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Purpose: Data on the prognostic impact of the micropapillary component in breast cancer are limited. The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of pure and mixed invasive micropapillary breast cancer (IMPC) patients compared to invasive ductal cancer (IDC) patients. Methods: This retrospective study analysed all IMPC and IDC patients treated at the European Institute of Oncology (IEO) between 1997 and 2019. The overall cohort of IMPC patients was divided in two groups, pure and mixed IMPC. Each patient with mixed or pure IMPC was matched with one patient with IDC, based on year of surgery, age, pT, pN, and molecular subtype. Results: A total of 30,115 IDC, 120 pure IMPC and 150 mixed IMPC patients were considered eligible. Compared to IDC, pure and mixed IMPC patients presented a higher rate of locally advanced disease (pT2-T3, pN2-N3), vascular invasion, and Luminal B subtype. After matching, pure and mixed IMPC showed a significant higher rate of vascular invasion compared to IDC patients (p < 0.001). Invasive disease-free survival was better in IDC compared to pure IMPC patients (p = 0.11). Long-term overall survival was significantly worse in pure IMPC group compared to IDC group (p = 0.004), being instead similar between mixed IMPC vs matched IDC (p = 0.07). Conclusion: These real-world data reported the worse prognosis of pure IMPC compared to IDC, highlighting the peculiar prognostic value of the micropapillary subtype itself in the decision-making process of IMPC management. An accurate pre-surgical diagnostic evaluation and a multidisciplinary approach are pivotal to best personalize its treatment. [ABSTRACT FROM AUTHOR]

Introduction: To offer an extensive retrospective experience on the management of male breast cancer. Methods: A multicenter retrospective observational cohort study was conducted, including male patients diagnosed with breast cancer (invasive or in situ) in 12 Italian breast units from January 1975 to December 2019. Patients aged 18 years or older were assessed for eligibility. Exclusion criteria were metastatic cancer at diagnosis, previous cancer(s), received neoadjuvant treatment, incomplete data on (neo) adjuvant treatment(s), and/or follow-up data. Data on radiological examinations, demographic characteristics, risk factors, histological features, receptor status, treatments, and follow-up were collected. Results: In a series of 671 male patients with breast cancer assessed for eligibility, 403 (28 in situ and 375 invasive neoplasms) were included in the study. All included patients underwent surgery. The median age at surgery was 63.8 years (IQR 56.1–72.1). In 68% of cases, patients underwent echography, and in 55.1%, a mammography. Most patients were ER and PR positive (63.8%), HER2 negative (80.4%), with high (≥ 20%) Ki67 values (61.3%), and luminal B subtype (51.1%). The 10-year overall survival was 73.6% (95% CI 67.0–79.1) for invasive breast cancer and 90% (95% CI 65.6–97.4) for in situ breast cancer. In patients with invasive breast cancer, at univariable analysis, having a G3 tumor (vs. G1), pT2/3/4 (vs. pT1), pN2/3 (vs. pN0), luminal B subtype with Ki67 ≥ 20% (vs. Luminal A), were significantly associated with a higher risk of death. In multivariable analyses, pT2/3/4 (vs. pT1) remained significantly associated with a higher risk of death (HR 3.14, 95% CI 1.83–5.39), and having a HER2 positive or a triple-negative subtype (vs. Luminal A) was also significantly associated with a higher risk of mortality (HR 4.76, 95% CI 1.26–18.1). Conclusion: Male breast cancer is a rare disease, the better understanding of which is necessary for a more effective diagnostic and therapeutic approach. [ABSTRACT FROM AUTHOR]

Through the use of an innovative method to identify original publications, we conducted a meta-analysis of all epidemiological studies evaluating the association between second-hand smoke (SHS) exposure and breast cancer risk among female non-smokers published in English up to October 2022. Pooled relative risks (RR) were obtained through the use of random-effects models. Dose–response relationships were derived using log-linear functions. Out of 73 identified eligible studies, 63 original articles were included in the meta-analysis. The pooled RR for breast cancer for overall exposure to SHS was 1.24 (95% confidence interval, CI, 1.15–1.34, number of articles, n = 52). Regarding the setting of exposure, RRs were 1.17 (95% CI 1.08–1.27, n = 37) for SHS exposure at home, 1.03 (95% CI 0.98–1.08, n = 15) at the workplace, 1.24 (95% CI 1.11–1.37, n = 16) at home or workplace, and 1.45 (95% CI 1.16–1.80, n = 13) for non-specified settings. The risk of breast cancer increased linearly with higher duration (RR 1.29; 95% CI 1.04–1.59 for 40 years of SHS exposure, n = 12), intensity (RR 1.38; 95% CI 1.14–1.67 for 20 cigarettes of SHS exposure per day, n = 6), and pack-years (RR 1.50; 95% CI 0.92–2.45 for 40 SHS pack-years, n = 6) of SHS exposure. This meta-analysis shows a statistically significant excess risk of breast cancer in women exposed to SHS. [ABSTRACT FROM AUTHOR]

