Barrett Esophagus 2008 년도 2 학기 의학과 석. 박사 공통과목 위장관의 외과병리

Introduction Is a premalignant condition in which the lower segment of the esophagus becomes lined with a metaplastic columnar epithelium instead of the native squamous epithelium, as a consequence of gastroesophageal reflux disease. The presence of specialized intestinal metaplasia anywhere in the esophagus represents a true metaplasia of the normal squamous epithelium and is currently regarded as the sole criteria for the diagnosis of BE. The clinical importance is related to it being the precursor of esophageal adenocarcinoma, a tumor whose incidence is rising more rapidly than any other in Western countries.

English thoracic surgeon ( ) Chronic peptic ulcer of the oesophagus and oesophagitis I submit that most of these cases are in truth examples of congenital short esophagus, in which there is neither general inflammation nor stricture formation, but in which a part of the stomach extends upwards into the mediastinum-or even to the neck-and that in this stomach a typical chronic gastric ulcer can form. Br J Surg 1950

Normal Anatomy and Histology of the Gastroesophageal Junction (GEJ) GEJ (Muscular GEJ) –The site at which the most distal portion of the esophagus (the distalmost segment of LES) meets the proximal stomach –Endoscopically, identifying the proximal margin of the gastric folds Squamocolumnar junction (SCJ) or Z-line (Mucosal GEJ) –The site at which the squamous mucosa of the esophagus meets columnar-lined mucosa –May be at the same level as the muscular GEJ or may lie 1- 2cm above the muscular GEJ in normal individuals

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Pathogenesis Extreme end of the pathophysiological spectrum of gastroesophageal reflux disease, with a high prevalence of associated hiatal hernia, lower esophageal sphincter failure, peristaltic failure and high levels of acid exposure, compounded by impaired mucosal sensitivity

The Endoscopic Diagnosis of BE Endoscopically, it may be difficult to definitively identify the presence of BE –The presence of hiatal hernia makes identification of the muscular GEJ difficult –There are no anatomic landmarks that clearly define the region of the LES A biopsy from the vicinity of the GEJ with intestinal metaplasia could either represent BE or intestinal metaplasia of the most proximal portion of the stomach

Biopsy Protocol One bx from proximal stomach, 2cm below LES, to evaluate gastric cardia and make sure distal part of BE is sampled One bx at the LES 2-4 bx every 2cm of the length of the Barrett’s segment, one from each wall or each quadrant One bx from squamous epithelium proximal to BE Bx of any masses, ulcers, strictures, or other lesions

Definition of BE Columnar-lined esophagus with intestinal metaplasia (Paris Workshop) Columnar-lined esophagus with or without intestinal metaplasia (Japanese Society for Esophageal Disease) Metaplastic, intestinalised columnar epithelial cells in the mucosa of the distal esophagus (German Society) Positive diagnosis of BE (BSG Guideline) –Segment of columnar metaplasia of any length must be visible endoscopically above the GEJ and confirmed or corroborated histologically

Definition (Including the American College of Gastroenterologists) Best definition of BE includes both clinical and pathologic conditions –Abnormal glandular mucosa of any length that is recognized in the esophagus at endoscopy –Intestinal metaplasia/goblet cells seen at biopsy Endoscopically, the squamocolumnar junction is displaced proximally, and salmon-pink to red, velvety tongues of glandular mucosa extend upward from the LES region

The Prague C and M criteria Measurement of the extent of BE is clinically relevant, since this influences the risk of developing adenocarcinoma. The grading of patients into those with variably defined short and long segment of BE is an unsatisfactorily crude approach. The Prague C and M criteria –Criteria to assess the circumferential and the maximal extent of esophageal columnar tissue –C3N5: circumferential BE extending to 3cm above the GEJ with a tongue extending 5cm above the GEJ

병리학적으로 바렛식도 진단시 선행되어야 할 요구 사항 내시경검사에서 바렛식도를 의심하고 병리학적 진단을 의뢰할 경우 columnar-lined esophagus 에서 적어도 2 개 이상 생검을 시행할 필요가 있다. 의뢰지에는 columnar- lined esophagus 의 길이를 포함한 내시경 소견, 특히 생 검위치를 정확히 표시하여 병리진단을 의뢰한다.

병리검사 결과 보고 양식 Columnar epithelium without intestinal metaplasia ( 가능한 경우 glands 의 종류에 따라 아래의 세가지로 세분하여 진단한다 ) –Columnar epithelium of cardiac type without intestinal metaplasia –Columnar epithelium of oxyntocardiac type without intestinal metaplasia –Columnar epithelium of oxyntic (fundic) type without intestinal metaplasia Columnar epithelium with intestinal metaplasia, consistent with Barrett’s esophagus ( 이때 definite goblet cell 이 보이는 경우는 1 개 만 보여도 진단한다. Alcian blue 등 특수염색은 바렛식도의 병리 학적 진단에 필수적이지 않다 )

AGA Chicago Workshop 2003

The Normal Gastric Cardia A narrow strip of mucosa that separates the most distal portion of the esophageal squamous mucosa from the acid-producing fundic mucosa Not a normal structure but rather that cardiac-type mucosa is metaplastic Pediatric autopsy –Cardiac mucosa was present, always on the gastric side of the GEJ, although it was quite small, ranging from only 1-4 mm in length

Gastroesophageal Junction Pathology The gastric cardia is the area of mucosa located distal to the GEJ, and proximal to the portion of stomach composed entirely of oxyntic mucosa. It varies in length between individuals. Cardia is congenital in origin, but that columnar metaplasia of squamous mucosa results in an apparent extension of the cardia into the distal esophagus. Etiology of inflammation and metaplasia in the GEJ region is most often due to GERD or H. pylori infection. However, the pathogenesis and risk of neoplasia in these two conditions are different. Multilayered epithelium is a precursor to BE and represents a histologic marker of GERD and columnar metaplasia of the distal esophagus.

Over Diagnosis of Barrett Esophagus Itself Definitional problems –Endoscopic and histologic components both required –Three anatomic landmarks Gastroesophageal junction Proximally displaced squamocolumnar junction or Z-line Intervening pink mucosa in tubular esophagus of possible Barrett epithelium –Not gastric cardiac or fundic type mucosa –Not a few metaplastic glands in the LES region Pseudo-goblet cells of gastric type mucosa mimicking BE Misinterpretation of Alcian blue staining at pH 2.5 Not confused with inlet patches, or ectopic gastric mucosa, in the upper cervical esophagus Not confused with pancreatic acinar metaplasia

Histopathologic Diagnosis of Dysplasia Dysplasia: defined as the presence of neoplastic epithelium that is confined within the basement membrane of the gland within which it arises Classified as low-grade dysplasia and high- grade dysplasia

Over Diagnosis of High-Grade Dysplasia in Barrett Esophagus Not reactive gastric cardiac-type mucosa Not atypia limited to basal glands of Barrett intestinal metaplasia Grading accuracy is both experience and volume dependent Dysplasia forms a morphologic spectrum for which precise boundaries cannot be defined Loss of nuclear polarity is under recognized as the most objective criterion to differentiate low and high-grade dysplasia

Neoplastic Risk Assessment in BE

Key Clinical Management Points Controlling symptoms of GERD Endoscopic therapies –Achieve a cure for early stage neoplasm avoiding the considerable mortality and morbidity of surgery –Photodynamic therapy –Laser therapy –Endoscopic mucosal resection Esophagectomy