Kent Lundholm

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology.

Parenteral nutrition offers the possibility of increasing or ensuring nutrient intake in patients in whom normal food intake is inadequate and enteral nutrition is not feasible, is contraindicated or is not accepted by the patient. These guidelines are intended to provide evidence-based recommendations for the use of parenteral nutrition in cancer patients. They were developed by an interdisciplinary expert group in accordance with accepted standards, are based on the most relevant publications of the last 30 years and share many of the conclusions of the ESPEN guidelines on enteral nutrition in oncology. Under-nutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis and, per se, responsible for excess morbidity and mortality. Many indications for parenteral nutrition parallel those for enteral nutrition (weight loss or reduction in food intake for more than 7-10 days), but only those who, for whatever reason cannot be fed orally or enterally, are candidates to receive parenteral nutrition. A standard nutritional regimen may be recommended for short-term parenteral nutrition, while in cachectic patients receiving intravenous feeding for several weeks a high fat-to-glucose ratio may be advised because these patients maintain a high capacity to metabolize fats. The limited nutritional response to the parenteral nutrition reflects more the presence of metabolic derangements which are characteristic of the cachexia syndrome (or merely the short duration of the nutritional support) rather than the inadequacy of the nutritional regimen. Perioperative parenteral nutrition is only recommended in malnourished patients if enteral nutrition is not feasible. In non-surgical well-nourished oncologic patients routine parenteral nutrition is not recommended because it has proved to offer no advantage and is associated with increased morbidity. A benefit, however, is reported in patients undergoing hematopoietic stem cell transplantation. Short-term parenteral nutrition is however commonly accepted in patients with acute gastrointestinal complications from chemotherapy and radiotherapy, and long-term (home) parenteral nutrition will sometimes be a life-saving maneuver in patients with sub acute/chronic radiation enteropathy. In incurable cancer patients home parenteral nutrition may be recommended in hypophagic/(sub)obstructed patients (if there is an acceptable performance status) if they are expected to die from starvation/under nutrition prior to tumor spread.

Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients

A trial in selected men suggested that antibiotic therapy could be an alternative to appendicectomy in appendicitis. This study aimed to evaluate antibiotic therapy in unselected men and women with acute appendicitis.

Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients

Weight loss and anorexia are frequent findings in advanced cancer. The progressive wasting could be attributed to changes in dietary intake and/or energy expenditure mediated by metabolic alterations. In this study, we analyzed dietary intake in generalized malignant disease of solid tumor type in relation to resting energy expenditure (REE) and reported weight loss. In a group of 297 unselected cancer patients from a university hospital outpatient clinic, dietary intake of energy and macronutrients from a 4‐day food record, REE by indirect calorimetry, height, weight and weight loss were recorded. Protein intake was validated against 24 hr urine nitrogen in a subgroup (n = 53), and no indication of systematic misreporting was found. Mean daily dietary intake was below maintenance requirements, 26 ± 10 kcal/kg. Weight loss of more than 10% was present in 43% of patients and elevated REE (>110% of predicted) in 48%. Dietary intake did not differ between normo‐ and hypermetabolic patients, nor was tumour type or gender related to energy and protein intake. Weight loss could not be accounted for by diminished dietary intake since energy intake in absolute amounts was not different and intake per kilogram body weight was higher in weight‐losing patients compared to weight‐stable patients. Dietary macronutrient composition did not differ from the general population. Dietary intake of energy and protein was decreased, but dietary macronutrient composition did not appear to be changed. Weight loss and hypermetabolism were frequent and not compensated for by an increase in spontaneous food intake. Our results indicate that an expected up‐regulation of dietary intake in response to elevated energy expenditure is frequently lost in cancer patients. This may be the explanation behind cancer cachexia rather than a primary decrease in appetite.

Intermittent claudication--surgical reconstruction or physical training? A prospective randomized trial of treatment efficiency.

