Q6. Does nutrition intervention improve outcomes? - Surgery
The European Society of Parenteral and Enteral Nutrition (ESPEN) Guidelines on Enteral Nutrition: Surgery Including Organ Transplantation  report that pre operative enteral nutrition should be given to patients with severe nutritional risk (weight loss of >10-15% in last 6 months, body mass index (BMI) <18.5, Subjective Global Assessment (SGA) C (i.e. severely malnourished), albumin <30 with no evidence of renal/liver dysfunction) for 10-14 days pre operatively (Grade A Recommendation, ESPEN, 2006).
Immunonutrition has been a focus of nutrition intervention in surgery and the critical care setting for several years. It is a term encompassing a form of nutritional supplement or enteral feeding formula, which has added nutrients for a proposed immune modulating effect. It is hypothesized that the nutrition factors may play a role in modulating the immune system, which can then impact upon patients’ clinical outcomes such as reduced infections. The most common types of formula have conditionally essential amino acids arginine and/or glutamine, n-3 fatty acids and/or ribonucleic acids added. The majority of studies have involved arginine enhanced feeds; however two studies have looked at the role of n-3 fatty acids as an immune modulating factor .
There are two level I studies, one positive quality paper  and one negative quality which report on results of a systematic review on the role of immunonutrition in patients undergoing surgery for head and neck cancer. The first paper included 10 randomised controlled trials (RCT’s)(total n=605), six were in patients with carcinoma of the oral cavity or larynx, three studies also included pharyngeal tumours, and one study did not fully specify the tumour groups for inclusion. Three studies only recruited patients with recent weight loss. The pooled data showed a significant reduction in length of stay by 3.5 days, but no effect on complication rates. The trials were deemed to be small with incomplete reporting of outcomes, and the results should be interpreted with some degree of caution given that six of the ten studies were also undertaken by the same author group. The conclusions state that adequately powered trials are required to substantiate the benefit and determine the mechanism. The second systematic review included 14 RCT’s (total n=836). Although the aim was to examine the effect of perioperative immunonutrition, only five of the 14 studies utilised preoperative supplementation. The remaining nine studies examined the effect of postoperative supplementation alone. The paper was more narrative than analytic in review style with no meta analysis, making it difficult to draw conclusions. However the authors concluded there was little evidence to guide the use or value of preoperative supplementation, while a suitably powered clinical trial is required before firm recommendations can be made regarding the use of post operative immunonutrition in this patient group. Another systematic review  reported on perioperative use of arginine supplemented diets in a range of elective surgical patients. Although this review was graded as a level I positive quality paper, there were concerns about the grouping of patients with head and neck cancer (3 RCT perioperative n=241, 6 RCT postoperative n=369), with upper gastrointestinal patients (5 RCT perioperative n=869, 12 RCT postoperative n=1353). There were no additional studies in head and neck cancer patients that had been identified since the publication of the systematic review in 2009, and so this was still deemed the most appropriate to use to guide practice.
For preoperative immunonutrition, all studies compare perioperative immunonutrition (i.e. given before and after surgery), which makes it difficult to determine at which point the intervention may be having an effect. In addition to the studies in the systematic review by Stableforth et al., one level II neutral study  demonstrated less major complications (infections and wound complications) in the group that received immunonutrition pre and postoperatively, compared to the group which received no preoperative nutrition support and standard postoperative enteral feeding. One level II neutral quality pilot study  was underpowered to show any statistical differences, other than reduced C-reactive protein levels in the perioperative immunonutrition group on day one postop only, compared to the standard feeds. Another level II neutral quality pilot study was unable to demonstrate any significant differences in inflammatory markers, postop complications or LOS between groups due to being underpowered. Two level II neutral quality studies , which were included in the systematic review, also included a third control group of no preoperative nutrition support. They found that malnourished patients with preoperative standard nutrition support compared to no preoperative nutrition support had improved quality of life . The addition of preoperative immunonutrition with arginine had no additional benefit compared to standard preoperative nutrition support . In a longitudinal study by the same group of authors, level II neutral quality,  the group that received immunonutrition pre and postoperatively had improved long term survival at 10 years compared to those that received standard formula.
There is one level III-1 neutral quality study  which studied the effect of preoperative nutrition support (either counselling or supplements) to reduce length of stay and complications, however the results need to be interpreted with caution as there was no statistical analysis. One level III-3 neutral quality study  describes patient outcomes pre and post implementation of Diagnosis Related Groups (DRGs). The impact of this change in the US health system had was a reduction in preoperative admission time, which resulted in less nutrition intervention preoperatively and therefore higher rates of malnutrition at the time of surgery which resulted in increased complications, infections and length of stay. This provides support for nutrition intervention preoperatively even if it can only be given as an outpatient. There was one level IV negative quality study  which examined the effect of preoperative nutrition intervention of counselling, supplements or tube feeding, but outcome data was limited.
