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Neutrophil-to-lymphocyte ratio (NLR) recently demonstrated predictive value for hepatocellular carcinoma (HCC) recurrence after thermal ablation. Microwave ablation (MWA) has been shown to induce changes in the immune landscape after HCC treatment. This study aims at identifying predictors of local tumor progression (LTP) and post-treatment NLR kinetics after MWA.Data from 108 consecutive patients who underwent percutaneous MWA of 119 HCCs with a 2450 Hz/100 W generator in two institutions from October 2014 to September 2021 were retrospectively reviewed. Forty-five HCCs (42 patients) met inclusion criteria for analysis (technique efficacy, pre- and post-treatment NLR availability, follow-up 6 months, absence of complications). NLR was analyzed prior to therapy and at 1-month follow-up; difference between the two time points was defined as ΔNLRAfter a median follow-up of 25 months, LTP occurred in 18 HCCs (40%) and 18 patients (42.9%). Multivariate competing risk regression comprising ΔNLRNLR increase after ablation was the only independent predictor of LTP, supporting the role of balance between systemic inflammation and immunity in recurrence after MWA. Ablation energy/tumor size predicted NLR increase, reinforcing the concept of immune ablation.III.

The results of the phase III ClarIDHy trial have led to US FDA approval of ivosidenib as a therapeutic option for patients with locally advanced or metastatic cholangiocarcinoma (CCA) harboring isocitrate dehydrogenase 1 (IDH1) mutations.In this study, we report the first real-world experience including eight patients with previously treated locally advanced or metastatic IDH1-mutated CCA treated with ivosidenib.Patients treated with ivosidenib as second and third line for advanced CCA were collected with the aim of evaluating the survival outcomes. A molecular study has been performed by next-generation sequencing assay.After a median follow up of 9.4 months, median progression-free survival (PFS) from the start of treatment with ivosidenib was 4.4 months (95% confidence interval [CI] 3.3-5.8), whereas median overall survival (OS) was not reached. The disease control rate was 62.5%, with two patients achieving a partial response (25%); 12.5% of patients experienced a treatment-related adverse event (AE), but no grade 3 or higher AEs were reported. The observed grade 2 AEs were prolonged QT interval and hypomagnesemia (25% of the sample). Molecular profiling was performed on six of eight patients, highlighting TP53, BAP1, CDKN2A and CDKN2B as the most common co-altered genes in these patients.Efficacy outcomes were consistent with those reported in the ClarIDHy trial. Real-world experiences on larger samples are needed in order to confirm our results.

