Skip to main content
SpringerLink
Log in

Pre-operative Sarcopenia Identifies Patients at Risk for Poor Survival After Resection of Biliary Tract Cancers

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Introduction

Biliary tract cancers (BTC) are aggressive malignancies that require complex surgical procedures. Patients with BTC can present with skeletal muscle depletion, yet the effects of muscle wasting (sarcopenia) on outcomes have not been well studied. The objective of the current study was to define the impact of sarcopenia on survival among patients undergoing resection of BTC.

Methods

Patients who underwent exploration for BTC who had a pre-operative CT scan available for review were identified. Body composition variables including total and psoas muscle area (cm2), muscle density (Hounsfield units), visceral fat area, subcutaneous fat area, and waist-to-hip ratio were analyzed at the level of L3. Outcomes were assessed according to the presence or absence of sarcopenia defined using sex- and BMI-specific threshold values for Psoas Muscle Index (PMI, cm2/m2).

Results

Among 117 patients with BTC, 78 (67%) underwent curative-intent resection and 39 (33%) were explored but did not undergo resection due to metastatic/locally advanced disease. Tumor type included distal cholangiocarcinoma (n = 18, 15.4%), hilar cholangiocarcinoma (n = 27, 23.1%), gallbladder carcinoma (n = 52, 44.4%), and intrahepatic cholangiocarcinoma (n = 20, 17.1%). Median patient age was 65.6 years and 43.6% were male. Mean patient BMI was 26.1 kg/m2 among men and 27.5 kg/m2 among women. Overall, 41 (35.0%) patients had sarcopenia. Sarcopenia was associated with an increased risk of death among patients who underwent resection (HR 3.52, 95%CI 1.60–7.78, p = 0.002), which was comparable to patients with unresectable metastatic disease. Other factors such as low serum albumin (HR 3.17, 95% CI 1.30–7.74, p = 0.011) and low psoas density (HR 2.96, 95% CI 1.21–7.21, p = 0.017) were also associated with increased risk of death. Survival was stratified based on sarcopenia, psoas density, and serum albumin. The presence of each variable was associated with an incremental increased risk of death (0 variables ref.; 1 variable HR 3.8, 95% CI 1.0–14, p = 0.043; 2 variables HR 13.1, 95% CI 3.0–57.7, p = 0.001; 3 variables HR 14.6, 95% CI 2.5–87.1, p = 0.003). Patients who had no adverse prognostic factors had a 3-year OS of 67% versus no survival among patients with all 3 factors.

Conclusions

Sarcopenia was common among patients undergoing resection of BTC, occurring in 1 of every 3 patients. Sarcopenia was associated with poor survival after resection, particularly among patients who experienced a recurrence. Body composition metrics such as sarcopenia and low psoas muscle density in addition to low albumin level were able to stratify patients into different prognostic categories.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jarnagin WR, Fong Y, DeMatteo RP, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234(4):507–517; discussion 517-509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bridgewater J, Lopes A, Wasan H, et al. Prognostic factors for progression-free and overall survival in advanced biliary tract cancer. Ann Oncol. 2016;27(1):134–140.

    Article  CAS  PubMed  Google Scholar 

  3. Mansour JC, Aloia TA, Crane CH, Heimbach JK, Nagino M, Vauthey JN. Hilar cholangiocarcinoma: expert consensus statement. HPB (Oxford). 2015;17(8):691–699.

    Article  PubMed  PubMed Central  Google Scholar 

  4. DeOliveira ML, Cunningham SC, Cameron JL, et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg. 2007;245(5):755–762.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tran TB, Norton JA, Ethun CG, et al. Gallbladder Cancer Presenting with Jaundice: Uniformly Fatal or Still Potentially Curable? J Gastrointest Surg. 2017;21(8):1245–1253.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wernberg JA, Lucarelli DD. Gallbladder cancer. Surg Clin North Am. 2014;94(2):343–360.

    Article  PubMed  Google Scholar 

  7. Weber SM, Ribero D, O'Reilly EM, Kokudo N, Miyazaki M, Pawlik TM. Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford). 2015;17(8):669–680.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Martin L, Birdsell L, Macdonald N, 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(12):1539–1547.

    Article  PubMed  Google Scholar 

  9. Cespedes Feliciano EM, Kroenke CH, Meyerhardt JA, et al. Association of Systemic Inflammation and Sarcopenia With Survival in Nonmetastatic Colorectal Cancer: Results From the C SCANS Study. JAMA Oncol. 2017:e172319.

