THE LOWER ESOPHAGUS LINED BY COLUMNAR EPITHELIUM

THE LOWER ESOPHAGUS LINED B Y COLUMNAR EPITHELIUM Its Association With Hiatal Hernia, Ulcer, Stricture, and Tumor Richard H. Adler, M.D., Buffalo, N.

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N 1950, Barrett 6 drew attention to a condition in which the lower esophagus (gullet) was lined by a continuous sheet of gastric epithelium. This immediately created confusion because, the esophagus by definition had to be lined by squamous epithelium, therefore, this structure was stomach not esophagus. In 1953, Allison and Johnstone 4 published their reasons for considering this congenital anomaly to be "Oesophagus Lined With Gastric Mucous Membrane" and not intrathoracic stomach: (1) this tubular structure resembled esophagus grossly and had no peritoneal covering as did the stomach, (2) the submucosa had mucous glands and the musculature resembled that of the esophagus, and (3) islets of squamous epithelium could be found within the sheet of gastric epithelium. These authors also noted that there were no acidproducing oxyntic cells in the gastric mucous membrane which lined this segment of esophagus. In 1957, Barrett 8 altered his views and suggested that the entity be referred to as "The Lower Esophagus Lined by Columnar Epithelium." It has also been referred to in the literature as the Barrett syndrome. During the past decade this newly recognized entity of columnar epithelium lining the lower half or third of the esophagus has become a subject of increasing clinical concern, largely because of the associated stricture and ulcer. A large part of the literature consists of individual case reports, 10 ' "' 3 5 - 3 8 > 3B-46 although reports of a few small series of patients have also been published. 4 ' 23 ' 32>44 Other instances referring to the lower esophagus lined by columnar epithelium have been found within publications of a more general nature which did not deal specifically with this subject. Despite the growing interest in this condition, many doctors either remain unaware of it or else have only a vague knowledge of its existence. The subject remains poorly understood, due in part to the small number of patients with well-documented clinical courses and the paucity of complete pathologic studies. Our knowledge of the normal esophageal mucosa is also quite incomplete, and a review of past studies shows frequent discrepancies and contradictions. It is From the Buffalo General Hospital, the Roswell Park Memorial Institute, and The University of Buffalo School of Medicine. Buffalo, N. T. Supported in part by the United Health Foundation. Read a t the Forty-second Annual Meeting of The American Association for Thoracic Surgery a t St. Louis, Mo., April 16-18, 1962. 13

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quite understandable, therefore, that the lower esophagus lined by columnar epithelium is a condition poor in fact but rich in theory. It invites speculation but resists laboratory reproduction. CLINICAL DATA

I. A. Lower Esophagus Lined by Columnar Epithelium—High Esophageal Stricture—Hiatal Hernia. CASE 1.—O. E., a 61-year-old white man, was admitted to Eoswell Park Memorial Institute in January, 1954, with a 6 month history of progressive dysphagia. He was able to swallow only liquids. Food would stick beneath the mid-sternum and frequently would be regurgitated. He denied ever having had indigestion or symptoms of esophagitis. X-ray studies showed a stricture at the level of the aortic arch which was diagnosed as carcinoma. A small hiatal hernia was also present distally, and there was free reflux of barium from stomach into esophagus. Esophagoscopy revealed a slightly irregular stenotic area 25 cm. from the incisors. Biopsies showed hyperplastic squamous mucosa and also epithelium with tall columnar cells which was diagnosed as ' ' gastric mucosa.'' No oxyntic cells were present. The stroma was vascular and widely infiltrated with inflammatory cells. Esophagoscopy and biopsy were repeated a short time later because of the clinical suspicion of an underlying carcinoma, but the findings were essentially the same. With a preoperative diagnosis of carcinoma of the esophagus, a right thoracotomy was performed in April, 1954. A bulbous thickening, 2 cm. long, of the esophagus was noted at the level of the aortic arch. The involved esophagus was opened longitudinally and found to be scarred and thickened with piled-up mucosa. Several biopsies were taken along the stenotic area. When frozen sections showed no tumor, the esophagus was closed. A program of dilatations rather than resection was selected because of the patient's poor condition. During August and September of 1954, two courses of dilatations performed with olive-tip bougies over a previously swallowed string resulted in considerable improvement. The patient was readmitted to the hospital in May, 1955, because of an impacted piece of meat; this was relieved by a digestant. Dilatation was performed and he was discharged improved. During the following 4 years he needed a total of 15 courses of dilatations as an out patient. When last contacted by telephone in March, 1962, he claimed to have remained free of further complications and said that, with care, he could eat a fairly regular diet. CASE 2.—E. H., a 60-year-old white woman, was admitted to Eoswell Park Memorial Institute in March, 1958, because of progressive dysphagia over a period of 2 years. At the time of admission she could swallow liquids and selected soft solids. I n December, 1957, when she first consulted her physician, x-ray studies showed a short stricture in the midthoracic esophagus. Esophagoscopio biopsy was reported as " a n adenoma of the esophagus with malignant c h a n g e . " The slide was subsequently reviewed by our pathologist and interpreted as ectopie gastric mucosa in the esophagus. An esophagram made in March, 1958 showed a short stricture in the mid-esophagus with a hiatal hernia distally. At esophagoscopy a moderate stenosis was encountered in the mid-esophagus. The mucosa at the stenosis was red and piled up in one area and resembled granulation tissue. Gastric fluid could be seen to reflux into the upper esophagus through the area of stenosis. Multiple biopsies revealed the presence of glandular columnar epithelium with cellular infiltration consisting mostly of lymphocytes. This was reported as ectopie gastric mucosa. On a strict medical regimen, including sleeping with the head of the bed elevated, the patient had improved markedly when seen 3 months later. Although her diet remains restricted, she has experienced no serious complications. CASE 3.—L. M., a 68-year-old white woman, was admitted to Roswell Park Memorial Institute in May, 1960, because of progressive dysphagia for 5 months. The main complaints

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were those of food sticking beneath the mid-sternum and regurgitation. She had had heartburn with considerable gas and also indigestion with f a t t y foods for about 5 years. Esophagram showed an irregular narrowing in the mid-thoracic esophagus. A hiatal hernia was noted distally with free regurgitation of barium from stomach to esophagus. A hiatal hernia was said to have been present in 1938, but these roentgenograms could not be obtained. Esophagoscopy in May, 1960, revealed an area of stenosis with redness and erosions 25 cm. from the incisors. This limited further passage of the esophagoscope. Biopsies showed the junction of squamous and columnar mucosa that was interpreted as stomach and esophagus. At repeat esophagoscopy, 2 weeks after intensive medical treatment, an esophagoscope 9 mm. in diameter could be passed beyond the stenosis. At 35 em. the mucosa changed to typical gastric rugi inside the herniated stomach. The columnar mucosa between 25 and 35 cm. had the gross appearance of normal esophageal mucosa.

