Em J Cardio-thorac
Surg (1991) 5: 13-16
The enigma of Barrett’s oesophagus: putting the record straight K. Moghissi Humberside
Cardiothoracic
Surgical Centre, Castle Hill Hospital, Cottingham,
“Most controversies would soon be ended if those engaged in them would first accurately define their terms, and then adhere to their definition.” Tyron Edwards
When in 3950 Barrett [6] published his article on chronic peptic ulcer of the oesophagus and oesophagitis, he was primarily concerned with dispelling the confusion which existed at that time about two types of oesophageal “peptic” ulcer. In one type the ulcer was associated with a fixed hiatal hernia and acquired short oesophagus (this had been previously described by Allison, Johnstone and Royce [3]). Contrasted with this was a second type of ulcer which Barrett believed to develop in a congenital intrathoracic (mediastinal) tubular stomach associated with congenital short oesophagus. Allison and Johnstone [4] showed conclusively that Barrett’s “mediastinal stomach” was in fact an “oesophagus lined with gastric type mucous membrane”. Barrett conceded this notion and in 1957 [7] published his article on “The lower oesophagus lined by columnar epithelium”, which formulated clearly the characteristics of the condition that has become known as Barrett’s oesophagus. Since, in recent publications, Barrett’s oesophagus has been defined with no reference to or correspondence with these characteristics, they may with advantage be recalled. Barrett said, “When the lower oesophagus is found to be lined by columnar cells, the abnormally placed mucous membrane extends upward from the oesophagogastric junction in a continuous unbroken sheet. There is no question of ectopic islets. The extent of the anomaly varies from a few centimetres to the upper oesophagus. This deformity is not associated with or complicated by other anatomic changes: that is (1) the external appearances and the muscular anatomy of the stomach and the oseophagus are normal; (2) there is no anatomic change in the mediastinum: (3) the blood supply from the aortic Received for publication: Accepted for publication
April 23, 1990 September 11, 1990
Hull, UK
segmental arteries and the left gastric artery is normal; and (4) the crus of the diaphragm and the peritoneal reflections in the neighbourhood of the hiatus are normal.” At that time opinions concerned with columnar epithelial lined oesophagus, now generally referred to as Barrett’s oesophagus, were not confined to Allison and Barrett. In 1957 Lortat-Jacob [32] also published his observations under “L’endo-brachy-oesophage”, and there is no doubt that “endobrachy oesophagus” and Barrett’s oesophagus are the same anatomopathological entity. Ever since these publications there has been controversy about the very existence of the condition, its aetiology and its complications. The development of the modern tibroscope and its widespread use by gastroenterologists has introduced yet another factor both into the confusion regarding definition of the condition and the frequency with which it is diagnosed. Prior to this development the diagnosis of Barrett’s oesophagus was based not only on endoscopy and mucosal biopsy, but also on the inspection of the thoracic oesophagus and mediastinum, either at thoracotomy or post mortem examination, in order to confirm the lack of pathological changes and conform with Barrett’s criteria. New developments meant that diagnosis became principally based on endoscopic findings and the recovery of columnar epithelium from the lower oesophagus (or what the endoscopist believed to be the lower oesophagus). The generally accepted definition of Barrett’s oesophagus came to be a condition in which the lower end (usually 3 cm or more) of the oesophagus is lined by columnar epithelium [l 1,44, 481. This, however, presupposes that the lower end of the oesophagus and the gastro-oesophageal junction can be identified readily at endoscopic examination which, in the absence of parallel manometric studies defining the lower oesophageal sphincter, is not the case [14, 27, 481. Even with parallel manometric studies it is debatable whether the physiological gastro-oesophageal junction defined by manometry would represent the anatomical junction which is the important part of the equation in oesophagus lined by co-
14
lumnar epithelium. If therefore follows that in a defmition based on endoscopy, the fundamental issue is where the endoscopist considers the gastro-oesophageal junction to be situated, which ipso facto is far from being precisely delineated, whereas the anatomical oesophagogastric junction can be identified more accurately at thoracotomy or autopsy [26]. Furthermore, one may question (a) whether the columnar lining of the lower oesophagus as diagnosed endoscopically (without Barrett’s other criteria) equates with the condition described by Barrett, and (b), in the face of such discrepancy between what has come to be the universally accepted endoscopic definition and Barrett’s original description, whether authentic Barrett’s oesophagus does exist. However, authors who have specifically studied the condition anatomopathologically testify to its existence [5,7,33,53, 541. It is therefore reasonable to suggest that Barrett’s oesophagus should be regarded as an anatomopathological entity, the