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PubMed1987

Malignant disease: nutritional implications of disease and treatment.

Protein-energy malnutrition (PEM) is common in cancer patients and may develop into the syndrome known as 'cancer cachexia'. This is characterised by complex disturbances in carbohydrate, lipid, protein, and electrolyte metabolism. The aetiology is equally complex, with host and therapeutic factors contributing to the reduced food intake and effects on host tissues. Anorexia is of prime importance, differing in its cause from one patient to another and often presenting a barrier to successful nutritional support. Further research is necessary to elucidate the interaction of central and peripheral factors that may be involved in the aetiology of anorexia. Because of the interplay of biochemical, physiological, and psychological consequences of cancer, the nutritional support of the patient presents a considerable challenge to the caring professions.

Anorexia↗
PubMed1975

Anorexia nervosa with transient hypopituitarism.

A case is presented with sudden onset of cachexia and anorexia with hypopituitarism, starting early and progressing gradually. After about 15 months the patient recovered; first he lost the anorexia, then the endocrine functions and growth became normal. Conflicting reports about hypopituitarism in anorexia nervosa and similar syndromes may be due to lack of longitudinal observations and the transient nature of the endocrine disorders.

Adolescent↗
PubMed1984

Different effects of hypercalcemic state induced by Walker tumor (HWCS 256) and 1,25 (OH)D3 intoxication on rat thyroid C cells. An ultrastructural, immunocytochemical, and biochemical study.

Two different models of chronic C cell stimulation by the hypercalcemic state were compared with respect to their morphology, immunocytochemistry, and biochemistry. In the chronic hypercalcemic state due to the HWCS 256 strain of the Walker tumor C cells show signs of degeneration such as vacuolation, on day 7 after tumor implantation. On day 10 tumor induced hypercalcemia leads to irreversible cell damage with karyopyknosis and karyorrhexis. These morphological changes are accompanied by a decline in radioimmunologically measurable calcitonin content of the thyroid and by the loss of response to acute stimulation of C cells. In contrast, in the hypercalcemic state due to 1,25(OH)2D3 intoxication we find an almost complete degranulation of C cells but no signs of degeneration or cell damage, although the thyroid calcitonin content and the calcitonin secretion capacity is greatly reduced. Tumor induced cachexia as a reason for C cell damage in tumor bearing rats could be excluded. Other possible reasons, such as acute overstimulation and tumor factors acting directly on C cells are discussed.

Animals↗
PubMed1997

Serum levels of tumour necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients.

Cancer anorexia-cachexia syndrome (CACS), which is characterized by progressive weight loss (WL) and anorexia (A), is present in 50% of advanced cancer patients and in 80% of terminally ill cancer patients. One of the most controversial aspects of CACS is its oetiopathogenesis; experimental studies have identified certain cytokines [Tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and gamma interferon (gamma-IFN)] as possible co-factors in the onset of the syndrome. The aim of our study was to investigate the correlation between serum levels of circulating cytokines and severity of CACS. The following series of parameters was identified in 61 patients with advanced and terminal cancer: stage of disease; Karnofsky performance status (KPS) and clinical symptoms; biohumoral, anthropometric and immunological situation; level of circulating cytokines. All these parameters were evaluated for a possible link with WL/A. Our data do not show any significant correlation between circulating cytokines and WL/A. A direct correlation was identified between WL/A and nausea (P = 0.03 and P < 0.001, respectively) whereas inverse correlations were observed for both factors as regards arm circumference (P < 0.001 for both), wrist circumference (P < 0.001 for both), KPS (P < 0.001 and P = 0.003, respectively) and creatinine (P = 0.005 and P = 0.03, respectively). Other biochemical factors, such as haemoglobin, haematocrit, glycaemia, prealbumin, sodium and chlorine were also correlated with at least one of two clinical parameters in question. Unexpected results were seen in the increases in CD20 and CD4 and in the CD4/CD8 ratio. Serum levels of these cytokines do not, therefore, appear to be critical in the onset of CACS. On the contrary, our findings confirmed the clinico-laboratory picture that is characteristic of CACS. If we consider the possibility that CACS is provoked by an aspecific response of the host's defence mechanisms against prolonged neoplastic attack, the increase in CD4 (helper lymphocytes) could be linked to the persistent response.

Adult↗
PubMed1984

Comparison of muscle and fat wasting in patients suffering from breast and other cancers: an anthropometric study.

