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Characteristics of the columnar-cell lined (Barrett's) esophagus
0016-5107/79/2504-0133$02.00/0 GASTROINTESTINAL ENDOSCOPY Copyright © 1979 by the American Society for Gastrointestinal Endoscopy
Characteristics of the columnar-cell lined (Barrett's) esophagus Eugene J. Burbige, MD Jeffrey J. Radigan, MD Davis, California
During a 6-month period, endoscopy in 203 patients established a diagnosis of Barrett's esophagus in 8 (4%). Esophagitis was present in the squamous-lined segment of the esophagus in 7 of these patients. Three patients had strictures, and 3 had esophageal ulcers, 2 of which were in the columnar segment distal to the squamocolumnar junction. During endoscopic examination an iodine-containing solution was instilled to better define the areas of squamous epithelium. This technique revealed islands of squamous epithelium in the columnar segment in 2 patients which were not visible before dye instillation. In the 2 patients with ulcers in the columnar segment, squamous epithelium was identified at the ulcer edge. By manometry, lower esophageal sphincter pressure was decreased in 6 patients and motility in the body of the esophagus was abnormal in 6. Acid perfusion tests were positive in 3 of 5 patients. Acid reflux and acid clearing were abnormal in all patients tested.
T he columnar-cell
lined (Barrett's) esophagus is an uncommon disorder which is often overlooked clinically. Although when first described in 1950 by Barrett 1 it was considered to be an attenuated esophagus and resultant intrathoracic stomach, it is now widely accepted to occur as a result of prolonged esophageal reflux and healing by metaplastic orad extension of columnar epithelium of the cardia. 2 - 6 Although uncommon, it is an important clinical entity, and it may be associated with esophageal ulcers and midesophageal strictures? and is considered to be a potentially premalignant condition. 2 .8 .9 The columnar-cell lined esophagus probably occurs more frequently than is commonly realized. Also, it may be associated with motor abnormalities of the esophagus? which may be the cause of reflux esophagitis or possibly may be the result of prolonged reflux and metaplastic changes in the epithelium. We have reviewed the endoscopic and manometric findings in 8 patients seen in a relatively short period of 6 months. Additionally, the results of acid perfusion, pH with reflux, and tests of acid clearing were available in several patients.
METHODS Patients. A review of all diagnostic and therapeutic upper gastrointestinal endoscopic examinations performed in a 6-month period was carried out to identify
patients with a diagnosis of macroscopic esophagitis and particularly Barrett's esophagus. The records of those patients with the gross appearance of Barrett's esophagus were then examined with regard to the histologic, endoscopic, and manometric findings as well as the results of acid perfusion, pH with reflux and acid clearing. Endoscopy and dye instillation. Endoscopy was performed in the customary fashion using either the Olympus GIFD-3 or GIFP-2 fiberoptic endoscopes. It is routine practice in our endoscopy clinic to instill an iodine-containing Lugol's solution into the esophagus under direct vision to better delineate areas for biopsy in all cases suspected of having columnar epithelium in the esophagus and in selected cases of esophagitis. lO All patients undergoing endoscopy are queried as to possible iodine sensitivity before examination. Iodine solution is not instilled into patients undergoing endocrinologic evaluation. A 1.4-mm Teflon tube is passed through the biopsy channel of the endoscope. The instrument is positioned in the esophagus several centimeters above the presumed squamocolumnar junction and 3 ml of full strength Lugol's solution (5% elemental iodine and 10% potassium iodide in aqueous solution) is instilled into the esophagus and allowed to remain in contact with the mucosa for 60 seconds. The esophagus is then rinsed with water. Biopsies are taken