For postoperative immunonutrition interventions, there is the level I positive quality paper , and in addition to the papers included within this review, there is one level II positive quality study , six level II neutral quality studies  and one level III-3 positive quality study. The level II positive quality study demonstrates a significant reduction in both length of stay of 12 days and fistula rates (17.6% compared to 5.2%), and no difference in infection rates. For the neutral studies, other statistical differences were seen with reduction in fistula rates in one study, reduced infections and wound complications in one study and improved survival in one study. The level III-3 study did not find any significant differences between groups apart from a reduced fistula rate in the immunonutrition group.
Despite the volume of literature in this area, well designed clinical studies are still required to confirm how the mechanism of immunonutrition is beneficial in this group of patients, with several studies unable to distinguish between effects seen preoperatively or postoperatively.
With regards to n-3 fatty acids, the level II neutral quality paper  compared arginine enriched oral nutrition support with n-3 fatty acid enriched oral nutrition support for 12 weeks post discharge. They found the n-3 fatty acid supplement resulted in significantly greater weight gain and fat mass gain. The level IV neutral quality study  demonstrated that patients who were given n-3 fatty acid enriched nutrition support (orally or tube fed) perioperatively had improved outcomes in terms of weight maintenance and increased lean body mass at the time of discharge.
In terms of general postoperative nutrition care, there are five level IV neutral quality studies  and one level IV negative quality study , examining outcomes with either postoperative nasogastric or gastrostomy feeding. All of the neutral studies, irrespective of method of feeding, demonstrate a significant weight loss or drop in Body Mass Index (BMI) in the immediate postoperative period (one week to one month). The negative quality study, demonstrated that following postoperative gastrostomy feeding, weight gain of 3kg was achieved by one month postoperatively.
|Pre operative immunonutrition has no additional benefits compared to standard nutrition support for patients undergoing surgery for head and neck cancer.||C|
|Post operative immunonutrition may be considered to reduce length of stay, although the mechanism is unclear, as other clinical benefits such as reduced complications and infections were not demonstrated.||B|
|Peri operative n-3 fatty acid enriched nutrition support may improve nutritional outcomes such as weight, lean body mass and fat mass.||C|
|Tube feeding using standard formula can be used to minimise weight loss in the acute post operative period.||C|
|Pre operative nutrition intervention in malnourished patients may lead to improved outcomes such as quality of life and reduce adverse related consequences of malnutrition.||B|
- Weimann A, Braga M, Harsanyi L, Laviano A, Ljungqvist O, Soeters P, et al. ESPEN Guidelines on Enteral Nutrition: Surgery including organ transplantation. Clin Nutr 2006 Apr;25(2):224-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16698152.
- de Luis DA, Izaola O, Aller R, Cuellar L, Terroba MC. A randomized clinical trial with oral Immunonutrition (omega3-enhanced formula vs. arginine-enhanced formula) in ambulatory head and neck cancer patients. Ann Nutr Metab 2005;49(2):95-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15802904.
- Weed HG, Ferguson ML, Gaff RL, Hustead DS, Nelson JL, Voss AC. Lean body mass gain in patients with head and neck squamous cell cancer treated perioperatively with a protein- and energy-dense nutritional supplement containing eicosapentaenoic acid. Head Neck 2011 Jul;33(7):1027-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20967868.
- Stableforth WD, Thomas S, Lewis SJ. A systematic review of the role of immunonutrition in patients undergoing surgery for head and neck cancer. Int J Oral Maxillofac Surg 2009 Feb;38(2):103-10 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19144498.
Cite error: Invalid
<ref>tag; name "Citation:Stableforth_WD.2C_Thomas_S.2C_Lewis_SJ_2009" defined multiple times with different content Cite error: Invalid
<ref>tag; name "Citation:Stableforth_WD.2C_Thomas_S.2C_Lewis_SJ_2009" defined multiple times with different content
- Casas Rodera P, de Luis DA, Gómez Candela C, Culebras JM. Immunoenhanced enteral nutrition formulas in head and neck cancer surgery: a systematic review. Nutr Hosp 2012 May;27(3):681-90 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23114931.
- Drover JW, Dhaliwal R, Weitzel L, Wischmeyer PE, Ochoa JB, Heyland DK. Perioperative use of arginine-supplemented diets: a systematic review of the evidence. J Am Coll Surg 2011 Mar;212(3):385-99, 399.e1 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21247782.
- Felekis D, Eleftheriadou A, Papadakos G, Bosinakou I, Ferekidou E, Kandiloros D, et al. Effect of perioperative immuno-enhanced enteral nutrition on inflammatory response, nutritional status, and outcomes in head and neck cancer patients undergoing major surgery. Nutr Cancer 2010;62(8):1105-12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21058198.
- Sorensen D, McCarthy M, Baumgartner B, Demars S. Perioperative immunonutrition in head and neck cancer. Laryngoscope 2009 Jul;119(7):1358-64 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19459146.
Cite error: Invalid
<ref>tag; name "Citation:Sorensen_D.2C_McCarthy_M.2C_Baumgartner_B.2C_Demars_S_2009" defined multiple times with different content
- Turnock A, Calder PC, West AL, Izzard M, Morton RP, Plank LD. Perioperative immunonutrition in well-nourished patients undergoing surgery for head and neck cancer: evaluation of inflammatory and immunologic outcomes. Nutrients 2013 Apr 9;5(4):1186-99 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23571650.
