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Purpose To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)—1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR − baseline eGFR; Δ2 = 6 months eGFR − POD-1 eGFR; Δ3 = 12 months eGFR − 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. Results A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR p p = 0.003), POD-1 AKI (OR 2.88, p p p p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR p p = 0.019), hydronephrosis (p p p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p Conclusion Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.

Objectives: Martini et al. developed a nomogram to predict significant (>25%) renal function loss after robot-assisted partial nephrectomy and identified four risk categories. We aimed to externally validate Martini’s nomogram on a large, national, multi-institutional data set including open, laparoscopic, and robot-assisted partial nephrectomy. Methods: Data of 2584 patients treated with partial nephrectomy for renal masses at 26 urological Italian centers (RECORD2 project) were collected. Renal function was assessed at baseline, on third postoperative day, and then at 6, 12, 24, and 48 months postoperatively. Multivariable models accounting for variables included in the Martini’s nomogram were applied to each approach predicting renal function loss at all the specific timeframes. Results: Multivariable models showed high area under the curve for robot-assisted partial nephrectomy at 6- and 12-month (87.3% and 83.6%) and for laparoscopic partial nephrectomy (83.2% and 75.4%), whereas area under the curves were lower in open partial nephrectomy (78.4% and 75.2%). The predictive ability of the model decreased in all the surgical approaches at 48 months from surgery. Each Martini risk group showed an increasing percentage of patients developing a significant renal function reduction in the open, laparoscopic and robot-assisted partial nephrectomy group, as well as an increased probability to develop a significant estimated glomerular filtration rate reduction in the considered time cutoffs, although the predictive ability of the classes was

Emergency department (ED) visits and readmissions after thoracic surgery are a major health care problem. We hypothesized that the addition of a novel post-discharge mobile app specific to thoracic surgery to an existing home care program would reduce ED visits and readmissions compared to a home care program alone.We conducted a prospective cohort study of patients undergoing major lung resection for malignant disease between November 2016 and May 2018. Patients received either home care alone (control group) or home care plus a patient-input mobile app (intervention group). Primary outcomes were 30-day readmission and ED visit rates. Secondary outcomes included reasons for ED visits and readmissions, perioperative complications, 30-day mortality, anxiety (assessed with the Generalized Anxiety Disorder-7 Scale [GAD-7]) and app-related adverse events. We compared outcomes between the 2 groups, analyzing the data on an intention-to-treat basis.Despite the greater number of open surgery and anatomic resections in the intervention cohort, patients in that group were less likely than those in the control group to visit the ED within 30 days of discharge (24.0% v. 38.8%,The addition of a mobile app to a home care program after thoracic surgery was associated with a reduced frequency of ED visits, in spite of the higher proportions of thoracotomies and anatomic resections in the app cohort. More studies are needed to evaluate the full effect of this new, emerging technology.

To investigate the clinical and surgical predictors of urinary tract endometriosis (UTE) relapse.Retrospective single institutional study.Italian multidisciplinary referral center for endometriosis.Consecutive patients affected by UTE and surgically treated between January 2016 and March 2020.Surgical excision for UTE. Uni- and multivariate logistic regression analyses were fitted to evaluate clinical and surgical predictors of recurrence.A total of 105 female age-reproductive patients were enrolled. Median age was 32 years (interquartile range, 24-37). Ureteral involvement was recorded in 53 patients (50.5%), being unilateral and bilateral in 46 patients (43.8%) and 7 patients (6.7%), respectively. Bladder involvement occurred in 52 patients (49.5%). Open surgical approach was performed in 24 cases (22.9%), whereas 30 patients (28.5%) and 51 patients (48.6%) were treated with laparoscopic and robot-assisted approach, respectively. Overall, 53 patients (50.5%) received adjuvant hormonal therapy. At a median follow-up of 39 months (interquartile range, 22-51), 30 patients (28.6%) experienced disease relapse, with 14 recurrences (13.3%) recorded at the level of the urinary tract. At multivariable analysis, age at first surgery25 years (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.10-1.84; p = .02) and the presence of a concomitant autoimmune disease (OR, 1.45; 95% CI, 1.24-2.17; p = .02) were found as predictors of deep infiltrating endometriosis recurrence, whereas adjuvant postsurgical therapy showed a protective role (OR, 0.83; 95% CI, 0.53-0.98; p = .01).Young age (25 years) and the presence of autoimmune diseases were significant predictors for the development of disease recurrence, whereas adjuvant hormonal therapy showed a protective role.

The maintenance of genome integrity is ensured by proper chromosome inheritance during mitotic and meiotic cell divisions. The chromosomal counterpart responsible for chromosome segregation to daughter cells is the centromere, at which the spindle apparatus attaches through the kinetochore. Although all mammalian centromeres are primarily composed of megabase-long repetitive sequences, satellite-free human neocentromeres have been described. Neocentromeres and evolutionary new centromeres have revolutionized traditional knowledge about centromeres. Over the past 20 years, insights have been gained into their organization, but in spite of these advancements, the mechanisms underlying their formation and evolution are still unclear. Today, through modern and increasingly accessible genome editing and long-read sequencing techniques, research in this area is undergoing a sudden acceleration. In this article, we describe the primary sequence of a previously described human chromosome 3 neocentromere and observe its possible evolution and repair results after a chromosome breakage induced through CRISPR-Cas9 technologies. Our data represent an exciting advancement in the field of centromere/neocentromere evolution and chromosome stability.

Treatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group.Multicenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group.Four hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P.001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups.Metastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances.

FloRIN reconfiguration technique was introduced in 2016 according to the IDEAL-Collaboration Guidelines, with the attempt to conjugate the advantages of both intracorporeal neobladder and robotic assistance. Herein we report functional outcomes of FloRIN reservoir, specifically focusing on urodynamic features.Consecutive patients treated with RARC and FloRIN reconstruction were prospectively collected from February 2016 to June 2020. Only patients with a minimum 6-month follow up were analyzed to obtain a stable grade of neobladder maturation before performing the urodynamic study (UDS). The FACT-BL and the QLQ-C30 EORTC questionnaires were used to evaluate urinary function and health-related QoL. Results were compared with a contemporary series of patients treated at the same Institution with open radical cystectomy (ORC) and Vescica Ileale Padovana (VIP).One hundred patients entered the study and 69 patients had complete functional data. Overall, 52 (75.4%) patients reached the daytime continence. Among these, 28 (40.6%) were dry (no pads during daytime), while 24 (34.8%) used one pad/12 h. Night-time continence was achieved by 45 (65.2%) patients. Complete UDS findings were available for 28 patients. No statistically significant differences were found with the VIP-ORC group except for neobladder compliance, being higher in the FloRIN group (p = 0.03). When evaluating QoL scores, RARC with FloRIN reconfiguration showed a better continence recovery, as well as a higher improvement in urgency domain (p = 0.01), psychological status (0.02) and physical self-acceptance (p = 0.02), compared to the VIP-ORC group.The FloRIN technique showed excellent functional outcomes when compared to the referral VIP-ORC procedure.