Background: The reconstruction of large breasts carries a heightened risk profile. While skin-reducing mastectomy (SRM) techniques facilitate the correction of breast ptosis, they are frequently associated with a high incidence of vascular complications. This study compares two SRM techniques—the horizontal incision and the classic inverted T incision—by examining their clinical and surgical outcomes. Methods: We retrospectively analyzed data from 24 patients (30 breasts) who underwent SRM with immediate prosthetic reconstruction between 2019 and 2023 at the European Institute of Oncology in Milan, Italy. Our comparison focused on breast aesthetic outcome, reconstruction quality, complication rates (early and late), and patient satisfaction, utilizing the BREAST-Q questionnaire to gauge the latter. Results: Among the 24 patients included in the study, 16 (20 breasts) were treated with the inverted T technique, and 8 (10 breasts) with the horizontal incision approach. A higher overall complication rate was observed with the inverted T technique compared to the horizontal method, with early complications outnumbering late ones. The most common issues were recurrent seroma and skin necrosis leading to implant exposure. Notably, there were no cases of implant infection. Although the horizontal incision technique achieved slightly higher patient satisfaction scores, the difference was not statistically significant. Discussion: The inverted T and horizontal incision techniques each have unique benefits and drawbacks. Our findings indicate enhanced patient satisfaction and reduced complication rates with the horizontal incision technique. The selection of the technique should be customized based on the patient's individual risk factors, tissue quality, and preferences. [ABSTRACT FROM AUTHOR]

Introduction: Several studies have demonstrated that, following a breast cancer (BC) diagnosis, patients are eager to obtain information on cancer and nutrition, in order to ameliorate both their quality of life (QoL) and disease outcome. To avoid BC survivors to get wrong information from unreliable sources, healthcare providers need to be aware of patients’ needs, to guide them toward optimal nutrition recommendations, aimed at preventing tumor recurrence and increasing survival rates. Material and methods: The cross-sectional web-based survey “Nutrition and breast cancer, what would you like to know?” has been conceived and conducted, in Italy, between the 2nd and the 25th of June 2023. The link to the 19-items questionnaire, structured in 6 sections, was distributed via social media (Facebook and Instagram), newsletter, institutional websites, and printed flyers. Patients’ responses were collected and analyzed, reporting absolute and relative frequencies. Results: A total of 1616 participants (98.9% female and 1.1% male), with an average age of 47.5 years, answered the survey. Only subjects who declared having previously received a BC diagnosis (N=1159, 71.7%) were included in the present analysis. Overall, the respondents showed a wide interest in understanding whether nutrition might help to manage therapy side effects, as well as knowing how specific diets, foods, nutrients, and supplements could affect disease onset, progression and prognosis. Importantly, the need to receive evidence-based information from the “referring physician/specialist” and “nutritionist/dietitian” was expressed by 95.8% and 88.8% of them, respectively Discussion: In this study, we primarily aimed at intercepting nutrition information needs and sources of an Italian BC survivors’ group. Based on that, we first organized a proactive digital intervention, to respond via Instagram live broadcasts to patients’ “cancer and nutrition”-related questions. Secondly, we arranged a healthcare providers dedicated-workshop focused on the latest evidence-based knowledge on nutrition and BC. It is crucial, in fact, that once healthcare professionals capture patients’ information needs, they can respond with appropriate nutritional guidance, counseling and education programs, while counteracting misleading and incorrect messages. [ABSTRACT FROM AUTHOR]

Background Lung cancer ranks as the leading cause of cancer-related deaths worldwide. There is evidence that second-hand smoke (SHS) exposure is a risk factor for the development of lung cancer in neversmokers. This systematic review and meta-analysis aims to provide the most accurate quantification of the association between SHS exposure and lung cancer risk in never-smokers. Materials and methods Through the use of an innovative method to identify original publications, we conducted a systematic review of the literature, with corresponding meta-analysis, of all epidemiological studies evaluating the association between SHS exposure and lung cancer risk among never-smokers, published up to May 2023. Pooled relative risks were obtained using random-effects models. Dose-response relationships were derived using log-linear functions or cubic splines. Results Out of 126 identified eligible studies, 97 original articles were included in the meta-analysis. The pooled relative risk for lung cancer for overall exposure to SHS was 1.24 (95% CI 1.16-1.32, number of articles, n=82). Setting-specific relative risks were 1.20 (95% CI 1.12-1.28, n=67) for SHS exposure at home, 1.38 (95% CI 1.28-1.62, n=30) at a workplace, 1.37 (95% CI 1.22-1.53, n=28) at home or a workplace and 1.27 (95% CI 1.11-1.44, n=24) in nonspecified settings. The risk of lung cancer significantly increased with the duration, intensity and pack-years of SHS exposure. Conclusions This meta-analysis shows that exposure to SHS increases by more than 20% the risk of lung cancer among never-smokers, providing definitive evidence of the association between SHS exposure and lung cancer risk. [ABSTRACT FROM AUTHOR]

PURPOSE: Electronic health records (EHRs) are valuable information repositories that offer insights for enhancing clinical research on breast cancer (BC) using real-world data. The objective of this study was to develop a natural language processing (NLP) model specifically designed to extract structured data from BC pathology reports written in natural language. METHODS: During the initial phase, the algorithm's development cohort comprised 193 pathology reports from 116 patients with BC from 2012 to 2016. A rule-based NLP algorithm was applied to extract 26 variables for analysis and was compared with the manual extraction of data performed by both a data entry specialist and an oncologist. Following the first approach, the data set was expanded to include 513 reports, and a Named Entity Recognition (NER)-NLP model was trained and evaluated using K-fold cross-validation. RESULTS: The first approach led to a concordance analysis, which revealed an 82.9% agreement between the algorithm and the oncologist, whereas the concordance between the data entry specialist and the oncologist was 90.8%. The second training approach introduced the definition of an NER-NLP model, in which the accuracy showed remarkable potential (97.8%). Notably, the model demonstrated remarkable performance, especially for parameters such as estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 (F1-score 1.0). CONCLUSION: The present study aligns with the rapidly evolving field of artificial intelligence (AI) applications in oncology, seeking to expedite the development of complex cancer databases and registries. The results of the model are currently undergoing postprocessing procedures to organize the data into tabular structures, facilitating their utilization in real-world clinical and research endeavors. A high-accuracy NLP model was developed to extract structured data from breast cancer pathology reports. [ABSTRACT FROM AUTHOR]