    Article  PubMed Central  Google Scholar 

  10. Buettner S, Wagner D, Kim Y, et al. Inclusion of Sarcopenia Outperforms the Modified Frailty Index in Predicting 1-Year Mortality among 1,326 Patients Undergoing Gastrointestinal Surgery for a Malignant Indication. J Am Coll Surg. 2016;222(4):397–407.e392.

    Article  PubMed  Google Scholar 

  11. Amini N, Spolverato G, Gupta R, et al. Impact Total Psoas Volume on Short- and Long-Term Outcomes in Patients Undergoing Curative Resection for Pancreatic Adenocarcinoma: a New Tool to Assess Sarcopenia. J Gastrointest Surg. 2015;19(9):1593–1602.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Peng PD, van Vledder MG, Tsai S, et al. Sarcopenia negatively impacts short-term outcomes in patients undergoing hepatic resection for colorectal liver metastasis. HPB (Oxford). 2011;13(7):439–446.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wagner D, Buttner S, Kim Y, et al. Clinical and morphometric parameters of frailty for prediction of mortality following hepatopancreaticobiliary surgery in the elderly. Br J Surg. 2016;103(2):e83–92.

    Article  CAS  PubMed  Google Scholar 

  14. Wang SL, Zhuang CL, Huang DD, et al. Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study. Ann Surg Oncol. 2016;23(2):556–564.

    Article  PubMed  Google Scholar 

  15. Wagner D, DeMarco MM, Amini N, et al. Role of frailty and sarcopenia in predicting outcomes among patients undergoing gastrointestinal surgery. World J Gastrointest Surg. 2016;8(1):27–40.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gani F, Cerullo M, Amini N, et al. Frailty as a Risk Predictor of Morbidity and Mortality Following Liver Surgery. J Gastrointest Surg. 2017;21(5):822–830.

    Article  PubMed  Google Scholar 

  17. Beal EW, Wei L, Ethun CG, et al. Elevated NLR in gallbladder cancer and cholangiocarcinoma - making bad cancers even worse: results from the US Extrahepatic Biliary Malignancy Consortium. HPB (Oxford). 2016;18(11):950–957.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Prado CM, Lieffers JR, McCargar LJ, 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(7):629–635.

    Article  PubMed  Google Scholar 

  19. Sabel MS, Terjimanian M, Conlon AS, et al. Analytic morphometric assessment of patients undergoing colectomy for colon cancer. J Surg Oncol. 2013;108(3):169–175.

    Article  PubMed  Google Scholar 

  20. WHO | Obesity. WHO. 2014.

  21. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–196.

    Article  PubMed  Google Scholar 

  22. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States Part III: Liver, biliary tract, and pancreas. Gastroenterology. 2009;136(4):1134–1144.

    Article  PubMed  Google Scholar 

  23. Kneuertz PJ, Pitt HA, Bilimoria KY, et al. Risk of morbidity and mortality following hepato-pancreato-biliary surgery. J Gastrointest Surg. 2012;16(9):1727–1735.

    Article  PubMed  Google Scholar 

  24. Al-Homoud S, Purkayastha S, Aziz O, et al. Evaluating operative risk in colorectal cancer surgery: ASA and POSSUM-based predictive models. Surgical oncology. 2004;13(2–3):83–92.

    Article  PubMed  Google Scholar 

  25. Bilimoria KY, Talamonti MS, Tomlinson JS, et al. Prognostic Score Predicting Survival After Resection of Pancreatic Neuroendocrine Tumors: Analysis of 3851 Patients. Annals of Surgery. 2008;247(3):490–500.

    Article  PubMed  Google Scholar 

  26. Braga M, Capretti G, Pecorelli N, et al. A prognostic score to predict major complications after pancreaticoduodenectomy. Annals of Surgery. 2011;254(5):702–708.

    Article  PubMed  Google Scholar 

  27. Ansell GL, Montgomery JE. Outcome of ASA III patients undergoing day case surgery. British Journal of Anaesthesia. 2004;92(1):71–74.

    Article  CAS  PubMed  Google Scholar 

  28. Audisio RA, Ramesh H, Longo WE, Zbar AP, Pope D. Preoperative assessment of surgical risk in oncogeriatric patients. The oncologist. 2005;10(4):262–268.

    Article  PubMed  Google Scholar 

  29. Spolverato G, Maqsood H, Kim Y, et al. Neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after resection for hepato-pancreatico-biliary malignancies. J Surg Oncol. 2015;111(7):868–874.

