Nutrient Intakes and Gastrointestinal Symptoms Among Esophagogastric Cancer Survivors up to 5 Years Post-Surgery.

A cross-sectional analysis explored nutritional intakes and gastrointestinal (GI) symptoms among esophagogastric cancer survivors up to 12, 13-36, and 37+ months post-surgery. Participants were identified from the Upper GI Cancer Registry at St James' Hospital, Ireland. The Short Nutritional Assessment Questionnaire, European Prospective Investigation of Cancer Food Frequency Questionnaire, World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score, and Gastrointestinal Symptoms Rating Scale assessed malnutrition risk, nutritional intake, adherence to (secondary) cancer prevention recommendations, and GI symptoms, respectively. Most (82.5%, n33) participants (n40) were male. Mean age was 65.5 ± 9.3 years. Time post-surgery ranged from 6-62 months. Half (50.0%, n20) had a BMI in the healthy range. A quarter (27.5%, n11) were at risk of malnutrition. Intakes of meat and meat products exceeded recommendations and intakes of fruits, vegetables, and fiber were below recommendations, with no significant between-group differences. The mean WCRF/AICR score was 3.6 ± 1.1, indicating adherence to 3.6 of 7 cancer prevention recommendations. It was not significantly different between subgroups. Minor to mild GI discomfort was reported, with no significant between-group differences in symptoms. As rates of long-term survivorship continue to increase, survivors must be supported to sustain behaviors that enhance quality of life and reduce secondary cancer risk.

Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

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). Serial plasma samples were collected before, and for 300 minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1 year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.

Cardiorespiratory Comorbidity and Postoperative Complications following Esophagectomy: a European Multicenter Cohort Study.

BACKGROUND: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. PATIENTS AND METHODS: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. RESULTS: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien-Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11-3.04], pneumonia (OR 1.65, 95% CI 1.10-2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04-2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien-Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. CONCLUSIONS: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk.

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. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s.e.m.) 17·1(3·2) per cent, P < 0·001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0·014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0·003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0·022). Mean(s.e.m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621·5(71·7) pg/ml; 10 days: 415·1(59·80) pg/ml; 6 weeks: 309·0(42·0) pg/ml; 12 weeks: 415·8(52·1) pg/ml; 52 weeks: 547·4(83·2) pg/ml; P < 0·001) and did not predict weight loss (P = 0·198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52 weeks (mean(s.e.m.) insulin AUC0-30 min : fold change 1·7(0·4), 2·0(0·4), 3·5(0·7) and 4·0(0·8) respectively; P = 0·001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0·001), with a 3·3(1·8)-fold increase at 1 year (P < 0·001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0·041) and symptomatic neuroglycopenia (Sigstad score, P = 0·017, R2 = 0·45). GLP-1 AUC predicted loss of weight (P = 0·008, R2 = 0·52) and fat mass (P = 0·010, R2 = 0·64) at 1 year. CONCLUSION: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.

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 41·4 Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were assessed at baseline and 1 month 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 < 0·001), 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 < 0·001). Five patients (2·2 per cent) developed radiation-induced lung injury precluding surgical resection. Smoking (P = 0·005) and increased age (P < 0·001) independently predicted percentage change in DLCO. Carboplatin and paclitaxel with 41·4 Gy resulted in a greater DLCO decline than cisplatin and 5-fluorouracil with 40 Gy (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.

