Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include
infection, family history of gastric cancer-in particular, hereditary diffuse gastric ...cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met.
Background and Aims Barrett’s esophagus (BE) surveillance with random biopsies is time-consuming, invasive, and can lead to sampling error. Acetic acid chromoendoscopy (AAC) with targeted biopsies ...has been proposed as an effective alternative. The aim of this study was to assess the diagnostic accuracy of AAC for the detection of early neoplasia (high-grade dysplasia HGD or early cancer EC) and specialized intestinal metaplasia (SIM) in patients with BE. Methods We performed a meta-analysis of all primary studies that compared AAC-based diagnoses (index test) with histopathology as the reference standard. The data were extracted on a per-patient, per-area, and per-procedure basis whenever available. Results Thirteen prospective studies met the inclusion criteria. For the diagnosis of HGD/EC, the pooled sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR−) for all included studies (9 studies, 1379 patients) were 0.92 (95% confidence interval CI, 0.83-0.97), 0.96 (95% CI, 0.85-0.99), 25.0 (95% CI, 5.9-105.3), and 0.08 (95% CI, 0.04-0.18), respectively. Results were not significantly different when considering only studies with a per-patient analysis. For the characterization of SIM, the pooled sensitivity, specificity, LR+, and LR− for all the included studies (8 studies, 516 patients) were 0.96 (95% CI, 0.83-0.99), 0.69 (95% CI, 0.54-0.81), 3.0 (95% CI, 2.0-4.7), and 0.06 (95% CI, 0.01-0.26), respectively. No significant sources of heterogeneity were identified on subgroup analysis. Conclusion AAC has an overall high diagnostic accuracy for detecting HGD/EC in patients with BE. For SIM characterization, AAC sensitivity is very high but has poor specificity, suggesting that histological confirmation is necessary when AAC is positive.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Some studies suggest that narrow-band imaging (NBI) can be more accurate at diagnosing gastric intestinal metaplasia and dysplasia than white-light endoscopy (WLE) alone. We aimed to assess the ...real-time diagnostic validity of high resolution endoscopy with and without NBI in the diagnosis of gastric premalignant conditions and to derive a classification for endoscopic grading of gastric intestinal metaplasia (EGGIM).
A multicenter prospective study (five centers: Portugal, Italy, Romania, UK, USA) was performed involving the systematic use of high resolution gastroscopes with image registry with and without NBI in a centralized informatics platform (available online). All users used the same NBI classification. Histologic result was considered the diagnostic gold standard.
A total of 238 patients and 1123 endoscopic biopsies were included. NBI globally increased diagnostic accuracy by 11 percentage points (NBI 94 % vs. WLE 83 %; P < 0.001) with no difference in the identification of Helicobacter pylori gastritis (73 % vs. 74 %). NBI increased sensitivity for the diagnosis of intestinal metaplasia significantly (87 % vs. 53 %; P < 0.001) and for the diagnosis of dysplasia (92 % vs. 74 %). The added benefit of NBI in terms of diagnostic accuracy was greater in OLGIM III/IV than in OLGIM I/II (25 percentage points vs. 15 percentage points, respectively; P < 0.001). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for EGGIM in the identification of extensive metaplasia was 0.98.
In a real-time scenario, NBI demonstrates a high concordance with gastric histology, superior to WLE. Diagnostic accuracy higher than 90 % suggests that routine use of NBI allows targeted instead of random biopsy samples. EGGIM also permits immediate grading of intestinal metaplasia without biopsies and merits further investigation.
Barrett's esophagus (BE) is a commonly undiagnosed condition that predisposes to esophageal adenocarcinoma. Routine endoscopic screening for BE is not recommended because of the burden this would ...impose on the health care system. The objective of this study was to determine whether a novel approach using a minimally invasive cell sampling device, the Cytosponge, coupled with immunohistochemical staining for the biomarker Trefoil Factor 3 (TFF3), could be used to identify patients who warrant endoscopy to diagnose BE.
A case-control study was performed across 11 UK hospitals between July 2011 and December 2013. In total, 1,110 individuals comprising 463 controls with dyspepsia and reflux symptoms and 647 BE cases swallowed a Cytosponge prior to endoscopy. The primary outcome measures were to evaluate the safety, acceptability, and accuracy of the Cytosponge-TFF3 test compared with endoscopy and biopsy. In all, 1,042 (93.9%) patients successfully swallowed the Cytosponge, and no serious adverse events were attributed to the device. The Cytosponge was rated favorably, using a visual analogue scale, compared with endoscopy (p < 0.001), and patients who were not sedated for endoscopy were more likely to rate the Cytosponge higher than endoscopy (Mann-Whitney test, p < 0.001). The overall sensitivity of the test was 79.9% (95% CI 76.4%-83.0%), increasing to 87.2% (95% CI 83.0%-90.6%) for patients with ≥3 cm of circumferential BE, known to confer a higher cancer risk. The sensitivity increased to 89.7% (95% CI 82.3%-94.8%) in 107 patients who swallowed the device twice during the study course. There was no loss of sensitivity in patients with dysplasia. The specificity for diagnosing BE was 92.4% (95% CI 89.5%-94.7%). The case-control design of the study means that the results are not generalizable to a primary care population. Another limitation is that the acceptability data were limited to a single measure.
