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Background: People experiencing homelessness are more likely to experience poor health with physical functioning deficits and frailty commonly reported. It is not well known how strategies to target physical functioning deficits and frailty work in practice in this group. The primary aim of this study was to explore the feasibility of an exercise intervention with protein supplementation to target physical functioning and frailty in people experiencing homelessness evaluated by recruitment and retention rates, adherence to the exercise sessions and protein supplement, adverse effects, programme feedback and characteristics of non-returners, sporadic and frequent attenders. The secondary aim was to evaluate changes in effectiveness outcomes of grip strength, muscle mass, lower extremity physical function, pain, frailty, and risk of malnutrition. Method: This prospective single-arm study evaluated the feasibility of a 16-week rolling, low-threshold, 'drop-in' once weekly exercise programme with protein supplementation. The main recruitment site was a day-service centre for people who are homeless. Feasibility was assessed by the recruitment and retention rates, adherence to the exercise sessions and protein supplement as well as adverse effects, programme feedback and evaluation of characteristics of non-returners, sporadic (≤50% of available sessions) and frequent attenders (≥50% of available sessions). Effectiveness outcomes included pain (Visual Analogue Scale), physical functioning and performance (hand-grip dynamometry, limb circumference, the Short Physical Performance Battery), frailty (SHARE-FI and Clinical Frailty Scale) and nutritional status (Mini Nutritional Assessment). Results: Thirty-one participants were recruited mean (SD) age 45(16) years. There was a recruitment rate of a median (IQR) of 2(1–3) new participants per week. The retention rate was 45% (n = 14) to the main recruitment site. Adherence to the exercise sessions and nutritional intervention was 90% and 100% respectively. Three adverse events were recorded during 74 interventions over the 16-week programme. The acceptability of the programme was highlighted in participant feedback. Characteristics of frequent returners (≥50%) were older age, female, more stably housed and more stable in addiction. The programme did not induce any changes in effectiveness outcomes. Conclusion: The feasibility of this programme was demonstrated. Overall, the programme was well received with higher retention rates in older participants, females, those more stably housed and those stable in addiction. A higher powered, more intense programme is needed to demonstrate programme effectiveness. [ABSTRACT FROM AUTHOR]

Introduction: To outline the development and implementation of a food science and nutrition module for dental undergraduate students that provides basic knowledge and clinical skills for improving oral health outcomes and understanding their importance for overall health. Materials and methods: Interdisciplinary discussions with professionals with expertise in food science and nutrition, including dentists, dietitians and nutritionists, were held to agree on core subject areas in line with the evidence base. The module was delivered online to 2nd‐year dental students due to COVID‐19 restrictions. Students completed an online evaluation on completing the module. Final examination consisted of one essay question. Results: Subject areas and learning outcomes were derived from current and previous approaches to curriculum development. A total of 14 prerecorded lectures, including healthy eating guidelines, dietary assessment, specific oral effects of diet and food constituents were delivered and tutorials provided. The evaluation survey had a 90% (n = 39/43) response rate. A majority indicated that the course was "interesting," "worth doing" (59%) and "provided a good evidence base to understand nutrition and oral health" (87%). Nearly all students (92%) agreed that the course was "sufficiently structured to allow understanding of the key topics" and that "a good understanding of nutrition is important for a dentist" (95%). Conclusion: A food science and nutrition module developed by a multidisciplinary team enabled dental students to gain an understanding of the role of diet in oral and overall health. The module facilitated the development of skills that enable students to utilise dietary assessment techniques and promote dietary interventions beneficial to oral health. The approach taken may act as a template for other institutions. [ABSTRACT FROM AUTHOR]

