Mouse extensor digitorum longus muscle preparation as a tool in nutrition research: a quantitative comparison to in vivo and cell culture experiments.

Incubated restrained and unrestrained extensor digitorum longus (EDL) muscles from adult non-growing mice were evaluated as a tool in non-steady state nutrition experiments. Energy state was determined by nucleotide determinations in muscles. Protein synthesis was estimated by the amount of L-[U-14C]phenylalanine incorporated into proteins, and protein balance was measured by tyrosine release from muscle proteins. Confluent cultured L6 rat muscle cells served as a reference system in steady state without hypoxia being sensitive to growth factors and regulatory peptides at physiologic concentrations. Irrespective of medium composition, incubated EDL muscles remained in negative protein balance, being unrelated to the resting tension of the incubated muscles. Energy-rich phosphates were not restored to normal levels during incubation, but protein synthesis was not attenuated by the decline in energy state. Fractional protein synthesis (0.05-0.15%/h) remained constant for up to 6 h of EDL incubation, and was comparable to protein synthesis in cultured confluent non-proliferating myocytes (0.20-0.30%/h) and to mixed leg muscles measured in vivo (0.10-0.20%/h). Protein synthesis in incubated EDL muscles reflected alterations in muscle peptide formation in vivo following either oral provision of food or parenteral injection of insulin. EDL muscles were sensitive to in vitro exposure to both insulin (60-125 microU/mL) and insulin-like growth factor 1 (IGF-1) (1000 ng/mL). The sensitivity to insulin seemed to be modified by the nutritional state (starved/fed) of the animals before sacrifice. Protein synthesis in EDL muscles was less responsive to serum-containing growth factors (IGF-1, epidermal growth factor [EGF], platelet-derived growth factor [PDGF]) compared to confluent L6 muscle cells, which probably reflected different receptor expression. Our results demonstrate that protein metabolism in incubated unrestrained mouse EDL muscles reflects in vivo protein metabolism.

Small bowel length in inflammatory bowel disease.

UNLABELLED: Small intestinal length has a particular significance in patients with inflammatory bowel disease (IBD). A determination of intestinal length by a standardised and simple technique is of interest for surgical decision making in primary and recurrent disease and in the evaluation and management of postoperative malabsorption. The aim of the present investigation was to analyse intestinal length in patients with IBD and define a standard method for this measurement. MATERIAL AND METHODS: Two consecutive series of patients. Crohn's disease (n = 279) and ulcerative colitis (n = 315) and a control group (n = 77) underwent standardised intra-operative small intestinal length measurement. RESULTS: Small intestinal length correlated to weight and height and was less in women than in men (P < 0.001) in both IBD groups and the controls. The small bowel in patients with Crohn's disease was significantly shorter than in patients with ulcerative colitis and in controls, P < 0.001. Also in Ulcerative Colitis small bowel length was significantly less than in controls, P < 0.001. In CD patients there was no difference in bowel length with regards to the anatomical extent of the disease. Original small bowel-length in patients with CD and one or two bowel resections (n = 67) was not different from that in patients with three or more resections (n = 88). CONCLUSION: Small bowel length correlated to weight, height and sex. Patients with CD had a significantly shorter small intestine at first laparotomy, compared with U.C. patients and controls. In CD-patients there was no difference between the anatomical subgroups.

Are cytokines possible mediators of cancer cachexia?

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.

Effects related to indomethacin prolonged survival and decreased tumor-growth in a mouse-tumor model with cytokine dependent cancer cachexia.

