Association between Expression of Connective Tissue Genes and Prostate Cancer Growth and Progression.

To find an association between genomic features of connective tissue and pejorative clinical outcomes on radical prostatectomy specimens. We performed a retrospective analysis of patients who underwent radical prostatectomy and underwent a Decipher transcriptomic test for localized prostate cancer in our institution (n = 695). The expression results of selected connective tissue genes were analyzed after multiple t tests, revealing significant differences in the transcriptomic expression (over- or under-expression). We investigated the association between transcript results and clinical features such as extra-capsular extension (ECE), clinically significant cancer, lymph node (LN) invasion and early biochemical recurrence (eBCR), defined as earlier than 3 years after surgery). The Cancer Genome Atlas (TCGA) was used to evaluate the prognostic role of genes on progression-free survival (PFS) and overall survival (OS). Out of 528 patients, we found that 189 had ECE and 27 had LN invasion. The Decipher score was higher in patients with ECE, LN invasion, and eBCR. Our gene selection microarray analysis showed an overexpression in both ECE and LN invasion, and in clinically significant cancer for COL1A1, COL1A2, COL3A1, LUM, VCAN, FN1, AEBP1, ASPN, TIMP1, TIMP3, BGN, and underexpression in FMOD and FLNA. In the TCGA population, overexpression of these genes was correlated with worse PFS. Significant co-occurrence of these genes was observed. When presenting overexpression of our gene selection, the 5-year PFS rate was 53% vs. 68% (p = 0.0315). Transcriptomic overexpression of connective tissue genes correlated to worse clinical features, such as ECE, clinically significant cancer and BCR, identifying the potential prognostic value of the gene signature of the connective tissue in prostate cancer. TCGAp cohort analysis showed a worse PFS in case of overexpression of the connective tissue genes.

Matrix effects on hydrogen bonding and proton transfer in fluoropyridine - HCl complexes.

We report an extensive computational and spectroscopic study of several fluoropyridine-HCl complexes, and the parent, pyridine-HCl system. Matrix-IR spectra for pentafluoropyridine-HCl, 2,6-difluororpyridine-HCl, and 3,5-difluororpyridine-HCl in solid neon exhibit shifts for the H-Cl stretching band that parallel the effects of fluorination on hydrogen-bond strength. Analogous spectral shifts observed across various host environments (solid neon, argon, and nitrogen) for pentafluoropyridine-HCl and 2,6-difluororpyridine-HCl convey a systematically varying degree of matrix stabilization on the hydrogen bonds in these complexes. An extended quantum-chemical study of pyridine-HCl and eight fluorinated analogs, including 2-, 3-, and 4-fluoropyridine-HCl, 2,6- and 3,5-difluororpyridine-HCl, 2,4,6- and 3,4,5-trifluropyridine-HCl, as well as pentafluoropyridine-HCl, was also performed. Equilibrium structures and binding energies for the gas-phase complexes illustrate two clear trends in how fluorine substitution affects hydrogen bond strength; increasing fluorination weakens these interactions, yet substitution at the 2- and 6-positions has the most pronounced effect. Bonding analyses for a select subset of these systems reveal shifts in electron density that accompany hydrogen bonding, and most notably, the values of the electron density at the N-H bond critical points among the stronger systems in this subset significantly exceed those typical for moderately strong hydrogen-bonds. We also explored the effects of dielectric media on the structural and bonding properties of these systems. For pyridine-HCl, 3-fluoropyridine-HCl, and 3,5-difluororpyridine-HCl, a transition to proton transfer-type structures is observed at ε-values of 1.2, 1.5, and 2.0, respectively. This is signaled by key structural changes, as well as an increase in the negative charge on the chorine, and dramatic shifts in topological properties of the H-Cl and N-H bonds. In the case of pentafluoropyridine-HCl, and 2,6-difluororpyridine-HCl, we do not predict proton transfer in dielectric media up to ε = 20.0. However, there are clear indications that the media enhance hydrogen-bond strength, and moreover, these observations are completely consistent with the experimental IR spectra.

Using biomarkers in patients with positive multiparametric magnetic resonance imaging: 4Kscore predicts the presence of cancer outside the index lesion.

