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Purpose: Personalized treatment schemes are being systematically applied to ensure best treatment outcome in oncologic patients. This is true also for personalized dosimetry in transarterial radioembolization (TARE) in hepatocellular carcinoma (HCC) patients. Precise and detailed volumetric and functional data derived from radiological and nuclear imaging methods are essential for personalized dosimetry. We sought to evaluate accuracy of dual-phase cone-beam CT (CBCT) in comparison to pre-treatment contrast-enhanced CT (CECT), and 99m Tc-macroaggregated albumin-SPECT/CT ([ 99m Tc]MAA SPECT/CT) to predict and assess the efficacy of TARE based on post-treatment 90 Y PET/CT., Material and Methods: Thirty consecutive patients with HCC treated with TARE were included. Intraprocedural dual-phase CBCT acquisition protocol was developed to distinguish tumor volume in the early arterial phase and perfused volume of non-affected liver in the late arterial phase. Volumetric data obtained from pre-treatment CECT, dual-phase CBCT and [ 99 m Tc]MAA SPECT/CT were compared to post-treatment 90 Y PET/CT considered the standard reference. Treatment simulations for final calculated dose from the different imaging derived volumes were then compared to post-treatment 90 Y PET/CT., Results: CBCT resulted as the most accurate method in predicting tumor- (R 2 0.88) and perfused volumes (R 2 0.82). Dosimetry prediction planning performed on derived volumes from the different methods did not show significant difference (p < 0.05), yet highest concordance with 90 Y PET/CT data was observed with dual-phase CBCT., Conclusion: Our study shows that dual-phase CBCT acquisition is a novel alternative method for correctly and safely administering more accurate and defined doses during TARE., Clinicaltrials: gov ID: NCT03981497., Competing Interests: Declarations. Conflict of interests: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments (EC approval 64/INT/2021). Consent to participate: Informed consent was obtained from all individual participants included in the study as described by Institutional Ethic Committee approval (64/INT/2021). Consent to publish: Consent for publication was obtained for every individual person’s data included in the study., (© 2024. The Author(s).)

Purpose: To evaluate the activity and safety of nivolumab with nab-paclitaxel as neoadjuvant therapy, followed by radical cystectomy (RC) and postsurgical adjuvant nivolumab in patients with muscle-invasive bladder cancer (MIBC)., Patients and Methods: Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤1 and a T2-4aN0-1M0 stage with >50% urothelial carcinoma histology and were ineligible for or refused cisplatin-based chemotherapy. Patients received four cycles of nivolumab 360 mg once every 3 weeks + nab-paclitaxel 125 mg/m 2 once on days 1 and 8, every 3 weeks, followed by RC, and then adjuvant nivolumab 360 mg once every 3 weeks × 13 cycles. The primary end point was the pathologic complete response (CR) rate (ypT0N0). Secondary end points were major pathologic response (ypT≤1N0), safety, event-free survival (EFS), and overall survival., Results: Thirty-one patients were enrolled from December 2021 to June 2023; 19 (61.3%) had a cT2 stage, two (6.5%) had N1 stage, and 16 (51.6%) had a variant histology. Five patients (16.1%) received less than four full courses of neoadjuvant treatment because of treatment-related adverse events (TRAEs). Grade 3/4 TRAEs occurred in eight patients (25.8%). Twenty-eight patients underwent RC, and three refused RC after evidence of clinical CR and received a redo transurethral resection of the bladder tumor (reTURBT). The trial met its primary end point: 10 patients (32.3%; 95% CI, 16.7 to 51.4) achieved an ypT0N0 response. By including those who underwent reTURBT, 22 (70.9%; 95% CI, 55 to 87) achieved an ypT≤1N0-x response. After a median follow-up of 12 months (range, 5-22), two patients had a disease relapse after surgery. The 12-month EFS was 89.8% (95% CI, 79.5 to 100)., Conclusion: To our knowledge, the first results from NURE-Combo trial suggest that this combination could expand the therapeutic opportunities of immune-chemotherapy in patients with MIBC.

