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.     

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.     

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 ablation of Barrett's neoplasia with a new focal radiofrequency device: initial experience with the Halo60

Radiofrequency ablation (RFA) is an accepted treatment for the eradication of dysplastic Barrett's esophagus (DBE) and residual Barrett's esophagus after endoscopic resection of intramucosal adenocarcinoma. Circumferential balloon-based and focal catheter-based RFA devices are currently used (the Halo360 and Halo90). However, a new smaller focal ablation device (the Halo60) has been developed, which may be of benefit in patients with short tongues of Barrett's neoplasia, small residual islands, difficult anatomy, or strictures. We report the first use of this device in 17 patients with either DBE or residual Barrett's esophagus after endoscopic resection of intramucosal adenocarcinoma.     

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 clinical strategy for the Barrett's esophagus

The treatment of Barrett's esophagus is controversial. Current treatments include endoscopic therapy, surgical procedures, gastric acid-suppressive therapy with proton pump inhibitors (PPIs), and cancer chemoprevention such as nonsteroidal anti-inflammatory drugs. Endoscopic therapy combined with gastric acid suppressive therapy can result in squamous reepithelialization of the Barrett's mucosa. Antireflux surgery and PPIs therapy are potential options for the treatment of gastroesophageal reflux symptoms in patients with Barrett's esophagus. But there are no prospective studies that support any alternative approach to treatment. Although chemoprevention therapy may reduce cancer risk in Barrett's esophagus, no randomized controlled trials that prove its efficacy have been reported.     

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.     

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.     

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.     

Radiologic diagnosis of Barrett's esophagus: Critical analysis of 65 cases

A recent increase in the number of Barrett's esophagis being diagnosed is probably directly related to a proportional increase in endoscopic biopsies of the esophagus and awareness of premalignant potential of Barrett's mucosa. While the endoscopist can detect Barrett's mucosa with fair degree of accuracy, the radiologic diagnosis of Barrett's esophagus still remains a diagnostic challenge despite several well established radiologic features. We reviewed 65 patients with pathologically proven Barrett's esophagus and found a wide spectrum of radiologic features. These include hiatus hernia in 49, gastroesophageal reflux in 38, strictures in 32, esophagitis in 20, and characteristic Barrett's ulcer in 12. In addition ascending or migrating strictures were found in 10, mucosal pattern simulating areae gastricae in 5, cricopharyngeal dysfunction in 4, and fixed spiral folds in 3 patients. This constellation of radiologic features, some of which have not been previously emphasized, should further assist radiologists in suggesting the diagnosis of Barrett's esophagus.     

Diagnosis and management of Barrett's esophagus: What's next?

The past decade has led to marked improvements in our understanding regarding the pathogenesis and risk of progression of Barrett's esophagus (BE), enhanced imaging technology to improve dysplasia detection, and the development and refinement of endoscopic techniques, such as mucosal ablation and endoscopic mucosal resection(EMR), to eradicate BE. However, many questions remain including identifying which, if any, candidates are most appropriate for screening for BE; how to improve current surveillance protocols; predicting which patients with BE will develop neoplastic progression; identifying the most appropriate candidates for endoscopic eradication therapy; developing algorithms for appropriate management posteradication; and understanding the potential role of chemoprophylaxis. This article describes potential future advances regarding screening, surveillance, risk stratification, endoscopic eradication therapies, and chemoprevention and provides a potential future management strategy for patients with BE.     

Curative treatment for high-grade intraepithelial neoplasia in Barrett's esophagus

BACKGROUND AND STUDY AIMS: The incidence of premalignant and malignant lesions in specialized intestinal metaplasia of the esophagus has increased dramatically in the industrialized world in recent years. This report evaluates the efficacy and safety of local endoscopic therapy for high-grade intraepithelial neoplasia (HGIN) in Barrett's esophagus. PATIENTS AND METHODS: Over a 5-year period between October 1996 and September 2001, a total of 379 patients were referred with a suspicion of early Barrett's cancer. In a prospective study, 44 patients with HGIN in Barrett's esophagus were selected for local endoscopic treatment. Endoscopic resection was carried out in 14 patients in whom the HGIN was re-detectable, and 27 patients in whom the HGIN was not re-detectable underwent photodynamic therapy (PDT). Endoscopic resection and PDT were combined in three patients. RESULTS: Complete remission was achieved in 43 of the 44 patients (97.7 %). No major complications occurred. A mean of 1 session was needed to achieve complete local remission. During a mean follow-up period of 36 months (range 7 - 61 months), recurrent or metachronous lesions were observed in six patients (17.1 %), all of whom received a second successful endoscopic treatment. CONCLUSIONS: Endoscopic therapy is a safe alternative treatment regimen for HGIN in Barrett's esophagus, providing a middle way between the widely promulgated options of a "watch-and-wait" policy and radical esophagectomy.     

