Publications by authors named "Andrea Mari"

336 Publications

Fighting the 'tobacco epidemic' - A call to action to identify Targeted Intervention Points (TIPs) for better counseling patients with urothelial cancer.

Urol Oncol 2021 Oct 7. Epub 2021 Oct 7.

Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The association between tobacco use and urothelial cancer of the bladder is well known. Given the worsening tobacco epidemic, here we make the case for systematic targeted points of intervention for urologists and other professionals to intervene against bladder cancer. Awareness of contemporary checkpoints where we can intervene for counseling patients may help medical education in a tobacco-pandemic difficult setting.
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http://dx.doi.org/10.1016/j.urolonc.2021.08.025DOI Listing
October 2021

Continuing acetylsalicylic acid during Robotic-Assisted Radical Cystectomy with intracorporeal urinary diversion does not increase hemorrhagic complications: results from a large multicentric cohort.

Urol Oncol 2021 Sep 24. Epub 2021 Sep 24.

Unit of Urology/Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy.

Objectives: To evaluate whether continuing the antiplatelet drug acetylsalicylic acid≤100mg (ASA) during Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) increases the risk of peri-and postoperative hemorrhagic complications and overall morbidity. Indeed, guidelines recommend interrupting antiplatelet therapy before radical cystectomy; however, RARC with ICUD is associated to reduced estimated blood loss and blood transfusions compared to its open counterpart.

Methods: Data from a multicentric European database were analyzed. All participating centers maintained a prospective database of patients undergoing RARC with ICUD. We identified patients receiving antiplatelet therapy by acetylsalicylic acid ≤100mg. Patients were divided into three groups: those not taking acetylsalicylic acid (no-ASA), those where ASA was continued perioperatively (c-ASA) and those where ASA was interrupted perioperatively (i-ASA). Estimated blood loss and peri-and post-operative transfusions were recorded. Hemorrhagic complications, ischemic, thrombotic and cardiac morbidity was recorded and classified using the Clavien-Dindo score by a senior urologist.

Results: 640 patients were analyzed. Patients on acetylsalicylic acid were significantly older and had more comorbidities. No significant difference was found for estimated blood loss between no-ASA, c-ASA and i-ASA (280 vs. 300 vs. 200ml respectively; P = 0.09). Similarly, no significant difference was found for intraoperative (5% vs. 9% vs. 11%; P = 0.07) and postoperative transfusion rate (11% vs. 13% vs. 18%; P = 0.17). Higher ischemic complications were noted in the i-ASA group compared to no-ASA and c-ASA (4% vs. 0.6% vs. 1.4%; P = 0.03). On uni and multivariate logistic regression, continuing acetylsalicylic acid was not significantly associated to either major complications or post-operative transfusions.

Conclusions: Peri-operative acetylsalicylic acid continuation in RARC with ICUD does not increase hemorrhagic complications. Interrupting acetylsalicylic acid peri-operatively may expose patients to a higher risk of ischemic events.
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http://dx.doi.org/10.1016/j.urolonc.2021.08.023DOI Listing
September 2021

A Nomogram for the Prediction of Intermediate Significant Renal Function Loss After Robot-assisted Partial Nephrectomy for Localized Renal Tumors: A Prospective Multicenter Observational Study (RECORd2 Project).

Eur Urol Focus 2021 Sep 21. Epub 2021 Sep 21.

Department of Urology, Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, University of Florence, Florence, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.euf.2021.09.012DOI Listing
September 2021

A comparative study of anticoagulant/antiplatelet therapy among men undergoing robot-assisted radical prostatectomy: a prospective single institution study.

J Robot Surg 2021 Sep 21. Epub 2021 Sep 21.

Department of Experimental and Clinical Medicine, University of Florence-Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, Largo Brambilla, 3, 70134, Florence, Italy.

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.
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http://dx.doi.org/10.1007/s11701-021-01308-2DOI Listing
September 2021

The Ile191Val is a partial loss-of-function variant of the TAS1R2 sweet-taste receptor and is associated with reduced glucose excursions in humans.

Mol Metab 2021 Sep 9;54:101339. Epub 2021 Sep 9.

Department of Biological Chemistry & Pharmacology, College of Medicine, The Ohio State University, Columbus, OH, USA. Electronic address:

Objective: Sweet taste receptors (STR) are expressed in the gut and other extra-oral tissues, suggesting that STR-mediated nutrient sensing may contribute to human physiology beyond taste. A common variant (Ile191Val) in the TAS1R2 gene of STR is associated with nutritional and metabolic outcomes independent of changes in taste perception. It is unclear whether this polymorphism directly alters STR function and how it may contribute to metabolic regulation.

Methods: We implemented a combination of in vitro biochemical approaches to decipher the effects of TAS1R2 polymorphism on STR function. Then, as proof-of-concept, we assessed its effects on glucose homeostasis in apparently healthy lean participants.

Results: The Ile191Val variant causes a partial loss of function of TAS1R2 through reduced receptor availability in the plasma membrane. Val minor allele carriers have reduced glucose excursions during an OGTT, mirroring effects previously seen in mice with genetic loss of function of TAS1R2. These effects were not due to differences in beta-cell function or insulin sensitivity.

Conclusions: Our pilot studies on a common TAS1R2 polymorphism suggest that STR sensory function in peripheral tissues, such as the intestine, may contribute to the regulation of metabolic control in humans.
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http://dx.doi.org/10.1016/j.molmet.2021.101339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476773PMC
September 2021

Survival Outcomes After Immediate Radical Cystectomy Versus Conservative Management with Bacillus Calmette-Guérin Among T1 High-grade Micropapillary Bladder Cancer Patients: Results from a Multicentre Collaboration.

Eur Urol Focus 2021 Aug 18. Epub 2021 Aug 18.

Department of Urology, Spedali Civili di Brescia, Brescia, Italy.

Background: Literature lacks clear evidence regarding the optimal treatment for non-muscle-invasive micropapillary bladder cancer (MPBC) due to its rarity and the presence of only small sample size and single-centre studies.