    Article  CAS  PubMed  Google Scholar 

  30. Cruz-Jentoft AJ, Michel JP. Sarcopenia: A useful paradigm for physical frailty. European Geriatric Medicine. 2013;4(2):102–105.

    Article  Google Scholar 

  31. Cooper C, Dere W, Evans W, et al. Frailty and sarcopenia: definitions and outcome parameters. Osteoporosis International. 2012;23(7):1839–1848.

    Article  CAS  PubMed  Google Scholar 

  32. Buettner S, van Vugt JL, Gani F, et al. A Comparison of Prognostic Schemes for Perihilar Cholangiocarcinoma. J Gastrointest Surg. 2016;20(10):1716–1724.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hyder O, Marques H, Pulitano C, et al. A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience. JAMA Surg. 2014;149(5):432–438.

    Article  PubMed  Google Scholar 

  34. Peng P, Hyder O, Firoozmand A, et al. Impact of Sarcopenia on Outcomes Following Resection of Pancreatic Adenocarcinoma. Journal of Gastrointestinal Surgery. 2012;16(8):1478–1486.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Lieffers J, Bathe O, Fassbender K, Winget M, Baracos V. Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery. British journal of cancer. 2012;107(6):931–936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Valero V, 3rd, Amini N, Spolverato G, et al. Sarcopenia adversely impacts postoperative complications following resection or transplantation in patients with primary liver tumors. J Gastrointest Surg. 2015;19(2):272–281.

    Article  PubMed  Google Scholar 

  37. Voron T, Tselikas L, Pietrasz D, et al. Sarcopenia Impacts on Short- and Long-term Results of Hepatectomy for Hepatocellular Carcinoma. Ann Surg. 2015;261(6):1173–1183.

    Article  PubMed  Google Scholar 

  38. Kobayashi A, Kaido T, Hamaguchi Y, et al. Impact of Sarcopenic Obesity on Outcomes in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma. Ann Surg. 2017.

  39. Bilimoria KY, Liu Y, Paruch JL, et al. Development and evaluation of the universal ACS NSQIP surgical risk calculator: a decision aid and informed consent tool for patients and surgeons. J Am Coll Surg. 2013;217(5):833–842.e831–833.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chow WB, Rosenthal RA, Merkow RP, Ko CY, Esnaola NF. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. J Am Coll Surg. 2012;215(4):453–466.

    Article  PubMed  Google Scholar 

  41. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–156.

    Article  CAS  PubMed  Google Scholar 

  42. Rubbieri G, Mossello E, Di Bari M. Techniques for the diagnosis of sarcopenia. Clin Cases Miner Bone Metab. 2014;11(3):181–184.

    PubMed  PubMed Central  Google Scholar 

  43. Granger CL, McDonald CF, Parry SM, Oliveira CC, Denehy L. Functional capacity, physical activity and muscle strength assessment of individuals with non-small cell lung cancer: a systematic review of instruments and their measurement properties. BMC Cancer. Vol 132013:135.

Download references

Authorship

Study design: JC, EWB, TMP

Data acquisition: JC, EWB, SHS, AC, JG

Data analysis/interpretation: JC, EWB, FB, IW, KM, TMP

Manuscript preparation/approval: JC, EWB, FB, KM, IW, MD, JC, TMP

Author information

Authors and Affiliations

  1. Department of Surgery, The Ohio State University, Wexner Medical Center and James Cancer Hospital and Solove Research Institute, 395 W. 12th Ave., Suite 670, Columbus, OH, 43210, USA

    Jeffery Chakedis, Gaya Spolverato, Eliza W. Beal, Ingrid Woelfel, Fabio Bagante, Katiuscha Merath, Steven H. Sun, Aaron Chafitz, Jason Galo, Mary Dillhoff, Jordan Cloyd & Timothy M. Pawlik

Authors
  1. Jeffery Chakedis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gaya Spolverato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eliza W. Beal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ingrid Woelfel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabio Bagante
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Katiuscha Merath
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Steven H. Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aaron Chafitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jason Galo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mary Dillhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jordan Cloyd
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Timothy M. Pawlik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy M. Pawlik.

Ethics declarations

The study was approved by the Institutional Review Board at The Ohio State University.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chakedis, J., Spolverato, G., Beal, E.W. et al. Pre-operative Sarcopenia Identifies Patients at Risk for Poor Survival After Resection of Biliary Tract Cancers. J Gastrointest Surg 22, 1697–1708 (2018). https://doi.org/10.1007/s11605-018-3802-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-018-3802-1

Keywords

Search

Navigation