The Incidence of Esophageal Cancer in Barrett Esophagus
Figure 1 is a flow diagram of our search strategy and results. Our initial and updated searches together identified 3450 citations. After exclusion of abstracts and non-peer-reviewed articles, 100 studies were initially identified; 18 redundant or duplicate studies were subsequently excluded. Twenty-four studies were excluded because they did not account for baseline dysplasia. One study that was limited to patients with ulcerated BO was excluded because such patients likely represent a high-risk group and their natural history should not be extrapolated to the general population of patients with NDBO. Therefore, we included 57 studies in the meta-analysis. Summary data are given in Table 1 .
(Enlarge Image)
Figure 1.
Search strategy for identifying studies to be included in the meta-analysis.
Combined, these 57 studies accounted for 11 434 patients with histologically confirmed NDBO and 58 547 patient-years of follow-up. The mean age of patients included in these studies ranged from 44 to 65 years. There were 186 incident cases of OAC documented during follow-up. Since there was no statistically significant heterogeneity among these studies (Cochran Q=64.6; p=0.20; I=13.3%), a fixed-effect model was used for meta-analysis. The pooled incidence of OAC among all 57 studies was 0.33% (95% CI 0.28% to 0.38%). There was no evidence of publication bias (Egger's test, p=0.19).
Ten studies were considered to be of the highest quality in that they had no evidence of selection bias, more than 5 years of mean follow-up and at least 1 year of minimum follow-up. These comprised 3345 patients and 23 984 patient-years of follow-up. There were 77 incident cases of OAC identified. Since there was no statistically significant heterogeneity among these studies (Cochran Q=11.8; p=0.23; I=23.5%), a fixed-effect model was applied (Figure 2). The pooled annual incidence of OAC remained at 0.33% (95% CI 0.26% to 0.40%). There was no evidence of publication bias among these studies (Egger's test, p=0.20). These 10 studies alone accounted for 41% of the total patient-years of follow-up and of the cases of OAC among all 57 studies.
(Enlarge Image)
Figure 2.
Forest plot of the post hoc meta-analysis of the 10 studies of highest methodological quality.
We identified 16 studies that supplied adequate information regarding the incidence of OAC among patients with SSBO, as defined above. Three of these studies were used only for the analysis of OAC incidence in SSBO. These studies were subsequently amalgamated into a larger study that is included in our overall analysis. The 16 studies comprised 967 patients and 4456 patient-years of follow-up. There were five incident cases of OAC, including one that arose from a BO segment of 3 cm. There was no significant heterogeneity among these studies (Cochran Q=5.74; p=0.98; I=0%). Using a fixed-effect model, the pooled annual incidence of OAC was 0.19% (95% CI 0.08% to 0.34%) (Figure 3). There was no evidence of publication bias (Egger's test, p=0.96).
(Enlarge Image)
Figure 3.
Forest plot of the planned subgroup analysis of the 16 studies that supplied adequate information on the incidence of oesophageal adenocarcinoma among patients with documented short segment Barrett's oesophagus.
After excluding studies that had employed surgical treatment for GORD and/or BO, 37 remained, accounting for 6599 patients and 33 549 patient-years of follow-up. There were 128 incident cases of OAC detected. There was statistically significant heterogeneity among these studies (Cochran Q=38.12; p=0.09; I=26.5%); accordingly, a random-effects model was used. The pooled annual incidence of OAC was 0.41% (95% CI 0.32% to 0.51%). There was evidence of significant publication bias (Egger's test, p=0.06).
Sixteen studies provided information about mortality during follow-up from causes unrelated to OAC. These accounted for 2916 patients and 17 214 patient-years of follow-up. There were 56 incident cases of OAC detected during follow-up and 684 deaths from causes apparently unrelated to OAC. There was no statistically significant heterogeneity among these studies (Cochran Q=15.4; p=0.42; I=2.9%). Using a fixed-effect model, the pooled annual incidence of OAC was 0.34% (95% CI 0.26% to 0.44%). There was, however, evidence of significant publication bias (Egger's test, p=0.08).
