Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Nutrition in acute and chronic diseases

Prognostic value of myosteatosis and systemic inflammation in patients with resectable gastric cancer: A retrospective study

Abstract

Background/Objectives

The association between systemic inflammation and myosteatosis upon diagnosis of gastric cancer (GC) and whether these factors could predict survival outcomes is not clear. Our aim was to explore the association between systemic inflammation and myosteatosis upon diagnosis of GC, specially whether the co-occurrence of these factors could predict survival outcomes.

Subjects/methods

Computed tomography (CT) was performed at the level of the third lumbar vertebra for body composition analysis in 280 patients with GC. Myoesteatosis was defined as the lowest tertile of the muscle radiodensity distribution or based on clinical significance using optimal stratification analysis. Inflammatory indexes were measured, including the neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte and lymphocyte-to-monocyte ratios.

Results

Patients with low skeletal muscle (SM) radiodensity were more likely to be older than 65 years, have a higher body mass index and have diabetes. They also had higher intermuscular visceral and subcutaneous adipose tissue areas and indexes. The highest tertile of SM radiodensity was associated with better disease-free survival (DFS) (HR = 0.51, 95% CI [0.31, 0.84], ptrend = 0.020) and overall survival (OS) (HR = 0.49, 95% CI [0.29, 0.82], ptrend = 0.022). Patients with NLR > 2.3 and myosteatosis had the worst DFS and OS (HR = 2.77, 95% CI [1.54, 5.00], p = 0.001; HR = 3.31, 95% CI [1.79, 6.15], p < 0.001, respectively).

Conclusion

Co-occurrence of myosteatosis and inflammation increased disease progression and death risk by almost three times. These regularly obtained biomarkers might improve prognostic risk prediction in resectable GC.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1
Fig. 2: Disease free survival and overall survival for skeletal muscle radiodensity.
Fig. 3: Disease free survival and overall survival for neutrophil-to-lymphocyte ratio and myosteatosis.

Data availability

Data described in the manuscript, codebook, and analytic code will be made available upon request pending application and approval.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. https://doi.org/10.3322/caac.21660.

    Article  PubMed  Google Scholar 

  2. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet 2020;396:635–48. https://doi.org/10.1016/S0140-6736(20)31288-5

    Article  CAS  PubMed  Google Scholar 

  3. Barchi LC, Ramos M, Yagi OK, Mucerino DR, Bresciani CJC, Ribeiro JU, et al. Brazilian gastric cancer association guidelines (Part 1): An update on diagnosis, staging, endoscopic treatment and follow-up. Arq Bras Cir Dig. 2020;33:e1535 https://doi.org/10.1590/0102-672020200003e1535

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wagner AD, Lordick F, Grabsch HI, Terashima M, Terada M, Yoshikawa T, et al. Multidisciplinary management of stage II-III gastric and gastro-oesophageal junction cancer. Eur J Cancer. 2020;124:67–76. https://doi.org/10.1016/j.ejca.2019.09.006

    Article  PubMed  Google Scholar 

  5. Szor DJ, Dias AR, Pereira MA, Ramos M, Zilberstein B, Cecconello I, et al. Prognostic role of neutrophil/lymphocyte ratio in resected gastric cancer: A systematic review and meta-analysis. Clin (Sao Paulo). 2018;73:e360 https://doi.org/10.6061/clinics/2018/e360

    Article  Google Scholar 

  6. Borggreve AS, den Boer RB, van Boxel GI, de Jong PA, Veldhuis WB, Steenhagen E, et al. The predictive value of low muscle mass as measured on CT scans for postoperative complications and mortality in gastric cancer patients: A systematic review and meta-analysis. J Clin Med. 2020;9:199 https://doi.org/10.3390/jcm9010199

    Article  PubMed Central  Google Scholar 

  7. Aleixo GFP, Shachar SS, Nyrop KA, Muss HB, Malpica L, Williams GR. Myosteatosis and prognosis in cancer: Systematic review and meta-analysis. Crit Rev Oncol Hematol. 2020;145:102839 https://doi.org/10.1016/j.critrevonc.2019.102839

    Article  CAS  PubMed  Google Scholar 

  8. Sjostrom L. A computer-tomography based multicompartment body composition technique and anthropometric predictions of lean body mass, total and subcutaneous adipose tissue. Int J Obes. 1991;15:19–30.

