Barrett's Esophagus: Risk of Dysplasia or Adenocarcinoma
Barrett's Esophagus: Risk of Dysplasia or Adenocarcinoma
Background & Aims: The risks of dysplasia and esophageal adenocarcinoma (EAC) are not clear for patients with nondysplastic Barrett's esophagus (NDBE); the rate of progression has been overestimated in previous studies. We studied the incidences of dysplasia and EAC and investigated factors associated with progression of BE.
Methods: The BE study is a multicenter outcomes project of a large cohort of patients with BE. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Patients followed up for at least 1 year after the index endoscopy examination were included, whereas those diagnosed with dysplasia and EAC within 1 year of diagnosis with BE (prevalent cases) were excluded. Of 3334 patients with BE, 1204 met the inclusion criteria (93.7% Caucasian; 88% male; mean age, 59.3 y) and were followed up for a mean of 5.52 years (6644.5 patient-years).
Results: Eighteen patients developed EAC (incidence, 0.27%/y; 95% confidence interval [CI], 0.17–0.43) and 32 developed HGD (incidence, 0.48%/y; 95% CI, 0.34–0.68). The incidence of HGD and EAC was 0.63%/y (95% CI, 0.47–0.86). There were 217 cases of low-grade dysplasia (incidence, 3.6%/y; 95% CI, 3.2–4.1). Five and 10 years after diagnosis, 98.6% (n = 540) and 97.1% (n = 155) of patients with NDBE were cancer free, respectively. The length of the BE was associated significantly with progression (EAC <6 cm, 0.09%/y vs EAC ≥6 cm, 0.65%/y; P = 0.001).
Conclusions: There is a lower incidence of dysplasia and EAC among patients with NDBE than previously reported. Because most patients are cancer free after a long-term follow-up period, surveillance intervals might be lengthened, especially for patients with shorter segments of BE.
Barrett's esophagus (BE), a known complication of chronic gastroesophageal reflux disease, is a well established premalignant lesion for esophageal and gastroesophageal adenocarcinoma. Approximately 10% to 15% of patients with chronic gastroesophageal reflux disease are diagnosed with BE. In addition, BE has been reported in patients with no reflux symptoms. The risk of esophageal adenocarcinoma (EAC) is increased 30 to 40 times among patients with BE compared with those without this condition. EAC continues to increase at a rate greater than any other cancer in the Western world (>500% since the 1970s), exceeding that of other more common cancers such as breast, colon, lung, and prostate cancer. In 2009, it is estimated that 16,470 new cases of esophageal cancer will be diagnosed in the United States, of which close to 60% will be adenocarcinomas. Despite all the recent advances in the diagnosis and management of this lethal cancer, the overall 5-year survival rate remains dismal (15%–20%).
Although not evaluated in randomized controlled trials, surveillance of patients with BE is recommended by all major gastroenterology societies and published guidelines. Multiple observational studies suggest that endoscopic surveillance is associated with detection of EAC at an earlier stage along with improved survival. However, the burden of endoscopic surveillance of BE patients is significant and continues to generate a great deal of controversy. In addition, there has been a lot of interest in the endoscopic ablation of nondysplastic BE (NDBE). The true incidence of EAC in patients with BE is central to determining the effectiveness of surveillance endoscopy or any intervention strategy. The exact incidence of EAC in BE patients is not clear and has ranged from 0.2% to 3.5% per year. This considerable variation has been attributed to the small number of patients being evaluated, short duration of follow-up evaluation, retrospective study designs, lead-time bias, length-time bias, and publication bias, with selective publications of smaller studies reporting a higher incidence of cancer and relatively larger studies reporting a lower incidence of cancer. We previously reported an incidence rate of 0.5% per year (95% confidence interval [CI], 0.0%–1.1%; 1 in 212 patient-years of follow-up evaluation) in this large multicenter cohort of 618 patients with NDBE (2546 patient-years; mean follow-up period, 4.12 y) in the United States.
In addition, data on the rate of progression of NDBE to the combined end point of high-grade dysplasia (HGD) and EAC are sparse. Given the advent of endoscopic eradication therapies for the management of HGD, rates of progression of NDBE to HGD and mucosal EAC assume greater importance. Although male predominance in patients with EAC is well recognized, the influence of sex on the rate of progression of NDBE to HGD/EAC is less clear and risk factors for progression have been poorly defined. The vast majority of the natural history studies in BE do not report on demographics and endoscopic characteristics. Hence, the reported incidence rates do not account for potentially important predictors associated with disease progression in BE.
Thus, the aims of this study were as follows: (1) to define the incidence rate of dysplasia and EAC in patients with NDBE, (2) to assess for gender differences in the incidence rates of dysplasia and EAC in a large multicenter cohort of NDBE patients, and (3) to identify predictors (demographic and endoscopic) for progression to dysplasia and EAC in patients with BE.
