Orthomolecular Oncology

Total Parenteral Nutrition

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TOTAL PARENTERAL NUTRITION IN CANCER PATIENTS

Samuel Chan
George L. Blackburn
Nutrition Support Service
Department of Surgery
Beth Israel Deaconess Medical Center/Harvard Medical School
Boston, Massachusetts



INTRODUCTION

In this era of evidence-based medicine, total parenteral nutrition (TPN) has been increasingly scrutinized. The efficacy of TPN - particularly how much nutritional support is appropriate in cancer patients - has been controversial. Since most patients with weight loss are receiving palliative therapy, the progressive weight loss may be due to the tumor itself or the adverse effect of treatment. The indications of implementing nutrition support in cancer patients as well as its safety have been studied (Klein et al., 1986; Detsky et al.,1987; McGeer et al., 1990; Kaminski et al., 1990; Buzby et al., 1988a,b; Anonymous, 1991). Nutrition biomarkers that measure loss of lean body mass, fluid electrolytes, acid-base status, and immune modulation have been established (Harvey et al., 1979, 1980). Important issues include the adjunctive use of nutrition support during antineoplastic therapy, treatment of cytokine-mediated cancer anorexia and host metabolism (Kawamura et al., 1982), and home total parenteral nutrition support in patients with cancer (Blackburn and Baptista, 1984).

HISTORICAL ASPECTS OF TPN

Two decades ago, Blackburn and Bistrian found that cancer patients had the highest prevalence of malnutrition of any hospitalized group of patients (Bistrian et al., 1976). Malnutrition associated with cancer is an indicator of poor prognosis, a higher mortality rate (Dewys et al., 1980), and higher perioperative morbidity rate (Nixon, 1982) in patients who have lost greater than 5% of their body weight and have a reduction in some of the indices of nutritional status (Keenan and Blackburn, 1981; Cohn and Blackburn, 1982). Thus, the rationale is to initiate nutrition support using TPN when patients are unable to consume an adequate intake orally or tolerate tube feeding. The role of TPN in the management of the cancer patients, however, continues to be an area of controversy. While some studies have demonstrated TPN's ability to favourably influence nutritional parameters, others have hypothesized that nutrition support may stimulate tumor growth (Brennan, 1981; Torosian, 1992). Some investigators have suggested that anorexia and semistarvation are associated with a slowing of tumor growth (Brennan, 1981).

ETIOLOGY OF MALNUTRITION IN THE CANCER PATIENT

The etiology of malnutrition is multifactorial, involving secretion of cytokines such as tumor necrosis factor (TNF) by tumor directly or from antigen-antibody allergic response to antineoplastic therapy. Unlike simple starvation, this metabolic response leads to visceral tissue depletion, labelled bypoalbuminemic malnutrition (Harvey et al., 1979). Additional tissue cytokines result in protein wasting, depletion of body fat, and decreased food intake (Fong et al., 1989). The consequence of this cancer cachexia is cell-mediated immune deficiency. Excess morbidity and mortality result from opportunistic infection and failure of wound healing. It is also important to recognize that in some patients specific micronutrient deficiencies, such as iron, calcium, magnesium, or vitamin B12 deficiency can be present even in the absence of weight loss and can be devastating (Blackburn et al., 1977).

ADJUNCTIVE NUTRITION SUPPORT DURING ANTINEOPLASTIC TREATMENT

Indications for TPN may arise from antineoplastic treatments that include perioperative, chemotherapy, radiotherapy, or bone marrow transplantation. Most cancer patients remain in normal nutrition status up to the time of initial diagnosis, and even during early periods of therapy. The majority of advanced cancer patients with a solid tumor of the abdomen become malnourished in association with cancer therapies involving multiple operations, palliative radiation, and repeated courses of chemotherapy particularly with high doses and combinations of toxic drugs. The use of nutritional therapy in the cancer patient is tailored to complement the primary treatment. The purpose is to improve fitness, metabolic status, and body composition - all of which will improve quality of life. Properly administered nutrition support using tailored prescription of macronutrients and micronutrients, such as in Table 1, can prevent most symptoms of malnutrition (Blackburn and Giardiello, 1995; Maliakkal et al., 1992).