OBJECTIVES: To evaluate if the blood biomarker, 4Kscore, in addition to multiparametric magnetic resonance imaging information could identify patients who would benefit from undergoing only a targeted biopsy. METHODS: We retrospectively analyzed a population of 256 men with positive multiparametric magnetic resonance imaging who underwent standard + targeted biopsy at Mount Sinai Hospital, New York, NY, USA. 4Kscore (OPKO Health, Miami, FL, USA) was sampled from all patients before biopsy. Uni- and multivariable binary logistic regression analyses were carried out to predict clinically significant prostate cancer, defined as International Society of Urological Pathology grade group ≥2, in standard biopsy cores. The model with the best area under the curve was selected and internal validation was carried out using the leave-one-out cross-validation. RESULTS: The developed model showed an area under the curve of 0.86. Carrying out only targeted biopsy in patients with a model-derived probability <12.5% resulted in 39.5% (n = 101) fewer standard biopsies and a 33.9% (n = 20) reduction of detecting grade group 1 disease, while missing grade group ≥2 in 5.2% (n = 4) using standard biopsy only and 1.1% (n = 1) using standard biopsy + targeted biopsy. CONCLUSIONS: 4Kscore in combination with multiparametric magnetic resonance imaging can help to reduce unnecessary standard biopsy and decrease detection of clinically insignificant prostate cancer.

Staging Accuracy of Multiparametric Magnetic Resonance Imaging in Caucasian and African American Men Undergoing Radical Prostatectomy.

PURPOSE: We compared the performance of multiparametric magnetic resonance imaging for the prediction of extraprostatic extension in African American and Caucasian American men and evaluated racial disparities in pathological outcomes after radical prostatectomy. MATERIALS AND METHODS: We identified 975 patients who underwent radical prostatectomy with preoperative multiparametric magnetic resonance imaging between January 2013 and April 2019 at our institution. Multivariable logistic regression analysis was performed predicting pathological extraprostatic extension, high grade prostate cancer (final pathology GGG [Gleason Grade Group] 3 or greater) in the overall population and pathological upgrading (final pathology GGG 3 or greater) in patients with a diagnosis of GGG 1-2 prostate cancer. Adverse pathology was defined as pT3 and/or GGG 3 or greater. RESULTS: A total of 221 (23%) patients were African American. Preoperatively 594 (60.9%) were GGG 1-2 (low risk group) and 381 (39.1%) GGG 3 or greater (high risk group). In the low risk group rates of pathological extraprostatic extension (18% vs 12.8%, p=0.14), adverse pathology (18% vs 13.4%, p=0.2) or upgrading (9.4% vs 12.1%, p=0.4) were similar between races. Similarly, in the high risk group there was no difference in rates of pathological extraprostatic extension. On multivariable analysis multiparametric magnetic resonance imaging predicted the presence of extraprostatic extension (OR 1.80, 95% CI 1.29-2.50) and high grade prostate cancer (OR 1.82, 95% CI 1.25-2.67) on final pathology. Conversely, race did not predict the outcomes of interest (all values p >0.05). Multiparametric magnetic resonance imaging showed comparable sensitivity (22.22% vs 27.84%), specificity (89.2% vs 79.2%), positive predictive value (89.2% vs 83.4%) and negative predictive value (89.2% vs 83.4%) between African American and Caucasian America men, respectively. CONCLUSIONS: The accuracy of multiparametric magnetic resonance imaging in staging prostate cancer was similar in African American and Caucasian American patients and no difference was found between races in pathological outcomes after radical prostatectomy. These findings suggest that access to and use of advanced diagnostic tests may help mitigate prostate cancer racial disparities.

A cohort of transperineal electromagnetically tracked magnetic resonance imaging/ultrasonography fusion-guided biopsy: assessing the impact of inter-reader variability on cancer detection.

