A nar epithelium lining the lower esophagus as early

Transcription

1 CURRENT REVIEW Current Concepts Concerning the Nature and Treatment of Barrett s Esophagus and Its Complications John M. Streitz, Jr, MD, Warren A. Williamson, MD, and F. Henry Ellis, Jr, MD, PhD Department of Thoracic and Cardiovascular Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts, and Division of Cardiothoracic Surgery, New England Deaconess Hospital, Boston, Massachusetts Current concepts regarding the nature and the treatment of Barrett s esophagus and its complications are reviewed. The columnar-lined lower esophagus is being increasingly recognized as an acquired condition caused by gastxoesophageal reflux. Many patients are asymptomatic. Barrett s esophagus occurs in about 10% to 15% of patients with reflux esophagitis. The diagnosis depends on endoscopy and biopsy. Complications are common and include ulceration, stricture, dysplasia, and adenocarcinoma. Esophagitis, ulceration, and stricture can usu- ally be treated medically. Surgical approaches are discussed for patients whose condition is refractory to medical therapy. The premalignant nature of Barrett s epithelium is well recognized, and strategies for surveillance and resection are discussed. Survival after resection of adenocarcinoma in Barrett s esophagus is not appreciably different from that of other carcinomas. Surveillance with endoscopy offers the best chance for early detection and cure. (Ann Thorac Surg 1992;54:586-91) lthough Tileston [l] described the existence of colum- A nar epithelium lining the lower esophagus as early as 1906, Barrett s [2] 1950 publication is considered the first detailed description of the disorder. He believed this condition represented a congenitally short esophagus with an intrathoracic stomach. In 1953, Allison and Johnstorte [3] correctly identified this condition as a columnar epithelium-lined distal esophagus and suggested that it might be acquired as a result of gastroesophageal reflux. Since that time, numerous clinical and experimental reports [P7] have confirmed their impression. However, many controversies regarding this disorder still exist, including the prevalence and incidence of malignant degeneradion, the importance of epithelial dysplasia, the effects of medical and surgical therapy on regression of the disease, and the indications for and results of surgical therapy in the treatment of benign and malignant complications. This review summarizes the current thinking regarding the pathogenesis, natural history, and management of Barrett s esophagus and its complications. Definition The usually accepted definition of Barrett s esophagus is a lower esophagus circumferentially lined by columnar epitheliurn for a distance of 3 cm or more cephalad to the gastroesophageal junction. This abnormal columnar epitheliurn is composed of three different randomly arranged cell types. The first is a gastric fundic type resembling the mucosa of the fundus of the stomach and containing chief and parietal cells. The second is a junc- - Address reprint requests to Dr Streitz, Department of Thoracic and Cardiovascular Surgery, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA tional epithelium that resembles the gastric cardia epithelium and contains cardiac mucous glands, but chief and parietal cells are absent. The third is a specialized intestinal columnar epithelium found nowhere else in the gastrointestinal tract, with a villous structure, secretion of glycoprotein, and mucous glands and goblet cells. This is the most common type of Barrett s epithelium and the cell type most likely to undergo malignant degeneration. Barrett s epithelium has typical gastrointestinal metabolic activity, including the secretion of pepsin, gastrointestinal hormones, mucin, and acid, although the volume of acid secretion is insignificant. Pathogenesis Although a congenital cause has been suggested in some patients [8, 91, most evidence today supports the view that Barrett s esophagus is an acquired condition and is the result of gastroesophageal reflux disease, which