An anthropometric study was undertaken to determine muscle and fat areas in 50 cancer patients and 258 control patients suffering from minor conditions, to assess the degree of cachexia in patients with breast cancer, and in patients with other types of cancer. Patients suffering from cancers other than those of the breast showed muscle and fat wasting when compared with matched standard values and when the muscle and fat area measurements were expressed as a percentage of the appropriate mean standard value. Breast cancer patients showed increased muscle and fat area values, irrespective of whether they were in remission, or had progressive disease. This is interesting in view of the strong association between dietary fat intake and breast cancer incidence, and correlates well with present ideas on nutrition and the incidence of breast cancer.

Adipose Tissue↗
PubMed1981

[New possibilities to improve ileostomy-function by extremely high water-binding substances (author's transl)].

When an ileostoma is performed on rats, they usually die as a result of cachexia, which is caused by poor utilization of ingesta on account of rapid intestinal transit times. Assuming that oral administration of hydrophilic substances would prolong this transit and thereby the time of survival, rats with an ileostoma were fed a newly developed organic monomer. Its capacity to bind water is about 100 times its own weight. This substance was supplemented with standard diet of different concentrations. A much firmer fecal consistency resulted when 33% monomer was added to the diet. Animals fed a diet containing 50% monomer produced well-formed feces. There was no difference in survival time of the animals on a normal diet. furthermore, administration of a special hypercaloric diet did not cause a prolonged survival time. The reasons and possible therapeutic implications for patients with an ileostoma are discussed.

Animals↗
PubMed1996

The possible role of glutamine in some cells of the immune system and the possible consequence for the whole animal.

Glutamine is important for the function of lymphocytes and macrophages. A role for the high rate of glutamine utilisation by these cells is presented. Since muscle syntheses, stores and releases glutamine, this tissue may play a role in the immune response. Since the number of immune cells utilising glutamine may be large, the demand for glutamine from muscle, especially during trauma, sepsis or burns, may be very high. A speculative suggestion is put forward that this requirement for glutamine from muscle may play a role in cachexia under some of these conditions.

Animals↗
PubMed1994

Effect of systemic insulin on protein kinetics in postoperative cancer patients.

BACKGROUND: Cancer cachexia is a significant cause of postoperative morbidity and mortality in patients with tumors of the upper gastrointestinal tract. Standard parenteral nutrition (TPN) has failed to alter this. The anabolic effect of insulin has been well documented, and its positive effect on protein economy in cancer patients has been recently demonstrated. This study examines the effect of high-dose insulin and parenteral nutrition on protein kinetics in postoperative cancer patients. METHODS: Eleven patients underwent surgery for pancreatic, esophageal, or gastric carcinoma. Postoperatively, patients received standard TPN for 4 days (1 g/kg/day amino acids, 1,000 kcal/day dextrose, 100 g/day lipid), and hyperinsulinemic parenteral nutrition for 4 days (same as standard TPN plus 1.44 U/kg/day regular human insulin) in a crossover design. All patients received both treatments, and the order of treatment was determined randomly. Euglycemia was maintained during insulin infusion via a variable 30% dextrose infusion. Patients underwent protein metabolic studies after each treatment period and rates of whole body and skeletal muscle protein synthesis, breakdown, and net balance were determined by radioisotopic tracer methods using 14C-leucine and 3H-phenylalanine. RESULTS: Compared with standard TPN (STD), hyperinsulinemic TPN (INS) resulted in a significant increase in skeletal muscle protein synthesis (INS: 52.04 +/- 10.22 versus STD: 26.06 +/- 6.71 nmol phe/100 g/min, p < 0.05) and net balance of protein (INS: 7.75 +/- 4.61 versus STD: -15.10 +/- 6.44 nmol phe/100 g/min, p < 0.01), but no difference in skeletal muscle protein breakdown (INS: 44.29 +/- 11.54 versus STD: 41.17 +/- 5.89 nmol phe/100 g/min). Whole-body net balance of protein also significantly increased with insulin-based TPN, compared with standard TPN (INS: 0.04 +/- 0.05 versus STD: -0.08 +/- 0.07 mumol leu/kg/min, p < 0.05), but no difference in whole-body protein synthesis (INS: 2.52 +/- 0.15 versus STD: 2.49 +/- 0.15 mumol leu/kg/min) or whole-body protein breakdown (INS: 2.48 +/- 0.16 versus STD: 2.58 +/- 0.19 mumol leu/kg/min) was observed. Patients received significantly more calories during the hyperinsulinemic TPN period than during the standard TPN period. There was no difference in total, essential, or branched-chain amino acids, and no difference in serum free fatty acids, triglycerides, or cholesterol was observed between the two treatment periods. CONCLUSION: High-dose insulin in conjunction with hypercaloric parenteral nutrition causes improved skeletal muscle protein synthesis, skeletal muscle protein net balance, and whole-body protein net balance compared with standard TPN in postoperative cancer patients.