OBJECTIVE: To evaluate the ability to detect clinically significant prostate cancer (PCa) using a novel electromagnetically (EM) tracked transperineal magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (transperineal TBx) platform and the impact of inter-reader variability on cancer detection. MATERIALS AND METHODS: A total of 176 patients with suspicious lesions detected on multiparametric MRI (mpMRI) underwent a systematic modified Barzel template biopsy (12-core) transperineal biopsy (transperineal SBx) and transperineal TBx with EM tracking (UroNav; Philips Healthcare, Best, the Netherlands) in the same setting. Cancer detection rates (CDRs) were stratified by Prostate Imaging Reporting and Data System (PI-RADS) v2 scores and compared with Fisher's exact test. Area under the curve (AUC) was calculated for prostate-specific antigen (PSA), PSA density (PSAD), PI-RADS score, and subgroup analysis of individual readers' PI-RADS scores with respect to overall CDR and clinically significant CDR. RESULTS: The overall CDR was 76.7% (135/176), of which 76.3% (103/135) was clinically significant PCa. Among the 135 patients with PCa, transperineal TBx detected 90.4% of cases (122/135), either alone or in combination with transperineal SBx. The remaining 9.6% of cases (13/135) missed by transperineal TBx were diagnosed by transperineal SBx alone, of which three were clinically significant. Conversely, transperineal SBx missed 14% of cases (19/135), 14 of which were clinically significant PCa. Sensitivities for transperineal TBx and transperineal SBx were 90.4% and 85.9%, respectively. On a per-lesion basis, PI-RADS score (AUC 0.74) outperformed both PSA (AUC 0.59) and PSAD (AUC 0.63) in discriminating clinically significant from non-clinically significant PCa on transperineal TBx. Although not formally statistically tested, AUCs amongst different mpMRI readers appeared to display considerable variability. There were no adverse events, including sepsis. CONCLUSIONS: Electromagnetically tracked transperineal TBx of MRI-visible lesions enhanced the ability of transperineal SBx to detect PCa, with greater sensitivity for clinically significant disease. These findings suggest transperineal TBx is a safe, alternative fusion platform for patients with a suspicious lesion on prostate MRI. The assessment of inter-reader variability, in conjunction with prediction of clinically significant PCa and CDR, is an important first step for quality control in implementing an MRI-based screening programme.

Sexual Activity After Bariatric Surgery: A Prospective Monocentric Study Using the PISQ-IR Questionnaire.

INTRODUCTION: Obesity can lead to pelvic floor disorders, interfering with women's sexual life; Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association-Revised (PISQ-IR) is a new instrument to measure sexual life in women with pelvic floor disorders. AIMS: To assess the utility of using PISQ-IR in morbidly obese women undergoing bariatric surgery and to show the improvement of bariatric surgery on sexuality. METHODS: This prospective monocentric study included all women who underwent bariatric surgery from June 2016-May 2017. Sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) was performed by 1 surgeon, and data were collected by 1 researcher. Demographics, medical history, number of deliveries, and type of bariatric surgery (SG or RYGB) were collected at baseline. At the 1-year follow-up consultation, postoperative complications, percentage of total body weight loss (TWL) and percentage excess weight loss were assessed. Questionnaires were given at baseline and at 1-year follow-up. MAIN OUTCOME MEASURES: Postoperative complications and total weight loss were measured at the 1-year follow-up. Sexual activity, using the PISQ-IR, and pelvic organ prolapse, urinary incontinence, and anal incontinence, using the urinary symptom profile and PFDI (Pelvic Floor Distress Inventory) 20, were compared before surgery and at 1-year follow-up. RESULTS: 72 patients were included at baseline, 54 (75%) were considered for final analysis (30 RYGB and 24 SG), and 51 patients were considered for PISQ-IR. The mean preoperative body mass index was 41 ± 5.4 kg/m2, and mean age was 43 ± 11.8 years. Both procedures induced an important weight loss (mean TWL of 33%) and had a similar percentage of TWL for each procedure: 31 (15-46) for SG vs 34 (9-51) for RYGB. 9 patients (17 [6%]) became sexually active 1 year after surgery. For the sexually inactive population after 1 year, there was no differences in the PISQ-IR in the follow-up. When body mass index loss was >13 kg/m2, a higher percentage of the sexually active population improved their different scores, and there were significant results for both global quality of life and desire (P = .026 and .046). The other questionnaires showed a significant decrease in urinary incontinence symptoms (P < .001) associated with weight loss, whereas there was no difference in terms of pelvic organ prolapse or anal incontinence. CONCLUSION: PISQ-IR is a useful instrument to measure sexual function regarding pelvic floor disorders. Bariatric surgery improves sexual activity in obese women 1 year after surgery. Treacy PJ, Mazoyer C, Falagario U, et al. Sexual Activity After Bariatric Surgery: A Prospective Monocentric Study Using the PISQ-IR Questionnaire. J Sex Med 2019;16:1930-1937.

Perioperative complications of sleeve gastrectomy: Review of the literature.