diagnosis of which depends on the existence of columnar epithelium in the lower oesophagus proximal to the anatomical oesophagogastric junction, the normality of oesophageal wall and its normal muscular and vascular anatomy. On the other hand, columnar epithelial lined oesophagus (CELO) should be considered as a condition in which the lower oesophagus (normal or abnormal) is lined by columnar epithelium diagnosed endoscopically. In such a definition it is still mandatory to ascertain that the biopsy material has been taken from the lower oesophagus and not from the stomach. The incidence of Barrett’s oesophagus or CELO in the general population is unknown, since the published data can only relate to symptomatic patients but cannot account for asymptomatic individuals. Furthermore, available figures are not only influenced by the criteria upon which the diagnosis was based, with all the aforementioned variations, but also represent only the incidence for that selected population of patients which happen to have been studied by an investigator. This may account for the variation in published literature concerning the incidence of CELO, which is reported to be between 4.5% and 44% in the patients studied [8,34,35,38, 461. The aetiology of CELO has been the subject of dispute. That it is congenital has been rejected by the majority of authors [2, 9, 10, 12, 17, 20, 22, 23, 28, 35, 37, 38, 461. Nevertheless, there is some evidence of the possibility of a congenital origin [l, 4,5,7,29,31,36,39,45,51,54]. It is possible, in fact, that there are two types of CELO [8, 33, 491. In the first type, the true Barrett’s oesophagus, there is a congenital persistence of columnar epithelium, whilst in the second type, acquired CELO, there is a metaplasia of the oesophageal mucosa occasioned by gastro-oesophageal reflux. This serves to strengthen the argument that Barrett’s oesophagus may not be the same condition as that which is described with increasing frequency by endoscopists. In his original article, Barrett referred to three types of complication arising within CELO namely, strictures, ulcers and carcinoma. Strictures formed in Barrett’s oesophagus are typically high in position, at or above the aortic arch at the
squamo-columnar epithelial junction of the oesophagus. The pathogenesis of these strictures was clearly described by Allison [5]. However, for a number of years the term “high stricture” implied a stricture associated with Barrett’s oesophagus [5, 16, 181. There is now no doubt that high oesophageal strictures are most commonly at the squamo-columnar oesophagogastric epithelial mucosal junction of a hiatal hernia with acquired short oesophagus, and that the term “high stricture” should have a topographical connotation. In fact, using strict criteria in conjunction with anatomopathological studies, we found only 7% of high strictures to be Barrett’s stricture [34], whilst Cooper and Barbezat [15] found 13% of all strictures arising in Barretts oesophagus. Allison referred to ulcers within Barrett’s oesophagus as “Barrett’s ulcer”. Endoscopists may not appreciate the depth of this type of ulcer, but every oesophageal surgeon must have seen examples of such ulcers, which appear within the columnar epithelial-lined oesophagus, and Allison’s [3] and Barrett’s [6] description of these ulcers remain valid to date. Typically, the ulcer is penetrating, often closely related or attached to the aorta, with a tendency to perforate and to cause severe haemorrhage [50, 53, 541, which means therefore that they require resection. Barrett [7] suggested that when adenocarcinoma is discovered at the level of the arch of the aorta, the usual explanation is that the patient has developed a columnar cancer “de nova” in columnar oesophageal mucosa. The association between adenocarcinoma and CELO has been the subject of numerous publications and the frequency of the association has been placed at about 10% [28,35,38,43]; it has been set as low as 0% [8] and as high as 46% [44]. Such figures as the latter, however, do not imply that nearly one-half of patients with Barrett’s oesophagus or CELO are at risk of developing adenocarcinema. They should be interpreted as the “prevalence”, or frequency, with which adenocarcinoma is found in a selected group of patients with Barrett’s oesophagus in a particular type of practice with its own pattern of referral. It has also to be noted that any data concerned with the incidence of adenocarcinoma in Barrett’s oesophagus may be considered as meaningless unless in the first place the criteria adopted to define Barrett’s oesophagus are stipulated and evidence is provided by the author that adenocarcinoma has arisen from the columnar epitheliurn of the oesophagus. There is undoubtedly a relationship between columnar-lined oesophagus and adenocarcinema, but the demonstration of the nature of the relationship, though of obvious therapeutic relevance, is difficult to assess precisely. Nevertheless, it can be deduced from three types of study. Firstly, there must be simultaneous discovery and/or diagnosis of adenocarcinoma and Barrett’s oesophagus. In this type of study it is important to realise that an adenocarcinoma in the oesophagus can be:
(a) An upward extension of carcinoma of the cardia. (b) Upward migration of carcinoma of the stomach within a hiatal hernia.