From the Department of Medicine, Veterans Administration Medical Center, Martinez, California, and University of California, Davis, California. Reprint requests: Eugene j. Burbige, MD, Veterans Administration Medical Center, 150 Muir Road, Martinez, California 94553. VOLUME 25. NO. 4, 1979
133
from appropriate areas. The instrument is advanced into the stomach, and the gastric pool is aspirated before terminating the procedure. Manometric methods. Manometric examinations had been performed on all 8 patients. Esophageal pressures were measured using an intraluminal transducer assembly (model MP-3 probe, Honeywell, Inc.) 11 and were recorded on a multichannel Visicorder. Lower esophageal sphincter pressures were measured by the rapid pull-through technique ' 2 Motility in the body of the esophagus was determined by staged pull-through at 1-cm intervals. Acid studies. Acid perfusion testing was performed in 5 patients by passing a tube 35 cm from the external nares and infusing normal saline at 120 drops per minute for 10 minutes. Then, without the patient's knowledge, the solution was changed to 0.1 N hydrochloric acid at the same infusion rate. This infusion was continued for at least 30 minutes. A positive test consisted of a reproduction of the patient's symptoms. Following acid perfusion studies, acid clearing ability was tested in 4 patients. This was performed by positioning the pH probe 5 cm above the lower esophageal sphincter. After ascertaining that intraluminal pH was greater than 5, 15 ml of 0.1 N HCI was then introduced into the esophagus. The patient was instructed to swallow at 30-second intervals, and the number of swallows required to raise the pH to 5 was recorded. Abnormal acid clearing was reported if more than 10 swallows failed to raise intraesophageal pH. The nasogastric tube was then advanced into the stomach in 4 patients, and 300 ml of 0.1 N HCI were infused. The nasogastric tube was removed, and a pH probe was positioned 5 cm above the lower esophageal sphincter. Reflux of gastric contents was reported as positive when the pH fell below 4.
RESULTS Patients. During the 6-month period, 271 peroral endoscopic examinations were performed on 203 patients. The diagnosis of macroscopic esophagitis was made in 41 of these patients. Eight patients were found to have esophaguses lined with columnar epithelium. All patients had circumferential involvement of the tubular esophagus which varied in length from 4 to 10 cm. Patients with "tongues" of gastric mucosa extending into the esophagus from the stomach were not included. Thus, abnormal columnar epithelium was found to be present in 20% of the patients with esophagitis and in 4% of all patients investigated. All 8 patients were men with a mean age of 59 years (range: 50 to 66). Six patients had a history of chronic ethanol abuse. Four patients complained of retrosternal and epigastric burning pain. Three patients complained of epigastric fullness, sharp epigastric pain, and cramping epigastric pain, respectively. Dysphagia was present in 4 patients. One patient had previously had hematemesis and melena, and 1 had had melena alone. Only 1 patient had pulmonary symptoms. None of the patients gave a history of possible predisposing conditions other than chronic alcohol abuse. One patient was suspected of having scleroderma, but intensive investigation failed to confirm this suspicion. Three pa134
tients had had attempts at antireflux surgery 1 to 6 years before presentation. Endoscopic findings. Seven of the 8 patients had macroscopic changes of esophagitis with linear erosions, erythema, pseudomembrane formation, and friability. The areas of involvement were located at the squamocolumnar junction and extended cephalad for varying distances. The squamocolumnar junction was irregular in all. Three of the 7 patients had strictures located at the squamocolumnar junction. Instillation of the iodine-containing solution allowed clear delineation of normal squamous epithelium from the columnar-lined segment( Figure 1A). In all patients biopsies of the unstained esophagus confirmed the presence of columnar epithelium while specimens from the stained esophagus showed squamous epithelium. Additionally, 2 patients were found