Olga Tucker

The changing face of esophageal cancer.

The two main histological esophageal cancer types, adenocarcinoma and squamous cell carcinoma, differ in incidence, geographic distribution, ethnic pattern and etiology. This article focuses on epidemiology with particular reference to geographic and temporal variations in incidence, along with a review of the evidence supporting environmental and genetic factors involved in esophageal carcinogenesis. Squamous cell carcinoma of the esophagus remains predominantly a disease of the developing world. In contrast, esophageal adenocarcinoma is mainly a disease of western developed societies, associated with obesity and gastro-esophageal reflux disease. There has been a dramatic increase in the incidence of adenocarcinoma in developed countries in parallel with migration of both esophageal and gastric adenocarcinomas towards the gastro-esophageal junction.

Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth in vitro and in vivo

Growing evidence implicates iron in the aetiology of gastrointestinal cancer. Furthermore, studies demonstrate that iron chelators possess potent anti‐tumour activity, although whether iron chelators show activity against oesophageal cancer is not known.

Macrophage migration inhibitory factor and DJ-1 in gastric cancer: differences between high-incidence and low-incidence areas

Background:There is a need for sensitive and specific blood-borne markers for the detection of gastric cancer. Raised serum macrophage inhibitory factor (MIF) levels have been proposed as a marker for gastric cancer diagnosis but, to date, studies have only encompassed patients from high-incidence areas.Methods:We have compared the serum concentration of MIF in a large cohort of UK and Japanese gastric cancer patients, together with appropriate control subjects (age and gender matched). Carcinoembryonic antigen and H. pylori IgG were also measured, as was DJ-1, a novel candidate protein biomarker identified by analysis of gastric cancer cell line secretomes.Results:Marked elevations of the serum concentration of MIF and DJ-1 were seen in Japanese patients with gastric cancer compared with Japanese controls, a trend not seen in the UK cohort. These results could not be accounted for by differences in age, disease stage or H. pylori status.Conclusion:In regions of high, but not low incidence of gastric cancer, both MIF and DJ-1 have elevated serum concentrations in gastric cancer patients, compared with controls. This suggests that differing mechanisms of disease pathogenesis may be at play in high- and low-incidence regions.

Epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma: a systematic review protocol

Introduction Barretts oesophagus (BO), a metaplastic condition affecting the lower oesophagus due to long-standing gastro-oesophageal reflux and chronic inflammation, is a precursor lesion for oesophageal adenocarcinoma (OADC). There is no clinical test to predict which patients with BO will progress to OADC. The British Society of Gastroenterology recommends endoscopic surveillance of patients with BO. Epigenetic changes have been well characterised in the neoplastic progression of ulcerative colitis to colonic carcinoma, another gastrointestinal cancer associated with chronic inflammation. This systematic review protocol aims to identify and evaluate studies which examine epigenetic biomarkers in BO and their association with progression to OADC. Methods and analysis All prospective and retrospective primary studies, and existing systematic reviews investigating epigenetic markers including DNA methylation, histone modification, chromatin remodelling, micro and non-coding RNAs of all types will be eligible for inclusion. Eligible patients are those over the age of 18 with BO, BO with dysplasia, OADC or unspecified oesophageal cancer. A comprehensive search of bibliographic databases using combinations of text and index words relating to the population, prognostic markers and outcome will be undertaken with no language restrictions. Results will be screened by 2 independent reviewers and data extracted using a standardised proforma. The quality and risk of bias of individual studies will be assessed using the Quality in Prognostic Studies (QUIPS) tool. A narrative synthesis of all evidence will be performed with key findings tabulated. Meta-analysis will be considered where studies and reported outcomes are considered sufficiently homogeneous, both clinically and methodologically. Findings will be interpreted in the context of the quality of included studies. The systematic review will be reported according to PRISMA guidelines. Ethics and dissemination This is a systematic review of completed studies and no ethical approval is required. Findings from the full systematic review will be submitted for publication and presentation at national and international conferences which will inform future research on risk stratification in patients with BO. Review registration number CRD42016038654.

