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Neoadjuvant chemotherapy is often used prior to surgical resection for oesophageal adenocarcinoma but remains ineffective in a high proportion of patients. The histological Mandard tumour regression grade is used to determine chemoresponse but is not available at the time of treatment decision-making. The aim of this cohort study was to identify factors that predict chemotherapy response prior to surgery. A prospectively collected database of patients undergoing surgical resection for oesophageal adenocarcinoma from a high-volume UK institution was used. Patients were subcategorised using pathological tumour response into 'responders' (Mandard grade 1–3) and 'non-responders' (Mandard grade 4 and 5). Multivariable logistic regression analysis was performed to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for responder status adjusting for a variety of parameters. Receiver operating characteristic (ROC) curves were calculated. Among 315 patients included, 102 (32%) were responders and 213 (68%) non-responders. A decrease in radiological tumour volume (OR 1.92 95%CI 1.02–3.62; p = 0.05), a 'partial response' RECIST score (OR 7.16 95%CI 1.49–34.36; p = 0.01), a clinically improved dysphagia score (OR 2.79 95%CI 1.05–7.04; p = 0.04) and lymphovascular invasion (OR 0.06 95%CI 0.02–0.13; p = 0.000) influenced responder status. ROC curve analysis for responder status utilising all available parameters had an area under the curve (AUC) of 0.86. This study has highlighted the potential for using pre-defined factors to identify those patients who have responded to neoadjuvant chemotherapy, prior to surgical resection, potentially facilitating a more individualised therapeutic approach. [ABSTRACT FROM AUTHOR]

Background Esophageal anastomoses performed following esophagectomy and total gastrectomy are technically challenging with a significant risk of anastomotic leak. A safe, reliable, and easy anastomotic technique is required to improve patient outcomes and reduce morbidity. Method This paper analyses 328 consecutive patients who underwent transoral circular stapled esophageal anastomosis (ORVIL™) from a prospectively collected single-center database between December 2011 and February 2019. Results Two hundred and twenty-seven esophagectomies and 101 gastrectomies were performed using OrVil™ anastomoses. The mean patient age was 63.7 years. Of 328 consecutive OrVil™-based anastomoses, there were 10 clinically significant anastomotic leaks requiring radiological or operative intervention (3.05%). Twenty-eight (8.54%) patients developed anastomotic stricture, all of which were successfully treated with endoscopic balloon dilatation (a median of 1 dilatation was required per patient). Conclusion The OrVil™ anastomotic technique is reliable and safe to perform. This is the largest reported series of the OrVil™ anastomotic technique to date. Leak rates and anastomotic dilations were similar to other reported series. Based on our experience, we consider the use of the OrVil™ device for reconstruction after major upper GI resection to be safe and reliable. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend critically ill adults receive more protein than most receive. We aimed to establish the feasibility of a trial to evaluate whether feeding protein to international recommendations would improve outcomes, in which 1 group received protein doses representative of international guideline recommendations (high protein) and the other received doses similar to usual practice. Methods: We conducted a prospective, randomized, blinded, parallel‐group, feasibility trial across 6 intensive care units. Critically ill, mechanically ventilated adults expected to receive enteral nutrition (EN) for ≥2 days were randomized to receive EN containing 63 or 100 g/L protein for ≤28 days. Data are mean (SD) or median (interquartile range). Results: The recruitment rate was 0.35 (0.13) patients per day, with 120 patients randomized and data available for 116 (n = 58 per group). Protein delivery was greater in the high‐protein group (1.52 [0.52] vs 0.99 [0.27] grams of protein per kilogram of ideal body weight per day; difference, 0.53 [95% CI, 0.38–0.69] g/kg/d protein), with no difference in energy delivery (difference, −26 [95% CI, −190 to 137] kcal/kg/d). There were no between‐group differences in the duration of feeding (8.7 [7.3] vs 8.1 [6.3] days), and blinding of the intervention was confirmed. There were no differences in clinical outcomes, including 90‐day mortality (14/55 [26%] vs 15/56 [27%]; risk difference, −1.3% [95% CI, −17.7% to 15.0%]). Conclusion: Conducting a multicenter blinded trial is feasible to compare protein delivery at international guideline–recommended levels with doses similar to usual care during critical illness. [ABSTRACT FROM AUTHOR]