to have isolated islands of squamous epithelium (Figure 18) detected only by iodine instillation and confirmed by biopsy under vision (Figure 1e). Three patients were found to have esophageal ulcers. One ulcer was found at the squamocolumnar junction, and the other 2 were located in the columnar-lined esophagus 8 and 10 cm distal to the squamocolumnar junction. Instillation of Lugol's solution in the latter 2 patients revealed squamous epithelium at the ulcer edge (Figure 10) which was confirmed by direct vision biopsy. Manometric findings. Lower esophageal sphincter pressure measured by rapid pull-through technique was decreased in 6 patients (mean: 8.5 mm Hg; range: 4 to 11 mm Hg). In the staged pull-through studies, the sphincter relaxed and contracted normally in 1 patient and abnormally in 6, and in the remaining patient the tracing was technically inadequate to determine sphincter function. Motility in the body of the esophagus was abnormal in 6 patients. There was virtual aperistalsis in 2 patients, decreased amplitude and frequency of contractions in 3, and occasional simultaneous and doublepeaked contractions in 4. One patient also demonstrated decreased amplitude of contractions in the area of his esophagitis. Acid studies. Acid perfusion studies were positive in 3 of 5 patients tested. Of the 5 patients tested, 4 had esophagitis in the squamous-lined segment. All of the patients with a positive acid perfusion study had esophagitis. Of the 2 patients with negative tests, 1 did not have esophagitis and the other had high esophagitis which, in retrospect, may have been located above the nasogastric tube. Acid reflux and acid clearing ability were examined in 4 patients and were markedly abnormal in all. After acid instillation none of the 4 patients was able to raise the esophageal pH above 4. Two of these patients had virtual aperistalsis on manometric examination, 1 had decreased amplitude and frequency of contractions, and 1 had a normal manometric examination.
DISCUSSION Since its first description in 1950 by Barrett,l the columnar-cell lined esophagus has attracted considerable interest. It is felt to be an acquired condition that results from gastroesophageal reflux, ulceration, and subsequent reparative changes. 2 - 6 Three types of columnar epithelium in the esophagus have been described: an GASTROINTESTINAL ENDOSCOPY
Figure 1. A, Typical endoscopic appearance of the squamocolumnar junction in Barrett's esophagus after instillation of an iodine-containing solution; the squamous epithelium stains black while the columnar epithelium is unstained. B, Islands of squamous epithelium stained by Lugo/'s solution (arrow). C, Section of biopsy specimen obtained from the stained epithelium in B; a fragment of columnar epithelium also is seen (H & E, X275). D, An ulcer in a columnar segment of esophagus shows iodine staining at its edge indicating a remnant of squamous epithelium (arrow).
atrophic, gastric fundic type with parietal and chief cells; a junctional type with cardiac mucous glands; and a specialized type with a villiform surface, mucous glands, and intestinal type goblet cells. 13 The prevalence of the columnar-lined esophagus is difficult to ascertain, but it has been considered an uncommon finding. Its detection in a clinical setting will vary according to the interest and the experience of the examiner. Although the population from which our patients were derived may yield an extraordinary frequency, our experience indicates that the columnar-cell lined esophagus can be found more often than is commonly thought. Various modalities have been employed to aid in the diagnosis of Barrett's esophagus. Radiologic examination of the esophagus with a barium swallow may suggest the diagnosis.? Classically one sees a high esophageal stricture or an esophageal ulcer. Recently, it has been claimed that the diagnosis of Barrett's esophagus can be made by pertechnetate scintigraphy 15 A positive study is one showing an increased uptake of technetium extending above the normal dense uptake of the stomach. However, of 4 patients tested, 1 case was missed. Also, patients with short segments of columnar epithelium might be overlooked by this technique. Endoscopically one might suspect the diagnosis of Barrett's esophagus by the presence of a high stricture, an esophageal ulcer, the change from a pale VOLUME 25, NO. 4, 1979
