Radio-Guided Surgery with a New-Generation ß-Probe for Radiolabeled Somatostatin Analog, in Patients with Small Intestinal Neuroendocrine Tumors.

BACKGROUND: Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs. OBJECTIVE: We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a ß-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives. METHODS: This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at 68Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a ß-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported. RESULTS: The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12-41 µSv). CONCLUSION: This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel ß-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs. CLINICAL TRIALS REGISTRATION: 68Ga-DOTATOC Radio-Guided Surgery with ß-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic. CLINICALTRIALS: gov/ct2/show/NCT05448157 ].

Vena cava replacement and major hepatectomy for liver tumors: international multicenter retrospective cohort study.

INTRODUCTION: Involvement of the inferior vena cava (IVC) and hepatic veins (HV) has been considered a relative contraindication to hepatic resection for primary and metastatic liver tumors. However, patients affected by tumors extending to the IVC have limited therapeutic options and suffer worsening of quality of life due to IVC compression. METHODS: Cases of primary and metastatic liver tumors with vena cava infiltration from 10 international centers were collected (7 European, 1 US, 2 Brazilian, 1 Indian) were collected. Inclusion criteria for the study were major liver resection with concomitant vena cava replacement. Clinical data and short-term outcomes were analyzed. RESULTS: 36 cases were finally included in the study. Median tumor max size was 98 mm (range: 25-250). A biliary reconstruction was necessary in 28% of cases, while a vascular reconstruction other than vena cava in 34% of cases. Median operative time was 462 min (range: 230-750), with 750 median ml of estimated blood loss and a median of one pRBC transfused intraoperatively (range: 0-27). Median ICU stay was 4 days (range: 1-30) with overall in-hospital stay of 15 days (range: 3-46), post-operative CCI score of 20.9 (range: 0-100), 12% incidence of PHLF grade B-C. Five patients died in a 90-days interval from surgery, 1 due to heart failure, 1 due to septic shock and 3 due to multiorgan failure. With a median follow-up of 17 months (interquartile range: 11-37), the estimated five-years overall survival was 48% (95% CI: 27%-66%), and five-year cumulative incidence of tumor recurrence was 55% (95% CI: 33%-73%). CONCLUSIONS: Major liver resections with vena cava replacement can be performed with satisfactory results in expert HPB centers. This surgical strategy represents a feasible alternative for otherwise unresectable lesions and is associated with favorable prognosis compared to non-operative management, especially in patients affected by intrahepatic cholangiocarcinoma.

Portal vein thrombosis and liver transplantation: management, matching, and outcomes: a retrospective multicenter cohort study.

BACKGROUND AND AIMS: Besides the increased risk of perioperative morbidity, graft failure, and mortality, the majority of PVT are diagnosed at liver transplantation (LT). Improving preoperative management and patient selection may lead to better short-term and long-term outcomes and reduce the risk of a futile LT. The authors aimed to identify predictors of adverse outcomes after LT in patients with nonmalignant portal vein thrombosis (PVT) and improve donor to recipient matching by analyzing the results of the Italian cohort of LT recipients. METHODS: Adult patients who underwent LT in Italy between January 2000 and February 2020 diagnosed with PVT pre-LT or at time of LT were considered eligible for inclusion. Based on a survey encompassing all 26 surgeons participating in the study, a binary composite outcome was defined. Patients were classified as having the composite event if at least one of these conditions occurred: operative time more than 600 min, estimated blood loss greater than 5000 ml, more than 20 ICU days, 90 days mortality, 90 days retransplant. RESULTS: Seven hundred fourteen patients were screened and 698 met the inclusion criteria. The analysis reports the results of 568 patients that fulfilled the criteria to enter the composite outcome analysis.Overall, 156 patients (27.5%) developed the composite outcome. PVT stage 3/4 at transplant and need for any surgical correction of PVT are independent predictors of the composite outcome occurrence. When stratified by PVT grade, overall survival at 1-year ranges from 89.0% with PVT grade 0/1 to 67.4% in patients with PVT grade 3/4 at LT (P<0.001). Nevertheless, patients with severe PVT can improve their survival when identified risk factors are not present. CONCLUSIONS: Potential LT candidates affected by PVT have a benefit from LT that should be adequately balanced on liver function and type of inflow reconstruction needed to mitigate the incidence of adverse events. Nonetheless, the absence of specific risk factors may improve the outcomes even in patients with PVT grades 3-4.