Objective: To assess cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and conservative management among T1 high-grade (HG) MPBC.

Design, Setting, And Participants: We retrospectively analysed a multicentre dataset including 119 T1 HG MPBC patients treated between 2005 and 2019 at 15 tertiary referral centres. The median follow-up time was 35 mo (interquartile range: 19-64).

Intervention: Patients underwent immediate RC versus conservative management with bacillus Calmette-Guérin.

Outcomes Measurements And Statistical Analysis: Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Multivariable Cox analyses were performed to assess independent predictors of disease recurrence and disease progression after conservative management; covariates consisted of pure MPBC, concomitant lymphovascular invasion (LVI), and carcinoma in situ at initial diagnosis.

Results And Limitations: Immediate RC and conservative management were performed in 27% and 73% of patients, respectively. CSM and OM did not differ significantly among patient treated with immediate RC versus conservative management (Pepe-Mori test p = 0.5 and log-rank test p = 0.9, respectively). Overall, 66.7% and 34.5% of patients experienced disease recurrence and disease progression after conservative management, respectively. At multivariable Cox analyses, concomitant LVI was an independent predictor of disease recurrence (p = 0.01) and progression (p = 0.03), while pure MPBC was independently associated with disease progression (p = 0.03). The absence of a centralised re-review and the retrospective design represent the main limitations of our study.

Conclusions: Conservative management could achieve satisfactory results among T1 HG MPBC patients with neither pure MPBC nor LVI at initial diagnosis.

Patient Summary: Bacillus Calmette-Guérin seems to be an effective therapy for T1 micropapillary bladder cancer patients with neither pure micropapillary disease nor lymphovascular invasion at initial diagnosis.
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http://dx.doi.org/10.1016/j.euf.2021.07.015DOI Listing
August 2021

Risk Stratification of Patients Candidate to Radical Prostatectomy Based on Clinical and Multiparametric Magnetic Resonance Imaging Parameters: Development and External Validation of Novel Risk Groups.

Eur Urol 2021 Aug 13. Epub 2021 Aug 13.

Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.

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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http://dx.doi.org/10.1016/j.eururo.2021.07.027DOI Listing
August 2021

New Insights on the Interactions Between Insulin Clearance and the Main Glucose Homeostasis Mechanisms.

Diabetes Care 2021 09 6;44(9):2115-2123. Epub 2021 Aug 6.

CNR Institute of Neuroscience, Padua, Italy.

Objective: Endogenous insulin clearance (EIC) is physiologically reduced at increasing insulin secretion rate (ISR). Computing EIC at the prevailing ISR does not distinguish the effects of hypersecretion from those of other mechanisms of glucose homeostasis. We aimed to measure EIC in standardized ISR conditions (i.e., at fixed ISR levels) and to analyze its associations with relevant physiologic factors.

Research Design And Methods: We estimated standardized EIC (EIC) by mathematical modeling in nine different studies with insulin and glucose infusions ( = 2,067). EIC association with various traits was analyzed by stepwise multivariable regression in studies with both euglycemic clamp and oral glucose tolerance test (OGTT) ( = 1,410). We also tested whether oral glucose ingestion, as opposed to intravenous infusion, has an independent effect on EIC ( = 1,555).

Results: Insulin sensitivity (as M/I from the euglycemic clamp) is the strongest determinant of EIC, approximately four times more influential than insulin resistance-related hypersecretion. EIC independently associates positively with M/I, fasting and mean OGTT glucose or type 2 diabetes, and β-cell glucose sensitivity and negatively with African American or Hispanic race, female sex, and female age. With oral glucose ingestion, an ISR-independent ∼10% EIC reduction is necessary to explain the observed insulin concentration profiles.

Conclusions: Based on EIC, we posit the existence of two adaptive processes involving insulin clearance: the first reduces EIC with insulin resistance (not with higher BMI per se) and is more relevant than the concomitant hypersecretion; the second reduces EIC with β-cell dysfunction. These processes are dysregulated in type 2 diabetes. Finally, oral glucose ingestion per se reduces insulin clearance.
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http://dx.doi.org/10.2337/dc21-0545DOI Listing
September 2021

Postoperative Chemotherapy Bladder Instillation After Radical Nephroureterectomy: Results of a European Survey from the Young Academic Urologist Urothelial Cancer Group.

Eur Urol Open Sci 2020 Dec 6;22:45-50. Epub 2020 Nov 6.

Urology Department, Bichat-Claude Bernard Hospital, Assistance-Publique Hôpitaux de Paris, Paris University, Paris, France.

Background: Level 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk.

Objective: The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues.

Design Setting And Participants: An online survey was shared with European Association of Urology Section of Oncological Urology (ESOU) 2017 participants via e-mail. Submissions were accepted from April to June 2017. The topics for 15 questions of this survey included the habit of delivering pIVC, the choice of drug, its dosage, related doubts or concerns, reasons not to perform pIVC, knowledge of the evidence, and surgical preferences for RNU.

Outcome Measurements And Statistical Analysis: Survey software was used for analyses. Logistic regression analyses were used to investigate the association between surgeons' experience and caseloads with pIVC utilization.

Results And Limitations: Overall, 127 responses were collected (11.6%). About half of the participants (47%) regularly administered pIVC following RNU. The drug most commonly utilized was mitomycin (85%); 82% adhered to the standard dosage of 40 mg. Different administration protocols were adopted: ≤48 h (39%), 7-10 postoperative days (35%), >10 d (11%), and intraoperatively (10%). The evidence was supported by prospective randomized clinical trials for only 65% of responders. Among interviewees who did not deliver pIVC, the most commonly reported reasons were lack of supporting data (55%), fear of potential side effects (18%), and organizational hurdles (15%).

Conclusions: Our research highlights the limited use of pIVC following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted.

Patient Summary: Level 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. Our research highlights the limited use of pIVC (47%) following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted.
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http://dx.doi.org/10.1016/j.euros.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317887PMC
December 2020

Perioperative outcomes of patients undergoing urological elective surgery during the COVID-19 pandemic: a national overview across 28 Italian institutions.

