Issues in Barrett's Esophagus: An Expert Interview With Prateek Sharma
Issues in Barrett's Esophagus: An Expert Interview With Prateek Sharma
Editor's Note:
Barrett's esophagus, defined by the presence of intestinal metaplasia within a columnar epithelium-lined esophagus, has been correlated with the frequency and duration of symptoms of gastroesophageal reflux, the presence and size of a hiatal hernia, and the degree of lower esophageal sphincter incompetence. Over the last decade, evidence has suggested that this specialized intestinal metaplasia, the hallmark histologic lesion of Barrett's esophagus, predisposes to dysplasia and esophageal adenocarcinoma, regardless of the endoscopic location. Medscape spoke with Prateek Sharma, MD, Associate Professor of Medicine, Gastroenterology Section, University of Kansas School of Medicine, VA Medical Center, Kansas City, Missouri, to discuss the latest advances in our understanding of this clinically important lesion, with a view toward the implications for screening and surveillance, as framed by data presented during the American College of Gastroenterology 2006 Annual Scientific Meeting and Postgraduate Course.
Medscape: Given the current state of the field, what, in your opinion, are the major outstanding gaps in our clinical knowledge about Barrett's esophagus?
Dr. Sharma: Barrett's esophagus continues to intrigue investigators as well as clinicians, given the increased recognition of this entity over the past several years. The increase in incidence of esophageal adenocarcinoma during the same time interval has also led to a plethora of research regarding this lesion. Screening and surveillance issues in Barrett's esophagus remain controversial. Identifying a high-risk patient group that can benefit from these procedures will be key. Alternative methods for screening and surveillance with the advent of technology such as wireless capsule endoscopy and other novel imaging techniques need to be further evaluated. With respect to therapy, chemoprevention and endoscopic therapies appear most promising in patients with Barrett's esophagus, but long-term data are lacking.
Medscape: The incidence of esophageal adenocarcinoma has been rapidly increasing in the United States and parts of Western Europe. A number of risk factors (gastroesophageal reflux, abdominal obesity, male sex) have been linked to Barrett's esophagus, the recognized precursor lesion of esophageal adenocarcinoma. In this context, Rubenstein and colleagues presented the results of an interesting study during this year's ACG meeting that looked at whether blood levels of adiponectin, a peptide secreted by adipocytes, were associated with the risk for Barrett's esophagus. What can you tell us about this study and what were the key findings?
Dr. Sharma: Adiponectin, a peptide secreted by adipocytes and postulated to reduce inflammation, has been inversely associated with abdominal obesity, and low levels of this peptide have been linked to different gastrointestinal cancers. In this case-control study, plasma levels of adiponectin were compared in patients with and without Barrett's esophagus. The study authors determined that for each 10-ng/mL decrease in adiponectin level, the odds of Barrett's esophagus increased by 5-fold (odds ratio, 5.0; 95% confidence interval = 1.2-20.0). This effect persisted when controlling for gastroesophageal reflux disease symptoms and body mass index. This study, thus, showed that low adiponectin blood levels were significantly associated with the presence of Barrett's esophagus, and one can speculate that the effect of obesity on esophageal diseases may be mediated through decreases in adiponectin levels. This is one of the first steps in our understanding of how increasing obesity in the Western World may be having an impact on the increased incidence of esophageal adenocarcinoma.
Medscape: Periodic endoscopic surveillance of Barrett's epithelium is recommended to help target patients at risk for adenocarcinoma of the esophagus. However, despite advances in our understanding of Barrett's esophagus, a number of issues relating to screening and surveillance remain controversial. During this year's ACG meeting, data were reported on the effect of prior esophagoduodenoscopy (EGD) on long-term survival from esophageal adenocarcinoma and on the efficacy of string-capsule endoscopy vs EGD in the screening of Barrett's esophagus. Can you briefly discuss the key findings of these studies, with a view toward their implications for clinical practice?
Dr. Sharma: Patients with Barrett's esophagus are typically enrolled in surveillance programs for the early detection of neoplasia, with the ultimate goal of reducing mortality from esophageal adenocarcinoma. However, there are no prospective randomized trials that have shown surveillance to be effective. Given the lack of such prospective randomized trials, cohort and case-controlled studies have attempted to address this issue. In this study by Rubinstein and colleagues, the national database of the Veterans Administration was used to identify patients with a prior diagnosis of esophageal adenocarcinoma during the years 1995-2003. The study authors identified 155 cases of esophageal adenocarcinoma, and data were collected for upper endoscopies performed within 5 years prior to the cancer diagnosis. Patients with a history of endoscopy within 1 year prior to cancer diagnosis were diagnosed at earlier stages and appeared to have a better short-term survival compared with those without history of a previous endoscopy -- but there was no survival advantage after 6 years of follow-up. These study findings do not suggest the advantage of surveillance endoscopy; however, the interpretation of the data is limited by the study design as well as the relatively few cases of esophageal adenocarcinoma that were evaluated. This calls for prospective randomized trials to evaluate the benefit of surveillance endoscopy and for better markers for cancer progression in Barrett's esophagus.