Background : PSMA PET radiomics is a promising tool for primary prostate cancer (PCa) characterisation. However, small single-centre studies and lack of external validation hinder definitive conclusions on the potential of PSMA PET radiomics in the initial workup of PCa. We aimed to validate a radiomics signature in a larger internal cohort and in an external cohort from a separate centre. Methods : One hundred and twenty-seven PCa patients were retrospectively enrolled across two independent hospitals. The first centre (IRCCS San Raffaele Scientific Institute, Centre 1) contributed 62 [ 68 Ga]Ga-PSMA-11 PET scans, 20 patients classified as low-grade (ISUP grade < 4), and 42 as high-grade (ISUP grade ≥ 4). The second centre (Stanford University Hospital, Centre 2) provided 65 [ 68 Ga]Ga-PSMA-11 PET scans, and 49 low-grade and 16 high-grade patients. A radiomics model previously generated in Centre 1 was tested on the two cohorts separately and afterward on the entire dataset. Then, we evaluated whether the radiomics features selected in the previous investigation could generalise to new data. Several machine learning (ML) models underwent training and testing using 100-fold Monte Carlo cross-validation, independently at both Centre 1 and Centre 2, with a 70-30% train-test split. Additionally, models were trained in one centre and tested in the other, and vice versa. Furthermore, data from both centres were combined for training and testing using Monte Carlo cross-validation. Finally, a new radiomics signature built on this bicentric dataset was proposed. Several performance metrics were computed. Results: The previously generated radiomics signature resulted in an area under the receiver operating characteristic curve (AUC) of 80.4% when tested on Centre 1, while it generalised poorly to Centre 2, where it reached an AUC of 62.7%. When the whole cohort was considered, AUC was 72.5%. Similarly, new ML models trained on the previously selected features yielded, at best, an AUC of 80.9% for Centre 1 and performed at chance for Centre 2 (AUC of 49.3%). A new signature built on this bicentric dataset reached, at best, an average AUC of 91.4% in the test set. Conclusions: The satisfying performance of radiomics models when used in the original development settings, paired with the poor performance otherwise observed, emphasises the need to consider centre-specific factors and dataset characteristics when developing radiomics models. Combining radiomics datasets is a viable strategy to reduce such centre-specific biases, but external validation is still needed.

Introduction: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a retrospective analysis of its first-line treatment outcomes., Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with cisplatin, gemcitabine plus durvalumab. The primary endpoint was overall survival (OS)., Results: 33 patients were enrolled. Median OS was NR and median PFS was 7.6 months, after a median follow up of 13.5 months. The investigator-assessed overall response rate was 34.5 %, with stable disease in 53.0 % of patients. High baseline CEA levels were associated with poor survival. Any grade adverse events (AEs) occurred in 97 % of patients. Immune-related AEs (irAEs) occurred in 16 % (grade >2: 6 %). Presence of TP53 mutation was related to a worse OS, conversely the presence of ARID1A genomic alteration was related to a better PFS. A tendence toward a better OS was found for BRCAness patients which did not reach the statistical significance. On the other hand, BRCAness patients showed significantly higher PFS compared to no BRCAness patients Conclusion: This real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC., (S. Karger AG, Basel.)