Visceral obesity (VO) and metabolic syndrome (MetS) are risk factors for esophageal adenocarcinoma (EAC); however, their impact on operative and oncological outcomes is unclear. The aim of this study was to determine the incidence of VO and MetS among patients with EAC, and to assess their independent impact on operative and oncological outcomes. A total of 454 consecutive patients undergoing treatment with curative intent were studied. Total, subcutaneous, visceral fat area (VFA), and lean body mass (LBM) were measured by computed tomography pretreatment, with VO defined as VFA >163.8cm2 for men and 80.1cm2 for women. MetS was defined per the ATPIII definition. Multivariable logistic and Cox proportional hazards regression were utilized to determine independent predictors of oncologic and operative outcomes. A total of 227 patients (50.0%) had VO. A total of 134 (30%) overall had MetS, 44% in the VO cohort. VO was associated with Barrett's esophagus (P  = 0.002) and lower cT (P  = 0.006) and cN stage (P  = 0.011), and improved disease-specific (P  = 0.021) and overall survival (P =  0.012). No survival benefit existed for patients with VO who also had MetS. For operative complications, neither VO nor MetS increased the severity of complications, or mortality. However, VO was significantly (P  = 0.035) associated with anastomotic leak and pneumonia (P  = 0.037). MetS alone did not increase complication risk. VO increases specific major operative complications with no increase in mortality. VO improved survival, mainly relating to earlier stage disease; however, co-existent MetS abrogated this benefit. These seemingly paradoxical outcomes highlight manageable and potentially targetable perioperative challenges in the context of an overall favorable oncologic vista. [ABSTRACT FROM AUTHOR]

Simple Summary: Throughout the COVID-19 pandemic, many cancer care services have safely been delivered via telehealth. Multi-disciplinary rehabilitation programmes can help address the complex physical, nutritional and quality of life needs of upper gastrointestinal (UGI) cancer survivors, but it is unknown how well these multi-component programmes translate to a telehealth model of delivery. Therefore, we assessed the feasibility of running a 12-week exercise and nutrition rehabilitation programme for UGI cancer via telehealth. Participants found the telehealth model safe, convenient and highly satisfactory. Lower levels of technology skills were a barrier to recruitment, and some participants needed help with using the technology. Some adaptations to how the exercise programme was delivered were required. Participants recommended that future versions of the programme would have some element of in-person contact. Cancer survivors should receive all possible supports to enable their participation in telehealth programmes. Background: Telehealth has enabled access to rehabilitation throughout the pandemic. We assessed the feasibility of delivering a multi-disciplinary, multi-component rehabilitation programme (ReStOre@Home) to cancer survivors via telehealth. Methods: This single-arm mixed methods feasibility study recruited participants who had completed curative treatment for oesophago-gastric cancer for a 12-week telehealth rehabilitation programme, involving group resistance training, remotely monitored aerobic training, one-to-one dietetic counselling, one-to-one support calls and group education. The primary outcome was feasibility, measured by recruitment rates, attendance, retention, incidents, acceptability, Telehealth Usability Questionnaire (TUQ) and analysis of semi-structured interviews. Results: Characteristics of the twelve participants were: 65.42 ± 7.24 years; 11 male; 10.8 ± 3.9 months post-op; BMI 25.61 ± 4.37; received neoadjuvant chemotherapy 7/12; received adjuvant chemotherapy 4/12; hospital length of stay 16 days (median). Recruitment rate was 32.4%, and retention rate was 75%. Mean attendance was: education 90%; dietetics 90%; support calls 84%; resistance training 78%. Mean TUQ score was 4.69/5. Adaptations to the planned resistance training programme were required. Participants reported that ReStOre@Home enhanced physical and psychological wellbeing, and online delivery was convenient. Some reported a preference for in-person contact but felt that the online group sessions provided adequate peer support. Conclusion: Telehealth delivery of ReStOre@Home was most feasible in individuals with moderate to high levels of digital skills. Low level of digitals skills was a barrier to recruitment and retention. Participants reported high levels of programme adherence and participant satisfaction. Adaptations to future programmes, including introducing elements of in-person contact, are required. [ABSTRACT FROM AUTHOR]