Cent European J Urol 2021 22;74(2):259-268. Epub 2021 Apr 22.

Urology Department, ASST Valle Olona, Busto Arsizio, Varese, Italy.

Introduction: The aim of this study was to assess the safety of elective urological surgery performed during the pandemic by estimating the prevalence of COVID-19-like symptoms in the postoperative period and its correlation with perioperative and clinical factors.

Material And Methods: In this multicenter, observational study we recorded clinical, surgical and postoperative data of consecutive patients undergoing elective urological surgery in 28 different institutions across Italy during initial stage of the COVID-19 pandemic (between February 24 and March 30, 2020, inclusive).

Results: A total of 1943 patients were enrolled. In 12%, 7.1%, 21.3%, 56.7% and 2.6% of cases an open, laparoscopic, robotic, endoscopic or percutaneous surgical approach was performed, respectively. Overall, 166 (8.5%) postoperative complications were registered, 77 (3.9%) surgical and 89 (4.6%) medical. Twenty-eight (1.4%) patients were readmitted to hospital after discharge and 13 (0.7%) died. In the 30 days following discharge, fever and respiratory symptoms were recorded in 101 (5.2%) and 60 (3.1%) patients. At multivariable analysis, not performing nasopharyngeal swab at hospital admission (HR 2.3; CI 95% 1.01-5.19; p = 0.04) was independently associated with risk of developing postoperative medical complications. Number of patients in the facility was confirmed as an independent predictor of experiencing postoperative respiratory symptoms (p = 0.047, HR:1.12; CI95% 1.00-1.05), while COVID-19-free type of hospitalization facility was a strong independent protective factor (p = 0.02, HR:0.23, CI95% 0.07-0.79).

Conclusions: Performing elective surgery during the COVID-19 pandemic does not seem to affect perioperative outcomes as long as proper preventive measures are adopted, including nasopharyngeal swab before hospital admission and hospitalization in dedicated COVID-19-free facilities.
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http://dx.doi.org/10.5173/ceju.2021.0374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318031PMC
April 2021

A risk-group classification model in patients with bladder cancer under neoadjuvant cisplatin-based combination chemotherapy.

Future Oncol 2021 Oct 19;17(30):3987-3994. Epub 2021 Jul 19.

Department of Urology, Humanitas Gavazzeni, Bergamo, Italy.

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.
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http://dx.doi.org/10.2217/fon-2020-1298DOI Listing
October 2021

Incidence, risk factors and outcomes of urethral recurrence after radical cystectomy for bladder cancer: A systematic review and meta-analysis.

Urol Oncol 2021 Jul 12. Epub 2021 Jul 12.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

We aimed to conduct a systematic review and meta-analysis assessing the incidence and risk factors of urethral recurrence (UR) as well as summarizing data on survival outcomes in patients with UR after radical cystectomy (RC) for bladder cancer. The MEDLINE and EMBASE databases were searched in February 2021 for studies of patients with UR after RC. Incidence and risk factors of UR were the primary endpoints. The secondary endpoint was survival outcomes in patients who experienced UR. Twenty-one studies, comprising 9,435 patients, were included in the quantitative synthesis. Orthotopic neobladder (ONB) diversion was associated with a decreased probability of UR compared to non-ONB (pooled OR: 0.44, 95% CI: 0.31-0.61, P < 0.001) and male patients had a significantly higher risk of UR compared to female patients (pooled OR: 3.16, 95% CI: 1.83-5.47, P < 0.001). Among risk factors, prostatic urethral or prostatic stromal involvement (pooled HR: 5.44, 95% CI: 3.58-8.26, P < 0.001; pooled HR: 5.90, 95% CI: 1.82-19.17, P = 0.003, respectively) and tumor multifocality (pooled HR: 2.97, 95% CI: 2.05-4.29, P < 0.001) were associated with worse urethral recurrence-free survival. Neither tumor stage (P = 0.63) nor CIS (P = 0.72) were associated with worse urethral recurrence-free survival. Patients with UR had a 5-year CSS that varied from 47% to 63% and an OS - from 40% to 74%; UR did not appear to be related to worse survival outcomes. Male patients treated with non-ONB diversion as well as patients with prostatic involvement and tumor multifocality seem to be at the highest risk of UR after RC. Risk-adjusted standardized surveillance protocols should be developed into clinical practice after RC.
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http://dx.doi.org/10.1016/j.urolonc.2021.06.009DOI Listing
July 2021

Neutrophil percentage-to-albumin ratio predicts mortality in bladder cancer patients treated with neoadjuvant chemotherapy followed by radical cystectomy.

Future Sci OA 2021 Aug 20;7(7):FSO709. Epub 2021 Apr 20.

Department of Emergency & Organ Transplantation-Urology, Andrology & Kidney Transplantation Unit, University of Bari, Bari, Italy.

Aim: To investigate the prognostic role of neutrophil percentage-to-albumin ratio (NPAR) in muscle-invasive bladder cancer (MIBC) patients treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).

Patients & Methods: 213 patients were included.

Inclusion Criteria: Nonmetastatic, MIBC (cT2-T4aN0M0), at least three cycles of NAC, undergone RC and with blood count within 30 days before NAC.

Results: Five-years overall survival (OS) with NPAR >18 was 34.06% (95% CI: 18.3-50.5) and 65.37% (95% CI: 52.4-75.6) with NPAR <18. Five years cancer-specific survival (CSS) with NPAR >18 was 42.9% (95% CI: 23.9-60.7) and 74.5% (95% CI: 62.6-83.1) with NPAR <18 (p < 0.001). In multivariable analysis, NPAR increased OS of 1.3 points and CSS of 4.37 points.

Conclusion: High NPAR prior to NAC seems to be a strong predictor of OS and CSS in MIBC patients treated with NAC and RC.
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http://dx.doi.org/10.2144/fsoa-2021-0008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256323PMC
August 2021

Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: An IMI DIRECT Study.

Diabetes 2021 Sep 7;70(9):2092-2106. Epub 2021 Jul 7.

