregulation of its expression spares muscle atrophy triggered by fasting, denervation, cachexia and sepsis. Overexpression of PHAF1/MYTHO is sufficient to induce muscle atrophy. Prolonged downregulation of PHAF1/MYTHO causes a severe myopathic phenotype, which is characterized by impaired autophagy, muscle weakness, myofiber degeneration, mammalian target of rapamycin complex 1 (mTORC1) hyperactivation and extensive ultrastructural defects, such as accumulation of proteinaceous and membranous structures and tubular aggregates. This myopathic phenotype is attenuated upon administration of the mTORC1 inhibitor rapamycin. These findings position PHAF1/MYTHO as a novel regulator of skeletal muscle autophagy and tissue integrity.

NAD+ repletion with niacin counteracts cancer cachexia.

Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD+ repletion therapy in cachectic mice reveals that NAD+ precursor, vitamin B3 niacin, efficiently corrects tissue NAD+ levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose NAD+ metabolism as a therapy target for cachectic cancer patients.

The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trial.

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.

MYTHO is a novel regulator of skeletal muscle autophagy and integrity.

Autophagy is a critical process in the regulation of muscle mass, function and integrity. The molecular mechanisms regulating autophagy are complex and still partly understood. Here, we identify and characterize a novel FoxO-dependent gene, d230025d16rik which we named Mytho (Macroautophagy and YouTH Optimizer), as a regulator of autophagy and skeletal muscle integrity in vivo. Mytho is significantly up-regulated in various mouse models of skeletal muscle atrophy. Short term depletion of MYTHO in mice attenuates muscle atrophy caused by fasting, denervation, cancer cachexia and sepsis. While MYTHO overexpression is sufficient to trigger muscle atrophy, MYTHO knockdown results in a progressive increase in muscle mass associated with a sustained activation of the mTORC1 signaling pathway. Prolonged MYTHO knockdown is associated with severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and extensive ultrastructural defects, such as accumulation of autophagic vacuoles and tubular aggregates. Inhibition of the mTORC1 signaling pathway in mice using rapamycin treatment attenuates the myopathic phenotype triggered by MYTHO knockdown. Skeletal muscles from human patients diagnosed with myotonic dystrophy type 1 (DM1) display reduced Mytho expression, activation of the mTORC1 signaling pathway and impaired autophagy, raising the possibility that low Mytho expression might contribute to the progression of the disease. We conclude that MYTHO is a key regulator of muscle autophagy and integrity.

Comparison between intra- and postoperative outcomes of the da Vinci SP and da Vinci Xi robotic platforms in patients undergoing radical prostatectomy.

The new SP robot incorporates a single trocar that houses a flexible camera and three bi-articulated arms, which minimize the number of incisions needed to assess the surgical site, allowing for a less invasive procedure. To compare the postoperative pain scale and outcomes in patients with similar demographic characteristics undergoing robotic-assisted radical prostatectomy (RARP) with SP and Xi robots, One-hundred consecutive patients undergoing RARP with the SP robot were matched, using a propensity score (PS), with 100 patients from a cohort of 1757 who were operated on with the da Vinci Xi from June 2019 to January 2021. We described and compared the perioperative pain scores and outcomes of both groups. The SP group had less blood loss (50 cc vs. 62.5 cc, P < 0.001) and longer operative time (114 min. vs. 94 min, P < 0.001). The only period we could show a difference in postoperative pain scores was 6 h after surgery, with a small advantage for the SP (2 vs. 2.5, P < 0.001). Both groups had satisfactory postoperative continence recovery, 91% vs. 90% for the SP and Xi, respectively. The groups had a mean follow-up of 24.5 and 22 months for SP and Xi, respectively. The tumor stage and percentage of positive surgical margins were similar between groups (15% vs. 15%, P = 1). Patients undergoing RARP with the SP had longer operative times with less blood loss than the Xi. However, despite the lower number of abdominal incisions on the SP, the groups had similar intraoperative performance, and we were unable to demonstrate clinically significant differences in postoperative pain scores between the groups 6, 12, and 18 h after surgery.

Simultaneous hernia repair following robotic-assisted radical prostatectomy is safe with low rates of mesh-related complications.