This study reports the initial evaluation of treatment efficiency in 75 patients with intermittent claudication who were randomized to three treatment groups: 1) reconstructive surgery, 2) recon structive surgery with subsequent physical training, and 3) physical training alone. Before treatment, there were no statistically significant differences between the groups in age, sex, smoking habits, symptom duration of claudication, ankle-arm blood pressure quotient (ankle-index), maximal plethysmographic calf blood flow, symptom-free and maximal walking distance, the history of other atherosclerotic manifestations or in the medical treatment. The walking performance was improved in all three groups at follow-up 13 ± 0.5 months after randomization. Surgery was most effective, but the addition of training to surgery improved the symptom-free walking distance even further. In pooled observations of the three groups, age, symptom duration, and a history of myocardial ischemic disease correlated negatively with walking performance after treatment. In the operated group, the duration of claudication and a history of myocardial ischemic disease correlated negatively with the walking performance. This was not the case when patients were censored if limited by other symptoms than intermittent claudication after treatment. In the trained group, the duration of claudication correlated negatively to symptom-free and maximal walking distance. Ankle-index and maximal plethysmographic calf blood flow after treatment and the change of these variables with treatment correlated positively with both symptom-free and maximal walking distance when results were pooled for all patients. Although this mainly was a consequence of the improved blood flow after surgery, the change of maximal plethysmographic calf blood flow also correlated with symptom-free but not with maximal walking distance in the trained group. The results demonstrate that, compared with physical training alone, operation alone or in combination with subsequent training are superior treatment modalities in patients with intermittent claudication.

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.

Clinical significance of preoperative nutritional status in 215 noncancer patients.

Preoperative nutritional status was assessed by: the percentage weight loss (% WL), body weight in relation to reference weight (WI), arm muscle circumference (AMC), and S-albumin (S-Alb) in a prospective study of 215 noncancer patients classified into three groups according to type of surgery: major vascular, minor vascular, and abdominal. The clinical significance of the nutritional markers was assessed by correlations to postoperative outcome and the time spent in the hospital after surgery. The influence of age on nutritional markers and clinical variables was evident but was ruled out in all correlations. If malnutrition was classified as two or more abnormal values in the nutritional markers (% WL, WI, AMC, S-Alb), the overall frequency was 12%, highest in the major vascular surgery group (18%) and lowest in the minor vascular group (4%). Patients with low nutritional status stayed an average of 29 days in the hospital compared to 14 days if the nutritional status was normal (p < 0.01). The overall complication frequency was higher in patients with low nutritional status compared to normal status (48% and 23%, respectively, p < 0.01). The frequency of serious complications was 31% in undernourished and 9% in well-nourished patients (p < 0.05). Various nonnutritional variables such as age, diagnosis, and duration of surgery were shown to increase the predictive ability of nutritional status. The results of this study confirm that nutritional state per se is predictive for postoperative outcome even when variables were stabilized for different backgrounds with covariation to nutritional status.

Skeletal muscle metabolism in patients with malignant tumor.

Abstract Skeletal muscle biopsies were taken from 43 cancer patients and 55 matched, presumably metabolically healthy controls for determinations of enzyme activities, capacity of glucose assimilation and metabolism and the incorporation rate of leucine into proteins. In muscle tissue from cancer patients the activities of the lysosomal enzymes, cathepsin-D and β-glucuronidase, were increased. Acid phosphatase activity was the same as in muscle tissue from the controls. The activities of hexokinase, phosphofructokinase, lactate dehydrogenase, and cytochrome-c-oxidase were significantly decreased. This decrease was accompanied by a decreased incorporation rate of glucose-carbon into glycogen, lactate and CO 2 . The incorporation rate of leucine into proteins was significantly decreased in cancer patients and the fractional degradation rate of proteins was increased. Amino acids caused the same degree of stimulation on the leucine incorporation rate into proteins as in the controls. The RNA concentration was unchanged in muscles from the cancer patients. The results suggest that malignant tumors provoke specific alterations of the skeletal muscle metabolism of the host. The rate of protein biosynthesis seems to be decreased together with an increased degradation rate. The capacity for glucose assimilation and metabolism is decreased indicating a disturbed energy regulation in the muscles of cancer patients.