Atypical Ductal Hyperplasia and Lobular In Situ Neoplasm: High-Risk Lesions Challenging Breast Cancer Prevention.

This retrospective study investigates the histopathological outcomes, upgrade rates, and disease-free survival (DFS) of high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. The study addresses the challenge posed by these lesions due to their association with synchronous or adjacent Breast Cancer (BC) and increased future BC risk. The research, comprising 320 patients who underwent stereotactic VABB, focuses on 246 individuals with a diagnosis of ADH (120) or LIN (126) observed at follow-up. Pathological assessments, categorized by the UK B-coding system, were conducted, and biopsy samples were compared with corresponding excision specimens to determine upgrade rates for in situ or invasive carcinoma. Surgical excision was consistently performed for diagnosed ADH or LIN. Finally, patient follow-ups were assessed and compared between LIN and ADH groups to identify recurrence signs, defined as histologically confirmed breast lesions on either the same or opposite side. The results reveal that 176 (71.5%) patients showed no upgrade post-surgery, with ADH exhibiting a higher upgrade rate to in situ pathology than LIN1 (Atypical Lobular Hyperplasia, ALH)/LIN2 (Low-Grade Lobular in situ Carcinoma, LCIS) (38% vs. 20%, respectively, p-value = 0.002). Considering only patients without upgrade, DFS at 10 years was 77%, 64%, and 72% for ADH, LIN1, and LIN2 patients, respectively (p-value = 0.92). The study underscores the importance of a multidisciplinary approach, recognizing the evolving role of VABB. It emphasizes the need for careful follow-up, particularly for lobular lesions, offering valuable insights for clinicians navigating the complex landscape of high-risk breast lesions. The findings advocate for heightened awareness and vigilance in managing these lesions, contributing to the ongoing refinement of clinical strategies in BC care.

Robotic ALPPS for primary and metastatic liver tumours: short-term outcomes versus open approach.

Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is one of the strategies available for patients initially unresectable. High risk of peri-operative morbidity and mortality limited its application and diffusion. We aimed to analyse short-term outcomes of robotic ALPPS versus open approach, to assess safety and reproducibility of this technique. A retrospective analysis of prospectively maintained databases at University of Modena and Reggio Emilia on patients that underwent ALPPS between January 2015 and September 2022 was conducted. The main aim of the study was to evaluate safety and feasibility of robotic approach, either full robotic or only first-stage robotic, compared to a control group of patients who underwent open ALPPS in the same Institution. 23 patients were included. Nine patients received a full open ALPPS (O-ALPPS), 7 received a full robotic ALPPS (R-ALPPS), and 7 underwent a robotic approach for stage 1, followed by an open approach for stage 2 (R + O-ALPPS). PHLF grade B-C after stage 1 was 0% in all groups, rising to 58% in the R + O-ALPPS group after stage 2 and remaining 0% in the R-ALPPS group. 86% of R-ALPPS cases were discharged from the hospital between stages 1 and 2, and median total in-hospital stay and ICU stay favoured full robotic approach as well. This contemporary study represents the largest series of robotic ALPPS, showing potential advantages from full robotic ALPPS over open approach, resulting in reduced hospital stay and complications and lower incidence of 90-day mortality.

Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): results from a single institutional retrospective analysis.

