Michael E. Burt

A controlled, prospective, randomized trial evaluating the metabolic effects of enteral and parenteral nutrition in the cancer patient.

In order to evaluate the metabolic effects of enteral versus parenteral nutritional support in the cancer patient, patients with localized, squamous cell carcinoma of the distal esophagus were randomized to one of three nutritional regimens: oral feeding, jejunal feeding, or total parenteral nutrition (TPN). Patients were initially studied in the postabsorptive state and again two weeks after beginning, and while receiving, enteral or parenteral feedings. Radioisotopic tracer methods were utilized to evaluate parameters of glucose and alanine kinetics, and arterial substrate and hormone levels were measured. Arterial plasma glucose and blood lactate levels increased and plasma free fatty acid, serum triglyceride, and serum cholesterol levels decreased to comparable levels in patients receiving jejunal feedings or TPN. Changes in serum insulin, plasma glucagon, serum cortisol, serum growth hormone, and serum thyroxine were similar in patients receiving enteral and parenteral nutrition. Enteral and parenteral nutrition also had comparable effects on both alanine and glucose kinetics. In particular, both jejunal feedings and TPN were equally efficacious in markedly suppressing gluconeogenesis in the cancer patient. Our data would support the conclusion that there are few, if any, differences in the measured metabolic effects of enteral versus parenteral nutritional support in the group of cancer patients studied.

Prospective evaluation of aspiration needle, cutting needle, transbronchial, and open lung biopsy in patients with pulmonary infiltrates.

Twenty consecutive patients with pulmonary infiltrates undiagnosed by routine, noninvasive methods were entered into a prospective study designed to evaluate the diagnostic yield of four methods of lung biopsy. Percutaneous aspiration needle, cutting needle, transbronchial, and open (anterior thoracotomy) biopsy were performed synchronously on all patients. Specimens were evaluated by microbiological, virological, and pathological methods. The diagnostic yields of the four methods were as follows: aspiration needle, 29%; cutting needle, 53%; transbronchial, 59%; and open lung biopsy, 94%. Open lung biopsy was significantly better in yielding a diagnosis than aspiration needle (p less than 0.001), cutting needle (p less than 0.001), and transbronchial biopsy (p less than 0.04).

Tendosynovial sarcoma. Clinicopathologic features, treatment, and prognosis

Background. Clinicopathologic features, treatment, and results are reported for 95 tendosynovial sarcomas identified from a prospective sarcoma data base established at Memorial Sloan‐Kettering Cancer Center (MSKCC) in 1982.

Fasting plasma amino acid levels in cancer patients

The concentration in plasma of 15 fasting amino acids were measured in 14 control volunteers and 55 cancer patients. In addition, 16 patients (7 with, 9 without total parenteral nutrition [TPN]) with metastatic sarcoma had sequential amino acid profiles measured during 6 weeks of ablative chemotherapy. In four cancer patient groups (lymphoma, sarcoma, osteosarcoma and metastatic sarcoma) with no or minimal weight loss, most plasma amino acid levels were similar to controls. Proline levels were significantly reduced in the lymphoma and sarcoma patients. Esophageal cancer patients with 20% body weight loss had a marked reduction in total and individual amino acid levels (except branched chain amino acids) compared to controls and all others. The metastatic sarcoma patients who received parenteral nutrition had higher levels of plasma lysine and tyrosine during chemotherapy than controls; however, TPN failed to change the majority of amino acid levels. It appears that plasma amino acid levels except proline were well maintained in cancer patients without weight loss. Esophageal cancer patients with weight loss demonstrated marked reduction in all circulating amino acids except branched chain. Parenteral nutrition did not significantly alter the amino acid profile of cancer patients undergoing chemotherapy.

In vivo utilization of substrate by human sarcoma‐bearing limbs

Human sarcoma‐bearing limb substrate utilization was characterized by studying 10 otherwise healthy patients with extremity sarcomas (five osteosarcomas, five soft tissue sarcomas). All patients were studied in the postabsorptive state. Extremity blood flow was measured using a non‐invasive capacitance plethysmograph. Percutaneous arterial and venous effluent blood samples from the tumor‐bearing (TB) and control extremity were obtained and flux was calculated for free fatty acids (FFA), glucose, and amino acids. The control limb showed a release of amino acids similar to that reported previously. There was a dramatic difference in the TB extremity, which consistently released fewer amino acids. Both the TB and control limbs released FFA at the same rate. A significant difference in glucose uptake between TB and control limbs was noted for soft tissue sarcoma patients but not osteogenic sarcoma patients. The amount extracted correlated with excised tumor size and gluconeogenic amino acid release from the contralateral normal limb. This study suggests that the tumor‐bearing limb ignores the inherent conservation mechanisms in the postabsorptive state and continues to utilize substrate, apparently at the expense of host tissues.