Tumor-bearing mice with two different locally growing malignant tumors (epithelial like, MCG 101; malignant melanoma, K1735-M2) were used to evaluate the putative role of prostaglandins for survival and local tumor growth in experimental cancer. Daily systemic injections of indomethacin (1 mu g/g bw) were used to block prostaglandin production in normal and T-cell deficient tumor-bearing nude mice. Tumor progression was determined by measurements of tumor weight, DNA-synthesis, cell cycle kinetics in vivo and in vitro (flow cytometry), tumor tissue concentrations of polyamines (putrescine, spermidine, spermine) and tumor tissue gene expression of growth regulating factors (IL-1 alpha, IL-6, TNF alpha, A,B-PDGF, EGF, VEGF, bFGF, TGF beta(3), angiogenin and transferrin receptor). Tumor tissue content of von Willebrandt factor VIII was estimated by immunohistochemistry. Indomethacin had no effect on survival, host nutritional state or local tumor growth in mice bearing the malignant melanoma with low PGE(2) production. In contrast, indomethacin prolonged survival, improved cachexia and decreased tumor growth in mice bearing the MCG 101 tumor with hundredfold higher prostaglandin tumor production, leading to elevated liver and muscle tissue as well as plasma concentrations of PGE(2). Indomethacin inhibited almost completely the high tumor PGE(2) production in MCG tumors, leading to prolonged potential doubling time for tumor growth in vivo, and a trend to decreased tumor tissue concentration of polyamines (spermidine). Indomethacin had no inhibitory effect on tumor cell proliferation in vitro, although PGE(2) production was decreased by 75%. The effect of indomethacin in vivo was independent of T-cells and was observed with similar magnitude irrespective of the number of MCG cells (10(4)-10(6)) implanted or the site of implantation (s.c., i.p., liver, lung, skeletal muscles). Tumor growth inhibition by indomethacin was not intrinsically transferable by tumor cells from indomethacin treated tumor-animals. Tumor expression of mRNA for several growth regulating factors were either increased (IL-6, TNF alpha, GM-CSF, TGF beta(3)) unchanged (EGF, VEGF, PDGF A,B, IL-1 alpha, transferrin receptor) or decreased (b-FGF and angiogenin) (p<0.05) by indomethacin treatment of MCG mice. Decreased tumor content of von Willebrandt factor VIII in combination with an attenuated tumor vasculature were associated with decreased tumor growth (p<0.05). Our results confirm that high tumor production of prostaglandins was related to reduced survival. Tumor prostaglandins probably promote local tumor growth by stimulation of tumor surrounding cells to produce growth factor(s) for tumor angiogenesis including tumor and matrix cell proliferation unrelated to immune cells.

Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors.

Eicosanoids may be important factors for tumor cell proliferation, metastatic formation, and development of cancer cachexia. The present study has evaluated the effect of anti-inflammatory treatment on tumor progression in clinical cancer. Patients (n = 135) with insidious or overt malnutrition due to generalized malignancy (various kinds of solid tumors) and an expected survival of more than 6 months were randomized by a computer-based algorithm to receive placebo, prednisolone (10 mg twice daily), or indomethacin (50 mg twice daily) p.o. until death. Patient groups were stratified in the randomization procedure for sex, tumor type, stage, nutritional state, and previous tumor treatment, and biochemical, physiological, and some functional variables (Karnowsky index, fatigue and pain score). A majority of these variables was then registered during the follow-up. Indomethacin and prednisolone treatment maintained Karnowsky index, while placebo-treated patients experienced a decreased index. Indomethacin-treated patients suffered less pain and consumed less additional analgetics compared to the other patient groups. Indomethacin prolonged mean survival compared to placebo-treated patients from 250 +/- 28 days to 510 +/- 28 days (P < 0.05). Survival analysis on observations from all patients treated with either indomethacin or prednisolone demonstrated a significantly prolonged survival by anti-inflammatory treatment compared to placebo treatment (log rank, P < 0.03). The results suggest that not only may prostaglandin synthesis inhibition offer palliative support to patients with solid advanced cancer, but it may also impact on pathways that ultimately determine outcome.

The effect of clenbuterol on body composition in spontaneously eating tumour-bearing mice.

The aim of this study was to investigate the effect of a selective beta 2-adrenoceptor agonist, clenbuterol, on body composition in tumour-bearing adult and growing mice. Therefore, adult female C57/BL6 mice (n = 20) were inoculated subcutaneously with a 3-methylcholanthrene-induced sarcoma and divided into two identical groups. One group received injections twice a day of clenbuterol corresponding to 1 mg/kg body weight, the other group received sham injections. Growing mice (n = 20) were similarly divided after tumour inoculation into one study group with clenbuterol injections and one control group. The growing animals were sacrificed on day 11 after commencement of treatment, the adult mice on day 16. Clenbuterol treatment had no statistically significant effect on accumulated food intake or body composition in the adult mice. However, food intake in these animals increased numerically compared to control animals after day 11 of the study. Tumour growth was also unaffected. The growing animals displayed an increased carcass dry weight with borderline significance (p = 0.06) and an increased quadriceps muscle fat free dry weight after clenbuterol treatment. Tumour growth was not affected. Food intake measured on a daily basis was significantly increased in the growing clenbuterol treated animals and accumulated food intake was increased with a trend towards statistical significance (p = 0.06). The results support the suggestion that treatment with a selective beta 2-adrenoceptor agonist does not improve body composition in tumour-bearing adult mice relying on spontaneous food intake while growing animals may benefit from such treatment.

