Endoscopic mucosal resection for lesions with endoscopic features suggestive of malignancy and high-grade dysplasia within Barrett's esophagus

BACKGROUND: Endoscopic mucosal resection has been used in the treatment of superficial squamous cell cancers and gastric malignancies. Our aim was to determine whether endoscopic mucosal resection can be used in the diagnosis of lesions within Barrett's esophagus whose endoscopic appearances raise suspicion of carcinoma or high-grade dysplasia. METHODS: Twenty-five patients with such lesions within Barrett's esophagus underwent endoscopic mucosal resection for diagnostic and therapeutic purposes. All patients underwent endoscopic ultrasound to determine the feasibility of endoscopic resection. Only lesions found to be uT0 or uT1 underwent EMR. The lift and cut technique was used in 23 patients and a variceal ligating device was used on 2 patients. RESULTS: Endoscopic mucosal resection was performed because of a nodule or polyp within Barrett's esophagus in 11 patients (44%) and suspected superficial cancer or high-grade dysplasia in 14 patients (56%). Endoscopic mucosal resection diagnosed superficial adenocarcinoma in 13 patients (52%) and high-grade dysplasia in 4 (16%); it confirmed lesions in 8 patients (40%) to be of lower neoplastic risk. No complications occurred due to the procedure itself. CONCLUSIONS: Endoscopic mucosal resection is a technique with low morbidity and mortality. It has led to a change in diagnosis in patients with Barrett's esophagus and lesions with endoscopic features that suggest neoplasia. Its major advantages include simplicity and retrieval of the specimen en bloc.     

Gastric metaplasia of the proximal esophagus associated with esophageal adenocarcinoma and Barrett's esophagus: what is the connection? Inlet patch revisited

BACKGROUND/AIM: The inlet patch is an area of heterotopic gastric mucosa found in the proximal esophagus at the level of the upper esophageal sphincter. Limited data are available regarding this form of gastric metaplasia and its incidence, significance, and possible association with other esophageal diseases. We report our observations of such gastric metaplasias in patients with esophageal adenocarcinoma or Barrett's esophagus and high-grade dysplasia. METHODS: All patients having Barrett's esophagus and adenocarcinoma referred for photodynamic therapy were included in this study. The patients were prospectively evaluated endoscopically for the presence of gastric metaplasia of the proximal esophagus (salmon-colored area of a least 5 mm in diameter with cardia-type gastric metaplasia on biopsy). RESULTS: A total of 36 patients were included in this study: 11 patients with dysplastic Barrett's esophagus (8 males, mean age 79 years) and 25 adenocarcinoma patients (18 males, mean age 71 years). At endoscopy prior to photodynamic therapy, 11 patients (31%; 8 adenocarcinoma, 3 dysplastic Barrett's esophagus) were noted to have an area of gastric mucosa in the proximal esophagus. In each patient, there was at least 5 cm of normal squamous mucosa between gastric metaplasia and distal esophageal pathology. CONCLUSIONS: In this selected group of patients with high-grade dysplastic Barrett's esophagus or adenocarcinoma referred for photodynamic therapy, gastric metaplasia of the proximal esophagus was found in nearly one third. Prospective studies are under way to test more widely for this association and to determine whether this is a marker of disease severity and the result of similar pathogenetic mechanisms.     

Prospective evaluation of the prevalence of gastric Helicobacter pylori infection in patients with GERD, Barrett's esophagus, Barrett's dysplasia, and Barrett's adenocarcinoma

