Skip to main content
Log in

Physical function in patients with resectable cancer of the pancreas and liver–a systematic review

  • Review
  • Published:
Journal of Cancer Survivorship Aims and scope Submit manuscript

Abstract

Purpose

Surgery is the only potentially curative treatment for pancreatic and liver cancer. However, even in high-volume centres, surgical resection is associated with significant morbidity with resultant physical decline. This systematic review explored physical function and its’ implications in the management of resectable cancer of the pancreas and liver.

Methods

EMBASE, Medline OVID, CINAHL, Cochrane Library and Web of Science were searched up to June 2019 using a predefined search strategy. Screening of titles, abstracts, and full texts, data extraction, and risk of bias assessment was performed independently by two reviewers. A third reviewer resolved disagreements by consensus.

Results

Sixteen studies with a total of 1224 participants were included. Heterogeneity of the literature prevented a meta-analysis. Physical function across the pancreatic/liver cancer trajectory has been under investigated. The relationship between physical function and pancreatic/liver cancer resection outcome remains unclear, although anaerobic threshold appears the strongest predictor of postoperative outcomes. Conclusions regarding the impact of rehabilitative interventions on physical function were limited due to risk of bias concerns.

Conclusions

High-quality evidence regarding the implications of physical function in resectable pancreatic and liver cancers is lacking. Well-designed trials are required to examine physical function across the pancreatic/liver cancer continuum and to measure the impact of rehabilitation on physical function.

Implications for Cancer Survivors

As survival rates for pancreatic and liver cancer slowly improve a greater understanding of the impact of these cancers and their treatments on physical function, and the potential impact of rehabilitative interventions for survivors is required.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

References

  1. Oberstein PE, Olive KP. Pancreatic cancer: why is it so hard to treat? Ther Adv Gastroenterol. 2013;6(4):321–37.

    Article  Google Scholar 

  2. Momin BR, Pinheiro PS, Carreira H, Li C, Weir HK. Liver cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study. Cancer. 2017(123 Suppl 24):5059–78.

  3. Chakraborty S, Singh S. Surgical resection improves survival in pancreatic cancer patients without vascular invasion- a population based study. Ann Gastroenterol. 2013;26(4):346–52.

    PubMed  PubMed Central  Google Scholar 

  4. Kim KH, Choi Y-K. Long-term survival after resection of hepatocellular carcinoma. Korean J Hepato-Biliary-Pancreat Surg. 2012;16(3):98–104.

    Article  CAS  Google Scholar 

  5. Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, et al. Recent progress in pancreatic cancer. CA Cancer J Clin. 2013;63(5):318–48.

  6. Li GZ, Speicher PJ, Lidsky ME, Darrabie MD, Scarborough JE, White RR, et al. Hepatic resection for hepatocellular carcinoma: do contemporary morbidity and mortality rates demand a transition to ablation as first-line treatment? J Am Coll Surg. 2014;218(4):827–34.

  7. Liu K, Mccaughan GW. How to select the appropriate “neoadjuvant therapy” for hepatocellular carcinoma. Expert Opin Pharmacother. 2018;19(11):1167–70.

    Article  PubMed  Google Scholar 

  8. Brown ZJ, Greten TF, Heinrich B. Adjuvant treatment of hepatocellular carcinoma: prospect of immunotherapy. Hepatology. 2019.

  9. Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet. 2016;388(10039):73–85.

    Article  CAS  PubMed  Google Scholar 

  10. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200–10.

  11. Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(14):1473–81.

  12. Springfeld C, Jäger D, Büchler MW, Strobel O, Hackert T, Palmer DH, et al. Chemotherapy for pancreatic cancer. Presse Med. 2019;48(3, Part 2):e159–74.

  13. Freiberger E, de Vreede P, Schoene D, Rydwik E, Mueller V, Frändin K, et al. Performance-based physical function in older community-dwelling persons: a systematic review of instruments. Age Ageing. 2012;41(6):712–21.