BACKGROUND: Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare tumors and available systemic therapies are limited. AIM: To explore the role of peptide receptor radionuclide therapy (PRRT) with Yttrium-90 (90Y) and Lutetium-177 (177Lu) peptides in pheochromocytomas (PCCs) and paragangliomas (PGLs). METHODS: We retrospectively analyzed more than 1500 patients with histologically proven neuroendocrine tumors treated with 177Lu- or 90Y-DOTA-TATE or -TOC between 1999 to 2017 at our Institute. Overall, 30 patients with confirmed malignant PCCs and PGLs matched inclusion/exclusion criteria and were considered eligible for this analysis. RESULTS: Thirty (n = 30) patients were treated: 22 with PGLs and 8 with PCCs (12 M and 18 F, median age 47 [IQR: 35-60 years]). Eighteen patients (n = 18) had head and neck PGLs, 3 patients thoracic PGLs and 1 patient abdominal PGL. Sixteen patients (53%) had locally advanced and fourteen (47%) had metastatic disease. Twenty-seven (90%) patients had disease progression at baseline. Four (13%) patients were treated with 90Y, sixteen (53%) with 177Lu and ten (33%) with 90Y + 177Lu respectively. The median total cumulative activity from treatment with 90Y- alone was 9.45 GBq (range 5.11-14.02 GBq), from 177Lu- alone was 21.9 GBq (7.55-32.12 GBq) and from the combination treatment was 4.94 GBq from 90Y- and 6.83 GBq from 177Lu- (ranges 1.04-10.1 and 2.66-20.13 GBq, respectively). Seven out of 30 (23%) patients had partial response and 19 (63%) stable disease. Median follow up was 8.9 years (IQR: 2.9-12). The 5-y and 10-y PFS was 68% (95% CI: 48-82) and 53% (95% CI: 33-69), respectively, whereas 5-y and 10-y OS was 75% (95% CI: 54-87) and 59% (95% CI: 38-75), respectively. Grade 3 or 4 acute hematological toxicity occurred in three patients, two with leucopenia and one with thrombocytopenia, respectively. CONCLUSION: PRRT with 177Lu- or 90Y-DOTA-TATE or -TOC is feasible and well tolerated in advanced PGLs and PCCs.

Radiological Features of Male Breast Neoplasms: How to Improve the Management of a Rare Disease.

The primary aim of our study was to assess the main mammographic and ultrasonographic features of invasive male breast malignancies. The secondary aim was to evaluate whether a specific radiological presentation would be associated with a worse receptor profile. Radiological images (mammography and/or ultrasound) of all patients who underwent surgery for male invasive breast cancer in our institution between 2008 and 2023 were retrospectively analyzed by two breast radiologists in consensus. All significant features of radiological presentation known in the literature were re-evaluated. Fifty-six patients were selected. The mean age at surgery of patients was 69 years (range: 35-81); in 82% of cases (46 patients), the histologic outcome was invasive ductal carcinoma. A total of 28 out of 56 (50%) patients had preoperative mammography; in 9/28 cases (32%), we found a mass with microcalcifications on mammography. The mass presented high density in 25 out of 28 patients (89%); the mass showed irregular margins in 15/28 (54%) cases. A total of 46 out of 56 patients had preoperative ultrasounds. The lesion showed a solid mass in 41/46 (89%) cases. In 5/46 patients (11%), the lesion was a mass with a mixed (partly liquid-partly solid) structure. We did not find any statistically significant correlation between major types of radiological presentation and tumor receptor arrangement. Knowledge of the main radiologic presentation patterns of malignant male breast neoplasm can help better manage this type of disease, which is rare but whose incidence is increasing.

Post-operative KEloids iRradiation (POKER): does the surgery/high-dose interventional radiotherapy association make a winning hand?

PURPOSE: To report the results involving post-operative interventional radiotherapy (POIRT) in a homogenous cohort of patients affected by keloid and treated at a single institution with the same fractionation schedule. PATIENTS AND METHODS: Inclusion criteria were: surgery with a histopathological diagnosis of keloid, subsequent high-dose rate interventional radiotherapy (HDR-IRT)-12 Gy in 4 fractions (3 Gy/fr) twice a day-and follow-up period ≥ 24 months. RESULTS: One-hundred and two patients and a total of 135 keloids were eligible for the analyses. Median follow-up was 64 [IQR: 25-103] months. Thirty-six (26.7%) recurrences were observed, 12-months and 36-months cumulative incidence of recurrence were 20.7% (95% CI 12.2-28.5) and 23.8% (95% CI 14.9-31.7) respectively. History of spontaneous keloids (HR = 7.00, 95% CI 2.79-17.6, p < 0.001), spontaneous cheloid as keloid cause (HR = 6.97, 95% CI 2.05-23.7, p = 0.002) and sternal (HR = 10.6, 95% CI 3.08-36.8, p < 0.001), ear (HR = 6.03, 95% CI 1.71-21.3, p = 0.005) or limb (HR = 18.8, 95% CI 5.14-68.7, p < 0.001) keloid sites were significantly associated to a higher risk of recurrence. CONCLUSIONS: The findings support the use of surgery and POIRT as an effective strategy for controlling keloid relapses. Further studies should focus on determining the optimal Biologically Effective Dose and on establishing a scoring system for patient selection.