esophageal mucosa to redder columnar mucosa located above the diaphragm,'4.16 or the presence of what appears to be a localized area of esophagitis high in the esophagus with uninflamed mucosa distally. However, in cases of esophagitis with mucosal friability and bleeding, these distinctions may be difficult to make. Instillation of an iodine-containing solution will safelylO and clearly demarcate the junction between normal squamous epithelium and columnar epithelium and will thus help to delineate the areas for biopsy. The finding of islands of squamous epithelium in the columnar segment points out the need for biopsy under direct vision when evaluating the effects of therapy in patients with Barrett's esophagus. It has been said that the esophageal ulcers occur in the columnar epithelium at the squamocolumnar junction.? The finding of squamous epithelium at the ulcer edge in 2 patients by iodine instillation might help explain the apparent discrepancy of finding ulcers distal to the squamocolumnar junction well within the columnar segment. Although few in number, previous studies have reported either normal manometric findings or have shown variably decreased amplitude, duration of contractions, and decreased lower esophageal sphincter pressure. 4.7.'4.,?18 Our patients showed similar abnormalities. Of note, however, is the marked decrease in peristalsis seen in 2 patients. Both of these patients had long (8- and lO-cm) segments 135
of columnar epithelium. Whether it was abnormal peristalsis that led to prolonged contact of the esophageal mucosa with refluxed material or whether the abnormal motility was a result of severe esophagitis is open to debate ' 9 - 21 Additionally, some degree of abnormality may be seen in esophageal motility patterns in the elderly.22 But the marked disturbances seen in these patients were greater than would be expected of age-related changes. All patients with positive acid perfusion tests had gross esophagitis. However, some patients with 'Barrett's esophagus give no history suggestive of reflux esophagitis. A few patients with severe esophagitis leading to stricture formation yet with no symptoms and with negative acid n perfusion studies have been reported An important factor in the development of severe esophagitis is the length of time that gastroduodenal contents are in contact with the esophageal mucosa. This is evidenced by the observation that all 4 of our patients who were tested had markedly abnormal acid clearing. It would be expected that impaired clearing be well correlated with abnormal motility patterns. However, delayed acid clearing 20 may be found with no evidence of abnormal peristalis.
6. 7. 8. 9.
10. 11. 12. 13. 14. 15. 16. 17. 18.
REFERENCES 1. BARRETT NR: Chronic peptic ulcer of the oesophagus and "oesophagitis." Br I Surg 38:175, 1950 2. NAEF AP, SAVARY M, OZZELLO L: Columnar-lined esophagus: an acquired lesion with malignant predisposition. I Thorac Cardiovasc Surg 70:826, 1975 3. BORRIE I. GOLDWATER L: Columnar cell-lined esophagus: assessment of etiology and treatment. I Thorac Cardiovasc Surg
71 :825, 1976 4. HEITMANN P, STRAUSZER T, SAPUNAR I ET Al.: Lower esophagus lined with columnar epithelium: morphological and physiological correlation. Gastroenterology 53:611,1%7 5. HAMILTON SR, YARDLEY JA: Regeneration of cardiac type mucosa
136
19. 20. 21. 22.
23.