    PubMed  Google Scholar 

  9. Miller KD, Jones E, Yanovski JA, Shankar R, Feuerstein I, Falloon J. Visceral abdominal-fat accumulation associated with use of indinavir. Lancet 1998;351:871–5. https://doi.org/10.1016/S0140-6736(97)11518-5

    Article  CAS  PubMed  Google Scholar 

  10. Aubrey J, Esfandiari N, Baracos VE, Buteau FA, Frenette J, Putman CT, et al. Measurement of skeletal muscle radiation attenuation and basis of its biological variation. Acta Physiol (Oxf). 2014;210:489–97. https://doi.org/10.1111/apha.12224

    Article  CAS  Google Scholar 

  11. Bhullar AS, Anoveros-Barrera A, Dunichand-Hoedl A, Martins K, Bigam D, Khadaroo RG, et al. Lipid is heterogeneously distributed in muscle and associates with low radiodensity in cancer patients. J Cachexia Sarcopenia Muscle. 2020;11:735–47. https://doi.org/10.1002/jcsm.12533

    Article  PubMed  PubMed Central  Google Scholar 

  12. Correa-de-Araujo R, Addison O, Miljkovic I, Goodpaster BH, Bergman BC, Clark RV, et al. Myosteatosis in the context of skeletal muscle function deficit: An interdisciplinary workshop at the national institute on aging. Front Physiol. 2020;11:963 https://doi.org/10.3389/fphys.2020.00963

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sjoblom B, Gronberg BH, Wentzel-Larsen T, Baracos VE, Hjermstad MJ, Aass N, et al. Skeletal muscle radiodensity is prognostic for survival in patients with advanced non-small cell lung cancer. Clin Nutr. 2016;35:1386–93. https://doi.org/10.1016/j.clnu.2016.03.010

    Article  PubMed  Google Scholar 

  14. Akahori T, Sho M, Kinoshita S, Nagai M, Nishiwada S, Tanaka T, et al. Prognostic significance of muscle attenuation in pancreatic cancer patients treated with neoadjuvant chemoradiotherapy. World J Surg. 2015;39:2975–82. https://doi.org/10.1007/s00268-015-3205-3

    Article  PubMed  Google Scholar 

  15. Xiao J, Caan BJ, Cespedes Feliciano EM, Meyerhardt JA, Peng PD, Baracos VE, et al. Association of low muscle mass and low muscle radiodensity with morbidity and mortality for colon cancer surgery. JAMA Surg. 2020;155:942–9. https://doi.org/10.1001/jamasurg.2020.2497

    Article  PubMed  Google Scholar 

  16. Sachs S, Zarini S, Kahn DE, Harrison KA, Perreault L, Phang T, et al. Intermuscular adipose tissue directly modulates skeletal muscle insulin sensitivity in humans. Am J Physiol Endocrinol Metab. 2019;316:E866–79. https://doi.org/10.1152/ajpendo.00243.2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, et al. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia. 1999;42:113–6. https://doi.org/10.1007/s001250051123

    Article  CAS  PubMed  Google Scholar 

  18. Hayashi N, Ando Y, Gyawali B, Shimokata T, Maeda O, Fukaya M, et al. Low skeletal muscle density is associated with poor survival in patients who receive chemotherapy for metastatic gastric cancer. Oncol Rep. 2016;35:1727–31. https://doi.org/10.3892/or.2015.4475

    Article  CAS  PubMed  Google Scholar 

  19. Eo W, Kwon J, An S, Lee S, Kim S, Nam D, et al. Clinical significance of paraspinal muscle parameters as a prognostic factor for survival in gastric cancer patients who underwent curative surgical resection. J Cancer. 2020;11:5792–801. https://doi.org/10.7150/jca.46637

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hacker UT, Hasenclever D, Linder N, Stocker G, Chung HC, Kang YK, et al. Prognostic role of body composition parameters in gastric/gastroesophageal junction cancer patients from the EXPAND trial. J Cachexia Sarcopenia Muscle. 2020;11:135–44. https://doi.org/10.1002/jcsm.12484

    Article  PubMed  Google Scholar 

  21. Zhuang CL, Shen X, Huang YY, Zhang FM, Chen XY, Ma LL, et al. Myosteatosis predicts prognosis after radical gastrectomy for gastric cancer: A propensity score-matched analysis from a large-scale cohort. Surgery 2019;166:297–304. https://doi.org/10.1016/j.surg.2019.03.020

    Article  PubMed  Google Scholar 

  22. Dolan RD, Lim J, McSorley ST, Horgan PG, McMillan DC. The role of the systemic inflammatory response in predicting outcomes in patients with operable cancer: Systematic review and meta-analysis. Sci Rep. 2017;7:16717 https://doi.org/10.1038/s41598-017-16955-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dolan RD, McSorley ST, Horgan PG, Laird B, McMillan DC. The role of the systemic inflammatory response in predicting outcomes in patients with advanced inoperable cancer: Systematic review and meta-analysis. Crit Rev Oncol Hematol. 2017;116:134–46. https://doi.org/10.1016/j.critrevonc.2017.06.002