High-dose chemotherapy and autologous stem cell transplant as first salvage treatment for relapsed or refractory Hodgkin Lymphoma in the era of PET-adapted strategies.

Data on the efficacy of high-dose chemotherapy and autologous stem cell transplantation (ASCT) for classical Hodgkin lymphoma (cHL) patients who failed a PET-driven first-line therapy are limited.We retrospectively evaluated 220 adult cHL patients who underwent ASCT from 2009 to 2021 at 11 centers in Italy. Overall, 49.5% had refractory disease, 23.2% relapsed < 12 and 27.3% ≥12 months from the end of first-line chemotherapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 73.8% and 89.4%. In univariable analysis for PFS events PET-2+ (HR 2.69, p = .001), anemia (HR 2.22, p = .019), refractory disease (HR 1.76, p = .045), less than CR before ASCT (HR 3.24, p < .001) and >2 lines of salvage therapy (HR 2.52; p = .004) were associated with a higher risk of failure after ASCT. In multivariable analysis, >2 lines of salvage therapy (HR 3.28, p = .004) and RT before ASCT (HR 3.00, p = 0.041) retained significance.ASCT is an effective salvage approach for cHL patients treated in the era of PET-adapted therapies.

Contrast-Enhanced Mammography (CEM) compared to Breast Magnetic Resonance (MRI) in the evaluation of breast lobular neoplasia.

PURPOSE: To compare the diagnostic performance (detection, assessment of correct disease extent and multifocality/centricity) of Contrast-Enhanced Mammography (CEM) Versus Breast Magnetic Resonance (MRI) in the study of lobular neoplasms. METHODS: We retrospectively selected all the patients who underwent surgery for a lobular breast neoplasm, either an in situ or an invasive tumor, and had undergone both breast CEM and MRI examinations during the pre-surgical planning. Wilcoxon Signed Rank test was performed to assess the differences between size measurements using the different methods and the post-surgical pathological measurements, considered the gold standard. The agreement in identifying multifocality/multicentricity among the different methods and the pathology was assessed using the Kappa statistics. RESULTS: We selected 19 patients, of which one presented a bilateral neoplasm. Then, the images of these 19 patients were analyzed, for a total of 52 malignant breast lesions. We found no significant differences between the post-surgical pathological size of the lesions and the calculated size with CEM and MRI (p-value of the difference respectively 0.71 and 0.47). In all 20 cases, neoplasm detection was possible both with CEM and MRI. CEM and MRI showed an excellent ability to identify multifocal and multicentric cases (K statistic equal to 0.93 for both the procedures), while K statistic was 0.11 and 0.59 for FFDM and US, respectively. CONCLUSION: The findings of this study suggest that CEM is a reliable imaging technique in the preoperative setting of patients with lobular neoplasm, with comparable results to breast MRI.

Breast Digital Tomosynthesis versus Contrast-Enhanced Mammography: Comparison of Diagnostic Application and Radiation Dose in a Screening Setting.