Background An accurate method of assessing the response of muscle-invasive bladder cancer (MIBC) to neoadjuvant treatment is needed for selecting candidates for bladder-sparing strategies. Purpose To evaluate the diagnostic accuracy and reproducibility of neoadjuvant chemotherapy Vesical Imaging Reporting and Data System (nacVI-RADS) scores and posttreatment Vesical Imaging Reporting and Data System (VI-RADS) scores when assessing MIBC response to neoadjuvant immunotherapy with multiparametric MRI (mpMRI). Materials and Methods A retrospective analysis of MRI scans was conducted in patients enrolled in the PURE-01 study (NCT02736266) from February 2017 to December 2019 who underwent pre- and postimmunotherapy mpMRI before radical cystectomy. Five readers independently reviewed the scans using VI-RADS and nacVI-RADS criteria. Diagnostic accuracy was evaluated for each reader, and the final histopathologic diagnosis served as the reference standard. Interreader agreement was assessed with the percentage of agreement, Conger κ, and Gwet agreement coefficient AC1. Results A total of 110 patients (median age, 67 years [IQR: 61-74]; 96 male) with 220 MRI scans were included; 80 (73%) patients had pure urothelial carcinoma. A total of 46 of 110 (42%) patients achieved a complete pathologic response. The sensitivity, specificity, and negative predictive value of nacVI-RADS 3 or higher for detecting residual disease (higher than stage ypT0) at radical cystectomy were 67%-84%, 63%-96%, and 63%-75%, respectively; for residual muscle-invasive disease (higher than stage ypT1), these values were 91%-98%, 55%-94%, and 93%-98%, respectively. The accuracy of nacVI-RADS was 72%-81% for stage ypT0 or higher disease and 71%-95% for stage ypT1 or higher disease. The accuracy of VI-RADS 3 or higher was 80%-95% for stage ypT1 or higher disease. The percentage of agreement for nacVI-RADS scores was 82% (κ = 0.62-0.65; AC1 = 0.65). Conclusion The nacVI-RADS scores showed good accuracy and reproducibility when assessing MIBC response to neoadjuvant immunotherapy. © RSNA, 2024 Supplemental material is available for this article.

Aims: To investigate possible associations of glucose patterns with outcomes of Corona Virus Disease 19 (COVID-19) using continuous glucose monitoring (CGM) in 43 patients hospitalized for COVID-19 mild-to-moderate pneumonia, regardless of diabetes., Methods: Prospective observational study conducted during two pandemic waves in 2020-2021. Glucose sensor metrics of 7-day recording were obtained from blinded CGM. Respiratory function was evaluated as arterial partial pressure of oxygen (PaO 2 ) to fraction of inspired oxygen (FiO 2 ) ratio (PaO 2 :FiO 2 )., Results: PaO 2 :FiO 2 ratio was positively correlated with time in tight range (TITR) 70-140 (r = 0.49, p < 0.001) and time in range (TIR) 70-180 (r = 0.32, p < 0.05), and negatively correlated with average glucose (r =- 0.31, p < 0.05), coefficient of glucose variation (CV) (r =- 0.47, p < 0.01) and time above range (TAR) > 140 (r =- 0.49, p < 0.001). No relations were observed with HbA1c. Multivariate regression analysis showed that normal respiratory function at time of CGM removal correlated positively with TITR 70-140 mg/dL (p < 0.01), negatively with CV and TAR > 140 mg/dL (both p < 0.05) and not with TIR 70-180 and average glucose., Conclusions: Lower glucose variability and optimal glucose control, expressed as CV and TITR, are CGM metrics predictive of a better prognosis in COVID-19 patients with pneumonia., Competing Interests: Declarations. Conflict of interest: EB declares non financial support from Medtronic. The other authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical approval: The study was performed in accordance with the declaration in agreement with the Helsinki Declaration and was approved by the Ethical Committee of San Raffaele University, Milan (protocol No. 34/int/2020 and specific approval for glucose sensor use (protocol No. 66/int/2020). Informed consent: All participants provided written informed consent. Human and animal rights section: The study was conducted under the Human Rights Act 1998 and within a study protocol approved by the Ethics Committee of the San Raffaele Hospital and signed an informed consent. No animals were involved in the study. under the European Convention on Human Rights, (© 2024. The Author(s).)

