Cancer Anorexia-cachexia Syndrome Research Articles

Ernährung in der Onkologie - die Bedeutung von Mikronährstoffen

Im Verlauf der Erkrankung entwickeln viele onkologische Patienten eine tumorassoziierte Malnutrition, gekennzeichnet durch eine defizitäre Versorgung an Makro- und Mikronährstoffen. Der defizitäre Ernährungsstatus und das damit in Zusammenhang stehende „cancer cachexia syndrome” ist von klinischer Bedeutung, da hierdurch das Ansprechen auf antineoplastische Verfahren wie die Radio- und die Chemotherapie vermindert, deren Nebenwirkungen verstärkt und die Lebensqualität sowie die Prognose der Patienten negativ beeinflusst wird. Entsprechend kommt der supportiven Ernährungstherapie von onkologischen Patienten eine zentrale Bedeutung zu. Dabei stoßen neben Energiesubstraten auch Vitamine, Mineralstoffe sowie langkettige Omega-3-Fettsäuren auf ein wachsendes Interesse, wobei der Nutzen entsprechender Supplemente kontrovers diskutiert wird. Ausgehend von einer Darstellung der Ätiopathogenese und der ernährungsphysiologischen Konsequenzen einer tumorassoziierten Malnutrition ist es Ziel dieses Beitrags, einen Überblick zur Bedeutung von Mikronährstoffen bei onkologischen Patienten zu vermitteln. Während bei eingeschränkter Nahrungsauswahl der Einsatz eines Multivitamin-Multimineral-Supplements mit physiologischen Dosierungen, d. h. Nährstoffmengen, die in etwa der Höhe der Tagesempfehlungen entsprechen, eine sinnvolle und sichere Maßnahme darstellt, sollte auf den Einsatz einzelner, hochdosierter Mikronährstoffe verzichtet werden. Eine Ausnahme bildet hierbei Vitamin D. Auch zur Verbesserung der postoperativen Wundheilung sowie zur Eindämmung der Kachexie sind höhere Mengen an Mikronährstoffen erforderlich als für gesunde Personen empfohlen.

Nutrition in oncology: the case of micronutrients (Review)

In the course of cancer disease, many oncological patients develop tumor-associated malnutrition characterized by an insufficient supply of macro- and micronutrients. The inadequate nutritional status and the cancer anorexia-cachexia syndrome related to it are clinically relevant, as the response to antineoplastic measures, such as radiation and chemotherapy, is diminished, their side effects aggravated and the patient's quality of life and prognosis negatively affected. Therefore, the supportive nutrition care of oncological patients is of central importance. In this context, vitamins, minerals and long-chain omega -3 fatty acids are becoming more and more relevant in oncology although the benefit of such supplements is discussed controversially. Starting from a description of the etiopathogenesis and the pathophysiological consequences of cancer-associated malnutrition, the present study provides an overview of the importance of micronutrients for oncological patients. In the case of reduced food intake and/or inappropriate food choice the use of a multi-vitamin-multimineral supplement administered in physiological doses, i.e. nutrient quantities approximately corresponding to the recommended daily allowances, can be generally recommended. However, to enhance postoperative wound healing, it seems that cancer patients require higher amounts of micronutrients than healthy individuals. Because vitamin D deficiency is highly prevalent in oncological patients, improvement of vitamin D status is of special interest.

Animal models of the cancer anorexia–cachexia syndrome

Cancer cachexia, a complex wasting syndrome, is common in palliative medicine. Animal models expand our understanding of its mechanisms. A review of cancer cachexia and anorexia animal models will help investigators make an informed choice of the study model. Cancer-anorexia cachexia animal models are numerous. No one is ideal. The choice should depend on the research question. To investigate cancer-anorexia cachexia independent of pro-inflammatory cytokine effects, the MAC16 ADK and XK1 are useful. MAC16 ADK helps study the host's tumor metabolic effects, independent of any anorexia or inflammation. XK1 is both anorectic and cachectic, but data about it is limited. All other models induce a host inflammatory response. The Walker 256 ADK and MCG 101 are best avoided due to excessive tumor growth. Since individual models do not address all aspects of the syndrome, use of a combination seems wise. Suggested combinations: MAC16-ADK (non-inflammatory and non-anorectic) with YAH-130 (inflammatory, anorectic, and cachectic), Lewis lung carcinoma (slow onset anorexia) or prostate adenocarcinoma (inflammatory, anorectic but not cachectic) with YAH-130.