Sleeve gastrectomy (SG) has known a spectacular rise worldwide during the last decade. The absence of digestive anastomosis simplifies the surgical technique, reducing anastomosis-related complications such as fistula, stricture and marginal ulcer. Furthermore, the respect for digestive continuity preserves the functions of pylorus, that regulates gastric emptying, and duodenum, where calcium, B vitamins and iron are absorbed. Despite the multiple advantages, SG also has specific complications such as bleeding, stenosis, portal thrombosis and leak. The staple line leak at the oesophagogastric junction is the most feared complication and its prevention remains difficult, as the involved mechanisms have been only partially elucidated. Its management is long and requires a multidisciplinary technical platform including Intensive Care Unit, digestive endoscopy and interventional radiology as well as a specialised surgeon. The aim of this review is to explain in detail the perioperative complications of SG, their prevention and treatment, referring to the most recent available literature.

Hyaluronidase for Dermal Filler Complications: Review of Applications and Dosage Recommendations.

BACKGROUND: Hyaluronidase (Hyal) can reverse complications of hyaluronic acid (HA) fillers, which has contributed substantially to the popularity of such procedures. Still, there are differing opinions regarding Hyal treatment, including dosage recommendations in filler complication management. OBJECTIVE: We aimed to address unanswered questions regarding Hyal treatment for HA filler complications, including timing and dosage, skin pretesting, properties of various Hyals and interactions with HA gels, and pitfalls of the treatment. METHODS: PubMed and Google Scholar databases were searched from inception for articles on Hyal therapy for filler complications. Articles were evaluated regarding their contribution to the field. The extensive literature review includes international leaders' suggestions and expert panels' recommendations. RESULTS: There are limited controlled data but increasing clinical experience with Hyal treatment. The currently used Hyals provide good results and have an acceptable safety profile. Nonemergent complications such as the Tyndall effect, noninflamed nodules, and allergic or hypersensitivity reactions should be treated with low or moderate Hyal doses. Hyal should be considered with prior or simultaneous oral antibiotic treatment in managing inflammatory nodules. Hyal may be tried for granulomas that have not responded to intralesional steroids. Emergent complications such as vascular occlusion and blindness require immediate, high-dose Hyal treatment. Regarding blindness, the injection technique, retrobulbar versus supraorbital, remains controversial. Ultrasound guidance can increase the efficacy of the above interventions. CONCLUSIONS: Hyal is essential in aesthetic practice because it can safely treat most HA filler complications. Immediate Hyal treatment is required for emergent complications. Aesthetic practitioners should be versed in using Hyal and effective dosage protocols.

The Sensitivity and Specificity of Multiparametric Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Predicting Seminal Vesicle Invasion in Clinically Significant Prostate Cancer: A Multicenter Retrospective Study.

Background/Objectives: The presence of seminal vesicle invasion (SVI) in prostate cancer (PCa) is associated with poorer postoperative outcomes. This study evaluates the predictive value of magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for SVI in PCa. Methods: This cohort study included consecutive robotic prostatectomy patients for PCa at three Australian tertiary referral centres between April 2016 and September 2022. MRI and PSMA PET/CT results, clinicopathological variables, including age, BMI, prostate-specific antigen (PSA), PSA density, DRE, Biopsy Gleason score, Positive biopsy cores, PIRADS v2.1 score, MRI volume and MRI lesion size were extracted. The sensitivity, specificity, and accuracy of MRI and PSMA PET/CT for predicting SVI were compared with the histopathological results by receiver operating characteristic (ROC) analysis. Subgroup univariate and multivariate analysis was performed. Results: Of the 528 patients identified, 86 had SVI on final pathology. MRI had a low sensitivity of 0.162 (95% CI: 0.088-0.261) and a high specificity of 0.963 (95% CI: 0.940-0.979). The PSMA PET/CT had a low sensitivity of 0.439 (95% CI: 0.294-0591) and a high specificity of 0.933 (95% CI: 0.849-0.969). When MRI and PSMA PET/CT were used in combination, the sensitivity and specificity improved to 0.514 (95%CI: 0.356-0.670) and 0.880 (95% CI: 0.813-0.931). The multivariate regression showed a higher biopsy Gleason score (p = 0.033), higher PSA (p < 0.001), older age (p = 0.001), and right base lesions (p = 0.003) to be predictors of SVI. Conclusions: MRI and PSMA PET/CT independently underpredicted SVI. The sensitivity and AUC improved when they were used in combination. Multiple clinicopathological factors were associated with SVI on multivariate regression and predictive models incorporating this information may improve oncological outcomes.

Robotic-Assisted Bladder Diverticulectomy: Indications, Technique, and Outcomes-A Case Series.

