Detection Of Intestinal Metaplasia Research Articles

The importance of blood parameters in the detection of intestinal metaplasia and early diagnosis of gastric cancer

Background: We aimed to determine whether complete blood count(CBC) parameters, such as the white blood count(WBC), hemoglobin(Hb), platelet(PLT), red cell distribution width(RDW), mean platelet volume(MPV), platelet distribution width(PDW), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and monocyte-to-lymphocyte ratio(MLR), have a predictive value in the detection of gastric cancer(GC) and intestinal metaplasia(IM). Methods: While proven GC, IM, and healthy control(HC) patients were included, patients with the comorbid disease were excluded, and univariate analyses compared three groups. The receiver operating characteristic(ROC) curve analysis was run for CBC parameters. The area under the curve(AUC) was evaluated, and a cut-off value was determined. The sensitivity and specificity of each parameter were considered. Results: The GC, IM, and HC groups consisted of 72(33%), 73(34%), and 72(33%) patients, respectively. RDW, PLT, NLR, PLR, and MLR were significant between GC and IM. The highest AUC (0.727) was obtained for the PLT yielding a 56.9% sensitivity and 79.4% specificity at a cut-off value of 151.8. The AUC of RDW was found as 0.691 and 0.626 for pairwise comparisons of GC-HC and IM-HC, respectively. At a cut-off value of 13.4, PLR yielded 70.8% sensitivity and 61.1% specificity in the detection of GC, while 64.4% sensitivity and 51.1% specificity for IM. Conclusion: CBC parameters, such as RDW, PLT, NLR, PLR, and MLR, have value in detecting GC. RDW also has diagnostic value in helping to detect IM. PLR can help to distinguish patients with GC from those with IM. These inexpensive, easily accessible parameters may help in the timely diagnosis of GC and IM. Keywords: Gastric cancer; intestinal Metaplasia; Monocyte to lymphocyte ratio; red cell distribution; hemoglobin; platelet; neutrophil-lymphocyte ratio; platelet-lymphocyte ratio; inflammation.

Methylene blue chromoendoscopy is more useful in detection of intestinal metaplasia in the stomach than mucosal pit pattern or vessel evaluation and predicts advanced Operative Link on Gastric Intestinal Metaplasia stages

Intestinal metaplasia (IM) of the stomach is a precancerous condition that is often not visible during conventional endoscopy. Hence, we evaluated the utility of magnification endoscopy and methylene blue (MB) chromoendoscopy to detect IM. We estimated the percentage of gastric mucosa surface staining with MB, mucosal pit pattern, and vessel visibility and correlated it with the presence of IM and the percentage of metaplastic cells in histology, similar to the Operative Link on Gastric Intestinal Metaplasia (OLGIM) stage. IM was found in 25 of 33 (75.8%) patients and in 61 of 135 biopsies (45.2%). IM correlated with positive MB staining (p<0.001) and other than dot pit patterns (p=0.015). MB staining indicated IM with better accuracy than the pit pattern or vessel evaluation (71.7% vs. 60.5% and 49.6%, respectively). At a cut-off point of 16.5% for the MB-stained gastric surface, the sensitivity, specificity, and accuracy of chromoendoscopy in the detection of advanced OLGIM stages were 88.9%, 91.7%, and 90.9%, respectively. The percentage of metaplastic cells detected on histology was the strongest predictor of positive MB staining. MB chromoendoscopy can serve as a screening method for detecting advanced OLGIM stages. MB mainly stains IM areas with a high concentration of metaplastic cells.