Table 1: Patient-Specific Feeding for Cancer Patients with Standard Stock Solutions Using a Single Source in 2000ml or Less
Nutritional Goals Met¹
Weight (kg) Amino acids
[conc./
vol (ml)]
Dextrose
[conc./
vol (ml)]
Lipids
[conc./
vol (ml)]
Final volume
[(ml)]
Protein or
amino acids
/kg/day
kcal/kg
/day
% of lipid calories²
40 5.5%/1000 40%/500 10%/250 1750 1.4 28 20¹
50 15%/500 30%/1000 10%/250 1750 1.5 31 15
60 8.5%/1000 70%/500 20%/250 1750 1.4 33 23
70 10%/1000 70%/500 20%/250 1750 1.4 29 22
80 11.4%/1000 70%/500 20%/250 1750 1.4 25 18
90 11.4%/1000 70%/500 20%/100
20%/250
1850 1.3 25 28
100 15%/1000 70%/500 10%/250
20%/250
2000 1.5 25 27
1) Nutritional Goals: 1.2-1.5 g protein/kg/day; 25-35kcal/kg (inc. protein); 15-30% kcal as lipids.
2) Does not include glycerol calories contained in lipid emulsion.
Adapted from Driscoll and Blackburn (1990)

Perioperative TPN Support of Cancer Therapy

Given the differing approaches to TPN therapy, cancer type, and status of malnutrition, meta-analysis is unsuitable for evaluation of preoperative and postoperative cancer surgery. Klein and Koretz (1994) reviewed 22 prospective randomized clinical studies evaluating the clinical efficacy of parenteral nutrition in cancer patients undergoing a surgical resection. Only 5 of the 22 studies showed statistically significant differences in clinical outcomes (Harvey et al., 1979; Maliakkal et al., 1992; Heatley et al., 1979; Muller et al., 1982; Yamada et al., 1980). Critical to this meta-analysis is identifying overfeeding reflected in hyperglycemia and excessive fluid retention (Anonymous, 1991; Muller et al., 1986). Also, patients with esophageal and gastric cancers should be separately evaluated, as they have significant malnutrition as a result of mechanical obstruction, anorexia, and resistance to nutritional support of body cell mass (Muller et al., 1982; Yamada et al., 1983).

Muller and colleagues (1982) reported that preoperative parenteral feeding in patients with gastrointestinal carcinoma decreased mortality and postoperative complications including infection. This report is important given the large sample size (n = 125) and controls of overfeeding (Muller et al., 1982). This study also confirmed the benefit of nutritional and immunologic biomarkers in patients given 10 days of preoperative nutrition support (Blackburn and Giardiello, 1995); Yamada et al.,1983). Likewise, Heatley reported beneficial effects of preoperative parenteral nutrition, including decreased postoperative complications (Heatley et al., 1979). A large multicenter Veterans Administration Cooperative Study found in a subset of malnourished patients decreased postoperative complications in the TPN group compared to the control group (Anonymous, 1991). However, the infection rate was higher in the TPN group than the control group. Further analysis of VA study showed that because the TPN group may have resulted in hyperglycemia and attributed to their higher infection rate. Askanazi and colleagues (1986) showed that immediate postoperative nutrition supports shorten the length of hospitalization. Fan and colleagues (1994) recently reported on the use of perioperative TPN in patients undergoing hepatectomy for hepatocellular carcinomas and demonstrated a clear benefit from TPN with fewer infection and better liver function. In summary, carefully crafted parenteral nutrition in a properly selected malnourished cancer patient in a perioperative setting is beneficial (Driscoll and Blackburn, 1990).

Total Parenteral Nutrition Support during Chemotherapy

In malnourished patients receiving chemotherapy, TPN induces improvements in body weight which is important for successful treatment at the optimal schedule (Shike et al., 1984; Lowry et al., 1981). although TPN can improve some nutritional parameters, the final outcome on mortality and morbidity when given in conjunction with effective chemotherapy is inconclusive. In reviewing eight prospective randomized clinical trials involving the use of TPN in patients undergoing chemotherapy (Popp et al., 1981; Nixon et al., 1981; Shamberger et al., 1983, 1984; Russell et al., 1984; Serrou and Cupissol, 1981; Jordan et al., 1981; DeCicco et al., 1993), the majority showed no advantage in overall survival in those receiving nutritional support. However, the combination of drugs used for chemotherapy were ineffective. Only one study reported by Serrou and Cupissol (1981) showed an increased survival of squamous cell lung cancer patients who were receiving parenteral nutrition support. Nixon and colleagues (1981) reported decreased survival in metastatic colorectal cancer patients receiving total parenteral nutrition. De Cicco and colleagues (1993) reported higher toxicity in those patients with adenocarcinoma of lung receiving chemotherapy and TPN. Two additional meta-analyses showed TPN provides no added benefit in survival, tumor response, or chemotherapy toxicity in cancer patients undergoing chemotherapy (Klein et al., 1986; McGeer et al., 1990). In summary, the provision of TPN during chemotherapy should be reserved for those patients with hypoalbuminemia or weight loss of greater than 10% who are responsive to prescribed dose and schedule of chemotherapy.

Total Parenteral Nutrition Support in Radiation Therapy

Most Studies examining the use of TPN during radiation therapy contained a small sample size and failed to stratify by disease, pretreatment group differences, nutritional status, or concomitant therapies. Four prospective and mixed controlled studies reviewed the effect of TPN in patients undergoing radiation therapy for cancer and showed no difference in survival or radiation therapy-induced side effects between those receiving TPN and the control group (Solassol et al., 1980; Kinsella et al., 1981; Valeiro et al., 1978; Ghavimi et al., 1982; Donaldson et al., 1982; Klein and Koretz, 1994). In addition, the infection rate was greater with hyperalimentation (TPN) in those who are undergoing abdominal radiation and chemotherapy (Ghavimi et al., 1982). Sikora and colleagues observed that TPN facilitates standard chemotherapy along with concomitant radiation therapy (CRT) administration in esophageal cancer patients (1998). Inadequate studies have been conducted with CRT to properly evaluate TPN and radiation therapy.

Total Parenteral Nutrition Support during Allogenic Bone Marrow Transplantation

Bone marrow transplantation requires intensive chemotherapy and often radiation leading to esophagitis and enteritis, resulting in severe malnutrition. It produced negative nitrogen balances and a greater loss of lean body mass than body weight or fat mass. Weisdorf reported increased survival and decreased relapse in those patients who received TPN compared to control subjects (Weisdorf et al., 1987). These results suggest that among patients receiving bone marrow transplants, those who cannot eat for a prolonged period, particularly if they are severely malnourished, may benefit from TPN. A prospective randomized study by Szeluga showed no differences in survival between TPN and enteral nutrition support in bone marrow transplant recipients (Szeluga et al., 1992). Schloerb found similar benefits in patients with both hematologic malignancies and solid tumors (Schloerb and Amare, 1993).

NUTRITION ASSESSMENT AND GOALS

Guidelines for assessment of nutritional status include subjective global assessment tools (Ottery, 1995) (Table 1), and individual screening tools, including body mass index, percent of weight loss, serum albumin and transferrin levels, anthropometric, and delayed hypersensitivity (Keenan and Blackburn, 1981; Cohn and Blackburn, 1982). Complete nutritional assessment of the cancer patient requires determination of nutrition needs as well as assessment of metabolic stress. Estimation of energy needs can be derived using Harris-Benedict equations:

BMR for males = 66 + 13.8W + 5H - 6.8A

BMR for females = 665 + 9.6W + 1.8H - 4.7A

where BMR is basal metabolic rate in kcal/24 hours, W is weight in kilograms, H is height in centimeters, and A is age in years (Harris and Benedict, 1919). The best method for determining the caloric needs for the critically ill cancer patient is the measurement of energy expenditure by indirect calorimetry. The resting energy expenditure can be easily obtainable at the bedside using a portable gas analyzer or "metabolic cart." The resting energy expenditure in the critically ill was estimated as 22 to 25 kcal/kg of body weight (Harris and Benedict, 1919). In addition, the simultaneous measurement of the respiratory quotient (RQ) by the metabolic cart is often helpful in determining the mixed-fuel requirement. If the RQ ration equals 1.0 the utilization of energy is strictly carbohydrate, whereas an RQ ratio of 0.7 means utilization of energy consists mainly of lipid. The RQ ratio of mixed fuel energy utilization is approximately 0.85. Protein requirements typically range from 1.2 to 1.5 g/kg of body weight per day. Protein provided in excess of 2.0 g/kg of body weight per day exceeds the body's maximal utilization rate and contributes to ureagenesis (Directors, 1986). In addition, the net lipogenesis significantly increases oxygen consumption and carbon dioxide production, resulting in an increased respiratory quotient (i.e. RQ > 1.0). One way to minimize the development of hepatic and respiratory problems associated with dextrose overfeeding is to provide a portion of the calories in the TPN as lipid. Lipid administration should provide approximately 30% of total calories. The excessive provision of lipids (i.e. >50% of total calories), specifically long-chain triglycerides of the omega-6 family, the principal source of lipids in parenteral lipid emulsions, has been associated with reticuloendothelial system dysfunction. A minimum of 3 to 4% of total calories as omega-6 fatty acids prevents essential fatty acid deficiency. A wide range of fluid abnormalities in cancer patients arises from the disease process and consequences of therapies (i.e., surgery, chemotherapy, radiation therapy). In the absence of fluid restriction, the average semistressed cancer patient requires approximately 30 to 35 ml of fluid per kg per day. Electrolyte (sodium, potassium, calcium, magnesium, phosphate), mineral, and vitamin requirements for patients with cancer are essentially the same as patients with nonmalignant forms of disease.

BIOCHEMICAL MEDIATORS AND TREATMENT OF CANCER ASSOCIATED WASTING

Cancer cachexia is a complex metabolic syndrome resulting from inadequate food intake, ineffective host utilization of nutrients, and persistent erosion of body cell mass in response to host or tumor-derived factors (Hunter et al., 1989; Kern and Norton, 1988). It often leads to death if not recognized and treated properly. Certain tumors predispose individuals to cancer cachexia. Breast cancer, hematologic cancers, and sarcomas rarely result in significant host weight loss compared with cancers involving the lung, prostate, or digestive organs such as the stomach, colon, and pancreas.

The cytokines tumor necrosis factor, interleukin 1 and 6, and alpha-interferon have been linked to cancer anorexia. These cytokines are secreted by immune cells and are part of the cell-mediated immunity host defense as well as antigen-mediated tumor cell death. In progressive therapy in advanced cancers, these cytokines have been shown to result in anorexia and alterations in carbohydrate, protein, and lipid metabolism. Mobilization of nutrients from fat and skeletal muscle during the acute phase of sepsis or in trauma patients rapidly provides a physiologic source of nutrients to the liver so that it can synthesize acute injury proteins. The low-grade release of cytokines persists in the cancer patients because of the metabolic activity of the tumor and eventually caused depletion of host cell mass. The anorexia of chemotherapy, radiotherapy, and surgery exacerbates this process, adding to the net effect of host depletion. The "at-risk" cancer patient can be identified by a rapid weight loss of greater than 10% of usual body weight (Cohn and Blackburn, 1982).

Insulin has been studied as an anabolic agent in the treatment of cancer cachexia because of its tumor-associated alterations in carbohydrate metabolism and insulin resistance. Pearlstone and colleagues (1994) have shown that parenteral nutrition administered with insulin (1mU per kg of body weight per minute for 4 days) to cancer patients results in improved skeletal muscle protein synthesis and whole-body protein net balance compared to TPN alone.

Another anabolic agent that has been extensively investigated is growth hormone. Ziegler and colleagues (1988) reported that growth hormone attenuates the loss of body protein when administered to patients without cancer. Studies involving growth hormone as a nutrition adjunct in patients with cancer have been limited due to fear of stimulating tumor growth (Brennan, 1981). Animal studies and in vivo human tumor studies showed no increase in tumor volume (Wolf et al., 1994; Harrison et al., 1997; Harrison and Brennan, 1995). Further studies in insulin and growth hormones are needed to examine clinical outcomes in cancer patients.

There has been recent emphasis on the use of glutamine supplementation in both enteral and parenteral nutrition. Glutamine is a nonessential and most abundant amino acid in the blood and tissues that is often depleted in patients with cancers. It is an important fuel for enterocyets, colonocytes and lymphoid tissue (Smith 1997). A nitrogen donor, it is necessary for the synthesis of purines and pyrimidines. Significant depletion occurs in catabolic states. Debate continues over whether glutamine is conditionally essential during critical illness in cancer patients. Standard TPN solutions in the United States do not contain glutamine because of instability issues. Glutamine in solution undergoes hydrolysis to produce pyroglutamate within days; this process is pH and temperature dependent. It has been reported that free glutamine supplemented TPN was able to be stored at 5oC for up to 6 weeks without loss of more than 5% of the glutamine (Smith, 1997; Akibi, 1989a). In the United States, the majority of studies involving glutamine supplemented nutrition used free L-glutamine. In Europe, glutamine dipeptide is utilized in parenteral nutrition (Akibi, 1989a,b). Glutamine-enriched TPN is hypothesized to decrease the recurrence of systemic infection in those patients who are predisposed. Klimberg and colleagues (1990) have shown that addition of glutamine in TPN improves nitrogen balance and promotes protein synthesis without stimulating tumor growth. Clinical and metabolic efficacy of glutamine-enriched TPN in patients undergoing a bone marrow transplant have been examined. Ziegler and colleagues (1992) in a double-blinded prospective trial found that patients receiving glutamine-enriched TPN had an improved nitrogen balance, fewer infections, less fluid accumulation, and shortened length of hospitalization compared with patients receiving standard TPN. In contrast, Schloerb and Amare (1993) have reported similar rates of survival, infections, and length of hospitalization when involving patients with both hematologic and solid tumors.

HOME TOTAL PARENTERAL NUTRITION FOR CANCER PATIENTS

The knowledge and understanding of benefits, risks and complications related to home parenteral nutrition (HPN) has increased in the past three decades. Long-term TPN in the home can be administered to appropriately selected patients (Blackburn and Baptista, 1984). The availability of HPN has broadened the scope of cancer and its related treatments. In the United States, cancer and its related treatments attributed to 40-60% of home parenteral nutrition population (Broviac and Scribner, 1974; Shils et al., 1970).

Patients with a curable malignancy who require aggressive treatment resulting in anorexia, nausea, vomiting, and/or ileus may benefit from home total parenteral nutrition (HPN). Individuals who are cured from their primary cancer but are left with bowel dysfunction from irradiation or extensive surgical resections (i.e., short gut) may also benefit from HPN. Survival rates and TPN-related complications in such patients are comparable to those seen in patients with benign diseases (Crohn's disease, ulcerative colitis, superior mesenteric artery thrombosis) who require HPN. Among patients with a metastatic disease and poor prognosis, HPN does not offer such a benefit. Only 15% of such patients survive longer than 1 year on HPN (Howard et al., 1995). HPN preserves nutritional status and improves weight, lymphocyte counts, and serum albumin.

Enteral feedings in the home setting are both physiologically and financially preferred to parenteral nutrition. However, patients who cannot tolerate enteral feedings may benefit from HPN. Approximately 20% of home patients receive parenteral nutrition support and 80% receive enteral nutrition support (Howard, 1993).

August and colleagues (1991) studied patients with inoperable malignant bowel obstruction using HPN and found beneficial effects with average survival of greter than 40 days. Bozzetti evaluated the use of TPN in severely cachectic patients with advanced cancer and found improvement in body weight, triceps skinfolds, arm fat area, retinol binding protein, and nitrogen balance (Bozzetti et al., 1982).

CONCLUSION

Cancer cachexia results from decreased intakes as well as metabolic alterations due to the influence of tumor or as a result of antineoplastic treatment. The clinician must not only identify those patients at risk for malnutrition but must also identify those who will benefit from nutrition support.

Parenteral nutrition is an effective method of delivering nutrients and providing metabolic support. It is invaluable and lifesaving for patients with chronic severe gastrointestinal insufficiency such as short bowel syndrome of radiation enteritis. The role of TPN is as an adjuvant therapy. Routine use of TPN in the well-nourished or mildly malnourished patient with cancer has not been shown to be beneficial. The clinician must carefully assess the severity of malnutrition (Mitch, 1998), treatment options, and potential improvement of quality of life in the cancer patient before opting for the use of nutrition support as an adjunctive therapy. Decisions regarding nonvolitional feeding require various consultations with attending physician, patient and family.

TPN as an adjuvant to chemotherapy does not seem to be useful unless there are prolonged periods of gastrointestinal toxicity such as allogenic bone marrow transplantations that severely limit oral intake and absorption. Conversely, perioperative TPN in a properly selected cancer patient has been shown to be beneficial. Optimal nutrition improves therapeutic modalities and the clinical course and outcome in cancer patients. The enteral route is always preferable to TPN in terms of function, cost, and convenience. Newer surgical and endoscopic techniques in placing feeding tubes make enteral feeding more accessible and the treatment of choice. Short-term transition as continuation of TPN and enteral may facilitate management of cancer cachexia.



References

Adibi, S.A. (1989a). Intravenous use of glutamine in peptide form: Clinical applications of old and new observations. Metab. Clin. Exp.38, 89-92.

Adibi, S.A. (1989b). Glycyl-dipeptides: New substrates for protein nutrition. J. Lab. Clin. Med. 113, 665-673.

Anonymous (1991). Perioperative total parenteral nutrition in surgical patients. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group [see comments]. N. Engl. J. Med, 325, 525-532.

Apovian, C.M.., Still, C.D., and Blackburn, G.L. (1998). Nutrition support. In "Principles and Practice of Supportive Oncology" (A.Berger, R.K. Portenoy, and D.E. Weissman, eds.), pp. 571-588. Lippincott-Raven, Philadelphia and New York.

Askanazi, J., Hensle, T.W., Starker, P.M. et al. (1986). Effect of immediate postoperative nutritional support on length of hospitalization. Ann. Surg. 203, 236-239.

August, D. A., Thorn, D., Fisher, R.L., and Welchek, C.M. (1991). Home parenteral nutrition for patients with inoperable malignant bowel obstruction [see comments]. JPEN, J. Parenter. Enteral. Nutr. 15, 323-327.

Bistrian, B.R., Blackburn, G.I., Vitale, J., Cochran, D., and Naylor, J. (1976). Prevalence of malnutition in general medical patients. JAMA, J. Am. Med. Assoc. 235,1567-1570.

Blackburn, G.L., and Baptista,, R.J. (1984). Home TPN: State of the Art, Am.J.Intraven.Ther.Clin.Nutr., p.p. 20-32.

Blackburn, G.L., and Giardiello, F.M. (1995). Developing strategies for intervention/prevention trials of individuals at risk of hereditary colon cancer. JNCI Monogr. 17, 107-110.

Blackburn, G.L., Maini, B.S., bistrian, B.R., and mcDermott, W.V. Jr., (1977). The effect of cancer on nitrogen, electrolyte, and mineral metabolism. Cancer Res. 37, 2348-2353.

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

Brennan, M.F., (1981). Total parenteral nutrition in the cancer patient. N.Engl.J.Med. 305 375-382.

Broviac, J.W., and Scribner, B.H. (1974). Prolonged parenteral nutrition in home. Surg.Gynecol.Obstet. 139, 24-28.

Buzby, G.P., Williford, W.O., Peterson, O.L. et al. (1988a). A randomized clinical trial of total parenteral nutrition in malnourished surgical patients: The rationale and impact of previous clinical trials and pilot study on protocol design. Am.J.Clin.Nutr. 47, 357-365.

Buzby, G.P., Knox, L.S., Crosby, L.O. et al. (1988b). Study protocol: a randomized clinical trial of total parenteral nutrition in malnourished surgical patients: the rationale and impact of previous clinical trials and pilot study on protocol design. Am.J.Clin.Nutr. 47, 366-381.

Cohn, K.H., and Blackburn, G.L., (1982). Nutritional assessment: Clinical and biometric measurements of hospital patients at risk. J.Med.Assoc., GA 71, 27-35.

De Cicco, M., Panarello, G., Fantin, D. et al. (1993). Parenteral nutrition in cancer patients receiving chemotherapy: Effects on toxicity and nutritional status. JPEN, J.Parenter.Enteral.Nutr.17, 513-518.

Detsky, A.S., Baker, J.P., O'Rourke, K., and Goel, V. (1987). Perioperative parenteral nutrition: A meta-analysis. Ann.Intern.Med. 10, 195-203.

Dewys, W.D., Begg, C., Lavin, P.T. et al. (1980). Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am.J.Med. 69, 491-497.

Directors, A.B. (1986). Guidelines for the use of total parenteral nutrition in the hospitalized patient. JPEN, J.Parenter.Enteral.Nutr., pp. 441-444.

Donaldson, S.S., Wesley, M.N., Ghavimi, F., Shils, M.E., Suskind, R.M., and DeWys, W.D. (1982): A prospective randomized clinical trial of total parenteral nutrition in children with cancer. Med.Pediatr.Oncol. 10, 129-139.

Driscoll, D.F., and Blackburn, G.L. (1990). Total parenteral nutrition. A review of its current status in hospitalized patients, and the need for patient-specific feeding. Drugs 40, 346-363.

Fan, S.T., Lo, C.M., Lai, E.C., Chu, K.M., Liu, C.L., and Wong, J. (1994). Perioperative nutritiona support in patients undergoing hepatectomy for hepatocellular carcinoma. N.EngJ.Med. 33, 1547-1552.

Fong, Y., Modawer, L.L., Marano, M., et al. (1989). Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. Am.J.Phys.Med. 256, R659-R665.

Ghavimi, F., Shils, M.E., Scott, B.F., Brown, M., and Tamaroff, M. (1982). Comparison of morbidity in children requiring abdominal radiation and chemotherapy, with and without total parenteral nutrition. J.Pediatr. 101, 530-537.

Harris, J.A., and Benedict, F.G. (1919). A biometric study of basal metabolism in man. Carnegie Inst. Washington Publ. 279.

Harrison, L.E., and Brennan, M.F. (1995). The role of total parenteral nutrition in the patient with cancer. Curr. Probl. Surg. 32, 833-917.

Harrison, L.E., Hochwald, S.N., Heslin, M.J., Berman, R., Burt, M., and Brennan, M.F. (1997). Early postoperative enteral nutrition improves peripheral protein kinetics in upper gastrointestinal cancer patients undergoing complete resection: a randomized trial. JPEN, J.Parenter.Enteral.Nutr. 21, 202-207.

Harvey, K.B., Bothe, A. Jr., and Blackburn, G.L. (1979). Nutritional assessment and patient outcome during oncological therapy. Cancer 43, 2065-2069.

Harvey, K.B., Blumenkrantz, M.J., Levine, S.E., and Blackburn, G.L. (1980). Nutritional assessment and treatment of chronic renal failure. Am.J.Clin.Nutr. 33, 1586-1597.

Heatley, R.V., Williams, R.H., and Lewis, M.H. (1979). Pre-operative intravenous feeding - a controlled trial. Postgrad.Med.J. 55, 541-554.

Howard, L. (1993). Home parenteral and enteral nutrition in cancer patients. Cancer 72, 3531-3541.

Howard, L., Ament, M., Fleming, C.R., Shike, M., and Steiger, F. (1995). Current use and clinical outcome of home parenteral and enteral nutrition therapies in the United States. Gastroenterology 109, 355-365.

Hunter, D.C., weintraub, M., Blackburn, G.I., and Bistrian, B.R. (1989). Branched chain amino acids as the protein component of parenteral nutrition in cancer cachexia. Br.J.Surg. 76, 149-153.

Jordan, W.M., Valdivieso, M., Frankmann, C. et al. (1981). Treatment of advanced adenocarcinoma of the lung with ftorafur, doxorubicin, cyclophosphamide, and cisplatin (FACP) and intensive IV hyperalimentation. Cancer Treat.Rep. 65, 197-205.

Kaminski, M.V. Jr., Haase, T.J., Rosas, M., and Butler, G. (1990). Parenteral nutrition in cancer patients undergoing chemotherapy: A meta-analysis [letter]. Nutrition 6, 336-337.

Kawamura, L., Moldawer, L.L., Keenan, R.A. et al (1982). Altered amino acid kinetics in rats with progressive tumor growth. Cancer Res. 42, 824-829.

Keenan, R.A., and Blackburn, G.L. (1981). Clinical nutritional assessment of the hospitalized patient. Surg.Rounds, pp.34-44.

Kern, K.A., and Norton, J.A. (1988). Cancer cachexia. JPEN, J.Parenter.Enteral.Nutr. 12, 286-298.

Kinsella, T.J., Malcolm, A.W., Bothe, A. Jr., Valerio, D., and Blackburn, G.L. (1981). Prospective study of nutritional support during pelvic irradiation. Int.J.Radiat. Oncol.Biol.Phys. 7, 543-548.

Klein, S., and Koretz, R.L. (1994). Nutrition support in patients with cancer: What do the data really show? [see comments]. Nutr.Clin.Pract. 9, 91-100.

Klein, S., Simes, J., and Blackburn, G.L. (1986). Total parenteral nutrition and cancer clinical trials. Cancer 58, 1378-1386.

Klimberg, V.S., Souba, W.W., Salloum, R.M. et al (1990). Glutamine-enriched diets support muscle glutamine metabolism without stimulating tumor growth. J.Surg.Res. 48, 319-323.

Lowry, S.F., Smith, J.C. Jr., and Brennan, M.F. (1981). Zinc and copper replacement during total parenteral nutrition. Am.J.Clin.Nutr. 34, 1853-1860.

Maliakkal, R.J., Blackburn, G.L., Willcutts, H.D. et al. (1992). Optimal design of clinical outcome studies in nutrition and cancer: Future directions. JPEN, J.Parenter.Enteral.Nutr. 16, 112S-116S.

McGeer, A.J., Detsky, A.S., O'Rourke, K. (1990). Parenteral nutrition in cancer patients undergoing chemotherapy: A meta-analysis. Nutrition 6, 233-240.

Mitch, W.E. (1998). Mechanisms causing loss of lean body mass in kidney disease. Am.J.Clin.Nutr. 67, 359-366.

Muller, J.M., Brenner, U., Dienst, C., and Pichlmaier, H. (1982). Preoperative parenteral feeding in patients with gastrointestinal carcinoma. Lancet 1, 68-71.

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

Nixon, D.W. (1982). Hyperalimentation in the undernourished cancer patient. Cancer Res. 42, 727s-728s.

Nixon, D.W., Moffitt, S., Lawson, D.H. et al. (1981) Total parenteral nutrition as an adjunct to chemotherapy of metastatic colorectal cancer. Cancer Treat.Rep. 65, 121-128.

Ottery, F.D. (1995). Supportive nutrition to prevent cachexia and improve quality of life. Semin.Oncol. 22, 98-111.

Pearlstone, D.B., Wolf, R.F., Berman, R.S., Burt, M., and Brennan, M.F. (1994). Effect of systemic insulin on protein kinetics in postoperative cancer patients. Ann.Surg.Oncol. 1, 321-332.

Popp, M.B., Fisher, R.I., Wesley, R., Aamodt, R., and Brennan, M.F. (1981). A prospective randomized study of adjuvant parenteral nutrition in the treatment of advanced diffuse lymphoma: Influence on survival. Surgery 90, 195-203.

Russell, D.M., Shike, M., Marliss, E.B. et al. (1984). Effects of total parenteral nutrition and chemotherapy on the metabolic derangements in small cell lung cancer. Cancer Res. 44, 1706-1711.

Schloerb, P.R., and Amare, M. (1993). Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study) [see comments]. JPEN, J.Parenter.Enteral.Nutr. 17, 407-413.

Serrou, B., and Cupissol, D. (1981). Nutritional support and the immune system in cancer management. A critical review. Cancer Treat.Rep. 65, 115-120.

Shamberger, R.C., Pizzo, P.A., Goodgame, J.T.Jr., et al. (1983). The effect of total parenteral nutrition on chemotherapy-induced myelosuppression. A randomized study. Am.J.Med. 74, 40-48.

Shamberger, R.C., Brennan, M.F., Goodgame, J.T. Jr., et al (1984). A prospective, randomized study of adjuvant parenteral nutrition in the treatment of sarcomas: Results of metabolic and survival studies. Surgery 96, 1-13.

Shike, M., Russel, D.M., Detsky, A.S. et al (1984). 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. 101, 303-390.

Shils, M.E., Wright, W.L., Turnbull, A., and Brescia, F. (1970). Long-term parenteral nutrition through an external arteriovenous shunt. N.Eng.J.Med. 283, 341-344.

Sikora, S.S., Riberiro, U., Kane, J.M., Landreneau, R.J., Lembersky, B., and Posner, M.C. (1998). Role of nutrition support during induction chemoradiation therapy in esophageal center. JPEN, J.Parenter.Enteral.Nutr. 22, 18-21.

Smith, R.J. (1997). Glutamine-supplemented nutrition [editorial; comment]. JPEN, J.Parenter.Enteral.Nutr. 21, 183-184.

Solassol, C., Joyeux, H., Astruc, B. et al (1980). Complete nutrients mixtures with lipids for total parenteral nutrition in cancer patients. Acto.Chir.Scand.Suppl. 498, 151-154.

Szeluga, D.J., Stuart, R.K., Brookmeyer, R., Utermoblen, V., and Santos, G.W. (1987). Nutritional support of bone marrow transplant recipients: A prospective, randomized clinical trial comparing total parenteral nutrition to an enteral feeding program. Cancer Res. 47, 3309-3316.

Torosian, M.H. (1992). Stimulation of tumor growth by nutrition support. JPEN, J.Parenter.Enteral.Nutr. 16, 72S-75S.

Valerio, D., Overett, L., Malcolm, A., and Blackburn, G.L. (1978). Nutritional support for cancer patients receiving abdominal and pelvic radiotherapy: A randomized prospective clinical experiment of intravenous versus oral feeding. Surg.Forum 29, 145-148.

Weisdorf, S.A., Lysne, J., Wind, D. et al. (1987). Positive effect of prophylactic total parenteral nutrition on long-term outcome of bone marrow transplantation. Transplantation 43, 833-838.

Wolf, R.F., Ng, B., Weksler, B., Burt, M., and Brennan, M.F. (1994). Effect of growth hormone on tumor and host in an animal model. Ann.Surg.Oncol. 1, 314-320.

Yamada, N., Koyama, H., Hioki, K., Yamada, T., and Yamamoto, M. (1983). Effect of postoperative total parenteral nutrition (TPN) as an adjunct to gastrectomy for advanced gastric carcinoma. Br.J.Surg. 70, 267-274.

Ziegler, T.R., Young, L.S., Manson, J.M., and Wilmore, D.W. (1988). Metabolic effects of recombinant human growth hormone in patients receiving parenteral nutrition. Ann.Surg. 208, 6-16.

Ziegler, T.R., Young, L.S., Benfall, K et al (1992). Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Ann.Intern.Med. 116, 821-828.

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