Cachexia Syndrome Research Articles

Association of estimated glomerular filtration rate with all-cause and cardiovascular mortality: the role of malnutrition-inflammation-cachexia syndrome.

BackgroundPrevious studies have demonstrated that high estimated glomerular filtration rate (eGFR) is paradoxically associated with an increased risk of mortality, and the association becomes more predominant in older people. However, the role of malnutrition–inflammation–cachexia syndrome (MICS) in the association between eGFR and mortality has never been explored.MethodsWe conducted a community‐based cohort study using data from the Taipei City Elderly Health Examination Database, collected during the period 2001–10. All participants aged ≥65 years were included and stratified by the absence or presence of MICS, which is defined as the presence of at least one of the following markers: body mass index <22 kg/m2, serum albumin <3.0 mg/dL, or Geriatric Nutritional Risk Index (GNRI) <98. The study endpoints were all‐cause and cardiovascular mortality.ResultsA total of 131 354 participants were identified and categorized according to the chronic kidney disease stage based on eGFR. Compared with the reference eGFR of 60–89 mL/min/1.73 m2, the overall and cardiovascular mortality risks were markedly high in the groups with eGFR of <30 mL/min/1.73 m2 [overall: adjusted hazard ratio (aHR), 1.86; 95% confidence interval (CI), 1.72–2.00; cardiovascular: aHR, 1.87; 95% CI, 1.60–2.19] and ≥90 mL/min/1.73 m2 (overall: aHR, 1.23; 95% CI, 1.13–1.34; cardiovascular: aHR, 1.28; 95% CI, 1.06–1.54). In the absence of MICS, high eGFR was associated with lower mortality risk (aHR, 0.71; 95% CI, 0.62–0.80), and the U‐shaped relationship disappeared. Subgroup analyses produced consistent results.ConclusionsMICS could influence the association observed between high eGFR and mortality in older people, particularly in those with low body mass index, albumin level, GNRI, and very low serum creatinine level.

Main Barriers in Control of Energy-Protein Deficit in Critical Oncologic Patient at Nutritional Risk

Introduction: The Nutrition Risk in Critically ill (NUTRIC) score is a specific tool for assessing the nutritional risk in the Intensive Care Unit (ICU). Under these conditions, it is extremely important to monitor Enteral Nutrition Therapy and identify main barriers in the control of energy-protein deficit. Objective: To identify main barriers to control the energy-protein deficit in critically ill patients at nutritional risk, on enteral nutrition (EN) and on mechanical ventilation (MV). Methods: Prospective, observational, descriptive study was conducted in an ICU in 2015. Patients >19 years of age on MV and underwent EN for >72 hours. The data collected were NUTRIC score, Subjective Global Assessment (SGA), Cachexia Syndrome, APACHE II, SOFA, ICU time, MV and EN times and main barriers for pausing EN. The protein-calorie deficit was compiled into total days of EN. Results: Total of 62 patients, 22 were excluded, 40 analyzed. The scores were NUTRIC 7 (+0.7), APACHE 26 (+5.2), SOFA 11.5 (+2.2), Body Mass Index 23.2 (+6.2) kg/m², 47% malnourished (SGA B+C), 70% cachexia syndrome and mortality rate of 52.5%. Among these patients, 77.5% underwent early EN and percentage of volume prescribed infused was 89%. It was observed total deficit of -296 (+339) calories and -28 (IQ -58:-2.95) g/protein. Main barriers for pausing EN were extubation 38%, hemodynamic instability 29%, tracheostomy, diarrhea and vomiting, both 6.5%. There was a statistically significant difference between calorie (p<0.003) and protein (p<0.002) deficits in the subgroups of adult patients compared to malnourished elderly patients with cachexia syndrome: -358.9 (+305) calories and -33 (+14.24) g/protein; -91.6 (+190) calories and -18.8 (+7.96) g/protein, respectively. Conclusion: The main barriers in control of energy-protein deficit in critical oncologic patient at nutritional risk on EN and on MV were extubation and hemodynamic instability.

Role of frailty and sarcopenia in predicting outcomes among patients undergoing gastrointestinal surgery.