The introduction of esophageal capsule endoscopy, a noninvasive and well-tolerated procedure for the detection of a columnar lined esophagus, represents a novel method of screening for Barrett's esophagus. Investigators from Phoenix, Arizona, have attempted to screen for Barrett's esophagus using a string capsule, whereby a capsule, with a string attached, is swallowed by the patient and the distal esophagus is examined by pulling the string back and forth. The accuracy of string-capsule endoscopy for the detection of suspected Barrett's esophagus was found to be 83% in these patients, suggesting that this technique may be a viable option for screening for Barrett's esophagus.
Medscape: Esophageal cancer most commonly develops after an insidious progression from intestinal metaplasia to low-grade dysplasia to high-grade dysplasia. There has been increasing application of endoscopic ablation therapy in patients with Barrett's esophagus with dysplasia. During ACG 2006, Wells and colleagues presented their experience with a new system that allows for circumferential ablation of Barrett's esophagus with dysplasia. What can you tell us about their findings, and what are the implications for treatment?
Dr. Sharma: There has been considerable interest in endoscopic therapies as potential alternatives to esophagectomy in Barrett's esophagus patients with high-grade dysplasia. Ablation using a circumferential balloon has been previously reported on in patients with nondysplastic Barrett's esophagus. In this current study, Wells and colleagues reported their results with this ablation technique in patients with dysplastic Barrett's esophagus. Five of 9 high-grade dysplasia patients treated had complete ablation of high-grade dysplasia and Barrett's esophagus; 2 had persistent high-grade dysplasia; and 2 had downstaging of dysplasia. Among the patients treated for low-grade dysplasia, 1 developed intramucosal cancer during follow-up. Thus, patients undergoing endoscopic therapy still need to be followed closely for assurance of complete ablation and to document residual intestinal metaplasia.
Medscape: What else is new regarding the emerging therapeutic landscape for Barrett's esophagus?
Dr. Sharma: Therapy for Barrett's esophagus has seen major advances in recent years, especially in the endoscopic treatment of dysplastic Barrett's esophagus. Patients with high-grade dysplasia now have the viable option of undergoing endoscopic therapy. However, accurate staging of neoplasia is critical before such therapy is preformed. If endoscopic treatment is performed by experienced endoscopists and in centers of excellence, we will probably see improved efficacy and reduced morbidity. However, given reports of recurrent and metachronous lesions, these patients still need to be followed in surveillance programs after endoscopic therapy. For patients with nondysplastic Barrett's esophagus, the therapy of the future will likely be a chemopreventative agent. Long-term randomized trials on chemoprevention have just been initiated and will eventually provide us with much-needed answers.
Editor's Note:
Barrett's esophagus, defined by the presence of intestinal metaplasia within a columnar epithelium-lined esophagus, has been correlated with the frequency and duration of symptoms of gastroesophageal reflux, the presence and size of a hiatal hernia, and the degree of lower esophageal sphincter incompetence. Over the last decade, evidence has suggested that this specialized intestinal metaplasia, the hallmark histologic lesion of Barrett's esophagus, predisposes to dysplasia and esophageal adenocarcinoma, regardless of the endoscopic location. Medscape spoke with Prateek Sharma, MD, Associate Professor of Medicine, Gastroenterology Section, University of Kansas School of Medicine, VA Medical Center, Kansas City, Missouri, to discuss the latest advances in our understanding of this clinically important lesion, with a view toward the implications for screening and surveillance, as framed by data presented during the American College of Gastroenterology 2006 Annual Scientific Meeting and Postgraduate Course.
Medscape: Given the current state of the field, what, in your opinion, are the major outstanding gaps in our clinical knowledge about Barrett's esophagus?
Dr. Sharma: Barrett's esophagus continues to intrigue investigators as well as clinicians, given the increased recognition of this entity over the past several years. The increase in incidence of esophageal adenocarcinoma during the same time interval has also led to a plethora of research regarding this lesion. Screening and surveillance issues in Barrett's esophagus remain controversial. Identifying a high-risk patient group that can benefit from these procedures will be key. Alternative methods for screening and surveillance with the advent of technology such as wireless capsule endoscopy and other novel imaging techniques need to be further evaluated. With respect to therapy, chemoprevention and endoscopic therapies appear most promising in patients with Barrett's esophagus, but long-term data are lacking.
Medscape: The incidence of esophageal adenocarcinoma has been rapidly increasing in the United States and parts of Western Europe. A number of risk factors (gastroesophageal reflux, abdominal obesity, male sex) have been linked to Barrett's esophagus, the recognized precursor lesion of esophageal adenocarcinoma. In this context, Rubenstein and colleagues presented the results of an interesting study during this year's ACG meeting that looked at whether blood levels of adiponectin, a peptide secreted by adipocytes, were associated with the risk for Barrett's esophagus. What can you tell us about this study and what were the key findings?