Sa1144 – Wide Area Transepithelial Sampling Improves Detection of Intestinal Metaplasia and Dysplasia Following Endoscopic Ablation of Barrett's Esophagus

Sa1144 – Wide Area Transepithelial Sampling Improves Detection of Intestinal Metaplasia and Dysplasia Following Endoscopic Ablation of Barrett's Esophagus

Detection of Intestinal Metaplasia among Sudanese Patients with Chronic Gastritis by Using Combined Alcian Blue- PAS Technique

Detection of Intestinal Metaplasia among Sudanese Patients with Chronic Gastritis by Using Combined Alcian Blue- PAS Technique

A preliminary feasibility study: Narrow-band imaging targeted versus standard white light endoscopy non-targeted biopsies in a surveillance Barrett's population

BackgroundNarrow band imaging (NBI) is used in the detection of intestinal metaplasia (IM) and dysplasia in patients with Barrett's oesophagus (BE). AimsThe study compared the usefulness of NBI with white-light standard endoscopy (WLSE) for the detection of dysplasia and IM in BE and determined the prediction of the histological diagnosis according to the mucosal and vascular patterns obtained by NBI. Patients and methodsA total of 84 patients were prospectively enrolled in the study. Every patient underwent a WLSE with random biopsies and after 4–6 weeks, a NBI examination was performed. ResultsNBI detected significant more IM positive biopsies than WLSE (74.5% vs. 35.9%; p<0.0001) and significant more patients with low grade dysplasia (LGD) (7.1% vs. 0%; p=0.03). Taking biopsy samples from the villous pattern determined the diagnosis of IM (80%) and biopsies from the area covered by the irregular pattern lead to the identification of LGD in 45.4% of the cases and indefinite dysplasia (ID) in 18.2% of the cases. ConclusionA thorough analysis of NBI patterns may lead to real-time IM diagnosis in the absence of the histological examination and may require targeted biopsies from the areas with an irregular pattern for diagnosing dysplasia.

A multicenter randomized comparison between high-definition white light endoscopy and narrow band imaging for detection of gastric lesions.

Narrow band imaging (NBI) is generally considered to be useful for lesion characterization, but not enhanced detection of gastric lesions, because of the dark endoscopic view. We tested whether the new generation of NBI (190-NBI or 290-NBI), which is twice as bright as the previous version, would improve detection of premalignant gastric lesions compared with high-definition white light endoscopy (HD-WLE). This was a multicenter prospective randomized study involving five tertiary institutions in the Asia-Pacific region. A total of 579 patients aged older than 50 years who underwent diagnostic upper gastrointestinal endoscopy were randomized to either HD-WLE or NBI. The outcome measurements were detection of intestinal metaplasia (IM), focal gastric lesions, and gastric cancers. Focal gastric lesions were detected in 83/286 (29%) and 119/293 patients (40.6%) by HD-WLE and by NBI, respectively (P=0.003). IM was detected in 22/286 patients (7.7%) by HD-WLE and in 52/293 patients (17.7%) by NBI (P<0.001). Gastric cancer were found in 7/286 (2.4%) and 3/293 patients (1%) in HD-WLE and NBI groups, respectively (P=0.189). NBI increased the detection rate of IM compared with HD-WLE.

Interobserver variation in assessment of gastric premalignant lesions

Either atrophy or intestinal metaplasia of the gastric mucosa are considered premalignant lesions. The new operative link for gastritis assessment staging system is based on the detection of atrophy, and the operative link for assessment of intestinal metaplasia staging system is based on the detection of intestinal metaplasia. Good interobserver agreement is necessary for identification of any premalignant condition. The aim of this study was to compare the agreement between findings of gastric atrophy and intestinal metaplasia by expert and general pathologists and to analyze the possible reasons behind any possible disagreement. Patients with dyspeptic symptoms, aged 55 years and above, without previous Helicobacter pylori eradication were enrolled and analyzed according to the updated Sydney Classification by two expert pathologists and an experienced general pathologist; the results were compared with the consensus driven by the two experts. Gastric biopsy specimens from 121 patients (91 women) were included in the analysis; the mean age of the patients was 67.4 years. H. pylori infection was present in 61.2% of patients. The level of agreement between the general pathologist and the two experts (κ-value) was 0.12, 0.46, and 0.87, respectively, for detecting atrophy in the corpus; 0.77, 0.77, and 0.65, respectively, for detecting intestinal metaplasia in the corpus; 0.06, 0.51, and 0.54, respectively, for detecting atrophy in the antrum; and 0.69, 0.85, and 0.79, respectively, for detecting metaplasia in the antrum. The agreement was substantially higher for intestinal metaplasia than for atrophy. This could result in discrepancies when the operative link for gastritis assessment and operative link for assessment of intestinal metaplasia staging systems are applied and can be caused by differences in the criteria used to define atrophy.

