Does size matter for resection of giant versus non-giant hepatocellular carcinoma? A meta-analysis

BACKGROUND Research on long-term survival after resection of giant (≥ 10 cm) and non-giant hepatocellular carcinoma (HCC) (< 10 cm) has produced conflicting results. AIM This study aimed to investigate whether oncological outcomes and safety profiles of resection differ between giant and non-giant HCC. METHODS PubMed, MEDLINE, EMBASE, and Cochrane databases were searched. Studies designed to investigate the outcomes of giant vs non-giant HCC were included. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were postoperative complications and mortality rates. All studies were assessed for bias using the Newcastle–Ottawa Scale. RESULTS 24 retrospective cohort studies involving 23747 patients (giant = 3326; non-giant = 20421) who underwent HCC resection were included. OS was reported in 24 studies, DFS in 17 studies, 30-d mortality rate in 18 studies, postoperative complications in 15 studies, and post-hepatectomy liver failure (PHLF) in six studies. The HR was significantly lower for non-giant HCC in both OS (HR 0.53, 95%CI: 0.50-0.55, P < 0.001) and DFS (HR 0.62, 95%CI: 0.58-0.84, P < 0.001). No significant difference was found for 30-d mortality rate (OR 0.73, 95%CI: 0.50-1.08, P = 0.116), postoperative complications (OR 0.81, 95%CI: 0.62-1.06, P = 0.140), and PHLF (OR 0.81, 95%CI: 0.62-1.06, P = 0.140). CONCLUSION Resection of giant HCC is associated with poorer long-term outcomes. The safety profile of resection was similar in both groups; however, this may have been confounded by reporting bias. HCC staging systems should account for the size differences.

[1]  V. Shelat,et al.  Predictors of mortality within the first year post-hepatectomy for hepatocellular carcinoma , 2021, Journal of the Egyptian National Cancer Institute.

[2]  V. Shelat,et al.  Clinical application of advances and innovation in radiation treatment of hepatocellular carcinoma , 2021, Journal of clinical and translational research.

[3]  J. Bruix,et al.  BCLC strategy for prognosis prediction and treatment recommendation Barcelona Clinic Liver Cancer (BCLC) staging system. The 2022 update. , 2021, Journal of hepatology.

[4]  Chi-Chih Wang,et al.  Liver resection for hepatocellular carcinoma larger than 10 cm: A multi-institution long-term observational study , 2021, World journal of gastrointestinal surgery.

[5]  J. Zucman‐Rossi,et al.  Hepatocellular carcinoma , 1998, Nature Reviews Disease Primers.

[6]  P. Viatour,et al.  Hepatocellular carcinoma: old friends and new tricks , 2020, Experimental & Molecular Medicine.

[7]  Ding-Hui Dong,et al.  Single Large Nodule (>5 cm) Prognosis in Hepatocellular Carcinoma: Kinship with Barcelona Clinic Liver Cancer (BCLC) Stage A or B? , 2020, Medical science monitor : international medical journal of experimental and clinical research.

[8]  Hashem B. El-Serag,et al.  Epidemiology of Hepatocellular Carcinoma , 2020, Hepatology.

[9]  Yi‐Hsiang Huang,et al.  Comparison of prognosis between surgical resection and transarterial chemoembolization for patients with solitary huge hepatocellular carcinoma , 2020, Annals of translational medicine.

[10]  V. Shelat,et al.  Trans-arterial chemoembolization + radiofrequency ablation versus surgical resection in hepatocellular carcinoma - A meta-analysis. , 2020, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[11]  X. Geng,et al.  Long-term outcomes after hepatectomy of huge hepatocellular carcinoma: A single-center experience in China. , 2019, Hepatobiliary & pancreatic diseases international : HBPD INT.

[12]  Gregory J. Gores,et al.  A global view of hepatocellular carcinoma: trends, risk, prevention and management , 2019, Nature Reviews Gastroenterology & Hepatology.

[13]  S. Saab,et al.  A Practical Guideline for Hepatocellular Carcinoma Screening in Patients at Risk , 2019, Mayo Clinic proceedings. Innovations, quality & outcomes.

[14]  Xiaoshun He,et al.  The power of tumor sizes in predicting the survival of solitary hepatocellular carcinoma patients , 2018, Cancer medicine.

[15]  Yitao Ding,et al.  Importance of tumor size at diagnosis as a prognostic factor for hepatocellular carcinoma survival: a population-based study , 2018, Cancer management and research.

[16]  D. Shibata,et al.  Outcomes Following Resection of Hepatocellular Carcinoma in the Absence of Cirrhosis , 2018, Journal of Gastrointestinal Cancer.

[17]  J. Llovet,et al.  Molecular therapies and precision medicine for hepatocellular carcinoma , 2018, Nature Reviews Clinical Oncology.

[18]  A. Zhu,et al.  Hepatocellular Carcinoma with Macrovascular Invasion: Defining the Optimal Treatment Strategy , 2017, Liver Cancer.

[19]  A. Cucchetti,et al.  Optimizing stage of single large hepatocellular carcinoma , 2017, Medicine.

[20]  Recinda L. Sherman,et al.  Annual Report to the Nation on the Status of Cancer, 1975–2014, Featuring Survival , 2017, Journal of the National Cancer Institute.

[21]  K. Wakayama,et al.  Huge hepatocellular carcinoma greater than 10 cm in diameter worsens prognosis by causing distant recurrence after curative resection , 2017, Journal of surgical oncology.

