Primary Motility  Disorders of the  Esophagus
 The Esophageal
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Volume: Barrett's Esophagus
Chapter: Dysplasia

In patients with high-grade dysplasia, can endosonography differentiate between benign and malignant wall thickening?

G.W. Falk (Cleveland)

There is no agreement on the most appropriate management of high-grade dysplasia (HGD) in patients with Barrett's esophagus. Esophagectomy is recommended by many authors to eliminate the risk of carcinoma or to detect and treat cancer at an early curable stage, because of the marked variability in the finding of unsuspected cancer in patients with HGD which ranges from 0% to 73% [1]. However, this approach has been criticized because of the high morbidity and mortality associated with esophagectomy, the lack of a systematic biopsy protocol prior to surgery and the variable natural history of HGD. Other experts recommend a rigorous endoscopic surveillance program utilizing a systematic biopsy protocol characterized by four quadrant biopsies with a large particle (jumbo) forceps at intervals = 2 cm accompanied by biopsies of any suspicious lesions, reserving esophagectomy for patients with a preoperative diagnosis of intramucosal or submucosal carcinoma [2]. Studies by Levine et al. suggest that this systematic biopsy protocol can reliably distinguish patients with HGD alone from those with intramucosal or submucosal adenocarcinoma, thereby avoiding the risk of unnecessary surgery in these patients [2]. Photodynamic therapy is another less invasive option currently under study [3]. This issue is of more than academic interest as esophageal adenocarcinoma is a lethal disease and survival is stage dependent. Lymph node metastases may be found in up to 5% of intramucosal carcinoma cases and up to 25% of submucosal carcinoma cases due to the rich lymphatic supply of the esophagus that extends into the lamina propria [4].

Detection of adenocarcinoma in Barrett's patients with HGD may be akin to looking for a "needle in a haystack." Cameron et al. systematically mapped 30 esophagectomy specimens from patients undergoing surgery for either HGD or early invasive adenocarcinoma with no endoscopic evidence of cancer [5]. They found the median surface area of total Barrett's esophagus to be 32 cm2; low-grade dysplasia (LGD) 13 cm2; HGD 1.3 cm2; and adenocarcinoma 1.1 cm2. The three smallest cancers had surface areas of 0.02, 0.3 and 0.4 cm2. Invasive adenocarcinoma was associated with either focal or extensive areas of HGD.

Barrett's epithelium. However, two patients with HGD without visible lesions on endoscopy had focal submucosal masses discovered by endoscopic ultrasonography that were found to be submucosal cancer at the time of surgery. Our group examined the ability of endosonography to detect early carcinoma in 9 patients with HGD but no adenocarcinoma on preoperative biopsy who subsequently underwent esophagectomy [8]. Postoperatively, 3 of the 9 patients had intramucosal carcinoma (Table I). Staging agreement was found in only 4 of the 9 patients studied. Of the 6 patients with HGD as the final diagnosis, endosonography correctly predicted absence of the tumor in 4. However, in 2 patients, endosonography incorrectly predicted T2, N0 lesions despite the absence of carcinoma. Among the 3 patients with intramucosal carcinoma, endosonography correctly predicted the presence of tumor in only 1. However, the tumor in this patient was overstaged as a T2,N1 lesion. In the other 2 patients, no endosonographic abnormalities were noted. Thus in these 9 patients, endosonography did not consistently predict the presence of intramucosal carcinoma in patients with Barrett's esophagus and HGD. Adrain et al. examined the utility of high resolution endosonography with a 20 MHz transducer in 17 Barrett's patients [9]. They found that Barrett's esophagus patients consistently had thickening of the second hypoechoic layer. However, both cases of dysplasia and one case of carcinoma in situ were indistinguishable from Barrett's esophagus without dysplasia. Finally, Gangorasa et al. found no difference in esophageal wall thickness between areas with LGD and no dysplasia in 9 patients with LGD [10].

Table I. Comparison of preoperative endoscopic ultrasonography assessment with postoperative histologic diagnosis (from [8], with permission).