Incidence and characteristics of pouchitis in the Kock continent ileostomy and the pelvic pouch.

The incidence, the median time to first appearance, and the clinical pattern of pouchitis were prospectively studied in 180 patients operated on for ulcerative proctocolitis with a continent ileostomy (CI; 84 patients) and a pelvic pouch (PP; 96 patients). Median follow-up for CI patients was 8.5 years (range, 2-15 years) and for PP patients, 5 years (range, 1-8 years). Pouchitis, with symptoms severe enough to require treatment, developed in 33% (28 of 84) of CI and 47% (45 of 96) of PP patients. The cumulative risk of developing one or more episodes of pouchitis over a 5-year follow-up was 34% in CI patients and 51% in PP patients. The median time to first appearance of pouchitis was 5 and 12 months, respectively. Eighty-six per cent of CI patients with pouchitis (24 of 28) and 71% of PP patients (32 of 45) experienced their initial episode within the first 2 years. Sixty-four per cent (18 of 28) of the CI patients and 76% (34 of 45) of PP patients had one single or a few short-lasting episodes of pouchitis with various symptom-free intervals, whereas 18% of patients in each group (5 of 28 CI patients, 8 of 45 PP patients) had frequent relapses. Most of these patients responded promptly to metronidazole treatment. Eighteen per cent (5 of 28) of CI patients and 6% (3 of 45) of PP patients had long-lasting episodes with a poor response to treatment. In this long-term study the pouch inflammation proved eventually to be Crohn's disease in four patients (2.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium and potassium excretion in patients with ileostomies.

The output of sodium and potassium from urine and ileostomy was investigated in 35 healthy patients with ileostomies; 17 had undergone proctocolectomy for ulcerative colitis and 18 for Crohn's colitis. Fifteen of the patients with Crohn's disease had also had small bowel resections, varying from 15 to 46% of the original bowel length. The patients were investigated at home because most studies of sodium and water balance in patients with ileostomies have been done in hospital wards, which may not reflect actual conditions. Mean (SD) ileostomy output was 565 (152) ml in patients with ulcerative colitis and 1,267 (540) ml in patients with Crohn's disease. The intrapatient variation was limited, whereas the interpatient variation was significant and correlated with the length of small bowel resected. The sodium concentration in the ileostomy discharge was 110 (9.2) mmol/l and did not change consistently with ileostomy volume. The potassium concentration was 10 (2.1) mmol/l. There was a significant inverse correlation between daily ileostomy sodium output and urinary sodium concentration (r = -0.44, p less than 0.01), and a significant correlation between the daily output of sodium in ileostomy contents and the sodium:potassium ratio in urine. We conclude that patients with ileostomies are at risk of sodium and water depletion, particularly those who have had small bowel resections. Increased sodium output from the ileostomy is associated with a reduction in the sodium:potassium ratio in the urine. To screen patients at risk, an estimate of the sodium balance can be made by measuring sodium and potassium concentrations in a single specimen of urine.

Gynaecological problems related to anatomical changes after conventional proctocolectomy and ileostomy.

Seventy-one women who had a proctocolectomy for ulcerative colitis (n = 41) or Crohn's disease (n = 30) were interviewed in the follow-up clinic about gynaecological problems and fertility. All women were examined by an independent gynaecologist and abnormalities of the internal genital tract were registered. Forty-nine per cent (35/71) of the women had a distressing vaginal discharge after proctocolectomy, compared with 9% (6/71) before surgery. At the gynaecological examination 45% (32/71) had a heavy vaginal secretion with- out any signs of an acute vaginal infection. In 68% (30/44) fluid retention in the vagina was associated with a caudally firmly fixed and dilated posterior vaginal fornix. Twelve per cent (8/66) of the women reported dyspareunia before surgery. After surgery, 27% (18/66) complained of this symptom. Fertility was significantly reduced after surgery since only 37% (10/27) of the women who attempted to become pregnant succeeded within 5 years follow-up. The corresponding figure before surgery was 72% (39/54). Those who conceived went through pregnancy and parturition without any incident, 6 of 21 delivered by caesarean incision. In conclusion, conventional proctocolectomy in women will result in distressing vaginal discharge, and dyspareunia in a considerable proportion of the patients. The operation also seems to decrease their chances of becoming pregnant.

