Surgical Oncology

Maureen B. Huhmann, DCN, RD, CSO David August, M D INTRODUCTION

Malnutrition is a significant contributor to surgical morbidity and mortality in cancer patients.1 The role of nutrition support therapy (NST)—either enteral or parenteral—in the prevention and treatment of the malnutrition in surgical oncology patients has been explored in depth.2-5 This research has elucidated both benefits and risks to these therapeutic interventions. This chapter discusses the role of NST in cancer patients undergoing primarily gastrointestinal (GI) surgery and the evidence on which it is based.

Consequences of Malnutrition

Malnutrition is defined as “any disorder of nutrition status, including disorders resulting from deficiency of nutrient intake, impaired nutrient metabolism, or overnutrition.”6 The prevalence of weight loss in oncology patients ranges from 31% to 100%, depending on tumor site, stage, and treatment (Table 5.1).27-10 Minimal weight loss, in the range of 5%, is associated with increased mortality and poor prognosis for a patients with a variety of tumor types.7 Multiple factors contribute to the weight loss observed in cancer patients, including complications arising from the tumor itself, such as obstruction or tumor-induced anorexia; treatment-induced complications such as gastrointestinal (GI) symptoms, fatigue, or loss of anatomy; and psychological stress.11-15

Cancer cachexia is another common cause of weight loss in this patient population. Cancer cachexia syndrome (CCS) is characterized by progressive, involuntary weight loss that often presents as host tissue wasting, anorexia, skeletal muscle atrophy, anergy, fatigue, anemia, and hypoalbu-minemia. This syndrome is potentially life-threatening; it is caused by physiologic and metabolic derangements1617 that lead to depletion of energy

Site of Cancer

Bozetti1

DeWys et al.2f

Hammerlid et al.3*

Others

Acute non-lymphocytic leukemia

 

39%

 

 

Breast

9%4-36%5

36%

 

 

Bronchial carcinoma

66%5

 

 

 

Colon

54%4

54%

 

 

Colorectal

60%6- 7

 

 

 

Diffuse lymphoma

55%8

 

 

 

Esophagus

79%5

 

100%

85%9f

Gastric

83%2

83-87%

 

44%9f

General cancer population

60%10-63%n

 

 

 

Head and neck

72%12

 

 

57%13*

Larynx

 

 

40%

 

Lung (all types)

50%4

 

 

 

Lung (non-small cell)

 

61%

 

 

Lung (small cell)

60%4

57%

 

 

Lung (squamous cell)

36%4

 

 

 

Neuroblastoma

56%14

 

 

 

Non-Hodgkin’s lymphoma (favorable)

 

31%

 

 

Non-Hodgkin’s lymphoma (unfavorable)

 

48%

 

 

Oral cavity

 

 

63%

41%15f

Pancreas

83%2

83%

 

 

Prostate

56%4

56%

 

 

Rectum

40%5

 

 

 

Sarcoma

39%4-66%16

40%

 

 

Sinus

 

 

30%

 

Skin

 

 

50%

 

Testicular

25%17

 

 

 

*Results described as “malnutrition.”

fResults described as “weight loss” of any amount.

(continues)

Data Sources

1. Bozzetti F. Rationale and indications for preoperative feeding of malnourished surgical cancer patients. Nutrition. 2002;18(11-12):953-959.

2. DeWys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients: Eastern Cooperative Oncology Group. Am J Med. 1980;69(4):491^97.

3. Hammerlid E, Wirblad B, Sandin C, et al. Malnutrition and food intake in relation to quality of life in head and neck cancer patients. Head Neck. 1998;20(6):540-548.

4. Issell BF, Valdivieso M, Zaren HA, et al. Protection against chemotherapy toxicity by IV hyperalimentation. Cancer Treat Rep. 1978;62(8):1139-1143.

5. Bashir Y, Graham TR, Torrance A, Gibson GJ, Corris PA. Nutritional state of patients with lung cancer undergoing thoracotomy. Thorax. 1990;45(3):183-186.

6. Nixon DW, Lawson DH, Kutner MH, et al. Effect of total parenteral nutrition on survival in advanced colon cancer. Cancer Detect Prev. 1981;4(1^):421^27.

7. Nixon DW, Moffitt S, Lawson DH, et al. Total parenteral nutrition as an adjunct to chemotherapy of metastatic colorectal cancer. Cancer Treat Rep. 1981;65(suppl 5):121-128.

8. Popp MB, Fisher RI, Wesley R, Aamodt R, Brennan MF. A prospective randomized study of adjuvant parenteral nutrition in the treatment of advanced diffuse lymphoma: Influence on survival. Surgery. 1981;90(2):195-203.

9. Haugstvedt TK, Viste A, Eide GE, Soreide O. Factors related to and consequences of weight loss in patients with stomach cancer: The Norwegian multicenter experience. Norwegian Stomach Cancer Trial. Cancer. 1991;67(3):722-729.

10. Bozzetti F, Migliavacca S, Scotti A, et al. Impact of cancer, type, site, stage and treatment on the nutritional status of patients. Ann Surg. 1982;196(2):170-179.

11. Tan YS, Nambiar R, Yo SL. Prevalence of protein calorie malnutrition in general surgical patients.

Ann Acad Med Singapore. 1992;21(3):334-338.

12. Goodwin WJ Jr, Torres J. The value of the Prognostic Nutritional Index in the management of patients with advanced carcinoma of the head and neck. Head Neck Surg. 1984;6(5):932-937.

13. Linn BS, Robinson DS, Klimas NG. Effects of age and nutritional status on surgical outcomes in head and neck cancer. Ann Surg. 1988;207(3):267-273.

14. Rickard KA, Loghmani ES, Grosfeld JL, et al. Short- and long-term effectiveness of enteral and parenteral nutrition in reversing or preventing protein-energy malnutrition in advanced neuroblastoma: A prospective randomized study. Cancer. 1985;56(12):2881-2897.

15. Nguyen TV, Yueh B. Weight loss predicts mortality after recurrent oral cavity and oropharyngeal carcinomas. Cancer. 2002;95(3):553-562.

16. Shamberger RC, Brennan MF, Goodgame JT Jr, et al. A prospective, randomized study of adjuvant parenteral nutrition in the treatment of sarcomas: Results of metabolic and survival studies. Surgery. 1984;96(1):1-13.

17. Samuels ML, Selig DE, Ogden S, Grant C, Brown B. IV hyperalimentation and chemotherapy for stage III testicular cancer: A randomized study. Cancer Treat Rep. 1981;65(7-8):615-627.

and protein stores in cancer patients.18 In contrast to starvation, CCS results in the loss of both adipose and skeletal muscle mass, while visceral muscle mass is preserved and hepatic mass increases.19 Also unlike starvation, the weight loss associated with CCS generally cannot be reversed with increases in nutrient intake alone,20 and it continues despite increased administration of nutrients.19 Appetite stimulants are only minimally effective for treatment of CCS.19 Whereas starvation elicits a conservation response in the host, CCS is characterized by increased cycling (synthesis and catabolism) of a variety of metabolic intermediaries, including amino acids, fatty acids, and carbohydrates.2122

Although there is no universally accepted model that adequately explains the etiology of CCS in all patients,23 CCS is caused in part by pro-inflammatory cytokines such as tumor necrosis factor, interferon-y, and interleukin-1 and -6. Tumor-produced substances such as proteolysis-inducing factor, lipid-mobilizing factor, and mitochondria-uncoupling proteins 1, 2, and 3 also affect nutrient metabolism.24

Diagnosis of CCS and the promotion of nutritional adequacy are essential in surgical patients with cancer. Indeed, the presence of malnutrition has important consequences for recovery following surgery. For example, preoperative malnutrition is highly correlated with postoperative morbidity.25 Suboptimal intake of nutrients produces changes in intermediary metabolism, tissue function, and body composition.26 In addition, major surgery itself is linked with deterioration in nutrition status,25 as major surgical procedures are associated with a higher incidence of complications, longer hospital stays, prolonged anorexia, and protein calorie malnutrition.25, 27

Nutrition Assessment

Oncology-related nutritional issues are best addressed within the context of the Nutrition Care Process (NCP). In 2003, the American Dietetic Association published a description of a model of the NCP,28 which provides a framework for the critical analysis and decision-making process regarding medical nutrition therapy. As illustrated in Figure 5.1, this process contains four steps: nutrition assessment, nutrition diagnosis, nutrition intervention, and nutrition monitoring and evaluation.28

Nutrition Screening

It is difficult to define and measure nutrition status in cancer patients. Many markers utilized for assessing nutrition status (e.g., serum albumin, total lymphocyte count, immune competence, anthropometric changes, body composition) may also be affected by the severity of the underlying cancer. Differentiation of the effects of malnutrition from the effects of disease severity is problematic.

Nevertheless, several parameters have been explored as indicators of nutrition status. Hypoalbuminemia is associated with increased surgical mortality and morbidity, especially that related to sepsis and poor healing.1 Unfortunately, the interaction between malnutrition and the acute-phase response

Figure 5.1 Nutrition Care Process Reprinted with permission from Lacey K, Pritchett E. Nutrition care process and model: ADA adopts road map to quality care and outcomes management. J Am Diet Assoc. 2003;103(8): 1061-1072.

proteins limits the use of nutrition indicators such as albumin and prealbumin for specifically assessing nutrition status. Weight loss, another suggested indicator, can also be an unreliable indicator of nutritional status in cancer patients owing to fluid shifts and the presence of edema. It has been suggested that neither albumin nor weight loss in isolation is a specific predictor of complications,29 although both are strong predictors within multivariable models. Many formulae have been developed to predict the impact of nutrition status related to morbidity and mortality in surgical patients; the predictive value of these formulae varies (Table 5.2).27

 

Nutrition screening, as a precursor step to identify those patients who should undergo a more formal nutrition assessment, facilitates the early recognition of malnutrition.28 The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) and the American Dietetic Association (ADA) recommend that all cancer patients undergo nutrition screening as a component of their initial evaluation.6- 30 The purpose of such screening is to identify quickly those individuals who are at risk for nutritional deterioration as well as those individuals who are malnourished. An effective screening process utilizes both objective and subjective data that can be obtained quickly.30 In this process, individual objective measures, such as a single laboratory parameter or current weight, are not specific enough to indicate nutrition risk.31 Instead, multiple objective measures must be combined with subjective measures related to nutrition.30 To facilitate routine screening of all patients, nutrition screening tools should also be easy to use, cost-effective, valid, reliable, and sensitive.6

Several nutrition screening tools have been used in the cancer population to identify those patients who are at greatest risk for developing nutritional problems. The Patient-Generated Subjective Global Assessment (PG-SGA)32 is a modification of an earlier screening tool called the Subjective Global Assessment (SGA)33. It is broken into two sections: a patient-completed section, which includes data regarding weight history, symptoms, dietary intake, and activity level; and a section completed by the healthcare professional, which evaluates metabolic demand, considers disease in relation to nutritional requirements, and incorporates a physical assessment (Table 5.3). A numeric score is calculated by adding the points obtained in both of the two sections. A score of 4-8 requires an intervention by a dietitian, and a score greater than 9 indicates the need for improved symptom management. A SGA score of mild, moderate, or severe malnutrition is assigned based on this overall assessment. The numeric scores generated in this way can be used as a triage system to initiate a formal nutrition assessment leading to intervention and to guide follow-up care.34' 35 The PG-SGA numeric score, when repeated at subsequent time points, is also useful for identifying small improvements or deteriorations in nutrition status.36