Reflux disease and Barrett's esophagus

Gastroesophageal reflux disease (GERD) is still an important clinical problem. Continuing efforts are being made to establish a classification of the condition that would allow improved communications for both clinical and research purposes. In medical treatment, the trends are toward proton-pump inhibitor therapy at all stages of GERD, calling into question the role of endoscopy for tailoring individual therapy. Arguments against the use of H. pylori eradication therapy in GERD have gained importance. Surgeons are continuing to report excellent results with fundoplication, but careful studies are needed to prove whether antireflux surgery is really capable of saving costs, as its proponents claim. Barrett's esophagus is still a topic of lively interest. Since there is no method of primary prevention, endoscopy has a crucial role in detecting affected patients and guiding them toward one of the various surveillance strategies--which are not yet clearly established. The debate over short-segment Barrett's esophagus, and especially over "microscopic" Barrett's esophagus (at the squamocolumnar junction), has not yet been resolved. However, there is now less doubt that GERD is a condition associated with a substantially higher risk for the development of esophageal adenocarcinoma. Given this risk of malignant transformation, there is continuing competition between different ablation techniques; however, careful data from much larger populations will be needed before ablation reaches the stage of broad clinical application. Until specific guidelines become available, patients with Barrett's esophagus should receive endoscopic follow-up until it can be ascertained which individuals are at risk for cancer and require ablation of Barrett's mucosa.     

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.     

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.     

Successful endoscopic resection of an esophageal metastasis from a preceding squamous-cell tonsillar carcinoma

This report describes the case of a 62-year-old man with tonsillar carcinoma who had undergone esophagectomy due to an esophageal metastasis. Subsequently, a second metastasis occurred in the residual esophagus, and he presented for evaluation for local endoscopic therapy. The initial upper endoscopy revealed a type IIa - c lesion at 21 cm from the incisors, within a segment suspicious for Barrett's mucosa. As part of the complex treatment approach in this patient, endoscopic resection of the lesion was carried out using the suck-and-cut technique with ligation. Histology showed that the lesion was a metastasis from a squamous-cell carcinoma, with focal infiltration of the upper submucosal layer and vascular invasion consistent with the hypothesis of hematogenous spread from the preceding tonsillar carcinoma. The resection margins were tumor-free. At the time of writing, the patient had been recurrence-free for more than 9 months. In summary, the present paper describes a unique case of successful endoscopic resection of an esophageal metastasis associated with an antecedent tonsillar carcinoma.     

Use of lasers in Barrett's esophagus

Lasers are used in the management of Barrett's esophagus for specific tasks. First is for the ablation of non-dysplastic and dysplastic Barrett's as part of an aggressive, minimally invasive, yet unproven preventive interventional strategy for both low-risk and high-risk of progression subgroups. Secondly is for potentially curative treatment of early mucosal cancers (Tis and T1mN0M0). Finally, lasers are used for palliation of dysphagia for advanced tumors. The first two laser uses should be considered experimental and undertaken in the setting of an institutionally approved research protocol. Paramount to the success of ablation of dysplastic and early cancerous Barrett's is careful selection of patients by meticulous video endoscopic inspection of the mucosa, use of high frequency and dedicated endosonography (to uncover unsuspected tumors that penetrate the submucosa or involve lymph nodes that cannot be targeted by laser treatment), and experienced GI pathologists. Lasers can also play an important adjuvant role in the management of dysphagia for advanced cancers: however, the specific patients' characteristics for this group of patients is currently not well-defined in this era of easily placed expandable metallic stents.     

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.     

Diagnosis of Barrett's esophagus using NBI endoscopy

There are some problems as to chromo-endoscopy. To resolve this point, we believe NBI will be one of the tools supporting the endoscopic diagnosis of Barrett's esophagus. By only changing the optical filters for sequential lighting from the conventional broadband type to the narrow band type, NBI system can be installed. Through our clinical evaluations as to Barrett's mucosa, we confirmed NBI has an advantage over a conventional system with the representation of the important observation and diagnosis such as the capillary and the fine mucosal structure.     

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.