  14. Kostanjsek N. Use of The International Classification of Functioning, Disability and Health (ICF) as a conceptual framework and common language for disability statistics and health information systems. BMC Public Health. 2011;11(4):S3.

    Article  PubMed  PubMed Central  Google Scholar 

  15. O'neill L, Moran J, Guinan EM, Reynolds JV, Hussey J. Physical decline and its implications in the management of oesophageal and gastric cancer: a systematic review. J Cancer Surviv. 2018.

  16. ATS/ACCP Statement on Cardiopulmonary Exercise Testing. Am J Respir Crit Care Med. 2003;167(2):211–77.

  17. Painter P, Stewart AL, Carey S. Physical functioning: definitions, measurement, and expectations. Adv Ren Replace Ther. 1999;6(2):110–23.

    Article  CAS  PubMed  Google Scholar 

  18. Herdy AH, Ritt LEF, Stein R, Cgsd A, Milani M, Meneghelo RS, et al. Cardiopulmonary exercise test: background, applicability and interpretation. Arq Bras Cardiol. 2016;107(5):467–81.

  19. Robsahm TE, Falk RS, Heir T, Sandvik L, Vos L, Erikssen J, et al. Cardiorespiratory fitness and risk of site-specific cancers: a long-term prospective cohort study. Cancer Med. 2017;6(4):865–73.

  20. Lakoski SG, Willis BL, Barlow CE, Leonard D, Gao A, Radford NB, et al. Midlife cardiorespiratory fitness, incident cancer, and survival after cancer in men: the Cooper Center Longitudinal Study. JAMA Oncol. 2015;1(2):231–7.

  21. Vainshelboim B, Lima RM, Myers J. Cardiorespiratory fitness and cancer in women: a prospective pilot study. J Sport Health Sci. 2019.

  22. Jensen MT, Holtermann A, Bay H, Gyntelberg F. Cardiorespiratory fitness and death from cancer: a 42-year follow-up from the Copenhagen Male Study. Br J Sports Med. 2017;51(18):1364–9.

    Article  PubMed  Google Scholar 

  23. Moran J, Wilson F, Guinan E, Mccormick P, Hussey J, Moriarty J. Role of cardiopulmonary exercise testing as a risk-assessment method in patients undergoing intra-abdominal surgery: a systematic review. Br J Anaesth. 2016;116(2):177–91.

    Article  CAS  PubMed  Google Scholar 

  24. Jack S, West MA, Raw D, Marwood S, Ambler G, Cope TM, et al. The effect of neoadjuvant chemotherapy on physical fitness and survival in patients undergoing oesophagogastric cancer surgery. Eur J Surg Oncol. 2014;40(10):1313–20.

  25. Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010;42(7):1409–26.

  26. Hayden JA, van der Windt DA, Cartwright JL, Cote P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158(4):280–6.

    Article  PubMed  Google Scholar 

  27. Sterne JACSJ, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; [IN PRESS].

  28. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.

  29. Pavon JM WJJ, Adam SS, et al.: Effectiveness of intermittent pneumatic compression devices for venous thromboembolism prophylaxis in high-risk surgical and medical patients [Internet]. In: APPENDIX B, Quality (Risk of Bias) Assesment of RCTS - Criteria used and detailed ratings. Edited by Affairs DoV. Washington DC; 2015.

  30. Ausania F, Snowden CP, Prentis JM, Holmes LR, Jaques BC, White SA, et al. Effects of low cardiopulmonary reserve on pancreatic leak following pancreaticoduodenectomy. Br J Surg. 2012;99(9):1290–4.

    Article  CAS  PubMed  Google Scholar 

  31. Chandrabalan VV, Mcmillan DC, Carter R, Kinsella J, Mckay CJ, Carter CR, et al. Pre-operative cardiopulmonary exercise testing predicts adverse post-operative events and non-progression to adjuvant therapy after major pancreatic surgery. HPB. 2013;15(11):899–907.