Adult↗
PubMed1984

Acute renal failure in patients with malnutrition following mitral valve replacement.

A retrospective study of 161 consecutive patients undergoing mitral valve replacement with or without other valve surgery was undertaken to examine the relation between cardiac cachexia and postoperative acute renal failure. The preoperative nutritional state was assessed according to percent of the ideal body weight (W/IW). There were 37 malnourished patients (W/IW less than 0.80) and 124 normally nourished patients (W/IW greater than or equal to 0.80). In nineteen in the malnourished group (51 per cent) and 37 of normal-nourished (28 per cent), postoperative acute renal failure developed. Malnourished patients showed a severe clinical picture preoperatively and complicated operative procedures had to be carried out. To match these clinical factors between the two groups, the observation was limited to the high risk patients who showed severe New York Heart Association Functional Class (III or IV) large cardiothoracic ratio (more than 65 per cent), and long cardio-pulmonary bypass time (exceeding 120 minutes). Even in this subgroup, malnourished patients were susceptible to renal failure (64 per cent versus 20 per cent, malnourished versus normal-nourished respectively). Thus, when malnutrition is superimposed on diminished cardiac performance, acute renal failure may ensue.

Acute Kidney Injury↗
PubMed1999

Artificial nutrition in cancer patients: which route, what composition?

The state of art of artificial nutrition in depleted cancer patients is reviewed in brief. Because cancer cachexia cannot be equated to simple nutrient deficiency but is due instead to complex metabolic abnormalities, the nutritional effects of total parenteral (TPN) and enteral (EN) nutrition are more limited than in starving subjects. TPN and EN usually prevent further deterioration of the nutritional status, although they are not able to fully reverse a state of depletion. There is evidence that quantitative and qualitative modulation of certain nutrients may obtain better results because of a favorable impact on host metabolism. Research in this field is fully warranted. Moreover, the effects of some substrates on tumor metabolism and tumor growth require further investigation to define a nutritional regimen able to maintain the host metabolism with minimum stimulation of tumor growth.

Cachexia↗
PubMed2000

Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites.

Leptin is a recently identified hormone produced by the adipocyte ob gene which acts as a negative feedback signal critical to the normal control of food intake and body weight. A number of proinflammatory cytokines, such as interleukin (IL) 1alpha, IL-6, tumor necrosis factor (TNF) alpha and interferon (IFN) gamma, have been proposed as mediators of cancer cachexia. These data suggest that abnormalities in leptin production/release or in its feedback mechanism play a role in cancer patients. To elucidate this we studied the relationship between total serum leptin and serum cytokines IL-1alpha, IL-6, TNFalpha as well as the production of leptin and cytokines by peripheral blood mononuclear cells (PBMC) isolated from cancer patients. Sixteen advanced cancer patients (mainly stage IV) with tumors at different sites were included in the study. The serum levels of leptin in cancer patients were significantly lower than those of healthy individuals at all times (7 a.m., noon, 3 p.m.). No significant differences were found in circadian rhythm between patients and controls. Serum levels of IL-1alpha, IL-6, and TNFalpha were significantly higher in cancer patients than in healthy individuals. An inverse correlation between serum levels of leptin and IL-6 was found in cancer patients. The production in culture of leptin by unstimulated PBMCs and those stimulated by phytohemagglutinin M or by phorbol myristate acetate isolated from cancer patients was very low; no differences were observed in comparison with leptin production by PBMCs from healthy individuals.

Adult↗
PubMed2000

Progressive esophageal leiomyomatosis with respiratory compromise.

Leiomyomatosis is a rare neoplastic condition of the pediatric esophagus. Presenting symptoms usually overlap with more common esophageal disorders, namely, gastroesophageal reflux. A patient is presented in whom leiomyomatosis progressed to the point of causing cachexia and respiratory compromise.