The cause of death in non-metastasizing sarcoma-bearing mice. A study with relevance for tumor treatment experiments in mice.

Adult sarcoma-bearing mice were used to demonstrate whether hypoglycemia was the immediate cause of death in experimental animals with rapidly growing tumors without metastases. This kind of tumor model is representative of the majority of animal models used in experimental cancer research. Tumor-bearing animals died with severe hypoglycemia under all experimental conditions, while pair-killed controls were normoglycemic. Anorexia prevented tumor-bearing animals from attenuating the hypoglycemia by drinking glucose-containing water while completely starved control animals survived more than 14 days with glucose-containing water as the only energy source. Adrenalectomy shortened survival in tumor-bearing animals, but survival of adrenalectomized tumor-bearing animals could be normalized by daily injections of pharmacologic doses of hydrocortisone (25 mg/25 g body wt/day) but not by physiologic replacement (20 micrograms/25 g body wt/day). Injections of pharmacologic doses of hydrocortisone did not influence on survival or body composition in tumor-bearing animals with intact adrenals. Glucagon was without effect on either survival, tumor growth or body composition. Based on the results in this study and in our previous reports we conclude that hypoglycemia is the cause of death in the majority of murine tumor models. This hypoglycemic theory is important, since any treatment modality in animal experiments that influences glucose metabolism in the host may indirectly change tumor growth and may thus be misinterpreted as a direct tumor effect.

Increased urinary excretion of cortisol and catecholami-NES in malnourished cancer patients.

Excretion of cortisol and catecholamines were measured from 24-hour urine samples collected over a period of 3 days from hospitalized cancer patients suffering from malnutrition and were compared with those of control patients equally malnourished and having a similar degree of inflammation. Compared with control patients, cancer patients had a higher excretion of cortisol, adrenaline, and noradrenaline, although noradrenaline excretion reached statistical significance only when normalized to creatinine excretion. Plasma glycerol concentrations after an overnight fast were significantly higher in cancer patients as compared with control patients, in keeping with an increased adrenal and adrenergic activity. This study demonstrates evidence of simultaneously elevated catecholamine and cortisol excretion in cancer patients, which could not be ascribed to alteration in body composition. The results may, in part, explain the mechanisms behind ongoing tissue breakdown in progressive cancer disease.

Interleukin 1 and tumor necrosis factor do not regulate protein balance in skeletal muscle.

Recent studies have claimed that interleukin 1-containing preparations increase skeletal protein degradation similar to that seen during infection and inflammation. However, preparations employed have contained other products of activated macrophages, including tumor necrosis factor-alpha. In the present report, we investigated the capability of recombinant-derived murine and human interleukins 1-alpha and 1-beta and human tumor necrosis factor-alpha to affect skeletal protein synthesis and degradation both in vitro and in vivo. Partially purified products of Staphylococcus albus-stimulated human blood monocytes increased skeletal protein degradation both in vivo and in vitro. However, none of the recombinant interleukin 1 nor the human tumor necrosis factor-alpha preparations had any impact on skeletal protein balance. Both recombinant interleukin 1 and tumor necrosis factor-alpha stimulated the production of prostaglandin E2 (PGE2). Furthermore, a polyclonal antibody to human interleukin 1 eliminated the lymphoproliferative response to partially purified monocyte preparations (interleukin 1 activity), but failed to abrogate the increased skeletal protein degradation in vitro. This study demonstrates that although interleukin 1 and tumor necrosis factor-alpha induce a PGE2 response by skeletal muscle in vitro, some macrophage product distinct from either interleukin 1 or tumor necrosis factor-alpha is responsible for the accelerated skeletal protein degradation seen with partially purified human blood monocyte products. Elevated PGE2 levels do not appear to regulate skeletal protein balance in vitro.

Growth hormone and experimental cancer cachexia.