Fig. 1.—Esophagram (Case 4) showing high stricture, columnar-lined segment, and hiatal hernia. A, Admission x-ray. B, Two months after esophagoscopy with dilatation. On conscientious medical treatment, the symptoms improved but the patient had to continue on a limited diet of liquids and soft solids. She was readmited for esophagoscopy and dilatation in March, 1962, with slowly progressive obstructing dysphagia and x-ray evidence of further stenosis of the stricture. The stricture was present at the same level. At esophagoscopy, free reflux of gastric fluid was seen above the stricture. There was moderate esophagitis proximal to 'the stricture. After dilatation, a bronchoscope was inserted through the stricture and biopsies were taken along the length of the esophagus. Although the esophagus looked normal grossly, biopsies showed it to be lined by heterotopic columnar epithelium. Acute and chronic inflammation and intestinal metaplasia were also noted. CASE. 4.—M. K., a 62-year-old white man, was admitted to Roswell Park Memorial Institute in July, 1961, with a 3 month history of progressive dysphagia. He was a poor

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historian, but did admit to indigestion in the past. X-ray studies showed a short stricture at the aortic arch level with a hiatal hernia distally (Fig. 1, A). Esophagoscopy revealed a narrow concentric stricture a t the 24 cm. level. This was readily dilated to a No. 30 F r . bougie through a Roberts esophagoscope 12 by 16 mm. in diameter. A bronchoscope was then passed distally with biopsies taken throughout the full length of the normal appearing esophagus. The biopsies revealed squamous epithelium proximal to the stricture and columnar epithelium distally. When- seen in the out-patient department 2 months later he was swallowing most foods without difficulty except for large pieces of meat. The stenosis was less pronounced on esophagram (Fig. 1, B).

Fig. 2.—Esophagram (Case 5) showing (A) triple segment on admission and, (B) penetrating ulcer (arrows) in columnar-lined esophagus 3 years later.

B. Lower Esophagus Lined by Columnar Epithelium—High Esophageal Stricture—Hiatal Hernia—Development of Ulcer Crater in Columnar-Lined Esophagus. CASE 5.—L. R., a 70-year-old white man, was admitted to the Buffalo General Hospital in November, 1958, because of a 4 month history of progressive dysphagia and food sticking beneath the upper sternum. He had also developed heartburn during the previous year, especially when lying flat. No past symptoms of reflux or indigestion could be obtained. X-ray examination showed a short stricture at the aortic arch level with a hiatal hernia distally (Fig. 2, A). Another endoscopist noted the stenosis at 25 cm. from the incisors and thought that a tumor was present. Because of a negative biopsy, a second esophagoscopy was performed 5 days later at which time biopsies were also taken from within the stricture. The specimens showed inflammatory reaction in the squamous epithelium proximal to the stricture and also ' ' g a s t r i c ' ' epithelium but no malignancy. Because of marked

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emphysema, the patient was discharged on an ulcer-hiatal hernia medical program. During the 3 years from 1959 through 1961, he was admitted to the hospital five times; four because of food impaetions at the stricture and once because of anemia, progressive dysphagia, and heartburn. Esophagoscopies and dilatations, along with a strict medical regimen, afforded considerable improvement. Biopsies of the entire length of the esophagus beyond the stricture after dilatation showed columnar epithelium with variable degrees of inflammatory reaction and intestinal metaplasia. The most recent admission was in January, 1962, because of extreme dysphagia, weight loss, debilitation, and severe bilateral aspiration pneumonia. Stools were positive for occult blood. The hemoglobin was 6 Gni. X-ray examination showed a less severe stricture at the aortic arch level. A large ulcer crater in the columnar-lined lower esophagus was noted, and it appeared to have penetrated and become walled off by periesophagcal tissues (Fig. 2, B). At esophagoscopy, the high stricture was considerably less severe than at previous examinations, and it could be readily dilated to allow passage of the 12 by 16 mm. wide Roberts esophagoscope. At the 30 cm. level, a fungating obstructive mass was encountered which

Fig. 3.—Deep ulcer crater with stenosis in esophagus lined by columnar epithelium (Case 6). A, Full-length view shows stomach and hiatal hernia. B, Close-up view shows ulcer. was located largely on the right posterior lateral wall and which, at first glance, resembled a tumor. I t produced a marked stenosis, and dilatation was difficult because of the extreme friability and inflammatory reaction. After dilatation, a bronchoscope was passed beyond the stenotic ulcerated area and multiple biopsies were taken which showed columnar epithelium above and below the ulcerated area with severe inflammatory reaction, polypoid proliferation, glandular hyperplasia, and intestinal metaplasia. After a short period of improvement the obstruction returned. A feeding gastrostomy was performed under local anesthesia to permit his transfer to a nursing home. His general condition improved considerably on gastrostomy feedings.

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C. Lower Esophagus Lined by Columnar Epithelium—Hiatal Hernia—Ulcer Crater in Columnar-Lined Esophagus.

CASE 6.—A. C , a 64-year-old white woman, was admitted to the Buffalo General Hospital in May, 1961, because of marked anemia and dysphagia. For the previous several years, swallowing had become progressively painful and was accompanied by intermittent obstruction to the passage of solids. The patient had had a gastric ulcer 20 years previously. A hiatal hernia was known to have been present for a t least 10 years. She had had indigestion and epigastric discomfort in the past. At the time of admission she could not lie flat because of the accompanying pain and gastric reflux. She was extremely obese and had been unable to lose weight claiming that she had in fact gained weight as a result of her milk-and-cream ulcer regimen. X-ray studies showed a rather long mid-csophageal stenosis with a punched-out ulcer crater (Fig. 3 ) . A hiatal hernia was present distally. Esophagoscopy showed a severe eccentric stenosis at a level 27

Fig. 4.—Stenotic esophagus above hiatal hernia; esophag'oscopic biopsies just above and within the stricture showed heterotopic columnar epithelium ■with inflammatory reaction (see text). cm. from the incisors. The mucosa proximal to the stenosis was injected and watery gastric fluid could be seen to well up into the proximal esophagus. There were inflamed edematous mucosal folds on the right posterior lateral wall of the esophagus at the stricture site which represented edematous tissue surrounding the ulcer. Biopsies taken above and below the stenosis showed columnar epithelium with marked inflammatory reaction and ulceration in one section. Numerous goblet cells were present with areas resembling intestinal metaplasia. The stenotic area resisted passage of the large esophagoscope and distal biopsies were obtained through a smaller bronchoscope. The patient's symptoms improved somewhat under medical treatment and transfusions. When last seen 9 months later, the ulcer crater was smaller and the stenosis less marked. Her diet continues to be restricted to liquids and soft solids.