ANTECEDENTES: El tema de si en el cáncer de esófago la quimiorradioterapia neoadyuvante (neoadjuvant chemoradiation, nCRT) repercute sobre la morbilidad postoperatoria, especialmente sobre la morbilidad pulmonar y la calidad de vida de los pacientes que sobreviven sigue siendo controvertido. Este estudio combina datos sobre resultados clínicos con una evaluación sistemática de la fisiología pulmonar para determinar el impacto de la nCRT sobre la fisiología pulmonar y los resultados clínicos en el cáncer de esófago localmente avanzado. MÉTODOS: Se incluyeron pacientes consecutivos tratados entre 2010-2016. La radioterapia conformal 3D fue la estándar, con un histograma dosis-volumen del pulmón V20 < 25% y radiación entre 40-41,4 Gy. Se evaluaron el volumen espiratorio forzado (forced expiratory volume, FEV1), la capacidad vital forzada (forced vital capacity, FVC) y la capacidad de difusión del monóxido de carbono (diffusion capacity for carbon monoxide, DLCO) al inicio y un mes tras la nCRT. La lesión pulmonar inducida por la radioterapia (EORTC grado ≥ 2), el índice de complicaciones integral (comprehensive complications index, CCI), grado de Clavien-Dindo, y complicaciones pulmonares fueron analizadas de manera prospectiva. Se evaluó la calidad de vida relacionada con la salud entre los pacientes supervivientes libres de enfermedad (EORTC QLQ-C30, OG25, OES18). RESULTADOS: Se estudiaron un total de 228 pacientes. Al comparar los valores de la fisiología pulmonar antes y después de la nCRT respectivamente, la FEV1 disminuyó de 96,8 ± 17,7% a 91,5 ± 20,4% (-3,6 ± 10,6%, P = 0,0002), la FVC de 104,9 ± 15,6 a 98,1 ± 19,8% (-3,2 ± 11,9%, P = 0,005) y la DLCO de 97,6 ± 20,7 a 82,2 ± 20,4% (-14,8 ± 14,0%, P < 0,0001). Cinco pacientes (2,2%) desarrollaron lesión pulmonar relacionada con la radioterapia impidiendo la resección quirúrgica. Los factores predictores independientes de %ΔDLCO fueron el hábito tabáquico (P = 0,005) y la edad avanzada (P < 0,001). El tratamiento con carboplatino/paclitaxel/41,4Gy determinó un mayor descenso de la DLCO en comparación con cisplatino/5-fluorouracilo/40Gy (P = 0,001). En el análisis multivariable, la DLCO tras el tratamiento fue una variable predictora de CCI (P = 0,006), fracaso respiratorio/intubación prolongada (P = 0,020) y reducción de la función física en los supervivientes (P = 0,047). CONCLUSIÓN: Estos datos indican que la moderna nCRT altera la fisiología pulmonar, especialmente la difusión pulmonar, con consecuencias clínicas a corto y largo plazo. La DLCO podría constituir un factor de riesgo potencialmente modificable.

Measuring the impact of oesophagectomy on physical functioning and physical activity participation: a prospective study.

BACKGROUND: Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from pre-surgery through 6-months post-oesophagectomy. METHODS: Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured pre-surgery (T0) and repeated at 1-month (T1) and 6-months (T2) post-surgery. HR-QOL was measured using the EORTC-QOL C30. RESULTS: Thirty-six participants were studied (mean age 62.4 (8.8) years, n = 26 male, n = 26 transthoracic oesophagectomy). Mean 6MWT distance decreased significantly from T0 to T1 (p = 0.006) and returned to T0 levels between T1 and T2 (p < 0.001). Percentage time spent sedentary increased throughout recovery (p < 0.001) and remained significantly higher at T2 in comparison to T0 (p = 0.003). In contrast, percentage time spent engaged in either light or moderate-to-vigorous intensity activity, all reduced significantly (p < 0.001 for both) and remained significantly lower at T2 in comparison to T0 (p = 0.009 and p = 0.01 respectively). Patients reported deficits in multiple domains of HR-QOL during recovery including global health status (p = 0.04), physical functioning (p < 0.001) and role functioning (p < 0.001). Role functioning remained a clinically important 33-points lower than pre-operative values at T2. CONCLUSION: Habitual physical activity participation remains significantly impaired at 6-months post-oesophagectomy. Physical activity is a measurable and modifiable target for physical rehabilitation, which is closely aligned with patient-reported deficits in role functioning. Rehabilitation aimed at optimising physical health in oesophageal cancer survivorship is warranted.

Prophylactic negative wound therapy in laparotomy wounds (PROPEL trial): randomized controlled trial.

BACKGROUND: Superficial surgical site infections are a common post-operative complication. They also place a considerable financial burden on healthcare. The use of prophylactic negative pressure wound therapy has been advocated to reduce wound infection rates. However, there is debate around its routine use. The purpose of this trial is to determine if prophylactic negative pressure wound therapy reduces post-operative wound complications in patients undergoing laparotomy. METHODS/DESIGN: This multi-centre randomised controlled trial will compare standard surgical dressings (control) to two competing negative pressure wound therapy dressings (Prevena™ and PICO™). All patients will be over 18 years, who are undergoing an emergency or elective laparotomy. It is intended to enrol a total of 271 patients for the trial. DISCUSSION: The PROPEL trial is a multi-centre randomised controlled trial of patients undergoing laparotomy. The comparison of standard treatment to two commercially available NPWT will help provide consensus on the routine management of laparotomy wounds. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov (NCT number NCT03871023).