Department of Epidemiology and Data Science, Amsterdam Medical Centre, location VUMC, Amsterdam, the Netherlands.

Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants ( = 2,111) underwent a 2-h 75-g oral glucose tolerance test (OGTT) at baseline and 48 months. HbA was also measured. We classified participants as having isolated prediabetes defect (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or HbA indicative of prediabetes [IA1c]), two defects (IFG+IGT, IFG+IA1c, or IGT+IA1c), or all defects (IFG+IGT+IA1c). β-Cell function (BCF) and insulin sensitivity were assessed from OGTT. At baseline, in pooling of participants with isolated defects, they showed impairment in both BCF and insulin sensitivity compared with healthy control subjects. Pooled groups with two or three defects showed progressive further deterioration. Among groups with isolated defect, those with IGT showed lower insulin sensitivity, insulin secretion at reference glucose (ISR), and insulin secretion potentiation ( < 0.002). Conversely, those with IA1c showed higher insulin sensitivity and ISR ( < 0.0001). Among groups with two defects, we similarly found differences in both BCF and insulin sensitivity. At 48 months, we found higher type 2 diabetes incidence for progressively increasing number of prediabetes defects (odds ratio >2, < 0.008). In conclusion, the prediabetes groups showed differences in type/degree of glucometabolic impairment. Compared with the pooled group with isolated defects, those with double or triple defect showed progressive differences in diabetes incidence.
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http://dx.doi.org/10.2337/db21-0227DOI Listing
September 2021

Imatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Lancet Diabetes Endocrinol 2021 08 29;9(8):502-514. Epub 2021 Jun 29.

University of California San Francisco, San Francisco, CA, USA.

Background: Type 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, and preclinical studies show that it reverses and prevents diabetes. Our aim was to evaluate the safety and efficacy of imatinib in preserving β-cell function in patients with recent-onset type 1 diabetes.

Methods: We did a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients with recent-onset type 1 diabetes (<100 days from diagnosis), aged 18-45 years, positive for at least one type of diabetes-associated autoantibody, and with a peak stimulated C-peptide of greater than 0·2 nmol L on a mixed meal tolerance test (MMTT) were enrolled from nine medical centres in the USA (n=8) and Australia (n=1). Participants were randomly assigned (2:1) to receive either 400 mg imatinib mesylate (4 × 100 mg film-coated tablets per day) or matching placebo for 26 weeks via a computer-generated blocked randomisation scheme stratified by centre. Treatment assignments were masked for all participants and study personnel except pharmacists at each clinical site. The primary endpoint was the difference in the area under the curve (AUC) mean for C-peptide response in the first 2 h of an MMTT at 12 months in the imatinib group versus the placebo group, with use of an ANCOVA model adjusting for sex, baseline age, and baseline C-peptide, with further observation up to 24 months. The primary analysis was by intention to treat (ITT). Safety was assessed in all randomly assigned participants. This study is registered with ClinicalTrials.gov, NCT01781975 (completed).

Findings: Patients were screened and enrolled between Feb 12, 2014, and May 19, 2016. 45 patients were assigned to receive imatinib and 22 to receive placebo. After withdrawals, 43 participants in the imatinib group and 21 in the placebo group were included in the primary ITT analysis at 12 months. The study met its primary endpoint: the adjusted mean difference in 2-h C-peptide AUC at 12 months for imatinib versus placebo treatment was 0·095 (90% CI -0·003 to 0·191; p=0·048, one-tailed test). This effect was not sustained out to 24 months. During the 24-month follow-up, 32 (71%) of 45 participants who received imatinib had a grade 2 severity or worse adverse event, compared with 13 (59%) of 22 participants who received placebo. The most common adverse events (grade 2 severity or worse) that differed between the groups were gastrointestinal issues (six [13%] participants in the imatinib group, primarily nausea, and none in the placebo group) and additional laboratory investigations (ten [22%] participants in the imatinib group and two [9%] in the placebo group). Per the trial protocol, 17 (38%) participants in the imatinib group required a temporary modification in drug dosing and six (13%) permanently discontinued imatinib due to adverse events; five (23%) participants in the placebo group had temporary modifications in dosing and none had a permanent discontinuation due to adverse events.

Interpretation: A 26-week course of imatinib preserved β-cell function at 12 months in adults with recent-onset type 1 diabetes. Imatinib might offer a novel means to alter the course of type 1 diabetes. Future considerations are defining ideal dose and duration of therapy, safety and efficacy in children, combination use with a complimentary drug, and ability of imatinib to delay or prevent progression to diabetes in an at-risk population; however, careful monitoring for possible toxicities is required.

Funding: Juvenile Research Diabetes Foundation.
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http://dx.doi.org/10.1016/S2213-8587(21)00139-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494464PMC
August 2021

Risk factors for progression of chronic kidney disease after robotic partial nephrectomy in elderly patients: results from a multi-institutional collaborative series.

Minerva Urol Nephrol 2021 Jun 22. Epub 2021 Jun 22.

Department of Urology, Regina Elena National Cancer Institute, Rome, Italy.

Background: Robotic partial nephrectomy (RPN) in patients ≥75 years is certainly underused with concerns regarding surgical quality and a negligible impact on renal function. The aim of this study was to identify predictors of progression of chronic kidney disease for purely off-clamp (ocRPN) and on-clamp RPN (onRPN) in elderly patients on a multi-institutional series.

Methods: A collaborative minimally-invasive renal surgery dataset was queried for "RPN" performed between July 2007 and March 2021 and "age≥75 years". A total of 205 patients matched the inclusion criteria. Descriptive analyses were used. Frequencies and proportions were reported for categorical variables while medians and interquartile ranges (IQR) were reported for continuous variables. Baseline, perioperative and functional data were compared between groups. New-onset of stages 3b,4,5 CKD in onRPN and ocRPN cohorts was computed by Kaplan-Meier analysis. Univariable and multivariable Cox regression analyses were performed to identify predictors of progression to severe CKD (sCKD [stages ≥3b]). For all statistical analyses, a two-sided p < 0.05 was considered significant.