and acquisition of Barrett's mucosa after esophagogastrostomy. Gastroenterology 72:669, 1977 MOSSBERG SM: The columnar-lined esophagus (Barrett's syndrome)-an acquired condition? Gastroenterology 50:671,1966 ROBBINS AH, HERMOS lA, SCHIMMEl EM, ET Al: The columnarlined esophagus-analysis of 26 cases. Radiology 123:1, 1977 BERENSON MM, RIDDELL RH, SKINNER DB, ET Al.: Malignant transformation of esophageal columnar epithelium. Cancer41: 554, 1978 McDONALD GB, BRAND DL, THORNING DR: Multiple adenomatous neoplasms arising from columnar-lined (Barrett's) esophagus. Gastroenterology 72:1317, 1977 NOHIMANN BI. WRIGHT JR, SCHUSTER MM: In vivo vital staining as an aid to identification of esophagogastric mucosal junction in man. Am I Dig Dis 17:919, 1972 HOLLIS IB, COSTELL GO: Amplitude of esophageal peristalsis as determined by rapid infusion. Gastroenterology 633:417, 1972 DODDS WI. HAGAN WI. STEFF II. ET Al.: A rapid pull-through technique for measuring lower esophageal sphincter pressure. Gastroenterology 68:437, 1975 PAULL A, TRIER jS, DALTON MD, ET Al.: The histologic spectrum of Barrett's esophagus. N Engll Med 295:476, 1976 BURGESS IN, PAYNE WS, ANDERSON HA, ET Al.: Barrett's esophagus: the columnar-epithelial-lined lower esophagus. Mayo Clin Proc 46:728, 1971 MANGLA J(, BROWN M: Diagnosis of Barrett's esophagus by pertechnetate radio nuclide. Am I Dig Dis 21:324,1976 DESBAILLETS LG, MANGlA IC: Endoscopic diagnosis of Barrett's esophagus. Endoscopy 8:65, 1976 PEDERSEN SA, HAGE E, NIELSEN PA, ET Al.: Barrett's syndrome: morphological and physiological characteristics. Scand I Thorac Cardiovasc Surg 5:191,1971 COHEN BR, WOLF BS, SONN M, ET Al.: Correlation of manometric, oesophagoscopic, and radiological findings in the columnar-lined gullet (Barrett's syndrome). Gut 4:406,1%3 EASTWOOD GL, CASTELL DO, HIGGS RH: Experimental esophagitis in cats impairs lower esophageal sphincter presence. Gastroenterology 69:146, 1975 STANCIU C, BENNETT JR: Oesophageal acid clearing: one factor in the production of reflux oesophagitis. Gut 15:852, 1974 SIMEONE IF, BURRELL M, TOFFLER R, ET Al.: Aperistalsis and esophagitis. Radiology 123:9, 1977 All KHAN T, SHRAGGE BW, CRISPIN IS, ET Al.: Esophageal motility in the elderly. Am I Dig Dis 22:1049, 1977 VOLPICELLI NA, BENDINE MS, HENDRIX TR: Absence of acid sensitivity in patients with benign peptic esophageal stricture. Gastroenterology 68:1007, 1975
GASTROINTESTINAL ENDOSCOPY
Characteristics of the columnar-cell lined (Barrett's) esophagus Eugene J. Burbige, MD Jeffrey J. Radigan, MD Davis, California
During a 6-month period, endoscopy in 203 patients established a diagnosis of Barrett's esophagus in 8 (4%). Esophagitis was present in the squamous-lined segment of the esophagus in 7 of these patients. Three patients had strictures, and 3 had esophageal ulcers, 2 of which were in the columnar segment distal to the squamocolumnar junction. During endoscopic examination an iodine-containing solution was instilled to better define the areas of squamous epithelium. This technique revealed islands of squamous epithelium in the columnar segment in 2 patients which were not visible before dye instillation. In the 2 patients with ulcers in the columnar segment, squamous epithelium was identified at the ulcer edge. By manometry, lower esophageal sphincter pressure was decreased in 6 patients and motility in the body of the esophagus was abnormal in 6. Acid perfusion tests were positive in 3 of 5 patients. Acid reflux and acid clearing were abnormal in all patients tested.
T he columnar-cell
lined (Barrett's) esophagus is an uncommon disorder which is often overlooked clinically. Although when first described in 1950 by Barrett 1 it was considered to be an attenuated esophagus and resultant intrathoracic stomach, it is now widely accepted to occur as a result of prolonged esophageal reflux and healing by metaplastic orad extension of columnar epithelium of the cardia. 2 - 6 Although uncommon, it is an important clinical entity, and it may be associated with esophageal ulcers and midesophageal strictures? and is considered to be a potentially premalignant condition. 2 .8 .9 The columnar-cell lined esophagus probably occurs more frequently than is commonly realized. Also, it may be associated with motor abnormalities of the esophagus? which may be the cause of reflux esophagitis or possibly may be the result of prolonged reflux and metaplastic changes in the epithelium. We have reviewed the endoscopic and manometric findings in 8 patients seen in a relatively short period of 6 months. Additionally, the results of acid perfusion, pH with reflux, and tests of acid clearing were available in several patients.