Robotic-assisted radical prostatectomy (RARP) is the gold-standard treatment for localized prostate cancer in the USA. However, performing RARP along with a concomitant hernia repair with mesh is debatable because of the lack of well-designed studies on this subject. Some argue that this procedure may result in mesh infections and increased complications due to possible contact of mesh and urine. This study reports our experience with simultaneous hernia repair with mesh placement in patients who underwent radical prostatectomy. We compared 244 patients (from August 2008 to August 2021) who underwent RARP with concomitant hernia repair (inguinal, umbilical, and ventral) and mesh placement with 244 patients from 6275 RARPs operated on the same period without hernia repair. We performed a propensity score matching analysis using preoperative covariates and compared the perioperative outcomes, and complications in 90 days after surgery. Median follow-up was 36.6 months for the control and hernia groups respectively (p = 0.81). Eighty-three patients had unilateral inguinal hernia repair, 22 had a bilateral inguinal hernia repair, 95 had a ventral hernia repair, and 44 had an umbilical hernia repair. The median operative time was 112 min for the control group and 160 min for hernia groups (p < 0.001). We did not find statistically significant differences in minor complications (Clavien ≤ 2). Although the postoperative readmissions in 90-days were higher in the hernia group (18 vs. 7, p = 0.038), none was associated with mesh complications. Limitation includes the retrospective design of the study. Robotic-assisted radical prostatectomy with simultaneous hernia repair and mesh placement is safe and does not increase complications related to the mesh. In our experience, hernia repair increases the operative time, usually due to initial peritoneal flap dissection and final suturing. Therefore, we believe that hernia repair with mesh during RARP is safe and spares patients the additional impacts of an additional surgical procedure.

Comparing the outcomes of robotic assisted radical prostatectomy in black and white men: Experience of a high-volume center

ABSTRACT Background: Global cancer incidence ranks Prostate Cancer (CaP) as the second highest overall, with Africa and the Caribbean having the highest mortality. Previous literature suggests disparities in CaP outcomes according to ethnicity, specifically functional and oncological are suboptimal in black men. However, recent data shows black men achieve post radical prostatectomy (RP) outcomes equivalent to white men in a universally insured system. Our objective is to compare outcomes of patients who self-identified their ethnicity as black or white undergoing RP at our institution. Materials and methods: From 2008 to 2017, 396 black and 4929 white patients underwent primary robotic-assisted radical prostatectomy (RARP) with a minimum follow-up of 5 years. Exclusion criteria were concomitant surgery and cancer status not available. A propensity score (PS) match was performed with a 1:1, 1:2, and 1:3 ratio without replacement. Primary endpoints were potency, continence recovery, biochemical recurrence (BCR), positive surgical margins (PSM), and post-operative complications. Results: After PS 1:1 matching, 341 black vs. 341 white men with a median follow-up of approximately 8 years were analyzed. The overall potency and continence recovery at 12 months was 52% vs 58% (p=0.3) and 82% vs 89% (p=0.3), respectively. PSM rates was 13.4 % vs 14.4% (p = 0.75). Biochemical recurrence and persistence PSA was 13.8% vs 14.1% and 4.4% vs 3.2% respectively (p=0.75). Clavien-Dindo complications (p=0.4) and 30-day readmission rates (p=0.5) were similar. Conclusion: In our study, comparing two ethnic groups with similar preoperative characteristics and full access to screening and treatment showed compatible RARP results. We could not demonstrate outcomes superiority in one group over the other. However, this data adds to the growing body of evidence that the racial disparity gap in prostate cancer outcomes can be narrowed if patients have appropriate access to prostate cancer management. It also could be used in counseling surgeons and patients on the surgical intervention and prognosis of prostate cancer in patients with full access to gold-standard screening and treatment.

Searching the half-full glass of COVID-19 pandemic: basic hygienic measures positively impact on postoperative infections after major elective urological surgery: a single-center matched pair analysis.

BACKGROUND: Since before the COVID-19 pandemic, hospital-acquired infections (HAIs) represented a global healthcare crisis. Few studies suggested that COVID-19-related basic hygiene measures (BHM) could lower HAIs rates, reaching inconclusive results. The aim of this study was to investigate the hypothetical benefit on HAIs rate of COVID-19-enhanced BHM systematic introduction after major elective urological surgery. METHODS: Since the pandemic began, our hospital has implemented BHM to limit the spread of COVID-19. We compared patients operated in the pre-COVID-19 era (no-BHM period) with those operated after the pandemic started (BHM period). Outcomes were the incidence of HAIs and postoperative complications, and the length of hospital stay (LOS). Two balanced groups were generated by propensity score 1:1 matching. RESULTS: Of 1053 major urological interventions, 604 were performed in the no-BHM period, and 449 in the BHM period. After matched analysis, the comparison groups consisted of 310 patients each. Of 107 recorded HAIs, 43 occurred during the BHM period (13.9%), and 64 during the no-BHM period (20.7%), with a statistically significant difference in multivariable analysis (OR 0.5 [95% CI 0.3-0.8], P=0.004). Postoperative complications rate was significantly lower in the BHM period than in the no-BHM period (29.0% versus 36.5%, OR 0.6 [95% CI 0.4-0.9], P=0.01). The LOS differed significantly between BHM and no-BHM periods: a median of 5 (5-8) days versus 6 (5-8), respectively (P<0.001). CONCLUSIONS: The risk of infections, postoperative complications, and prolonged LOS after major urological surgery was significantly reduced with the systematic introduction of COVID-19-related BHM, their application could, therefore, be prolonged with lasting benefits.