The Cytosponge-TFF3 test is safe and acceptable, and has accuracy comparable to other screening tests. This test may be a simple and inexpensive approach to identify patients with reflux symptoms who warrant endoscopy to diagnose BE.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Minimally invasive tests for Barrett's esophagus (BE) detection have raised the prospect of broader nonreflux-based testing. Cost-effectiveness studies have largely studied men aged 50 years with ...chronic gastroesophageal reflux disease (GERD) symptoms. We evaluated the comparative cost effectiveness of BE screening tests in GERD-based and GERD-independent testing scenarios.
Markov modeling was performed in 3 scenarios in 50 years old individuals: (i) White men with chronic GERD (GERD-based); (ii) GERD-independent (all races, men and women), BE prevalence 1.6%; and (iii) GERD-independent, BE prevalence 5%. The simulation compared multiple screening strategies with no screening: sedated endoscopy (sEGD), transnasal endoscopy, swallowable esophageal cell collection devices with biomarkers, and exhaled volatile organic compounds. A hypothetical cohort of 500,000 individuals followed for 40 years using a willingness to pay threshold of $100,000 per quality-adjusted life year (QALY) was simulated. Incremental cost-effectiveness ratios (ICERs) comparing each strategy with no screening and comparing screening strategies with each other were calculated.
In both GERD-independent scenarios, most non-sEGD BE screening tests were cost effective. Swallowable esophageal cell collection devices with biomarkers were cost effective (<$35,000/QALY) and were the optimal screening tests in all scenarios. Exhaled volatile organic compounds had the highest ICERs in all scenarios. ICERs were low (<$25,000/QALY) for all tests in the GERD-based scenario, and all non-sEGD tests dominated no screening. ICERs were sensitive to BE prevalence and test costs.
Minimally invasive nonendoscopic tests may make GERD-independent BE screening cost effective. Participation rates for these strategies need to be studied.
Endoscopic treatment of Barrett's oesophagus often leads to further damage of healthy tissue causing fibrotic tissue formation termed as strictures. This study shows that synthetic, self‐assembling ...peptide hydrogels (PeptiGelDesign) support the activity and function of primary oesophageal cells, leading to epithelialization and stratification during in vitro 3D co‐culture. Following buffering in culture media, rat oesophageal stromal fibroblasts (rOSFs) are incorporated into a library of peptide hydrogels, whereas mouse oesophageal epithelial cells (mOECs) are seeded on the surface. Optimal hydrogels (PGD‐AlphaProC and PGD‐CGD2) support mOEC viability (>95%), typical cell morphology (cobblestone‐like), and slower migration over a shorter distance compared to a collagen control, at 48 h. Positive expression of typical epithelial markers (ZO‐1 and cytokeratins) is detected using immunocytochemistry at day 3 in culture. Furthermore, optimal hydrogels are identified which support rOSF viability (>95%) with homogeneous distribution when incorporated into the hydrogels and also promote the secretion of collagen type I detected using an enzyme linked immunosorbent assay (ELISA), at day 7. A 3D co‐culture model using optimal hydrogels for both cell types supports a stratified epithelial layer (expressing involucrin and AE1/AE3 markers). Findings from this study could lead to the use of peptide hydrogels as a minimally invasive endoscopic therapy to manage oesophageal strictures.
Synthetic, peptide hydrogels support the activity and function of primary oesophageal epithelial cells and stromal fibroblasts during in vitro 3D co‐culture. Epithelial markers were positively detected (at day 3) as well as the secretion of collagen I by stromal fibroblasts (day 7 and 14). Peptide hydrogels can be delivered endoscopically to manage oesophageal strictures.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We examined the accuracy of narrow-band imaging (NBI) findings in nonerosive reflux disease (NERD) patients compared with control subjects and the impact of proton pump inhibitor (PPI) therapy on ...these mucosal changes in a multicenter, double-blind, randomized controlled trial.