The cancer anorexia-cachexia syndrome: myth or reality?

Controversy exists as what constitutes the cancer anorexia-cachexia syndrome (CACS), and whether it truly is a distinct clinical disorder. In this study, we aimed to: (1) assess if CACS is a distinct clinical disorder, (2) identify the symptoms characteristic of CACS, (3) evaluate CACS impact on patient outcomes (symptom burden and survival time from referral). Consecutive patients referred to palliative medicine were assessed by 38-symptom questionnaire. Demographics, Eastern Cooperative Oncology Group (ECOG), disease and extent, and survival were recorded. CACS, defined as anorexia plus weight loss (>10% of pre-illness weight). For analysis, patients were divided into four groups: (1) group CACS; (2) group A (only anorexia, NO >10% pre-illness weight loss); (3) group WL (weight loss >10% pre-illness weight only but NO anorexia); and (4) group N (NO weight loss >10% pre-illness weight and NO anorexia). Symptoms present in > or =5%, and patients with complete data were analyzed. Four hundred eighty-four patients had complete data, metastatic cancer, and 26 symptoms present in > or =5%. Groups had significantly different ECOG, symptom burden, and survival. Significantly different symptom prevalence between groups: dry mouth,*early satiety,*constipation,*nausea,*taste changes,*vomiting,*dysphagia,*fatigue,*weak,*lack of energy, insomnia, dyspnea, depression, hoarseness, and anxiety. The nine symptoms with asterisk were CACS specific. Symptom Burden: CACS independently predicted greatest burden. Survival: Group N had significantly longer survival. CACS appeared to be a distinct disorder with unique clinical characteristics in our advanced cancer population. Nine other symptoms constituted CACS. CACS independently predicted higher symptom burden. CACS absence predicted longer survival. More evidence is needed to better characterize this syndrome and generate a valid CACS consensus. A comprehensive validated CACS assessment instrument is required.

Review Article: Cytokines and Cancer Anorexia Cachexia Syndrome

Cancer anorexia cachexia syndrome is frequent yet still a not well understood cancer-related problem. The pathophysiology of cancer cachexia is multifactorial. It is suggested to be the result of tumor-host interactions and studies of the disturbances seen during cancer anorexia cachexia syndrome, such as anorexia, hyper-metabolism, tissue wasting, metabolic abnormalities, and hormonal changes, all point to the involvement in one way or another of one key factor: cytokines. The purpose of this review is to summarize the latest developments in the field of cytokines and their role in cancer anorexia cachexia syndrome. The emphasis is on the role of cytokines in anorexia and tissue wasting.

Oxidative stress and wasting in cancer

Cancer anorexia-cachexia syndrome is becoming a critical component in the comprehensive approach to cancer patients because it influences morbidity, mortality and quality of life. Consequently, pathogenic mechanisms have been elucidated to facilitate development of better therapies. Reported findings indicate that increased production of reactive oxygen species and reduced activity of antioxidant enzymes contribute to development of anorexia and cachexia in cancer. Systemic inflammation impairs tryptophan handling, promoting oxidative stress, which appears to mimic hypothalamic negative feedback signalling. Thus, tryptophan contributes to cancer anorexia by stimulating hypothalamic serotonergic activity and promoting oxidative stress, because neuroinflammation facilitates tryptophan degradation into free radical generators via the kynurenine pathway. Upregulation of protein degradation by increased oxidative stress has been documented in cancer. Also, hypothalamic, cytokine-mediated suppression of fatty acid oxidation reduces food intake, and triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle, thus potentially increasing oxidative stress. Increased oxidative stress contributes to cancer anorexia and cachexia. Preliminary clinical data on the efficacy of antioxidant therapy in cancer patients are encouraging, but uncertainty persists regarding the optimal dose and timing of administration. Also, better biological/genetic characterization of those cancer patients who are more likely to obtain significant clinical benefits appears necessary.