Plasma proteome profiling of healthy subjects undergoing bed rest reveals unloading-dependent changes linked to muscle atrophy.

BACKGROUND: Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed-ridden patients care, but it is also a ground-based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion. METHODS: We applied mass spectrometry-based proteomics to measure plasma protein abundance changes in response to 10 days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age-matched controls. Our analysis resulted in the quantification of over 500 proteins. RESULTS: Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin-4 increased 1.6-fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P = 0.02) and decreased to 0.6-fold the initial abundance after 2 days of recovery at normal daily activity (R + 2, 2.7E9, P = 3.3E-4); the extracellular matrix protein lumican was decreased to 0.7-fold (1.2E9 vs. 8.5E8, P = 1.5E-4) at BR10 and remained as low at R + 2. We identified six proteins distinguishing subjects developing unloading-mediated muscle atrophy (decrease of >4% of quadriceps cross-sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone-binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P = 0.001). Haptoglobin-related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls. CONCLUSIONS: Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy-prone and atrophy-resistant subjects after 10 days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity-triggered muscle loss in humans.

OPA1 drives macrophage metabolism and functional commitment via p65 signaling.

Macrophages are essential players for the host response against pathogens, regulation of inflammation and tissue regeneration. The wide range of macrophage functions rely on their heterogeneity and plasticity that enable a dynamic adaptation of their responses according to the surrounding environmental cues. Recent studies suggest that metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the metabolic pathways orchestrating macrophage activation are still under scrutiny. Optic atrophy 1 (OPA1) is a mitochondria-shaping protein controlling mitochondrial fusion, cristae biogenesis and respiration; clear evidence shows that the lack or dysfunctional activity of this protein triggers the accumulation of metabolic intermediates of the TCA cycle. In this study, we show that OPA1 has a crucial role in macrophage activation. Selective Opa1 deletion in myeloid cells impairs M1-macrophage commitment. Mechanistically, Opa1 deletion leads to TCA cycle metabolite accumulation and defective NF-κB signaling activation. In an in vivo model of muscle regeneration upon injury, Opa1 knockout macrophages persist within the damaged tissue, leading to excess collagen deposition and impairment in muscle regeneration. Collectively, our data indicate that OPA1 is a key metabolic driver of macrophage functions.

Features of patients referring to the outpatient office due to benign prostatic hyperplasia: analysis of a national prospective cohort of 5815 cases.

BACKGROUND: Evidence on clinical presentation of benign prostatic hyperplasia (BPH) is scarce, and studies involving outpatients are lacking. We aimed to provide an insight into the contemporary Italian scenario of BPH-affected outpatients using symptom scores (International Prostate Symptom Score [IPSS], BPH Impact Index [BII]), and to compare characteristics of patients with known BPH and those first-diagnosed at the visit. METHODS: "IMPROVING THE PATH" project working group designed a questionary prospectively administered to BPH-affected outpatients by urologists. A cross-sectional study was performed. Data were adjusted for patient age as a potential confounding factor. RESULTS: Of 5815 patients enrolled, BPH was already diagnosed in 4144 (71.3%), and not in 1671 (28.7%). Patients with known BPH, compared to newly diagnosed, were older (median 68 versus [vs] 55), had more frequent smoking (smoker 27.2 vs 22.6%, and ex-smoker 16.4 vs 12.5%) and drinking habits (55.4 vs 45.1%), were more frequently affected by hypertension (60.0 vs 42.4%), obesity (15.3 vs 9.6%), diabetes (17.9 vs 12.5%), and cardiovascular diseases (14.2 vs 9.5%), p < 0.001. At IPSS, moderate and severe symptoms correlated with already known BPH (56.1 vs 47.3% and 24.8 vs 7.8%), whereas newly diagnosed patients showed milder symptoms (44.9 vs 19.1%), all p < 0.001. At BII, concern for one's health and time lost due to urinary problems were higher in patients with known BPH (p < 0.001). For these patients, the urologist changes at least one of the ongoing medications in 63.5%. For patients newly diagnosed, supplements/phytotherapeutics, alpha-blockers, and 5-alfa reductase inhibitors were prescribed in 54.6%, 21.6%, and 7.1%, respectively. CONCLUSIONS: Despite medical treatment, natural history of BPH leads to a progressive deterioration of symptoms. This may reflect the difference between newly diagnosed patients and those with known BPH in lifestyle and associated comorbidities. A healthy lifestyle and treatments including local anti-inflammatory agents may delay worsening of symptoms and improve quality of life.