Purpose: This case series describes the experiences and outcomes of multiple Australian surgeons performing robotic-assisted bladder diverticulectomy (RABD), highlighting the procedural effectiveness and safety, for both benign and malignant indications for diverticulectomy. Methods: Outcomes were analyzed from 13 experienced Australian urologists who performed RABD between 2016 and 2023. Retrospective analysis was performed on prospectively collected data, which included patient demographics, diverticulum characteristics, surgical approaches, and post-operative outcomes. Surgical techniques included the extravesical and intravesical approaches, with the focus on maintaining oncological principles in cases of malignancy. Results: A total of 28 patients underwent RABD, with the majority being male and a mean age of 63.9 years. All surgeons utilized a four-port transperitoneal approach and opted for the extravesical dissection of the diverticular neck; one case utilized both an extravesical and a trans-diverticular approach. Functional outcomes demonstrated symptomatic resolution in patients with nonmalignant diverticula, whereas oncological outcomes indicated clear margins in 90% of malignant cases. The average length of the procedure was 106 minutes, with minimal blood loss and a mean hospital stay of 2.67 days. Early complications occurred in 14% with the majority Clavien-Dindo grade II. Conclusion: Robotic bladder diverticulectomy, predominantly via the transperitoneal extravesical approach, has emerged as a safe, effective, and reliable surgical intervention for both malignant and nonmalignant bladder diverticula. The consistent surgical approach and excellent outcomes demonstrated in this case series reinforce the procedure's potential as a safe option, even in the setting of malignancy within a diverticulum.

What are the Most Important Objectives of Patients Undergoing Radical Prostatectomy? A Narrative Review.

Purpose: This study aimed to evaluate what objectives are most important to men undergoing radical prostatectomy to allow treating physicians to personalize perioperative counselling and improve patient quality of life outcomes. Materials and Methods: A predefined search protocol of the Medline and Embase databases was performed from database inception to May 2023. The search was limited to English language and full text. All articles with a specific consideration of patient objectives, preferences or reasons for decision to undergo radical prostatectomy were included for review. Results: Ten articles out of 375 screened met inclusion criteria for review. All 10 articles utilized a qualitative design and originated across 5 countries across the developed world. A common theme of men placing importance on having their tumor physically removed was found. Methodologies allowing free response beyond predefined categories identified a breadth of considerations including personal circumstance, personal belief and current function in the decision-making process. An investigation on radical prostatectomy performed robotically found some men placed preference on the quicker treatment time with surgery compared to radiation therapy, reflective of shorter recovery times with the robotic approach. Conclusion: Variability in results across studies highlights the heterogeneity in patient preferences. Directed investigation of patient objectives with an open-ended questioning approach would personalize the perioperative experience and may improve patient satisfaction and quality of life outcomes.

A Chance Finding of High Grade Prostate Cancer in a 35-Year-Old Male - A Case Report and Outcomes of Robotic Radical Prostatectomy in Young Men with Prostate Cancer.

Background: Prostate cancer is often considered a disease of older men and this indeed fits with its peak incidence between 65-79 years of age. Reports of prostate cancer in men younger than 40 years of age and the outcomes of this age group following treatment are few in the literature. Here, we present the case of an unusual diagnosis of high grade prostate cancer in a very young man and outline early outcomes following treatment with robotic-assisted radical prostatectomy. Case Presentation: A 35-year-old male, intermittently taking finasteride for hair loss, was found to have an elevated prostate-specific antigen (PSA) of 12.5ng/mL leading to an incidental diagnosis of high grade prostate cancer. Targeted trans-perineal prostate biopsy found Gleason 4+5=9 acinar adenocarcinoma, without cribriform architecture but with features suspicious for extracapsular extension. Robotic radical prostatectomy with bilateral pelvic lymph node dissection was performed and found Gleason 4+5=9 adenocarcinoma with focal cribriform architecture, extra prostatic extension and clear margins, stage pT3a N0 M0. PSA was undetectable at 12 months, continence was immediate, and the patient reported strong erections soon after surgery. Family history of prostate cancer and genetic testing were both negative. Conclusion: This case highlights that not all clinically significant cancers will be identified by following PSA screening guidelines starting at 50 years of age (or 40 years of age for men with a family history of prostate cancer). While high grade prostate cancer in a man less than 40 years of age is uncommon, the literature suggests the incidence is increasing. Our case alongside series in the literature indicate that these men have better functional outcomes and equal oncological outcomes with early surgical intervention for localized disease when compared to the older population.

