J Liver Cancer.  2024 Mar;24(1):102-112. 10.17998/jlc.2024.01.31.

Liver resection in selective hepatocellular carcinoma with Vp3 or Vp4 portal vein tumor thrombosis improves prognosis

• Lim M
• Kim J
• Rhu J
• Choi GS
• Joh JW

• KMID: 2553822
• DOI: http://doi.org/10.17998/jlc.2024.01.31

Abstract

Background
/Aim: Hepatocellular carcinoma (HCC) tumor thrombi located in the first branch of the portal vein (Vp3) or in the main portal trunk (Vp4) are associated with poor prognosis. This study aimed to investigate the clinicopathological characteristics and risk factors for HCC recurrence and mortality following liver resection (LR) in patients with Vp3 or Vp4 HCC.
Methods
The study included 64 patients who underwent LR for HCC with Vp3 or Vp4 portal vein tumor thrombosis (PVTT).
Results
Fifty-eight patients (90.6%) had Vp3 PVTT, whereas the remaining six patients exhibited Vp4 PVTT. The median tumor size measured 8 cm, with approximately 36% of patients presented with multiple tumors. Fifty-four patients (84.4%) underwent open LR, whereas 10 patients underwent laparoscopic LR. In the Vp4 cases, combined LR and tumor thrombectomy were performed. The 3-year cumulative disease-free survival rate was 42.8% for the Vp3 group and 22.2% for the Vp4 group. The overall survival (OS) rate at 3 years was 47.9% for the Vp3 group and 60.0% for the Vp4 group. Intrahepatic metastasis has been identified as an important contributor to HCC recurrence. High hemoglobin levels are associated with high mortality.
Conclusion
LR is a safe and effective treatment modality for selected patients with Vp3 or Vp4 HCC PVTT. This suggests that LR is a viable option for these patients, with favorable outcomes in terms of OS.

Keyword

Recurrence; Survival; Mortality; Neoadjuvant therapy

Figure

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  Figure 1. (A) Disease-free survival and (B) overall survival in Vp3 and Vp4. HCC, hepatocellular carcinoma.

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  Figure 2. (A) Overall survival following TACE-based locoregional therapies before liver resection and (B) overall survival following combination therapies with TACE and external beam radiation therapy (EBRT) before liver resection. TACE, transarterial chemoembolization; LRT, locoregional therapy; RT, radiation therapy.

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Reference

References

1. Jonas S, Bechstein WO, Steinmüller T, Herrmann M, Radke C, Berg T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001; 33:1080–1086.

2. Villa E, Moles A, Ferretti I, Buttafoco P, Grottola A, Del Buono M, et al. Natural history of inoperable hepatocellular carcinoma: estrogen receptors’ status in the tumor is the strongest prognostic factor for survival. Hepatology. 2000; 32:233–238.

3. Tarantino L, Busto G, Nasto A, Fristachi R, Cacace L, Talamo M, et al. Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: a feasibility study. World J Gastroenterol. 2017; 23:906–918.

4. Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol. 2012; 57:821–829.

5. Korean Liver Cancer Association (KLCA); National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. J Liver Cancer. 2023; 23:1–120.

6. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020; 382:1894–1905.

7. Yang J, Kim JM, Rhu J, Choi GS, Kwon CHD, Joh JW. surgical resection is preferred in selected solitary hepatocellular carcinoma with portal vein tumor thrombosis. Dig Surg. 2022; 39:42–50.

8. Kim JM, Kwon CH, Joh JW, Ko JS, Park JB, Lee JH, et al. C-reactive protein may be a prognostic factor in hepatocellular carcinoma with malignant portal vein invasion. World J Surg Oncol. 2013; 11:92.

9. Chen XP, Qiu FZ, Wu ZD, Zhang ZW, Huang ZY, Chen YF, et al. Effects of location and extension of portal vein tumor thrombus on long-term outcomes of surgical treatment for hepatocellular carcinoma. Ann Surg Oncol. 2006; 13:940–946.

10. Ikai I, Yamamoto Y, Yamamoto N, Terajima H, Hatano E, Shimahara Y, et al. Results of hepatic resection for hepatocellular carcinoma invading major portal and/or hepatic veins. Surg Oncol Clin N Am. 2003; 12:65–75. ix.

11. Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954; 7:462–503.

12. Kim JM, Rhu J, Ha SY, Choi GS, Kwon CHD, Kim G, et al. Realization of improved outcomes following liver resection in hepatocellular carcinoma patients aged 75 years and older. Ann Surg Treat Res. 2021; 101:257–265.

13. Yun SO, Kim JM, Rhu J, Choi GS, Joh JW. Fibrosis-4 index, a predictor for prognosis of hepatocellular carcinoma patients after curative hepatectomy even in hepatitis B virus dominant populations. Ann Surg Treat Res. 2023; 104:195–204.

14. Cerrito L, Annicchiarico BE, Iezzi R, Gasbarrini A, Pompili M, Ponziani FR. Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: beyond the known frontiers. World J Gastroenterol. 2019; 25:4360–4382.

15. Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, et al. Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial. JAMA Oncol. 2018; 4:661–669.

16. Finn RS, Zhu AX, Farah W, Almasri J, Zaiem F, Prokop LJ, et al. Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: a systematic review and meta-analysis. Hepatology. 2018; 67:422–435.

17. Yang Z, Zou R, Zheng Y, Qiu J, Shen J, Liao Y, et al. Lipiodol deposition in portal vein tumour thrombus predicts treatment outcome in HCC patients after transarterial chemoembolisation. Eur Radiol. 2019; 29:5752–5762.

18. Hatano E, Uemoto S, Yamaue H, Yamamoto M; Japanese Society of Hepato-Biliary-Pancreatic Surgery. Significance of hepatic resection and adjuvant hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombus in the first branch of portal vein and the main portal trunk: a project study for hepatic surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci. 2018; 25:395–402.

19. Inoue Y, Hasegawa K, Ishizawa T, Aoki T, Sano K, Beck Y, et al. Is there any difference in survival according to the portal tumor thrombectomy method in patients with hepatocellular carcinoma? Surgery. 2009; 145:9–19.

20. Kondo K, Chijiiwa K, Kai M, Otani K, Nagaike K, Ohuchida J, et al. Surgical strategy for hepatocellular carcinoma patients with portal vein tumor thrombus based on prognostic factors. J Gastrointest Surg. 2009; 13:1078–1083.

21. Han SR, Kim JM, Choi GS, Park JB, Kwon CH, Kim SJ, et al. Protrusion of hepatocellular carcinoma is a predictor of early recurrence in hepatectomy patients after spontaneous rupture. Ann Surg Treat Res. 2016; 91:17–22.

22. Kim DS, Kim BW, Hatano E, Hwang S, Hasegawa K, Kudo A, et al. Surgical outcomes of hepatocellular carcinoma with bile duct tumor thrombus: a Korea-Japan multicenter study. Ann Surg. 2020; 271:913–921.

23. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003; 362:1907–1917.

24. Matsumata T, Kanematsu T, Takenaka K, Yoshida Y, Nishizaki T, Sugimachi K. Patterns of intrahepatic recurrence after curative resection of hepatocellular carcinoma. Hepatology. 1989; 9:457–460.

25. Ban D, Shimada K, Yamamoto Y, Nara S, Esaki M, Sakamoto Y, et al. Efficacy of a hepatectomy and a tumor thrombectomy for hepatocellular carcinoma with tumor thrombus extending to the main portal vein. J Gastrointest Surg. 2009; 13:1921–1928.

26. Aapro M, Österborg A, Gascón P, Ludwig H, Beguin Y. Prevalence and management of cancer-related anaemia, iron deficiency and the specific role of i.v. iron. Ann Oncol. 2012; 23:1954–1962.

27. Huang P, Liu C, Li B, Zheng Y, Zou R, Huang J, et al. Preoperative mean corpuscular hemoglobin affecting long-term outcomes of hepatectomized patients with hepatocellular carcinoma. Mol Clin Oncol. 2016; 4:229–236.

28. Trotter JF, Cohn A, Grant R. Erythrocytosis in a patient with hepatocellular carcinoma. J Clin Gastroenterol. 2002; 35:365–366.

29. Korean Liver Cancer Association (KLCA); National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol. 2022; 28:583–705.

30. Lee S, Song SK, Bae B, Park Y. Comparing efficacies of different treatment regimens in patients with hepatocellular carcinoma accompanied by portal vein tumor thrombus using network meta-analysis. Ann Surg Treat Res. 2022; 103:280–289.

31. Cho Y, Choi JW, Kwon H, Kim KY, Lee BC, Chu HH, et al. Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association. J Liver Cancer. 2023; 23:241–261.

32. Wei Z, Zhao J, Bi X, Zhang Y, Zhou J, Li Z, et al. Neoadjuvant radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a systematic review. Hepatobiliary Surg Nutr. 2022; 11:709–717.

33. Huang DQ, Tran A, Tan EX, Nerurkar SN, Teh R, Teng MLP, et al. Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients. Hepatobiliary Surg Nutr. 2022; 11:848–860.

34. Jin S, Choi WM, Shim JH, Lee D, Kim KM, Lim YS, et al. Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment. J Liver Cancer. 2023; 23:177–188.

35. Wei X, Jiang Y, Zhang X, Feng S, Zhou B, Ye X, et al. Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study. J Clin Oncol. 2019; 37:2141–2151.