Advertisement

General Thoracic and Cardiovascular Surgery

, Volume 66, Issue 12, pp 716–722 | Cite as

Positive correlation between sarcopenia and elevation of neutrophil/lymphocyte ration in pathological stage IIIA (N2-positive) non-small cell lung cancer patients

  • Takuma TsukiokaEmail author
  • Nobuhiro Izumi
  • Shinjiro Mizuguchi
  • Chung Kyukwang
  • Hiroaki Komatsu
  • Michihito Toda
  • Kantaro Hara
  • Hikaru Miyamoto
  • Noritoshi Nishiyama
Original Article

Abstract

Objective

Surgical indication in stage IIIA (N2) non-small cell lung cancer is still controversial. Hence, there is a need for the identification of predictors of the postoperative outcome in these patients. Although sarcopenia is expected to be a novel predictor of postoperative outcome in these patients, the underlying clinical features of sarcopenia have not been well investigated. Elevation of neutrophil/lymphocyte ratio indicates cancer-associated inflammation and depression of anticancer immunity. We analyzed the influence of sarcopenia on postoperative prognosis, and investigated the relationship between sarcopenia and neutrophil/lymphocyte ratio in patients with stage IIIA (N2) non-small cell lung cancer.

Methods

We retrospectively investigated 69 patients with stage IIIA (N2) non-small cell lung cancer. We used the L3 muscle index as a clinical measurement of sarcopenia, and divided patients into the sarcopenic (n = 21) and the non-sarcopenic group (n = 48). We then investigated the effect of sarcopenia on postoperative prognosis, and evaluated the correlation between sarcopenia and neutrophil/lymphocyte ratio.

Results

This study included 47 males and 22 females. Univariate analysis revealed that sarcopenia, performance status, and serum cytokeratin-19 fragment level were predictors of poor prognosis; multivariate analysis revealed that performance status and sarcopenia were independent predictors of poor prognosis. The presence of sarcopenia was significantly correlated with neutrophil/lymphocyte ratio elevation.

Conclusions

Sarcopenia is a novel predictor of poor prognosis in patients with stage IIIA (N2) non-small cell lung cancer. Neutrophil/lymphocyte ratio elevation might be the reason for poor prognosis in sarcopenic patients.

Keywords

Sarcopenia Non-small cell lung cancer Lymph node metastasis Neutrophil/lymphocyte ratio 

Notes

Compliance with ethical standards

Conflict of interest

All the authors have no conflicts of interest.

