Analysis of risk factors and establishment of nomogram for predicting metachronous liver metastasis of gastric cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

JU Jiahua ¹ , WANG Chaoyang ¹ , ZHANG Haibao ¹ , LIN Hao ¹ ,  YU Yongjiang ²

1. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of Gastrointestinal and Hernia and Abdominal Wall Surgery, The First Hospital of Lanzhou Univerity, Lanzhou 730000, P. R. China;

Corresponding author：

YU Yongjiang, Email: ylongy@163.com

Keywords：

gastric cancer; radical surgery; metachronous liver metastasis; nomogram

DOI：

10.7507/1007-9424.202306014

Video：

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Objective To investigate the risk factors and establish the predictive pattern of the metachronous liver metastasis after curative surgery for patientswith gastric cancer. Methods The clinicopathologic data of patients who underwent radical gastric cancer surgery and met the inclusion and exclusion criteria from January 1, 2015 and January 1, 2018 in the First Hospital of Lanzhou University were retrospectively analyzed. The risk factors affecting metachronous liver metastasis of gastric cancer were screened out by univariate and multivariate logistic regression analysis. And a nomogram prediction model based on the risk factors screened out was established and its predictive efficiency was evaluated. Results A total of 203 patients were collected in this study, of whom 41 (20.4%) developed metachronous liver metastasis of gastric cancer. The results of multivariate logistic regression analysis showed that the tumor diameter ≥5 cm, increasing intraoperative bleeding, carcinoembryonic antigen (CEA) ≥5 μg/L, and lymphovascular invasion increased the risks of metachronous liver metastasis of gastric cancer (all P<0.05). The area under the receiver operating characteristic curve and its 95% confidence interval (95%CI) of the nomogram based on these risk factors in predicting metachronous liver metastasis of gastric cancer was 0.850 (0.793, 0.908), and the consistency index (95%CI) was 0.812 (0.763, 0.859). The calibration curve for predicting the risk of metachronous liver metastasis in gastric cancer by the nomogram was close to the 45° ideal curve and had a stronger calibration (Hosmer Limeshow goodness-of-fit test, χ²=2.116, P=0.347). Conclusions The results of this study conclude metachronous liver metastasis of gastric cancer is not low, and the patient with lymphovascular invasion, higher level of CEA (≥5 μg/L), more intraoperative bleeding, and larger tumor diameter (≥5 cm) has a higher risk of metachronous liver metastasis of gastric cancer. The nomogram prediction model established based on these risk factors has a good predictive efficiency and can provide reference for clinicians to identify high-risk patient and take early interventions.

Citation： JU Jiahua, WANG Chaoyang, ZHANG Haibao, LIN Hao, YU Yongjiang. Analysis of risk factors and establishment of nomogram for predicting metachronous liver metastasis of gastric cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(9): 1073-1078. doi: 10.7507/1007-9424.202306014 Copy