Pre-operative prediction of extracapsular extension of prostate cancer: first external validation of the PRECE model on an independent dataset.

INTRODUCTION: The PRECE is a model predicting the risk of extracapsular extension (ECE) of prostate cancer: it has been developed on more than 6000 patients who underwent robotic radical prostatectomy (RARP) at the Global Robotic Institute, FL, USA. Up to now, it is the single tool predicting either the side and the amount of ECE. The model has a free user-friendly interface and is made up from simple and available covariates, namely age, PSA, cT, GS and percent of positive core, the latter topographically distributed within the prostate gland. Despite the successful performance at internal validation, the model is still lacking an external validation (EV). The aim of the paper is to externally validate the PRECE model on an Italian cohort of patients elected to RARP. METHODS: 269 prostatic lobes from 141 patients represented the validation dataset. The EV was performed with the receiver operating characteristics (ROC) curves and calibration, to address the ability of PRECE to discriminate between patients with or without ECE. RESULTS: Overall, an ECE was found in 91 out of the 269 prostatic lobes (34%). Twenty-five patients out of pT3 had a bilateral ECE. The ROC curve showed an AUC of 0.80 (95% CI 0.74-0.85). Sensitivity and specificity were 77% and 69%, respectively. The model showed an acceptable calibration with tendency towards overestimation. CONCLUSIONS: From the current EV, the PRECE displays a good predictive performance to discriminate between cases with and without ECE; despite preliminary, outcomes may support the generalizability of the model in dataset other than the development one.

Comparing the outcomes of robotic assisted radical prostatectomy in black and white men: Experience of a high-volume center.

BACKGROUND: Global cancer incidence ranks Prostate Cancer (CaP) as the second highest overall, with Africa and the Caribbean having the highest mortality. Previous literature suggests disparities in CaP outcomes according to ethnicity, specifically functional and oncological are suboptimal in black men. However, recent data shows black men achieve post radical prostatectomy (RP) outcomes equivalent to white men in a universally insured system. Our objective is to compare outcomes of patients who self-identified their ethnicity as black or white undergoing RP at our institution. MATERIALS AND METHODS: From 2008 to 2017, 396 black and 4929 white patients underwent primary robotic-assisted radical prostatectomy (RARP) with a minimum follow-up of 5 years. Exclusion criteria were concomitant surgery and cancer status not available. A propensity score (PS) match was performed with a 1:1, 1:2, and 1:3 ratio without replacement. Primary endpoints were potency, continence recovery, biochemical recurrence (BCR), positive surgical margins (PSM), and post-operative complications. RESULTS: After PS 1:1 matching, 341 black vs. 341 white men with a median follow-up of approximately 8 years were analyzed. The overall potency and continence recovery at 12 months was 52% vs 58% (p=0.3) and 82% vs 89% (p=0.3), respectively. PSM rates was 13.4 % vs 14.4% (p = 0.75). Biochemical recurrence and persistence PSA was 13.8% vs 14.1% and 4.4% vs 3.2% respectively (p=0.75). Clavien-Dindo complications (p=0.4) and 30-day readmission rates (p=0.5) were similar. CONCLUSION: In our study, comparing two ethnic groups with similar preoperative characteristics and full access to screening and treatment showed compatible RARP results. We could not demonstrate outcomes superiority in one group over the other. However, this data adds to the growing body of evidence that the racial disparity gap in prostate cancer outcomes can be narrowed if patients have appropriate access to prostate cancer management. It also could be used in counseling surgeons and patients on the surgical intervention and prognosis of prostate cancer in patients with full access to gold-standard screening and treatment.

Randomized Clinical Trial Comparing On-clamp Versus Off-clamp Laparoscopic Partial Nephrectomy for Small Renal Masses (CLOCK II Laparoscopic Study): A Intention-to-treat Analysis of Perioperative Outcomes.

