Latest Advances in Endoscopic Detection of Oesophageal and Gastric Neoplasia.

Endoscopy is the gold standard for the diagnosis of cancers and cancer precursors in the oesophagus and stomach. Early detection of upper GI cancers requires high-quality endoscopy and awareness of the subtle features these lesions carry. Endoscopists performing surveillance of high-risk patients including those with Barrett's oesophagus, previous squamous neoplasia or chronic atrophic gastritis should be familiar with endoscopic features, classification systems and sampling techniques to maximise the detection of early cancer. In this article, we review the current approach to diagnosis of these conditions and the latest advanced imaging and diagnostic techniques.

Virtual chromoendoscopy by using optical enhancement improves the detection of Barrett's esophagus-associated neoplasia.

BACKGROUND AND AIMS: The Seattle protocol for endoscopic Barrett's esophagus (BE) surveillance samples a small portion of the mucosal surface area, risking a potentially high miss rate of early neoplastic lesions. We assessed whether the new iScan Optical Enhancement system (OE) improves the detection of early BE-associated neoplasia compared with high-definition white-light endoscopy (HD-WLE) in both expert and trainee endoscopists to target sampling of suspicious areas. Such a system may both improve early neoplasia detection and reduce the need for random biopsies. METHODS: A total of 41 patients undergoing endoscopic BE surveillance from January 2016 to November 2017 were recruited from 3 international referral centers. Matched still images in both HD-WLE (n = 130) and iScan OE (n = 132) were obtained from endoscopic examinations. Two experts, unblinded to the videos and histology, delineated known neoplasia, forming a consensus criterion standard. Seven expert and 7 trainee endoscopists marked 1 position per image where they would expect a target biopsy to identify dysplastic tissue. The same expert panel then reviewed magnification images and, using a previously validated classification system, attempted to classify mucosa as dysplastic or nondysplastic, based on the mucosal and vascular (MV) patterns observed on magnification endoscopy. Diagnostic accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated. Improvements in dysplasia detection in HD-WLE versus OE and interobserver agreement were assessed by multilevel logistic regression analysis and Krippendorff alpha, respectively. Improvements in diagnostic performance were expressed as an odds ratio between the odds of improvement in OE compared with the odds of improvement in HD-WLE. RESULTS: Accuracy of neoplasia detection was significantly higher in all trainees who used OE versus HD-WLE (76% vs 63%) and in 6 experts (84% vs 77%). OE improved sensitivity of dysplasia detection compared with HD-WLE in 6 trainees (81% vs 71%) and 5 experts (77% vs 67%). Specificity improved in 6 trainees who used OE versus HD-WLE (70% vs 55%) and in 5 experts (92% vs 86%). PPV improved in both an expert and trainee cohort, but NPV improved significantly only in trainees. By using the MV classification and OE magnification endoscopy compared with HD-WLE, we demonstrated improvements in accuracy (79.9% vs 66.7%), sensitivity (86.3% vs 83.4%), and specificity (71.2% vs 53.6%) of dysplasia detection. PPV improved (62%-76.6%), as did NPV (67.7%-78.5%). Interobserver agreement also improved by using OE from 0.30 to 0.55. CONCLUSION: iScan OE may improve dysplasia detection on endoscopic imaging of BE as well as the accuracy of histology prediction compared with HD-WLE, when OE magnification endoscopy is used in conjunction with a simple classification system by both expert and non-expert endoscopists.

Machine Learning Creates a Simple Endoscopic Classification System that Improves Dysplasia Detection in Barrett's Oesophagus amongst Non-expert Endoscopists.

