Lili Chen1, Shuling Chen2, Qian Zhou3, Qinghua Cao1, Yu Dong1, Shiting Feng4, Han Xiao2, Yuanqi Wang5, Xin Liu5, Guanrui Liao5, Zhenwei Peng6,7, Bin Li7, Li Tan5, Zunfu Ke1,8, Dongming Li5, Baogang Peng5, Sui Peng7,8,9, Luying Zhu10, Bing Liao11, Ming Kuang12,13,14. 1. Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 2. Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 3. Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 4. Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 5. Department of Liver Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 6. Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 7. Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 8. Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 9. Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 10. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. 11. Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. liaob@mail.sysu.edu.cn. 12. Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. kuangm@mail.sysu.edu.cn. 13. Department of Liver Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. kuangm@mail.sysu.edu.cn. 14. Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. kuangm@mail.sysu.edu.cn.
Abstract
BACKGROUND: The aim of this work is to explore the impact of the number of sampling sites (NuSS) and sampling location on microvascular invasion (MVI) detection rate and long-term survival of hepatocellular carcinoma (HCC), and determine the minimum NuSS for sufficient MVI detection. PATIENTS AND METHODS: From January 2008 to March 2017, 1144 HCC patients who underwent hepatectomy were retrospectively enrolled. Associations between NuSS and MVI positive rates and overall survival were investigated. NuSS thresholds were determined by Chow test and confirmed prospectively in 305 patients from April 2017 to February 2019. In the prospective cohort, the distribution of MVI in different sampling locations and its prognostic effect was evaluated. RESULTS: MVI positive rates increased as NuSS increased, steadily reaching a plateau when NuSS reached a threshold. A threshold of four, six, eight, and eight sampling sites within paracancerous parenchyma ≤ 1 cm from tumor was required for detecting MVI in solitary tumors measuring 1.0-3.0, 3.1-4.9, and ≥ 5.0 cm and multiple tumors. Patients with adequate NuSS achieved longer survival than those with inadequate NuSS [hazard ratio (HR) = 0.75, P = 0.043]. For all MVI-positive patients, MVI could be detected positive in paracancerous parenchyma ≤ 1 cm from tumor. Patients with MVI positive in paracancerous parenchyma > 1 cm had higher recurrence risk than those with MVI positive only in parenchyma ≤ 1 cm (HR = 6.05, P < 0.001). CONCLUSIONS: Adequate NuSS is associated with higher MVI detection rate and better survival of HCC patients. We recommend four, six, eight, and eight as the cut-points for evaluating MVI sampling quality and patients' prognostic stratification in the subgroups of solitary tumors measuring 1.0-3.0 cm, 3.1-4.9 cm and ≥ 5.0 cm and multiple tumors, respectively.
BACKGROUND: The aim of this work is to explore the impact of the number of sampling sites (NuSS) and sampling location on microvascular invasion (MVI) detection rate and long-term survival of hepatocellular carcinoma (HCC), and determine the minimum NuSS for sufficient MVI detection. PATIENTS AND METHODS: From January 2008 to March 2017, 1144 HCC patients who underwent hepatectomy were retrospectively enrolled. Associations between NuSS and MVI positive rates and overall survival were investigated. NuSS thresholds were determined by Chow test and confirmed prospectively in 305 patients from April 2017 to February 2019. In the prospective cohort, the distribution of MVI in different sampling locations and its prognostic effect was evaluated. RESULTS:MVI positive rates increased as NuSS increased, steadily reaching a plateau when NuSS reached a threshold. A threshold of four, six, eight, and eight sampling sites within paracancerous parenchyma ≤ 1 cm from tumor was required for detecting MVI in solitary tumors measuring 1.0-3.0, 3.1-4.9, and ≥ 5.0 cm and multiple tumors. Patients with adequate NuSS achieved longer survival than those with inadequate NuSS [hazard ratio (HR) = 0.75, P = 0.043]. For all MVI-positive patients, MVI could be detected positive in paracancerous parenchyma ≤ 1 cm from tumor. Patients with MVI positive in paracancerous parenchyma > 1 cm had higher recurrence risk than those with MVI positive only in parenchyma ≤ 1 cm (HR = 6.05, P < 0.001). CONCLUSIONS: Adequate NuSS is associated with higher MVI detection rate and better survival of HCC patients. We recommend four, six, eight, and eight as the cut-points for evaluating MVI sampling quality and patients' prognostic stratification in the subgroups of solitary tumors measuring 1.0-3.0 cm, 3.1-4.9 cm and ≥ 5.0 cm and multiple tumors, respectively.