METHODS Patients. A review of all diagnostic and therapeutic upper gastrointestinal endoscopic examinations performed in a 6-month period was carried out to identify
patients with a diagnosis of macroscopic esophagitis and particularly Barrett's esophagus. The records of those patients with the gross appearance of Barrett's esophagus were then examined with regard to the histologic, endoscopic, and manometric findings as well as the results of acid perfusion, pH with reflux and acid clearing. Endoscopy and dye instillation. Endoscopy was performed in the customary fashion using either the Olympus GIFD-3 or GIFP-2 fiberoptic endoscopes. It is routine practice in our endoscopy clinic to instill an iodine-containing Lugol's solution into the esophagus under direct vision to better delineate areas for biopsy in all cases suspected of having columnar epithelium in the esophagus and in selected cases of esophagitis. lO All patients undergoing endoscopy are queried as to possible iodine sensitivity before examination. Iodine solution is not instilled into patients undergoing endocrinologic evaluation. A 1.4-mm Teflon tube is passed through the biopsy channel of the endoscope. The instrument is positioned in the esophagus several centimeters above the presumed squamocolumnar junction and 3 ml of full strength Lugol's solution (5% elemental iodine and 10% potassium iodide in aqueous solution) is instilled into the esophagus and allowed to remain in contact with the mucosa for 60 seconds. The esophagus is then rinsed with water. Biopsies are taken
From the Department of Medicine, Veterans Administration Medical Center, Martinez, California, and University of California, Davis, California. Reprint requests: Eugene j. Burbige, MD, Veterans Administration Medical Center, 150 Muir Road, Martinez, California 94553. VOLUME 25. NO. 4, 1979
133
from appropriate areas. The instrument is advanced into the stomach, and the gastric pool is aspirated before terminating the procedure. Manometric methods. Manometric examinations had been performed on all 8 patients. Esophageal pressures were measured using an intraluminal transducer assembly (model MP-3 probe, Honeywell, Inc.) 11 and were recorded on a multichannel Visicorder. Lower esophageal sphincter pressures were measured by the rapid pull-through technique ' 2 Motility in the body of the esophagus was determined by staged pull-through at 1-cm intervals. Acid studies. Acid perfusion testing was performed in 5 patients by passing a tube 35 cm from the external nares and infusing normal saline at 120 drops per minute for 10 minutes. Then, without the patient's knowledge, the solution was changed to 0.1 N hydrochloric acid at the same infusion rate. This infusion was continued for at least 30 minutes. A positive test consisted of a reproduction of the patient's symptoms. Following acid perfusion studies, acid clearing ability was tested in 4 patients. This was performed by positioning the pH probe 5 cm above the lower esophageal sphincter. After ascertaining that intraluminal pH was greater than 5, 15 ml of 0.1 N HCI was then introduced into the esophagus. The patient was instructed to swallow at 30-second intervals, and the number of swallows required to raise the pH to 5 was recorded. Abnormal acid clearing was reported if more than 10 swallows failed to raise intraesophageal pH. The nasogastric tube was then advanced into the stomach in 4 patients, and 300 ml of 0.1 N HCI were infused. The nasogastric tube was removed, and a pH probe was positioned 5 cm above the lower esophageal sphincter. Reflux of gastric contents was reported as positive when the pH fell below 4.
