Effects of Nutritional Prehabilitation, With and Without Exercise, on Outcomes of Patients Who Undergo Colorectal Surgery: A Systematic Review and Meta-analysis

  • Chelsia Gillis
    Reprint requests Address requests for reprints to: Chelsia Gillis, RD, MSc, Department of Community Health Sciences, University of Calgary, Teaching Research Wellness Building, 3280 Hospital Dr NW, Calgary, AB, Canada T2N 4Z6.
    Cumming School of Medicine, Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
    Search for articles by this author
  • Katherine Buhler
    Cumming School of Medicine, Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
    Search for articles by this author
  • Lauren Bresee
    Cumming School of Medicine, Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada

    Canadian Agency for Drugs and Technologies in Health, Ottawa, Ontario, Canada

    O’Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada
    Search for articles by this author
  • Francesco Carli
    Department of Anesthesia, McGill University Health Center, Montreal, Quebec, Canada
    Search for articles by this author
  • Leah Gramlich
    Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
    Search for articles by this author
  • Nicole Culos-Reed
    Faculty of Kinesiology and Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

    Psychosocial Resources, Tom Baker Cancer Centre, Alberta Health Services, Calgary, Alberta, Canada
    Search for articles by this author
  • Tolulope T. Sajobi
    Cumming School of Medicine, Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada

    O’Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada
    Search for articles by this author
  • Tanis R. Fenton
    Department of Community Health Sciences, Institute of Public Health, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Nutrition Services, Alberta Health Services, Calgary, Canada
    Search for articles by this author

      Background & Aims

      Although there have been meta-analyses of the effects of exercise-only prehabilitation on patients undergoing colorectal surgery, little is known about the effects of nutrition-only (oral nutritional supplements with and without counseling) and multimodal (oral nutritional supplements with and without counseling and with exercise) prehabilitation on clinical outcomes and patient function after surgery. We performed a systemic review and meta-analysis to determine the individual and combined effects of nutrition-only and multimodal prehabilitation compared with no prehabilitation (control) on outcomes of patients undergoing colorectal resection.


      We searched Medline, EMBASE, CINAHL, CENTRAL, and ProQuest for cohort and randomized controlled studies of adults awaiting colorectal surgery who received at least 7 days of nutrition prehabilitation with or without exercise. We performed a random-effects meta-analysis to estimate the pooled risk ratio for categorical data and the weighted mean difference for continuous variables. The primary outcome was length of hospital stay; the secondary outcome was recovery of functional capacity based on results of a 6-minute walk test.


      We identified 9 studies (5 randomized controlled studies and 4 cohort studies) composed of 914 patients undergoing colorectal surgery (438 received prehabilitation and 476 served as controls). Receipt of any prehabilitation significantly decreased days spent in the hospital compared with controls (weighted mean difference of length of hospital stay = −2.2 days; 95% confidence interval = −3.5 to −0.9). Only 3 studies reported on functional outcomes but could not be pooled owing to methodologic heterogeneity. In the individual studies, multimodal prehabilitation significantly improved results of the 6-minute walk test at 4 and 8 weeks after surgery compared with standard Enhanced Recovery Pathway care and at 8 weeks compared with standard Enhanced Recovery Pathway care with added rehabilitation. The 4 observational studies had a high risk of bias.


      In a systematic review and meta-analysis, we found that nutritional prehabilitation alone or combined with an exercise program significantly decreased length of hospital stay by 2 days in patients undergoing colorectal surgery. There is some evidence that multimodal prehabilitation accelerated the return to presurgical functional capacity.