The objective of the current research was to explore the potential prognostic value of readily available clinical and pathologic variables in bladder cancer. The novel association found between cholesterol levels and prognosis may provide the rationale for exploring novel treatments. Patients included had histologically confirmed urothelial bladder cancer and were treated with at least 3 cycles of cisplatin-based neoadjuvant chemotherapy before radical cystectomy with lymphadenectomy. A total of 245 patients at low, intermediate and high risk, presenting with 0-1, 2 or 3-4 risk factors, including positive lymph nodes, Hb 12.8, NLR ≥2.7 and cholesterol levels ≥199, were included. Five-year cancer-specific survival rate was 0.67, 0.78 and 0.94 at high, intermediate and low risk, respectively. Total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and may be incorporated in a clinically meaningful risk-group classification model.Lay abstract This present study assessed a large group of patients with urothelial bladder cancer treated with chemotherapy followed by radical cystectomy, to capture the predictive power of commonly collected clinical, pathological and biochemical factors. The design of the study highlighted that higher cholesterol levels at the time of cystectomy were associated with shorter cancer-specific survival. This finding suggests that high blood-cholesterol levels truly have a negative influence on surviving cancer. In conclusion, total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and could be incorporated into a clinically meaningful and valuable risk-group classification model.

BACKGROUND: Ischemia time during partial nephrectomy (PN) is among the greatest determinants of acute kidney injury (AKI). Whether this association is affected by the preoperative risk of AKI has never been investigated.OBJECTIVE: To assess the effect of the interaction between the preoperative risk of AKI and ischemia time on the probability of AKI during PN.DESIGN, SETTING, AND PARTICIPANTS: Data of 944 patients treated with on-clamp PN for cT1 renal tumors were extracted from the Registry of Conservative and Radical Surgery for Cortical Renal Tumor Disease (RECORD2) database, a prospective multicenter project.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We estimated the preoperative risk of AKI (defined according to the risk/injury/failure/loss/end-stage [RIFLE] criteria) according to age, baseline renal function, clinical stage, preoperative aspects and dimensions used for an anatomical (PADUA) score, and surgical approach. Classification and regression tree (CART) analysis identified patients at "high" and "low" risk of AKI. Finally, we plotted the probability of AKI over ischemia time stratified by the preoperative risk of AKI.RESULTS AND LIMITATIONS: Overall, 235 (25%) patients experienced AKI after surgery. At multivariable analysis, older patients, those with more complex tumors, those with higher baseline function, and those treated with open surgery had an increased risk of AKI (all p ≤ 0.011). According to the first split at CART analysis, patients were categorized as those with "high" and "low" risk of AKI having a probability of >40% or 20 min of ischemia was 13% versus 28% (absolute risk increase 15%). The risk of AKI for high-risk patients who had 20 min of ischemia was 31% versus 77%. This corresponds to an absolute risk increase of 45%. Limitations include retrospective data analyses and lack of surgeons' prior experience.CONCLUSIONS: Ischemia time during PN has different implications for patients with different health status. Clamp time seems less clinically relevant for patients in good conditions who may endure prolonged ischemia with a mild increase in the risk of AKI, whereas frail patients seem to be more vulnerable to ischemic damage even for short clamp time. For individualized intra- and postoperative management, duration of ischemia needs to be questioned in the context of the individual health status.PATIENT SUMMARY: Functional sequelae related to ischemia time during partial nephrectomy depend on baseline health status. The correlation between the duration of ischemia and baseline health status should be taken into account toward individualized intra- and postoperative management.

The SARS-CoV-2 pandemic is maintained by the emergence of successive variants, highlighting the flexibility of the protein sequences of the virus. We show that experimentally determined intrinsically disordered regions (IDRs) are abundant in the SARS-CoV-2 viral proteins, making up to 28% of disorder content for the S1 subunit of spike and up to 51% for the nucleoprotein, with the vast majority of mutations occurring in the 13 major variants mapped to these IDRs. Strikingly, antigenic sites are enriched in IDRs, in the receptor-binding domain (RBD) and in the N-terminal domain (NTD), suggesting a key role of structural flexibility in the antigenicity of the SARS-CoV-2 protein surface. Mutations occurring in the S1 subunit and nucleoprotein (N) IDRs are critical for immune evasion and antibody escape, suggesting potential additional implications for vaccines and monoclonal therapeutic strategies. Overall, this suggests the presence of variable regions on S1 and N protein surfaces, which confer sequence and antigenic flexibility to the virus without altering its protein functions.

Prolonged air leaks are increasingly treated in the outpatient setting, with patients discharged with chest tubes in place. We evaluated the incidence and risk factors associated with readmission, empyema development and further interventions in this patient population.We undertook a retrospective cohort analysis of all patients from 4 tertiary academic centres (January 2014 to December 2017) who were discharged home with a chest tube after lung resection for a postoperative air leak lasting more than 5 days. We analyzed demographics, patient factors, surgical details, hospital readmission, reintervention, antibiotics at discharge, empyema and death.Overall, 253 of 2794 patients were analyzed (9.0% of all resections), including 30 of 759 from centre 1 (4.0%), 67 of 857 from centre 2 (7.8%), 9 of 247 from centre 3 (3.6%) and 147 of 931 from centre 4 (15.8%) (Discharge with chest tube after lung resection is associated with serious adverse events. Given the high risk of empyema development, removal of chest tubes should be considered, when appropriate, within 20 days of surgery. Our data suggest a potential need for proactive postdischarge outpatient management programs to diminish risk of morbidity and death.

Background Postoperative renal function impairment represents a main limitation for delivering adjuvant chemotherapy after radical nephroureterectomy (RNU). Objective To create a model predicting renal function decline after minimally invasive RNU. Design, setting, and participants A total of 490 patients with nonmetastatic UTUC who underwent minimally invasive RNU were identified from a collaborative database including 17 institutions worldwide (February 2006 to March 2020). Renal function insufficiency for cisplatin-based regimen was defined as estimated glomerular filtration rate (eGFR) 50 ml/min/1.73 m2 (n = 361) were geographically divided into a training set (n = 226) and an independent external validation set (n = 135) for further analysis. Outcome measurements and statistical analysis Using transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines, a nomogram to predict postoperative eGFR Results and limitations The model that incorporated age, body mass index, preoperative eGFR, and hydroureteronephrosis was developed with an area under the curve of 0.771, which was confirmed to be 0.773 in the external validation set. The calibration curve demonstrated good agreement. Besides, the model was converted into a risk score with a cutoff value of 0.583, and the difference between the low- and high-risk groups both in overall death risk (hazard ratio [HR]: 4.59, p Conclusions A nomogram incorporating immediately available clinical variables can accurately predict renal insufficiency for cisplatin-based adjuvant chemotherapy after minimally invasive RNU and may serve as a tool facilitating patient selection. Patient summary We have developed a model for the prediction of renal function loss after radical nephroureterectomy to facilitate patient selection for perioperative chemotherapy.

