Utilising Pancreatic Exocrine Insufficiency in the Detection of Resectable Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed late, leading to a high mortality rate. Early detection facilitates better treatment options. The aim of this UK-based case-control study was to determine whether two validated tests for pancreatic exocrine insufficiency (PEI), namely, the 13C-mixed triglyceride breath test (13C-MTGBT) and a faecal elastase (FE-1) test, can discriminate between patients with resectable PDAC versus healthy volunteers (HVs) along with a comparison group with chronic pancreatitis (CP). Discrimination between disease states and HVs was tested with receiver operator characteristic (ROC) curves. In total, 59 participants (23 PDAC (16 men), 24 HVs (13 men) and 12 CP (10 men)) were recruited, with a similar age in each population, and a combined median (IQR) age of 66 (57-71). The areas under the ROC curve for discriminating between PDAC and HVs were 0.83 (95% CI: 0.70-0.96) for the 13C-MTGBT, and 0.85 (95% CI: 0.75-0.95) for the FE-1 test. These were similar to CP vs. HV. In conclusion, PEI occurs in resectable PDAC to a similar extent as in CP; further large-scale, prospective studies using these tests in the primary care setting on high-risk groups are warranted.

Elevated Glycated Haemoglobin (HbA1c) Is Associated with an Increased Risk of Pancreatic Ductal Adenocarcinoma: A UK Biobank Cohort Study.

BACKGROUND: The role of dysglycaemia as a risk marker for Pancreatic Ductal Adenocarcinoma (PDAC) is uncertain. We investigated the relationship between glycated haemoglobin (HbA1c) and incident PDAC using a retrospective cohort study within the UK Biobank. METHODS: A study involving 499,804 participants from the UK Biobank study was undertaken. Participants were stratified by diabetes mellitus (DM) status, and then by HbA1c values < 42 mmol/mol, 42-47 mmol/mol, or ≥48 mmol/mol. Cox proportional hazard models were used to describe the association between HbA1c category (with time-varying interactions) and incident PDAC. RESULTS: PDAC occurred in 1157 participants during 11.6 (10.9-12.3) years follow up [(median (interquartile range)]. In subjects without known DM at baseline, 12 months after recruitment, the adjusted hazard ratios (aHR, 95% CI) for incident PDAC for HbA1c 42-47 mmol/mol compared to HbA1c < 42 mmol/mol (reference group) was 2.10 (1.31-3.37, p = 0.002); and was 8.55 (4.58-15.99, p < 0.001) for HbA1c ≥ 48 mmol/mol. The association between baseline HbA1c and incident PDAC attenuated with increasing duration of time of follow-up to PDAC diagnosis. CONCLUSIONS: Dysglycaemia detected by elevated HbA1c is associated with an increased risk of PDAC. The strength of the association between elevated HbA1c and incident PDAC is inversely proportional to the time from detecting dysglycaemia but remains significant for at least 60 months following HbA1c testing.

DEPEND study protocol: early detection of patients with pancreatic cancer - a pilot study to evaluate the utility of faecal elastase-1 and 13C-mixed triglyceride breath test as screening tools in high-risk individuals.

INTRODUCTION: Pancreatic cancer (PC) is the fifth leading cause of cancer-related death in the UK. The incidence of PC is increasing, with little or no improvement in overall survival and the best chance for long-term survival in patients with PC relies on early detection and surgical resection. In this study, we propose the use of a diagnostic algorithm that combines tests of pancreatic exocrine function (faecal elastase-1 (FE-1) test and the 13C-mixed triglyceride (13C-MTG) breath test) to identify patients with PC that urgently needs imaging studies. METHODS AND ANALYSIS: This prospective pilot (proof of concept) study will be carried out on 25 patients with resectable PC, 10 patients with chronic pancreatitis and 25 healthy volunteers. This study will construct a predictive algorithm for PC, using two tests of pancreatic exocrine function, FE-1 test and the 13C-MTG breath test. Continuous flow isotope ratio mass spectrometry in the 13C-MTG breath test will be used to analyse enriched 13CO2 in exhaled breath samples. The additional predictive benefit of other potential biomarkers of PC will also be considered. Potential biomarkers of PC showing abilities to discriminate between patients with PC from healthy subjects or patients with chronic pancreatitis will be selected by metabolomic analysis. ETHICS AND DISSEMINATION: The study was approved by the North of Scotland Research and Ethics Committee on 1 October 2020 (reference: 20/NS/0105, favourable opinion granted). The results will be disseminated in presentations at academic national/international conferences and publication in peer-review journals.

Metabolic syndrome is a predictor of all site and liver-specific recurrence following primary resection of colorectal cancer: Prospective cohort study of 1006 patients.

