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Risk factors and long-term prognosis of beyond-Milan recurrence after hepatectomy for BCLC stage 0/A hepatocellular carcinoma: A large-scale multicenter study

  • Zi-Han Feng
    Affiliations
    Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China

    Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, China

    Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
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  • Ming-Da Wang
    Affiliations
    Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
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  • Zhong Chen
    Affiliations
    Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
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  • Li-Yang Sun
    Affiliations
    Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, China
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  • Xiao Xu
    Affiliations
    Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
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  • Qing-Yu Kong
    Affiliations
    Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
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  • Zi-Xiang Chen
    Affiliations
    Department of Hepatobiliary Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China
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  • Yong-Yi Zeng
    Affiliations
    Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, China
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  • Ying-Jian Liang
    Affiliations
    Department of Hepatobiliary Surgery, First Affiliated Hospital of Harbin Medical University, China
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  • Zhi-Yu Chen
    Affiliations
    Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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  • Hong Wang
    Affiliations
    Department of General Surgery, Liuyang People’s Hospital, China
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  • Ya-Hao Zhou
    Affiliations
    Department of Hepatobiliary Surgery, Pu’er People’s Hospital, China
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  • Ting-Hao Chen
    Affiliations
    Department of General Surgery, Ziyang First People’s Hospital, China
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  • Lan-Qing Yao
    Affiliations
    Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
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  • Chao Li
    Affiliations
    Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
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  • Timothy M. Pawlik
    Affiliations
    Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH
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  • Wan Yee Lau
    Affiliations
    Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China

    Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China
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  • Feng Shen
    Correspondence
    Reprint requests: Prof. Feng Shen, MD, Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai 200438, China.
    Affiliations
    Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China

    Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China
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  • Tian Yang
    Correspondence
    Reprint requests: Prof. Tian Yang, MD, Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai 200438, China.
    Affiliations
    Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China

    Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, China

    Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China
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      Abstract

      Background

      Data on recurrence are important to inform surveillance and improve long-term surgical outcomes for patients with hepatocellular carcinoma. We sought to identify risk factors and long-term prognosis among patients who experienced beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma.

      Methods

      Patients who underwent hepatectomy for Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma were identified from a multi-institutional database. Predictors of beyond-Milan recurrence and risk factors associated with post-recurrence survival among patients with beyond-Milan recurrence were assessed using univariate and multivariate Cox regression analyses.

      Results

      Among 753 patients (median follow-up, 51.8 months), 138 (18.3%) developed beyond-Milan recurrence. Regular surveillance (interval follow-up ≤3 months within 1 year and ≤6 months in subsequent years after surgery) was not carried out for 53 (38.4%) patients who developed beyond-Milan recurrence. On multivariate analysis, increased risk of beyond-Milan recurrence was independently associated with preoperative alpha-fetoprotein level >400 ng/mL, tumor size >5.0 cm, multifocal disease, microvascular invasion, and no/irregular recurrence surveillance. Median post-recurrence survival among patients with beyond-Milan recurrence was only 8.4 months (95% confidence interval: 7.0–9.8 months). Among patients who developed beyond-Milan recurrence, Child-Pugh grade B/C, early recurrence within 1 year after surgery, macrovascular invasion/distant metastasis, and noncurative treatment of recurrence were independent risk factors associated with worse post-recurrence survival.

      Conclusion

      Nearly 1 in 5 patients developed beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. Patients with beyond-Milan recurrence had a median survival of less than 1 year after diagnosis of the recurrence. Regular surveillance is an important and actionable measure to decrease beyond-Milan recurrence and, in turn, improve long-term survival among patients treated with hepatectomy for hepatocellular carcinoma.

      Graphical abstract

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