The impact of the acute respiratory distress syndrome on outcome after oesophagectomy

BACKGROUND The Acute Respiratory Distress Syndrome (ARDS) is a serious complication of major surgery and consumes substantial healthcare resources. Oesophagectomy is associated with high rates of ARDS. The aim of this study was to characterize patients and identify risk factors for developing ARDS after oesophagectomy. METHODS A secondary analysis of data from 331 patients gathered during the Beta Agonists Lung Injury Prevention Trial was undertaken. Characteristics and outcomes of patients with early (first 72 h postoperatively) and late (after 72 h) ARDS were determined. Linear and multivariate regression analysis was used to study the differences between early and late ARDS and identify risk factors. RESULTS ARDS was associated with more non-respiratory organ failure (early 44.1%, late 75.0%, no ARDS 27.6% P<0.001), longer ICU stay (mean early 12.1, late 20.2, no ARDS 7.3 days P<0.001) and longer hospital stay (mean early 18.1, late 24.5, no ARDS 14.2 days P<0.001) but no difference in mortality or quality of life. Older patients (OR 1.06 (1.00 to 1.13), P=0.045) and those with mid-oesophageal tumours (OR 7.48 (1.62-34.5), P=0.010) had a higher risk for ARDS. CONCLUSIONS Early and late ARDS after oesophagectomy increases intensive care and hospital length of stay. Given the high incidence of ARDS, cohorts of patients undergoing oesophagectomy may be useful as models for studies investigating ARDS prevention and treatment. Further investigations aimed at reducing perioperative ARDS are warranted.

A comparative study of the iron status of patients with oesophageal adenocarcinoma to determine suitability for a clinical trial of iron chelation therapy

INTRODUCTION The incidence of oesophageal adenocarcinoma (OAC) is rising dramatically and overall survival remains extremely poor. Iron has been shown to potentiate tumourigenesis in OAC, and iron chelation therapy demonstrates promise in vivo as an adjunct to neoadjuvant and palliative chemotherapy. OAC, however, has traditionally been associated with iron deficiency anaemia. The aim of this study was therefore to formally quantify the iron status of OAC patients in order to guide the design of future clinical trials involving iron chelation therapy. METHODS Demographic and cancer specific data were collected prospectively from all patients presenting with OAC and gastric adenocarcinoma (GAC). Patients had haemoglobin, serum iron, serum ferritin and serum transferrin receptor (sTfR) levels measured to assess systemic iron status. In addition, the sTfR/log ferritin (sTfR-F) index was calculated. RESULTS Average haemoglobin, serum iron, serum ferritin, sTfR and sTfR-F index values for all patients presenting with OAC were within normal sex specific reference ranges. No statistical difference in iron status was observed between OAC patients presenting with resectable and advanced OAC. Patients with OAC are relatively iron replete compared with those presenting with GAC. Iron parameters were not significantly altered by standard neoadjuvant chemotherapy. CONCLUSIONS Patients presenting with resectable or advanced OAC could be considered as candidates for a clinical trial of iron chelation therapy as an addition to standard neoadjuvant or palliative treatments.

An alternative option in the management of blunt splenic injury

Splenic injury is a preventable cause of mortality following blunt trauma. The majority of splenic injuries can be managed conservatively. Laparotomy is indicated in the haemodynamically unstable patient, or those with other intra-abdominal injuries requiring surgery. Angio-embolization can be used to achieve haemostasis and preserve splenic parenchyma. The expertise and experience of the multidisciplinary trauma team and resources of the receiving facility are critical in determining the optimal management approach. We present a patient with a successful outcome following selective angio-embolization for ongoing bleeding from a Grade 4 splenic injury.

