Multicenter, Prospective Cohort Study of Oesophageal Injuries and Related Clinical Outcomes (MUSOIC study).

OBJECTIVE: To identify prognostic factors associated with 90-day mortality in patients with oesophageal perforation (OP), and characterize the specific timeline from presentation to intervention, and its relation to mortality. BACKGROUND: OP is a rare gastro-intestinal surgical emergency with a high mortality rate. However, there is no updated evidence on its outcomes in the context of centralized esophago-gastric services; updated consensus guidelines; and novel non-surgical treatment strategies. METHODS: A multi-center, prospective cohort study involving eight high-volume esophago-gastric centers (January 2016 to December 2020) was undertaken. The primary outcome measure was 90-day mortality. Secondary measures included length of hospital and ICU stay, and complications requiring re-intervention or re-admission. Mortality model training was performed using random forest, support-vector machines, and logistic regression with and without elastic net regularisation. Chronological analysis was performed by examining each patient's journey timepoint with reference to symptom onset. RESULTS: The mortality rate for 369 patients included was 18.9%. Patients treated conservatively, endoscopically, surgically, or combined approaches had mortality rates of 24.1%, 23.7%, 8.7%, and 18.2%, respectively. The predictive variables for mortality were Charlson comorbidity index, haemoglobin count, leucocyte count, creatinine levels, cause of perforation, presence of cancer, hospital transfer, CT findings, whether a contrast swallow was performed, and intervention type. Stepwise interval model showed that time to diagnosis was the most significant contributor to mortality. CONCLUSIONS: Non-surgical strategies have better outcomes and may be preferred in selected cohorts to manage perforations. Outcomes can be significantly improved through better risk-stratification based on afore-mentioned modifiable risk factors.

Multimodal Prehabilitation During Neoadjuvant Therapy Prior to Esophagogastric Cancer Resection: Effect on Cardiopulmonary Exercise Test Performance, Muscle Mass and Quality of Life-A Pilot Randomized Clinical Trial.

BACKGROUND: Neoadjuvant therapy reduces fitness, muscle mass, and quality of life (QOL). For patients undergoing chemotherapy and surgery for esophagogastric cancer, maintenance of fitness is paramount. This study investigated the effect of exercise and psychological prehabilitation on anaerobic threshold (AT) at cardiopulmonary exercise testing (CPET). Secondary endpoints included peak oxygen uptake (peak VO2), skeletal muscle mass, QOL, and neoadjuvant therapy completion. METHODS: This parallel-arm randomized controlled trial assigned patients with locally advanced esophagogastric cancer to receive prehabilitation or usual care. The 15-week program comprised twice-weekly supervised exercises, thrice-weekly home exercises, and psychological coaching. CPET was performed at baseline, 2 weeks after neoadjuvant therapy, and 1 week preoperatively. Skeletal muscle cross-sectional area at L3 was analyzed on staging and restaging computed tomography. QOL questionnaires were completed at baseline, mid-neoadjuvant therapy, at restaging laparoscopy, and postoperatively at 2 weeks, 6 weeks and 6 months. RESULTS: Fifty-four participants were randomized (prehabilitation group, n = 26; control group, n = 28). No difference in AT between groups was observed post-neoadjuvant therapy. Prehabilitation resulted in an attenuated peak VO2 decline {-0.4 [95% confidence interval (CI) -0.8 to 0.1] vs. -2.5 [95% CI -2.8 to -2.2] mL/kg/min; p = 0.022}, less muscle loss [-11.6 (95% CI -14.2 to -9.0) vs. -15.6 (95% CI -18.7 to -15.4) cm2/m2; p = 0.049], and improved QOL. More prehabilitation patients completed neoadjuvant therapy at full dose [prehabilitation group, 18 (75%) vs. control group, 13 (46%); p = 0.036]. No adverse events were reported. CONCLUSIONS: This study has demonstrated some retention of cardiopulmonary fitness (peak VO2), muscle, and QOL in prehabilitation subjects. Further large-scale trials will help determine whether these promising findings translate into improved clinical and oncological outcomes. Trial Registration ClinicalTrials.gov NCT02950324.

COVID-19-induced sarcopenia and physical deconditioning may require reassessment of surgical risk for patients with cancer.