Table 5.2 Nutritional Assessment Formulae/Methods in Gastrointestinal Surgery

 

History/Uses

Formula

Subjective Global

Assessment

(SGA)1

Validated in a number of diverse patient populations1

Utilizes physical assessment, weight change, change in intake, GI symptoms, and functional capacity to assign a score: SGA-A: well nourished SGA-B: moderately malnourished SGA-C: severely malnourished

Prognostic Nutritional

Index (PNI)2

Validated prospectively

Calculates percentage risk of an operative complication occurring in an individual

Can distinguish patients at low risk for nutrition-related complications (<10%) from those at high risk (>50%)

Percentage risk of complication = 158 — 16.6(serum albumin; g/dL) - 0.78(TSF; mm) - 0.20(serum transferrin; g/dL) -5.8 (delayed hypersensitivity reaction)

Nutrition Risk Index (NRI)3, 4

Used to stratify nutrition risk in the Veterans Affairs Total Parenteral Nutrition Cooperative Study Group trial of perioperative PN

Classifies individuals as either well nourished or malnourished

NRI = 1.519(serum albumin; g/dL) + 41.7(current weight/usual weight)

Hospital Prognostic Index (HPI)5

Identifies high-risk patients and evaluates the efficacy of hospital therapy

HPI = 0.91(serum albumin; g/dL) — 1.0(delayed hypersensitivity reaction) — 1.44(sepsis rating) + 0.98(diagnosis rating) - 1.09

TSF: triceps skin fold.

Delayed hypersensitivity reaction: 0 = nonreactive, 1 = 5-mm induration, 2 = >5-mm induration. PN: total parenteral nutrition.

Sepsis rating: 1 = present, 2 = absent.

Diagnosis rating: 1 = cancer present, 2 = cancer not present.

Data Sources

1. Detsky AS, McLaughlin JR, Baker JP, et al. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr. 1987;11(1):8-13.

2. Buzby GP, Mullen JL, Matthews DC, Hobbs CL, Rosato EF. Prognostic Nutritional Index in gastrointestinal surgery. Am J Surg. 1980;139(1):160—167.

3. Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med. 1991;325(8):525-532.

4. Franch-Arcas G. The meaning of hypoalbuminaemia in clinical practice. Clin Nutr. 2001;20(3):265-269.

5. Harvey KB, Moldawer LL, Bistrian BR, Blackburn GL. Biological measures for the formulation of a hospital prognostic index. Am J Clin Nutr. 1981;34(10):2013-2022.

Table Source: Adapted with permission from August DA, Huhmann MB. Nutritional care of cancer patients. In: Norton J, Barie P, Bollinger R, et al., eds. Surgery: Basic Science and Clinical Evidence. 2nd ed. New York, NY: Springer; 2008:2123-2150.

Section

Components

Patient-completed section

Weight history Symptoms Food intake Activity level

Healthcare professional—completed section

Metabolic demand Diagnosis and comorbidities Physical examination

Scoring

Each question is assigned a numeric score.

Score 2—3: Patient and family education

Score 4—8: Intervention by dietitian

Score > 9: Improved symptom management and/or nutrient intervention

Source: Ottery FD. Definition of standardized nutritional assessment and interventional pathways in oncology. Nutrition. 1996;12(1)(suppl):S15-S19.

The Nestle Mini Nutritional Assessment (MNA), an 18-item screening tool commonly used in older adult patients, was developed by Guigoz with Nestle Nutritional Corporation.37 This tool can be broken into two main components: screening and assessment. The six-item screen takes approximately three minutes to complete and includes questions related to changes in food intake, weight loss, mobility, stress, and body mass index (BMI). If the score is I I or less, the healthcare practitioner should complete the assessment section of the MNA.37 The assessment component includes specific medical history and eating habits as well as some anthropometric measurements. Empirical evidence on the use of this instrument in the cancer population is limited, making it an area of focus for research.

Several abbreviated nutrition screening tools have also been developed. The Malnutrition Screening Tool (MST) is a short nutrition screening tool that is rarely used in the United States. This three-item tool utilizes data on weight history and appetite to predict nutrition risk. The MST has been validated in both hospitalized non-oncology patients38 and oncology patients receiving radiation therapy.39 Another short tool, the Malnutrition Universal Screening Tool (MUST), also utilizes a score derived from three items.40 However, the MUST has been found to be unsuitable for use in an oncology population because of its low sensitivity and specificity.41

The Nutrition Risk Assessment (NRA) tool, developed in 1999 by the American Dietetic Association and the Consultant Dietitians in Health Care Facilities Practice Group, is widely used in U.S. long-term care facilities.42 It utilizes data collected for the Minimum Data Set (MDS), a government-mandated screening and assessment form for Medicare- and Medicaid-certified long-term care facilities.43 A randomized, prospective trial is currently under way to assess the validity of this tool in nursing home residents.42 As yet, the NRA has not been validated in a population of cancer patients.

Nutrition Assessment

Nutrition screening is of little benefit if it is not followed by a formal, systematic nutrition assessment and development of a clearly outlined plan for intervention and reassessment in those patients whose screen demonstrates risk. Nutrition assessment is a thorough evaluation that assimilates data obtained from the medical history, dietary history, physical examination, anthropometric measurements, and laboratory data.30 A comprehensive assessment of nutritional status typically integrates a review of anthropomet-rics with data on disease and clinical status to evaluate their effects on the patient’s metabolism and nutrient need.6 In addition, an appraisal of disease-and treatment-related symptoms is necessary to plan nutrition interventions. This step is especially important in surgical patients, as preoperative planning in the oncology patient for postoperative feeding can help to prevent feeding delays and other nutrition-related complications.

Nutrition Diagnosis

The process of nutrition assessment results in a nutrition diagnosis. The nutrition diagnosis identifies the actual occurrence of, the risk of occurrence of, or the potential for developing a nutrition-related problem.28 The nutrition assessment includes evaluation of the etiology and signs and symptoms of nutrition problems, which in turn directs the selection of an appropriate nutrition intervention.28

The ADA has developed standardized nomenclature to use for determining nutrition diagnoses.44 An example of a nutrition diagnostic term frequently utilized in cancer patients is “involuntary weight loss,” which is defined as “decrease in body weight that is not planned or desired.”45

Nutrition Intervention

Nutrition intervention refers to the specific activities required to address and correct the nutrition diagnosis.28 The nutrition intervention is designed, planned, and implemented with the intent of improving the patient’s nutrition status.28 Planning of the intervention requires the input of all disciplines involved in the care of the patient.

Nutrition Monitoring and Evaluation

The goals of the intervention must be documented and reevaluated frequently.28 The intervention must be patient-specific and accommodate the patient’s comfort and wishes.28, 34 Although they vary between and among patients, common nutrition goals for surgical patients include symptom management, weight maintenance, and preservation of functional status and body composition.34 Attaining these goals often requires modulation of dietary components, the addition of oral nutritional supplements, or provision of enteral or parenteral nutrition (NST). Figure 5.2 illustrates the recommendations for nutrition intervention in cancer patients undergoing surgery.

Nutrition Support Therapy in Surgical Patients

In 2002, A.S.P.E.N. published guidelines for the use of specialized nutrition support (SNS) in hospitalized patients. These guidelines are currently being updated. The guidelines provide evidence-based direction regarding the use of enteral nutrition (EN) and parenteral nutrition (PN) support (Table 5.4). This section discusses the historical use as well as the current recommendations for use of EN and PN in surgical oncology patients.

The use of EN in surgical oncology patients has been explored in depth.2, 46 Although EN is associated with improvements in nitrogen balance in patients with cancer, improvements in weight gain have been more inconsis-tent.2 PN has also been associated with improvements in nitrogen balance, and PN appears to support weight gain more consistently.2 However, this weight gain reportedly consists of primarily fat.47 While PN may improve patient comfort and sense of well-being, it has little impact on the physiologic effects of malnutrition.2, 48 Because of the underlying metabolic abnormalities induced by CCS, SNS appears to have fewer benefits in cancer patients than in noncancer patients.6 Neither EN nor PN in cancer patients has beneficial effects on serum proteins, such as albumin, when administered for 7-49 days.2, 46

The use of SNS in cancer patients has been approached with caution in the past, reflecting concerns that provision of nutrients might stimulate tumor growth and metastasis. Murine models indicate that PN provision in excess of energy requirements more than doubles the rate of tumor growth.49-51 Some human data on this issue are also available. For example, a study of malnourished gastric cancer patients receiving PN indicated no increase in tumor proliferation.52 Conversely, an increase in tumor cell proliferation and protein synthesis was observed in head and neck and colorectal Table

Figure 5.2 Nutrition Assessment Process in Surgical Patients Reprinted with permission from A.S.P.E.N. Standards for Nutrition Support: Hospitalized Patients. Nutrition in Clinical Practice.1995;10:208-219.

5.4 Route of Nutrition Administration

 

Route

Risks/Benefits

Enteral

Requires functioning GI tract Reduced cost Better maintenance of gut integrity; prevention of bacterial translocation Earlier return of bowel function postoperatively Reduced infection rate Shorter length of stay

Parenteral

Should be avoided with functioning GI tract Invasive therapy Increased cost Increased risk of infection Decreased incidence of gastrointestinal upset (i.e., nausea, diarrhea)

Source: Reprinted with permission from Huhmann M, August D. General gastrointestinal and vascular surgery. In: Marian M., Russell M., Shikora S, eds. Clinical Nutrition for Surgical Patients. Sudbury, MA: Jones and Bartlett; 2007:99-128.

cancer patients receiving PN. It is unlikely that this effect is of clinical significance, although it often comes up as an issue in clinical practice.53-55

The American Gastroenterological Association56 and A.S.P.E.N.6 hold similar positions on the use of PN in oncology patients. According to these organizations, the use of SNS for patients with cancer should generally be reserved for those circumstances when a patient is moderately or severely malnourished; and in whom active therapy is planned to treat the underlying malignancy; and who is unlikely to be able to meet his or her nutritional requirements orally for more than 7-10 days.6 PN should not routinely be administered to patients undergoing cancer chemotherapy or radiation therapy. Instead, PN is appropriate only in malnourished patients who are anticipated to be unable to ingest and/or absorb adequate nutrients for a prolonged period of time, defined as greater than 7-10 days.6 This type of nutrition is considered aggressive because its invasive nature. Aggressive nutrition support such as PN should be avoided in most cases if a patient’s life expectancy is less than 40-60 days.6 If maintenance of fluid balance in a patient with a life expectancy of less than 40 days is desired, hydration therapy with intravenous fluids is recommended rather than PN.6