According to the United States census bureau 20% of Americans will be older than 65 years in 2030 and half of them will need an operation - equating to about 36 million older surgical patients. Older adults are prone to complications during gastrointestinal cancer treatment and therefore may need to undergo special pretreatment assessments that incorporate frailty and sarcopenia assessments. A focused, structured literature review on PubMed and Google Scholar was performed to identify primary research articles, review articles, as well as practice guidelines on frailty and sarcopenia among patients undergoing gastrointestinal surgery. The initial search identified 450 articles; after eliminating duplicates, reports that did not include surgical patients, case series, as well as case reports, 42 publications on the impact of frailty and/or sarcopenia on outcome of patients undergoing gastrointestinal surgery were included. Frailty is defined as a clinically recognizable state of increased vulnerability to physiologic stressors resulting from aging. Frailty is associated with a decline in physiologic reserve and function across multiple physiologic systems. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Unlike cachexia, which is typically associated with weight loss due to chemotherapy or a general malignancy-related cachexia syndrome, sarcopenia relates to muscle mass rather than simply weight. As such, while weight reflects nutritional status, sarcopenia - the loss of muscle mass - is a more accurate and quantitative global marker of frailty. While chronologic age is an important element in assessing a patient's peri-operative risk, physiologic age is a more important determinant of outcomes. Geriatric assessment tools are important components of the pre-operative work-up and can help identify patients who suffer from frailty. Such data are important, as frailty and sarcopenia have repeatedly been demonstrated among the strongest predictors of both short- and long-term outcome following complicated surgical procedures such as esophageal, gastric, colorectal, and hepato-pancreatico-biliary resections.

PC-FACS

PC-FACS

The therapeutic potential of exercise to treat cachexia.

To discuss the role of physical exercise in the attenuation of cancer cachexia-associated symptoms, and upon the outcome of chemotherapy, with special focus on the anti-inflammatory role of chronic exercise. The review addresses the recent findings regarding the positive effects of endurance and strength exercise training upon metabolic dysfunction, systemic inflammation and body composition alterations in the syndrome of cachexia. The employment of different exercise protocol strategies, in respect to intensity, duration, work load and in concomitance with pharmacological treatment is considered. Cachexia is a multifactorial wasting syndrome afflicting patients with cancer, chronic obstructive pulmonary disease, chronic heart failure, trauma, among other diseases. This condition markedly compromises the quality of life, treatment outcome and survival. Recent literature indicates an unequivocal role of chronic exercise in modulating cachexia and other cancer-associated dysfunctions. Exercise is proposed as a complementary treatment in cancer, and represents a function-preserving, anti-inflammatory and metabolism-modulating strategy with low cost, and high versatility and availability. Furthermore, exercise decreases cancer recurrence and presents a positive impact on public health management, reducing hospitalization and medication costs.

Request for regulatory guidance for cancer cachexia intervention trials.

Request for regulatory guidance for cancer cachexia intervention trials.

Pathophysiology of anorexia in the cancer cachexia syndrome.

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients.

Cancer Cachexia and SMA (Superior Mesenteric Artery) Syndrome

Cancer Cachexia and SMA (Superior Mesenteric Artery) Syndrome

Cancer Cachexia: One Step Ahead

Cachexia is one of the most common manifestations in advanced cancer patients, but too often it remains under- recognized and under-treated. Starvation is not the same of cachexia. Cachexia is defined by "weight loss >5% over past 6 months in absence of simple starvation or the combination of ongoing weight loss>2% with BMI <20 or sarcopenia". The pathogenesis of cancer cachexia is not fully understood, but inflammation and an increased catabolic response to a number of cancer-related factors seem to represent the basis of any assumption. Early diagnosis of a pre-cachectic or cachectic state is a key moment for the treatment of this complex syndrome, in order to guarantee an adequate food intake and suitable exercise and to interfere with the inflammatory processes that are typical of cachexia. Therefore, one of the main aims is to identify those patients most likely to develop the syndrome early. A multimodality baseline approach to cancer cachexia addresses reversible clinical contributory factors. There are currently no medicinal products that have a proven efficacy in the medical approach to cancer cachexia. Recently, anamorelin, a synthetic orally active ghrelin receptor agonist, showed promising results, but the best approach to cancer cachexia probably remains an early multimodal interventions consisting in nutritional intervention, exercise and rehabilitation program, and multi-target drug therapies. This review summarizes what we know and what still need to know about cancer cachexia syndrome.