RESULTS Patients. During the 6-month period, 271 peroral endoscopic examinations were performed on 203 patients. The diagnosis of macroscopic esophagitis was made in 41 of these patients. Eight patients were found to have esophaguses lined with columnar epithelium. All patients had circumferential involvement of the tubular esophagus which varied in length from 4 to 10 cm. Patients with "tongues" of gastric mucosa extending into the esophagus from the stomach were not included. Thus, abnormal columnar epithelium was found to be present in 20% of the patients with esophagitis and in 4% of all patients investigated. All 8 patients were men with a mean age of 59 years (range: 50 to 66). Six patients had a history of chronic ethanol abuse. Four patients complained of retrosternal and epigastric burning pain. Three patients complained of epigastric fullness, sharp epigastric pain, and cramping epigastric pain, respectively. Dysphagia was present in 4 patients. One patient had previously had hematemesis and melena, and 1 had had melena alone. Only 1 patient had pulmonary symptoms. None of the patients gave a history of possible predisposing conditions other than chronic alcohol abuse. One patient was suspected of having scleroderma, but intensive investigation failed to confirm this suspicion. Three pa134
tients had had attempts at antireflux surgery 1 to 6 years before presentation. Endoscopic findings. Seven of the 8 patients had macroscopic changes of esophagitis with linear erosions, erythema, pseudomembrane formation, and friability. The areas of involvement were located at the squamocolumnar junction and extended cephalad for varying distances. The squamocolumnar junction was irregular in all. Three of the 7 patients had strictures located at the squamocolumnar junction. Instillation of the iodine-containing solution allowed clear delineation of normal squamous epithelium from the columnar-lined segment( Figure 1A). In all patients biopsies of the unstained esophagus confirmed the presence of columnar epithelium while specimens from the stained esophagus showed squamous epithelium. Additionally, 2 patients were found to have isolated islands of squamous epithelium (Figure 18) detected only by iodine instillation and confirmed by biopsy under vision (Figure 1e). Three patients were found to have esophageal ulcers. One ulcer was found at the squamocolumnar junction, and the other 2 were located in the columnar-lined esophagus 8 and 10 cm distal to the squamocolumnar junction. Instillation of Lugol's solution in the latter 2 patients revealed squamous epithelium at the ulcer edge (Figure 10) which was confirmed by direct vision biopsy. Manometric findings. Lower esophageal sphincter pressure measured by rapid pull-through technique was decreased in 6 patients (mean: 8.5 mm Hg; range: 4 to 11 mm Hg). In the staged pull-through studies, the sphincter relaxed and contracted normally in 1 patient and abnormally in 6, and in the remaining patient the tracing was technically inadequate to determine sphincter function. Motility in the body of the esophagus was abnormal in 6 patients. There was virtual aperistalsis in 2 patients, decreased amplitude and frequency of contractions in 3, and occasional simultaneous and doublepeaked contractions in 4. One patient also demonstrated decreased amplitude of contractions in the area of his esophagitis. Acid studies. Acid perfusion studies were positive in 3 of 5 patients tested. Of the 5 patients tested, 4 had esophagitis in the squamous-lined segment. All of the patients with a positive acid perfusion study had esophagitis. Of the 2 patients with negative tests, 1 did not have esophagitis and the other had high esophagitis which, in retrospect, may have been located above the nasogastric tube. Acid reflux and acid clearing ability were examined in 4 patients and were markedly abnormal in all. After acid instillation none of the 4 patients was able to raise the esophageal pH above 4. Two of these patients had virtual aperistalsis on manometric examination, 1 had decreased amplitude and frequency of contractions, and 1 had a normal manometric examination.
DISCUSSION Since its first description in 1950 by Barrett,l the columnar-cell lined esophagus has attracted considerable interest. It is felt to be an acquired condition that results from gastroesophageal reflux, ulceration, and subsequent reparative changes. 2 - 6 Three types of columnar epithelium in the esophagus have been described: an GASTROINTESTINAL ENDOSCOPY
Figure 1. A, Typical endoscopic appearance of the squamocolumnar junction in Barrett's esophagus after instillation of an iodine-containing solution; the squamous epithelium stains black while the columnar epithelium is unstained. B, Islands of squamous epithelium stained by Lugo/'s solution (arrow). C, Section of biopsy specimen obtained from the stained epithelium in B; a fragment of columnar epithelium also is seen (H & E, X275). D, An ulcer in a columnar segment of esophagus shows iodine staining at its edge indicating a remnant of squamous epithelium (arrow).