INTRODUCTION: Barrett's oesophagus (BE) is a precursor to oesophageal adenocarcinoma (OAC). Endoscopic surveillance is performed to detect dysplasia arising in BE as it is likely to be amenable to curative treatment. At present, there are no guidelines on who should perform surveillance endoscopy in BE. Machine learning (ML) is a branch of artificial intelligence (AI) that generates simple rules, known as decision trees (DTs). We hypothesised that a DT generated from recognised expert endoscopists could be used to improve dysplasia detection in non-expert endoscopists. To our knowledge, ML has never been applied in this manner. METHODS: Video recordings were collected from patients with non-dysplastic (ND-BE) and dysplastic Barrett's oesophagus (D-BE) undergoing high-definition endoscopy with i-Scan enhancement (PENTAX®). A strict protocol was used to record areas of interest after which a corresponding biopsy was taken to confirm the histological diagnosis. In a blinded manner, videos were shown to 3 experts who were asked to interpret them based on their mucosal and microvasculature patterns and presence of nodularity and ulceration as well as overall suspected diagnosis. Data generated were entered into the WEKA package to construct a DT for dysplasia prediction. Non-expert endoscopists (gastroenterology specialist registrars in training with variable experience and undergraduate medical students with no experience) were asked to score these same videos both before and after web-based training using the DT constructed from the expert opinion. Accuracy, sensitivity, and specificity values were calculated before and after training where p < 0.05 was statistically significant. RESULTS: Videos from 40 patients were collected including 12 both before and after acetic acid (ACA) application. Experts' average accuracy for dysplasia prediction was 88%. When experts' answers were entered into a DT, the resultant decision model had a 92% accuracy with a mean sensitivity and specificity of 97% and 88%, respectively. Addition of ACA did not improve dysplasia detection. Untrained medical students tended to have a high sensitivity but poor specificity as they "overcalled" normal areas. Gastroenterology trainees did the opposite with overall low sensitivity but high specificity. Detection improved significantly and accuracy rose in both groups after formal web-based training although it did it reach the accuracy generated by experts. For trainees, sensitivity rose significantly from 71% to 83% with minimal loss of specificity. Specificity rose sharply in students from 31% to 49% with no loss of sensitivity. CONCLUSION: ML is able to define rules learnt from expert opinion. These generate a simple algorithm to accurately predict dysplasia. Once taught to non-experts, the algorithm significantly improves their rate of dysplasia detection. This opens the door to standardised training and assessment of competence for those who perform endoscopy in BE. It may shorten the learning curve and might also be used to compare competence of trainees with recognised experts as part of their accreditation process.

Systematic assessment with I-SCAN magnification endoscopy and acetic acid improves dysplasia detection in patients with Barrett's esophagus.

Background and study aims Enhanced endoscopic imaging with chromoendoscopy may improve dysplasia recognition in patients undergoing assessment of Barrett's esophagus (BE). This may reduce the need for random biopsies to detect more dysplasia. The aim of this study was to assess the effect of magnification endoscopy with I-SCAN (Pentax, Tokyo, Japan) and acetic acid (ACA) on dysplasia detection in BE using a novel mucosal and vascular classification system. Methods BE segments and suspicious lesions were recorded with high definition white-light and magnification endoscopy enhanced using all I-SCAN modes in combination. We created a novel mucosal and vascular classification system based on similar previously validated classifications for narrow-band imaging (NBI). A total of 27 videos were rated before and after ACA application. Following validation, a further 20 patients had their full endoscopies recorded and analyzed to model use of the system to detect dysplasia in a routine clinical scenario. Results The accuracy of the I-SCAN classification system for BE dysplasia improved with I-SCAN magnification from 69 % to 79 % post-ACA (P = 0.01). In the routine clinical scenario model in 20 new patients, accuracy of dysplasia detection increased from 76 % using a "pull-through" alone to 83 % when ACA and magnification endoscopy were combined (P = 0.047). Overall interobserver agreement between experts for dysplasia detection was substantial (0.69). Conclusions A new I-SCAN classification system for BE was validated against similar systems for NBI with similar outcomes. When used in combination with magnification and ACA, the classification detected BE dysplasia in clinical practice with good accuracy.Trials registered at ISRCTN (58235785).