BACKGROUND: The long-term physiological consequences of SARS-CoV-2 (severe acute respiratory syndrome coronavirus) infection are not known. The ability of COVID-19 to cause chronic illness, sarcopenia, and physical deconditioning may be underestimated and go beyond the anticipated respiratory sequelae. Myalgia, lethargy, and anorexia are common symptoms even in mild to moderate cases and have the potential to exacerbate frailty. How this impacts on risk-stratification for patients requiring surgery for time-critical conditions, such as malignancy, requires further urgent investigation. MAIN BODY: The deleterious effect of sarcopenia and poor physical capacity are well recognised in cancer surgery. This review commentary highlights current evidence which suggests skeletal muscle as an under recognised cause of COVID-19-related functional deconditioning. The mechanisms behind this are via direct (viral induced myositis, nutritional decline, cytokine-mediated myopathy) and indirect mechanisms (social isolation, inactivity, and psychological consequences). CONCLUSION: Further mechanistic research is required to explore the processes behind the deconditioning effects of SARS-CoV-2 infection and how this impacts on treatment of malignant disease.

Laparoscopic versus open subtotal gastrectomy for adenocarcinoma of the stomach in a Western population: peri-operative and 5-year oncological outcomes.

BACKGROUND: This study compares the peri-operative and long-term oncological outcomes for laparoscopic subtotal gastrectomy (LSG) versus open subtotal gastrectomy (OSG) for adenocarcinoma of the stomach in a Western population. METHODS: A retrospective, intention-to-treat analysis study was conducted for consecutive patients undergoing gastrectomy with curative intent for adenocarcinoma of the stomach between November 2006 and October 2016. Univariate analysis was used to compare peri-operative outcomes between LSG and OSG. Logistic regression with bootstrapping validation was used to identify independent risk factors for predicting 2-year overall survival. RESULTS: The final analysis included 79 patients. When comparing LSG (n = 30) to OSG (n = 49), there was no difference in the number of resected lymph nodes (36 (IQR 24.3-44) vs. 42 (IQR 28-59), p = 0.165), a reduction in intra-operative blood loss (150 ml (IQR 100-250) vs. 553 ml (IQR 338-1075), p < 0.001) and an increase incidence of post-operative bleeding (3 patients vs. 0, p = 0.024), respectively. Five-year overall survival for LSG (n = 22) versus OSG (n = 20) was 63.6% and 50% (p = 0.372), respectively. The number of positive lymph nodes [OR 0.64 (CI 0.47-0.88), p = 0.006] was the only significant independent risk factor for 2-year overall survival. Pre-operative ASA grading and operative approach did not influence survival outcomes at 2 years. CONCLUSION: This study suggests that LSG is comparable to OSG in Western patients with respect to oncological quality and peri-operative morbidity. Two-year overall survival is predicted by the number of positive lymph nodes and not the operative access employed for resection.

Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

The current landscape of nutrition care in oesophageal and gastric cancer - insights from the national oesophagogastric nutrition audit (NONA) survey.

BACKGROUND AND AIMS: Specialist nutritional support is important during treatment for oesophagogastric (OG) cancer yet current practice remains unstandardised across the UK. The National Oesophagogastric Nutrition Audit (NONA) aimed to describe the current landscape of OG dietetic services in the UK and Ireland, with a specific focus on resource allocation, barriers to dietetic support, and the provision of support throughout the cancer pathway. METHODS: Tertiary cancer units, secondary care, and community services across the UK and Ireland were invited to complete a 28-point electronic questionnaire. Team leaders and senior specialist OG dietitians were the target respondents. All data points were peer-reviewed, piloted, and revised by the NONA steering committee before distribution. Data points covered a range of areas related to resources, skill mix, provision of support throughout the cancer pathway, and involvement with national audit and research. RESULTS: Complete responses were received from 50 individual units (tertiary surgical units, n = 35 and tertiary oncology units, n = 10). Secondary care and community services were underrepresented (n = 5). Of the units proving tertiary cancer care, the majority (77%) agreed or strongly agreed they were able to provide adequate nutritional care in the post-operative period. However, confidence dropped significantly in the early diagnostic phase and in the neoadjuvant period, with 52% and 67% of tertiary units disagreeing that they could provide adequate dietetic support during these parts of the cancer pathway, respectively. Inadequate funding, understaffing, and the prioritisation of inpatients were commonly reported barriers. There was significant variation in practice regarding nutritional assessment, service structure, and staffing resource allocation across specialist units. CONCLUSION: The NONA survey provides a 'real-world' landscape of nutritional care for patients with OG cancer. Lack of funding, resource, and evidence-base may explain the variation seen in services provided across the UK. Further research and consensus is required to help standardise nutritional care, guide service specification, and improve nutritional outcomes for patients with OG cancer.

