Ulla Körner

Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: Effects on survival, metabolism, and function

The role of nutrition in the palliative treatment of patients with malignancy‐related cachexia is unclear. The goal of the current study was to determine whether specialized, nutrition‐focused patient care could improve integrated whole‐body metabolism and functional outcome in unselected weight‐losing patients with malignant disease who were receiving systemic antiinflammatory (cyclooxygenase [COX]‐inhibitory) treatment along with erythropoietin (EPO) support.

Insulin Treatment in Cancer Cachexia: Effects on Survival, Metabolism, and Physical Functioning

Purpose: The present study was designed to evaluate whether daily insulin treatment for weight-losing cancer patients attenuates the progression of cancer cachexia and improves metabolism and physical functioning in palliative care. Experimental Design: One hundred and thirty-eight unselected patients with mainly advanced gastrointestinal malignancy were randomized to receive insulin (0.11 ± 0.05 units/kg/d) plus best available palliative support [anti-inflammatory treatment (indomethacin), prevention of anemia (recombinant erythropoietin), and specialized nutritional care (oral supplements + home parenteral nutrition)] according to individual needs. Control patients received the best available palliative support according to the same principles. Health-related quality of life, food intake, resting energy expenditure, body composition, exercise capacity, metabolic efficiency during exercise, and spontaneous daily physical activity as well as blood tests were evaluated during follow-up (30-824 days) according to intention to treat. Results: Patient characteristics at randomizations were almost identical in study and control groups. Insulin treatment for 193 ± 139 days (mean ± SD) significantly stimulated carbohydrate intake, decreased serum-free fatty acids, increased whole body fat, particularly in trunk and leg compartments, whereas fat-free lean tissue mass was unaffected. Insulin treatment improved metabolic efficiency during exercise, but did not increase maximum exercise capacity and spontaneous physical activity. Tumor markers in blood (CEA, CA-125, CA 19-9) did not indicate the stimulation of tumor growth by insulin; a conclusion also supported by improved survival of insulin-treated patients (P < 0.03). Conclusion: Insulin is a significant metabolic treatment in multimodal palliation of weight-losing cancer patients.

Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: a randomized double-blind study.

The short‐term provision of ghrelin to patients with cancer indicates that there may be benefits from long‐term provision of ghrelin for the palliative treatment of weight‐losing cancer patients. This hypothesis was evaluated in a randomized, double‐blind, phase 2 study.

Daily Physical-Rest Activities in Relation to Nutritional State, Metabolism, and Quality of Life in Cancer Patients with Progressive Cachexia

Purpose: To evaluate daily physical-rest activities in cancer patients losing weight in relation to disease progression. Experimental Design: Physical activity-rest rhythms were measured (ActiGraph, armband sensor from BodyMedia) in relation to body composition (dual-energy X-ray absorptiometry), energy metabolism, exercise capacity (walking test), and self-scored quality of life (SF-36, Hospital Anxiety and Depression Scale) in weight-losing outpatients with systemic cancer (71 ± 2 years, n = 53). Well-nourished, age-matched, and previously hospitalized non–cancer patients served as controls (74 ± 4 years, n = 8). Middle-aged healthy individuals were used as reference subjects (49 ± 5 years, n = 23). Results: Quality of life was globally reduced in patients with cancer (P < 0.01), accompanied by significantly reduced spontaneous physical activity during both weekdays and weekends compared with reference subjects (P < 0.01). Spontaneous physical activity declined over time during follow-up in patients with cancer (P < 0.05). However, overall physical activity and the extent of sleep and bed-rest activities did not differ between patients with cancer and age-matched non–cancer patients. Spontaneous physical activity correlated weakly with maximum exercise capacity in univariate analysis (r = 0.41, P < 0.01). Multivariate analysis showed that spontaneous physical activity was related to weight loss, blood hemoglobin concentration, C-reactive protein, and to subjectively scored items of physical functioning and bodily pain (SF-36; P < 0.05-0.004). Anxiety and depression were not related to spontaneous physical activity. Patient survival was predicted only by weight loss and serum albumin levels (P < 0.01), although there was no such prediction for spontaneous physical activity. Conclusions: Daily physical-rest activities represent variables which probably reflect complex mental physiologic and metabolic interactions. Thus, activity-rest monitoring provides a new dimension in the evaluation of medical and drug interventions during palliative treatment of patients with cancer.

