Annals of Surgical Oncology

, Volume 26, Issue 7, pp 2081–2089 | Cite as

Influence of Neoadjuvant Therapy on Poor Long-Term Outcomes of Postoperative Complications in Patients with Esophageal Squamous Cell Carcinoma: A Retrospective Cohort Study

  • Masashi Takeuchi
  • Hirofumi KawakuboEmail author
  • Shuhei Mayanagi
  • Tomoyuki Irino
  • Kazumasa Fukuda
  • Rieko Nakamura
  • Norihito Wada
  • Hiroya Takeuchi
  • Yuko Kitagawa
Thoracic Oncology



Postoperative complications have a negative impact on overall survival after esophagectomy because systemic inflammation may induce residual cancer cell growth. A solution that could suppress micrometastasis is neoadjuvant therapy; however, to date, no study has shown that neoadjuvant therapy suppresses proliferation of cancer cells due to postoperative complications after esophagectomy. The aim of this study is to investigate the influence of neoadjuvant therapy on poor long-term outcomes of postoperative complications in patients with esophageal carcinoma.

Patients and Methods

In total, 431 patients who underwent esophagectomy for esophageal squamous cell carcinoma were included in this study. We investigated the relationship between complications, such as pneumonia, and long-term oncologic outcomes with and without neoadjuvant therapy.


Among the patients, the 3-year overall survival (OS) rate was 69.5% and the disease-free survival (DFS) rate was 59.0%. The patients were categorized into two groups: the neoadjuvant therapy (+) group (n = 217) and neoadjuvant therapy (−) group (n = 214). Among patients not undergoing neoadjuvant therapy, patients with pneumonia or pyothorax had significantly poorer OS and DFS than patients without these complications. However, among patients undergoing neoadjuvant therapy, there were no significant differences in long-term outcomes, regardless of presence of complications. On multivariate analysis, pneumonia (p = 0.003), pyothorax (p < 0.001), and chylothorax (p = 0.002) were identified as predictors of death in the neoadjuvant therapy (−) group.


The negative impact of postoperative complications on long-term prognoses can be reduced by performing neoadjuvant therapy in patients with esophageal carcinoma.



The authors thank Kumiko Motooka, a staff member at the Department of Surgery in Keio University School of Medicine, for help in preparation of the manuscript.


Yuko Kitagawa reports personal fees from ETHICON PART OF JOHNSON AND JOHNSON FAMILY OF COMPANIES, grants from KYOWA HAKKO KIRIN CO., LTD, personal fees from Medtronic Japan Co., Ltd., outside the submitted work.

Supplementary material

10434_2019_7312_MOESM1_ESM.tiff (332 kb)
Supplemental Figure 1 Kaplan–Meier curves for disease-free survival (DFS) associated with pneumonia in the (A-1) neoadjuvant therapy (+) group and (A-2) neoadjuvant therapy (−) group; Kaplan–Meier curves for cancer-specific survival (CSS) associated with pneumonia in the (B-1) neoadjuvant therapy (+) group and (B-2) neoadjuvant therapy (−) group. Red and blue lines indicate groups with and without pneumonia, respectively (TIFF 332 kb)
10434_2019_7312_MOESM2_ESM.docx (35 kb)
Supplementary material 2 (DOCX 34 kb)


