What's New in BE: An Expert Interview With Prateek Sharma
What's New in BE: An Expert Interview With Prateek Sharma
Editor's Note:
Barrett's esophagus, an acquired metaplastic condition in which healthy squamous epithelium is replaced by specialized columnar epithelium, occurs secondary to damage associated with chronic gastroesophageal reflux disease. The fundamental criteria for diagnosing Barrett's esophagus have transitioned over time, and although the disorder is thought to represent the major risk factor for the development of esophageal adenocarcinoma, most patients will not progress to malignancy. However, for those who do, the carcinogenic sequence may proceed as follows: nondysplastic to low-grade dysplasia to high-grade dysplasia to carcinoma. Data regarding the natural history of Barrett's esophagus remain limited, and therefore questions persist as to the utility of surveillance measures and mechanisms of acid reduction.Medscape spoke with Prateek Sharma, MD, Associate Professor of Medicine, Gastroenterology Section, University of Kansas School of Medicine, Kansas City, Kansas,to explore the impact of this clinically important lesion, with a view toward implications for the treating physician, as framed by data presented during Digestive Disease Week (DDW) 2006.
Medscape: On the basis of the current state of the field, what do you think are the major clinical controversies regarding Barrett's esophagus that treating physicians need to address?
Dr. Sharma: The major clinical controversies include the endoscopic recognition and diagnosis of Barrett's esophagus, as well as screening, surveillance, and management of dysplastic Barrett's esophagus.
Medscape: Endoscopic assessment of Barrett's esophagus remains a diagnostic challenge, in large part due to the absence of explicit, consensus-developed criteria. In this context, endoscopic diagnosis and grading criteria were developed and validated in a study presented during this year's DDW meeting. Can you briefly discuss the key findings of this study, with a view toward the implications for clinical practice?
Dr. Sharma: The initial step in the diagnosis of Barrett's esophagus relies on the endoscopic detection of a columnar-lined esophagus (endoscopic or suspected Barrett's). This appears to be a simple proposition; however, in reality, the accurate identification of landmarks such as the diaphragmatic hiatus and the gastroesophageal junction are not straightforward. Besides recognizing these landmarks, a number of terminologies, such as short, long, and ultra-short Barrett's, have been used ambiguously to describe various extents of Barrett's esophagus. Moreover, the interobserver variability in the detection of these landmarks and measuring the extent of Barrett's esophagus have not been carefully studied. An international working group with a special interest in Barrett's esophagus developed consensus-based criteria, which were then studied to evaluate the ability of endoscopists to accurately use these criteria in defining the endoscopic extent of Barrett's esophagus. These criteria, termed the Prague C and M criteria, had excellent reliability in the detection of segments of Barrett's lengths > 1 cm. For patients with Barrett's esophagus in both clinical and research settings, the Prague C and M criteria (shown to have excellent agreement) should be used.
Medscape: The management of high-grade dysplasia in Barrett's esophagus remains a particularly difficult area in clinical decision-making. It can be challenging to differentiate high-grade dysplasia from invasive adenocarcinoma on endoscopic biopsy, even for the expert pathologist. The "Seattle" protocol -- random 4-quadrant biopsies taken at 1- to 2-cm intervals using jumbo biopsy forceps -- has been considered reliable for the detection of early cancer in patients with high-grade dysplasia. However, this method has never been validated outside of Seattle. During this year's meeting proceedings, Kariv and colleagues set out to validate this biopsy protocol in patients with Barrett's esophagus who underwent esophagectomy for high-grade dysplasia. What can you tell us about this study and what are the clinical implications?
Dr. Sharma: The diagnosis of high-grade dysplasia in patients with Barrett's esophagus requires an intervention in the form of either surgical referral or endoscopic therapy, such as mucosal resection or ablation. Moreover, it is important to rule out coexisting adenocarcinoma because the distribution of dysplasia and adenocarcinoma within the Barrett's segment may be extremely mosaic and patchy. At the current time, it is recommended that 4-quadrant biopsies every 1 to 2 cm be obtained from the Barrett's segment. A study by Kariv and colleagues highlighted that coexisting adenocarcinoma can be detected in patients with high-grade dysplasia undergoing either a 1- or 2-cm biopsy protocol (33% vs 27%). This underscores the need for advanced endoscopic techniques that may help target areas of dysplasia, thus assisting in the accurate diagnosis of dysplasia and cancer. For patients with a diagnosis of high-grade dysplasia, intensive biopsy protocol including mucosal resection should be performed to rule out coexisting adenocarcinoma. Biopsy samples should be reviewed by expert pathologists.