Comparing outcome of radiofrequency ablation in Barrett's with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry.

BACKGROUND AND STUDY AIM: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01). CONCLUSION: The Registry reports on endoscopic therapy for Barrett's neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.

Advances in upper gastrointestinal endoscopy.

The rapidly moving technological advances in gastrointestinal endoscopy have enhanced an endoscopist's ability to diagnose and treat lesions within the gastrointestinal tract. The improvement in image quality created by the advent of high-definition and magnification endoscopy, alongside image enhancement, produces images of superb quality and detail that empower the endoscopist to identify important lesions that have previously been undetectable. Additionally, we are now seeing technologies emerge, such as optical coherence tomography and confocal laser endomicroscopy, that allow the endoscopist to visualize individual cells on a microscopic level and provide a real time, in vivo histological assessment. Within this article we discuss these technologies, as well as some of the results from their early use in clinical studies.

Radiofrequency ablation and endoscopic mucosal resection for dysplastic barrett's esophagus and early esophageal adenocarcinoma: outcomes of the UK National Halo RFA Registry.

BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or early neoplasia increasingly receive endoscopic mucosal resection and radiofrequency ablation (RFA) therapy. We analyzed data from a UK registry that follows the outcomes of patients with BE who have undergone RFA for neoplasia. METHODS: We collected data on 335 patients with BE and neoplasia (72% with HGD, 24% with intramucosal cancer, 4% with low-grade dysplasia [mean age, 69 years; 81% male]), treated at 19 centers in the United Kingdom from July 2008 through August 2012. Mean length of BE segments was 5.8 cm (range, 1-20 cm). Patients' nodules were removed by endoscopic mucosal resection, and the patients then underwent RFA every 3 months until all areas of BE were ablated or cancer developed. Biopsies were collected 12 months after the first RFA; clearance of HGD, dysplasia, and BE were assessed. RESULTS: HGD was cleared from 86% of patients, all dysplasia from 81%, and BE from 62% at the 12-month time point, after a mean of 2.5 (range, 2-6) RFA procedures. Complete reversal dysplasia was 15% less likely for every 1-cm increment in BE length (odds ratio = 1.156; SE = 0.048; 95% confidence interval: 1.07-1.26; P < .001). Endoscopic mucosal resection before RFA did not provide any benefit. Invasive cancer developed in 10 patients (3%) by the 12-month time point and disease had progressed in 17 patients (5.1%) after a median follow-up time of 19 months. Symptomatic strictures developed in 9% of patients and were treated by endoscopic dilatation. Nineteen months after therapy began, 94% of patients remained clear of dysplasia. CONCLUSIONS: We analyzed data from a large series of patients in the United Kingdom who underwent RFA for BE-related neoplasia and found that by 12 months after treatment, dysplasia was cleared from 81%. Shorter segments of BE respond better to RFA; http://www.controlled-trials.com, number ISRCTN93069556.

High resolution colonoscopy in a bowel cancer screening program improves polyp detection.

AIM: To compare high resolution colonoscopy (Olympus Lucera) with a megapixel high resolution system (Pentax HiLine) as an in-service evaluation. METHODS: Polyp detection rates and measures of performance were collected for 269 colonoscopy procedures. Five colonoscopists conducted the study over a three month period, as part of the United Kingdom bowel cancer screening program. RESULTS: There were no differences in procedure duration (χ² P = 0.98), caecal intubation rates (χ² P = 0.67), or depth of sedation (χ² P = 0.64). Mild discomfort was more common in the Pentax group (χ² P = 0.036). Adenoma detection rate was significantly higher in the Pentax group (χ² test for trend P = 0.01). Most of the extra polyps detected were flat or sessile adenomas. CONCLUSION: Megapixel definition colonoscopes improve adenoma detection without compromising other measures of endoscope performance. Increased polyp detection rates may improve future outcomes in bowel cancer screening programs.