Plasma levels of growth hormone (GH) and the effect of GH treatment have been evaluated in adult nongrowing sarcoma-bearing mice (C57BL/6J). Prepubertal tumor-bearing mice, tumor-bearing hypophysectomized Sprague-Dawley rats, and malnourished non-tumor-bearing animals served as additional groups of study and control animals. Adult sarcoma-bearing mice showed an increase in plasma levels of GH early following tumor implantation. GH levels increased further with tumor progression. The anorexia and the state of malnutrition in sarcoma-bearing mice were the major factors behind increased GH levels. Muscle wasting and body composition in the tumor-bearing host were not improved by GH treatment at doses that increased growth rate in normal growing mice with intact pituitaries or partially normalized growth rate in hypophysectomized rats. Exogenous GH supported tumor growth and host body growth to the same extent in hypophysectomized rats. Exogenous GH in excess of endogenous GH did not stimulate tumor growth further. It is suggested that increased GH production in a tumor-bearing host acts in concert with other hormones to stimulate endogenous substrate mobilization and in tumor-bearing animals to prevent substrate deficiency and hypoglycemia. On the basis of this conclusion, it is unlikely that GH supplementation to a freely eating tumor-bearing host will support replenishment of host tissues.

Tumor-host wasting not explained by adrenal hyperfunction in tumor-bearing animals.

This study addressed the question of whether hypercorticism in tumor-bearing animals contributes to the wasting of body fat and lean body mass, particularly that of skeletal muscles. For this purpose, hydrocortisone-substituted nongrowing sarcoma-bearing and control C57BL/6J mice were used that were either adrenalectomized or sham-operated prior to experimentation. Adrenalectomy in itself did not alter food intake or body composition in normal animals. Tumor-bearing mice and pair-weighted control animals had elevated urinary excretion of corticosteroids compared with the urinary excretion in freely fed controls. The malignant tumor induced the well-recognized wasting in tumor-bearing animals, irrespective of the presence of the adrenal glands. Therefore, an elevated corticosteroid production did not account for the wasting of body fat, lean body mass, skeletal muscle proteins, or decreased RNA activity in quadriceps muscles from tumor-bearing animals, although such muscles were sensitive to physiologic doses of injected hydrocortisone (20 micrograms/day). Tyrosine aminotransferase (TAT) activity in liver tissue from tumor-bearing animals was higher than that induced by pharmacologic doses of hydrocortisone in normal animals. Physiologic doses of hydrocortisone induced hepatic TAT activity, but pair-weighed control animals with the same degree of hypercorticism as was found in tumor-bearing animals had normal TAT activity in liver tissue. Although hypercorticism is present in tumor-bearing animals, the results demonstrate that cancer cachexia can start and proceed independently of the adrenal glands. Therefore, adrenal hyperfunction is not the proximate cause for the development of experimental cancer cachexia induced by anorexia.

Antibiotic prophylaxis in high-risk gastric surgery. A prospective, randomized clinical comparison of cefuroxime and doxycycline.

The efficacy of two antibiotics as prophylaxis in high-risk gastric surgery was evaluated in a prospective, randomized trial: 400 mg doxycycline in a single dose (98 patients) was compared with 1.5 g cefuroxime given twice with an 8-hour interval (101 patients). The two groups were comparable in regard to all relevant factors of importance for susceptibility to infection. The incidence of postoperative abdominal infection was 8.2% in the doxycycline group and 7.9% in the cefuroxime group. The most common extraabdominal infectious complications were in the lungs (20% of the patients in both groups). No subgroup of patients was identifiable in which one antibiotic was superior to the other. The efficacy of the two investigated prophylaxis regimens was apparently identical.

The Kock continent ileostomy: influence of a defunctioning ileostomy and nipple valve stapling on early and late morbidity.

Early and late morbidity was studied in 45 consecutive patients submitted to the Kock continent ileostomy reservoir procedure protected by a temporary loop ileostomy. In 24 patients the nipple valve was made by simple intussusception of the ileal segment after stripping of its mesenteric peritoneum and fat, whereas in 21 patients the nipple valve was stapled in addition. The early complication rate was low with necrosis of the nipple valve occurring in 3 patients and a nipple valve fistula in 1. These complications were easily dealt with and revision was done subsequently on an elective basis. The overall revision rate for late nipple valve dysfunction, mainly caused by sliding of the nipple valve was 29%. The majority of these complications occurred within the first postoperative year. Stapling of the nipple valve did not significantly reduce the rate of sliding. The overall complication rate was significantly less compared with a historical series of 21 patients not provided with a loop ileostomy. A temporary defunctioning ileostomy may reduce early complications and their consequences. Whether it may also lessen the risk of later nipple valve sliding is, however, not clear from this study. The observation that sliding was as common in both unstapled and stapled patients could imply either that the loop ileostomy is beneficial in preventing this complication or that the stapling procedure is in this respect unimportant. Which step or steps among all the measures employed are important in increasing the success rate of this operation remains unclear. Randomised controlled studies are needed for a true evaluation of this issue.