Medscape: Given the lack of long-term follow-up data on endoscopic treatment, surgical esophagectomy has represented the standard therapy for high-grade dysplasia and early cancer in Barrett's esophagus. However, there is an associated mortality and morbidity of 3%-5% and 40%-50%, respectively, with this procedure. Local endoscopic therapy may therefore stand as an effective, minimally invasive treatment alternative. During DDW 2006, Pech and colleagues reported on the first 5-year follow-up from a large series involving patients with high-grade dysplasia and early adenocarcinoma who underwent endoscopic resection. What were the key findings of this study, and what are the practical implications?
Dr. Sharma: Endoscopic therapies including mucosal resection and photodynamic ablation hold promise given the alternative -- esophagectomy. However, long-term data are lacking in this field, and the number of patients treated with endoscopic therapies has also been small. This group of investigators from Germany are to be commended for reporting 5-year follow-up data on Barrett's esophagus with high-grade dysplasia and early carcinoma. Excellent complete remission rates (86%) were observed over a follow-up period of 5 years. The 5-year survival rate was 89% with an overall complication rate of 15%. Recurrences as well as metrachronous lesions were observed in 20% of patients, indicating that close follow-up after endoscopic treatment is still required in this setting. Such patients should probably be referred to high-volume and expert endoscopy centers to minimize the morbidity associated with endoscopic resection and ablation.
Medscape: As our understanding of the pathogenesis underlying Barrett's esophagus continues to evolve, what, in your opinion, are the key issues on the horizon?
Dr. Sharma: The key issues for the future include identification of a group of patients with Barrett's esophagus who are at high risk for the development of high-grade dysplasia and adenocarcinoma. Detection of neoplastic lesions during surveillance using novel endoscopic technologies will continue to evolve and will eventually replace standard white-light endoscopy. Moreover, as more long-term data become available on the use of endoscopic therapies, these patients could be offered potential curative therapy with a low morbidity and mortality.
Editor's Note:
Barrett's esophagus, an acquired metaplastic condition in which healthy squamous epithelium is replaced by specialized columnar epithelium, occurs secondary to damage associated with chronic gastroesophageal reflux disease. The fundamental criteria for diagnosing Barrett's esophagus have transitioned over time, and although the disorder is thought to represent the major risk factor for the development of esophageal adenocarcinoma, most patients will not progress to malignancy. However, for those who do, the carcinogenic sequence may proceed as follows: nondysplastic to low-grade dysplasia to high-grade dysplasia to carcinoma. Data regarding the natural history of Barrett's esophagus remain limited, and therefore questions persist as to the utility of surveillance measures and mechanisms of acid reduction.Medscape spoke with Prateek Sharma, MD, Associate Professor of Medicine, Gastroenterology Section, University of Kansas School of Medicine, Kansas City, Kansas,to explore the impact of this clinically important lesion, with a view toward implications for the treating physician, as framed by data presented during Digestive Disease Week (DDW) 2006.
Medscape: On the basis of the current state of the field, what do you think are the major clinical controversies regarding Barrett's esophagus that treating physicians need to address?
Dr. Sharma: The major clinical controversies include the endoscopic recognition and diagnosis of Barrett's esophagus, as well as screening, surveillance, and management of dysplastic Barrett's esophagus.
Medscape: Endoscopic assessment of Barrett's esophagus remains a diagnostic challenge, in large part due to the absence of explicit, consensus-developed criteria. In this context, endoscopic diagnosis and grading criteria were developed and validated in a study presented during this year's DDW meeting. Can you briefly discuss the key findings of this study, with a view toward the implications for clinical practice?