A controlled, randomized trial evaluating the effects of enteral and parenteral nutrition on protein metabolism in cancer-bearing man

To characterize the effects of enteral versus parenteral nutritional support on protein metabolism in the cancer patient, patients with localized, squamous cell carcinoma of the distal esophagus were randomized to receive nutritional support as follows: (1) if there was a loss of less than 20% of the preillness body weight, patients were randomized to continue eating ad libitum (group I) versus receiving total parenteral nutrition (TPN) (group II); (2) if there was a loss greater than 20% of the preillness body weight and/or the patient was unable to swallow, patients were randomized to jejunostomy feedings (group III) versus TPN (group IV). Patients were initially studied in the postabsorptive state and again 2 weeks after beginning, and while receiving, enteral or parenteral feedings. Stable isotopic tracer methods utilizing constant infusion of [15N]glycine were used to determine whole-body protein turnover (flux), synthesis, and catabolism. Skeletal muscle catabolism was determined by measuring the urinary excretion of 3-methylhistidine and lean tissue mass was evaluated by determining total-body potassium by 40K whole-body scanning. Positive nitrogen balance was obtained in groups II and IV associated with significant weight gain in both; the changes in weight were not significant in groups I and III. Whole-body protein flux increased in all groups, but significantly only in group II. Synthesis increased in groups II and IV and decreased in I and III, but not significantly. Catabolism tended to decrease in all groups but group I. Urinary 3-methylhistidine excretion decreased in groups II and IV signifying decreased skeletal muscle catabolism, but increased in groups I and III. Total body potassium tended to increase in groups II and IV. In this group of patients with localized squamous cell carcinoma of the esophagus, both TPN and jejunal feedings tended to stabilize nutritional status and whole-body protein economics. TPN appeared to be slightly more efficacious, although the differences between enteral and parenteral nutritional support in this study were slight.

Peripheral tissue metabolism in cancer-bearing man.

Whole-body tracer studies have documented abnormal glucose and amino acid kinetics in cancer-bearing man. Whether these abnormalities are related to systemic or local tumor effects is questioned. Forearm metabolism was examined in six patients with localized squamous cell carcinoma of the distal esophagus and six healthy normal male volunteers. Substrate arterio-venous differences and blood flow across forearm tissues were determined and substrate flux calculated. The mean forearm blood flow (ml min-1 100 ml forearm-1) was not significantly different between cancer patients (3.67 ± 0.12) and normal subjects (2.80 ± 0.40). The uptake of glucose (μmol min-1 100 ml forearm-1) was significantly higher in cancer patients (1.99 ± 0.45) compared to control subjects without weight loss (0.47 ± 0.18). Lactic acid release (μmol min-1 100 ml forearm-1) was significantly higher in cancer patients (-1.15 ± 0.35) compared to control subjects (-0.26 ± 0.14). There was no significant difference in the flux of individual amino acids between the groups, although the mean total nitrogen released from forearms of cancer-bearing patients was greater than that from normal controls. The arterial serum insulin level was significantly lower and the arterial plasma glucagon level significantly higher in cancer patients compared to control subjects. These data cannot be explained by weight loss alone and suggest a peripheral defect in metabolism in this group of cancer-bearing patients.

