Neel Sharma

Raman Spectroscopy for the Endoscopic Diagnosis of Esophageal, Gastric, and Colonic Diseases.

Globally white-light endoscopy with biopsy sampling is the gold standard diagnostic modality for esophageal, gastric, and colonic pathologies. However, there is overwhelming evidence to highlight the deficiencies of an approach based predominantly on eyeball visualization. Biopsy sampling is also problematic due in part to excessive sampling and hence attendant cost. Various innovations are currently taking place in the endoscopic domain to aid operators in diagnosis forming. These include narrow band imaging which aims to enhance the surface anatomy and vasculature, and confocal laser endomicroscopy which provides real time histological information. However, both of these tools are limited by the skill of the operator and the extensive learning curve associated with their use. There is a gap therefore for a new form of technology that relies solely on an objective measure of disease and reduces the need for biopsy sampling. Raman spectroscopy (RS) is a potential platform that aims to satisfy these criteria. It enables a fingerprint capture of tissue in relation to the protein, DNA, and lipid content. This focused review highlights the strong potential for the use of RS during endoscopic gastroenterological examination.

CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer

Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro. The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro, a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach.

CEACAM 6, a novel marker for the diagnosis of Barrett's esophagus

Barretts esophagus (BE) is a premalignant condition associated with the development of esophageal adenocarcinoma (EAC). Despite the low risk of progression to EAC, evidence highlights the notably poor survival rates of this malignancy. The mainstay form of diagnosis of BE is endoscopy and biopsy sampling. However, research emphasizes limitations with regards to the histological detection of BE and associated dysplasia. The aim of this study is to evaluate the clinical significance of CEACAM6 as a potential biomarker for the diagnosis of BE and beyond. Retrospective tissue samples were obtained from columnar lined esophagus without goblet cells (n = 27), BE (n = 18), BE associated dysplasia (n = 16), and EAC (n = 24). Standardized immunohistochemistry for CEACAM6 was performed followed by quantitative staining analysis. Statistical analysis across the BE spectrum for CEACAM6 was undertaken and a P value <0.05 was considered significant. CEACAM6 expression increased from columnar lined epithelium (CLE) to BE with a subsequent decrease to dysplasia and adenocarcinoma. The expression of CEACAM6 was significant from CLE to BE at p 0.001, CLE to dysplasia at p 0.001, BE to dysplasia at p 0.006, CLE to adenocarcinoma at p 0.001 and BE to adenocarcinoma at p 0.001. There was no significant difference in expression between dysplasia and adenocarcinoma (P = 0.15). Our findings highlight the increasing expression of CEACAM6 from CLE to BE with a subsequent decrease to dysplasia and adenocarcinoma. In view of this, we advocate the utilization of this marker for the enhanced diagnosis of BE and for the distinction of BE and dysplasia.

Endoscopic modalities for the diagnosis of Barrett’s oesophagus

Barrett’s oesophagus is a pre-malignant condition associated with the development of oesophageal adenocarcinoma. Currently white light endoscopy and biopsy is the mainstay diagnostic tool. Yet this approach is troubled by issues related to cumbersome biopsy sampling, biopsy sampling errors and cost. Therefore in order to overcome such adversity, there needs to be evolutionary advancement in terms of diagnosis, which should address these concerns and ideally enhance risk stratification in order to provide timely management in real time. This review highlights the current endoscopic tools aimed to enhance the diagnosis of Barrett’s oesophagus and its subsequent progression.

FABP1 and Hepar expression levels in Barrett’s esophagus and associated neoplasia in an Asian population

INTRODUCTION Barretts esophagus (BE) is a premalignant condition associated with esophageal adenocarcinoma (EAC). Evidence highlights that EAC is associated with an estimated 5-year survival of approximately 10-15%. Therefore, there is a need to determine which biomarkers are of value in the diagnosis of BE and beyond. The aim of our study was to evaluate the clinical significance of markers known to be expressed across BE and associated neoplasia. METHODS Retrospective tissues were obtained from columnar lined esophagus (CLE) without goblet cells (n=22), BE (n=29), dysplasia (n=14), and EAC (n=10). Standardised immunohistochemistry for FABP1, Hepar, CDH17, and CDX2 were performed followed by quantitative staining and statistical analysis. RESULTS FABP1 expression was negligible in CLE and was highest in BE, with a further decrease in expression in dysplasia and EAC. Hepar expression was also negligible in CLE and was highest in dysplasia and BE, with a reduced expression in EAC. CDH17 and CDX2 showed a significantly higher expression in BE, dysplasia, and EAC compared to CLE. CONCLUSION All 4 markers were excellent diagnostic panels to clearly discriminate BE from CLE. Moreover, as FABP1 and Hepar have different expression levels in dysplasia and EAC, these markers could function as key diagnostic aids in helping to determine the state of disease progression.

Colonoscopy Procedure Time: Does the Learning Environment Matter?

Jain and colleagues pushed boundaries in their study by focusing on colonoscopy procedure time and the factors that may influence this. Two of these factors included the level of experience of the endoscopist and the time of day with procedures performed in the afternoon associated with poorer outcomes. As a medical educationalist and gastroenterologist, I want to share scholarship with the academic community regarding current movements allied to the learning environment. Research is now emerging on the learning space in question to enhance competency. Many case studies have indicated the value added in ensuring that the learning environment promotes appropriate engagement between learners and mentors, with workspaces that are technology specific to learning complimented with flipped learning approaches, team-based interactions, debriefing rooms, inter-professional discussions, writing spaces, and so on. This also has implications on the physical construct, with alterations in seating design to ensure this is optimized. The learning environment is a novel element to competency and, from a gastroenterologist’s perspective, is an often-overlooked facet. Research on the endoscopy center environment and its physicality may have relevance in endoscopy procedure performance and efficiency. Further work is needed in this regard.

Educating patients in IBD

Larsen et al. have highlighted their positive findings for the use of touch screens in the inflammatory bowel disease outpatient clinic.[1] With the advent of technology there is certainly value in the use of this platform in healthcare. I wanted to also share the potential of technology in educating patients in their disease. One such example is that of MOOCs or massive open online courses. MOOCs are educational courses available online delivered by experts in the field from high ranking university institutions. They have been praised for their ability to allow learners to access expert knowledge anytime anywhere 24/7 with the added benefit of accreditation and learner connectivity.[2] They also aim to provide instant feedback on areas where users are unsure and aim to assess learners on the knowledge gained with recognised accreditation. An example of MOOCs in an educational setting comes from the University of Birmingham and its focus on hepatology.[3] By gathering large quantities of data (big data) in this regard programmes can be refashioned and user-specific. There is therefore potential for the use of MOOCs in terms of patient care. Could MOOCs aim to educate patients in their condition not just by their specific home situated specialists but also by wider expert access? This could allow for greater patient involvement in their care. Often care is still unidirectional with specialists primarily instigating management. However, if patients were keen to obtain greater information free of cost MOOCs could provide such a potential. This could allow for greater cross-talk between doctor and patient in terms of long-term management options. With technology we of course can utilise this for our benefit as doctors but over the next few years we need to be able to provide technology to also benefit our patients.

Columnar lined Barrett's oesophagus

Over the past few years, the definition of Barretts oesophagus has altered with no real agreement on histological understanding. This article highlights the increasing confusion regarding Barretts oesophagus with a focus on the all-too-frequently ignored aspect of the columnar lined oesophagus.