Dr. Sharma: Adiponectin, a peptide secreted by adipocytes and postulated to reduce inflammation, has been inversely associated with abdominal obesity, and low levels of this peptide have been linked to different gastrointestinal cancers. In this case-control study, plasma levels of adiponectin were compared in patients with and without Barrett's esophagus. The study authors determined that for each 10-ng/mL decrease in adiponectin level, the odds of Barrett's esophagus increased by 5-fold (odds ratio, 5.0; 95% confidence interval = 1.2-20.0). This effect persisted when controlling for gastroesophageal reflux disease symptoms and body mass index. This study, thus, showed that low adiponectin blood levels were significantly associated with the presence of Barrett's esophagus, and one can speculate that the effect of obesity on esophageal diseases may be mediated through decreases in adiponectin levels. This is one of the first steps in our understanding of how increasing obesity in the Western World may be having an impact on the increased incidence of esophageal adenocarcinoma.
Medscape: Periodic endoscopic surveillance of Barrett's epithelium is recommended to help target patients at risk for adenocarcinoma of the esophagus. However, despite advances in our understanding of Barrett's esophagus, a number of issues relating to screening and surveillance remain controversial. During this year's ACG meeting, data were reported on the effect of prior esophagoduodenoscopy (EGD) on long-term survival from esophageal adenocarcinoma and on the efficacy of string-capsule endoscopy vs EGD in the screening of Barrett's esophagus. Can you briefly discuss the key findings of these studies, with a view toward their implications for clinical practice?
Dr. Sharma: Patients with Barrett's esophagus are typically enrolled in surveillance programs for the early detection of neoplasia, with the ultimate goal of reducing mortality from esophageal adenocarcinoma. However, there are no prospective randomized trials that have shown surveillance to be effective. Given the lack of such prospective randomized trials, cohort and case-controlled studies have attempted to address this issue. In this study by Rubinstein and colleagues, the national database of the Veterans Administration was used to identify patients with a prior diagnosis of esophageal adenocarcinoma during the years 1995-2003. The study authors identified 155 cases of esophageal adenocarcinoma, and data were collected for upper endoscopies performed within 5 years prior to the cancer diagnosis. Patients with a history of endoscopy within 1 year prior to cancer diagnosis were diagnosed at earlier stages and appeared to have a better short-term survival compared with those without history of a previous endoscopy -- but there was no survival advantage after 6 years of follow-up. These study findings do not suggest the advantage of surveillance endoscopy; however, the interpretation of the data is limited by the study design as well as the relatively few cases of esophageal adenocarcinoma that were evaluated. This calls for prospective randomized trials to evaluate the benefit of surveillance endoscopy and for better markers for cancer progression in Barrett's esophagus.
The introduction of esophageal capsule endoscopy, a noninvasive and well-tolerated procedure for the detection of a columnar lined esophagus, represents a novel method of screening for Barrett's esophagus. Investigators from Phoenix, Arizona, have attempted to screen for Barrett's esophagus using a string capsule, whereby a capsule, with a string attached, is swallowed by the patient and the distal esophagus is examined by pulling the string back and forth. The accuracy of string-capsule endoscopy for the detection of suspected Barrett's esophagus was found to be 83% in these patients, suggesting that this technique may be a viable option for screening for Barrett's esophagus.
Medscape: Esophageal cancer most commonly develops after an insidious progression from intestinal metaplasia to low-grade dysplasia to high-grade dysplasia. There has been increasing application of endoscopic ablation therapy in patients with Barrett's esophagus with dysplasia. During ACG 2006, Wells and colleagues presented their experience with a new system that allows for circumferential ablation of Barrett's esophagus with dysplasia. What can you tell us about their findings, and what are the implications for treatment?
Dr. Sharma: There has been considerable interest in endoscopic therapies as potential alternatives to esophagectomy in Barrett's esophagus patients with high-grade dysplasia. Ablation using a circumferential balloon has been previously reported on in patients with nondysplastic Barrett's esophagus. In this current study, Wells and colleagues reported their results with this ablation technique in patients with dysplastic Barrett's esophagus. Five of 9 high-grade dysplasia patients treated had complete ablation of high-grade dysplasia and Barrett's esophagus; 2 had persistent high-grade dysplasia; and 2 had downstaging of dysplasia. Among the patients treated for low-grade dysplasia, 1 developed intramucosal cancer during follow-up. Thus, patients undergoing endoscopic therapy still need to be followed closely for assurance of complete ablation and to document residual intestinal metaplasia.
Medscape: What else is new regarding the emerging therapeutic landscape for Barrett's esophagus?
Dr. Sharma: Therapy for Barrett's esophagus has seen major advances in recent years, especially in the endoscopic treatment of dysplastic Barrett's esophagus. Patients with high-grade dysplasia now have the viable option of undergoing endoscopic therapy. However, accurate staging of neoplasia is critical before such therapy is preformed. If endoscopic treatment is performed by experienced endoscopists and in centers of excellence, we will probably see improved efficacy and reduced morbidity. However, given reports of recurrent and metachronous lesions, these patients still need to be followed in surveillance programs after endoscopic therapy. For patients with nondysplastic Barrett's esophagus, the therapy of the future will likely be a chemopreventative agent. Long-term randomized trials on chemoprevention have just been initiated and will eventually provide us with much-needed answers.
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