PURPOSE: Electronic health records (EHRs) are valuable information repositories that offer insights for enhancing clinical research on breast cancer (BC) using real-world data. The objective of this study was to develop a natural language processing (NLP) model specifically designed to extract structured data from BC pathology reports written in natural language. METHODS: During the initial phase, the algorithm's development cohort comprised 193 pathology reports from 116 patients with BC from 2012 to 2016. A rule-based NLP algorithm was applied to extract 26 variables for analysis and was compared with the manual extraction of data performed by both a data entry specialist and an oncologist. Following the first approach, the data set was expanded to include 513 reports, and a Named Entity Recognition (NER)-NLP model was trained and evaluated using K-fold cross-validation. RESULTS: The first approach led to a concordance analysis, which revealed an 82.9% agreement between the algorithm and the oncologist, whereas the concordance between the data entry specialist and the oncologist was 90.8%. The second training approach introduced the definition of an NER-NLP model, in which the accuracy showed remarkable potential (97.8%). Notably, the model demonstrated remarkable performance, especially for parameters such as estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 (F1-score 1.0). CONCLUSION: The present study aligns with the rapidly evolving field of artificial intelligence (AI) applications in oncology, seeking to expedite the development of complex cancer databases and registries. The results of the model are currently undergoing postprocessing procedures to organize the data into tabular structures, facilitating their utilization in real-world clinical and research endeavors. A high-accuracy NLP model was developed to extract structured data from breast cancer pathology reports. [ABSTRACT FROM AUTHOR]

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 β-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 β-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 β-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 β-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic.clinicaltrials.gov/ct2/show/NCT05448157] [ABSTRACT FROM AUTHOR]

Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy. Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes. Design: Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery. Methods: Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS). Results: Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10–1.26), p = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02–1.07), p = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63–8.36, p = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35–4.06, p = 0.79). Conclusion: Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC. [ABSTRACT FROM AUTHOR]

Background: We compared computed tomography (CT) images and holograms (HG) to assess the number of arteries of the lung lobes undergoing lobectomy and assessed easiness in interpretation by radiologists and thoracic surgeons with both techniques. Methods: Patients scheduled for lobectomy for lung cancer were prospectively included and underwent CT for staging. A patient-specific three-dimensional model was generated and visualized in an augmented reality setting. One radiologist and one thoracic surgeon evaluated CT images and holograms to count lobar arteries, having as reference standard the number of arteries recorded at surgery. The easiness of vessel identification was graded according to a Likert scale. Wilcoxon signed-rank test and κ statistics were used. Results: Fifty-two patients were prospectively included. The two doctors detected the same number of arteries in 44/52 images (85%) and in 51/52 holograms (98%). The mean difference between the number of artery branches detected by surgery and CT images was 0.31 ± 0.98, whereas it was 0.09 ± 0.37 between surgery and HGs (p = 0.433). In particular, the mean difference in the number of arteries detected in the upper lobes was 0.67 ± 1.08 between surgery and CT images and 0.17 ± 0.46 between surgery and holograms (p = 0.029). Both radiologist and surgeon showed a higher agreement for holograms (κ = 0.99) than for CT (κ = 0.81) and found holograms easier to evaluate than CTs (p < 0.001). Conclusions: Augmented reality by holograms is an effective tool for preoperative vascular anatomy assessment of lungs, especially when evaluating the upper lobes, more prone to anatomical variations. Trial registration: ClinicalTrials.gov, NCT04227444 Relevance statement: Preoperative evaluation of the lung lobe arteries through augmented reality may help the thoracic surgeons to carefully plan a lobectomy, thus contributing to optimize patients' outcomes. Key points: • Preoperative assessment of the lung arteries may help surgical planning. • Lung artery detection by augmented reality was more accurate than that by CT images, particularly for the upper lobes. • The assessment of the lung arterial vessels was easier by using holograms than CT images. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study aims at providing an accurate and up-to-date quantification of the dose–response association between cigarette smoking and gastric cancer (GC) risk, overall and by subsite. We conducted a systematic review and meta-analysis of case–control and cohort studies on the association between cigarette smoking and GC risk published up to January 2023. We estimated pooled relative risks (RR) of GC and its subsites according to smoking status, intensity, duration, and time since quitting. Among 271 eligible articles, 205 original studies were included in this meta-analysis. Compared with never smokers, the pooled RR for GC was 1.53 (95% confidence interval; CI 1.44–1.62; n = 92) for current and 1.30 (95% CI 1.23–1.37; n = 82) for former smokers. The RR for current compared with never smokers was 2.08 (95% CI 1.66–2.61; n = 21) for gastric cardia and 1.48 (95% CI 1.33–1.66; n = 8) for distal stomach cancer. GC risk nonlinearly increased with smoking intensity up to 20 cigarettes/day (RR:1.69; 95% CI 1.55–1.84) and levelled thereafter. GC risk significantly increased linearly with increasing smoking duration (RR: 1.31; 95% CI 1.25–1.37 for 20 years) and significantly decreased linearly with increasing time since quitting (RR: 0.65; 95% CI 0.44–0.95 for 30 years since cessation). The present meta-analysis confirms that cigarette smoking is an independent risk factor for GC, particularly for gastric cardia. GC risk increases with a low number of cigarettes up to 20 cigarettes/day and increases in a dose-dependent manner with smoking duration. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study investigates histopathological outcomes, upgrade rates, and disease-free survival (DFS) in high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN 1 and 2), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. Focusing on 320 patients who underwent stereotactic VABB, with 246 individuals diagnosed with ADH (120) or LIN (126), 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 study underscores the importance of a multidisciplinary approach, acknowledging the evolving role of VABB, and emphasizes the need for careful follow-up, particularly for lobular lesions. It offers valuable insights for clinicians navigating the complex landscape of high-risk breast lesions, advocating for heightened awareness and vigilance in managing these lesions and contributing to the ongoing refinement of clinical strategies in BC care. 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. [ABSTRACT FROM AUTHOR]