Muscle wastingas main evidence of energy impairment in cancer cachexia: future therapeutic approaches.

The present review aimed at discussing the impact, pathogenesis and therapeutic approaches of muscle wasting, which is a major clinical feature of cancer-related cachexia syndrome. The pathogenesis of muscle wasting in cancer cachexia lies in a discrepancy between anabolic and catabolic pathways mediated by chronic inflammation. Effective interventions specifically aimed at hampering muscle loss and enhancing muscle function are still lacking. Promising agents include anti-inflammatory, orexigenic and anabolic drugs, alongside with nutritional supplements that influence the STAT3 and PI3K/Akt/mTOR pathways involved in muscle wasting. Personalized physical activity combined with pharmacological and nutritional support hold promise. A greater understanding of the pathogenetic processes of cancer cachexia-related muscle wasting will enable the development of an early and effective targeted mechanism-based multimodal approach.

Mechanisms of anorexia-cachexia syndrome and rational for treatment with selective ghrelin receptor agonist.

Cancer cachexia is a multi-organ, multifactorial and often irreversible syndrome affecting many patients with cancer. Cancer cachexia is invariably associated with weight loss, mainly from loss of skeletal muscle and body fat, conditioning a reduced quality of life due to asthenia, anorexia, anaemia and fatigue. Treatment options for treating cancer cachexia are limited. The approach is multimodal and may include: treatment of secondary gastrointestinal symptoms, nutritional treatments, drug, and non-drug treatments. Nutritional counselling and physical training may be beneficial in delaying or preventing the development of anorexia-cachexia. However, these interventions are limited in their effect, and no definitive pharmacological treatment is available to address the relevant components of the syndrome. Anamorelin is a first-in-class, orally active ghrelin receptor agonist that binds and stimulates the growth hormone secretagogue receptor centrally, thereby mimicking the appetite-enhancing and anabolic effects of ghrelin. It represents a new class of drug and an additional treatment option for this patient group, whose therapeutic options are currently limited. In this review we examine the mechanisms of anamorelin by which it contrasts catabolic states, its role in regulation of metabolism and energy homeostasis, the data of recent trials in the setting of cancer cachexia and its safety profile.

Abstract IA05: Novel function of microRNAs.