15
(c) A cancer arising in a tubular intrathoracic stomach associated with acquired short oesophagus appearing as oesophageal adenocarcinoma. (d) A carcinoma arising from columnar epithelial-lined oesophagus (true adenocarcinoma in Barrett’s oesophagus). (e) Very exceptionally, carcinoma arising from mucous glands. It is therefore necessary to set strict criteria before acceptance of an adenocarcinoma as originating from Barrett’s oesophagus. Failure to do so would result in overestimation of the incidence. Only serial section of the resected specimen showing adenocarcinoma adjacent to normal columnar epithelium of the oesophagus should, in our opinion, be taken as proof of authenticity. Review of the literature indicates that, in many publications, either the criteria by which the adenocarcinoma is believed to have arisen from Barrett’s oesophagus are not stated or, when the criteria are given, they do not meet with the strict requirements which we feel to be necessary. It is interesting that Keen, Dodd and Smith [30] indicate that when they re-studied and scrutinized 113 patients with a discharge diagnosis of adenocarcinoma arising in oesophageal columnar epithelium, in only 17 (15%) was the diagnosis finally confirmed as adenocarcinoma arising in Barrett’s oesophagus. Some authors, however, have applied these rigid diagnostic criteria [13,21,40-42, 44, 521. Even in these studies, however, the frequency with which the two pathologies, namely Barrett’s oesophagus and adenocarcinoma, are met cannot be accurately deduced because in the majority of publications the authors do not state the incidence of this coexistence in the total number of operated adenocarcinomas in their series. Also, in order to draw a meaningful conclusion it is necessary not only to have the relevant figures but also to know the incidence of adenocarcinoma in their population. The second line of investigation is related to the prospective study of patients with an endoscopic diagnosis of CELO who subsequently develop adenocarcinoma. Here the incidence has been variably recorded between 0% and 3% [8, 13,21,25,41,47]. These figures also require interpretation and adjustment by taking into account the criteria by which the diagnosis of Barrett’s oesophagus had been initially made, which has not always been stated, and by considering the interval between the diagnosis of CELO and the development of adenocarcinoma. The final figure may then be expressed in patient-years, as has been done by some authors [21, 41, 471. Yet this final figure will underestimate the real incidence, since that “sample” population is not representative of all cases of Barrett’s oesophagus but of the symptomatic and investigated subgroup. The third type of investigation has concentrated on the follow up of patients with Barrett’s oesophagus with epithelial cellular dysplasia who subsequently developed carcinoma. The subject of cellular dysplasia, particularly in a diseased oesophagus, is a controversial one with respect to both interpretation and implication. The presence of high-grade columnar epithelial dysplasia demon-
strated at biopsy should be regarded as a case of carcinoma in situ or even of invasive carcinoma. This is supported by the fact that, first, the oesophagectomy specimen in some of these cases shows a definite infiltrating cancer, and, secondly, in some reported cases, the interval between dysplasia and the development of cancer has been of the order of weeks rather than months [24]. One may therefore justifiably question the accuracy of the initial diagnosis of “dysplasia”. What, then, can we conclude? Forty years on from Barrett’s original definition, controversy reigns, and, in spite of the evolution of investigatory techniques, many features associated with the condition remain enigmatic. Experience and study of the literature draw one to conclude that: 1. Barrett’s oesophagus is a columnar epithelial-lined oesophagus the diagnosis of which requires inspection of the lower oesophageal wall and the surrounding structures to confirm their normality as suggested by Barrett. 2. Columnar epithelial-lined oesophagus (CELO) is a condition in which the lower oesophagus is found at endoscopy and biopsy to have columnar epithelial mucosa, the diagnosis of which requires confirmation (possibly by parallel manometric studies) that the biopsy has been recovered from the oesophagus. 3. Complications of Barrett’s oesophagus, particularly those related to adenocarcinoma, have been generally overrated. Although patients with Barrett’s oesophagus or CELO appear to be at higher risk of cancer development than the general population, the risk is not such as to consider these lesions as precancerous.
References 1. Abrams
2. 3. 4. 5. 6. 7. 8.
9.
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L, Heath D (1965) Lower oesophagus lined intestinal and gastric epithelia. Thorax 20: 66-72 Adler RH (1963) The lower esophagus lined by columnar epithelium. J Thorac Cardiovasc Surg 45: 13 - 34 Allison PR, Johnstone AS, Royce GB (1943) Short esophagus with simple peptic ulceration. J Thorac Surg 12:432 Allison PR, Johnstone AS (1953) The oesophagus lined with gastric mucous membrane. Thorax 8: 87-101 Allison PR (1970) Peptic oesophagitis and oesophageal stricture. Lancet ii: 199-201 Barrett NR (1950) Chronic peptic ulcer of the oesophagus and ‘oesophagitis’. Br J Surg 38: 175-182 Barrett NR (1957) The lower esophagus lined by columnar epithelium. Surgery 41: 881-894 Borrie J, Goldwater L (1976) Columnar cell-lined esophagus: assessment of etiology and treatment. J Thorac Cardiovasc Surg 71: 825-834 Brand DL, Ylvisaker JT, Gelfand M, Pope CE (1980) Regression of columnar esophageal (Barrett’s) epithelium after antireflux surgery. N Engl J Med 302: 844-848 Bremner CG, Lynch VP, Ellis FH Jr (1970) Barrett’s oesophagus, congenital or acquired? An experimental study of oesophageal mucosal regeneration in dog. Surgery 68: 209-216 Bremner CG, Hamilton DG (1985) Barrett’s oesophagus: controversial aspects. In: DeMeester TR, Skinner DB (eds) Oesophageal disorders, pathophysiology and therapy. Raven, New York, pp 233-239 Burgess JN, Payne WS, Anderson HA, Weiland LH, Carlson HC (1971) Barrett’s oesophagus: the columnar epithelial lined lower oesophagus. Mayo Clin Proc 46: 728-734
16 13. Cameron AJ, Ott BJ, Payne WS (1985) The incidence of carcinoma in columnar-lined (Barrett’s) esophagus. N Engl J Med 313: 857-859 14. Cohen BR, Wolf BS, Som ML, Janowitz HD (1963) Correlation of manometric oesophagoscopic and radiological findings in the columnar-lined gullet (Barrett syndrome). Gut 4:406412 15. Cooper BT, Barbezat GO (1987) Barrett’s oesophagus: a clinical study of 52 patients. Q J Med 62:91-108 16. Corrin B, Kent-Harrison G, Johnstone HRM (1970) High oesophageal stricture with hiatal hernia and a lower oesophagus lined by columnar epithelium. Thorax 25: 89-90 17. Dahms BB, Rothstein FC (1984) A consequence of chronic gastro-oesophageal reflux. Gastroenterology 86: 318-323 18. Davidson JS (1976) High peptic stricture of the oesophagus. Thorax 31:1-14 19. Endo M, Kobayashi S, Kosu T, Takemoto T, Nakayama K (1974) A case of Barrett’s epithelialisation followed up for five years. Endoscopy 6: 48- 51 20. Goldman MC, Beckman RC (1960) Barrett syndrome: case report with discussion about concept of pathogenesis. Gastroenterology 39: 104- 110 21. Haggitt RC, Tryzelaar J, Ellis FH, Colcher H (1977) Adenocarcinema complicating columnar epithelium-lined (Barrett’s) esophagus. Am J Clin Path01 70(l): l-5 22. Halvorsen JF, Senib BKH (1975) The Barrett syndrome. An acquired condition secondary to reflux oesophagitis. Acta Clin Stand 141:683-687 23. Hamilton SR, Yardley JM (1977) Regeneration of cardiac type of mucosa after esophagogastrostomy. Gastroenterology 72: 669-675 24. Hamilton SR, Smith RRL (1987) The relationship between columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett’s oesophagus. Am J Clin Path01 87: 301-312 25. Harle IA, Finley RJ, Belsheim M, Bondy DC, Booth M, Lioyod D, McDonald JWD, Sullivan S, Balberg LS, Watson WL, Frei JV, Slinger R, Troster M, Meads GE, Duff JH (1985) Management of adenocarcinoma in a columnar lined esophagus. Ann Thorac Surg 40: 330-336 26. Hayward J (1961) The phreno-esophageal ligament in hiatal hernia repair. Thorax 16: 41-45 27. Heitman P, Strauszer T, Sapunar J, Larrain A (1967) Lower esophagus lined with columnar epithelium: morphological and physiological correlation. Gastroenterology 53: 61 l-624 28. Hennessy TPJ (1985) Barrett’s oesophagus. Br J Surg 72: 336340 29. Ismail-Begi F, Pope II CE (1974) Distribution of the histological changes of gastroesophageal reflux in the distal esophagus of man. Gastroenterology 66: 1109 - 1113 30. Keen SJ, Dodd GD, Smith JL (1984) Adenocarcinoma arising in Barrett’s oesophagus, pathologic and radiologic features. Mount Sinai J Med 51: 442-449 31. Law SW, Sheehan EE (1965) Benign esophageal stricture and the lower esophagus lined by columnar epithelium: report of two cases. Chest 48: 214-222 32. Lortat-Jacob JL (1957) L’endo-brachy-oesophage. Ann Chir 11: 1247-1254 33. Moghissi K (1988) Barrett’s oesophagus: does it exist? Is it congenital? In: Siewert JR, Holscher AM (eds) Diseases of the oesophagus. Springer, Berlin Heidelberg New York 34. Moghissi K, Goebells P (1990) Relevance of anatomopathology of high oesophageal strictures to the design of surgical treatment. Eur J Cardio-thorac Surg 4:91-96 35. Monnier P, Fontolliet C, Savary M, 011~0 JB (1987) Barrett’s oesophagus or columnar epithelium of the lower oesophagus. Baillieres Clin Gastroenterol 1:769-789
36. Morris KN (1955) Gastric mucosa within the oesophagus Aust NZ J Surg 25:24-33 37. Mossberg SM (1966) The columnar lined oesophagus (Barrett syndrome) an acquired condition? Gastroenterology 50: 671676 38. Naef AP, Ozzello L (1975) Columnar lined lower esophagus: an acquired lesion with malignant predisposition. J Thorac Cardiovasc Surg 70: 5 826-835 39. Raebum C (1951) Columnar ciliated epithelium in the adult oesophagus. J Path01 Bacterial 63: 157-162 40. Reid BJ, Haggit RC, Rubin CE, Roth G, Surawicz CM, Van Belle G, Lewin K, Weinstein WM, Antonioli DA, Goldman H, McDonald W, Owen D (1988) Observer variation in the diagnosis of dysplasia in Barrett’s esophagus. Human Path01 19: 166- 179 41. Ribet M, Mensier E, Pruvot FR (1987) Barrett’s oesophagus and adenocarcinoma. Eur J Cardio-thorac Surg 1:29-32 42. Saubier EC, Gouillat C, Samaniego C, Buillard M, Moulinier B (1985) Adenocarcinoma in columnar lined Barrett’s esophagus: analysis of 13 esophagectomies. Am J Surg 150: 365-369 43. Sjogren RW JR, Johnson LF (1983) Barrett’s esophagus: a review. Am J Med 74: 313-321 44. Skinner DB, Walther BC, Riddell RH, Schmidt H, Iascone C, DeMeester TR (1983) Barrett’s esophagus: comparison of benign and malignant cases. Ann Surg 198: 544-565 45. Som ML, Wolf BS (1956) Peptic ulcer of the esophagus in gastric lined esophagus. JAMA 162: 641-644 46. Spechler SJ, Sperber H, Doos WG, Schimmel EA (1983) The prevalence of Barrett’s esophagus in patients with chronic peptic esophageal strictures. Dig Dis Sci 28: 9 769-774 47. Spechler SJ, Robbins AH, Rubins HB, Vincent ME, Heeren P, Doos WG, Colton T, Schimmel EM (1984) Adenocarcinoma and Barrett’s oesophagus: an overrated risk? Gastroenterology 87:927-933 48. Spechler SJ, Goyal RK (1986) Barrett’s esophagus. N Engl J Med 315: 362-371 49. Stadelmann 0, Elster K, Kuhn HA (1981) Columnar lined oesophagus (Barrett’s syndrome): congenital or acquired? Endoscopy 13:140-147 50. Ustach TJ, Tobon F, Schuster MM (1969) Demonstration of acid secretion from esophageal mucosa in Barrett’s ulcer. Gastrointest Endosc 16:98-100 51. Van De Kerckhof J, Gahagan T (1963) Regeneration of the mucosal lining of the oesophagus. Henry Ford Hosp Med Bull 11:129-134 52. Witt TR, Bains MS, Zaman MB, Martini N (1983) Adenocarcinema in Barrett’s esophagus. J Thorac Cardiovasc Surg 85: 3 337-345 53. Wolf BS, Marshak RH, Som ML, Winkelstein A (1955) Peptic esophagitis, peptic ulcer of the esophagus and marginal esophagogastric ulceration. Gastroenterology 29: 744 54. Wolf BS, Marshak RH, Som ML (1958) Peptic esophagitis and peptic ulceration of the esophagus. A J R 79: 741
Mr. K. Moghissi, FRCS Consultant Cardiothoracic Surgeon Humberside Cardiothoracic Surgical Centre Castle Hill Hospital Cottingham Hull N. Humberside HU16 5JQ United Kingdom
Surg (1991) 5: 13-16
The enigma of Barrett’s oesophagus: putting the record straight K. Moghissi Humberside
Cardiothoracic
Surgical Centre, Castle Hill Hospital, Cottingham,
“Most controversies would soon be ended if those engaged in them would first accurately define their terms, and then adhere to their definition.” Tyron Edwards
When in 3950 Barrett [6] published his article on chronic peptic ulcer of the oesophagus and oesophagitis, he was primarily concerned with dispelling the confusion which existed at that time about two types of oesophageal “peptic” ulcer. In one type the ulcer was associated with a fixed hiatal hernia and acquired short oesophagus (this had been previously described by Allison, Johnstone and Royce [3]). Contrasted with this was a second type of ulcer which Barrett believed to develop in a congenital intrathoracic (mediastinal) tubular stomach associated with congenital short oesophagus. Allison and Johnstone [4] showed conclusively that Barrett’s “mediastinal stomach” was in fact an “oesophagus lined with gastric type mucous membrane”. Barrett conceded this notion and in 1957 [7] published his article on “The lower oesophagus lined by columnar epithelium”, which formulated clearly the characteristics of the condition that has become known as Barrett’s oesophagus. Since, in recent publications, Barrett’s oesophagus has been defined with no reference to or correspondence with these characteristics, they may with advantage be recalled. Barrett said, “When the lower oesophagus is found to be lined by columnar cells, the abnormally placed mucous membrane extends upward from the oesophagogastric junction in a continuous unbroken sheet. There is no question of ectopic islets. The extent of the anomaly varies from a few centimetres to the upper oesophagus. This deformity is not associated with or complicated by other anatomic changes: that is (1) the external appearances and the muscular anatomy of the stomach and the oseophagus are normal; (2) there is no anatomic change in the mediastinum: (3) the blood supply from the aortic Received for publication: Accepted for publication
April 23, 1990 September 11, 1990
Hull, UK
segmental arteries and the left gastric artery is normal; and (4) the crus of the diaphragm and the peritoneal reflections in the neighbourhood of the hiatus are normal.” At that time opinions concerned with columnar epithelial lined oesophagus, now generally referred to as Barrett’s oesophagus, were not confined to Allison and Barrett. In 1957 Lortat-Jacob [32] also published his observations under “L’endo-brachy-oesophage”, and there is no doubt that “endobrachy oesophagus” and Barrett’s oesophagus are the same anatomopathological entity. Ever since these publications there has been controversy about the very existence of the condition, its aetiology and its complications. The development of the modern tibroscope and its widespread use by gastroenterologists has introduced yet another factor both into the confusion regarding definition of the condition and the frequency with which it is diagnosed. Prior to this development the diagnosis of Barrett’s oesophagus was based not only on endoscopy and mucosal biopsy, but also on the inspection of the thoracic oesophagus and mediastinum, either at thoracotomy or post mortem examination, in order to confirm the lack of pathological changes and conform with Barrett’s criteria. New developments meant that diagnosis became principally based on endoscopic findings and the recovery of columnar epithelium from the lower oesophagus (or what the endoscopist believed to be the lower oesophagus). The generally accepted definition of Barrett’s oesophagus came to be a condition in which the lower end (usually 3 cm or more) of the oesophagus is lined by columnar epithelium [l 1,44, 481. This, however, presupposes that the lower end of the oesophagus and the gastro-oesophageal junction can be identified readily at endoscopic examination which, in the absence of parallel manometric studies defining the lower oesophageal sphincter, is not the case [14, 27, 481. Even with parallel manometric studies it is debatable whether the physiological gastro-oesophageal junction defined by manometry would represent the anatomical junction which is the important part of the equation in oesophagus lined by co-
14
lumnar epithelium. If therefore follows that in a defmition based on endoscopy, the fundamental issue is where the endoscopist considers the gastro-oesophageal junction to be situated, which ipso facto is far from being precisely delineated, whereas the anatomical oesophagogastric junction can be identified more accurately at thoracotomy or autopsy [26]. Furthermore, one may question (a) whether the columnar lining of the lower oesophagus as diagnosed endoscopically (without Barrett’s other criteria) equates with the condition described by Barrett, and (b), in the face of such discrepancy between what has come to be the universally accepted endoscopic definition and Barrett’s original description, whether authentic Barrett’s oesophagus does exist. However, authors who have specifically studied the condition anatomopathologically testify to its existence [5,7,33,53, 541. It is therefore reasonable to suggest that Barrett’s oesophagus should be regarded as an anatomopathological entity, the diagnosis of which depends on the existence of columnar epithelium in the lower oesophagus proximal to the anatomical oesophagogastric junction, the normality of oesophageal wall and its normal muscular and vascular anatomy. On the other hand, columnar epithelial lined oesophagus (CELO) should be considered as a condition in which the lower oesophagus (normal or abnormal) is lined by columnar epithelium diagnosed endoscopically. In such a definition it is still mandatory to ascertain that the biopsy material has been taken from the lower oesophagus and not from the stomach. The incidence of Barrett’s oesophagus or CELO in the general population is unknown, since the published data can only relate to symptomatic patients but cannot account for asymptomatic individuals. Furthermore, available figures are not only influenced by the criteria upon which the diagnosis was based, with all the aforementioned variations, but also represent only the incidence for that selected population of patients which happen to have been studied by an investigator. This may account for the variation in published literature concerning the incidence of CELO, which is reported to be between 4.5% and 44% in the patients studied [8,34,35,38, 461. The aetiology of CELO has been the subject of dispute. That it is congenital has been rejected by the majority of authors [2, 9, 10, 12, 17, 20, 22, 23, 28, 35, 37, 38, 461. Nevertheless, there is some evidence of the possibility of a congenital origin [l, 4,5,7,29,31,36,39,45,51,54]. It is possible, in fact, that there are two types of CELO [8, 33, 491. In the first type, the true Barrett’s oesophagus, there is a congenital persistence of columnar epithelium, whilst in the second type, acquired CELO, there is a metaplasia of the oesophageal mucosa occasioned by gastro-oesophageal reflux. This serves to strengthen the argument that Barrett’s oesophagus may not be the same condition as that which is described with increasing frequency by endoscopists. In his original article, Barrett referred to three types of complication arising within CELO namely, strictures, ulcers and carcinoma. Strictures formed in Barrett’s oesophagus are typically high in position, at or above the aortic arch at the
squamo-columnar epithelial junction of the oesophagus. The pathogenesis of these strictures was clearly described by Allison [5]. However, for a number of years the term “high stricture” implied a stricture associated with Barrett’s oesophagus [5, 16, 181. There is now no doubt that high oesophageal strictures are most commonly at the squamo-columnar oesophagogastric epithelial mucosal junction of a hiatal hernia with acquired short oesophagus, and that the term “high stricture” should have a topographical connotation. In fact, using strict criteria in conjunction with anatomopathological studies, we found only 7% of high strictures to be Barrett’s stricture [34], whilst Cooper and Barbezat [15] found 13% of all strictures arising in Barretts oesophagus. Allison referred to ulcers within Barrett’s oesophagus as “Barrett’s ulcer”. Endoscopists may not appreciate the depth of this type of ulcer, but every oesophageal surgeon must have seen examples of such ulcers, which appear within the columnar epithelial-lined oesophagus, and Allison’s [3] and Barrett’s [6] description of these ulcers remain valid to date. Typically, the ulcer is penetrating, often closely related or attached to the aorta, with a tendency to perforate and to cause severe haemorrhage [50, 53, 541, which means therefore that they require resection. Barrett [7] suggested that when adenocarcinoma is discovered at the level of the arch of the aorta, the usual explanation is that the patient has developed a columnar cancer “de nova” in columnar oesophageal mucosa. The association between adenocarcinoma and CELO has been the subject of numerous publications and the frequency of the association has been placed at about 10% [28,35,38,43]; it has been set as low as 0% [8] and as high as 46% [44]. Such figures as the latter, however, do not imply that nearly one-half of patients with Barrett’s oesophagus or CELO are at risk of developing adenocarcinema. They should be interpreted as the “prevalence”, or frequency, with which adenocarcinoma is found in a selected group of patients with Barrett’s oesophagus in a particular type of practice with its own pattern of referral. It has also to be noted that any data concerned with the incidence of adenocarcinoma in Barrett’s oesophagus may be considered as meaningless unless in the first place the criteria adopted to define Barrett’s oesophagus are stipulated and evidence is provided by the author that adenocarcinoma has arisen from the columnar epitheliurn of the oesophagus. There is undoubtedly a relationship between columnar-lined oesophagus and adenocarcinema, but the demonstration of the nature of the relationship, though of obvious therapeutic relevance, is difficult to assess precisely. Nevertheless, it can be deduced from three types of study. Firstly, there must be simultaneous discovery and/or diagnosis of adenocarcinoma and Barrett’s oesophagus. In this type of study it is important to realise that an adenocarcinoma in the oesophagus can be:
(a) An upward extension of carcinoma of the cardia. (b) Upward migration of carcinoma of the stomach within a hiatal hernia.
15
(c) A cancer arising in a tubular intrathoracic stomach associated with acquired short oesophagus appearing as oesophageal adenocarcinoma. (d) A carcinoma arising from columnar epithelial-lined oesophagus (true adenocarcinoma in Barrett’s oesophagus). (e) Very exceptionally, carcinoma arising from mucous glands. It is therefore necessary to set strict criteria before acceptance of an adenocarcinoma as originating from Barrett’s oesophagus. Failure to do so would result in overestimation of the incidence. Only serial section of the resected specimen showing adenocarcinoma adjacent to normal columnar epithelium of the oesophagus should, in our opinion, be taken as proof of authenticity. Review of the literature indicates that, in many publications, either the criteria by which the adenocarcinoma is believed to have arisen from Barrett’s oesophagus are not stated or, when the criteria are given, they do not meet with the strict requirements which we feel to be necessary. It is interesting that Keen, Dodd and Smith [30] indicate that when they re-studied and scrutinized 113 patients with a discharge diagnosis of adenocarcinoma arising in oesophageal columnar epithelium, in only 17 (15%) was the diagnosis finally confirmed as adenocarcinoma arising in Barrett’s oesophagus. Some authors, however, have applied these rigid diagnostic criteria [13,21,40-42, 44, 521. Even in these studies, however, the frequency with which the two pathologies, namely Barrett’s oesophagus and adenocarcinoma, are met cannot be accurately deduced because in the majority of publications the authors do not state the incidence of this coexistence in the total number of operated adenocarcinomas in their series. Also, in order to draw a meaningful conclusion it is necessary not only to have the relevant figures but also to know the incidence of adenocarcinoma in their population. The second line of investigation is related to the prospective study of patients with an endoscopic diagnosis of CELO who subsequently develop adenocarcinoma. Here the incidence has been variably recorded between 0% and 3% [8, 13,21,25,41,47]. These figures also require interpretation and adjustment by taking into account the criteria by which the diagnosis of Barrett’s oesophagus had been initially made, which has not always been stated, and by considering the interval between the diagnosis of CELO and the development of adenocarcinoma. The final figure may then be expressed in patient-years, as has been done by some authors [21, 41, 471. Yet this final figure will underestimate the real incidence, since that “sample” population is not representative of all cases of Barrett’s oesophagus but of the symptomatic and investigated subgroup. The third type of investigation has concentrated on the follow up of patients with Barrett’s oesophagus with epithelial cellular dysplasia who subsequently developed carcinoma. The subject of cellular dysplasia, particularly in a diseased oesophagus, is a controversial one with respect to both interpretation and implication. The presence of high-grade columnar epithelial dysplasia demon-
strated at biopsy should be regarded as a case of carcinoma in situ or even of invasive carcinoma. This is supported by the fact that, first, the oesophagectomy specimen in some of these cases shows a definite infiltrating cancer, and, secondly, in some reported cases, the interval between dysplasia and the development of cancer has been of the order of weeks rather than months [24]. One may therefore justifiably question the accuracy of the initial diagnosis of “dysplasia”. What, then, can we conclude? Forty years on from Barrett’s original definition, controversy reigns, and, in spite of the evolution of investigatory techniques, many features associated with the condition remain enigmatic. Experience and study of the literature draw one to conclude that: 1. Barrett’s oesophagus is a columnar epithelial-lined oesophagus the diagnosis of which requires inspection of the lower oesophageal wall and the surrounding structures to confirm their normality as suggested by Barrett. 2. Columnar epithelial-lined oesophagus (CELO) is a condition in which the lower oesophagus is found at endoscopy and biopsy to have columnar epithelial mucosa, the diagnosis of which requires confirmation (possibly by parallel manometric studies) that the biopsy has been recovered from the oesophagus. 3. Complications of Barrett’s oesophagus, particularly those related to adenocarcinoma, have been generally overrated. Although patients with Barrett’s oesophagus or CELO appear to be at higher risk of cancer development than the general population, the risk is not such as to consider these lesions as precancerous.
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Mr. K. Moghissi, FRCS Consultant Cardiothoracic Surgeon Humberside Cardiothoracic Surgical Centre Castle Hill Hospital Cottingham Hull N. Humberside HU16 5JQ United Kingdom
