The impact of Nutrition and Gastrointestinal Symptoms on Health-related Quality of Life in Survivorship after Oesophageal Cancer Surgery

Summary Background and Aims Oesophagectomy is the primary curative treatment for oesophageal cancer but is associated with considerable postoperative morbidity and mortality. To better understand the aetiology of impaired health-related quality of life (HRQL) in oesophageal cancer survivors (OCS), this study sought to determine the longitudinal changes in nutritional status, nutrition-impact symptoms (NIS), and HRQL in this cohort, and to determine which variables have the greatest impact on postoperative HRQL decline. Methods Data, derived from St. James\u27 Hospital, Dublin, included patients who underwent oesophagectomy from October 2017 to May 2019 and attended clinic preoperatively and 6 months postoperatively. A subset attended a further 12-month appointment. HRQL and symptom data were collected using validated questionnaires and anthropometric measures were completed by clinicians. Data were analysed using SPSS. Results A total of 66 patients were studied preoperatively and 6 months postoperatively, of whom 37 were studied at 12 months postoperatively. Malnutrition remained prevalent at each time-point, although rates did not significantly change longitudinally. Conversely, the prevalence of malabsorption (7.6%–14.3%, P\u3c0.001) and dumping syndrome (67.7%–74.3%, P=0.003) significantly increased with increasing time postoperatively. NIS were significantly associated with impaired HRQL function scores and were independent predictors of global quality of life (gQOL) score postoperatively (P=0.004). A diagnostic threshold of gastrointestinal symptom severity (11.5) that identifies patients at risk of impaired gQOL was therefore reported. Conclusion Malnutrition and NIS are prevalent post-oesophagectomy, the latter significantly associated with reduced HRQL. Targeted intervention in those with severe NIS could be highly beneficial, highlighting the need for dietetic input in OCS

Patient experiences of a physiotherapy-led multidisciplinary rehabilitative intervention after successful treatment for oesophago-gastric cancer

Purpose To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing. Methods Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach. Results At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the intervention. These improvements led to increased confidence and social connectivity. Other participants were a valuable source of information and reassurance, while support from family members was variable. Future interventions should educate participants on how to maintain gains achieved during the intervention. Conclusions Participating in an exercise-based multidisciplinary rehabilitative intervention reduces isolation and helps oesophago-gastric cancer survivors to safely negotiate their physical, emotional and social needs as they move further down the path of recovery

Proopiomelanocortin Neurons in Nucleus Tractus Solitarius Are Activated by Visceral Afferents: Regulation by Cholecystokinin and Opioids

The nucleustractus solitarius (NTS) receives dense terminations from cranial visceral afferents, including those from the gastrointestinal (GI) system. Although the NTS integrates peripheral satiety signals and relays this signal to central feeding centers, little is known about which NTS neurons are involved or what mechanisms are responsible. Proopiomelanocortin (POMC) neurons are good candidates for GI integration, because disruption of the POMC gene leads to severe obesity and hyperphagia. Here, we used POMC– enhanced green fluorescent protein (EGFP) transgenic mice to identify NTS POMC neurons. Intraperitoneal administration of cholecystokinin (CCK) induced c-fos gene expression in NTS POMC–EGFP neurons, suggesting that they are activated by afferents stimulated by the satiety hormone. We tested the synaptic relationship of these neurons to visceral afferents and their modulation by CCK and opioids using patch recordings in horizontal brain slices. Electrical activation of the solitary tract (ST) evoked EPSCs in NTS POMC–EGFP neurons. The invariant latencies, low failure rates, and substantial paired-pulse depression of the ST-evoked EPSCs indicate that NTS POMC–EGFP neurons are second-order neurons directly contacted by afferent terminals. The EPSCs were blocked by the glutamate antagonist 2,3- dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline. CCK increased the amplitude of the ST-stimulated EPSCs and the frequency of miniature EPSCs, effects attenuated by the CCK1 receptor antagonist lorglumide. In contrast, the orexigenic opioid agonists [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin and met-enkephalin inhibited both ST-stimulated EPSCs and the frequency of miniature EPSCs. These findings identify a potential satiety pathway in which visceral afferents directly activate NTS POMC–EGFP neurons with excitatory inputs that are appropriately modulated by appetite regulators

Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance

Purpose Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. Methods Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). Results Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to postneoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (presarcopenic n=2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). Conclusions Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted

Effect of neoadjuvant chemoradiation on preoperative pulmonary physiology, postoperative respiratory complications and quality of life in patients with oesophageal cancer

Background: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer. Methods: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose–volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41⋅4Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were assessed at baseline and 1month after nCRT. Radiation-induced lung injury (grade 2 or greater), comprehensive complications index (CCI) and pulmonary complications were monitored prospectively. Health-related quality of life was assessed among disease-free patients in survivorship. Results: Some 228 patients were studied. Comparing pulmonary physiology values before with those after nCRT, FEV1 decreased from mean(s.d.) 96⋅8(17⋅7) to 91⋅5(20⋅4) per cent (–3⋅6(10⋅6) per cent; P \u3c0⋅001), FVC from 104⋅9(15⋅6) to 98⋅1(19⋅8) per cent (–3⋅2(11⋅9) per cent; P =0⋅005) and DLCO from 97⋅6(20⋅7) to 82⋅2(20⋅4) per cent (–14⋅8(14⋅0) per cent; P \u3c0⋅001). Five patients (2⋅2 per cent) developed radiation-induced lung injury precluding surgical resection. Smoking (P =0⋅005) and increased age (P \u3c0⋅001) independently predicted percentage change in DLCO. Carboplatin and paclitaxel with 41⋅4Gy resulted in a greater DLCO decline than cisplatin and 5-fluorouracil with 40Gy (P =0⋅001). On multivariable analysis, post-treatment DLCO predicted CCI (P =0⋅006), respiratory failure (P =0⋅020) and reduced physical function in survivorship (P =0⋅047). Conclusion: These data indicate that modern nCRT alters pulmonary physiology, in particular diffusion capacity, which is linked to short- and longer-term clinical consequences, highlighting a potentially modifiable index of risk