OBJECTIVE: This study was undertaken to prospectively determine the prevalence of gastric H. pylori infection in Barrett's esophagus and Barrett's complicated by dysplasia or adenocarcinoma. METHODS: The prevalence of H. pylori was determined in Barrett's esophagus patients compared to a control population of patients with gastroesophageal reflux disease (GERD) only. All patients had a minimum of 10 gastric surveillance biopsies obtained. H. pylori colonization was determined upon the basis of hematoxylin and eosin and use of a modified Giemsa and or Steiner's silver stain of all gastric biopsy specimens. RESULTS: Two hundred and eighty-nine Barrett's patients and 217 GERD control patients were included in the study. H. pylori was found in 95/289 (32.9%) of the Barrett's patients, compared with 96/217 (44.2%) of the GERD controls (NS). Forty-seven of the Barrett's patients had low-grade dysplasia/indefinite dysplasia, 14 high-grade dysplasia, and 20 Barrett's adenocarcinoma. When Barrett's was subgrouped according to absence of dysplasia, and presence of low-grade dysplasia, high-grade dysplasia, or adenocarcinoma, H. pylori prevalence was found to be significantly less for patients with Barrett's high-grade dysplasia (14.3%) and adenocarcinoma (15.0%) versus patients with GERD alone (44.2%), Barrett's alone (35.1%), or Barrett's with low-grade dysplasia (36.2%) (p = 0.016). This difference could not be explained by differences between Barrett's esophagus patients infected with H. pylori and those who were not with respect to gender, smoking history, alcohol consumption, use of proton pump inhibitor, or length of Barrett's mucosa. CONCLUSIONS: Barrett's high-grade dysplasia and adenocarcinoma are significantly more prevalent in patients who are not infected with H. pylori. H. pylori appears to have a protective effect against the development of Barrett's adenocarcinoma.     

Comprehensive esophageal microscopy by using optical frequency-domain imaging (with video)

BACKGROUND: Optical coherence tomography (OCT) has been used for high-resolution endoscopic imaging and diagnosis of specialized intestinal metaplasia, dysplasia, and intramucosal carcinoma of the esophagus. However, the relatively slow image-acquisition rate of the present OCT systems inhibits wide-field imaging and limits the clinical utility of OCT for diagnostic imaging in patients with Barrett's esophagus. OBJECTIVE: This study describes a new optical imaging technology, optical frequency-domain imaging (OFDI), derived from OCT, that enables comprehensive imaging of large esophageal segments with microscopic resolution. DESIGN: A prototype OFDI system was developed for endoscopic imaging. The system was used in combination with a balloon-centering catheter to comprehensively image the distal esophagus in swine. RESULTS: Volumetric images of the mucosa and portions of the muscularis propria were obtained for 4.5-cm-long segments. Image resolution was 7 microm in depth and 30 microm parallel to the lumen, and provided clear delineation of each mucosal layer. The 3-dimensional data sets were used to create cross-sectional microscopic images, as well as vascular maps of the esophagus. Submucosal vessels and capillaries were visualized by using Doppler-flow processing. CONCLUSIONS: Comprehensive microscopic imaging of the distal esophagus in vivo by using OFDI is feasible. The unique capabilities of this technology for obtaining detailed information of tissue microstructure over large mucosal areas may open up new possibilities for improving the management of patients with Barrett's esophagus.     

Interobserver Agreement for the Detection of Barrett’s Esophagus with Optical Frequency Domain Imaging

Background

Optical frequency domain imaging (OFDI) is a second-generation form of optical coherence tomography (OCT) providing comprehensive cross-sectional views of the distal esophagus at a resolution of ~7 μm.

Aim

Using validated OCT criteria for squamous mucosa, gastric cardia mucosa, and Barrett’s esophagus (BE), the objective of this study was to determine the inter- and intra-observer agreements by a large number of OFDI readers for differentiating these tissues.

Methods

OFDI images were obtained from nine subjects undergoing screening and surveillance for BE. Sixty-four OFDI image regions of interest were randomly selected for review. A training set of 19 images was compiled distinguishing squamous mucosa from gastric cardia and BE using previously validated OCT criteria. The ten readers then interpreted images in a test set of 45 different images of squamous mucosa (n = 15), gastric cardia (n = 15), or BE (n = 15). Interobserver agreement differentiating the three tissue types and BE versus non-BE mucosa was determined using multi-rater Fleiss’s κ value. The images were later randomized again and four readers repeated the test 3 weeks later to assess intraobserver reliability.

Results

All ten readers showed excellent agreement for the differentiation of BE versus non-BE mucosa (κ = 0.811 p < 0.0001) and for differentiating BE versus gastric cardia versus squamous mucosa (κ = 0.866, p < 0.0001). For the four readers who repeated the test, the median intraobserver agreement (BE vs. non-BE) was high (κ = 0.975, IQR: 0.94, 1.0).