NERD patients (typical symptoms using a validated GERD questionnaire, absence of erosive esophagitis, and abnormal 48-hour pH study) and control subjects underwent high-definition white-light endoscopy followed by NBI and biopsy sampling of the distal esophagus. Then, NERD patients were randomized to esomeprazole 40 mg/day or placebo for 8 weeks, followed by repeat endoscopy. The presence of distal esophageal mucosal changes on NBI were recorded at baseline and after treatment: intrapapillary capillary loops (IPCLs; number, dilation, and tortuosity), microerosions, increased vascularity, columnar islands, and ridge/villous pattern (RVP) above the squamocolumnar junction.
Of 122 screened, 21 NERD and 21 control subjects were identified (mean age, 49.5 ± 14.6 years; 62% men; and 85% white). The combination of IPCL tortuosity, RVP, and microerosions (62% vs 19%, P < .05) had a high specificity (86%) and moderate sensitivity (60%) for NERD with an area under the curve of .74. In 10 NERD patients treated with PPIs, resolution of microerosions was most significant (P = .047) compared with placebo (n = 11). RVP resolved in all NERD patients after therapy (P = .02) and correlated with acid exposure time (P = .004). Papillary length (P = .02) and basal cell thickness (P = .02) significantly correlated with a combination of IPCL tortuosity, RVP, and microerosions.
In this randomized controlled trial, RVP on NBI demonstrated a high specificity, correlated with acid exposure time, and improved with PPI therapy, suggesting that it could be used as a surrogate marker for diagnosis of NERD. (Clinical trial registration number: NCT02081404.)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma and current practice is to establish endoscopic surveillance once diagnosed, in order to identify early dysplasia and neoplasia ...that has the potential to undergo endoscopic eradication therapy (EET). Before embarking upon EET the clinical team has a duty to consider all viable options and come to a plan based on recent evidence. The therapeutic approach varies greatly but largely adheres to the mantra of ‘Detect–Resect–Ablate’, in which high‐quality endoscopy identifies BE associated pathology, associated lesions (if present) undergo safe endoscopic resection and remaining intestinal metaplasia in the esophagus is ablated to prevent recurrence of dysplasia. In this review, current practice, pitfalls, complications, and the future perspectives on practice in this field are discussed. The Western perspective is focused on here, with an outline of the differences in clinical practice with Asian nations and attempts to bridge these differences.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
In ulcerative colitis surveillance, chromoendoscopy improves dysplasia detection 3 – 5-fold compared with white light endoscopy (WLE). The aim of this study was to investigate whether narrow band ...imaging (NBI) can improve dysplasia detection compared with WLE.
This was a randomized, parallel-group trial. A total of 220 patients were needed to be recruited to detect a threefold increase in dysplasia detection. In all, 112 patients with long-standing ulcerative colitis were randomized to colonoscopic extubation with NBI (56) or WLE (56) (1:1 ratio) at two tertiary endoscopy units in the United Kingdom. Targeted biopsies of suspicious areas and quadrantic random biopsies every 10 cm were taken in both groups. The primary outcome measure was the proportion of patients with at least one area of dysplasia detected. In a prespecified mid-point analysis, the criteria for trial discontinuation were met and the trial was stopped and analyzed at this point.
There was no difference in the primary outcome between the two groups, with 5 patients having at least one dysplastic lesion in each group (odds ratio (OR) 1.00, 95 % confidence interval (95 % CI) 0.27 – 3.67, P = 1.00). This remained unchanged when adjusted for other variables (OR 0.69, 95 % CI 0.16 – 2.96, P = 0.62). Overall, dysplasia detection was 9 % in each arm. Yield of dysplasia from random nontargeted biopsies was 1 / 2,707 (0.04 % ).
Overall, in this multicenter parallel-group trial, there was no difference in dysplasia detection when using NBI compared with high-definition WLE colonoscopy. Random background biopsies were ineffective in detecting dysplasia.
The first commercial artificial intelligence system in endoscopy called EndoBRAIN, which was developed in collaboration with academic endoscopists from Showa University Northern Yokohama Hospital ...(Yokohama, Japan), was recently launched on March 4, 2019, by Olympus.1 This software allows for artificial intelligence-assisted differentiation of neoplastic and non-neoplastic colon polyps during real-time colonoscopy.2 Artificial intelligence is here to stay; however, it is important that endoscopists and clinicians have in-depth understanding of its application and limitations in modern endoscopy. ...in the real world, clinicians rely on good quality, high-definition white light endoscopy for routine endoscopy. There is a lot of excitement in the medical community; however, uncertainty and anxiety about artificial intelligence in medicine is also evident.5 A global unified approach is necessary for the development of such artificial intelligence systems develop and validate artificial intelligence platforms, so that all ethnicities and pathologies are represented and tested.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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