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Comment: All patients had hiatal hernias and were in the sixth and seventh decades. Symptoms of reflux esophagitis were occasionally lacking, and the short history of progressive dysphagia suggested the diagnosis of carcinoma. Four patients with gastric analyses had normal or moderately elevated fasting acid values. In general, symptoms recurred if the gastroesophageal reflux was not adequately controlled. Meat impactions at the stricture site were annoying complications in 2 male patients. None of the biopsies showed parietal cells in the columnar epithelium. Inflammatory reaction was common. Mucosal changes resembling "gastritis" and intestinal metaplasia were seen, particularly at the sites of ulcers and strictures.

Fig. 5.—Progressive ascending stricture above hiatal hernia. Esophagoseopic biopsies showed inflammatory columnar epithelium with intestinal metaplasia at proximal orifice and within stricture. A, Esophagram made in 1958. Bf Esophagram made in 1961.

II. Columnar Epithelium With Lower Esophageal Stricture and Hiatal Hernia. Five additional patients with elongated strictures above hiatal hernias were found by esophagoseopic biopsy to have the same columnar epithelium directly above and within the strictures, although they did not present the more classical picture of a high stricture with a longer distensible columnar-lined segment (Fig. 4). In the interest of brevity, histories will be omitted. All were in the fifth through seven decades. In 3 patients, progression and ascent of the strictures were documented over 3 to 5 years (Fig. 5). In the absence of resection, however, the extent of the columnar epithelium in these individuals remains uncertain.

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DISCUSSION

One starts with the observed fact that the lower half of the esophagus may be lined by a more or less continuous sheet of columnar epithelium and that this may be associated with clinically significant complications. Uncertainties immediately follow as to the pathogenesis and proper management of the condition. Although certain observations based upon our own findings will be presented, a born speculator cannot resist the temptation to venture several opinions that extend beyond the realm of absolute factual support and experimental proof. This is done with the full realization that some statements may be entirely repudiated in the light of future investigations. However, it may stimulate further interest in this condition which should prove to be more common when looked for than heretofore suspected, especially in an expanding geriatric population. v Pathogenesis.—The etiology of the columnar lining in the esophagus may be considered in two categories, congenital and acquired. Congenital theory: This is the generally accepted concept based upon the fact that the embryonic esophagus first has a lining of columnar epithelium and that this is later incompletely replaced with squamous epithelium which leaves the lower esophagus lined by the fetal columnar layer. Some like to think of this as a congenitally short squamous esophagus in which only the squamous lining failed to reach its complete development.30 Classical teaching states that embryonic columnar and glandular gastric epithelia may persist in the esophagus after birth. Islets of ciliated columnar epithelium have been noted in postmortem examination of esophagi from premature and newborn infants. 16 ' 19 ' S4 A sheet of ciliated columnar epithelium has also been found lining the lower esophagus of one asymptomatic adult who died of an unrelated condition.33 Acquired theory: It has been difficult to understand why the sheet of columnar epithelium is always found in the lower esophagus since the squamous replacement of fetal columnar epithelium begins about mid-esophagus and progresses toward each end.19 Also, it is generally stated that islets of congenital ectopic gastric mucosa are most common in the cervical esophagus since this appears to be the last area to lose the embryonic columnar lining. Relatively recent observations, 14> 2 3 ' 3 9 ' 4 5 documenting the ascent up the esophagus of a stricture at the squamo-columnar junction (as squamous epithelium is replaced by that of a columnar type), supports the concept of an acquired dynamic epithelium. The occurrence of islets of squamous epithelium within the sheet of columnar epithelium could be interpreted as the more resistant remnants of squamous epithelium that survived the erosive action of the digestive secretions. This finding of squamous islets is less easily explained by the congenital theory. The acquired theory in essence interprets the columnar epithelium to be an adaptive change in response to the continued foreign (acid-pepsin) environment present in the esophagus. Following repeated cycles of destruction and regeneration, in some individuals, a simple columnar type of epithelium more resistant to digestive action finally replaces the destroyed squamous epithelium. This is the same sort of mucus-secreting columnar epithelium that lines the surface of the stomach and covers an organ such as the kidney or spleen when it is sutured

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into a surgically created window in the stomach and left exposed to the gastric secretions. The columnar lining is usually discovered in middle or late life as a result of the development of an ulcer or stricture. However, references to 2 children with the lower esophagus lined by columnar epithelium were uncovered in the literature. 32 ' 46 The patient of Wyndham 46 was a 9-year-old boy and that of Postlethwait and Sealy32 a 10-year-old girl. Both children had experienced dysphagia since infancy. It is common to find a hiatal hernia with evidence of gastroesophageal reflux. In this situation, the refluxing gastric sections would appear to be responsible for the acquired heterotopic columnar epithelium. Those favoring the congenital theory point to the patients having columnar epithelium in the esophagus without a hiatal hernia. Here it is assumed that the lesion becomes symptomatic later in life as a result of the development of a hiatal hernia and gastroesophageal reflux. That the mucosa may occasionally have been present since birth cannot be denied. If the congenital columnar epithelium lining the esophagus produces significant acid and pepsin itself as some believe, it is difficult to understand why complications do not occur early in life such as are usually found associated with Meckel's diverticulum when functioning ectopic gastric mucosa is present. It might be argued that more specialized acid and enzyme secreting cells could develop in the columnar epithelium, but our evidence suggests that, if anything, the epithelium regresses under the continued irritating environment toward less specialized forms resembling gastritis and intestinal metaplasia. It remains to be determined whether the heterotopic columnar epithelium can assume a more specialized form or revert to a squamous type when the abnormal internal environment is corrected. Sources of Columnar Epithelium in the Esophagus.—The acquired (adaptive) columnar epithelium may be considered as coming from one or more of three sources: (1) upward extension from the stomach, (2) metaplasia from squamous epithelium, and (3) from the superficial (cardiac) glands of the esophagus. 1. Extension upward from the stomach: The cardiac end of the stomach is lined by the same simple columnar epithelium essentially devoid of digestive cells as is found in the lower esophagus lined by columnar epithelium. The same epithelium also lines a variable extent of the most distal normal esophagus, forming, together with that of the proximal stomach, a buffer zone between the true digestive gastric epithelium below and the sensitive squamous epithelium above. It is not uncommon to see tongues of columnar epithelium extending up the esophagus above a hiatal hernia to form a zone of mixed epithelium. It is questionable whether columnar epithelium from this source alone could extend to levels as high as the aortic arch. 2. Metaplasia from squamous to columnar epithelium: Despite the extensive writings on metaplasia in various areas of the body, practically nothing is known of the adaptive responses that might occur in the unique exposure of squamous epithelium to chronic acid-pepsin digestion. There is no direct evi-