A systematic review of epigenetic biomarkers in progression from non-dysplastic Barrett’s oesophagus to oesophageal adenocarcinoma

Objectives The objective of this systematic review is to identify and summarise studies which examine epigenetic biomarkers in patients with Barrett’s oesophagus (BO) and their association with progression to oesophageal adenocarcinoma (OADC). BO is a precursor lesion for OADC. There is no clinical test to predict patients who are likely to progress to OADC. An epigenetic biomarker could predict patients who are at high risk of progression from BO to OADC which could facilitate earlier diagnosis and spare those unlikely to develop cancer from regular invasive surveillance endoscopy. Setting A systematic search was conducted of the following databases: MEDLINE, MEDLINE in Process, EMBASE, Cochrane Central, ISI Conference Proceedings Citation Index and the British Library’s ZETOC. Studies were conducted in secondary and tertiary care settings. Participants All studies measuring epigenetic change in patients over 18 years old who progressed from non-dysplastic BO to OADC were included. Genetic, in vitro and studies which did not measure progression in the same patient cohort were excluded. Study inclusion and risk of bias of individual eligible studies were assessed in duplicate by two reviewers using a modified Quality in Prognostic Studies tool. Results 14 studies met the inclusion criteria. 42 epigenetic markers were identified, and 5 studies developed models aiming to predict progression to OADC. Conclusions The evidence from this systematic review is suggestive of a role for p16 as an epigenetic biomarker for the progression of BO to OADC. Prospero number CRD42016038654.

ARDS following oesophagectomy: a comparison of two trials

Introduction The Beta Agonist Lung Injury Trial-Prevention (BALTI-P) translational substudy and Vitamin D to Prevent Acute Lung Injury Following Oesophagectomy (VINDALOO) trials recruited patients undergoing oesophagectomy, 4 years apart. The acute respiratory distress syndrome (ARDS) rates were lower in the VINDALOO trial. We sought to identify changes between these two trials and identify risk factors for ARDS in oesophagectomy. Methods There were data available from 61 patients in the BALTI-P substudy and 68 from VINDALOO. Databases were available for both trials; additional data were collected. Multivariate logistic regression was used to analyse risk factors for ARDS and postoperative complications in the cohorts combined. Results Logistic regression analysis showed active smoking was associated with an increase in ARDS (OR 3.91; 95% CI 1.33 to 11.5) and dihydropyridine use (OR 5.34;95% CI 1.56 to 18.3). Hospital length of stay was longer for those who took dihydropyridines (median 29 days (IQR 17–42) vs 13 days (IQR 10–18), P=0.0007) or were diabetic (median 25 days (IQR 14–39) vs 13 (IQR 10–19), P=0.023) but not for current smokers (median in never/ex-smokers 13 (IQR 10–23) vs current smokers 15 (IQR 11–20), P=0.73). Conclusions Smoking cessation trials should be promoted. Dihydropyridine effects perioperatively require further clinical and mechanistic evaluation. Patients undergoing oesophagectomy are a useful model for studying perioperative ARDS.

Potential cost savings by minimisation of blood sample delays on care decision making in urgent care services

Background Timely availability of blood sample results for interpretation affects planning and delivery of patient care from initial assessment in Accident and Emergency (A&E) departments. Materials and methods Rates of, and reasons for, rejected blood samples submitted from all clinical areas over one month were evaluated. Haemoglobin (Hb) represented haematology and potassium (K+), biochemistry. A prospective observational study evaluated the methodology of sample collection and impact on utility. Results 16,061 haematology and 16,209 biochemistry samples were evaluated; 1.4% (n = 229, range 0.5–7.3%) and 4.7% (n = 762, range 0.9–14%) respectively were rejected, with 14% (n = 248/1808) K+ rejection rate in A&E. Patients with rejected K+ and Hb had a longer median in-hospital stay of 9 and 76 h respectively and additional stay fixed costs of £26,824.74 excluding treatment. The rejection rate with Vacutainer and butterfly (4.0%) was lower than Vacutainer and cannula (28%). Conclusion Sample rejection rate is high and is associated with increased in-hospital stay and cost. Blood sampling technique impacts on rejection rates. Reduction in sample rejection rates in emergency care areas in acute hospitals has the potential to impact on patient flow and reduce cost.