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The influence of alternate forms of nutritional support on primary tumor growth rate, tumor DNA synthesis rate, and number of lung metastases was examined in Swiss mice bearing subcutaneously implanted Lewis lung carcinoma (LLC). From Day 14 through 22 postimplant, mice were fed by continuous intravenous infusion of dextrose/amino acid (TPN), were offered the same solution from a feeding bottle (PO), were offered a casein-based, solid diet (CASEIN), or were infused with an electrolyte (ELECT) solution while energy and nitrogen were provided from the casein diet. Tumor weight and doubling time were decreased in the PO group compared to CASEIN; however, host weight decreased by 22% in the PO group. Tumor weight and DNA synthesis were decreased in the TPN group compared to CASEIN, and host weight increased by 4.6%. The decreased rate of tumor growth in the PO group was not reflected in a decrease in DNA synthesis, perhaps a result of the circadian pattern of DNA synthesis as previously reported for LLC. The number of metastatic lung nodules was significantly decreased in both the TPN and ELECT groups compared to PO and CASEIN, suggesting that intravenous fluid load rather than nutrient intake was the causative factor. In this host-tumor system, parenteral feeding was associated with a decrease in primary tumor weight and DNA synthesis rate, maintenance of host weight, and a decrease in pulmonary metastatic disease compared to mice fed a conventional diet.

The effect of N-free energy substrate manipulation on tumor growth and metastasis, host maintenance, and intermediary metabolism was studied in parenterally fed Swiss mice bearing subcutaneously implanted Lewis lung carcinoma. Non-N energy was provided from dextrose (CHO), lipid emulsion (FAT), or a 75:25 balanced (BAL) solution, infused from day 14 through day 22 postimplant. Control mice were offered equivalent energy and N from a balanced, casein-based solid diet (CAS). Tumor-doubling time was significantly prolonged in the CHO group compared to FAT and CAS. Pulmonary metastatic nodules were decreased in number in all parenterally fed mice compared to CAS, suggesting that the route of administration altered pulmonary physiology in such a way that the transmissability and/or growth of the tumor cells was inhibited. Tumor-free body weight was maintained in the CHO (+ 1.3%) and BAL (+ 0.3%) groups. However, significant weight loss occurred, despite equal intake, in the FAT (-4.7%) and CAS (-7.5%) groups. The energy appeared to be channeled into nonoxidative pathways, reflected by an increase in hepatic and adipose tissue lipogenesis and hepatic glycogen content. During the period studied, parenteral dextrose/amino acid infusion in this host-tumor system resulted in a decrease in primary tumor growth and optimal host maintenance compared to fat-based TPN and enteral feeding of a balanced, solid diet. Tumor metastasis was decreased in all parenterally fed mice, a phenomenon related to the route of administration and apparently independent of energy substrate.

The role of dietary manipulation of tumor growth, metastasis and immunologic parameters was studied in mice bearing Lewis lung carcinoma. Fourteen days following subcutaneous tumor implant, groups with tumor and their non-tumor bearing counterparts were assigned to one of the following feeding protocols: total parenteral nutrition (TPN), per oral (PO) intake of the parenteral diet, an oral casein diet (CAS), or electrolyte infusion plus the casein diet (ELECT). Intakes of energy and nitrogen were similar among all groups. Mice were killed 12 days later and peritoneal macrophages were tested for phagocytic activity. Tumor growth and metastasis were decreased from both infusion regimens with minimal loss of body weight as compared with casein fed mice. PO mice also showed lower tumor weight but metastasis was as great as in the casein group. Non-tumor-bearing infused mice showed depressed thymic weight, but thymic weight was not further reduced in tumor-bearing infused mice. PO feeding afforded no such protection in the presence of the carcinoma. Splenomegaly was observed in tumor-bearing mice on all regimens, but mice maintained on the parenteral diet demonstrated the largest proportion of macrophages containing nuclear debris. Analysis of free macrophages indicated no effect of diet regimen on non-immune phagocytic activity in both tumor-free and tumor-bearing mice. Possible alteration of splenic macrophage intracellular digestive capacity or phagocytic activity was suggested as a result of TPN.

Malnutrition is a common accompaniment of malignant disease and clearly places the cancer patient at increased risk. Adequate nutritional rehabilitation of the malnourished cancer patient can correct abnormal nutritional indices. In the surgical patient, this has been shown to decrease perioperative morbidity and mortality. Nutritionally repleted patients undergoing radiation or chemotherapy may be more tolerant and, therefore, more likely to respond to treatment although, thus far, a favorable effect on outcome has not been demonstrated conclusively. Patients who are to receive multimodal treatment with chemotherapy, radiotherapy, and surgery are at a particularly high risk for the development of malnutrition, and the institution of one treatment may be predicated on recovery from the previous therapy. When a major abdominal surgical procedure is part of the treatment plan, TPN may be required to prevent malnutrition in an otherwise nutritionally intact patient at the outset of therapy. For patients in whom TPN is indicated, adequate nutritional restoration is of paramount importance. Calories and nitrogen in excess of amounts predicted for noncancer patients may be required. Sequential nutritional assessment is a must to assure the adequacy of nutritional repletion. Considerations of cost and simplicity make the enteral route the preferred avenue for nutritional repletion if the gut is available for use. Certainly, when indicated, however, the risk and expense of parenteral nutrition is justified, particularly in the surgical patient. At present there are no data to justify the use of one particular amino acid formulation or energy source over another. A balanced amino acid solution with glucose as the primary energy source seems equally as efficacious as specialized amino acid formulas and lipid as the primary calorie source.

Total parenteral nutrition (TPN) with fat and/or glucose as the caloric source is associated with a decrease in pulmonary metastasis in mice bearing subcutaneously implanted Lewis lung carcinoma. Five groups of white mice bearing Lewis lung carcinoma were assigned to receive various isocaloric and isonitrogenous oral and parenteral feedings: TPN, utilizing all nonnitrogen energy from glucose; per os, utilizing all nonnitrogen calories from glucose; electrolyte, utilizing nonnitrogen calories provided from a balanced casein diet and receiving an isovolemic infusion of electrolytes in the same composition as the TPN formula; 1/4 normal saline, also consuming the casein diet and receiving an isovolemic infusion of 1/4 normal saline; and an oral casein control (CON) without infusion. Results showed that there were no significant differences in tumor volume changes or tumor doubling time among the groups. However, tumor weight was significantly lower in groups receiving the TPN solution either orally or parenterally in comparison to the oral casein control. Pulmonary metastases were significantly lower in all parenteral groups, irrespective of solution composition, compared to the CON group. Thus it appears that parenteral fluid load rather than composition of the solution is the causative factor for the decrease in pulmonary metastases.