Cachexia is a multifactorial process of skeletal muscle and adipose tissue atrophy resulting in progressive weight loss. It is associated with poor quality of life, poor physical function, and poor prognosis in cancer patients. It involves multiple pathways: procachectic and proinflammatory signals from tumour cells, systemic inflammation in the host, and widespread metabolic changes (increased resting energy expenditure and alterations in metabolism of protein, fat, and carbohydrate). Whether it is primarily driven by the tumour or as a result of the host response to the tumour has yet to be fully elucidated. Cachexia is compounded by anorexia and the relationship between these two entities has not been clarified fully. Inconsistencies in the definition of cachexia have limited the epidemiological characterisation of the condition and there has been slow progress in identifying therapeutic agents and trialling them in the clinical setting. Understanding the complex interplay of tumour and host factors will uncover new therapeutic targets.

This paper presents emerging evidence linking visceral adiposity and the metabolic syndrome (MetSyn) with carcinogenesis. The link between obesity and cancer has been clearly identified in a multitude of robust epidemiological studies. Research is now focusing on the role of visceral adipose tissue in carcinogenesis; as it is recognised as an important metabolic tissue that secretes factors that systemically alter the immunological, metabolic and endocrine milieu. Excess visceral adipose tissue gives rise to a state of chronic systemic inflammation with associated insulin resistance and dysmetabolism, collectively known as the MetSyn. Prospective cohort studies have shown associations between visceral adiposity, the MetSyn and increased risk of breast cancer, colorectal cancer and oesophageal adenocarcinoma. Furthermore, visceral adiposity and the MetSyn have been associated with increased tumour progression and reduced survival. The mechanisms by which visceral adiposity and the MetSyn are thought to promote tumorigenesis are manifold. These include alterations in adipokine secretion and cell signalling pathways. In addition, hyperinsulinaemia, subsequent insulin resistance and stimulation of the insulin-like growth factor-1 axis have all been linked with visceral adiposity and promote tumour progression. Furthermore, the abundance of inflammatory cells in visceral adipose tissue, including macrophages and T-cells, create systemic inflammation and a pro-tumorigenic environment. It is clear from current research that excess visceral adiposity and associated dysmetabolism play a central role in the pathogenesis of certain cancer types. Further research is required to elucidate the exact mechanisms at play and identify potential targets for intervention. Visceral adiposity: Metabolic syndrome: Insulin resistance: Inflammation: TumorigenesisThe prevalence of obesity has increased rapidly in recent years (1) . Being overweight or obese is now the most prevalent body composition in some countries, accounting for 71% of males and 62 % of females in the United States (2) . Similar trends exist in Western Europe with greater than 66% of men and 49-57 % of women being overweight or obese in the UK and Ireland (3,4) . This pattern shows no signs of abating as obesity rates are increasing among children (5) and overweight children tend to become overweight adults (6) . In countries where sedentary lifestyles and high-energy foods are abundant it is easy to see how energy intake exceeds that expended. It has been estimated that ingestion of 5 % more energy than expended may result in an accumulation of 5 kg adipose tissue in a single year (7) . Epidemiological studies have demonstrated a robust link between obesity and cancer development at numerous sites, in particular the oesophagus, pancreas, colorectum, breast (postmenopausal), endometrium and kidney (8,9) . This association carries relative risk (RR) estimates of 1 . 1-1 . 6 per 5 kg/m 2 incremental increase in BMI (8) . Obesity also increases cancer-related mo...

BackgroundThere is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective.MethodsRelevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance.ResultsNumerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy.ConclusionsThere is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

BackgroundNeoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens.MethodsThis open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research.DiscussionThis RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG).Trial registration NCT01726452. Protocol 10-14. Date of registration 06/11/2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3386-2) contains supplementary material, which is available to authorized users.

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Background: There is emerging evidence of a strong association between obesity and gastrointestinal cancer. This review summarizes the evidence from an epidemiological and pathophysiological perspective. Methods: Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles were identified. Selection of articles was based on peer review, journal and relevance.Results: Numerous epidemiological studies consistently identified an increased risk of developing oesophageal adenocarcinoma and colorectal carcinoma in the obese. The association between obesity and other gastrointestinal malignancies was less robust. Sex seems important with respect to cancer risk. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the insulin-like growth factor axis, adipocytokines and sex steroids. Conclusion:A better understanding of the mechanisms that link obesity and cancer may uncover targets for intervention. Tackling obesity may result in a reduction in the incidence in addition to mortality of certain cancers in future.

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This novel study examined the differential role of the IGF system in esophageal adenocarcinoma and SCC, and its association with visceral obesity. These results indicate that the IGF-1 axis has a key role in malignant progression of esophageal cancer, and represents a plausible mechanism through which visceral obesity impacts on esophageal adenocarcinoma risk and tumor biology.