Introduction: There is debate on which are the best surrogate endpoint and metric to capture treatment effect on overall survival (OS) in RCTs testing immune-checkpoint inhibitors (ICIs). Methods: We systematically searched for RCTs testing ICIs in patients with advanced solid tumors. Inclusion criteria were: RCTs i) assessing PD-(L)1 and CTLA-4 inhibitors either as monotherapy or in combination with another ICI, and/or targeted therapy, and/or chemotherapy, in patients with advanced solid tumors; ii) randomizing at least 100 patients. We performed a meta-analysis of RCTs to compare the surrogacy value of PFS and modified-PFS (mPFS) for OS in RCTs testing ICIs, when the treatment effect is measured by the hazard ratio (HR) for OS, and by the HR and the ratio of restricted mean survival time (rRMST) for PFS and mPFS. Results: 61 RCTs (67 treatment comparisons and 36,034 patients) were included in the analysis. In comparisons testing ICI plus chemotherapy, HRPFS and HRmPFS both had a strong surrogacy value (R2 = 0.74 and R2 = 0.81, respectively). In comparisons testing ICI as monotherapy, HRPFS was the best surrogate, although having a moderate correlation (R2 = 0.58). In comparisons testing ICI plus other treatment(s), the associations were very weak for all the surrogate endpoints and treatment effect measures, with R2 ranging from 0.01 to 0.22. Conclusion: In RCTs testing ICIs, the value of potential surrogates for HROS was strongly affected by the type of treatment(s) tested. The evidence available supports HRPFS as the best surrogate, and disproves the use of alternative endpoints, such as the mPFS, or treatment effect measures, such as the RMST. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers—including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others—using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95–0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07–1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65–0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicotinate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02–5.02], P < 0.0001, KORA: OR 1.3 [95% CI 1.16–1.52], P < 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97–8], P = 0.0002). Although these are host-produced metabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve >70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P < 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset. Article Highlights: Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We investigated whether there is a fecal metabolite signature of impaired fasting glucose (IFG) and the possible underlying mechanisms of action. We identified a fecal metabolite signature of IFG associated with prevalent IFG in two independent cohorts and incident type 2 diabetes in a subanalysis. Although the signature consists of metabolites of nonmicrobial origin, it is strongly correlated with gut microbiome composition. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes by affecting intestinal absorption or excretion of host compounds and xenobiotics. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome. Methods: Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant. Results: We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) (p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC (p = 0.021). Conclusions: Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC. [ABSTRACT FROM AUTHOR]

Purpose: Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes. Methods: We retrospectively collected LAGC patients treated with NAC and surgery +/- adjuvant chemotherapy from 2006 to 2018. HER2 and MSI were assessed on endoscopic and surgical samples. Pathologic complete response (pCR) rate, overall survival (OS), and event‐free survival (EFS) were estimated and evaluated for association with downstaging and MSI. Results: We included 76 patients, 8% were classified as MSI-H, entirely consistent between endoscopic and surgical samples. Six percent of patients were HER2 positive on endoscopic and 4% on surgical samples. Tumor downstaging was observed in 52.5% of cases, with three pCR (5.1%), none in MSI-H cancers. According to MSI status, event-free survival (EFS) and overall survival (OS) were higher for MSI-H patients to MSS [EFS not reached vs 30.0 months, p = 0.08; OS not reached vs 39.6 months, p = 0.10]. Conclusion: Our work confirms the positive prognostic effect of MSI-H in the curative setting of LAGC, not correlated with pathologic tumor downstaging. Prospective ad-hoc trial and tumor molecular profiling are eagerly needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims The 2010 Task Force Criteria (TFC) require that both right ventricular (RV) regional wall-motion abnormalities (WMA) and specific RV size cut-offs be met in order to fulfil one of the major criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Currently, 2D echocardiography (2DE) and cardiovascular magnetic resonance imaging (cMRI) are used to determine if these criteria are met. Little is known about the diagnostic value of 3D echocardiography (3DE) in ARVC. The aim of this study was to determine whether a combination of 2DE-3DE is non-inferior to the currently used 2DE-cMRI combination in the diagnosis of patients with ARVC. Methods and results Thirty-nine individuals (47±15 years) with suspected ARVC underwent evaluation of the RV with cMRI, 2DE, and 3DE. 3DE and cMRI were independently used to obtain RV volumes, ejection fraction (EF) and determine the presence of segmental RV WMA. Studies were blindly classified as meeting criteria for ARVC in accordance with the 2010 TFC. Kappa statistics were used to test the concordance between 2DE–cMRI and 2DE–3DE approaches. Using the 2DE–cMRI approach, 3/39 were not affected, 5/39 possible, 8/39 borderline, and 23/39 definite ARVC. The proposed 2DE–3DE approach yielded 5/39 not affected, 7/39 possible, 8/39 borderline, and 19/39 definite diagnoses. The two approaches were highly concordant (k = 0.71; 95% confidence interval: 0.44–0.84). Although 3DE underestimated RV volumes in comparison with cMRI, interfering, in some instances with the fulfilment of a major criterion, it was able to identify more RV WMA (28/39) than 2DE (11/39), with a detection-rate comparable to cMRI (33/39) highlighting a unique advantage. Conclusion The combination of 2DE–3DE for ARVC diagnosis is comparable to the conventional 2DE–cMRI approach. 3DE should be performed in all suspected ARVC patients to aide in the detection of WMA. [ABSTRACT FROM AUTHOR]