Endosonography, while intuitively appealing, does not consistently predict the presence of intramucosal or submucosal cancer in Barrett's esophagus patients. However, studies to date have examined only a limited number of patients. Prospective studies of larger number of patients with HGD will be difficult to accomplish due to the rarity of this finding. The microscopic changes of HGD and intramucosal carcinoma may well be beyond the resolution capacity of endosonography. Other optical techniques such as fluorescence spectroscopy, light spectroscopy, optical coherence tomography, light scattering spectroscopy, and light induced fluorescence endoscopy all offer greater promise at present.

Table II. Accuracy of endoscopic ultrasonography in identifying high-grade dysplasia or intramucosal carcinoma in 9 patients with Barrett's esophagus (from [8], with permission).

All of these techniques are based on the principle that benign and malignant tissue have different optical qualities. In theory, this would permit optical sampling of larger areas of the columnar-lined esophagus and improve the efficiency of biopsies by targeting areas thought to harbor dysplasia or cancer. While promising, these techniques need to decrease the overlap encountered between normal mucosa, Barrett's epithelium and all grades of dysplasia [11-13]. The routine use of endosonography to decide when to operate in patients with HGD cannot be recommended based on currently available data.


1. Falk GW, Rice TW, Goldblum JR, Richter JE. Jumbo biopsy forceps protocol still misses unsuspected cancer in Barrett's esophagus with high-grade dysplasia. Gastrointest Endosc 1999;49:170-176.

2. Levine DS, Haggitt RC, Blount PL, Rabinovitch PS, Rusch VW, Reid BJ. An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus. Gastroenterology 1993;105:40-50.

3. Gossner L, Stolte M, Sroka R, Rick K, May A, Hahn EG, Ell C. Photodynamic ablation of high-grade dysplasia in Barrett's esophagus by means of 5-aminolevulinic acid. Gastroenterology 1998;114:448-455.

4. Rice TW, Zuccaro G, Adelstein DJ, Rybicki LA, Blackstone, Goldblum JR. Esophageal carcinoma: depth of tumor invasion is predictive of regional lymph node status. Ann Thorac Surg 1998;65:787-792.

5. Cameron AJ, Carpenter HA. Barrett's esophagus, high-grade dysplasia, and early adenocarcinoma: a pathological study. Am J Gastroenterol 1997;92:586-591.

6. Dancygier H, Classen M. Endoscopic ultrasonography in esophageal diseases. Gastrointest Endosc 1989;35:220-225.

7. Srivastava AK, Vanagunas A, Kamel P, Cooper R. Endoscopic ultrasound in the evaluation of Barrett's esophagus: a preliminary report. Am J Gastroenterol 1994;89:2192-2195.

8. Falk GW, Catalano MF, Sivak MV, Rice TW, Van Dam J. Endosonography in the evaluaton of patients with Barrett's esophagus and high-grade dysplasia. Gastrointest Endosc 1994;40:207-212.

9. Adrain AL, Ter HC, Cassidy MJ, Schiano T, Liu JB, Miller LS. High-resolution endoluminal sonography is a sensitive modality for the identification of Barrett's metaplasia. Gastrointest Endosc 1997;46:147-151.

10. Gangarosa LM, Halter S, Mertz H. Methylene blue staining and endoscopic ultrasound evaluation of Barrett's esophagus with low-grade dysplasia. Dig Dis Sci 2000;45:225-229.

11. Panjehpour M, Overholt BF, Vo-Dinh T, Haggitt RC, Edwards DH, Buckley FP. Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus. Gastroenterology 1996;111:93-101.

12. Von Holstein CS, Nilsson AM, Engels SA, Willen R, Walther B, Svanberg K. Detection of adenocarcinoma in Barrett's oesophagus by means of laser induced fluorescence. Gut 1996;39:711-716.

13. Haringsma J, Prawirodirdjo W, Tytgat GNJ. Accuracy of fluorescence imaging of dysplasia in Barrett's esophagus. Gastroenterology 1999;116:A418.

Publication date: August 2003 OESO©2015