This study aims to evaluate the Average Glandular Dose (AGD) and diagnostic performance of CEM versus Digital Mammography (DM) as well as versus DM plus one-view Digital Breast Tomosynthesis (DBT), which were performed in the same patients at short intervals of time. A preventive screening examination in high-risk asymptomatic patients between 2020 and 2022 was performed with two-view Digital Mammography (DM) projections (Cranio Caudal and Medio Lateral) plus one Digital Breast Tomosynthesis (DBT) projection (mediolateral oblique, MLO) in a single session examination. For all patients in whom we found a suspicious lesion by using DM + DBT, we performed (within two weeks) a CEM examination. AGD and compression force were compared between the diagnostic methods. All lesions identified by DM + DBT were biopsied; then, we assessed whether lesions found by DBT were also highlighted by DM alone and/or by CEM. We enrolled 49 patients with 49 lesions in the study. The median AGD was lower for DM alone than for CEM (3.41 mGy vs. 4.24 mGy, p = 0.015). The AGD for CEM was significantly lower than for the DM plus one single projection DBT protocol (4.24 mGy vs. 5.55 mGy, p < 0.001). We did not find a statistically significant difference in the median compression force between the CEM and DM + DBT. DM + DBT allows the identification of one more invasive neoplasm one in situ lesion and two high-risk lesions, compared to DM alone. The CEM, compared to DM + DBT, failed to identify only one of the high-risk lesions. According to these results, CEM could be used in the screening of asymptomatic high-risk patients.

Intensity-modulated radiotherapy and cisplatin-based chemotherapy for anal cancer: long-term outcomes at a single institution.

PURPOSE: To evaluate oncological outcomes and late toxicities in a retrospective series of patients with locally-extended anal squamous cell carcinoma (ASCC), treated with curative Intensity Modulated Radiotherapy (IMRT) and chemotherapy. METHODS: ASCC patients who underwent chemo-radiotherapy with IMRT from 2010 to 2020 were included. Oncological outcomes were assessed in terms of overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS) and event-free survival (EFS). Late toxicity was detected according to CTCAE v.5.0 and RTOG late radiation morbidity scoring system. RESULTS: Ninety-five patients were included. Most patients (83%) received chemotherapy with oral Fluoropyrimidine plus Cisplatin. The median follow-up was 5.5 years. The OS was 85.2%, 82.1% and 79.3% at 3, 5 and 8 years, respectively. The DFS was 73.1%, 70%, and 65.3% at 3, 5 and 8 years, respectively; 3, 5 and 8 years CFS was 86.2%, 84.3% and 84.3%, respectively. The EFS was 71%, 67.9% and 63.1%, at 3, 5 and 8 years, respectively. On univariable analysis, a statistically significant lower OS was found for patients with T3-T4 stage (HR = 4.58, p = 0.005) and overall treatment time (OTT) ≥ 47 days (HR = 3.37, p = 0.038). A statistically significant lower DFS was reported for patients with T3-T4 stage (HR = 2.72, p = 0.008) and Serum Squamous Cell Carcinoma Antigen (SCC) value post-RT > 1.5 (HR = 2.90, p = 0.038.). Ten severe late toxicity (≥ G3) events were reported in 8 patients (8.6%). CONCLUSIONS: Our data confirm IMRT concomitant with a Cisplatin-based chemotherapy as an effective treatment of ASCC, ensuring acceptable long-term toxicities and good oncological outcomes.

Robotic Versus Laparoscopic Donor Nephrectomy: A Retrospective Bicentric Comparison of Learning Curves and Surgical Outcomes From 2 High-volume European Centers.

BACKGROUND: Although laparoscopic donor nephrectomy (LDN) represents the gold-standard technique for kidney living donation, robotic donor nephrectomy (RDN) settled as another appealing minimally invasive technique over the past decades. A comparison between LDN and RDN outcomes was performed. METHODS: RDN and LDN outcomes were compared, focusing on operative time and perioperative risk factors affecting surgery duration. Learning curves for both techniques were compared through spline regression and cumulative sum models. RESULTS: The study analyzed 512 procedures (154 RDN and 358 LDN procedures) performed between 2010 and 2021 in 2 different high-volume transplant centers. The RDN group presented a higher prevalence of arterial variations (36.2 versus 22.4%; P = 0.001) compared with the LDN cohort. No open conversions occurred; operative time (210 versus 195 min; P = 0.011) and warm ischemia time (WIT; 230 versus 180 s; P < 0.001) were longer in RDN. Postoperative complication rate was similar (8.4% versus 11.5%; P = 0.49); the RDN group showed shorter hospital stay (4 versus 5 d; P < 0.001). Spline regression models depicted a faster learning curve in the RDN group ( P = 0.0002). Accordingly, cumulative sum analysis highlighted a turning point after about 50 procedures among the RDN cohort and after about 100 procedures among the LDN group.Higher body mass index resulted as an independent risk factor for longer operative time for both techniques; multiple arteries significantly prolonged operative time in LDN, whereas RDN was longer in right kidney procurements; both procedures were equally shortened by growing surgical experience. CONCLUSIONS: RDN grants a faster learning curve and improves multiple vessel handling. Incidence of postoperative complications was low for both techniques.

