Comparative analysis of the immediate results of surgical treatment in patients with early (BCLC A) and intermediate (BCLC B) stage hepatocellular carcinoma

Introduction. The intermediate stage (Barcelona Clinic Liver Cancer, stage B, BCLC B) of hepatocellular carcinoma (HCC) is relevant for study in terms of existing problems associated with the treatment of patients with this type of pathology. The BCLC B subgroup comprises approximately 30 % of patients at the time of diagnosis of HCC. However, liver resection may be a more effective treatment option in a selected group of patients with intermediate stage disease that is not included in current BCLC guidelines.

Aim. Aim of the study is a comparative assessment of the frequency of postoperative complications and mortality in surgical treatment of patients with HCC BCLC A and BCLC B, analysis of risk factors for the development of severe postoperative complications.

Materials and methods. The retrospective analysis included patients who underwent surgery for BCLC A and BCLC B stages of HCC at the N. N. Blokhin National Medical Research Center of Oncology in the period from 2000 to 2022. The main clinical and laboratory data, intraoperative parameters, severity of postoperative complications according to Clavien– Dindo that arose within 30 days after surgery, postoperative mortality, and factors influencing the risk of developing severe postoperative complications were analyzed.

Results. The BCLC A group included 120 patients, the BCLC B group included 110 patients. Six (5.5 %) patients in the BCLC B group had Сhild – Pugh В cirrhosis, and none in BCLC A group. Model for end-stage liver disease index 10–19 was more often observed in the BCLC B group than in BCLC A group (20 (18.2 %) vs 8 (6.7 %), р = 0.009), more patients had bilobar involvement (38 (34.5 %) vs 11 (9.2 %), р < 0.0001). There were no other significant differences between groups. The median duration of surgery was 160 (60–360) min and 200 (70–360) min in BCLC A and BCLC B groups (p = 0.001), the median blood loss was 700 (10–8000) ml and 1000 (5–7500) ml (p = 0.152), postoperative mortality was 3 (2.5 %) and 3 (2.7 %), respectively (p > 0.99). There were also no statistically significant differences in the total number of early postoperative complications: 46 (38.3 %) in the BCLC B group and 22 (29.1 %) in the BCLC A group, p = 0.164. When conducting a multivariate analysis, only the presence of portal hypertension (hazard ratio 10.596, 95 % confidence interval 3.351–33.500, p < 0.0001) was associated with an increased risk of postoperative complications, while when performing sparing liver resection, a decrease was noted (hazard ratio 0.157, 95 % confidence interval 0.040–0.617, p = 0.008).

Conclusion. During the comparative group analysis, the incidence of postoperative complications and mortality did not differ statistically significantly, which may indicate the safety of surgical treatment in the BCLC B group of patients and indicate the possibility of liver resection in the selected group of patients.

1. Reig M., Forner A., Rimola J. et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022;76(3):681–93. DOI: 10.1016/j.jhep.2021.11.018

2. Lopez-Lopez V., Kalt F., Zhong J.H. et al. The role of resection in hepatocellular carcinoma BCLC stage B: A multi-institutional patient-level meta-analysis and systematic review. Langenbecks Arch Surg 2024;409(1):277. DOI: 10.1007/s00423-024-03466-x. Erratum in: Langenbecks Arch Surg 2024;409(1):324. DOI: 10.1007/s00423-024-03518-2

3. Dindo D., The Clavien–Dindo classification of surgical complications. In: Treatment of postoperative complications after digestive surgery. Springer, 2014. Pp.13–17. DOI: 10.1007/978-1-4471-4354-3_3

4. Rahbari N.N., Garden O.J., Padbury R. et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 2011;149(5):713–24. DOI: 10.1016/j.surg.2010.10.001

5. Mehrabi A., Abbasi Dezfouli S., Schlösser F. et al. Validation of the ISGLS classification of bile leakage after pancreatic surgery: A rare but severe complication. Eur J Surg Oncol 2022;48(12):2440–7. DOI: 10.1016/j.ejso.2022.06.030

6. Rahbari N.N., Garden O.J., Padbury R. et al. Post-hepatectomy haemorrhage: a definition and grading by the International Study Group of Liver Surgery (ISGLS). HPB (Oxford) 2011;13(8):528– 35. DOI: 10.1111/j.1477-2574.2011.00319.x

7. Emenena I., Emenena B., Kweki A.G. et al. Model for end stage liver disease (MELD) score: a tool for prognosis and prediction of mortality in patients with decompensated liver cirrhosis. Cureus 2023;15(5):e39267. DOI: 10.7759/cureus.39267

