Search

Simple Summary: Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited response rates to current treatment modalities and is strongly linked to obesity status and metabolic dysfunction. This study for the first time has conducted a detailed assessment of adipose tissue metabolism, as well as assessing adipose secreted pro-inflammatory, metabolite, and lipid profiles to determine whether these profiles correlate with significant clinical parameters in OAC patients including obesity, metabolic dysfunction, previous treatment exposure, and tumour regression grades. Overall, in this study, increases in metabolic profiles linked with oxidative phosphorylation, pro-inflammatory cytokines, and metabolites associated with aiding tumorigenesis have been identified in the most viscerally obese OAC patients and in patients with metabolic dysfunction. These results raise the question of whether targeting these altered signalling mechanisms could aid current treatment strategies. Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited response rates to current treatment modalities and has a strong link to obesity. To better elucidate the role of visceral adiposity in this disease state, a full metabolic profile combined with analysis of secreted pro-inflammatory cytokines, metabolites, and lipid profiles were assessed in human ex vivo adipose tissue explants from obese and non-obese OAC patients. These data were then related to extensive clinical data including obesity status, metabolic dysfunction, previous treatment exposure, and tumour regression grades. Real-time energy metabolism profiles were assessed using the seahorse technology. Adipose explant conditioned media was screened using multiplex ELISA to assess secreted levels of 54 pro-inflammatory mediators. Targeted secreted metabolite and lipid profiles were analysed using Ultra-High-Performance Liquid Chromatography coupled with Mass Spectrometry. Adipose tissue explants and matched clinical data were collected from OAC patients (n = 32). Compared to visceral fat from non-obese patients (n = 16), visceral fat explants from obese OAC patients (n = 16) had significantly elevated oxidative phosphorylation metabolism profiles and an increase in Eotaxin-3, IL-17A, IL-17D, IL-3, MCP-1, and MDC and altered secretions of glutamine associated metabolites. Adipose explants from patients with metabolic dysfunction correlated with increased oxidative phosphorylation metabolism, and increases in IL-5, IL-7, SAA, VEGF-C, triacylglycerides, and metabolites compared with metabolically healthy patients. Adipose explants generated from patients who had previously received neo-adjuvant chemotherapy (n = 14) showed elevated secretions of pro-inflammatory mediators, IL-12p40, IL-1α, IL-22, and TNF-β and a decreased expression of triacylglycerides. Furthermore, decreased secreted levels of triacylglycerides were also observed in the adipose secretome of patients who received the chemotherapy-only regimen FLOT compared with patients who received no neo-adjuvant treatment or chemo-radiotherapy regimen CROSS. For those patients who showed the poorest response to currently available treatments, their adipose tissue was associated with higher glycolytic metabolism compared to patients who had good treatment responses. This study demonstrates that the adipose secretome in OAC patients is enriched with mediators that could prime the tumour microenvironment to aid tumour progression and attenuate responses to conventional cancer treatments, an effect which appears to be augmented by obesity and metabolic dysfunction and exposure to different treatment regimes. [ABSTRACT FROM AUTHOR]

Simple Summary: Oesophageal adenocarcinoma (OAC) is a type of cancer of the oesophagus (food pipe) which is associated with poor patient outcomes. Barrett's oesophagus (BO) is a precancerous condition of the oesophagus associated with chronic heartburn. Currently, surveillance programs exist which monitor patients with BO to prevent it from developing into OAC. However, these surveillance programs are expensive and unpleasant for patients. Prognostic biomarkers are signs which could be measured to determine the chance of someone with BO developing OAC, allowing more targeted surveillance. Similarly, diagnostic biomarkers are indicators which could be measured to see if someone has OAC. Developing new diagnostic biomarkers could allow wider population testing. Only a small proportion of patients with OAC respond to treatment before surgery. Predictive biomarkers could be measured to predict whether someone would respond to the treatments, allowing more individualized therapy. This review focuses on potential biomarkers which could improve patient outcomes in BO/OAC. Oesophageal adenocarcinoma (OAC) incidence has increased dramatically in the developed world, yet outcomes remain poor. Extensive endoscopic surveillance programs among patients with Barrett's oesophagus (BO), the precursor lesion to OAC, have aimed to both prevent the development of OAC via radiofrequency ablation (RFA) and allow earlier detection of disease. However, given the low annual progression rate and the costs of endoscopy/RFA, improvement is needed. Prognostic biomarkers to stratify BO patients based on their likelihood to progress would enable a more targeted approach to surveillance and RFA of high-risk precursor lesions, improving the cost–risk–benefit ratio. Similarly, diagnostic biomarkers for OAC could enable earlier diagnosis of disease by allowing broader population screening. Current standard treatment for locally advanced OAC includes neoadjuvant chemotherapy (+/− radiotherapy) despite only a minority of patients benefiting from neoadjuvant treatment. Accordingly, biomarkers predictive of response to neoadjuvant therapy could improve patient outcomes by reducing time to surgery and unnecessary toxicity for the patients who would have received no benefit from the therapy. In this mini-review, we will discuss the emerging biomarkers which promise to dramatically improve patient outcomes along the BO-OAC disease sequence. [ABSTRACT FROM AUTHOR]

Simple Summary: An esophageal cancer diagnosis signals the start of a difficult period of health-related physical, psychological, and social challenges. To date, relatively few studies have explored the diagnosis, treatment, and recovery experiences of esophageal cancer survivors. Esophageal cancer diagnosis and treatment pose challenges to all aspects of wellbeing, and necessitate an extended period of recovery. As such, supportive education and rehabilitative interventions must encompass a range of strategies to help survivors maintain an adequate quality of life during treatment and recovery. This study aimed to examine patient experiences of esophageal cancer diagnosis, treatment, and recovery, to enable researchers and health professionals to better understand the education and rehabilitative needs of esophageal cancer survivors. Esophageal cancer poses challenges to all domains of wellbeing. This qualitative study aimed to explore the experiences of esophageal cancer diagnosis, treatment, and recovery, with a view to informing the health education needs of this group. Eighteen persons who had undergone an esophagectomy participated in one of four audio-taped focus groups in a specialist hospital for cancer care. Transcriptions were analyzed thematically. Fear and uncertainty underpinned all stages of diagnosis, treatment, and recovery. Participants emphasized: (a) a lack of understanding over what to expect throughout treatment and recovery; (b) the demanding and traumatic period of adjustment required as a result of changes to their physical, psychological, and social functioning; and, (c) that support provided by family, friends, and acquaintances was variable and uninformed, often to the point of being counterproductive to physical and psychosocial recovery. Tailored education is needed to enable patients to prepare for each stage of their cancer journey. Equally, families and wider social networks should receive education that enables them to provide esophageal cancer survivors with appropriate support. Education should be provided at intervals that enable patients, survivors, and support networks to prepare for the physical, emotional, and social challenges experienced during diagnosis, treatment, and recovery. [ABSTRACT FROM AUTHOR]