Cross-cultural perspectives on patient expectations in cosmetic dermatology: A comparative analysis across countries and ethnicities.

Patient expectations in cosmetic dermatology exhibit significant variations across countries, cultures, and ethnicities, thereby reflecting individual desires, concerns, and goals. While some individuals seek aesthetic enhancements, others prioritize addressing specific skin conditions within the context of beauty norms in their respective countries. The provision of personalized and culturally sensitive care plays a crucial role in meeting these diverse expectations. Skin characteristics and concerns differ among ethnicities, influencing treatment preferences. For instance, individuals with darker skin tones may prioritize the treatment of pigmentation disorders, whereas those with lighter skin tones may focus on achieving a fair complexion. Furthermore, differences in facial anatomy among various ethnicities necessitate tailored treatment approaches. This commentary aims to contribute to the effective understanding and management of patient expectations, ultimately leading to satisfactory outcomes. Additional research and regional studies are required to further deepen our understanding of patient expectations in cosmetic dermatology and enable the delivery of improved and culturally appropriate care on a global scale.

Impact of Preoperative Mental Health on Surgical Outcomes Following Robotic-assisted Radical Prostatectomy.

OBJECTIVES: To explore the association between preoperative mental health status and surgical outcomes following robotic-assisted radical prostatectomy (RARP). METHODS: This cohort study included consecutive patients undergoing RARP surgery for prostate cancer between October 2016 and May 2022 at a major public hospital in Sydney, Australia. The primary outcome was preoperative self-reported mental health status measured using the mental component score from the Short Form 36 survey. Other variables included patients' characteristics, surgical outcomes, postoperative quality of life, pain and decision regret. Data were analysed using linear regression analysis. RESULTS: A total of 266 men underwent RARP during the studied period. Of these, 242 patients (91%) completed the preoperative survey and were analyzed. Poorer preoperative mental health had significant univariate associations with younger age (P = .025), reduced access to economic resources (P = .043), diagnosis of a mental illness (P = .033), poorer mental health at 6 weeks and 6 months postoperatively (both P <.001), greater pain (P = .001), and higher decision regret (P = .001) 6 weeks following surgery. In the multivariate analysis, poorer preoperative mental health status was associated with younger age (P = .028) and poorer mental health at 6 weeks (P <.001) and 6 months (P = .025) postoperatively. CONCLUSION: For patients undergoing RARP, poor preoperative mental health status was associated with younger age and poorer postoperative mental health. Future studies should investigate if targeted preoperative psychological interventions would improve postoperative mental health outcomes, specifically in younger men undergoing RARP.

Value of multiphoton microscopy in uro-oncology: a narrative review.

Background and Objective: Multi-photon microscopy (MPM) is a 3-dimension fluorescence imaging technique that combines the excitation of two low-energy photons, enabling less photo-bleaching and deeper penetration of the imaged tissue. Two signals are detected, autofluorescence (AF), from natural intracellular fluorophores [such as nicotinamide adenine dinucleotide phosphate (NADP) and flavine adenine dinucleotide (FAD) transformation], and second harmonic generation (SHG), a physical property of the laser enhancing non-centrosymmetric structures such as collagen fibers. MPM can give both visual and quantitative information of a fresh tissue (without the need of processing, cutting or staining the tissue), aiding in the progress towards optimizing a real-time imaging device. The objective of this review is to show the value and benefits of the use of MPM in uro-oncology. Methods: A structured literature review was performed using PubMed and Web of Sciences, including all articles with the following keywords: "multiphoton microscopy", "two-photon microscopy", "non-linear microscopy", "second harmonic generation", "urology", "prostate", "bladder", "kidney", "upper tract", "oncology", "surgical margins", "frozen section". Articles were reviewed to summarize the use of this tool in performing biopsies, assessing surgical margins, staging and grading complementary tool, and real-time imaging. Key Content and Findings: A total of 476 articles were identified with these keywords, and later screened for inclusion. We finally included 47 publications that were relevant to our topic. The advantages of this technique have led to its application in the management of several cancers, allowing cellular description as well as quantitative measurements of AF or SHG and their correlation with clinical outcomes. Conclusions: MPM has shown great improvement in providing a real time assessment of fresh tissue, giving oncologic diagnosis, performing in vivo imaging and quantitative analysis of the tissue as well as increasing precision of the diagnosis. This nonlinear optical technique has the potential of guiding both biopsy and surgery, as well as helping the surgeon with interesting additional tissue information intra-operatively.

