High-resolution endoscopy plus chromoendoscopy or narrow-band imaging in Barrett's esophagus: a prospective randomized crossover study

BACKGROUND AND STUDY AIMS: High-resolution endoscopy (HRE) may improve the detection of early neoplasia in Barrett's esophagus. Indigo carmine chromoendoscopy (ICC) and narrow-band imaging (NBI) may be useful techniques to complement HRE. The aim of this study was to compare HRE-ICC with HRE-NBI for the detection of high-grade dysplasia or early cancer (HGD/EC) in patients with Barrett's esophagus. PATIENTS AND METHODS: Twenty-eight patients with Barrett's esophagus underwent HRE-ICC and HRE-NBI (separated by 6 - 8 weeks) in a randomized sequence. The two procedures were performed by two different endoscopists, who were blinded to the findings of the other examination. Targeted biopsies were taken from all detected lesions, followed by four-quadrant biopsies at 2-cm intervals. Biopsy evaluation was supervised by a single expert pathologist, who was blinded to the imaging technique used. RESULTS: Fourteen patients were diagnosed with HGD/EC. The sensitivity for HGD/EC was 93 % and 86 % for HRE-ICC and HRE-NBI, respectively. Targeted biopsies had a sensitivity of 79 % with HRE alone. HGD was diagnosed from random biopsies alone in only one patient. ICC and NBI detected a limited number of additional lesions occult to HRE, but these lesions did not alter the sensitivity for identifying patients with HGD/EC. CONCLUSIONS: In most patients with high-grade dysplasia or early cancer in Barrett's esophagus, subtle lesions can be identified with high-resolution endoscopy. Indigo carmine chromoendoscopy and narrow-band imaging are comparable as adjuncts to high-resolution endoscopy.     

Endoscopic fluorescence detection of intraepithelial neoplasia in Barrett's esophagus after oral administration of aminolevulinic acid

BACKGROUND AND STUDY AIMS: Barrett's esophagus is strongly associated with adenocarcinoma. Early malignant transformation of the Barrett's mucosa is often not visible endoscopically and may remain undetected until the invasive adenocarcinoma stage. Endoscopic surveillance is currently carried out on random four-quadrant biopsies at 1-2 cm intervals. Endoscopic fluorescence detection of protoporphyrin IX induced by 5-aminolevulinic acid can identify premalignant lesions. This study evaluates endoscopic fluorescence detection in patients having Barrett's esophagus and compares the results to those of standard endoscopy with random four-quadrant biopsies. PATIENTS AND METHODS: The study included 30 examinations in 28 patients (22 men, 6 women; age range 37-78 years, mean age 60 years,), with five patients having known intraepithelial neoplasia. A dose of 20 mg/kg of 5-aminolevulinic acid was given orally 5 hours before examination. Random four-quadrant biopsies were performed 4-6 weeks before endoscopic fluorescence detection. RESULTS: Of the biopsies taken during the endoscopic fluorescence detection procedure, 28 % (23/81) were true positives. More than one-third of the false-positive results were due to inflammation. None of the 97 control biopsies taken on nonfluorescing areas during endoscopic fluorescence detection were dysplastic. Endoscopic fluorescence detection showed low-grade intraepithelial neoplasia in five patients which was not diagnosed with random four-quadrant biopsies, while random four-quadrant biopsies alone showed three low-grade intraepithelial neoplasias that were invisible during endoscopic fluorescence detection. All high-grade intraepithelial neoplasias or adenocarcinomas (2/2) were detected with both methods. CONCLUSIONS: Fluorescence detection achieved a similar performance when compared with four-quadrant random biopsy, but resulted in fewer biopsies (81 for endoscopic fluorescence detection vs 531 for random four-quadrant biopsies).     

