Annals of Hepato-Biliary-Pancreatic Surgery (한국간담췌외과학회지)

The Korean Association of Hepato-Biliary-Pancreatic Surgery (한국간담췌외과학회)
권호 표지
DOI QR코드

DOI QR Code

Seizing tumor factors for mortality and survival outcomes following liver resection in Indonesia's hepatocellular carcinoma patients

  • Lam Sihardo (Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia) ;
  • Arnetta Naomi Louise Lalisang (Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia) ;
  • Ridho Ardhi Syaiful (Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia) ;
  • Afid Brilliana Putra (Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia) ;
  • Yarman Mazni (Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia) ;
  • Agi Satria Putranto (Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia) ;
  • Toar Jean Maurice Lalisang (Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia)
  • Received : 2024.09.21
  • Accepted : 2024.11.19
  • Published : 2025.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Backgrounds/Aims: The 3-year mortality rate for hepatocellular carcinoma (HCC) in Indonesia was 94.4%. This underscores a significant health issue in Southeast Asia, particularly in Indonesia due to its large population. This study aimed to characterize the outcomes of liver resection for HCC at a National Referral Center in Indonesia. Methods: Between 2010 and 2020, all patients with HCC undergoing liver resection were included as subjects. Variables collected included sex, age, hepatitis status, and tumor's characteristics. Mortality and survival were the primary outcomes of the study. Results: Among seventy patients, the mortality rate was 71.4%, with a median overall survival of 19.0 months (95% confidence interval [95%CI]: 6.831.2). Thirty-one patients (44.3%) had extra-large HCC tumors (> 10 cm). Those with extra-large tumors had a lower median survival of 8.0 months. Child-Pugh B and Edmonson-Steiner grade 4 were associated with an increased mortality risk, with unadjusted hazard ratios (HRs) of 2.2 (95%CI: 1.14.3, p = 0.026) and 3.2 (95%CI: 1.37.7, p = 0.011), respectively. Multivariate analysis indicated that Child-Pugh class B significantly increased the risk of mortality, with an adjusted HR of 2.3 (95%CI: 1.05.2, p = 0.046). Conclusions: While surgical resection is feasible for tumors of any size, most clinical features are not statistically significantly associated with survival outcomes. The prevalence of extra-large tumors among Indonesian HCC patients highlights the importance of early diagnosis and intervention. Surgical intervention at an earlier stage and with better grade tumors could potentially enhance survival outcomes.

