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.     

Photodynamic therapy and endoscopic mucosal resection for Barrett's dysplasia and early esophageal adenocarcinoma

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic ablation with porfimer sodium photodynamic therapy (PDT) have recently been combined to improve the accuracy of histologic staging and remove superficial carcinomas. MATERIALS AND METHODS: All patients with Barrett's esophagus and high-grade dysplasia were evaluated with computed tomography and endosonography. Patients with nodular or irregular folds underwent EMR followed by PDT. RESULTS: In three patients, endoscopic mucosal resection upstaged the diagnosis to mucosal adenocarcinoma (T1N0M0). PDT successfully ablated the remaining glandular mucosa. Complications were limited to transient chest discomfort and odynophagia. CONCLUSIONS: The use of EMR resection in Barrett's high-grade dysplasia patients with mucosal irregularities resulted in histologic upstaging to mucosal adenocarcinoma, requiring higher laser light doses for PDT. PDT after EMR appears to be safe and effective for the complete elimination of Barrett's mucosal adenocarcinoma. EMR should be strongly considered for Barrett's dysplasia patients being evaluated for endoscopic ablation therapy.     

Squamous reepithelialization after circumferential endoscopic mucosal resection of superficial carcinoma arising in Barrett's esophagus

Recent reports on the results of endoscopic ablation of Barrett's mucosa have been promising, particularly when total mucosal ablation is coupled with aggressive acid-suppression treatment using high-dose proton-pump inhibitor therapy. There is also a considerable literature on reepithelialization after ablative treatments in Barrett's esophagus. This report describes a case of multifocal superficial adenocarcinoma arising in Barrett's mucosa that was successfully treated with total circumferential endoscopic mucosal resection, with a subsequent follow-up of more than 2 years. This is the first report describing the process of squamous reepithelialization after endoscopic mucosal resection in Barrett's esophagus.     

Endoluminal therapy for Barrett's esophagus

This article reviews methods to minimize the complications associated with endoscopic therapy for patients with Barrett's esophagus. To place this discussion in context, the natural history of Barrett's esophagus and the risks associated with progression to dysplasia and invasive carcinoma are reviewed. Operative esophageal resection traditionally is recommended for patients with Barrett's high-grade dysplasia and early carcinoma, and these surgical risks also are reviewed. Finally, all currently approved and commercially available methods for endoscopic ablation and resection of Barrett's disease are categorized according to their application methods of ablation: focal ablation, field ablation, and mucosal resection. The clinical experience with these devices is reviewed with their associated adverse events and complications. Caveats, concerns, and recommendations are discussed to help minimize the complications associated with the use of these important technologies that hold the promise of removing or destroying Barrett's disease to prevent the development of invasive carcinoma.     

Reflux disease and Barrett's esophagus

Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders. The key feature of GERD is reflux of gastric contents into the esophagus. Medical treatment with proton-pump inhibitors (PPIs) is well established and is considered the standard treatment. Given the high prevalence of the condition and the excellent response to medical therapy, antireflux surgery is an option for patients with volume reflux that is not properly controlled by medical therapy. Adenocarcinoma is a rare but life-threatening complication of GERD. The only known precursor lesion for esophageal adenocarcinoma is Barrett's esophagus. In recent years, a clearer understanding of the development of Barrett's and of its progression toward invasive cancer has developed. Genetic factors almost certainly determine the individual risk. The length of the Barrett's esophagus segment and the size of a hiatal hernia are associated with the risk of developing high-grade dysplasia and esophageal adenocarcinoma.With regard to the clinical management of GERD patients with Barrett's, endoscopic surveillance at 3-year intervals is now considered appropriate in the absence of dysplasia. In patients with high-grade dyspepsia, the situation is more difficult. While a considerable proportion of these patients may already have invasive cancers, there is also the possibility that there is only focal dysplasia. For this reason, it is justifiable to carry out curative endoscopic resection. Mucosal ablation procedures may also be appropriate, but these still need to be properly investigated in clinical trials.     

Radiofrequency ablation is effective for the treatment of high-grade dysplasia in Barrett's esophagus after failed photodynamic therapy

Endoscopic radiofrequency ablation (RFA) is an effective treatment for high-grade dysplasia in Barrett's esophagus in ablation-na?ve patients, but no studies have evaluated its use in patients in whom ablative therapy has previously failed. We describe 14 patients with residual high-grade dysplasia following aminolevulinic acid or Photofrin (porfimer sodium) photodynamic therapy (PDT). An overall complete reversal of dysplasia was achieved in 86?% with a combination of RFA and rescue endoscopic mucosal resection. The median total follow-up is 19 months. The rate of strictures was 7?% (1/14) and there was a low rate of buried glands (0.5?% follow-up biopsies). These data suggest RFA is both safe and effective for eradication of high-grade dysplasia in patients in whom PDT has failed.     