Methylene blue chromoendoscopy for the detection of Barrett's esophagus in a Greek cohort

BACKGROUND AND STUDY AIMS: Specialized columnar epithelium of Barrett's esophagus is a precursor of dysplasia and adenocarcinoma, and methylene blue selectively stains this type of epithelium. The present prospective study examined the detection of short-segment and long-segment Barrett's esophagus using methylene blue chromoendoscopy-directed biopsies, in comparison with biopsies directed using conventional endoscopic criteria. PATIENTS AND METHODS: Biopsies were obtained from macroscopically conspicous areas in the distal esophagus observed during conventional endoscopy in a total of 975 patients. Immediately after conventional biopsies, the distal esophagus was sprayed with methylene blue and directed biopsies were then obtained from the stained regions. All patients with a histologically established Barrett's esophagus underwent a second upper gastrointestinal endoscopy within 1 year in order to assess the reproducibility of the method. RESULTS: In a total of 3,900 conventional biopsy specimens (without staining), 54 specimens (1.4%) were found to show Barrett's esophagus and were confined to 16 of the 975 patients (1.6%). Of the total 130 directed biopsy specimens obtained during chromoendoscopy, 114 (87.7%) revealed Barrett's esophagus (P<0.00001) and were confined to 35 of the 975 patients (3.5%; P < or = 0.001). The findings were confirmed within 1 year in all dye-positive patients. CONCLUSIONS: Chromoendoscopy with methylene blue appears to be an accurate, simple, safe, inexpensive, and reproducible method of detecting specialized columnar epithelium in Barrett's esophagus.     

The burden of upper gastrointestinal endoscopy in patients with Barrett's esophagus

BACKGROUND AND STUDY AIMS: Patients with Barrett's esophagus are recommended to undergo regular surveillance with upper gastrointestinal endoscopy, an invasive procedure that may cause anxiety, pain, and discomfort. We assessed to what extent patients perceived this procedure as burdensome. PATIENTS AND METHODS: A total of 192 patients with Barrett's esophagus were asked to fill out questionnaires at 1 week and immediately before endoscopy, and at 1 week and 1 month afterwards. Four variables were assessed: (i) pain and discomfort experienced during endoscopy; (ii) symptoms; (iii) psychological burden, i. e., anxiety, depression and distress levels (Hospital Anxiety and Depression scale, Impact of Event Scale); and (iv) perceived risk of developing adenocarcinoma. RESULTS: At least one questionnaire was returned by 180 patients (94 %), 151 completed all four (79 %). Of all patients, only 14 % experienced the endoscopy as painful. However, 59 % reported it to be burdensome. Apart from an increase in throat ache (47 % after endoscopy versus 12 % before), the procedure did not cause physical symptoms. Patients' anxiety, depression, and distress levels were significantly increased in the week before endoscopy compared with the week after. Patients perceiving their risk of developing adenocarcinoma as high reported higher levels of psychological distress and that the procedure was a greater burden. CONCLUSIONS: Upper gastrointestinal endoscopy is burdensome for many patients with Barrett's esophagus and causes moderate distress. Perception of a high risk of adenocarcinoma may increase distress and the burden experienced from the procedure. The benefits of endoscopic surveillance for patients with Barrett's esophagus should be weighed against its drawbacks, including the short-term burden for patients.     

Follow-up for high-grade dysplasia in Barrett's esophagus

This article will focus on the value of endoscopic follow-up for patients with high-grade dysplasia (HGD). Because the diagnosis of HGD in Barrett's esophagus is not a simple straightforward task, the article first will discuss the controversies regarding the histological diagnosis, followed by a discussion of the importance of endoscopic imaging for making the clinical diagnosis of HGD, and a systematic review of the literature relating to the presence of synchronous cancers in patients with HGD and the occurrence of cancer during endoscopic follow-up in these patients (metachronous cancers). Furthermore, the article will also discuss endoscopic techniques currently available for surveillance of these patients and make recommendations regarding surveillance intervals and the optimal biopsy protocol.     

Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a condition commonly managed in the primary care setting. Patients with GERD may develop reflux esophagitis as the esophagus repeatedly is exposed to acidic gastric contents. Over time, untreated reflux esophagitis may lead to chronic complications such as esophageal stricture or the development of Barrett's esophagus. Barrett's esophagus is a premalignant metaplastic process that typically involves the distal esophagus. Its presence is suspected by endoscopic evaluation of the esophagus, but the diagnosis is confirmed by histologic analysis of endoscopically biopsied tissue. Risk factors for Barrett's esophagus include GERD, white or Hispanic race, male sex, advancing age, smoking, and obesity. Although Barrett's esophagus rarely progresses to adenocarcinoma, optimal management is a matter of debate. Current treatment guidelines include relieving GERD symptoms with medical or surgical measures (similar to the treatment of GERD that is not associated with Barrett's esophagus) and surveillance endoscopy. Guidelines for surveillance endoscopy have been published; however, no studies have verified that any specific treatment or management strategy has decreased the rate of mortality from adenocarcinoma.     

Another look at Barrett's esophagus. Current thinking on screening and surveillance strategies

Barrett's esophagus remains a major health problem and a risk factor for the development of esophageal adenocarcinoma. Given the low incidence of this disorder, efforts should be made to identify risk factors that target patients with GERD or known Barrett's esophagus who would most benefit from screening and surveillance strategies. It is clear that identifying esophageal adenocarcinoma at an early and treatable stage reduces morbidity and mortality. However, currently available screening tools (endoscopy with surveillance biopsies every 2 years) are expensive and not easily applied. Identification of tumor markers and other specific risk factors may be helpful in predicting who is at risk for dysplasia. Current therapeutic strategies are successful in the treatment of GERD symptoms, but further research and longer follow-up studies are needed to determine if these strategies bring about regression of Barrett's esophagus, reversal of dysplasia, or prevention of cancer.     

Clinical impact of conventional endosonography and endoscopic ultrasound-guided fine-needle aspiration in the assessment of patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma who have been referred for endoscopic ablation therapy

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection and photodynamic therapy are exciting, minimally invasive curative techniques that represent an alternative to surgery in patients with Barrett's esophagus and high-grade dysplasia or intramucosal adenocarcinoma. However, there is lack of uniformity regarding which staging method should be used prior to therapy, and some investigators even question whether staging is required prior to ablation. We report our experience with a protocol of conventional endoscopic ultrasound staging prior to endoscopic therapy. PATIENTS AND METHODS: A total of 25 consecutive patients with a diagnosis of high-grade dysplasia or intramucosal adenocarcinoma in Barrett's esophagus who had been referred to the University of Chicago for staging in preparation for endoscopic therapy between March 2002 and November 2004 were included in the study. All 25 patients underwent repeat diagnostic endoscopy and conventional endosonography with a radial echo endoscope. Any suspicious lymph nodes that were detected were sampled using endoscopic ultrasound-guided fine-needle aspiration. RESULTS: Baseline pathology in the 25 patients (mean age 70, range 49-85) revealed high-grade dysplasia in 12 patients and intramucosal carcinoma in 13 patients. Five patients were found to have submucosal invasion on conventional endosonography. Seven patients had suspicious adenopathy, six regional (N1) and one metastatic to the celiac axis (M1a). Fine-needle aspiration confirmed malignancy in five of these seven patients. Based on these results, five patients (20%) were deemed to be unsuitable candidates for endoscopic therapy. CONCLUSIONS: By detecting unsuspected malignant lymphadenopathy, conventional endosonography and endoscopic ultrasound with fine-needle aspiration dramatically changed the course of management in 20% of patients referred for endoscopic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma. Based on our results, we believe that conventional endosonography and endoscopic ultrasound with fine-needle aspiration when nodal disease is present should be performed routinely in all patients referred for endoscopic therapy in this setting.     

Medical management of Barrett's esophagus

Barrett's metaplasia of some extent is found commonly in patients with GERD. Detection is possible only by endoscopy and biopsy of the columnar appearing mucosa; no symptoms or signs distinguish patients with Barrett's metaplasia from those without. The management goals in patients with Barrett's are to alleviate reflux symptoms and to control the risk of adenocarcinoma. Symptom control is achieved primarily with PPIs. Acid inhibition does not, however, cause regression of Barrett's metaplasia and has not been shown to reduce the risk of esophageal adenocarcinoma. The risk of adenocarcinoma is managed by surveillance with endoscopy and biopsy searching for dysplastic change. LGD merits more intense surveillance. The optimal management of HGD, however, remains controversial, as evidenced by the multitude of ablation therapies that have been introduced recently. These techniques will be discussed in depth in subsequent articles in this volume.     