Abnormality of growth hormone and insulin-like growth factor I axis in advanced cancer patients

19671 Background: Pituitary and thyroid hormones are known to be altered in anorexia nervosa, but few hormonal studies have been performed in cancer anorexia-cachexia syndrome. This study focused on growth hormone (GH) and Insulin-like Growth Factor (IGF)-I axis in cancer patients. Methods: To investigate the relationship among performance status (PS), nutritional and hormonal status, blood sampling was performed to measure GH, IGF-I, IGF-binding protein 3(IGFBP-3), T3, T4, complete blood counts and blood chemistry profiles for 15 cancer patients in each of PS0–1, PS2, PS3 and PS4 after the informed consent was obtained. Results: A total of 58 patients were evaluated including 15 patients in PS0–1, PS2 and PS3 and 13 in PS4. Hemoglobin and albumin levels went down along with progression of PS. GH level was high and T3 was low in poor PS. T4 and IGFBP-3 were lower in PS4 than those of other PS. There is a tendency of low IGF-I and thyroid hormones and high GH levels in poor PS as compared with those of good PS (p=0.0064 for IGF-I, p<0.001 for T3, and T4, not significant for GH analyzed by ANOVA). Conclusions: Abnormal GH - IGF-I axis was more pronounced in poor PS. It is conceivable that normalization of this abnormality can improve cancer anorexia-cachexia syndrome and new drug development for such normalizing agents is warranted. No significant financial relationships to disclose.

VEGF in the Cancer Anorexia-Cachexia Syndrome in Patients with Lung Cancer

Cancer anorexia-cachexia syndrome( CACS) occurs in 30-80% of patients with cancer. CACS is connected with poor prognosis and higher risk of treatment complications. CACS belongs to the common cause of death in cancer patients. Main role in the development of this syndrome play cytokines like TNF, interleukin 1 and 6 and interferon alpha and gamma. The importance of a lot of other substances is still unknown. VEGF promotes new vessels development,enhance vascular permeability and plays a role in inflammatory reaction. The aim of this study was comparison of VEGF levels in patients with lung cancer with and without CACS and in control group. The serum levels of VEGF were measured by ELISA method. The VEGF was significatly higher in patients with lung cancer then in control group (p = 0.004). There were no correlations between VEGF and weight lost, histological type and stage of disease. This suggest that VEGF doesnt play a role in development of CACS.

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in cancer patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards, are based on all relevant publications since 1985 and were discussed and accepted in a consensus conference. Undernutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis. EN should be started if undernutrition already exists or if food intake is markedly reduced for more than 7-10 days. Standard formulae are recommended for EN. Nutritional needs generally are comparable to non-cancer subjects. In cachectic patients metabolic modulators such as progestins, steroids and possibly eicosapentaenoic acid may help to improve nutritional status. EN is indicated preoperatively for 5-7 days in cancer patients undergoing major abdominal surgery. During radiotherapy of head/neck and gastrointestinal regions dietary counselling and ONS prevent weight loss and interruption of radiotherapy. Routine EN is not indicated during (high-dose) chemotherapy.

Prognostic Factors in Advanced Cancer Patients: Evidence-Based Clinical Recommendations—A Study by the Steering Committee of the European Association for Palliative Care

To offer evidence-based clinical recommendations concerning prognosis in advanced cancer patients. A Working Group of the Research Network of the European Association for Palliative Care identified clinically significant topics, reviewed the studies, and assigned the level of evidence. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results. A systematic electronic literature search within the main available medical literature databases was performed for each of the following four areas identified: clinical prediction of survival (CPS), biologic factors, clinical signs and symptoms and psychosocial variables, and prognostic scores. Only studies on patients with advanced cancer and survival < or = 90 days were included. A total of 38 studies were evaluated. Level A evidence-based recommendations of prognostic correlation could be formulated for CPS (albeit with a series of limitations of which clinicians must be aware) and prognostic scores. Recommendations on the use of other prognostic factors, such as performance status, symptoms associated with cancer anorexia-cachexia syndrome (weight loss, anorexia, dysphagia, and xerostomia), dyspnea, delirium, and some biologic factors (leukocytosis, lymphocytopenia, and C-reactive protein), reached level B. Prognostication of life expectancy is a significant clinical commitment for clinicians involved in oncology and palliative care. More accurate prognostication is feasible and can be achieved by combining clinical experience and evidence from the literature. Using and communicating prognostic information should be part of a multidisciplinary palliative care approach.

Cancer Anorexia-Cachexia Syndrome

The majority of patients with advanced cancer experience weight loss, reduced appetite, fatigue, and weakness. Chronic nausea and early satiety may also occur. This constellation of symptoms is known as the cancer anorexia-cachexia syndrome. Together with cancer pain, cancer anorexia-cachexia syndrome has been identified as 1 of the 2 most frequent and devastating problems affecting individuals with advanced malignancies. Research examining the issue of cancer anorexia-cachexia syndrome has been conducted; however, such work is largely biomedical in orientation. In contrast, the psychologic dimensions of the cancer anorexia-cachexia syndrome experience from the perspective of terminally ill patients and their family members is less well explored or described. The ability to provide psychosocial support to patients and families requires that caregivers appreciate the psychologic effect of cancer anorexia and cachexia on these individuals. This article examines that effect in light of existing knowledge and discusses the clinical implications arising from this work.

