Nutritional Support of the Cancer Patient: Delivery Systems and Formulations

Nutrition and Cancer II

0039-6109/86 $0.00 + .20

Nutritional Support of the Cancer Patient: Delivery Systems and Formulations

Edward T. Chory, M.D.,* and]ames L. Mullen, M.D.t

Malnutrition is common in cancer patients and adversely affects their clinical outcome. In 1932 Warren reviewed 500 cases of varying types of carcinoma and concluded that associated cachexia was the most common immediate cause of death. 52 DeWys found the prevalence of weight loss varied from 31 per cent in non-Hodgkin's lymphoma to 87 per cent in gastric carcinoma in a retrospective review of more than 3000 patients in 12 multicenter protocols." Survival was' significantly shorter in those patients who had lost weight in 9 of 12 protocols. Given these impressions, cancer patients have been viewed as prime candidates for aggressive interventional nutritional therapy. As sophisticated parenteral and enteral techniques evolved with both over- and underutilization, this imprecise early experience led to numerous retrospective studies that have documented the ability to safely and effectively nutritionally replete or maintain the majority of malnourished cancer patients. 2, 6-8 Whether such nutritional maintenance or repletion can produce a secondary benefit of improved antineoplastic response rates or enhanced tolerance to therapy still remains a crucial unanswered question. Such' secondary improvements in response rates, tolerance, and complication rates with chemotherapy and/or radiotherapy have been difficult to document in controlled trials. This area is addressed in another article in this issue. *Formerly, Clinical Fellow, Nutrition Support Service, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; currently, Assistant Professor of Surgery, Rutgers Medical School and Muhlenberg Regional Medical Center, Plainfield, New Jersey t Associate Professor of Surgery and Director, Nutrition Support Service, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania

Surgical Clinics of North America-Vol. 66, No.6, December 1986

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In contrast, several studies have documented the efficacy of preoperative parenteral nutrition. Heatley and colleagues reported a statistically significant decrease in the incidence of wound infections in a series of 79 patients with esophageal and gastric carcinoma. 23 Smale documented the importance of identifying those patients at risk for increased morbidity and mortality. In a study of 159 cancer patients undergoing major intra-abdominal, thoracic, or head and neck cancer surgery, there was a statistically significant reduction in both morbidity and mortality in only those patients in the high-risk, severely malnourished group as determined by the preoperative Prognostic Nutritional Index (PNI).47 Muller and associates similarly reported a statistically significant improvement in morbidity and mortality in a prospective, randomized trial with a lO-day course of parenteral nutrition in malnourished patients with gastrointestinal carcinoma. 36 In these studies, the positive clinical outcomes of nutritional therapy were particularly evident in malnourished patients, as one would expect. Nutritional support treats nutritional deficits, not cancer. This point is addressed in depth in another article in this issue.

PRINCIPLES OF NUTRITIONAL THERAPY AND DECISION MAKING Rational use of nutritional support in cancer patients depends on the accurate identification of malnourished patients or those at high risk of becoming malnourished because of the natural history and/or planned treatment of the patient's malignancy. Detailed knowledge of both the general and specific effects of the various tumor types and their antineoplastic treatment is therefore a prerequisite to effective nutritional decision making. One cannot effectively manage the nutritional care of a cancer patient without a moderate appreciation of all oncologic aspects of the case. Likewise, oncologists must possess more than a passing knowledge of nutritional and metabolic principles. Adjuvant nutritional support is indicated when both response rates of antineoplastic therapy and the morbidity of confirmed or anticipated malnutrition are moderate or high. Such adjuvant nutritional support should be reserved for malnourished cancer patients for whom there are realistic expectations of an effective response to ongoing or planned antineoplastic therapy. At times, this becomes a philosophic rather than a medical judgment, with social factors and issues regarding quality of life being more prominent than other considerations.

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NUTRIENT PRESCRIPTION The design of a nutrient prescription can proceed in stepwise fashion after several preliminary steps: preliminary identification of the actually or potentially malnourished cancer patient, an assessment of the severity of disability through detailed nutritional assessment, and a positive clinical decision to employ adjuvant nutritional support. Baseline nutritional assessment provides the data necessary to help design a safe, efficacious nutritional regimen, as well as the baseline reference points to evaluate serially the response to nutritional therapy. A detailed consideration of nutritional assessment is provided in the first article of this issue. Each component of the nutrient prescription (water, protein, energy, minerals, and vitamins) needs to be addressed individually in a logical, sequential fashion.

WATER

Evaluation of the patient's volume status requires a thorough knowledge of the patient's critical organ function, particularly the cardiovascular, renal, hepatic, and pulmonary systems. Careful physical examination is performed to detect signs of fluid retention, such as peripheral edema, ascites, pulmonary edema, and pleural effusion. Subtle dehydration may be even more difficult to detect clinically. Careful review of both intake and output, urine specific gravity, serum electrolytes, blood urea nitrogen (BUN), and osmolarity will help further define volume status. Fluid requirements for normal maintenance can be estimated from either body weight (30 ml per kg) or body surface area (1400 ml per m") and adjusted for existing deficits and ongoing abnormal losses or pre-existing overload. The physician must be familiar with the electrolyte composition of common fluids from various parts of the gastrointestinal tract. Increased insensible losses can be substantial in febrile patients. Serial monitoring of physical signs, precise intake and output records, daily weights, and serum values are essential. In the sick cancer patient, critical organ dysfunction and accompanying exogenous fluid restrictions often limit our capability to provide the required amounts of all nutrients.

PROTEIN

The chief priority in nutritional support is preservation or repletion of the body cell mass. If fluid tolerance is limited, meeting

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protein requirements is given precedence over achieving caloric goals. Even in the healthy patient, precise determination of the status of body protein and protein requirements is difficult. A malnourished cancer patient poses even more assessment difficulties because commonly used clinical indicators of protein status (serum proteins, anthropometries, and indirect measures of body composition) are often distorted by non-nutritional influences. Given these limitations, protein status is determined by the following indicators and cutoff values: mid-arm muscle circumference (80 per cent of standard), serum albumin (3.5 gm%), and total iron-binding capacity (220 mcg%). When our assessment indicates that the patient demonstrates preservation of both visceral and somatic protein, we provide 1.0 to 1.5 gm of protein per kg of current body weight (CBW) for maintenance of protein and nitrogen status. We provide 1.5 to 2.0 gm of protein per kg of CBW to the protein-depleted patient. Greenberg and Jeejeebhoy achieved positive nitrogen balance in nonstressed, obese patients with varied gastrointestinal disorders by providing 1.8 gm of protein per kg in the absence of any nonprotein caloric source." Elwyn and associates have achieved nitrogen retention with intakes of 1.6 gm of protein per kg when only 50 per cent of measured energy expenditure was provided as nonprotein kilocalories to nonstressed, protein-depleted patients. 15 Dickerson and colleagues achieved the same in morbidly obese patients with postoperative complications by supplying 2.1 gm of protein per kg of ideal body weight. 14

QUANTITY OF CALORIES

CBW expressed as a percentage of ideal body weight (IBW) helps provide a reasonable estimate of body fat status and assists in defining the patient's goal for caloric intake. Those patients whose CBW is between 90 and 120 per cent of ideal body weight receive 130 per cent of their measured resting energy expenditure (REE) in nonprotein kilocalories to maintain current body fat status. If the patient's fat stores are depleted, as evidenced by a CBW < 90 per cent IBW, the patient's caloric goal is increased to 150 per cent of his or her measured REE. Obese patients with excess fat stores (CBW > 120 per cent IBW) should receive a caloric goal of < 100 per cent REE, designed to allow utilization of excess endogenous adipose tissue as a caloric substrate. Caloric requirements are most precisely defined by the direct measurement of the patient's individual REE. Application of the Harris-Benedict (H-B) equation to hospitalized patients is inappro-

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priate, as these classic formulas were derived from healthy subjects with presumed normal body composition, and the resultant regression equations describe a population, not individuals. It is not surprising that energy expenditure is not accurately predicted by these equations in over 50 per cent of hospitalized patients. Other formulas, based solely on weight or body surface area, also assume normal body composition and uniform intensity of metabolic activity per unit of body mass. Neither assumption is correct in malnourished cancer patients. In 200 heterogeneous cancer patients, Knox and colleagues found that only 41 per cent had measured REEs within 10 per cent of the Harris-Benedict predictiou.f In a more homogeneous study of 173 malnourished patients with gastrointestinal malignancy, Dempsey noted that predictions of energy expenditure were inaccurate in a like proportion. 11 There was a clear relationship between measured metabolic rates and groups of patients with a certain tumor type. Patients with pancreatic and hepatobiliary tumors were predominantly hypometabolic (REE < 90 per cent H-B). Gastric cancer patients, on the other hand, tended toward hypermetabolism (REE > 110 per cent H-B). Patients with esophageal and colorectal malignancies did not show such trends. In another study of only colorectal cancer patients, tumor stage was, not surprisingly, an independent determinant of energy expenditure.F Recommended caloric requirements based on these inaccurate predictive formulas exceed actual measured energy expenditure by more than 1000 kcal per day. The clinical consequences of overfeeding, such as hepatic steatosis and increased CO 2 production, are not inconsequential. The economic impact is also significant. Based on our annual total parenteral nutrition (TPN) experience totaling 11,000 patient-days, using these predictive formulas to define caloric goals rather than the actual measured energy expenditure would have resulted in the inappropriate administration of nearly 7000 excess liters of TPN per year. 17 Indirect calorimetry also provides vital information quantitating use of substrates." This allows documentation of the efficacy of our selective substrate approach regarding fat synthesis or oxidation. In obese patients with CBW > 120 per cent IBW, the patient's caloric goal is designed to allow depletion of endogenous adipose caloric reserves. Dickerson and associates achieved positive nitrogen balance, increased serum protein levels, and healing of fistulas in a study involving 13 obese patients while providing only 51 per cent of the measured energy expenditure in nonprotein kilocalories and 2.1 gm of protein per kg of IBW. 14 These patients lost an average of 2.3 kg per week while maintaining a mean positive nitrogen balance of + 2.4 gm of nitrogen per day. The mean respiratory quotient was

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0.80, indicating that fat oxidation accounted for approximately two thirds of the nonprotein energy expenditure. Our standard caloric prescription for weight maintenance, 130 per cent of measured REE in nonprotein kilocalories, is derived in part from studies of the interrelationship of energy and protein metabolism by Elwyn and co-workers, who pioneered the concept of both an individual and a coordinated consideration of nitrogen and energy balance. 15, 46 Indirect calorimetry measures REE, the major component of total daily energy expenditure, which also includes expenditure secondary to musculoskeletal activity. It is necessary to provide exogenous calories in excess of the measured REE to achieve neutral energy balance due to "losses" secondary to dietary thermogenesis, physical activities, and other inefficiencies. Nonprotein caloric intakes in excess of 130 per cent of measured REE are necessary for positive energy balance and subsequent repletion of adipose stores. King and colleagues documented positive fat balance with anthropometric changes and respiratory quotients greater than unity with nonprotein caloric intakes of 150 per cent of REE. 27 Dempsey and associates found that further increases of energy supply beyond 115 per cent ofREE did not improve nitrogen balance." There are no obvious survival advantages to excess fat synthesis and several documented disadvantages, such as hepatic steatosis and excess CO 2 production.

QUALITY OF CALORIES

After quantitating caloric requirements, the nutrient prescription must be further defined with regard to nonprotein caloric quality. Gamble documented the minimum glucose requirement of 100 gm per day to maximally "spare" protein from gluconeogenetic pathways. 18 Wilmore and colleagues further outlined glucose requirements of 250 gm per day for effective healing of burn wounds. 54 At the other end of the spectrum, Wolfe and co-workers have suggested a maximal glucose oxidation capacity (7 gm per kg per day), above which both metabolic rate and respiratory quotient rapidly increase. 55 Although the plasma clearance rate of glucose increased with increasing glucose infusion rates, glucose oxidation did not rise in a corresponding parallel manner. Glucose that is not oxidized is stored as either glycogen or lipid. Given the limited capacity for glycogen storage, lipogenesis increased as documented by the increasing respiratory quotient. During infusion of 9 mg of glucose per kg per minute, triglyceride synthesis was 206 gm per day. Hepatic steatosis

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and increased carbon dioxide production are two adverse clinical consequences of such excess carbohydrate infusions. The amount of lipid emulsion that can be safely infused is similarly limited by problems of cholestasis at rates exceeding 2 gm per kg per day. In Allardyce's study, 10 of the 18 patients in the high lipid infusion group (3 gm per kg per day) developed progressive cholestatic jaundice associated with significant elevation of serum alkaline phosphatase." None of the 17 patients receiving 1 gm per kg per day developed jaundice, and only one had a rise in alkaline phosphatase. The rate of infusion of lipid emulsion can also be important. Greene and associates documented changes in oxygen-diffusing capacity when 500 ml of 10 per cent lipid emulsion were infused over 4 hours, generating an associated hypertriglyceridemia." Arterial P0 2 levels were not significantly affected, and pulmonary diffusion reverted to normal when the lipemia cleared. Administration of heparin, by increasing the activity of endothelial lipoprotein lipase, prevented the increase in serum lipids and the pulmonary function abnormalities. 26, 37 Given these practical limitations, energy requirements are most effectively provided using a mixed fuel system with lipids supplying 30 to 50 per cent of the nonprotein kilocalories. 26, 37

MACROELEMENTS

Nutritional and metabolic support includes electrolytes, vitamins, and trace elements. Daily requirements of electrolytes are as follows: sodium (60 to 120 mEq), potassium (60 to 100 mEq), chloride (60 to 120 mEq), magnesium (8 to 10 mEq), calcium (200 to 400 mg), phosphorus (300 to 400 mg), and iron (1 to 2 ~g). These must be provided and the amounts constantly re-evaluated in light of existing deficits and/or abnormal losses. The physician must be aware of the more common electrolyte abnormalities related to the primary malignant disease process, complications of that disease, and its treatment.

VITAMINS AND TRACE ELEMENTS

Vitamin and trace element preparations are commercially available, providing the crudely defined daily parenteral requirements of these essential nutrients. Hoffman has extensively reviewed the alterations in micronutrient metabolism specific to cancer patients. 25 Specific chemotherapeutic agents are associated with well-doc-

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umented deficiencies or alterations in micronutrient metabolism: 5fluorouracil with thiamine deficiency, cis-platinum with increased urinary excretion of divalent cations (that is, magnesium), and methotrexate with competitive inhibition of folate. When these agents are employed, additional supplementation may be required to prevent deficiencies.

DELIVERY SYSTEMS To achieve the goals of nutritional therapy, reliable delivery of the nutrient prescription must be assured. The array of available techiques and equipment continues to expand, allowing a specialized delivery system for almost any clinical situation. Enteral alimentation avoids the intravenous catheter-related mechanical and infectious complications of TPN but has its own mechanical complications. TPN allows almost immediate delivery of a given patient's nutrient prescription. Enteral alimentation, on the other hand, usually requires a slower progression, advancing to the complete nutrient prescription over days to weeks. One must always remember that the inside of the gastrointestinal tract is still outside the body. Enteral feedings that ultimately leave the gastrointestinal tract by means of vomiting and/or diarrhea cannot be considered intake. If complete, adequate nutrient intake can be safely achieved through the gastrointestinal tract, this delivery route is preferred, but its role in cancer patients is sometimes limited, as the required functional ability of the gastrointestinal tract may be impaired as a result of malignancy or anticancer treatment. It is important to emphasize that parenteral and enteral alimentation techniques are complementary and not competitive and often are employed in combination. Parenteral nutrition is often necessary to initiate repletion, as severe nutritional depletion may in itself impair gastrointestinal tolerance. A slower transition to enteral support can then be undertaken, allowing recovery of gastrointestinal digestive and absorptive function. The trophic effects of intraluminal enteral nutrients play an important role in this recovery process. Metabolically, the two routes are equivalent in most regards, such as in the ability to suppress gluconeogenesis and conserve lean body mass, as documented by Burt and colleagues in 18 patients with localized squamous cell carcinoma of the distal esophagus. 4 The choice of the nutrient delivery route follows the determination of nutrient requirements. Only after the patient's specific requirements are determined and a nutrient prescription designed should the decision regarding the mode of delivery be addressed.

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Evaluation of the gastrointestial tract's function and availability is foremost and determines whether enteral or parenteral therapy is more appropriate. The anticipated duration of interventional nutritional therapy is another major variable important in this decision. Plans for adjuvant antineoplastic therapy, neurologic status (that is, aspiration risk), and history of central venous thrombosis must also be evaluated routinely when options for nutritional access are being assessed.

ENTERAL FORCED FEEDING

Access to the gastrointestinal tract for enteral forced feeding can be obtained from the upper esophagus to the proximal jejunum. Several recent reviews have exhaustively discussed the technical aspects of obtaining and maintaining such access. 33, 43, 45, 50 Hunter first described nasogastric feedings in the eighteenth century, and this route is still the most commonly used. Recent refinements in tube design and construction (small bore, weighted, Silastic) have minimized complications such as mucosal irritations and erosions, otitis, and sinusitis. Operative or percutaneous esophageal and pharyngeal access is predominantly used for patients with a malignancy Involving the head and neck." 34, 44 Gastric feeding can be accomplished with transnasal tubes, with surgical gastrostomy (temporary or permanent allowing removal of the tube between feedings), and more recently with percutaneous endoscopically placed tubes."? The anticipated duration of the need for forced feedings (greater than or less than 6 weeks) is important in deciding whether nasally passed tubes are appropriate or whether operative or endoscopic placement is necessary. Duodenal or jejunal feedings are indicated for patients with gastric emptying disorders or esophagogastric reflux and for others with an increased risk of aspiration. Feedings can be delivered distal to the pylorus by means of a transnasal, transgastric, or surgically placed jejunal tube. Jejunal tubes can be operatively placed as an adjunct procedure secondary to the primary resection or palliative bypass of esophageal, gastric, duodenal, hepatobiliary, or pancreatic neoplasms. The plethora of gastrointestinal access techniques and devices is paralleled by the number of enteral formulations available. Heimberger and Weinsier categorized those available into "therapeutic equivalents" based on major, minor, and inconsequential characteristics. 24 Caloric density, protein content, route of administration, and cost were the major characteristics. Of more minor importance were

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osmolality, complexity, fat content, fat source, residue content, lactose content, electrolyte and mineral content, and preparation requirements. The four main categories are milk-based oral supplements, nutritionally complete lactose-free formulations, modular components, and specialized formulations for specific clinical conditions (renal or hepatic formulations). A more defined formula may be necessry if the absorptive function of the gastrointestinal tract is impaired with residual disease or fistulas. We use specialized formula only after a trial of standard, nutritionally complete, lactose-free formula. Modular components supplement standard formula to individualize a regimen to meet a patient's requirements.

PARENTERAL FORCED FEEDING

The high osmolarity (> 900 mOsm/L) of some parenteral nutrient solutions requires access to a high-flow vein to pevent chemical endothelial phlebitis and possible thrombosis. The standard approach for parenteral central venous access is percutaneous, infraclavicular subclavian vein catheterization. The most common alternatives are internal jugular and supraclavicular subclavian vein catheterizations. The use of long Silastic catheters passed through the deep brachial or basilic vein into the central venous system is a less desirable alternative that can be useful in certain patients after postoperative head and neck surgery or in those with burns involving the chest and neck, tracheostomies with copious secretions, and infected sternotomy incisions. 19, 20 When long-term access (greater than 6 weeks) is necessary, more "permanent" Hickman or Broviac Silastic catheters with a Dacron cuff are used. A proximal portion of the catheter, including the Dacron cuff, is tunneled in the subcutaneous tissues so the skin exit site is remote (> 10 em) from the venotomy site. Multiple-lumen catheters allow concomitant administration of solutions or medications physically incompatible with nutrient solutions, such as certain antibiotics and chemotherapeutic agents. Catheters with end reservoirs implanted in the subcutaneous tissue are also used for sequential administration of both nutrient solutions and chemotherapy. The reservoir is percutaneously accessed intermittently through its self-sealing diaphragm with noncoring Huber needles. Such reservoir catheters may decrease the incidence of catheter sepsis, be cosmetically preferable, and allow for increased physical activities such as swimming. With increasing long-term use of central venous catheters,

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Table 1. Standard Parenteral Formulations SOLUTION

1 2 3 4 5 6

7

DEXTROSE

AMINO ACIDS

10% 10% 8.5% 5.4%* 5.4%* 10% 10%

50 50 29 10 10 25 25

gm gm gm gm gm gm gm

(500 (500 (350 (250 (250 (250 (250

ml) ml) ml) ml) ml) ml) ml)

50% 70% 7.7% 50% 70% 50% 70%

250 350 50 250 350 250 350

gm gm gm gm gm gm gm

(500 (500 (650 (500 (500 (500 (500

CALORIES

ml) ml) ml) ml) ml) ml) ml)

850 1200 170 850 1200 850 1200

kcallL kcallL kcallunit kcallunit kcallunit kcal/unit kcal/unit

*Essential amino acids

thrombosis has become increasingly recognized as a significant clinical problem. Ruberg reported a significant reduction in central venous thrombosis with 3000 units of heparin per liter of TPN solution. We also use low-dose warfarin, elevating the prothrombin time 2 seconds greater than control in addition to the 3000 units of heparin per liter. When complete superior vena cava thrombosis is encountered, direct right atrial catheterization by way of an anterior thoracotomy may be necessary." Direct cannulation of the azygous venous system through a right posterolateral thoracotomy is an alternative technique for central venous catheterization.:" Occasionally, saphenous vein cannulation is performed, but the risks of sepsis and chance of inferior vena caval thrombosis affecting renal and hepatic venous drainage are significant. Catheterization of the inferior vena cava by way of the inferior epigastric vein has been described as an alternative to decrease the risk of sepsis, but the possibility of thrombosis is unchanged. 29 Torosian recently reported a combined surgical and angiographic technique that may obviate the need for either thoracotomy or inferior vena cava catheterization in patients with severe thrombotic complications of long-term central venous catheterization.t" This technique involves the retrograde passage of a guidewire under fluoroscopic guidance through the thrombosed area to a patent peripheral collateral vein after venography has been performed to identify all the available patent peripheral and collateral veins. A cutdown is then performed over the guidewire, and a Dormia basket is used to draw the tip of the catheter into the right atrium. All patients receive an individually designed nutrient prescription. For logistical and economic reasons, precriptions are often met by using standard stock TPN solutions (Table 1). In our experience, combinations of these solutions can be used to meet the needs of 95 per cent of patients. Parenteral nutrient solutions can also be delivered into peripheral veins when osmolarity is maintained below 900 mOsm/L. This approach can minimize net protein catabolism over a short period of

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Table 2. Unavoidable Complications TYPE

Mechanical Pneumothorax Catheter intravascular malposition Subclavian thrombosis Infectious Catheter-related fever Catheter-tip infection Catheter-tip infection and septicemia Catheter exit site infection Metabolic Anemia

FREQUENCY (%)

1

5 2-4*

5-10 2-3 1-2* 1-2

o

*Clinically significant

time, anticipating an early resumption of either adequate oral intake or enteral feedings. Massar and associates have documented a high incidence of phlebitis (40 per cent) and subcutaneous infiltration (60 per cent) in peripheral parenteral nutrition.i" Use of stainless steel butterfly needles, frequent rotation of intravenous sites, and solution additives such as steroids, bicarbonate, and heparin have all been recommended to minimize these complications. 53 If the nutrient prescription can be delivered parenterally within the osmolarity limits of the peripheral route, this approach may be preferable in the occasional patient in whom central venous catheterization carries a very high risk. Nutrients can also be delivered during hemodialysis and peritoneal dialysis. These techniques are reserved for special cases requiring nutrient supplementation of inadequate oral intake in patients with severely restricted intravenous and gastrointestinal access or volume intolerance. 39, 40 The timing of nutrient delivery can be very flexible and modified to accommodate the administration of other intravenous medications. Both nutrient solutions and intravenous medications can be delivered through the same central line without an increased complication rate, provided that meticulous care of the catheter continues.

MONITORING Most feeding complications are iatrogenic, avoidable, and in reality an indictment of the quality of care rather than the technique itself. 5, 35, 51 Few of the complications of forced feeding are unique to cancer patients. Complications of parenteral nutrition are legion and can be divided into mechanical, infectious, and metabolic. Several of these complications seem unavoidable (Table 2) and merit further

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Table 3. Monitoring Treatment Efficacy: Measurement of Goal Achievement A. Fluid Volume 1. Daily intake and output 2. Daily accurate weights 3. Physical examination: signs of imbalance 4. Serial serum levels 5. Effectiveness of organ and tissue perfusion B. Body Protein 1. Nitrogen balance 2. Serial serum proteins a. Albumin b. Total iron-binding capacity c. Retinol-binding protein/prealbumin d. Acute phase proteins 3. Wound evaluation 4. Anthropometries Meaningful differences if > 3 weeks between measures 5. Protein synthesis/catabolism measures Whole body versus individual tissues versus individual proteins 6. Urea generation 7. Amino acid profiles C. Body Fat 1. Serial respiratory quotients 2. Serial weekly weights (%IBW) 3. Anthropometries every month 4. Underwater weighing D. Caloric Substrate Profile 1. Glucose clearance/oxidation 2. Fat clearance/oxidation 3. Respiratory quotient 4. Oxygen consumption 5. Carbon dioxide production E. Mineral Serial serum/plasma levels F. Vitamin Assays as indicated clinically G. Essential Fatty Acids 1. Physical examination 2. Tetra/triene levels

discussion. An increased risk of catheter sepsis in the leukopenic, immunologically compromised cancer patient is often cited as a relative contraindication to TPN. Acceptably low rates of catheter sepsis document the ability to safely aliment these patients parenterally.42 Complications of enteral feeding are probably less frequent and severe, but mechanical complications of surgically placed feeding tubes can be serious. Peritonitis can result from leakage or perforation from a surgical gastrostomy or jejunostomy. Parastomal hernias and volvulus are other major mechanical complications that involve major morbidity. Gastrointestinal symptoms, most notably diarrhea,

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bloating, and crampy abdominal pain, are the most common reasons why enteral feedings do not provide effective nutritional support. Diarrhea can be a particularly difficult management problem. The etiology can be multifactorial, with contributions from antineoplastic therapy (chemotherapy and irradiation) as well as antibiotics and hyperosmolar tube feedings.

EFFICACY Careful serial monitoring must be targeted to assess the efficacy of nutritional intervention (Table 3). Fluid volume status must be evaluated with daily weights, accurate records of intake and output, and physical exmination. Serial assessment of anthropometric measurements, serum proteins, urine urea nitrogen, and respiratory quotient is performed to document substrate utilization and changes in both lean body mass and adipose stores. Micronutrient levels (electrolytes, minerals, vitamins, and trace elements) must also be routinely monitored.

CONCLUSIONS Multiple retrospective studies have documented our capacity to safely provide enteral and parenteral nutritional support to cancer patients. Nutritional maintenance or repletion is possible in the majority of cancer patients but is dependent on control of the primary disease process as well as concurrent medical conditions. Only in the context of the patient's primary disease (type and stage) and primary antineoplastic therapy can rational decisions be made regarding nutrition therapy. Safe and efficacious nutritional support requires a thorough knowledge of the varied enteral and parenteral formulations and delivery systems, as well as their specific indications and complications. Except for preoperative nutritional support, prospective trials have not conclusively documented that successful nutritional maintenance or repletion of cancer patients also provides the secondary benefit of improving their survival or response rates to antineoplastic therapy.

REFERENCES 1. Allardyce, D. B.: Cholestasis caused by lipid emulsions. Surg. Gynecol. Obstet., 154:641, 1982. 2. Brennan, M. F.: Total parenteral nutrition in the cancer patient. N. Engl. J. Med., 305:375, 1981.

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