      Abbreviations used in this paper:

      6MWT (6-minute walk test), CI (confidence interval), ERAS (Enhanced Recovery After Surgery), ERP (Enhanced Recovery Pathway), LOS (length of hospital stay), ONS (oral nutritional supplements), RCT (randomized controlled trial), RR (risk ratio), WMD (weighted mean difference)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Carli F.
        • Gillis C.
        • Scheede-Bergdahl C.
        Promoting a culture of prehabilitation for the surgical cancer patient.
        Acta Oncol. 2017; 56: 128-133
        • Gillis C.
        • Li C.
        • Lee L.
        • et al.
        Prehabilitation versus rehabilitation: a randomized control trial in patients undergoing colorectal resection for cancer.
        Anesthesiology. 2014; 121: 937-947
        • Chen B.P.
        • Awasthi R.
        • Sweet S.N.
        • et al.
        Four-week prehabilitation program is sufficient to modify exercise behaviors and improve preoperative functional walking capacity in patients with colorectal cancer.
        Support Care Cancer. 2017; 25: 33-40
        • Simunovic M.
        • Rempel E.
        • Theriault M.E.
        • et al.
        Influence of delays to nonemergent colon cancer surgery on operative mortality, disease-specific survival and overall survival.
        Can J Surg. 2009; 52: E79-E86
        • Barberan-Garcia A.
        • Ubre M.
        • Roca J.
        • et al.
        Personalised prehabilitation in high-risk patients undergoing elective major abdominal surgery: a randomized blinded controlled trial.
        Ann Surg. 2018; 267: 50-56
        • Lemanu D.P.
        • Singh P.P.
        • MacCormick A.D.
        • et al.
        Effect of preoperative exercise on cardiorespiratory function and recovery after surgery: a systematic review.
        World J Surg. 2013; 37: 711-720
        • Moran J.
        • Guinan E.
        • McCormick P.
        • et al.
        The ability of prehabilitation to influence postoperative outcome after intra-abdominal operation: a systematic review and meta-analysis.
        Surgery. 2016; 160: 1189-1201
        • Santa Mina D.
        • Clarke H.
        • Ritvo P.
        • et al.
        Effect of total-body prehabilitation on postoperative outcomes: a systematic review and meta-analysis.
        Physiotherapy. 2014; 100: 196-207
        • Cabilan C.J.
        • Hines S.
        • Munday J.
        The impact of prehabilitation on postoperative functional status, healthcare utilization, pain, and quality of life: a systematic review.
        Orthop Nurs. 2016; 35: 224-237
        • Moran J.
        • Guinan E.
        • McCormick P.
        • et al.
        Response to: Is prehabilitation limited to preoperative exercise?.
        Surgery. 2017; 162: 192-193
        • Biolo G.
        • Tipton K.D.
        • Klein S.
        • et al.
        An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein.
        Am J Physiol Endocrinol Metab. 1997; 273: E122-E129
        • Phillips S.M.
        • Tipton K.D.
        • Aarsland A.
        • et al.
        Mixed muscle protein synthesis and breakdown after resistance exercise in humans.
        Am J Physiol Endocrinol Metab. 1997; 273: E99-E107
        • Tipton K.D.
        • Ferrando A.A.
        • Phillips S.M.
        • et al.
        Postexercise net protein synthesis in human muscle from orally administered amino acids.
        Am J Physiol Endocrinol Metab. 1999; 276: E628-E634
        • Johnston M.
        Dimensions of recovery from surgery.
        Appl Psychol. 1984; 33: 505-520
        • Miller T.E.
        • Mythen M.
        Successful recovery after major surgery: moving beyond length of stay.
        Perioper Med (Lond). 2014; 3: 4
        • Weimann A.
        • Braga M.
        • Harsanyi L.
        • et al.
        ESPEN guidelines on enteral nutrition: surgery including organ transplantation.
        Clin Nutr. 2006; 25: 224-244
        • Egger M.
        • Smith G.D.
        • Schneider M.
        Systematic reviews of observational studies. Systematic reviews in health care.
        BMJ Publishing Group, London2008: 211-227
        • Jüni P.
        • Altman D.G.
        • Egger M.