Can Ki-67 predict radiotherapy response in neuroendocrine tumors? Retrospective analysis of a monocentric series of patients.

BACKGROUND: The impact of radiotherapy (RT) in neuroendocrine neoplasms is still unknown, and outcomes could be improved by a better insight in RT response predictors. This retrospective analysis investigates the potential correlation between Ki-67 and RT response to evaluate its role as biological marker of radiosensitivity. MATERIAL AND METHODS: Data from patients treated at an Italian NET-referral center between 2015 and 2020 were retrieved. Inclusion criteria included: histologically-proven diagnosis of NEN, Ki-67 status, indication (symptomatic and/or ablative) and at least one post-RT radiological assessment. RESULTS: Forty-two patients and 63 different treatment lines were included. Primary tumors presented Ki-67 values < 3% in 21% of cases, between 3 and 20% in 45% and >20% in the remaining 33%. Almost all patients were metastatic at the time of RT, which was performed with symptomatic purpose in 43% of cases. At a median time of three months, a complete response on the target lesion was observed in nine cases (14%), a partial response in 17 (27%), stability in 23 (37%) and local progression in 14 (22%). With median FU of 22.8 months, OS does not show statistically significant differences among three Ki-67 groups. Considering all lines of therapy, the relationship between ORR and Ki-67, did not show statistically significant differences, even following adjustments for drug types and delivered RT doses. CONCLUSION: No association between Ki67 and local tumor response to RT could be observed in the present cohort, regardless of whether the evaluation was performed on a categorical or continuous scale.

COVID-19 in patients with neuroendocrine neoplasms: 2-year results of the INTENSIVE study.

We conducted a retrospective/prospective worldwide study on patients with neuroendocrine neoplasms (NENs) and a molecularly proven SARS-CoV-2 positivity. Preliminary results regarding 85 patients of the INTENSIVE study have been published in 2021. Now we are reporting the 2-year analysis.Here, we are reporting data from consecutive patients enrolled between 1 June 2020, and 31 May 2022. Among the 118 contacted centers, 25 were active to enroll and 19 actively recruiting at the time of data cut-off for a total of 280 patients enrolled. SARS-CoV-2 positivity occurred in 47.5% of patients in 2020, 35.1% in 2021, and 17.4% in 2022. The median age for COVID-19 diagnosis was 60 years. Well-differentiated tumors, non-functioning, metastatic stage, and gastroenteropancreatic (GEP) primary sites represented most of the NENs. COVID-19-related pneumonia occurred in 22.8% of the total, with 61.3% of them requiring hospitalization; 11 patients (3.9%) needed sub-intensive or intensive care unit therapies and 14 patients died (5%), in 11 cases (3.9%) directly related to COVID-19. Diabetes mellitus and age at COVID-19 diagnosis > 70 years were significantly associated with COVID-19 mortality, whereas thoracic primary site with COVID-19 morbidity. A significant decrease in both hospitalization and pneumonia occurred in 2022 vs 2020. In our largest series of NEN patients with COVID-19, the NEN population is similar to the general population of patients with NEN regardless of COVID-19. However, older age, non-GEP primary sites and diabetes mellitus should be carefully considered for increased COVID-19 morbidity and mortality. Relevant information could be derived by integrating our results with NENs patients included in other cancer patients with COVID-19 registries.

Breast Imaging Reporting and Data System and Contrast Enhancement Mammography: Lesion Conspicuity Likelihood of Malignancy and Relationship With Breast Tumor Receptor Status.

