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1. Single large hepatocellular carcinoma > 5 cm with surgical indication: is it mandatory a major hepatectomy? a propensity-score weighted analysis.

Author

Garancini M, Serenari M, Famularo S, Cipriani F, Ardito F, Russolillo N, Conci S, Nicolini D, Perri P, Zanello M, Iaria M, Lai Q, Romano M, La Barba G, Molfino S, Germani P, Dominioni T, Zimmiti G, Conticchio M, Fumagalli L, Zago M, Troci A, Sciannamea I, Ferrari C, Scotti MA, Griseri G, Antonucci A, Crespi M, Pinotti E, Chiarelli M, Memeo R, Hilal MA, Maestri M, Tarchi P, Baiocchi G, Ercolani G, Zanus G, Rossi M, Valle RD, Jovine E, Frena A, Patauner S, Grazi GL, Vivarelli M, Ruzzenente A, Ferrero A, Giuliante F, Aldrighetti L, Torzilli G, Cescon M, Bernasconi D, and Romano F

Subjects
Humans, Male, Female, Retrospective Studies, Middle Aged, Aged, Postoperative Complications etiology, Treatment Outcome, Survival Rate, Adult, Hepatectomy methods, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular mortality, Liver Neoplasms surgery, Liver Neoplasms pathology, Liver Neoplasms mortality, Propensity Score
Abstract

Purpose: Single large hepatocellular carcinoma >5cm (SLHCC) traditionally requires a major liver resection. Minor resections are often performed with the goal to reduce morbidity and mortality. Aim of the study was to establish if a major resection should be considered the best treatment for SLHCC or a more limited resection should be preferred., Methods: A multicenter retrospective analysis of the HE.RC.O.LE.S. Group register was performed. All collected patients with surgically treated SLHCC were divided in 5 groups of treatment (major hepatectomy, sectorectomy, left lateral sectionectomy, segmentectomy, non-anatomical resection) and compared for baseline characteristics, short and long-term results. A propensity-score weighted analysis was performed., Results: 535 patients were enrolled in the study. Major resection was associated with significantly increased major complications compared to left lateral sectionanectomy, segmentectomy and non-anatomical resection (all p<0.05) and borderline significant increased major complications compared to sectorectomy (p=0.08). Left lateral sectionectomy showed better overall survival compared to major resection (p=0.02), while other groups of treatment resulted similar to major hepatectomy group for the same item. Absence of oncological benefit after major resection and similar outcomes among the 5 groups of treatment was confirmed even in the sub-population excluding patients with macrovascular invasion., Conclusion: Major resection was associated to increased major post-operative morbidity without long-term survival benefit; when technically feasible and oncologically adequate, minor resections should be preferred for the surgical treatment of SLHCC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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2. Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma.

Author

Vitale A, Romano P, Cillo U, Lauterio A, Sangiovanni A, Cabibbo G, Missale G, Marseglia M, Trevisani F, Foschi FG, Cipriani F, Famularo S, Marra F, Saitta C, Serenari M, Vidili G, Morisco F, Caturelli E, Mega A, Pelizzaro F, Nicolini D, Ardito F, Garancini M, Masotto A, Baroni GS, Azzaroli F, Giannini E, Perri P, Scarinci A, Fontana AP, Brunetto MR, Iaria M, Di Marco M, Nardone G, Dominioni T, Lai Q, Ferrari C, Rapaccini GL, Rodolfo S, Romano M, Conci S, Zoli M, Conticchio M, Zanello M, Zimmitti G, Fumagalli L, Troci A, Germani P, Gasbarrini A, La Barba G, De Angelis M, Patauner S, Molfino S, Zago M, Pinotti E, Frigo AC, Baiocchi GL, Frena A, Boccia L, Ercolani G, Tarchi P, Crespi M, Chiarelli M, Abu Hilal M, Cescon M, Memeo R, Ruzzenente A, Zanus G, Griseri G, Rossi M, Maestri M, Della Valle R, Ferrero A, Grazi GL, Romano F, Giuliante F, Vivarelli M, Jovine E, Torzilli G, Aldrighetti L, and De Carlis L

Subjects
Humans, Male, Female, Middle Aged, Retrospective Studies, Aged, Survival Rate, Radiofrequency Ablation, Treatment Outcome, Carcinoma, Hepatocellular therapy, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular surgery, Liver Neoplasms therapy, Liver Neoplasms mortality, Liver Neoplasms pathology, Hepatectomy, Chemoembolization, Therapeutic
Abstract

Importance: The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller., Objective: To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC., Design, Setting, and Participants: This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023., Interventions: LR, PRFA, or TACE., Main Outcomes and Measures: Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes., Results: A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE., Conclusions and Relevance: For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.

Published
2024
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3. The Effect of a Liver Transplant Program on the Outcomes of Resectable Hepatocellular Carcinoma: A Nationwide Multicenter Analysis.

Author

Serenari M, Lenzi J, Cucchetti A, Cipriani F, Donadon M, Ardito F, Fazio F, Nicolini D, Iaria M, Famularo S, Perri P, Ansaloni L, Zanello M, Lai Q, Conci S, Molfino S, Ferrari C, Germani P, Zago M, Romano M, Zimmitti G, Antonucci A, Fumagalli L, Troci A, Ferraro V, Memeo R, Crespi M, Chiarelli M, Ercolani G, Hilal MA, Zanus G, Pinotti E, Tarchi P, Griseri G, Baiocchi GL, Ruzzenente A, Rossi M, Jovine E, Maestri M, Grazi GL, Romano F, Dalla Valle R, Ravaioli M, Vivarelli M, Ferrero A, Giuliante F, Torzilli G, Aldrighetti L, and Cescon M

Subjects
Humans, Liver Cirrhosis complications, Neoplasm Recurrence, Local epidemiology, Retrospective Studies, Carcinoma, Hepatocellular surgery, Liver Transplantation, Liver Neoplasms, Liver Failure complications
Abstract

Objective: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC)., Background: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program., Methods: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival., Results: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival., Conclusions: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2023
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4. Machine Learning Predictive Model to Guide Treatment Allocation for Recurrent Hepatocellular Carcinoma After Surgery.

Author

Famularo S, Donadon M, Cipriani F, Fazio F, Ardito F, Iaria M, Perri P, Conci S, Dominioni T, Lai Q, La Barba G, Patauner S, Molfino S, Germani P, Zimmitti G, Pinotti E, Zanello M, Fumagalli L, Ferrari C, Romano M, Delvecchio A, Valsecchi MG, Antonucci A, Piscaglia F, Farinati F, Kawaguchi Y, Hasegawa K, Memeo R, Zanus G, Griseri G, Chiarelli M, Jovine E, Zago M, Abu Hilal M, Tarchi P, Baiocchi GL, Frena A, Ercolani G, Rossi M, Maestri M, Ruzzenente A, Grazi GL, Dalla Valle R, Romano F, Giuliante F, Ferrero A, Aldrighetti L, Bernasconi DP, and Torzilli G

Subjects
Humans, Female, Aged, Male, Sorafenib therapeutic use, Retrospective Studies, Neoplasm Recurrence, Local pathology, Hepatectomy, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular pathology, Liver Neoplasms surgery, Liver Neoplasms pathology, Chemoembolization, Therapeutic
Abstract