BACKGROUND: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved. OBJECTIVE: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN. DESIGN, SETTING, AND PARTICIPANTS: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC]). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores. RESULTS AND LIMITATIONS: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (

Resumen Objetivo La pandemia de la COVID-19 ha alterado sustancialmente las actividades de formacion de los residentes. Si bien recientemente se han implementado nuevos programas de aprendizaje virtual, aun debe investigarse su utilidad desde la perspectiva de los aprendices de urologia. Metodos Encuesta online transversal de 30 items, distribuida a traves de Twitter, entre el 4 y el 18 de abril de 2020, con el objetivo de evaluar la perspectiva de los residentes de urologia sobre las modalidades (videos pregrabados, seminarios web, podcasts y redes sociales [RRSS]) y contenidos (lecciones frontales, discusiones de casos clinicos, actualizaciones sobre guias y ensayos clinicos, videos quirurgicos, clubes de revistas y seminarios sobre liderazgo y habilidades no tecnicas) del aprendizaje inteligente (Smart learning). Resultados En total, 501 residentes de urologia de 58 paises completaron la encuesta. De estos, 78,4, 78,2, 56,9 y 51,9% consideraron los videos pregrabados, seminarios web interactivos, podcasts y RRSS, respectivamente, como modalidades de aprendizaje inteligente muy utiles. Los contenidos considerados como muy utiles por la mayor proporcion de residentes fueron las actualizaciones de guias clinicas (84,8%) y videos quirurgicos (81,0%). Ademas, mas de la mitad de los residentes consideraron los seminarios de liderazgo y los de habilidades no tecnicas (58,9 y 56,5%, respectivamente) como contenidos utiles para el aprendizaje inteligente. Las tres combinaciones preferidas de modalidad y contenido de aprendizaje inteligente fueron: videos quirurgicos pregrabados, seminarios web interactivos sobre casos clinicos y videos pregrabados sobre guias. Conclusion Nuestro estudio proporciona la primera «vision global» de las modalidades y contenidos de aprendizaje inteligente que deben priorizarse con el objetivo de optimizar la educacion virtual en urologia. Aunque este estudio se llevo a cabo durante la pandemia de la COVID-19, nuestros hallazgos podrian tener un impacto aun mayor en el futuro.

Several studies have shown the efficacy of rituximab (RTX) in preventing relapses in patients suffering from Neuromyelitis Optica spectrum disorder (NMSOD) and have explored different therapeutic schemes. Given the extreme inter-individual variability of the disease course, there is the need to identify biomarkers to tailor the retreatment schedule and dosage. This review aimed to identify the most useful biomarker to guide reinfusion and, in turn, the optimal retreatment schedule of RTX for NMSOD.The literature search was conducted in the Web of Science, Scopus and Pubmed electronic databases. We limited document type to articles written in English and published up to 28 February 2022. Inclusion criteria were: (i) Patients affected by NMSOD and treated with RTX, (ii) followed up for at least one year and for whom Annualized Relapse rate (ARR) was collected over a period of at least 12 months before and after therapy initiation and (iii) induction protocols consisting of 375 mg / m2 / week for four weeks or 1000 mg infused once or twice two weeks apart. Collected information was: first authors' name, publication year, study design, sample size, sex, age, percentage of patients positive for antibodies to aquaporin 4 (AQP4-IgG), maintenance regimen, primary outcome, mean ARR pre-therapy and mean ARR post-therapy initiation, percentage of relapse-free patients. The primary outcome that we considered was the ARR reduction. Further, we considered the number of relapses that occurred when B cells and memory B cells were under the chosen threshold and the percentage of relapse-free patients when available.Among 31 potentially eligible studies, 9 fulfilled the inclusion criteria. ARR reduction was not comparable between studies. The studies that monitored CD19+ and CD27+ cell kinetics showed a higher number of relapses when CD19+ lymphocyte count was below the threshold compared to the number of relapses that occurred when CD27+ cell count was below the threshold. Further, a higher percentage of patients achieved the relapse-free condition with a reinfusion schedule when CD27+ reached 0, 05% of peripheral blood mononuclear cells (PBMCs) compared to the reinfusion when CD19+ reached 0, 1% of PBMCs.To date, the optimal retreatment schedule for RTX in NMOSD has not yet been determined. However, the presented findings suggest that CD27+ B cells might be a reliable biomarker to guide retreatment in AQP4-IgG positive patients, at least in the first six months from the infusion. Further effort is needed to identify those factors influencing anti-CD20 therapy effectiveness to tailor dosage and treatment schedule to achieve the most favourable risk/benefit ratio.

Introduction: The aim of this multicenter study was to investigate the role of age (cut-off 70 years) at diagnosis in predicting oncologic behavior of pure carcinoma in situ of the bladder. Material and Methods: Inclusion criteria were: patients with pure CIS confirmed and that followed intravesical BCG treatment. Pure CIS was defined at any CIS not associated with another urothelial cancer. Exclusion criteria were: any CIS associated with invasive urothelial carcinoma. A total of 172 with pure CIS treated between January 1, 2002 and December 31, 2012 at 8 academic institutions met the inclusion criteria. The maintenance schedule was generally according to the EAU guidelines at the time Results: A total of 99 (57.6%) patients had an age >70 years prior to TURBT. There was no difference between clinico-pathologic features among groups (group 1, age ≤ 70 years and group 2, age > 70 years), except that patients aged ≤ 70 years presented a larger size of CIS (35.6% vs. 21.2%), P =.02. In multivariable Cox regression analyses, the same clinico-pathologic factors (age, multifocality, and recurrent tumor state) were independently associated with worse RFS. Harrell's C-index was 65.75.In multivariable Cox regression analyses in addition to age (P =.006) and multifocality (P

Few data are available regarding metachronous liver metastases from gastric cancer. We aimed to identify data regarding the survival of these patients, considering the chosen treatment, with particular attention to the role of surgery.A systematic review was carried out from 2000 to 2020. We chose articles reporting data from patients with metachronous liver metastases after curative gastrectomy. Data regarding 1-, 3- and 5-year overall survival were analyzed.Survival was improved in patients eligible for surgery (absence of extrahepatic non-curative factors and feasible complete macroscopic removal of liver deposits, i.e., H1 and H2 liver involvement, metastases less than 5 cm in size) when curative liver resection was performed, with a median overall survival of 24 months (vs. 3.13 in patients treated with chemotherapy). N Status, extent and maximum size of liver metastases, and hepatic surgical treatment were identified as independent prognostic factors.Selected patients with metachronous liver metastases from gastric cancer may benefit from multimodal 'aggressive' treatment. When hepatic involvement is limited (H1 and H2) and the size of metastases less than 5 cm, surgery was shown to increase survival.