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.     

Intraepithelial high-grade neoplasia and early adenocarcinoma in short-segment Barrett's esophagus (SSBE): curative treatment using local endoscopic treatment techniques

BACKGROUND AND STUDY AIMS: In recent years, short-segment Barrett's esophagus (SSBE) has attracted increasing attention in the context of reflux disease. However, there is continuing controversy regarding its potential for malignant transformation. PATIENTS AND METHODS: Between October 1996 and September 1999, 50/115 patients (43 %) with intraepithelial high-grade neoplasia or early Barrett's adenocarcinoma, who underwent local endoscopic treatment, had developed a malignant lesion in an (SSBE). In the framework of a prospective observational study, 28 patients were treated with endoscopic mucosal resection (EMR), 13 with photodynamic therapy, and three with argon plasma coagulation; six patients received combinations of these treatments. RESULTS: Complete local remission was achieved in 48/49 patients (98 %). One patient switched to surgery after the first EMR, because there was submucosal tumor infiltration, and in one patient out of 50 local endoscopic treatment failed. A mean of 1.7 +/- 1.4 treatment sessions was required for local endoscopic treatment. The method-associated mortality was 0 %. The rate of relevant complications (stenosis, bleeding) was 6 % (3/50 patients). No cases of severe hemorrhage (Hb fall >2 g/dl) or perforation occurred. During a mean follow-up period of 34 +/- 10 months, metachronous intraepithelial high-grade neoplasms or early adenocarcinomas were seen in 11/48 patients (23 %), who received further successful endoscopic treatment. Four patients died during the follow-up period, but in only one patient was this due to his Barrett's adenocarcinoma (this was the patient who underwent esophageal resection). CONCLUSIONS: The malignant potential of short-segment Barrett's esophagus must not be underestimated. Organ-preserving local endoscopic treatment shows good acute-phase and long-term results. Local endoscopic treatment represents an alternative to esophageal resection in the case of intraepithelial high-grade neoplasia and selected early adenocarcinomas in Barrett's esophagus.     

Circumferential endoscopic mucosal resection in Barrett's esophagus with high-grade intraepithelial neoplasia or mucosal cancer. Preliminary results in 21 patients

BACKGROUND AND STUDY AIMS: Treatment by endoscopic mucosal resection (EMR) has been established for early lesions in Barrett's esophagus. However, the remaining Barrett's esophagus epithelium remains at risk of developing further lesions. The aim of this study was to evaluate the efficacy of circumferential endoscopic mucosectomy (circumferential EMR)s in removing not only the index lesion (high-grade intraepithelial neoplasia (HGIN) or mucosal cancer), but also the remaining Barrett's esophagus epithelium. PATIENTS AND METHODS: A total of 21 patients were included in the study (11 men, 10 women), who had Barrett's esophagus and either HGIN (n = 12) or mucosal cancer (n = 9). Of the patients, 17/21 were at high surgical risk and five had refused surgery. On the basis of preprocedure endosonography their lesions were classified as T1N0 (n = 19) or T0N0 (n = 2). The lesions and the Barrett's esophagus epithelium were removed by polypectomy after submucosal injection of 10-15 ml of saline; a double-channel endoscope was used in 15/21 cases. Circumferential EMR was performed in two sessions, the lesion and the surrounding half of the circumferential Barrett's esophagus mucosa being removed in the first session. In order to prevent the formation of esophageal stenosis, the second half of the Barrett's esophagus mucosa was resected 1 month later. RESULTS: Complications occurred in 4/21 patients (19 %), consisting of bleeding which was successfully managed by endoscopic hemostasis in all cases. No strictures were observed during follow-up (mean duration 18 months) and endoscopic resection was considered complete in 18/21 patients (86 %). For three patients, histological examination showed incomplete removal of tumor: one of these underwent surgery; two received chemoradiotherapy, and showed no evidence of residual tumor at 18 months' and 24 months' follow-up, respectively. Two patients in whom resection was initially classified as complete later presented with local recurrence and were treated again by EMR. Barrett's esophagus mucosa was completely replaced by squamous cell epithelium in 15/20 patients (75 %). CONCLUSIONS: Circumferential EMR is a noninvasive treatment of Barrett's esophagus with HGIN or mucosal cancer, with a low complication rate and good short-term clinical efficacy. Further studies should focus on long-term results and on technical improvements.     