Background: The Rehabilitation Strategies Following Esophagogastric cancer (ReStOre) randomized control trial demonstrated a significant improvement in cardiorespiratory fitness of esophagogastric cancer survivors. This follow-up, exploratory study analyzed the biological effect of exercise intervention on levels of 55 serum proteins, encompassing mediators of angiogenesis, inflammation, and vascular injury, from participants on the ReStOre trial. Methods: Patients >6 months disease free from esophagogastric cancer were randomized to usual care or the 12-week ReStOre program (exercise training, dietary counselling, and multidisciplinary education). Serum was collected at baseline (T0), post-intervention (T1), and at 3-month follow up (T2). Serum biomarkers were quantified by enzyme-linked immunosorbent assay (ELISA). Results: Thirty-seven patients participated in this study; 17 in the control arm and 20 in the intervention arm. Exercise intervention resulted in significant alterations in the level of expression of serum IP-10 (mean difference (MD): 38.02 (95% CI: 0.69 to 75.35)), IL-27 (MD: 249.48 (95% CI: 22.43 to 476.53)), and the vascular injury biomarkers, ICAM-1 (MD: 1.05 (95% CI: 1.07 to 1.66)), and VCAM-1 (MD: 1.51 (95% CI: 1.04 to 2.14)) at T1. A significant increase in eotaxin-3 (MD: 2.59 (95% CI: 0.23 to 4.96)), IL-15 (MD: 0.27 (95% CI: 0 to 0.54)) and decrease in bFGF (MD: 1.62 (95% CI: -2.99 to 0.26)) expression was observed between control and intervention cohorts at T2 (p<0.05). Conclusions: Exercise intervention significantly altered the expression of a number of serum biomarkers in disease-free patients who had prior treatment for esophagogastric cancer. Impact: Exercise rehabilitation causes a significant biological effect on serum biomarkers in esophagogastric cancer survivors. Clinical Trial Registration: ClinicalTrials.gov (NCT03314311). [ABSTRACT FROM AUTHOR]

Abstract Background There 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. Methods Relevant 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. Results Numerous 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. Conclusions There 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.

Objectives Cancer patient outcomes and selection for novel therapies are heavily influenced by the immune contexture of the tumor microenvironment. Esophageal cancer is associated with poor outcomes. In contrast to colorectal cancer, where the immunoscore is increasingly used in prognostic staging, little is known about the immune cell populations in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (SCC), and their clinical significance. Methods Tissue microarrays were constructed from resected tumor tissue of 72 EAC patients and 23 SCC patients. Immunohistochemical staining of CD3, CD8, CD56, CD68, CD45RO, CD69, IFN-γ, IL-10, IL-4, IL-17, TGF-β, FOXP3 and CD107a was performed. Positivity was examined in both the stromal and epithelial compartments. Statistical analysis was performed to identify differences in immune cell infiltration and functional phenotypes between cancer subtypes and tissue compartments. Results This study identified that esophageal tumors are enriched with CD45RO+ and CD8+ cells and such positivity is significantly higher in SCC compared with EAC. Furthermore, the expression of CD45RO positively correlates with that of CD8 within the tumors of both patient cohorts, suggesting a dominance of memory cytotoxic T cells. This is supported by strong positivity of degranulation marker CD107a in the stromal compartment of EAC and SCC tumors. Cytokine staining revealed a mixed pro- and anti-inflammatory profile within EAC tumors. Conclusions Esophageal tumors are enriched with memory cytotoxic T cells. Applying these measurements to a larger cohort will ascertain the clinical utility of assessing specific lymphocyte infiltrates in EAC and SCC tumors with regards to future immunotherapy use, patient prognosis and outcomes. [ABSTRACT FROM AUTHOR]