Keywords

Acknowledgement

Authors thank to all staff of Digestive Division, Department of Surgery, Dr. Cipto Mangunkusumo Hospital who performed liver resection during 2010-2020. Also, Muhammad Luthfi Prasetyo, MD and Natan Kevin Partogu Siagian, MD for their assistance in HCC registry management during this research.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-249. https://doi.org/10.3322/caac.21660
  2. Liang CW, Yang HC, Islam MM, Nguyen PAA, Feng YT, Hou ZY, et al. Predicting hepatocellular carcinoma with minimal features from electronic health records: development of a deep learning model. JMIR Cancer 2021;7:e19812. https://doi.org/10.2196/19812
  3. Loho IM, Hasan I, Lesmana CR, Dewiasty E, Gani RA. Hepatocellular carcinoma in a tertiary referral hospital in Indonesia: lack of improvement of one-year survival rates between 1998-1999 and 2013-2014. Asian Pac J Cancer Prev 2016;17:2165-2170. https://doi.org/10.7314/APJCP.2016.17.4.2165
  4. Jasirwan COM, Hasan I, Sulaiman AS, Lesmana CRA, Kurniawan J, Kalista KF, et al. Risk factors of mortality in the patients with hepatocellular carcinoma: a multicenter study in Indonesia. Curr Probl Cancer 2020;44:100480. https://doi.org/10.1016/j.currproblcancer.2019.05.003
  5. Sithinamsuwan P, Piratvisuth T, Tanomkiat W, Apakupakul N, Tongyoo S. Review of 336 patients with hepatocellular carcinoma at Songklanagarind Hospital. World J Gastroenterol 2000;6:339-343. https://doi.org/10.3748/wjg.v6.i3.339
  6. Somboon K, Siramolpiwat S, Vilaichone RK. Epidemiology and survival of hepatocellular carcinoma in the central region of Thailand. Asian Pac J Cancer Prev 2014;15:3567-3570. https://doi.org/10.7314/APJCP.2014.15.8.3567
  7. Lucas ZDF, Pangan CP, Patal PC, Ong J. The clinical profile of hepatocellular carcinoma patients at the Philippine General Hospital. Philipp J Intern Med 2009;47:1-9. https://doi.org/10.3860/pjim.v47i1.877
  8. Norsa'adah B, Nurhazalini-Zayani CG. Epidemiology and survival of hepatocellular carcinoma in north-east Peninsular Malaysia. Asian Pac J Cancer Prev 2013;14:6955-6959. https://doi.org/10.7314/APJCP.2013.14.11.6955
  9. Daez MLO, Ong JP, Lomboy ARB, Libuit JM, Vicente IMG, Firmalino GC, et al. Demographic profile and treatment outcomes of Filipino patients with hepatocellular carcinoma in a liver tumor registry. Acta Medica Philippina 2014;48:4-8. https://doi.org/10.47895/amp.v48i1.1174
  10. Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 2017;11:317-370. https://doi.org/10.1007/s12072-017-9799-9
  11. Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology 2016;150:835-853. https://doi.org/10.1053/j.gastro.2015.12.041
  12. European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012;56:908-943. https://doi.org/10.1016/j.jhep.2011.12.001
  13. Torzilli G, Belghiti J, Kokudo N, Takayama T, Capussotti L, Nuzzo G, 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;257:929-937. https://doi.org/10.1097/SLA.0b013e31828329b8
  14. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-1022. https://doi.org/10.1002/hep.24199
  15. Han KH, Kudo M, Ye SL, Choi JY, Poon RT, Seong J, et al. Asian consensus workshop report: expert consensus guideline for the management of intermediate and advanced hepatocellular carcinoma in Asia. Oncology 2011;81 Suppl 1:158-164. https://doi.org/10.1159/000333280
  16. Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y, et al.; Liver Cancer Study Group of Japan. JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer 2014;3:458-468. https://doi.org/10.1159/000343875
  17. Kudo M, Kitano M, Sakurai T, Nishida N. General rules for the clinical and pathological study of primary liver cancer, nationwide follow-up survey and clinical practice guidelines: the outstanding achievements of the liver cancer study group of Japan. Dig Dis 2015;33:765-770. https://doi.org/10.1159/000439101
  18. Kokudo N, Hasegawa K, Akahane M, Igaki H, Izumi N, Ichida T, et al. Evidence-based clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res 2015. https://doi.org/10.1111/hepr.12464
  19. Yau T, Tang VY, Yao TJ, Fan ST, Lo CM, Poon RT. Development of Hong Kong liver cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology 2014;146:1691-1700.e1693. https://doi.org/10.1053/j.gastro.2014.02.032
  20. Korean Liver Cancer Study Group (KLCSG); National Cancer Center, Korea (NCC). 2014 KLCSG-NCC Korea Practice Guideline for the management of hepatocellular carcinoma. Gut Liver 2015;9:267-317.
  21. Cuschieri S. The STROBE guidelines. Saudi J Anaesth 2019;13(Suppl 1):S31-S34. https://doi.org/10.4103/sja.SJA_543_18
  22. Kawasaki Y, Yang SJ, Choi GH, Han DH, Lee JH, Iino S, et al. New scoring system for resectable hepatocellular carcinoma with a maximum tumor size of ≤5 cm based on preoperative tumor factors. HPB (Oxford) 2019;21:1393-1399. https://doi.org/10.1016/j.hpb.2019.02.018