Perioperative Nutrition Support

Studies in the 1980s and 1990s indicated reduced morbidity and mortality with perioperative PN supplementation in cancer patients, especially those with GI malignancies.57 Viewed in retrospect, these studies had serious design flaws (e.g., the inclusion of heterogeneous populations, variable and likely suboptimal macronutrient provision, and inadequate sample sizes).58 More recent studies of routine (e.g., not guided by nutrition risk and the results of a formal nutrition assessment) perioperative PN, primarily in GI cancer patients, indicate increased incidence of infection in patients receiving PN, with no improvements in survival being noted.46, 59, 60 The limited data in significantly malnourished GI cancer patients also indicate no benefit of perioperative PN over EN, but do indicate a benefit over standard isotonic fluids.46, 59, 60 In any event, the use of PN in cancer patients is not without risk, including increased infection rate, increased surgical complication rate, and increased cost.59, 61-63

Enteral administration of nutrients postoperatively is generally acknowledged to be the initial intervention of choice in surgical patients64 because it is theoretically more physiologic, may be associated with fewer complications, and is less expensive.65 Studies confirm that EN has advantages over PN. For example, an early meta-analysis suggested that EN has cost benefits relative to PN.66 Subsequent meta-analyses have confirmed this economic advantage and also indicated a decreased risk of infection associated with EN in comparison to PN.6, 67 Studies also indicate decreased intestinal permeability and a lower incidence of hyperglycemia in comparison to PN.6 Enteral nutrition is generally well tolerated postoperatively, with gastrointestinal side effects including diarrhea and vomiting that can usually be corrected with temporary decreases in the enteral formula infusion rate.58 Table

5.5 summarizes the studies utilizing nutrition support therapy for surgical cancer patients.

Immunonutrition

The use of enteral and parenteral formulas supplemented with macronutrients and micronutrients intended to preserve or improve immune function has increased in the last two decades. Multiple studies have investigated the use of “immunonutrition” and its effects on outcomes in GI cancer patients. Meta-analyses have demonstrated improved outcomes (reductions in morbidity and mortality) with the use of immunonutrition perioperatively in patients undergoing major GI cancer resections.5 Immune-enhancing nutrients that have been explored include omega-3 fatty acids (Q-3), glutamine (GLN), arginine (ARG), nucleic acids, and combinations of these nutrients.

Glutamine (GLN), which is the most abundant amino acid in the human body, is an important substrate for rapidly proliferating cells such as lymphocytes, macrophages, enterocytes, fibroblasts, and renal epithelium.4, 68 Although several studies have investigated the use of GLN in the prevention or treatment of chemotherapy-induced side effects such as diarrhea and neuropathy,69-73 few studies have examined GLN as a “single agent” in surgical

Issue

Studies (Patients)

Findings

Preoperative NST

4 (449)

Improved morbidity and mortality1-4

Perioperative NST

8 (1,659)

Improved morbidity3, 4 and mortality1, 2 5-8

Immune-enhancing formulae

ARG, RNA, Q-3 FA: 9 (1,281)

ARG, Q-3 FA:

1 (200)

ARG:

2 (139)

GLN:

1 (28)

Improved immune parameters6-8 and clinical outcomes9-11 Improved immune parameters and gut profusion9-16 Improved GI function17

Improved immune parameters18

Enteral nutrition versus 11 (1,742) parenteral nutrition

Few differences in morbidity19 or mortality20-24

EN preserved gut integrity2, 20, 21, 23 and immune markers24-26

Better glycemic management7, 22, 27, 28 with EN

ARG = arginine; RNA

= ribonucleic acid; ^-3 FA = omega-3 fatty acids; GLN = glutamine.

Data Sources

1. Muller JM, Keller HW, Brenner U, Walter M, Holzmuller W. Indications and effects of preoperative parenteral nutrition. World J Surg. 1986;10(1):53-63.

2. Meijerink WJ, von Meyenfeldt MF, Rouflart MM, Soeters PB. Efficacy of perioperative nutritional support. Lancet. 1992;340(8812):187-188.

3. Foschi D, Cavagna G, Callioni F, Morandi E, Rovati V. Hyperalimentation of jaundiced patients on percutaneous transhepatic biliary drainage. Br J Surg. 1986;73(9):716-719.

4. Muller JM, Brenner U, Dienst C, Pichlmaier H. Preoperative parenteral feeding in patients with gastrointestinal carcinoma. Lancet. 1982;1(8263):68-71.

5. Snyder-Ramos SA, Seintsch H, Bottiger BW, Motsch J, Martin E, Bauer M. Patient satisfaction and information gain after the preanesthetic visit: A comparison of face-to-face interview, brochure, and video. Anesth Analg. 2005;100(6):1753-1758.

6. Asilioglu K, Celik SS. The effect of preoperative education on anxiety of open cardiac surgery patients. Patient Educ Couns. 2004;53(1):65-70.

7. Bozzetti F, Braga M, Gianotti L, Gavazzi C, Mariani L. Postoperative enteral versus parenteral nutrition in malnourished patients with gastrointestinal cancer: A randomised multicentre trial. Lancet. 2001;358(9292):1487-1492.

8. Wu GH, Liu ZH, Wu ZH, Wu ZG. Perioperative artificial nutrition in malnourished gastrointestinal cancer patients. World J Gastroenterol. 2006;12(15):2441-2444.

9. Daly JM, Lieberman MD, Goldfine J, et al. Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: Immunologic, metabolic, and clinical outcomes. Surgery. 1992;112(1):56-67.

10. Daly JM, Weintraub FN, Shou J, Rosato EF, Lucia M. Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients. Ann Surg. 1995;221(4):327-338.

11. Di Carlo V, Gianotti L, Balzano G, Zerbi A, Braga M. Complications of pancreatic surgery and the role of perioperative nutrition. Dig Surg. 1999;16(4):320-326.

12. Braga M, Gianotti L, Vignali A, Cestari A, Bisagni P, Di Carlo V. Artificial nutrition after major abdominal surgery: Impact of route of administration and composition of the diet. Crit Care Med. 1998;26(1):24-30.

13. Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology. 2002;122(7):1763—1770.

14. DeWys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients: Eastern Cooperative Oncology Group. Am J Med. 1980;69(4):491^97.

15. Farreras N, Artigas V, Cardona D, Rius X, Trias M, Gonzalez JA. Effect of early postoperative enteral immunonutrition on wound healing in patients undergoing surgery for gastric cancer. Clin Nutr. 2005;24(1):55-65.

16. Senkal M, Zumtobel V, Bauer KH, et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: A prospective randomized study. Arch Surg. 1999;134(12):1309-1316.

17. Braga M, Gianotti L, Vignali A, Carlo VD. Preoperative oral arginine and ^-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer. Surgery. 2002;132(5):805-814.

18. de Luis DA, Izaola O, Cuellar L, Terroba MC, Aller R. Randomized clinical trial with an enteral arginine-enhanced formula in early postsurgical head and neck cancer patients. Eur J Clin Nutr. 2004;58(11):1505-1508.

19. Morlion BJ, Stehle P, Wachtler P, et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: A randomized, double-blind, controlled study. Ann Surg. 1998;227(2):302-308.

20. Gianotti L, Braga M, Vignali A, et al. Effect of route of delivery and formulation of postoperative nutritional support in patients undergoing major operations for malignant neoplasms. Arch Surg. 1997;132(11):1222-1229, discussion 1229-1230.

21. Sand J, Luostarinen M, Matikainen M. Enteral or parenteral feeding after total gastrectomy: Prospective randomised pilot study. Eur J Surg. 1997;163(10):761-766.

22. Shirabe K, Matsumata T, Shimada M, et al. A comparison of parenteral hyperalimentation and early enteral feeding regarding systemic immunity after major hepatic resection: The results of a randomized prospective study. Hepatogastroenterology. 1997;44(13):205-209.

23. Braga M, Gianotti L, Gentilini O, Parisi V, Salis C, Di Carlo V. Early postoperative enteral nutrition improves gut oxygenation and reduces costs compared with total parenteral nutrition. Crit Care Med. 2001;29(2):242-248.

24. Aiko S, Yoshizumi Y, Sugiura Y, et al. Beneficial effects of immediate enteral nutrition after esophageal cancer surgery. Surg Today. 2001;31(11):971-978.

25. Jiang XH, Li N, Li JS. Intestinal permeability in patients after surgical trauma and effect of enteral nutrition versus parenteral nutrition. World J Gastroenterol. 2003;9(8):1878-1880.

26. Hyltander A, Drott C, Unsgaard B, et al. The effect on body composition and exercise performance of home parenteral nutrition when given as adjunct to chemotherapy of testicular carcinoma. Eur J Clin Invest. 1991;21(4):413^20.

27. Aiko S, Yoshizumi Y, Matsuyama T, Sugiura Y, Maehara T. Influences of thoracic duct blockage on early enteral nutrition for patients who underwent esophageal cancer surgery. Jpn J Thorac Cardiovasc Surg. 2003;51(7):263-271.

28. Goonetilleke KS, Siriwardena AK. Systematic review of peri-operative nutritional supplementation in patients undergoing pancreaticoduodenectomy. Jop. 2006;7(1):5-13.

cancer patients. One prospective, randomized study of perioperative parenteral GLN in colorectal cancer patients indicated improved nitrogen balance with glutamine supplementation.74 Most of the other available data focus on the use of GLN in the prevention of mucositis in bone marrow transplant patients.75-89 At this time, there is not enough evidence to support the use of glutamine in surgical cancer patients, although this intervention may have other applications in cancer patients receiving chemotherapy.

The Q-3 fatty acids, which are essential in the diet, favor production of prostaglandins in the 3-series (PGE3) and leukotrienes in the 5-series. Studies of enteral Q-3 fatty acid administration in pancreatic cancer patients indicate that Q-3 fatty acid supplementation in the range of 2-3 g per day may help prevent weight loss.90-92 Parenteral Q-3 fatty acid supplementation in colorectal cancer patients increases leukotriene-5 levels and decreases TNF levels.93 Some evidence indicates that surgical cancer patients who are losing weight may benefit from the use of a formula that contains Q-3 fatty acids in doses of 2 g/day. However, clinical experience indicates poor compliance with oral nutritional supplements containing Q-3 fatty acids owing to palatability issues.

Another amino acid, arginine (ARG), has been studied as an additive to enteral and parenteral preparations. ARG in combination with other immunonutrients has been associated with improvements in immune parameters such as leukotriene B4, and decreases in the incidence of infection among patients undergoing elective upper and lower GI surgery for cancer.94-98 Additionally, patients with colorectal cancer receiving perioperative parenteral ARG have been found to experience enhanced immune responsiveness when compared to controls.94-96 ARG may be useful in some cancer patients undergoing surgery, although the advantages associated with the use of these formulas must outweigh the burden of their higher costs.