Whole‐body protein metabolism in cancer‐bearing patients. Effect of total parenteral nutrition and associated serum insulin response

Aggressive nutritional support of the cancer patient undergoing treatment has become widespread standard practice. In order to evaluate the effect of total parenteral nutrition (TPN) on protein metabolism, 11 patients with localized squamous cell carcinoma of the distal esophagus were studied in the postabsorptive state and again after 2 weeks of TPN. After two weeks of TPN, these cancer patients demonstrated a significant increase in body weight associated with positive nitrogen balance and an insignificant increase in total body potassium (determined by whole body 40K scanning), a measure of lean body mass. Serum transferrin, ceruloplasmin, and total protein did not change significantly, whereas serum albumin decreased significantly (3.5 ± 0.1 to 3.1 ± 0.1 g dl−1). Evaluation of whole‐body protein kinetics by constant infusion of 15N‐glycine demonstrated a significant increase in protein flux (2.79 ± 0.20 to 4.02 ± 0.33 g protein kg−1 day−1). In the group as a whole, protein synthesis increased and catabolism decreased, but not significantly. Skeletal muscle protein catabolism, as measured by the rate of excretion of urinary 3‐methylhistidine (μmol kg−1 day−1) decreased significantly after 2 weeks of TPN (2.5 ± 0.1 to 1.9 ± 0.2). A change from basal to stimulated (TPN) serum insulin level of 40 to 120 μU/ml was found to be associated with optimal changes in protein synthesis and skeletal muscle catabolism. Five patients fell within this optimal range of serum insulin, and demonstrated a significant increase in the rate of whole‐body protein synthesis (2.13 ± 0.35 to 3.56 ± 0.45 g protein kg−1 day−1) with an insignificant increase in whole‐body protein catabolism (2.74 ± 0.42 to 3.16 ± 0.43), and a significant decrease in urinary 3‐methylhistidine excretion (2.50 ± 0.35 to 1.53 ± 0.24) after 2 weeks of TPN. It is concluded that optimum nutritional support with TPN is beneficial to the cancer patients protein economy by stimulating whole body protein synthesis while decreasing skeletal muscle protein catabolism. It is also concluded that there exists a range of serum insulin in which whole‐body protein synthesis and catabolism are optimized. Cancer 53:1246‐1252, 1984.

Germ‐cell tumors in patients with apparently normal testes

Germ‐cell tumors occasionally occur in patients with clinically normal testes. Although data exist correlating serial serum hCG and AFP in germ‐cell neoplasms of testicular origin, the literature is sparse concerning the patients presenting with clinically normal testes. Presented in this report are data to confirm the reliability and usefulness of serial serum hCG and AFP levels in those patients with extragonadal germ‐cell tumors and apparently normal testes. Six patients with nonseminomatous extragonadal tumors are presented. Serial serum hCG and AFP levels correlated with the clinical course in each of the patients. The serum hCG and/or AFP decreased with response to therapy and increased with progression of disease. It is concluded that serial serum hCG and AFP determinations are very useful parameters to evaluate and follow the course of disease in this group of patients.

Growth Hormone, Alone and in Combination With Insulin, Increases Whole Body and Skeletal Muscle Protein Kinetics in Cancer Patients After Surgery

OBJECTIVEnTo investigate the impact of growth hormone, alone and in combination with insulin, on the protein kinetics of patients with upper gastrointestinal (GI) tract cancer who have undergone surgery and are receiving total parenteral nutrition (TPN).nnnSUMMARY BACKGROUND DATAnPatients with malignancies of the upper GI tract are at increased risk for malnutrition and perioperative death and complications. Standard nutritional support has not significantly altered outcome. Growth hormone (GH) and insulin have been shown to have some benefit in patients with cancer; however, their action in patients undergoing resection has not previously been studied.nnnMETHODSnThirty patients undergoing surgery for upper GI tract malignancies were prospectively randomized into one of three nutritional support groups after surgery: 10 patients received standard TPN, 10 received TPN plus daily injections of GH, and 10 received daily GH, systemic insulin, and TPN. The patients underwent a protein kinetic radiotracer study on the fifth day after surgery to determine whole body and skeletal muscle protein kinetics.nnnRESULTSnPatients who received standard TPN only were in a state of negative skeletal muscle protein net balance. Those who received GH and insulin had improved skeletal muscle protein net balance compared with the TPN only group. Whole body protein net balance was improved in the GH and the GH and insulin groups compared with the TPN only group. GH and insulin combined did not improve whole body net balance more than GH alone. GH administration significantly increased serum IGF-1 and GH levels. Insulin infusion significantly increased serum insulin levels and the insulin/glucagon ratio.nnnCONCLUSIONnGrowth hormone and GH plus insulin regimens improve protein kinetic parameters in patients with upper GI tract cancer who are receiving TPN after undergoing surgery.