Importance: Clear indications on how to select retreatments for recurrent hepatocellular carcinoma (HCC) are still lacking., Objective: To create a machine learning predictive model of survival after HCC recurrence to allocate patients to their best potential treatment., Design, Setting, and Participants: Real-life data were obtained from an Italian registry of hepatocellular carcinoma between January 2008 and December 2019 after a median (IQR) follow-up of 27 (12-51) months. External validation was made on data derived by another Italian cohort and a Japanese cohort. Patients who experienced a recurrent HCC after a first surgical approach were included. Patients were profiled, and factors predicting survival after recurrence under different treatments that acted also as treatment effect modifiers were assessed. The model was then fitted individually to identify the best potential treatment. Analysis took place between January and April 2021., Exposures: Patients were enrolled if treated by reoperative hepatectomy or thermoablation, chemoembolization, or sorafenib., Main Outcomes and Measures: Survival after recurrence was the end point., Results: A total of 701 patients with recurrent HCC were enrolled (mean [SD] age, 71 [9] years; 151 [21.5%] female). Of those, 293 patients (41.8%) received reoperative hepatectomy or thermoablation, 188 (26.8%) received sorafenib, and 220 (31.4%) received chemoembolization. Treatment, age, cirrhosis, number, size, and lobar localization of the recurrent nodules, extrahepatic spread, and time to recurrence were all treatment effect modifiers and survival after recurrence predictors. The area under the receiver operating characteristic curve of the predictive model was 78.5% (95% CI, 71.7%-85.3%) at 5 years after recurrence. According to the model, 611 patients (87.2%) would have benefited from reoperative hepatectomy or thermoablation, 37 (5.2%) from sorafenib, and 53 (7.6%) from chemoembolization in terms of potential survival after recurrence. Compared with patients for which the best potential treatment was reoperative hepatectomy or thermoablation, sorafenib and chemoembolization would be the best potential treatment for older patients (median [IQR] age, 78.5 [75.2-83.4] years, 77.02 [73.89-80.46] years, and 71.59 [64.76-76.06] years for sorafenib, chemoembolization, and reoperative hepatectomy or thermoablation, respectively), with a lower median (IQR) number of multiple recurrent nodules (1.00 [1.00-2.00] for sorafenib, 1.00 [1.00-2.00] for chemoembolization, and 2.00 [1.00-3.00] for reoperative hepatectomy or thermoablation). Extrahepatic recurrence was observed in 43.2% (n = 16) for sorafenib as the best potential treatment vs 14.6% (n = 89) for reoperative hepatectomy or thermoablation as the best potential treatment and 0% for chemoembolization as the best potential treatment. Those profiles were used to constitute a patient-tailored algorithm for the best potential treatment allocation., Conclusions and Relevance: The herein presented algorithm should help in allocating patients with recurrent HCC to the best potential treatment according to their specific characteristics in a treatment hierarchy fashion.

Published
2023
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5. Benchmarking postoperative outcomes after open liver surgery for cirrhotic patients with hepatocellular carcinoma in a national cohort.

Author

Famularo S, Russolillo N, Donadon M, Cipriani F, Ardito F, Perri P, Giani A, De Stefano F, Lai Q, Molfino S, Zanello M, Iaria M, La Barba G, Pinotti E, Germani P, Conci S, Ferrari C, Fumagalli L, Romano M, Antonucci A, Zimmitti G, Troci A, Floridi A, Ferraro V, Patauner S, Frena A, Memeo R, Crespi M, Hilal MA, Zanus G, Chiarelli M, Percivale A, Ruzzenente A, Tarchi P, Zago M, Ercolani G, Dalla Valle R, Jovine E, Baiocchi GL, Rossi M, Maestri M, Romano F, Grazi GL, Giuliante F, Aldrighetti L, Ferrero A, and Torzilli G

Subjects
Benchmarking, Hepatectomy adverse effects, Hepatectomy methods, Humans, Liver Cirrhosis complications, Liver Cirrhosis pathology, Liver Cirrhosis surgery, Postoperative Complications, Retrospective Studies, Carcinoma, Hepatocellular, Liver Failure etiology, Liver Neoplasms complications, Liver Neoplasms surgery
Abstract

Background: Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined., Methods: Patients were identified from the Italian national registry HE.RC.O.LE.S. The Achievable Benchmark of Care (ABC) method was employed to identify the benchmarks. The outcomes assessed were the rate of complications, major comorbidities, post-operative ascites (POA), post-hepatectomy liver failure (PHLF), 90-day mortality. Benchmarking was stratified for surgical complexity (CP1, CP2 and CP3)., Results: A total of 978 of 2698 patients fulfilled the inclusion criteria. 431 (44.1%) patients were treated with CP1 procedures, 239 (24.4%) with CP2 and 308 (31.5%) with CP3 procedures. Patients submitted to CP1 had a worse underlying liver function, while the tumor burden was more severe in CP3 cases. The ABC for complications (13.1%, 19.2% and 28.1% for CP1, CP2 and CP3 respectively), major complications (7.6%, 11.1%, 12.5%) and 90-day mortality (0%, 3.3%, 3.6%) increased with the surgical difficulty, but not POA (4.4%, 3.3% and 2.6% respectively) and PHLF (0% for all groups)., Conclusion: We propose benchmarks for open liver resections in HCC cirrhotic patients, stratified for surgical complexity. The difference between the benchmark values and the results obtained during everyday practice reflects the room for potential growth, with the aim to encourage constant improvement among liver surgeons., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Published
2022
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6. The largest western experience on salvage hepatectomy for recurrent hepatocellular carcinoma: propensity score-matched analysis on behalf of He.RC.O.Le.Study Group.

Author

Iaria M, Bianchi G, Fazio F, Ardito F, Perri P, Pontarolo N, Conci S, Donadon M, Zanello M, Lai Q, Famularo S, Molfino S, Sciannamea I, Fumagalli L, Germani P, Floridi A, Ferrari C, Zimmitti G, Troci A, Zago M, Ferraro V, Cipriani F, Patauner S, La Barba G, Romano M, Zanus G, Ercolani G, Frena A, Aldrighetti L, Memeo R, Pinotti E, Crespi M, Hilal MA, Griseri G, Tarchi P, Chiarelli M, Antonucci A, Baiocchi GL, Romano F, Rossi M, Jovine E, Torzilli G, Ruzzenente A, Maestri M, Grazi GL, Giuliante F, Ferrero A, and Dalla Valle R

Subjects
Hepatectomy adverse effects, Humans, Neoplasm Recurrence, Local pathology, Propensity Score, Retrospective Studies, Treatment Outcome, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology
Abstract

Background: We aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments., Methods: Data were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments)., Results: 2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS., Conclusion: SH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Published
2022
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7. Hepatectomy for Metabolic Associated Fatty Liver Disease (MAFLD) related HCC: Propensity case-matched analysis with viral- and alcohol-related HCC.

