Do 40% of Patients Resected for Barrett Esophagus With High-Grade Dysplasia Have Unsuspected Adenocarcinoma?

Archives of Pathology & Laboratory Medicine, Feb 2005 by Tschanz, Elizabeth R

Results of studies conducted in the last 2 decades suggest that the detection of high-grade dysplasia in patients with Barrett esophagus is the harbinger of a synchronous adenocarcinoma, which remains undetected even by rigorous biopsy protocols but is discovered during resection of the esophagus. The reported prevalence of synchronous carcinomas ranges from 0% to 75%. Other researchers maintain that appropriate surveillance programs can be used to detect carcinomas at a curable stage and to prevent unnecessary esophagectomies. Both logistical difficulties and potential methodological pitfalls have plagued many studies designed to investigate this issue. A large multicenter study that would stratify participants for hitherto unexplored variables (eg, age, gender, and ethnic background) may be required before the 40% occult cancer prevalence can be either confirmed or refuted. However, the large scale needed for such a study to provide reliable data and new developments in endoscopic imaging (eg, magnification endoscopy and optical coherence tomography) and endoscopic therapy (eg, mucosectomy) are likely to make such a study both ethically unacceptable and logistically and financially unfeasible. Future research should utilize the combination of new endoscopic technologies with the continuing search for validated biomarkers that help predict the biological behavior of Barrett epithelium in individual patients, with a particular focus on the possible development of preneoplastic and neoplastic lesions. Pathologists who chose to shift their focus from the traditional morphological investigation of dysplasia to the search for usable biomarkers can position themselves at the center of innovative research projects that could radically modify the management of patients with Barrett esophagus.

(Arch Pathol Lab Med. 2005;129:177-180)

Results of several studies conducted in the last 2 decades suggest that the detection of high-grade dysplasia in patients with Barrett esophagus is the harbinger of a synchronous adenocarcinoma. According to such reports, these carcinomas, variously defined as occult, unexpected, or unsuspected, remain undetected even by the most rigorous biopsy protocols, only to be discovered when the esophagus is resected and thoroughly sampled. The reported prevalence of such tumors, which I prefer to call synchronous, previously undetected carcinomas rather than unexpected, ranges from 0% to 75%.1-6

Other researchers, based on the careful initial endoscopic and bioptic screening of Barrett patients, maintain that an appropriate surveillance program will detect carcinomas at an early and still curable stage, thus preventing unwarranted esophagectomies.7,8

NO EVIDENCE IN THE LITERATURE

In the presence of conflicting data, particularly when the evidence is provided by numerous studies that each involve a small number of cases, meta-analysis is now considered the approach of choice. By selecting published articles according to rigorous pre-established criteria, usable data are sifted from the unusable, and a reasonable evidence-based answer is ultimately extracted.9

Attempts to apply meta-analytic methods to evaluate the literature concerning the simultaneous presence of high-grade dysplasia and adenocarcinoma in cases of Barrett esophagus would likely prove futile; the number of published cases found in resection-based studies is just more than 300, with more than half of the series consisting of fewer than 20 cases. The reported biopsy protocols that led to the resection are widely different, the methods used to examine the resected specimens are often incompletely described, and the endpoint (invasive vs superficial or intramucosal carcinoma) is not always clearly stated. Only a handful of the reports provide sociodemographic, ethnic, and medical information that would allow the stratification of patients in categories with potentially different progression rates.

The study that could address the issue of the 40% occult cancer prevalence has not yet been carried out, and a constellation of methodological, ethical, and logistical issues and new developments in interventional endoscopy will probably prevent it from ever being performed.

THE STUDY THAT NEVER WILL BE

Two methodological approaches can be used to determine the prevalence of synchronous carcinoma in patients with high-grade dysplasia in Barrett mucosa: the biopsy-based and the resection-based study. The former includes an initial extensively mapped biopsy protocol to characterize each patient's Barrett mucosa as accurately as possible at enrollment. Participants are then followed by endoscopy and systematic biopsies at intervals whose length may be adjusted depending on the presence of lesions of increasing neoplastic potential. The detection of high-grade dysplasia may lead to more intense surveillance and more aggressive biopsy protocols, but esophagectomy is performed only when carcinoma is detected. Resection-based studies have similar foundations but differ in the indication for esophagectomy, which in this case is triggered by the finding of high-grade dysplasia.