The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy (NAC) and surgery is contentious. In UK practice, surgical resection margin status is often used to classify patients into receiving adjuvant treatment. This study aimed to assess any survival benefit of adjuvant therapy in patients with clear resection margins. This was a retrospective collaborative cohort study combining two prospectively collected UK institutional databases of patients with oesophageal adenocarcinoma. Multivariable Cox regression and propensity matched analyses were used to compare overall and recurrence-free survival according to the adjuvant treatment. Of 374 patients with clear resection margins, 221 patients (59%) had no adjuvant treatment, 137 patients (37%) had adjuvant chemotherapy and 16 patients (4%) had adjuvant chemoradiotherapy. For patients who had received NAC (290, 76%), when adjuvant chemotherapy was compared to no adjuvant treatment, hazard ratios (HRs) favoured adjuvant chemotherapy but did not reach independent significance (overall survival [OS] HR 0.65 95% confidence interval [CI] 0.40–1.06; p.0.087). Responders to NAC (Mandard 1–3) were seemingly more likely to demonstrate a survival benefit from adjuvant chemotherapy (HR 0.42 95% CI 0.15–1.11; p.1.081). Although no independent survival benefit was observed, the point estimates favoured adjuvant treatment, predominantly in patients with chemo-responsive tumours. [ABSTRACT FROM AUTHOR]

Rationale: The long-term effects of delivering approximately 100% of recommended calorie intake via the enteral route during critical illness compared with a lesser amount of calories are unknown.Objectives: Our hypotheses were that achieving approximately 100% of recommended calorie intake during critical illness would increase quality-of-life scores, return to work, and key life activities and reduce death and disability 6 months later.Methods: We conducted a multicenter, blinded, parallel group, randomized clinical trial, with 3,957 mechanically ventilated critically ill adults allocated to energy-dense (1.5 kcal/ml) or routine (1.0 kcal/ml) enteral nutrition.Measurements and Main Results: Participants assigned energy-dense nutrition received more calories (percent recommended energy intake, mean [SD]; energy-dense: 103% [28] vs. usual: 69% [18]). Mortality at Day 180 was similar (560/1,895 [29.6%] vs. 539/1,920 [28.1%]; relative risk 1.05 [95% confidence interval, 0.95-1.16]). At a median (interquartile range) of 185 (182-193) days after randomization, 2,492 survivors were surveyed and reported similar quality of life (EuroQol five dimensions five-level quality-of-life questionnaire visual analog scale, median [interquartile range]: 75 [60-85]; group difference: 0 [95% confidence interval, 0-0]). Similar numbers of participants returned to work with no difference in hours worked or effectiveness at work (n = 818). There was no observed difference in disability (n = 1,208) or participation in key life activities (n = 705).Conclusions: The delivery of approximately 100% compared with 70% of recommended calorie intake during critical illness does not improve quality of life or functional outcomes or increase the number of survivors 6 months later. [ABSTRACT FROM AUTHOR]