Objective: Renal Tumor biopsy (RTB) can assist clinicians in determining the most suitable approach for treatment of renal cancer. However, RTB's limitations in accurately determining histology and grading have hindered its broader adoption and data on the concordance rate between RTB results and final pathology after surgery are unavailable. Therefore, we aimed to develop a machine learning algorithm to optimize RTB technique and to investigate the degree of concordance between RTB and surgical pathology reports., Materials and Methods: Within a prospectively maintained database, patients with indeterminate renal masses who underwent RTB at a single tertiary center were identified. We recorded and analyzed the approach (US vs. CT), the number of biopsy cores (NoC), and total core tissue length (LoC) to evaluate their impact on diagnostic outcomes. The K-Nearest Neighbors (KNN), a non-parametric supervised machine learning model, predicted the probability of obtaining pathological characterization and grading. In surgical patients, final pathology reports were compared with RTB results., Results: Overall, 197 patients underwent RTB. Overall, 89.8% (n=177) and 44.7% (n=88) of biopsies were informative in terms of histology and grading, respectively. The discrepancy rate between the pathology results from renal tissue biopsy (RTB) and the final pathology report following surgery was 3.6% (n=7) for histology and 5.0% (n=10) for grading. According to the machine learning model, a minimum of 2 cores providing at least 0.8 cm of total tissue should be obtained to achieve the best accuracy in characterizing the cancer. Alternatively, in cases of RTB with more than two cores, no specific minimum tissue threshold is required., Conclusions: The discordance rates between RTB pathology and final surgical pathology are notably minimal. We defined an optimal renal biopsy strategy based on at least 2 cores and at least 0.8 cm of tissue or at least 3 cores and no minimum tissue threshold., Patients Summary: RTB is a useful test for kidney cancer, but it's not always perfect. Our study shows that it usually matches up well with what doctors find during surgery. Using machine learning can make RTB even better by helping doctors know how many samples to take. This helps doctors treat kidney cancer more accurately., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The aim of the present study is to assess the effectiveness of indocyanine-green (ICG)-guided lymphography (ICG-Lg) in reducing the incidence of chyle leak (CL) after esophagectomy., Background: Chylothorax may severely impact esophageal cancer surgery, and the pre-emptive ligation of the thoracic duct (TD) is the most widespread control of this complication. Intraoperative ICG-Lg has been recently embedded in minimally invasive esophagectomy to facilitate TD detection and pre-emptive ligation., Methods: This retrospective analysis included consecutive patients who underwent minimally invasive Ivor Lewis esophagectomy for cancer at a tertiary referral center between January 2018 and August 2023. Patients were routinely submitted to extended lymphadenectomy with TD ligation and removal. All patients treated after January 2021 underwent ICG-Lg for TD identification and ligation (ICG group) and compared with the previous series (no-ICG group). The primary outcome was the incidence of postoperative CL, while univariate and backward stepwise multivariate logistic regression models were performed to identify associated factors., Results: After including 320 patients, 151 (ICG group) were submitted to ICG-Lg before the pre-emptive TD ligation. Both groups presented similar characteristics, except for neoadjuvant therapy ( P <0.001) and preoperative comorbidities ( P =0.045). Intraoperative ICG-Lg significantly reduced the incidence of postoperative CL (11.8% vs 4.6%, P =0.026) and was significantly associated with shorter median length of hospital stay (13 vs 9 d, P =0.006). However, CL after ICG-Lg was more likely to require repairing reoperation ( P =0.050)., Conclusions: Intraoperative ICG-Lg demonstrated significantly lower rates of CL after total minimally invasive esophagectomy and, therefore, it should be routinely embedded in the standardized surgical technique of high-volume centers for esophageal cancer., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: In recent years, significant progress has been made in treatment strategies for intermediate-stage hepatocellular carcinoma (HCC), which is a highly heterogeneous patient population requiring tailored therapies based on tumor characteristics., Methods: We conducted a comprehensive review of treatment approaches for intermediate-stage HCC, highlighting the evolution of treatment options over time. While chemoembolization remains the standard therapy for many patients, it has advanced to include combinations with systemic therapies, known as combination therapy, which is becoming the new standard of care for this group., Conclusion: Based on our clinical and research experience, combination therapy is increasingly recognized as the preferred first-line treatment for intermediate-stage HCC patients. This approach allows most patients to be candidates for subsequent curative-intent treatments, while a smaller number will require palliative care.

Introduction: Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown., Materials & Methods: Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([ 99m Tc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed., Results: Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients., Conclusions: PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios., (© 2024. The Author(s).)