β-Adrenoceptor activity and resting energy metabolism in weight losing cancer patients

This study was aimed at comparing the blocking of beta-adrenoceptor activity to changes in the resting energy metabolism of 10 cancer patients with progressive weight loss due to solid malignant tumours. Resting energy expenditure (REE) as well as whole body carbohydrate and fat oxidation were investigated and related to plasma substrate levels (glucose, glycerol, free fatty acids (FFA)) before and after 5 days of oral administration of specific beta1 receptor blocker (atenolol, 50 mg/day) and non-specific beta1,beta2-adrenoceptor (propranolol, 80 mg/day) blockade. The administration order of the drugs was random, and a 3-day washout period was used in all individuals between the provision of the first and the second drug in order to minimise the risk of carry-over effects. Resting measurements in the morning after an overnight fast were performed by indirect calorimetry. Atenolol treatment reduced REE by 77+/-14 kcal/day and propranolol by 48+/-13 kcal/day, respectively (P<0.05 versus pretreatment values). Whole body oxygen uptake and carbon dioxide production were decreased similarly by both atenolol and propranolol treatment (P<0.05). Carbohydrate oxidation was increased by atenolol and decreased by propranolol, whilst fat oxidation was decreased by atenolol and unchanged by propranolol. The decrease in REE, accounting for the decline in heart rate, was significantly more pronounced following treatment with propranolol compared with atenolol (P<0.05). Atenolol and propranolol had no effect on blood glucose, plasma glycerol and FFA. We conclude that wastage in cancer patients is in part explained by increased beta(1) and beta(2)-adrenoceptor activity, in part secondary to elevated cardiovascular activity as a result of anaemia, loss of cardiac contractile capacity and altered host metabolism.

Structured Triglycerides Were Well Tolerated and Induced Increased Whole Body Fat Oxidation Compared With Long-Chain Triglycerides in Postoperative Patients:

BACKGROUND It has been proposed, on the basis of animal experiments, that medium-chain triglycerides (MCT) may exert more favorable effects on whole body metabolism of injured animals than long-chain triglycerides (LCT). Therefore, the present study was designed to evaluate whether structured triglycerides are associated with increased whole body fat oxidation without promotion of ketogenesis in postoperative patients. METHODS A structured lipid emulsion (73403 Pharmacia, Sweden) containing medium- and long-chain fatty acids, esterified randomly to glycerol in a triglyceride structure, was used. Whole body fat oxidation was determined by indirect calorimetry in the postoperative period. Patients were randomized to receive structured lipids 1 day followed by LCT (Intralipid, Pharmacia) the next day or vice versa during 6 postoperative days. In part 1 of the study patients received fat at 1.0 g/kg per day in the presence of 80% of the basal requirement of nonprotein calories. In part 2 patients received fat at 1.5 g/kg per day in the presence of 120% of the nonprotein caloric requirement. Amino acids were always provided at 0.15 g N/kg per day. RESULTS Structured lipids were not associated with any side effects, were rapidly cleared from the plasma compartment, and were rapidly oxidized without any significant hyperlipidemia or ketosis. Provision of structured lipids in the presence of excess of nonprotein calories (part 2) caused a significantly higher whole body fat oxidation (2.4 +/- 0.05 g/kg per day) compared with LCT provision (1.9 +/- 0.06 g/kg per day) (p < .0001) examined in the same patients. CONCLUSIONS The results demonstrated for the first time in man that provision of structured triglycerides were associated with increased whole body fat oxidation in stressed postoperative patients, which is in line with the original metabolic and biochemical concept for structured triglycerides. The study provided evidence to support that structured lipids may represent a next generation of IV fat emulsions that may be clinically advantageous compared with conventional LCT emulsions in certain clinical conditions.

Structured triglycerides to postoperative patients : a safety and tolerance study

Long-chain triglycerides are still the standard in fat emulsions, although medium-chain triglycerides have been suggested to have metabolic advantages even though pure medium-chain triglycerides are toxic in large doses. The next generation of fat emulsions may be structured triglycerides, which are assumed to provide a higher oxidation rate, faster clearance from blood, improved nitrogen sparing, and less of a tendency to accumulate in the reticuloendothelial system compared with long-chain triglyceride emulsions. This study was designed to evaluate the safety and tolerance of structured triglyceride fat emulsion 73403 (Kabi Pharmacia Parenterals, Stockholm, Sweden) compared with that of a standard long-chain triglyceride emulsion (Intralipid 20%) in postoperative patients requiring total parenteral nutrition after major surgery. The study was randomized and of the double-blind, parallel group type. Twenty patients were included and treated for 5 to 7 days. Safety and tolerance variables demonstrated no major differences between the study and control groups. Physiologic and biochemical variables suggested that structured lipids were rapidly cleared and metabolized. This study represents the first report of administration of structured triglycerides to postoperative patients. The structured triglyceride emulsion (73403) demonstrated no difference in safety and tolerance compared with Intralipid 20%. Therefore, it will now be possible to follow up with studies on metabolic efficiencies of structured triglycerides in postoperative patients.

Supportive nutrition on recovery of metabolism, nutritional state, health-related quality of life, and exercise capacity after major surgery: a randomized study.