  32. Hayashi F, Kaibori M, Sakaguchi T, Matsui K, Ishizaki M, Kwon AH, et al. Loss of skeletal muscle mass in patients with chronic liver disease is related to decrease in bone mineral density and exercise tolerance. Hepatol Res. 2018;48(5):345–54.

  33. Hayashi K, Yokoyama Y, Nakajima H, Nagino M, Inoue T, Nagaya M, et al. Preoperative 6-minute walk distance accurately predicts postoperative complications after operations for hepato-pancreato-biliary cancer. Surgery (United States). 2017;161(2):525–32.

  34. Itoh S, Yoshizumi T, Sakata K, Motomura T, Mano Y, Toshima T, et al. Slow gait speed is a risk factor for complications after hepatic resection. J Gastrointest Surg. 2018.

  35. Ngo-Huang A, Holmes HM, des Bordes JKA, Parker NH, Fogelman D, Petzel MQB, et al. Association between frailty syndrome and survival in patients with pancreatic adenocarcinoma. Cancer Med. 2019;8(6):2867–76.

  36. Dale W, Hemmerich J, Kamm A, Posner MC, Matthews JB, Rothman R, et al. Geriatric assessment improves prediction of surgical outcomes in older adults undergoing pancreaticoduodenectomy: a prospective cohort study. Ann Surg. 2014;259(5):960–5.

    Article  PubMed  Google Scholar 

  37. Kaibori M, Ishizaki M, Matsui K, Nakatake R, Sakaguchi T, Habu D, et al. Assessment of preoperative exercise capacity in hepatocellular carcinoma patients with chronic liver injury undergoing hepatectomy. BMC Gastroenterol. 2013:13(1).

  38. Junejo MA, Mason JM, Sheen AJ, Bryan A, Moore J, Foster P, et al. Cardiopulmonary exercise testing for preoperative risk assessment before pancreaticoduodenectomy for cancer. Ann Surg Oncol. 2014;21(6):1929–36.

  39. Kaibori M, Ishizaki M, Matsui K, Nakatake R, Yoshiuchi S, Kimura Y, et al. Perioperative exercise for chronic liver injury patients with hepatocellular carcinoma undergoing hepatectomy. Am J Surg. 2013;206(2):202–9.

  40. Wiskemann J, Clauss D, Tjaden C, Hackert T, Schneider L, Ulrich CM, et al. Progressive resistance training to impact physical fitness and body weight in pancreatic cancer patients: a randomized controlled trial. Pancreas. 2019;48(2):257–66.

  41. Clauss D, Tjaden C, Hackert T, Schneider L, Ulrich CM, Wiskemann J, et al. Cardiorespiratory fitness and muscle strength in pancreatic cancer patients. Support Care Cancer. 2017;25(9):2797–807.

  42. Goonetilleke KS, Hathurusinghe HR, Burden S, Siriwardena AK. Nutritional and anthropometric assessment of the scope for dietary optimization during staging prior to pancreaticoduodenectomy. J Pancreatol. 2008;9(4):415–21.

    Google Scholar 

  43. Parker NH, Ngo-Huang A, Lee RE, O’connor DP, Basen-Engquist KM, Petzel MQB, et al. Physical activity and exercise during preoperative pancreatic cancer treatment. Support Care Cancer. 2019;27(6):2275–84.

  44. Royall D, Jeejeebhoy KN, Oconnor B, Taylor BR, Langer B, Mcleod RS. Nutritional status and function in patients following Whipple procedure compared with controls. J Am Coll Nutr. 1996;15(1):73–8.

    Article  CAS  PubMed  Google Scholar 

  45. Nakajima H, Yokoyama Y, Inoue T, Nagaya M, Mizuno Y, Kadono I, et al. Clinical benefit of preoperative exercise and nutritional therapy for patients undergoing hepato-pancreato-biliary surgeries for malignancy. Ann Surg Oncol. 2019;26(1):264–72.

  46. Antoun S, Borget I, Lanoy E. Impact of sarcopenia on the prognosis and treatment toxicities in patients diagnosed with cancer. Curr Opin Support Palliat Care. 2013;7(4):383–9.

    Article  PubMed  Google Scholar 

  47. Dale W, Wallace J, Hemmerich J, Roggin K. Fried’s exhaustion, weak grip strength, and age predict in-hospital vulnerability in older patients undergoing pancreaticoduodenectomy (Whipple): a pilot study. J Am Geriatr Soc. 2010;58:S75.

    Google Scholar 

  48. Kaibori M, Ishizaki M, Matsui K, Kwon AH. Perioperative rehabilitation with diet and exercise in cirrhotic patients with hepatocellular carcinoma undergoing hepatectomy. Hepatol Int. 2011;5(1):459.

    Google Scholar 

  49. Takahashi C, Shridhar R, Huston J, Meredith K. Esophagectomy from then to now. J Gastrointest Oncol. 2018;9(5):903–9.

    Article  PubMed  PubMed Central  Google Scholar 

  50. O’neill L, Moran J, Guinan EM, Reynolds JV, Hussey J. Physical decline and its implications in the management of oesophageal and gastric cancer: a systematic review. J Cancer Surviv. 2018;12(4):601–18.

    Article  PubMed  Google Scholar 

  51. Guinan EM, Bennett AE, Doyle SL, O’neill L, Gannon J, Foley G, et al. Measuring the impact of oesophagectomy on physical functioning and physical activity participation: a prospective study. BMC Cancer. 2019;19(1):682.

  52. Stout NL, Sleight A, Pfeiffer D, Galantino ML, de Souza B. Promoting assessment and management of function through navigation: opportunities to bridge oncology and rehabilitation systems of care. Support Care Cancer. 2019;27(12):4497–505.

    Article  PubMed  Google Scholar 

  53. Guinan EM, Doyle SL, Bennett AE, O'neill L, Gannon J, Elliott JA, et al. Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance. Support Care Cancer. 2017.

  54. Kumar R, Garcea G. Cardiopulmonary exercise testing in hepato-biliary & pancreas cancer surgery – a systematic review: are we any further than walking up a flight of stairs? Int J Surg. 2018;52:201–7.

    Article  CAS  PubMed  Google Scholar 

  55. Brunelli A, Kim AW, Berger KI, Addrizzo-Harris DJ. Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e166S–90S.

    Article  CAS  PubMed  Google Scholar 

  56. Optimal Resources for Cancer Care - 2020 Standard [https://www.facs.org/-/media/files/quality-programs/cancer/coc/optimal_resources_for_cancer_care_2020_standards.ashx].

  57. Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, et al. Exercise guidelines for cancer survivors: consensus statement from international multidisciplinary roundtable. Med Sci Sports Exerc. 2019;51(11):2375–90.

  58. Patel AV, Friedenreich CM, Moore SC, Hayes SC, Silver JK, Campbell KL, et al. American College of Sports Medicine roundtable report on physical activity, sedentary behavior, and cancer prevention and control. Med Sci Sports Exerc. 2019;51(11):2391–402.

  59. Schmitz KH, Campbell AM, Stuiver MM, Pinto BM, Schwartz AL, Morris GS, et al. Exercise is medicine in oncology: engaging clinicians to help patients move through cancer. CA Cancer J Clin. 2019;69(6):468–84.

  60. Prehabilitation for people with cancer: principles and guidance for prehabilitation within the management and support of people with cancer [https://www.macmillan.org.uk/assets/prehabilitation-guidance-for-people-with-cancer.pdf].

  61. Hughes MJ, Hackney RJ, Lamb PJ, Wigmore SJ, Christopher Deans DA, Skipworth RJE. Prehabilitation before major abdominal surgery: a systematic review and meta-analysis. World J Surg. 2019;43(7):1661–8.

    Article  PubMed  Google Scholar 

  62. Trepanier M, Minnella EM, Paradis T, Awasthi R, Kaneva P, Schwartzman K, et al. Improved disease-free survival after prehabilitation for colorectal cancer surgery. Ann Surg. 2019.