1.	Sung H, Ferlay J, Siegel RL, 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(3): 209-249.
2.	Roukos DH. Current status and future perspectives in gastric cancer management. Cancer Treat Rev, 2000, 26(4): 243-255.
3.	Jin X, Zhu Z, Shi Y. Metastasis mechanism and gene/protein expression in gastric cancer with distant organs metastasis. Bull Cancer, 2014, 101(1): E1-E12.
4.	Spolverato G, Ejaz A, Kim Y, et al. Rates and patterns of recurrence after curative intent resection for gastric cancer: a United States multi-institutional analysis. J Am Coll Surg, 2014, 219(4): 664-675.
5.	Liu J, Chen L. Current status and progress in gastric cancer with liver metastasis. Chin Med J (Engl), 2011, 124(3): 445-456.
6.	Markar SR, Mikhail S, Malietzis G, et al. Influence of surgical resection of hepatic metastases from gastric adenocarcinoma on long-term survival: systematic review and pooled analysis. Ann Surg, 2016, 263(6): 1092-1101.
7.	刘慧, 王鹏, 陈艳钊等. 多肿瘤标志物联合检测在胃癌辅助诊断中的临床价值探讨. 中国卫生检验杂志, 2020, 30(17): 2064-2068, 2079.
8.	Chen XB, Xu ZJ, Liu T, et al. Analysis of related risk factors and prognostic factors of gastric cancer with bone metastasis: a SEER-based study. J Immunol Res, 2022, 2022: 3251051.
9.	Mranda GM, Xue Y, Zhou XG, et al. Revisiting the 8th AJCC system for gastric cancer: a review on validations, nomograms, lymph nodes impact, and proposed modifications. Ann Med Surg (Lond), 2022, 75: 103411.
10.	Thelen A, Jonas S, Benckert C, et al. Liver resection for metastatic gastric cancer. Eur J Surg Oncol, 2008, 34(12): 1328-1334.
11.	中国研究型医院学会消化道肿瘤专业委员会, 中国医师协会外科医师分会上消化道外科医师委员会, 中国抗癌协会胃癌专业委员会, 等. 胃癌肝转移诊断与综合治疗中国专家共识(2019版). 中国实用外科杂志, 2019, 39(5): 405-411.
12.	Lin Z, Wang R, Zhou Y, et al. Prediction of distant metastasis and survival prediction of gastric cancer patients with metastasis to the liver, lung, bone, and brain: research based on the SEER database. Ann Transl Med, 2022, 10(1): 16.
13.	Xiao Y, Zhang B, Wu Y. Prognostic analysis and liver metastases relevant factors after gastric and hepatic surgical treatment in gastric cancer patients with metachronous liver metastases: a population-based study. Ir J Med Sci, 2019, 188(2): 415-424.
14.	吴娟, 郑丹, 阮丽蒽, 等. 多项肿瘤标志物联合检测在胃肠道肿瘤诊断中的价值. 标记免疫分析与临床, 2020, 27(1): 10-14, 18.
15.	Zhao ZS, Li L, Wang HJ, et al. Expression and prognostic significance of CEACAM6, ITGB1, and CYR61 in peripheral blood of patients with gastric cancer. J Surg Oncol, 2011, 104(5): 525-529.
16.	Zang M, Zhang B, Zhang Y, et al. CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway. PLoS One, 2014, 9(11): e112908.
17.	Zhang Y, Zang M, Li J, et al. CEACAM6 promotes tumor migration, invasion, and metastasis in gastric cancer. Acta Biochim Biophys Sin (Shanghai), 2014, 46(4): 283-290.
18.	Liang YX, Guo HH, Deng JY, et al. Impact of intraoperative blood loss on survival after curative resection for gastric cancer. World J Gastroenterol, 2013, 19(33): 5542-5550.
19.	Mizuno A, Kanda M, Kobayashi D, et al. Adverse effects of intraoperative blood loss on long-term outcomes after curative gastrectomy of patients with stage Ⅱ/Ⅲ gastric cancer. Dig Surg, 2016, 33(2): 121-128.
20.	Ito Y, Kanda M, Ito S, et al. Intraoperative blood loss is associated with shortened postoperative survival of patients with stage Ⅱ/Ⅲ gastric cancer: analysis of a multi-institutional dataset. World J Surg, 2019, 43(3): 870-877.
21.	Bruns CJ, Schäfer H, Wolfgarten B, et al. Effect of intraoperative blood loss on the function of natural killer cells in tumors of the upper gastrointestinal tract. Langenbecks Arch Chir Suppl Kongressbd, 1996, 113: 146-149.
22.	Misawa K, Kurokawa Y, Mizusawa J, et al. Stomach Cancer Study Group of the Japan Clinical Oncology Group. Negative impact of intraoperative blood loss on long-term outcome after curative gastrectomy for advanced gastric cancer: exploratory analysis of the JCOG1001 phase Ⅲ trial. Gastric Cancer, 2022, 25(2): 459-467.
23.	Kooby DA, Suriawinata A, Klimstra DS, et al. Biologic predictors of survival in node-negative gastric cancer. Ann Surg, 2003, 237(6): 828-835.
24.	Kumagai K, Shimizu K, Yokoyama N, et al. Gastrointestinal cancer metastasis and lymphatic advancement. Surg Today, 2010, 40(4): 301-306.
25.	Moriguchi S, Maehara Y, Korenaga D, et al. Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer. Surg Oncol, 1992, 1(5): 341-346.
26.	Zhong J, Chen Y, Wang LJ. Emerging molecular basis of hematogenous metastasis in gastric cancer. World J Gastroenterol, 2016, 22(8): 2434-2440.
27.	王闯, 梁文全, 鲁意迅, 等. 循环肿瘤细胞对胃癌手术患者预后的判断价值. 中国普外基础与临床杂志, 2022, 29(1): 17-23.
28.	Marrelli D, Roviello F, De Stefano A, et al. Risk factors for liver metastases after curative surgical procedures for gastric cancer: a prospective study of 208 patients treated with surgical resection. J Am Coll Surg, 2004, 198(1): 51-58.