Conclusions

Trained readers have a high interobserver agreement for differentiating BE, squamous, and gastric cardia mucosa using OFDI.     

p53 immunoreactivity in Barrett's metaplasia, dysplasia, and adenocarcinoma--a case report

Barrett's esophagus is a condition in which the stratified squamous epithelium of the esophagus is replaced by a columnar epithelium with malignant potential. Mutations of the tumor-suppressor gene p53 have been implicated in the evolution of esophageal carcinomas. The aim of this study was to determine whether p53 immunoreactivity in Barrett's esophagus is a marker of neoplasia and, if so, when it occurs in the metaplasia-dysplasia-carcinoma sequence. We treated a patient with esophageal carcinoma arising from the Barrett's esophagus. Consecutive evidence existed for a metaplasia-dysplasia-carcinoma in the same specimen. Immunohistochemical staining with the monoclonal antibody was used to detect the intranuclear protein product of mutated p53. No p53 immunoreactivity was seen in specimen of Barrett's mucosa. p53 immunoreactivity was found only in specimen of dysplasia and carcinoma. Immunoreactivity occurs late in the metaplasia-dysplasia-carcinoma sequence, during the transition to high-grade dysplasia.     

Visible endoscopic and histologic changes in the cardia, before and after complete Barrett's esophagus ablation

BACKGROUND: Adverse events associated with the thermal ablation of Barrett's esophagus (BE) include the generation of gastric mucosa buried beneath the neosquamous regrowth, and unrecognized development and growth of adenocarcinomas. No reports exist regarding the endoscopic appearance and histology of the cardia before and after BE ablation. The aim of our study was to assess the relative frequency of the occurrence of visible endoscopic and histologic changes in the cardia, before and after complete BE ablation. METHODS: A subset analysis of patients with uncomplicated BE, BE with dysplasia, or early carcinoma, who had been enrolled into one of 4 ongoing prospective studies of mucosal ablation, was examined. Eighty-two patients were identified who entered a BE ablation study, with 75 of these completing BE mucosal ablation. Cardia biopsy specimens were taken in all patients before ablation and serially after BE ablation. Cardia histology was graded by using the modified Sydney System for gastritis. RESULTS: Before ablation, cardia nodules were noted in 3, cardia intestinal metaplasia (IM) in 7 (8.5%), and none harbored cardia dysplasia. Postablation surveillance ranged from 3 to 75 months (mean 31.1 months [19.5]). Six subjects (8%) developed cardia nodules during surveillance; cardia IM was found in 21(28%), with 17 of these being a new finding (incidence of 25%). Cardia low-grade dysplasia incidence was 1.3% and high-grade dysplasia was 4% after BE ablation. CONCLUSIONS: The pathophysiology of the abnormal cardia histology and the endoscopic lesions (nodules) is unclear, but endoscopic surveillance of not only the neosquamous epithelium but also the cardia should be considered after ablation, especially in those high-grade dysplasia and early adenocarcinoma BE patients.     

Barrett''s esophagus: current and future role of endosonography and optical coherence tomography

This paper reviews the role of endosonography and optical coherence tomography (OCT) for imaging of Barrett's esophagus (BE). The routine use of endoscopic ultrasound (EUS) to screen patients with BE is neither justified nor cost effective. EUS does appear to have a role in patients who have BE and high-grade dysplasia or intramucosal carcinoma, in whom a non-operative therapy is being contemplated. For patients with a diagnosis of esophageal cancer with or without BE, EUS is superior to computed tomography or magnetic resonance imaging for assessing esophageal wall penetration and for detecting regional lymph node involvement. In its current state, OCT is not yet ready for application in clinical practice. However, given its superior resolution compared with other modalities such as EUS, OCT has great potential as a powerful adjunct to standard endoscopy in surveillance of BE and may enhance the ability of endoscopists to detect high-grade dysplasia at an early stage. With further technical refinement, this technique may become a mainstay in the surveillance of BE and other premalignant conditions of the gastrointestinal tract.     