Abstract MicroRNAs (miRNAs) are small noncoding RNAs, 19-24 nucleotides in length, which regulate gene expression, and are aberrantly expressed in most types of cancer. MiRNAs have also been detected in the blood of cancer patients, and can serve as circulating biomarkers. It has been shown that secreted miRNAs within exosomes can be transferred from cell to cell, and can regulate gene expression in the receiving cells by canonical binding to their target messenger RNAs. Here we show that tumor secreted miR-21 and miR-29a can also function by a novel mechanism, by binding as ligands to receptors of the Toll-like receptor family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response, which ultimately may lead to tumor growth and metastasis. Thus, by acting as peregrine agonists of TLRs, secreted miRNAs are key regulators of the tumor microenvironment. This mechanism of action of miRNAs is implicated in the tumor-immune system communication, and is important in tumor growth and spread, therefore representing a new possible target for cancer treatment. The cachexia syndrome is a debilitating state of cancer that predominantly results from the loss of skeletal muscle mass, which is in part associated with apoptosis. How tumors promote apoptosis in distally located skeletal muscles has not been explored. Using both tumor cell lines and patient samples, we show that tumor-derived microvesicles induce apoptosis of skeletal muscle cells. This pro- apoptotic activity is mediated by a microRNA cargo, miR-21, which signals through the Toll-like 7 receptor (TLR7) on murine myoblasts to promote cell death. Furthermore, tumor microvesicles and miR-21 require c-Jun N-terminal kinase activity to regulate this apoptotic response. Together, these results describe a unique pathway by which tumor cells promote muscle loss, which might provide a great insight into elucidating the causes and treatment options of cancer cachexia. Apoptosis has been associated with cancer cachexia. However, it is not clear so far as to the signals inducing cell death and the type of cells undergoing apoptosis. Our results indicate that circulating MVs secreted by mouse and human cancer cells cause apoptosis of muscle cells, and that this phenomenon is dependent on TLR7 (mouse) or TLR8 (human). Importantly, cancer cell lines that are usually associated with cancer cachexia, such as lung cancer and pancreatic cancer cell lines, were able to induce myoblast cell death, but not breast cancer cell lines. These results suggest the specificity of MV-mediated cell death in the context of muscle wasting associated with cancer cachexia. We further found that miR-21 levels secreted into the MVs were elevated in those cell lines that induced muscle cell death. One of the pancreatic cell lines, PC1, induced the strongest effect of cell death and contained the highest levels of miR-21 in the MV cargo. Inhibition of miR-21, a ligand of TLR7 and TLR8, inhibited the induction of apoptosis of the muscle cells. Thus, on the basis of these findings, we predict that MVs secreted by cancer cells overexpressing miR-21, similar to those derived from pancreatic and lung malignancies, fuse with muscle cells and induce apoptosis by activating TLR7/8. One interesting observation is that cancer cell lines that induce muscle cell death also seem to secrete more MVs), which contributes to the phenomenon of a higher level of miR21 expression. Future studies will investigate whether a higher number of MVs is associated with the deregulation of other miRNAs or signaling pathways, as blocking TLR7 does not completely rescue miR21-induced cell death. Taken together, our results provide insights into therapeutic avenues for cachexia, possibly by inhibiting MV secretion, inhibiting fusion of MV with muscle cells, or blocking the binding of miR-21 to TLR7/8, which are currently under investigation. Citation Format: Carlo M. Croce. Novel function of microRNAs. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA05.

Abstract 4695: Dual targeting of MEK and PI3K pathways can act via tumor-intrinsic mechanisms to overcome resistance and tumor-extrinsic mechanisms to modulate immunity and limit cancer cachexia

Abstract Prior studies by our group have shown that single-agent MEK inhibitors have clinical activity in cholangiocarcinoma (CC), including objective responses. Yet no relationship was found between clinical benefit, and oncogenic driver mutations such as KRAS or BRAF. Strategies to expand upon MEKi have focused on combinations with agents targeting resistance, such as the PI3K/Akt pathway. CC patients treated with MEKi also had reduced pro-inflammatory cytokines and weight gain with restoration of muscle mass. These findings are clinically significant, and led us to hypothesize that MEKi act via tumor-extrinsic mechanisms to modulate immunity and limit cancer cachexia, while overcoming tumor-intrinsic resistance. We used the colon-26 adenocarcinoma model to evaluate the effect of single and combined treatment with MEK162 (30mg/kg) and buparlisib (25mg/kg) on muscle wasting, tumor growth, and immune modulation. This murine model depends on interleukin-6 (IL-6) and recapitulates the cancer cachexia syndrome. Single agent MEK162 inhibited growth initially, but after 14 days, tumor volume was comparable between MEKi and vehicle treated mice, possibly from acquired MEK162 resistance. Despite these data, reduced serum IL-6 and splenic Gr1+CD11b+ cells were evident compared to control mice (mean = 358 pg/mL to 43 pg/mL, and 13.8% to 8.4%, respectively), while body weight from MEK162 treated mice was spared (mean = 24.0g to 20.5g in control mice). In addition, markers of muscle catabolism, including the E3 ubiquitin ligases Atrogin-1 (from 1 to 0.043 in combo) and MuRF1 (from 1 to 0.03 in combo), and the autophagy gene, Bnip3, were all reduced in tibialis anterior muscles from tumor-bearing mice treated with MEK162. Similar to our clinical data, these results suggest MEK162 modulates immune biomarkers, and acts as an anti-cachexia agent. Since cross talk between MAPK and PI3K/AKT pathways promotes resistance to monotherapy, we next investigated the effects of MEK162 combined with buparlisib in the colon-26 model. As before, single agent MEK162 had a modest growth inhibitory effect, yet rescued body weight. Consistent with in vitro studies, single agent buparlisib was cytostatic, but not as effective as MEK162 in rescuing weight loss. However, dual treatment with MEK162 + buparlisib significantly inhibited tumor growth. This combination also significantly reduced splenic MDSC (mean = 37% to 9% in control mice) and increased CD4+ and CD8+ (mean = 24% to 6%, and 7.7% to 2%, respectively) T cells. These results suggest that dual inhibition of MEK and PI3K has efficacy, while MEKi may have under-appreciated tumor-extrinsic mechanisms of activity that can be leveraged to benefit patients with advanced malignancy. This treatment combination will be evaluated in CC patients in the setting of a Phase II clinical trial. Citation Format: Jennifer Yang, Erin Talbert, Omar Elnaggar, Priyani Rajasekera, Thomas Mace, Matthew Farren, Zheng Che, Benjamin Swanson, Gregory Young, Ericka Haverick, Cynthia Timmers, Mark Bloomston, Tanios Bekaii-Saab, Denis Guttridge, Gregory Lesinski. Dual targeting of MEK and PI3K pathways can act via tumor-intrinsic mechanisms to overcome resistance and tumor-extrinsic mechanisms to modulate immunity and limit cancer cachexia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4695. doi:10.1158/1538-7445.AM2015-4695