Elevated energy expenditure in cancer patients with solid tumours

Cancer patients (n = 106) and non-cancer subjects (n = 96) were classified as weight stable (n = 70) or weight-losing (n = 132). Cancer patients had elevated resting energy expenditure (REE) compared with either weight-losing (23.6 [0.4] vs. 20.5 [0.5] kcal/kg per day, P less than 0.001) or weight-stable controls (22.0 [0.6] vs. 17.9 [0.4], P less than 0.001). Cancer patients had increased fat oxidation irrespective of weight loss (1.24 [0.07] vs. 0.87 [0.04] mg/kg per min; 1.07 [0.04] vs. 0.78 [0.04], P less than 0.001). Elevated energy expenditure was counter-regulated by a decrease in thyroid hormones. Abnormal liver function had no impact on REE in either group. Heart rate was the most powerful factor for prediction of high energy expenditure in both patients and controls. Elevated energy expenditure was related to the increased heart rate in cancer patients in a significantly higher proportion than that in controls. Increased metabolic rate is a significant component behind weight loss in cancer disease, independent of malnutrition and an elevated adrenergic state may be a likely explanation.

Glucose turnover, gluconeogenesis from glycerol, and estimation of net glucose cycling in cancer patients

A double isotope method was used in patients with progressive malignancy and in control patients to measure: glucose turnover, conversion rate of carbon skeleton of glycerol into glucose, and the interorgan cycling of glucose carbons (Cori‐cycle plus alanine‐glucose cycle). [U‐14Clglycerol and [6‐3H]glucose were given intravenously as a single dose injection. The time course of the specific radioactivities of [6‐3H] and [U‐14C]glucose was followed in blood. The pool size and the turnover rate of glucose were increased in the cancer group as compared with the control patients. The net recycling of glucose carbons was not increased in the cancer group, despite the increased turnover of glucose. The alterations in the metabolism of glucose did not correlate with the plasma levels of insulin or thyroid hormones (T4, T3, rT3) neither in the entire cancer group nor in those cancer patients who were repeatedly investigated at different intervals of time. The turnover rate of glucose in the cancer patients correlated inversely to their body weight index. The gluconeogenesis rate, given as the fractional conversion rate of the injected radioactive dose of [14C]glycerol, or as mol glucose · kg body weight−1 · day−1, was increased in the cancer group, but still contributed only 3% of the glucose turnover rate in both cancer and control patients. We conclude that an increased gluconeogenesis from glycerol is not significant in terms of energy expenditure in patients with progressive malignancy, as has previously been concluded for the gluconeogenesis from alanine.15 It seems that increased turnover of glucose may contribute to inappropriately high energy expenditure in cancer patients.

Diagnostic Criteria for the Classification of Cancer-Associated Weight Loss

PURPOSE Existing definitions of clinically important weight loss (WL) in patients with cancer are unclear and heterogeneous and do not consider current trends toward obesity. METHODS Canadian and European patients with cancer (n = 8,160) formed a population-based data set. Body mass index (BMI) and percent WL (%WL) were recorded, and patients were observed prospectively until death. Data were entered into a multivariable analysis controlling for age, sex, cancer site, stage, and performance status. Relationships for BMI and %WL to overall survival were examined to develop a grading system. RESULTS Mean overall %WL was -9.7% ± 8.4% and BMI was 24.4 ± 5.1 kg/m(2), and both %WL and BMI independently predicted survival (P < .01). Differences in survival were observed across five categories of BMI (< 20.0, 20.0 to 21.9, 22.0 to 24.9, 25.0 to 27.9, and ≥ 28.0 kg/m(2); P < .001) and five categories of %WL (-2.5% to -5.9%, -6.0% to -10.9%, -11.0% to -14.9%, ≥ -15.0%, and weight stable (± 2.4%); P < .001). A 5 × 5 matrix representing the five %WL categories within each of the five BMI categories was graded based on median survival and prognostic significance. Weight-stable patients with BMI ≥ 25.0 kg/m(2) (grade 0) had the longest survival (20.9 months; 95% CI, 17.9 to 23.9 months), and %WL values associated with lowered categories of BMI were related to shorter survival (P < .001), as follows: grade 1, 14.6 months (95% CI, 12.9 to 16.2 months); grade 2, 10.8 months (95% CI, 9.7 to 11.9 months); grade 3, 7.6 months (95% CI, 7.0 to 8.2 months); and grade 4, 4.3 months (95% CI, 4.1 to 4.6 months). Survival discrimination by grade was observed within specific cancers, stages, ages, and performance status and in an independent validation sample (n = 2,963). CONCLUSION A robust grading system incorporating the independent prognostic significance of both BMI and %WL was developed.