        Assessing the quality of randomised controlled trials. Systematic reviews in health care.
        BMJ Publishing Group, London2008: 87-108
        • Higgins J.P.
        • Altman D.G.
        • Gotzsche P.C.
        • et al.
        The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
        • Juni P.
        • Witschi A.
        • Bloch R.
        • et al.
        The hazards of scoring the quality of clinical trials for meta-analysis.
        JAMA. 1999; 282: 1054-1060
        • Greenland S.
        • O’Rourke K.
        On the bias produced by quality scores in meta-analysis, and a hierarchical view of proposed solutions.
        Biostatistics. 2001; 2: 463-471
        • Schulz K.F.
        • Chalmers I.
        • Hayes R.J.
        • et al.
        Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.
        JAMA. 1995; 273: 408-412
        • Wood L.
        • Egger M.
        • Gluud L.L.
        • et al.
        Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study.
        BMJ. 2008; 336: 601-605
        • Lau J.
        • Ioannidis J.P.
        • Schmid C.H.
        Summing up evidence: one answer is not always enough.
        Lancet. 1998; 351: 123-127
        • Thompson S.G.
        • Sharp S.J.
        Explaining heterogeneity in meta-analysis: a comparison of methods.
        Stat Med. 1999; 18: 2693-2708
        • Gustafsson U.O.
        • Hausel J.
        • Thorell A.
        • et al.
        Adherence to the enhanced recovery after surgery protocol and outcomes after colorectal cancer surgery.
        Arch Surg. 2011; 146: 571-577
        • Hozo S.P.
        • Djulbegovic B.
        • Hozo I.
        Estimating the mean and variance from the median, range, and the size of a sample.
        BMC Med Res Methodol. 2005; 5: 13
        • Moriello C.
        • Mayo N.E.
        • Feldman L.
        • et al.
        Validating the six-minute walk test as a measure of recovery after elective colon resection surgery.
        Arch Phys Med Rehabil. 2008; 89: 1083-1089
        • Hennekens C.H.
        • Buring J.E.
        • Mayrent S.L.
        Epidemiology in medicine.
        Little, Brown, Boston1987
        • Sterne J.A.C.
        • Bradburn M.J.
        • Egger M.
        Meta-analysis in Stata™. Systematic reviews in health care.
        BMJ Publishing Group, London2008: 347-369
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • et al.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Gillis C.
        • Loiselle S.E.
        • Fiore Jr., J.F.
        • et al.
        Prehabilitation with whey protein supplementation on perioperative functional exercise capacity in patients undergoing colorectal resection for cancer: a pilot double-blinded randomized placebo-controlled trial.
        J Acad Nutr Diet. 2016; 116: 802-812
        • Burden S.T.
        • Hill J.
        • Shaffer J.L.
        • et al.
        An unblinded randomised controlled trial of preoperative oral supplements in colorectal cancer patients.
        J Hum Nutr Diet. 2011; 24: 441-448
        • MacFie J.
        • Woodcock N.P.
        • Palmer M.D.
        • et al.
        Oral dietary supplements in pre- and postoperative surgical patients: a prospective and randomized clinical trial.
        Nutrition. 2000; 16: 723-728
        • Smedley F.
        • Bowling T.
        • James M.
        • et al.
        Randomized clinical trial of the effects of preoperative and postoperative oral nutritional supplements on clinical course and cost of care.
        Br J Surg. 2004; 91: 983-990
        • Maňásek V.
        • Bezděk K.
        • Foltys A.
        • et al.
        The impact of high protein nutritional support on clinical outcomes and treatment costs of patients with colorectal cancer.
        Klin Onkol. 2016; 29: 351-357
        • Chia C.L.
        • Mantoo S.K.
        • Tan K.Y.
        ‘Start to finish trans-institutional transdisciplinary care’: a novel approach improves colorectal surgical results in frail elderly patients.
        Colorectal Dis. 2016; 18: O43-O50
        • Li C.
        • Carli F.
        • Lee L.
        • et al.
        Impact of a trimodal prehabilitation program on functional recovery after colorectal cancer surgery: a pilot study.
        Surg Endosc. 2013; 27: 1072-1082