There is a paucity of data describing the ability of margin, ischemia, complications, score (MIC) and trifecta in predicting long-term outcomes of robotic-assisted partial nephrectomy (RAPN).To compare a novel trifecta (negative margins, no significant complications, and perioperative estimated glomerular filtration rate [eGFR] decrease ≤30%) versus standard MIC as predictors of oncologic and functional results in a large series of RAPNs.Between 2009 and 2019, a multicenter dataset was queried for patients with nonmetastatic renal masses who underwent RAPN at eight participating institutions.RAPN.MIC and trifecta achievement were determined for the overall cohort and a subgroup undergoing off-clamp RAPN (ocRAPN), respectively. The overall survival (OS), recurrence-free survival (RFS), and new onset of end-stage renal disease (ESRD; defined as eGFR30 ml/min) probabilities were assessed by the Kaplan-Meier method. Cox regression analyses were used to identify predictors of OS, RFS, and ESRD. For all analyses, two-sided p0.05 was considered significant.Out of 1807 patients, MIC and trifecta were achieved in 71.1% (n = 1285) and 82.6% (n = 1492), respectively, and once restricted to the ocRAPN cohort, in 95.6% (n = 625) and 81.6% (n = 534), respectively. On Kaplan-Meier analysis, both MIC and trifecta achievement predicted higher OS and lower ESRD probabilities (all p0.014), while only trifecta achievement was a predictor of RFS probabilities (p = 0.009). On multivariable Cox regression, MIC did not predict any of the endpoints independently, while trifecta achievement was an independent predictor of higher OS (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.18-0.86; p = 0.019) and lower ESRD development probabilities (HR 0.32, 95% CI 0.15-0.72; p = 0.005).Trifecta, initially described as comprehensive measures of perioperative outcomes, needs to stand the test of time. Compared with MIC, the recent trifecta was an independent predictor of clinically significant endpoints, namely, survival and ESRD development probabilities.Our novel trifecta represents a reliable method for estimating survival and development of end-stage renal disease after robotic-assisted partial nephrectomy.

Objectives The Rotterdam Prostate Cancer Risk calculator (RPCRC) has been validated in the past years. Recently a new version including multiparametric magnetic resonance imaging (mpMRI) data has been released. The aim of our study was to analyze the performance of the mpMRI RPCRC app. Methods A series of men undergoing prostate biopsies were enrolled in eleven Italian centers. Indications for prostate biopsy included: abnormal Prostate specific antigen levels (PSA>4 ng/ml), abnormal DRE and abnormal mpMRI. Patients’ characteristics were recorded. Prostate cancer (PCa) risk and high-grade PCa risk were assessed using the RPCRC app. The performance of the mpMRI RPCRC in the prediction of cancer and high-grade PCa was evaluated using receiver operator characteristics, calibration plots and decision curve analysis. Results Overall, 580 patients were enrolled: 404/580 (70%) presented PCa and out of them 224/404 (55%) presented high-grade PCa. In the prediction of cancer, the RC presented good discrimination (AUC = 0.74), poor calibration (p = 0.01) and a clinical net benefit in the range of probabilities between 50 and 90% for the prediction of PCa (Fig. 1). In the prediction of high-grade PCa, the RC presented good discrimination (AUC = 0.79), good calibration (p = 0.48) and a clinical net benefit in the range of probabilities between 20 and 80% (Fig. 1). Conclusions The Rotterdam prostate cancer risk App accurately predicts the risk of PCa and particularly high-grade cancer. The clinical net benefit is wide for high-grade cancer and therefore its implementation in clinical practice should be encouraged. Further studies should assess its definitive role in clinical practice.

Aim of the study was to evaluate the Florence intracorporeal neobladder (FloRIN) oncological and functional outcomes at the end of assessment phase (phase 3) IDEAL-Guidelines.This single-institution prospective series included consecutive patients treated with robot-assisted radical cystectomy (RARC) and FloRIN reconfiguration technique from February 2016 to June 2020. Functional features were evaluated six months after surgery. Patients were grouped into four quartiles according to time of radical cystectomy and impact of learning curve improvement was evaluated.One-hundred FloRIN were completed with a median console time of 373 (IQR: 312-415) minutes. Two cases were converted to open surgery. No intraoperative complications occurred. At pathological examination, 30% of patients were staged as pT ≤ 1 and 47% as pT ≥ 3. Transitional cell carcinoma was present in 87% of cases. Carcinoma in situ (CIS) and nodal involvement were observed in 38% and 29% of patients, respectively. At a median follow-up time of 17 (IQR: 7-28) months, 20 clinically relevant events (Clavien-Dindo≥3) occurred. Operative time significantly decreased throughout the series (median minutes 435; 395; 365 and 330 in the four quartiles, respectively; p 0.001). Similarly, early Clavien-Dindo≥3 postoperative complications rate significantly decreased across the series (number of events: 1; 4; 0; 0; p = 0.03). Overall, 75% and 65% of patients achieved day-time and nigh-time continence, respectively. Twenty-seven patients experienced disease recurrence. Cancer-specific and overall survival were equal to 80%.RARC with FloRIN reconfiguration showed worthy functional and survival outcomes, with learning curve improvement significantly influencing operative time and early complications rate across series.

The mitochondrial ATP synthase is a multi-subunit enzyme complex located in the inner mitochondrial membrane which is essential for oxidative phosphorylation under physiological conditions. In this review, we analyse the enzyme functions involved in cancer progression by dissecting specific conditions in which ATP synthase contributes to cancer development or metastasis. Moreover, we propose the role of ATP synthase in the formation of the permeability transition pore (PTP) as an additional mechanism which controls tumour cell death. We further describe transcriptional and translational modifications of the enzyme subunits and of the inhibitor protein IF1 that may promote adaptations leading to cancer metabolism. Finally, we outline ATP synthase gene mutations and epigenetic modifications associated with cancer development or drug resistance, with the aim of highlighting this enzyme complex as a potential novel target for future anti-cancer therapy.

Background Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. Objective We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. Design, setting, and participants Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). Outcome measurements and statistical analysis Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. Results and limitations Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08–1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38–5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08–2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03–0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20–7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era. Conclusions Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients. Patient summary We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications.

