Influencing factors and construction of a nomogram predictive model for postoperative anastomotic leak in patients with carcinoma of the esophagus and gastroesophageal junction_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

PENG Hao ¹ , SHENG Siqi ² , CHEN Jing ³ , MAIRHABA Maitiasen ¹ , SONG Haizhu ² ,  YI Jun ¹

1. Department of Cardiothoracic Surgery, Jinling Hospital Affiliated to Nanjing University School of Medicine, Nanjing, 210002, P. R. China;
2. Department of Oncology, Jinling Hospital Affiliated to Nanjing University School of Medicine, Nanjing, 210002, P. R. China;
3. Department of Cardiothoracic Surgery, Jinling Clinical Medical College, Nanjing University of Traditional Chinese Medicine, Nanjing, 210002, P. R. China;

Corresponding author：

YI Jun, Email: drjunyi@163.com

Keywords：

Esophageal cancer; gastroesophageal junction carcinoma; anastomotic leak; nomogram predictive model

DOI：

10.7507/1007-4848.202306059

Video：

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Objective To analyze the influencing factors for postoperative anastomotic leak (AL) in carcinoma of the esophagus and gastroesophageal junction and construct a nomogram predictive model. Methods The patients who underwent radical esophagectomy at Jinling Hospital Affiliated to Nanjing University School of Medicine from January 2018 to June 2020 were included in this study. Relevant variables were screened using univariate and multivariate logistic regression analyses. A nomogram was then developed to predict the risk factors associated with postoperative AL. The predictive performance of the nomogram was validated using the receiver operating characteristic (ROC) curve. Results A total of 468 patients with carcinoma of the esophagus and gastroesophageal junction were included in the study, comprising 354 males and 114 females, with a mean age of (62.8±7.2) years. The tumors were predominantly located in the middle or lower esophagus, and 51 (10.90%) patients experienced postoperative AL. Univariate logistic regression analysis indicated that age, body mass index (BMI), tumor location, preoperative albumin levels, diabetes mellitus, anastomosis technique, anastomosis site, and C-reactive protein (CRP) levels were potentially associated with AL (P<0.05). Multivariate logistic regression analysis identified age, BMI, tumor location, diabetes mellitus, anastomosis technique, and CRP levels as independent risk factors for AL (P<0.05). A nomogram was developed based on the findings from the multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was 0.803, indicating a strong concordance between the actual observations and the predicted outcomes. Furthermore, decision curve analysis demonstrated that the newly established nomogram holds significant value for clinical decision-making. Conclusion The predictive model for postoperative AL in patients with carcinoma of the esophagus and gastroesophageal junction demonstrates strong predictive validity and is essential for guiding clinical monitoring, early detection, and preventive strategies.

Citation： PENG Hao, SHENG Siqi, CHEN Jing, MAIRHABA Maitiasen, SONG Haizhu, YI Jun. Influencing factors and construction of a nomogram predictive model for postoperative anastomotic leak in patients with carcinoma of the esophagus and gastroesophageal junction. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2025, 32(2): 208-215. doi: 10.7507/1007-4848.202306059 Copy

