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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]

OBJECTIVE. Cystic fibrosis (CF) is a multisystemic life-limiting disorder. The leading cause of morbidity in CF is chronic pulmonary disease. Chest CT is the reference standard for detection of bronchiectasis. Cumulative ionizing radiation limits the use of CT, particularly as treatments improve and life expectancy increases. The purpose of this article is to summarize the evidence on low-dose chest CT and its effect on image quality to determine best practices for imaging in CF. CONCLUSION. Low-dose chest CT is technically feasible, reduces dose, and renders satisfactory image quality. There are few comparison studies of low-dose chest CT and standard chest CT in CF; however, evidence suggests equivalent diagnostic capability. Low-dose chest CT with iterative reconstructive algorithms appears superior to chest radiography and equivalent to standard CT and has potential for early detection of bronchiectasis and infective exacerbations, because clinically significant abnormalities can develop in patients who do not have symptoms. Infection and inflammation remain the primary causes of morbidity requiring early intervention. Research gaps include the benefits of replacing chest radiography with low-dose chest CT in terms of improved diagnostic yield, clinical decision making, and patient outcomes. Longitudinal clinical studies comparing CT with MRI for the monitoring of CF lung disease may better establish the complementary strengths of these imaging modalities.