Background Despite better renal function following nephron-sparing surgery (NSS) relative to radical nephrectomy (RN), there is no consensus with respect to the long-term sequelae associated with surgery. Objective To investigate the effect of surgery and the temporal pattern of two different cardiovascular event (CVe) categories after NSS versus RN. Design, setting, and participants We collected data of 898 patients with cT1–2 N0 M0 renal mass and no history of CVe treated with NSS versus RN. CVe categories were dichotomised in (1) de novo hypertension (HT) and (2) other major cardiovascular events (MCEs). Outcome measurements and statistical analysis Multivariable competing regression analyses (MVAs) tested the adjusted effect of surgery type on each CVe category. Results and limitations Among patients treated with RN, 38% of HT events occurred immediately after surgery. Conversely, in NSS counterparts, the onset of HT was diluted over the years after surgery (10% of HT events in the first 6 mo). When an MCE was considered, an increasing long-term time-dependent prevalence of the outcome was observed in both groups, with no statistically significantly difference between NSS and RN. At MVA, RN was associated with a higher HT risk (hazard ratio [HR] 2.89; p = 0.006) than but a similar MCE risk (HR 0.85; p = 0.6) to NSS. Conclusions Relative to RN, NSS showed an independent protective effect on HT but not on MCEs. In patients with no history of preoperative HT or MCEs, the onset of HT after RN is a very early event, due probably to the acute loss of renal parenchyma. This is not the case for the other cardiovascular morbidity, which develops in the long-term period, regardless of the type of surgery performed. Patient summary In renal cancer patients without a medical history of cardiopathy, preserving healthy kidney tissue at surgery is associated with a decreased risk of developing postoperative hypertension.

Temporomandibular joint (TMJ) osteoarthritis is a degenerative disease, characterized by gradual cartilage degradation, bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical therapy have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In last years, stem cell-based therapy has collected much attention as a possible approach toward tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will describe the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ, particularly focusing on the MSC-based therapy and tissue engineering.

Background: The impact of warm ischemia time (WIT) on renal functional recovery remains controversial. We examined the length of WIT >30 min. on the long-term renal function following on-clamp partial nephrectomy (PN). Methods: Data from 23 centers for patients undergoing on-clamp PN between 2000 and 2018 were analyzed. We included patients with two kidneys, single tumor, cT1, minimum 1-year followup, and preoperative eGFR ≥60 ml/min/1.73m2. Patients were divided into two groups according to WIT length: group Ⅰ "WIT ≤30 min." and group Ⅱ "WIT >30 min.". A propensity-score matched analysis (1:1 match) was performed to eliminate potential confounding factors between groups. We compared eGFR values, eGFR (%) preservation, eGFR decline, events of chronic kidney disease (CKD) upgrading, and CKD-free progression rates between both groups. Cox regression analysis evaluated WIT impact on upgrading of CKD stages. Results: The primary cohort consisted of 3526 patients: group Ⅰ (n=2868) and group Ⅱ (n=658). After matching the final cohort consisted of 344 patients in each group. At last followup, there were no significant differences in median eGFR values at 1, 3, 5, and 10 years (P>0.05) between the matched groups. In addition, the median eGFR (%) preservation and absolute eGFR change were similar (89% in group Ⅰ vs. 87% in group Ⅱ, p=0.638) and (-10 in group Ⅰ vs. -11 in group Ⅱ, p=0.577), respectively. The 5 years new-onset CKD-free progression rates were comparable in the non-matched groups (79% in group Ⅰ vs. 81% in group Ⅱ, log-rank, p=0.763) and the matched groups (78.8% in group Ⅰ vs. 76.3% in group Ⅱ, log-rank, p=0.905). Univariable Cox regression analysis showed that WIT >30 min. was not a predictor of overall CKD upgrading (HR:0.953, 95%CI 0.829-1.094, p=0.764) nor upgrading into CKD stage ≥Ⅲ (HR:0.972, 95%CI 0.805-1.173, p=0.764). Retrospective design is a limitation of our study. Conclusions: Our analysis based on a large multicenter international cohort study suggests that WIT length during PN has no effect on the long-term renal function outcomes in patients having two kidneys and preoperative eGFR ≥60 ml/min/1.73m2.

Mutations in the RYR1 gene, encoding ryanodine receptor 1 (RyR1), are a well-known cause of Central Core Disease (CCD) and Multi-minicore Disease (MmD). We screened a cohort of 153 patients carrying an histopathological diagnosis of core myopathy (cores and minicores) for RYR1 mutation. At least one RYR1 mutation was identified in 69 of them and these patients were further studied. Clinical and histopathological features were collected. Clinical phenotype was highly heterogeneous ranging from asymptomatic or paucisymptomatic hyperCKemia to severe muscle weakness and skeletal deformity with loss of ambulation. Sixty-eight RYR1 mutations, generally missense, were identified, of which 16 were novel. The combined analysis of the clinical presentation, disease progression and the structural bioinformatic analyses of RYR1 allowed to associate some phenotypes to mutations in specific domains. In addition, this study highlighted the structural bioinformatics potential in the prediction of the pathogenicity of RYR1 mutations. Further improvement in the comprehension of genotype–phenotype relationship of core myopathies can be expected in the next future: the actual lack of the human RyR1 crystal structure paired with the presence of large intrinsically disordered regions in RyR1, and the frequent presence of more than one RYR1 mutation in core myopathy patients, require designing novel investigation strategies to completely address RyR1 mutation effect.

Telemedicine is a subunit of telehealth, and it uses telecommunication technology, video, digital images, and electronic medical records to allow the exchange of clinical information and images over remote distances for dental consultation, diagnosis, and treatment planning. Dental clinical practice requires face-to-face interaction with the patients, and therefore, during the COVID-19 pandemic, it has mostly been suspended. In this view, teledentistry offers the opportunity to continue dental practice, avoiding the face-to-face examination that put patients and healthcare professionals at infection risk. Teledentistry encompasses several subunits such as teleconsultation, telediagnosis, telemonitoring, and teletriage. To date, there are several experiences described in literature that suggest that teledentistry could be applied to support traditional care of different oral diseases. However, there are some issues that need to be addressed. Reimbursement concerns, costs, license regulations, limits in physical examinations, and expert equipment are principal issues that should be overcome in telemedicine and in teledentistry. In this narrative review, we provide an overview of the different teledentistry approaches in the care of patients with dental and temporomandibular disorders, as well as discussing the issues that need to be addressed to implement this approach in clinical practice.