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dence to show that the esophageal squamous epithelium undergoes metaplasia into the columnar epithelium under discussion. In our laboratory studies, resection of canine esophageal mucosa is followed by regeneration of squamous mucosa. Studies are in progress to evaluate the epithelial regeneration in a preparation chronically exposed to an acid-pepsin environment similar to that encountered clinically. 3. From cardiac glands: In contrast to the deep or submucosal glands of the esophagus, the cardiac glands lie superficial to the muscularis mucosa, just beneath the squamous epithelium. Remarkably little is known about the cardiac glands. They vary widely among mammals, their true function remains in question, and parietal cells have been noted occasionally within them. 9 ' 13,17 ' 1 8 > 2 0 ' 4 0

Fig. 6.—Photomicrograph of rolled esophageal mucosa from stomach (S) to pharynx. Note patch of glandular columnar epithelium (between arrows) near cervical end of strip (see text).

The entire esophageal mucosae from over 250 routine autopsies have been cut into lengthwise strips and each narrow strip wound up in jelly-roll fashion.2 This permits complete histologic examination of the entire esophageal mucosa (Fig. 6). Several findings pertinent to this discussion, but at variance with generally accepted views founded on random sectioning of esophagi, merit comment. Unlike the classical description of the cardiac glands which states that they are located at either end of the esophagus, the glands have been seen scattered diffusely throughout the length of some esophagi (Fig. 7). In no instance were parietal cells seen. In some areas, glandular islets presented on the surface as though the squamous epithelium had been eroded or wiped away. This picture resembled what could have been called islets of ectopic gastric mucosa. The exposed glands were commonly associated with a chronic type of cellular infiltration. The superficial glands in our patients with the lower esophagus lined by columnar epithelium often appeared to be growing out in an effort to cover

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the surface denuded of its squamous epithelium (Pig. 8). Glandular hyperplasia was common, and the deeper penetration of the glands resulted in an appearance resembling that seen normally in the prepyloric area of the stomach. The glands appeared to hypertrophy and increase their mucous secretions as if to protect deeper layers of the esophagus from damage. With a little imagination, one can conceive of the occasional esophagus generously provided with superficial (cardiac) glands as being able to prevent deeper destruction by progressively replacing the digested squamous epithelium with the more resistant proliferating glandular columnar lining. The extent of replacement and the depth of protection may vary with the number and distribution of the superficial glands.

Fig. 7.—Close-up photomicrographs encompassing several layers within roll of esophageal mucosa from two different individuals to show (A) esophagus with many superficial (cardiac) glands throughout, and (S) esophagus with practically no glands.

Ulcer.—In 1950, Barrett 6 helped dispel the confusion on esophageal ulcerations by distinguishing between the deep ulcer crater in columnar epithelium— the chronic peptic ulcer of the esophagus—and the more common superficial ulcerations (erosions) in squamous epithelium associated with reflux esophagitis. Pathologists had long known of the ulcer crater occasionally found in the esophagus, and they had noted its adjacent columnar epithelium; but this had been interpreted as a peptic ulcer in a patch of eetopic gastric mucosa. It may be assumed that a thorough study of the mucosa (if it had not undergone postmortem autolysis) would have shown a more extensive stretch of columnar epithelium in the esophagus. It seems rather unlikely that an islet of columnar

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epithelium, essentially devoid of parietal cells, could produce an ulcer in an esophagus adequately bathed by mucus and saliva. A deep ulcer may be found in the junctional area of columnar and squamous epithelium. Wolf and his associates45 referred to this as a marginal ulcer. The ulcer may be located within the mixed zone of columnar and squamous epithelial interdigitations above a hiatal hernia which makes its exact classification difficult.

Fig. 8.—Representative photomicrographs of esophagoscopic biopsy specimens from lower esophagi lined by columnar epithelium. A, Simple columnar epithelium (X140; reduced % ) . B, Squamocolumnar epithelial junction a t proximal end of stricture near aortic arch with moderate inflammatory reaction shown in glandular columnar lining (X140; reduced tyi).

Stenosis and Stricture.—In this discussion, strictures and stenoses of the esophagus may be considered as of two general types: that in squamous epithelium and that in columnar epithelium. The stricture at the squamocolumnar junction involving predominantly squamous epithelium tends to be superficial and short, although its length and depth may vary. In the lower esophagus,

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lined by columnar epithelium, the stricture is characterized by being situated higher in the esophagus at a distance from the gastroesophageal junction (see Figs. 1 and 2). The penetrating ulcer in the columnar-lined esophagus tends to produce a more eccentric type of stenosis with a large component of inflammatory edema and congestion. Although this ulcer may cause deeper fibrosis, it is seldom of a circular constricting type as seen with the stricture in the functional squamous epithelium.

Fig. 8.—Cont'd. C, Erosion in columnar epithelium with glands and inflammatory reaction extending through lamina propria to muscularis mucosa (X50 ; reduced % ) . D, Papillary villus-like proliferation with inflammatory reaction, increase in goblet cells, and evidences of intestinal metaplasia (X50; reduced % ) .

Barrett 8 has stressed the importance of muscular hypertrophy as the outstanding feature of the strictures he has examined and Moersch and his coworkers22 have noted this in a single instance. In general, it would appear that fibrosis rather than muscle hypertrophy is the predominant finding. The finding of a progressive stricture with columnar epithelium at its