Author

Conci S, Cipriani F, Donadon M, Marchitelli I, Ardito F, Famularo S, Perri P, Iaria M, Ansaloni L, Zanello M, La Barba G, Patauner S, Pinotti E, Molfino S, Germani P, Romano M, Sciannamea I, Ferrari C, Manzoni A, Troci A, Fumagalli L, Delvecchio A, Floridi A, Memeo R, Chiarelli M, Crespi M, Zimmitti G, Griseri G, Antonucci A, Zanus G, Tarchi P, Baiocchi GL, Zago M, Frena A, Ercolani G, Jovine E, Maestri M, Valle RD, Grazi GL, Romano F, Giuliante F, Torzilli G, Aldrighetti L, and Ruzzenente A

Subjects
Aged, Body Mass Index, Carcinoma, Hepatocellular etiology, Comorbidity, Disease-Free Survival, Female, Humans, Liver Cirrhosis complications, Liver Neoplasms etiology, Male, Middle Aged, Neoplasms, Multiple Primary etiology, Propensity Score, Survival Rate, Tumor Burden, Carcinoma, Hepatocellular surgery, Hepatectomy, Hepatitis B, Chronic complications, Hepatitis C, Chronic complications, Liver Diseases, Alcoholic complications, Liver Neoplasms surgery, Neoplasms, Multiple Primary surgery, Non-alcoholic Fatty Liver Disease complications
Abstract

Background and Aims: We investigated the clinical impact of the newly defined metabolic-associated fatty liver disease (MAFLD) in patients undergoing hepatectomy for HCC (MAFLD-HCC) comparing the characteristics and outcomes of patients with MAFLD-HCC to viral- and alcoholic-related HCC (HCV-HCC, HBV-HCC, A-HCC)., Methods: A retrospective analysis of patients included in the He.RC.O.Le.S. Group registry was performed. The characteristics, short- and long-term outcomes of 1315 patients included were compared according to the study group before and after an exact propensity score match (PSM)., Results: Among the whole study population, 264 (20.1%) had MAFLD-HCC, 205 (15.6%) had HBV-HCC, 671 (51.0%) had HCV-HCC and 175 (13.3%) had A-HCC. MAFLD-HCC patients had higher BMI (p < 0.001), Charlson Comorbidities Index (p < 0.001), size of tumour (p < 0.001), and presence of cirrhosis (p < 0.001). After PSM, the 90-day mortality and severe morbidity rates were 5.9% and 7.1% in MAFLD-HCC, 2.3% and 7.1% in HBV-HCC, 3.5% and 11.7% in HCV-HCC, and 1.2% and 8.2% in A-HCC (p = 0.061 and p = 0.447, respectively). The 5-year OS and RFS rates were 54.4% and 37.1% in MAFLD-HCC, 64.9% and 32.2% in HBV-HCC, 53.4% and 24.7% in HCV-HCC and 62.0% and 37.8% in A-HCC (p = 0.345 and p = 0.389, respectively). Cirrhosis, multiple tumours, size and satellitosis seems to be the independent predictors of OS., Conclusion: Hepatectomy for MAFLD-HCC seems to have a higher but acceptable operative risk. However, long-term outcomes seems to be related to clinical and pathological factors rather than aetiological risk factors., Competing Interests: Declaration of competing interest The Authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Published
2022
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8. The Impact of Postoperative Ascites on Survival After Surgery for Hepatocellular Carcinoma: a National Study.

Author

Famularo S, Donadon M, Cipriani F, Ardito F, Iaria M, Carissimi F, Perri P, Dominioni T, Zanello M, Conci S, Molfino S, D'Acapito F, Germani P, Ferrari C, Patauner S, Pinotti E, Sciannamea I, Garatti M, Lodo E, Troci A, Delvecchio A, Floridi A, Bernasconi DP, Fumagalli L, Chiarelli M, Memeo R, Crespi M, Zanus G, Zimmitti G, Antonucci A, Zago M, Frena A, Griseri G, Tarchi P, Ercolani G, Baiocchi GL, Ruzzenente A, Jovine E, Maestri M, Grazi G, Valle RD, Giuliante F, Aldrighetti L, Romano F, and Torzilli G

Subjects
Ascites epidemiology, Ascites etiology, Disease-Free Survival, Hepatectomy adverse effects, Humans, Neoplasm Recurrence, Local epidemiology, Postoperative Complications epidemiology, Postoperative Complications etiology, Retrospective Studies, Carcinoma, Hepatocellular surgery, Liver Neoplasms surgery
Abstract

Background: Postoperative ascites (POA) is the most common complication after liver surgery for hepatocarcinoma (HCC), but its impact on survival is not reported. The aim of the study is to investigate its impact on overall survival (OS) and disease-free survival (DFS), and secondarily to identify the factors that may predict the occurrence., Method: Data were collected from 23 centers participating in the Italian Surgical HCC Register (HE.RC.O.LE.S. Group) between 2008 and 2018. POA was defined as ≥500 ml of ascites in the drainage after surgery. Survival analysis was conducted by the Kaplan Meier method. Risk adjustment analysis was conducted by Cox regression to investigate the risk factors for mortality and recurrence., Results: Among 2144 patients resected for HCC, 1871(88.5%) patients did not experience POA while 243(11.5%) had the complication. Median OS for NO-POA group was not reached, while it was 50 months (95%CI = 41-71) for those with POA (p < 0.001). POA independently increased the risk of mortality (HR = 1.696, 95%CI = 1.352-2.129, p < 0.001). Relapse risk after surgery was not predicted by the occurrence of POA. Presence of varices (OR = 2.562, 95%CI = 0.921-1.822, p < 0.001) and bilobar disease (OR = 1.940, 95%CI = 0.921-1.822, p: 0.004) were predictors of POA, while laparoscopic surgery was protective (OR = 0.445, 95%CI = 0.295-0.668, p < 0.001). Ninety-day mortality was higher in the POA group (9.1% vs 1.9% in NO-POA group, p < 0.001)., Conclusion: The occurrence of POA after surgery for HCC strongly increases the risk of long-term mortality and its occurrence is relatively frequent. More efforts in surgical planning should be made to limit its occurrence., (© 2021. The Society for Surgery of the Alimentary Tract.)

Published
2021
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9. Curative versus palliative treatments for recurrent hepatocellular carcinoma: a multicentric weighted comparison.

Author

Famularo S, Donadon M, Cipriani F, Bernasconi DP, LaBarba G, Dominioni T, Iaria M, Molfino S, Conci S, Ferrari C, Garatti M, Delvecchio A, Troci A, Patauner S, Frassani S, Cosimelli M, Zanus G, Giuliante F, Jovine E, Valsecchi MG, Grazi G, Antonucci A, Frena A, Crespi M, Memeo R, Zimmitti G, Griseri G, Ruzzenente A, Baiocchi G, DallaValle R, Maestri M, Ercolani G, Aldrighetti L, Torzilli G, and Romano F

Subjects
Humans, Neoplasm Recurrence, Local therapy, Palliative Care, Retrospective Studies, Treatment Outcome, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic, Liver Neoplasms therapy
Abstract

Background: Management of recurrence after surgery for hepatocellular carcinoma (rHCC) is still a debate. The aim was to compare the Survival after Recurrence (SAR) of curative (surgery or thermoablation) versus palliative (TACE or Sorafenib) treatments for patients with rHCC., Methods: This is a multicentric Italian study, which collected data between 2007 and 2018 from 16 centers. Selected patients were then divided according to treatment allocation in Curative (CUR) or Palliative (PAL) Group. Inverse Probability Weighting (IPW) was used to weight the groups., Results: 1,560 patients were evaluated, of which 421 experienced recurrence and were then eligible: 156 in CUR group and 256 in PAL group. Tumor burden and liver function were weighted by IPW, and two pseudo-population were obtained (CUR = 397.5 and PAL = 415.38). SAR rates at 1, 3 and 5 years were respectively 98.3%, 76.7%, 63.8% for CUR and 91.7%, 64.2% and 48.9% for PAL (p = 0.007). Median DFS was 43 months (95%CI = 32-74) for CUR group, while it was 23 months (95%CI = 18-27) for PAL (p = 0.017). Being treated by palliative approach (HR = 1.75; 95%CI = 1.14-2.67; p = 0.01) and having a median size of the recurrent nodule>5 cm (HR = 1.875; 95%CI = 1.22-2.86; p = 0.004) were the only predictors of mortality after recurrence, while time to recurrence was the only protective factor (HR = 0.616; 95%CI = 0.54-0.69; p<0.001)., Conclusion: Curative approaches may guarantee long-term survival in case of recurrence., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Published
2021
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10. Hepatocellular carcinoma surgical and oncological trends in a national multicentric population: the HERCOLES experience.