Identifying a Novel Role for Fractalkine (CX3CL1) in Memory CD8(+) T Cell Accumulation in the Omentum of Obesity-Associated Cancer Patients

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

Investigating Whether Consuming Meals in a Dining Room Impacts Patients’ Mood, Level of Interaction, and Subsequent Nutrient Intake in a Stroke Rehabilitation Ward.

Background/objectivesMalnutrition is evident in hospitals and stroke patients are at increased risk. Protected mealtimes may help increase nutrient intake especially when patients interact and enjoy the dining room atmosphere. The aim of this research is to investigate if eating in a communal dining room increases nutritional intake compared to eating at the bedside and to investigate whether patient interaction and mood affects patient nutrient intake. Population/methods:A randomised cross-sectional study of 20 patients, assessing a comparison of patient’s mealtime consumption at lunchtime in the dining room and at the beside. Patients’ meals were weighed before and after consumption as well as an estimated percentage of their meals consumed. Patients’ interaction was observed and noted using a modified case report form. The Hammond depression scale was used to score patients’ mood. Patient and staff satisfaction surveys were completed at the end of the study period. Results:There was no significant difference in protein and energy consumption in the dining room (16.4g protein and 379.2kcal) compared to at the bedside (13.2g protein and 333.8kcal), p=0.160 and p=0.110 respectively. Interaction was higher in the dining room. The percentage mealtime consumption increased the more interactive a patient was from a mean of 74% in less interactive patients to 98% in highly interactive patients (p=0.193). There was no significant association between depression score and mealtime consumption. All 19 patients enjoyed eating in the dining room and 14 out of the 19 patients preferred eating in the dining room. Conclusion:Further studies are required to explore how intake can be improved among stroke rehabilitation patients

Telehealth Delivery of a Multi-Disciplinary Rehabilitation Programme for Upper Gastro-Intestinal Cancer: ReStOre@Home Feasibility Study

Advances in diagnosis and the treatment for upper gastro-intestinal (UGI) cancers have led to improved survival rates and, consequently, to a larger population of survivors of many types of UGI cancer [1,2]. Progress in survivorship care for UGI cancer remains poor, and many survivors experience ongoing negative physical and psychosocial impacts of treatment, which can have profound and long-term impacts on physical function and quality of life (QOL) [3,4]. At one year post-op, 40% of survivors report poor physical function, and significant reductions in walking distance, cardiorespiratory fitness and muscle strength are observed, along with a high prevalence of fatigue (41%), sarcopenia (35%) and dyspnoea (20%) [5–7]. Nutritional compromise in UGI cancer survivors is frequently reported, with eating restrictions are observed in 49% at 1 year post-surgery and malabsorption in 73% at two years post-op [6,8]. This can lead to significant reductions in fat-free body mass and skeletal muscle [8]. From a psychosocial perspective, anxiety (36%), fear of recurrence (29%) and high rates of sleep difficulties (51%) are reported. An integrated, multi-disciplinary specialist rehabilitation approach focusing on patient-centred outcomes is indicated to address the substantial, complex, multi-dimensional rehabilitation needs of UGI cancer survivors and to enable them to achieve the best possible quality of life and to reintegrate into family, social and working life [9–12]

DRAFTS: A Deep, Rapid Archival Flare Transient Search in the Galactic Bulge

We utilize the Sagittarius Window Eclipsing Extrasolar Planet Search (SWEEPS) HST/ACS dataset for a Deep Rapid Archival Flare Transient Search (DRAFTS) to constrain the flare rate toward the older stellar population in the Galactic bulge. During 7 days of monitoring 229,293 stars brighter than V=29.5, we find evidence for flaring activity in 105 stars between V=20 and V=28. We divided the sample into non-variable stars and variable stars whose light curves contain large-scale variability. The flare rate on variable stars is \sim 700 times that of non-variable stars, with a significant correlation between the amount of underlying stellar variability and peak flare amplitude. The flare energy loss rates are generally higher than those of nearby well-studied single dMe flare stars. The distribution of proper motions is consistent with the flaring stars being at the distance and age of the Galactic bulge. If they are single dwarfs, they span a range of \approx 1.0 - 0.25M\odot. A majority of the flaring stars exhibit periodic photometric modulations with P <3d. If these are tidally locked magnetically active binary systems, their fraction in the bulge is enhanced by a factor of \sim20 compared to the local value. These stars may be useful for placing constraints on the angular momentum evolution of cool close binary stars. Our results expand the type of stars studied for flares in the optical band, and suggest that future sensitive optical time-domain studies will have to contend with a larger sample of flaring stars than the M dwarf flare stars usually considered.Comment: accepted for publication in the Astrophysical Journa