Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Dysplasia

What is the prevalence of undetected carcinoma in resection specimens for high-grade dysplasia?

R. Romagnoli, C. Gutschow, J.-M. Collard (Brussels)

Dysplasia arising in Barrett's esophagus may be defined [1-3] as unequivocal neoplastic abnormalities in both the mucosal architecture and cellular morphology of the epithelium without any invasion of the lamina propria through the basement membrane. These abnormalities are mild and mainly located in the lower half of the epithelium in low-grade dysplasia (LGD), whereas they are more marked and extend over full thickness of the epithelium in high-grade dysplasia (HGD). Carcinoma arising in Barrett's esophagus is called invasive whenever neoplastic epithelial cells are found in the lamina propria beyond the basement membrane.

Reliable differentiation of HGD from invasive carcinoma on endoscopic biopsies may be impossible. For instance, a biopsy error rate for detecting invasive carcinoma in patients sent for esophagectomy because of the existence of HGD without endoscopically visible lesion may be as high as 43% [4] in spite of the fact that four-quadrant biopsies are taken every 2 cm throughout the whole length of the Barrett's area. Moreover, the use of large-bite "jumbo" spiked-biopsy forceps [5] does not seem to reduce the risk for erroneous staging. In the same way, there may be both inter- and intraobserver variations in the classification of dysplasia [6]. This is particularly true when the pathologist wavers between LGD an regenerative features. As for HGD, if no agreement exists among two independent, experienced pathologists, a second set of biopsies must be taken for further histologic analysis of the Barrett's area before making the final decision of an esophagectomy.

Table I shows the results of an in-depth review of both the medical and surgical literature on the subject: invasive carcinoma was found in about 40% of the resection specimens from patients who underwent esophagectomy because HGD had been evidenced in endoscopic biopsy material.

Table I. Prevalence of undetected invasive carcinoma in 228 patients who were offered an esophagectomy for HGD arising in Barrett's esophagus (data from the literature).

Data from 171 HGD patients from the literature for whom detailed histologic information was available indicate that 62 patients (36%) had, in fact, an invasive carcinoma that remained confined to the esophageal wall whereas 6 patients (3.5%) had an invasive carcinoma that had spread into loco-regional lymph nodes. Detailed information on the postoperative tumor-node staging [29] of these 68 invasive carcinoma patients is displayed in Table II. So, invasive carcinoma were classified as T1, T2 and T3 in 77.9%, 13.2% and 8.8%, respectively, and loco-regional lymph nodes were metastatic in 8.8% whereas they were histologically normal in 91.2%.

In addition to the discovery of an invasive carcinoma in the resected specimen of patients operated on for HGD, invasive carcinoma may be evidenced on the examination of a second set of biopsies taken a few weeks after a first set had settled the diagnosis of HGD. So, three of the 24 HGD patients we had to deal with in our department over a 14-year period had an invasive carcinoma disclosed on a second set of esophageal biopsies taken just to get some more histologic material and make sure of the presence of dysplastic lesions in the Barrett's area.

Table II. Staging according to T and N factors in 68 cancer patients from the literature for whom detailed histologic information is available.

There is no reliable endoscopic features for accurate prediction of the existence of an invasive carcinoma in a patient having HGD in endoscopic biopsy material. Indeed, data from the literature [3-5, 9-11, 13-15, 25, 26] indicate that, in comparison with the absence of any visible lesion in the Barrett's area, the presence of such a lesion (i.e. a nodule or an ulceration) does not increase the likelihood of finding an invasive carcinoma on postoperative examination of the resected specimen. Likewise, the predictive value of endosonography for the presence of an invasive carcinoma in patients having HGD has been shown to be rather low [30]. However, data from our institution [28] suggest that the adoption of a prompt surgical attitude by performing an esophagectomy as soon as HGD has been found on a first set of biopsies or at the latest, when an invasive carcinoma has been seen on biopsy samples taken a few weeks after the first histologic examination is much safer than the adoption of an expectant attitude towards HGD. Indeed, all 11 patients who underwent an esophagectomy a few weeks after HGD had been found for the first time were operated on for a mucosal disease. In contrast, four of our 13 patients in whom HGD was either followed up endoscopically for a long period (mean: 2 years) or disregarded until obstructive symptoms justified an endoscopic control, or who had been operated on after an invasive carcinoma had developped in the course of an endoscopic surveillance program of HGD, had metastatic lymph nodes in the resected specimen. This suggests that making the decision of an esophagectomy only after numerous successive sets of biopsies have shown the persistence of HGD, following a wait-and-see policy until neoplastic invasion beyond the basement membrane becomes evident in endoscopic biopsy material, or disregarding HGD until the patient re-consults for obstructive esophageal symptoms are three attitudes that expose to the risk of spontaneous progression of the disease to an advanced stage with poor long-term outcome [31].


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Publication date: August 2003 OESO©2015