A group of three miRNAs can act as candidate circulating biomarkers in liquid biopsies from melanoma patients

Background: Staging of melanoma and follow up after melanoma diagnosis aims at predicting risk and detecting progression or recurrence at early stage, respectively in order to timely start and/or change treatment. Tumor thickness according to Breslow, status of the sentinel node and value of the lactate dehydrogenase (LDH) are well-established prognostic markers for metastatic risk, but reliable biomarkers identifying early recurrence or candidates who may benefit best from medical treatment are still warranted. Liquid biopsy has emerged to be a suitable method for identifying biomarkers for early cancer diagnosis, prognosis, therapeutic response prediction, and patient follow-up. Liquid biopsy is a blood- based non-invasive procedure that allows analyzing circulating analytes, including extracellular vesicles. Methods: In this study we have explored the use of 7 miRNAs, namely hsa- miR-149-3p, hsa-miR-150-5p, hsa-miR-21-5p, hsa-miR-200c-3p, hsa-miR-134- 5p, hsa-miR-144-3p and hsa-miR-221-3p in plasma exosomes to discriminate melanoma patients from controls without melanoma in a cohort of 92 individuals. Results and discussion: Our results showed that three out seven miRNAs, namely hsa-miR-200c-3p, hsa-miR-144-3p and hsa-miR-221-3p were differentially expressed in plasma-derived exosomes from melanoma patients and controls. Furthermore, the expression of the three miRNAs may be a promising ancillary tool as a melanoma biomarker, even for discriminating between nevi and melanoma

Does age impact outcomes of retrograde intrarenal surgery in the elderly? Results from 366 patients from the FLEXible ureteroscopy outcomes registry (FLEXOR)

Background: There has been a consistent increase in the last decades in prevalence of renal stones in elderly. Aims: To evaluate outcomes of retrograde intrarenal surgery (RIRS) for renal stones in elderly and factors associated with postoperative complications and residual fragments (RFs). Methods: Data from 12 centers were retrospectively reviewed. Inclusion criteria: ≥ 75 years, renal stones only, normal renal anatomy. Patients were divided into three groups; Group 1: patients aged 75–79 years; Group 2: age 80–84 years; Group 3: age ≥ 85 years. Multivariable logistic regression analyses were performed to assess factors associated with perioperative complications, sepsis, and RFs. Results: 366 patients were included. There were 189 patients in Group 1, 113 in Group 2, and 64 in Group 3. There was no difference between groups regarding stone features and total surgical time. Median length of stay was significantly longer in Group 3 (6.0 days, vs 2.0 days in Group 2 vs 2.5 days in Group 1, p = 0.043). There was no significant difference in postoperative complications and RFs between the groups. At multivariable logistic regression analysis, female gender (OR 2.82) and maximum stone diameter (OR 1.14) were associated with higher odds of sepsis, while surgical time (OR 1.12) and the use of a reusable ureteroscope (OR 6.51) with overall complications. Stone size (OR 1.23) was associated with higher odds of RFs. Conclusion: RIRS showed safety and efficacy for kidney stones in elderly patients. Surgical time should be kept as short as possible to avoid higher odds of postoperative complications, particularly in females

Scoping Review of Experimental and Clinical Evidence and Its Influence on Development of the Suction Ureteral Access Sheath

The ureteral access sheath (UAS) has been a boon and a bane in flexible ureteroscopy (FURS), with its merits and demerits well established. Its design and dimensions were instrumental in reshaping the way flexible scopes were used and were key adjuncts to establishing retrograde intrarenal surgery (RIRS) as a standard of care in the endourological management of renal stones. With the ever-changing landscape of RIRS over the decades shaped by technological advancements in lasers and flexible scopes, the UAS has also continuously evolved. The utility of suction in endourology has recently changed the way RIRS is performed and is a game changer for FURS outcomes. With strong clinical and experimental evidence to support its use, the UAS has undergone a transformative change in the recent past, with its ability to monitor intrarenal pressure and provide a superior vacuum-cleaner effect that improves the trifecta of RIRS, namely an improved single-stage stone-free rate (SFR), minimise complications, and reduce reinterventions. Our comprehensive review outlines the key clinical and experimental evidence and traces the developments that were key to modifying the traditional UAS into a flexible and navigable suction ureteric access sheath (FANS) and highlights how the design and modifications, in turn, influence the ability to push the boundaries of RIRS

Outcomes of lateral approach in robot-assisted radical prostatectomy: insights from a single-surgeon experience

In the era of robotic prostate surgery, various techniques have been developed to improve functional outcomes. Urinary continence has shown satisfactory results, but the preservation of lateral nerves to the periprostatic capsule is only achievable by sparing the pubovesical complex. This study aims to present the first cases of lateral-approach robot-assisted radical prostatectomy (LRRP) performed by a novice surgeon. We conducted a retrospective analysis of 70 prostate cancer patients who underwent LRRP between October 2019 and September 2021, analyzing the perioperative and functional outcomes. The median operative time and intraoperative blood loss were 102 (92–108) minutes and 150 (130–180) mL, respectively. Five minor postoperative complications were reported, and the median hospital stay was 2 (1–2) days. Eleven positive surgical margins occurred. Potency and urinary continence recovery were achieved in 59 (84%) and 66 (94%) patients, respectively, 12 months after surgery. Our analysis shows that LRRP is a safe and effective procedure for prostate cancer surgery. Continence and potency recovery required a short learning curve, with an acceptable recovery rate even in the initial cases

Real Life Clinical Management and Survival in Advanced Cutaneous Melanoma: The Italian Clinical National Melanoma Registry Experience

Background: Cutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR). Methods: Melanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. Results: The median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62). Conclusions: The nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment

Trends in pediatric epilepsy surgery in Europe between 2008 and 2015: Country‐, center‐, and age‐specific variation

OBJECTIVE: To profile European trends in pediatric epilepsy surgery (<16 years of age) between 2008 and 2015. METHODS: We collected information on volumes and types of surgery, pathology, and seizure outcome from 20 recognized epilepsy surgery reference centers in 10 European countries. RESULTS: We analyzed retrospective aggregate data on 1859 operations. The proportion of surgeries significantly increased over time (P < .0001). Engel class I outcome was achieved in 69.3% of children, with no significant improvement between 2008 and 2015. The proportion of histopathological findings consistent with glial scars significantly increased between the ages of 7 and 16 years (P for trend = .0033), whereas that of the remaining pathologies did not vary across ages. A significant increase in unilobar extratemporal surgeries (P for trend = .0047) and a significant decrease in unilobar temporal surgeries (P for trend = .0030) were observed between 2008 and 2015. Conversely, the proportion of multilobar surgeries and unrevealing magnetic resonance imaging cases remained unchanged. Invasive investigations significantly increased, especially stereo‐electroencephalography. We found different trends comparing centers starting their activity in the 1990s to those whose programs were developed in the past decade. Multivariate analysis revealed a significant variability of the proportion of the different pathologies and surgical approaches across countries, centers, and age groups between 2008 and 2015. SIGNIFICANCE: Between 2008 and 2015, we observed a significant increase in the volume of pediatric epilepsy surgeries, stability in the proportion of Engel class I outcomes, and a modest increment in complexity of the procedures

Controversy and consensus on the management of elevated sperm DNA fragmentation in male infertility: a global survey, current guidelines, and expert recommendations

PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians