Edward M. Copeland

Intravenous hyperalimentation in cancer patients

Abstract Anabolism has been maintained in a series of oncologic patients without a clinically detectable change in the growth characteristics of the cancer. Tumor response to chemotherapy was not abolished, surgical morbidity and mortality were minimized, and the undesirable side effects of radiotherapy and chemotherapy were reduced.

Intravenous hyperalimentation as an adjunct to radiation therapy

Radiation therapy may induce anorexia with resultant weight loss and inanition that can limit the dose of radiation therapy administered. The purpose of this study was to evaluate 39 nutritionally‐depleted patients who had a variety of malignant diseases treated with radiation therapy and concomitant nutritional support with intravenous hyperalimentation (IVH). The average dose of radiation delivered was 3827 rads in an average of 3.5 weeks. Ninety‐five percent of the patients completed their planned course of radiation therapy and improved symptomatically. Fifty‐four percent of the patients responded with a greater than 50% reduction in tumor size. Responding patients gained an average weight of 13.0 ± 6.5 lbs. during IVH (av. 36.2 days) and radiation therapy (av. 3832 rads), whereas non‐responding patients gained only 4.9 ± 8.8 lbs. (p < 0.001) during IVH (av. 42.8 days) and radiation therapy (av. 3819 rads). Serum albumin concentrations rose from 3.12 ± 0.49 gm/100 ml to 3.51 ± 0.68 gm/100 ml (p < 0.05) during treatment in responding patients but did not rise significantly from 3.09 ± 0.48 gm/100 ml in non‐responding patients. In conclusion, IVH allowed a planned course of radiation therapy to be delivered to a group of poor‐risk, malnourished cancer patients, and a positive correlation between tumor response and nutritional status was identified. Moreover, IVH was a valuable adjunct in the treatment of six patients who had enteric fistulas that originated from radiated bowel.

Immune Function during Intravenous Administration of a Soybean Oil Emulsion

The effect of a continuous infusion of a soybean oil emulsion on immune function was evaluated in 40 malnourished patients who were randomized to receive preoperatively either a 25% glucose-5% amino acid solution (group G) or a 15% glucose-3.3% Intralipid-5% amino acid solution (group G-F). Average length of total parenteral nutrition (TPN) was 10.3 +/- 0.9 days for group G and 9.0 +/- 0.8 days for group G-F. Initial nutritional status and response to TPN were similar for both groups. Immune function was assessed before TPN and after nutritional repletion prior to surgery for each patient. The levels of immunoglobulins, C3, C4, circulating B lymphocytes and T lymphocytes, suppressor T lymphocytes, natural killer cell activity, and monocytes were normal before TPN and after nutritional therapy. However, the total number of T cells and helper T cells were low before TPN and remained so after TPN. In addition, lymphocyte function measured by the lymphocyte blastogenic response to phytohemagglutinin and pokeweed mitogen was depressed prior to TPN and was not improved by either regimen. Neutrophil chemotaxis and bactericidal activity were not affected by either nutritional regimen while neutrophil phagocytosis was enhanced before TPN and remained elevated throughout TPN with either regimen. There were no differences in infection rates during TPN. The addition of Intralipid to the TPN regimen did not alter immune function in these patients who showed depressed cell-mediated immunity before TPN compared with the standard glucose TPN regimen.

The effect of protein nutrition on host and tumor metabolism

Since the introduction of intravenous hyperalimentation (IVH) as a nutritional adjunct in multimodal cancer therapy (X), the risk of providing nutrient substrates for more rapid tumor growth has been a concern of those who use IVH to rehabilitate malnourished cancer patients nutritionally. Because of the technical difficulties in studying glucose and amino acid utilization in cancer patients, an experimental model was designed to simulate the nutritional problems encountered in cachectic cancer patients. Tumor-bearing rats were protein depleted with a protein-free diet, and then randomized into three groups which either continued on the protein-free diet, resumed a regular protein diet, or received intravenous hyperalimentation. By manipulating the dietary protein intake, the effects of protein restriction and repletion on host and tumor metabolism could be compared and related to the clinical situation in which hyperalimentation is used to replete malnourished cancer patients nutritionally. Host and tumor metabolism were evaluated by measuring the activity of three important enzymes that control glucose production and specific amino acid degradation. Fructose 1,6-diphosphatase (FDPase, EC 3.1.3.11) is considered one of the rate-limiting enzymes in the gluconeogenic pathway because of its slow kinetics and irreversible catalytic action (25). Glutamate -pyruvate transaminate (GPT, L-alanine:Z

Interorgan glutamine metabolism in the tumor-bearing rat

The effects of progressive malignant disease on gut/liver glutamine metabolism were studied in order to gain further insight into the altered glutamine metabolism that characterizes the host with cancer and to further elucidate the causes and consequences of glutamine depletion in tumor-bearing rats. Rats were inoculated on Day 0 with 2 X 10(6) viable fibrosarcoma cells and blood glutamine was measured every 6 days. On Day 24 the animals underwent laparotomy and sampling of arterial, portal venous, and hepatic venous blood. Arterial glutamine fell by more than one-third in tumor-bearing rats and the arterial-portal venous concentration difference for glutamine across the intestinal tract was diminished by 50% (P less than 0.01). Simultaneously the fractional extraction of glutamine by the gut was reduced from 21 to 15% (P less than 0.05). The liver switched from an organ of near glutamine balance in control rats to one of marked glutamine output in tumor-bearing rats (P less than 0.01). The wet weight of the small intestine was diminished by 15% in tumor-bearing rats and villous height was uniformly decreased in tumor-bearing rats with an average reduction in villous height of 26% (P less than 0.05). The causes of glutamine depletion in this tumor-bearing rat model remain unclear. The growing tumor may behave as a glutamine trap but also appears to alter glutamine metabolism in vital metabolic processing centers such as the gut and liver. Malignant cells may compete with gut mucosal cells for glutamine resulting in a diminished gut glutamine utilization and detrimental changes in mucosal architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutrition, cancer, and intravenous hyperalimentation

In over 1000 cancer patients treated with intravenous hyperalimentation (IVH), tumor growth has not been identified and catheter‐related sepsis has been minimal. Studies in rats demonstrated that the host benefits more than the tumor during nutritional repletion, and any stimulation of tumor growth in the rat‐tumor model could be manipulated with DNA specific drugs to benefit the host. A study of 65 malnourished cancer patients undergoing oncologic therapy and treated with IVH indicated that much of the immune suppression in these patients was the result of malnutrition coincident with or secondary to oncologic treatment. Conclusions reached in this study were that nutritional repletion resulted in a return of skin test reactivity, proper wound healing in the surgical patient, and possibly an increase in response to chemotherapy. Certainly, the use of IVH allowed specific oncologic therapy to be administered to a group of malnourished patients who otherwise might not have been acceptable candidates for intensive antineoplastic therapy.

Intravenous hyperalimentation as an adjunct to cancer chemotherapy with 5-fluorouracil

Abstract In a series of 30 male Sprague-Dawley rats fed orally, the LD-80 dosage of 5-FU was determined to be 15 mg/kg/day for 7 days. When this dosage was given to a series of rats nourished entirely parenterally by intravenous hyperalimentation, there was a lower incidence of gastrointestinal toxicity, and the mean survival rate was twice that obtained in the orally fed group. In a pilot series of 10 cachectic human beings with metastatic adenocarcinoma of the colon, who were treated simultaneously with 5-FU and intravenous hyperalimentation, the incidence of gastrointestinal side effects was significantly reduced, tolerance to 5-FU per unit time was doubled, and response rate (50% reduction in measurable tumor mass) was 40%, which is greater than that usually reported in comparable patients fed by mouth.

Intravenous hyperalimentation in patients with head and neck cancer.

Intravenous hyperalimentation was utilized to support nutritionally 23 malnourished patients with major head and neck tumors during surgical treatment, radiotherapy, or the convalescent period. Fifteen patients were treated during the perioperative period and 12 survived. Six patients received convalescent nutritional support successfully 4 to 24 months following operation or radiation treatment. Two patients received treatment with hyperalimentation throughout a protracted course of radiation therapy. Weight gain, wound healing, and recovery were achieved in all but 3 patients. Subclavian vein thrombosis occurred in 1 patient, and catheter‐related sepsis occurred in 2 patients. Otherwise, hyperalimentation was safe and efficacious in the debilitated patients. These patients may now become acceptable risks for surgical treatment or radiation therapy by nutritional repletion with intravenous hyperalimentation.

Inguinal node metastases

Twenty‐two hundred and thirty‐two patients with inguinal node metastases were reviewed. The primary site of malignancy was determined in 2210 (99%) of these patients and was, in order of frequency, skin of the lower extremities, cervix, vulva, skin of the trunk, rectum and anus, ovary and penis. The determinant three‐year survival rate for the remaining 22 patients with metastatic disease from an unknown primary site was 50%. The source of the primary (stomach) was discovered in only one of the 22 patients; however, the treatment of choice was superficial groin dissection, and if surgical excision was adequate, radiation therapy did not appear to be necessary to obtain local control.

Nutritional repletion of malnourished tumor-bearing and nontumor-bearing rats: Effects on body weight, liver, muscle, and tumor☆

Effects of nutritional repletion were evaluated in malnourished rats with either no tumor (NTB), small tumor burdens (TB), or large tumor burdens (TB). One hundred and four Sprague-Dawley rats were inoculated with Walker-256 carcinosarcoma and were fed regular diet (RD) for 5 days in Study A. At this time, one group was maintained on RD while the remaining rats were fed a high carbohydrate, protein-free diet (PFD). On Day 15, one PFD group was switched to RD; one PFD group continued on PFD. Eighty-nine NTB rats received an identical dietary protocol. Animals were killed on Days 15, 21, and 33. Mean food intake and carcass weight changes were similar in corresponding groups of TB and NTB rats in Study A. After Day 15, mean carcass weight and liver and muscle protein content increased rapidly in PFD → RD TB and NTB rats, becoming similar to the RD group by Day 33. By Day 33, mean tumor weights and mean total tumor protein content in the PFD group were significantly less than the RD or PFD → RD groups. In Study B, tumor-bearing animals were fed regular diet for 20 days after tumor inoculation to produce a larger tumor burden prior to nutritional depletion. Twelve rats were given PFD; six rats continued on the RD. On Day 30, one PFD group (n = 6) was switched to RD while the other PFD group (n = 6) continued on PFD. On Day 36, all rats were sacrificed. Mean carcass weight, liver, and muscle protein levels at sacrifice were significantly less in the PFD → RD group compared with the RD group, but mean serum protein levels were similar in the two groups. Animals co