Brian I Carr1, Vito Guerra2, Rossella Donghia2, Fabio Farinati3, Edoardo G Giannini4, Fabio Piscaglia5, Gian Ludovico Rapaccini6, Maria Di Marco7, Eugenio Caturelli8, Marco Zoli9, Rodolfo Sacco10, Giuseppe Cabibbo11, Fabio Marra12, Andrea Mega13, Filomena Morisco14, Antonio Gasbarrini15, Gianluca Svegliati-Baroni16, Francesco Giuseppe Foschi17, Gabriele Missale18, Alberto Masotto19, Gerardo Nardone20, Giovanni Raimondo21, Francesco Azzaroli22, Gianpaolo Vidili23, Filippo Oliveri24, Franco Trevisani25. 1. Inonu University, Liver Transplant Institute, Malatya, Turkey. 2. National Institute of Digestive Diseases. IRCCS S. de Bellis Research Hospital, Castellana Grotte, Italy. 3. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. 4. Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genova, Italy. 5. Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Internal Medicine-Piscaglia Unit, Bologna, Italy. 6. Gastroenterology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italy. 7. Medicine Unit, Bolognini Hospital, Seriate, Italy. 8. Gastroenterology Unit, Belcolle Hospital, Viterbo, Italy. 9. Department of Medical and Surgical Sciences, Internal Medicine-Zoli Unit, Alma Mater Studiorum - University of Bologna, Bologna, Italy. 10. Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy. 11. Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy. 12. Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Firenze, Italy. 13. Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy. 14. Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Napoli "Federico II", Napoli, Italy. 15. Internal Medicine and Gastroenterology Unit, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy. 16. Gastroenterology Unit, Polytechnic University of Marche, Ancona, Italy. 17. Department of Internal Medicine, Ospedale per gli Infermi of Faenza, Faenza, Italy. 18. Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy. 19. Gastroenterology Unit, Sacred Heart hospital, Negrar, Italy. 20. Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli "Federico II", Napoli, Italy. 21. Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy. 22. Department of Surgical and Medical Sciences, Gastroenterology Unit, Alma Mater Studiorum - University of Bologna, Bologna, Italy. 23. Department of Medical, Surgical and Experimental Sciences. Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria of Sassari, Sassari, Italy. 24. Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine, University of Pisa, Pisa, Italy. 25. Department of Medical and Surgical Sciences, Semeiotics Unit, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
Abstract
BACKGROUND: Hepatocellular carcinoma prognosis depends on both liver and tumor determinants, especially on maximum tumor diameter, multifocality, and presence of portal vein thrombosis, despite apparently complete tumor removal by resection or liver transplantation. AIMS: To examine parameters of hepatocellular carcinoma aggressiveness as tumor size increases. METHODS: A large hepatocellular carcinoma database was examined for trends in serum alpha-fetoprotein and the percentage of patients with macroscopic portal vein thrombosis or tumor multifocality. RESULTS: A total of 13,016 hepatocellular carcinoma patients were identified having full tumor and survival data. Of these, 76.56% were male and 23.44% were female, with a median age of 64.4 years. We found that as the maximum tumor diameter increased, there was a significant trend for increased alpha-fetoprotein levels (P<0.001) and an increased percentage of patients with either portal vein thrombosis or tumor multifocality, each P<0.0001. Furthermore, the increases of both alpha-fetoprotein and portal vein thrombosis were proportionately greater than the related maximum tumor diameter increases. These trends of increased alpha-fetoprotein, portal vein thrombosis, and multifocality with increasing maximum tumor diameter had non-linear patterns. Within alpha-fetoprotein and multifocality trends, there were identifiable sub-trends associated with specific maximum tumor diameter ranges. CONCLUSIONS: The greater fold-increases in alpha-fetoprotein and portal vein thrombosis compared with increases in maximum tumor diameter imply that hepatocellular carcinoma characteristics may change with increasing size to a more aggressive phenotype, suggesting that follow-up tumor sampling might be useful, in addition to baseline tumor sampling, for optimal therapeutic choices to be made.
BACKGROUND: Hepatocellular carcinoma prognosis depends on both liver and tumor determinants, especially on maximum tumor diameter, multifocality, and presence of portal vein thrombosis, despite apparently complete tumor removal by resection or liver transplantation. AIMS: To examine parameters of hepatocellular carcinoma aggressiveness as tumor size increases. METHODS: A large hepatocellular carcinoma database was examined for trends in serum alpha-fetoprotein and the percentage of patients with macroscopic portal vein thrombosis or tumor multifocality. RESULTS: A total of 13,016 hepatocellular carcinoma patients were identified having full tumor and survival data. Of these, 76.56% were male and 23.44% were female, with a median age of 64.4 years. We found that as the maximum tumor diameter increased, there was a significant trend for increased alpha-fetoprotein levels (P<0.001) and an increased percentage of patients with either portal vein thrombosis or tumor multifocality, each P<0.0001. Furthermore, the increases of both alpha-fetoprotein and portal vein thrombosis were proportionately greater than the related maximum tumor diameter increases. These trends of increased alpha-fetoprotein, portal vein thrombosis, and multifocality with increasing maximum tumor diameter had non-linear patterns. Within alpha-fetoprotein and multifocality trends, there were identifiable sub-trends associated with specific maximum tumor diameter ranges. CONCLUSIONS: The greater fold-increases in alpha-fetoprotein and portal vein thrombosis compared with increases in maximum tumor diameter imply that hepatocellular carcinoma characteristics may change with increasing size to a more aggressive phenotype, suggesting that follow-up tumor sampling might be useful, in addition to baseline tumor sampling, for optimal therapeutic choices to be made.