Results: Mean age of the cohort considered was 78 years (IQR 76-80). At a median follow-up of 29 months (IQR 14.5-44.5), new onset CKD-3b and CKD-4,5 stages was observed in 16.6% and 2.4% of patients, respectively. At Kaplan-Meier analysis, onRPN was associated with a significantly higher risk of developing sCKD (p=0.002). On multivariable analysis, hypertension (HR 2.64; 95% CI 1.14-6.11; p=0.023), on-clamp approach (HR 3.41; 95% CI 1.50-7.74; p=0.003) non-achievement of trifecta (HR 0.36; 95% CI 0.17-0.78; p=0.01) were independent predictors of sCKD.

Conclusions: RPN in patients≥75 years is a safe surgical option. On-clamp approach, hypertension and non-achievement of trifecta were independent predictors of sCKD in the elderly after RPN.
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http://dx.doi.org/10.23736/S2724-6051.21.04469-4DOI Listing
June 2021

Robot-assisted partial nephrectomy with 3D preoperative surgical planning: video presentation of the florentine experience.

Int Braz J Urol 2021 Nov-Dec;47(6):1272-1273

Department of Experimental and Clinical Medicine, University of Florence - Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, Florence, Italy.

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http://dx.doi.org/10.1590/S1677-5538.IBJU.2020.1075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486435PMC
September 2021

Accuracy of Frozen Section Analysis of Urethral and Ureteral Margins During Radical Cystectomy for Bladder Cancer: A Systematic Review and Diagnostic Meta-Analysis.

Eur Urol Focus 2021 Jun 11. Epub 2021 Jun 11.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Context: The question of the ability of frozen section analysis (FSA) to accurately detect malignant pathology intraoperatively has been discussed for many decades.

Objective: We aimed to conduct a systematic review and meta-analysis assessing the diagnostic estimates of FSA of the urethral and ureteral margins in patients treated with radical cystectomy (RC) for bladder cancer (BCa).

Evidence Acquisition: The MEDLINE and EMBASE databases were searched in February 2021 for studies analyzing the association between FSA and the final urethral and ureteral margin status in patients treated with RC for BCa. The primary endpoint was the value of pathologic detection of urethral and ureteral malignant involvement with FSA during RC compared with the final margin status. We included studies that provided true positive, true negative, false positive, and false negative values for FSA, which allowed us to calculate the diagnostic estimates.

Evidence Synthesis: Fourteen studies, comprising 8208 patients, were included in the quantitative synthesis. Forest plots revealed that the pooled sensitivity and specificity for FSA of urethral margins during RC were 0.83 (95% confidence interval [CI] 0.38-0.97) and 0.95 (95% CI 0.91-0.97), respectively. While for the FSA of ureteral margins, the pooled sensitivity and specificity were 0.77 (95% CI 0.67-0.84) and 0.97 (95% CI 0.95-0.98), respectively. Calculated diagnostic odds ratios indicated high FSA effectiveness, and patients with a positive urethral or ureteral margin at final pathology are over 100 times more likely to have positive FSA than patients without margin involvement at final pathology. Area under the curves of 96.6% and 96.7% were reached for FSA detection of urethral and ureteral tumor involvement, respectively.

Conclusions: Intraoperative FSA demonstrated high diagnostic performance in detecting both urethral and ureteral malignant involvement at the time of RC for BCa. FSA of both urethral and ureteral margins during RC is accurate enough to be of great value in the routine management of BCa patients treated with RC. While its specificity was great to guide intraoperative decision-making, its sensitivity remains suboptimal yet.

Patient Summary: We believe that the frozen section analysis of both urethral and ureteral margins during radical cystectomy should be considered more often in urologic practice, until quality of life-based cost-effectiveness studies can identify patients within each institution who are unlikely to benefit from it.
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http://dx.doi.org/10.1016/j.euf.2021.05.010DOI Listing
June 2021

Is off-clamp robot-assisted partial nephrectomy beneficial for renal function? Data from the CLOCK trial.

BJU Int 2021 Jun 4. Epub 2021 Jun 4.

Urology Unit Careggi Hospital, University of Florence, Florence, Italy.

Objectives: To compare the functional outcomes of on- vs off-clamp robot-assisted partial nephrectomy (RAPN) within a randomized controlled trial (RCT).

Materials And Methods: The CLOCK study (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy; NCT02287987) is a multicentre RCT including patients with normal baseline function, two kidneys and masses with RENAL scores ≤ 10. Pre- and postoperative renal scintigraphy was prescribed. Renal defatting and hilum isolation were required in both study arms; in the on-clamp arm, ischaemia was imposed until the completion of medullary renorraphy, while in the off-clamp condition it was not allowed throughout the procedure. The primary endpoint was 6-month absolute variation in estimated glomerular filtration rate (AV-GFR); secondary endpoints were: 12, 18 and 24-month AV-GFR; 6-month estimated glomerular filtration rate variation >25% rate (RV-GFR >25); and absolute variation in ipsilateral split renal function (AV-SRF). The planned sample size was 102 + 102 cases, after taking account crossover of cases to the alternate study arm; a 1:1 randomization was performed. AV-GFR and AV-SRF were compared using analysis of covariation, and RV-GFR >25 was assessed using multivariable logistic regression. Intention-to-treat (ITT) and per-protocol analyses (PP) were performed.

Results: A total of 160 and 164 patients were randomly assigned to on- and off-clamp RAPN, respectively; crossover was observed in 14% and 43% of the on- and off-clamp arms, respectively. We were unable to find any statistically significant difference between on- vs off-clamp with regard to the primary endpoint (ITT: 6-month AV-GFR -6.2 vs -5.1 mL/min, mean difference 0.2 mL/min, 95% confidence interval [CI] -3.1 to 3.4 [P = 0.8]; PP: 6-month AV-GFR -6.8 vs -4.2 mL/min, mean difference 1.6 mL/min, 95% CI -2.3 to 5.5 [P = 0.7]) or with regard to the secondary endpoints. The median warm ischaemia time was 14 vs 15 min in the ITT analysis and 14 vs 0 min in the PP analysis.

