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1. Survival benefit of transplantation for recurrence of hepatocellular carcinoma after liver resection.

Author

Tuci F, Vitale A, D'Amico F, Gringeri E, Neri D, Zanus G, Bassi D, Polacco M, Boetto R, Lodo E, Germani G, Burra P, Angeli P, and Cillo U

Subjects
Adult, Aged, Carcinoma, Hepatocellular mortality, Female, Humans, Intention to Treat Analysis, Liver Neoplasms mortality, Male, Middle Aged, Neoplasm Recurrence, Local mortality, Salvage Therapy mortality, Survival Rate, Treatment Outcome, Carcinoma, Hepatocellular surgery, Hepatectomy, Liver Neoplasms surgery, Liver Transplantation mortality, Neoplasm Recurrence, Local surgery
Abstract

Background: Liver transplantation (LT) for hepatocellular carcinoma (HCC) can be used for tumor recurrence after liver resection (LR) both for initially transplant-eligible patients as conventional salvage therapy (ST) and for non-transplant-eligible patients (beyond Milan criteria) with a goal of downstaging (DW). The aim of this study was to compare the intention-to-treat (ITT) survival rates of patients who are listed for LT, according to these two strategies., Methods: We analyzed a prospective database of 399 consecutive patients who underwent hepatic resection for HCC from 2002 to 2011 to identify patients included in the waiting list for tumor recurrence. Intention-to-treat (ITT) survivals were compared with those of patients resected for HCC within and beyond Milan criteria in the same period and not included in the LT waiting list., Results: The study group consisted of 42 patients, 28 in the ST group (within Milan) and 14 in the DW group (beyond Milan). The 5-year ITT survival rate was similar between the 2 groups, being 64% for ST and 60% for DW (P=.84). Twenty-five patients (15 ST and 10 DW) underwent LT, 13 (10 ST and 3 DW) were still awaiting LT, 4 (3 ST and 1 DW) dropped out of the waiting list because of tumor progression, and 7 (5 ST [33%] and 2 DW [20%]) had tumor recurrence. The 5-year ITT survival of ST patients was similar to that of 252 in-Milan HCC patients resected only (P=.3), whereas 5-year ITT survival of DW patients was significantly higher (P<.01) than that of 105 beyond-Milan HCC patients resected only., Conclusions: LR seems to be a safe and effective therapy both as alternative to transplantation and as downstaging strategy for intermediate-advanced HCC. The survival benefit of salvage LT, however, seems to be higher in the 2nd than in the 1st group., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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2. A new liver autotransplantation technique using subnormothermic machine perfusion for organ preservation in a porcine model.

Author

Gringeri E, Polacco M, D'Amico FE, Scopelliti M, Bassi D, Bonsignore P, Luisetto R, Lodo E, Carraro A, Zanus G, and Cillo U

Subjects
Alanine Transaminase blood, Animals, Aspartate Aminotransferases blood, Biomarkers blood, Disaccharides administration & dosage, Disaccharides adverse effects, Electrolytes administration & dosage, Electrolytes adverse effects, Glutamates administration & dosage, Glutamates adverse effects, Glutathione administration & dosage, Glutathione adverse effects, Hepatic Artery diagnostic imaging, Hepatic Artery surgery, Histidine administration & dosage, Histidine adverse effects, Isotonic Solutions adverse effects, L-Lactate Dehydrogenase blood, Mannitol administration & dosage, Mannitol adverse effects, Models, Animal, Organ Preservation adverse effects, Organ Preservation Solutions adverse effects, Portal Vein diagnostic imaging, Portal Vein surgery, Reperfusion Injury blood, Reperfusion Injury diagnostic imaging, Reperfusion Injury etiology, Reperfusion Injury prevention & control, Replantation, Swine, Time Factors, Transplantation, Autologous, Ultrasonography, Doppler, Color, Vascular Surgical Procedures, Vena Cava, Inferior diagnostic imaging, Vena Cava, Inferior surgery, Hepatectomy adverse effects, Isotonic Solutions administration & dosage, Liver Transplantation adverse effects, Organ Preservation methods, Organ Preservation Solutions administration & dosage, Perfusion adverse effects, Temperature
Abstract

Background: Hepatic resection is the gold standard of therapy for primary and secondary liver tumors, but few patients are eligible for this procedure because of the extent of their neoplasms. Improvements in surgical experience of liver transplantation (OLT), hepatic resection and preservation with sub-normothermic machine perfusion (MP) have prompted the development of a new model of large animal autotransplantation., Methods: Landrace pigs were used in this experiment. After intubation, hepatectomy was performed according to the classic technique. The intrahepatic caval vein was replaced with a homologous tract of porcine thoracic aorta. The liver was perfused with hypothermic Celsior solution followed by MP at 20 °C with oxygenated Krebs solution. An hepatectomy was performed during the period of preservation, which lasted 120 minutes, then the liver was reimplanted into the same animal in a 90° counterclockwise rotated position. The anastomoses were performed in the classic sequence. Samples of intravascular fluid, blood and liver biopsies were obtained at the end of the period of preservation in MP and again at 1 and 3 hours after liver reperfusion to evaluate graft function and microscopic damage., Results: All animals survived the procedure. The peak of aspartate aminotransferase was recorded 60 minutes after reperfusion and the peak of alanine aminotransferase and lactate dehydrogenase after 180 minutes. Histopathologic examination under the light microscope identified no necrosis or congestion. Intraoperative echo-color Doppler documented good patency of the anastomosis and normal venous drainage., Conclusion: This system made it possible to perform hepatic resections and vascular reconstructions ex situ while preserving the organ with mechanical perfusion (ex vivo, ex situ surgery). Improving surgical techniques regarding autotransplantation and our understanding of ischemia-reperfusion damage may enable the development of interesting scenarios for aggressive surgical treatment or radiochemotherapy options to treat primary and secondary liver tumors unsuitable for conventional in situ surgery., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Published
2011
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3. 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

4. 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

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