Dr. Sharma: The initial step in the diagnosis of Barrett's esophagus relies on the endoscopic detection of a columnar-lined esophagus (endoscopic or suspected Barrett's). This appears to be a simple proposition; however, in reality, the accurate identification of landmarks such as the diaphragmatic hiatus and the gastroesophageal junction are not straightforward. Besides recognizing these landmarks, a number of terminologies, such as short, long, and ultra-short Barrett's, have been used ambiguously to describe various extents of Barrett's esophagus. Moreover, the interobserver variability in the detection of these landmarks and measuring the extent of Barrett's esophagus have not been carefully studied. An international working group with a special interest in Barrett's esophagus developed consensus-based criteria, which were then studied to evaluate the ability of endoscopists to accurately use these criteria in defining the endoscopic extent of Barrett's esophagus. These criteria, termed the Prague C and M criteria, had excellent reliability in the detection of segments of Barrett's lengths > 1 cm. For patients with Barrett's esophagus in both clinical and research settings, the Prague C and M criteria (shown to have excellent agreement) should be used.
Medscape: The management of high-grade dysplasia in Barrett's esophagus remains a particularly difficult area in clinical decision-making. It can be challenging to differentiate high-grade dysplasia from invasive adenocarcinoma on endoscopic biopsy, even for the expert pathologist. The "Seattle" protocol -- random 4-quadrant biopsies taken at 1- to 2-cm intervals using jumbo biopsy forceps -- has been considered reliable for the detection of early cancer in patients with high-grade dysplasia. However, this method has never been validated outside of Seattle. During this year's meeting proceedings, Kariv and colleagues set out to validate this biopsy protocol in patients with Barrett's esophagus who underwent esophagectomy for high-grade dysplasia. What can you tell us about this study and what are the clinical implications?
Dr. Sharma: The diagnosis of high-grade dysplasia in patients with Barrett's esophagus requires an intervention in the form of either surgical referral or endoscopic therapy, such as mucosal resection or ablation. Moreover, it is important to rule out coexisting adenocarcinoma because the distribution of dysplasia and adenocarcinoma within the Barrett's segment may be extremely mosaic and patchy. At the current time, it is recommended that 4-quadrant biopsies every 1 to 2 cm be obtained from the Barrett's segment. A study by Kariv and colleagues highlighted that coexisting adenocarcinoma can be detected in patients with high-grade dysplasia undergoing either a 1- or 2-cm biopsy protocol (33% vs 27%). This underscores the need for advanced endoscopic techniques that may help target areas of dysplasia, thus assisting in the accurate diagnosis of dysplasia and cancer. For patients with a diagnosis of high-grade dysplasia, intensive biopsy protocol including mucosal resection should be performed to rule out coexisting adenocarcinoma. Biopsy samples should be reviewed by expert pathologists.
Medscape: Given the lack of long-term follow-up data on endoscopic treatment, surgical esophagectomy has represented the standard therapy for high-grade dysplasia and early cancer in Barrett's esophagus. However, there is an associated mortality and morbidity of 3%-5% and 40%-50%, respectively, with this procedure. Local endoscopic therapy may therefore stand as an effective, minimally invasive treatment alternative. During DDW 2006, Pech and colleagues reported on the first 5-year follow-up from a large series involving patients with high-grade dysplasia and early adenocarcinoma who underwent endoscopic resection. What were the key findings of this study, and what are the practical implications?
Dr. Sharma: Endoscopic therapies including mucosal resection and photodynamic ablation hold promise given the alternative -- esophagectomy. However, long-term data are lacking in this field, and the number of patients treated with endoscopic therapies has also been small. This group of investigators from Germany are to be commended for reporting 5-year follow-up data on Barrett's esophagus with high-grade dysplasia and early carcinoma. Excellent complete remission rates (86%) were observed over a follow-up period of 5 years. The 5-year survival rate was 89% with an overall complication rate of 15%. Recurrences as well as metrachronous lesions were observed in 20% of patients, indicating that close follow-up after endoscopic treatment is still required in this setting. Such patients should probably be referred to high-volume and expert endoscopy centers to minimize the morbidity associated with endoscopic resection and ablation.
Medscape: As our understanding of the pathogenesis underlying Barrett's esophagus continues to evolve, what, in your opinion, are the key issues on the horizon?
Dr. Sharma: The key issues for the future include identification of a group of patients with Barrett's esophagus who are at high risk for the development of high-grade dysplasia and adenocarcinoma. Detection of neoplastic lesions during surveillance using novel endoscopic technologies will continue to evolve and will eventually replace standard white-light endoscopy. Moreover, as more long-term data become available on the use of endoscopic therapies, these patients could be offered potential curative therapy with a low morbidity and mortality.
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