Decipher Score predicts prostate specific antigen persistence after prostatectomy.

BACKGROUND: The aim of this study was to evaluate genomic risk of patients with persistent prostate specific antigen (PSA) using mRNA expression analysis and a validated prognostic genomic-risk classifier. METHODS: Monocentric retrospective study including all patients who underwent radical prostatectomy (RP) by one surgeon and Decipher Test from October 2013 to December 2018. PSA persistent population was defined as all patients with two consecutive PSA>0.1 ng/mL at follow-up after the surgery. Neurovascular Structure-adjacent Frozen-section Examination (NeuroSAFE) was performed intraoperatively for research of positive surgical margins. Multivariate analysis was performed for persistent PSA (pPSA) predictors. A specific localized, organ-confined, and negative margins sub-population with PSA persistence was compared to a similar sub-population without PSA persistence for genomic differential expression analyses. RESULTS: A total of 564 patients were included and 61 of them had pPSA. Preoperative PSA was higher in the PSA persistent group (11.6 [6.4, 21.2] vs. 6.2 [4.7, 9.2] P=0.00010), as well as PSA density (PSAd) (0.3 [0.2, 0.5] vs. 0.2 [0.1, 0.3] P=0.0001). Postoperative characteristics, Gleason Score, and positive surgical margins were significantly higher in the PSA persistent population. 31 patients had pPSA in our specific subpopulation and were compared to 217 patients with no pPSA. On multivariate analysis, only Decipher Score (OR=5.64 [1.28; 24.89], P=0.022) and preoperative PSA (OR=1.06, [1.02; 1.09], P=0.001) were significant predictors for PSA persistence. We found two genes to be significantly upregulated with a 2.5-fold change in our specific subpopulation (SERPINB11 and PDE11A). CONCLUSIONS: We found unique genomic features of patients with pPSA, whilst confirming previous clinical findings that this condition behaves to a worse prognosis. Given this high genomic risk, further imaging studies should be performed to select patients for early treatment intensification.

Is night-time surgical procedure for renal graft at higher risk than during the day? A single center study cohort of 179 patients.

INTRODUCTION: Various surgical centers tend to postpone a kidney transplantation (KT) to the following morning than to operate at night-time. The objective of our study was to assess whether there was any difference between daytime and night-time renal transplantation in our institution. METHOD: This study is a retrospective monocentric study including all the KTs that were performed between 2012 and 2013 by transplant expert surgeons in our institution. Clavien-Dindo (CD) complications were classified according to 7 variables going from 1 to 5. Time before postgraft diuresis and delayed graft function (DGF) were also analyzed. Two groups of patients were formed according to threshold value of incision time (6.30 p.m.). Data comparison were performed using the Kruskal-Wallis nonparametric test. RESULTS: A total of 179 patients were included. Median follow-up was 24 months. Cold ischemia time was longer in the night-time transplantation (1082 vs. 807 min, p < .001), but rewarming time was shorter (47.24 vs. 52.15 min, p = .628). No statistically significant differences were observed between the two groups using the Kruskal-Wallis method for CD complications (Qobs: 0.076; p = .735). CD complications proportion was similar, with a majority of grade II complications (72.7% daytime group vs. 75.4% night-time group (p = .735). DGF (19 patients for daytime group vs. 13 patients for night-time group, p = .359) and time before postgraft diuresis (4.65 days daytime group vs. 5.27 days night-time group, p = .422) were similar between both groups. Multivariate analysis did not show significant predictors of CD complications Grade 3 and more. CONCLUSION: Night-time renal transplantation did not induce more postoperative CD complications than diurnal procedures in our cohort, challenging the false preconceptions that allow surgical teams to delay this surgery.

Multiphoton Microscopy for Identifying Collagen Signatures Associated with Biochemical Recurrence in Prostate Cancer Patients.

Prostate cancer is a heterogeneous disease that remains dormant for long periods or acts aggressively with poor clinical outcomes. Identifying aggressive prostate tumor behavior using current glandular-focused histopathological criteria is challenging. Recent evidence has implicated the stroma in modulating prostate tumor behavior and in predicting post-surgical outcomes. However, the emergence of stromal signatures has been limited, due in part to the lack of adoption of imaging modalities for stromal-specific profiling. Herein, label-free multiphoton microscopy (MPM), with its ability to image tissue with stromal-specific contrast, is used to identify prostate stromal features associated with aggressive tumor behavior and clinical outcome. MPM was performed on unstained prostatectomy specimens from 59 patients and on biopsy specimens from 17 patients with known post-surgery recurrence status. MPM-identified collagen content, organization, and morphological tumor signatures were extracted for each patient and screened for association with recurrent disease. Compared to tumors from patients whose disease did not recur, tumors from patients with recurrent disease exhibited higher MPM-identified collagen amount and collagen fiber intensity signal and width. Our study shows an association between MPM-identified stromal collagen features of prostate tumors and post-surgical disease recurrence, suggesting their potential for prostate cancer risk assessment.