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proximal end in 5 of our patients needs further study. This may be an intermediate stage of the so-called lower esophagus lined by columnar epithelium in which the esophagus distal to the stricture is short and not distensible. Perhaps our patients had inadequate glandular protection against deeper fibrosis or there may have been an insufficient covering of columnar epithelium after squamous digestion to prevent constriction. Our laboratory studies with sleeve resections of esophageal mucosa have demonstrated the rapidity with which the denuded esophagus becomes stenotic. If this segment of esophagus is kept open by a stent or by endoscopic dilatations, it once again becomes distensible when it becomes covered by epithelium if deeper scarring from infection and trauma has been avoided during the period of epithelial regeneration. Tumor and Associated Epithelial Alterations.—Although conclusive proof is lacking, there is intriguing evidence which suggests that the columnar glandular epithelium lining the lower esophagus may give rise to tumors, particularly adenocarcinoma. Adenocarcinoma of the esophagus is more common than previously suspected, and an increasing number of such tumors have been reported in recent years in association with the esophagus lined by columnar epithelium.4' 5 > 7 - 1 2 ' 2 1 ' 2 4 ' 36>41 Other reports of adenocarcinoma of the esophagus may be found in which only limited examination of the adjacent mucosa was performed so that the authors assumed that the tumor arose from an islet of ectopic gastric mucosa or from cardiac glands. In other cases no comment was made concerning the type of surrounding mucosa. There is also increasing evidence to suggest that the association of carcinoma, especially adenocarcinoma, with certain chronic hiatal hernias may be one of a cause and effect relationship. 3 ' 29 ' 37 Adenocarcinoma in the esophagus near the gastroesophageal functional area can no longer be automatically classified as a carcinoma of the stomach with an upward extension (Fig. 9). Impressive pathologic evidence exists to suggest that some forms of so-called gastric atrophy or atrophic gastritis and the accompanying metaplasia of the gastric epithelium to an intestinal type of epithelium constitute a premalignant condition. Morson,25"27 in particular, has championed the view that repeated attacks of inflammatory gastritis may lead to the premalignant phase in which the gastric epithelium acquires an appearance similar to that seen in the intestine. These gastric epithelial changes are also seen commonly in pernicious anemia and are found quite often, particularly in the mucosa adjacent to gastric carcinoma. Nevertheless, similar epithelial changes may be found at times in association with other nonmalignant conditions, and there is no universal agreement as to the true significance of these mucosal findings in the stomach. Eecent histochemical studies have shown a high activity of the enzyme aminopeptidase in gastric mucosa which has undergone metaplasia to an intestinal appearing type of epithelium, as well as in most instances of gastric carcinoma. This enzyme is not encountered in normal gastric mucosa, further suggesting some relationship between so-called "intestinal metaplasia" of the gastric epithelium and gastric carcinoma. 31 ' 42 We have observed the same atrophic chronic inflammatory changes and intestine-like metaplasia in the columnar epithelium lining the lower esophagus

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Fig. 9.—Adenocarcinoma arising in lower esophagus with columnar epithelial lining. A, Esophagram shows hiatal hernia and stenosis in lower esophagus resembling peptic stricture. B, Opened surgical specimen shows minimal tumor (arrmv) presenting in esophageal lumen.

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as described in gastric mucosa. It is tempting to hypothesize that the same premalignant potential could develop in the columnar epithelium of the esophagus as may be present in the stomach. We are presently determining aminopeptidase activity in fresh frozen esophagoscopic biopsies from several patients with metaplastic changes in the columnar-lined lower esophagus. Diagnosis.—History: The patients are almost always in the older age group. Some may deny any past difficulties suggestive of reflux esophagitis, and carcinoma is then suspected. Those with a high stricture point to a higher level of food sticking beneath the sternum in contrast to that seen with the stenosis commonly encountered directly above a hiatal hernia. A penetrating ulcer in the columnar-lined esophagus will give rise to a deep discomfort or pain on swallowing. All other symptoms commonly associated with reflux esophagitis may also be present. X-ray examination: A stricture considerably above the stomach, especially if a hiatal hernia exists, should suggest the diagnosis of lower esophagus lined by columnar epithelium (see Pigs. 1 and 2). An ulcer crater or niche well up in the esophagus should also suggest the presence of columnar epithelium (see Pig. 3). The so-called triple segment4 formed by the squamous-lined esophagus proximal to the high stricture, the intermediate columnar-lined segment, and the pouch of the herniated stomach may be considered diagnostic of the condition (see Pigs. 1 and 2). A hiatal hernia may not always be present, but the presence of reflux from the stomach may be just as significant. It must be recognized that failure to demonstrate a hiatal hernia or gastroesophageal reflux on a single examination does not necessarily exclude the existence of gastroesophageal incompetency. Esophagoscopy: The diagnosis can be confirmed by esophagoscopy with biopsy. The junctional stricture involving the squamous epithelium is usually concentric. Esophagitis and refluxing gastric fluids may be observed proximal to the stricture. When a tight stricture prevents distal inspection, it is most important to take multiple blind biopsies from deep within the depths of the stricture using small-angled cupped forceps. This has been most helpful in differentiating the heterotopic columnar epithelium from carcinoma. The advantages of a large lumen esophagoscope have been described elsewhere. 1 The stricture may be effectively dilated under direct vision to a size that will permit passage of a smaller esophagoscope or bronehoscope through which the entire esophagus beyond the stricture may be inspected and biopsied. The thin layer of simple columnar epithelium resembles squamous epithelium, and its presence may not be appreciated without a biopsy. With glandular hyperplasia, it appears thickened and it may have prominent folds. When it becomes polypoid, it may resemble a glandular polyp, an adenoma, or even be mistaken for a malignancy. The Barrett-type columnar ulcer may be obscured by the friable edematous mucosal folds. The resulting stenosis is usually eccentric and, although resembling a tumor, the associated inflammatory reaction should suggest the true underlying nature of the process.

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Treatment.—Treatment will remain inexact until the pathogenesis of columnar epithelium in the esophagus and its complications are better understood and sufficient time has elapsed in which to evaluate methods of management currently employed. Nevertheless, certain suggestions may be put forth, based upon current observations with the realization that they may be altered with time. The main aim is to remove the abnormal (acid-pepsin) environment from the esophagus. Reversible inflammatory lesions should then subside. Remaining areas of permanent damage, such as fibrotic strictures, may need additional attention. Since many of these individuals are elderly patients in too poor a condition for extensive surgery, an aggressive surgical plan of excising all abnormal tissue must be tempered by a philosophy of willingness to achieve palliation with the use of less risky methods. Hiatal hernia and gastroesophageal reflux are commonly present; therefore, a strict program of medical management including an ulcer-like regimen, weight loss for the obese, and the permanent use of supports to keep the head of the bed elevated must be undertaken promptly. In the presence of an established ulcer or stricture, medical treatment may be only partially successful. Although the occasional patient may become asymptomatic under this form of therapy, others will continue to limp along on a restricted diet ever fearful of an obstructing food impaction. When symptoms of reflux esophagitis and ulceration persist, surgical intervention becomes necessary. Proper surgical repair of the hiatal hernia will usually correct the reflux. The approach will vary, depending upon many factors beyond the scope of this discussion. The transthoracic route should be used when extensive esophageal mobilization is necessary, when there is marked pcriesophagitis or a penetrating ulcer, when the possibility of neoplasm remains, and when a high stricture is present that requires local attention. The transabdominal approach also permits gastric drainage and resectional procedures which may be desirable, especially in the patient with an ulcer diathesis. In extremely poor risk patients, a gastropexy, as described by Nissen,28 might be of benefit when conservative measures fail. Feeding jejunostomies or gastrostomies have been used with benefit in a few severely incapacitated, poor risk patients. Since columnar epithelium lining the lower esophagus has been incriminated as the source of the injurious acid-pepsin environment, it has been recommended that the entire columnar-lined esophagus be resected. This radical approach should not be undertaken initially unless, perhaps, the segment is irreversibly damaged. Resection should be deferred until the columnar-lined esophagus can be shown to have a clinically significant acid-enzyme secreting epithelium. Because the columnar epithelium is usually devoid of acid- and pepsin-secreting cells, except occasionally as it approaches the stomach, resecting the columnarlined segment of esophagus should rarely prove to be necessary. The type of epithelium can be evaluated by studying multiple esophagoscopic biopsies taken throughout the length of the columnar-lined esophagus. It may also be possible to assess the acid-enzyme secretory potential of this segment of esophagus by blocking gastric reflux by the use of a tampon or properly positioned balloon.