leads to destruction of the normal epithelium [1&12]. The denuded distal esophagus is reepithelialized with columnar cells ascending from the gastric cardia or esophagogastric junction. Bremner and associates [4] demonstrated experimentally in dogs that excision of the distal esophageal squamous lining in the presence of an incompetent cardia and histamine-induced hyperacidity would lead to a columnar epithelial esophageal lining, presumably by the cephalad migration of junctional epithelium, although the possibility of an origin from the subepithelial mucous glands of the esophagus was also considered. Numerous clinical studies have confirmed the association of Barrett s esophagus with gastroesophageal reflux disease, and little evidence supports a congenital cause except in rare instances by The Society of Thoracic Surgeons /92/$5.00

2 Ann Thorac Surg 1992;54: REVIEW STREITZ ET AL 587 SURVEILLANCE OF BARRETT S ESOPHAGUS Prevalence The prevalence of this disorder is unknown because a substantial number of patients with Barrett s esophagus are asymptomatic. It reportedly [6, 111 occurs in about 10% to 15% of patients with reflux esophagitis undergoing endoscopy. In a study from the Mayo Clinic [13], the prevalence of Barrett s esophagus found at autopsy in the population of Olmstead county was 21 times higher than was predicted based on a population-based study of clinically diagnosed patients. The estimated prevalence at autopsy was 376 cases per 100,000 population compared with an age- and sex-adjusted prevalence of 22.6 cases per 100,000 population in the clinically diagnosed patients. This confirms the suspicion that many patients go undiagnosed during life. The documented [14] insensitivity of Barrett s esophagus to acid is the likely explanation for the lack of symptoms in many of these patients despite the presence of reflux. Diagnosis Symptoms Most patients with Barrett s esophagus diagnosed clinically have symptoms or complications of gastroesophageal reflux disease. The age when first seen usually ranges from 50 to 60 years, with a predominance in men and whites. Heartburn and regurgitation are the most common symptoms. In the presence of an esophageal stricture, patients may also complain of dysphagia and weight loss. In our [15] review of 241 patients with endoscopically diagnosed Barrett s esophagus, heartburn, dysphagia, and regurgitation were the most common symptoms, occurring in 81%, 51%, and 33% of patients with benign Barrett s esophagus. When adenocarcinoma developed in conjunction with Barrett s esophagus, dysphagia and weight loss were initial symptoms in 68% and 44% of patients, respectively. Radiography Contrast radiography is not a sensitive diagnostic tool in evaluating patients suspected of having Barrett s esophagus. In one study [16] the rate of sensitivity was only 24%. The specificity, however, was Y4%, suggesting that when the characteristic radiographic appearance of Barrett s esophagus is present, the diagnosis is usually reliable. The typical appearance is that of a small sliding esophageal hiatus hernia with the esophagogastric junction lying a short distance above the hiatus. The squamocolumnar junction lies cephalad to the esophagogastric junction, sometimes at the aortic level or higher where an indentation or true stricture may be noted on esophagography. The intervening tubular esophagus represents the portion lined by columnar epithelium. Endoscopy The key to a definitive diagnosis of Barrett s esophagus is endoscopy, which will identify the abnormal pinkappearing mucosa that lines the distal esophagus above the esophagogastric junction. The squamocolumnar junction can be identified by the transition of the pale squamous lining to the pink columnar epithelium and may appear at the level of the aortic arch or higher. Multiple biopsies of the abnormal-appearing mucosa are recommended, usually in four quadrants at each centimeter of tubular lining. This is required not only to confirm the diagnosis of Barrett s esophagus but also to identify dysplasia when present and to assess its degree of severity. Manometry and ph Reflux Testing Esophageal manometric studies and 24-hour ph monitoring will, in most patients, show a decreased amplitude of lower esophageal sphincter pressure and abnormal reflux of acid characteristic of gastroesophageal reflux disease. Although these studies commonly show more pronounced abnormalities in patients with Barrett s esophagus than in patients with uncomplicated reflux [5, 171, neither test is specific for this disorder. Complications Ulceration and Stricture Esophageal stricture and ulceration are common complications in patients with Barrett s esophagus. The penetrating ulcers found within the columnar epithelium, Barrett s ulcers, are distinct from the superficial ulcerations associated with reflux esophagitis. These ulcers behave like gastric ulcers and may bleed and perforate and cause stenosis. The cause of Barrett s ulcer is unclear. Some authors [18] contend that local secretion of acid and pepsin from heterotopic epithelium results in formation of the ulcer. Other authors [ly] claim that ulcers develop as a result of acid-peptic erosion of islands of squamous epithelium within the columnar mucosa. Another theory implicates acid reflux onto the specialized columnar-type epithelium, which is less resistant to acid-peptic erosion than squamous epithelium. Alkaline reflux may also contribute to the development of Barrett s ulcers. It has been shown [17] that patients with complications of Barrett s esophagus, namely, ulceration, stricture, and carcinoma, have appreciably more alkaline reflux than patients without complications, but they have a similar degree of acid exposure. Because most Barrett s ulcers heal in response to medical therapy directed against acid reflux, it is unlikely that alkaline reflux plays a causative role. It may play a role in chronicity, however, and may explain why some ulcers fail to heal when treated with standard H, antagonists. The initial symptom of Barrett s ulcers may be bleeding or anemia or dysphagia when associated with scarring and formation of a stricture. Less common complications include deep penetration, perforation, and, rarely, fistulization into the pericardium, pulmonary vein, lung, and mediastinum [20]. Deeply penetrating ulcers may be accompanied by symptoms of precordial or lower dorsal pain. Benign strictures are common, occurring in about half of patients with Barrett s esophagus [S]. They usually occur at the squamocolumnar junction but may develop

3 588 REVIEW STREITZ ET AL SURVEILLANCE OF BARRETT S ESOPHAGUS Ann Thorac Surg 1992;54: within the columnar lining as well, perhaps caused by healing of a Barrett s ulcer [21]. Dysplusiu Although the exact risk of malignant degeneration of Barrett s esophagus is unknown, it is widely accepted that the metaplastic epithelium is premalignant and may progress from benign to dysplasia to a malignant lesion. The currently accepted method of grading dysplasia is based on the guidelines outlined by the inflammatory bowel disease-dysplasia morphology study group [22]. Mild or low-grade dysplasia is characterized by nuclei largely confined to the basal portion of the cells and severe or high-grade dysplasia by nuclei situated in the upper pole of the cell. Besides polarity, other cytologic and architectural features used to grade dysplasia include hyperchromatism, nuclear enlargement, stratification, pleomorphism, and abnormal mitoses. Most pathologists now agree that high-grade dysplasia and carcinoma in situ are indistinguishable histologically. Intramucosal carcinoma is distinguished from carcinoma in situ by its penetration through the basement membrane of the gland into the lamina propria, signaling the onset of invasiveness [23]. Dysplasia is commonly found in association with adenocarcinoma developing in Barrett s esophagus, occurring in 74% of our 65 patients with adenocarcinoma [24]. Adenocurcinomu Adenocarcinoma arising in Barrett s esophagus should be distinguished from carcinoma of the cardia arising coincidentally in a patient with Barrett s epithelium. The former has been defined [24] as a tumor of which 75% lies above the gastroesophageal junction and that has adjacent benign columnar epithelium (Fig 1). Although Barrett s esophagus is widely accepted as a premalignant condition, the risk of adenocarcinoma developing is not known. Prospective and retrospective studies of patients with Barrett s esophagus show risks of carcinoma ranging from 1 per 52 to 441 patient-years of follow-up, which is 30 to 125 times that of the general population [ (Table 1). The risk of carcinoma in Barrett s esophagus has been exaggerated in the past by prevalence reporting in surgical series, with rates of prevalence varying from 8.6% to 46% [ll, 34-36]. Our prevalence rate [15] is 27% (65 of 241 patients). These reports reflect practice patterns and referral bias and not the true incidence of the development of carcinoma over time. The disease predominates in white men more than 50 years of age. Only about half of patients have a history of chronic reflux symptoms; most patients have dysphagia as their initial complaint. Most, as a result, have advanced tumors when first seen. Although smoking and abuse of alcohol have been implicated as causative factors [36], this is not a consistent finding. Persistent acid reflux onto the columnar epithelium may play a role in malignant change. However, most studies [24, 371 have demonstrated that antireflux operation neither completely eliminates the abnormal mucosa nor protects against the development of carcinoma. The extent of Barrett s esoph- Fig 1. Adenocarcinoma arising in Barrett s esophagus. Radiographic appearance is seen on the left, and the resected specimen is shown on the right. (Roentgenogram on the left is from Andersen HA, Pluth IR. Benign tumors, cysts, and duplications of the esophagus. In: Payne W, Olsen A, eds. The esophagus. Philadelphia: Lea G. Febiger, 1974:231. Reproduced with permission. Illustration on the right is from Ellis FH It-, Shahiun DM. Tumors of the esophagus. In: Glenn WLW, Baue AE, Geha AS, Hammond GL, Laks H, eds. Thoracic & Cardiovascular Surgery, 4th ed. Norwalk: Appleton-Century-Crofts, , with permission.) agus does not appear to correlate with the risk of carcinoma because malignant degeneration occurs with equal frequency in patients with limited or extensive Barrett s epithelium. Treatment Benign Asymptomatic patients with uncomplicated Barrett s esophagus do not require therapy. Symptomatic patients should undergo standard medical treatment for gastroesophageal reflux, including such antireflux measures as elevation of the head of the bed, weight loss, avoidance of food before bedtime, avoidance of smoking, and dietary modifications. The use of antacids and H, blockers is routine as well as the use of metoclopramide to increase pressure in the lower esophageal sphincter and to improve gastric emptying. Omeprazole, a parietal cell H+-K+ adenosine triphosphatase inhibitor, may be useful

4 Ann Thorac Surg 1992: REVIEW STREITZ ET AL 589 SURVEILLANCE OF BARRETS ESOPHAGUS Table 1. Reported Incidence of Adenocarcinoma in Patients With Barrett s Esophaxus Study, Year Hameeteman et al, 1989 [25] van der Veen et al, 1989 [26] Robertson et al, 1988 [27] Cameron et al, 1985 [28] Spechler et al, 1984 [33] Skinner, 1989 [29] Ovaska et al, 1989 [30] Sampliner et al, 1985 [31] Ollyo et al, 1989 [32] Williamson et al, 1991 I151 Incidence/ Patient-Years of Follow-Up Study 1/52 1/170 1/ /48 1/ /99 No. of Times Greater Than the Incidence in General Population Not given 90 Not given Not given 74.8 Adapted from Williamson WA, Ellis FH Jr, Gibb SP, et al. Barrett s esophagus: prevalence and incidence of adenocarcinoma. Arch Intern Med 1991;151: Copyright 1991, American Medical Association. in patients whose disease is refractory to standard therapy [38, 391. Antireflux operation is reserved for patients with intractable symptoms despite medical therapy or for patients whose complications are unresponsive to conservative measures. Any of the standard antireflux operations may be employed. However, patients with poor peristalsis should not have a 360-degree fundoplication because of the increased likelihood of postoperative dysphagia, and patients with esophageal shortening or distal esophageal strictures may require a lengthening procedure, such as the Collis gastroplasty. Despite controlling acid reflux, antireflux operation infrequently results in regression of the Barrett s epithelium. A minority of patients show any sign of regression, and, when present, it is rarely complete [35, 36, 40, 411. Some evidence [36] suggests that apparent regression may represent the growth of squamous epithelium over the glandular lining. Barrett s Ulcer Regardless of their size, most uncomplicated Barrett s ulcers will heal with medical therapy that includes H, antagonists. Complete healing often takes 8 weeks or more, and ulcers may recur after discontinuation of treatment. The use of omeprazole has been shown to result in healing of ulcers that fail to heal when H, antagonists are taken and should be prescribed for these patients. In most patients, 85% in our experience, the ulcers can be expected to heal with proper medical treatment Surgical therapy should be undertaken when no evidence of healing is apparent after 4 months of medical therapy. An antireflux procedure should be performed, employing Collis gastroplasty in patients with esophageal shortening from chronic esophageal inflammation. With deeply penetrating Barrett s ulcers that fail to heal with medical therapy, some controversy exists as to whether antireflux procedures or resection should be undertaken. Pearson and colleagues [43] reported healing in 9 of 11 patients with deeply penetrating ulcers after Belsey repair and Collis gastroplasty. Likewise, we have had excellent results with Nissen repair and Collis gastroplasty in such patients. Panmural inflammation is often present and does not contraindicate the use of an antireflux procedure, but resection would be indicated in patients with transmural penetration of the ulcer A transthoracic approach is advocated for deeply penetrating ulcers to make this distinction. The complications of Barrett s ulcers, which include perforation, uncontrollable hemorrhage, and deep mediastinal penetration with formation of a fistula, are indications for urgent esophagectomy. Dysplasia and Adenocarcinoma The appearance of dysplasia in Barrett s epithelium is a worrisome finding that indicates possible subsequent malignant degeneration. Low-grade dysplasia may regress with medical treatment, which should be employed in such patients even in the absence of symptoms. In our 1151 series of 241 patients with Barrett s esophagus, the prevalence of dysplasia was 11%. Of 18 patients in whom low-grade dysplasia developed during surveillance, 15 patients had disappearance of these changes with medical therapy. Progression to high-grade dysplasia and eventually carcinoma occurred in 3 patients, however, despite medical treatment, underscoring the need for more frequent surveillance in patients with low-grade dysplasia. High-grade dysplasia should be considered an indication for resection because of the frequent development of invasive adenocarcinoma. The 5 patients in our [15] series in whom high-grade dysplasia developed subsequently had adenocarcinoma, 3 of whom had previously undergone a successful antireflux operation. Rates of operability and resectability for adenocarcinoma developing in Barrett s esophagus, 94% and loo%, respectively, are higher than for squamous cell carcinoma of the esophagus or carcinoma of the cardia Survival rates [24] of surgically treated patients, however, are not statistically different, being 23.7% at 5 years in our experience. Resection must encompass all of the Barrett s epithelium to eliminate the possibility of a second carcinoma developing in residual glandular epithelium. Operative mortality and morbidity for resection should not differ from those associated with other esophageal resections. Adjuvant therapy is of no proved benefit in improving long-term survival. Surveillance Patients in whom Barrett s esophagus is discovered at the time when adenocarcinoma is diagnosed usually have advanced tumors. Careful and frequent surveillance of patients with Barrett s esophagus, however, may permit detection of carcinoma at an early stage, making surgical cure more likely. The risk of the development of carcinoma appears to be high enough to warrant the cost and risk of endoscopic surveillance, although other authors 1331 have questioned its cost effectiveness. Patients with Barrett s esophagus should undergo

5 590 REVIEW STREITZ ET AL SURVEILLANCE OF BARRETT S ESOPHAGUS Ann Thorac Surg 1992;54:58&91 Fig 2. Algorithm for the management of Barrett s esophagus. (43 = euey 3; Rx = treatment.) k Carcinoma High-Grade Dysplasia Endoscopy blow-grade Dysplasia - Medical Rx - Q3 Month Suweillance Eysplasle Disappears yearly esophagoscopy and biopsy. When low-grade dysplasia is detected, the frequency of endoscopy should increase to every 3 months until the dysplasia disappears, recognizing that the apparent disappearance of dysplasia may reflect only sampling error. When high-grade dysplasia is discovered, resection is recommended (Fig 2). References Tileston W. Peptic ulcer of the oesophagus. Am J Med Sci 1906;132:24(!-65. Barrett NR. Chronic peptic ulcer of oesophagus and oesophagitis. Br J Surg 1950;38: Allison PR, Johnstone AS. Oesophagus lined with gastric mucous membrane. Thorax 1953;8: Bremner CG, Lynch VP, Ellis FH Jr. Barrett s esophagus: congenital or acquired? An experimental study of esophageal mucosal regeneration in the dog. Surgery 1970;68: Iascone C, DeMeester TR, Little AG, Skinner DB. Barrett s esophagus: functional assessment, proposed pathogenesis, and surgical therapy. Arch Surg 1983;118: Herlihy KJ, Orlando RC, Bryson JC, Bozymski EM, Carney CN, Powell DW. Barrett s esophagus: clinical, endoscopic, histologic, manometric, and electrical potential difference characteristics. Gastroenterology 1984;86: Hennessy TPJ, Edlich RF, Buchin RJ, Tsung MS, Prevost M, Wangensteen OH. Influence of gastroesophageal incompetence on regeneration of esophageal mucosa. Arch Surg 1968; Naef AP, Savary M. Conservative operations for peptic esophagitis with stenosis in columnar-lined lower esophagus. Ann Thorac Surg 1972;13: Borrie J, Goldwater L. Columnar cell-lined esophagus: assessment of etiology and treatment. A 22 year experience. J Thorac Cardiovasc Surg 1976;71: Endo M, Kobayashi S, Kozu T, Takemoto T, Nakayama K. A case of Barrett epithelialization followed up for 5 years. Endoscopy 1974;6: Naef AP, Savary M, Ozzello L. Columnar-lined lower esophagus: an acquired lesion with malignant predisposition. Report on 140 cases of Barrett s esophagus with 12 adenocarcinomas. J Thorac Cardiovasc Surg 1975;70: Hassall E, Weinstein WM, Ament ME. Barrett s esophagus in childhood. Gastroenterology 1985;89: Cameron AJ, Zinsmeister AR, Ballard DJ, Carney JA. Prevalence of columnar-lined (Barrett s) esophagus: comparison of population-based clinical and autopsy findings. Gastroenterology 1990;99: Johnson DA, Winters C, Spurling TJ, Chobanian SJ, Cattau EL Jr. Esophageal acid sensitivity in Barrett s esophagus. J Clin Gastroenterol 1987;9:23-7. Williamson WA, Ellis FH Jr, Gibb SP, et al. Barrett s esophagus: prevalence and incidence of adenocarcinoma. Arch Intern Med 1991;151: Winters C Jr, Spurling TJ, Chobanian SJ, et al. Barrett s esophagus: a prevalent, occult complication of gastroesophageal reflux disease. Gastroenterology 1987;92: DeMeester TRt Attwood SE, TCr DH8 Hinder RA. Surgical therapy in Barrett s esophagus. Ann Surg 1990;212: Ustach TJ, Tobon F, Schuster MM. Demonstration of acid secretion from esophageal mucosa in Barrett s ulcer. Gastrointest Endosc 1969;16: Fontolliet Ch, Wellinger J, Monnier P, Ollyo JB, Savary M. Barrett s ulcer: a heterogeneous group of disorders [Abstract]? Presented at the 4th World-Congress of the International Society for Diseases of the Esophagus, Chicago, IL, Sep 8, Anderson R, Nilsson S. Perforated Barrett s ulcer with esophago-pleural fistula. Acta Chir Scand 1985;151: Lackey C, Rankin RA, Welsh JD. Stricture location in Barrett s esophagus. Gastrointest Endosc 1984;30: Riddell