Photodynamic therapy for Barrett's esophagus with dysplasia and/or early stage carcinoma: long-term results

BACKGROUND: Photodynamic therapy has been shown to eliminate Barrett's dysplasia. This report presents long-term follow-up data after photodynamic therapy of Barrett's esophagus with high-grade dysplasia, low-grade dysplasia, or early stage carcinoma. METHODS: Porfimer-photodynamic therapy was performed in 103 patients. The Nd:YAG laser was used to photoablate small areas of residual or untreated Barrett's mucosa. Acid suppression was maintained in all patients (omeprazole, 20 mg twice a day). RESULTS: Mean follow-up was 50.65 (SD 20.57) months (range 2-122 months). For the 82 patients not lost to follow-up, mean follow-up was 58.5 (12.89) months (range 41-132 months). After photodynamic therapy, the length of Barrett's mucosa decreased by a mean of 6.92 cm (range 1-22 cm). Of the 65 patients with high-grade dysplasia, 60 (94%) had elimination of high-grade dysplasia. Three (4.6%) patients developed subsquamous adenocarcinoma. Subsquamous, nondysplastic, metaplastic epithelium was found in 4 patients (4.9%). Strictures occurred in 18% with one session of photodynamic therapy, and 50% with two treatments, 30% overall. For the 103 patients, intention-to-treat success rates were 92.9%, 77.5%, and 44.4% for, respectively, low-grade dysplasia, high-grade dysplasia, and early stage carcinoma groups. CONCLUSION: Porfimer-photodynamic therapy with supplemental Nd:YAG photoablation and continuous treatment with omeprazole reduces the length of Barrett's mucosa, eliminates high-grade dysplasia, and, by comparison with historical data, may reduce the expected frequency of carcinoma.     

Methylene Blue Staining and Endoscopic Ultrasound Evaluation of Barrett's Esophagus with Low-Grade Dysplasia

This study was performed to determine if either methylene blue staining or endoscopic ultrasound helped direct biopsies in patients with a history of Barrett's esophagus with low-grade dysplasia. Patients underwent radial endoscopic ultrasound scanning to measure esophageal wall thickness, followed by endoscopy with methylene blue staining and biopsies. Mean esophageal wall thickness for squamous mucosa (2.3 ± 0.2 mm), nondysplastic Barrett's (2.6 ± 0.2 mm), and Barrett's with dysplasia (2.9 ± 0.3 mm) were similar. With staining, Barrett's mucosa stained blue more often than gastric epithelium (68% vs 15%, respectively; P < 0.001). The sensitivity and specificity for strong staining detecting Barrett's were 68% and 85%, respectively. Barrett's with low-grade dysplasia stained blue less frequently (52%) than nondysplastic Barrett's (74%; P < 0.05), but the positive predictive value for poor staining indicating dysplasia was 41%. Endoscopic ultrasound was not helpful in directing biopsies in these patients. The utility of methylene blue for detecting dysplasia needs further investigation.     

Hiatal hernia size,Barrett's length,and severity of acid reflux are all risk factors for esophageal adenocarcinoma

OBJECTIVE: The reasons for the development of dysplasia and adenocarcinoma in Barrett's mucosa are not well understood. The aims of this study were to characterize risk factors for the transition from Barrett's esophagus without dysplasia to Barrett's esophagus with high-grade dysplasia or esophageal adenocarcinoma. METHODS: A group of 131 patients with high-grade dysplasia or esophageal adenocarcinoma were selected as case subjects. A first population of 2170 patients without gastroesophageal reflux disease (GERD) and a second population of 1189 patients with Barrett's esophagus served as two control groups. Logistic regression analyses were used to compare the risk factors associated with the occurrence of high-grade dysplasia or esophageal adenocarcinoma. RESULTS: Patients with high-grade dysplasia or esophageal adenocarcinoma shared many characteristics with other forms of severe GERD, such as older age, male gender, and white ethnicity. The length of Barrett's esophagus and the size of hiatus hernia increased the risk for both conditions. Subjects with high-grade dysplasia and adenocarcinoma had more severe acid reflux than patients with other forms of GERD. Smoking and alcohol consumption did not affect the risk for developing high-grade dysplasia or adenocarcinoma in patients with Barrett's esophagus. CONCLUSIONS: High-grade dysplasia and esophageal adenocarcinoma seem to stem from an extreme and unfavorable constellation of all risk factors that are generally held responsible for the development of GERD and Barrett's esophagus.     