  1. 1.
    Takeuchi H, Miyata H, Gotoh M, et al. A risk model for esophagectomy using data of 5354 patients included in a Japanese nationwide web-based database. Ann Surg. 2014;260:259–66.CrossRefPubMedGoogle Scholar
  2. 2.
    Mariette C, Taillier G, Van Seuningen I, et al. Factors affecting postoperative course and survival after en bloc resection for esophageal carcinoma. Ann Thorac Surg. 2004;78:1177–83.CrossRefPubMedGoogle Scholar
  3. 3.
    Pennathur A, Luketich JD, Landreneau RJ, et al. Long-term results of a phase II trial of neoadjuvant chemotherapy followed by esophagectomy for locally advanced esophageal neoplasm. Ann Thorac Surg. 2008;85:1930–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Booka E, Takeuchi H, Nishi T, et al. The impact of postoperative complications on survivals after esophagectomy for esophageal cancer. Medicine (Baltimore). 2015;94:e1369.CrossRefGoogle Scholar
  5. 5.
    Takeuchi M, Kawakubo H, Mayanagi S, et al. Postoperative pneumonia is associated with long-term oncologic outcomes of definitive chemoradiotherapy followed by salvage esophagectomy for esophageal cancer. J Gastrointest Surg.  2018;22:1881–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Kataoka K, Takeuchi H, Mizusawa J, et al. Prognostic impact of postoperative morbidity after esophagectomy for esophageal cancer. Ann Surg. 2017;265:1152–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Baba Y, Yoshida N, Shigaki H, et al. Prognostic impact of postoperative complications in 502 patients with surgically resected esophageal squamous cell carcinoma: a retrospective single-institution study. Ann Surg. 2016;264:305–11.CrossRefPubMedGoogle Scholar
  8. 8.
    Saeki H, Tsutsumi S, Tajiri H, et al. Prognostic significance of postoperative complications after curative resection for patients with esophageal squamous cell carcinoma. Ann Surg. 2017;265:527–33.CrossRefPubMedGoogle Scholar
  9. 9.
    Takeuchi M, Takeuchi H, Kawakubo H, et al. Perioperative risk calculator predicts long-term oncologic outcome for patients with esophageal carcinoma. Ann Surg Oncol. 2018;25:837–43.CrossRefPubMedGoogle Scholar
  10. 10.
    Ando N, Kato H, Igaki H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2011;19:68–74.CrossRefPubMedGoogle Scholar
  11. 11.
    Japan Esophageal Society. Japanese classification of esophageal cancer, 11th edition: part II and III. Esophagus. 2017;14:37–65.CrossRefGoogle Scholar
  12. 12.
    Sobin L, Gospodarowicz MWC (eds). TNM classification of malignant tumours. 7th ed. New York: Wiley-Liss; 2009.Google Scholar
  13. 13.
    Japan Esophageal Society. Japanese classification of esophageal cancer, 11th edition: part I. Esophagus. 2017;14:1–36.CrossRefGoogle Scholar
  14. 14.
    Kaburagi T, Takeuchi H, Kawakubo H, et al. Clinical utility of a novel hybrid position combining the left lateral decubitus and prone positions during thoracoscopic esophagectomy. World J Surg. 2013;38:410–8.CrossRefGoogle Scholar
  15. 15.
    Matsuda S, Takeuchi H, Kawakubo H, et al. Clinical outcome of transthoracic esophagectomy with thoracic duct resection: number of dissected lymph node and distribution of lymph node metastasis around the thoracic duct. Medicine. 2016;95:e3839.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Dindo D, Demartines N, Clavien P-A. Classification of surgical complications. Ann Surg. 2004;240:205–13.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Takeuchi H, Saikawa Y, Oyama T, et al. Factors influencing the long-term survival in patients with esophageal cancer who underwent esophagectomy after chemoradiotherapy. World J Surg. 2009;34:277–84.CrossRefGoogle Scholar
  18. 18.
    Eto K, Hiki N, Kumagai K, et al. Prophylactic effect of neoadjuvant chemotherapy in gastric cancer patients with postoperative complications. Gastric Cancer. 2018;21:703–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Rizk NP, Bach PB, Schrag D, et al. The impact of complications on outcomes after resection for esophageal and gastroesophageal junction carcinoma. J Am Coll Surg. 2004;198:42–50.CrossRefPubMedGoogle Scholar
  20. 20.
    Okamura A, Takeuchi H, Matsuda S, et al. Factors affecting cytokine change after esophagectomy for esophageal cancer. Ann Surg Oncol. 2015;22:3130–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Ogura M, Takeuchi H, Kawakubo H, et al. Clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma. Surgery. 2013;154:512–20.CrossRefPubMedGoogle Scholar
  22. 22.
    Chen MF, Chen PT, Chen WC, et al. The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression. Oncotarget. 2016;7:7913–24.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Nakamura K, Kato K, Igaki H, et al. Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol. 2013;43:752–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Hirao M, Ando N, Tsujinaka T, et al. Influence of preoperative chemotherapy for advanced thoracic oesophageal squamous cell carcinoma on perioperative complications. Br J Surg. 2011;98:1735–41.CrossRefPubMedGoogle Scholar
  25. 25.
    Kranzfelder M, Gertler R, Hapfelmeier A, et al. Chylothorax after esophagectomy for cancer: impact of the surgical approach and neoadjuvant treatment: systematic review and institutional analysis. Surg Endosc. 2013;27:3530–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Mc Cormack O, Zaborowski A, King S, et al. New-onset atrial fibrillation post-surgery for esophageal and junctional cancer: incidence, management, and impact on short- and long-term outcomes. Ann Surg. 2014;260:772–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Ancona E, Cagol M, Epifani M, et al. Surgical complications do not affect longterm survival after esophagectomy for carcinoma of the thoracic esophagus and cardia. J Am Coll Surg. 2006;203:661–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Rutegard M, Lagergren P, Rouvelas I, et al. Surgical complications and long-term survival after esophagectomy for cancer in a nationwide Swedish cohort study. Eur J Surg Oncol. 2012;38:555–61.CrossRefPubMedGoogle Scholar
  29. 29.
    Low DE, Alderson D, Cecconello I, et al. International consensus on standardization of data collection for complications associated with esophagectomy: esophagectomy complications consensus group (ECCG). Ann Surg. 2015;262:286–94.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Masashi Takeuchi
    • 1
  • Hirofumi Kawakubo
    • 1
    Email author
  • Shuhei Mayanagi
    • 1
  • Tomoyuki Irino
    • 1
  • Kazumasa Fukuda
    • 1
  • Rieko Nakamura
    • 1
  • Norihito Wada
    • 1
  • Hiroya Takeuchi
    • 1
    • 2
  • Yuko Kitagawa
    • 1
  1. 1.Department of SurgeryKeio University School of MedicineShinjuku-kuJapan
  2. 2.Department of SurgeryHamamatsu University School of MedicineHamamatsuJapan

Personalised recommendations