Better predictive markers are needed to deliver individualized care for patients with primary esophagogastric cancer. This exploratory study aimed to assess whether pre-treatment imaging parameters from dynamic contrast-enhanced MRI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT are associated with response to neoadjuvant therapy or outcome. Following ethical approval and informed consent, prospective participants underwent dynamic contrast-enhanced MRI and 18F-FDG PET/CT prior to neoadjuvant chemotherapy/chemoradiotherapy ± surgery. Vascular dynamic contrast-enhanced MRI and metabolic 18F-FDG PET parameters were compared by tumor characteristics using Mann Whitney U test and with pathological response (Mandard tumor regression grade), recurrence-free and overall survival using logistic regression modelling, adjusting for predefined clinical variables. 39 of 47 recruited participants (30 males; median age 65 years, IQR: 54, 72 years) were included in the final analysis. The tumor vascular-metabolic ratio was higher in patients remaining node positive following neoadjuvant therapy (median tumor peak enhancement/SUV max ratio: 0.052 vs. 0.023, p = 0.02). In multivariable analysis adjusted for age, gender, pre-treatment tumor and nodal stage, peak enhancement (highest gadolinium concentration value prior to contrast washout) was associated with pathological tumor regression grade. The odds of response decreased by 5% for each 0.01 unit increase (OR 0.95; 95% CI: 0.90, 1.00, p = 0.04). No 18F-FDG PET/CT parameters were predictive of pathological tumor response. No relationships between pre-treatment imaging and survival were identified. Pre-treatment esophagogastric tumor vascular and metabolic parameters may provide additional information in assessing response to neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Nutrition is one of the fundamentals of care provided to critically ill adults. The volume of enteral nutrition received, however, is often much less than prescribed due to multiple functional and process issues. To deliver the prescribed volume and correct the energy deficit associated with enteral nutrition alone, parenteral nutrition can be used in combination (termed "supplemental parenteral nutrition"), but benefits of this method have not been firmly established. A multi-centre, randomised, clinical trial is currently underway to determine if prescribed energy requirements can be provided to critically ill patients by using a supplemental parenteral nutrition strategy in the critically ill.Methods/design: This prospective, multi-centre, randomised, stratified, parallel-group, controlled, phase II trial aims to determine whether a supplemental parenteral nutrition strategy will reliably and safely increase energy intake when compared to usual care. The study will be conducted for 100 critically ill adults with at least one organ system failure and evidence of insufficient enteral intake from six intensive care units in Australia and New Zealand. Enrolled patients will be allocated to either a supplemental parenteral nutrition strategy for 7 days post randomisation or to usual care with enteral nutrition. The primary outcome will be the average energy amount delivered from nutrition therapy over the first 7 days of the study period. Secondary outcomes include protein delivery for 7 days post randomisation; total energy and protein delivery, antibiotic use and organ failure rates (up to 28 days); duration of ventilation, length of intensive care unit and hospital stay. At both intensive care unit and hospital discharge strength and health-related quality of life assessments will be undertaken. Study participants will be followed up for health-related quality of life, resource utilisation and survival at 90 and 180 days post randomisation (unless death occurs first).Discussion: This trial aims to determine if provision of a supplemental parenteral nutrition strategy to critically ill adults will increase energy intake compared to usual care in Australia and New Zealand. Trial outcomes will guide development of a subsequent larger randomised controlled trial.Trial Registration: NCT01847534 (First registered 5 February 2013, last updated 14 October 2015). [ABSTRACT FROM AUTHOR]

