Langenbeck's Archives of Surgery

, Volume 403, Issue 2, pp 245–253 | Cite as

Implication of visceral obesity in patients with esophageal squamous cell carcinoma

  • Akihiko Okamura
  • Masayuki Watanabe
  • Kotaro Yamashita
  • Masami Yuda
  • Masaru Hayami
  • Yu Imamura
  • Shinji Mine



Visceral obesity is considered to be associated not only with chronic systemic inflammation but also with aggressive cancer behavior. However, the implication of visceral obesity in patients with esophageal squamous cell carcinoma (ESCC) is unclear.


Computed tomography volumetry was performed in 364 patients who underwent esophagectomy for ESCC. We calculated the ratio of the visceral fat area to the subcutaneous fat area (VS ratio), which is a valuable parameter of visceral obesity. Then, the clinicopathological characteristics were compared between patients with low VS ratio and those with high VS ratio.


Overall and disease-specific survivals of patients with high VS ratio were significantly worse than those with low VS ratio (P < 0.001 in both). Patients with high VS ratio had considerably more advanced pN factor, higher prevalence of lymphatic invasion, and more number of metastatic lymph nodes than those with low VS ratio (P = 0.044, < 0.001, and 0.006, respectively). Among patients who received preoperative treatment, high VS ratio correlated with poor response to preoperative treatment (P = 0.040).


Visceral obesity was associated with lymphatic invasiveness and poor response to preoperative treatment in patients with ESCC, which may negatively influence their prognosis.


Esophageal squamous cell carcinoma Visceral obesity Lymphatic invasion Lymph node metastasis Response prediction 


Authors’ contributions

Study conception and design: all authors. Acquisition of data: all authors. Analysis and interpretation of data: Okamura, Watanabe, Yamashita, Yuda, Mine. Drafting manuscript: Okamura, Watanabe, Hayami, Imamura. Critical revision of manuscript: all authors.

Funding information

This work was supported in part by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (M.W. grant number 15K10122).

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. This article does not contain any studies with animals performed by any of the authors.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supplementary material