Conclusion: In patients with regular baseline function and two kidneys, we found no evidence of differences in functional outcomes for on- vs off-clamp RAPN.
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http://dx.doi.org/10.1111/bju.15503DOI Listing
June 2021

Current application of the enhanced recovery after surgery protocol for patients undergoing radical cystectomy: lessons learned from European excellence centers.

World J Urol 2021 Jun 2. Epub 2021 Jun 2.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Purpose: There is no consensus on which items of Enhanced Recovery After Surgery (ERAS) should and should not be implemented in radical cystectomy (RC). The aim of this study is to report current practices across European high-volume RC centers involved in ERAS.

Methods: Based on the recommendations of the ERAS society, we developed a survey with 17 questions that were validated by the Young Academic Urologists-urothelial group. The survey was distributed to European expert centers that implement ERAS for RC. Only one answer per-center was allowed to keep a representative overview of the different centers.

Results: 70 surgeons fulfilled the eligibility criteria. Of note, 28.6% of surgeons do not work with a referent anesthesiologist and 25% have not yet assessed the implementation of ERAS in their center. Avoiding bowel preparation, thromboprophylaxis, and removal of the nasogastric tube were widely implemented (> 90%application). On the other hand, preoperative carbohydrate loading, opioid-sparing anesthesia, and audits were less likely to be applied. Common barriers to ERAS implementation were difficulty in changing habits (55%), followed by a lack of communication across surgeons and anesthesiologist (33%). Responders found that performing a regular audit (14%), opioid-sparing anesthesia (14%) and early mobilization (13%) were the most difficult items to implement.

Conclusion: In this survey, we identified the ERAS items most and less commonly applied. Collaboration with anesthesiologists as well as regular audits remain a challenge for ERAS implementation. These results support the need to uniform ERAS for RC patients and develop strategies to help departments implement ERAS.
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http://dx.doi.org/10.1007/s00345-021-03746-xDOI Listing
June 2021

Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis.

Front Oncol 2021 11;11:651745. Epub 2021 May 11.

Division of Urology of European Institute of Oncology (IEO), IRCCS, Milan, Italy.

Background: Three or four cycles of cisplatin-based chemotherapy is the standard neoadjuvant treatment prior to cystectomy in patients with muscle-invasive bladder cancer. Although NCCN guidelines recommend 4 cycles of cisplatin-gemcitabine, three cycles are also commonly administered in clinical practice. In this multicenter retrospective study, we assessed a large and homogenous cohort of patients with urothelial bladder cancer (UBC) treated with three or four cycles of neoadjuvant cisplatin-gemcitabine followed by radical cystectomy, in order to explore whether three vs. four cycles were associated with different outcomes.

Methods: Patients with histologically confirmed muscle-invasive UBC included in this retrospective study had to be treated with either 3 (cohort A) or 4 (cohort B) cycles of cisplatin-gemcitabine as neoadjuvant therapy before undergoing radical cystectomy with lymphadenectomy. Outcomes including pathologic downstaging to non-muscle invasive disease, pathologic complete response (defined as absence of disease -ypT0), overall- and cancer-specific- survival as well as time to recurrence were compared between cohorts A vs. B.

Results: A total of 219 patients treated at 14 different high-volume Institutions were included in this retrospective study. Patients who received 3 (cohort A) vs. 4 (cohort B) cycles of neoadjuvant cisplatin-gemcitabine were 160 (73,1%) vs. 59 (26,9%).At univariate analysis, the number of neoadjuvant cycles was not associated with either pathologic complete response, pathologic downstaging, time to recurrence, cancer specific, and overall survival. Of note, patients in cohort B vs. A showed a worse non-cancer specific overall survival at univariate analysis (HR= 2.53; 95 CI= 1.05 - 6.10; p=0.046), although this finding was not confirmed at multivariate analysis.

Conclusions: Our findings suggest that 3 cycles of cisplatin-gemcitabine may be equally effective, with less long-term toxicity, compared to 4 cycles in the neoadjuvant setting.
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http://dx.doi.org/10.3389/fonc.2021.651745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144638PMC
May 2021

Robot assisted radical cystectomy with Florence robotic intracorporeal neobladder (FloRIN): Analysis of survival and functional outcomes after first 100 consecutive patients upon accomplishment of phase 3 IDEAL framework.

Eur J Surg Oncol 2021 Oct 15;47(10):2651-2657. Epub 2021 May 15.

Department of Experimental and Clinical Medicine, University of Florence - Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, Florence, Italy.

Introduction: 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.

Materials And Methods: 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.

Results: 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%.

Conclusions: RARC with FloRIN reconfiguration showed worthy functional and survival outcomes, with learning curve improvement significantly influencing operative time and early complications rate across series.
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http://dx.doi.org/10.1016/j.ejso.2021.05.007DOI Listing
October 2021

Pretreatment Risk Stratification for Endoscopic Kidney-sparing Surgery in Upper Tract Urothelial Carcinoma: An International Collaborative Study.

Eur Urol 2021 Oct 20;80(4):507-515. Epub 2021 May 20.

Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background: Several groups have proposed features to identify low-risk patients who may benefit from endoscopic kidney-sparing surgery in upper tract urothelial carcinoma (UTUC).

Objective: To evaluate standard risk stratification features, develop an optimal model to identify ≥pT2/N+ stage at radical nephroureterectomy (RNU), and compare it with the existing unvalidated models.

Design, Setting, And Participants: This was a collaborative retrospective study that included 1214 patients who underwent ureterorenoscopy with biopsy followed by RNU for nonmetastatic UTUC between 2000 and 2017.

Outcome Measurements And Statistical Analysis: We performed multiple imputation of chained equations for missing data and multivariable logistic regression analysis with a stepwise selection algorithm to create the optimal predictive model. The area under the curve and a decision curve analysis were used to compare the models.