Background: Critically ill patients typically receive ~60% of estimated calorie requirements. Objectives: We aimed to determine whether the substitution of a 1.5-kcal/mL enteral nutrition solution for a 1.0-kcal/mL solution resulted in greater calorie delivery to critically ill patients and establish the feasibility of conducting a multicenter, double-blind, randomized trial to evaluate the effect of an increased calorie delivery on clinical outcomes. Design: A prospective, randomized, double-blind, parallel-group, multicenter study was conducted in 5 Australian intensive care units. One hundred twelve mechanically ventilated patients expected to receive enteral nutrition for ≥2 d were randomly assigned to receive 1.5 (n = 57) or 1.0 (n = 55) kcal/mL enteral nutrition solution at a rate of 1 mL/kg ideal body weight per hour for 10 d. Protein and fiber contents in the 2 solutions were equivalent. Results: The 2 groups had similar baseline characteristics (1.5 compared with 1.0 kcal/mL). The mean (±SD) age was 56.4 ± 16.8 compared with 56.5 ± 16.1 y, 74% compared with 75% were men, and the Acute Physiology and Chronic Health Evaluation II score was 23 ± 9.1 compared with 22 ± 8.9. The groups received similar volumes of enteral nutrition solution [1221 mL/d (95% CI: 1120, 1322 mL/d) compared with 1259 mL/d (95% CI: 1143, 1374 mL/d); P = 0.628], which led to a 46% increase in daily calories in the group given the 1.5-kcal/mL solution [1832 kcal/d (95% CI: 1681, 1984 kcal/d) compared with 1259 kcal/d (95% CI: 1143, 1374 kcal/d); P < 0.001]. The 1.5-kcal/mL solution was not associated with larger gastric residual volumes or diarrhea. In this feasibility study, there was a trend to a reduced 90-d mortality in patients given 1.5 kcal/mL [11 patients (20%) compared with 20 patients (37%); P = 0.057]. Conclusions: The substitution of a 1.0- with a 1.5-kcal/mL enteral nutrition solution administered at the same rate resulted in a 46% greater calorie delivery without adverse effects. The results support the conduct of a large-scale trial to evaluate the effect of increased calorie delivery on clinically important outcomes in the critically ill. This trial was registered at Australian New Zealand Clinical Trials (http://www.anzctr.org.au/) as ACTRN 12611000793910. [ABSTRACT FROM AUTHOR]

Importance: Systematic reviews suggest adult patients in intensive care units (ICUs) with relative contraindications to early enteral nutrition (EN) may benefit from parenteral nutrition (PN) provided within 24 hours of ICU admission.Objective: To determine whether providing early PN to critically ill adults with relative contraindications to early EN alters outcomes.Design, Setting, and Participants: Multicenter, randomized, single-blind clinical trial conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zealand. Participants were critically ill adults with relative contraindications to early EN who were expected to remain in the ICU longer than 2 days.Interventions: Random allocation to pragmatic standard care or early PN.Main Outcomes and Measures: Day-60 mortality; quality of life, infections, and body composition.Results: A total of 1372 patients were randomized (686 to standard care, 686 to early PN). Of 682 patients receiving standard care, 199 patients (29.2%) initially commenced EN, 186 patients (27.3%) initially commenced PN, and 278 patients (40.8%) remained unfed. Time to EN or PN in patients receiving standard care was 2.8 days (95% CI, 2.3 to 3.4). Patients receiving early PN commenced PN a mean of 44 minutes after enrollment (95% CI, 36 to 55). Day-60 mortality did not differ significantly (22.8% for standard care vs 21.5% for early PN; risk difference, -1.26%; 95% CI, -6.6 to 4.1; P = .60). Early PN patients rated day-60 quality of life (RAND-36 General Health Status) statistically, but not clinically meaningfully, higher (45.5 for standard care vs 49.8 for early PN; mean difference, 4.3; 95% CI, 0.95 to 7.58; P = .01). Early PN patients required fewer days of invasive ventilation (7.73 vs 7.26 days per 10 patient × ICU days, risk difference, -0.47; 95% CI, -0.82 to -0.11; P = .01) and, based on Subjective Global Assessment, experienced less muscle wasting (0.43 vs 0.27 score increase per week; mean difference, -0.16; 95% CI, -0.28 to -0.038; P = .01) and fat loss (0.44 vs 0.31 score increase per week; mean difference, -0.13; 95% CI, -0.25 to -0.01; P = .04).Conclusions and Relevance: The provision of early PN to critically ill adults with relative contraindications to early EN, compared with standard care, did not result in a difference in day-60 mortality. The early PN strategy resulted in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays.Trial Registration: anzctr.org.au Identifier: ACTRN012605000704695. [ABSTRACT FROM AUTHOR]