daw
06-01-2005, 12:54 PM
From Medscape Gastroenterology
Expert Interview
Ongoing Challenges in Barrett's Esophagus: An Expert Interview With Prateek Sharma, MD
Editor's Note:
Barrett's esophagus occurs as a complication of long-standing gastroesophageal reflux and is an important risk factor for the development of esophageal adenocarcinoma. The condition is defined by the presence of intestinal metaplasia within the setting of columnar epithelium-lined distal esophagus. One of the key challenges facing the clinician at the front lines of management is that the majority of patients with this lesion go unrecognized and that Barrett's esophagus-related cancers usually present at a late stage with symptoms of dysphagia and weight loss. With the incidence of esophageal adenocarcinoma increasing in most countries in the Western hemisphere, and the poor prognosis associated with this malignancy, proper screening and surveillance of these patients is key to detecting cancer at an early and potentially curable stage. Medscape spoke with Prateek Sharma, MD, Associate Professor of Medicine, Gastroenterology Section, University of Kansas School of Medicine, Overland Park, Kansas; Director of Gastroenterology Fellowship Training, VA Medical Center, Kansas City, Missouri, to discuss the impact of this clinically important lesion as well as the current challenges facing the physician treating the patient with Barrett's esophagus, as framed by data presented during Digestive Disease Week (DDW) 2005.
Medscape: Although the etiology and risk factors for Barrett's esophagus have not been completely defined, its presence has been correlated with the frequency and duration of symptoms of gastroesophageal reflux, the presence and size of a hiatal hernia, and the status of the lower esophageal sphincter. Additionally, data have suggested that the nature of the refluxed material is also clinically important. During this year's DDW meeting, Sital and colleagues[1] presented the results of a study examining the impact of bile reflux on the pathogenesis of Barrett's esophagus. What can you tell us about this study and what were the key findings?
Dr. Sharma: Both acid and bile reflux have been implicated in the pathogenesis of Barrett's esophagus. It is well known that both acid and bilirubin exposure are significantly higher in patients with Barrett's esophagus compared with in patients with gastroesophageal reflux disease (GERD) without Barrett's esophagus. In this study, Sital and colleagues demonstrated significantly higher levels of bilirubin exposure in patients with Barrett's esophagus compared with in patients with GERD or controls without Barrett's esophagus. The study authors also examined the levels of bile acid in patients with Barrett's esophagus taking acid-suppressive therapy (proton-pump inhibitors). In bile samples obtained from the duodenum during endoscopy; the levels of glycine ursodeoxycholic acid ("protective") was low, whereas levels of taurine deoxycholic acid ("toxic" secondary bile acid) were high. This study emphasizes the role of bile reflux in patients with Barrett's esophagus. However, whether the change in the milieu of the refluxate in patients on acid-suppressive therapy has a role in the progression of Barrett's esophagus remains to be further studied.
Medscape: It is recognized that Barrett's esophagus is associated with an increased risk of esophageal adenocarcinoma. Indeed, early malignant transformation of Barrett's mucosa is frequently not visible endoscopically and may therefore go undetected until disease progresses to invasive adenocarcinoma. The difficulties encountered even with the use of advanced endoscopic technology are evident in this setting, in that high-grade intraepithelial neoplasia (HGIN) may be incidentally detected in random biopsies in the absence of a lesion visible by endoscopic examination.
Within this context, 2 key studies were presented during DDW 2005 that looked at new techniques for detecting intraepithelial neoplasia. In the first of these studies, Haringsma and colleagues[2] presented the results of a pilot trial involving the use of a novel fluorescence endoscopy system, and in the second, Kara and colleagues[3] examined the utility of combination video autofluorescence imaging, and narrow band imaging in improving the detection of HGIN. Can you briefly discuss the key findings of these studies, with a view toward their implications for clinical practice?
Dr. Sharma: Currently, the detection of dysplasia and cancer in the setting of Barrett's esophagus requires random biopsies obtained during standard conventional endoscopy. These biopsies sample a very small surface area of the Barrett's segment, and dysplasia and adenocarcinoma can easily be missed, especially in flat Barrett's mucosa. A number of novel imaging techniques, such as those studied by these 2 groups of investigators from The Netherlands, are being evaluated in patients with Barrett's esophagus, including high-resolution magnification endoscopy, autofluorescence imaging, and narrow-band imaging, to name a few. In the study by Kara and colleagues,[3] areas of high-grade dysplasia and early adenocarcinoma were readily detected by autofluorescence imaging as compared with standard endoscopy. One of the advantages of using an imaging technique is its ability to scan larger areas of the Barrett's segment, as well as demonstrating in real-time the high-risk areas that could then be targeted for biopsy or therapy. Validation of these preliminary results in the future will dramatically change clinical practice from taking random biopsies to performing more targeted biopsies and possibly treatment during the same endoscopy session. Haringsma and colleagues[2] evaluated the role of light-induced fluorescence endoscopy and had encouraging results similar to those obtained in the previous study by Kara and colleagues.
