Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract

Parakrama Chandrasoma M.D., M.R.C.P., Tom DeMeester M.D., Parakrama Chandrasoma, Tom DeMeester

Marnix Jansen, Nicholas A. Wright

Diagnosis of gastroesophageal reflux disease (GORD) is delayed by the lack of uniform histopathologic criteria for diagnosis. The only practical value of pathology is the assessment of columnar lined esophagus (CLO). As a result, GORD is treated with acid suppressive drug therapy until there is a failure to control symptoms and/or advanced adenocarcinoma develops. The reasons why there is a failure of pathologic diagnosis are two false dogmas that result in two widely believed fundamental errors. These are the belief that cardiac epithelium normally lines the proximal stomach (1) and that the gastroesophageal junction (GOJ) is defined by the proximal limit of rugal folds (2). When these false dogmas are eradicated by existing powerful evidence, the pathology of GERD falls into the following stages, all defined by histology: (a) The normal state where the esophageal squamous epithelium transitions at the GOJ to gastric oxyntic epithelium with no intervening cardiac epithelium; (b) cardiac metaplasia of the squamous epithelium due to exposure to gastric juice results in cephalad movement of the squamo-columnar junction (SCJ). This creates the squamo-oxyntic gap and the dilated distal esophagus, which is distal to the endoscopic GOJ. The length of the squamo-oxyntic gap in the dilated distal esophagus is concordant with the shortening of the abdominal segment of the lower esophageal sphincter (LOS); (c) in the early stages, the gap is <5 mm and the LOS retains its competence. Reflux is uncommon and patients are asymptomatic; (d) the squamo-oxyntic gap increases in length, concordant with the amount of shortening of the LOS, which becomes increasingly incompetent. At a gap length of 5-15 mm, reflux is sufficient to cause symptoms, but in most patients, symptoms are controllable and the patients are normal at endoscopy. The gap is entirely within the dilated distal esophagus, which is mistaken by present criteria for proximal stomach. (e) The last stage of GORD is when the squamo-oxyntic gap is >15 mm. In these patients, reflux is severe with increasingly uncontrollable symptoms and columnar lined esophagus, both irreversible states.Understanding this pathophysiology of GORD by these new histologic criteria will allow diagnosis at the earliest and eminently reversible stages of the disease. This can open the door to new methods of treatment that will have the potential to prevent progression to the irreversible phase of GORD, including columnar lined esophagus. If successful, this will effectively prevent progression to adenocarcinoma.