Trends in Tumor Indices in Relation to Increased Hepatocellular Carcinoma Size: Evidence for Tumor Evolution as a Functi
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ORIGINAL RESEARCH
Trends in Tumor Indices in Relation to Increased Hepatocellular Carcinoma Size: Evidence for Tumor Evolution as a Function of Growth Brian I. Carr 1,2 & V. Guerra 3 & R. Donghia 3 & S. Yilmaz 1 Accepted: 28 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background The prognosis of HCC depends in large measure on maximum tumor diameter (MTD). Aims To examine characteristics of tumor aggressiveness over an MTD range of < 2 to 8 cm. Methods A large HCC database was examined retrospectively for trends in serum alpha-fetoprotein (AFP), and percent of patients with macroscopic portal vein thrombosis (PVT) or tumor multifocality. Results There was a significant trend to increased serum AFP levels and percent of patients with PVT, for each, p < 0.001. Within those trends, there were clearly identifiable sub-trends for variations of AFP or percent PVT patients, associated with specific MTD ranges. Calculation of the fold increase for either AFP or percent PVT patients over distinct MTD ranges showed a greater increase of AFP or percent PVT patients compared with the related MTD increase. Interestingly, the increase in percent PVT was mainly independent of AFP. Conclusions Patterns of AFP and PVT increase can be discerned with increasing MTD, which are nonlinear. The greater fold increase in tumor aggressiveness factors compared with MTD suggests that HCCs may change with increasing size to a more aggressive phenotype. Baseline HCC biopsies might therefore be insufficient in future rational HCC management, and repeated liquid biopsies have potential in following HCC evolution and thus choices of therapies. Keywords HCC . MTD . PVT . Evolution
Abbreviations HCC Hepatocellular carcinoma PVT Macroscopic portal vein thrombosis AFP Alpha-fetoprotein MTD Maximum tumor diameter CT Computerized axial tomography scan
* Brian I. Carr [email protected] 1
İnönü University, Malatya, Turkey
2
Liver Transplant Institute, Inonu University, Bulgurlu Mah, Elazig Yolu 15 km, 44289 Merkez Battalgazi, Malatya, Turkey
3
National Institute of Gastroenterology, S. de Bellis Research Hospital, Castellana Grotte (BA), Italy
Introduction The idea that 5 cm or below is a key number for tumor size that relates to long-term outcomes after liver transplant for hepatocellular carcinoma (HCC) single lesions (or 3 cm for up to 3 lesions) has become an accepted part of established clinical practice since it was first published [1]. However, small extensions to this number have also been subsequently shown to be associated with good outcomes [2–4]. Similarly, 3 cm has been reported to be optimal in inducing necrosis by radiofrequency ablation [5] or percutaneous ethanol injection [6]. Several tumor factors influence HCC aggressiveness, including multifocality, portal vein invasion by tumor (PVT), and serum levels of tumor-secreted alpha-fetoprotein (AFP) [7–10], in addition to degree of tumor differentiation and likely other factors [11, 12]. We were interested to know whether HCC b
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