        • Khrykov G.N.
        • Manikhas G.M.
        • Strukov E.
        • et al.
        [Influence of nutritive support on surgery outcomes in elderly patients with colon cancer].
        Vestn Khir Im I I Grek. 2014; 173: 77-81
        • Feldman L.S.
        • Lee L.
        • Fiore Jr., J.
        What outcomes are important in the assessment of Enhanced Recovery After Surgery (ERAS) pathways?.
        Can J Anaesth. 2015; 62: 120-130
        • Guyatt G.H.
        • Oxman A.D.
        • Sultan S.
        • et al.
        GRADE guidelines: 9. Rating up the quality of evidence.
        J Clin Epidemiol. 2011; 64: 1311-1316
        • Paddon-Jones D.
        • Sheffield-Moore M.
        • Urban R.J.
        • et al.
        Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest.
        J Clin Endocrinol Metab. 2004; 89: 4351-4358
        • Wolfe R.R.
        Protein supplements and exercise.
        Am J Clin Nutr. 2000; 72: 551s-557s
        • Glover E.I.
        • Oates B.R.
        • Tang J.E.
        • et al.
        Resistance exercise decreases eIF2Bepsilon phosphorylation and potentiates the feeding-induced stimulation of p70S6K1 and rpS6 in young men.
        Am J Physiol Regul Integr Comp Physiol. 2008; 295: R604-R610
        • Phillips S.M.
        Protein requirements and supplementation in strength sports.
        Nutrition. 2004; 20: 689-695
        • Wolfe R.R.
        The underappreciated role of muscle in health and disease.
        Am J Clin Nutr. 2006; 84: 475-482
        • Gillis C.
        • Carli F.
        Promoting perioperative metabolic and nutritional care.
        Anesthesiology. 2015; 123: 1455-1472
        • Gaudreau P.
        • Morais J.A.
        • Shatenstein B.
        • et al.
        Nutrition as a determinant of successful aging: description of the Quebec longitudinal study Nuage and results from cross-sectional pilot studies.
        Rejuvenation Res. 2007; 10: 377-386
        • Phillips S.M.
        • Chevalier S.
        • Leidy H.J.
        Protein “requirements” beyond the RDA: implications for optimizing health.
        Appl Physiol Nutr Metab. 2016; 41: 565-572
        • Cawood A.L.
        • Elia M.
        • Stratton R.J.
        Systematic review and meta-analysis of the effects of high protein oral nutritional supplements.
        Ageing Res Rev. 2012; 11: 278-296
        • Kabata P.
        • Jastrzebski T.
        • Kakol M.
        • et al.
        Preoperative nutritional support in cancer patients with no clinical signs of malnutrition—prospective randomized controlled trial.
        Support Care Cancer. 2015; 23: 365-370
        • Chan L.N.
        • Compher C.
        • DiBaise J.K.
        • et al.
        American Society for Parenteral and Enteral Nutrition research agenda.
        JPEN J Parenter Enteral Nutr. 2014; 38: 13-18
        • Schricker T.
        • Wykes L.
        • Meterissian S.
        • et al.
        The anabolic effect of perioperative nutrition depends on the patient’s catabolic state before surgery.
        Ann Surg. 2013; 257: 155-159
        • McNair A.G.
        • Whistance R.N.
        • Forsythe R.O.
        • et al.
        Synthesis and summary of patient-reported outcome measures to inform the development of a core outcome set in colorectal cancer surgery.
        Colorectal Dis. 2015; 17: O217-O229
        • Aloia T.A.
        • Zimmitti G.
        • Conrad C.
        • et al.
        Return to intended oncologic treatment (RIOT): a novel metric for evaluating the quality of oncosurgical therapy for malignancy.
        J Surg Oncol. 2014; 110: 107-114
        • Buzby G.P.
        • Knox L.S.
        • Crosby L.O.
        • Eisenberg J.M.
        • Haakenson C.M.
        • McNeal G.E.
        • et al.
        Study protocol: a randomized clinical trial of total parenteral nutrition in malnourished surgical patients.
        Am J Clin Nutr. 1988; 47: 366-381
        • Copeland G.P.
        • Jones D.
        • Walters M.
        POSSUM: a scoring system for surgical audit.
        Br J Surg. 1991; 78: 355-360
        • Dindo D.
        • Demartines N.
        • Clavien P.A.
        Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.
        Ann Surg. 2004; 240: 205-213