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  1. 1.
    Cao Y (2007) Angiogenesis modulates adipogenesis and obesity. J Clin Invest 117(9):2362–2368. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    van Kruijsdijk RC, van der Wall E, Visseren FL (2009) Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomark Prev 18(10):2569–2578. CrossRefGoogle Scholar
  3. 3.
    Nieman KM, Romero IL, Van Houten B, Lengyel E (2013) Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta 1831(10):1533–1541. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Freese KE, Kokai L, Edwards RP, Philips BJ, Sheikh MA, Kelley J, Comerci J, Marra KG, Rubin JP, Linkov F (2015) Adipose-derived stems cells and their role in human cancer development, growth, progression, and metastasis: a systematic review. Cancer Res 75(7):1161–1168. CrossRefPubMedGoogle Scholar
  5. 5.
    Moon HG, Ju YT, Jeong CY, Jung EJ, Lee YJ, Hong SC, Ha WS, Park ST, Choi SK (2008) Visceral obesity may affect oncologic outcome in patients with colorectal cancer. Ann Surg Oncol 15(7):1918–1922. CrossRefPubMedGoogle Scholar
  6. 6.
    Guiu B, Petit JM, Bonnetain F, Ladoire S, Guiu S, Cercueil JP, Krause D, Hillon P, Borg C, Chauffert B, Ghiringhelli F (2010) Visceral fat area is an independent predictive biomarker of outcome after first-line bevacizumab-based treatment in metastatic colorectal cancer. Gut 59(3):341–347. CrossRefPubMedGoogle Scholar
  7. 7.
    Clark W, Siegel EM, Chen YA, Zhao X, Parsons CM, Hernandez JM, Weber J, Thareja S, Choi J, Shibata D (2013) Quantitative measures of visceral adiposity and body mass index in predicting rectal cancer outcomes after neoadjuvant chemoradiation. J Am Coll Surg 216(6):1070–1081. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Fujiwara N, Nakagawa H, Kudo Y, Tateishi R, Taguri M, Watadani T, Nakagomi R, Kondo M, Nakatsuka T, Minami T, Sato M, Uchino K, Enooku K, Kondo Y, Asaoka Y, Tanaka Y, Ohtomo K, Shiina S, Koike K (2015) Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma. J Hepatol 63(1):131–140. CrossRefPubMedGoogle Scholar
  9. 9.
    Okamura A, Watanabe M, Mine S, Nishida K, Imamura Y, Kurogochi T, Kitagawa Y, Sano T (2016) Clinical impact of abdominal fat distribution on prognosis after esophagectomy for esophageal squamous cell carcinoma. Ann Surg Oncol 23(4):1387–1394. CrossRefPubMedGoogle Scholar
  10. 10.
    Sobin LH, Gospodarowicz MK, Wittekind C, International Union against Cancer (2010) TNM classification of malignant tumours. 7th ed. Chichester, West Sussex, UK; Hoboken, NJ: Wiley-Blackwell, xx, 309 pGoogle Scholar
  11. 11.
    Edge SBBD, Compton CC, Fritz AG, Greene FL, Trotti A (eds) (2010) AJCC cancer staging manual, 7th edn. Springer, New York, NYGoogle Scholar
  12. 12.
    Japan Esophageal S (2017) Japanese classification of esophageal cancer, 11th edition: part I. Esophagus 14(1):1–36. CrossRefGoogle Scholar
  13. 13.
    Mariette C, Piessen G, Briez N, Triboulet JP (2008) The number of metastatic lymph nodes and the ratio between metastatic and examined lymph nodes are independent prognostic factors in esophageal cancer regardless of neoadjuvant chemoradiation or lymphadenectomy extent. Ann Surg 247(2):365–371. CrossRefPubMedGoogle Scholar
  14. 14.
    Hou X, Wei JC, Xu Y, Luo RZ, Fu JH, Zhang LJ, Lin P, Yang HX (2013) The positive lymph node ratio predicts long-term survival in patients with operable thoracic esophageal squamous cell carcinoma in China. Ann Surg Oncol 20(5):1653–1659. CrossRefPubMedGoogle Scholar
  15. 15.
    Zhang H, Liang H, Gao Y, Shang X, Gong L, Ma Z, Sun K, Tang P, Yu Z (2016) Metastatic lymph node ratio demonstrates better prognostic stratification than pN staging in patients with esophageal squamous cell carcinoma after esophagectomy. Sci Rep 6(1):38804. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kuwano H, Nishimura Y, Oyama T, Kato H, Kitagawa Y, Kusano M, Shimada H, Takiuchi H, Toh Y, Doki Y, Naomoto Y, Matsubara H, Miyazaki T, Muto M, Yanagisawa A (2015) Guidelines for diagnosis and treatment of carcinoma of the esophagus April 2012 edited by the Japan Esophageal Society. Esophagus 12(1):1–30. CrossRefPubMedGoogle Scholar
  17. 17.
    Frezza EE, Wachtel MS, Chiriva-Internati M (2006) Influence of obesity on the risk of developing colon cancer. Gut 55(2):285–291. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tran TT, Yamamoto Y, Gesta S, Kahn CR (2008) Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab 7(5):410–420. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Donohoe CL, Doyle SL, Reynolds JV (2011) Visceral adiposity, insulin resistance and cancer risk. Diabetol Metab Syndr 3(1):12. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Doyle SL, Donohoe CL, Lysaght J, Reynolds JV (2012) Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc 71(01):181–189. CrossRefPubMedGoogle Scholar
  21. 21.
    Ye S, Wen H, Jiang Z, Wu X (2016) The effect of visceral obesity on clinicopathological features in patients with endometrial cancer: a retrospective analysis of 200 Chinese patients. BMC Cancer 16(1):209. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kim B, Chung MJ, Park SW, Park JY, Bang S, Park SW, Song SY, Chung JB (2016) Visceral obesity is associated with poor prognosis in pancreatic adenocarcinoma. Nutr Cancer 68(2):201–207. CrossRefPubMedGoogle Scholar
  23. 23.
    Park SW, Lee HL, YW J et al (2015) Inverse association between visceral obesity and lymph node metastasis in gastric cancer. J Gastrointest Surg 19(2):242–250. CrossRefPubMedGoogle Scholar
  24. 24.
    Park SW, Lee HL, Doo EY, Lee KN, Jun DW, Lee OY, Han DS, Yoon BC, Choi HS, Lee KH (2015) Visceral obesity predicts fewer lymph node metastases and better overall survival in colon cancer. J Gastrointest Surg 19(8):1513–1521. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Trevellin E, Scarpa M, Carraro A, Lunardi F, Kotsafti A, Porzionato A, Saadeh L, Cagol M, Alfieri R, Tedeschi U, Calabrese F, Castoro C, Vettor R (2015) Esophageal adenocarcinoma and obesity: peritumoral adipose tissue plays a role in lymph node invasion. Oncotarget 6(13):11203–11215.  10.18632/oncotarget.3587 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Incio J, Liu H, Suboj P, Chin SM, Chen IX, Pinter M, Ng MR, Nia HT, Grahovac J, Kao S, Babykutty S, Huang Y, Jung K, Rahbari NN, Han X, Chauhan VP, Martin JD, Kahn J, Huang P, Desphande V, Michaelson J, Michelakos TP, Ferrone CR, Soares R, Boucher Y, Fukumura D, Jain RK (2016) Obesity-induced inflammation and desmoplasia promote pancreatic cancer progression and resistance to chemotherapy. Cancer Discov 6(8):852–869. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lashinger LM, Rossi EL, Hursting SD (2014) Obesity and resistance to cancer chemotherapy: interacting roles of inflammation and metabolic dysregulation. Clin Pharmacol Ther 96(4):458–463. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Akihiko Okamura
    • 1
  • Masayuki Watanabe
    • 1
  • Kotaro Yamashita
    • 1
  • Masami Yuda
    • 1
  • Masaru Hayami
    • 1
  • Yu Imamura
  • Shinji Mine
    • 1
  1. 1.Department of Gastroenterological Surgery, Gastroenterology CenterThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan

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