The current use of ultrasound to measure skeletal muscle and its ability to predict clinical outcomes: a systematic review.

Quantification and monitoring of lean body mass is an important component of nutrition assessment to determine nutrition status and muscle loss. The negative impact of reduced muscle mass and muscle function is increasingly evident across acute and chronic disease states but is particularly pronounced in patients with cancer. Ultrasound is emerging as a promising tool to directly measure skeletal muscle mass and quality. Unlike other ionizing imaging techniques, ultrasound can be used repeatedly at the bedside and may compliment nutritional risk assessment. This review aims to describe the current use of skeletal muscle ultrasound (SMUS) to measure muscle mass and quality in patients with acute and chronic clinical conditions and its ability to predict functional capacity, severity of malnutrition, hospital admission, and survival. Databases were searched from their inception to August 2021 for full-text articles in English. Relevant articles were included if SMUS was investigated in acute or chronic clinical contexts and correlated with a defined clinical outcome measure. Data were synthesized for narrative review due to heterogeneity between studies. This review analysed 37 studies (3100 patients), which met the inclusion criteria. Most studies (n = 22) were conducted in critical care. The clinical outcomes investigated included functional status at discharge (intensive care unit-acquired weakness), nutritional status, and length of stay. SMUS was also utilized in chronic conditions such as chronic obstructive pulmonary disease, chronic heart failure, and chronic renal failure to predict hospital readmission and disease severity. Only two studies investigated the use of SMUS in patients with cancer. Of the 37 studies, 28 (76%) found that SMUS (cross-sectional area, muscle thickness, and echointensity) showed significant associations with functional capacity, length of stay, readmission, and survival. There was significant heterogeneity in terms of ultrasound technique and outcome measurement across the included studies. This review highlights that SMUS continues to gain momentum as a potential tool for skeletal muscle assessment and predicting clinically important outcomes. Further work is required to standardize the technique in nutritionally vulnerable patients, such as those with cancer, before SMUS can be widely adopted as a bedside prognostic tool.

Spontaneous regression of oesophageal squamous cell carcinoma.

Partial or complete spontaneous regression (SR) of cancer is unusual, particularly in patients with oesophageal cancer. This case report describes a patient with biopsy-proven squamous cell carcinoma of the oesophagus which spontaneously regressed without any treatment. Regression of the primary tumour was confirmed on histological examination of the resected specimen. The process of SR remains an enigma, but potential mechanisms are considered.

Implementing a system-wide cancer prehabilitation programme: The journey of Greater Manchester's 'Prehab4cancer'.

Patients undergoing major cancer interventions such as major surgical resection, chemotherapy, radiotherapy, and immunotherapy are prone to the adverse effects of their cancer, as well as to the side effects of the treatments designed to cure them. The Prehabilitation process supports cancer patients in preparing for the physiological challenges of their cancer treatments, whilst aiming to shorten recovery time, reduce peri-operative complications and improve compliance with non-surgical treatments. Prehabilitation will be most useful in older patients. Greater Manchester Integrated Care system is the first regional system in the UK to introduce delivery of system-wide, large scale physical activity supported multi-modal prehabilitation and recovery programme, Prehab4Cancer as a standard of care for cancer patients. It builds upon the successful implementation of Enhanced Recovery After Surgery + programme to improve surgical care in Greater Manchester. During this review we describe the journey to develop a system wide prehabilitation model for patients with cancer. Prehab4Cancer to date has focused on robust co-design, development, and implementation of an effective service model with attention paid to stakeholder engagement. This has led to receipt of high numbers of referrals from across Greater Manchester for the all the cancer groups involved. The successful implementation of the P4C pathway in GM presents a best practice model that might be adopted by other local and combined authority areas nationally.

Nutrient digestibility and feedlot performance of lambs fed diets varying protein and energy contents.