MicroRNA in Cancer and Cachexia--A Mini-Review.

MicroRNAs (miRNAs) are short noncoding RNAs with a length of approximately 22 nucleotides that are involved in posttranscriptional regulation of gene expression. miRNAs cover an important role in all biological processes, and aberrant miRNA expression is commonly associated with cancer. Recent discoveries have associated the involvement of miRNA in an increasingly large number of biological processes, including cachexia. The cachexia syndrome is a debilitating state of cancer that is, at least in part, associated with apoptosis. The mechanism through which tumors promote the characteristic distal loss of muscle and fat mass during the cachectic process is still not deeply investigated. In this review, we briefly describe the role of miRNAs in cancer development and cachexia.

Food connections: A qualitative exploratory study of weight- and eating-related distress in families affected by advanced cancer

PurposeWeight loss and eating problems are common in cancer and have a profound effect on quality of life. They are symptoms of cancer cachexia syndrome.This paper examines interdependency between advanced cancer patient and family carer experience of weight- and eating-related problems, leading to proposition of how weight- and eating-related distress might be alleviated in both patients and their family members. MethodsThe study was of cross-sectional design. Interpretive phenomenology informed the analytic process. Patient participants had advanced cancer and concern about weight and/or eating. Semi-structured interviews were conducted with 31 patient-spouse/partner dyads (62 interviews), which focused on weight loss and eating problems in the patient and how these had been managed. ResultsThis study found change in weight and eating habits in advanced cancer to disrupt food connections. Food connects us with others physically by fuelling the body and sustaining physical activity and life, emotionally by communicating feelings about self and others, and socially by providing a reason for sharing time with others. The study found three dyadic responses to disruption in food connections; dual acceptance, dual resistance and mismatched resistance. They are of interest, because they can help discriminate between those patient-family carer dyads who might benefit from psychosocial interventions and those who will cope without such help. ConclusionThe findings challenge clinicians and researchers to seek ways of aiding not only with concerns of the individual patients and carers, but also with interactions between distressed family members affected by symptoms of cancer cachexia syndrome.

Randomised Controlled Trial of Fish Oil Supplement to Treat Cancer Cachexia

Patients with advanced cancer often suffer from cachexia, a debilitating and complex extreme weight loss syndrome which is also associated with shorter survival times. A pragmatic randomised controlled trial was conducted to determine whether an oral nutritional supplement containing the omega-3 fatty acid eicosapentaenoic acid (EPA) was able to improve quality of life and survival times of patients with advanced solid tumour cancer in a mixed tumour cancer type population.

