Early Diagnosis of Gastroesophageal Cancers and the Cytosponge: A Work in Progress.

Dear Editor:

In the Perspective article in the March issue of Cellular and Molecular Gastroenterology and Hepatology, the Cytosponge erroneously was cited during the publication process as a Medtronic device (Medtronic, Minneapolis, MN). We would like to clarify that all published studies on Cytosponge to date have been performed using a research design patented by the Medical Research Council UK and made by local manufacturers and performed under permission from the Medical Health Regulatory Agency of the United Kingdom. This prototype device currently is being used in a 9000-patient primary care study in the United Kingdom (Barrett's ESophagus Trial 3 [BEST3]; trial ID ISRCTN68382401). This important study takes major steps to improve care for patients with Barrett’s esophagus.

In addition, 2 citations were attributed to the Cytosponge.2, 3 A citation error occurred during compilation of references such that Ross-Innes et al (2015) was cited rather than the correct Ross-Innes et al (2017) article. In this recent study a biomarker panel was designed with particular emphasis on identifying patients at low risk who can be spared unnecessary endoscopy. We would like to highlight the important advances being made with these biomarker assays using the Cytosponge device as discussed in the accompanying commentary by Zakko et al.

The Perspective article stated that the current iteration of Cytosponge would detect only Tumor protein p53 (TP53) mutations and neglected to cite the application of a risk-stratification panel to Trefoil Factor 3-positive Cytosponge samples. The following statement appears on the second page of the Lancet Gastroenterol Hepatol 2017 article, “We have shown that TP53 mutations qualify for a risk stratification biomarker and are detectable using the Cytosponge…However, for a risk stratification tool to be clinically applicable, it is important not to miss patients with high-grade dysplasia or early cancer because its prevalence is 70-80%.” In the Perspective article, the statement “the current iteration of Cytosponge would only detect TP53 mutations” intended to address this limitation in screening for patients with high-risk BE while simultaneously excluding low-risk BE. As noted by Ross-Innes et al (2017), in multiple studies TP53 is mutated in approximately 70%–80% of esophageal adenocarcinomas, thus screening for TP53 mutations in BE will detect at most an upper limit of approximately 70%–80% of high-risk patients. Although this would be a great improvement over current approaches, it still would not be optimal because 20%–30% of high-risk patients would not be detected.

The concluding statement about the Medtronic device needs some clarification. The device and associated assays were licensed to Covidien GI Solutions (now Medtronic), who are developing a device for high-throughput manufacture. This commercial version is correctly being tested for safety and performance in Medtronic-led clinical studies. There were 2 detachments early in their testing that led Medtronic to issue a voluntary recall under the Food and Drug Administration requirement for a 510(K) device. They now are performing further work on this device, in a research setting, to ensure that the product for commercial use is safe and fit for purpose. To date, no Medtronic devices have been sold and data on their device have not yet been published. Hence, this withdrawal does not reflect on the research device from which the cited data pertain. The voluntary recall of the device by the company under the Food and Drug Administration requirement has been well received, and we anticipate much-needed future studies with this device. It is a major tool on the horizon to improve screening for Barrett’s esophagus in the population and is an advance that greatly is needed in the field.