Adolescent↗
PubMed2000

Disordered metabolic response with cancer and its management.

The metabolic changes in cancer cachexia appear to be mediated by a complex network of proinflammatory cytokines, neuroendocrine hormones, neurotransmitters, eicosanoids, and tumor-derived factors produced by the body in response to the tumor and by the tumor itself. The relative importance of these various mediator pathways in relation to either the anorexia or hypermetabolism associated with weight loss in cancer remains to be fully elucidated. Our current understanding suggests that proinflammatory mediators may indeed be a valid target for therapeutic intervention. Trials attempting to modify the inflammatory response to cancer with the hope of improving appetite and reversing catabolism and perhaps thereby improving qualityof life and survival are currently underway.

Animals↗
PubMed2005

Therapeutic effect of tamoxifen and energy-modulating vitamins on carbohydrate-metabolizing enzymes in breast cancer.

BACKGROUND: Cancer cells have an abnormal energetic metabolism. One of the earliest discovered hallmarks of cancer had its roots in bioenergetics, as many tumours were found in the 1920s to exhibit a high glycolytic phenotype. An animal with cancer shows significant and progressive energy loss from the host (i.e. noncancerous) tissues, which could occur by the establishment of a systemic energy-depriving cycle involving the interaction of tumour glycolysis and host gluconeogenesis. Tamoxifen (TAM) is a nonsteroidal antioestrogen that is widely used in adjuvant therapy for all stages of breast carcinoma. To improve the therapeutic efficacy of TAM and to expand its usage in the treatment of breast cancer, it is necessary to establish an energy-enhancing programme. In order to provide sufficient energy and to prevent cancer cachexia, TAM can be supplemented with energy-modulating vitamins (EMV). In this investigation the augmentation of the efficacy of TAM by the effects of EMV supplementation on carbohydrate-metabolizing enzymes, the mitochondrial Krebs cycle and respiratory enzymes was evaluated in the mammary gland of carcinoma-bearing rats. METHODS: Female albino Sprague-Dawley rats were selected for the investigation. The experimental set-up included one control and four experimental groups. Mammary carcinoma was induced with 7,12- dimethyl benz(a)anthracene (25 mg), and TAM was administered orally (10 mg/kg body weight per day) along with EMV which comprised riboflavin (45 mg/kg per day), niacin (100 mg/kg per day) and coenzyme Q(10) (40 mg/kg per day). RESULTS: Measurements were made on tumour tissue and surrounding normal tissue in all experimental groups. Tumour tissue showed significant (P<0.05) increases in the glycolytic enzymes hexokinase, phosphoglucoisomerase and aldolase, and significant decreases in the gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-biphosphatase. In contrast, the surrounding tissue showed significant decreases in glycolytic enzymes and significant increases in gluconeogenic enzymes. The activities of the mitochondrial Krebs cycle enzymes isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase, and respiratory chain enzymes NADH dehydrogenase and cytochrome c oxidase were significantly reduced in both tumour and surrounding tissue of the mammary carcinoma-bearing rats. These biochemical disturbances were effectively counteracted by supplementation with EMV, which restored the activities of all these enzyme to their respective control levels. CONCLUSION: Combination therapy of TAM with EMV not only alters carbohydrate metabolism but can also prevent body weight loss by enhancing the host energy metabolism.

Animals↗
PubMed2003

Pansclerotic morphea in childhood: a case report.

Scleroderma can be differentiated into progressive systemic and circumscript forms. The extensive form with lethal outcome is known from case reports of children and adolescents. The present case report concerns a boy who died at 16 years of age. In the 5th year of life, he experienced weight loss and developed multiple, firm, partially atrophic plaques in the skin of the extremities. These plaques gradually became confluent and extended over the whole torso and head. Plaque ulceration resulted in massive mutilations to the body. Later the patient's cachexia worsened and he developed keratose, moderately differentiated squamous cell carcinoma of the right leg. The prognosis of pansclerotic morphea for children is worse than for adults. No successful therapy is known.

Adolescent↗
PubMed2003

Concomitant laparoscopic gastric and biliary bypass and bilateral thoracoscopic splanchnotomy: the full package of minimally invasive palliation for pancreatic cancer.