8. Johnson P.J., Berhane S., Kagebayashi C. et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidencebased approach-the ALBI grade. J Clin Oncol 2015;33(6):550–8. DOI: 10.1200/JCO.2014.57.9151

9. Wai C.T., Greenson J.K., Fontana R.J. et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38(2):518–26. DOI: 10.1053/jhep.2003.50346

10. Mazzaferro V., Llovet J.M., Miceli R. et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 2009;10(1):35–43. DOI: 10.1016/S1470-2045(08)70284-5

11. Sarin S.K., Kumar A. Gastric varices: profile, classification, and management. Am J Gastroenterol 1989;84(10):1244–9. PMID: 2679046

12. Di Sandro S., Centonze L., Pinotti E. et al. Surgical and oncological outcomes of hepatic resection for BCLC-B hepatocellular carcinoma: a retrospective multicenter analysis among 474 consecutive cases. Updates Surg 2019;71:285–93. DOI: 10.1007/s13304-019-00649-w

13. Jianyong L., Lunan Y., Wentao W. et al. Barcelona clinic liver cancer stage B hepatocellular carcinoma: transarterial chemoembolization or hepatic resection? Medicine (Baltimore) 2014;93(26):e180. DOI: 10.1097/MD.0000000000000180

14. Sadamori H., Matsuda H., Shinoura S. et al. Intractable bile leakage after hepatectomy for hepatocellular carcinoma in 359 recent cases. Dig Surg 2012;29(2):149–56. DOI: 10.1159/000337313

15. Shehta A., Farouk A., Said R. et al. Bile leakage after hepatic resection for hepatocellular carcinoma: does it impact the shortand long-term outcomes? J Gastrointest Surg 2022;26(10):2070–81. DOI: 10.1007/s11605-022-05433-7

16. Torzilli G., Donadon M., Marconi M. et al. Hepatectomy for stage B and stage C hepatocellular carcinoma in the Barcelona Clinic Liver Cancer classification: results of a prospective analysis. Arch Surg 2008;143(11):1082–90. DOI: 10.1001/archsurg.143.11.1082

17. Brozzetti S., D’Alterio C., Bini S. et al. Surgical resection is superior to TACE in the treatment of HCC in a well selected cohort of BCLC-B elderly patients – a retrospective observational study. Cancers (Basel) 2022;14(18):4422. DOI: 10.3390/cancers14184422

18. Truant S., Bouras A.F., Hebbar M. et al. Laparoscopic resection vs. open liver resection for peripheral hepatocellular carcinoma in patients with chronic liver disease: a case-matched study. Surg Endosc 2011;25(11):3668–77. DOI: 10.1007/s00464-011-1775-1

19. Kim H.H., Park E.K., Seoung J.S. et al. Liver resection for hepatocellular carcinoma: case-matched analysis of laparoscopic versus open resection. J Korean Surg Soc 2011;80(6):412–9. DOI: 10.4174/jkss.2011.80.6.412

20. Yang J., Choi W.M., Lee D. et al. Outcomes of liver resection and transarterial chemoembolization in patients with multinodular BCLC-A hepatocellular carcinoma. J Liver Cancer 2024;24(2):178–91. DOI: 10.17998/jlc.2024.03.25

21. Santambrogio R., Kluger M.D., Costa M. et al. Hepatic resection for hepatocellular carcinoma in patients with Child–Pugh’s A cirrhosis: is clinical evidence of portal hypertension a contraindication? HPB (Oxford) 2013;15(1):78–84. DOI: 10.1111/j.1477-2574.2012.00594.x

22. Azoulay D., Ramos E., Casellas-Robert M. et al. Liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension. JHEP Rep 2021;3(1):100190. DOI: 10.1016/j.jhepr.2020.100190

23. Cortese S., Tellado J.M. Impact and outcomes of liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension. Cir Cir 2022;90(5):579–87. DOI: 10.24875/CIRU.22000041

24. He W., Zeng Q., Zheng Y. et al. The role of clinically significant portal hypertension in hepatic resection for hepatocellular carcinoma patients: a propensity score matching analysis. BMC Cancer 2015;15:263. DOI: 10.1186/s12885-015-1280-3

25. Choi S.B., Kim H.J., Song T.J. et al. Influence of clinically significant portal hypertension on surgical outcomes and survival following hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis. J Hepatobiliary Pancreat Sci 2014;21(9):639–47. DOI: 10.1002/jhbp.124

26. Torzilli G., Belghiti J., Kokudo N. et al. A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations?: an observational study of the HCC East-West study group. Ann Surg 2013;257(5):929–37. DOI: 10.1097/SLA.0b013e31828329b8