Role of insulin in development of cancer cachexia in nongrowing sarcoma-bearing mice: special reference to muscle wasting.

This study evaluated whether altered insulin metabolism is a key factor behind weight loss during sarcoma growth in nongrowing mice (C57BL/6J). Fasted sarcoma-bearing mice had decreased blood glucose concentrations but unchanged levels of insulin, compared with those in pair-weighed and freely fed controls. During refeeding, insulin levels were inappropriately low for the degree of glycemia in sarcoma-bearing mice compared with those of pair-weighed and freely fed controls. Injections ip of glucose to tumor-bearing animals resulted in insulin levels comparable to postabsorptive values in healthy control animals, indicating that hypoinsulinemia in freely eating tumor-bearing animals was due to a reduced glycemic sensitivity for pancreatic insulin release. Insulin supplementation at doses [4 IU/100 g (body wt)] that increase body fat in normal animals could not protect the tumor-bearing host from progressive loss of body fat or lean tissues. Exogenous insulin in excess of endogenous insulin production did not stimulate tumor growth. Nitrogen and RNA-DNA content were significantly decreased in the quadriceps muscle of tumor-bearing mice. This reduction was independent of altered insulin levels and could not be prevented by exogenous insulin. The depressed capacity of protein synthesis in extensor digitorum longus (EDL) muscle could be entirely attributed to the state of malnutrition in tumor-bearing animals. The sensitivity and responsiveness of protein synthesis in EDL muscles to insulin were normal in tumor-bearing mice, regardless of whether exogenous insulin exerted its effect in vivo or in vitro. This study confirms insulin resistance for glucose metabolism in an experimental sarcoma animal model. Such changes are concluded to be secondary to anorexia and necessary to counteract hypoglycemia. In non-growing sarcoma-bearing mice, malnutrition and anorexia account entirely for depressed muscle protein synthesis, which is not explained by insulin resistance at the translational level. Insulin metabolism is not a key factor behind progression of wasting in sarcoma-bearing mice, but anorexia is.

Thermic effect and substrate oxidation in response to intravenous nutrition in cancer patients who lose weight.

This study examined oxidative metabolism and thermogenesis in the acute response to controlled intravenous nutrition in seven cancer patients who lost weight. Six weight-losing and malnourished patients without cancer served as controls. Indirect calorimetry was used and measurements of arterial concentrations of various substrates, metabolic end products, and insulin were performed. Resting energy expenditure (REE) was measured after an overnight fast. The resting energy need was calculated for each patient according to REE. The nutrition program consisted of glucose and lipids (Intralipid KabiVitrum AB, Stockholm, Sweden) each as 50% of nonprotein calories and amino acids (6.9 mg N/kcal). These substrates were infused simultaneously at rates equivalent to one, two, and three times REE, over periods of 6.5 hours on 3 consecutive days after a 12-hour fast. Arterial substrate levels and energy expenditure were measured between 6 and 6.5 hours after the start of the infusion. The cancer patients had well-recognized metabolic changes in the fasted state, such as elevated plasma levels of glycerol, triglycerides, free fatty acids, and lactate, and higher energy expenditure than predicted. The cancer patients responded to strictly defined substrate challenge in a similar way as the malnourished patients without cancer. Whole body oxidative capacity and the proportion of infused glucose and lipids that were oxidized at different levels of infusion rates were not decreased in cancer patients compared with control patients. Similar arterial substrate concentrations among the groups during infusions argues for a maintained plasma clearance of the substrate in the cancer patients. This study supports the suggestion that cachectic cancer patients can generate and conserve energy normally in response to intravenous nutrition. This refers to cancer patients with a history of weight loss up to 15% of their normal body weight. Therefore, weight loss due to altered tumor-host metabolism in cancer patients is of quantitative importance in the fasted state rather than in the fed state.