Background: 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.Methods: Consecutive patients were allocated to study (antibiotics) or control (surgery) groups according to date of birth. Study patients received intravenous antibiotics for 24 h and continued at home with oral antibiotics for 10 days. Control patients had a standard appendicectomy. Follow-up at 1 and 12 months was carried out according to intention and per protocol.

BACKGROUNDSeveral investigations that yielded different results in terms of net changes in body composition of weight‐losing cancer patients have been reported that employed a variety of methods based on fundamentally different technology. Most of those reports were cross‐sectional, whereas to the authors' knowledge there is sparse information available on longitudinal follow‐up measurements in relation to other independent methods for the assessment of metabolism and performance.METHODSFor the current report, the authors evaluated time course changes in body composition (dual‐energy X‐ray absorptiometry) with measurements of whole body and regional distribution of fat and lean tissue in relation to food and dietary intake, host metabolism (indirect calorimetry), maximum exercise capacity (walking test), and circulating hormones in cancer patients who were receiving palliative care during 4–62 months of follow‐up. The entire cohort comprised 311 patients, ages 68 years ± 3 years who were diagnosed with solid gastrointestinal tumors (84 colorectal tumors, 74 pancreatic tumors, 73 upper gastrointestinal tumors, 51 liver‐biliary tumors, 3 breast tumors, 5 melanomas, and 21 other tumor types).RESULTSDecreased body weight was explained by loss of body fat, preferentially from the trunk, followed by leg tissue and arm tissue, respectively. Lean tissue (fat‐free mass) was lost from arm tissue, whereas trunk and leg tissue compartments increased, all concomitant with declines in serum albumin, increased systemic inflammation (C‐reactive protein, erythrocyte sedimentation rate), increased serum insulin, and elevated daily caloric intake; whereas serum insulin‐like growth factor 1 (IGF‐1), resting energy expenditure, and maximum exercise capacity remained unchanged in the same patients. Serum albumin levels (P < 0.001), whole body fat (P < 0.02), and caloric intake (P < 0.001) predicted survival, whereas lean tissue mass did not. Daily intake of fat and carbohydrate was more important for predicting survival than protein intake. Survival also was predicted by serum IGF‐1, insulin, leptin, and ghrelin levels (P < 0.02 – P < 0.001). Serum insulin, leptin, and ghrelin (total) levels predicted body fat (P < 0.001), whereas IGF‐1 and thyroid hormone levels (T3, free T3) predicted lean tissue mass (P < 0.01). Systemic inflammation primarily explained variation in lean tissue and secondarily explained loss in body fat. Depletion of lean arm tissue was related most to short survival compared with the depletion of lean leg and trunk tissue.CONCLUSIONSThe current results demonstrated that body fat was lost more rapidly than lean tissue in progressive cancer cachexia, a phenomenon that was related highly to alterations in the levels of circulating classic hormones and food intake, including both caloric amount and diet composition. The results showed importance in the planning of efficient palliative treatment for cancer patients. Cancer 2005. © 2005 American Cancer Society.

BACKGROUND 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. METHODS Three hundred nine patients with malignant disease who experienced progressive cachexia due to solid tumors (primarily gastrointestinal lesions) were randomized to receive a COX inhibitor (indomethacin, 50 mg twice daily) and EPO (15–40,000 units per week) along with specialized, nutrition‐focused patient care (oral nutritional support and home total parenteral nutrition [TPN]) provided on a patient‐by‐patient basis to attenuate inflammation, prevent anemia, and improve nutritional status. Control patients received the same indomethacin and EPO doses that study patients received without the added nutritional support. All patients were treated and followed until death. Biochemical assays (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurement of whole‐body respiratory gas exchange before and during exercise were performed before the start of treatment and then at regular intervals during the treatment period (every 2–30 months after treatment initiation). Statistical analyses were performed on ‘intention‐to‐treat’ and ‘as‐treated’ bases. RESULTS Home TPN was provided to approximately 50% of the study patients without severe complications. Over the entire observation period, rhEPO prevented the development of anemia in both study patients and control patients. Intention‐to‐treat analysis revealed an improvement in energy balance for nutritionally supported patients (P < 0.03); no other significant differences in outcome between study patients and control patients were observed. As‐treated analysis demonstrated that patients receiving nutrition experienced prolonged survival (P < 0.01), which was accompanied by improved energy balance (P < 0.001), increasing body fat (P < 0.05), and a greater maximum exercise capacity (P < 0.04). A trend toward increased metabolic efficiency at maximum exercise (P < 0.06) for study patients relative to control patients also was observed. CONCLUSIONS The results of the current study strongly support that nutrition is a limiting factor influencing survival and that nutritional support protects integrated metabolism and metabolic function in patients with progressive cachexia secondary to malignant disease. Cancer 2004. © 2004 American Cancer Society.

This population-based study confirms previous results of randomized studies. Antibiotic treatment can be offered as the first-line therapy to a majority of unselected patients with acute appendicitis without medical drawbacks other than the unknown risk for long-term relapse, which must be weighed against the unpredicted but well-known risk for serious major complications following surgical intervention.

Purpose:The present study was designed to evaluate whether daily insulin treatment for weightlosing 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 F 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 F 139 days (mean F 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.

Synthesis and degradation of globular and myofibrillar proteins across arm and leg muscles were examined during stepwise increased intravenous infusion of amino acids (0.1, 0.2, 0.4, and 0.8 g N.kg-1.day-1) to healthy volunteers. Protein dynamics were measured by a primed constant infusion of L-[ring-2H5]phenylalanine and the release of 3-methylhistidine from skeletal muscles. Arterial concentrations and flux of glucose, lactate, and free fatty acids were unchanged despite increasing concentrations of plasma amino acids from 2.6 to 5.7 mM. Plasma insulin, insulin-like growth factor I (IGF-I), and plasma concentrations of IGF-I-binding proteins-1 and -3 remained at fasting levels throughout the investigation. Amino acid infusion caused a significant uptake of the majority of amino acids across arm and leg tissues, except tyrosine, tryptophan, and cysteine, probably due to low concentrations of these amino acids in the formulation. The balance of globular proteins improved significantly (P < 0.01) due to stimulation of synthesis and attenuation of degradation across arm and leg tissues, despite insignificant uptake of tyrosine, tryptophan, and cysteine. Degradation of myofibrillar proteins was uninfluenced by provision of amino acids. The results demonstrate that neither insulin nor circulating IGF-I explained improved protein balance in skeletal muscles after elevation of plasma amino acids. Rather, some amino acids in themselves trigger cellular reactions that initiate peptide formation. Limited availability of some extracellular amino acids was overcome by increased reutilization of the intracellular amino acid.

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 F 2 years, n = 53). Well-nourished, age-matched, and previously hospitalized non^cancer patients served as controls (74 F 4 years, n = 8). Middle-aged healthy individuals were used as reference subjects (49 F 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.

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