Simple Summary: Screening mammography reduces mortality from breast malignancy. However, breast cancer screening is, unfortunately, hindered due to the poor sensitivity of mammography in dense breasts: up to 15–30% of all cancers may be missed. Given the rapid development of Contrast-Enhanced Mammography (CEM) and its potential for diagnostic use, even in an asymptomatic population, it seems very important to correctly assess the Average Glandular Dose (AGD) for a single CEM examination. Few studies have compared the AGD of CEM versus Digital Mammography (DM) and protocols, including Digital Breast Tomosynthesis (DBT) plus DM, in the same group of patients. The additional role of tomosynthesis versus digital mammography in asymptomatic patients with dense breasts in screening examinations has been well investigated with encouraging results. In this study, we intend to compare the AGD and the diagnostic performance of CEM versus DM, and of CEM versus DM + DBT, performed in the same group of patients over the same period of time 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. [ABSTRACT FROM AUTHOR]

INTRODUCTION Predicting the success of smoking cessation might be crucial to guide towards the treatment of smoking dependence in a clinical setting. We analyzed the potential determinants of successful smoking cessation with a specific focus on self-efficacy in predicting quitting smoking. METHODS All consecutive smokers (n=478; 224 men and 254 women) attending the Careggi University Hospital Smoking Cessation Service in Florence (Italy) in 2018-2019 provided information on self-efficacy in predicting smoking cessation, using a 1-10 rating scale during their first visit. Patients were followed up for success in quitting smoking at 3, 6 and 12 months, validated through CO exhaled measurement. To evaluate the association between self-efficacy and the probability of success, we estimated multivariable relative risks (RRs) and corresponding 95% confidence intervals (CIs) through log-binomial models for longitudinal data. RESULTS Overall, 47.9% of smokers succeeded in their attempt to quit at 3 months, 40.2% at 6 months, and 33.9% at 12 months. Compared to low self-efficacy (rating scale 1-5), the RR of success in quitting smoking was 1.40 (95% CI: 1.06-1.85) for intermediate self-efficacy (scale 6-7) and 1.64 (95% CI: 1.28-2.12) for high self-efficacy (scale 8-10). CONCLUSIONS Self-efficacy is an independent determinant of smoking cessation. We recommend to systematically collect self-efficacy, together with other relevant variables, to predict successful smoking cessation. Moreover, strategies to develop and maintain high levels of self-efficacy are essential to increase quit success and improve treatment. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Image-guided vacuum-assisted breast biopsy (VABB) of the tumour bed, performed after neoadjuvant therapy, is increasingly being used to assess residual cancer and to potentially identify to identify pathological complete response (pCR). In this study, the accuracy of preoperative VABB specimens was assessed and compared with surgical specimens in patients with triple-negative or human epidermal growth factor receptor 2 (HER2)-positive invasive ductal breast cancer after neoadjuvant therapy. As a secondary endpoint, the performance of contrast-enhanced MRI of the breast and PET-CT for response prediction was assessed. Methods: This single-institution prospective pilot study enrolled patients from April 2018 to April 2021 with a complete response on imaging (iCR) who subsequently underwent VABB before surgery. Those with a pCR at VABB were included in the primary analysis of the accuracy of VABB. The performance of imaging (MRI and PET-CT) was analysed for prediction of a pCR considering both patients with an iCR and those with residual disease at postneoadjuvant therapy imaging. Results: Twenty patients were included in the primary analysis. The median age was 44 (range 35-51) years. At surgery, 18 of 20 patients showed a complete response (accuracy 90 (95 per cent exact c.i. 68 to 99) per cent). Only two patients showed residual ductal intraepithelial neoplasia of grade 2 and 3 respectively. In the secondary analysis, accuracy was similar for MRI and PET-CT (77 versus 78 per cent; P=0.76). Conclusion: VABB in patients with an iCR might be a promising method to select patients for de-escalation of surgical treatment in triple-negative or HER2-positive breast cancer. The present results support such an approach and should inform the design of future trials on de-escalation of surgery. [ABSTRACT FROM AUTHOR]