Background Despite the key importance of magnetic resonance imaging (MRI) parameters, risk classification systems for biochemical recurrence (BCR) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) are still based on clinical variables alone. Objective We aimed at developing and validating a novel classification integrating clinical and radiological parameters. Design, setting, and participants A retrospective multicenter cohort study was conducted between 2014 and 2020 across seven academic international referral centers. A total of 2565 patients treated with RP for PCa were identified. Outcome measurements and statistical analysis Early BCR was defined as two prostate-specific antigen (PSA) values of ≥0.2 ng/ml within 3 yr after RP. Kaplan-Meier and Cox regressions tested time and predictors of BCR. Development and validation cohorts were generated from the overall patient sample. A model predicting early BCR based on Cox-derived coefficients represented the basis for a nomogram that was validated externally. Predictors consisted of PSA, biopsy grade group, MRI stage, and the maximum diameter of lesion at MRI. Novel risk categories were then identified. The Harrel’s concordance index (c-index) compared the accuracy of our risk stratification with the European Association of Urology (EAU), Cancer of the Prostate Risk Assessment (CAPRA), and International Staging Collaboration for Cancer of the Prostate (STAR-CAP) risk groups in predicting early BCR. Results and limitations Overall, 200 (8%), 1834 (71%), and 531 (21%) had low-, intermediate-, and high-risk disease according to the EAU risk groups. The 3-yr overall BCR-free survival rate was 84%. No differences were observed in the 3-yr BCR-free survival between EAU low- and intermediate-risk groups (88% vs 87%; p = 0.1). The novel nomogram depicted optimal discrimination at external validation (c-index 78%). Four new risk categories were identified based on the predictors included in the Cox-based nomogram. This new risk classification had higher accuracy in predicting early BCR (c-index 70%) than the EAU, CAPRA, and STAR-CAP risk classifications (c-index 64%, 63%, and 67%, respectively). Conclusions We developed and externally validated four novel categories based on clinical and radiological parameters to predict early BCR. This novel classification exhibited higher accuracy than the available tools. Patient summary Our novel and straightforward risk classification outperformed currently available preoperative risk tools and should, therefore, assist physicians in preoperative counseling of men candidate to radical treatment for prostate cancer.

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Background To assess the predictability of crowding resolution and the efficacy of different strategies to gain space during clear aligners treatment. Methods A total of 10 clinicians were randomly recruited using the Doctor Locator by Align Technology (California). For each clinician, four consecutive patients treated with aligners and manual stripping were selected for a total of 40 subjects. Thus, 80 arches were collected and uploaded on the Orthoanalyzer software for arch measurements. The data were gained on the starting arch form (T0), on the virtual arch developed with digital planning (vT1), and on the arch form achieved at the end of the aligner sequences (T1). The following parameters were scored: Little's Irregularity Index, transversal arch diameters, (intercuspid, interpremolar, and intermolar width), incisor position/arch length, and enamel interproximal reduction (IPR). Results For all the measurements, statistically significant differences were found at different stages. The predictability of crowding resolution was very high, ranging from 87% in the upper arch and 81% in the lower one. Among the different strategies to gain space, variations in sagittal incisor position were predictable, with a value of 70% both in the upper and lower arch. Conversely, changes in arch diameters were less reliable varying between 49 and 67% in the lower arch and 59–83% in the upper one. Moreover, IPR was the least accurate procedure, wavering at 49% in the upper arch and 42% in the lower arch. Conclusions The predictability of crowding resolution during treatment with aligners was high. However, the virtual arch forms obtained at the end of digital planning (vT1) did not correspond with the arch forms at the end of the aligner sequences (T1). The IPR was the least predictable strategy to gain space, being, perhaps, an operator-dependent procedure.

The present study aimed to assess the safety and efficacy of robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (PCa) under anticoagulant (AC) and/or antiplatelet (AP) therapy, as compared to a control group, and to establish possible differences in postoperative-related morbidity. Data of all consecutive patients submitted to elective RARP for PCa from June 2017 to May 2020 at our institution were prospectively collected. Patients were divided according to the use of AC/AP therapy at surgery. The primary endpoint was to determine differences in 90-day postoperative complication rate, while secondary endpoints included differences in transfusion rate, readmission rate and postoperative oncological outcomes between the two groups. Sub-groups analysis was separately performed for patients undergoing pelvic lymphadenectomy and nerve-sparing procedures. Overall, 822 patients were included in the study and divided in 704 control-group patients (group A) and 118 patients under AC/AP therapy at surgery (group B). Despite the higher estimated blood loss between AC/AP takers and the control group, we did not find a significant difference in terms of 90-day postoperative complication rate, transfusion rate, readmission rate and postoperative oncological outcomes (all p > 0.05). In the cohort of patients undergoing nerve-sparing prostatectomy, a higher rate of complications and transfusions were found. At multivariate analysis, ASA score and ongoing medications were independently associated with complication in this sub-group. RARP can be safely and effectively performed in patients with PCa and ongoing AC/AP agents. Attention has to be paid in candidates for nerve-sparing procedures.

Patient with "very small" (2 cm) renal mass can be offered active surveillance, thermal ablation, or partial nephrectomy. The management strategy will consider patient preferences and prioritize potential harms associated with each of these options. To date, outcomes of robot-assisted partial nephrectomy (RAPN) in patients with "very small" renal masses have not been reported.To assess the outcomes of RAPN among patients with "very small" renal masses.This was a retrospective analysis of a multi-institutional database including RAPN cases performed at eight high-volume US and European centers between 2009 and 2019. Patients were stratified into two groups according to clinical tumor size:2 cm ("very small" renal mass, study group) and 2-4 cm (control group).RAPN for renal masses.Baseline characteristics and intraoperative, pathological, and postoperative data were compared between the study and the control group. A "trifecta" was used as surrogate of "surgical quality."Overall, a total of 1019 patients were included in the analysis. Of these, 352 had a renal mass of2 cm (34.5%) and 667 (65.5%) had a renal mass of 2-4 cm. At baseline, the study group presented a lower rate of chronic kidney disease ≥stage III (p0.001), a lower RENAL score (p = 0.001), and lower rates of hilar (p = 0.04) and endophytic (p = 0.02) masses. Warm ischemia time was shorter for the study group (median 14 vs 18 min, p0.001), which also showed a lower rate of overall postoperative complications (9.6% vs 14.7%, p0.001) and no major complications. In terms of oncological outcomes, three and ten patients developed a local recurrence in the study and the control group, respectively (p = 0.1). In the study group, higher estimated glomerular filtration rates were found at discharge (p = 0.001) and at the last follow-up (p = 0.007), which showed a "trifecta" achievement of 90.6%. The retrospective design may limit the generalizability of the findings.Whenever an active treatment is indicated or warranted, RAPN represents a minimally invasive management option for "very small" renal masses, as it carries minimal risk of complications and has minimal impact on renal function. While both active surveillance and kidney ablation remain valid management options in these cases, RAPN can be offered and discussed with patients as it provides excellent outcomes with low morbidity.In this report, we observed that robot-assisted partial nephrectomy represents a true minimally invasive active treatment for "very small" renal masses (2 cm), as it carries minimal risk of complications and has minimal impact on renal function.

Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) has an incidence of approximately 20%-50%. Studies to date have been composed of mixed treatment cohorts-open, laparoscopic and robotic. The objective of this study is to assess clinicopathological risk factors for intravesical recurrence after RNU for UTUC in a completely minimally invasive cohort.We performed a multicenter, retrospective analysis of 485 patients with UTUC without prior or concurrent bladder cancer who underwent robotic or laparoscopic RNU. Patients were selected from an international cohort of 17 institutions across the United States, Europe and Asia. Univariate and multiple Cox regression models were used to identify risk factors for bladder recurrence.A total of 485 (396 robotic, 89 laparoscopic) patients were included in analysis. Overall, 110 (22.7%) of patients developed IVR. The average time to recurrence was 15.2 months (SD 15.5 months). Hypertension was a significant risk factor on multiple regression (HR 1.99, CI 1.06; 3.71, p=0.030). Diagnostic ureteroscopic biopsy incurred a 50% higher chance of developing IVR (HR 1.49, CI 1.00; 2.20, p=0.048). Treatment specific risk factors included positive surgical margins (HR 3.36, CI 1.36; 8.33, p=0.009) and transurethral resection for bladder cuff management (HR 2.73, CI 1.10; 6.76, p=0.031).IVR after minimally invasive RNU for UTUC is a relatively common event. Risk factors include a ureteroscopic biopsy, transurethral resection of the bladder cuff, and positive surgical margins. When possible, avoidance of transurethral resection of the bladder cuff and alternative strategies for obtaining biopsy tissue sample should be considered.

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Recently, the use of targeted biopsy has been subject to critics, as it has been speculated that targeted biopsy might lead to overdiagnosis of clinically significant prostate cancer (PCa). In this study, we tried to evaluate whether targeted sampling in patients with organ-confined disease and ISUP 2 disease was associated with downgrading of the prostatectomy specimen, hence, leading to an unnecessary treatment, in terms of radical surgery. We relied on a prospectively-maintained multi-institutional database and identified 1293 patients with ISUP 2 disease on targeted biopsy only. Median (IQR) patients' age at diagnosis was 65 (60, 70) years. Median PSA was 6.8 (5.0, 9.6) ng/ml. Overall, only 33 (2.6%) patients presented downgrading on their RP specimens. Patients who experienced downgrading were biopsied more frequently trans-rectally, had a lower total tumor length in mm and lower percentage of maximum core involvement and lower rates of cancer on systematic biopsy (all p ≤ 0.03). The strongest factors associated with reduced risk of downgrading were total tumor length, in mm, (OR: 0.71, 95% CI: 0.62,0.82, p 0.001) and transperineal biopsy route (OR: 0.38, 95% CI: 0.14,1.00, p = 0.05).

To assess whether socio-economic disparities exist on access to care, treatment options and outcomes among patients with renal mass amenable of surgical treatment within the universal healthcare system.Data of consecutive patients submitted to partial nephrectomy (PN) or radical nephrectomy (RN) at our Institution between 2017 and 2020 were retrospectively evaluated. Patients were grouped according to their income level (low, intermediate, and high) based on the Indicator of Equivalent Economic Situation national criterion. Survival analysis was performed. Cox regression models were employed to analyse the impact of socio-economic variables on survival outcomes.One thousand forty-two patients were included (841 PN and 201 RN). Patients at the lowest income level were found more likely symptomatic and with a higher pathological tumour stage in the RN cohort (p 0.05). The guidelines adherence on surgical indication rate as well as the access to minimally invasive surgery did not differ according to patient's income level in both cohorts (p 0.05). Survival curves were comparable among the groups. Cox regression analysis showed that none of the included socio-economic variables was associated with survival outcomes in our series.Universal healthcare system may increase the possibility to ensure egalitarian treatment modalities for patients with renal cancer.

Objective The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. Methods We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns. Results Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033–1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054–1.344, respectively). These results were confirmed after the propensity score matching analysis. Conclusions pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors.

Hepatocellular adenomas (HCAs), hepatocellular carcinomas (HCCs), and intrahepatic cholangiocarcinomas (iCCAs) are a highly heterogeneous group of liver tumors with diverse pathomolecular features and prognoses. High-throughput gene sequencing techniques have allowed discovery of distinct genetic and molecular underpinnings of these tumors and identified distinct subtypes that demonstrate varied clinicobiologic behaviors, imaging findings, and complications. The combination of histopathologic findings and molecular profiling form the basis for the morphomolecular classification of liver tumors. Distinct HCA subtypes with characteristic imaging findings and complications include

Purpose Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. Methods The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). Results The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%,p < 0.001) and NS prostatectomy (58.4% vs. 52.9%,p = 0.04), but received LND less frequently (47.7% vs. 76.7%,p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS >= (4 + 3) and positive cancer cores >= 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. Conclusions PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Background: To investigate the perioperative and morbidity outcomes after partial nephrectomy (PN) in patients with short life expectancy (SLE) (≥95% 10-year expected mortality (10y-EM)), to assess the main predictors of outcomes in this population and to compare these results with those of a group at the opposite upper range with long LE (LLE, ≤5% 10y-EM) relying on a multicenter Italian prospective registry of kidney surgery (the RECORD 2 project). Methods: Clinical data of 4,325 patients undergone kidney surgery were collected at 26 urological Italian Centers from 2013 to 2016. SLE was defined as a ≥95% 10y-EM (assessed using the age-adjusted Charlson comorbidity index [CCI]). A multivariable logistic regression for overall postoperative complications, acute kidney injury (AKI), positive surgical margins (SM) and ∆ estimated glomerular filtration rate (eGFR) ≥25% at 2 years from surgery was performed in patients with SLE including clinically relevant variables. Adjusted outcomes reported as mean (SD) of the 2 groups were generated using separate multivariable logistic regression models and compared. Results: Overall, 559 patients with SLE were selected. Patients had an ASA score ≥3 in 58.4% of cases. A clinical T1a, T1b, and T2 stage was found in 412 (74.5%), 124 (22.4%), and 17 (3.1%) patients. The median PADUA score was 7 (6–8). Surgical and medical postoperative complication rates were registered in 14.8% and 6% cases. Postoperative AKI was reported in 27.3% cases, positive surgical margins (PSM) in 9.3% cases. In this subgroup of patients, ASA score, cerebrovascular disease, surgery in low volume centers, and open surgery were independent predictors of overall complications. ASA and PADUA scores, renal clamping, resection technique and lower eGFR at baseline were independent predictors of AKI. PADUA score, open approach and resection technique were independent predictors of PSM. Cardiovascular disease, hilar clamping, and resection technique were independent predictors of eGFR decrease >25% at 2 years from surgery. Patients with SLE were compared with those with LLE (n = 302). All analyzed parameters at baseline were significantly different among the groups with the exception of cancer laterality. After adjusting for several clinical variables, the SLE group had a significantly higher risk rate of adjusted overall postoperative complication rate compared to the LLE group (20.6% ± 0.36 vs. 9.9% ± 0.65, P < 0.0001), while the overall intraoperative complications (4.1% ±0.13 vs. 2.3% ± 0.23), overall postoperative major complications (3.8% ± 0.09 vs. 1.9% ± 0.14) adjusted AKI (24.2% ± 0.37 vs. 22.6% ± 0.92), positive surgical margins (8% ± 0.22 vs. 6.4% ± 0.49), and 2-year RF loss (13.4% ± 0.17 vs. 12.4% ± 0.74). Conclusion: In selected patients with SLE, PN is feasible with an acceptable safety profile that is overall comparable to patients with no LE limitations. While a robotic approach and surgery performed in high volume centers could reduce the risk of complications, an off-clamp approach and a SE surgical technique may decrease the risk of postoperative AKI and of longer term eGFR decrease.