Medscape: Barrett's esophagus is characterized by the replacement of normal esophageal squamous epithelium by a specialized columnar epithelium. During this year's meeting proceedings, Glickman and colleagues[4] presented the results of an interesting study testing their hypothesis that a distinctive type of multilayered epithelium, exhibiting features of both squamous and columnar epithelium, represents an early phase in the columnar metaplasia of Barrett's esophagus. What were the key findings of this study and what, in your view, are the clinical implications?
Dr. Sharma: The cell of origin and the pathogenesis of Barrett's esophagus have been the focus of recent research. It has been postulated that there is a distinctive type of epithelium, termed the "multilayered epithelium," that exhibits features of both squamous and columnar mucosa that may represent an early step in the pathogenesis and origin of Barrett's esophagus. In this study, Glickman and colleagues[4] evaluated the presence of this specific type of epithelium in patients with GERD, Barrett's esophagus, and in controls. Multilayered epithelium was diagnosed in 27% of patients with long-segment Barrett's esophagus, in 36% of patients with short-segment Barrett's esophagus, in 25% of patients with GERD, and in only 10% of controls ( P < .05 [for comparison of prevalence with controls]). It appears that this epithelium is a marker for the presence of intestinal metaplasia, although the study authors speculate that it may be present before Barrett's esophagus is endoscopically detected. Clinically, this may be useful for the identification of patients at risk for Barrett's esophagus.
Medscape: As our understanding of the pathogenesis of Barrett's esophagus continues to evolve, what key issues are next on the horizon?
Dr. Sharma: The key issues of extreme importance for clinical practice in the future are as follows:
.Define the group of patients with and without reflux disease who are at risk for developing Barrett's esophagus.
.Apply our understanding of the pathogenesis of Barrett's esophagus and neoplasia to devise chemoprevention strategies to reduce the incidence of dysplasia and cancer in Barrett's esophagus.
.Determine the role of new technologies in diagnosing dysplasia and adenocarcinoma in Barrett's esophagus.
Expert Interview
Ongoing Challenges in Barrett's Esophagus: An Expert Interview With Prateek Sharma, MD
Editor's Note:
Barrett's esophagus occurs as a complication of long-standing gastroesophageal reflux and is an important risk factor for the development of esophageal adenocarcinoma. The condition is defined by the presence of intestinal metaplasia within the setting of columnar epithelium-lined distal esophagus. One of the key challenges facing the clinician at the front lines of management is that the majority of patients with this lesion go unrecognized and that Barrett's esophagus-related cancers usually present at a late stage with symptoms of dysphagia and weight loss. With the incidence of esophageal adenocarcinoma increasing in most countries in the Western hemisphere, and the poor prognosis associated with this malignancy, proper screening and surveillance of these patients is key to detecting cancer at an early and potentially curable stage. Medscape spoke with Prateek Sharma, MD, Associate Professor of Medicine, Gastroenterology Section, University of Kansas School of Medicine, Overland Park, Kansas; Director of Gastroenterology Fellowship Training, VA Medical Center, Kansas City, Missouri, to discuss the impact of this clinically important lesion as well as the current challenges facing the physician treating the patient with Barrett's esophagus, as framed by data presented during Digestive Disease Week (DDW) 2005.
Medscape: Although the etiology and risk factors for Barrett's esophagus have not been completely defined, its presence has been correlated with the frequency and duration of symptoms of gastroesophageal reflux, the presence and size of a hiatal hernia, and the status of the lower esophageal sphincter. Additionally, data have suggested that the nature of the refluxed material is also clinically important. During this year's DDW meeting, Sital and colleagues[1] presented the results of a study examining the impact of bile reflux on the pathogenesis of Barrett's esophagus. What can you tell us about this study and what were the key findings?
Dr. Sharma: Both acid and bile reflux have been implicated in the pathogenesis of Barrett's esophagus. It is well known that both acid and bilirubin exposure are significantly higher in patients with Barrett's esophagus compared with in patients with gastroesophageal reflux disease (GERD) without Barrett's esophagus. In this study, Sital and colleagues demonstrated significantly higher levels of bilirubin exposure in patients with Barrett's esophagus compared with in patients with GERD or controls without Barrett's esophagus. The study authors also examined the levels of bile acid in patients with Barrett's esophagus taking acid-suppressive therapy (proton-pump inhibitors). In bile samples obtained from the duodenum during endoscopy; the levels of glycine ursodeoxycholic acid ("protective") was low, whereas levels of taurine deoxycholic acid ("toxic" secondary bile acid) were high. This study emphasizes the role of bile reflux in patients with Barrett's esophagus. However, whether the change in the milieu of the refluxate in patients on acid-suppressive therapy has a role in the progression of Barrett's esophagus remains to be further studied.