Nucleotides, administered in the form of nucleic acids, appear to stimulate nonspecific parameters of immune function, although the precise mechanism of action involved is not clearly understood.98 Nucleotides are known to affect the growth of cells that experience rapid turnover, such as entero-cytes. In animal models, supplementation with nucleotides improves jejunal adaptive growth after massive small bowel resection.98 However, in one study of human patients with colorectal cancer, there was no effect on survival with nucleotide supplementation.99 Similar to the situation with GLN, it does not appear that nucleotide supplementation provides any benefits for surgical oncology patients at this time.

Conversely, ingestion of formulas containing immunonutrients holds promise for improving nutrition in cancer patients. Studies investigating the use of a combination of arginine, RNA, and Q-3 fatty acids perioperatively indicate improved immune parameters100-107 and clinical outcomes with this type of supplementation.3, 95, 96, 100-104 Because of the diversity of methods used in these studies, the relative effects of preoperative versus postoperative treatment have not yet been determined. For some of the nutrients, such as glutamine and arginine, more information is needed to determine the optimal dosing and administration. However, based on the results of studies utilizing a combination of arginine, RNA, and Q-3 fatty acids with clinical endpoints, it appears that EN supplemented with these nutrients may be beneficial in malnourished patients who are undergoing major thoracic or abdominal procedures.94, 104-107 Future studies exploring the benefits associated with consumption of these nutrients should focus on larger populations of cancer patients and elucidate the preferred timing of supplementation in relation to the surgical procedure. The rationale for utilizing these kinds of nutraceuti-cals is summarized in Table 5.6.

Palliative Specialized Nutrition Support

Despite published guidelines that state that the palliative use of NST is rarely appropriate,108 this issue remains controversial.6 The use of home PN in patients with a cancer diagnosis is becoming more frequent.108, 109 In general, PN is indicated only in those patients with incurable cancer when they are receiving active anticancer therapy, are malnourished, and are unable to consume adequate oral or enteral nutrients for a significant period of time.110 A small subset of terminally ill cancer patients (e.g., patients with ovarian cancer) not receiving cancer-directed therapy with dysfunctional GI tracts has been identified in whom long-term, home PN may provide palliative benefits6 and improve quality of life; it may even lengthen survival.

It is important to remember that PN is complex, intrusive, and expensive. If patients are to benefit they (1) must be very strongly motivated and physically capable of participating in the their own care, (2) should have an estimated life expectancy of greater than 40 to 60 days, and (3) require strong social and financial support at home, including a dedicated in-home lay care provider. They must also fail trials of less invasive therapies, including aggressive medical management with antiemetics, narcotics, anticholinergics, and antidepressants.111-115 Those patients with a life expectancy of less than 40 days are often well palliated with home intravenous fluid therapy. Most patients evaluated for palliative care with home PN do not meet these criteria.

Substrate

Metabolic Activities

Clinical Use

Glutamine

Most abundant amino acid in the human body, nonessential

Important substrate for rapidly proliferating cells such as lymphocytes, macrophages, enterocytes, fibroblasts, and renal epithelium

Nitrogen shuttle between tissues

Precursor for the synthesis of purines, pyrimidines, and amino acids

Potentially beneficial in stimulating postoperative return of gastrointestinal function and decrease in permeability1, 2; may reverse postoperative immunodepression3

Arginine

Nonessential amino acid, may become conditionally essential during periods of physiologic stress

Substrate in the urea cycle; roles in protein, creatinine, and polyamine synthesis

Affects nitrogen metabolism, wound healing, immune competence, and tumor metabolism

May improve immunologic indices postoperatively4; decreased incidence of postoperative fistula5

Nucleic acids

Stimulatory effects on nonspecific parameters of immune function

Mechanism of action not understood

No clinical studies performed

Essential fatty acids

Q-3 polyunsaturated fatty acids (PUFAs) favor production of 3-series prostaglandins (PGE3) and 5-series leukotrienes (immune-enhancing and anti-inflammatory)

Q-3 PUFAs reduce production of 2-series prostaglandins (PGE2) and 4-series leukotrienes (immunosuppressive and pro-inflammatory)

May improve postoperative inflammatory and immune response6; may decrease need for ventilator and length of stay in patients with major abdominal surgery7

PUFA, polyunsaturated fatty acids; PGE3, prostaglandin E3; PGE2, prostaglandin E2; LOS, length of stay

Data Sources

1. De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Crit Care Med. May 2005;33(5):1125-1135.

2. Morlion BJ, Stehle P, Wachtler P, et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled study. Ann Surg. Feb

1998;227(2):302-308.

3. Yao GX, Xue XB, Jiang ZM, Yang NF, Wilmore DW. Effects of perioperative parenteral glutamine-dipeptide supplementation on plasma endotoxin level, plasma endotoxin inactivation capacity and clinical outcome. Clin Nutr. Aug 2005;24(4):510-515.

4. Song JX, Qing SH, Huang XC, Qi DL. Effect of parenteral nutrition with L-arginine supplementation on postoperative immune function in patients with colorectal cancer. Di Yi Jun Yi Da Xue Xue Bao. Jun 2002;22(6):545-547.

5. de Luis DA, Izaola O, Cuellar L, Terroba MC, Aller R. Randomized clinical trial with an enteral arginine-enhanced formula in early postsurgical head and neck cancer patients. Eur J Clin Nutr. Nov 2004;58(11):1505-1508.

6. Nakamura K, Kariyazono H, Komokata T, Hamada N, Sakata R, Yamada K. Influence of preoperative administration of omega-3 fatty acid-enriched supplement on inflammatory and immune responses in patients undergoing major surgery for cancer. Nutrition. Jun 2005;21(6):639-649.

7. Tsekos E, Reuter C, Stehle P, Boeden G. Perioperative administration of parenteral fish oil supplements in a routine clinical setting improves patient outcome after major abdominal surgery. Clin Nutr. Jun 2004;23(3):325-330.

Table Source:

Adapted with permission from: August DA, Huhmann MB. Nutritional Care of Cancer Patients. In:

Norton J, Barie P, Bollinger R, et al., eds. Surgery: Basic Science and Clinical Evidence. 2nd ed. New York: Springer Publishing; 2006.

Nutrition Issues in Specific Gastrointestinal Malignancies

Esophageal Cancer

Esophageal cancer resections have significant nutritional consequences. In particular, patients with esophageal cancer often present with some degree of dysphagia and weight loss preoperatively.116, 117 Approximately 79% to 100%118-119 of these individuals are malnourished at presentation, and esophagectomy can worsen their malnutrition.

Reflux (because the lower esophageal sphincter is generally sacrificed with the resection), dysmotility of the remaining esophagus, gastric dysmotility secondary to resection of the vagus nerves with the esophagus, and dumping syndrome are common side effects of esophagectomy. Patients may complain of dysphagia postoperatively. This problem may be caused by multiple factors, including stricture, poor gastric emptying, or dysmotility. Stricture may occur after esophagectomy as a result of anastomotic ischemia, which is not uncommon when the stomach is mobilized as a conduit.118, 120 Dilatation of the stricture can allow for normal oral intake, although it may require several dilatations to achieve “normal” swallowing. Disruptions of the vagal nerves can lead to altered sensations in the stomach, causing overeating and regurgitation.118 Placement of a feeding jejunostomy tube during surgery allows for early enteral support. Postoperative diet modifications, including the consumption of small, frequent, energy-dense meals, can help in reducing regurgitation.

Dumping syndrome can also occur post esophagectomy. The rapid passage of hyperosmotic, undigested food into the small bowel with secondary hypersecretion of succus and extracellular fluid into the bowel lumen may cause hypotension, flushing, and diarrhea. This condition is a result of the rapid distention of the bowel. If left untreated, it can lead to weight loss, malnutrition, and increased mortality.119 Postoperative diet changes, including limiting simple carbohydrates and liquids with meals, can assist in preventing the cramping, diarrhea, and flushing associated with dumping syndrome.

Gastric Cancer

Gastric resection can alter gastric reservoir function and vitamin B12 absorption. The capacity of the GI tract to “store” food following gastrectomy can vary greatly, which may lead to unintentional food regurgitation.118, 121 Resection decreases stomach capacitance, with resultant compromise of reservoir function. Removal of either the pylorus or the lower esophageal sphincter (LES) may also be problematic. Post gastrectomy, the absence of the LES eliminates the barrier for the reflux of food and digestive juices. Reflux is observed in as many as 58% of patients who undergo esophagectomy119 and 80% of patients who undergo a total gastrectomy.120 If the procedure includes disruption of pyloric function or a gastrojejunostomy, bile reflux into the esophagus can occur. This complication is particularly difficult to manage because, unlike with acid, there are no drugs available to “neutralize” the irritant effects of bile on the esophageal squamous epithelium.

Dumping syndrome may also occur as a result of disruption of the pyloric sphincter and gastrojejunostomy. Restriction of simple carbohydrates and limiting liquids with meals can help to prevent dumping syndrome.

The acidic environment of the stomach assists in the release of vitamin B^ from food. Loss of intrinsic factor occurs with resection of the parietal cells in the proximal stomach and results in vitamin B^ malabsorption. Vitamin B12 deficiency can, in turn, lead to megaloblastic anemia and dementia.121 Such a deficiency can develop as early as one year after total gastrectomy.122 Patients in whom all of the proximal stomach is removed should be evaluated for the need for vitamin B^ replacement. Supplementation is available in enteral and parenteral formulations,123 and routine prescription of 1000 mcg monthly intramuscular vitamin B^ is recommended for patients undergoing proximal or total gastrectomy to prophylactically prevent deficiency.124

Small Bowel Cancer

Small bowel resection, when carried out because of the presence of primary malignancy or malignancy in adjacent organs, can have significant effects on the ability to absorb both micronutrients and macronutrients. The small bowel plays a major role in nutrient absorption. Its anatomy, as well as the hormones that are released into the small intestine, affect the effectiveness of this absorption. Resection of any significant portion of the small bowel can result in decreased transit time, thereby producing malabsorption. Hormones released in response to the entry of food into the small intestine—for example, secretin, cholecystokinin, and enteropeptidase— affect pancreatic and gallbladder function as well as gastric emptying and feelings of satiety. The practitioner must evaluate these sources as potential etiologies in the cancer patient who has undergone a resection of the small intestine.

Micronutrient and macronutrient absorption is also altered based on the location and size of the resection. The duodenum is the primary site of absorption for calcium and magnesium. The jejunum is responsible for absorption of carbohydrate, protein, water-soluble vitamins, and iron. Jejunal resections can result in inappropriate secretion of digestive enzymes and accelerated gastric emptying. Lipid, fat-soluble vitamins, cholesterol, bile salts, and vitamin B12 are absorbed in the ileum. Patients with ileostomies must be educated about proper supplemental fluid and electrolyte intake because they have an increased risk for dehydration.124, 125 Many of these individuals will have a need for increased sodium and water intake to balance increased losses in the stool. To counteract these losses, patients should be instructed to consume at least one liter more fluid daily than their stoma out-put.125 Significant resection of the jejunum and ileum can also cause reduced intestinal absorption secondary to the loss of absorptive surface, or short bowel syndrome. Depending on the amount of intestine resected, fluid and electrolyte needs may not be met with oral feeding alone, such that enteral or parenteral nutrition intervention is required.126

The small bowel plays a significant role in bacterial homeostasis. An acidic environment in the small bowel lumen, which can occur after small bowel resection because of increased gastric acid secretion and decreased transit time, deactivates digestive enzymes and deconjugates bile acids, which in turn leads to further malabsorption. The malabsorbed food moves into the colon, where carbohydrate is fermented by bacteria into D-lactic acid. Build-up of D-lactic acid can cause metabolic acidosis characterized by increased serum D-lactate, an increased anion gap, and decreased serum bicarbonate.127 This relatively rare neurologic syndrome occurs with short bowel syndrome or following jejuno-ileal bypass surgery. Symptoms include altered mental status, slurred speech, and ataxia, and typically present after the ingestion of high-carbohydrate feedings.128 Carbohydrate restriction, antibiotics, and probiotics are generally recommended for the management or prevention of this adverse effect.128, 129

Bacterial growth in the small intestine is carefully regulated through several mechanisms, including the pH of stomach contents, intestinal peristalsis, and innate intestinal wall immune factors.130 Massive bowel resection frequently leads to bacterial overgrowth, increasing the risk of bacterial translocation, and possibly sepsis. Bacterial overgrowth is diagnosed through culture or biopsy of the bowel or by a hydrogen breath test. Nutritional consequences of intestinal bacterial overgrowth include steatorrhea (fat malabsorption) as well as decreased intestinal micellar uptake of triglycerides, fatty acids, cholesterol, and lipophilic vitamins.131

Bacterial overgrowth is commonly treated with antibiotics and probiotics.132 Probiotics are live microorganisms, such as lactobacillus or bifidobacterium, that may produce beneficial health effects in humans.133138

Colon Cancer

The colon is responsible for fluid and electrolyte resorption. Resections of the terminal ileum and colon can, therefore, significantly affect the body’s electrolyte and fluid balance. In response, the intestine may undergo structural and functional adaptation to increase fluid and nutrient absorption over a period of two years or more.126

The colon may contain as many as 1011 or 1012 bacterial cells/gram luminal contents.6 Impaired intestinal peristalsis or anatomical abnormalities that alter luminal flow following surgery can cause bacterial overgrowth.137 Dysfunctions of the gut barrier following colon resection have been hypothesized to lead to translocation of microorganisms, sepsis, shock, multisystem organ failure, and even death.138 Bacterial overgrowth in the terminal ileum following ileocecal valve resection can adversely affect the specialized absorptive functions of the ileum. In particular, ileocolectomy has been associated with a significant increase in ileal and colonic bacterial counts.139 As mentioned earlier, bacterial overgrowth can produce metabolic acidosis and malabsorption of both micronutrients and macronutrients.

Pancreatic Cancer

Digestion of starches, proteins, and lipids requires pancreatic enzymes. Pancreatic enzyme excretion can be impaired due to pancreatic duct obstruction, resection, or dysregulation. To compensate for this dysfunction, interventions may include oral administration of pancreatic enzymes, diet modification, and a physiologic shift of the site of digestion to the distal small intestine.140 In general, derangements in postoperative pancreatic exocrine function are determined by type of resection, resection of adjacent organs, the underlying disease, and preoperative pancreatic function. The dysfunction often does not result in symptoms of obvious malabsorption such as diarrhea; instead, it may manifest as continued weight loss in spite of apparent adequate intake.

After major pancreatic surgery, enzyme replacement may be required. Pancreatic enzyme supplementation starts with 40,000-120,000 IU of lipase and is titrated according to patient response.140 The addition of a protonpump inhibitor assists in the prevention of early activation of enzymes by gastric acid.140 Pancreaticocibal asynchrony occurs when pancreatic enzyme secretion is mistimed, resulting in malabsorption; it occurs in 16% to 43% of gastrectomy patients.141 Oral pancreatic enzyme replacement in this setting is helpful in overcoming the malabsorption problem.

The type of pancreatic resection affects the extent of endocrine insufficiency. After a Whipple procedure (Figure 5.3), 20% to 40% of patients develop diabetes mellitus.142 In some patients, hypoglycemia occurs as a result of postoperative insulin sensitivity in the presence of decreased glucagon secretion.141, 142 Pylorus-preserving Whipple procedures seem to impair endocrine function more than a traditional Whipple procedure.143 In some cases, such as in chronic pancreatitis, pancreatic head resection can improve endocrine secretion.140 Functional islet cell, or neuroendocrine, tumors such as insulinomas, gastrinomas, glucagonomas, and VIPomas (vasoactive intestinal peptide-producing tumors), can cause a host of nutritional issues, ranging from hypoglycemia (insulinoma) to ulcers (gastrinoma).144 Drugs such as octreotide can palliate the endocrine mediation effects of these tumors; however, the only curative option is surgery.144, 145 Fortunately, complete resection alleviates these symptoms.

Cancers of the Liver and Gallbladder

The liver plays important roles in protein synthesis, glucose homeostasis, bilirubin excretion, and detoxication, among other functions.146 Hepatic

Figure 5.3 Anatomy Removed in a Whipple Procedure Reprinted with permission from Cancer Research UK. Surgery to try to cure pancreatic cancer. Accessed at: http://www.cancerhelp.org.uk/help/default.asp?page=3124#whipple.

protein synthesis is altered in response to trauma and critical illness.147 Whole-body protein synthesis is modified after surgery of moderate severity.147 Production of positive acute-phase proteins (i.e., complement system, transport proteins, and antiproteases) increases with stress, whereas production of negative acute-phase proteins (i.e., albumin, prealbumin, and transferrin) decreases with stress.147 Mediators of inflammation, including cytokines, seem to affect serum protein levels through two mechanisms: (1) alteration of normal synthesis and catabolism and (2) induction of capillary leak.146

The key functions carried out by the liver in nutrient metabolism include synthesis and degradation of glucose and glycogen, fatty acid metabolism, synthesis and degradation of serum proteins, detoxification of lipid-soluble toxins, and metabolism of bilirubin.146 Poor nutritional status, which often manifests as fluid retention and low levels of serum proteins, is correlated to mortality in patients undergoing liver resections.148 Preoperative liver disease may produce hypoalbuminemia, hyperglucagonemia, increased energy expenditure, depleted skeletal muscle mass, and anorexia prior to surgery.149 In addition, patients may develop symptoms that limit food intake before and after liver surgery—for example, altered taste sensation, early satiety due to ascites, steatorrhea due to bile salt deficiency, anorexia, nausea, and vomiting.150 Protein calorie malnutrition is evident in 20% of patients with compensated cirrhosis and in 60% of patients with liver insufficiency.151

Postoperative tolerance of liver resection and the liver’s ability to regenerate and regain function after liver surgery vary greatly. The presence of malnutrition clearly affects the return of liver function and regeneration, and it has important implications for morbidity and mortality. Preoperative malnutrition is a predictor for first bleeding episode and survival, and is associated with both refractory ascites and postoperative complications.152 Surgical techniques such as portal vein embolization can assist in preserving functional liver volume by inducing preoperative hepatic hypertrophy.152 When the size of the liver is increased preoperatively, this organ may require less time to adapt to the resection, potentially limiting the previously mentioned complications. Despite this measure, however, patients still may need nutrition support postoperatively. Early EN after liver resection is associated with a lower rate of wound- and catheter-related complications and improved immune competence compared to PN.153

Perioperative Feeding Considerations

Maintenance of nutrition status perioperatively can be facilitated by careful preoperative planning and creation of a postoperative nutrition care plan.154, 155

Failure to consider nutrition and diet issues perioperatively can result in lost opportunities to maintain nutrition status and to avoid nutrition-related complications. The postoperative nutrition care plan should be determined and discussed with the patient prior to surgery.154

Historically, postoperative “bowel rest” has been recommended to promote anastomotic healing and prevent nausea and vomiting.67 Early postoperative oral and enteral feedings are now recommended to encourage the return of gastrointestinal function by enhancing bowel hypertrophy and anastomotic healing.155 Even in the absence of peristalsis, the small intestine regains the ability to absorb nutrients quickly after surgery.

It has become common practice to establish enteral feeding access during major gastrointestinal procedures.156 Early enteral nutrition in malnourished surgical patients is associated with improved wound healing, maintenance of gut function, and improved gut immune function. It is also associated with decreased length of stay in intensive care.156, 157 Furthermore, early resumption of oral/enteral feeding is only occasionally associated with undesirable side effects such as nausea, vomiting, colic, and anorexia.65155158 In patients with established preoperative malnutrition, the benefits of enteral access outweigh the risks of enteral access-related complications.6, 58, 159 For this reason, intraoperative placement of a gastrostomy or jejunostomy tube for enteral access should be strongly considered in patients who are malnourished preoperatively or in whom a prolonged period of poor oral intake is anticipated (7-14 days). Studies specifically assessing the use of NST for 7-14 days preoperatively160 in moderately or severely malnourished patients indicate that this intervention provides a benefit in terms of both morbidity1, 161, 162 and mortality.1, 2 57, 59, 162, 163

In addition to planning for nutrition support access preoperatively, it is important to discuss the patient’s transition to an oral diet. Upper gastrointestinal surgical resection may be associated with significant postoperative morbidity, including dumping syndrome, delayed gastric emptying, prolonged ileus, obstruction, gastroesophageal reflux, and post-gastrectomy syndrome (dumping, fat maldigestion, gastric stasis, and lactose intoler-ance).2, 59, 162 These complications can lead to weight loss, malnutrition, and increased mortality.164, 165

Preoperative education by a registered dietitian (RD) to inform patients about both normal and abnormal postoperative events can assist patients in taking an active role in their recovery. As yet, few data have been published on the role of nutrition education in patients undergoing gastrointestinal cancer surgery. Several studies indicate that patients who receive preoperative education regarding expectations and pain management121 experience less anxiety166 and pain,167, 168 and have improved outcomes169, 170 and increased satisfaction.171, 172 Preoperative nutrition education by an RD also has the potential to improve outcomes and facilitate a quicker return to oral diet (see Table 5.7).

Category

Issue

Manifestation

Nutrition Intervention

Abnormal transit

Dumping syndrome

Early: Diarrhea, bloating, nausea, tachycardia immediately—

30 minutes after a meal Late: Hypoglycemic symptoms, dizziness 90—180 minutes after a meal

Small frequent meals Separation of solids and fluids at meals Reduction in simple carbohydrate and concentrated fat intake Increased soluble fiber intake1

 

Reflux esophagitis

Regurgitation of food and digestive juices causing heartburn, nausea, or vomiting

Small frequent meals Use of antacids or sucralfate2

 

Delayed gastric emptying/gastric stasis

Early satiety, postprandial fullness, heartburn, dysphagia, aspiration2

Small frequent meals Prokinetic agents3

 

Pancreaticocibal asynchrony

Steatorrhea, frequent light greasy stools

Addition of pancreatic enzymes at meals and snacks

Malassimilation

Reduced intake,

impaired absorption,

disturbed metabolism,

increased loss1

Micronutrient deficiencies

Enteral or parenteral replacement

Obstruction

Stricture, gastric outlet obstruction

Vomiting,

constipation

Enteral or parenteral nutrition support depending upon extent Endoscopic balloon dilation or surgical stenting Promotility agent2

Pancreatic insufficiency

Pancreatic enzyme

insufficiency

Steatorrhea, bloating

Pancreatic enzyme replacement4

Data Sources

1. Scholmerich J. Postgastrectomy syndromes—diagnosis and treatment. Best Pract Res Clin Gastroenterol. Oct 2004;18(5):917-933.

