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Trends in Tumor Indices in Relation to Increased Hepatocellular Carcinoma Size: Evidence for Tumor Evolution as a Function of Growth

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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.

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Abbreviations

HCC:

Hepatocellular carcinoma

PVT:

Macroscopic portal vein thrombosis

AFP:

Alpha-fetoprotein

MTD:

Maximum tumor diameter

CT:

Computerized axial tomography scan

References

  1. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.

    Article  CAS  PubMed  Google Scholar 

  2. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.

    Article  CAS  Google Scholar 

  3. Llovet JM, Pavel M, Rimola J, Diaz MA, Colmenero J, Saavedra-Perez D, et al. Pilot study of living donor liver transplantation for patients with hepatocellular carcinoma exceeding Milan Criteria (Barcelona Clinic Liver Cancer extended criteria). Liver Transpl. 2018;24:369–79.

    Article  Google Scholar 

  4. Ince V, Akbulut S, Otan E, Ersan V, Karakas S, Sahin TT, et al. Liver transplantation for hepatocellular carcinoma: Malatya experience and proposals for expanded criteria. J Gastrointest Cancer. 2020;51:998–1005.

    Article  CAS  Google Scholar 

  5. Masayoshi T, Wakui N, Sumino Y. Use of radiofrequency ablation in the treatment of hepatocellular carcinoma: experience of ablation protocols. Exp Ther Med. 2012;4:959–61.

    PubMed  Google Scholar 

  6. Ishii H, Okada S, Nose H, Okusaka T, Yoshimori M, Takayama T, et al. Local recurrence of hepatocellular carcinoma after percutaneous ethanol injection. Cancer. 1996;77:1792–6.

    Article  CAS  PubMed  Google Scholar 

  7. Suner A, Carr BI, Akkiz H, Üsküdar O, Yalçın K, et al. Inflammatory markers C-reactive protein and PLR in relation to HCC characteristics. J Transl Sci. 2019;5(3). https://doi.org/10.15761/JTS.1000260.

  8. Carr BI, Akkiz H, Guerra V, Üsküdar O, Kuran S, et al. C-reactive protein and hepatocellular carcinoma: analysis of its relationships to tumor factors. Clin Pract (London). 2018;15:625–34.

    Google Scholar 

  9. Carr BI, Guerra V. A hepatocellular carcinoma aggressiveness index and its relationship to liver enzyme levels. Oncology. 2016;90:215–20.

    Article  CAS  PubMed  Google Scholar 

  10. Carr BI, Guerra V, Giannini EG, Farinati F, Ciccarese F, et al. A liver index and its relationship to indices of HCC aggressiveness. J Integr Oncol. 2016;5:178. https://doi.org/10.4182/2329-6771.1000168.

    Article  PubMed  Google Scholar 

  11. Utsonomiya T, Shimada M, Imura S, Morine Y, Ikemoto T, et al. Molecular signatures of noncancerous liver tissue can predict the risk of late recurrence of hepatocellular carcinoma. J Gastroenterol. 2010;45:146–52.

    Article  Google Scholar 

  12. Nault J-C, De Reynies A, Villanueva A, Caldero J, Rebouissou S, et al. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection. Gastroenterology. 2013;145:176–87.

    Article  CAS  PubMed  Google Scholar 

  13. Pancoska P, Lu S-N, Carr BI. Phenotypic categorization and profiles is small and large hepatocellular carcinomas. J Gastrointest Dig Sys. 2013. https://doi.org/10.4172/2161-069X.S12-001.

  14. Carr BI, Pancoska P, Branch RA. Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study. Hepatol Int. 2009;4:396–405.

    Article  PubMed  Google Scholar 

  15. Duan M, Hao J, Cui S, Wortley DL, Zhang S, et al. Diverse modes of clonal evolution in HBV-related hepatocellular carcinoma revealed by single-cell genome sequencing. Cell Res. 2018;28:359–73.

    Article  CAS  PubMed  Google Scholar 

  16. Craig AJ, von Felden J, Garcia-Lezana T, Sarcognato S, Villanueva AS. Tumor evolution in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2020;17:139–52.

    Article  PubMed  Google Scholar 

  17. Castelli G, Pelosi E, Testa U. Liver cancer: molecular characterization, clonal evolution and cancer stem cells. Cancers (Basel). 2017;9:127. https://doi.org/10.3390/cancers9090127.

    Article  CAS  Google Scholar 

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Funding

This work was supported in part by the NIH grant CA 82723 (B.I.C).

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Authors and Affiliations

  1. İnönü University, Malatya, Turkey

    Brian I. Carr & S. Yilmaz

  2. Liver Transplant Institute, Inonu University, Bulgurlu Mah, Elazig Yolu 15 km, 44289 Merkez Battalgazi, Malatya, Turkey

    Brian I. Carr

  3. National Institute of Gastroenterology, S. de Bellis Research Hospital, Castellana Grotte (BA), Italy

    V. Guerra & R. Donghia

Authors
  1. Brian I. Carr
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  2. V. Guerra
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  3. R. Donghia
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  4. S. Yilmaz
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Contributions

BIC: concept, ideas, and writing

VG and RD: biostatistics

All authors have read and agree with this paper.

Corresponding author

Correspondence to Brian I. Carr.

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The authors declare that they have no conflict of interest.

Statement of Ethics

This work complies with the guidelines of the World Medical Association, Declaration of Helsinki. This work was approved by the institution’s IRB as documented in the methods section.

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Carr, B.I., Guerra, V., Donghia, R. et al. Trends in Tumor Indices in Relation to Increased Hepatocellular Carcinoma Size: Evidence for Tumor Evolution as a Function of Growth. J Gastrointest Canc 51, 1215–1219 (2020). https://doi.org/10.1007/s12029-020-00530-9

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  • DOI: https://doi.org/10.1007/s12029-020-00530-9

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