Dr Sebastian Zeki is a consultant gastroenterologist at St Thomas’ Hospital in London. His research interests include upper gastrointestinal physiology, upper gastrointestinal cancer, natural language programming and quality metrics in endoscopy. He co-leads the Gastroenterology data sciences Institute in London
PhD - Genomics of Barrett's related malignancy, 2013
University of London
Member of the Royal College of Physician, 2006
MSc Health Informatics, 2003
MBBS MBChir Medicine, 2001
University College London
MA in experimental psychology, 1998
Barretts oesophagus represents the most significant risk factor for the development of oesophageal adenocarcinoma (OAC), although the majority of patients will not develop cancer. However, early detection of OAC and its precursors significantly improves outcome and underlines the importance of endoscopic surveillance programmes. Clearly there is a discrepancy between the small number of people who need to undergo surveillance because they are at significant progression risk, and the large number that do. Research is therefore now concentrated on risk stratification. Currently such stratification is currently based on clinical findings, endoscopic diagnosis and histopathological grade. Histopathology can be imperfect and is likely to require molecular confirmation of different grades, thus molecular stratification is becoming more important in this regard and p53 immunohistochemistry is already clinically useful, with other molecular biomarkers likely to prove beneficial in the future. The hope is that non-endoscopic methods, such as the Cytosponge may be able to combine molecular biomarkers with histopathology and therefore perhaps benefit a population screening as well as a surveillance programme.
OBJECTIVES: Radiofrequency ablation (RFA) is used to successfully eliminate Barrett’s esophagus (BE)-related dysplasia or intramucosal carcinoma and aims to cause reversion to squamous epithelium. However, in 20% of cases RFA fails to return the epithelium to squamous phenotype. Follow-up studies show a similar dysplasia recurrence rate. We hypothesize that failed RFA is due to clonally mutated epithelial populations harbored in RFA-privileged sites and that RFA can select for the mutant clonal expansionMETHODS:A longitudinal case series of 19 patients with BE and high-grade dysplasia or intramucosal carcinoma were studied. DNA was extracted from individual Barrett’s glands, deep esophageal glands within mucosal resections and biopsy specimens before and after RFA. Mutations were identified by targeted sequencing of genes commonly mutated in Barrett’s adenocarcinoma.RESULTS:Five patients demonstrated persistent post-RFA pathology with persistent mutations, sometimes detected in deep esophageal glands or neighboring squamous epithelium after several rounds of RFA preceded by mucosal resection. Recurrence of pathology in three other patients was characterized by de novo mutations.CONCLUSIONS:Protumorigenic mutations can be found in post-ablation squamous mucosa as well as in mutant deep esophageal glands; both are associated with dysplasia recurrence. Following RFA, non-dysplastic Barrett’s epithelium can contain mutant clones that are found in a subsequent adenocarcinoma. Ablation may also drive the clonal expansion of pre-existing clones after a “bottleneck” created by the RFA. Overall, recurrence of dysplasia post RFA reflects the multicentric origins of Barrett’s clones and highlights the role of clonal selection in carcinogenesis.
Medical data is increasingly kept in an electronic format worldwide (Bretthauer M. 2016).This serves many purposes including more efficient storage, distribution and accessibility of patient-focussed data. As important is the ability to analyse healthcare data for to optimize resource deployment and usage. The tools for the analysis are often statistical and rely on the provision of ‘clean’ datasets before this can be done. ‘Cleaning’ a dataset is often the most difficult aspect of any data analysis and involves the provision of meaningful and well-formatted data so that the interpretation of the analysis is not subject to the doubts of the data quality. The British Society of Gastroenterology recommends that all endoscopic data is kept in an electronic format particularly to facilitate audit and maintain standards through the Global Rating Scale (GRS) (Stebbing J. 2011). The endoscopic dataset is however only part of the patient’s story as many aspects of a patient’s gastroenterological care depend on the results of histopathological analysis of tissue taken during the examination. Pathology results are often available many days after the endoscopic result and usually stored in a separate data repository, although this may change with the arrival of an encompassing electronic patient record. Regardless of the method of storage, it is often difficult to associate the particular histopathological result with an endoscopic result. Further, even if the two data sets can be merged, a problem occurs in the isolation of various parts of each report such that each part can be individually analysed. Examples include the isolation of who the endoscopist was or the presence of dysplasia within a histopathology report. This is all the more difficult if the report is unstructured or partially structured free text. However if this can be done then many downstream analyses which benefit individual patients as well as the department, can be automated and include more complex analyses to determine follow-up regimes or endoscopic –pathologic lesion recognition performance. The EndoMineR package provides a comprehensive way to extract information from natural language endoscopy ann pathology reports as well as merging the two datasets so that pathology specimens are relevant to the endoscopy they came from. Furthermore the package also provides functions for the following types of analysis of endoscopic and pathological datasets: • 1. Patient surveillance. Examples including determining when patients should return for surveillance and who is overdue. • 2. Patient tracking. -Examples include determining the length of time since the last endoscopy, as well as aggregate functions such as finding how many endoscopies of a certain type have been done and predicting future burden.
Dietary intervention is effective for the management of eosinophilic oesophagitis (EoE) in both adults and children. The majority of research has been conducted in Spain or the United States, with no studies of dietary intervention published in the United Kingdom. Restrictive elimination diets can be challenging and swallowed topical corticosteroids have also been shown to be an effective treatment in adults. Despite their efficacy, disadvantages include risk of candidiasis,3 potential long‐term effects such as adrenal suppression3 and off‐label medication use. Proton pump inhibitors (PPIs) are effective for a proportion of patients although with both PPIs and corticosteroids, the underlying triggers of this presumed antigen‐mediated condition are not identified and continued use is required to maintain efficacy. A key aspect in the management of any allergic disease is avoidance of relevant allergens.Through a multidisciplinary collaboration between Adult Allergy, Gastroenterology, and Dietetics, we launched a service to provide dietary intervention for adults with EoE in a UK tertiary referral centre. We recently undertook a retrospective evaluation with the aim to describe the clinical phenotype of EoE in our service and to determine the clinico‐pathological response to dietary or medical interventions in this cohort (GSTT service evaluation 6195).