Abstract and Introduction
Abstract
Background & Aims: The risks of dysplasia and esophageal adenocarcinoma (EAC) are not clear for patients with nondysplastic Barrett's esophagus (NDBE); the rate of progression has been overestimated in previous studies. We studied the incidences of dysplasia and EAC and investigated factors associated with progression of BE.
Methods: The BE study is a multicenter outcomes project of a large cohort of patients with BE. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Patients followed up for at least 1 year after the index endoscopy examination were included, whereas those diagnosed with dysplasia and EAC within 1 year of diagnosis with BE (prevalent cases) were excluded. Of 3334 patients with BE, 1204 met the inclusion criteria (93.7% Caucasian; 88% male; mean age, 59.3 y) and were followed up for a mean of 5.52 years (6644.5 patient-years).
Results: Eighteen patients developed EAC (incidence, 0.27%/y; 95% confidence interval [CI], 0.17–0.43) and 32 developed HGD (incidence, 0.48%/y; 95% CI, 0.34–0.68). The incidence of HGD and EAC was 0.63%/y (95% CI, 0.47–0.86). There were 217 cases of low-grade dysplasia (incidence, 3.6%/y; 95% CI, 3.2–4.1). Five and 10 years after diagnosis, 98.6% (n = 540) and 97.1% (n = 155) of patients with NDBE were cancer free, respectively. The length of the BE was associated significantly with progression (EAC <6 cm, 0.09%/y vs EAC ≥6 cm, 0.65%/y; P = 0.001).
Conclusions: There is a lower incidence of dysplasia and EAC among patients with NDBE than previously reported. Because most patients are cancer free after a long-term follow-up period, surveillance intervals might be lengthened, especially for patients with shorter segments of BE.
Introduction
Barrett's esophagus (BE), a known complication of chronic gastroesophageal reflux disease, is a well established premalignant lesion for esophageal and gastroesophageal adenocarcinoma. Approximately 10% to 15% of patients with chronic gastroesophageal reflux disease are diagnosed with BE. In addition, BE has been reported in patients with no reflux symptoms. The risk of esophageal adenocarcinoma (EAC) is increased 30 to 40 times among patients with BE compared with those without this condition. EAC continues to increase at a rate greater than any other cancer in the Western world (>500% since the 1970s), exceeding that of other more common cancers such as breast, colon, lung, and prostate cancer. In 2009, it is estimated that 16,470 new cases of esophageal cancer will be diagnosed in the United States, of which close to 60% will be adenocarcinomas. Despite all the recent advances in the diagnosis and management of this lethal cancer, the overall 5-year survival rate remains dismal (15%–20%).
Although not evaluated in randomized controlled trials, surveillance of patients with BE is recommended by all major gastroenterology societies and published guidelines. Multiple observational studies suggest that endoscopic surveillance is associated with detection of EAC at an earlier stage along with improved survival. However, the burden of endoscopic surveillance of BE patients is significant and continues to generate a great deal of controversy. In addition, there has been a lot of interest in the endoscopic ablation of nondysplastic BE (NDBE). The true incidence of EAC in patients with BE is central to determining the effectiveness of surveillance endoscopy or any intervention strategy. The exact incidence of EAC in BE patients is not clear and has ranged from 0.2% to 3.5% per year. This considerable variation has been attributed to the small number of patients being evaluated, short duration of follow-up evaluation, retrospective study designs, lead-time bias, length-time bias, and publication bias, with selective publications of smaller studies reporting a higher incidence of cancer and relatively larger studies reporting a lower incidence of cancer. We previously reported an incidence rate of 0.5% per year (95% confidence interval [CI], 0.0%–1.1%; 1 in 212 patient-years of follow-up evaluation) in this large multicenter cohort of 618 patients with NDBE (2546 patient-years; mean follow-up period, 4.12 y) in the United States.
In addition, data on the rate of progression of NDBE to the combined end point of high-grade dysplasia (HGD) and EAC are sparse. Given the advent of endoscopic eradication therapies for the management of HGD, rates of progression of NDBE to HGD and mucosal EAC assume greater importance. Although male predominance in patients with EAC is well recognized, the influence of sex on the rate of progression of NDBE to HGD/EAC is less clear and risk factors for progression have been poorly defined. The vast majority of the natural history studies in BE do not report on demographics and endoscopic characteristics. Hence, the reported incidence rates do not account for potentially important predictors associated with disease progression in BE.
Thus, the aims of this study were as follows: (1) to define the incidence rate of dysplasia and EAC in patients with NDBE, (2) to assess for gender differences in the incidence rates of dysplasia and EAC in a large multicenter cohort of NDBE patients, and (3) to identify predictors (demographic and endoscopic) for progression to dysplasia and EAC in patients with BE.
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