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Venous thromboembolism after esophagectomy for cancer: a systematic review of the literature to evaluate incidence, risk factors, and prophylaxis

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Abstract

Purpose

Although esophagectomy remains the preferred treatment for esophageal cancer, it is still associated with a number of complications, including post-operative venous thromboembolism (VTE). The aim of this study was to summarize the reported incidence of VTE after esophagectomy, its risk factors, and prevention strategies.

Methods

We conducted a systematic search of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results

Fourteen studies met our inclusion criteria and were selected in the present review. Overall, we identified 9768 patients who underwent esophagectomy, with a post-operative VTE rate of 4% (440 patients). The reported risk factors for VTE included advanced age, American Society of Anesthesiologists (ASA) class III or IV, a history of cardiovascular or pulmonary disease, and the implementation of preoperative chemo-radiotherapy. Postoperative acute respiratory distress syndrome was also associated with VTE. No universally applied prevention strategies for VTE after esophagectomy were identified in the literature.

Conclusions

Despite advances in perioperative care, VTE after esophagectomy still represents a source of morbidity for about 4% of patients. Low molecular weight heparin is suggested as the routine standard prophylactic regimen after esophageal cancer surgery.

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References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. https://doi.org/10.3322/caac.21262.

    Article  PubMed  Google Scholar 

  2. Low DE, Alderson D, Cecconello I, Chang A, Darling G, D’Journo X, et al. International consensus on standardization of data collection for complications associated with esophagectomy: Esophagectomy Complications Consensus Group (ECCG). Ann Surg. 2015;262(2):286–94. https://doi.org/10.1097/SLA.0000000000001098.

    Article  PubMed  Google Scholar 

  3. Schizas D, Kosmopoulos M, Giannopoulos S, Giannopoulos S, Kokkinidis D, Karampetsou N, et al. Meta-analysis of risk factors and complications associated with atrial fibrillation after oesophagectomy. Br J Surg. 2019;106(5):534–47. https://doi.org/10.1002/bjs.11128.

    Article  CAS  PubMed  Google Scholar 

  4. Mboumi IW, Reddy S, Lidor AO. Complications After Esophagectomy. Surg Clin North Am. 2019;99(3):501–10. https://doi.org/10.1016/j.suc.2019.02.011.

    Article  PubMed  Google Scholar 

  5. Kushner A., West William P., Pillarisetty L.S. (2020) “Virchow Triad,” Treasure Island (FL).

  6. Byrne M, Reynolds J, O’Donnell J, Keogan M, White B, Byrne M, et al. Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery. Br J Cancer. 2010;102(1):73–9. https://doi.org/10.1038/sj.bjc.6605463.

    Article  CAS  PubMed  Google Scholar 

  7. Jadad A, Moore R, Carroll D, Jenkinson C, Reynolds D, Gavaghan D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12. https://doi.org/10.1016/0197-2456(95)00134-4.

    Article  CAS  PubMed  Google Scholar 

  8. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5. https://doi.org/10.1007/s10654-010-9491-z.

    Article  PubMed  Google Scholar 

  9. Adiamah A., Ban L., West J., Humes D.J. (2019) “The risk of venous thromboembolism after surgery for esophagogastric malignancy and the impact of chemotherapy : a population-based cohort study,” pp. 1–9. https://doi.org/10.1093/dote/doz079.

  10. Kato F, Takeuchi H, Matsuda S, Kawakubo H, Omori T, Kitagawa Y. Incidence of and risk factors for venous thromboembolism during surgical treatment for esophageal cancer: a single-institution study. Surg Today. 2016;46(4):445–52. https://doi.org/10.1007/s00595-015-1196-1.

    Article  CAS  PubMed  Google Scholar 

  11. Cooke DT, Calhoun RF, Kuderer V, David EA. A defined esophagectomy perioperative clinical care process can improve outcomes and costs. Am Surg. 2017;83(1):103–11.

    Article  Google Scholar 

  12. Bosch DJ, Van Dalfsen QA, Mul VEM, Hospers GAP, Plukker JTM. Increased risk of thromboembolism in esophageal cancer patients treated with neoadjuvant chemoradiotherapy. Am J Surg. 2014;208(2):215–21. https://doi.org/10.1016/j.amjsurg.2013.10.031.