Results And Limitations: Overall, 659 (54.3%) and 555 (45.7%) patients had ≤pT1N0/Nx and ≥pT2/N+ disease, respectively. In the multivariable logistic regression analysis of our model, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.0-1.03, p = 0.013), high-grade biopsy (OR 1.81, 95% CI 1.37-2.40, p < 0.001), biopsy cT1+ staging (OR 3.23, 95% CI 1.93-5.41, p < 0.001), preoperative hydronephrosis (OR 1.37 95% CI 1.04-1.80, p = 0.024), tumor size (OR 1.09, 95% CI 1.01-1.17, p = 0.029), invasion on imaging (OR 5.10, 95% CI 3.32-7.81, p < 0.001), and sessile architecture (OR 2.31, 95% CI 1.58-3.36, p < 0.001) were significantly associated with ≥pT2/pN+ disease. Compared with the existing models, our model had the highest performance accuracy (75% vs 66-71%) and an additional clinical net reduction (four per 100 patients).

Conclusions: Our proposed risk-stratification model predicts the risk of harboring ≥pT2/N+ UTUC with reliable accuracy and a clinical net benefit outperforming the current risk-stratification models.

Patient Summary: We developed a risk stratification model to better identify patients for endoscopic kidney-sparing surgery in upper tract urothelial carcinoma.
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http://dx.doi.org/10.1016/j.eururo.2021.05.004DOI Listing
October 2021

Effects of Low-Carbohydrate versus Mediterranean Diets on Weight Loss, Glucose Metabolism, Insulin Kinetics and β-Cell Function in Morbidly Obese Individuals.

Nutrients 2021 Apr 18;13(4). Epub 2021 Apr 18.

Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.

Low-calorie Mediterranean-style or low-carbohydrate dietary regimens are widely used nutritional strategies against obesity and associated metabolic diseases, including type 2 diabetes. The aim of this study was to compare the effectiveness of a balanced Mediterranean diet with a low-carbohydrate diet on weight loss and glucose homeostasis in morbidly obese individuals at high risk to develop diabetes. Insulin secretion, insulin clearance, and different β-cell function components were estimated by modeling plasma glucose, insulin and C-peptide profiles during 75-g oral glucose tolerance tests (OGTTs) performed at baseline and after 4 weeks of each dietary intervention. The average weight loss was 5%, being 58% greater in the low-carbohydrate-group than Mediterranean-group. Fasting plasma glucose and glucose tolerance were not affected by the diets. The two dietary regimens proved similarly effective in improving insulin resistance and fasting hyperinsulinemia, while enhancing endogenous insulin clearance and β-cell glucose sensitivity. In summary, we demonstrated that a low-carbohydrate diet is a successful short-term approach for weight loss in morbidly obese patients and a feasible alternative to the Mediterranean diet for its glucometabolic benefits, including improvements in insulin resistance, insulin clearance and β-cell function. Further studies are needed to compare the long-term efficacy and safety of the two diets.
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http://dx.doi.org/10.3390/nu13041345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074206PMC
April 2021

Alfuzosin for the medical treatment of benign prostatic hyperplasia and lower urinary tract symptoms: a systematic review of the literature and narrative synthesis.

Ther Adv Urol 2021 Jan-Dec;13:1756287221993283. Epub 2021 Apr 12.

Division of Urology, Ospedale Sant'Andrea, Sapienza University of Rome, Rome, Italy.

Background: Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) are a bothersome frequent symptom in adult males. This systematic review analyzed the available evidence on the pharmacokinetic and pharmacodynamic features of alfuzosin, and its clinical efficacy both as monotherapy and in combination with other drugs for the treatment of male LUTS/BPH.

Methods: A systematic review of the last 10 years was performed using the MEDLINE, EMBASE and Cochrane libraries in March 2020. The protocol for this systematic review was registered on PROSPERO (Central Registration Depository: CRD42020136120) and is available in full on the University of York website.

Results: Alfuzosin is a quinazoline derivative and, although a nonspecific α1-blocker, exhibits a selective concentration in the prostate compared with plasma in patients with BPH. Three registration trials assessed the safety and efficacy of alfuzosin. The 10 mg daily formulation has a three-layered matrix containing the active substance between two inactive coats allowing a drug release over 20 h. Alfuzosin showed high tolerability, few vasodilatory effects and a low rate of ejaculation disorders over older alpha-blocking compounds thanks to the high uroselectivity of alfuzosin and its preferential concentration at urinary level. Six randomized clinical trials (RCTs) assessed efficacy and safety of alfuzosin other alpha-blockers ± placebo: three studies comparing with tamsulosin, one with doxazosin, and two with silodosin or tamsulosin. One RCT investigated the clinical outcomes of alfuzosin with finasteride, two with propiverine and two with phosphodiesterase-5 inhibitors.

Conclusions: Alfuzosin is an effective drug for the treatment of LUTS/BPH, with a lower rate of sexual disorders compared with other alpha-blockers. Alfuzosin is also safe with low adverse events in case of concomitant antihypertensive therapy and in patients with cardiovascular morbidity. Safety and efficacy of alfuzosin has been reported also in case of combination therapy with antimuscarinic agents and PDE5i.
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http://dx.doi.org/10.1177/1756287221993283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047826PMC
April 2021

Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional β cells in predicting diabetes.

