Analysis of influencing factors and construction of a nomogram predictive model for anastomotic leak after radical esophageal and gastroesophageal junction carcinoma_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：

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 influencing factors and construction of a nomogram predictive model for anastomotic leak after radical esophageal and gastroesophageal junction carcinoma. Methods The patients who underwent radical esophagectomy at Jinling Hospital affiliated to Nanjing University School of Medicine from January 2018 to June 2020 were selected. After screening for related variables using SPSS univariate and multivariate logistic regression analysis, the "nomogram" was used to predict the risk of anastomotic leak based on R language. The predicted effects were verified by the receiver operating characteristic (ROC) curves. Results A total of 468 patients with esophageal carcinoma were collected, including 354 (75.64%) males and 114 (24.35%) females with a mean age of 62.8±7.2 years. The tumor was mainly located in the middle or lower stage; 51 (10.90% ) patients had postoperative anastomotic leak. In univariate logistic regression analysis, age, BMI, tumor location, preoperative albumin, diabetes mellitus, anastomosis mode, anastomosis site, and CRP might be associated with anastomotic leak (P＜0.05). The above data suggested by multivariate logistic regression analysis illustrate that age, BMI, tumor location, diabetes mellitus, anastomosis mode, and CRP were independent risks of anastomotic leak (P＜0.05). The nomogram was constructed according to the results of multivariate logistic regression analysis. The area under the curve (AUC) of ROC curve was 0.803 showing that the actual observations agree well with the predicted results. In addition, the decision curve analysis concluded that the newly established nomogram was significant for clinical decision-making. Conclusion The predictive model of anastomotic leak after radical esophageal and gastroesophageal junction carcinoma has a good predictive effect and is critical for guiding clinical observation, early screening and prevention.

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.
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.
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.
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.
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.

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