The evolution of more sophisticated imaging techniques has initiated a renewed interest in stereotactic devices, methods, and applications. The Brown-Roberts-Wells instrument was available to us early in its prototype stage, and this report reviews the first 500 cases using the system at the University of Southern California Medical Center Hospitals. Procedures were undertaken after recognition of apparent structural alterations on imaging studies, with objectives being both diagnostic and therapeutic. Target locations were predominantly within the cerebral centrum-basal ganglia (284 cases) and diencephalic-mesencephalic regions (129 cases). Operative objectives included: histological and microbiological assay, cyst and abscess aspiration, installation of temporary or permanent drainage conduits, point source and colloid base brachytherapy, cerebroscopy and ventriculoscopy with biopsy, aspiration, and excision, and intraoperative vascular localization. Using multiple instrumentation at the target point (741 point placements), we realized procedural objectives in 95.6% of the cases. The mortality was 0.2% and the morbidity was 1%: hematoma, 2 cases; infection, 1 case; increased deficit, 1 case; intraprocedural seizure, 1 case. A specific diagnosis was not obtained in 4.4% (necrosis, 10 cases; inflammatory response, 9 cases; granuloma, 1 case; gliosis, 1 case; diagnostic error, 1 case). Individual guidelines for case selection, technique, institutional requirements, and applications of the method are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Current diagnostic criteria for reflux disease and Barrett's esophagus are based on the belief that the gastroesophageal junction normally contains 2 cm of cardiac mucosa composed of mucous glands devoid of parietal cells. This autopsy study disproves this belief. Even when the entire circumference of the gastroesophageal junction is examined, pure cardiac mucosa was completely absent in 56% of patients. All patients had oxyntocardiac mucosa, in which glands contained a mixture of mucous and parietal cells. Cardiac and oxyntocardiac mucosae were present only in part of the circumference of the junction in 50% of patients. The measured maximum length of cardiac plus oxyntocardiac mucosa was less than 0.5 cm in 76% of patients. There was a tendency for the presence and extent of cardiac mucosa to increase with age. Cardiac mucosa at the junction is therefore frequently absent, has considerable individual variation, is very small in extent when present, is commonly absent from some part of the circumference of the junction, and increases in prevalence and length with age. These characteristics of cardiac mucosa make it highly unlikely that it is a normal structure. We develop the hypothesis that cardiac mucosa represents an early histologic manifestation of gastroesophageal reflux.

An abnormal columnar-lined esophagus (CLE) is characterized by the presence of cardiac mucosa (CM) oxynto-cardiac mucosa (OCM), and intestinal metaplastic epithelium (IM) between gastric oxyntic mucosa and esophageal squamous epithelium. Thirty-two patients with CLE measuring 2-16 cm long had 5-37 biopsies per patient that showed CM, OCM, or IM for a total of 424 biopsies. Detailed mapping of the distribution of epithelial types within the CLE showed a distinct zonation of epithelial types; CM was present throughout the CLE, whereas OCM and IM tended to occur in the distal and proximal part of the CLE, respectively. All 32 patients (64 of 68 biopsies) showed IM at the most proximal level, compared with 22 of 32 patients (40 of 102 biopsies) in the most distal level biopsies. The density of goblet cells was highest in the most proximal level. The differences in prevalence and density of goblet cells between most proximal and most distal level biopsies were highly significant. These data suggest that for a given number of biopsies within the CLE, the likelihood of finding IM is greatest when the biopsies are concentrated in the most proximal area of the CLE. We suggest that glandular transformation of squamous epithelium results in CM. which evolves into OCM and IM by development of specialized parietal cells and goblet cells, respectively. The severity and nature of reflux cause these epithelial transformations in a constant and predictable manner. Recognition of these changes permits the development of morphologic definitions of reflux disease and the characterization of the sequence of epithelial changes that represent the reflux-adenocarcinoma sequence.

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All histologic features presently ascribed to IEE can occur in other esophageal diseases, notably GERD. As such, the finding of intraepithelial eosinophilia in any number is not specific for IEE. When a patient with GERD has an esophageal biopsy with an eosinophil count >20/hpf, it does not mean that the patient has IEE.