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Secretions from the esophagus can then be collected from the lower esophagus over a prolonged period through a small plastic catheter connected to suction. The variations of an acid environment in the esophagus can also be determined through an intraluminal indwelling sensing device connected to a pH meter. The literature contains several references to individuals who have become asymptomatic following repair of the hiatal hernia without excision of the columnar-lined esophagus. 11 ' 43 Allison4 described one patient who subsequently required resection of the columnar-lined esophagus after repair of the associated hiatal hernia. Examination of the case history, however, reveals that reflux of barium into the esophagus continued after the hiatal hernia repair, although the stomach remained below the diaphragm. Stricture: Superficial strictures respond nicely to dilatation (see Fig. 1). A number of patients have been able to get along with the use of self-bougienage. Unless the reflux esophagitis is effectively controlled, however, the strictures will recur and require more aggressive and repeated dilatations. At the time of transthoracic repair of the hiatal hernia, the stricture may be forcibly fractured as recommended by Hayward, 15 particularly when plastic or excisional surgery is contraindicated. Several patients with short strictures treated by local excision and end-to-end anastomosis have had satisfactory results. 23 Ulcer: The ulcer in columnar epithelium may erode into a major intrathoracic vessel and cause immediate death. When it perforates into the mediastinum, emergency thoracotomy with drainage or resection may be lifesaving. Tumor: The possibility of a malignancy developing in the esophagus lined by columnar epithelium should be kept in mind, although this complication is quite uncommon when compared with stricture and ulcer. Nevertheless, a recent change in symptoms may suggest the need for a barium esophagram, esophagoscopy with biopsy if necessary, and, even, a thoracotomy if doubt remains. The author has seen a carcinoma develop in a chronically inflamed esophagus above a hiatal hernia during an 18 month period; this was documented by esophagoscopies and biopsies. Adenocarcinoma of the esophagus should be aggressively approached since the prognosis may be better than is generally anticipated for a gastric carcinoma. SUMMARY

A condition is described in which as much as the lower half of the esophagus has been found to be lined by a sheet of columnar (gastric-like) epithelium. It is usually first discovered in later life as a result of a stricture or ulcer. The physician unfamiliar with the condition will commonly make the mistaken diagnosis of carcinoma. Although generally held to be of congenital origin, a concept is discussed which suggests that this state of affairs represents an adaptive epithelial change in response to the chronic abnormal (acid-pepsin) environment within the esophagus. The commonly associated hiatal hernia is usually responsible for the gastroesophageal incompetence and reflux esophagitis. The condition may be diagnosed by x-ray examination and proved by esophagoscopy with multiple biopsies.

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Examinations of the entire length of uninterrupted esophageal mucosa from over 250 autopsies have shown variations in the superficial (cardiac) glands that may have a bearing on the genesis of the heterotopic columnar epithelium. Biopsies from patients with esophageal columnar epithelium have shown inflammatory changes resembling atrophic "gastritis" and intestinal metaplasia similar to that encountered in the stomach. The possibility that the metaplastic changes may be related to the development of adenocarcinoma in the esophagus is discussed. Although generally referred to as a recognizable entity, the lower esophagus lined by columnar epithelium (Barrett syndrome) may exist in various intermediate forms that need further study and clarification. The process should prove to be more common than generally realized, and its significant clinical implications make it a matter of practical concern. Observations relating to its pathogenesis and treatment are discussed. REFERENCES

1. Adler, R. H . : Editorial: The Modern Role of the Esophagoscope in Surgery, Surgery 51: 420, 1962. 2. Adler, R. H., De L a Pava, S., and Nigogosyan, G.: Unpublished data. 3. Adler, R. H., and Rodriguez, J . : The Association of Hiatus Hernia and Gastroesophageal Malignancy, J . THORACIC SURG. 37: 553, 1959.

4. Allison, P . R., and Johnstone, A. S.: The Oesophagus Lined With Gastric Mucous Membrane, Thorax 8: 87, 1953. 5. Armstrong, R. A., Blalock, J . B., and Carrera, G. M.: Adenocarcinoma of the Middle Third of the Esophagus Arising From Ectopic Gastric Mucosa, J . THORACIC SURG. 37: 398, 1959. 6. Barrett, N . R.: Chronic Peptic Ulcer of t h e Oesophagus a n d "Oesophagitis," Brit. J . Surg. 38: 175, 1950. 7. Barrett, N. R.: The Lower Oesophagus Lined by Columnar Epithelium in Modern Trends in Gastroenterology, edited b y Francis A. Jones, New York, 1958, Paul B. Hoeber, Inc., chapt. 9. 8. Barrett, N . R.: The Lower Esophagus Lined b y Columnar Epithelium, Surgery 4 1 : 881, 1957, 9. Bensley, R. R.: The Cardiac Glands of Mammals, Am. J . Anat. 2: 105, 1902-1903. 10. Bosher, L. H., and Taylor, F . H . : Heterotopic Gastric Mucosa in the Esophagus With Ulceration and Stricture Formation, J . THORACIC SURG. 2 1 : 306, 1951.