Author

Famularo S, Donadon M, Cipriani F, Ardito F, Carissimi F, Perri P, Iaria M, Dominioni T, Zanello M, Conci S, Molfino S, LaBarba G, Ferrari C, Germani P, Patauner S, Pinotti E, Lodo E, Garatti M, Sciannamea I, Troci A, Conticchio M, Floridi A, Chiarelli M, Fumagalli L, Memeo R, Crespi M, Antonucci A, Zimmitti G, Zanus G, Zago M, Frena A, Tarchi P, Griseri G, Ercolani G, Baiocchi GL, Ruzzenente A, Jovine E, Maestri M, DallaValle R, Grazi GL, Giuliante F, Aldrighetti L, Torzilli G, and Romano F

Subjects
Aged, Carcinoma, Hepatocellular epidemiology, Female, Hepatectomy methods, Hepatectomy trends, Humans, Italy epidemiology, Laparoscopy methods, Laparoscopy trends, Liver Neoplasms epidemiology, Male, Middle Aged, Neoplasm Recurrence, Local, Registries, Reoperation, Carcinoma, Hepatocellular surgery, Datasets as Topic, Liver Neoplasms surgery, Outcome Assessment, Health Care methods
Abstract

Liver surgery is the first line treatment for hepatocarcinoma. Hepatocarcinoma Recurrence on the Liver Study (HERCOLES) Group was established in 2018 with the goal to create a network of Italian centres sharing data and promoting scientific research on hepatocellular carcinoma (HCC) in the surgical field. This is the first national report that analyses the trends in surgical and oncological outcomes. Register data were collected by 22 Italian centres between 2008 and 2018. One hundred sixty-four variables were collected, regarding liver functional status, tumour burden, radiological, intraoperative and perioperative data, histological features and oncological follow-up. 2381 Patients were enrolled. Median age was 70 (IQR 63-75) years old. Cirrhosis was present in 1491 patients (62.6%), and Child-A were 89.9% of cases. HCC was staged as BCLC0-A in almost 50% of cases, while BCLC B and C were 20.7% and 17.9% respectively. Major liver resections were 481 (20.2%), and laparoscopy was employed in 753 (31.6%) cases. Severe complications occurred only in 5%. Postoperative ascites was recorded in 10.5% of patients, while posthepatectomy liver failure was observed in 4.9%. Ninety-day mortality was 2.5%. At 5 years, overall survival was 66.1% and disease-free survival was 40.9%. Recurrence was intrahepatic in 74.6% of cases. Redo-surgery and thermoablation for recurrence were performed up to 32% of cases. This is the most updated Italian report of the national experience in surgical treatment for HCC. This dataset is consistently allowing the participating centres in creating multicentric analysis which are already running with a very large sample size and strong power.

Published
2020
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12. The Impact of Postoperative Ascites on Survival After Surgery for Hepatocellular Carcinoma: a National Study

Author

Famularo, S., Donadon, M., Cipriani, F., Ardito, F., Iaria, M., Carissimi, F., Perri, P., Dominioni, T., Zanello, M., Conci, S., Molfino, S., D'Acapito, F., Germani, P., Ferrari, C., Patauner, S., Pinotti, E., Sciannamea, I., Garatti, M., Lodo, E., Troci, A., Delvecchio, A., Floridi, A., Bernasconi, D. P., Fumagalli, L., Chiarelli, M., Memeo, R., Crespi, M., Zanus, G., Zimmitti, G., Antonucci, A., Zago, M., Frena, A., Griseri, G., Tarchi, P., Ercolani, G., Baiocchi, G. L., Ruzzenente, A., Jovine, E., Maestri, M., Grazi, G. L., Valle, R. D., Giuliante, F., Aldrighetti, L., Romano, F., Torzilli, G., Costa, G., Ciulli, C., Giani, A., Ratti, F., Bellobono, M., Cremaschi, E., Valsecchi, M. G., De Peppo, V., Calabrese, F., Desario, G., Lazzari, G., Cucchetti, A., Cosola, D., Percivale, A., Ciola, M., Montuori, M., Frassani, S., Manzoni, A., Salvador, L., Pennacchi, L., Corleone, P., Conticchio, M., Famularo, S., Donadon, M., Cipriani, F., Ardito, F., Iaria, M., Carissimi, F., Perri, P., Dominioni, T., Zanello, M., Conci, S., Molfino, S., D'Acapito, F., Germani, P., Ferrari, C., Patauner, S., Pinotti, E., Sciannamea, I., Garatti, M., Lodo, E., Troci, A., Delvecchio, A., Floridi, A., Bernasconi, D. P., Fumagalli, L., Chiarelli, M., Memeo, R., Crespi, M., Zanus, G., Zimmitti, G., Antonucci, A., Zago, M., Frena, A., Griseri, G., Tarchi, P., Ercolani, G., Baiocchi, G. L., Ruzzenente, A., Jovine, E., Maestri, M., Grazi, G. L., Valle, R. D., Giuliante, F., Aldrighetti, L., Romano, F., Torzilli, G., Costa, G., Ciulli, C., Giani, A., Ratti, F., Bellobono, M., Cremaschi, E., Valsecchi, M. G., De Peppo, V., Calabrese, F., Desario, G., Lazzari, G., Cucchetti, A., Cosola, D., Percivale, A., Ciola, M., Montuori, M., Frassani, S., Manzoni, A., Salvador, L., Pennacchi, L., Corleone, P., Conticchio, M., Famularo S., Donadon M., Cipriani F., Ardito F., Iaria M., Carissimi F., Perri P., Dominioni T., Zanello M., Conci S., Molfino S., D'Acapito F., Germani P., Ferrari C., Patauner S., Pinotti E., Sciannamea I., Garatti M., Lodo E., Troci A., Delvecchio A., Floridi A., Bernasconi D.P., Fumagalli L., Chiarelli M., Memeo R., Crespi M., Zanus G., Zimmitti G., Antonucci A., Zago M., Frena A., Griseri G., Tarchi P., Ercolani G., Baiocchi G.L., Ruzzenente A., Jovine E., Maestri M., Grazi G.L., Valle R.D., Giuliante F., Aldrighetti L., Romano F., Torzilli G., Costa G., Ciulli C., Giani A., Ratti F., Bellobono M., Cremaschi E., Valsecchi M.G., De Peppo V., Calabrese F., DeSario G., Lazzari G., Cucchetti A., Cosola D., Percivale A., Ciola M., Montuori M., Frassani S., Manzoni A., Salvador L., Pennacchi L., Corleone P., Conticchio M., Famularo, S, Donadon, M, Cipriani, F, Ardito, F, Iaria, M, Carissimi, F, Perri, P, Dominioni, T, Zanello, M, Conci, S, Molfino, S, D'Acapito, F, Germani, P, Ferrari, C, Patauner, S, Pinotti, E, Sciannamea, I, Garatti, M, Lodo, E, Troci, A, Delvecchio, A, Floridi, A, Bernasconi, D, Fumagalli, L, Chiarelli, M, Memeo, R, Crespi, M, Zanus, G, Zimmitti, G, Antonucci, A, Zago, M, Frena, A, Griseri, G, Tarchi, P, Ercolani, G, Baiocchi, G, Ruzzenente, A, Jovine, E, Maestri, M, Grazi, G, Valle, R, Giuliante, F, Aldrighetti, L, Romano, F, Torzilli, G, Costa, G, Ciulli, C, Giani, A, Ratti, F, Bellobono, M, Cremaschi, E, Valsecchi, M, De Peppo, V, Calabrese, F, Desario, G, Lazzari, G, Cucchetti, A, Cosola, D, Percivale, A, Ciola, M, Montuori, M, Frassani, S, Manzoni, A, Salvador, L, Pennacchi, L, Corleone, P, and Conticchio, M