INTRODUCTION: Pancreatic cancer is unresectable in 80% or more of patients. Biliary and duodenal obstruction and intractable abdominal and back pain are the most common complications of the disease. These complications may be palliated effectively using minimally invasive techniques. Their combined application in a single setting is presented and discussed in this article. CASE REPORT: A 59-year-old man with a locally advanced carcinoma of the head of the pancreas presented with obstructive jaundice and intractable pain requiring opiate analgesia. An attempt at endoscopic biliary stenting was unsuccessful, and a percutaneous biopsy was deemed unsafe. Preoperative magnetic resonance cholangiography showed cystic duct insertion abutting the upper limit of the biliary stricture. A laparoscopic Roux-en-Y hepaticojejunostomy, prophylactic loop gastroenterostomy, and tumor biopsy were combined with a bilateral thoracoscopic splanchnotomy. RESULT: Surgery and subsequent recovery were uneventful, and the patient was discharged from hospital on the fourth postoperative day off opiates. He remained free of jaundice and severe pain, until 6 months later, when he represented with jaundice, cachexia, and proximal small bowel obstruction secondary to multiple liver and peritoneal metastases. He underwent further palliative laparoscopic enteric bypass with resolution of the intestinal obstruction, but died of the disease 10 days later. CONCLUSION: Laparoscopic gastric and biliary bypass and bilateral thoracoscopic splanchnotomy may be safely combined to provide an effective comprehensive minimally invasive palliation of incurable pancreatic cancer.

Anastomosis, Roux-en-Y↗
PubMed2004

[Cannabinoids and the immune system. Of men, mice and cells].

The medical use of cannabis or cannabinoid compounds is controversial. Cannabinoids like the Delta(9)-THC (tetrahydrocannabinol) or the synthetic derivative Nabilone are available against cancer- and HIV-associated cachexia, nausea and vomiting. Over the last 20 years, the cannabinoid receptors CB(1) and CB(2) and their endogenous ligands have been found. The involvement of this endogenous cannabinoid signalling system in feeding, appetite, pain perception and immunomodulation could be demonstrated using animal and in vitro studies. Thus, the concern about immunosuppressive effects in humans using medical cannabinoid preparations grew. However, up to now most human studies have failed to demonstrate a well-defined and reproducible immunosuppressive cannabinoid-effect. Only the smoking of marijuana showed a significant local immunosuppression of the bactericidal activity of human alveolar macrophages. In animal studies, cannabinoids were identified as potent modulators of cytokine production, causing a shift from Th1 to Th2 cytokines. In consequence, a compromised cellular immunity was observed in these animals, resulting in enhanced tumor growth and reduced immunity to viral infections. In vitro, immunosuppressive effects were shown in all immune cells, but only at high micromolar cannabinoid concentrations not reached under normal clinical conditions. In conclusion, there is no evidence that cannabinoids induce a serious, relevant immunosuppression in humans, with the exception of marijuana-smoking which may affect local broncho-alveolar immunity.

Animals↗
PubMed1997

Assessment of nutritional status in cancer patients: widely neglected?

Frank cachexia is usually evident in the clinical evaluation, but important metabolic alterations in tumour-bearing patients with slight weight changes are frequently overlooked. Since several factors are involved in cancer-induced malnutrition (marasmus type descriptive of general inadequate food intake, kwashiorkor type descriptive of inadequate protein intake/increased turnover), medical/dietary history and physical examination (dynamic weight loss, vitamin/mineral deficiency) should be complemented by simple additional laboratory tests. Minimal baseline testing may include: weight loss (> 5%/month = severe) and serum albumin (< 24 g/l = severe). Anthropometric measurements (triceps skin fold, midarm muscle circumference) for the assessment of fat deposits and lean body mass are rarely used in a routine clinical setting owing to great variations among individuals and interobserver measurement variability. The Prognostic Nutritional Index (PNI), including serum parameters, immune competence testing and anthropometrics (but no further dietary parameters, i.e. dynamic weight loss), has proved to be quite a reliable method of predicting postoperative morbidity/mortality and of selecting cancer patients for aggressive preoperative nutritional interventions. For clinical studies including the evaluation of nutritional status (stratification, prognostic impact) and/or outcome (nutritional interventions), a simple standardized and validated assessment protocol including dietary history, specific physical examination and widely available laboratory testing should be implemented to document significant nutritional alterations. Body weight alone will often fail to demonstrate important disease- or therapy-related changes in caloric intake or metabolic rate.

Anthropometry↗