INTRODUCTION: Large epidemiological studies have demonstrated the link between metabolic syndrome and cancer development, including colorectal cancer. However, the influence of metabolic syndrome on disease progression is less well studied, particularly in the post-surgical setting. This study investigates the effect of metabolic syndrome on colorectal cancer recurrence (all-site and liver-specific) after curative surgery for Stage I-III disease. MATERIALS AND METHODS: Consecutive patients who underwent curative resection for Stage I-III colorectal cancer in a single UK centre were prospectively recruited. Disease-free and overall survival with metabolic syndrome as a factor, were determined using the Kaplan-Meier technique. Hazard ratios for all-site and liver-specific recurrence were determined using univariable and multivariable Cox-regression models. RESULTS: 1006 patients were recruited and followed up for a median of 50 months (IQR 30-67). 177 patients (17.6%) met the criteria for metabolic syndrome. 245 patients (25.4%) developed recurrence, 161 (16.0%) of these had liver recurrence. The presence of metabolic syndrome was associated with a reduction in disease-free survival from 69 to 58 months (p < 0.001) and overall survival from 74 to 61 months (p < 0.001). Metabolic syndrome was an independent predictor of all-site (HR 1.76; p < 0.001) and liver-specific (HR 1.74; p = 0.01) recurrence. CONCLUSION: Metabolic syndrome is a predictor of all-site and liver-specific recurrence after primary resection of stage I-III colorectal cancer.

Over-admission and over-treatment of patients with cellulitis: a 5-year audit against international guidelines.

BACKGROUND/AIMS: Application of evidence-based guidelines in the management of cellulitis is poorly studied in Ireland and it is observed that current admission and prescription practices in this country vary widely from internationally accepted standards of care. We aimed to examine the management of cellulitis with regard to hospital admission and initial antibiotic therapy. METHODS: A retrospective audit of patients admitted with cellulitis from 2013 to 2017 in an Irish district general hospital. Exclusion criteria included specialist regions of the body and surgical site infections. Appropriateness of admission and management was compared against international guidelines (Clinical Research Efficiency Support Team (CREST) and Infectious Disease Society of America (IDSA)). RESULTS: Five hundred twenty emergency admissions with cellulitis were analysed. Thirty-five percent (n = 182) were deemed inappropriate admissions compared with CREST and IDSA guidelines, with an estimated cost of €152,203 per annum. Ninety-six percent (n = 501) of patients with cellulitis were treated with a combination of flucloxacillin and benzylpenicillin, despite level 1 evidence showing combination therapy to provide no benefit over appropriate monotherapy. CONCLUSIONS: There is a significant discrepancy between current clinical practice and international guidelines for the management of cellulitis in Ireland; local guidelines are not in keeping with newer evidence and there is a lack of national guidelines for this common condition. Closer adherence to international guidelines would significantly reduce costs by reducing unnecessary admissions and initial monotherapy would improve antibiotic stewardship. This study shows a clear need for local institutions to re-examine antibiotic guidelines to ensure the HSE provides effective evidence-based treatment in the correct setting.

Epidemiology and outcomes of pregnancy and obstetric complications in trauma in the United Kingdom.

OBJECTIVE: To understand the epidemiology of pregnancy and obstetric complications encountered in the management of pregnant trauma patients. METHODS AND DESIGN: Retrospective analysis of national trauma registry for recording of pregnancy status or obstetric complication in cases of trauma. Sub-division of patient cohort by severity of trauma and stage of pregnancy. Comparison of data sets between pregnant trauma patients and age-matched non-pregnant female trauma patients to determine patterns of injury and impact upon clinical outcomes. SETTINGS: National registry data for the United Kingdom. OUTCOME: For the five year period between 2009 and 2014, a total of 15,140 female patients, aged between 15 years old and 50 years old were identified within the trauma registry. A record of pregnancy was identified in 173 patients (1.14%) from within this cohort. Mechanisms of injury within the cohort of pregnant trauma patients saw increased rate of vehicular collision and interpersonal violence, especially penetrating trauma. Higher abbreviated injury scores were recorded for the abdominal region in pregnancy than in the non-pregnant cohort. Maternal mortality rates were seen to be higher, when compared with the non-pregnant trauma patient. Foetal survival rate from this series was 56% following trauma. Foetal death in pregnant trauma patients most frequently occurred in the 2nd trimester. No cases of isolated foetal survival were recorded following maternal trauma. CONCLUSIONS: Trauma to pregnant patients is rare in the United Kingdom, encountered in 1% of female trauma patients of child bearing age. Observations in altered mechanisms of injury and clinical outcomes were recorded. This provides useful information regarding the clinical management of pregnant trauma patients and offers potential areas to investigate to optimise their care, as well as to focus injury prevention measures. LEVEL OF EVIDENCE: IV--Case series.