1. Sung H, Ferlay J, Siegel RL, 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(3): 209-249.
2. Roukos DH. Current status and future perspectives in gastric cancer management. Cancer Treat Rev, 2000, 26(4): 243-255.
3. Jin X, Zhu Z, Shi Y. Metastasis mechanism and gene/protein expression in gastric cancer with distant organs metastasis. Bull Cancer, 2014, 101(1): E1-E12.
4. Spolverato G, Ejaz A, Kim Y, et al. Rates and patterns of recurrence after curative intent resection for gastric cancer: a United States multi-institutional analysis. J Am Coll Surg, 2014, 219(4): 664-675.
5. Liu J, Chen L. Current status and progress in gastric cancer with liver metastasis. Chin Med J (Engl), 2011, 124(3): 445-456.
6. Markar SR, Mikhail S, Malietzis G, et al. Influence of surgical resection of hepatic metastases from gastric adenocarcinoma on long-term survival: systematic review and pooled analysis. Ann Surg, 2016, 263(6): 1092-1101.
7. 刘慧, 王鹏, 陈艳钊等. 多肿瘤标志物联合检测在胃癌辅助诊断中的临床价值探讨. 中国卫生检验杂志, 2020, 30(17): 2064-2068, 2079.
8. Chen XB, Xu ZJ, Liu T, et al. Analysis of related risk factors and prognostic factors of gastric cancer with bone metastasis: a SEER-based study. J Immunol Res, 2022, 2022: 3251051.
9. Mranda GM, Xue Y, Zhou XG, et al. Revisiting the 8th AJCC system for gastric cancer: a review on validations, nomograms, lymph nodes impact, and proposed modifications. Ann Med Surg (Lond), 2022, 75: 103411.
10. Thelen A, Jonas S, Benckert C, et al. Liver resection for metastatic gastric cancer. Eur J Surg Oncol, 2008, 34(12): 1328-1334.
11. 中国研究型医院学会消化道肿瘤专业委员会, 中国医师协会外科医师分会上消化道外科医师委员会, 中国抗癌协会胃癌专业委员会, 等. 胃癌肝转移诊断与综合治疗中国专家共识(2019版). 中国实用外科杂志, 2019, 39(5): 405-411.
12. Lin Z, Wang R, Zhou Y, et al. Prediction of distant metastasis and survival prediction of gastric cancer patients with metastasis to the liver, lung, bone, and brain: research based on the SEER database. Ann Transl Med, 2022, 10(1): 16.
13. Xiao Y, Zhang B, Wu Y. Prognostic analysis and liver metastases relevant factors after gastric and hepatic surgical treatment in gastric cancer patients with metachronous liver metastases: a population-based study. Ir J Med Sci, 2019, 188(2): 415-424.
14. 吴娟, 郑丹, 阮丽蒽, 等. 多项肿瘤标志物联合检测在胃肠道肿瘤诊断中的价值. 标记免疫分析与临床, 2020, 27(1): 10-14, 18.
15. Zhao ZS, Li L, Wang HJ, et al. Expression and prognostic significance of CEACAM6, ITGB1, and CYR61 in peripheral blood of patients with gastric cancer. J Surg Oncol, 2011, 104(5): 525-529.
16. Zang M, Zhang B, Zhang Y, et al. CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway. PLoS One, 2014, 9(11): e112908.
17. Zhang Y, Zang M, Li J, et al. CEACAM6 promotes tumor migration, invasion, and metastasis in gastric cancer. Acta Biochim Biophys Sin (Shanghai), 2014, 46(4): 283-290.
18. Liang YX, Guo HH, Deng JY, et al. Impact of intraoperative blood loss on survival after curative resection for gastric cancer. World J Gastroenterol, 2013, 19(33): 5542-5550.
19. Mizuno A, Kanda M, Kobayashi D, et al. Adverse effects of intraoperative blood loss on long-term outcomes after curative gastrectomy of patients with stage Ⅱ/Ⅲ gastric cancer. Dig Surg, 2016, 33(2): 121-128.
20. Ito Y, Kanda M, Ito S, et al. Intraoperative blood loss is associated with shortened postoperative survival of patients with stage Ⅱ/Ⅲ gastric cancer: analysis of a multi-institutional dataset. World J Surg, 2019, 43(3): 870-877.
21. Bruns CJ, Schäfer H, Wolfgarten B, et al. Effect of intraoperative blood loss on the function of natural killer cells in tumors of the upper gastrointestinal tract. Langenbecks Arch Chir Suppl Kongressbd, 1996, 113: 146-149.
22. Misawa K, Kurokawa Y, Mizusawa J, et al. Stomach Cancer Study Group of the Japan Clinical Oncology Group. Negative impact of intraoperative blood loss on long-term outcome after curative gastrectomy for advanced gastric cancer: exploratory analysis of the JCOG1001 phase Ⅲ trial. Gastric Cancer, 2022, 25(2): 459-467.
23. Kooby DA, Suriawinata A, Klimstra DS, et al. Biologic predictors of survival in node-negative gastric cancer. Ann Surg, 2003, 237(6): 828-835.
24. Kumagai K, Shimizu K, Yokoyama N, et al. Gastrointestinal cancer metastasis and lymphatic advancement. Surg Today, 2010, 40(4): 301-306.
25. Moriguchi S, Maehara Y, Korenaga D, et al. Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer. Surg Oncol, 1992, 1(5): 341-346.
26. Zhong J, Chen Y, Wang LJ. Emerging molecular basis of hematogenous metastasis in gastric cancer. World J Gastroenterol, 2016, 22(8): 2434-2440.
27. 王闯, 梁文全, 鲁意迅, 等. 循环肿瘤细胞对胃癌手术患者预后的判断价值. 中国普外基础与临床杂志, 2022, 29(1): 17-23.
28. Marrelli D, Roviello F, De Stefano A, et al. Risk factors for liver metastases after curative surgical procedures for gastric cancer: a prospective study of 208 patients treated with surgical resection. J Am Coll Surg, 2004, 198(1): 51-58.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Analysis of risk factors and establishment of nomogram for predicting metachronous liver metastasis of gastric cancer

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