Endoscopic diagnosis of dysplasia in Barrett’s esophagus

Evaluation of: Sharma P, Hawes RH, Bansal A et al. Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial. Gut 62(1), 15–21 (2013).Barrett’s esophagus, or columnar metaplasia with gastric cardiac cells or intestinal cells, develops in the squamous epithelium of the esophageal mucosa in relation to gastroesophageal reflux. An increased risk of neoplasia justifies surveillance at regular intervals. Conventional guidelines recommend detection of areas with intestinal metaplasia or dysplasia by taking random four-quadrant biopsies at every 1 or 2 cm. Alternatively, image processing with narrow band imaging (NBI), is proposed to improve detection. This international and randomized study in persons with Barrett’s esophagus compares conventional endoscopy in white light with random four-quadrant biopsies and NBI imaging with focused biopsies only. Randomization enrolled 123 patients with Barrett’s esophagus who successively underwent exploration with the two methods. The study confirmed that NBI had the same efficacy as white light in the detection of intestinal metaplasia, with a higher proportion of dysplasia detected (30 vs 21%) and a lower number of biopsies per patient (3.6 vs 7.6).

Screening and surveillance of Barrett’s esophagus

Esophageal adenocarcinoma (EAC) is the most rapidly increasing cancer in the Western world and Barrett's esophagus (BE) is the only known precursor lesion for this lethal cancer. Long-term survival may be improved if EAC is diagnosed early, providing an opportunity for early intervention. Screening for BE in patients with gastroesophageal reflux disease is not routinely recommended; however, if diagnosed, enrollment into a surveillance program may be beneficial. Surveillance of all patients with known BE is probably not cost-effective and factors predictive of BE progression to dysplasia/EAC are poorly understood. Screening and surveillance examinations are also faced with challenges in the endoscopic detection of intestinal metaplasia and dysplasia. Future application of molecular biomarkers may help identify the patients with BE most likely to progress, and the use of novel imaging methods may improve outcomes of BE screening and surveillance.

Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus

Objective. In the USA, detection of intestinal metaplasia is a requirement for enrolment in surveillance programmes for dysplasia or adenocarcinoma in columnar-lined oesophagus. In the UK, it is believed that failure to detect intestinal metaplasia at index endoscopy does not imply its absence within the columnarized segment or that the tissue is not at risk of neoplastic transformation. The aim of this study was to investigate the factors predicting the probability of detection of intestinal metaplasia in the columnarized segment. Material and methods. Demonstration of intestinal metaplasia was analysed in 3568 biopsies of non-dysplastic columnar-lined oesophagus from 1751 patients from 7 centres in the UK. Development of dysplasia and adenocarcinoma was analysed in 322 patients without intestinal metaplasia and compared with that in 612 patients with intestinal metaplasia. Results. Intestinal metaplasia was more commonly detected in males than in females (odds ratio 1.244), longer segment length (10.3% increase per centimetre) and increasing number of biopsies taken (24% increase per unit increase). After 5 years of follow-up, 54.8% of patients without intestinal metaplasia at index endoscopy demonstrated intestinal metaplasia, and 90.8% after 10 years. There was no significant difference in the rate of development of dysplasia or adenocarcinoma between patients with or without intestinal metaplasia detection at index endoscopy. Conclusions. Detection of intestinal metaplasia is subject to significant sampling error. It increases with segment length and number of biopsies taken. In the majority of patients, if sufficient biopsies are taken over time, intestinal metaplasia will be demonstrated. The decision to offer surveillance should not be based upon the presence or absence of intestinal metaplasia at index endoscopy as the risk of dysplasia and adenocarcinoma is similar in both groups.

