Measurement and optimization of perioperative risk among patients undergoing surgery for esophageal cancer.

Esophagectomy is an exemplar of complex oncological surgery and is associated with a relatively high risk of major morbidity and mortality. In the modern era, where specific complications are targeted in prevention and treatment pathways, and where the principles of enhanced recovery after surgery are espoused, optimum outcomes are targeted via a number of approaches. These include comprehensive clinical and physiological risk assessment, specialist perioperative care by a high-volume team, and multimodal inputs throughout the patient journey that aim to preserve or restore nutritional deficits, muscle mass and function.

Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysis.

Background: Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition.

Methods: This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, sympathetic-adrenal-medullary (SAM) axis, parasympathetic nervous system functioning, oxidative stress, immunological/inflammatory, cardiovascular, respiratory, lipidemia, anthropometric, glucose metabolism, kidney, and liver.

The Associations of Selenoprotein Genetic Variants with the Risks of Colorectal Adenoma and Colorectal Cancer: Case-Control Studies in Irish and Czech Populations.

Background: Selenium manifests its biological effects through its incorporation into selenoproteins, which play several roles in countering oxidative and inflammatory responses implicated in colorectal carcinogenesis. Selenoprotein genetic variants may contribute to colorectal cancer (CRC) development, as we previously observed for SNP variants in a large European prospective study and a Czech case-control cohort.

Methods: We tested if significantly associated selenoprotein gene SNPs from these studies were also associated with CRC risk in case-control studies from Ireland (colorectal neoplasia, i.

C-Reactive Protein and C-Reactive Protein-Based Scores to Predict Survival in Esophageal and Junctional Adenocarcinoma: Systematic Review and Meta-Analysis.

Background: Esophageal adenocarcinoma (EAC) has a poor prognosis; predictive markers of prognosis would facilitate advances in personalized therapy. C-reactive protein (CRP) and CRP-based scores are increasingly recommended across oncology; however, their role and value in EAC is unclear. This systematic review and meta-analysis examined CRP cut-point and scores and how they may best be applied in predicting survival in EAC.

Fractalkine Elicits Chemotactic, Phenotypic, and Functional Effects on CX3CR1CD27 NK Cells in Obesity-Associated Cancer.

Esophagogastric adenocarcinomas (EAC) are obesity-associated malignancies underpinned by severe immune dysregulation and inflammation. Our previous work indicates that NK cells migrate to EAC omentum, where they undergo phenotypic and functional alterations and apoptosis. In this study, we investigate whether such erroneous chemotaxis to omentum is paralleled by compromised NK cell infiltration of EAC patient tumor and examine the role of the inflammatory chemokine fractalkine in shaping the NK cell-mediated response.

Preoperative high intensity interval training for oncological resections: A systematic review and meta-analysis.

Exercise prehabilitation prior to major surgery targets a reduction in postoperative complications through improved conditioning and respiratory function. However its effectiveness in cancer surgery is unclear. The objective of this review was to determine if preoperative high-intensity interval training (HIIT) improves preoperative fitness in patients scheduled for oncologic resection, and whether postoperative complications are impacted.

Complement in Tumourigenesis and the Response to Cancer Therapy.

In recent years, our knowledge of the complement system beyond innate immunity has progressed significantly. A modern understanding is that the complement system has a multifaceted role in malignancy, impacting carcinogenesis, the acquisition of a metastatic phenotype and response to therapies. The ability of local immune cells to produce and respond to complement components has provided valuable insights into their regulation, and the subsequent remodeling of the tumour microenvironment.

Visceral Obesity, Metabolic Syndrome, and Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) represents an exemplar of obesity-associated carcinogenesis, with a progressive increase in EAC risk with increased body mass index. In this context, there is increased focus on visceral adipose tissue and associated metabolic dysfunction, including hypertension, diabetes mellitus and hyperlipidemia, or combinations of these in the metabolic syndrome. Visceral obesity (VO) may promote EAC both directly impacting on gastro-esophageal reflux disease and Barrett's esophagus, as well as reflux-independent effects, involving adipokines, growth factors, insulin resistance, and the microbiome.

The Protein Secretome Is Altered in Rectal Cancer Tissue Compared to Normal Rectal Tissue, and Alterations in the Secretome Induce Enhanced Innate Immune Responses.

Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy; however, only ~22% of patients achieve a complete response, and resistance mechanisms are poorly understood. The role of inflammation and immune cell biology in this setting is under-investigated. In this study, we profiled the inflammatory protein secretome of normal (non-cancer) ( = 8) and malignant rectal tissue ( = 12) pre- and post-radiation in human ex vivo explant models and examined the influence of these untreated and treated secretomes on dendritic cell biology ( = 8 for cancer and normal).

A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy.

Background: Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss.

Exaggerated postprandial GLP-1 secretion following esophagectomy is not associated with gastric emptying and intestinal transit.

Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1 year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT).

Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder.

Coeliac disease is a common small bowel enteropathy arising in genetically predisposed individuals and caused by ingestion of gluten in the diet. Great advances have been made in understanding the role of the adaptive immune system in response to gluten peptides. Despite detailed knowledge of these adaptive immune mechanisms, the complete series of pathogenic events responsible for development of the tissue lesion remains less certain.