References

  1. 1.
    Mao Q, Xia W, Dong G, Chen S, Wang A, Jin G, et al. A nomogram to predict the survival of stage IIIA-N2 non-small cell lung cancer after surgery. J Thorac Cardiovasc Surg. 2018;155:1784–92.CrossRefGoogle Scholar
  2. 2.
    Rami-Porta R, Bolejack V, Crowley J, Ball D, Kim J, Lyons G, et al. IASLC Staging and Prognostic Factors Committee, Advisory Boards and Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for the revisions of the T descriptors in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol. 2015;10:990–1003.CrossRefGoogle Scholar
  3. 3.
    Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 2011;12:249–56.CrossRefGoogle Scholar
  4. 4.
    Ali S, Garcia JM. Sarcopenia, cachexia and aging: diagnosis, mechanisms and therapeutic options—a mini-review. Gerontology. 2014;60:294–305.CrossRefGoogle Scholar
  5. 5.
    Fearon KC. Cancer cachexia and fat-muscle physiology. N Engl J Med. 2011;365:565–7.CrossRefGoogle Scholar
  6. 6.
    Kimura M, Naito T, Kenmotsu H, Taira T, Wakuda K, Oyakawa T, et al. Prognostic impact of cancer cachexia in patients with advanced non-small cell lung cancer. Support Care Cancer. 2015;23:1699–708.CrossRefGoogle Scholar
  7. 7.
    Suzuki Y, Okamoto T, Fujishita T, Katsura M, Akamine T, Takamori S, et al. Clinical implications of sarcopenia in patients undergoing complete resection for early non-small cell lung cancer. Lung Cancer. 2016;101:92–7.CrossRefGoogle Scholar
  8. 8.
    Tsukioka T, Nishiyama N, Izumi N, Mizuguchi S, Komatsu H, Okada S, et al. Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer. Jpn J Clin Oncol. 2017;474:363–8.CrossRefGoogle Scholar
  9. 9.
    Kim EY, Kim YS, Park I, Ahn HK, Cho EK, Jeong YM. Prognostic significance of CT-determined sarcopenia in patients with small-cell lung cancer. J Thorac Oncol. 2015;10:1795–9.CrossRefGoogle Scholar
  10. 10.
    Shimizu K, Okita R, Saisho S, Maeda A, Nojima Y, Nakata M. Preoperative neutrophil/lymphocyte ratio and prognostic nutritional index predict survival in patients with non-small cell lung cancer. World J Surg Oncol. 2015.  https://doi.org/10.1186/s12957-015-0710-7.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Wang J, Kalhor N, Hu J, Wang B, Chu H, Zhang B, et al. Pretreatment neutrophil to lymphocyte ratio is associated with poor survival in patients with stage I–III non-small cell lung cancer. PLoS One. 2016.  https://doi.org/10.1371/journal.pone.0163397.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Nagaraj S, Schrum AG, Cho HI, Celis E, Gabrilovich DI. Mechanism of T cell tolerance induced by myeloid-derived suppressor cells. J Immunol. 2010;184:3106–16.CrossRefGoogle Scholar
  13. 13.
    Shau HY, Kim A. Suppression of lymphokine-activated killer induction by neutrophils. J Immunol. 1988;141:4395–402.PubMedGoogle Scholar
  14. 14.
    Fridlender ZG, Albelda SM. Tumor-associated neutrophils: friend or foe? Carcinogenesis. 2012;33:949–55.CrossRefGoogle Scholar
  15. 15.
    Shen W, Punyanitya M, Wang Z, Gallagher D, St-Onge MP, Albu J, et al. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. J Appl Physiol. 2004;97:2333–8.CrossRefGoogle Scholar
  16. 16.
    Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9:629–35.CrossRefGoogle Scholar
  17. 17.
    Yoshizumi T, Shirabe K, Nakagawara H, Ikegami T, Harimoto N, Toshima T, et al. Skeletal muscle area correlates with body surface area in healthy adults. Hepatol Res. 2014;44:313–8.CrossRefGoogle Scholar
  18. 18.
    WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363:157–63.CrossRefGoogle Scholar
  19. 19.
    Inoue M, Takakuwa T, Minami M, Shiono H, Utsumi T, Kadota Y, et al. Clinicopathologic factors influencing postoperative prognosis in patients with small-sized adenocarcinoma of the lung. J Thorac Cardiovasc Surg. 2008;135:830–6.CrossRefGoogle Scholar
  20. 20.
    Grunnet M, Sorensen JB. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer. 2012;76:138–43.CrossRefGoogle Scholar
  21. 21.
    Kawai T, Ohkubo A, Hasegawa S, Kuriyama T, Kato H, Fukuoka M, et al. Study of standard level, cut off level, diagnostic specificity and sensitivity for a new tumor marker CYFRA in lung cancer measured by EIA (in Japanese). Kiki Shiyaku Jpn. 1993;16:1232–8.Google Scholar
  22. 22.
    Fishman P, Bar-Yehuda S, Vagman L. Adenosine and other low molecular weight factors released by muscle cells inhibit tumor cell growth. Cancer Res. 1998;58:3181–7.PubMedGoogle Scholar
  23. 23.
    Tomita M, Shimizu T, Ayabe T, Nakamura K, Onitsuka T. Elevated preoperative inflammatory markers based on neutrophil-to-lymphocyte ratio and C-reactive protein predict poor survival in resected non-small cell lung cancer. Anticancer Res. 2012;32:3535–8.PubMedGoogle Scholar
  24. 24.
    Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001;294:1704–8.CrossRefGoogle Scholar
  25. 25.
    Hetzler KL, Hardee JP, Puppa MJ, Narsale AA, Sato S, Davis JM, et al. Sex differences in the relationship of IL-6 signaling to cancer cachexia progression. Biochim Biophys Acta. 2015;1852:816–25.CrossRefGoogle Scholar
  26. 26.
    Jones SE, Maddocks M, Kon SS, Canavan JL, Nolan CM, Clark AL, et al. Sarcopenia in COPD: prevalence, clinical correlates and response to pulmonary rehabilitation. Thorax. 2015;70:213–8.CrossRefGoogle Scholar
  27. 27.
    Wei N, Pang MY, Ng SS, Ng GY. Optimal frequency/time combination of whole-body vibration training for improving muscle size and strength of people with age-related muscle loss (sarcopenia): a randomized controlled trial. Geriatr Gerontol Int. 2016.  https://doi.org/10.1111/ggi.12878.CrossRefPubMedGoogle Scholar
  28. 28.
    Yao X, Huang J, Zhong H, Shen N, Faggioni R, Fung M, Yao Y. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. Pharmacol Ther. 2014;141:125–39.CrossRefGoogle Scholar
  29. 29.
    Zeligs KP, Neuman MK, Annunziata CM. Molecular pathways: the balance between cancer and the immune system challenges the therapeutic specificity of targeting nuclear factor-κB signaling for cancer treatment. Clin Cancer Res. 2016;22:4302–8.CrossRefGoogle Scholar
  30. 30.
    Kanamaru R, Ohzawa H, Miyato H, Matsumoto S, Haruta H, Kurashina K, et al. Low density neutrophils (LDN) in postoperative abdominal cavity assist the peritoneal recurrence through the production of neutrophil extracellular traps (NETs). Sci Rep. 2018.  https://doi.org/10.1038/s41598-017-19091-2.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Fukushima H, Yokoyama M, Nakanishi Y, Tobisu K, Koga F. Sarcopenia as a prognostic biomarker of advanced urothelial carcinoma. PLoS One. 2015.  https://doi.org/10.1371/journal.pone.0115895.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Kamachi S, Mizuta T, Otsuka T, Nakashita S, Ide Y, Miyoshi A, et al. Sarcopenia is a risk factor for the recurrence of hepatocellular carcinoma after curative treatment. Hepatol Res. 2016;46:201–8.CrossRefGoogle Scholar

Copyright information

© The Japanese Association for Thoracic Surgery 2018

Authors and Affiliations

  • Takuma Tsukioka
    • 1
    Email author
  • Nobuhiro Izumi
    • 1
  • Shinjiro Mizuguchi
    • 1
  • Chung Kyukwang
    • 1
  • Hiroaki Komatsu
    • 1
  • Michihito Toda
    • 1
  • Kantaro Hara
    • 1
  • Hikaru Miyamoto
    • 1
  • Noritoshi Nishiyama
    • 1
  1. 1.Department of Thoracic SurgeryOsaka City University HospitalOsakaJapan

Personalised recommendations