11. d'Abreu, A. L . : Thoracic Surgery in the Commonwealth of Medicine, J . THORACIC SURG. 42: 150, 1961. 12. Dodge, O. G.: Intraoesophageal Adenocarcinoma, Gut 1: 351, 1960. 13. Goetsch, E . : The Structure of t h e Mammalian Oesophagus, Am. J . Anat. 10: 1, 1910. 14. Goldman, M. C , and Beckman, R. C : B a r r e t t Syndrome: Case Report W i t h Discussion About Concepts of Pathogenesis, Gastroenterology 39: 104, 1960. 15. Hayward, J . : The Treatment of Fibrous Stricture of t h e Oesophagus Associated W i t h Hiatal Hernia, Thorax 16: 45, 1961. 16. Healey, F . H . : Note on t h e Occurrence of Ciliated Epithelium in t h e Esophagus of a 7 Month Human Fetus, J . Anat. 64: 180, 1920. 17. Hewlett, A. W . : The Superficial Glands of t h e Oesophagus, J . Exper. Med. 5 : 319, 1900. 18. Ireland, P . E . : Glands of Esophagus, Laryngoscope 4 3 : 351, 1933. 19. Johns, B . A. E.: Developmental Changes in t h e Oesophageal Epithelium in Man, J . Anat. 26: 29, 1952. 20. Johnson, F . P . : The Development of t h e Mucous Membrane of t h e Esophagus, Stomach and Small Intestine in t h e H u m a n Embryo, Am. J . Anat. 10: 521, 1910. 21. McCorkle, R. G., a n d Blades, B . : Adenocarcinoma of t h e Esophagus Arising in Aberrant Gastric Mucosa, Am. Surgeon 2 1 : 781-785, 1955. 22. Moersch, R. N., Ellis, F . H., J r . , and McDonald, J . R.: Pathologic Changes Occurring in Severe Reflux Esophagitis, Surg. Gynec. & Obst. 108: 476, 1959. 23. Morris, K. N . : Gastric Mucosa Within t h e Oesophagus, Australia & N e w Zealand J . Surg. 2 5 : 24, 1955.

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24. Morson, B. C , and Belcher, J. R.: Adenocarcinoma of the Oesophagus and Ectopic Gastric Mucosa, Brit. J. Cancer 6: 127, 1953. 25. Morson, B. C : Carcinoma Arising From Areas of Intestinal Metaplasia in t h e Gastrie Mucosa, Brit. J . Cancer 9: 377, 1955. 26. Morson, B. C.: Gastric Polyps Composed of Intestinal Epithelium, Brit. J. Cancer 9: 550, 1955. 27. Morson, B. C.: Intestinal Metaplasia of the Gastric Mucosa, Brit. J. Cancer 9: 365, 1955. 28. Nissen, R.: Gastropexy as Lone Procedure in Surgical Repair of Hiatus Hernia, Am. J. Surg. 92: 389, 1956. 29. Pattinson, J . N., Osborne, G., and Morson, B. C.: Hiatus Hernia With Adenocarcinoma Arising in t h e Region of the Cardia, J. Fac. Radiol. (Lond.) 7: 90, 1955. 30. Peters, P . M.: The Congenital Short Oesophagus, Thorax 13: 1, 1958. 31. Planteydt, H. T., and Willeghagen, R. G. J.: Enzyme Histochemistry of the H u m a n Stomach With Special Reference to Intestinal Metaplasia, J . Path. & Bact. 80: 317, 1960. 32. Postlethwait, R. W., and Sealy, W. C : Surgery of the Esophagus, Springfield, 111., 1961, Charles C Thomas, Publisher. 33. Raeburn, C.: Columnar Ciliated Epithelium in the Adult Oesophagus, J . P a t h . & Bact. 6 3 : 157, 1951. 34. Rector, L. E., and Connerley, M. L.: Aberrant Mucosa in the Esophagus in I n f a n t s and in Children, A. M. A. Arch. P a t h . 3 1 : 285, 1941. 35. Reid, W. O., and Robinson, A. W.: H i a t u s Herniation, Gastric Mucosa Lining t h e Lower Oesophagus, and Reflux Oesophagitis Above, J. Laryng. & Otol. 7 1 : 760, 1957. 36. Smithers, D. W.: Adenocarcinoma of the Oesophagus, Thorax 11: 257, 1956. 37. Smithers, D. W.: The Association of Cancer of the Stomach and Oesophagus W i t h Herniation of the Oesophageal Hiatus of the Diaphragm, Brit. J . Radiol. 28: 554, 1955. 38. Som, M. L., Shapiro, J . H., and Jacobson, H. G.: The "Gastric-Lined" Esophagus With Esophagitis, Radiology 69: 856, 1957. 39. Som, M. L., and Wolf, B. S.: Peptic Ulcer of the Esophagus and Esophagitis in Gastric-Lined Esophagus, J. A. M. A. 162: 641, 1956. 40. Taylor, A. L.: The Epithelial Heterotopias of the Alimentary Tract, J. P a t h . & Bact. 30: 415, 1927. 41. Thomas, J . V., and Hay, L. J . : Adenocarcinoma of the Esophagus. Report of a Case of Glandular Metaplasia of t h e Esophageal Mucosa, Surgery 35: 635, 1954. 42. Wattenberg, L. W.: Histochemical Study of Aminopeptidase in Metaplasia and Carcinoma of t h e Stomach, A. M. A. Arch. P a t h . 67: 281, 1959. 43. Wooler, G.: The Diagnosis and Treatment of Peptic Oesophagitis, Gut 2: 91, 1961. 44. Wolf, B. S., Marshak, R. H., and Som, M. L.: Peptic Esophagitis and Peptic Ulceration of the Esophagus, Am. J. Roentgenol. 79: 741, 1958. 45. Wolf, B. S., Marshals, R. H., Som, M. L., and Winkelstein, A.: Peptic Esophagitis, P e p t i c Ulcer of the Esophagus and Marginal Esophagogastric Ulceration, Gastroenterology 29: 744, 1955. 46. Wyndham, N . : The Significance of Gastric Mucosa in the Oesophagus, Brit. J . Surg. 23: 409, 1956. DISCUSSION

DR. GABRIEL P . SELEY, New York, N. Y.—I want to compliment Dr. Adler on a wellpresented and well-conceived paper. The reason I arise is to present a case which I think is a little unusual but is in line with the presentation today. This man was an 81-year-old, extremely debilitated patient who presented because of recurrent bouts of pneumonitis, mainly of the right lower and middle lobes. His chief complaint actually was regurgitation; everything he ate, whether it was fluid or solid, was regurgitated. He had lost a tremendous amount of weight. He was seen at the hospital and a barium swallow was ordered. At the time of the barium swallow he regurgitated some of the barium. The x-rays which were taken at the time showed a constricting lesion of the lower third of the esophagus which appeared to be a divertieulum. I n addition to that, there was evidence of a hiatal hernia, and, on the delayed x-ray plates that were taken, there was an excellent bronchogram of the right middle and lower lobes. Because of the extremely poor condition of this patient, a palliative procedure was