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. Methods: Disease-free patients treated for esophagogastric cancer were randomized to either usual care or the 12-week RESTORE program (exercise training, dietary counseling, and multidisciplinary education). The primary outcome was cardiopulmonary exercise testing (VO2peak). Secondary outcomes included body composition (bioimpedance analysis), and HRQOL (EORTC-QLQ-C30). Outcomes were assessed at baseline (T0), postintervention (T1), and at 3-month follow-up (T2). Results: Twenty-two participants were randomized to the control group [mean (standard deviation) age 64.14 (10.46) yr, body mass index 25.67 (4.83) kg/m2, time postsurgery 33.68 (19.56) mo], and 21 to the intervention group [age 67.19(7.49) yr, body mass index 25.69(4.02) kg/m2, time postsurgery 23.52(15.23) mo]. Mean adherence to prescribed exercise sessions were 94(12)% (supervised) and 78(27)% (unsupervised). Correcting for baseline VO2peak, the intervention arm had significantly higher VO2peak at both T1, 22.20 (4.35) versus 21.41 (4.49) mL · min−1 · kg−1, P < 0.001, and T2, 21.75 (4.27) versus 20.74 (4.65) mL · min−1 · kg−1, P = 0.001, compared with the control group. Correcting for baseline values, no changes in body composition or HRQOL were observed. Conclusions: The RESTORE program significantly improved cardiorespiratory fitness of disease-free patients after esophagogastric cancer surgery, without compromise to body composition. This randomized controlled trial provides proof of principle for rehabilitation programs in esophagogastric cancer. Clinical Trial Registration Number: NCT03314311. [ABSTRACT FROM AUTHOR]

The omentum is enriched with pro-inflammatory effector memory CD8+ T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8+ T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8+ T cells expressing intermediate levels (CX3CR1INT) are defined as peripheral memory, those expressing the highest levels (CX3CR1HI) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1NEG) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8+ T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8+ T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8+ T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1INT and CX3CR1HI CD8+ T cells in the fractalkine-rich environment of omentum in EAC, relative to matched blood. Fractalkine-mediated endocytosis of CX3CR1 by CD8+ T cells is sustained and is followed by enhanced surface expression of L-selectin (CD62L). These novel data align with our findings that circulating CX3CR1NEG CD8+ T cells express higher levels of L-selectin than CX3CR1INT CD8+ T cells. This is consistent with previous reports and implicates fractalkine in the conversion of CX3CR1INT CD8+ T cells to a CX3CR1NEG phenotype characterized by alterations in the migratory capacity of these T cells. For the first time, these findings identify fractalkine as a driver of T cell migration to the omentum in EAC and indicate that CD8+ T cells undergo sequenced fractalkine-mediated alterations in CX3CR1 and L-selectin expression. These data implicate fractalkine as more than a chemotactic cytokine in obesity-associated meta-inflammation and reveal a role for this chemokine in the maINTenance of the CX3CR1NEG CD8+ T cell populations. [ABSTRACT FROM AUTHOR]

Objective: To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy. Background: With improved oncologic outcomes in esophageal cancer, there is an increasing focus on functional status and health-related quality of life in survivorship. Early satiety and weight loss are common after esophagectomy, but the pathophysiology of these phenomena remains poorly understood. Methods: In this prospective study, consecutive patients undergoing esophagectomy with gastric conduit reconstruction were studied preoperatively and at 10 days, 6 weeks, and 3 months postoperatively. Glucagon-like peptide 1 (GLP-1) immunoreactivity of plasma collected immediately before and at 15, 30, 60, 90, 120, 150, and 180 minutes after a standardized 400-kcal mixed meal was determined. Gastrointestinal symptom scores were computed using European Organization for Research and Treatment of Cancer questionnaires. Results: Body weight loss at 6 weeks and 3 months postoperatively among 13 patients undergoing esophagectomy was 11.1±2.3% (P < 0.001) and 16.3±2.2% (P < 0.0001), respectively. Early satiety (P = 0.043), gastrointestinal pain and discomfort (P = 0.01), altered taste (P = 0.006), and diarrhea (P = 0.038) scores increased at 3 months postoperatively. Area under the curve for the satiety gut hormone GLP-1 was significantly increased from 10 days postoperatively (2.4±0.2-fold increase, P < 0.01), and GLP-1 peak increased 3.8±0.6-, 4.7±0.8-, and 4.4±0.5-fold at 10 days, 6 weeks, and 3 months postoperatively (all P < 0.0001). Three months postoperatively, GLP-1 area under the curve was associated with early satiety (P = 0.0002, R2 = 0.74), eating symptoms (P= 0.007, R2 =0.54), and trouble enjoying meals (P = 0.0004, R² = 0.73). Conclusions: After esophagectomy, patients demonstrate an exaggerated postprandial satiety gut hormone response, which may mediate postoperative changes in satiety, body weight, and gastrointestinal quality of life. [ABSTRACT FROM AUTHOR]