RATIONALE AND OBJECTIVES: The new version of the Contrast Enhanced Mammography (CEM) Breast imaging Reporting and Data System (BIRADs) encourages investigations of a new enhancement descriptor: "Lesion Conspicuity" (LC). The study aims to assess the diagnostic performance and the relationship with the receptor profile of this new enhancement descriptor. MATERIALS AND METHODS: Three hundred twenty-five patients with 381 breast lesions who underwent CEM before histological assessmentwere selected. Four radiologists, blinded to each other, categorized LC into the following levels: absent, low, moderate, and high. Considering moderate and high evaluations as predictive of malignancy, the diagnostic performance of CEM was calculated using histological results of the biopsy as the gold standard. The association between LC values and the receptor profile of the neoplasms was also evaluated. RESULTS: The median age at the CEM examination was 50 years (IQR: 45-59). Considering the value of LC of the most experienced radiologist with the interpretation of Low Energy images (LE), we obtained a sensitivity (SE) of 91.9% (95% CI: 88.6%-95.2%) and a specificity (SP) of 67.2% (95% CI: 58.9%-75.5%). An association between "high" lesion conspicuity with ER/PgR not expressed (p = 0.025), with Ki-67>20% (p = 0.033), and with Grading G3 (p = 0.020) was observed. CONCLUSION: The new feature of enhancement, "Lesion Conspicuity", demonstrated satisfactory performance in predicting the malignancy of lesions and significant correlation with the receptor profile of malignant breast neoplasms.

Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer.

Importance: The assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event. Objective: To validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer. Design, Setting, and Participants: ONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019. Exposures: The ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period. Main Outcomes and Measures: The primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism. Results: A total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0, 1, 2, and greater than 2 (P < .001). The time-dependent area under the curve at 3, 6, and 12 months was 70.1% (95% CI, 62.1%-78.7%), 72.9% (95% CI, 65.6%-79.1%), and 72.2% (95% CI, 65.2%-77.3%), respectively. Conclusions and Relevance: This study suggests that, because the ONKOTEV score has been validated in this independent study population as a novel predictive RAM for cancer-associated thrombosis, it can be adopted into practice and into clinical interventional trials as a decision-making tool for primary prophylaxis.

[18F]FDG PET/CT: Lung Nodule Evaluation in Patients Affected by Renal Cell Carcinoma.

Renal Cell Carcinoma (RCC) is generally characterized by low-FDG avidity, and [18F]FDG-PET/CT is not recommended to stage the primary tumor. However, its role to assess metastases is still unclear. The aim of this study was to evaluate the diagnostic accuracy of [18F]FDG-PET/CT in correctly identifying RCC lung metastases using histology as the standard of truth. The records of 350 patients affected by RCC were retrospectively analyzed. The inclusion criteria were: (a) biopsy- or histologically proven RCC; (b) Computed Tomography (CT) evidence of at least one lung nodule; (c) [18F]FDG-PET/CT performed prior to lung surgery; (d) lung surgery with histological analysis of surgical specimens; (e) complete follow-up available. A per-lesion analysis was performed, and diagnostic accuracy was reported as sensitivity and specificity, using histology as the standard of truth. [18F]FDG-PET/CT semiquantitative parameters (Standardized Uptake Value [SUVmax], Metabolic Tumor Volume [MTV] and Total Lesion Glycolysis [TLG]) were collected for each lesion. Sixty-seven patients with a total of 107 lesions were included: lung metastases from RCC were detected in 57 cases (53.3%), while 50 lesions (46.7%) were related to other lung malignancies. Applying a cut-off of SUVmax ≥ 2, the sensitivity and the specificity of [18F]FDG-PET/CT in detecting RCC lung metastases were 33.3% (95% CI: 21.4-47.1%) and 26% (95%CI: 14.6-40.3%), respectively. Although the analysis demonstrated a suboptimal diagnostic accuracy of [18F]FDG-PET/CT in discriminating between lung metastases from RCC and other malignancies, a semiquantitative analysis that also includes volumetric parameters (MTV and TLG) could support the correct interpretation of [18F]FDG-PET/CT images.

Contrast-Enhanced Spectral Mammography in the Evaluation of Breast Microcalcifications: Controversies and Diagnostic Management.