RH, Goldman H, Ransohoff DF, et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical information. Hum Pathol 1983; Reid BJ, Haggitt RC, Rubin CE, et al. Observer variation in the diagnosis of dysplasia in Barrett s esophagus. Hum Pathol 1988;19: Streitz JM Jr, Ellis FH Jr, Gibb SP, Balogh K, Watkins E Jr. Adenocarcinoma in Barrett s esophagus: a clinicopathologic study of 65 cases. Ann Surg 1991;213: Hameeteman W, Tytgat GNJ, Houthoff HJ, van den Tweel JG. Barrett s esophagus: development of dysplasia and adenocarcinoma. Gastroenterology 1989;96: Van der Veen AH, Dees J, Blankensteijn JD, Van Blankenstein M. Adenocarcinoma in Barrett s oesophagus: an overrated risk. Gut 1989;30: Robertson CS, Mayberry JF, Nicholson DA, James PD, Atkinson M. Value of endoscopic surveillance in the detection of neoplastic change in Barrett s oesophagus. Br J Surg 1988;75: Cameron AJ, Ott BJ, Payne WS. The incidence of adenocarcinoma in columnar-lined (Barrett s) esophagus. N Engl J Med 1985;313: Skinner DB. The incidence of cancer in Barrett s esophagus vary according to series. In: Giuli R, McCallum RW, eds. Benign lesions of the esophagus and cancer. Answers to 210 questions. Berlin: Springer-Verlag, 1989:76& Ovaska J, Miettinen M, Kivilaakso E. Adenocarcinoma arising in Barrett s esophagus. Dig Dis Sci 1989; Sampliner RE, Kogan FJ, Morgan TR, Tripp M. Progressionregression of Barrett s esophagus [Abstract]. Gastroenterology 1985;88: Ollyo JB, Savary M, Monnier P, Wellinger J, Gonvers JJ, Fontolliet C. Is their prevalence in patients with Barrett s esophagus overestimated? In: Giuli R, McCallum RW, eds. Benign lesions of the esophagus and cancer. Answers to 210 questions. Berlin: Springer-Verlag, 1989: Spechler SJ, Robbins AH, Rubins HB, et al. Adenocarcinoma in Barrett s esophagus: an overrated risk? Gastroenterology 1984;87:

6 Ann Thorac Surg 1992:543S91 REVIEW STREITZ ET AL 591 SURVEILLANCE OF BARRETS ESOPHAGUS 34. Starnes VA, Adkins RB, Ballinger JF, Sawyers JL. Barrett's esophagus: a surgical entity. Arch Surg 1984;119: Radigan LR, Glover JL, Shipley FE, Shoemaker RE. Barrett's esophagus. Arch Surg 1977;11248& Skinner DB, Walther BC, Riddell RH, Schmidt H, Iascone C, DeMeester TR. Barrett's esophagus: comparison of benign and malignant cases. Ann Surg 1983;198: Williamson WA, Ellis FH Jr, Gibb SP, Shahian DM, Aretz HT. Effect of antireflux operation on Barrett's mucosa. Ann Thorac Surg 1990; Deviere J, Buset M, Dumonceau JM, Rickaert F, Cremer M. Regression of Barrett's epithelium with omeprazole [Letter]. N Engl J Med 1989;320: Lee FI, Isaacs PE. Barrett's ulcer: response to standard dose ranitidine, high dose ranitidine, and omeprazole. Am J Gastroenterol 1988;83: Ransom JM, Pate1 GK, Clift SA, Womble NE, Read RC. Extended and limited types of Barrett's esophagus in the adult. Ann Thorac Surg 1982;33: Brand DL, Mvisaker JT, Gelfand M, Pope CE 2nd. Regression of columnar esophageal (Barrett's) epithelium after antireflux surgery. N Engl J Med 1980;302: Williamson WA, Ellis FH Jr, Gibb SP, Aretz HT. Barrett's ulcer: a surgical disease? J Thorac Cardiovasc Surg 1991;103: Pearson FG, Cooper JD, Patterson GA, Prakash D. Peptic ulcer in acquired columnar-lined esophagus: results of surgical treatment. Ann Thorac Surg 1987;43: Altorki NK, Skinner DB, Segalin A, Stephens JK, Ferguson MK, Little AG. Indications for esophagectomy in nonmalignant Barrett's esophagus: a 10-year experience. Ann Thorac Surg 1990;49: Notice From the American Board of Thoracic Surgery The part I (written) examination will be held at the Hilton A candidate applying for admission to the certifying Conference center, Dallas Fort worth Airport, examination must fulfill all the requirements of the board Dallas, TX, on February 13, The closing date for in force at the time the application is received. registration is August 1, To be admissible for the part II (oral) examination, a Please address all communications to the American candidate must have successfullv comdeted the Dart I Board of Thoracic Surgery, One Rotary Center, Suite 803, (written) examination. Evanston, IL