Subjects
Laparoscopic surgery, medicine.medical_specialty, endocrine system, Carcinoma, Hepatocellular, Disease-free survival, Hepatocellular carcinoma, medicine.medical_treatment, Settore MED/18 - CHIRURGIA GENERALE, 030230 surgery, NO, Liver surgery, Overall survival, Postoperative ascites, Postoperative complications, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, Ascites, Risk of mortality, Medicine, Hepatectomy, Humans, Survival analysis, LS7_4, Retrospective Studies, business.industry, Proportional hazards model, Carcinoma, Liver Neoplasms, Gastroenterology, Hepatocellular, medicine.disease, Surgery, Postoperative complication, Postoperative ascite, Neoplasm Recurrence, Local, 030220 oncology & carcinogenesis, Ascite, medicine.symptom, Neoplasm Recurrence, Local, business, Complication, Varices, Human
Abstract

Background: Postoperative ascites (POA) is the most common complication after liver surgery for hepatocarcinoma (HCC), but its impact on survival is not reported. The aim of the study is to investigate its impact on overall survival (OS) and disease-free survival (DFS), and secondarily to identify the factors that may predict the occurrence. Method: Data were collected from 23 centers participating in the Italian Surgical HCC Register (HE.RC.O.LE.S. Group) between 2008 and 2018. POA was defined as ≥500 ml of ascites in the drainage after surgery. Survival analysis was conducted by the Kaplan Meier method. Risk adjustment analysis was conducted by Cox regression to investigate the risk factors for mortality and recurrence. Results: Among 2144 patients resected for HCC, 1871(88.5%) patients did not experience POA while 243(11.5%) had the complication. Median OS for NO-POA group was not reached, while it was 50 months (95%CI = 41–71) for those with POA (p < 0.001). POA independently increased the risk of mortality (HR = 1.696, 95%CI = 1.352–2.129, p < 0.001). Relapse risk after surgery was not predicted by the occurrence of POA. Presence of varices (OR = 2.562, 95%CI = 0.921–1.822, p < 0.001) and bilobar disease (OR = 1.940, 95%CI = 0.921–1.822, p: 0.004) were predictors of POA, while laparoscopic surgery was protective (OR = 0.445, 95%CI = 0.295–0.668, p < 0.001). Ninety-day mortality was higher in the POA group (9.1% vs 1.9% in NO-POA group, p < 0.001). Conclusion: The occurrence of POA after surgery for HCC strongly increases the risk of long-term mortality and its occurrence is relatively frequent. More efforts in surgical planning should be made to limit its occurrence.

Published
2021

13. Hepatocellular carcinoma surgical and oncological trends in a national multicentric population: the HERCOLES experience

Author

Famularo, S., Donadon, M., Cipriani, Fabrizio, Ardito, Francesco, Carissimi, F., Perri, Pierluigi, Iaria, M., Dominioni, T., Zanello, M., Conci, S., Molfino, S., Labarba, G., Ferrari, C., Germani, P., Patauner, S., Pinotti, E., Lodo, E., Garatti, M., Sciannamea, I., Troci, A., Conticchio, M., Floridi, A., Chiarelli, M., Fumagalli, L., Memeo, R., Crespi, M., Antonucci, Anna Maria, Zimmitti, Giuseppe, Zanus, G., Zago, M., Frena, A., Tarchi, P., Griseri, G., Ercolani, G., Baiocchi, G. L., Ruzzenente, A., Jovine, E., Maestri, Marta, Dallavalle, R., Grazi, G. L., Giuliante, Felice, Aldrighetti, L., Torzilli, Guido, Romano, Federica, Bernasconi, D. P., Ciulli, C., Giani, A., Costa, G., Ratti, F., Bellobono, M., Calabrese, F., Cremaschi, E., De Peppo, V., Cucchetti, A., Lazzari, Giovanni, Percivale, A., Ciola, M., Sega, V., Frassani, S., Del Vecchio, Arianna, Pennacchi, L., Corleone, P., Cosola, D., Salvador, L., Montuori, M., Famularo, Simone, Donadon, Matteo, Cipriani, Federica, Ardito, Francesco, Carissimi, Francesca, Perri, Pasquale, Iaria, Maurizio, Dominioni, Tommaso, Zanello, Matteo, Conci, Simone, Molfino, Sarah, LaBarba, Giuliano, Ferrari, Cecilia, Germani, Paola, Patauner, Stefan, Pinotti, Enrico, Lodo, Enrico, Garatti, Marco, Sciannamea, Ivano, Troci, Albert, Conticchio, Maria, Floridi, Antonio, Chiarelli, Marco, Fumagalli, Luca, Memeo, Riccardo, Crespi, Michele, Antonucci, Adelmo, Zimmitti, Giuseppe, Zanus, Giacomo, Zago, Mauro, Frena, Antonio, Tarchi, Paola, Griseri, Guido, Ercolani, Giorgio, Baiocchi, Gian Luca, Ruzzenente, Andrea, Jovine, Elio, Maestri, Marcello, DallaValle, Raffaele, Grazi, Gian Luca, Giuliante, Felice, Aldrighetti, Luca, Torzilli, Guido, Romano, Fabrizio, Famularo, S., Donadon, M., Cipriani, F., Ardito, F., Carissimi, F., Perri, P., Iaria, M., Dominioni, T., Zanello, M., Conci, S., Molfino, S., Labarba, G., Ferrari, C., Germani, P., Patauner, S., Pinotti, E., Lodo, E., Garatti, M., Sciannamea, I., Troci, A., Conticchio, M., Floridi, A., Chiarelli, M., Fumagalli, L., Memeo, R., Crespi, M., Antonucci, A., Zimmitti, G., Zanus, G., Zago, M., Frena, A., Tarchi, P., Griseri, G., Ercolani, G., Baiocchi, G. L., Ruzzenente, A., Jovine, E., Maestri, M., Dallavalle, R., Grazi, G. L., Giuliante, F., Aldrighetti, L., Torzilli, G., Romano, F., Bernasconi, D. P., Ciulli, C., Giani, A., Costa, G., Ratti, F., Bellobono, M., Calabrese, F., Cremaschi, E., De Peppo, V., Cucchetti, A., Lazzari, G., Percivale, A., Ciola, M., Sega, V., Frassani, S., Del Vecchio, A., Pennacchi, L., Corleone, P., Cosola, D., Salvador, L., and Montuori, M.