Thirty-six Thalli male growing lambs were used in a completely randomized design with 2 x 2 factorial arrangement of treatments to evaluate the effect of varying levels of energy and protein on nutrient intake, digestibility, weight gain, and gain to feed ratio. Four experimental diets, i.e., low energy-low protein (LE-LP), low energy-high protein (LE-HP), high energy-low protein (HE-LP), and high energy-high protein (HE-HP) were formulated. The low- and high-energy diets contained 2.3 and 2.7 MJ/kg dry matter (DM) with 12% and 14% of crude protein. The lambs were fed ad libitum. Dietary energy and protein levels and their interactions influenced the nutrient intake. Maximum dry matter intake was noted in animals fed LE-HP diet followed by LE-LP, HE-HP, and HE-LP diets. Digestibility of DM and N increased (P < 0.01) and that of neutral detergent fiber decreased (P < 0.01) linearly with increasing levels of dietary energy and protein. Digestibility of N was only affected by protein level and interaction between energy and protein levels. Average daily gain was higher (P < 0.01) in lambs fed HE-HP diet followed by LE-HP, LE-LP, and HE-LP diets. Dietary energy and protein levels and their interaction had significant effect (P < 0.01) on gain to feed ratio.

Heavy metal residues in the milk of cattle and goats during winter season.

Cadmium (Cd), chromium (Cr), nickel (Ni) and lead (Pb) residues (mg/L) were determined in the milk of cattle and goats. The milk samples of cattle from area 1 have higher levels of residues than area 2; Cd 0.089 +/- 0.002 vs. 0.062 +/- 0.01 Cr 1.14 +/- 0.046 vs. 0.995 +/- 0.017 Ni 23.38 +/- 0.564 vs. 21.407 +/- 0.275 Pb 21.781 +/- 0.172 vs. 15.958 +/- 1.00. The residual levels of Cd (0.084 +/- 0.003) and Pb (42.687 +/- 0.051) have been found higher in goat milk. The Ni residues in cattle milk (22.395 +/- 0.988) are higher than in goat milk (19.522 +/- 0.011) while residues of Cr are non significantly different in both species.

A randomised controlled trial to assess whether prehabilitation improves fitness in patients undergoing neoadjuvant treatment prior to oesophagogastric cancer surgery: study protocol.

INTRODUCTION: Neoadjuvant therapy prior to oesophagogastric resection is the gold standard of care for patients with T2 and/or nodal disease. Despite this, studies have taught us that chemotherapy decreases patients' functional capacity as assessed by cardiopulmonary exercise (CPX) testing. We aim to show that a multimodal prehabilitation programme, comprising supervised exercise, psychological coaching and nutritional support, will physically, psychologically and metabolically optimise these patients prior to oesophagogastric cancer surgery so they may better withstand the immense physical and metabolic stress placed on them by radical curative major surgery. METHODS AND ANALYSIS: This will be a prospective, randomised, controlled, parallel, single-centre superiority trial comparing a multimodal 'prehabilitation' intervention with 'standard care' in patients with oesophagogastric malignancy who are treated with neoadjuvant therapy prior to surgical resection. The primary aim is to demonstrate an improvement in baseline cardiopulmonary function as assessed by anaerobic threshold during CPX testing in an interventional (prehab) group following a 15-week preoperative exercise programme, throughout and following neoadjuvant treatment, when compared with those that undergo standard care (control group). Secondary objectives include changes in peak oxygen uptake and work rate (total watts achieved) at CPX testing, insulin resistance, quality of life, chemotherapy-related toxicity and completion, nutritional assessment, postoperative complication rate, length of stay and overall mortality. ETHICS AND DISSEMINATION: This study has been approved by the London-Bromley Research Ethics Committee and registered on ClinicalTrials.gov. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02950324; Pre-results.

Perioperative diagnosis of euglycaemic ketoacidosis.

Euglycaemic diabetic ketoacidosis is a term describing features of diabetic ketoacidosis but with normoglycaemia. We present a case of a perioperative diagnosis of euglycaemic ketoacidosis in a patient not known to be diabetic, and the subsequent management of the patient. A 65-year-old lady was scheduled for re-exploration of a giant paraoesophageal hernia, which had been initially repaired over six weeks previously. She developed dysphagia soon after the initial surgery and had low caloric intake. Arterial blood gases performed intraoperatively revealed metabolic acidosis with a normal lactate level. It did not respond to intravenous fluid therapy and sodium bicarbonate. Euglycaemic ketoacidosis was confirmed with raised serum ketone level. Insulin and dextrose infusions were commenced and she was managed in intensive care unit where the metabolic acidosis resolved over a 12-h period.