Cardiopulmonary Exercise Testing in Oesophagogastric Surgery: a Systematic Review.

Background: Cardiopulmonary exercise testing (CPX) can objectively measure fitness and oxygen uptake at anaerobic threshold. The relationship between fitness and postoperative outcomes after upper gastro-intestinal surgery is unclear. The aim of the present review is to assess the prognostic ability of CPX in predicting postoperative outcome associated with oesophagogastric surgery.

Early experience with a nutrition and survivorship clinic in esophageal cancer.

Improved cure rates in esophageal cancer care have increased focus on health-related quality of life (HRQL) in survivorship. To optimize recovery after esophagectomy, particularly nutritional well-being, a personalized multidisciplinary survivorship clinic was established at this center. Assessments at 6 and 12 months postoperatively include validated European Organization for the Research and Treatment of Cancer (EORTC) symptom and health-related quality of life (HRQL) questionnaires, functional status review, anthropometry, and biochemical screening for micronutrient deficiencies.

The Radiation-Induced Bystander Effect (RIBE) and its Connections with the Hallmarks of Cancer.

Radiation therapy is one of the pillars of cancer treatment, with approximately one half of all cancer patients receiving it as part of their standard of care. Emerging evidence indicates that the biological effects of radiation are not limited to targeted cells. The radiation-induced bystander effect (RIBE) refers to the plethora of biological phenomena occurring in nonirradiated cells as a result of signal transmission from an irradiated cell.

Physical recovery in the first six months following oesophago-gastric cancer surgery. Identifying rehabilitative needs: a qualitative interview study.

Purpose: To investigate patients' perspectives of their physical recovery in the first six months post oesophago-gastric cancer surgery.

Materials And Methods: Semi-structured interviews were held at St James's Hospital, Dublin, with participants who were 4 weeks to 6 months post-oesophagectomy/gastrectomy. Interviews were an average of 14 min and included questions pertaining to physical recovery post-oesophagectomy/gastrectomy.

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy.

Background: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy.

Methods: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52 weeks after surgery.

Attenuation of satiety gut hormones increases appetitive behavior after curative esophagectomy for esophageal cancer.

Background: Reduced appetite and weight loss are common after esophagectomy (ES), and this cohort demonstrates an exaggerated postprandial satiety gut hormone response. Satiety gut hormones modulate food reward, resulting in reduced energy intake.

Objectives: This study aimed to determine the effect of satiety gut hormone modulation by measuring the effect of the somatostatin analog octreotide on appetitive behavior among patients after ES.

Risk factors for loss of bone mineral density after curative esophagectomy.

Unlabelled: Micronutrient and fat malabsorption and altered enteroendocrine signaling occur after esophagectomy for cancer; however, the impact of malnutrition on bone health in this cohort has not been previously investigated. In this study, the prevalence of osteoporosis increased after curative surgery, associated with disease-specific, treatment-related, and population risk factors.

Purpose: Improved oncologic outcomes in esophageal cancer (EC) have resulted in increased survivorship and a focus on long-term quality of life.

The Mitochondrial Genes , and are Linked with Alterations in Mitochondrial Membrane Potential in Barrett's Esophagus.

Barrett's esophagus and esophageal cancer lack prognostic markers that allow the tailoring of personalized medicine and biomarkers with potential to provide insight into treatment response. This study aims to characterize mitochondrial function across the metaplasia-dysplasia-adenocarcinoma disease sequence in Barrett's esophagus and examines the functional effect of manipulating mitochondrial genes. Mitochondrial genes of interest were validated in in vitro cell lines across the metaplasia (QH), dysplasia (GO) and adenocarcinoma (OE33) sequence and in in vivo patient tissue samples.

Obesity and gastrointestinal cancer: the interrelationship of adipose and tumour microenvironments.

Increasing recognition of an association between obesity and many cancer types exists, but how the myriad of local and systemic effects of obesity affect key cellular and non-cellular processes within the tumour microenvironment (TME) relevant to carcinogenesis, tumour progression and response to therapies remains poorly understood. The TME is a complex cellular environment in which the tumour exists along with blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, signalling molecules and the extracellular matrix. Obesity, in particular visceral obesity, might fuel the dysregulation of key pathways relevant to both the adipose microenvironment and the TME, which interact to promote carcinogenesis in at-risk epithelium.

The RESTORE Randomized Controlled Trial: Impact of a Multidisciplinary Rehabilitative Program on Cardiorespiratory Fitness in Esophagogastric cancer Survivorship.

Objective: The Rehabilitation Strategies in Esophagogastric cancer (RESTORE) randomized controlled trial evaluated the efficacy of a 12-week multidisciplinary program to increase the cardiorespiratory fitness and health-related quality of life (HRQOL) of esophagogastric cancer survivors.

Background: Patients following treatment for esophagogastric cancer are at risk of physical deconditioning, nutritional compromise, and sarcopenia. Accordingly, compelling rationale exists to target these impairments in recovery.