The aim of this study was to evaluate the diagnostic performance of contrast-enhanced spectral mammography (CESM) in predicting breast lesion malignancy due to microcalcifications compared to lesions that present with other radiological findings. Three hundred and twenty-one patients with 377 breast lesions that underwent CESM and histological assessment were included. All the lesions were scored using a 4-point qualitative scale according to the degree of contrast enhancement at the CESM examination. The histological results were considered the gold standard. In the first analysis, enhancement degree scores of 2 and 3 were considered predictive of malignity. The sensitivity (SE) and positive predictive value (PPV) were significative lower for patients with lesions with microcalcifications without other radiological findings (SE = 53.3% vs. 82.2%, p-value < 0.001 and PPV = 84.2% vs. 95.2%, p-value = 0.049, respectively). On the contrary, the specificity (SP) and negative predictive value (NPV) were significative higher among lesions with microcalcifications without other radiological findings (SP = 95.8% vs. 84.2%, p-value = 0.026 and NPV = 82.9% vs. 55.2%, p-value < 0.001, respectively). In a second analysis, degree scores of 1, 2, and 3 were considered predictive of malignity. The SE (80.0% vs. 96.8%, p-value < 0.001) and PPV (70.6% vs. 88.3%, p-value: 0.005) were significantly lower among lesions with microcalcifications without other radiological findings, while the SP (85.9% vs. 50.9%, p-value < 0.001) was higher. The enhancement of microcalcifications has low sensitivity in predicting malignancy. However, in certain controversial cases, the absence of CESM enhancement due to its high negative predictive value can help to reduce the number of biopsies for benign lesions.

Safety and Efficacy of Robotic vs Open Liver Resection for Hepatocellular Carcinoma.

Importance: Long-term oncologic outcomes of robotic surgery remain a hotly debated topic in surgical oncology, but sparse data have been published thus far. Objective: To analyze short- and long-term outcomes of robotic liver resection (RLR) for hepatocellular carcinoma (HCC) from Western high-volume centers to assess the safety, reproducibility, and oncologic efficacy of this technique. Design, Setting, and Participants: This cohort study evaluated the outcomes of patients receiving RLR vs open liver resection (OLR) for HCC between 2010 and 2020 in 5 high-volume centers. After 1:1 propensity score matching, a group of patients who underwent RLR was compared with a validation cohort of OLR patients from a high-volume center that did not perform RLR. Main Outcomes and Measures: A retrospective analysis was performed of prospectively maintained databases at 2 European and 2 US institutions of patients who underwent RLR for HCC between January 1, 2010, and September 30, 2020. The main outcomes were safety and feasibility of RLR for HCC and its oncologic outcomes compared with a European OLR validation cohort. A 2-sided P < .05 was considered significant. Results: The study included 398 patients (RLR group: 125 men, 33 women, median [IQR] age, 66 [58-71] years; OLR group: 315 men, 83 women; median [IQR] age, 70 [64-74] years), and 106 RLR patients were compared with 106 OLR patients after propensity score matching. The RLR patients had a significantly longer operative time (median [IQR], 295 [190-370] minutes vs 200 [165-255] minutes, including docking; P < .001) but a significantly shorter hospital length of stay (median [IQR], 4 [3-6] days vs 10 [7-13] days; P < .001) and a lower number of admissions to the intensive care unit (7 [6.6%] vs 21 [19.8%]; P = .002). Incidence of posthepatectomy liver failure was significantly lower in the RLR group (8 [7.5%] vs 30 [28.3%]; P = .001), with no cases of grade C failure. The 90-day overall survival rate was comparable between the 2 groups (RLR, 99.1% [95% CI, 93.5%-99.9%]; OLR, 97.1% [95% CI, 91.3%-99.1%]), as was the cumulative incidence of death related to tumor recurrence (RLR, 8.8% [95% CI, 3.1%-18.3%]; OLR, 10.2% [95% CI, 4.9%-17.7%]). Conclusions and Relevance: This study represents the largest Western experience to date of full RLR for HCC. Compared with OLR, RLR performed in tertiary centers represents a safe treatment strategy for patients with HCC and those with compromised liver function while achieving oncologic efficacy.