    Article  PubMed  Google Scholar 

  24. Dolan RD, Daly LE, Simmons CP, Ryan AM, Sim WM, Fallon M, et al. The relationship between ECOG-PS, mGPS, BMI/WL grade and body composition and physical function in patients with advanced cancer. Cancers (Basel). 2020;12:1187 https://doi.org/10.3390/cancers12051187

    Article  CAS  Google Scholar 

  25. Feliciano EMC, Kroenke CH, Meyerhardt JA, Prado CM, Bradshaw PT, Kwan ML, et al. Association of systemic inflammation and sarcopenia with survival in nonmetastatic colorectal cancer: Results from the C SCANS study. JAMA Oncol. 2017;3:e172319 https://doi.org/10.1001/jamaoncol.2017.2319

    Article  PubMed  Google Scholar 

  26. Gabiatti CTB, Martins MCL, Miyazaki DL, Silva LP, Lascala F, Macedo LT, et al. Myosteatosis in a systemic inflammation-dependent manner predicts favorable survival outcomes in locally advanced esophageal cancer. Cancer Med. 2019;8:6967–76. https://doi.org/10.1002/cam4.2593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Amin MB, American Joint Committee on Cancer, American Cancer Society. AJCC cancer staging manual. Eight edition / editor-in-chief, Mahul B. Amin, MD, FCAP; editors, Stephen B. Edge, MD, FACS and 16 others; Donna M. Gress, RHIT, CTR - Technical editor; Laura R. Meyer, CAPM - Managing editor. ed. Chicago IL: American Joint Committee on Cancer, Springer, 2017.

  28. Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol (1985). 1998;85:115–122. https://doi.org/10.1152/jappl.1998.85.1.115

    Article  CAS  Google Scholar 

  29. Camus V, Lanic H, Kraut J, Modzelewski R, Clatot F, Picquenot JM, et al. Prognostic impact of fat tissue loss and cachexia assessed by computed tomography scan in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Eur J Haematol. 2014;93:9–18. https://doi.org/10.1111/ejh.12285

    Article  CAS  PubMed  Google Scholar 

  30. Heymsfield SB, Wang Z, Baumgartner RN, Ross R. Human body composition: Advances in models and methods. Annu Rev Nutr. 1997;17:527–558. https://doi.org/10.1146/annurev.nutr.17.1.527

    Article  CAS  PubMed  Google Scholar 

  31. Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol. 2013;31:1539–47. https://doi.org/10.1200/JCO.2012.45.2722

    Article  PubMed  Google Scholar 

  32. Doyle SL, Bennett AM, Donohoe CL, Mongan AM, Howard JM, Lithander FE, et al. Establishing computed tomography-defined visceral fat area thresholds for use in obesity-related cancer research. Nutr Res. 2013;33:171–9. https://doi.org/10.1016/j.nutres.2012.12.007

    Article  CAS  PubMed  Google Scholar 

  33. Templeton AJ, Ace O, McNamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomark Prev. 2014;23:1204–12. https://doi.org/10.1158/1055-9965.EPI-14-0146

    Article  CAS  Google Scholar 

  34. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13:159–75. https://doi.org/10.1038/nri3399

    Article  CAS  PubMed  Google Scholar 

  35. Sun X, Liu X, Liu J, Chen S, Xu D, Li W, et al. Preoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio in predicting survival for patients with stage I-II gastric cancer. Chin J Cancer. 2016;35:57 https://doi.org/10.1186/s40880-016-0122-2

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lin JX, Lin JP, Xie JW, Wang JB, Lu J, Chen QY, et al. Prognostic value and association of sarcopenia and systemic inflammation for patients with gastric cancer following radical gastrectomy. Oncologist 2019;24:e1091–e101. https://doi.org/10.1634/theoncologist.2018-0651

    Article  PubMed  PubMed Central  Google Scholar 

  37. Contal C, O’Quigley J. An application of changepoint methods in studying the effect of age on survival in breast cancer. Computational Stat Data Anal. 1999;30:253–70. https://doi.org/10.1016/S0167-9473(98)00096-6

    Article  Google Scholar 

  38. Caan BJ, Meyerhardt JA, Kroenke CH, Alexeeff S, Xiao J, Weltzien E, et al. Explaining the obesity paradox: The association between body composition and colorectal cancer survival (C-SCANS Study). Cancer Epidemiol Biomark Prev. 2017;26:1008–15. https://doi.org/10.1158/1055-9965.EPI-17-0200

    Article  Google Scholar 

  39. da Cunha ADJ, Silveira MN, Takahashi MES, de Souza EM, Mosci C, Ramos CD, et al. Adipose tissue radiodensity: A new prognostic biomarker in people with multiple myeloma. Nutrition. 2021;86:111141 https://doi.org/10.1016/j.nut.2021.111141