atrophic, gastric fundic type with parietal and chief cells; a junctional type with cardiac mucous glands; and a specialized type with a villiform surface, mucous glands, and intestinal type goblet cells. 13 The prevalence of the columnar-lined esophagus is difficult to ascertain, but it has been considered an uncommon finding. Its detection in a clinical setting will vary according to the interest and the experience of the examiner. Although the population from which our patients were derived may yield an extraordinary frequency, our experience indicates that the columnar-cell lined esophagus can be found more often than is commonly thought. Various modalities have been employed to aid in the diagnosis of Barrett's esophagus. Radiologic examination of the esophagus with a barium swallow may suggest the diagnosis.? Classically one sees a high esophageal stricture or an esophageal ulcer. Recently, it has been claimed that the diagnosis of Barrett's esophagus can be made by pertechnetate scintigraphy 15 A positive study is one showing an increased uptake of technetium extending above the normal dense uptake of the stomach. However, of 4 patients tested, 1 case was missed. Also, patients with short segments of columnar epithelium might be overlooked by this technique. Endoscopically one might suspect the diagnosis of Barrett's esophagus by the presence of a high stricture, an esophageal ulcer, the change from a pale VOLUME 25, NO. 4, 1979
esophageal mucosa to redder columnar mucosa located above the diaphragm,'4.16 or the presence of what appears to be a localized area of esophagitis high in the esophagus with uninflamed mucosa distally. However, in cases of esophagitis with mucosal friability and bleeding, these distinctions may be difficult to make. Instillation of an iodine-containing solution will safelylO and clearly demarcate the junction between normal squamous epithelium and columnar epithelium and will thus help to delineate the areas for biopsy. The finding of islands of squamous epithelium in the columnar segment points out the need for biopsy under direct vision when evaluating the effects of therapy in patients with Barrett's esophagus. It has been said that the esophageal ulcers occur in the columnar epithelium at the squamocolumnar junction.? The finding of squamous epithelium at the ulcer edge in 2 patients by iodine instillation might help explain the apparent discrepancy of finding ulcers distal to the squamocolumnar junction well within the columnar segment. Although few in number, previous studies have reported either normal manometric findings or have shown variably decreased amplitude, duration of contractions, and decreased lower esophageal sphincter pressure. 4.7.'4.,?18 Our patients showed similar abnormalities. Of note, however, is the marked decrease in peristalsis seen in 2 patients. Both of these patients had long (8- and lO-cm) segments 135
of columnar epithelium. Whether it was abnormal peristalsis that led to prolonged contact of the esophageal mucosa with refluxed material or whether the abnormal motility was a result of severe esophagitis is open to debate ' 9 - 21 Additionally, some degree of abnormality may be seen in esophageal motility patterns in the elderly.22 But the marked disturbances seen in these patients were greater than would be expected of age-related changes. All patients with positive acid perfusion tests had gross esophagitis. However, some patients with 'Barrett's esophagus give no history suggestive of reflux esophagitis. A few patients with severe esophagitis leading to stricture formation yet with no symptoms and with negative acid n perfusion studies have been reported An important factor in the development of severe esophagitis is the length of time that gastroduodenal contents are in contact with the esophageal mucosa. This is evidenced by the observation that all 4 of our patients who were tested had markedly abnormal acid clearing. It would be expected that impaired clearing be well correlated with abnormal motility patterns. However, delayed acid clearing 20 may be found with no evidence of abnormal peristalis.
6. 7. 8. 9.
10. 11. 12. 13. 14. 15. 16. 17. 18.
REFERENCES 1. BARRETT NR: Chronic peptic ulcer of the oesophagus and "oesophagitis." Br I Surg 38:175, 1950 2. NAEF AP, SAVARY M, OZZELLO L: Columnar-lined esophagus: an acquired lesion with malignant predisposition. I Thorac Cardiovasc Surg 70:826, 1975 3. BORRIE I. GOLDWATER L: Columnar cell-lined esophagus: assessment of etiology and treatment. I Thorac Cardiovasc Surg
71 :825, 1976 4. HEITMANN P, STRAUSZER T, SAPUNAR I ET Al.: Lower esophagus lined with columnar epithelium: morphological and physiological correlation. Gastroenterology 53:611,1%7 5. HAMILTON SR, YARDLEY JA: Regeneration of cardiac type mucosa
136
19. 20. 21. 22.
23.
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GASTROINTESTINAL ENDOSCOPY