EUS in the management of the patient with dysplasia in Barrett's esophagus

Barrett's esophagus is the most important risk factor in the development of adenocarcinoma of the esophagus. Barrett's esophagus is generally regarded as the most significant complication of gastroesophageal reflux disease. Adenocarcinoma occurs more frequently in the setting of high-grade dysplasia. The prognosis of adenocarcinoma of the esophagus is strongly correlated with the stage of disease. The prognosis of late stage disease is extremely poor. Cure may be achieved when disease is found at an early stage. Esophagectomy has been the definitive treatment of limited stage adenocarcinoma of the esophagus. The morbidity and mortality rate for esophagectomy is high. Therefore, alternative endoscopic methods for curative treatments have gained popularity. The two main endoscopic therapies, photodynamic therapy and endoscopic mucosal resection, are both effective when applied to early-stage disease. Traditional evaluation of the patient with Barrett's esophagus with high-grade dysplasia includes esophago-gastro-duodenoscopy (EGD) with biopsy and computed tomography of the chest. Endoscopic ultrasound (EUS) has gained popularity in the evaluation of the patient with Barrett's esophagus and high-grade dysplasia because it is the only imaging technique capable of delineating the separate histologic layers of the gastrointestinal tract. The principal role of EUS in evaluating patients with Barrett's-associated dysplasia is to identify patients who may be candidates for endoscopic ablative (endoscopic mucosal resection, photodynamic therapy) therapies. EUS has been shown to be superior to computed tomography (including high resolution spiral CT) or magnetic resonance imaging for preoperative staging in patients with high-grade dysplasia and carcinoma. This review of the literature summarizes the ability of EUS to evaluate patients with Barrett's esophagus and high-grade dysplasia.     

Esophageal cancer prevention, cure, and palliation

Adenocarcinoma of the esophagus and gastric cardia are the most rapidly increasing cancers in developed countries. Adenocarcinoma of the esophagus is associated with chronic gastroesophageal reflux, and Barrett's esophagus is a precursor. This disease most frequently affects middle-aged white men. Endoscopic surveillance should be performed on patients with Barrett's esophagus, and esophagectomy is often performed on persons with high-grade dysplasia. Ablation of Barrett's esophagus has been proposed to prevent cancer but the outcomes are unproven. Squamous carcinoma of the esophagus most often affects black men and is associated with alcohol and tobacco use. The diagnosis of esophageal cancer is made by endoscopy with biopsy. Optimal staging is with endoscopic ultrasonography for depth of invasion and regional nodes and CT scanning for distant metastases. Neoadjuvant chemotherapy and radiation therapy followed by surgery is widely practiced, but survival benefits remain to be proven. Palliation of dysphagia may be achieved with surgery, radiation therapy, or endoscopic means, with the latter having fewer complications.     

Dysplastic gastroesophageal junction nodules--a precursor to junctional adenocarcinoma

Adenocarcinoma of the gastroesophageal junction is a disease rapidly increasing in prevalence. The origin of these tumors is unclear. Barrett's esophagus, gastric cardia lesions, and mucus glands of the distal esophagus have been implicated. This case report presents two cases of patients who had chest pain leading to esophagogastroduodenoscopy. Both had small, benign-appearing nodules at the gastroesophageal junction in the absence of Barrett' s esophagus or gastric lesions. Biopsies revealed intestinal metaplasia with dysplasia in one patient and dysplasia of the mucus glands of the esophagus in the other. The first patient was followed for 8 months with serial biopsies, during which time the lesion became progressively more dysplastic, culminating in invasive cancer. These cases are presented to show that 1) benign-appearing gastroesophageal junction nodules may have malignant behavior, and 2) junctional cancer and high grade dysplasia can occur in the absence of Barrett's esophagus or gastric cardia lesions. Gastroesophageal junctional dysplasia/carcinoma may occur in small foci of intestinal metaplasia or in the mucus glands of the distal esophagus.     

Ornithine decarboxylase activity in Barrett's esophagus: a potential marker for dysplasia

Ornithine decarboxylase activity is known to be increased in certain premalignant conditions. We determined the activity of this enzyme in mucosal biopsy specimens from 15 patients with Barrett's esophagus. Ornithine decarboxylase was greater in Barrett's mucosa than in squamous esophageal or gastric mucosa. In Barrett's mucosa from 4 patients with dysplasia, the enzyme activity was greater than in 11 patients without dysplasia (1.6 +/- 0.35 vs. 0.19 +/- 0.08 U/mg protein; p less than 0.005). Increased ornithine decarboxylase activity in biopsy specimens of Barrett's mucosa may represent a marker for dysplasia.     

Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett's esophagus without grossly recognizable neoplastic lesions

There is uncertainty regarding the value of endoscopic biopsy surveillance in Barrett's esophagus because, in retrospective studies, some patients with high-grade dysplasia in endoscopic biopsy specimens have had unexpected advanced adenocarcinoma discovered at the time of esophageal resection. We compared the accuracy of preoperative endoscopic biopsy diagnoses with the final pathologic diagnoses in esophagectomy specimens in 4 patients who had both high-grade dysplasia and intramucosal carcinoma and 4 other patients who had only high-grade dysplasia preoperatively. The histologic lesions in all 8 patients were documented in intact mucosa with no gross evidence of neoplasia by endoscopy. The preoperative diagnoses were defined with an endoscopic biopsy protocol in which specimens were taken with large-channel biopsy forceps at least every 2 cm throughout the length of Barrett's epithelium. Final pathologic diagnoses derived from detailed analysis of the resected specimens confirmed high-grade dysplasia without carcinoma in 4 patients and intramucosal carcinoma in 2 patients. The remaining 2 patients with a preoperative diagnosis of intramucosal carcinoma had focal submucosal invasion by carcinoma in the resected specimens, but no involvement of the muscularis propria or adventitial lymph nodes. Because the natural history of high-grade dysplasia is not known, the decision to operate on patients with this lesion must be carefully weighed and individualized for each patient. Two of our patients who underwent esophageal resection for high-grade dysplasia without cancer died, one immediately postoperatively and the other 9 mo later after a postoperative stroke. Once intramucosal carcinoma is documented, surgery should be considered if the patient is an acceptable operative risk. We conclude that systematic preoperative endoscopic biopsy of intact mucosa in Barrett's esophagus can correctly detect high-grade dysplasia, either alone or in combination with early, treatable adenocarcinoma.     

The pathology of epithelial pre-malignancy of the gastrointestinal tract

This chapter deals with pre-malignant epithelial lesions of the gastrointestinal tract that have the potential to become cancers. Pre-malignant lesions are divided into two types: those characterized by dysplastic mucosa and those without dysplasia. Examples of the two types are present in the oesophagus, stomach and intestine.In the oesophagus, dysplasia of the squamous epithelium is a precursor to squamous carcinoma. There are differences in interpretation between Western and Japanese pathologists in the diagnosis of oesophageal squamous lesions. Dysplasia in Barrett's oesophagus is regarded as a precursor of adenocarcinoma. The goal of endoscopic surveillance in Barrett's mucosa is the detection of high-grade dysplasia. There are several problems with our current knowledge of high-grade dysplasia and controversies regarding its management. There are differences in the interpretation of biopsies of gastric epithelial dysplasia between Japanese and Western pathologists. In the colon, pre-malignant lesions include dysplasia seen in inflammatory bowel disease and colonic adenomas. The most significant predictor of the risk of malignancy in patients with inflammatory bowel disease is the presence of dysplasia in colonic biopsies.Because of the similarity of neoplasia throughout the gastrointestinal tract, there have been attempts to unify its classification, terminology and diagnostic criteria internationally, the most recently proposed modified classification of gastrointestinal neoplasia being the Vienna classification. Dysplasia of the columnar mucosa has a similar appearance in Barrett's oesophagus, the stomach and the colon. Criteria for its histological diagnosis and grading are reviewed, with an emphasis on areas of diagnostic difficulty such as interobserver variation, and discrepancies between Western and Japanese pathologists. Implication of the presence of dysplasia that are specific to each organ site are discussed, highlighting weaknesses and controversies in current knowledge.     

Autofluorescence endoscopy for detection of high-grade dysplasia in short-segment Barrett's esophagus

BACKGROUND: The occurrence of precancerous lesions, such as high-grade dysplasia, in patients with short-segment Barrett's esophagus is controversial. This study assessed the efficacy of autofluorescence endoscopy for detection of high-grade dysplasia in short-segment Barrett's esophagus. METHODS: A total of 34 patients (28 men, 6 women; age range 40-77 years) with histopathologically proven short-segment Barrett's esophagus were studied. Autofluorescence endoscopy was performed by using monochromatized blue light (425-455 nm) filtered from a conventional xenon light source. A total of 136 and 109 biopsy specimens were taken from Barrett's mucosa under control, respectively, white light endoscopy and autofluorescence endoscopy. RESULTS: High-grade dysplasia was found in 9 (8.3%) autofluorescence-guided biopsy specimens, which was significantly greater than the number of white light endoscopy-guided biopsy specimens with this finding (one positive biopsy specimen, 0.7% of total biopsy specimens obtained). Autofluorescence endoscopy detected high-grade dysplasia in 7 patients, 6 more than were identified with white light endoscopy. In the one patient with high-grade dysplasia detected by white light endoscopy-guided biopsy specimens, autofluorescence-guided biopsy specimens revealed only low-grade dysplasia. CONCLUSION: Autofluorescence endoscopy in patients with short-segment Barrett's esophagus increases the detection rate of high-grade dysplasia.     