Staging of early adenocarcinoma in Barrett's esophagus

The main goal in the staging of patients with early neoplasia arising in the context of Barrett's esophagus (BE) is to identify individuals who are eligible for endoscopic therapy and differentiate them from those who require surgical management. To make the proper patient selection a combined staging strategy consisting of endoscopy evaluation, endoscopic ultrasonography, and endoscopic mucosal resection is necessary. In this article, the authors summarize the evidence behind each different staging modality in the setting of early BE adenocarcinoma and propose a staging approach that helps to select patients who are suitable for endoscopic therapy.     

What you need to know about Barrett's esophagus.

The incidence of Barrett's esophagus is increasing and this diagnosis is being seen more frequently in endoscopy units. Barrett's esophagus is a premalignant condition where the cells that normally line the esophagus are replaced with specialized columnar cells. Patients with Barrett's require close surveillance to monitor their condition and screen for the development of esophageal adenocarcinoma.This article provides an overview of Barrett's esophagus to better prepare gastroenterology nurses for educating and caring for this population of patients. Included is a discussion of the pathophysiology, signs and symptoms, and diagnostics of this disease entity. Current treatment options including medical management with proton pump inhibitors, endoscopic mucosal ablation techniques such as photodynamic therapy, and surgical intervention are also discussed. Current patient education approaches are also discussed.     

Autofluorescence imaging and narrow-band imaging for the detection of early neoplasia in patients with Barrett's esophagus

High-resolution endoscopy (HRE), magnifying endoscopy, auto-fluorescence endoscopy, and narrow-band imaging (NBI) are promising techniques that could improve the detection of early neoplasia and the efficacy of endoscopic surveillance in patients with Barrett's esophagus. HRE improves the detection of lesions by white light, and video autofluorescence imaging (AFI) may have additional value in terms of sensitivity. The strengths ofAFI are its high sensitivity and a high negative predictive value,while potential limitations are its moderate specificity and positive predictive value. NBI enhances the mucosal and vascular patterns (i. e. the mucosal morphology) without the need for chromoendoscopy. The mucosal morphology features may be used to distinguish early neoplasia from nondysplastic Barrett's esophagus. Magnification is required for optimal use of NBI,which is a limitation of this technique. NBI with magnifying endoscopy could, however, be used for targeted inspection of lesions detected first by HRE or AFI. This approach has been shown to reduce the false-positive rate associated with AFI while maintaining its high sensitivity. To date, AFI and NBI have been used separately in two different prototypes, but a prototype endoscope that incorporates all of these techniques has recently become available. It is expected that future refinement of the autofluorescence and narrow-band modules may further increase their diagnostic value and ultimately improve the effectiveness of surveillance of Barrett's esophagus.     

Latest developments in the endoscopic management of gastroesophageal reflux disease and Barrett's esophagus: an overview of the year's literature

The development of endoscopic techniques for the treatment of gastroesophageal reflux disease has come to an abrupt halt after some of the most widely disseminated and best evaluated techniques were withdrawn from the market. This underlines the importance of conducting high-quality endoscopic research before techniques are adopted in routine practice. The endoscopic surveillance of patients with Barrett's esophagus needs to be improved in order to be cost-effective. Alternative techniques for tissue sampling are being explored (e. g., brush cytology, imaging cytometry), as well as the use of molecular markers, to select patients who are at risk and to improve compliance by patients. New endoscopic imaging techniques (such as autofluorescence endoscopy) may improve the detection of early neoplasia in those Barrett's patients who are at risk for malignant degeneration. Subsequent endoscopic treatment should primarily consist of an endoscopic resection technique with restricted use of ablative therapies. Future studies should focus on the development of endoscopic resection techniques that allow en-bloc resection of Barrett's lesions, stepwise complete resection of the whole Barrett's segment, and/or easier and safer tissue ablation. Finally, histopathological studies are needed in order to detect risk factors for an adverse outcome after endoscopic treatment for early neoplasia in Barrett's patients.     