BACKGROUND & AIMS The aim of this study was to investigate whether specialized supportive enteral and parenteral feeding have superior effects compared to oral nutrition on recovery during long-term postoperative treatment of cancer patients with preoperative weight loss and reduced maximum exercise capacity. METHODS One hundred twenty-six patients referred for resection of the esophagus (n = 48), stomach (n = 28), or pancreas (n = 50) were considered to be included before operation. Included patients (n = 80) received supportive enteral or parenteral nutrition postoperatively at home corresponding to 1000 kcal/d until the patients did not wish to continue with artificial nutrition for any reason. Patients randomized to oral nutrition only served as control subjects. Caloric intake, body composition (dual-energy x-ray absorptiometry), and respiratory gas exchanges at rest and during exercise were measured including health-related quality of life. RESULTS Survival and hospital stay did not differ among the groups, whereas overall complications were higher on artificial nutrition (P < .05). Changes in resting energy expenditure and biochemical tests did not differ during follow-up among the groups. Body weight and whole body fat declined similarly over time in all groups (P < .005), whereas lean body mass was unchanged during follow-up compared to preoperative values. Maximum exercise capacity and maximum oxygen consumption were normalized within 6 months postoperatively in all groups. There was no difference in recovery of food intake among the groups. Parenteral feeding was associated with the highest rate of nutrition-related complications, whereas enteral feeding reduced quality of life most extensively. CONCLUSION After major surgery, specialized supportive enteral and parenteral nutrition are not superior to oral nutrition only when guided by a dietitian.

Effects of Recombinant Erythropoietin in Palliative Treatment of Unselected Cancer Patients

Purpose: The purpose is to evaluate relationships between objectively assessed exercise capacity and subjectively assessed scoring of physical functioning and well-being after erythropoietin treatment in cancer patients on palliative care. Experimental Design: Unselected cancer patients (n = 108) who experienced progressive cachexia were randomized to receive either anti-inflammatory treatment alone (indomethacin) or recombinant erythropoietin plus indomethacin to prevent the appearance of disease-induced anemia and thereby protect patients’ exercise capacity. Follow-up investigations of nutritional status, exercise capacity, and health-related quality of life assessed by SF-36 and the European Organization for Research and Treatment of Cancer QLQ-C30 were compared. Results: Effective treatment by erythropoietin on top of basal whole body anti-inflammatory treatment was confirmed and indicated by time course changes of biochemical, physiologic, and nutritional objectives, whereas individual self-reported scoring of physical functioning and general health did not indicate a clear-cut effectiveness, particularly at moderately subnormal hemoglobin levels. Conclusions: Discrepancies between objective and subjective self-reported measures may be either fundamental or indicate scoring limitations for evaluation of therapeutic results. Present results demonstrate a clinical benefit of erythropoietin treatment in cancer patients with subnormal to normal hemoglobin levels, whereas the patients’ own subjective scoring was insufficient to sense such improvements. The discrepancy may be either fundamental or methodological but emphasizes the importance to document therapeutic outcome in both subjective and objective perspectives in palliative care of cancer patients.

Relationships between self-reported health related quality of life and measures of standardized exercise capacity and metabolic efficiency in a middle-aged and aged healthy population

Background: The purpose of this study was to evaluate to what extent self-reported health related quality of life (HRQL), assessed by the Swedish standard version of the Medical Outcome Study Short-Form 36 (SF-36), is related to measured exercise capacity and metabolic efficiency in a cohort of healthy subjects from the Gothenburg area of Sweden. Material and methods: Individuals were invited to take part in the evaluation where HRQL was compared with the maximal power output expressed in Watts assessed during a standardized treadmill test with incremental work loads. Whole body respiratory gas exchanges (CO2/O2) were simultaneously measured. Estimate of metabolic efficiency was derived from oxygen uptake per Watt produced (ml O2/min/W) near maximal work. Results: The health status profile in the current population largely agreed with normative data from an age- and gender-matched reference group, although some measured scores were slightly better than reference scores. Males and females had a similar relationship between energy cost (ml O2/min) for production of maximal work (W), while the regressions for maximal exercise power and age were significantly different between males and females (p < 0.01). The overall metabolic efficiency was the same in individuals between 40 and 74 years of age (10.4 ± 0.07 ml O2/min/Watt). Maximal exercise power was only related to the SF-36 subscale physical functioning (PF), but unrelated to other physical subscales such as role limitations due to physical problems, good general health and vitality. There was also a discrepancy between measured maximal power and PF in many subjects, particularly in males who experienced either intact or severely reduced PF. Conclusions: Our results demonstrate that simultaneous measurements of self-reported and objective measures of PF should add a more integrated view for evaluation of therapeutic effectiveness, since the overall correlation was poor between objective and subjective scores among individuals.