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Columnar Mucosa and Intestinal Metaplasia of the Esophagus Fifty Years of Controversy

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Columnar Mucosa and Intestinal Metaplasia of the Esophagus Fifty Years of Controversy ANNALS OF SURGERY REVIEW Vol. 231, No. 3, 303–321 © 2000 Lippincott Williams & Wilkins, Inc. Columnar Mucosa and Intestinal Metaplasia of the Esophagus Fifty Years of Controversy Steven R. DeMeester, MD,* and Tom R. DeMeester, MD† From the Departments of *Cardiothoracic Surgery and †Surgery, The University of Southern California School of Medicine, Los Angeles, California Objective esophageal reflux. Intestinal metaplasia, even a short To outline current concepts regarding etiology, diagnosis, and length, is premalignant, and the presence of dysplasia indi- treatment of intestinal metaplasia of the esophagus and cardia. cates progression on the pathway to adenocarcinoma. An- tireflux surgery, as opposed to medical therapy, may in- Summary Background Data duce regression or halt progression of intestinal Previously, endoscopic visualization of columnar mucosa ex- metaplasia. The presence of high-grade dysplasia is fre- tending a minimum of 3 cm into the esophagus was sufficient quently associated with an unrecognized focus of adeno- for the diagnosis of Barrett’s esophagus, but subsequently carcinoma. Vagal-sparing esophagectomy removes the the importance of intestinal metaplasia and the premalignant diseased esophagus and is curative in patients with high- nature of Barrett’s have been recognized. It is now apparent grade dysplasia. Invasion beyond the mucosa is associated that shorter lengths of intestinal metaplasia are common, and with a high likelihood of lymph node metastases and re- share many features of traditional 3-cm Barrett’s esophagus. quires lymphadenectomy. Methods Themes and concepts pertaining to intestinal metaplasia of the esophagus and cardia are developed based on a review Conclusions of the literature published between 1950 and 1999. Despite improved understanding of this disease, controversy about the definition and best treatment of Barrett’s esopha- Results gus continues, but new molecular insights, coupled with care- Cardiac mucosa is the precursor of intestinal metaplasia of ful patient follow-up, should further enhance knowledge of the esophagus. Both develop as a consequence of gastro- this disease. Originally the term “Barrett’s esophagus” was used to HISTORY describe an esophagus in which a portion of the normal squamous mucosa was replaced by columnar epithelium. Stomach Versus Esophagus Since the 1950s, when the term became popularized, much Since the early 1900s, the presence of ulcers within a has been learned about this condition, and new concepts columnar epithelial-lined, tubular structure of the foregut continue to emerge that force reevaluation of this disorder. have been described. In the mid-1900s, the debate raged In fact, the meaning of the term Barrett’s esophagus is over whether these ulcers were located in a tubularized perhaps more ambiguous now than ever before. portion of stomach or in the esophagus. Using criteria “relevant to the physiologist, surgeon, and physician,” Dr. Norman Barrett, an influential British surgeon, wrote in 1950 that sections of the gastrointestinal tract are defined by Correspondence: Steven R. DeMeester, MD, Dept. of Cardiothoracic Sur- gery, Norris Comprehensive Cancer Center, 1441 Eastlake Ave., MS their mucosa, and therefore the esophagus is “that part of the 74, Los Angeles, CA 90033. foregut distal to the cricopharyngeal sphincter which is Accepted for publication November 4, 1999. lined by squamous epithelium.”1 He went on to state that 303 304 DeMeester and DeMeester Ann. Surg. ● March 2000 when ulcers are found below the squamocolumnar junction, Evolving Definition they represent gastric ulcers within “a pouch of stomach . The 3-cm Rule drawn up by scar tissue into the mediastinum” or more likely represent “examples of a congenital short esopha- In the late 1950s, the term Barrett’s esophagus was un- gus.” derstood to mean a columnar-lined esophagus, and this In 1953, Allison and Johnstone demonstrated that the rather vague definition persisted until the 1980s. Refine- tubularized portion of the foregut declared by Dr. Barrett to ments in the definition came about as a result of two issues. be stomach had no peritoneal covering, normal esophageal The first was that as endoscopy became more common, it musculature, and typical esophageal mucous glands. They was recognized that many patients had hiatal hernias and concluded that “it appears better to refer to that congenital esophagitis, and that it was difficult and error-prone for an abnormality which from the outside looks like esophagus endoscopist to determine precisely where the esophagus ended and the stomach began. In addition, Hayward in and from the inside looks like stomach as ‘esophagus lined 19616 had written that the “normal” esophagus could have with gastric mucous membrane.’ ”2 Although they called 1 to 2 cm of columnar mucosa at the distal end. Therefore, the mucosa “gastric,” they recognized that oxyntic cells to avoid an overdiagnosis of Barrett’s resulting either from were not present. failure to recognize a tubularized portion of herniated stom- In 1957, Dr. Barrett accepted the viewpoint that in ach on endoscopy, or from failure to allow for the “normal” some patients the columnar epithelium extended further 2 cm of columnar mucosa in the distal esophagus, a 3-cm proximally into the esophagus than could be accounted rule was introduced in the early 1980s. This rule stipulated for by a hiatal hernia. Further, he concurred with Allison that a diagnosis of Barrett’s esophagus required a minimum and Johnstone that the columnar mucosa, despite its of 3 cm of columnar mucosa to be present above the “gastric” appearance, did not contain oxyntic cells and perceived gastroesophageal junction. Although various au- did not function like gastric mucosa. He agreed to the thors used between 2 and 5 cm of columnar mucosa, some term “columnar-lined lower esophagus,” and subse- minimum length requirement was adopted by most physi- quently his name became synonymous with the condi- cians and persists in the minds of many people to this day. tion. Importance of Intestinal Metaplasia The second issue that forced refinement in the definition Congenital Versus Acquired of Barrett’s esophagus was the identification of a subset of patients with a columnar-lined esophagus who were at risk In their 1953 report, Allison and Johnstone had noted that for developing adenocarcinoma. In 1951, Bosher and Tay- the presence of a columnar-lined esophagus was usually lor7 described goblet cells indicative of intestinal metaplasia associated with a hiatal hernia, and that all of the patients within a columnar-lined esophagus. In subsequent publica- had reflux esophagitis. Still, like Dr. Barrett, they consid- tions Allison, Barrett, and others noted that the columnar ered it to be of congenital origin. Later Dr. Barrett, while mucosa of Barrett’s esophagus, although “gastric” in ap- 2,3 still favoring a congenital etiology, conceded that “if the pearance, was not normal gastric mucosa. Despite these cardiac valve of a normal person were to become incompe- observations, most physicians paid no particular attention to tent and if the lower esophagus were, as a result, to be the histology of the columnar lining within the esophagus. 8 bathed for a long time by digestive gastric juice, the squa- This changed in 1976 after a report by Paull et al described mous epithelium could be eaten away and totally replaced the results of manometrically guided biopsies at multiple levels from 11 patients with a columnar-lined esophagus. by columnar cells.”3 Each patient was found to have one or a combination of In 1959, Moersch et al4 reviewed the specimens from three histologic types of columnar epithelium: a gastric 36 patients who had undergone esophageal resections at fundic type composed of chief and parietal cells; a junc- the Mayo Clinic for esophagitis. They noted that “cells tional type composed of mucous glands without parietal resembling young columnar cells were seen occasionally, cells; and a specialized type with intestinal characteristics and thus the question of inflammatory metaplasia had to including villiform surface, mucous glands, Alcian blue- be considered.” This was the first convincing evidence staining goblet cells, and no parietal or chief cells. In these that the columnar epithelium of Barrett’s esophagus was 11 patients, Paull et al noted that the most prevalent type of acquired, and that it was caused by repetitive exposure of columnar epithelium was the specialized type, and when the distal esophagus to refluxed gastric juice. Subse- present, the specialized mucosa was always found adjacent quently several studies, including the 1970 landmark to the squamous epithelium in the most proximal portion of experimental report by Bremner et al,5 confirmed the the columnar epithelium. If the specialized mucosa did not association between a columnar-lined esophagus and gas- involve the entire columnar segment, then junctional mu- troesophageal reflux disease (GERD), and the congenital cosa was present below the specialized mucosa, and the theory was discarded. gastric fundic type of epithelium was found most distal. The Vol. 231 ● No. 3 Columnar Mucosa and Intestinal Metaplasia of the Esophagus 305 importance of the specialized or intestinal type of epithe- for Barrett’s. Using the traditional definition of at least 3 cm lium within a columnar-lined esophagus was hinted at in of columnar mucosa above the gastroesophageal junction, this report, in which 1 of the 11 patients was noted to have Barrett’s has been reported in
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