Obesity is a global health problem presenting serious risk of disease fuelled by chronic inflammation, including type 2 diabetes mellitus, cardiovascular disease, liver disease and cancer. Visceral fat, in particular the omentum and liver of obese individuals are sites of excessive inflammation. We propose that chemokine‐mediated trafficking of pro‐inflammatory cells to the omentum and liver contributes to local and subsequent systemic inflammation. Oesophagogastric adenocarcinoma (OAC) is an exemplar model of obesity and inflammation driven cancer. We have demonstrated that T cells actively migrate to the secreted factors from the omentum and liver of OAC patients and that both CD4+ and CD8+ T cells bearing the chemokine receptor CCR5 are significantly more prevalent in these tissues compared to matched blood. The CCR5 ligand and inflammatory chemokine MIP‐1α is also secreted at significantly higher concentrations in the omentum and liver of our OAC patient cohort compared to matched serum. Furthermore, we report that MIP‐1α receptor antagonism can significantly reduce T cell migration to the secreted factors from OAC omentum and liver. These novel data suggest that chemokine receptor antagonism may have therapeutic potential to reduce inflammatory T cell infiltration to the omentum and liver and in doing so, may ameliorate pathological inflammation in obesity and obesity‐associated cancer. [ABSTRACT FROM AUTHOR]

There is increasing recognition of the impact of being overweight and obese on the development of cancers at diverse sites including the gastrointestinal tract. Large epidemiological studies indicate that up to 14% of tumours may be related to obesity. Pathophysiological mechanisms underpinning this association are not well understood and so are discussed in this review. [ABSTRACT FROM PUBLISHER]

OBJECTIVES:The insulin-like growth factor (IGF) pathway and visceral obesity have been independently linked with esophageal cancer. This study aimed to delineate the differential and interlinked role of visceral obesity and the IGF-1 system in esophageal adenocarcinoma and esophageal squamous-cell carcinoma (SCC).METHODS:IGF-1 receptor (IGF-1R) mRNA and protein were examined in esophageal SCC (KYSE 410, OE21) and esophageal adenocarcinoma (OE19, OE33) cell lines by western blotting. Tumor cell proliferation in response to IGF-1 was assessed by bromodeoxyuridine incorporation assay. In esophageal tumor sections, expression of IGF-1R and CD68+ cell numbers were assessed by immunohistochemistry. IGF-1 was measured in serum from esophageal cancer patients, Barrett's esophagus patients, and healthy controls by enzyme-linked immunosorbent assay.RESULTS:Higher IGF-1R protein expressions were observed in SCC cells compared with esophageal adenocarcinoma cells however only adenocarcinoma cell lines significantly increased proliferation in response to IGF-1 (P<0.01). Serum IGF-1 levels were highest in esophageal adenocarcinoma patients (P<0.01) and higher in viscerally obese vs. nonobese (P<0.05) patients. In resected esophageal cancer, increased expression of IGF-1R was observed in the tumor and invasive edge compared with tumor-associated stroma (P<0.05), which coincided with increased CD68+ cells in stromal tissue surrounding invasive tumor edge (P<0.01).CONCLUSIONS: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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Malnutrition and muscle wasting are associated with impaired physical functioning and quality of life in oncology patients. Patients diagnosed with upper gastrointestinal (GI) cancers are considered at high risk of malnutrition and impaired function. Due to continuous improvement in upper GI cancer survival rates, there has been an increased focus on multimodal interventions aimed at minimizing the adverse effects of cancer treatments and enhancing survivors' quality of life. The present study aimed to evaluate the effectiveness of combined nutritional and exercise interventions in improving muscle wasting, physical functioning, and quality of life in patients with upper GI cancer. A comprehensive search was conducted in MEDLINE, EMBASE, Web of Science, Cochrane Library, and CINHAL. Of the 4780 identified articles, 148 were selected for full-text review, of which 5 studies met the inclusion criteria. Whilst reviewed studies showed promising effects of multimodal interventions on physical functioning, no significant differences in postoperative complications and hospital stay were observed. Limited available evidence showed conflicting results regarding the effectiveness of these interventions on preserving muscle mass and improving health-related quality of life. Further studies examining the impact of nutrition and exercise interventions on upper GI patient outcomes are required and would benefit from reporting a core outcome set. [ABSTRACT FROM AUTHOR]

Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continues to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells. Treatment of omental and hepatic T cells with anti-PD-1 (clone EH12.2H7) did not enhance inflammatory cytokine expression or proliferation, but transiently increased CD107a expression by CD8+ T cells. Importantly, PD-1-expressing T cells are significantly lower in EAC tumor post neoadjuvant chemoradiotherapy, suggesting that combination with specific conventional treatments may severely impair the efficacy of anti-PD-1 immunotherapy. This study provides evidence that systemically administered anti-PD-1 treatment is unlikely to exacerbate pre-existing T cell-mediated inflammation outside the tumor in obesity-associated cancers, such as EAC. Furthermore, our data suggests that studies are required to identify the negative impact of concomitant therapies on PD-1 expression in order to boost overall response rates. [ABSTRACT FROM AUTHOR]

Background: Exercise rehabilitation programmes, traditionally involving supervised exercise sessions, have had to rapidly adapt to virtual delivery in response to the coronavirus disease 2019 (COVID-19) pandemic to minimise patient contacts. In the absence of an effective vaccine, the pandemic is likely to persist in the medium term and during this time it is important that the feasibility and effectiveness of remote solutions is considered.  We have previously established the feasibility of the Rehabilitation Strategies following Oesophago-gastric Cancer (ReStOre) intervention - a face to face multidisciplinary rehabilitation programme for upper gastrointestinal (UGI) cancer survivors. This study will examine the feasibility of a virtually delivered 12-week multi-component ReStOre@Home programme. Methods: This single arm feasibility study will recruit 12 patients who have completed curative treatment for oesophago-gastric cancer. Participants will complete the 12-week ReStOre@Home programme consisting of exercise (aerobic and resistance training), 1:1 dietary counselling and group education sessions through virtual delivery. Underpinned by the Medical Research Council (MRC) Framework, feasibility will be determined by recruitment rates, adherence, retention, incidents, and acceptability. Acceptability will be assessed qualitatively through post-intervention interview and the Telehealth Usability Questionnaire. Secondary outcomes will be assessed pre and post-intervention and will include measures of physical performance (cardiopulmonary exercise test, short physical performance battery, hand grip strength, Godin Leisure Time Questionnaire, and body composition), health related quality of life (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) and oesophago-gastric cancer specific subscale (EORTC-QLQ-OG25), fatigue (Multidimensional Fatigue Inventory (MFI-20), and venous blood samples will be collected for the UGI Cancer Survivorship Biobank. Discussion: The ReStOre@Home feasibility study will provide important data regarding the amenability of a multidisciplinary programme designed for UGI cancer survivors to virtual delivery. Trial registration: ClinicalTrials.gov NCT04603339 (26/10/2020)., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 O'Neill L et al.)