1.	Ajani JA, D'Amico TA, Bentrem DJ, et al. Esophageal and esophagogastric junction cancers, version 2. 2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2019, 17(7): 855-883.
2.	Mboumi IW, Reddy S, Lidor AO. Complications after esophagectomy. Surg Clin North Am, 2019, 99(3): 501-510.
3.	Chen K. Definition, classification and prediction of complications related to esophageal resection. Zhonghua Wei Chang Wai Ke Za Zhi, 2015, 18(9): 855-859.
4.	Seesing MFJ, Gisbertz SS, Goense L, et al. A propensity score matched analysis of open versus minimally invasive transthoracic esophagectomy in the Netherlands. Ann Surg, 2017, 266(5): 839-846.
5.	Fransen LFC, Berkelmans GHK, Asti E, et al. The effect of postoperative complications after minimally invasive esophagectomy on long-term survival: An international multicenter cohort study. Ann Surg, 2021, 274(6): e1129-e1137.
6.	Rutegård M, Lagergren P, Rouvelas I, et al. Intrathoracic anastomotic leakage and mortality after esophageal cancer resection: A population-based study. Ann Surg Oncol, 2012, 19(1): 99-103.
7.	Messager M, Warlaumont M, Renaud F, et al. Recent improvements in the management of esophageal anastomotic leak after surgery for cancer. Eur J Surg Oncol, 2017, 43(2): 258-269.
8.	Zafirellis KD, Fountoulakis A, Dolan K, et al. Evaluation of POSSUM in patients with oesophageal cancer undergoing resection. Br J Surg, 2002, 89(9): 1150-1155.
9.	Haga Y, Wada Y, Takeuchi H, et al. Prediction of anastomotic leak and its prognosis in digestive surgery. World J Surg, 2011, 35(4): 716-722.
10.	Fabbi M, Hagens ERC, van Berge Henegouwen MI, et al. Anastomotic leakage after esophagectomy for esophageal cancer: Definitions, diagnostics, and treatment. Dis Esophagus, 2021, 34(1): doaa039.
11.	Moon SW, Kim JJ, Cho DG, et al. Early detection of complications: Anastomotic leakage. J Thorac Dis, 2019, 11(Suppl 5): S805-S811.
12.	Verstegen MHP, Bouwense SAW, van Workum F, et al. Management of intrathoracic and cervical anastomotic leakage after esophagectomy for esophageal cancer: A systematic review. World J Emerg Surg, 2019, 14: 17.
13.	Noble F, Curtis N, Harris S, et al. Risk assessment using a novel score to predict anastomotic leak and major complications after oesophageal resection. J Gastrointest Surg, 2012, 16(6): 1083-1095.
14.	Bundred J, Hollis AC, Hodson J, et al. Validation of the NUn score as a predictor of anastomotic leak and major complications after esophagectomy. Dis Esophagus, 2020, 33(1): doz041.
15.	Van Daele E, Van de Putte D, Ceelen W, et al. Risk factors and consequences of anastomotic leakage after Ivor Lewis oesophagectomy. Interact Cardiovasc Thorac Surg, 2016, 22(1): 32-37.
16.	Huang J, Zhou Y, Wang C, et al. Logistic regression analysis of the risk factors of anastomotic fistula after radical resection of esophageal-cardiac cancer. Thorac Cancer, 2017, 8(6): 666-671.
17.	Fjederholt KT, Okholm C, Svendsen LB, et al. Ketorolac and other NSAIDs increase the risk of anastomotic leakage after surgery for GEJ cancers: A cohort study of 557 patients. J Gastrointest Surg, 2018, 22(4): 587-594.
18.	Gao C, Xu G, Wang C, et al. Evaluation of preoperative risk factors and postoperative indicators for anastomotic leak of minimally invasive McKeown esophagectomy: A single-center retrospective analysis. J Cardiothorac Surg, 2019, 14(1): 46.
19.	张磊, 李辉, 侯生才, 等. 基于累积评分的食管癌术后吻合口瘘的风险分级系统. 中华胸部外科电子杂志, 2016, 3(1): 15-20.Zhang L, Li H, Hou SC, et al. An aggregate score system to stratify the risk of anastomotic leakage after esophageal carcinoma surgery. Chin J Thorac Surg (Electronic Edition), 2016, 3(1): 15-20.
20.	Schweigert M, Solymosi N, Dubecz A, et al. Current outcome of esophagectomy in the very elderly: Experience of a German high-volume center. American Surgeon, 2013, 79(8): 754-763.
21.	Markar SR, Arya S, Karthikesalingam A, et al. Technical factors that affect anastomotic integrity following esophagectomy: Systematic review and meta-analysis. Ann Surg Oncol, 2013, 20(13): 4274-4281.
22.	Urschel JD. Esophagogastrostomy anastomotic leaks complicating esophagectomy: A review. Am J Surg, 1995, 169(6): 634-640.
23.	Pierie JP, de Graaf PW, van Vroonhoven TJ, et al. Healing of the cervical esophagogastrostomy. J Am Coll Surg, 1999, 188(4): 448-454.
24.	邱龙, 李向楠, 赵松, 等. 食管癌术后颈部食管胃吻合口瘘的危险因素分析. 中华消化外科杂志, 2017, 16(5): 483-489.Qiu L, Li XN, Zhao S, et al. Risk factors analysis of cervical esophagogastric anastomotic fistula after esophagectomy of esophageal cancer. Chin J Dig Surg, 2017, 16(5): 483-489.
25.	Cooke DT, Lin GC, Lau CL, et al. Analysis of cervical esophagogastric anastomotic leaks after transhiatal esophagectomy: Risk factors, presentation, and detection. Ann Thorac Surg, 2009, 88(1): 177-184.
26.	Okamura A, Watanabe M, Imamura Y, et al. Preoperative glycosylated hemoglobin levels predict anastomotic leak after esophagectomy with cervical esophagogastric anastomosis. World J Surg, 2017, 41(1): 200-207.
27.	Honda M, Kuriyama A, Noma H, et al. Hand-sewn versus mechanical esophagogastric anastomosis after esophagectomy: A systematic review and meta-analysis. Ann Surg, 2013, 257(2): 238-248.
28.	Deng XF, Liu QX, Zhou D, et al. Hand-sewn vs linearly stapled esophagogastric anastomosis for esophageal cancer: A meta-analysis. World J Gastroenterol, 2015, 21(15): 4757-4764.
29.	Liu QX, Qiu Y, Deng XF, et al. Comparison of outcomes following end-to-end hand-sewn and mechanical oesophagogastric anastomosis after oesophagectomy for carcinoma: A prospective randomized controlled trial. Eur J Cardiothorac Surg, 2015, 47(3): e118-e123.
30.	Warschkow R, Tarantino I, Ukegjini K, et al. Diagnostic study and meta-analysis of C-reactive protein as a predictor of postoperative inflammatory complications after gastroesophageal cancer surgery. Langenbecks Arch Surg, 2012, 397(5): 727-736.
31.	Aiolfi A, Asti E, Rausa E, et al. Use of C-reactive protein for the early prediction of anastomotic leak after esophagectomy: Systematic review and Bayesian meta-analysis. PLoS One, 2018, 13(12): e0209272.
32.	Kano K, Aoyama T, Nakajima T, et al. Prediction of postoperative inflammatory complications after esophageal cancer surgery based on early changes in the C-reactive protein level in patients who received perioperative steroid therapy and enhanced recovery after surgery care: A retrospective analysis. BMC Cancer, 2017, 17(1): 812.

1. Ajani JA, D'Amico TA, Bentrem DJ, et al. Esophageal and esophagogastric junction cancers, version 2. 2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2019, 17(7): 855-883.
2. Mboumi IW, Reddy S, Lidor AO. Complications after esophagectomy. Surg Clin North Am, 2019, 99(3): 501-510.
3. Chen K. Definition, classification and prediction of complications related to esophageal resection. Zhonghua Wei Chang Wai Ke Za Zhi, 2015, 18(9): 855-859.
4. Seesing MFJ, Gisbertz SS, Goense L, et al. A propensity score matched analysis of open versus minimally invasive transthoracic esophagectomy in the Netherlands. Ann Surg, 2017, 266(5): 839-846.
5. Fransen LFC, Berkelmans GHK, Asti E, et al. The effect of postoperative complications after minimally invasive esophagectomy on long-term survival: An international multicenter cohort study. Ann Surg, 2021, 274(6): e1129-e1137.
6. Rutegård M, Lagergren P, Rouvelas I, et al. Intrathoracic anastomotic leakage and mortality after esophageal cancer resection: A population-based study. Ann Surg Oncol, 2012, 19(1): 99-103.
7. Messager M, Warlaumont M, Renaud F, et al. Recent improvements in the management of esophageal anastomotic leak after surgery for cancer. Eur J Surg Oncol, 2017, 43(2): 258-269.
8. Zafirellis KD, Fountoulakis A, Dolan K, et al. Evaluation of POSSUM in patients with oesophageal cancer undergoing resection. Br J Surg, 2002, 89(9): 1150-1155.
9. Haga Y, Wada Y, Takeuchi H, et al. Prediction of anastomotic leak and its prognosis in digestive surgery. World J Surg, 2011, 35(4): 716-722.
10. Fabbi M, Hagens ERC, van Berge Henegouwen MI, et al. Anastomotic leakage after esophagectomy for esophageal cancer: Definitions, diagnostics, and treatment. Dis Esophagus, 2021, 34(1): doaa039.
11. Moon SW, Kim JJ, Cho DG, et al. Early detection of complications: Anastomotic leakage. J Thorac Dis, 2019, 11(Suppl 5): S805-S811.
12. Verstegen MHP, Bouwense SAW, van Workum F, et al. Management of intrathoracic and cervical anastomotic leakage after esophagectomy for esophageal cancer: A systematic review. World J Emerg Surg, 2019, 14: 17.
13. Noble F, Curtis N, Harris S, et al. Risk assessment using a novel score to predict anastomotic leak and major complications after oesophageal resection. J Gastrointest Surg, 2012, 16(6): 1083-1095.
14. Bundred J, Hollis AC, Hodson J, et al. Validation of the NUn score as a predictor of anastomotic leak and major complications after esophagectomy. Dis Esophagus, 2020, 33(1): doz041.
15. Van Daele E, Van de Putte D, Ceelen W, et al. Risk factors and consequences of anastomotic leakage after Ivor Lewis oesophagectomy. Interact Cardiovasc Thorac Surg, 2016, 22(1): 32-37.
16. Huang J, Zhou Y, Wang C, et al. Logistic regression analysis of the risk factors of anastomotic fistula after radical resection of esophageal-cardiac cancer. Thorac Cancer, 2017, 8(6): 666-671.
17. Fjederholt KT, Okholm C, Svendsen LB, et al. Ketorolac and other NSAIDs increase the risk of anastomotic leakage after surgery for GEJ cancers: A cohort study of 557 patients. J Gastrointest Surg, 2018, 22(4): 587-594.
18. Gao C, Xu G, Wang C, et al. Evaluation of preoperative risk factors and postoperative indicators for anastomotic leak of minimally invasive McKeown esophagectomy: A single-center retrospective analysis. J Cardiothorac Surg, 2019, 14(1): 46.
19. 张磊, 李辉, 侯生才, 等. 基于累积评分的食管癌术后吻合口瘘的风险分级系统. 中华胸部外科电子杂志, 2016, 3(1): 15-20.Zhang L, Li H, Hou SC, et al. An aggregate score system to stratify the risk of anastomotic leakage after esophageal carcinoma surgery. Chin J Thorac Surg (Electronic Edition), 2016, 3(1): 15-20.
20. Schweigert M, Solymosi N, Dubecz A, et al. Current outcome of esophagectomy in the very elderly: Experience of a German high-volume center. American Surgeon, 2013, 79(8): 754-763.
21. Markar SR, Arya S, Karthikesalingam A, et al. Technical factors that affect anastomotic integrity following esophagectomy: Systematic review and meta-analysis. Ann Surg Oncol, 2013, 20(13): 4274-4281.
22. Urschel JD. Esophagogastrostomy anastomotic leaks complicating esophagectomy: A review. Am J Surg, 1995, 169(6): 634-640.
23. Pierie JP, de Graaf PW, van Vroonhoven TJ, et al. Healing of the cervical esophagogastrostomy. J Am Coll Surg, 1999, 188(4): 448-454.
24. 邱龙, 李向楠, 赵松, 等. 食管癌术后颈部食管胃吻合口瘘的危险因素分析. 中华消化外科杂志, 2017, 16(5): 483-489.Qiu L, Li XN, Zhao S, et al. Risk factors analysis of cervical esophagogastric anastomotic fistula after esophagectomy of esophageal cancer. Chin J Dig Surg, 2017, 16(5): 483-489.
25. Cooke DT, Lin GC, Lau CL, et al. Analysis of cervical esophagogastric anastomotic leaks after transhiatal esophagectomy: Risk factors, presentation, and detection. Ann Thorac Surg, 2009, 88(1): 177-184.
26. Okamura A, Watanabe M, Imamura Y, et al. Preoperative glycosylated hemoglobin levels predict anastomotic leak after esophagectomy with cervical esophagogastric anastomosis. World J Surg, 2017, 41(1): 200-207.
27. Honda M, Kuriyama A, Noma H, et al. Hand-sewn versus mechanical esophagogastric anastomosis after esophagectomy: A systematic review and meta-analysis. Ann Surg, 2013, 257(2): 238-248.
28. Deng XF, Liu QX, Zhou D, et al. Hand-sewn vs linearly stapled esophagogastric anastomosis for esophageal cancer: A meta-analysis. World J Gastroenterol, 2015, 21(15): 4757-4764.
29. Liu QX, Qiu Y, Deng XF, et al. Comparison of outcomes following end-to-end hand-sewn and mechanical oesophagogastric anastomosis after oesophagectomy for carcinoma: A prospective randomized controlled trial. Eur J Cardiothorac Surg, 2015, 47(3): e118-e123.
30. Warschkow R, Tarantino I, Ukegjini K, et al. Diagnostic study and meta-analysis of C-reactive protein as a predictor of postoperative inflammatory complications after gastroesophageal cancer surgery. Langenbecks Arch Surg, 2012, 397(5): 727-736.
31. Aiolfi A, Asti E, Rausa E, et al. Use of C-reactive protein for the early prediction of anastomotic leak after esophagectomy: Systematic review and Bayesian meta-analysis. PLoS One, 2018, 13(12): e0209272.
32. Kano K, Aoyama T, Nakajima T, et al. Prediction of postoperative inflammatory complications after esophageal cancer surgery based on early changes in the C-reactive protein level in patients who received perioperative steroid therapy and enhanced recovery after surgery care: A retrospective analysis. BMC Cancer, 2017, 17(1): 812.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Influencing factors and construction of a nomogram predictive model for postoperative anastomotic leak in patients with carcinoma of the esophagus and gastroesophageal junction

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