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decided upon, which consisted of passing a plastic tube down the esophagus and fixing it to the stomach by gastrotomy. This was done, and at the same time a tracheostomy was performed. Unfortunately the patient died 6 hours after operation. At postmortem examination, the findings were extremely interesting. The mucosa of the lower third of the esophagus was definitely diiferent from the remainder of the esophagus and resembled gastric mucosa. There was a massive perforated peptic u'cer of the lower third of the esophagus with direct communication with the intermediate bronchus, thereby explaining the bronchogram of the right middle and right lower lobes. There was also a hiatal hernia present. I agree with the author that these patients, if a t all feasible, should be esophagoscoped, because one can never rule out all the conditions that might be present, and we have had other instances in which a diagnosis of carcinoma was made on x-ray examination, whereas actually these were benign lesions. I would like to ask the author if he had any cases which were similar to the one I have just presented and, if so, what his management would have been. MB. NORMAN R. BARRETT, London, England.—Thank you very much for allowing me to discuss this paper. I want first to apologize for all the confusion I may have created in the last 10 years. Second, I want to say that if I could only have put the matter as clearly as Dr. Adler has put it this morning, I would have saved myself and you a great deal of thinking, and the patients might have been better off. This has not been an easy problem. I t sounds easy now as you hear it propounded by Dr. Adler; but in the first place it never occurred to anybody that the lower esophagus might be lined by columnar epithelium, a thing which now seems so obvious—was not clear at all in the beginning. I have not myself hoard a simpler and more straightforward exposition of this than Dr. Adler has put to us. I am naturally a ' ' doubting T h o m a s , ' ' and I don't agree with everything he said, but that is all right. I would emphasize that this business is not yet solved. We have confusion at the moment on a number of very important points. Nobody knows for certain how this columnar epithelium contains oxyntic cells. Nobody is certain whether is secretes anything but mucus. Nobody knows at what stage in life it develops, or whether it is congenital or acquired. A difficulty about this is that if you believe it to be acquired, then it is odd that these patients have never had a history of esophagitis or inflammation such as you might have expected to destroy the squamous epithelium before it was replaced by the other sort. There are still doubts as to what actual lesions may occur in the segment that is lined by columnar epithelium, as opposed to the stomach and the esophagus itself. So, you see, there is plenty of room for more papers, which I hope you will send me, and there is plenty of room for discussion. About diagnosis: I absolutely agree that it is necessary to do an esophagoscopy, and it is necessary to do multiple biopsies. But we have had considerable success recently with another type of investigation. Brian Creamer, who worked at the Mayo Clinic some time ago, brought back to us this pressure measurement business, which I think has confused the poor surgeons a great deal; but we have used it in the diagnosis of this condition with considerable success, as well as using biopsies. The segment lined by columnar epithelium behaves like esophagus and not like stomach in the movements of the musculature and the pressures recorded. So, I think there are two methods of diagnosis. The fourth thing is that I agree with Dr. Adler that for the moment you should be conservative in your treatment, because, if you can stop acid-pepsin reaching the area which is pathological, there is no need to do very much about the lower esophagus lined by columnar epithelium. But you must bear in mind that this lower esophagus lined by columnar epithelium is itself liable to diseases like cancer. If cancer occurs in such a segment it will, of course, be columnar celled histologically.

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DR. ADLER (Closing).—I would like to thank the discussers for their comments. The remarks of Mr. Barrett are particularly appreciated. In fact I feel rather humble in replying to Mr. Barrett who first brought this condition to our attention and who has had so much to say about it during the past 10 years. First let me say that the broad concept drawn together here, both from our own work and the observations of others, does not necessarily imply that this is the final answer to this intriguing condition. Many findings can be more logically explained by this dynamic, acquired concept than by the static congenital theory, and it also opens areas for future study. Nevertheless, we know that there arc instances of columnar epithelium, particularly of the ciliated type, which have been fcund in the esophagus after birth, representing congenital lesions. Perhaps these mucosal aberrations may participate in or undergo later alterations related to environmental changes. I believe that it is most important for surgeons to appreciate the value of the esophagoscope as a means of studying the inside of the esophagus during life. Mere inspection is not enough at times, and careful mucosal biopsies must be taken freely. By subjecting properly prepared, fresh, esophagoscopic biopsy material to new techniques of study, such as enzyme histoehemistry, electron microscopy, and tissue culture, we may come to understand the nature of mucosal abnormalities. Our knowledge of the mucosa which lines our interior lags far behind what we know of the more readily available skin covering our exterior. The handicap of studying even the routine histology of the esophagus after death has been a deterrent to understanding of the esophageal mucosa in the past. For example, one of our elderly poor-risk patients, with the lower esophagus lined by columnar epithelium as proved by mutiple esophagoscopic biopsies, was recently readmitted to the hospital for terminal care. The end was in sight for a number of reasons, and we anticipated immediate postmortem removal of the esophagus and stomach for extensive studies. Unfortunately, an accidental 6 hour delay between the time of death and postmortem examination resulted in the frustrating situation of finding the mucosa gone as a result of digestion and autolysis. Dr. Seley's patient represents an instance of a penetrating ulcer in the columnar-lined esophagus which has been shown by Mr. Barrett to behave quite similarly to a peptic ulcer in the columnar epithelium of the stomach or duodenum. From this similarity one would hope that further penetration of the ulcer would stop and healing begin if the acid-peptic environment associated with the hiatal hernia and reflux could be controlled. In answer to Dr. Seley's question, I would immediately place the patient on a strict ulcer regimen with the head of the bed elevated. If this failed to control the process, surgical repair of the hiatal hernia, perhaps with concomitant procedures to promote gastric drainage and diminish acidpepsin secretions, might become necessary to prevent the fatal outcome from perforation into a vascular structure as described. In a poor risk individual, not responding to medical treatment, some might do only a pyloroplasty or gastropexy to control the acid-pepsin reflux. I would prefer not to resect the columnar-lined esophagus with the acutely penetrating ulcer unless perforation was imminent. Definitive re-establishment of gastrointestinal continuity might possibly have to be delayed following an extensive resection in the critically ill patient. Mr. B a r r e t t ' s comments on the fact that a long history of symptoms is not present in some of these individuals with columnar-lined lower esophagus brings to mind a number of people we have seen in their 60 's and 70 's whoso first symptoms dated back only a few months and consisted of progressive dysphagia which suggested carcinoma but were due to a peptic stricture directly above a previously asymptomatic hiatal hernia. Acute esophagitis may not be apparent at this time, although the process has been present for some time. The discrepancies between severity of symptoms and evidence of esophagitis that one occasionally encounters are well known. I do not believe that a lack of symptoms, as interpreted by the patient, rules out the occurrence of chronic reflux and esophagitis. Certainly the last word has yet to be said concerning the nature of columnar epithelium in the esophagus and its relationship to the conditions discussed in this presentation.