    Article  CAS  Google Scholar 

  40. da Cunha Junior AD, Silveira MN, Takahashi MES, de Souza EM, Mosci C, Ramos CD, et al. Visceral adipose tissue glucose uptake is linked to prognosis in multiple myeloma patients: An exploratory study. Clin Nutr. 2021. https://doi.org/10.1016/j.clnu.2021.02.010

    Article  PubMed  Google Scholar 

  41. Ebadi M, Moctezuma-Velazquez C, Meza-Junco J, Baracos VE, DunichandHoedl AR, Ghosh S, et al. Visceral adipose tissue radiodensity is linked to prognosis in hepatocellular carcinoma patients treated with selective internal radiation therapy. Cancers (Basel). 2020;12:306 https://doi.org/10.3390/cancers12020356

    Article  CAS  Google Scholar 

  42. Tegels JJ, van Vugt JL, Reisinger KW, Hulsewe KW, Hoofwijk AG, Derikx JP, et al. Sarcopenia is highly prevalent in patients undergoing surgery for gastric cancer but not associated with worse outcomes. J Surg Oncol. 2015;112:403–7. https://doi.org/10.1002/jso.24015

    Article  PubMed  Google Scholar 

  43. Daly LE, Ni Bhuachalla EB, Power DG, Cushen SJ, James K, Ryan AM. Loss of skeletal muscle during systemic chemotherapy is prognostic of poor survival in patients with foregut cancer. J Cachexia Sarcopenia Muscle. 2018;9:315–25. https://doi.org/10.1002/jcsm.12267

    Article  PubMed  PubMed Central  Google Scholar 

  44. Miyamoto Y, Baba Y, Sakamoto Y, Ohuchi M, Tokunaga R, Kurashige J, et al. Sarcopenia is a negative prognostic factor after curative resection of colorectal cancer. Ann Surg Oncol. 2015;22:2663–8. https://doi.org/10.1245/s10434-014-4281-6

    Article  PubMed  Google Scholar 

  45. da Cunha LP, Silveira MN, Mendes MCS, Costa FO, Macedo LT, de Siqueira NS, et al. Sarcopenia as an independent prognostic factor in patients with metastatic colorectal cancer: A retrospective evaluation. Clin Nutr ESPEN. 2019;32:107–12. https://doi.org/10.1016/j.clnesp.2019.04.004

    Article  PubMed  Google Scholar 

  46. Hamrick MW, McGee-Lawrence ME, Frechette DM. Fatty infiltration of skeletal muscle: Mechanisms and comparisons with bone marrow adiposity. Front Endocrinol (Lausanne). 2016;7:69 https://doi.org/10.3389/fendo.2016.00069

    Article  Google Scholar 

  47. Miljkovic I, Cauley JA, Wang PY, Holton KF, Lee CG, Sheu Y, et al. Abdominal myosteatosis is independently associated with hyperinsulinemia and insulin resistance among older men without diabetes. Obes (Silver Spring). 2013;21:2118–25. https://doi.org/10.1002/oby.20346

    Article  Google Scholar 

  48. Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: A new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14:576–90. https://doi.org/10.1038/s41574-018-0059-4

    Article  CAS  PubMed  Google Scholar 

  49. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006;444:881–7. https://doi.org/10.1038/nature05488

    Article  CAS  PubMed  Google Scholar 

  50. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141:39–51. https://doi.org/10.1016/j.cell.2010.03.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Matheus B.O. Duarte for performing the statistical analysis of optimal stratification and Andreza Vertuan, Debora S. da Rocha, Grazielle M. Tavares, Giuliano Barbosa, Higor K. Mantovani and Isis R. T. C. Sálame for their assistance with data acquisition.

Funding

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). Grant/award number: 2018/23428‐0 | Recipient: JBCC. Conselho nacional de desenvolvimento científico e tecnológico (CNPq). Grant/award number: 302535/2018-7 | Recipient: JBCC.

Author information

Authors and Affiliations

Authors

Contributions

MCSM and JBCC designed the research; FL, BKSK, MBC, SRB, and MCSM collected the data; FL and BKSK performed computed tomography analyses; FL, BKSK, MCSM ADCJ, LTM, NAA, LRL, CMP, and JBCC analyzed and interpreted the data and provided comments; ADCJ, FL, MCSM, CMP, and JBCC wrote the manuscript. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to José Barreto Campello Carvalheira.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lascala, F., da Silva Moraes, B.K., Mendes, M.C.S. et al. Prognostic value of myosteatosis and systemic inflammation in patients with resectable gastric cancer: A retrospective study. Eur J Clin Nutr (2022). https://doi.org/10.1038/s41430-022-01201-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41430-022-01201-7

Search

Quick links