Background: Recent randomized trials (RCTs) in the field of robotic partial nephrectomy (PN) showed no significant differences in perioperative outcomes between the off- and on-clamp approaches. Objective: To compare the perioperative outcomes of on- versus off-clamp pure laparoscopic PN (LPN). Design setting and participants: A multi-institutional analysis of the on- versus off-clamp approach during LPN in the setting of an RCT (CLOCK II trial; ClinicalTrials.gov NCT02287987) was performed. Intervention: Off- versus on-clamp LPN. Outcome measurements and statistical analysis: Baseline patient and tumor variables, and peri- and postoperative data were collected. Randomized allocation with a 1:1 ratio was assigned. Surgical strategy for managing the renal pedicle was dictated by the study protocol. In the off-clamp arm, the renal artery had to remain unclamped for the duration of the whole procedure. Reporting the intention-to-treat analysis is the purpose of the study. Results and limitations: The study recruited 249 patients. Of them, 123 and 126 were randomized and allocated into the on- and off-clamp treatment groups, respectively. Treatment groups were comparable at baseline after randomization with respect to patients' demographics, comorbidities, renal function, and tumor size and complexity. A univariable analysis found no differences in the perioperative outcomes between the groups, including median (interquartile range) estimated blood loss (150 [100-200] vs 150 [100-250] ml, p = 0.2), grade ≥2 complication rate as classified according to the Clavien-Dindo system (5.7% vs 4.8%, p = 0.6), and positive surgical margin rate (8.2% vs 3.5% for the on- vs off-clamp group, p = 0.1). No differences were found in terms of the 1st (81.3 [66.7-94.3] vs 85.3 [71.0-97.7] ml/min, p = 0.2) and 5th postoperative days estimated glomerular filtration rate (83.3 [70.5-93.7] vs 83.4 [68.6-139.3] ml/min, p = 0.2). A multivariable analysis found each +1 increase in RENAL score corresponded to an increase in the protection from the occurrence of complications (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.54-0.97, p = 0.034), while each +1 cm increase in tumor size corresponded to an increase in the risk of blood transfusion (OR 1.39, 95% CI 1.14-1.70, p = 0.001). Conclusions: In the setting of an RCT, no differences were found in the perioperative and early functional outcomes between on- and off-clamp LPN. Patient summary: In this study, we investigated, by means of a randomized trial, whether avoiding the clamping of renal artery during laparoscopic resection of renal mass is able to translate into benefits. We found no differences in terms of safety, efficacy, and renal function from the standard approach, which includes arterial clamping.

Thulium laser enucleation of prostate versus laparoscopic trans-vesical simple prostatectomy in the treatment of large benign prostatic hyperplasia: head-to-head comparison

ABSTRACT Objectives: To compare thulium laser enucleation of prostate (ThuLEP) versus laparoscopic trans-vesical simple prostatectomy (LSP) in the treatment of benign prostatic hyperplasia (BPH). Materials and Methods: Data of patients who underwent surgery for "large" BPH (>80mL) at three Institutions were collected and analyzed. Two institutions performed ThuLEP only; the third institution performed LSP only. Preoperative (indwelling catheter status, prostate volume (PVol), hemoglobin (Hb), Qmax, post-voiding residual volume (PVR), IPSS, QoL, IIEF-5) and perioperative data (operative time, enucleated adenoma, catheterization time, length of stay, Hb-drop, complications) were compared. Functional (Qmax, PVR, %ΔQmax) and patient-reported outcomes (IPSS, QoL, IIEF-5, %ΔIPSS, %ΔQoL) were compared at last follow-up. Results: 80 and 115 patients underwent LSP and ThuLEP, respectively. At baseline, median PVol was 130 versus 120mL, p <0.001; Qmax 9.6 vs. 7.1mL/s, p=0.005; IPSS 21 versus 25, p <0.001. Groups were comparable in terms of intraoperative complications (1 during LSP vs. 3 during ThuLEP) and transfusions (1 per group). Differences in terms of operative time (156 vs. 92 minutes, p <0.001), Hb-drop (-2.5 vs. −0.9g/dL, p <0.001), catheterization time (5 vs. 2 days, p <0.001) and postoperative complications (13.8% vs. 0, p <0.001) favored ThuLEP. At median follow-up of 40 months after LSP versus 30 after ThuLEP (p <0.001), Qmax improved by 226% vs. 205% (p=0.5), IPSS decreased by 88% versus 85% (p=0.9), QoL decreased by 80% with IIEF-5 remaining almost unmodified for both the approaches. Conclusions: Our analysis showed that LSP and ThuLEP are comparable in relieving from BPO and improving the patient-reported outcomes. Invasiveness of LSP is more significant.