Cervico-vaginal (CV) localization of extra-mammary Paget's disease (EMPD) of the vulva is extremely rare. In order to investigate the incidence risk and the pathognomonic clinical and pathological features of this condition, a retrospective analysis was conducted including 94 women treated for vulvar EMPD at the European Institute of Oncology, Milan, Italy, from October 1997 to May 2020. Overall nine patients developed CV involvement from EMPD, with a cumulative incidence of 2.5% (95% CI: 0.5–8.0%) at 5 years, 6.5% (95% CI: 1.9–15.1%) at 10 years and 14.0% (95% CI: 4.8–27.8%) at 15 years, respectively. All cases except one were firstly detected by abnormal glandular cytology. None reported vaginal bleeding or other suspicious symptoms. The colposcopic findings were heterogeneous and could sometimes be misdiagnosed. Cervical and/or vaginal biopsies were always performed for histopathological diagnosis by identification of Paget cells in the epithelium or stroma. Most patients developed invasive EMPD (5/9) of the cervix and/or vagina and underwent hysterectomy with partial or total colpectomy. CV involvement from EMPD should not be underestimated in women with a long-standing history of vulvar Paget's disease. Liquid-based cytology with immunocytochemistry represents a valuable tool for early diagnosis and should be routinely performed during the required lifelong follow-up. [ABSTRACT FROM AUTHOR]

Background: Data on molecular alterations harbored by melanoma brain metastases (MBMs) are limited, and this has hampered the development of more effective therapeutic strategies. We conducted a systematic review and meta-analysis of all the studies reporting DNA sequencing data of MBMs, in order to identify recurrently mutated genes and molecular pathways significantly enriched for genetic alterations. Methods: We searched PubMed, Embase and Scopus for articles published from the inception of each database to June 30, 2021. We included in the analysis all the studies that reported individual patient data on DNA sequencing of MBMs, assessing single nucleotide variants (SNVs) and/or gene copy number variations (CNVs) in at least five tumor samples. Meta-analysis was performed for genes evaluated for SNVs and/or CNVs in at least two studies. Pooled proportions of samples with SNVs and/or CNVs was calculated by applying random-effect models based on the DerSimonian–Laird method. Gene-set enrichment analysis (GSEA) was performed to identify molecular pathways significantly enriched for mutated genes. Results: Ten studies fulfilled the inclusion criteria and were included in the analysis, for a total of 531 samples of MBMs evaluated. Twenty-seven genes were found recurrently mutated with a meta-analytic rate of SNVs higher than 5%. GSEA conducted on the list of these 27 recurrently mutated genes revealed vascular endothelial growth factor-activated receptor activity and transmembrane receptor protein tyrosine kinase activity to be among the top 10 gene ontology (GO) molecular functions significantly enriched for mutated genes, while regulation of apoptosis and cell proliferation were among the top 10 significantly enriched GO biological processes. Notably, a high meta-analytic rate of SNVs was found in several actionable cancer-associated genes, such as all the vascular endothelial growth factor (VEGF) receptor isoforms (i.e., Flt1 and Flt2 genes, for both SNV rate: 0.22, 95% CI 0.04–0.49; KDR gene, SNV rate: 0.1, 95% CI 0.05–0.16). Finally, two tumor suppressor genes were characterized by a high meta-analytic rate of CNVs: CDKN2A/B (CNV rate: 0.59, 95% CI 0.23–0.90) and PTEN (CNV rate: 0.31, 95% CI 0.02–0.95). Conclusion: MBMs harbored actionable molecular alterations that could be exploited as therapeutic targets to improve the poor prognosis of patients. [ABSTRACT FROM AUTHOR]

Purpose: To present an overview of the management of male patients with Ductal Carcinoma In Situ of the breast (male DCIS). Methods: We retrospectively studied all male patients with a diagnosis of pure DCIS from January 1999 to December 2018: 20 patients were identified in our cancer referral center. We collected data regarding clinical presentation, age of onset, radiological features, receptor status of the neoplasm, histological type, and the follow-up of those patients. Results: The median age was 62 years (range 21–80). All patients underwent surgery, in 15/20 (75%) cases a mastectomy was carried out. Two patients (10%) underwent endocrine treatment and 1/20 (5%) underwent radiotherapy. The receptor status for 15/20 patients was documented: 13/15 patients were ER+/Pr+. In 3 cases the Ki 67% was positive (i.e., > 20%). All cases were negative for Her2. The median follow-up time was 9.0 years (IQR 4.0–13.7). Only one patient had an ipsilateral recurrence with the finding of an infiltrating carcinoma in the same breast after 14 years. The 5-year disease-free survival was 92.9%. Conclusion: Pure DCIS in men is an extremely rare disease: proper diagnosis and management allow an excellent prognosis. [ABSTRACT FROM AUTHOR]

Purpose: To compare the accuracy of Contrast-Enhanced Spectral Mammography (CESM), MG, US, and breast MRI in estimating the size of breast lesions requiring surgery. The postoperative histology size of the lesion was used as the gold standard. Material and methods: Two hundred thirty-three non-benign lesions in 189 patients were included in the analyses. All the selected patients underwent CESM and at least one other conventional diagnostic exam (US, MG, or MRI). Subsequently, all the patients underwent surgery preceded by cytological/histological examination. The largest diameter of the lesion at imaging was measured by a radiologist with more than 10 years' experience and then compared with the size of the lesion in the histological sample at the surgery (gold standard). Results: Among the 233 breast lesions, 196 were evaluated with US, 206 with MG and 160 with MRI. We found no statistically significant differences between size measurements using CESM and MRI compared with the measurements at the surgery (p value 0.63 and 0.51), whereas a significant difference was found for MG and US (p < 0.001). Conclusion: CESM is a reliable method for estimating the size of breast lesions: its performance seems superior to US and MG and comparable to MRI. [ABSTRACT FROM AUTHOR]

