Low-Grade Dysplasia Is a Risk Factor for Esophageal Adenocarcinom in BE
Low-Grade Dysplasia Is a Risk Factor for Esophageal Adenocarcinom in BE
Objectives: Previous studies that evaluated extent of high-grade dysplasia (HGD) as a risk factor for esophageal adenocarcinoma (EA) in Barrett's esophagus (BE) were conflicting, and no prior study has evaluated extent of low-grade dysplasia (LGD) as a risk factor. The aim of this discovery study was to evaluate the hypothesis that extent of LGD and HGD are risk factors for progression to EA.
Methods:We evaluated baseline biopsies from 77 BE patients with dysplasia including 44 who progressed to EA and 33 who did not progress during follow-up. The total numbers of LGD and HGD crypts were determined separately by counting all crypts and the extent of LGD, HGD, and total dysplasia were correlated with EA outcome.
Results: Thirty-one and 46 patients had a maximum diagnosis of LGD and HGD, respectively. When the crypts were stratified by dysplasia grade, the mean number of LGD crypts per patient was borderline higher in progressors (93.9) compared with nonprogressors (41.2, P = 0.07), and the mean proportion of LGD crypts per patient was significantly higher in progressors (46.4% vs 26.0%, P = 0.037). Neither the mean number of HGD crypts per patient (P = 0.14) nor the mean proportion of HGD crypts per patient (P = 0.20) was significantly associated with EA outcome.
Conclusions: The extent of LGD is a significant risk factor for the development of EA in BE in this study. Although the presence of HGD is significantly associated with a greater relative risk for development of EA, the extent of HGD was not an independent risk factor for progression.
Barrett's esophagus (BE) is defined as columnar metaplasia, with goblet cells, of the distal esophagus, a condition most often caused by chronic gastroesophageal reflux disease (GERD). BE affects approximately 1% of unselected patients who undergo endoscopy and is detected in 5-15% of patients with GERD. Patients with BE have a 30- to 100-fold greater risk of developing esophageal adenocarcinoma (EA) over that of the general population, with an absolute risk of approximately 0.5-1.0% per year. Adenocarcinoma develops in BE through a metaplasia-dysplasia-carcinoma sequence. Dysplasia is the first morphologically recognizable lesion in the neoplastic progression of BE to adenocarcinoma, and it is the most common basis of risk stratification in affected patients.
Although somewhat controversial, periodic endoscopic surveillance is recommended for early detection of potentially curable EA in patients with BE. Because most patients with BE do not progress to EA, surveillance at shorter intervals is recommended for individuals with a diagnosis of dysplasia. Morphologically, dysplasia is categorized as either low-grade (LGD) or high-grade (HGD) based on a constellation of pathologic features. However, the estimated risk of progression to EA among patients with dysplasia varies widely among different studies. For instance, the results of three prospective studies show a rate of progression to EA that varies between 15% and 60% for patients with HGD. Unfortunately, at present, it is not possible to predict which patients with HGD will progress to EA. In a recent longitudinal study by Buttar et al., not only the presence, but also the extent, of HGD was reported to be a significant risk factor for progression to EA during the 3 yr after diagnosis. However, in a cross-sectional study by Dar et al., the extent of HGD was not found to be a significant predictor of coexisting EA at esophagectomy. Thus, the management of patients with HGD remains controversial. Although some investigators advocate esophagectomy, others recommend continued aggressive endoscopic surveillance and reserve esophagectomy only for patients who develop intramucosal adenocarcinoma. Other techniques, such as endoscopic ablation therapy or endoscopic mucosal resection, have also gained popularity recently for the treatment of HGD in BE.
The natural history of LGD in BE is even less well defined. Most studies show a low rate of progression to EA, but some recent studies suggest that the risk may be higher, particularly in cases in which a consensus diagnosis is reached by more than one pathologist. Patient diagnoses of LGD are more prevalent among BE patients than HGD, but because of the higher level of interobserver disagreement with regard to the former, compared with the latter, the prevalence may be overestimated. At present, it is not possible to predict which BE patients with LGD will progress to EA based on histologic criteria. To our knowledge, there have been no previous studies that evaluated the extent of LGD as a risk factor for EA progression in BE.
Therefore, the purpose of this discovery study was to evaluate the extent of dysplasia, using standardized criteria for LGD and HGD as a risk factor for EA development in BE. To perform this study, we selected 77 BE patients from the Seattle Barrett's Esophagus Study at the Fred Hutchinson Cancer Research Center. Forty-four cases progressed to EA and 33 cases did not progress during follow-up. Our hypothesis was that the extent of LGD was a significant risk factor for the development of EA in BE.