[22]  C. Compton,et al.  The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population‐based to a more “personalized” approach to cancer staging , 2017, CA: a cancer journal for clinicians.

[23]  H. Selçuk Prognostic Factors and Staging Systems in Hepatocellular Carcinoma. , 2017, Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation.

[24]  K. Chung,et al.  Long‐term survival of patients undergoing liver resection for very large hepatocellular carcinomas , 2016, The British journal of surgery.

[25]  K. Ahn,et al.  Prognostic factors after hepatic resection for the single hepatocellular carcinoma larger than 5 cm , 2016, Annals of surgical treatment and research.

[26]  Chia-Yang Hsu,et al.  Prognosis of hepatocellular carcinoma: Assessment of eleven staging systems. , 2016, Journal of hepatology.

[27]  Chang Ho Jung,et al.  BCLC stage B is a better designation for single large hepatocellular carcinoma than BCLC stage A , 2016, Journal of gastroenterology and hepatology.

[28]  Yun-fei Yuan,et al.  Preoperative mean corpuscular hemoglobin affecting long-term outcomes of hepatectomized patients with hepatocellular carcinoma. , 2016, Molecular and clinical oncology.

[29]  Lequn Li,et al.  Efficacy of hepatic resection for huge (≥ 10 cm) hepatocellular carcinoma: good prognosis associated with the uninodular subtype. , 2015, International journal of clinical and experimental medicine.

[30]  K. Madhavan,et al.  Outcomes of resection of giant hepatocellular carcinoma in a tertiary institution: does size matter? , 2015, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[31]  Robert C. G. Martin,et al.  Assessment of the reporting of quality and outcome measures in hepatic resections: a call for 90-day reporting in all hepatectomy series. , 2015, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[32]  Lequn Li,et al.  Efficacy of hepatic resection vs transarterial chemoembolization for solitary huge hepatocellular carcinoma. , 2015, World journal of gastroenterology.

[33]  J. Fujimoto,et al.  Outcomes of Hepatic Resection for Large Hepatocellular Carcinoma: Special Reference to Postoperative Recurrence , 2015, The American surgeon.

[34]  Jiayin Yang,et al.  Is hepatectomy for huge hepatocellular carcinoma (≥ 10 cm in diameter) safe and effective? A single-center experience. , 2014, Asian Pacific journal of cancer prevention : APJCP.

[35]  S. Fan,et al.  Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. , 2014, Gastroenterology.

[36]  Y. Paik,et al.  Long‐term survival after surgical resection for huge hepatocellular carcinoma: Comparison with transarterial chemoembolization after propensity score matching , 2014, Journal of gastroenterology and hepatology.

[37]  F. Giuliante,et al.  Clinical Characteristics and Survival of European Patients with Resectable Large Hepatocellular Carcinomas , 2013, Journal of Gastrointestinal Cancer.

[38]  Di-peng Ou,et al.  Hepatectomy for Huge Hepatocellular Carcinoma: Single Institute’s Experience , 2013, World Journal of Surgery.

[39]  N. Demartines,et al.  Long-term Outcome after Liver Resection for Hepatocellular Carcinoma Larger than 10 cm , 2013, World Journal of Surgery.

[40]  Nicky J Welton,et al.  Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves , 2012, BMC Medical Research Methodology.

[41]  Y. Maehara,et al.  Outcomes of hepatic resection for huge hepatocellular carcinoma (≥10 cm in diameter) , 2011, Journal of surgical oncology.

[42]  S. Jo Outcome of Hepatectomy for Huge Hepatocellular Carcinoma , 2011, Korean journal of hepato-biliary-pancreatic surgery.

[43]  K. Owzar,et al.  The importance of identifying and validating prognostic factors in oncology. , 2010, Seminars in oncology.

[44]  Y. N. Park,et al.  Outcome after curative resection for a huge (>or=10 cm) hepatocellular carcinoma and prognostic significance of gross tumor classification. , 2009, American journal of surgery.

[45]  T. Tajiri,et al.  Adaptation of hepatectomy for huge hepatocellular carcinoma. , 2008, Journal of hepato-biliary-pancreatic surgery.

[46]  S. Gallinger,et al.  Prognosis and Results After Resection of Very Large (≥10 cm) Hepatocellular Carcinoma , 2007, Journal of Gastrointestinal Surgery.

[47]  M. Gonen,et al.  Outcome of partial hepatectomy for large (> 10 cm) hepatocellular carcinoma , 2005, Cancer.

[48]  I. Endo,et al.  Efficacy of Hepatic Resection for Hepatocellular Carcinomas Larger than 10 cm , 2004, World Journal of Surgery.

[49]  C. Yeh,et al.  Hepatic Resection and Prognosis for Patients With Hepatocellular Carcinoma Larger Than 10 cm: Two Decades of Experience at Chang Gung Memorial Hospital , 2003, Annals of Surgical Oncology.

[50]  S. Fan,et al.  Selection criteria for hepatic resection in patients with large hepatocellular carcinoma larger than 10 cm in diameter. , 2002, Journal of the American College of Surgeons.

[51]  Bernardino,et al.  Prospective validation of the CLIP score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma , 2000, Hepatology.

[52]  F. Izzo,et al.  A new prognostic system for hepatocellular carcinoma: A retrospective study of 435 patients , 1998, Hepatology.

[53]  N. Okazaki,et al.  Prognosis of Primary Hepatocellular Carcinoma , 1984, Hepatology.