EAC risk remains elevated despite successful endoscopies in Barrett’s oesophagus patients
Multiple consecutive endoscopies with persistent non-neoplastic Barrett’s oesophagus (BE) do not appear to be a protective factor against the risk of oesophageal adenocarcinoma (EAC), according to a team of US-based investigators.
“These findings argue against discontinuation of endoscopic surveillance among patients with persistent nondysplastic BE after multiple negative endoscopies,” said principal investigator Dr Hashem El-Serag from the Baylor College of Medicine in Houston, Texas.
Practice guidelines recommend endoscopic surveillance of patients with BE, but the cost-effectiveness of surveillance has been questioned as the overall risk of EAC in BE is low. So it has been suggested that patients with persistent non-neoplastic BE can be considered for surveillance discontinuation due to their low risk of EAC. [Gastroenterology 2013;145:548–53]
In a large retrospective cohort study involving 27,561 male veterans (mean age 62 years) with newly diagnosed BE, El-Serag and colleagues evaluated EAC risk in relation to the number of successive endoscopies, years of follow-up and calendar year to investigate whether all BE patients might benefit from long-term surveillance. A total of 406 developed EAC during 140,499 person-years of follow-up (median 4.9 years).
Poisson regression models showed that EAC incidence rates increased by 43 percent with each additional esophagogastroduodenoscopy (EGD) following a previous negative EGD (rate ratio [RR] per additional EGD, 1.43; 95 percent CI, 1.25 to 1.64). The incidence rate rose ninefold between the first and the fifth follow-up EGD (adjusted RR, 8.82; 4.90 to 15.9). [Am J Gastroenterol 2017;112:1049–1055]
With regard to years of follow-up, EAC incidence rate was highest at the first year after the BE index date (5.34 per 1,000 person-years). However, during successive years, there was a significant increase in EAC rates that started at the second follow-up year. Compared with the EAC incidence rate at year 2, the rate was 1.5-fold higher in EGDs conducted ≥5 years after the index BE date (adjusted RR, 1.49; 1.07 to 2.10).
No significant change in EAC incidence rates was observed by calendar year.
“The relatively high incidence rate of 5.34 per 1,000 person-years in the first year of follow-up is likely a reflection of both prevalent and incident EAC and confirms the high neoplastic yield of the BE-diagnosing endoscopy reported in previous studies,” El-Serag said. [N Engl J Med 2011;365:1375–83; Gut 2016;65:548–54; Clin Gastroenterol Hepatol 2010;8:235–44]
On the other hand, the present data are in contrast from those reported in a previous study showing that patients with multiple endoscopies who had persistent non-neoplastic BE had a lower risk of EAC relative to risk at initial follow-up endoscopic examinations, while controlling for age, sex and length of BE. [Gastroenterology 2013;145:548–53]
El Serag noted that the said study had only 1,401 BE patients, with too few participants and events to accurately examine the risk of EAC in the fourth and fifth years of follow-up.
Nondysplastic BE as risk stratification tool
Dr Sachin Wani from the University of Colorado Anschutz Medical Campus and Dr Srinivas Gaddam from the Cedars-Sinai Medical Center wrote in an accompanying editorial that the current study has successfully brought to the forefront the issue of persistent nondysplastic BE as a potential risk stratification tool. [Am J Gastroenterol 2017;112:1056–1060]
However, Wani and Gaddam stressed that the results should be interpreted in light of several limitations, as pointed out by El Serag and colleagues themselves. These include the lack of data on dysplasia status in the vast majority of patients, the inability to control for BE length (which is an established factor for progression) in the final model, and the limited generalizability of the results due to the inclusion of only male veterans in the study cohort.
It can be quite difficult to address the question of where the medical community currently stands with regard to the utility of persistence of nondysplastic BE as a risk stratification tool in the surveillance of patients with BE, given the variability of the results and associated methodologies from previous studies.
“Future studies should report and account for all potential confounders (age, obesity, smoking, PPI use, NSAID use, BE length, presence of visible lesion and presence of dysplasia) and include indications for endoscopy (surveillance vs diagnostic endoscopy),” Wani and Gaddam said.
They added that evaluating the true risk of EAC would warrant individual overlapping cohorts.“While there are several factors and challenges that ultimately impact outcomes related to surveillance, cognitive knowledge, training, use of standardized grading system and high-definition white light endoscopy, and meticulous examination techniques are of paramount importance in improving the effectiveness of surveillance programmes,” Wani and Gaddam concluded.