Study protocol of a single-arm pre-post study to assess the preliminary effectiveness and feasibility of a home-based bimodal prehabilitation program on preoperative aerobic fitness in high-risk patients scheduled for liver or pancreatic resection

Annefleur E. M. Berkel, Laura Van Wijk, Bart C. Bongers, Job Van Der Palen, Carlijn I. Buis, Muriel Reudink, Mike S. L. Liem, Gerrit D. Slooter, Nico L. U. Van Meeteren, Joost M. Klaase


Background: Controversial evidence currently exists regarding the feasibility and effectiveness to improve preoperative aerobic fitness during home-based prehabilitation in patients scheduled for liver or pancreatic resection, whereas morbidity rates are high following these resections. The primary aim of this study is to evaluate the preoperative oxygen uptake (VO2) at the ventilatory anaerobic threshold before and after a four-week home-based preoperative training program with nutritional supplementation in high-risk patients scheduled for elective liver or pancreatic resection. Secondary aims are to evaluate program feasibility, immune system function, cardiopulmonary exercise test responses, individual progression profiles on training responses, quality of life, and postoperative course.

Methods: In this multicenter study with a pretest-posttest design, patients with a liver or pancreatic tumor scheduled for elective resection will be recruited. To select the high-risk fraction of this surgical population, their VO2 at the ventilatory anaerobic threshold should be <11 ml/kg/min for final inclusion. A planned total of 24 high-risk patients will participate in a four-week (three sessions per week) home-based bimodal prehabilitation program. The partly supervised home-based preoperative training program consists of individualized goal setting followed by titration of interval and endurance training on an advanced cycle ergometer, combined with functional task exercises. Additionally, patients will be given protein and vitamin/mineral supplementation.

Discussion: Effects of a partly supervised home-based bimodal prehabilitation regimen are unknown in high-risk patients opting for liver or pancreatic resection. Improved preoperative aerobic fitness might translate into improved postoperative outcomes and a reduced demand on care resources.

Trial Registration: The study is registered in the Netherlands Trial Registry (NL6151) and was approved by the Institutional Ethics Committee, Twente, Enschede, the Netherlands (P17-08).


Aerobic fitness, Cardiopulmonary exercise testing, Cardiorespiratory fitness, Hepatopancreatobiliary surgery, Home-based training, Prehabilitation

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Van der Werf LR, Kok NFM, Buis CI, Grünhagen DJ, Hoogwater FJH, Swijnenburg RJ, et al. Implementation and first results of a mandatory, nationwide audit on liver surgery. HPB (Oxford). 2019;21(10):1400-10.

Dutch Institute for Clinical Auditing (DICA) Leiden. DICA jaarrapportage 2018: Dutch Pancreatic Cancer Audit (DPCA). Available at: Accessed on 02 September 2019.

Wilson RJ, Davies S, Yates D, Redman J, Stone M.. Impaired functional capacity is associated with all-cause mortality after major elective intra-abdominal surgery. Br J Anaesth. 2010;105(3):297-303.

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.

Junejo MA, Mason JM, Sheen AJ, Moore J, Foster P, Atkinson D, et al. Cardiopulmonary exercise testing for preoperative risk assessment before hepatic resection. Br J Surg. 2012;99(8):1097-104.

Moran J, Wilson F, Guinan E. McCormick P, Hussey J, Moriarty J, et al. 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.

Older P, Smith R, Courtney P, Hone R. Preoperative evaluation of cardiac failure and ischemia in elderly patients by cardiopulmonary exercise testing. Chest. 1993;104(3):701-4.

Bruns ER, van den Heuvel B, Buskens CJ, et al. The effects of physical prehabilitation in elderly patients undergoing colorectal surgery: a systematic review. Colorectal Dis. 2016;18(8):O267-77.

Thomas G, Tahir MR, Bongers BC, van Duijvendijk P, Festen S, Wassenaar EB, et al. Prehabilitation before major intra-abdominal cancer surgery: A systematic review of randomised controlled trials. Eur J Anaesthesiol. 2019;36(12):933-45.

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.

Bongers BC, Punt IM, van Meeteren NL. On Prehabilitation: The emperor's new clothes or a new arena for physical therapists? Phys Ther. 2018;12:127-30.

Barberan-Garcia A, Ubre M, Roca J, Lacy AM, Burgos F, Risco R, et al. Personalised Prehabilitation in High-risk Patients Undergoing Elective Major Abdominal Surgery: A Randomized Blinded Controlled Trial. Ann Surg. 2018;267(1):50-6.

Driessen EJ, Peeters ME, Bongers BC, Maas HA, Bootsma GP, van Meeteren NL, et al. Effects of prehabilitation and rehabilitation including a home-based component on physical fitness, adherence, treatment tolerance, and recovery in patients with non-small cell lung cancer: A systematic review. Crit Rev Oncol Hematol. 2017;114:63-76.

Ferreira V, Agnihotram RV, Bergdahl A, van Rooijen SJ, Awasthi R, Carli F, et al. Maximizing patient adherence to prehabilitation: what do the patients say?. Support Care Cancer. 2018;26(8):2717-23.