Background: Exercise rehabilitation programmes, traditionally involving supervised exercise sessions, have had to rapidly adapt to virtual delivery in response to the coronavirus disease 2019 (COVID-19) pandemic to minimise patient contacts. In the absence of an effective vaccine, the pandemic is likely to persist in the medium term and during this time it is important that the feasibility and effectiveness of remote solutions is considered.  We have previously established the feasibility of the Rehabilitation Strategies following Oesophago-gastric Cancer (ReStOre) intervention - a face to face multidisciplinary rehabilitation programme for upper gastrointestinal (UGI) cancer survivors. This study will examine the feasibility of a virtually delivered 12-week multi-component ReStOre@Home programme. Methods: This single arm feasibility study will recruit 12 patients who have completed curative treatment for oesophago-gastric cancer. Participants will complete the 12-week ReStOre@Home programme consisting of exercise (aerobic and resistance training), 1:1 dietary counselling and group education sessions through virtual delivery. Underpinned by the Medical Research Council (MRC) Framework, feasibility will be determined by recruitment rates, adherence, retention, incidents, and acceptability. Acceptability will be assessed qualitatively through post-intervention interview and the Telehealth Usability Questionnaire. Secondary outcomes will be assessed pre and post-intervention and will include measures of physical performance (cardiopulmonary exercise test, short physical performance battery, hand grip strength, Godin Leisure Time Questionnaire, and body composition), health related quality of life (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) and oesophago-gastric cancer specific subscale (EORTC-QLQ-OG25), fatigue (Multidimensional Fatigue Inventory (MFI-20), and venous blood samples will be collected for the UGI Cancer Survivorship Biobank. Discussion: The ReStOre@Home feasibility study will provide important data regarding the amenability of a multidisciplinary programme designed for UGI cancer survivors to virtual delivery. Trial registration: ClinicalTrials.gov NCT04603339 (26/10/2020)., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 O'Neill L et al.)

Background: Whilst the potential benefits of exercise rehabilitation in cancer survivorship are plentiful, recruitment to survivorship rehabilitation trials remains suboptimal. There is growing evidence that Public and Patient Involvement (PPI) initiatives can increase the rate of recruitment to research. This study within a trial (SWAT) will examine if participant information co-developed by patients and their families can lead to greater recruitment rates, retention and understanding of the Rehabilitation Strategies in Oesophago-gastric and Hepatopancreaticobiliary Cancer (ReStOre II) trial when compared to standard participant information. Methods: This SWAT will be carried out over two phases. Phase I will utilise qualitative methods to develop (Phase Ia) and refine (Phase Ib) the new participant information. Phase Ia will recruit up to 20 survivors of upper gastrointestinal or hepatopancreaticobiliary cancer, or their family members, to take part in a focus group or interview to develop the new participant information. Focus groups/interviews will be recorded, transcribed verbatim and analysed thematically. In Phase Ib, participants will return for a second focus group/interview to refine the participant information. Once finalised, the participant information will be submitted to ethics for approval. In Phase II, potential participants for the ReStOre II trial will be randomly assigned to receive either the standard or patient and family co-developed participant information. The two forms of participant information will be compared by recruitment and retention rates, and participant understanding of the trial (Decision-Making Questionnaire). Discussion: We anticipate that engaging with patients and their families to develop participant information will help to increase patient understanding of the ReStOre II trial and therefore recruitment and retention rates. The results of this SWAT will indicate the usefulness of this strategy for optimising recruitment to exercise rehabilitation trials in cancer survivorship. Registration: SWAT: Northern Ireland Hub for Trials Methodology Research SWAT Repository Store ( SWAT-100). ReStOre II: ClinicalTrials.gov ( NCT03958019)., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 O'Neill L et al.)

Background: Whilst the potential benefits of exercise rehabilitation in cancer survivorship are plentiful, recruitment to survivorship rehabilitation trials remains suboptimal. There is growing evidence that Public and Patient Involvement (PPI) initiatives can increase the rate of recruitment to research. This study within a trial (SWAT) will examine if participant information co-developed by patients and their families can lead to greater recruitment rates, retention and understanding of the Rehabilitation Strategies in Oesophago-gastric and Hepatopancreaticobiliary Cancer (ReStOre II) trial when compared to standard participant information. Methods: This SWAT will be carried out over two phases. Phase I will utilise qualitative methods to develop (Phase Ia) and refine (Phase Ib) the new participant information. Phase Ia will recruit up to 20 survivors of upper gastrointestinal or hepatopancreaticobiliary cancer, or their family members, to take part in a focus group or interview to develop the new participant information. Focus groups/interviews will be recorded, transcribed verbatim and analysed thematically. In Phase Ib, participants will return for a second focus group/interview to refine the participant information. Once finalised, the participant information will be submitted to ethics for approval. In Phase II, potential participants for the ReStOre II trial will be randomly assigned to receive either the standard or patient and family co-developed participant information. The two forms of participant information will be compared by recruitment and retention rates, and participant understanding of the trial (Decision-Making Questionnaire). Discussion: We anticipate that engaging with patients and their families to develop participant information will help to increase patient understanding of the ReStOre II trial and therefore recruitment and retention rates. The results of this SWAT will indicate the usefulness of this strategy for optimising recruitment to exercise rehabilitation trials in cancer survivorship. Registration: SWAT: Northern Ireland Hub for Trials Methodology Research SWAT Repository Store ( SWAT-100). ReStOre II: ClinicalTrials.gov ( NCT03958019)., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 O'Neill L et al.)

Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Response to neoadjuvant chemoradiotherapy (NA CRT) is a clinical challenge. We examined if visceral adipose tissue and obesity status alter radiosensitivity in OAC. The radioresistant (OE33R) and radioresponsive (OE33P) OAC isogenic model was cultured with adipose tissue conditioned media from three patient cohorts: non-cancer patients, surgery only OAC patients and NA CRT OAC patients. Cell survival was characterised by clonogenic assay, metabolomic profiling by nuclear magnetic resonance spectroscopy and adipokine receptor gene expression by qPCR. A retrospective in vivo study compared tumour response to NA CRT in normal weight (n=53) versus overweight/obese patients (n=148). Adipose conditioned media (ACM) from all patient cohorts significantly increased radiosensitivity in radioresistant OE33R cells. ACM from the NA CRT OAC cohort increased radiosensitivity in OE33P cells. Metabolomic profiling demonstrated separation of the non-cancer and surgery only OAC cohorts and between the non-cancer and NA CRT OAC cohorts. Gene expression profiling of OE33P versus OE33R cells demonstrated differential expression of the adiponectin receptor-1 (AR1), adiponectin receptor-2 (AR2), leptin receptor (LepR) and neuropilin receptor-1 (NRP1) genes. In vivo overweight/obese OAC patients achieved an enhanced tumour response following NA CRT compared to normal weight patients. This study demonstrates that visceral adipose tissue modulates the cellular response to radiation in OAC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

The omentum is enriched with pro-inflammatory effector memory CD8 + T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8 + T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8 + T cells expressing intermediate levels (CX3CR1 INT ) are defined as peripheral memory, those expressing the highest levels (CX3CR1 HI ) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1 NEG ) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8 + T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8 + T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8 + T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1 INT and CX3CR1 HI CD8 + T cells in the fractalkine-rich environment of omentum in EAC, relative to matched blood. Fractalkine-mediated endocytosis of CX3CR1 by CD8 + T cells is sustained and is followed by enhanced surface expression of L-selectin (CD62L). These novel data align with our findings that circulating CX3CR1 NEG CD8 + T cells express higher levels of L-selectin than CX3CR1 INT CD8 + T cells. This is consistent with previous reports and implicates fractalkine in the conversion of CX3CR1 INT CD8 + T cells to a CX3CR1 NEG phenotype characterized by alterations in the migratory capacity of these T cells. For the first time, these findings identify fractalkine as a driver of T cell migration to the omentum in EAC and indicate that CD8 + T cells undergo sequenced fractalkine-mediated alterations in CX3CR1 and L-selectin expression. These data implicate fractalkine as more than a chemotactic cytokine in obesity-associated meta-inflammation and reveal a role for this chemokine in the maintenance of the CX3CR1 NEG CD8 + T cell populations.

The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly higher. Interestingly, our data suggest that reduced frequencies of NK cells in omentum and liver of OAC patients are not a result of impaired NK cell chemotaxis to these tissues. In fact, our functional data revealed that secreted factors from omentum and liver of OAC patients induce significant levels of NK cell death and lead to reduced percentages of TNF-α + and NKP46 + NK cells and higher frequencies of IL-10-producing NK cells. Together, these data suggest that the omental and hepatic microenvironments of OAC patients alter the NK cell phenotype to a more anti-inflammatory homeostatic role., (© Society for Leukocyte Biology.)