  63. Cooper AB, Holmes HM, des Bordes JK, Fogelman D, Parker NH, Lee JE, et al. Role of neoadjuvant therapy in the multimodality treatment of older patients with pancreatic cancer. J Am Coll Surg. 2014;219(1):111–20.

  64. Griffin OM, Duggan SN, Ryan R, McDermott R, Geoghegan J, Conlon KC: Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer. Pancreatology 2019.

  65. Minnella EM, Awasthi R, Loiselle S-E, Agnihotram RV, Ferri LE, Carli F. Effect of exercise and nutrition prehabilitation on functional capacity in esophagogastric cancer surgery: a randomized clinical trial. JAMA Surg. 2018;153(12):1081–9.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Xu Y-J, Cheng JC-H, Lee J-M, Huang P-M, Huang G-H, Chen CC-H. A walk-and-eat intervention improves outcomes for patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy. Oncologist. 2015;20(10):1216–22.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Melloul E, Hubner M, Scott M, Snowden C, Prentis J, Dejong CH, et al. Guidelines for perioperative care for liver surgery: enhanced recovery after surgery (ERAS) society recommendations. World J Surg. 2016;40(10):2425–40.

  68. Chan MY, Chok KSH. Sarcopenia in pancreatic cancer - effects on surgical outcomes and chemotherapy. World J Gastrointest Oncol. 2019;11(7):527–37.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Iritani S, Imai K, Takai K, Hanai T, Ideta T, Miyazaki T, et al. Skeletal muscle depletion is an independent prognostic factor for hepatocellular carcinoma. J Gastroenterol. 2015;50(3):323–32.

  70. O'neill LM, Guinan E, Doyle SL, Bennett AE, Murphy C, Elliott JA, et al. The RESTORE randomized controlled trial: impact of a multidisciplinary rehabilitative program on cardiorespiratory fitness in esophagogastric cancer survivorship. Ann Surg. 2018;268(5):747–55.

  71. O’neill L, Guinan E, Doyle SL, Elliott JA, O’sullivan J, Reynolds JV, et al. Rehabilitation strategies following esophageal cancer (the ReStOre trial): a feasibility study. Dis Esophagus. 2017;30(5):1–8.

  72. Bennett AE, O’neill L, Connolly D, Guinan EM, Boland L, Doyle SL, et al. Patient experiences of a physiotherapy-led multidisciplinary rehabilitative intervention after successful treatment for oesophago-gastric cancer. Support Care Cancer. 2018;26(8):2615–23.

  73. Guinan EM, Doyle SL, O’neill L, Dunne MR, Foley EK, O’sullivan J, et al. Effects of a multimodal rehabilitation programme on inflammation and oxidative stress in oesophageal cancer survivors: the ReStOre feasibility study. Support Care Cancer. 2017;25(3):749–56.

  74. Sun V, Ferrell B, Juarez G, Wagman LD, Yen Y, Chung V. Symptom concerns and quality of life in hepatobiliary cancers. Oncol Nurs Forum. 2008;35(3):E45–52.

    Article  PubMed  Google Scholar 

  75. Bauer MR, Bright EE, Macdonald JJ, Cleary EH, Hines OJ, Stanton AL. Quality of life in patients with pancreatic cancer and their caregivers: a systematic review. Pancreas. 2018;47(4):368–75.

    Article  PubMed  Google Scholar 

Download references

Funding

This systematic review was performed as part of the body of work for the Health Research Board funded Rehabilitation Strategies Following Oesophagogastric and Hepatopancreaticobiliary Cancer (ReStOre II) Trial [HRB-DIFA-FA-2018-009].

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Linda O’Neill.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Additional information

Publisher’s note

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

Electronic supplementary material

ESM 1

(PDF 196 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

O’Neill, L., Reynolds, S., Sheill, G. et al. Physical function in patients with resectable cancer of the pancreas and liver–a systematic review. J Cancer Surviv 14, 527–544 (2020). https://doi.org/10.1007/s11764-020-00875-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11764-020-00875-x

Keywords

Navigation