    Article  PubMed  Google Scholar 

  13. Dhungel B, Diggs BS, Hunter JG, Sheppard BC, Vetto JT, Dolan JP. Patient and Peri-operative predictors of morbidity and mortality after Esophagectomy: American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), 2005–2008. J Gastrointest Surg. 2010;14(10):1492–501. https://doi.org/10.1007/s11605-010-1328-2.

    Article  PubMed  Google Scholar 

  14. Mantziari S, Gronnier C, Pasquer A, Gagnière J, Théreaux J, Demartines N, et al. Incidence and risk factors related to symptomatic venous thromboembolic events after esophagectomy for cancer. Ann Thorac Surg. 2016;102(3):979–84. https://doi.org/10.1016/j.athoracsur.2016.03.093.

    Article  PubMed  Google Scholar 

  15. Porteous GH, Neal JM, Slee A, Schmidt H, Low DE. A standardized anesthetic and surgical clinical pathway for esophageal resection: impact on length of stay and major outcomes. Reg Anesth Pain Med. 2015;40(2):139–49. https://doi.org/10.1097/AAP.0000000000000197.

    Article  CAS  PubMed  Google Scholar 

  16. Martin J, Mahan A, Ferraris V, Saha S, Mullett T, Zwischenberger J, et al. Identifying esophagectomy patients at risk for predischarge versus postdischarge venous thromboembolism. Ann Thorac Surg. 2015;100(3):932–8. https://doi.org/10.1016/j.athoracsur.2015.04.042.

    Article  PubMed  Google Scholar 

  17. Rajabi MM, Bagheri R, Abdollahi A, Ghamari M, Shahidsales S, Salehi M, et al. The effect of neoadjuvant therapy on early complications of esophageal cancer surgery. Iran J Otorhinolaryngol. 2015;27(81):279–84. https://doi.org/10.22038/ijorl.2015.4247.

    Article  Google Scholar 

  18. Song J, Xuan L, Wu W, Huang J, Zhong M. Low molecular weight heparin once versus twice for thromboprophylaxis following esophagectomy: a randomised, double-blind and placebo-controlled trial. J Thorac Dis. 2015;7(7):1158–64. https://doi.org/10.3978/j.issn.2072-1439.2015.06.15.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Song J, Xuan L, Wu W, Shen Y, Tan L, Zhong M. Fondaparinux versus nadroparin for thromboprophylaxis following minimally invasive esophagectomy: a randomized controlled trial. Thromb Res. 2018;166(March):22–7. https://doi.org/10.1016/j.thromres.2018.04.001.

    Article  CAS  PubMed  Google Scholar 

  20. Tanaka Y, Yamada A, Hirata S, Tanaka H, Sakuratani T, Matsuhashi N, et al. Efficacy and safety of Enoxaparin for prophylaxis of postoperative venous Thromboembolism after esophagectomy: a single-center prospective randomized controlled phase II study. Anticancer Res. 2019;39(5):2615–25. https://doi.org/10.21873/anticanres.13385.

    Article  CAS  PubMed  Google Scholar 

  21. Larsen A, Frøkjær J, Fisker R, Iyer V, Mortensen P, Yilmaz M, et al. Treatment-related frequency of venous thrombosis in lower esophageal, gastro-esophageal and gastric cancer—a clinical prospective study of outcome and prognostic factors. Thromb Res. 2015;135(5):802–8. https://doi.org/10.1016/j.thromres.2015.01.021.

    Article  CAS  PubMed  Google Scholar 

  22. Yoshida N., Baba Y., Miyamoto Y., Iwatsuki M. “Prophylaxis of postoperative venous Thromboembolism using enoxaparin after Esophagectomy : a prospective observational study of effectiveness and safety,” Ann. Surg. Oncol., vol. 3. https://doi.org/10.1245/s10434-018-6552-0.

  23. De Martino R, Goodney P, Spangler E, Wallaert J, Corriere M, Rzucidlo E, et al. Variation in thromboembolic complications among patients undergoing commonly performed cancer operations. J Vasc Surg. 2012;55(4):1035-1040.e4. https://doi.org/10.1016/j.jvs.2011.10.129.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Beckers M, Ruven H, Seldenrijk C, Prins M, Biesma D. Risk of thrombosis and infections of central venous catheters and totally implanted access ports in patients treated for cancer. Thromb Res. 2010;125(4):318–21. https://doi.org/10.1016/j.thromres.2009.06.008.