Background: Pancreatogenic diabetes, a consequence of pancreatic tissue loss following pancreatectomy, poses a significant challenge for patients undergoing pancreatic surgery. Islet autotransplantation (IAT) offers a promising approach to prevent or alleviate pancreatogenic diabetes, but its application has been limited to individuals with painful chronic pancreatitis., Methods: This study presents a 15-y clinical experience with the Milan Protocol, which expands IAT after pancreatectomy to a broader spectrum of patients with malignant and nonmalignant pancreatic diseases. The analysis evaluates feasibility, efficacy, and safety of IAT. Modified Igls criteria validated through the arginine test and mixed meal tolerance tests were used to assess long-term metabolic outcomes., Results: Between November 2008 and June 2023, IAT procedures were performed on 114 of 147 candidates. IAT-related complications occurred in 19 of 114 patients (16.7%), with 5 being potentially serious. Patients exhibited sustained C-peptide secretion over the 10-y follow-up period, demonstrating a prevalence of optimal and good beta-cell function. Individuals who underwent partial pancreatectomy demonstrated superior metabolic outcomes, including sustained C-peptide secretion and a reduced risk of developing diabetes or insulin dependence compared with those who underwent total pancreatectomy. For patients who had total pancreatectomy, the quantity of infused islets and tissue volume were identified as critical factors influencing metabolic outcomes. An increased risk of recurrence or progression of baseline diseases was not observed in subjects with neoplasms., Conclusions: These findings provide valuable insights into the benefits and applications of IAT as a therapeutic option for pancreatogenic diabetes after pancreatic surgery, expanding its potential beyond painful chronic pancreatitis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: In absence of predictive models, preoperative estimation of the probability of completing partial (PN) relative to radical nephrectomy (RN) is invariably inaccurate and subjective. We aimed to develop an evidence-based model to assess objectively the probability of PN completion based on patients' characteristics, tumor's complexity, urologist expertise and surgical approach., Design, Setting and Participants: 675 patients treated with PN or RN for cT 1-2 cN 0 cM 0 renal mass by seven surgeons at one single experienced centre from 2000 to 2019., Outcomes Measurements and Statistical Analyses: The outcome of the study was PN completion. We used a multivariable logistic regression (MVA) model to investigate predictors of PN completion. We used SPARE score to assess tumor complexity. We used a bootstrap validation to compute the model's predictive accuracy. We investigated the relationship between the outcomes and specific predictors of interest such as tumor's complexity, approach and experience., Results: Of 675 patients, 360 (53%) were treated with PN vs. 315 (47%) with RN. Smaller tumors [Odds ratio (OR): 0.52, 95%CI 0.44-0.61; P < 0.001], lower SPARE score (OR: 0.67, 95%CI 0.47-0.94; P = 0.02), more experienced surgeons (OR: 1.01, 95%CI 1.00-1.02; P < 0.01), robotic (OR: 10; P < 0.001) and open (OR: 36; P < 0.001) compared to laparoscopic approach resulted associated with higher probability of PN completion. Predictive accuracy of the model was 0.94 (95% CI 0.93-0.95)., Conclusions: The probability of PN completion can be preoperatively assessed, with optimal accuracy relaying on routinely available clinical information. The proposed model might be useful in preoperative decision-making, patient consensus, or during preoperative counselling., Patient Summary: In patients with a renal mass the probability of completing a partial nephrectomy varies considerably and without a predictive model is invariably inaccurate and subjective. In this study we build-up a risk calculator based on easily available preoperative variables that can predict with optimal accuracy the probability of not removing the entire kidney., Competing Interests: Declaration of competing interest A. Necchi reports honoraria from Roche, Merck Sharp & Dohme, AstraZeneca, Janssen Pharmaceuticals and Foundation Medicine; has served as a consultant or advisor for Merck Sharp & Dohme, Bristol-Myers Squibb, Rainier Therapeutics, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen Pharmaceuticals, Incyte, Seattle Genetics, Astellas Pharma and Rainier Therapeutics; has received research funding