Therapy Insight: cancer anorexia–cachexia syndrome—when all you can eat is yourself

Tumor growth is associated with profound metabolic and neurochemical alterations, which can lead to the onset of anorexia-cachexia syndrome. Anorexia is defined as the loss of the desire to eat, while cachexia results from progressive wasting of skeletal muscle mass--and to a lesser extent adipose tissue--occurring even before weight loss becomes apparent. Cancer anorexia-cachexia syndrome is highly prevalent among cancer patients, has a large impact on morbidity and mortality, and impinges on patient quality of life. However, its clinical relevance is frequently overlooked, and treatments are usually only attempted during advanced stages of the disease. The pathogenic mechanisms of cachexia and anorexia are multifactorial, but cytokines and tumor-derived factors have a significant role, thereby representing a suitable therapeutic target. Energy expenditure in anorexia is frequently increased while energy intake is decreased, which further exacerbates the progressive deterioration of nutritional status. The optimal therapeutic approach to anorectic-cachectic cancer patients should be based on both changes in dietary habits, achieved via nutritional counseling; and drug therapy, aimed at interfering with cytokine expression or activity. Our improved understanding of the influence a tumor has on the host's metabolism is advancing new therapeutic approaches, which are likely to result in better preservation of nutritional status if started concurrently with specific antineoplastic treatment.

Cancer anorexia-cachexia syndrome: cytokines and neuropeptides.

Cancer anorexia-cachexia syndrome is observed in 80% of patients in the advanced stages of cancer and is a strong independent risk factor for mortality. Numerous cytokines produced by tumor and immune cells, interacting with the neuropeptidergic system, mediate the cachectic effect of cancer. Since there is currently no effective pharmacological treatment and the anorexia-cachexia syndrome continues to be defined biochemically, we review the role of cytokines and neuropeptides in this process. Currently data suggest that cancer anorexia-cachexia syndrome results from a multifactorial process involving many mediators, including hormones (e.g. leptin), neuropeptides (e.g. neuropeptide Y, melanocortin, melanin-concentrating hormone and orexin) and cytokines (e.g. interleukin 1, interleukin 6, tumor necrosis factor alpha and interferon gamma). It is likely that close interrelation among these mediators exists in the hypothalamus, decreasing food intake and leading to cachexia. In the pathogenesis of cancer anorexia, cytokines play a pivotal role influencing the imbalance of orexigenic and anorexigenic circuits that regulate the homeostatic loop of body-weight regulation, leading to cachexia. Interfering pharmacologically with cytokine expression or neural transduction of cytokine signals can be an effective therapeutic strategy in anorectic patients before they develop cancer anorexia-cachexia syndrome.

癌性悪液質の病態と治療―特に高齢者において

Cachexia is among the most debilitating and life-threatening aspects of cancer and is more common in children and elderly patients. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. This could be caused by persistent inhibition of the feeding-stimulatory circuitry including neuropeptide Y. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a 3-6-month period. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.

Treatment of the Cancer Anorexia-Cachexia Syndrome: A Critical Reappraisal

Cancer anorexia-cachexia syndrome (CACS) is a combination of anorexia, tissue wasting, weight loss and poor performance status. Some CACS symptoms are due to a macrophage production of TNF and IL-1, while the metabolic effects are mainly explained by the release of IL-6 from tumor cells. Clinical treatment of CACS involves progestational agents (medroxyprogesterone acetate, MPA, megestrol acetate, MA) for long term treatment. The use of prokinetic agents (like metoclopramide) is recommended, especially if patients need concomitant opioid treatment for pain; if otherwise indicated, corticosteroids are useful for short periods. The administration of artificial nutrition should be individualized following the clinical condition of the patient and possibly taking into account the wishes of the patient. The practical evaluation criteria of the drugs employed for CACS are based on weight increase and appetite stimulation. Hence, a new approach to the mechanism of action of MPA, MA and of other agents is urgently needed.

The Cancer Anorexia–Cachexia Syndrome: A Survey of the Prognostic Inflammatory and Nutritional Index (PINI) in Advanced Disease

Other than weight loss, most traditional methods of nutritional assessment are not acceptable in advanced cancer patients because they are inaccurate, too expensive for routine use, or too difficult for a debilitated person to complete. The prognostic inflammatory and nutritional index (PINI) is a formula devised to evaluate nutritional status and prognosis in critically ill patients. It has been suggested that the PINI score can be used to follow most pathological conditions. It has been measured in several settings and has been found to be a reliable indicator of both nutritional status and prognosis in trauma, burn, infected, and cardiac patients. In this pilot study, we evaluated the PINI in 50 consecutive patients referred to a palliative care service. Compared to a value in normal, healthy people of <1, the mean score in this sample was 102 (SD = 142, 95% CI = 62–142). The mean protein values were: alpha-1-acid glycoprotein 1409 mg/l (SD = 556, 95% CI = 1251–1567); C-reactive protein (CRP) 106 mg/l (SD = 89, 95% CI = 81–131); albumin 24 g/l (SD = 7, 95% CI = 23–26); and prealbumin 147 mg/l (SD = 73, 95% CI = 126–168). There was no significant association between the PINI and corticosteroid use, weight loss over time, age, or sex. These data indicate that the PINI is highly abnormal in our population. The CRP may be the most important value.

Cancer anorexia-cachexia syndrome: current issues in research and management.

Cachexia is among the most debilitating and life-threatening aspects of cancer. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a six-month period. The two major options for pharmacological therapy have been either progestational agents, such as megestrol acetate, or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide--all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.

Modern management of the cancer anorexia-cachexia syndrome.

The cancer anorexia-cachexia syndrome is common, occurring in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death in patients with cancer. It is a complex problem involving abnormalities in protein, carbohydrate, and fat metabolism. Tumors have both direct and indirect effects that result in anorexia and weight loss. The disease burden does not necessarily correlate with the degree of cachexia. In addition to the physical manifestations, the resulting abnormalities have a significant psychologic effect on patients and their families. Although there is no treatment to reverse the process, pharmacologic and nonpharmacologic measures can enhance food intake and improve quality of life.

Modern management of the cancer anorexia-cachexia syndrome.

The cancer anorexia-cachexia syndrome is common, occurring in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death in patients with cancer. It is a complex problem involving abnormalities in protein, carbohydrate, and fat metabolism. Tumors have both direct and indirect effects that result in anorexia and weight loss. The disease burden does not necessarily correlate with the degree of cachexia. In addition to the physical manifestations, the resulting abnormalities have a significant psychologic effect on patients and their families. Although there is no treatment to reverse the process, pharmacologic and nonpharmacologic measures can enhance food intake and improve quality of life.

Serotonergic blockade in the treatment of the cancer anorexia-cachexia syndrome

Imbalanced amino acid diets in animals rapidly produce anorexia and weight loss. Blockade of type 3 serotonergic receptors (5HT(3)) can ameliorate anorexia in this animal model. Imbalanced plasma amino acid levels also have been documented in both animal models and human patients with cancer cachexia. Therefore a trial of the 5HT(3) receptor antagonist, ondansetron, was undertaken in the treatment of patients with cancer cachexia. Patients with metastatic cancer who were not undergoing chemotherapy or radiotherapy and who had lost >5% of their body weight were eligible. Baseline physical examination; weight; anthropometric studies; levels of retinol binding protein, albumin, and prealbumin; and skin testing for anergy were obtained. The ability to enjoy food was assessed utilizing a seven-point hedonic category scale for specific foods. Therapy was comprised of oral ondansetron, 8 mg twice a day. Twenty-seven patients were enrolled; all were evaluable for toxicity and 20 patients were evaluable for response. Toxicity of ondansetron was minimal. Patients demonstrated significant weight loss prior to disease entry (mean baseline weight of 76.9 kg vs. 72. 1 kg; P < 0.000002). Patients continued to lose weight on study (Week 0: 72.5 kg vs. Week 4: 71.4 kg; P = 0.027); in addition, there was significant deterioration of midarm circumference and hand grip strength, all of which indicated worsening nutritional status. However, a significant improvement in food enjoyment was noted (P = 0.04). Although it apparently improved the ability of patients to enjoy food, the blockade of 5HT(3) receptors failed to prevent weight loss in patients with cancer cachexia or alter laboratory parameters of protein nutrition.