Dunne DF, Jack S, Jones RP, Jones L, Lythgoe DT, Malik HZ, et al. Randomized clinical trial of prehabilitation before planned liver resection. Br J Surg. 2016;103(5):504-12.

Ngo-Huang A, Parker NH, Wang X, Petzel MQB, Fogelman D, Schadler KL, et al. Home-based exercise during preoperative therapy for pancreatic cancer. Langenbecks Arch Surg. 2017;402(8):1175-85.

Burd NA, Tang JE, Moore DR, Phillips SM. Exercise training and protein metabolism: influences of contraction, protein intake, and sex-based differences. J Appl Physiol (1985). 2009;106(5):1692-701.

Deutz NE, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-Westphal A, et al. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr. 2014;33(6):929-36.

Gillis C, Wischmeyer PE. Pre-operative nutrition and the elective surgical patient: why, how and what? Anaesthesia. 2019;74:27-35.

Sallam N, Laher I. Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases. Oxid Med Cell Longev. 2016;2016:7239639.

Snowden CP, Prentis JM, Anderson HL, Roberts DR, Randles D, Renton M, et al. Submaximal cardiopulmonary exercise testing predicts complications and hospital length of stay in patients undergoing major elective surgery. Ann Surg. 2010;251(3):535-41.

Hoogeboom TJ, Oosting E, Vriezekolk JE, Veenhof C, Siemonsma PC, de Bie RA, et al. Therapeutic validity and effectiveness of preoperative exercise on functional recovery after joint replacement: a systematic review and meta-analysis. PLoS One. 2012;7(5):e38031.

Glasziou P, Irwig L, Mant D. Monitoring in chronic disease: a rational approach. BMJ. 2005;330(7492):644-8.

Siemonsma PC, Blom JW, Hofstetter H, van Hespen ATH, Gussekloo J, Drewes YM, et al. The effectiveness of functional task exercise and physical therapy as prevention of functional decline in community dwelling older people with complex health problems. BMC Geriatr. 2018;18(1):164,018-0859-3.

Salles J, Chanet A, Giraudet C, Patrac V, Pierre P, Jourdan M, et al. 1,25(OH)2-vitamin D3 enhances the stimulating effect of leucine and insulin on protein synthesis rate through Akt/PKB and mTOR mediated pathways in murine C2C12 skeletal myotubes. Mol Nutr Food Res. 2013;57(12):2137-46.

Voedingscentrum. Vitamine D. Available at: Accessed on 2 September 2019.

van Rooijen S, Carli F, Dalton S. Multimodal prehabilitation in colorectal cancer patients to improve functional capacity and reduce postoperative complications: the first international randomized controlled trial for multimodal prehabilitation. BMC Cancer. 2019;19(1):98,018-5232-6.

Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol (1985). 1986;60(6):2020-7.

Borley NR, Achan V. Respiratory Physiology. Instant Physiology. Blackwell Science; 2000.

American Thoracic Society, American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167(2):211-77.

Bongers BC, Takken T. The paediatric version of the steep ramp test. J Physiother 2014;60(2):113.

Van Beijsterveld CA, Bongers BC, Den Dulk M. The association between preoperative physical functioning and short-term postoperative outcomes: a cohort study of patients undergoing elective hepatic resection. HPB (Oxford). 2019;21(10):1362-70.

Fien S, Henwood T, Climstein M. Feasibility and benefits of group-based exercise in residential aged care adults: a pilot study for the GrACE programme. Peer J. 2016;4:e2018.

Bossers WJ, Scherder EJ, Boersma F. Feasibility of a combined aerobic and strength training program and its effects on cognitive and physical function in institutionalized dementia patients. A pilot study. PLoS One. 2014;9(5):e97577.

Cheema BS, Davies TB, Stewart M. The feasibility and effectiveness of high-intensity boxing training versus moderate-intensity brisk walking in adults with abdominal obesity: a pilot study. BMC Sports Sci Med Rehabil. 2015;7:3,1847-7-3.

Aaronson NK, Muller M, Cohen PD. Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations. J Clin Epidemiol. 1998;51(11):1055-68.

Brazier J, Jones N, Kind P. Testing the validity of the Euroqol and comparing it with the SF-36 health survey questionnaire. Qual Life Res. 1993;2(3):169-80.

Dronkers JJ, Lamberts H, Reutelingsperger IM. Preoperative therapeutic programme for elderly patients scheduled for elective abdominal oncological surgery: a randomized controlled pilot study. Clin Rehabil. 2010;24(7):614-22.

Bongers BC, Berkel AE, Klaase JM. An evaluation of the validity of the pre-operative oxygen uptake efficiency slope as an indicator of cardiorespiratory fitness in elderly patients scheduled for major colorectal surgery. Anaesthesia. 2017;72(10):1206-16.

Barberan-Garcia A, Ubre M, Pascual-Argente N. Post-discharge impact and cost-consequence analysis of prehabilitation in high-risk patients undergoing major abdominal surgery: secondary results from a randomised controlled trial. Br J Anaesth. 2019;123(4):450-6.