Valentina Burgio,1 Massimo Iavarone,2 Giovanni Giuseppe Di Costanzo,3 Fabio Marra,4 Sara Lonardi,5,6 Emiliano Tamburini,7 Fabio Piscaglia,8 Gianluca Masi,9,10 Ciro Celsa,11 Francesco Giuseppe Foschi,12 Marianna Silletta,13 Daniela Caterina Amoruso,14 Margherita Rimini,15 Mariangela Bruccoleri,2 Raffaella Tortora,3 Claudia Campani,4 Caterina Soldà ,6 Massimo Giuseppe Viola,16 Antonella Forgione,8 Fabio Conti,12 Francesca Salani,9,10 Silvia Catanese,9,10 Carmelo Marco Giacchetto,17 Claudia Fulgenzi,13 Carmine Coppola,14 Pietro Lampertico,18 Antonio Pellino,6,19 Gabriele Rancatore,17 Giuseppe Cabibbo,17 Francesca Ratti,20 Federica Pedica,21 Angelo Della Corte,22 Massimo Colombo,18 Francesco De Cobelli,23 Luca Aldrighetti,20 Stefano Cascinu,1,23 Andrea Casadei-Gardini1,23 1Department of Medical Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 2Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; 3Department of Hepatology, Naples, 80131, Italy; 4Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Firenze, Italy; 5Early Phase Clinical Trial Unit, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; 6Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy; 7Department of Oncology and Palliative Care, Cardinale Hospital, Naples, Italy; 8Division of Internal Medicine, Hepatobiliary and Immunoallergic Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 9Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; 10Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 11Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, 90127, Italy; 12Internal Medicine, Infermi Hospital, Faenza (AUSL ROMAGNA), Ravenna, Italy; 13Department of Oncology, Campus Bio Medico, Roma, Italy; 14Hepatology Unit, Internal Medicine, Area Stabiese Hospital, Naples, Italy; 15Department of Oncology and Hematology, Division of Oncology, University of Modena and Reggio Emilia, Modena, 4121, Italy; 16Department of General Surgery and Emergency Surgery, Cardinale Hospital, Tricase, Italy; 17Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, 90127, Italy; 18Liver Center, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 19Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; 20Hepatobiliary Surgery Division, Liver Center, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 21Department of Experimental Oncology, Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 22Department of Radiology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 23School of Medicine, Vita-Salute San Raffaele University, Milan, 20132, ItalyCorrespondence: Andrea Casadei-GardiniDepartment of Medical Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, ItalyEmail casadeigardini@gmail.comBackground: Lenvatinib has been approved in Italy since October 2019 as a first-line therapy for advanced hepatocellular carcinoma (HCC) and to date data on effectiveness and safety of lenvatinib are not available in our region. To fill this gap, we performed a multicentric analysis of the real-world treatment outcomes with the propensity score matching in a cohort of Italian patients with unresectable HCC who were treated with either sorafenib or lenvatinib.Aims and Methods: To evaluate the effectiveness of sorafenib and lenvatinib as primary treatment of advanced HCC in clinical practice we performed a multicentric analysis of the treatment outcomes of 288 such patients recruited in 11 centers in Italy. A propensity score was used to mitigate confounding due to referral biases in the assessment of mortality and progression-free survival.Results: Over a follow-up period of 11 months the Cox regression model showed 48% reduction of death risk for patients treated with lenvatinib (95% CI: 0.34– 0.81; p = 0.0034), compared with those treated with sorafenib. The median PFS was 9.0 and 4.9 months for lenvatinib and sorafenib arm, respectively. Patients treated with lenvatinib showed a higher percentage of response rate (29.4% vs 2.8%; p < 0.00001) compared with patients treated with sorafenib. Sorafenib was shown to be correlated with more HFSR, diarrhea and fatigue, while lenvatinib with more hypertension and fatigue.Conclusion: Our study highlighted for the first time the efficacy and safety of lenvatinib in an Italian cohort of patients.Keywords: hepatocarcinoma, sorafenib, lenvatinib

Objectives Oligometastatic colorectal cancer benefits of locoregional treatments but data concerning microwave ablation (MWA) are limited and interactions with systemic therapy are still debated. The aim of this study is to evaluate safety and effectiveness of Thermosphere™ MWA (T-MWA) of colorectal liver metastases (CLM) and factors affecting local tumor progression-free survival (LTPFS). Methods In this multi-institutional retrospective study (January 2015–September 2019), patients who underwent T-MWA for CLM were enrolled. Complications according to SIR classification were collected, primary efficacy and LTP were calculated. Analyzed variables included CLM size at diagnosis and at ablation, CLM number, ablation margins, intra-segment progression, chemotherapy before ablation (CBA), variations in size (ΔSDIA-ABL), and velocity of size variation (VDIA-ABL) between CLM diagnosis and ablation. Uni/multivariate analyses were performed using mixed effects Cox model to account for the hierarchical structure of data, patient/lesions. Results One hundred thirty-two patients with 213 CLM were evaluated. Complications were reported in 6/150 procedures (4%); no biliary complications occurred. Primary efficacy was achieved in 204/213 CLM (95.7%). LTP occurred in 58/204 CLM (28.4%). Six-, twelve-, and eighteen-month LTPFS were 88.2%, 75.8%, and 69.9%, respectively. At multivariate analysis, CLM size at ablation (p = 0.00045), CLM number (p = 0.046), ablation margin p = 0.0035), and intra-segment progression (p DIA-ABL (p = 0.63) and VDIA-ABL (p = 0.38) did not affect LTPFS. Ablation margins in the chemo-naïve group were larger than those in the CBA group (p Conclusion T-MWA is a safe and effective technology with adequate LTPFS rates. Intra-segment progression is significantly linked to LTPFS. CBA does not affect LTPFS. Anticipating ablation before chemotherapy may take the advantages of adequate tumor size with correct ablation margin planning. Key Points • Thermosphere™-Microwave ablation is a safe and effective treatment for colorectal liver metastases with no registered biliary complications in more than 200 ablations. • Metastases size at time of ablation, intra-segment progression, and minimal ablation margin • Chemotherapy before ablation modifies kinetics growth of the lesions but deteriorates ablation margins and does not significantly impact local tumor progression-free survival.