from Incyte, Merck Sharp & Dohme (institution), and AstraZeneca (institution); and has received travel funding from Roche, Merck Sharp & Dohme, Astra Zeneca, and Janssen Pharmaceuticals outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Whether the observed lower total testosterone (tT) levels in male patients with COVID-19 are caused by a direct impact of SARS-CoV-2 infection or are collateral phenomena shared by other systemic inflammatory conditions has not yet been clarified., Objectives: To investigate the independent role of COVID-19 in reducing circulating tT levels in men., Materials and Methods: We compared demographic, clinical, and hormonal values of patients with laboratory confirmed COVID-19 admitted during the first wave of the pandemic with a cohort of consecutive male patients admitted to the intensive care unit (ICU) of the same academic center because of severe acute respiratory distress syndrome (ARDS) but without SARS-CoV-2 infection and no previous history of COVID-19. Linear regression model tested the independent impact of COVID-19 on circulating tT levels. Logistic regression model was used to test predictors of death in the entire cohort., Results: Of 286 patients with COVID-19, 70 men had been admitted to the ICU ( = cases) and were compared to 79 patients equally admitted to ICU because of severe ARDS but negative for SARS-CoV-2 infection and without previous history of COVID-19 ( = controls). Controls were further grouped into noninfective (n = 49) and infective-ARDS (n = 30) patients. At baseline, controls were older (p = 0.01) and had more comorbidities (p < 0.0001). Overall, cases admitted to ICU had significantly lower circulating tT levels compared to controls (0.9 nmol/L vs. 2.1 nmol/L; vs. 1.2 nmol/L; p = 0.03). At linear regression, being negative for COVID-19 was associated with higher tT levels (Coeff: 2.13; 95% confidence interval - CI 0.71-3.56; p = 0.004) after adjusting for age, BMI, comorbidities and IL-6 levels. Only age and IL-6 levels emerged to be associated with higher risk of death regardless of COVID-19 status., Conclusions: This case-control ex post facto study showed lower tT levels in men with COVID-19 compared to those without COVID-19 despite both groups have been equally admitted to ICU for severe ARDS, thus suggesting a possible direct impact of SARS-CoV-2 infection toward circulating tT levels and a consequent more severe clinical outcome., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: A significant proportion of patients with positive multiparametric magnetic resonance imaging (mpMRI; Prostate Imaging-Reporting and Data System [PI-RADS] scores of 3-5) have negative biopsy results., Objective: To systematically assess all prostate-specific antigen density (PSAD) values and identify an appropriate cutoff for identification of patients with positive mpMRI who could potentially avoid biopsy on the basis of their PI-RADS score., Design, Setting, and Participants: The study included a cohort of 1341 patients with positive mpMRI who underwent combined targeted and systematic biopsies., Outcome Measurements and Statistical Analysis: Multivariable logistic regression analysis (MVA) was used to assess the association between PSAD and the risk of clinically significant prostate cancer (csPCa, grade group ≥2) after adjusting for confounders. We used locally weighted scatterplot smoothing to explore csPCa risk according to PSAD and PI-RADS scores. PSAD utility was observed only for patients with PI-RADS 3 lesions, so we plotted the effect of each PSAD value as a cutoff for this subgroup in terms of biopsies saved, csPCa cases missed, and clinically insignificant PCa (ciPCa, grade group 1) cases not detected., Results and Limitations: Overall, 667 (50%) csPCa cases were identified. On MVA, PSAD independently predicted csPCa (odds ratio 1.57; p < 0.001). For PI-RADS ≥4 lesions, the csPCa risk was ≥40% regardless of PSAD. Conversely, among patients with PI-RADS 3 lesions, csPCa risk ranged from 0% to 60% according to PSAD values, and a PSAD cutoff of 0.10 ng/ml/cm 3 corresponded to a threshold probability of 10% for csPCa. Using this PSAD cutoff for patients with PI-RADS 3 lesions would have saved 32% of biopsies, missed 7% of csPCa cases, and avoided detection of 34% of ciPCa cases. Limitations include selection bias and the high experience of the radiologists and urologists involved., Conclusions: Patients with PI-RADS ≥4 lesions should undergo prostate biopsy regardless of their PSAD, while PSAD should be used to