Reply

We thank Drs Goldblum and Falk for their erudite review. We agree that the histologic confirmation of Barrett’s esophagus is currently confusing, lacking evidence, and poorly adhered to, no more so than in the UK, which has the highest conversion of Barrett’s to adenocarcinoma in the world (Gastroenterology 2002;122:588–590). Because intestinal metaplasia (IM), rather than cardiac or gastric metaplasia, is the precursor for adenocarcinoma, we sought to find an evidence-based approach for the number, location, and method of sampling biopsies from those who have endoscopically suspected Barrett’s esophagus (Gastroenterology 2006;13:1392–1399). This latter issue was specifically highlighted by an international working group because biopsy sampling protocols were poorly adhered to by clinicians outside a handful of centers (Gastroenterology 2004;127:310–330). Furthermore, to compound matters further, the hope that “molecular biomarkers” might replace the need for conventional intense histologic sampling has largely receded (Gut 2006;55:1377–1379). Our study fills this evidence gap and clinicians now know that if they take 8 biopsies they will successfully harvest IM in over two thirds of cases as opposed to under one third with only 3 biopsies (the current national average; Am J Gastroenterol 2007;102:1154–1161). Further improvement is not achieved unless >16 biopsies are taken! In addition, the distribution of IM in the proximal esophagus in the elderly is a reminder that as in the stomach, IM migrates over time and moves more proximally. We also show that special stains, whether they be Alcian blue or cytokeratin staining, add little to further the diagnosis of IM (5% and 0% diagnostic improvement, respectively). This should lead to improved adherence to the guidelines by endoscopists because now there is an evidence base for surveillance methodology (Nat Clin Pract Gastroenterol Hepatol 2006;3:101–111). In summary, we have identified for the first time that the minimum acceptable biopsy regimen is 8 biopsies for Barrett’s ≥1 cm long. Furthermore, we have shown that in the elderly biasing these 8 biopsies to proximal zones of Barrett’s esophagus will help IM identification. Finally, we are currently following up this study by others using the 5000-patient Aspirin Esomeprazole Chemoprevention Trial (AspECT; J Natl Cancer Inst 2004;96:885–887), aimed at deciding whether the 4-quadrant biopsy method is best or whether we should concentrate more on the 3- and 6-o’clock esophageal folds, which apparently have greatest malignant risk (Dis Esophagus 2007;20:232–238). How Exactly Do I Diagnose Intestinal Metaplasia in Barrett’s Esophagus?GastroenterologyVol. 133Issue 6PreviewHarrison R, Perry I, Haddadin W, et al. (Department of Pathology, Leicester General Hospital, Leicester, UK.) Detection of intestinal metaplasia in Barrett’s esophagus: an observational comparator study suggests the need for a minimum of eight biopsies. Am J Gastroenterol 2007;102:1154–1161. Full-Text PDF

Narrow band imaging in Barrett’s esophagus

Barrett’s esophagus is a well-recognized premalignant condition for the development of esophageal adenocarcinoma, the most rapidly rising cancer in the USA and Western Europe. Detection of intestinal metaplasia and neoplasia arising in Barrett’s esophagus patients continues to be a challenge. Limitations of conventional endoscopy with random biopsies provide the necessary impetus for the development of new approaches aimed at improving current screening and surveillance strategies. Narrow band imaging is a novel endoscopic technique that uses a higher intensity of blue light with narrow band filters, which allows a detailed inspection of mucosal and vascular surface patterns with high-level resolution and contrast. Preliminary studies have provided encouraging results for Narrow band imaging alone or in combination with other advanced endoscopic techniques in the screening and surveillance of Barrett’s esophagus patients.