Endoscopic therapy for Barrett's esophagus

There are many foreign reports about the endoscopic ablation therapy for Barrett's esophagus. Endoscopic ablation therapy include thermal therapy (electrocoagulation, laser etc.), photodynamic therapy or endoscopic resection and so on. Ablation of Barrett's esophagus by these therapy in combination with adequate acid suppression lead to mucosal replacement by squamous epithelium. But the true value of these endoscopic therapy has not been fully investigated. Further studies are required.     

The role of radiofrequency ablation in the management of Barrett's esophagus

Studies in the last several years have consistently shown radiofrequency ablation (RFA) to be effective, safe, and well tolerated in the treatment of nondysplastic and dysplastic Barrett's esophagus (BE). The results found at academic medical centers have been reproduced in the community setting. RFA provides a safe and cost-effective alternative to surgery or surveillance in the management of high-grade dysplasia (HGD). RFA should be given serious consideration as first-line therapy for HGD. This article reviews the evidence behind RFA to differentiate it from other management strategies in terms of efficacy, durability, safety, tolerability, and cost-effectiveness. The role of RFA in the management of BE is described, including endoscopic resection. Future directions are identified for research that will help to better define the role of RFA in the management of BE.     

Barrett's adenocarcinoma

Esophageal adenocarcinoma has seen a rapid increase in incidence throughout the Western world. Gastroesophageal reflux disease is an important risk factor for this cancer that develops in patients with Barrett's esophagus, but infection with Helicobacter pylori may reduce the risk. The diagnosis of Barrett's adenocarcinoma is often at an advanced stage and is generally associated with a poor prognosis. Several innovative techniques (eg, chromoendoscopy, magnifying endoscopy, and narrow-band imaging) have recently been developed to improve the accuracy of diagnosis. Although surgical resection has been a mainstream treatment for advanced cancer, endoscopic submucosal dissection is becoming a promising treatment procedure for mucosal cancer. Surveillance, endoscopic ablative therapies, chemoprevention, and anti-reflux surgery have been developed for cancer prevention, but are of unproven value. Further evaluation is warranted to define the optimal method and standardize the procedures for diagnosis and management of Barrett's esophagus.     

Barrett's esophagus: treatment with 5-aminolevulinic acid photodynamic therapy

Barrett's esophagus has been identified as the premalignant precursor of esophageal adenocarcinoma. The eradication of metaplastic or dysplastic columnar-lined (Barrett's) esophagus may prevent progression to esophageal adenocarcinoma. 5-Aminolevulinic acid photodynamic therapy is a simple method for the mucosal ablation of the abnormal segment. Areas of metaplastic epithelium may remain buried after treatment and continued surveillance is necessary. Repeated treatments often are necessary but are very well tolerated with few complications.     

Preface: Recent perspectives of the Barrett's esophagus

As the prevalence of reflux esophagitis is increasing in Japan, due to increased amount of energy intake and improved hygiene with the reduced H. pylori infection, the number of patients having Barrett's esophagus is also increasing. In the Western countries, adenocarcinoma of the esophagus is rapidly increasing among the white elder male, where the reflux esophagitis is more common. Terminology of Barrett's esophagus is still confusing. Recent proposal of endoscopic evaluation of Barrett's esophagus is based on the endoscopic findings, not histologic findings. In the development of adenocarcinoma of the esophagus, several steps of genetic abnormalities might be involved. We still do not know whether we may experience an increase of adenocarcinoma of the esophagus in Japan or not.     

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.     

Barrett's esophagus

Esophageal cancer staging is a widely accepted indication for endoscopic ultrasonography (EUS). The evaluation of Barrett's esophagus (BE) with EUS is indicated only when there is high-grade dysplasia or a concern for malignancy in an endoscopic lesion. Because the options for the management of BE and early adenocarcinoma are diverse, proper selection of patients by accurate staging with EUS is critical, particularly when nonoperative management is considered. For example, patients with BE with high-grade dysplasia may be offered esophagectomy in some medical centers, but nonoperative therapies such as endoscopic ablative therapy or mucosal resection may be the preferred treatment options in other gastroenterology practices. This article discusses the scientific evidence for the use of EUS in BE or early esophageal adenocarcinoma.     

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.     

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.     

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.     

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.