- Van Bokhorst-de Van der Schuer MA, Langendoen SI, Vondeling H, Kuik DJ, Quak JJ, Van Leeuwen PA. Perioperative enteral nutrition and quality of life of severely malnourished head and neck cancer patients: a randomized clinical trial. Clin Nutr 2000 Dec;19(6):437-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11104595.
- van Bokhorst-De Van Der Schueren MA, Quak JJ, von Blomberg-van der Flier BM, Kuik DJ, Langendoen SI, Snow GB, et al. Effect of perioperative nutrition, with and without arginine supplementation, on nutritional status, immune function, postoperative morbidity, and survival in severely malnourished head and neck cancer patients. Am J Clin Nutr 2001 Feb;73(2):323-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11157331.
Cite error: Invalid
<ref>tag; name "Citation:Van_Bokhorst-De_Van_Der_Schueren_MA.2C_Quak_JJ.2C_von_Blomberg-van_der_Flier_BM.2C_Kuik_DJ.2C_Langendoen_SI.2C_Snow_GB_et_al._2001" defined multiple times with different content
- Buijs N, van Bokhorst-de van der Schueren MA, Langius JA, Leemans CR, Kuik DJ, Vermeulen MA, et al. Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival. Am J Clin Nutr 2010 Nov;92(5):1151-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20881073.
Cite error: Invalid
<ref>tag; name "Citation:Buijs_N.2C_van_Bokhorst-de_van_der_Schueren_MA.2C_Langius_JA.2C_Leemans_CR.2C_Kuik_DJ.2C_Vermeulen_MA_et_al._2010" defined multiple times with different content
- Flynn MB, Leightty FF. Preoperative outpatient nutritional support of patients with squamous cancer of the upper aerodigestive tract. Am J Surg 1987 Oct;154(4):359-62 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3661837.
- Linn BS, Robinson DS. The possible impact of DRGs on nutritional status of patients having surgery for cancer of the head and neck. JAMA 1988 Jul;260(4):514-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3133497.
- Bertrand PC, Piquet MA, Bordier I, Monnier P, Roulet M. Preoperative nutritional support at home in head and neck cancer patients: from nutritional benefits to the prevention of the alcohol withdrawal syndrome. Curr Opin Clin Nutr Metab Care 2002 Jul;5(4):435-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12107380.
- De Luis DA, Izaola O, Cuellar L, Terroba MC, Martin T, Aller R. High dose of arginine enhanced enteral nutrition in postsurgical head and neck cancer patients. A randomized clinical trial. Eur Rev Med Pharmacol Sci 2009;13(4):279-83 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19694342.
- Casas-Rodera P, Gómez-Candela C, Benítez S, Mateo R, Armero M, Castillo R, et al. Immunoenhanced enteral nutrition formulas in head and neck cancer surgery: a prospective, randomized clinical trial. Nutr Hosp 2008;23(2):105-10 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18449445.
- de Luis DA, Izaola O, Aller R, Cuellar L, Terroba MC, Martin T. A randomized clinical trial with two omega 3 fatty acid enhanced oral supplements in head and neck cancer ambulatory patients. Eur Rev Med Pharmacol Sci 2008;12(3):177-81 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18700689.
- Unable to find the reference "Citation:Van Bandokhorst-de Van der Schuer MA, Langendoen SI, Vondeling H, Kuik DJ, Quak JJ, Van Leeuwen PA 2000"
- De Luis DA, Izaola O, Cuellar L, Terroba MC, Martin T, Ventosa M. A randomized double-blind clinical trial with two different doses of arginine enhanced enteral nutrition in postsurgical cancer patients. Eur Rev Med Pharmacol Sci 2010 Nov;14(11):941-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21284343.
- Dovsak T, Ihan A, Didanovic V, Kansky A, Hren N. Influence of surgical treatment and radiotherapy of the advanced intraoral cancers on complete blood count, body mass index, liver enzymes and leukocyte CD64 expression. Radiother Oncol 2009;43:282-92.
- van den Berg MG, Rasmussen-Conrad EL, van Nispen L, van Binsbergen JJ, Merkx MA. A prospective study on malnutrition and quality of life in patients with head and neck cancer. Oral Oncol 2008 Sep;44(9):830-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18243771.
- Chandu A, Smith AC, Douglas M. Percutaneous endoscopic gastrostomy in patients undergoing resection for oral tumors: a retrospective review of complications and outcomes. J Oral Maxillofac Surg 2003 Nov;61(11):1279-84 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14613083.
- Smith A, Chandu A. Percutaneous endoscopic gastrostomy for patients undergoing resection of oral tumours. Ann R Australas Coll Dent Surg 2000 Oct;15:349-51 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11709973.
- Koehler J, Buhl K. Percutaneous endoscopic gastrostomy for postoperative rehabilitation after maxillofacial tumor surgery. Int J Oral Maxillofac Surg 1991 Feb;20(1):38-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1902250.