    Article  CAS  PubMed  Google Scholar 

  25. Oppelt P, Betbadal A, Nayak L. Approach to chemotherapy-associated thrombosis. Vasc Med. 2015;20(2):153–61. https://doi.org/10.1177/1358863X14568705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Elice F, Fink L, Tricot G, Barlogie B, Zangari M. Acquired resistance to activated protein C (aAPCR) in multiple myeloma is a transitory abnormality associated with an increased risk of venous thromboembolism. Br J Haematol. 2006;134(4):399–405. https://doi.org/10.1111/j.1365-2141.2006.06208.x.

    Article  CAS  PubMed  Google Scholar 

  27. Amrani DL. Regulation of fibrinogen biosynthesis: glucocorticoid and interleukin-6 control. Blood Coagul Fibrinolysis. 1990;1(4–5):443–6.

    Article  CAS  Google Scholar 

  28. Lyman G, Bohlke K, Khorana A, Kuderer N, Lee A, Arcelus J, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014. J Clin Oncol. 2015;33(6):654–6. https://doi.org/10.1200/JCO.2014.59.7351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tsutsumi K, Udagawa H, Kajiyama Y, Kinoshita Y, Ueno M, Nakamura T, et al. Pulmonary thromboembolism after surgery for esophageal cancer: its features and prophylaxis. Surg Today. 2000;30(5):416–20. https://doi.org/10.1007/s005950050614.

    Article  CAS  PubMed  Google Scholar 

  30. “Venous thromboembolism in over 16s : reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism,” no. March 2018, 2019.Please check and provide full details for the reference 9, 22, 30, 41.9. Adiamah A., Ban L., West J., and Humes D.J., “The risk of venous thromboembolism after surgery for esophagogastric malignancy and the impact of chemotherapy : a population-based cohort study,” Dis.Esophagus pp. 1–9, 2019, doi: 10.1093/dote/doz079. 22. Yoshida N., Baba Y., Miyamoto Y., and Iwatsuki M. et al, “Prophylaxis of Postoperative Venous Thromboembolism Using Enoxaparin After Esophagectomy : A Prospective Observational Study of Effectiveness and Safety,” Ann. Surg. Oncol., vol. 3, doi: 10.1245/s10434-018-6552-0. 30. Gee.E, “The National VTE Exemplar Centres Network response to implementation of updated NICE guidance: venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism (NG89).,” British journal of haematology, vol. 186, no. 5. England, pp. 792–793, Sep. 2019, doi: 10.1111/bjh.16010. 41. Shargall Y. and . Litle V.R., “European perspectives in Thoracic Surgery , the ESTS venous thromboembolism ( VTE ) working group,” J.Thorac Dis, vol. 10, no. 6, pp. 963–968, 2018, doi: 10.21037/jtd.2018.04.70.

  31. Gould M, Garcia D, Wren S, Karanicolas P, Arcelus J, Heit J, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e227S-e277S. https://doi.org/10.1378/chest.11-2297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kim J, Khavanin N, Rambachan A, McCarthy R, Mlodinow A, De Oliveria G, et al. Surgical duration and risk of venous thromboembolism. JAMA Surg. 2015;150(2):110–7. https://doi.org/10.1001/jamasurg.2014.1841.

    Article  PubMed  Google Scholar 

  33. Hotoleanu C. Association between obesity and venous thromboembolism. Med Pharm Reports. 2020;93(2):162–8. https://doi.org/10.15386/mpr-1372.

    Article  Google Scholar 

  34. Connolly G, Francis C. Cancer-associated thrombosis. Hematol Am Soc Hematol Educ Progr. 2013;2013:684–91. https://doi.org/10.1182/asheducation-2013.1.684.

    Article  Google Scholar 

  35. Agnelli G, Bolis G, Capussotti L, Scarpa R, Tonelli F, Bonizzoni E, et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg. 2006;243(1):89–95. https://doi.org/10.1097/01.sla.0000193959.44677.48.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bhagya RB, Kalayarasan R, Kate V, Ananthakrishnan N. Venous thromboembolism in cancer patients undergoing major abdominal surgery: prevention and management. ISRN Vasc Med. 2012;2012:783214. https://doi.org/10.5402/2012/783214.