Pharmacological management of diarrhea.

According to the World Health Organization, there are approximately 2 billion annual cases of diarrhea worldwide. Diarrhea is the leading cause of death in children younger than 5 years and kills 1.5 million children each year. It is especially prevalent in the developing world, where mortality is related to dehydration, electrolyte disturbance, and the resultant acidosis, and in 2001, it accounted for 1.78 million deaths (3.7% of total deaths) in low- and middle-income countries. However, diarrhea is also a common problem in the developed world, with 211 million to 375 million episodes of infectious diarrheal illnesses in the United States annually, resulting in 73 million physician consultations, 1.8 million hospitalizations, and 3100 deaths. Furthermore, 4% to 5% of the Western population suffers from chronic diarrhea. Given the high prevalence of diarrhea, research has been directed at learning more about the cellular mechanisms underlying diarrheal illnesses in order to develop new medications directed at novel cellular targets. These cellular mechanisms and targets are discussed in this article.

Antisecretory actions of a novel vasoactive intestinal polypeptide (VIP) antagonist in human and rat small intestine.

Vasoactive intestinal peptide (VIP) has been demonstrated in intestinal mucosal neurones and elicits chloride secretion from enterocytes. These findings have led to the proposal that VIP is a secretomotor neurotransmitter. Confirmation of such a role may now be possible with the development of PG 97-269, a high-affinity, selective antagonist of VIP type 1 (VPAC1) receptor, which is expressed by gut epithelial cells. We have evaluated the VIP antagonism and antisecretory potential of this novel compound using in vitro and in vivo models of intestinal secretion. Monolayers of the human colonic cell line (T84) and muscle-stripped preparations of rat jejunum and human ileum were set up in Ussing chambers for recording of transepithelial resistance and short-circuit current. Ussing chambers were modified to allow electrical stimulation of mucosal neurones. Effects of PG 97-269 on enterotoxin-induced secretion were investigated in perfused rat jejunum in vivo. PG 97-269 competitively antagonised VIP in T84 monolayers. In rat jejunum and human ileum, responses to VIP were inhibited as were responses of rat jejunum to electrical stimulation of mucosal neurons. In perfused rat jejunum, PG 97-269 abolished the effects of VIP on fluid and electrolyte transport and attenuated cholera toxin and Escherichia coli heat labile toxin-induced net fluid and electrolyte secretion. PG 97-269 is a competitive antagonist of enterocyte VIP receptors and effectively inhibits responses of rat and human intestinal mucosa to VIP. Antagonism of secretory responses to electrical stimulation of mucosal neurons and lumenal application of enterotoxins imply a secretory role for VIP in these processes.

Fluid and electrolyte transport in the small intestine.

The small intestine is in a dynamic state of secretion and absorption, the sum of which results in net absorption. Secretion is principally the result of chloride and bicarbonate extrusion through apical chloride channels after the activation of the second messengers cAMP, cGMP, and calcium. In addition to the cystic fibrosis transmembrane conductance regulator, several other candidate chloride channels have been identified and proposed to play a role in intestinal secretion, including the calcium-dependent chloride channel hCLCA1. Pathways leading to the negative control of secretion have been described that use cellular messengers, including inositol (3,4,5,6) tetrakisphosphate and phosphatidylinositol 3-kinase, which may act via basolateral potassium channels. The control of ion transport can also be viewed in terms of the enteric nervous system. The reflex neural pathways involved in enterotoxin-induced secretion have been substantiated and shown to involve 5-hydroxytryptamine, substance P, and the neurokinin 1 and 2 receptors in the sensory arm, and vasoactive intestinal peptide in the secretomotor efferents. Absorption of glucose in addition to active cotransport with sodium via the Na/glucose cotransporter protein has also been shown to occur passively through a carrier-mediated mechanism, using the membrane protein glucose transporter protein 2.