Introduction: The prognostic nutritional index (PNI) is a multiparametric score introduced by Onodera based on the blood levels of lymphocytes and albumin in patients with gastrointestinal neoplasms. Regarding hepatocellular carcinoma (HCC), its prognostic role has been demonstrated in patients treated with sorafenib and lenvatinib. The aim of this real-world study is to investigate the association between clinical outcomes and PNI in patients being treated with atezolizumab plus bevacizumab. Methods: The overall cohort of this multicentric study included 871 consecutive HCC patients from 4 countries treated with atezolizumab plus bevacizumab in first-line therapy. The PNI was calculated as follows: 10 × serum albumin concentration (g/dL) + 0.005 × peripheral lymphocyte count (number/mm3). Results: For only 773 patients, data regarding lymphocyte counts and albumin levels were available, so only these patients were included in the final analysis. The cut-off point of the PNI was determined to be 41 by receiver operating characteristic (ROC) analysis. 268 patients (34.7%) were categorized as the PNI-low group, while the remaining 505 (65.3%) patients as the PNI-high group. At the univariate analysis, high PNI was associated with longer overall survival (OS) (22.5 vs. 10.1 months, HR 0.34, p < 0.01) and progression-free survival (PFS) (8.7 vs. 5.8 months, HR 0.63, p < 0.01) compared to patients with low PNI. At the multivariate analysis, high versus low PNI resulted as an independent prognostic factor for OS (HR 0.49 , p < 0.01) and PFS (HR 0.82, p = 0.01). There was no difference in objective response rate (ORR) between the two groups (high 26.1% vs. low 19.8%, p = 0.09), while disease control rate (DCR) was significantly higher in the PNI-high group (76.8% vs. 66.4%, p = 0.01). Conclusion: PNI is an independent prognostic factor for OS and PFS in HCC patients on first-line treatment with atezolizumab plus bevacizumab.

Recent advances in systemic therapeutic options have led to improved survival in patients with advanced hepatocellular carcinoma. In order to optimize patient outcomes across different disease stages, attempts are being made at exploiting combinations of loco-regional treatments and systemic therapeutic regimens. The possibilities of a beneficial synergistic effect are strongly supported by biological evidence of changes in tumor microenvironment and systemic immunity. With the advent of newer interventional technologies and newer biological and immunological drugs, these possibilities keep on gaining interest and expectations, yet many questions remain unanswered as to how to best manipulate and combine the two therapeutic approaches.This review aims at providing a general overview of biological foundations, preliminary clinical applications, critical issues and future directions of this constantly growing field.

Atezolizumab plus bevacizumab and lenvatinib have not been compared in a randomised controlled trial. We conducted a retrospective multi-centre study to compare the clinical efficacy and safety of lenvatinib and atezolizumab with bevacizumab as a first-line treatment for patients with unresectable HCC in the real-world scenario.Clinical features of lenvatinib and atezolizumab plus bevacizumab patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival (OS) was the primary end-point.The analysis included 1341 patients who received lenvatinib, and 864 patients who received atezolizumab plus bevacizumab. After IPTW adjustment, atezolizumab plus bevacizumab did not show a survival advantage over lenvatinib HR 0.97 (p = 0.739). OS was prolonged by atezolizumab plus bevacizumab over lenvatinib in viral patients (HR: 0.76; p = 0.024). Conversely, OS was prolonged by lenvatinib in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (HR: 1.88; p = 0.014). In the IPTW-adjusted population, atezolizumab plus bevacizumab provided better safety profile for most of the recorded adverse events.Our study did not identify any meaningful difference in OS between atezolizumab plus bevacizumab and lenvatinib. Although some hints are provided suggesting that patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease might benefit more from lenvatinib therapy and patients with viral aetiology more from atezolizumab plus bevacizumab.