Barrett's esophagus surveillance: When, how often, does it work?

Barrett's esophagus is a well-known risk factor for the development of esophageal adenocarcinoma. Current practice guidelines recommend endoscopic surveillance of patients with Barrett's esophagus in an attempt to detect cancer at an early and potentially curable stage. This review addresses the rationale behind surveillance and criteria for inclusion of patients in surveillance programs as well as the appropriate technique and intervals that should be used. This work addresses other key topics in Barrett's esophagus surveillance, including the efficacy of surveillance programs, physician compliance with surveillance guidelines, cost-effectiveness of surveillance programs, and areas for future research.     

Reflux disease and Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a common clinical problem. New information suggests that infection with Helicobacter pylori may protect patients from developing GERD and its complications. Endoscopy may be used by clinicians to tailor GERD therapy, but an empirical trial of a proton-pump inhibitor may be an alternative diagnostic approach. Studies continue to show that laparoscopic antireflux surgery is a cost-effective treatment option for patients requiring maintenance therapy with proton-pump inhibitors. However, the minimally invasive nature of the operation should not alter the indications for antireflux surgery, especially for patients with atypical symptoms. It remains unclear why some patients with GERD develop Barrett's esophagus, whereas others do not. Recent guidelines suggest that patients with long-standing GERD symptoms, especially white men over 50 years of age, should undergo endoscopy at least once to screen for Barrett's esophagus. Debate concerning short-segment Barrett's esophagus continues. Intestinal metaplasia at a normal-appearing gastroesophageal junction may be associated with intestinal metaplasia of the stomach and infection with H. pylori, whereas short tongues of intestinal metaplasia in the esophagus are associated with GERD. Cancer surveillance is indicated in short-segment Barrett's esophagus, as dysplasia may develop in these patients. Barrett's esophagus is the only known risk factor for the development of esophageal adenocarcinoma, but the incidence of adenocarcinoma may be lower than previously reported. New clinical guidelines for endoscopic surveillance suggest that the surveillance interval should be lengthened to every two years in patients without dysplasia. Newer treatment options, such as thermal ablation and photodynamic therapy, continue to show promise, but are not yet ready for routine clinical use.     

Detection of Barrett's epithelium by acoustic microscopy

Barrett's esophagus is associated with increased risk of adenocarcinoma of the gastroesophageal junctional region. The presence of goblet cells (intestinal metaplasia) in columnar cell-lined esophageal mucosa defines Barrett's change. The diagnosis of Barrett's esophagus is based on the presence of intestinal metaplasia in a biopsy from an endoscopically visualized abnormal columnar epithelium. In this pilot study, acoustic microscopy was used to identify the mucosal structure of 10 distal esophageal biopsies. Sections cut at 5 microm of archival paraffin blocks on glass slides were used for this study. Acoustic microscopy permitted the identification of low- and high-power images of epithelial architecture and cellular detail, including Barrett's epithelium. This modality of visualization has the potential to detect lesions such as Barrett's metaplasia, low- and high-grade dysplasia and early carcinoma. If it can be applied to in vivo endoscopy, acoustic microscopy has the potential to increase the accuracy of the diagnosis of Barrett's esophagus, dysplasia and malignancy by providing a method of accurately directing biopsies at endoscopy.     

Mucosectomy for high-grade dysplasia in Barrett's esophagus.

Reports on the natural history of high-grade dysplasia (HGD) are sometimes contradictory, but suggest that 10-30% of patients with HGD in Barrett's esophagus (BE) will develop a demonstrable malignancy within five years of the initial diagnosis. Surgery has to be considered the best treatment for HGD or superficial carcinoma, but is contraindicated in patients with severe comorbidities. Non-surgical treatments such as intensive endoscopic surveillance, endoscopic ablative therapies, and endoscopic mucosal resection (EMR) have been proposed. EMR is a newly developed procedure promising to become a safe and reliable non-operative option for the endoscopic removal of HGD or early cancer within BE. It is important to assess the depth of invasion of the lesion and lymph node involvement before choosing EMR. This technique permits more effective staging of disease obtaining a large sample leading to a precise assessment of the depth of malignant invasion. Complications such as bleeding and perforation may occur, but can be treated endoscopically. Trials are needed to compare endoscopic therapy with surgical resection to establish clear criteria for EMR and ablative therapies.     