Effect of preoperative inspiratory muscle training on physical functioning following esophagectomy.

This study aims to examine the effect of preoperative inspiratory muscle training (IMT) on pre- and postoperative functional exercise performance in patients undergoing esophagectomy. A subcohort of patients recruited to the PREPARE randomized control trial were studied. Following evaluation of respiratory muscle function (spirometry, maximum inspiratory pressure (MIP), and inspiratory muscle endurance), postoperative mobilization (accelerometry) and postoperative physical functioning (6-minute walk test (6MWT)), participants scheduled for esophagectomy were randomly assigned to either 2 weeks of preoperative IMT or a control group. Measures were repeated on the day before surgery and postoperatively. Sixty participants (mean (standard deviation) age 64.13 (7.8) years; n = 42 male; n = 43 transthoracic esophagectomy; n = 17 transhiatial esophagectomy) were included in the final analysis (n = 28 IMT; n = 32 control). There was a significant improvement in preoperative MIP (P = 0.03) and inspiratory muscle endurance (P = 0.04); however preoperative 6MWT distance did not change. Postoperatively, control participants were more active on postoperative day (POD)1, and from POD1-POD5 (P = 0.04). Predischarge, 6MWT distance was significantly lower in the IMT group (305.61 (116.3) m) compared to controls (380.2 (47.1) m, P = 0.03). Despite an increase in preoperative respiratory muscle function, preoperative IMT does not improve pre- or postoperative physical functioning or postoperative mobilization following esophagectomy.

Oesophagectomy in End-Stage Achalasia.

Presentation A 53 year old male with known Chicago Classification type II achalasia, and successful pneumatic dilatation five years previously, presented with severe dysphagia and 17.5 kg weight loss over 3 months. Diagnosis He underwent OGD and contrast imaging to reveal a mega oesophagus secondary to progressive achalasia. Treatment After initial nutritional pre-habilitation with naso-enteric feeding, he underwent a laparoscopic heller's myotomy with clinical and radiological improvement. However quick relapse of symptoms and a failed, atonic, massively dilated oesophagus lead to the decision to proceed to transhiatal oesophagectomy. Discussion Achalasia is a spectrum of motility disorder, and where it has progressed to mega-oesophagus, the success of standard therapeutic approaches is limited. End stage achalasia in this context, with nutritional failure or recurrent pneumonia/bronchiectasis, can be safely treated with an oesophageal resection which is curative, removing a "failed" oesophagus in its entirety.

Multicentre randomized clinical trial of inspiratory muscle training versus usual care before surgery for oesophageal cancer.

BACKGROUND: Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy. METHODS: Patients with oesophageal cancer were randomized to a home-based IMT programme before surgery or usual care. IMT included the use of a flow-resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning. RESULTS: Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH2 O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH2 O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050). CONCLUSION: Despite an increase in preoperative inspiratory muscle function, home-based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 (https://www.clinicaltrials.gov).

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 post-neoadjuvant 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 (pre-sarcopenic 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.

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.

Point Prevalence of Adult Intestinal Failure in Republic Of Ireland.

Parenteral Nutrition (PN) is a life-saving treatment used for patients with Intestinal Failure (IF). PN is complex and demands highly specialised care to avoid serious complications in the home setting. All tertiary centres in the Republic of Ireland (ROI) were contacted to assess the prevalence of IF requiring PN and complications, over a one year period. Sixty-seven patients were treated across 15 centres: a period prevalence of 14.6 and 9.6 patients per million for long-term PN and home PN respectively. Three-quarters of patients experienced at least one major complication with 18% mortality rate over the study period. There were 2.86 admissions per HPN patient, each lasting mean 13.4 days. One-third experienced catheter-related infections. There was a reduced length of stay during emergency re-admissions in high volume centres (mean 31 v 43 days, p=0.17). The establishment of a National Centre for IF/HPN in ROI is integral to reducing PN-associated complications.