Background Based on patient and tumor characteristics, some authors favor laparoscopic microwave ablation (LMWA) over the percutaneous approach (PMWA) for treatment of hepatocellular carcinoma (HCC). We compared the two techniques in terms of technique efficacy, local tumor progression (LTP) and complication rates. Study design A retrospective comparative analysis was performed on 91 consecutive patients (102 HCC tumors) who underwent PMWA or LMWA between October 2014 and May 2019. Technique efficacy at one-month and LTP at follow-up were assessed by contrast-enhanced CT/MRI. Kaplan–Meier estimates and Cox regression were used to compare LTP-free survival (LTPFS). Results At baseline analysis, LMWA group showed higher frequency of multinodular disease (p

Aim The identification of new prognostic factors able to stratify hepatocellular carcinoma patients candidate to first-line therapy is urgent. In the present work we validated the prognostic value of the lenvatinib prognostic index. Methods Data of Eastern and Western patients treated with lenvatinib as first-line for Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma were recollected. The lenvatinib prognostic index was composed by three classes of risk according with our previous study. The "low risk" group includes patients with prognostic nutritional index (PNI) >43.3 and with previous transarterial chemoembolization. The "medium risk" group includes patients with PNI >43.3, but without previous transarterial chemoembolization and patients with PNI

Cholangiocarcinoma (CC) is a malignancy with a very heterogeneous spectrum of morphopathological and prognostic characteristics. Diagnostic imaging is fundamental for early detection, preoperative staging, and resectability assessment, as well as early recognition of prognostic factors. Radical surgical treatment is limited by disease stage and technical feasibility. Interventional radiology has acquired a critical function in addressing disease control and survival improvement through loco-regional therapies, specifically in the setting of intrahepatic CC. In this review, we will describe the current state of art of diagnostic imaging, focusing on intrahepatic CC and proximal extrahepatic CC, and delineate the available loco-regional therapies strategies for unresectable intrahepatic CC.

The aim of the present study is to analyze the feasibility and the impact of a two-step approach in the treatment of giant hemangiomas (GH) i.e., exceeding 10 cm in maximum diameter, consisting of transarterial embolization (TAE) followed by laparoscopic liver resection (LLR). Ten patients with 11 GH were treated with TAE and subsequent LLR between 2017 and 2020 (Group A). A matched cohort of 10 patients with GH treated with upfront LLR between 2014 and 2017 was identified for comparison (Group B). Data were analyzed regarding intraoperative and postoperative outcomes, including successful completion of LLR, morbidity, and mortality. Successful microparticle embolization of the GH-feeding arteries was performed in all patients in group A. In three cases a liquid embolic agent (Squid-18) was also injected to obtain complete embolization. No complications were observed after TAE. Successful surgery was performed after a mean time interval of 2.2 days from TAE without any case of conversion to laparotomy. Statistically significant differences between group A and group B were found in intraoperative blood loss (250 ± 200 vs. 400 ± 300 mL, p = 0.039), operative time (245 ± 60 vs. 420 ± 60 min, p = 0.027), and length of stay (5 ± 1 vs. 8 ± 2 days, p = 0.046). Our data suggest that two-step TAE + LLR might be a safe and effective option for surgical treatment of GH &gt, 10 cm.

Future liver remnant (FLR) volume is an important indicator of the risk of posthepatectomy liver failure (PHLF) and limits the feasibility of major hepatectomies. A case series of 5 patients treated with a novel approach is presented. Laparoscopic liver partitioning was combined with subsequent liver venous deprivation (embolization of both the portal and the hepatic veins). Baseline average FLR was 28.8%. All procedures were successfully performed without major complications. Mean 1-, 2- and 4-week hypertrophy of the FLR were 35%, 40.3%, and 46.4%, respectively. Four patients underwent planned surgery after a mean interval of 28 days. Of these, 2 patients achieved sufficient FLR volume and function after 2 weeks and underwent surgery before the 4-week volumetric analysis. One patient did not undergo surgery because of intraoperative diagnosis of peritoneal metastases. No cases of PHLF were observed at 5-day follow-up.

Digital breast tomosynthesis (DBT) as a breast cancer screening modality, through generation of three dimensional images during standard mammographic compression, can reduce interference from breast tissue overlap, increasing conspicuity of invasive cancers while concomitantly reducing falsepositive results. We here conducted a systematic review on previous studies to synthesize the evidence of DBT efficacy, eventually 18 articles being included in the analysis. The most commonly emerging topics were advantages of DBT screening tool in terms of recall rates, cancer detection rates and costeffectiveness, preventing unnecessary burdens on women and the healthcare system. Further research is needed to evaluate the potential impact of DBT on longerterm outcomes, such as interval cancer rates and mortality, to better understand the broader clinical and economic implications of its adoption.