    Article  Google Scholar 

  37. Emoto S, Nozawa H, Kawai K, Hata K, Tanaka T, Shuno Y, et al. Venous thromboembolism in colorectal surgery: Incidence, risk factors, and prophylaxis. Asian J Surg. 2019;42(9):863–73. https://doi.org/10.1016/j.asjsur.2018.12.013.

    Article  PubMed  Google Scholar 

  38. Osaki T, Saito H, Fukumoto Y, Kono Y, Murakami Y, Shishido Y, et al. Risk and incidence of perioperative deep vein thrombosis in patients undergoing gastric cancer surgery. Surg Today. 2018;48(5):525–33. https://doi.org/10.1007/s00595-017-1617-4.

    Article  PubMed  Google Scholar 

  39. Wada T, Fujiwara H, Morita S, Fukagawa T, Katai H. Incidence of and risk factors for preoperative deep venous thrombosis in patients undergoing gastric cancer surgery. Gastric Cancer. 2017;20(5):872–7. https://doi.org/10.1007/s10120-017-0690-0.

    Article  PubMed  Google Scholar 

  40. Beal E, Tumin D, Chakedis J, Porter E, Moris D, Zhang X, et al. Which patients require extended thromboprophylaxis after colectomy? Modeling risk and assessing indications for post-discharge pharmacoprophylaxis. World J Surg. 2018;42(7):2242–51. https://doi.org/10.1007/s00268-017-4447-z.

    Article  PubMed  Google Scholar 

  41. Shargall Y, Litle V.R. (2018) European perspectives in Thoracic Surgery, the ESTS venous thromboembolism (VTE) working group. 10(6): 963–968. https://doi.org/10.21037/jtd.2018.04.70.

  42. Golemi I, Salazar AJ, Tafur A, Caprini J. Venous thromboembolism prophylaxis using the Caprini score. Dis Mon. 2019;65(8):249–98. https://doi.org/10.1016/j.disamonth.2018.12.005.

    Article  PubMed  Google Scholar 

  43. Whiteway A, Burton C., “Guideline for the Prevention of Venous Thrombo-Embolism ( VTE ) in Adults,” Prevention, no. December 2005, 2008.

  44. Gould M, Garcia D, Wren S, Karanicolas P, Arcelus J, Heit J, et al. Prevention of VTE in nonorthopedic surgical patients. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e227S-e277S. https://doi.org/10.1378/chest.11-2297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Amalia Fleming General Hospital, 29 Parnithos, 16344, Athens, Ilioupolis, Greece

    Nikoletta A. Theochari

  2. Third Department of Internal Medicine, National and Kapodistrian University of Athens, Thoracic Diseases General Hospital Sotiria, Athens, Greece

    Christina A. Theochari

  3. Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Damianos G. Kokkinidis

  4. Department of Gastrointestinal Surgery, Kanta-Häme Central Hospital, Hämeenlinna, Finland

    Aristotelis Kechagias

  5. Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany

    Orestis Lyros

  6. Department of Surgery, VA and Hellenic Air Force Hospital, 251, Athens, Greece

    Stefanos Giannopoulos

  7. Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland

    Styliani Mantziari

  8. First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece

    Dimitrios Schizas

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  1. Nikoletta A. Theochari
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  2. Christina A. Theochari
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  3. Damianos G. Kokkinidis
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  4. Aristotelis Kechagias
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  6. Stefanos Giannopoulos
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  7. Styliani Mantziari
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  8. Dimitrios Schizas
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Contributions

Study concept and design: Schizas, Kokkinidis, TNA, TCA. Acquisition of data: TNA, TCA, Kokkinidis, Giannopoulos. Analysis and interpretation of data: TNA, TCA, Lyros, Giannopoulos. Drafting of the manuscript: NA, TCA, Kokkinidis, Mantziari, Kechagias, Lyros. Critical revision of the manuscript for important intellectual content: Schizas, Kokkinidis, TNA, Mantziari, Kechagias, Lyros.

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Correspondence to Nikoletta A. Theochari.

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Theochari, N.A., Theochari, C.A., Kokkinidis, D.G. et al. Venous thromboembolism after esophagectomy for cancer: a systematic review of the literature to evaluate incidence, risk factors, and prophylaxis. Surg Today 52, 171–181 (2022). https://doi.org/10.1007/s00595-021-02260-2

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