Barrett's esophagus and esophageal adenocarcinoma: the scope of the problem

Conclusion Barrett's esophagus is probably a more common condition than previously recognized. Although the classic radiologic findings of Barrett's esophagus are present in only a small percentage of patients, this condition should be suspected whenever reflux esophagitis or peptic strictures are demonstrated on double-contrast esophagography. Recent literature also suggests that Barrett's carcinomas comprise up to 50% of all esophageal cancers. Because of the increased risk of developing adenocarcinoma in Barrett's esophagus, endoscopic surveillance has been advocated to detect dysplastic or carcinomatous changes at the earliest possible stage. When barium studies are performed on patients with known Barrett's esophagus, the radiographs should be carefully evaluated for signs of early adenocarcinoma, so these patients can be referred for appropriate management prior to the development of advanced, unresectable tumors.     

Argon plasma coagulation in the treatment of Barrett's high-grade dysplasia and in situ adenocarcinoma

BACKGROUND AND STUDY AIMS: Endoscopic therapy of high-grade dysplasia (HGD) and superficial adenocarcinoma associated with Barrett's esophagus (BE), using Nd:YAG laser, KTP laser, or photodynamic therapy (PDT), has been reported to be effective in a curative role. Argon plasma coagulation (APC) appears to be effective in the eradication of nondysplastic Barrett's mucosa, but no results are available in the management of early neoplasms complicating BE. We report our initial experience in the application of APC in this indication. PATIENTS AND METHODS: Ten patients (mean age 74.2) with histologically proven HGD (n = 7) or in situ adenocarcinoma (n = 3) associated with BE (mean length 6 cm) and unfit for surgery were treated using APC and high-dose omeprazole (40 mg daily) until squamous re-epithelialization or complete eradication of the initially apparent lesions. Endoscopic follow-up was maintained at every 3 months. RESULTS: Complete eradication of HGD and in situ adenocarcinoma was achieved after a mean number of 3.3+/-1.5 APC sessions in 8/10 patients (80%). The eight patients with complete clearance of the neoplastic areas did not show any evidence of local recurrence during a median follow-up of 24 months (range 12-36 months). One patient with initial HGD had persistence of HGD 30 months after initial diagnosis, and one patient progressed to invasive adenocarcinoma after failure of APC and PDT. CONCLUSIONS: APC is safe and effective in the management of HGD and in situ adenocarcinoma associated with BE, and might represent an interesting alternative in selected patients who are not candidates for surgery.     

Endoscopic diagnosis of Barrett's esophagus

In Japan Barrett's mucosa is defined as columnar lined esophagus (CLE). The prevalence of Barrett's esophagus and Barrett's adenocarcinoma is very low. But in Western countries Barrett's mucosa is defined as CLE with intestinal metaplasia, and many cases of Barrett's esophagus and Barrett's adenocarcinoma are reported. The definite endoscopic diagnosis of Barrett's mucosa cannot be so easy. We investigated the positional relationship between the esophageal hiatus, squamo-columnar junction, and longitudinal vessels in persons who underwent esophagogastroduodenoscopy. Subepithelial longitudinal vessels were found at the lower esophagus in all cases. In no cases were the longitudinal vessels observed under the gastric mucosa beyond the esophageal hiatus. It is peculiar to the esophagus to be able to observe subepithelial longitudinal vessels in the vicinity of the esophago-gastric junction. When longitudinal vessels are found only under the columnar epithelium at the oral side over the esophageal hiatus from the stomach, this indicates Barrett's epithelium. Thus the definite diagnosis of Barrett's epithelium can be made by endoscopy.