Results
Figure 1 is a flow diagram of our search strategy and results. Our initial and updated searches together identified 3450 citations. After exclusion of abstracts and non-peer-reviewed articles, 100 studies were initially identified; 18 redundant or duplicate studies were subsequently excluded. Twenty-four studies were excluded because they did not account for baseline dysplasia. One study that was limited to patients with ulcerated BO was excluded because such patients likely represent a high-risk group and their natural history should not be extrapolated to the general population of patients with NDBO. Therefore, we included 57 studies in the meta-analysis. Summary data are given in Table 1 .
(Enlarge Image)
Figure 1.
Search strategy for identifying studies to be included in the meta-analysis.
Combined, these 57 studies accounted for 11 434 patients with histologically confirmed NDBO and 58 547 patient-years of follow-up. The mean age of patients included in these studies ranged from 44 to 65 years. There were 186 incident cases of OAC documented during follow-up. Since there was no statistically significant heterogeneity among these studies (Cochran Q=64.6; p=0.20; I=13.3%), a fixed-effect model was used for meta-analysis. The pooled incidence of OAC among all 57 studies was 0.33% (95% CI 0.28% to 0.38%). There was no evidence of publication bias (Egger's test, p=0.19).
Ten studies were considered to be of the highest quality in that they had no evidence of selection bias, more than 5 years of mean follow-up and at least 1 year of minimum follow-up. These comprised 3345 patients and 23 984 patient-years of follow-up. There were 77 incident cases of OAC identified. Since there was no statistically significant heterogeneity among these studies (Cochran Q=11.8; p=0.23; I=23.5%), a fixed-effect model was applied (Figure 2). The pooled annual incidence of OAC remained at 0.33% (95% CI 0.26% to 0.40%). There was no evidence of publication bias among these studies (Egger's test, p=0.20). These 10 studies alone accounted for 41% of the total patient-years of follow-up and of the cases of OAC among all 57 studies.
(Enlarge Image)
Figure 2.
Forest plot of the post hoc meta-analysis of the 10 studies of highest methodological quality.
We identified 16 studies that supplied adequate information regarding the incidence of OAC among patients with SSBO, as defined above. Three of these studies were used only for the analysis of OAC incidence in SSBO. These studies were subsequently amalgamated into a larger study that is included in our overall analysis. The 16 studies comprised 967 patients and 4456 patient-years of follow-up. There were five incident cases of OAC, including one that arose from a BO segment of 3 cm. There was no significant heterogeneity among these studies (Cochran Q=5.74; p=0.98; I=0%). Using a fixed-effect model, the pooled annual incidence of OAC was 0.19% (95% CI 0.08% to 0.34%) (Figure 3). There was no evidence of publication bias (Egger's test, p=0.96).
(Enlarge Image)
Figure 3.
Forest plot of the planned subgroup analysis of the 16 studies that supplied adequate information on the incidence of oesophageal adenocarcinoma among patients with documented short segment Barrett's oesophagus.
After excluding studies that had employed surgical treatment for GORD and/or BO, 37 remained, accounting for 6599 patients and 33 549 patient-years of follow-up. There were 128 incident cases of OAC detected. There was statistically significant heterogeneity among these studies (Cochran Q=38.12; p=0.09; I=26.5%); accordingly, a random-effects model was used. The pooled annual incidence of OAC was 0.41% (95% CI 0.32% to 0.51%). There was evidence of significant publication bias (Egger's test, p=0.06).
Sixteen studies provided information about mortality during follow-up from causes unrelated to OAC. These accounted for 2916 patients and 17 214 patient-years of follow-up. There were 56 incident cases of OAC detected during follow-up and 684 deaths from causes apparently unrelated to OAC. There was no statistically significant heterogeneity among these studies (Cochran Q=15.4; p=0.42; I=2.9%). Using a fixed-effect model, the pooled annual incidence of OAC was 0.34% (95% CI 0.26% to 0.44%). There was, however, evidence of significant publication bias (Egger's test, p=0.08).
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