Endoscopic Surface Imaging of Barrett’s Esophagus: An Optimistic View

Barrett’s esophagus (BE) is a well-recognized premalignant condition for the development of esophageal adenocarcinoma (EAC), the most rapidly rising cancer in the Western world. Endoscopic screening of subjects with chronic reflux symptoms has been recommended as a method of detecting BE and early cancer. Despite the lack of clinical evidence, BE patients are then routinely enrolled in surveillance programs to detect EAC at a preinvasive stage and ultimately reduce cancer-related deaths. Detection of intestinal metaplasia and early neoplasia arising in BE patients using standard endoscopic techniques combined with random 4-quadrant biopsies continues to be a challenge.

Evaluation of Initial and Deeper Sections of Esophageal Biopsy Specimens for Detection of Intestinal Metaplasia

Evaluation of Initial and Deeper Sections of Esophageal Biopsy Specimens for Detection of Intestinal Metaplasia

Detection of intestinal metaplasia at the gastro-oesophageal junction using magnifying endoscopy

Detection of intestinal metaplasia at the gastro-oesophageal junction using magnifying endoscopy

Evaluation of sensitivity and inter- and intra-observer variability in the detection of intestinal metaplasia and dysplasia in Barrett's esophagus with enhanced magnification endoscopy

Objective. Magnification endoscopy with acetic acid or dye for diagnosis of Barrett's esophagus is presently undergoing clinical evaluation. Current studies report good accuracy in predicting specialized intestinal metaplasia. To date, however, there is no definitive information on the inter- and intra-observer variability of these methods applied to the diagnosis of normal and dysplastic Barrett's mucosa. Material and methods. Sixty patients with endoscopically suspected Barrett's esophagus were investigated prospectively with the zoom endoscope after contrast enhancement of the mucosa with 1.5% acetic acid. Two hundred and twenty-three enlarged and histologically investigated areas of gastric, cardiac, normal and dysplastic Barrett's mucosa were photodocumented and in randomized sequence presented to 4 endoscopists in a blinded manner (2 with and 2 without experience of zoom endoscopy for evaluation). The reference for the first evaluation (A1) was standard endoscopic photographs of the respective, histologically confirmed mucosal entity. In a second evaluation (A2), the pictures were again interpreted by the same blinded investigators, but this time a modified pit-pattern classification as proposed by Sharma et al. was employed as the evaluation reference. Results. The diagnostic sensitivity for specialized intestinal metaplasia and dysplasia in Barrett's esophagus calculated for the A1 evaluation ranged – investigator dependently – from 54.9% to 80.7% and for A2 from 42.2% to 81.5%. The inter- and intra-observer variability for the evaluation procedure A1 and A2 was high (all kappa values <0.4). In particular, the inexperienced investigators demonstrated high intra-observer variability and low sensitivity in comparison with the experienced investigators. Conclusions. The diagnosis of Barrett's mucosa using enhanced magnification endoscopy after acetic acid instillation is associated with a high level of interobserver variability. One reason is a frequent mismatch between cardiac mucosa and non-dysplastic Barrett's mucosa.

Evaluation of Initial and Deeper Sections of Esophageal Biopsy Specimens for Detection of Intestinal Metaplasia

There are wide variations in the preparation of histologic sections from endoscopic esophageal biopsy specimens. We evaluated serial step sections from 261 esophageal or gastroesophageal junction biopsies at 4 levels to determine the first level at which goblet cell metaplasia (GCM) was detected. Deeper step sections of 152 paraffin blocks also were obtained to determine whether additional sections are useful in detecting GCM not seen in initial levels. GCM was identified in 95.3% of blocks in 3 levels. GCM was seen at level 4 in 12 blocks (4.7%). In the blocks that did not reveal intestinal metaplasia in the initial 4 levels, deeper sections disclosed GCM in only 1 (0.8%) of 120 blocks. However, deeper sections revealed initially undetected GCM in 4 of 32 blocks from patients with a history of documented Barrett esophagus. We conclude that 4 levels of step sections are adequate in routine processing of esophageal biopsy specimens for demonstration of GCM. Deeper sections may be obtained for patients with known Barrett esophagus to better evaluate for dysplasia or find additional foci of GCM.

