Protocol for the CoNoR Study: A prospective multi-step study of the potential added benefit of two novel assessment tools in colorectal liver metastases technical resectability decision-making.

INTRODUCTION: Liver resection is the only curative treatment for colorectal liver metastases (CLM). Resectability decision-making is therefore a key determinant of outcomes. Wide variation has been demonstrated in resectability decision-making, despite the existence of criteria. This paper summarises a study protocol to evaluate the potential added value of two novel assessment tools in assessing CLM technical resectability: the Hepatica preoperative MR scan (MR-based volumetry, Couinaud segmentation, liver tissue characteristics and operative planning tool) and the LiMAx test (hepatic functional capacity). METHODS AND ANALYSIS: This study uses a systematic multistep approach, whereby three preparatory workstreams aid the design of the final international case-based scenario survey:Workstream 1: systematic literature review of published resectability criteria.Workstream 2: international hepatopancreatobiliary (HPB) interviews.Workstream 3: international HPB questionnaire.Workstream 4: international HPB case-based scenario survey.The primary outcome measures are change in resectability decision-making and change in planned operative strategy, resulting from the novel test results. Secondary outcome measures are variability in CLM resectability decision-making and opinions on the role for novel tools. ETHICS AND DISSEMINATION: The study protocol has been approved by a National Health Service Research Ethics Committee and registered with the Health Research Authority. Dissemination will be via international and national conferences. Manuscripts will be published. REGISTRATION DETAILS: The CoNoR Study is registered with ClinicalTrials.gov (registration number NCT04270851). The systematic review is registered on the PROSPERO database (registration number CRD42019136748).

Frailty in Older Patients Undergoing Emergency Laparotomy: Results From the UK Observational Emergency Laparotomy and Frailty (ELF) Study.

OBJECTIVE: This study aimed to document the prevalence of frailty in older adults undergoing emergency laparotomy and to explore relationships between frailty and postoperative morbidity and mortality. SUMMARY BACKGROUND DATA: The majority of adults undergoing emergency laparotomy are older adults (≥65 y) that carry the highest mortality. Improved understanding is urgently needed to allow development of targeted interventions. METHODS: An observational multicenter (n=49) UK study was performed (March-June 2017). All older adults undergoing emergency laparotomy were included. Preoperative frailty score was calculated using the progressive Clinical Frailty Score (CFS): 1 (very fit) to 7 (severely frail). Primary outcome measures were the prevalence of frailty (CFS 5-7) and its association to mortality at 90 days postoperative. Secondary outcomes included 30-day mortality and morbidity, length of critical care, and overall hospital stay. RESULTS: A total of 937 older adults underwent emergency laparotomy: frailty was present in 20%. Ninety-day mortality was 19.5%. After age and sex adjustment, the risk of 90-day mortality was directly associated with frailty: CFS 5 adjusted odds ratio (aOR) 3.18 [95% confidence interval (CI), 1.24-8.14] and CFS 6/7 aOR 6·10 (95% CI, 2.26-16.45) compared with CFS 1. Similar associations were found for 30-day mortality. Increasing frailty was also associated with increased risk of complications, length of Intensive Care Unit, and overall hospital stay. CONCLUSIONS: A fifth of older adults undergoing emergency laparotomy are frail. The presence of frailty is associated with greater risks of postoperative mortality and morbidity and is independent of age. Frailty scoring should be integrated into acute surgical assessment practice to aid decision-making and development of novel postoperative strategies.

Prospective study of change in liver function and fat in patients with colorectal liver metastases undergoing preoperative chemotherapy: protocol for the CLiFF Study.

INTRODUCTION: Preoperative chemotherapy in patients undergoing resection for colorectal liver metastases (CLM) improves oncological outcomes. However, chemotherapy-associated liver injury (occurring in two patterns: vascular and fat deposition) is a real clinical concern prior to hepatic resection. After major liver resection, regeneration of the residual liver is a prerequisite for recovery and avoidance of liver failure, but this regenerative capacity may be hindered by chemotherapy. Thus, there is a need to predict for this serious complication. Over the past two decades, several tests and derived indices have been developed, which have failed to achieve clinical utility, mainly as they were indirect measurements of liver function. Here, we will use a novel test of liver function (the liver maximum capacity (LiMAx) test), and measure liver fat using MRI. METHODS AND ANALYSIS: This prospective study will assess changes in liver function longitudinally, measured by the LiMAx test, and liver fat, measured by advanced MRI using both MR spectroscopy and the modified Dixon method, in up to 35 patients undergoing preoperative chemotherapy for CLM. The primary outcomes will be the changes in liver function and fat compared with baseline prechemotherapy measurements. Secondary outcome measures include: routinely measured liver function blood tests, anthropometric measurements, postoperative histology and digital quantification of fat, postoperative complications and mortality and quality of life. ETHICS AND DISSEMINATION: The study was approved by a National Health Service Research Ethics Committee and registered with the Health Research Authority. Dissemination will be via international and national conferences and the National Institute for Health Research network. Manuscripts will be published. TRIAL REGISTRATION NUMBER: This study is registered online at www.clinicaltrials.gov (registration number NCT03562234).

Influence of frailty in older patients undergoing emergency laparotomy: a UK-based observational study.

INTRODUCTION: The National Emergency Laparotomy Audit (NELA) has reported that older patients (≥65 years) form a large percentage of emergency high-risk cases with increased postoperative morbidity and mortality. With the population continuing to age rapidly, it is clear that a greater understanding of the factors affecting surgical outcomes in older patients is required. Frailty is a relatively new concept taking into account a variety of factors that increase an individual's vulnerability to increased dependency and death. Research has suggested that high frailty scores increase postoperative complications, length of stay and mortality but the majority of these studies have been carried out on elective patients. Knowledge of how frailty affects patients in an emergency setting would aid clinicians' and patients' decision-making process. METHODS AND ANALYSIS: This multicentre study will include consecutive adult patients aged 65 years and over undergoing emergency laparotomies over a 3-month period at 52 National Health Service hospitals across the UK. The primary outcome will be 90-day mortality. Secondary outcomes will include length of hospital stay, 30-day complications, change in level of independence and 30-day readmission. This study has been powered to detect a 10% change in mortality associated with frailty (n=500 patients). ETHICS AND DISSEMINATION: This study has been approved by the National Health Service Research Ethics Committee. It has been registered centrally with HRA for English sites, NRSPCC for Scottish sites and Health and Care Research Permissions Service for sites in Wales.Dissemination will be via international and national surgical and geriatric conferences. In addition, manuscripts will be prepared following the close of the project. TRIAL REGISTRATION NUMBER: This study is also registered online at www.clinicaltrials.gov (registration number NCT02952430).