Cervical inlet patch-optical coherence tomography imaging and clinical significance

AIM: To demonstrate the feasibility of optical coherence tomography (OCT) imaging in differentiating cervical inlet patch (CIP) from normal esophagus, Barrett’s esophagus (BE), normal stomach and duodenum.METHODS: This study was conducted at the Veterans Affairs Boston Healthcare System (VABHS). Patients undergoing standard esophagogastroduodenoscopy at VABHS, including one patient with CIP, one representative patient with BE and three representative normal subjects were included. White light video endoscopy was performed and endoscopic 3D-OCT images were obtained in each patient using a prototype OCT system. The OCT imaging probe passes through the working channel of the endoscope to enable simultaneous video endoscopy and 3D-OCT examination of the human gastrointestinal (GI) tract. Standard hematoxylin and eosin (H and E) histology was performed on biopsy or endoscopic mucosal resection specimens in order to compare and validate the 3D-OCT data.RESULTS: CIP was observed from a 68-year old male with gastroesophageal reflux disease. The CIP region appeared as a pink circular lesion in the upper esophagus under white light endoscopy. OCT imaging over the CIP region showed columnar epithelium structure, which clearly contrasted the squamous epithelium structure from adjacent normal esophagus. 3D-OCT images obtained from other representative patients demonstrated distinctive patterns of the normal esophagus, BE, normal stomach, and normal duodenum bulb. Microstructures, such as squamous epithelium, lamina propria, muscularis mucosa, muscularis propria, esophageal glands, Barrett’s glands, gastric mucosa, gastric glands, and intestinal mucosal villi were clearly observed with OCT and matched with H and E histology. These results demonstrated the feasibility of using OCT to evaluate GI tissue morphology in situ and in real-time.CONCLUSION: We demonstrate in situ evaluation of CIP microstructures using 3D-OCT, which may be a useful tool for future diagnosis and follow-up of patients with CIP.     

Predictors for squamous re-epithelialization of Barrett's esophagus after endoscopic biopsy

BACKGROUND AND AIM: Acid suppressive therapy has been reported to regress Barrett's esophagus. However, it is still controversial as to whether all Barrett's esophagus patients respond to this therapy. The factors that might facilitate newly developed squamous re-epithelialization after biopsy excision of Barrett's mucosa were evaluated to identity individuals who may favorably respond to the regression therapy. METHODS: Two hundred and forty-seven biopsy sites from 185 patients with Barrett's esophagus were examined by endoscopy to investigate possible squamous re-epithelialization of Barrett's mucosa after endoscopic biopsy. Before endoscopic examination, all participants were requested to answer questionnaires concerning sociodemographic characteristics, lifestyle habits and drugs usage. The mucin phenotype, Cdx2 expression, cyclooxygenase-2 expression, cellular proliferation and apoptosis of Barrett's mucosa were immunohistochemically investigated in the biopsy samples taken from Barrett's esophagus. The influence of these factors on the newly developed squamous re-epithelialization of Barrett's mucosa after endoscopic biopsy excision was evaluated. RESULTS: By multivariate analysis, the independent factors that favored squamous re-epithelialization were the gastric mucin predominant phenotype of Barrett's mucosa and the absence of Cdx2 protein expression. In Barrett's mucosa with the gastric predominant mucin phenotype, proton pump inhibitor administration, the absence of reflux esophagitis and a low proliferating cell nuclear antigen index were found to be independent predictors for squamous re-epithelialization. CONCLUSIONS: The absence of the intestinal predominant mucin phenotype was a positive predictor for newly developed squamous re-epithelialization at the site of biopsy of Barrett's mucosa. Only Barrett's esophagus with the gastric predominant mucin phenotype may predict a favorable response to acid suppressive therapy.