Zusammenfasssung. Grundlagen: Definition und Bedeutung des Zylinderepithel-Ösophagus hat sich seit der Erstbeschreibung 1953 oft geändert. Es wurden verschiedene Definitionen des Ösophagus-Magen-Über-gangs verwendet, wobei nicht ganz klar war, wo eigentlich der Ösophagus endet und der Magen beginnt. Die gegenwärtig akzeptierte Definition des Ösophagus-Magen-Übergangs ist das Ende des tubulären Ösophagus und der proximale Beginn der Magenfalten. Kardia Mukosa wird daher teilweise als metaplastisches Epithel und teilweise als normales Epithel des proximalen Magens angesehen. Methodik: Diese Übersicht analysiert die relevante Literatur zur Definition des Übergangs Ösophagus -Magen, Zylinderepithel -Ösophagus, mit Berücksichti-gung der Histologie. Ziel der Analyse ist es, die echte Ösophagus-Magen-Grenze zu definieren. Ergebnisse: Die echte Ösophagus-Magen-Grenze findet sich häufig distal des Endes des tubulären Ösopha-gus und des Beginns der gerundeten Schleimhautfalten. Die Definition der wirklichen Mukosa-Grenze Ösophagus -Magen wird erst durch die submukösen Drüsen möglich. Über den submukösen Drüsen findet sich sogenannte Kardia-Mukosa mit oder ohne intestinaler Metaplasie. Unterhalb oxyntischer (= Säure bildender) Mukosa des Magens finden sich nie submuköse Drüsen. Diese Daten lassen vermuten, dass die echte Ösophagus-MagenGrenze histologisch nur durch die proximale Grenze der oxyntischen Mukosa definiert werden kann. Kardia-Mukosa mit und ohne intestinaler Metaplasie ist ZylinderepithelÖsophagus. Der distale Anteil des durch Reflux geschä-digten Zylinderepithel-Ösophagus dilatiert und wirft dadurch Falten, die mit Magenfalten verwechselt werden. Schlussfolgerungen: Die korrekte Definition des Über-gangs Ösophagus-Magen erlaubt genaue Definitionen für die Refluxerkrankung (Reflux-Karditis), die Schwere der Refluxschädigung zu erheben (Länge des ZylinderepithelÖsophagus) und das Risiko abzuschätzen, ein Refluxinduziertes Adenokarzinom zu entwickeln. Das geschieht mit Hilfe histologischer Kriterien, welche den klinischen Kriterien der Refluxkrankheit überlegen sind.Conclusions: Correct definition of the true gastroesophageal junction permits the development of precise definitions for reflux disease (reflux carditis), assess the severity of reflux damage (length of columnar lined esophagus) and assess progression within the reflux-adenocarcinoma sequence. This is done with histologic criteria that are superior to the present clinical criteria for the diagnosis of gastroesophageal reflux disease.

A series of 71 patients with multiple measured biopsies of the gastroesophageal junctional region permitting assessment of the presence and length of different glandular epithelial types is presented. All but nine of 53 patients in whom a 24-hour pH study was performed had abnormal reflux, suggesting that endoscopic recognition of an abnormal columnar mucosa at the gastroesophageal junction sufficient to precipitate multiple-level biopsies indicates a high probability of abnormal reflux. All patients had cardiac mucosa (CM) or oxyntocardiac mucosa (OCM). CM was present in 68 of 71 patients. The prevalence of intestinal metaplasia increased with increasing CM+OCM length, and was present in all 22 patients with a CM+OCM length >2 cm and in 20 of 49 patients with a CM+OCM length <2 cm. Patients with a CM+OCM length >2 cm had a markedly higher acid exposure than patients with a CM+OCM length <2 cm. The findings suggest that the presence of CM and OCM in the junctional region are predictive of abnormal acid exposure, and that increasing OCM+CM length correlates strongly with the amount of acid exposure. The histologic finding of CM and OCM represents a sensitive histologic criterion for gastroesophageal reflux rather than normal epithelia. These diagnostic criteria represent the first useful histologic definitions for assessing the presence and severity of reflux.

This study consists of 959 consecutive patients in whom endoscopic biopsies were taken according to a protocol that permitted mapping and measurement of epithelial types in the gastroesophageal region. The epithelial types were classified as normal (oxyntic and squamous) and questionably abnormal (oxyntocardiac, cardiac, intestinal) by strict histologic criteria. Patients were classified into four groups based on the length of histologically defined abnormal glandular epithelium in the measured biopsies. A total of 811 (84.6%) patients had 0 to 0.9 cm of questionably abnormal columnar epithelium between normal oxyntic mucosa and squamous epithelium. Of these, 161 (19.9%) patients had no abnormal epithelium, 158 (19.4%) patients had oxyntocardiac mucosa, 372 (45.9%) patients had cardiac mucosa, and 120 (14.8%) patients had intestinal metaplasia. A total of 148 (15.4%) patients had >or=1 cm of abnormal columnar epithelium. All but one patient in this group had cardiac or intestinal epithelia. The prevalence of intestinal epithelium increased progressively with increasing length of abnormal columnar epithelium, being present in 70.4% in the 1- to 2-cm group, 89.5% in the 3- to 4-cm group, and 100% with in the >or=5 cm group. We propose a histologic grading system of biopsies based on these findings.