Objectives: Previous studies that evaluated extent of high-grade dysplasia (HGD) as a risk factor for esophageal adenocarcinoma (EA) in Barrett's esophagus (BE) were conflicting, and no prior study has evaluated extent of low-grade dysplasia (LGD) as a risk factor. The aim of this discovery study was to evaluate the hypothesis that extent of LGD and HGD are risk factors for progression to EA.
Methods:We evaluated baseline biopsies from 77 BE patients with dysplasia including 44 who progressed to EA and 33 who did not progress during follow-up. The total numbers of LGD and HGD crypts were determined separately by counting all crypts and the extent of LGD, HGD, and total dysplasia were correlated with EA outcome.
Results: Thirty-one and 46 patients had a maximum diagnosis of LGD and HGD, respectively. When the crypts were stratified by dysplasia grade, the mean number of LGD crypts per patient was borderline higher in progressors (93.9) compared with nonprogressors (41.2, P = 0.07), and the mean proportion of LGD crypts per patient was significantly higher in progressors (46.4% vs 26.0%, P = 0.037). Neither the mean number of HGD crypts per patient (P = 0.14) nor the mean proportion of HGD crypts per patient (P = 0.20) was significantly associated with EA outcome.
Conclusions: The extent of LGD is a significant risk factor for the development of EA in BE in this study. Although the presence of HGD is significantly associated with a greater relative risk for development of EA, the extent of HGD was not an independent risk factor for progression.
Barrett's esophagus (BE) is defined as columnar metaplasia, with goblet cells, of the distal esophagus, a condition most often caused by chronic gastroesophageal reflux disease (GERD). BE affects approximately 1% of unselected patients who undergo endoscopy and is detected in 5-15% of patients with GERD. Patients with BE have a 30- to 100-fold greater risk of developing esophageal adenocarcinoma (EA) over that of the general population, with an absolute risk of approximately 0.5-1.0% per year. Adenocarcinoma develops in BE through a metaplasia-dysplasia-carcinoma sequence. Dysplasia is the first morphologically recognizable lesion in the neoplastic progression of BE to adenocarcinoma, and it is the most common basis of risk stratification in affected patients.
Although somewhat controversial, periodic endoscopic surveillance is recommended for early detection of potentially curable EA in patients with BE. Because most patients with BE do not progress to EA, surveillance at shorter intervals is recommended for individuals with a diagnosis of dysplasia. Morphologically, dysplasia is categorized as either low-grade (LGD) or high-grade (HGD) based on a constellation of pathologic features. However, the estimated risk of progression to EA among patients with dysplasia varies widely among different studies. For instance, the results of three prospective studies show a rate of progression to EA that varies between 15% and 60% for patients with HGD. Unfortunately, at present, it is not possible to predict which patients with HGD will progress to EA. In a recent longitudinal study by Buttar et al., not only the presence, but also the extent, of HGD was reported to be a significant risk factor for progression to EA during the 3 yr after diagnosis. However, in a cross-sectional study by Dar et al., the extent of HGD was not found to be a significant predictor of coexisting EA at esophagectomy. Thus, the management of patients with HGD remains controversial. Although some investigators advocate esophagectomy, others recommend continued aggressive endoscopic surveillance and reserve esophagectomy only for patients who develop intramucosal adenocarcinoma. Other techniques, such as endoscopic ablation therapy or endoscopic mucosal resection, have also gained popularity recently for the treatment of HGD in BE.
The natural history of LGD in BE is even less well defined. Most studies show a low rate of progression to EA, but some recent studies suggest that the risk may be higher, particularly in cases in which a consensus diagnosis is reached by more than one pathologist. Patient diagnoses of LGD are more prevalent among BE patients than HGD, but because of the higher level of interobserver disagreement with regard to the former, compared with the latter, the prevalence may be overestimated. At present, it is not possible to predict which BE patients with LGD will progress to EA based on histologic criteria. To our knowledge, there have been no previous studies that evaluated the extent of LGD as a risk factor for EA progression in BE.
Therefore, the purpose of this discovery study was to evaluate the extent of dysplasia, using standardized criteria for LGD and HGD as a risk factor for EA development in BE. To perform this study, we selected 77 BE patients from the Seattle Barrett's Esophagus Study at the Fred Hutchinson Cancer Research Center. Forty-four cases progressed to EA and 33 cases did not progress during follow-up. Our hypothesis was that the extent of LGD was a significant risk factor for the development of EA in BE.
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