  23. Shehta A, Elsabbagh AM, Medhat M, Farouk A, Monier A, Said R, et al. Impact of tumor size on the outcomes of hepatic resection for hepatocellular carcinoma: a retrospective study. BMC Surg 2024;24:7. https://doi.org/10.1186/s12893-023-02296-w
  24. Wu G, Wu J, Wang B, Zhu X, Shi X, Ding Y. Importance of tumor size at diagnosis as a prognostic factor for hepatocellular carcinoma survival: a population-based study. Cancer Manag Res 2018;10:4401-4410. https://doi.org/10.2147/CMAR.S177663
  25. Lim C, Compagnon P, Sebagh M, Salloum C, Calderaro J, Luciani A, et al. Hepatectomy for hepatocellular carcinoma larger than 10 cm: preoperative risk stratification to prevent futile surgery. HPB (Oxford) 2015;17:611-623. https://doi.org/10.1111/hpb.12416
  26. Lu XY, Xi T, Lau WY, Dong H, Xian ZH, Yu H, et al. Pathobiological features of small hepatocellular carcinoma: correlation between tumor size and biological behavior. J Cancer Res Clin Oncol 2011;137:567-575. https://doi.org/10.1007/s00432-010-0909-5
  27. Syaiful RA, Mazni Y, Siagian NKP, Putranto AS, Jeo WS, Rahadiani N, et al. Surgical resection for hepatocellular carcinoma: a single-centre's one decade of experience. Ann Med Surg (Lond) 2024;86:1289-1296. https://doi.org/10.1097/MS9.0000000000001746
  28. Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018;68:723-750. https://doi.org/10.1002/hep.29913
  29. Sanyal S, Kron P, Wylie N, Hildalgo E, Toogood GJ, Lodge P. Outcomes of liver resection for hepatocellular carcinoma in octogenarians. HPB (Oxford) 2020;22:1324-1329. https://doi.org/10.1016/j.hpb.2020.01.006
  30. Yasuda S, Nomi T, Hokuto D, Yoshikawa T, Matsuo Y, Sho M. Liver regeneration after major liver resection for hepatocellular carcinoma in the elderly. J Invest Surg 2020;33:332-338. https://doi.org/10.1080/08941939.2018.1517839
  31. Orcutt ST, Anaya DA. Liver resection and surgical strategies for management of primary liver cancer. Cancer Control 2018;25:1073274817744621. https://doi.org/10.1177/1073274817744621
  32. Hyder O, Marques H, Pulitano C, Marsh JW, Alexandrescu S, Bauer TW, et al. A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience. JAMA Surg 2014;149:432-438. https://doi.org/10.1001/jamasurg.2013.5168
  33. Dai CY, Lin CY, Tsai PC, Lin PY, Yeh ML, Huang CF, et al. Impact of tumor size on the prognosis of hepatocellular carcinoma in patients who underwent liver resection. J Chin Med Assoc 2018;81:155-163. https://doi.org/10.1016/j.jcma.2017.06.018
  34. Liang BY, Gu J, Xiong M, Zhang EL, Zhang ZY, Chen XP, et al. Tumor size may influence the prognosis of solitary hepatocellular carcinoma patients with cirrhosis and without macrovascular invasion after hepatectomy. Sci Rep 2021;11:16343. https://doi.org/10.1038/s41598-021-95835-5
  35. Retnowulan IA, Stephanie M, Rahadiani N, Syaiful RA, Krisnuhoni E. Hepatocellular carcinoma's characteristics in an endemic country: a closer examination of tumor grade and microvascular invasion. Siriraj Med J 2023;75:817-826. https://doi.org/10.33192/smj.v75i11.264786
  36. Azoulay D, Ramos E, Casellas-Robert M, Salloum C, Lladó L, Nadler R, et al. Liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension. JHEP Rep 2021;3:100190. https://doi.org/10.1016/j.jhepr.2020.100190
  37. Kementerian Kesehatan Republik Indonesia. Keputusan Menteri Kesehatan Nomor HK.01.07/MENKES/1355/2022: Pedoman Nasional Pelayanan Kedokteran Tata Laksana Karsinoma Sel Hati Pada Dewasa. Kementerian Kesehatan Republik Indonesia; 2022.
  38. Liu YW, Lin CC, Yong CC, Wang CC, Chen CL, Wang JH, et al. Prognosis after resection of single large hepatocellular carcinoma: results from an Asian high-volume liver surgery center. PLoS One 2020;15:e0230897. https://doi.org/10.1371/journal.pone.0230897
  39. Cauchy F, Soubrane O, Belghiti J. Liver resection for HCC: patient's selection and controversial scenarios. Best Pract Res Clin Gastroenterol 2014;28:881-896. https://doi.org/10.1016/j.bpg.2014.08.013
  40. Kurniawan J, Sulaiman AS, Matondang S, Lalisang TJM, Krisnuhoni E, Zulkif ly S. Complete remission after sequential therapy of drug eluting beads transarterial chemoembolization and liver resection in large solitary nodule hepatocellular carcinoma. Case Reports Hepatol 2017;2017:3682614. https://doi.org/10.1155/2017/3682614
  41. Lalisang ANL, Putra AB, Zacharia NJ, Marbun VMG, Sihardo L, Syaiful RA, et al. Characteristics of living liver donors in a national referral hospital in Indonesia: a 13-year experience with living donor liver transplantation. Korean J Transplant 2023;37:179-188. https://doi.org/10.4285/kjt.23.0030