stratify patients with PI-RADS 3 lesions. Using a threshold probability of 10% for csPCa, our data suggest that the appropriate strategy is to avoid biopsy in patients with PI-RADS 3 lesions and PSAD <0.10 ng/ml/cm 3 . Our results also provide information to help in tailoring an appropriate strategy for every patient with positive mpMRI findings., Patient Summary: We investigated whether a cutoff value for PSAD (prostate-specific antigen density) could identify patients with suspicious prostate lesions on MRI (magnetic resonance imaging) who could avoid biopsy according to the PI-RADS score for their scan. We found that patients with PI-RADS ≥4 should undergo prostate biopsy regardless of their PSAD. A PSAD cutoff of 0.10 should be used to stratify patients with PI-RADS 3., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Hepatic resection combined with intraoperative ablation has been described as a technical solution potentially widening the resectability rate of patients with colorectal liver metastases (CRLM). Nevertheless, the perioperative and oncological benefit provided by this combined approach remains unclear. We hypothesized that textbook outcome (TO), which is a composite measure achieved for patients for whom some desired health indicators are met, may help to refine the indications of this approach., Methods: Patients submitted to hepatectomy with curative intent in combination with radiofrequency ablation or microwave ablation for CRLM ≤ 3 cm in two tertiary referral centers were included. TO was defined according to a recent definition for liver surgery based on a Delphi process including also the achievement of complete radiological response of the ablated lesion/s at 4 weeks., Results: Between 2015 and 2022, 112 patients were enrolled. Among them, 63 (56.2%) achieved a TO. According to multivariate analysis, minimally invasive (MI) approach (OR 2.72, 95% CI 0.99-7.48, p = 0.050), simultaneous CR resection (OR 0.28, 95% CI 0.11-0.70, p = 0.007), tumor burden score (OR 0.89, 95% CI 0.82-0.96, p = 0.004), and major hepatectomy (OR 0.12, 95% CI 0.03-0.52, p = 0.004) were significantly associated with the achievement of TO. Median overall survival was longer in those patients who were able to achieve a TO compared to those who did not., Conclusions: The combination of hepatectomy and ablation constitutes a valuable solution in patients affected by multiple CRLM and it may provide, also using a MI approach, adequate perioperative and oncological outcomes, allowing to achieve TO, however, in a selected number of patients and depending on several factors including the burden of disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: It remains unclear whether preoperative body composition may affect the prognosis of pancreatic cancer patients undergoing surgery. The aim of the present study was to assess the extent to which preoperative body composition impacts on postoperative complication severity and survival in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC)., Methods: A retrospective cohort study was performed on consecutive patients who underwent pancreatoduodenectomy with preoperative CT scan imaging available. Body composition parameters including total abdominal muscle area (TAMA), visceral fat area (VFA), subcutaneous fat area and liver steatosis (LS) were assessed. Sarcopenic obesity was defined as a high VFA/TAMA ratio. Postoperative complication burden was evaluated with the comprehensive complication index (CCI)., Results: Overall, 371 patients were included in the study. At 90 days after surgery, 80 patients (22%) experienced severe complications. The median CCI was 20.9 (IQR 0-30). At multivariate linear regression analysis, preoperative biliary drainage, ASA score ≥3, fistula risk score and sarcopenic obesity (37% increase; 95%CI 0.06-0.74; p = 0.046) were associated to an increase in CCI. Patient characteristics associated to sarcopenic obesity were older age, male gender and preoperative LS. At a median follow-up of 25 months (IQR 18-49), median disease-free survival (DFS) was 19 months (IQR 15-22). At cox-regression analysis, only pathological features were associated with DFS, while LS and other body composition measures did not show any prognostic role., Conclusion: The combination of sarcopenia and visceral obesity was significantly associated with increased complication severity after pancreatoduodenectomy for cancer. Patients' body composition did not affect disease free survival after pancreatic cancer surgery., Competing