J Clin Invest 2021 06;131(12)

UOS Centro Malattie Endocrine e Metaboliche, UOC Endocrinologia e Diabetologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

BACKGROUNDThe appearance of hyperglycemia is due to insulin resistance, functional deficits in the secretion of insulin, and a reduction of β cell mass. There is a long-standing debate as to the relative contribution of these factors to clinically manifesting β cell dysfunction. The aim of this study was to verify the acute effect of one of these factors, the reduction of β cell mass, on the subsequent development of hyperglycemia.METHODSTo pursue this aim, nondiabetic patients, scheduled for identical pancreaticoduodenectomy surgery, underwent oral glucose tolerance tests (OGTT) and hyperglycemic clamp (HC) procedures, followed by arginine stimulation before and after surgery. Based on postsurgery OGTT, subjects were divided into 3 groups depending on glucose tolerance: normal glucose tolerance (post-NGT), impaired glucose tolerance (post-IGT), or having diabetes mellitus (post-DM).RESULTSAt baseline, the 3 groups showed similar fasting glucose and insulin levels; however, examining the various parameters, we found that reduced first-phase insulin secretion, reduced glucose sensitivity, and rate sensitivity were predictors of eventual postsurgery development of IGT and diabetes.CONCLUSIONDespite comparable functional mass and fasting glucose and insulin levels at baseline and the very same 50% mass reduction, only reduced first-phase insulin secretion and glucose sensitivity predicted the appearance of hyperglycemia. These functional alterations could be pivotal to the pathogenesis of type 2 diabetes (T2DM).TRIAL REGISTRATIONClinicalTrials.gov NCT02175459.FUNDINGUniversità Cattolica del Sacro Cuore; Italian Ministry of Education, University and Research; European Foundation for the Study of Diabetes.
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http://dx.doi.org/10.1172/JCI146788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203447PMC
June 2021

Intraoperative and postoperative surgical complications after ureteroscopy, retrograde intrarenal surgery, and percutaneous nephrolithotomy: a systematic review.

Minerva Urol Nephrol 2021 Jun 22;73(3):309-332. Epub 2021 Apr 22.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Introduction: Retrograde ureteroscopy (URS), intra-renal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) represent routine interventions for the treatment of ureteral and renal stones, although at times associated with serious adverse events. Of note, the evidence on perioperative complications after these procedures remains sparse and controversial. Moreover, there is a lack of standardized reporting of adverse events using uniform systems. The aim of the present study was to systematically review of the available evidence on URS/RIRS and PCNL for the surgical treatment of urinary stone, assessing the incidence of intra- and postoperative events, classified according to the modified Clavien-Dindo scale.

Evidence Acquisition: A systematic review of the literature was performed according to PRISMA recommendations and was conducted on intra- and postoperative complications, as well as on their management, following URS, RIRS and PCNL procedures, particularly focusing on major events.

Evidence Synthesis: Overall, 26 studies (13 on URS/RIRS and 11 on PCNL) met the inclusion criteria and were evaluated. The highest intraoperative complication rate was 11.5% and 8.5% for RIRS and PCNL, respectively. Major complication rate following URS/RIRS and PCNL ranged between 0.3-31.7% and 2-17.1%, respectively. The most frequent adverse events were obstructive pyelonephritis or urinary leakage requiring the placement of a double J stent or a drainage. Among PCNLs series, life-threatening adverse events have also been reported, including bleeding requiring renal angioembolization and urothorax.

Conclusions: Despite the inclusion of series using a standardized reporting system, the complication rate after URS/RIRS/PCNL remains extensively heterogeneous in the literature; in addition, a non-negligible proportion of studies did not characterize the adverse events nor report the actual management strategy to solve them. Future research is needed to standardize the classification and reporting of surgical complications after endourological procedures (taking into consideration the surgeon's experience and skills), aiming to improve patient counseling and potentially the strategy for their prevention.
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http://dx.doi.org/10.23736/S2724-6051.21.04294-4DOI Listing
June 2021

Risk Factors for Intravesical Recurrence after Minimally Invasive Nephroureterectomy for Upper Tract Urothelial Cancer (ROBUUST Collaboration).

J Urol 2021 Sep 21;206(3):568-576. Epub 2021 Apr 21.

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York.

Purpose: 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.

Materials And Methods: 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.

Results: 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).

Conclusions: 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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http://dx.doi.org/10.1097/JU.0000000000001786DOI Listing
September 2021

Novel Classification for Upper Tract Urothelial Carcinoma to Better Risk-stratify Patients Eligible for Kidney-sparing Strategies: An International Collaborative Study.

Eur Urol Focus 2021 Mar 24. Epub 2021 Mar 24.

Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background: The European Association of Urology risk stratification dichotomizes patients with upper tract urothelial carcinoma (UTUC) into two risk categories.

Objective: To evaluate the predictive value of a new classification to better risk stratify patients eligible for kidney-sparing surgery (KSS).

Design, Setting, And Participants: This was a retrospective study including 1214 patients from 21 centers who underwent ureterorenoscopy (URS) with biopsy followed by radical nephroureterectomy (RNU) for nonmetastatic UTUC between 2000 and 2017.

Outcome Measurements And Statistical Analysis: A multivariate logistic regression analysis identified predictors of muscle invasion (≥pT2) at RNU. The Youden index was used to identify cutoff points.

Results And Limitations: A total of 811 patients (67%) were male and the median age was 71 yr (interquartile range 63-77). The presence of non-organ-confined disease on preoperative imaging (p < 0.0001), sessile tumor (p < 0.0001), hydronephrosis (p = 0.0003), high-grade cytology (p = 0.0043), or biopsy (p = 0.0174) and higher age at diagnosis (p = 0.029) were independently associated with ≥pT2 at RNU. Tumor size was significantly associated with ≥pT2 disease only in univariate analysis with a cutoff of 2 cm. Tumor size and all significant categorical variables defined the high-risk category. Tumor multifocality and a history of radical cystectomy help to dichotomize between low-risk and intermediate-risk categories. The odds ratio for muscle invasion were 5.5 (95% confidence interval [CI] 1.3-24.0; p = 0.023) for intermediate risk versus low risk, and 12.7 (95% CI 3.0-54.5; p = 0.0006) for high risk versus low risk. Limitations include the retrospective design and selection bias (all patients underwent RNU).

Conclusions: Patients with low-risk UTUC represent ideal candidates for KSS, while some patients with intermediate-risk UTUC may also be considered. This classification needs further prospective validation and may help stratification in clinical trial design.

Patient Summary: We investigated factors predicting stage 2 or greater cancer of the upper urinary tract at the time of surgery for ureter and kidney removal and designed a new risk stratification. Patients with low or intermediate risk may be eligible for kidney-sparing surgery with close follow-up. Our classification scheme needs further validation based on cancer outcomes.
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http://dx.doi.org/10.1016/j.euf.2021.03.018DOI Listing
March 2021
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