Medscape: It is recognized that Barrett's esophagus is associated with an increased risk of esophageal adenocarcinoma. Indeed, early malignant transformation of Barrett's mucosa is frequently not visible endoscopically and may therefore go undetected until disease progresses to invasive adenocarcinoma. The difficulties encountered even with the use of advanced endoscopic technology are evident in this setting, in that high-grade intraepithelial neoplasia (HGIN) may be incidentally detected in random biopsies in the absence of a lesion visible by endoscopic examination.
Within this context, 2 key studies were presented during DDW 2005 that looked at new techniques for detecting intraepithelial neoplasia. In the first of these studies, Haringsma and colleagues[2] presented the results of a pilot trial involving the use of a novel fluorescence endoscopy system, and in the second, Kara and colleagues[3] examined the utility of combination video autofluorescence imaging, and narrow band imaging in improving the detection of HGIN. Can you briefly discuss the key findings of these studies, with a view toward their implications for clinical practice?
Dr. Sharma: Currently, the detection of dysplasia and cancer in the setting of Barrett's esophagus requires random biopsies obtained during standard conventional endoscopy. These biopsies sample a very small surface area of the Barrett's segment, and dysplasia and adenocarcinoma can easily be missed, especially in flat Barrett's mucosa. A number of novel imaging techniques, such as those studied by these 2 groups of investigators from The Netherlands, are being evaluated in patients with Barrett's esophagus, including high-resolution magnification endoscopy, autofluorescence imaging, and narrow-band imaging, to name a few. In the study by Kara and colleagues,[3] areas of high-grade dysplasia and early adenocarcinoma were readily detected by autofluorescence imaging as compared with standard endoscopy. One of the advantages of using an imaging technique is its ability to scan larger areas of the Barrett's segment, as well as demonstrating in real-time the high-risk areas that could then be targeted for biopsy or therapy. Validation of these preliminary results in the future will dramatically change clinical practice from taking random biopsies to performing more targeted biopsies and possibly treatment during the same endoscopy session. Haringsma and colleagues[2] evaluated the role of light-induced fluorescence endoscopy and had encouraging results similar to those obtained in the previous study by Kara and colleagues.
Medscape: Barrett's esophagus is characterized by the replacement of normal esophageal squamous epithelium by a specialized columnar epithelium. During this year's meeting proceedings, Glickman and colleagues[4] presented the results of an interesting study testing their hypothesis that a distinctive type of multilayered epithelium, exhibiting features of both squamous and columnar epithelium, represents an early phase in the columnar metaplasia of Barrett's esophagus. What were the key findings of this study and what, in your view, are the clinical implications?
Dr. Sharma: The cell of origin and the pathogenesis of Barrett's esophagus have been the focus of recent research. It has been postulated that there is a distinctive type of epithelium, termed the "multilayered epithelium," that exhibits features of both squamous and columnar mucosa that may represent an early step in the pathogenesis and origin of Barrett's esophagus. In this study, Glickman and colleagues[4] evaluated the presence of this specific type of epithelium in patients with GERD, Barrett's esophagus, and in controls. Multilayered epithelium was diagnosed in 27% of patients with long-segment Barrett's esophagus, in 36% of patients with short-segment Barrett's esophagus, in 25% of patients with GERD, and in only 10% of controls ( P < .05 [for comparison of prevalence with controls]). It appears that this epithelium is a marker for the presence of intestinal metaplasia, although the study authors speculate that it may be present before Barrett's esophagus is endoscopically detected. Clinically, this may be useful for the identification of patients at risk for Barrett's esophagus.
Medscape: As our understanding of the pathogenesis of Barrett's esophagus continues to evolve, what key issues are next on the horizon?
Dr. Sharma: The key issues of extreme importance for clinical practice in the future are as follows:
.Define the group of patients with and without reflux disease who are at risk for developing Barrett's esophagus.
.Apply our understanding of the pathogenesis of Barrett's esophagus and neoplasia to devise chemoprevention strategies to reduce the incidence of dysplasia and cancer in Barrett's esophagus.
.Determine the role of new technologies in diagnosing dysplasia and adenocarcinoma in Barrett's esophagus.