The color of dysplasia in ulcerative colitis

The color of dysplasia in ulcerative colitis

Atrophy–metaplasia–dysplasia–carcinoma sequence in the stomach: a reality or merely an hypothesis?

The results of recent investigations have suggested that the old hypothesis of an atrophy–metaplasia–dysplasia–carcinoma sequence in the stomach needs to be qualified. The most common cause of intestinal metaplasia is Helicobacter pylori gastritis. The consequence of this intestinal metaplasia is focal atrophy.Helicobacter pylori infection may also trigger an autoimmune gastritis of the corpus mucosa, with atrophy and intestinal metaplasia. Most intestinal metaplasias are only ‘paracancerous’ but not ‘precancerous’ lesions. Diffuse gastric carcinomas, such as the signet ring cell carcinoma, arise independently of intestinal metaplasia. Histogenetically, numerous carcinomas of the stomach are primarily of the gastric type, and may secondarily change into the intestinal type.High-grade intra-epithelial neoplasias (dysplasias) detected during the biopsy-based diagnostic work-up appear to be a marker for carcinoma and must, therefore, be removed endoscopically.The detection of intestinal metaplasia in routinely obtained biopsy material is subject to sampling error and is, therefore, not a suitable marker for an increased risk of a gastric carcinoma developing. As an alternative, the concept of gastritis of the carcinoma phenotype, which is more frequently found in early gastric carcinomas and in the relatives of gastric carcinoma patients, has been developed. In this concept, the diffuse parameters of grade and activity of the gastritis in the antrum and corpus, which are independent of sampling error, are subjected to a comparative analysis. A risk gastritis of the carcinoma phenotype is diagnosed when the grade and activity of the gastritis in the corpus are at least equally as pronounced as in the antrum. Currently, this concept is being tested in a prospective ongoing study. Future studies must show whether, and if so which, immunohistochemical or molecular-genetically detectable changes can be applied as risk markers in the diagnostic work-up.Helicobacter pylori eradication probably does not lead to complete regression of the intestinal metaplasia and ensuing focal atrophy. However, eradication ofH. pylori does lead to the normalization of changes that can lead to mutations of the stem cells of the gastric mucosa (free radicals, nitric oxide, cell proliferation and vitamin C secretion).

Comparison of methylene blue-directed biopsies and conventional biopsies in the detection of intestinal metaplasia and dysplasia in Barrett's esophagus: A preliminary study

Background: The diagnostic advantage of methylene blue (MB) chromoendoscopy in Barrett's esophagus is unclear. Methods: Patients with columnar-lined esophagus (CLE) were enrolled into a prospective, randomized crossover trial of MB-directed biopsy versus conventional biopsy. Results: Forty-seven patients (19 long-segment CLE; 28 short-segment CLE) were enrolled and underwent MB-directed biopsy. Sensitivity and specificity of MB for specialized intestinal metaplasia were 53% and 51%, respectively. Sensitivity and specificity of MB for dysplasia were 51% and 48%, respectively. Thirty-five patients (15 long-segment CLE; 20 short-segment CLE) completed the crossover trial. Relative frequencies for specialized intestinal metaplasia were 73% and 71% from MB-directed and conventional biopsy specimens, respectively ( p = 0.73). Relative frequencies for dysplasia were 20% and 18% from MB-directed and conventional biopsy specimens, respectively ( p = 0.65). In patients with long-segment CLE, dysplasia was diagnosed in 10 patients with MB and 7 patients with conventional biopsy methods ( p = 0.25). The number of biopsy specimens per EGD was greater with MB, which may have influenced the diagnosis. Histologically, the grade of dysplasia was indefinite/low in nearly all of the dysplastic specimens. Conclusions: Results of MB-directed biopsy were similar to conventional biopsy in detecting specialized intestinal metaplasia and indefinite/low-grade dysplasia. MB was not useful in short-segment Barrett's esophagus. (Gastrointest Endosc 2001;54:294-301.)