Hood Technique for Robotic Radical Prostatectomy-Preserving Periurethral Anatomical Structures in the Space of Retzius and Sparing the Pouch of Douglas, Enabling Early Return of Continence Without Compromising Surgical Margin Rates.

BACKGROUND: A common side effect following radical prostatectomy is urinary incontinence. Here, we describe a novel surgical technique to reduce postoperative urinary incontinence and facilitate early return of continence. OBJECTIVE: To describe the novel "hood technique" for robotic-assisted radical prostatectomy (RARP). DESIGN, SETTING, AND PARTICIPANTS: This is an institutional review board-approved prospective study of 300 patients (median age 64 yr) with localized prostate cancer treated with the RARP hood technique at a major urban hospital between April 2018 and March 2019. The exclusion criteria were as follows: patients with anterior tumor location based on biopsy or multiparametric magnetic resonance imaging. All but one patient participated in follow-up over 12 mo after the procedure. SURGICAL PROCEDURE: The RARP "hood technique" was performed to preserve the detrusor apron, puboprostatic ligament complex, arcus tendineus, endopelvic fascia, and pouch of Douglas. MEASUREMENTS: Clinical data collected included pre- and intraoperative variables, and postoperative functional and oncological outcomes and complications. Descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: Continence rates at 1, 2, 4, 6 12, 24, and 48 wk after catheter removal were 21%, 36%, 83%, 88%, 91%, 94%, and 95%, respectively. Positive surgical margin rate was 6%. Thirty patients (9.7%) experienced complications after RARP: 17 (5.7%), 11 (3.6%), and one (0.4%) had Clavien-Dindo grade I, II, and III complications, respectively. This study was conducted within a single health system and may not be generalizable. The study lacked randomization and a comparative arm. CONCLUSIONS: Results indicate that the hood technique spares musculofascial structures anterior to the urethral sphincter complex with early return of continence after surgery, without compromising positive surgical margin rates. Exclusion of anterior tumor location contributed to a reduction in positive surgical margins. PATIENT SUMMARY: By better preservation of anatomical structures around the urethra, we were able to achieve early return of urinary continence without a negative impact on complications and cancer outcomes.

Neoadjuvant versus adjuvant chemotherapy for upper tract urothelial carcinoma.

BACKGROUND: Presently, no level I evidence is available to support the use of neoadjuvant chemotherapy (N)(AC) in patients diagnosed with high-grade upper tract urothelial carcinoma (UTUC). We aimed to compare outcomes of patients treated with radical nephroureterectomy (RNU) who received NAC vs. those who received AC. METHODS: The National Cancer Database was queried for UTUC patients with cT2-4N0M0 disease treated with RNU and NAC or AC. The role of NAC or AC on overall survival (OS) was evaluated by means of a multivariable Cox regression. Time to death was evaluated from diagnosis. RESULTS: Overall, 936 patients were identified, 128 (14%) received NAC whereas 808 (86%) received AC. No difference was observed between NAC vs. AC in terms of OS (P = 0.9). When sub-stratifying patients who received NAC in responders (cT>pT, given pN0; n = 46 [36%]) vs. nonresponders (n = 82 [64%]), we found that, relatively to AC, the subgroup of patients who did not respond to NAC had higher risk of dying from any cause (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.03,1.91; P = 0.03), whereas the sub-group who responded to NAC had better OS (HR: 0.45; 95% CI: 0.24,0.85; P = 0.01). The 5-year OS rates for responders to NAC vs. nonresponders vs. AC were: 71% vs. 26% vs. 43%, respectively. A landmark analysis fitted at 6 months after diagnosis, including 903 patients (NAC: 126 vs. AC: 777) confirmed our findings. CONCLUSION: while we found no difference in outcomes between NAC vs. AC in high-grade UTUC, we found a hypothesis-generating association between survival and response to NAC. Further studies aimed at identifying potential responders to NAC are warranted.