Simple Summary: The diagnosis of active neoplastic disease was traditionally judged an absolute contraindication for extracorporeal membrane oxygenator (ECMO) because of long-term results uncertainty and co-existing acquired coagulation disorders often diagnosed in this group of patients. There is a growing body of evidence that circulating tumor cells (CTCs) can be detected in the blood of patients before the primary tumor is diagnosed and in the case of carcinoma recurrence; moreover, on some occasions, they persist in the blood of patients after radical resection of the primary tumor. The aim of this prospective, two-arm study is to compare the number of CTCs before and after surgery in patients undergoing lung cancer resection with and without intraoperative ECMO support. Intraoperative ECMO for lung cancer resections did not impact CTC variation after the procedure and did not impact postoperative complications, ICU stay, hospital total length of stay, and post operative C-reactive protein increase. Background: The diagnosis of active neoplastic disease was traditionally judged an absolute contraindication for extracorporeal membrane oxygenator (ECMO) because of the fear of tumor cells being scattered or seeded. The aim of this study is to compare the number of circulating tumor cells (CTCs) before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. Methods: This is a prospective, non-randomized, two-arms observational study comparing the number of CTCs before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. The ECMO arm includes patients suffering from lung cancer undergoing pulmonary resection with planned intraoperative ECMO support. The non-ECMO arm includes patients suffering from non-early-stage lung cancer undergoing pulmonary resection without planned intraoperative ECMO support. Results: Twenty patients entered the study, eight in the ECMO arm and twelve in the non-ECMO arm. We did not observe any significant difference between the ECMO and non-ECMO groups in terms of postoperative complications (p = 1.00), ICU stay (p = 0.30), hospital stay (p = 0.23), circulating tumor cells' increase or decrease after surgery (p = 0.24), and postoperative C-reactive protein and C-reactive protein increase (p = 0.80). The procedures in the non-ECMO arm were significantly longer than those in the ECMO arm (p = 0.043). Conclusions: Intraoperative ECMO for lung cancer resections did not impact CTC increase or decrease after the procedure. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors (NETs) are more commonly slow‐growing, therefore patients often receive chronic systemic therapies for tumor growth control and preservation of quality of life. Metronomic chemotherapy (mCT) is in line with this goal as it leads to stabilization of tumor growth over time without severe systemic toxicity. This is a retrospective analysis of patients with metastatic NETs receiving metronomic capecitabine (mCAP) or temozolomide (mTEM), at a NET‐referral center. The aims of the study were to explore activity and safety of mCT and relationships between some characteristics of the patient population and clinical outcomes. Among a total of 67 patients with metastatic well or moderately differentiated (W/M‐D) NETs, mostly gastroenteropancreatic (GEP) and nonfunctioning, 1.2 years (95% CI: 0.8–1.8) median progression‐free survival (mPFS), and 3.0 years (95% CI: 2.3–4.9) median overall survival (mOS) were observed. Disease control rate was 85%. Grade 3 adverse events occurred in 15% of patients in mCAP and 13% in mTEM, and were mostly hematological and gastrointestinal. At univariate and multivariate analysis none of the variables analyzed (treatment regimen, sex, age at diagnosis, site of primary tumor and metastases, number of previous mCT lines, baseline tumor status before mCT, Ki67 value) were significantly correlated to OS and PFS. Our retrospective study suggested that mCAP and mTEM can be active and well tolerated in patients with metastatic W/M‐D NETs, irrespective of the primary site, site of metastases, line of treatment and baseline tumor status. [ABSTRACT FROM AUTHOR]

Background: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. Objective: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. Methods: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. Results: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. Conclusions: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Contrast-enhanced spectral mammography (CESM) represents a novel, reliable imaging adjunct for the early detection and management of breast lesions by coupling high sensitivity and specificity. Early diagnosis of breast tumors using this innovative diagnostic method could help in reducing the high number of unnecessary biopsies for breast lesions considered as suspicious by standard radiological examination (such as mammography, ultrasound, and magnetic resonance). Considering its relative recent introduction, there are still no standardized methods for assessing the diagnostic performance of CESM enhancement descriptors. Here, we aim to create a score that takes account four CESM enhancement descriptors able to efficiently predict the malignancy of a breast lesion prior to biopsy. Background: To create a predictive score of malignancy of a breast lesion based on the main contrast enhancement features ascertained by contrast-enhanced spectral mammography (CESM). Methods: In this single-centre prospective study, patients with suspicious breast lesions (BIRADS > 3) were enrolled between January 2013 and February 2022. All participants underwent CESM prior to breast biopsy, and eventually surgery. A radiologist with 20 years' experience in breast imaging evaluated the presence or absence of enhancement and the following enhancement descriptors: intensity, pattern, margin, and ground glass. A score of 0 or 1 was given for each descriptor, depending on whether the enhancement characteristic was predictive of benignity or malignancy (both in situ and invasive). Then, an overall enhancement score ranging from 0 to 4 was obtained. The histological results were considered the gold standard in the evaluation of the relationship between enhancement patterns and malignancy. Results: A total of 321 women (median age: 51 years; range: 22–83) with 377 suspicious breast lesions were evaluated. Two hundred forty-nine lesions (66%) have malignant histological results (217 invasive and 32 in situ). Considering an overall enhancement score ≥ 2 as predictive of malignancy, we obtain an overall sensitivity of 92.4%; specificity of 89.8%; positive predictive value of 94.7%; and negative predictive value of 85.8%. Conclusions: Our proposed predictive score on the enhancement descriptors of CESM to predict the malignancy of a breast lesion shows excellent results and can help in early breast cancer diagnosis and in avoiding unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate survival outcomes and safety after chemoembolization using irinotecan-loaded small-size beads (DEB-IRI) in patients with colorectal liver metastases unresponsive to standard chemotherapy. Materials and methods: Between December 2013 and August 2019, fifty-five patients (32 males, median age 64.5 years) with pretreated colorectal liver metastases unresponsive to standard chemotherapy underwent 197 chemoembolization procedures (mean 3.6 ± 2.3 SD per patient). Thirty patients (30/55; 55%) had extrahepatic disease metastatic to the lungs, lymph nodes or peritoneum. Local tumor control was evaluated at 3, 6, 9 and 12 months. Median overall survival, survival rates at 1 and 2 year and adverse events were evaluated. Results: Local tumor control was achieved in 32/55 (58%), 12/55 (22%), 4/55 (7%) and 2/55 (4%) patients at 3, 6, 9 and 12 months, respectively. Median overall survival was 9.9 months (95% CI: 6.2–14.2 months) with 1- and 2-year survival rates of 45% and 15%, respectively. A total of 30 (15%) G1-G3 treatment-related adverse events occurred across all embolization procedures. No severe treatment-related adverse events occurred. Conclusion: Chemoembolization using irinotecan-loaded small-size beads is a safe and effective procedure as a salvage treatment in patients with colorectal liver metastases, showing good results in terms of liver-specific progression free survival and overall survival. [ABSTRACT FROM AUTHOR]