Background: Partial nephrectomy (PN) has a non-negligible perioperative morbidity. Comparative evidence of the available surgical techniques is limited. Objective: To compare the perioperative outcomes of open, laparoscopic, and robotic PN. Methods: Data of 2331 patients treated with PN for cT1 renal tumors were extracted from the RECORd2 database, a prospective multicenter project. Multivariable regression models assessed the relationship between surgical technique and surgical margins, warm ischemia time, postoperative complications, and acute kidney injury (AKI). The probability of achieving a modified trifecta (negative margins, warm ischemia time

Multicenter retrospective analysis of robotic partial nephrectomy for completely endophytic renal tumors (i.e. 3 points for the 'E' domain of the R.E.N.A.L. nephrometry score) was performed.Patients' demographics, tumor characteristics, perioperative, functional, pathological and oncological data were analyzed and compared with those of patients with exophytic and mesophytic masses (i.e. 1 and 2 points for the 'E' domain, respectively). Multivariable logistic regression analysis was used to assess variables for trifecta achievement (negative margin, no postoperative complications, and 90% estimated glomerular filtration rate [eGFR] recovery).Overall, 147 patients were included in the study group. Patients with a completely endophytic mass had bigger tumors (mean 4.2 vs. 4.1 vs. 3.2 cm; p 0.001) on preoperative imaging and higher overall R.E.N.A.L. score. There was no difference in mean operative time. Estimated blood loss was higher in the endophytic group (mean 177.75 vs. 185.5 vs. 130 ml; p = 0.001). Warm ischemia time was shorter for the exophytic group (median 16 vs. 21 vs. 22 min; p 0.001). Postoperative complications were more frequent in patients with endophytic tumor (24.8% vs. 19.5% vs. 14.8%; p 0.001). Six (4.5%) patients had positive surgical margins, there was no difference between groups. Trifecta was achieved in 44 patients in endophytic group (45.4 vs. 68.8 and 50.9%, p 0.001). Multivariable analysis for trifecta revealed that clinical tumor size (odds ratio: 0.667, 95% confidence interval: 0.56-0.79, p 0.001) was only significant predictor for trifecta achievement.Our findings confirm that RAPN in case of completely endophytic renal masses can be performed with acceptable outcomes in centers with significant robotic expertise.

We sought to evaluate outcomes of lymph node dissection (LND) in patients with upper tract urothelial carcinoma.We performed a multicenter retrospective analysis utilizing the ROBUUST (for RObotic surgery for Upper Tract Urothelial Cancer Study) registry for patients who did not undergo LND (pNx), LND with negative lymph nodes (pN0) and LND with positive nodes (pN+). Primary and secondary outcomes were overall survival (OS) and recurrence-free survival (RFS). Multivariable analyses evaluated predictors of outcomes and pathological node positivity. Kaplan-Meier analyses (KMAs) compared survival outcomes.A total of 877 patients were analyzed (LND performed in 358 [40.8%]/pN+ in 73 [8.3%]). Median nodes obtained were 10.2 for pN+ and 9.8 for pN0. Multivariable analyses noted increasing age (OR 1.1, p0.001), pN+ (OR 3.1, p0.001) and pathological stage pTis/3/4 (OR 3.4, p0.001) as predictors for all-cause mortality. Clinical high-grade tumors (OR 11.74, p=0.015) and increasing tumor size (OR 1.14, p=0.001) were predictive for lymph node positivity. KMAs for pNx, pN0 and pN+ demonstrated 2-year OS of 80%, 86% and 42% (p0.001) and 2-year RFS of 53%, 61% and 35% (p0.001), respectively. KMAs comparing pNx, pN0 ≥10 nodes and pN010 nodes showed no significant difference in 2-year OS (82% vs 85% vs 84%, p=0.6) but elicited significantly higher 2-year RFS in the pN0 ≥10 group (60% vs 74% vs 54%, p=0.043).LND during nephroureterectomy in patients with positive lymph nodes provides prognostic data, but is not associated with improved OS. LND yields ≥10 in patients with clinical node negative disease were associated with improved RFS. In high-grade and large tumors, lymphadenectomy should be considered.

Background: Robot-assisted partial nephrectomy (RAPN) is increasingly adopted for the treatment of localized renal tumors; however, rates and predictors of significant renal function (RF) loss after RAPN are still poorly investigated, especially at a long-term evaluation. Objective: To analyze the predictive factors and develop a clinical nomogram for predicting the likelihood of ultimate RF loss after RAPN. Design, setting, and participants: We prospectively evaluated all patients treated with RAPN in a multicenter series (RECORd2 project). Outcome measurements and statistical analysis: Significant RF loss was defined as >25% reduction in estimated glomerular filtration rate (eGFR) from preoperative assessment at 48th month follow-up after surgery. Uni- and multivariable logistic regression analyses for RF loss were performed. The area under the receiving operator characteristic curve (AUC) was used to quantify predictive discrimination. A nomogram was created from the multivariable model. Results and limitations: A total of 981 patients were included. The median age at surgery was 64.2 (interquartile range [IQR] 54.3–71.4) yr, and 62.4% of patients were male. The median Charlson Comorbidity Index (CCI) was 1 (IQR 0–2), 12.9% of patients suffered from diabetes mellitus, and 18.6% of patients showed peripheral vascular disease (PVD). The median Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score was 7 (IQR 7–9). Imperative indications to partial nephrectomy were present in 3.6% of patients. Significant RF loss at 48th month postoperative evaluation was registered in 108 (11%) patients. At multivariable analysis, age (p = 0.04), female gender (p < 0.0001), CCI (p < 0.0001), CCI (p < 0.0001), diabetes (p < 0.0001), PVD (p < 0.0001), eGFR (p = 0.02), imperative (p = 0.001) surgical indication, and PADUA score (p < 0.0001) were found to be predictors of RF loss. The developed nomogram including these variables showed an AUC of 0.816. Conclusions: We developed a clinical nomogram for the prediction of late RF loss after RAPN using preoperative and surgical variables from a large multicenter dataset. Patient summary: We developed a nomogram that could represent a clinical tool for early detection of patients at the highest risk of significant renal function impairment after robotic conservative surgery for renal tumors.