2. Lerut TE, van Lanschot JJ. Chronic symptoms after subtotal or partial oesophagectomy: diagnosis and treatment. Best Pract Res Clin Gastroenterol. Oct 2004;18(5):901-915.

3. Radigan A. Post-Gastrectomy: Managing the nutrition fall-out. Practical Gastroenterology. 2004 2004;28(6):63-75.

4. Kahl S, Malfertheiner P. Exocrine and endocrine pancreatic insufficiency after pancreatic surgery.

Best Pract Res Clin Gastroenterol. Oct 2004;18(5):947-955.

Table Source: Reprinted with permission from Huhmann M, August D. General gastrointestinal and vascular surgery. In: Marian M., Russel M., Shikora S, eds., Clinical Nutrition for Surgical Patients. Sudbury, MA: Jones and Bartlett; 2007:99-128.

SUMMARY Surgical oncology patients can develop complex nutritional issues. Preoperative nutrition assessment and planning can assist in decreasing the development or progression of malnutrition. Postoperative follow-up is also crucial for preventing deteriorations in nutritional status and addressing any procedure-related issues that may result in negative nutrition-related outcomes.

REFERENCES 1 1 2 3 4 5 6 7 8 9

1. Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med. 1991;325(8):525—532.

2. Bozzetti F. Rationale and indications for preoperative feeding of malnourished surgical cancer patients. Nutrition. 2002;18(11-12):953-959.

3. Braga M, Gianotti L, Nespoli L, Radaelli G, Di Carlo V. Nutritional approach in malnourished surgical patients: A prospective randomized study. Arch Surg. 2002; 137(2):174-180.

4. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutri-tion become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001;286(8):944—953.

5. Heys SD, Ogston KN. Peri-operative nutritional support: Controversies and debates. Int J Surg Investig. 2000;2(2):107—115.

6. American Society for Enteral and Parenteral Nutrition. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enteral Nutr. 2002;26(1)(suppl):1SA-138SA.

7. DeWys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients: Eastern Cooperative Oncology Group. Am J Med. 1980;69(4):491-497.

8. Linn BS, Robinson DS, Klimas NG. Effects of age and nutritional status on surgical outcomes in head and neck cancer. Ann Surg. 1988;207(3):267—273.

9. Nguyen TV, Yueh B. Weight loss predicts mortality after recurrent oral cavity and oropharyngeal carcinomas. Cancer. 2002;95(3):553—562.

10. Haugstvedt TK, Viste A, Eide GE, Soreide O. Factors related to and consequences of weight loss in patients with stomach cancer: The Norwegian multicenter experience. Norwegian Stomach Cancer Trial. Cancer. 1991;67(3):722—729.

11. McCullum P, Poliseria C, eds. The Clinical Guide to Oncology Nutrition. Chicago, IL: American Dietetic Association; 2000.

12. Rivadeneira DE, Evoy D, Fahey TJ 3rd, Lieberman MD, Daly JM. Nutritional support of the cancer patient. CA Cancer J Clin. 1998;48(2):69-80.

13. Capra S, Ferguson M, Ried K. Cancer: Impact of nutrition intervention outcome— Nutrition issues for patients. Nutrition. 2001;17(9):769-772.

14. Parnes HL, Aisner J. Protein calorie malnutrition and cancer therapy. Drug Saf. 1992;7(6):404—416.

15. Bloch A, Charuhas P. Cancer and cancer therapy. In: Gottschlich M, ed. The Science and Practice of Nutrition Support. Dubuque, IA: Kendall Hunt; 2001:643—662.

16. Kern KA, Norton JA. Cancer cachexia. JPEN J Parenter Enteral Nutr. 1988; 12(3):286-298.

17. Brennan MF. Total parenteral nutrition in the cancer patient. N Engl J Med. 1981; 305(7):375-382.

18. Barber M. The pathophysiology and treatment of cancer cachexia. Nutr Clin Prac. 2002;17(4):203-209.

19. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer. 2002;2(11):862—871.

20. MacDonald N, Easson AM, Mazurak VC, Dunn GP, Baracos VE. Understanding and managing cancer cachexia. J Am Coll Surg. 2003;197(1):143—161.

21. Tisdale MJ. Cancer cachexia: Metabolic alterations and clinical manifestations. Nutrition. 1997;13(1):1-7.

22. Tisdale MJ. Pathogenesis of cancer cachexia. J Support Oncol. 2003;1(3):159—168.

23. Lind D, Souba W, Copeland E. Weight loss and cachexia. In: Abeloff M, Armitage J, Lichter A, Niederhuber J, eds. Clinical Oncology. New York, NY: Churchill Livingstone; 1995:393-407.

24. Tisdale MJ. Tumor-host interactions. J Cell Biochem. 2004;93(5):871-877.

25. Dannhauser A, Van Zyl JM, Nel CJ. Preoperative nutritional status and prognostic nutritional index in patients with benign disease undergoing abdominal operations: Part I. J Am Coll Nutr. 1995;14(1):80-90.

26. Sungurtekin H, Sungurtekin U, Balci C, Zencir M, Erdem E. The influence of nutritional status on complications after major intraabdominal surgery. J Am Coll Nutr. 2004;23(3):227-232.

27. Hirsch S, de Obaldia N, Petermann M, et al. Nutritional status of surgical patients and the relationship of nutrition to postoperative outcome. J Am Coll Nutr. 1992;11(1):21-24.

28. Lacey K, Pritchett E. Nutrition Care Process and model: ADA adopts road map to quality care and outcomes management. J Am Diet Assoc. 2003;103(8):1061-1072.

29. Jensen GL. Inflammation as the key interface of the medical and nutrition universes: A provocative examination of the future of clinical nutrition and medicine. JPEN J Parenter Enteral Nutr. 2006;30(5):453-463.

30. Committee CoPCQM. Identifying patients at risk: ADA’s definitions for nutrition screening and nutrition assessment. J Am Diet Assoc. 1994;94(8):838-839.

31. Sarhill N, Mahmoud F, Walsh D, et al. Evaluation of nutritional status in advanced metastatic cancer. Support Care Cancer. 2003;11(10):652-659.

32. Ottery FD. Definition of standardized nutritional assessment and interventional pathways in oncology. Nutrition. 1996;12(1)(suppl):S15-S19.

33. Detsky AS, McLaughlin JR, Baker JP, et al. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr. 1987;11(1):8-13.

34. Luthringer S, Kulakowski K. Medical nutrition therapy protocols. In: McCallum P, Polisena C, eds. The Clinical Guide to Oncology Nutrition. Chicago, IL: American Dietetic Association; 2000:24—44.

35. Ottery F, Bender F, Kasenic S. The design and implementation of a model nutritional oncology clinic. Oncology Issues: Integrating Nutrition into Your Cancer Program. 2002;2-6.

36. Ferguson M. Patient-Generated Subjective Global Assessment. Oncology (Hunt-ingt). 2003;17(2)(suppl)(2):13-14, discussion 14-16.

37. Guigoz Y, Vellas B, Garry PJ. Assessing the nutritional status of the elderly: The Mini Nutritional Assessment as part of the geriatric evaluation. Nutr Rev. 1996; 54(1 Pt 2):S59-S65.

38. Ferguson M, Capra S, Bauer J, Banks M. Development of a valid and reliable malnutrition screening tool for adult acute hospital patients. Nutrition. 1999;15(6):458-464.

39. Ferguson ML, Bauer J, Gallagher B, Capra S, Christie DR, Mason BR. Validation of a malnutrition screening tool for patients receiving radiotherapy. Australas Radiol. 1999;43(3):325-327.

40. Group MA. A consistent and reliable tool for malnutrition screening. Nurs Times. 2003;99(46):26-27.

41. Bauer J, Capra S. Comparison of a malnutrition screening tool with Subjective Global Assessment in hospitalised patients with cancer: Sensitivity and specificity. Asia Pac J Clin Nutr. 2003;12(3):257-260.

42. Association NCD. Skill-building success! Link: NC Diet Assoc Newsletter. 2004;3(1):5.

43. Services CfMaM. The assessment schedule for the RAI. In: Services CfMaM, ed. Revised Long Term Care Resident Assessment Instrument User’s Manual for the Minimum Data Set (MDS), Version 2.0. Baltimore, MD: Centers for Medicare and Medicaid Services; 2002:1-40.

44. Hakel-Smith N, Lewis NM, Eskridge KM. Orientation to Nutrition Care Process standards improves nutrition care documentation by nutrition practitioners. J Am Diet Assoc. 2005;105(10):1582-1589.

45. American Dietetic Association. International Dietetics and Nutrition Terminology (IDNT) Reference Manual: Standardized Language for the Nutrition Care Process. Chicago, IL: Author; 2007.

46. NHS Center for Reviews and Dissemination. Nutrition support in patients with cancer. Database Abstr Rev Effectiveness. 2004;2.

47. Shike M, Russel DM, Detsky AS, et al. Changes in body composition in patients with small-cell lung cancer: The effect of total parenteral nutrition as an adjunct to chemotherapy. Ann Intern Med. 1984;101(3):303-309.

48. Hyltander A, Drott C, Unsgaard B, et al. The effect on body composition and exercise performance of home parenteral nutrition when given as adjunct to chemotherapy of testicular carcinoma. Eur J Clin Invest. 1991;21(4):413-420.

49. Popp MB, Wagner SC, Brito OJ. Host and tumor responses to increasing levels of intravenous nutritional support. Surgery. 1983;94(2):300-308.

50. Daly J, Thorn A. Neoplastic diseases. In: Kinney J, Jeejeebhoy K, Hill G, Owen O, eds. Nutrition and Metabolism in Patient Care. Philadelphia, PA: Saunders; 1988: 567-587.

51. Torosian MH. Stimulation of tumor growth by nutrition support. JPEN J Parenter Enteral Nutr. 1992;16(6)(suppl):72S-75S.

52. Pacelli F, Bossola M, Teodori L, et al. Parenteral nutrition does not stimulate tumor proliferation in malnourished gastric cancer patients. JPEN J Parenter Enteral Nutr. 2007;31(6):451-455.

53. Baron PL, Lawrence W Jr, Chan WM, White FK, Banks WL Jr. Effects of parenteral nutrition on cell cycle kinetics of head and neck cancer. Arch Surg. 1986;121(11):1282-1286.

54. Frank JL, Lawrence W Jr, Banks WL Jr, McKinnon JG, Chan WM, Collins JM. Modulation of cell cycle kinetics in human cancer with total parenteral nutrition. Cancer. 1992;69(7):1858-1864.

55. Heys SD, Park KG, McNurlan MA, et al. Stimulation of protein synthesis in human tumours by parenteral nutrition: Evidence for modulation of tumour growth. Br J Surg. 1991;78(4):483-487.

56. American Gastroenterological Association. Medical position statement: Parenteral nutrition. Gastroenterology. 2001;121(4):966-969.

57. Muller JM, Keller HW, Brenner U, Walter M, Holzmuller W. Indications and effects of preoperative parenteral nutrition. World J Surg. 1986;10(1):53—63.

58. August D, Huhmann M. Nutritional care of cancer patients. In: Norton JA, Barie PS, Bollinger RR, et al, eds. Surgery: Basic Science and Clinical Evidence. 2nd ed. New York, NY: Springer-Verlag; 2008:2123-2150.

59. Bozzetti F, Braga M, Gianotti L, Gavazzi C, Mariani L. Postoperative enteral versus parenteral nutrition in malnourished patients with gastrointestinal cancer: A randomised multicentre trial. Lancet. 2001;358(9292):1487-1492.

60. Koretz RL, Lipman TO, Klein S. AGA technical review on parenteral nutrition. Gastroenterology. 2001;121(4):970-1001.

61. Papapietro K, Diaz E, Csendes A, et al. Early enteral nutrition in cancer patients subjected to a total gastrectomy [in Spanish]. Rev Med Chil. 2002;130(10):1125-1130.

62. Braga M, Gianotti L, Gentilini O, Parisi V, Salis C, Di Carlo V. Early postoperative enteral nutrition improves gut oxygenation and reduces costs compared with total parenteral nutrition. Crit Care Med. 2001;29(2):242-248.

63. Aiko S, Yoshizumi Y, Sugiura Y, et al. Beneficial effects of immediate enteral nutrition after esophageal cancer surgery. Surg Today. 2001;31(11):971-978.

64. Huckleberry Y. Nutritional support and the surgical patient. Am J Health Syst Pharm. 2004;61(7):671-682, quiz 683-674.

65. Fearon KC, Luff R. The nutritional management of surgical patients: Enhanced recovery after surgery. Proc Nutr Soc. 2003;62(4):807-811.

66. Lipman TO. Grains or veins: Is enteral nutrition really better than parenteral nutrition? A look at the evidence. JPEN J Parenter Enteral Nutr. 1998;22(3): 167-182.

67. Braunschweig CL, Levy P, Sheean PM, Wang X. Enteral compared with parenteral nutrition: A meta-analysis. Am J Clin Nutr. 2001;74(4):534-542.

68. Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: A systematic review of clinical outcome. Crit Care Med. 1999;27(12):2799-2805.

69. Markman M. Prevention of paclitaxel-associated arthralgias and myalgias. J Support Oncol. 2003;1(4):233-234.

70. Savarese D, Boucher J, Corey B. Glutamine treatment of paclitaxel-induced myalgias and arthralgias. J Clin Oncol. 1998;16(12):3918-3919.

71. Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B. Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev. 2003;29(6): 501-513.

72. Stubblefield MD, Vahdat LT, Balmaceda CM, Troxel AB, Hesdorffer CS, Gooch CL. Glutamine as a neuroprotective agent in high-dose paclitaxel-induced peripheral neuropathy: A clinical and electrophysiologic study. Clin Oncol (R Coll Radiol). 2005;17(4):271-276.

73. Vahdat L, Papadopoulos K, Lange D, et al. Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res. 2001;7(5):1192—1197.

74. Morlion BJ, Stehle P, Wachtler P, et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: A randomized, double-blind, controlled study. Ann Surg. 1998;227(2):302-308.

75. Aquino VM, Harvey AR, Garvin JH, et al. A double-blind randomized placebocontrolled study of oral glutamine in the prevention of mucositis in children undergoing hematopoietic stem cell transplantation: A pediatric blood and marrow transplant consortium study. Bone Marrow Transplant. 2005;36(7):611—616.

76. Blijlevens NM, Donnelly JP, Naber AH, Schattenberg AV, DePauw BE. A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients. Support Care Cancer. 2005; 13(10) 790-796.

77. Piccirillo N, De Matteis S, Sora F, et al. Glutamine parenteral supplementation in stem cell transplant. Bone Marrow Transplant. 2004;33(4):455, author reply 457.

78. Sykorova A, Horacek J, Zak P, Kmonicek M, Bukac J, Maly J. A randomized, double blind comparative study of prophylactic parenteral nutritional support with or without glutamine in autologous stem cell transplantation for hematological malignancies: Three years’ follow-up. Neoplasm. 2005;52(6):476-482.

79. Ziegler TR, Young LS, Benfell K, et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation: A randomized, double-blind, controlled study. Ann Intern Med. 1992;116(10):821-828.

80. Young LS, Bye R, Scheltinga M, Ziegler TR, Jacobs DO, Wilmore DW. Patients receiving glutamine-supplemented intravenous feedings report an improvement in mood. JPEN J Parenter Enteral Nutr. 1993;17(5):422-427.

81. Schloerb PR, Amare M. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications: A randomized, double-blind study. JPEN J Parenter Enteral Nutr. 1993;17(5):407-413.

82. Jebb SA, Marcus R, Elia M. A pilot study of oral glutamine supplementation in patients receiving bone marrow transplants. Clin Nutr. 1995;14(3):162-165.

83. Anderson PM, Ramsay NK, Shu XO, et al. Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant. 1998;22(4):339-344.

84. Schloerb PR, Skikne BS. Oral and parenteral glutamine in bone marrow transplantation: A randomized, double-blind study. JPEN J Parenter Enteral Nutr. 1999; 23(3):117-122.

85. Coghlin Dickson TM, Wong RM, Offrin RS, et al. Effect of oral glutamine supplementation during bone marrow transplantation. JPEN J Parenter Enteral Nutr. 2000;24(2):61-66.

86. Pytlik R, Benes P, Patorkova M, et al. Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: A randomized, double-blind, placebo controlled study. Bone Marrow Transplant. 2002;30(12):953-961.

87. Murray SM, Pindoria S. Nutrition support for bone marrow transplant patients. Cochrane Database Syst Rev. 2002;2:CD002920.

88. Piccirillo N, De Matteis S, Laurenti L, et al. Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: Effects on immune reconstitution and mucositis. Haematologica. 2003;88(2):192—200.

89. Scheid C, Hermann K, Kremer G, et al. Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy. Nutrition. 2004;20(3): 249-254.

90. Jatoi A, Rowland K, Loprinzi CL, et al. An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: A North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. J Clin Oncol. 2004;22(12):2469-2476.

91. Fearon K, von Meyenfeldt MF, Moses A, et al. An energy and protein dense, high Q-3 fatty acid oral supplement promotes weight gain in cancer cachexia. Eur J Cancer. 2001;37(suppl 6):S27-S28.

92. Moses AW, Slater C, Preston T, Barber MD, Fearon KC. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with Q-3 fatty acids. Br J Cancer. 2004;90(5):996-1002.

93. Wachtler P, Konig W, Senkal M, Kemen M, Koller M. Influence of a total parenteral nutrition enriched with omega-3 fatty acids on leukotriene synthesis of peripheral leukocytes and systemic cytokine levels in patients with major surgery. J Trauma. 1997;42(2):191-198.

94. Braga M, Gianotti L, Vignali A, Carlo VD. Preoperative oral arginine and Q-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer. Surgery. 2002;132(5):805-814.

95. Farreras N, Artigas V, Cardona D, Rius X, Trias M, Gonzalez JA. Effect of early postoperative enteral immunonutrition on wound healing in patients undergoing surgery for gastric cancer. Clin Nutr. 2005;24(1):55-65.

96. Senkal M, Zumtobel V, Bauer KH, et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: A prospective randomized study. Arch Surg. 1999;134(12): 1309-1316.

97. Song JX, Qing SH, Huang XC, Qi DL. Effect of parenteral nutrition with L-arginine supplementation on postoperative immune function in patients with colorectal cancer. Di Yi Jun Yi Da Xue Xue Bao. 2002;22(6):545-547.

98. Heys SD, Gough DB, Khan L, Eremin O. Nutritional pharmacology and malignant disease: A therapeutic modality in patients with cancer. Br J Surg. May 1996; 83(5):608-619.

99. Evans ME, Tian J, Gu LH, Jones DP, Ziegler TR. Dietary supplementation with orotate and uracil increases adaptive growth of jejunal mucosa after massive small bowel resection in rats. JPEN J Parenter Enteral Nutr. 2005;29(5):315-320, discussion 320-311.

100. Daly JM, Lieberman MD, Goldfine J, et al. Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: Immunologic, metabolic, and clinical outcome. Surgery. 1992;112(1):56-67.

101. Daly JM, Weintraub FN, Shou J, Rosato EF, Lucia M. Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients. Ann Surg. 1995;221(4):327-338.

102. Di Carlo V, Gianotti L, Balzano G, Zerbi A, Braga M. Complications of pancreatic surgery and the role of perioperative nutrition. Dig Surg. 1999;16(4):320-326.

103. Braga M, Gianotti L, Vignali A, Cestari A, Bisagni P, Di Carlo V. Artificial nutrition after major abdominal surgery: Impact of route of administration and composition of the diet. Crit Care Med. 1998;26(1):24-30.

104. Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology. 2002;122(7):1763—1770.

105. Tepaske R, Velthuis H, Oudemans-van Straaten HM, et al. Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: A randomised placebo-controlled trial. Lancet. 2001;358 (9283):696-701.

106. Bistrian BR. Practical recommendations for immune-enhancing diets. J Nutr. 2004;134(10)(suppl):2868S-2872S, discussion 2895S.

107. Lacour J, Laplanche A, Malafosse M, et al. Polyadenylic-polyuridylic acid as an adjuvant in resectable colorectal carcinoma: A 6'/2 year follow-up analysis of a multicentric double blind randomized trial. Eur J Surg Oncol.

1992;18(6):599-604.

108. Fainsinger RL, Gramlich LM. How often can we justify parenteral nutrition in terminally ill cancer patients? J Palliat Care. 1997;13(1):48—51.

109. Fan BG. Parenteral nutrition prolongs the survival of patients associated with malignant gastrointestinal obstruction. JPEN J Parenter Enteral Nutr. 2007;31(6):508—510.

110. Howard L. Home parenteral nutrition in patients with a cancer diagnosis. JPEN J Parenter Enteral Nutr. 1992;16(6)(suppl):93S-99S.

111. Bozzetti F. Home total parenteral nutrition in incurable cancer patients: A therapy, a basic humane care or something in between? Clin Nutr. 2003;22(2):109—111.

112. August DA, Thorn D, Fisher RL, Welchek CM. Home parenteral nutrition for patients with inoperable malignant bowel obstruction. JPEN J Parenter Enteral Nutr. 1991;15(3):323-327.

113. King LA, Carson LF, Konstantinides N, et al. Outcome assessment of home parenteral nutrition in patients with gynecologic malignancies: What have we learned in a decade of experience? Gynecol Oncol. 1993;51(3):377—382.