Background: To evaluate the performance, quality and effectiveness of "IEO-TIRADS" in assigning a TI-RADS score to thyroid nodules (TN) when compared with "EU-TIRADS" and the US risk score calculated with the S-Detect software ("S-Detect"). The primary objective is the evaluation of diagnostic accuracy (DA) by "IEO-TIRADS", "S-Detect" and "EU-TIRADS", and the secondary objective is to evaluate the diagnostic performances of the scores, using the histological report as the gold standard. Methods: A radiologist collected all three scores of the TNs detected and determined the risk of malignancy. The results of all the scores were compared with the histological specimens. The sensitivity (SE), specificity (SP), and diagnostic accuracy (DA), with their 95% confidence interval (95% CI), were calculated for each method. Results: 140 TNs were observed in 93 patients and classified according to all three scores. "IEO-TIRADS" has an SE of 73.6%, an SP of 59.2% and a DA of 68.6%. "EU-TIRADS" has an SE of 90.1%, an SP of 32.7% and a DA of 70.0%. "S-Detect" has an SE of 67.0%, an SP of 69.4% and a DA of 67.9%. Conclusion: "IEO-TIRADS" has a similar diagnostic performance to "S-Detect" and "EU-TIRADS". Providing a comparable DA with other reporting systems, IEO-TIRADS holds the potential of being applied in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: Risk stratification of patients with long QT syndrome (LQTS) represents a difficult task. In 2018, we proposed a granular estimate of the baseline 5-year risk of life-threatening arrhythmias (LAE) for patients with LQTS, based on the genotype (long QT syndrome Type 1, long QT syndrome Type 2, and long QT syndrome Type 3) and the duration of the QTc interval. We sought to externally validate a novel risk score model (1-2-3-LQTS-Risk model) in a geographically diverse cohort from the USA and to evaluate its performance and assess potential clinical implication of this novel model.Methods and Results: The prognostic model (1-2-3-LQTS-Risk model) was derived using data from a prospective, single-centre longitudinal cohort study published in 2018 (discovery cohort) and was validated using an independent cohort of 1689 patients enrolled in the International LQTS Registry (Rochester NY, USA). The validation study revealed a C-index of 0.69 [95% confidence interval (CI): 0.61-0.77] in the validation cohort, when compared with C-index of 0.79 (95% CI: 0.70-0.88) in the discovery cohort. Adopting a 5-year risk ≥5%, as suggested by the ROC curve analysis as the most balanced threshold for implantable cardioverter-defibrillator (ICD) implantation, would result in a number needed to treat (NNT) of nine (NNT = 9; 95% CI: 6.3-13.6).Conclusion: The 1-2-3-LQTS-Risk model, the first validated 5-year risk score model for patients with LQTS, can be used to aid clinicians to identify patients at the highest risk of LAE who could benefit most from an ICD implant and avoid unnecessary implants. [ABSTRACT FROM AUTHOR]

The objective of this study was to determining the frequency of different sub-types of pathogenic CDH1 germline mutations in healthy and asymptomatic individuals from families with the hereditary diffuse gastric cancer (HDGC) syndrome. Relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations. The collected variants were classified according to their subtype into the following classes: missense, non-sense, splicing, insertions and deletions. The X² test was used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was statistically significant. CDH1 genetic screening data were retrieved for 224 patients with GC and 289 healthy individuals. Among the subjects that had tested CDH1 positive, splicing mutations were found in 30.4% of the healthy individuals and in 15.2% of the patients with GC (p=0.0076). Missense mutations were also found to occur in healthy subjects with higher frequency (22.2%) than in GC-affected individuals (18.3%), but the difference was not significant in this case. In families meeting the clinical criteria for the HDGC syndrome, CDH1 splicing and missense germline mutations have been reported to occur with higher frequency in healthy subjects than in patients with cancer. This preliminary observation suggests that not all pathogenic CDH1 germline mutations confer the same risk of developing GC. [ABSTRACT FROM AUTHOR]