Subjects
Male, Cirrhosis, Outcome Assessment, Hepatocellular carcinoma, Settore MED/18 - CHIRURGIA GENERALE, Datasets as Topic, HERCOLES, Hepatocarcinoma recurrence, Liver surgery, Redo surgery, Outcome Assessment, Health Care, Ascites, Registries, Laparoscopy, education.field_of_study, medicine.diagnostic_test, Liver Neoplasms, Middle Aged, Italy, Local, Radiological weapon, Female, medicine.symptom, Reoperation, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, NO, Internal medicine, medicine, Hepatectomy, Humans, education, LS7_4, Aged, business.industry, Carcinoma, Hepatocellular, Perioperative, Hepatology, medicine.disease, Surgery, Health Care, Neoplasm Recurrence, Neoplasm Recurrence, Local, business
Abstract

Liver surgery is the first line treatment for hepatocarcinoma. Hepatocarcinoma Recurrence on the Liver Study (HERCOLES) Group was established in 2018 with the goal to create a network of Italian centres sharing data and promoting scientific research on hepatocellular carcinoma (HCC) in the surgical field. This is the first national report that analyses the trends in surgical and oncological outcomes. Register data were collected by 22 Italian centres between 2008 and 2018. One hundred sixty-four variables were collected, regarding liver functional status, tumour burden, radiological, intraoperative and perioperative data, histological features and oncological follow-up. 2381 Patients were enrolled. Median age was 70 (IQR 63-75) years old. Cirrhosis was present in 1491 patients (62.6%), and Child-A were 89.9% of cases. HCC was staged as BCLC0-A in almost 50% of cases, while BCLC B and C were 20.7% and 17.9% respectively. Major liver resections were 481 (20.2%), and laparoscopy was employed in 753 (31.6%) cases. Severe complications occurred only in 5%. Postoperative ascites was recorded in 10.5% of patients, while posthepatectomy liver failure was observed in 4.9%. Ninety-day mortality was 2.5%. At 5years, overall survival was 66.1% and disease-free survival was 40.9%. Recurrence was intrahepatic in 74.6% of cases. Redo-surgery and thermoablation for recurrence were performed up to 32% of cases. This is the most updated Italian report of the national experience in surgical treatment for HCC. This dataset is consistently allowing the participating centres in creating multicentric analysis which are already running with a very large sample size and strong power. Liver surgery is the first line treatment for hepatocarcinoma. Hepatocarcinoma Recurrence on the Liver Study (HERCOLES) Group was established in 2018 with the goal to create a network of Italian centres sharing data and promoting scientific research on hepatocellular carcinoma (HCC) in the surgical field. This is the first national report that analyses the trends in surgical and oncological outcomes. Register data were collected by 22 Italian centres between 2008 and 2018. One hundred sixty-four variables were collected, regarding liver functional status, tumour burden, radiological, intraoperative and perioperative data, histological features and oncological follow-up. 2381 Patients were enrolled. Median age was 70 (IQR 63–75) years old. Cirrhosis was present in 1491 patients (62.6%), and Child-A were 89.9% of cases. HCC was staged as BCLC0-A in almost 50% of cases, while BCLC B and C were 20.7% and 17.9% respectively. Major liver resections were 481 (20.2%), and laparoscopy was employed in 753 (31.6%) cases. Severe complications occurred only in 5%. Postoperative ascites was recorded in 10.5% of patients, while posthepatectomy liver failure was observed in 4.9%. Ninety-day mortality was 2.5%. At 5years, overall survival was 66.1% and disease-free survival was 40.9%. Recurrence was intrahepatic in 74.6% of cases. Redo-surgery and thermoablation for recurrence were performed up to 32% of cases. This is the most updated Italian report of the national experience in surgical treatment for HCC. This dataset is consistently allowing the participating centres in creating multicentric analysis which are already running with a very large sample size and strong power.

Published
2020

14. The largest western experience on salvage hepatectomy for recurrent hepatocellular carcinoma: propensity score-matched analysis on behalf of He.RC.O.Le.Study Group

Author

Iaria, M, Bianchi, G, Fazio, F, Ardito, F, Perri, P, Pontarolo, N, Conci, S, Donadon, M, Zanello, M, Lai, Q, Famularo, S, Molfino, S, Sciannamea, I, Fumagalli, L, Germani, P, Floridi, A, Ferrari, C, Zimmitti, G, Troci, A, Zago, M, Ferraro, V, Cipriani, F, Patauner, S, La Barba, G, Romano, M, Zanus, G, Ercolani, G, Frena, A, Aldrighetti, L, Memeo, R, Pinotti, E, Crespi, M, Hilal, Ma, Griseri, G, Tarchi, P, Chiarelli, M, Antonucci, A, Baiocchi, Gl, Romano, F, Rossi, M, Jovine, E, Torzilli, G, Ruzzenente, A, Maestri, M, Grazi, Gl, Giuliante, F, Ferrero, A, Dalla Valle, R, Group, HE. RC. O. LE. S., HERCOLES GROUP Contributors: Mario Giuffrida, Nadia, Russolillo, Francesco, Razionale, DE PEPPO, Valerio, Matteo, Tomasoni, Ivan, Marchitelli, Guido, Costa, LARGHI LAUREIRO, Zoe, Mauro, Scotti, Pietro, Calcagno, Davide, Cosola, Angelo, Franceschi, Alberto, Manzoni, Luca, Pennacchi, Mauro, Montuori, Maria, Conticchio, Francesca, Ratti, Francesca, Notte, Alessandro, Cucchetti, Luca, Salvador, Pio, Corleone, Mattia, Garancini, and Cristina, Ciulli.

Subjects
long-term outcome, recurrence, Carcinoma, Hepatocellular, Hepatology, Liver resection, Hepatocellular carcinoma, Settore MED/18 - CHIRURGIA GENERALE, Carcinoma, Liver Neoplasms, Gastroenterology, Hepatocellular, NO, Neoplasm Recurrence, Treatment Outcome, Local, Recurrent disease, Hepatectomy, Humans, HCC, Neoplasm Recurrence, Local, Liver surgery, Propensity Score, Retrospective Studies
Abstract

We aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments.Data were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments).2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS.SH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented.

Published
2021

15. Hepatectomy for Metabolic Associated Fatty Liver Disease (MAFLD) related HCC: Propensity case-matched analysis with viral- and alcohol-related HCC

Author

Paola Tarchi, Pasquale Perri, Gian Luca Grazi, Marcello Maestri, Maurizio Romano, Giorgio Ercolani, Gian Luca Baiocchi, Michele Crespi, Federica Cipriani, Luca Fumagalli, Guido Torzilli, Matteo Donadon, Cecilia Ferrari, Paola Germani, Ivano Sciannamea, Raffaele Dalla Valle, Antonio Floridi, Sarah Molfino, A. Frena, Ivan Marchitelli, Francesco Ardito, Simone Famularo, Elio Jovine, Fabrizio Romano, Andrea Ruzzenente, G. Griseri, Luca Ansaloni, Antonella Delvecchio, Simone Conci, Giuliano La Barba, Giacomo Zanus, A. Antonucci, M. Iaria, Marco Chiarelli, Luca Aldrighetti, Enrico Pinotti, Stefan Patauner, Matteo Zanello, Riccardo Memeo, Mauro Zago, Felice Giuliante, Alberto Manzoni, Giuseppe Zimmitti, Albert Troci, Conci, S., Cipriani, F., Donadon, M., Marchitelli, I., Ardito, F., Famularo, S., Perri, P., Iaria, M., Ansaloni, L., Zanello, M., La Barba, G., Patauner, S., Pinotti, E., Molfino, S., Germani, P., Romano, M., Sciannamea, I., Ferrari, C., Manzoni, A., Troci, A., Fumagalli, L., Delvecchio, A., Floridi, A., Memeo, R., Chiarelli, M., Crespi, M., Zimmitti, G., Griseri, G., Antonucci, A., Zanus, G., Tarchi, P., Baiocchi, G. L., Zago, M., Frena, A., Ercolani, G., Jovine, E., Maestri, M., Valle, R. D., Grazi, G. L., Romano, F., Giuliante, F., Torzilli, G., Aldrighetti, L., Ruzzenente, A., Conci S., Cipriani F., Donadon M., Marchitelli I., Ardito F., Famularo S., Perri P., Iaria M., Ansaloni L., Zanello M., La Barba G., Patauner S., Pinotti E., Molfino S., Germani P., Romano M., Sciannamea I., Ferrari C., Manzoni A., Troci A., Fumagalli L., Delvecchio A., Floridi A., Memeo R., Chiarelli M., Crespi M., Zimmitti G., Griseri G., Antonucci A., Zanus G., Tarchi P., Baiocchi G.L., Zago M., Frena A., Ercolani G., Jovine E., Maestri M., Valle R.D., Grazi G.L., Romano F., Giuliante F., Torzilli G., Aldrighetti L., and Ruzzenente A.

Subjects
Liver Cirrhosis, Male, Hepatocellular carcinoma, Settore MED/18 - CHIRURGIA GENERALE, medicine.medical_treatment, Disease, Comorbidity, Gastroenterology, Body Mass Index, Neoplasms, Multiple Primary, Non-alcoholic Fatty Liver Disease, Multiple Primary, Neoplasms, Chronic, Liver resection, Liver Diseases, Fatty liver, Liver Neoplasms, General Medicine, Middle Aged, Hepatitis B, Alcoholic, Metabolic syndrome, Hepatitis C, Tumor Burden, Survival Rate, Oncology, Metabolic associated fatty liver disease, Population study, Female, medicine.medical_specialty, Carcinoma, Hepatocellular, Disease-Free Survival, NO, Hepatitis B, Chronic, Hepatectomy, NAFLD, Internal medicine, medicine, Humans, Propensity Score, neoplasms, Pathological, Liver Diseases, Alcoholic, Aged, business.industry, Carcinoma, Hepatocellular, Hepatitis C, Chronic, medicine.disease, digestive system diseases, Propensity score matching, Surgery, business
Abstract

Background and aims: We investigated the clinical impact of the newly defined metabolic-associated fatty liver disease (MAFLD) in patients undergoing hepatectomy for HCC (MAFLD-HCC) comparing the characteristics and outcomes of patients with MAFLD-HCC to viral- and alcoholic-related HCC (HCV-HCC, HBV-HCC, A-HCC). Methods: A retrospective analysis of patients included in the He.RC.O.Le.S. Group registry was performed. The characteristics, short- and long-term outcomes of 1315 patients included were compared according to the study group before and after an exact propensity score match (PSM). Results: Among the whole study population, 264 (20.1%) had MAFLD-HCC, 205 (15.6%) had HBV-HCC, 671 (51.0%) had HCV-HCC and 175 (13.3%) had A-HCC. MAFLD-HCC patients had higher BMI (p < 0.001), Charlson Comorbidities Index (p < 0.001), size of tumour (p < 0.001), and presence of cirrhosis (p < 0.001). After PSM, the 90-day mortality and severe morbidity rates were 5.9% and 7.1% in MAFLD-HCC, 2.3% and 7.1% in HBV-HCC, 3.5% and 11.7% in HCV-HCC, and 1.2% and 8.2% in A-HCC (p = 0.061 and p = 0.447, respectively). The 5-year OS and RFS rates were 54.4% and 37.1% in MAFLD-HCC, 64.9% and 32.2% in HBV-HCC, 53.4% and 24.7% in HCV-HCC and 62.0% and 37.8% in A-HCC (p = 0.345 and p = 0.389, respectively). Cirrhosis, multiple tumours, size and satellitosis seems to be the independent predictors of OS. Conclusion: Hepatectomy for MAFLD-HCC seems to have a higher but acceptable operative risk. However, long-term outcomes seems to be related to clinical and pathological factors rather than aetiological risk factors.

Published
2022

16. Laparoscopic liver resection of hepatocellular carcinoma located in unfavorable segments: a propensity score-matched analysis from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry

Author

G.L. Grazi, Fausto Zamboni, Fulvio Calise, Giovanni Sgroi, Giorgio Rossi, Antonio Giuliani, G.B. Levi Sandri, S. Berti, Abdallah Slim, Antonio Floridi, Roberto Santambrogio, P. Mezzatesta, Felice Giuliante, Giulio Belli, Giovanni Vennarecci, Salvatore Gruttadauria, Vincenzo Mazzaferro, R. Dalla Valle, Alberto Brolese, Alessandro Ferrero, A. Coratti, Francesca Ratti, Nadia Russolillo, Andrea Ruzzenente, Giuseppe Maria Ettorre, A. Antonucci, Giuseppe Navarra, M. Iaria, L. Vincenti, P. Bonsignore, P. Maida, Ugo Boggi, G. Griseri, A. Parisi, Alfredo Guglielmi, Elio Jovine, Enrico Gringeri, Guido Torzilli, Umberto Cillo, Michele Colledan, F. Di Benedetto, Paolo Magistri, A. Frena, Fabio Ferla, Andrea Scotti, Matteo Virdis, A.D. Pinna, Luca Aldrighetti, L. De Carlis, Graziano Ceccarelli, Sandri, Gbl, Ettorre, Gm, Aldrighetti, L, Cillo, U, Dalla Valle, R, Guglielmi, A, Mazzaferro, V, Ferrero, A, Di Benedetto, F, Gruttadauria, S, De Carlis, L, Vennarecci, G, Antonucci, A, Belli, G, Berti, S, Boggi, U, Bonsignore, P, Brolese, A, Calise, F, Ceccarelli, G, Colledan, M, Coratti, A, Ferla, F, Floridi, A, Frena, A, Giuliani, A, Giuliante, F, Grazi, Gl, Gringeri, E, Griseri, G, Iaria, M, Jovine, E, Paolo, M, Maida, P, Mezzatesta, P, Russolillo, N, Navarra, G, Parisi, A, Pinna, Ad, Ratti, F, Rossi, Ge, Ruzzenente, A, Santambrogio, R, Scotti, A, Sgroi, G, Slim, A, Torzilli, G, Vincenti, L, Virdis, M, Zamboni, F, Levi Sandri G.B., Ettorre G.M., Aldrighetti L., Cillo U., Dalla Valle R., Guglielmi A., Mazzaferro V., Ferrero A., Di Benedetto F., Gruttadauria S., De Carlis L., Vennarecci G., Antonucci A., Belli G., Berti S., Boggi U., Bonsignore P., Brolese A., Calise F., Ceccarelli G., Colledan M., Coratti A., Ferla F., Floridi A., Frena A., Giuliani A., Giuliante F., Grazi G.L., Gringeri E., Griseri G., Iaria M., Jovine E., Magistri P., Maida P., Mezzatesta P., Russolillo N., Navarra G., Parisi A., Pinna A.D., Ratti F., Rossi G.E., Ruzzenente A., Santambrogio R., Scotti A., Sgroi G., Slim A., Torzilli G., Vincenti L., Virdis M., Zamboni F., Levi Sandri, G, Ettorre, G, Grazi, G, Magistri, P, Pinna, A, and Rossi, G

Subjects
Laparoscopic surgery, Registrie, Male, Hepatocellular carcinoma, medicine.medical_treatment, Settore MED/18 - CHIRURGIA GENERALE, Laparoscopic HCC, Posterior segment, Hepatocellular carcinoma, IGoMILS, Child B, Laparoscopic liver resection, 0302 clinical medicine, Postoperative Complications, Prospective Studies, Registries, Laparoscopy, Prospective cohort study, medicine.diagnostic_test, Laparoscopic HCC, Liver Neoplasms, Margins of Excision, IGoMILS, Middle Aged, Laparoscopic liver resection, Child B, Italy, Liver Neoplasm, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Human, medicine.medical_specialty, Carcinoma, Hepatocellular, Matched-Pair Analysis, Operative Time, NO, 03 medical and health sciences, medicine, Humans, Hepatectomy, Blood Transfusion, Matched-Pair Analysi, Posterior segment, Aged, Postoperative Care, LS7_4, Surgery, business.industry, Carcinoma, Hepatocellular, Perioperative, medicine.disease, digestive system diseases, Child B, Hepatocellular carcinoma, IGoMILS, Laparoscopic HCC, Laparoscopic liver resection, Posterior segment, Aged, Blood Transfusion, Carcinoma, Hepatocellular, Female, Humans, Italy, Liver Neoplasms, Male, Margins of Excision, Matched-Pair Analysis, Middle Aged, Operative Time, Postoperative Care, Postoperative Complications, Prospective Studies, Registries, Hepatectomy, Laparoscopy, Prospective Studie, Propensity score matching, Postoperative Complication, business, Abdominal surgery
Abstract

Objective: Laparoscopic liver resection (LLR) for Hepatocellular Carcinoma (HCC) is one of the most important indications for the minimally invasive approach. Our study aims to analyze the experience of the Italian Group of Minimally Invasive Liver Surgery with laparoscopic surgical treatment of HCC, with a focus on tumor location and how it affects morbidity and mortality. Methods: 38 centers participated in this study; 372 cases of LLR for HCC were prospectively enrolled. Patients were divided into two groups according to the HCC nodule location. Group 1 favorable location and group 2 unfavorable location. Perioperative outcomes were compared between the two groups before and after a propensity score match (PS) 1:1. Results: Before PS in group 2 surgical time was longer; conversion rate was higher; postoperative transfusion and comprehensive complication index were also higher. PS was performed with a cohort of 298 patients (from 18 centers), with 66 and 232 patients with HCC in unfavorable and favorable locations, respectively. After PS matching, 62 patients from group 1 and group 2 each were compared. Operative and postoperative course were similar in patients with HCC in favorable and unfavorable LLR locations. Surgical margins were found to be identical before and after PS. Conclusions: These results show that LLR in patients with HCC can be safely performed in all segments because of the extensive experience of all surgeons from multiple centers in performing traditional open liver surgery as well as laparoscopic surgery.

Published
2019

17. Curative versus palliative treatments for recurrent hepatocellular carcinoma: a multicentric weighted comparison

Author

Simone Famularo, Matteo Donadon, Federica Cipriani, Davide P. Bernasconi, Giuliano LaBarba, Tommaso Dominioni, Maurizio Iaria, Sarah Molfino, Simone Conci, Cecilia Ferrari, Marco Garatti, Antonella Delvecchio, Albert Troci, Stefan Patauner, Silvia Frassani, Maurizio Cosimelli, Giacomo Zanus, Felice Giuliante, Elio Jovine, Maria G. Valsecchi, GianLuca Grazi, Adelmo Antonucci, Antonio Frena, Michele Crespi, Riccardo Memeo, Giuseppe Zimmitti, Guido Griseri, Andrea Ruzzenente, Gianluca Baiocchi, Raffaele DallaValle, Marcello Maestri, Giorgio Ercolani, Luca Aldrighetti, Guido Torzilli, Fabrizio Romano, Cristina Ciulli, Alessandro Giani, Francesca Carissimi, Guido Costa, Francesca Ratti, Alessandro Cucchetti, Francesco Calabrese, Elena Cremaschi, Giovanni Lazzari, Angelo Franceschi, Valentina Sega, Maria Conticchio, Luca Pennacchi, Michele Ciola, Ivano Sciannamea, Valerio De Peppo, Famularo S., Donadon M., Cipriani F., Bernasconi D.P., LaBarba G., Dominioni T., Iaria M., Molfino S., Conci S., Ferrari C., Garatti M., Delvecchio A., Troci A., Patauner S., Frassani S., Cosimelli M., Zanus G., Giuliante F., Jovine E., Valsecchi M.G., Grazi G., Antonucci A., Frena A., Crespi M., Memeo R., Zimmitti G., Griseri G., Ruzzenente A., Baiocchi G., DallaValle R., Maestri M., Ercolani G., Aldrighetti L., Torzilli G., Romano F., Ciulli C., Giani A., Carissimi F., Costa G., Ratti F., Cucchetti A., Calabrese F., Cremaschi E., Lazzari G., Franceschi A., Sega V., Conticchio M., Pennacchi L., Ciola M., Sciannamea I., De Peppo V., Famularo, Simone, Donadon, Matteo, Cipriani, Federica, Bernasconi, Davide P, Labarba, Giuliano, Dominioni, Tommaso, Iaria, Maurizio, Molfino, Sarah, Conci, Simone, Ferrari, Cecilia, Garatti, Marco, Delvecchio, Antonella, Troci, Albert, Patauner, Stefan, Frassani, Silvia, Cosimelli, Maurizio, Zanus, Giacomo, Giuliante, Felice, Jovine, Elio, Valsecchi, Maria G, Grazi, Gianluca, Antonucci, Adelmo, Frena, Antonio, Crespi, Michele, Memeo, Riccardo, Zimmitti, Giuseppe, Griseri, Guido, Ruzzenente, Andrea, Baiocchi, Gianluca, Dallavalle, Raffaele, Maestri, Marcello, Ercolani, Giorgio, Aldrighetti, Luca, Torzilli, Guido, and Romano, Fabrizio

Subjects
Sorafenib, medicine.medical_specialty, recurrence, Carcinoma, Hepatocellular, Tumor burden, 030230 surgery, liver, Gastroenterology, NO, 03 medical and health sciences, 0302 clinical medicine, hepatectomy, Retrospective Studie, Internal medicine, Humans, Medicine, Chemoembolization, Therapeutic, Liver surgery, Retrospective Studies, LS7_4, Hepatology, business.industry, Palliative Care, Liver Neoplasms, hepatocellular carcinoma, medicine.disease, Recurrent Hepatocellular Carcinoma, multicentric, Treatment Outcome, Time to recurrence, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Liver function, Neoplasm Recurrence, Local, business, medicine.drug, Human
Abstract

Background Management of recurrence after surgery for hepatocellular carcinoma (rHCC) is still a debate. The aim was to compare the Survival after Recurrence (SAR) of curative (surgery or thermoablation) versus palliative (TACE or Sorafenib) treatments for patients with rHCC. Methods This is a multicentric Italian study, which collected data between 2007 and 2018 from 16 centers. Selected patients were then divided according to treatment allocation in Curative (CUR) or Palliative (PAL) Group. Inverse Probability Weighting (IPW) was used to weight the groups. Results 1,560 patients were evaluated, of which 421 experienced recurrence and were then eligible: 156 in CUR group and 256 in PAL group. Tumor burden and liver function were weighted by IPW, and two pseudo-population were obtained (CUR = 397.5 and PAL = 415.38). SAR rates at 1, 3 and 5 years were respectively 98.3%, 76.7%, 63.8% for CUR and 91.7%, 64.2% and 48.9% for PAL (p = 0.007). Median DFS was 43 months (95%CI = 32-74) for CUR group, while it was 23 months (95%CI = 18-27) for PAL (p = 0.017). Being treated by palliative approach (HR = 1.75; 95%CI = 1.14–2.67; p = 0.01) and having a median size of the recurrent nodule>5 cm (HR = 1.875; 95%CI = 1.22–2.86; p = 0.004) were the only predictors of mortality after recurrence, while time to recurrence was the only protective factor (HR = 0.616; 95%CI = 0.54–0.69; p Conclusion Curative approaches may guarantee long-term survival in case of recurrence.

Published
2021

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