Deletion of TLR4 Attenuates Adipose Tissue Inflammation in Cancer Cachexia

Several studies have shown that syndrome of cachexia associated with cancer induces a drastic decrease in body weight and adipose tissue. Stimulation of TLR4 activates proinflammatory pathways and induces cytokine expression in a variety of cell types. Inflammatory pathways are activated in tissues of cachectic animals and play an important role in cancer‐cachexia syndrome. Loss of adipose tissue mass and inflammation occurred early considering the appearance of classical cachexia markers. In this study we evaluated cachexia development in TLR4 ‐/‐ mice. Male C57BL/6 mice, with 300µl (3,5 ×105) of LLC tumor cells or vehicle‐saline. Adipose tissue (SCAT, MEAT, RPAT) were collected on 27th day after cells injection. The SVF of AT was isolated and measured the infiltrated immune cells (macrophage and T lymphocytes) by Flow cytometry. SCAT (TWT 37,2% and TM 70,7%), MEAT (TWT 27,1% and TM 28,8%), RPAT (TWT 27,4% and TM 76,9%) showed an decrease of total mass on 27th. In flow cytometry using GR and MAC1 showed an accentuated decrease in MEAT of the TLR4 ‐/‐ mice when compared whit the Wild type mice, in both groups (CWT 77,5% and TWT 66,3%). We observed an accentuated body weight loss in both groups, WT and TLR4 ‐/‐. Therefore when we look at the MEAT, compared with the other depots of TLR4 ‐/‐ mice, presents an attenuated in tissue mass, besides occurring decreased of the most important inflammatory cells in to adipose tissue, characteristic during of the cachectic syndrome. Suggesting that deletion of TLR4 protein may play a role in adipose tissue inflammation.

Cachexia syndrome: The present state of the problem and importance in clinical practice

Available updates have changed our idea about cachexia as a terminal condition, which could consider it as a combined metabolic syndrome that gives rise to the worse course of the underlying disease, the lower efficiency of specific therapy, and higher death rates. Chronic inflammatory factors are recognized to be the main mechanisms for the development of cachexia syndrome (CS). In addition, diagnostic criteria for this pathological condition are well defined. These criteria are rather simple for use in clinical practice and they should be assessed by physicians at all stages of a follow-up of patients with severe chronic diseases, since cachexia may develop long before the appearance of the so-called extreme emaciation. The earlier the physician will anticipate the onset of CS, the more successful attempts to correct the latter and accordingly the better prognosis of the underlying disease will be. Available updates on the possibilities of correcting cachexia - anorexia are considered although there are no established standards for the management and treatment of patients with CS now. The elaboration of a step-by-step algorithm for following up the patients and a search for medications with proven clinical efficacy are relevant.

Cancer, Malnutrition and Cachexia: We Must Break the Triad

Many factors can modify nutritional status in cancer patients, including cachexia, nausea and vomiting, decreased caloric intake or oncologic treatments causing malabsorption. The cachexia-anorexia syndrome is a complex metabolic syndrome associated with cancer and some other palliative conditions characterized by involuntary weight loss involving fat and muscle, anorexia, early satiety, fatigue and weakness due to shifts in metabolism caused by tumour by-products and cytokines. Cachexia is a distressing and debilitating condition, affecting significant numbers of patients with advanced disease and is the primary cause of death in about 20% of all patients with cancer. Though cachexia is most commonly associated with particular tumours, such as head and neck, gastrointestinal tract, pancreas, central nervous system and lung, it may affect any patient with any tumour at any site; no patient and no tumour are excluded. Current treatment for principally depends on its prevention rather than reversing the present disease state, and the clinical results are far from being satisfactory. A careful decision based on good clinical judgement is necessary before deciding to start either enteral or parenteral nutrition, to avoid a useless, costly and difficult treatment. Treatment should be directed toward improvement in the quality of life of the patient and should often include nutritional counseling. It should take into consideration both disease and treatment related factors as well as the cachexia syndrome itself.

Cancer as a Proinflammatory Environment: Metastasis and Cachexia.

The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines.