Norman Barrett (1903-1979): Unorthodox pioneer of thoracic and oesophageal surgery.

It is an interesting quirk of medical history that the legacy of Norman Barrett most ostensibly lies in the name of a disease the he was quite emphatically wrong about, at least when he first described it. Indeed, there are those who argue to remove the eponym in favour of the title 'Columnar Lined Epithelium', in part because of what little Barrett actually had to do with the correct initial characterisation of this disease. Yet the sum of Norman Barrett's contributions to modern medicine is much more than a mistaken characterisation of a pathological process. Barrett was truly a pioneer of chest surgery in the UK - a speciality in its embryonic stages when he first qualified. He was also renowned as a teacher and academic of the highest calibre. In tracing the story of his life we can see how his natural attributes, life experiences and keen appreciation of the arts (especially history) facilitated personal success and such sharp insight into the vagaries of modern academic medicine.

Barrett esophagus: history, definition and etiopathogeny.

The injury of the esophageal epithelium may be determined by the reflux of the gastric acid in the esophagus. Barrett's esophagus (BE) is characterized by the replacement of the normal squamous epithelium with the columnar epithelium, when the healing of the lesion occurs. According to some studies, the incidence of the esophageal adenocarcinoma in patients with BE is of about 0,5% per year. The term Barrett's esophagus is subjected to interpretation nowadays, so it lacks the clarity needed for the clinical and scientific communication on the subject of columnar metaplasia of the esophageal mucosa. The major pathogenetic factor in the development of BE is represented by the reflux disease. The cellular origin of BE is controversial and it represents an issue that needs to be resolved because it will have implications in the putative molecular mechanisms underlying the metaplastic process. The epigenetic or genetic changes, which alter protein expression, function, and/ or activity, in post-mitotic cells to drive transdifferentiation or in stem/ progenitor cells such that they are reprogrammed to differentiate into columnar rather than squamous cells, are driven by the inflammatory environment created by chronic reflux. In order to be able to develop better therapeutic strategies for the patients with this disease, an increasing interest in understanding the pathogenesis of BE at the cellular and molecular level presents these days.

Norman Barrett (1903-79): unorthodox pioneer of thoracic and oesophageal surgery.

It is an interesting quirk of medical history that the legacy of Norman Barrett most ostensibly lies in the name of a disease the he was quite emphatically wrong about, at least when he first described it. Indeed, there are those who argue to remove the eponym in favour of the title 'Columnar Lined Epithelium', in part because of what little Barrett actually had to do with the correct initial characterization of this disease. Yet the sum of Norman Barrett's contributions to modern medicine is much more than a mistaken characterization of a pathological process. Barrett was truly a pioneer of chest surgery in the UK - a specialty in its embryonic stages when he first qualified. He was also renowned as a teacher and academic of the highest calibre. In tracing the story of his life we can see how his natural attributes, life experiences and keen appreciation of the arts (especially history) facilitated personal success and such sharp insight into the vagaries of modern academic medicine.

Gastroesophageal reflux disease in Asia: A historical perspective and present challenges.

Gastroesophageal reflux disease (GERD), previously uncommon in Asia, has now become an important disease in the region. Although much variability exists between studies, most endoscopy-based studies show a prevalence of erosive esophagitis of more than 10%. Symptom-based studies also show a prevalence of 6-10%. Two longitudinal follow-up studies on GERD symptoms have shown an increase with time, and several endoscopy-based time trend studies have also shown a significant increase in erosive reflux esophagitis. Studies on Barrett's esophagus have been confounded by the description of short (SSBE) and long segment (LSBE) Barrett's esophagus. Great variation in prevalence rates has been reported. SSBE vary from 0.1% to more than 20% while LSBE vary from 1-2%. Of the putative causative factors, obesity has been the most important. Many studies have linked GERD-esophagitis as well as occurrence of reflux symptoms with an increase in body mass index (BMI), obesity, especially visceral or central obesity, and metabolic syndrome. A decline in Helicobacter pylori infection with growing affluence in Asia has been broadly thought to result in healthier stomachs and a higher gastric acid output resulting in reflux disease. However, variable results have been obtained from association and H. pylori eradication studies.

Barrett's esophagus: A historical perspective, an update on core practicalities and predictions on future evolutions of management.

Interpretation of exploding knowledge about Barrett's esophagus is impaired by use of several conflicting definitions. Because any histological type of esophageal columnar metaplasia carries risk for esophageal adenocarcinoma, the diagnosis of Barrett's esophagus should no longer require demonstration of intestinal-type metaplasia. Endoscopic recognition and grading of Barrett's esophagus remains a significant source of ambiguity. Reflux disease is a key factor for development of Barrett's esophagus, but other factors must underlie its development, since it occurs in only a minority of reflux disease patients. Neither antireflux surgery nor proton pump inhibitor (PPI) therapy has major impacts on cancer risk. Within a year, a major trial should indicate whether low-dose aspirin usefully reduces cancer risk. The best referral centers have transformed the accuracy of screening and surveillance for early curable esophageal adenocarcinoma by use of enhanced and novel endoscopic imaging, visually-guided, rather than blind biopsies and by partnership with expert pathologists. General endoscopists now need to upgrade their skills and equipment so that they can rely mainly on visual targeting of biopsies on mucosal areas of concern in their surveillance practice. General pathologists need to greatly improve their interpretation of biopsies. Endoscopic therapy now achieves very high rates of cure of high-grade dysplasia and esophageal adenocarcinoma with minimal morbidity and risk. Such results will only be achieved by skilled interventional endoscopists. Esophagectomy should now be mainly restricted to patients whose cancer has extended into and beyond the submucosa. Weighing risks and benefits in the management of Barrett's esophagus is difficult, as is the process of adequately informing patients about their specific cancer risk.

History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus.

This report is an adjunct to the American Gastroenterological Association Institute's medical position statement and technical review on the management of Barrett's esophagus, which will be published in the near future. Those documents will consider a number of broad questions on the diagnosis, clinical features, and management of patients with Barrett's esophagus, and the reader is referred to the technical review for an in-depth discussion of those topics. In this report, we review historical, molecular, and endoscopic therapeutic aspects of Barrett's esophagus that are of interest to clinicians and researchers.

Columnar-lined esophagus: time to drop the eponym of "Barrett": Historical review.

There can be few medical conditions that have been surrounded by as much confusion about their definition or terminology as columnar-lined esophagus (CLE); approximately 30 different terms and eponyms have been used to describe this condition. The history of this condition can be divided into five stages: (i) descriptive stage, 1906-1950; (ii) "argument" stage, 1950-1963; (iii) "significant" stage, 1963-1973; (iv) surveillance stage, 1973-1990; and (v) refined research stage, 1990-present. The use of the eponym "Barrett's" to describe CLE is not justified from a historical point of view. Lining of the lower esophagus by columnar epithelium was termed "Barrett's esophagus" after the presentation by Barrett in 1957. Although this finding has been attributed to Barrett, the work of others, including Tileston, Lortat-Jacob, and Allison and Johnstone, preceded Barrett's description. The historical aspects of CLE were reviewed to show how little Norman Barrett had contributed to the core concept of this condition in comparison to the contributions of other investigators, particularly the contribution of Philip Allison. Based on many discussed historical facts, we are not in favor of retaining the term "Barrett's esophagus" and we propose that CLE be henceforth referred to as "columnar-lined esophagus".

Review article: from 1906 to 2006--a century of major evolution of understanding of gastro-oesophageal reflux disease.

BACKGROUND: Our understanding of gastro-oesophageal reflux disease has undergone significant changes over the last century. AIM: To trace the rise in understanding of gastro-oesophageal reflux disease and highlight remaining areas of uncertainty. METHODS: Literature review. RESULTS: In 1906, Tileston published his observations on 'peptic ulcer of the oesophagus'. Winkelstein, in 1934, first correlated symptoms of heartburn with acid regurgitation and reflux oesophagitis. In 1946, Allison described hiatus hernia as a causal factor in the development of gastro-oesophageal reflux disease. In 1958, Bernstein and Baker showed a direct relationship between oesophageal acidification and heartburn in patients with gastro-oesophageal reflux disease, irrespective of endoscopic findings, leading to the recognition of non-erosive gastro-oesophageal reflux disease. In the 1980s, continuous recordings of the lower oesophageal sphincter showed that episodes of reflux were related to transient relaxations of lower oesophageal sphincter tone. There is now increasing recognition that gastro-oesophageal reflux disease arises from the interaction of several anatomical and physiological factors. A turning point in the medical treatment of gastro-oesophageal reflux disease came with the introduction of the first proton pump inhibitor, omeprazole, in 1989. CONCLUSIONS: Future efforts need to identify the multifactorial interactions of gastro-oesophageal junction anatomy and physiology in patients with gastro-oesophageal reflux disease. Increased understanding of the disease will guide development of new therapies.

[Surgical management of Barrett's esophagus]. / Barrett-oesophagus sebészi kezelése.

Barrett's esophagus is a complication of gastroesophageal reflux disease in which metaplastic, intestinal-type epithelium containing mucin-producing goblet cells with characteristic staining on histology replaces the squamous epithelium normally found in the esophagus. This condition is named after the British thoracic surgeon, N. R. Barrett. Treatment in various stages of the disease continues to provoke controversy. Different surgical procedures are suggested in dysplasia free patients, in low grade dysplasia, high grade dysplasia and adenocarcinoma. Instead of the widely accepted surgical procedure with high grade dysplasia and early carcinoma we suggest an intervention which is oncologically radical, functionally adequate and less inconvenient and stressing for the patients: left side thoraco-laparotomy, distal esophageal and proximal (lesser curvature) gastric resection with adequate lymphadenectomy and reconstruction with esophago-jejuno-gastric interposition.

GERD 2004: issues from the past and a consensus for the future.

In the early 1900's, gastroesophageal reflux disease (GERD) was an almost unknown entity with less than 200 cases reported worldwide. Currently the disease is regarded as almost endemic with as much as 25% of the population in some countries exhibiting signs or symptoms of reflux. Early therapies directed at chemical neutralization (milk drip, antacids) were of modest effect and required constant administration for efficacy. The introduction of histamine 2 receptor antagonists in the 1970's dramatically improved the management of GERD, but was limited by problems of tachyphylaxis and adverse events. The advent of the PPI class of drugs revolutionized medical care of GERD, given their efficacy and safety profile. As a consequence, the surgical approach with its pronounced dependence on individual operator skill and its high morbidity and even mortality has fallen into disregard. Thus, modest surgical outcome results as compared to the efficacy of PPIs has led to the widespread recognition that pharmacological therapy for GERD represents the platinum standard of care and the current consensus is that the PPI class of drugs provide the safest and most effective form of therapy for GERD. Furthermore, it is apparent based on acid suppression, symptom relief and healing rates, that all PPIs are on a milligram for milligram basis similarly efficacious for the management of GERD. While a consensus exists in regard to the current management of GERD with PPIs there is little agreement as to the management of the associated mucosal metaplastic process. At this time there is inadequate understanding of the biological basis of the mucosal transformation and minimal information about the mechanistic regulation of this event and its perpetuation. A future consensus thus requires the identification of the appropriate tools to detect Barrett's early, identify the specific molecular markers associated with neoplastic transformation and establish a definitive therapeutic algorithm.

The history of Barrett esophagus.

The term Barrett esophagus has become well established in the medical literature to indicate columnar metaplasia of the distal esophagus associated with chronic gastroesophageal reflux disease. However, the historical events that led to the use of this term have become obscured. Here, the historical aspects of Barrett esophagus are reviewed, providing insight not only to this condition but also to the evolution of medical thought in general.

The histopathology and biologic prognostic factors of Barrett's esophagus: a review.

In Barrett's esophagus, stratified squamous mucosa of the lower third of the esophagus is replaced by columnar mucosa, as a complication of chronic gastroesophageal reflux. The presence of Barrett's esophagus appears to be a major factor in the progression to adenocarcinoma of the lower third of the esophagus. Therefore it is crucial to identify the subset of patients at risk for the development of adenocarcinoma. Dysplasia is an important histologic feature to evaluate because it identifies those patients who require follow-up. The diagnosis of biopsies with lesser degrees of abnormalities, however, makes microscopic evaluation less helpful in identifying patients who need more frequent endoscopic biopsy surveillance. DNA ploidy and the use of monoclonal antibodies, such as suppressor gene product p53, oncogene cerbB-2, and Ki-67, have added dramatically to our understanding of the biology of Barrett's metaplasia and have given us objective indicators to predict the presence of an increased risk of developing cancer.

The columnar-lined esophagus. History, terminology, and clinical issues.

Recently, there has been intense controversy regarding diagnostic criteria for Barrett's esophagus. Some authorities have defined the condition according to an arbitrary extent of esophageal columnar lining, whereas others have felt that the presence of specialized intestinal metaplasia anywhere in the esophagus establishes the diagnosis. This article discusses the problems that arise when either of these diagnostic approaches are used and proposes an alternative classification system for the columnar-lined esophagus.

[Esophageal cancer on the increase. Is Barrett esophagus the cause?]. / Matstrupscancern ökar. Barretts esofagus orsaken?

At the Dept of Surgery, Lund University, during the 10-year period 1985-95, 54 patients with adenocarcinoma of the gastro-oesophageal junction (17 with Barrett's epithelium, and 37 without) underwent oesophageal resection: oesophagectomy and gastric pull-up (n = 10), extended total gastrectomy (n = 37), or oesophageal resection and interposition of colon (n = 2) or jejunum (n = 5). Hospital mortality was 3.7% (2/54), and the mean duration of hospitalisation 13 days (range, 9-42). Long-term survival was significantly better in the Barrett's oesophagus subgroup than in the carcinoma of the cardia (non-Barrett's oesophagus) subgroup, the respective rates being 50% vs. 10% (p = 0.0052; Log rank test). The better survival in the Barrett's oesophagus subgroup is probably to be explained by the earlier stage of disease among these patients, in turn due to a history of gastro-oesophageal reflux, whereas the predominant symptom in the cardia carcinoma subgroup was dysphagia.