114. Cozzaglio L, Balzola F, Cosentino F, et al. Outcome of cancer patients receiving home parenteral nutrition: Italian Society of Parenteral and Enteral Nutrition (S.I.N.P.E.). JPEN J Parenter Enteral Nutr. 1997;21(6):339-342.

115. Baines M, Oliver DJ, Carter RL. Medical management of intestinal obstruction in patients with advanced malignant disease: A clinical and pathological study. Lancet. 1985;2(8462):990-993.

116. Larrea J, Vega S, Martinez T, Torrent JM, Vega V, Nunez V. The nutritional status and immunological situation of cancer patients [in Spanish]. Nutr Hosp. 1992; 7(3):178-184.

117. Hammerlid E, Wirblad B, Sandin C, et al. Malnutrition and food intake in relation to quality of life in head and neck cancer patients. Head Neck. 1998;20(6):540-548.

118. Lerut TE, van Lanschot JJ. Chronic symptoms after subtotal or partial oesophagec-tomy: Diagnosis and treatment. Best Pract Res Clin Gastroenterol. 2004; 18(5): 901-915.

119. Scholmerich J. Postgastrectomy syndromes: Diagnosis and treatment. Best Pract Res Clin Gastroenterol. 2004;18(5):917-933.

120. Shibuya S, Fukudo S, Shineha R, et al. High incidence of reflux esophagitis observed by routine endoscopic examination after gastric pull-up esophagectomy. World J Surg. 2003;27(5):580-583.

121. Rey-Ferro M, Castano R, Orozco O, Serna A, Moreno A. Nutritional and immunologic evaluation of patients with gastric cancer before and after surgery. Nutrition. 1997;13(10):878-881.

122. Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin for cognition and dementia. Cochrane Database Syst Rev. 2003;4:CD004514.

123. Adachi S, Kawamoto T, Otsuka M, Todoroki T, Fukao K. Enteral vitamin B^ supplements reverse postgastrectomy B^ deficiency. Ann Surg. 2000;232(2):199—201.

124. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003;67(5):979-986.

125. Phang PT, Hain JM, Perez-Ramirez JJ, Madoff RD, Gemlo BT. Techniques and complications of ileostomy takedown. Am J Surg. 1999;177(6):463—466.

126. Beyer P. Medical nutrition therapy for lower gastrointestinal tract disorders. In: Maham L, Escott-Stump S, eds. Krause’s Food, Nutrition, and Diet Therapy. 11th ed. New York, NY: Elsevier; 2004:705-737.

127. Petersen C. D-Lactic acidosis. Nutr Clin Pract. 2005;20(6):634-645.

128. Azhar SS, Beach RE. D-Lactic acidosis in a diabetic patient with a short bowel. J Am Board Fam Pract. 2002;15(4):316-318.

129. Uchida H, Yamamoto H, Kisaki Y, Fujino J, Ishimaru Y, Ikeda H. D-Lactic acidosis in short-bowel syndrome managed with antibiotics and probiotics. J Pediatr Surg. 2004;39(4):634-636.

130. Neale G, Gompertz D, Schonsby H, Tabaqchali S, Booth CC. The metabolic and nutritional consequences of bacterial overgrowth in the small intestine. Am J Clin Nutr. 1972;25(12):1409-1417.

131. Bongaerts GP, Severijnen RS, Tangerman A, Verrips A, Tolboom JJ. Bile acid deconjugation by lactobacilli and its effects in patients with a short small bowel. J Gastroenterol. 2000;35(11):801-804.

132. Mogilner JG, Srugo I, Lurie M, et al. Effect of probiotics on intestinal regrowth and bacterial translocation after massive small bowel resection in a rat. J Pediatr Surg. 2007;42(8):1365-1371.

133. Quigley EM, Quera R. Small intestinal bacterial overgrowth: Roles of antibiotics, prebiotics, and probiotics. Gastroenterology. 2006;130(2)(suppl 1):S78-S90.

134. Seehofer D, Rayes N, Schiller R, et al. Probiotics partly reverse increased bacterial translocation after simultaneous liver resection and colonic anastomosis in rats. J Surg Res. 2004;117(2):262-271.

135. van Minnen LP, Timmerman HM, Lutgendorff F, et al. Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis. Surgery. 2007;141(4):470-480.

136. Salminen S, von Wright A, Morelli L, et al. Demonstration of safety of probiotics: A review. Int J Food Microbiol. 1998;44(1-2):93-106.

137. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361 (9356):512-519.

138. Husebye E. The pathogenesis of gastrointestinal bacterial overgrowth. Chemotherapy. 2005;51(suppl 1):1-22.

139. Neut C, Bulois P, Desreumaux P, et al. Changes in the bacterial flora of the neoterminal ileum after ileocolonic resection for Crohn’s disease. Am J Gastroenterol. 2002;97(4):939-946.

140. Kahl S, Malfertheiner P. Exocrine and endocrine pancreatic insufficiency after pancreatic surgery. Best Pract Res Clin Gastroenterol. 2004;18(5):947-955.

141. Riediger H, Adam U, Fischer E, et al. Long-term outcome after resection for chronic pancreatitis in 224 patients. J Gastrointest Surg. 2007;11(8):949-959; discussion 959-960.

142. Slezak LA, Andersen DK. Pancreatic resection: Effects on glucose metabolism. World J Surg. 2001;25(4):452-460.

143. Buchler MW, Friess H, Muller MW, Wheatley AM, Beger HG. Randomized trial of duodenum-preserving pancreatic head resection versus pylorus-preserving Whipple in chronic pancreatitis. Am J Surg. 1995;169(1):65-69, discussion 69-70.

144. Pereira PL, Wiskirchen J. Morphological and functional investigations of neuroendocrine tumors of the pancreas. Eur Radiol. 2003;13(9):2133-2146.

145. Nikou GC, Toubanakis C, Nikolaou P, et al. VIPomas: An update in diagnosis and management in a series of 11 patients. Hepatogastroenterology. 2005;52(64): 1259-1265.

146. Fuhrman MP, Charney P, Mueller CM. Hepatic proteins and nutrition assessment. J Am Diet Assoc. 2004;104(8):1258-1264.

147. Barle H, Nyberg B, Essen P, et al. The synthesis rates of total liver protein and plasma albumin determined simultaneously in vivo in humans. Hepatology. 1997; 25(1):154-158.

148. Sanchez AJ, Aranda-Michel J. Nutrition for the liver transplant patient. Liver Transpl. 2006;12(9):1310-1316.

149. Schneider PD. Preoperative assessment of liver function. Surg Clin North Am. 2004;84(2):355-373.

150. Marchesini G, Marzocchi R, Noia M, Bianchi G. Branched-chain amino acid supplementation in patients with liver diseases. J Nutr. 2005;135(6)(suppl):1596S-1601S.

151. Kondrup J. Nutrition in end stage liver disease. Best Pract Res Clin Gastroenterol. 2006;20(3):547-560.

152. Schiff E, Sorrell M, Maddrey W, eds. Schiffs Diseases of the Liver. 10th ed. New York, NY: Lippincott Williams & Wilkins; 2006.

153. Richter B, Schmandra TC, Golling M, Bechstein WO. Nutritional support after open liver resection: A systematic review. Dig Surg. 2006;23(3):139-145.

154. Kudsk KA. Early enteral nutrition in surgical patients. Nutrition. 1998;14(6): 541-544.

155. Gabor S, Renner H, Matzi V, et al. Early enteral feeding compared with parenteral nutrition after oesophageal or oesophagogastric resection and reconstruction. Br J Nutr. 2005;93(4):509-513.

156. Date RS, Clements WD, Gilliland R. Feeding jejunostomy: Is there enough evidence to justify its routine use? Dig Surg. 2004;21(2):142-145.

157. Jensen GL, Sporay G, Whitmire S, Taraszewski R, Reed MJ. Intraoperative placement of the nasoenteric feeding tube: A practical alternative? JPEN J Parenter Enteral Nutr. 1995;19(3):244-247.

158. Andersen H, Lewis S, Thomas S. Early enteral nutrition within 24h of colorectal surgery versus later commencement of feeding for postoperative complications. Cochrane Database of Systematic Reviews, Vol. 4; 2005.

159. Klein S, Koretz RL. Nutrition support in patients with cancer: What do the data really show? Nutr Clin Pract. 1994;9(3):91-100.

160. Gerndt SJ, Orringer MB. Tube jejunostomy as an adjunct to esophagectomy. Surgery. 1994;115(2):164-169.

161. Bozzetti F, Gavazzi C, Miceli R, et al. Perioperative total parenteral nutrition in malnourished, gastrointestinal cancer patients: A randomized, clinical trial. JPEN J Parenter Enteral Nutr. 2000;24(1):7-14.

162. Wu GH, Liu ZH, Wu ZH, Wu ZG. Perioperative artificial nutrition in malnourished gastrointestinal cancer patients. World J Gastroenterol. 2006;12(15):2441-2444.

163. Meijerink WJ, von Meyenfeldt MF, Rouflart MM, Soeters PB. Efficacy of perioperative nutritional support. Lancet. 1992;340(8812):187-188.

164. Gupta D, Lammersfeld CA, Vashi PG, Burrows J, Lis CG, Grutsch JF. Prognostic significance of Subjective Global Assessment (SGA) in advanced colorectal cancer. Eur J Clin Nutr. 2005;59(1):35-40.

165. Radigan A. Post-gastrectomy: Managing the nutrition fall-out. Pract Gastroenterol. 2004;28(6):63-75.

166. Watt-Watson J, Stevens B, Katz J, Costello J, Reid GJ, David T. Impact of preoperative education on pain outcomes after coronary artery bypass graft surgery. Pain. 2004;109(1-2):73-85.

167. Danino AM, Chahraoui K, Frachebois L, et al. Effects of an informational CD-ROM on anxiety and knowledge before aesthetic surgery: A randomised trial. Br J Plast Surg. 2005;58(3):379-383.

168. Pager CK. Randomised controlled trial of preoperative information to improve satisfaction with cataract surgery. Br J Ophthalmol. 2005;89(1):10—13.

169. Sjoling M, Nordahl G, Olofsson N, Asplund K. The impact of preoperative information on state anxiety, postoperative pain and satisfaction with pain management. Patient Educ Couns. 2003;51(2):169-176.

170. Ratanalert S, Soontrapornchai P, Ovartlarnporn B. Preoperative education improves quality of patient care for endoscopic retrograde cholangiopancreatography. Gastroenterol Nurs. 2003;26(1):21-25.

171. Buzby GP, Mullen JL, Matthews DC, Hobbs CL, Rosato EF. Prognostic Nutritional Index in gastrointestinal surgery. Am J Surg. 1980;139(1):160—167.

172. Giraudet-Le Quintrec JS, Coste J, Vastel L, et al. Positive effect of patient education for hip surgery: A randomized trial. Clin Orthop Relat Res. 2003(414):112—120.

Рекомендуем к просомтру

www.kievoncology.com благодарны автору и издательству, которые способствует образованию медицинских работников. При нарушении авторских прав, сообщите нам и мы незамедлительно удалим материалы.