Interests: Declaration of competing interest The authors have no related conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: To assess the variation of multiparametric magnetic resonance imaging (mpMRI) positive predictive value (PPV) according to each patient's risk of clinically significant prostate cancer (csPCa) based exclusively on clinical factors., Methods: We evaluated 999 patients with positive mpMRI (PI-RADS ≥ 3) receiving targeted (TBx) plus systematic prostate biopsy. We built a multivariable logistic regression analysis (MVA) using clinical risk factors to calculate the individual patients' risk of harboring csPCa at TBx. A second MVA tested the association between individual patients' clinical risk and mpMRI PPV accounting for the PI-RADS score. Finally, we plotted the PPV of each PI-RADS score by the individual patient pretest probability of csPCa using a LOWESS approach., Results: Overall, TBx found csPCa in 21%, 51%, and 80% of patients with PI-RADS 3, 4, and 5 lesions, respectively. At MVA, age, PSA, digital rectal examination (DRE), and prostate volume were significantly associated with the risk of csPCa at biopsy. DRE yielded the highest odds ratio (OR: 2.88; p < 0.001). The individual patient's clinical risk was significantly associated with mpMRI PPV (OR: 2.49; p < 0.001) using MVA. Plotting the mpMRI PPV according to the predicted clinical risks, we observed that for patients with clinical risk close to 0 versus patients with risk higher than 90%, the mpMRI PPV of PI-RADS 3, 4, and 5 ranged from 0% to 75%, from 0% to 96%, and from 45% to 100%, respectively., Conclusion: mpMRI PPV varies according to the individual pretest patient's risk based on clinical factors. These findings should be considered in the decision-making process for patients with suspect MRI findings referred for a prostate biopsy. Moreover, our data support the need for further studies to create an individualized risk prediction tool., (© 2023 Wiley Periodicals LLC.)

Introduction: A genetic predisposition seems to be involved in biliary tract cancer, but the prevalence of germline mutations in BTC remains unclear, and the therapeutic role of the germline pathologic variants is still unknown., Area Covered: The aim of the present work is to systematically review the data available on the hereditary predisposition of biliary tract cancer by a specific research on PubMed, in order to highlight the most important critical points and to define the current possible role of germinal testing and genetic counseling in this setting of patients., Expert Opinion: Basing on data already available, we decided to start in our institution a specific genetic protocol focused on biliary tract cancer patients, which includes genetic counseling and, if indicated, germline test. The inclusion criteria are: 1) Patient with personal history of oncologic disease other than BTC, 2) Patient with familiar history of oncologic disease (considering relatives of first and second grade), 3) Patient with ≤ 50 years old, 4) Patient presenting a somatic mutation in genes involved in DNA damage repair pathways and mismatch repair. The aim of the presented protocol is to identify germline pathogenic variants with prophylactic and therapeutic impact, and to collect and integrate a significant amount of clinical, familial, somatic, and genetic data.

Introduction: Pancreatic Neuroendocrine Neoplasms (PanNENs) are characterized by a highly heterogeneous clinical and biological behavior, making their diagnosis challenging. PanNENs diagnostic work-up mainly relies on biochemical markers, pathological examination, and imaging evaluation. The latter includes radiological imaging (i.e. computed tomography [CT] and magnetic resonance imaging [MRI]), functional imaging (i.e. 68Gallium [68 Ga]Ga-DOTA-peptide PET/CT and Fluorine-18 fluorodeoxyglucose [18F]FDG PET/CT), and endoscopic ultrasound (EUS) with its associated procedures., Areas Covered: This review provides a comprehensive assessment of the recent advancements in the PanNENs diagnostic field. PubMed and Embase databases were used for the research, performed from inception to October 2023., Expert Opinion: A deeper understanding of PanNENs biology, recent technological improvements in imaging modalities, as well as progresses achieved in molecular and cytological assays, are fundamental players for the achievement of early diagnosis and enhanced preoperative characterization of PanNENs. A multimodal diagnostic approach is required for a thorough disease assessment.