Multimodality treatment for esophageal adenocarcinoma: multi-center propensity-score matched study.

Background: The primary aim of this study was to compare survival from neoadjuvant chemoradiotherapy plus surgery (NCRS) versus neoadjuvant chemotherapy plus surgery (NCS) for the treatment of esophageal or junctional adenocarcinoma. The secondary aims were to compare pathological effects, short-term mortality and morbidity, and to evaluate the effect of lymph node harvest upon survival in both treatment groups. Methods: Data were collected from 10 European centers from 2001 to 2012. Six hundred and eight patients with stage II or III oesophageal or oesophago-gastric junctional adenocarcinoma were included; 301 in the NCRS group and 307 in the NCS group. Propensity score matching and Cox regression analyses were used to compensate for differences in baseline characteristics. Results: NCRS resulted in significant pathological benefits with more ypT0 (26.7% versus 5%; P < 0.001), more ypN0 (63.3% versus 32.1%; P < 0.001), and reduced R1/2 resection margins (7.7% versus 21.8%; P < 0.001). Analysis of short-term outcomes showed no statistically significant differences in 30-day or 90-day mortality, but increased incidence of anastomotic leak (23.1% versus 6.8%; P < 0.001) in NCRS patients. There were no statistically significant differences between the groups in 3-year overall survival (57.9% versus 53.4%; Hazard Ratio (HR)= 0.89, 95%C.I. 0.67-1.17, P = 0.391) nor disease-free survival (52.9% versus 48.9%; HR = 0.90, 95%C.I. 0.69-1.18, P = 0.443). The pattern of recurrence was also similar (P = 0.660). There was a higher lymph node harvest in the NCS group (27 versus 14; P < 0.001), which was significantly associated with a lower recurrence rate and improved disease free survival within the NCS group. Conclusion: The survival differences between NCRS and NCS maybe modest, if present at all, for the treatment of locally advanced esophageal or junctional adenocarcinoma. Future large-scale randomized trials must control and monitor indicators of the quality of surgery, as the extent of lymphadenectomy appears to influence prognosis in patients treated with NCS, from this large multi-center European study.

ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

The physiotherapist and the esophageal cancer patient: from prehabilitation to rehabilitation.

Esophageal cancer is a serious malignancy often treated with multimodal interventions and complex surgical resection. As treatment moves to centers of excellence with emphasis on enhanced recovery approaches, the role of the physiotherapist has expanded. The aim of this review is to discuss the rationale behind both the evolving prehabilitative role of the physiotherapist and more established postoperative interventions for patients with esophageal cancer. While a weak association between preoperative cardiopulmonary fitness and post-esophagectomy outcome is reported, cardiotoxicity during neoadjuvant chemotherapy and/or radiotherapy may heighten postoperative risk. Preliminary studies suggest that prehabilitative inspiratory muscle training may improve postoperative outcome. Weight and muscle loss are a recognized sequelae of esophageal cancer and the functional consequences of this should be assessed. Postoperative physiotherapy priorities include effective airway clearance and early mobilization. The benefits of respiratory physiotherapy post-esophagectomy are described by a small number of studies, however, practice increasingly recognizes the importance of early mobilization as a key component of postoperative recovery. The benefits of exercise training in patients with contraindications to mobilization remain to be explored. While there is a strong basis for tailored physiotherapy interventions in the management of patients with esophageal cancer, this review highlights the need for studies to inform prehabilitative and postoperative interventions.

Reduced fitness and physical functioning are long-term sequelae after curative treatment for esophageal cancer: a matched control study.

Reduced physical functioning is common following resections for esophageal cancer; however, objective data on physical performance outcomes in this cohort are rare. The aim of this study was to assess the physical performance and health related quality of life (HRQOL) of disease free survivors and compare findings in a case matched noncancer control group. Twenty-five males (mean (±SD) aged 63 (±6) years) who were over 6 months postesophagectomy and disease-free were compared with 25 controls (60 ± 6 years). Physical functioning was assessed through hand grip strength (dynamometry), exercise capacity (incremental shuttle walk test), physical activity levels (RT3 accelerometer), and body composition (bio-electrical impedance analysis). Health-related quality of life was measured using the EORTC QLQ-C30 questionnaire. Esophageal cancer survivors demonstrated significantly lower fitness (P < 0.001) and time spent in moderate (P < 0.001) and vigorous (P < 0.001) intensity physical activity compared with controls. Global health status and quality of life were similar in both groups (P = 0.245); however, physical and role functioning domains were lower in the cancer survivors (P < 0.001, and P = 0.001, respectively). These data show that disease-free survivors of curative esophageal cancer treatment demonstrate a significant compromise in physical functioning compared with controls, thus highlighting the multiple, complex rehabilitative needs of this cohort.

Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma.

Visceral obesity and metabolic syndrome (MetSyn) represent a constellation of inflammation, insulin resistance, and hyperglycemia and are established risk factors for gastrointestinal cancer. However, their impact on the immune and inflammatory response after major upper gastrointestinal oncologic surgery is unknown. In 125 consecutive patients who underwent esophagectomy, C-reactive protein (CRP) and CRP:albumin levels were recorded preoperatively and on days 1, 3, 7, and 14 postoperatively. In a subset of 30 patients, circulating levels of IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TGF-ß, and cortisol were measured. Incidences of postoperative complications were prospectively recorded. In the study cohort, 51% of patients were viscerally obese, 40.7% had MetSyn, and 33.6% were hyperglycemic. Viscerally obese and MetSyn-positive patients demonstrated greater postoperative CRP levels and CRP:albumin levels on day 7 and day 14 compared with nonobese and MetSyn-negative patients (P < 0.05). Higher postoperative circulating levels of cortisol were observed in the viscerally obese and hyperglycemic patients compared to nonobese and normoglycemic patients. No association was observed between visceral obesity, MetSyn or hyperglycemia, and postoperative cytokine profile. Viscerally obese patients had an increased overall incidence of postoperative complications compared to nonobese patients (67.2% vs. 47.5%, P = 0.031) on univariate but not multivariate analysis (P = 0.078) and visceral obesity was not associated with an increased incidence of specific complications. Visceral obesity, MetSyn, and hyperglycemia are prevalent in patients undergoing major upper gastrointestinal resection and are associated with an exaggerated acute-phase inflammatory response postoperatively. Further research is warranted to determine whether this association is directly causal.

Impact of supplemental home enteral feeding postesophagectomy on nutrition, body composition, quality of life, and patient satisfaction.

The aim of this prospective cohort study is to analyze the impact of supplemental home enteral nutrition (HEN) post-esophageal cancer surgery on nutritional parameters, quality of life (QL), and patient satisfaction. A systematic review reported that over 60% of patients lose >10% of both body weight and BMI by 6 months after esophagectomy. Enteral feeding (EF) is increasingly a modern standard postoperatively; however, the impact of extended HEN postdischarge has not been systematically studied. One hundred forty-nine consecutive patients [mean age 62 ± 9, 80% male,76% adenocarcinoma, 66% on multimodal protocols, and 69% with BMI ≥ 25 kg/m2] were studied. Jejunal EF commenced day 1 postoperatively, and supplemental overnight HEN (764 kcal; 32g protein) continued on discharge for a planned further 4 weeks. Weight, BMI, and body composition analysis (bioimpedance analysis) were measured at baseline, preoperatively and at 1, 3, and 6 months, along with the EORTC QLQ-C30/OES18 QL measures. A patient satisfaction questionnaire addressed eight key items in relation to HEN (max score 100/item). Median (range) total duration of EF was 49 days (28-96). Overall compliance was 96%. At 6 months, compared with preoperatively, 58 (39%) patients lost >10% weight, with median (IQR) loss of 6.8 (4-9) kg, and 62 (41%) patients lost >10% BMI. Lean body mass and body fat were significantly (p < 0.001) decreased. Mean global QL decreased (p < 0.01) from 82 to 72. A high mean satisfaction score (>70 ± 11/100) was reported, >80 for practical training, activities of daily living, pain, anxiety, recovery and impact on caregivers, with lower scores for appetite (33 ± 24) and sleep (63 ± 30). Supplemental HEN for a minimum of one month postdischarge is associated with high compliance and patient satisfaction. Weight and BMI loss may still be substantial, however this may be less than published literature, in addition the impact on HR-QL may be attenuated. HEN has both subjective and objective rationale and merits further validation toward optimizing nutritional recovery and overall wellbeing.