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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. Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario.

Author

Famularo S, Cillo U, Lauterio A, Donadon M, Vitale A, Serenari M, Cipriani F, Fazio F, Giuffrida M, Ardito F, Dominioni T, Garancini M, Lai Q, Nicolini D, Molfino S, Perri P, Pinotti E, Conci S, Ferrari C, Zanello M, Patauner S, Zimmitti G, Germani P, Chiarelli M, Romano M, De Angelis M, La Barba G, Troci A, Ferraro V, Izzo F, Antonucci A, Belli A, Memeo R, Crespi M, Ercolani G, Boccia L, Zanus G, Tarchi P, Hilal MA, Frena A, Jovine E, Griseri G, Ruzzenente A, Zago M, Grazi G, Baiocchi GL, Vivarelli M, Rossi M, Romano F, Maestri M, Giuliante F, Valle RD, Ferrero A, Aldrighetti L, De Carlis L, Cescon M, and Torzilli G

Subjects
Humans, Hepatectomy adverse effects, Retrospective Studies, Neoplasm Recurrence, Local, Salvage Therapy, Carcinoma, Hepatocellular, Liver Neoplasms, Liver Transplantation adverse effects
Abstract

Background: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group)., Methods: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups., Results: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011)., Conclusion: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed., Competing Interests: Conflict of interest None., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. 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. 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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6. 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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7. 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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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, 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

9. 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

10. 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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