Histologic Study of the Esophagogastric Junction of Organ Donors Reveals Novel Glandular Structures in Normal Esophageal and Gastric Mucosae.

INTRODUCTION: Whether cardiac mucosa at the esophagogastric junction is normal or metaplastic is controversial. Studies attempting to resolve this issue have been limited by the use of superficial pinch biopsies, abnormal esophagi resected typically because of cancer, or autopsy specimens in which tissue autolysis in the stomach obscures histologic findings. METHODS: We performed histologic and immunohistochemical studies of the freshly fixed esophagus and stomach resected from 7 heart-beating, deceased organ donors with no history of esophageal or gastric disease and with minimal or no histologic evidence of esophagitis and gastritis. RESULTS: All subjects had cardiac mucosa, consisting of a mixture of mucous and oxyntic glands with surface foveolar epithelium, at the esophagogastric junction. All also had unique structures we termed compact mucous glands (CMG), which were histologically and immunohistochemically identical to the mucous glands of cardiac mucosa, under esophageal squamous epithelium and, hitherto undescribed, in uninflamed oxyntic mucosa throughout the gastric fundus. DISCUSSION: These findings support cardiac mucosa as a normal anatomic structure and do not support the hypothesis that cardiac mucosa is always metaplastic. However, they do support our novel hypothesis that in the setting of reflux esophagitis, reflux-induced damage to squamous epithelium exposes underlying CMG (which are likely more resistant to acid-peptic damage than squamous epithelium), and proliferation of these CMG as part of a wound-healing process to repair the acid-peptic damage could result in their expansion to the mucosal surface to be recognized as cardiac mucosa of a columnar-lined esophagus.

Earlobe-like peritoneal appendage near the angle of His: a useful landmark for demarcating the lateral margin of the gastric cardia.

The gastric cardia-the small area around the cardiac orifice including the abdominal esophagus-is an important target area for abdominal and thoracic surgeries, especially for laparoscopic procedures. In this study of 28 cadavers, a peritoneal earlobe-like appendage near the angle of His was identified as a useful indicator of the lateral margin of the abdominal esophagus, which is otherwise obscure because the peritoneum continues to the diaphragm without definite demarcation of this margin. This structure, which appears equivalent to the epiploic appendages, was commonly found to be present (in 22/28, 78.6 % of the 28 cadavers) and was 4-21 mm × 6-40 mm × 1-4 mm in size, triangular, round, or leaf-like in shape, contained fat, and was on an imaginary line along which the lesser omentum adheres to the lesser curvature and continues to the diaphragm (18/22, 81.8 %). This indicator is associated with the lesser omentum and is part of the gastrophrenic ligament, and could serve as a useful indicator of the margin of the gastric cardia, thus aiding surgeons performing laparoscopic surgery in this region.

Obesity and related risk factors in gastric cardia adenocarcinoma.

Over recent decades, the incidence of cancers of the gastroesophageal junction, including gastric cardia tumors, has increased markedly. This is a trend that has been well documented, especially in studies from the USA and northern Europe that have also demonstrated a concomitant rise in the ratio of cardia to distal gastric cancers. The rise in the prevalence of gastric cardia adenocarcinoma has been paralleled by the worldwide obesity epidemic, with almost all epidemiological studies reporting increased body mass index and obesity increase the risk of cardia cancer development. However, the strength of this association is less marked than the link between obesity and esophageal adenocarcinoma, and the mechanisms remain poorly understood. Other possible confounders of the relationship between obesity and cardia cancer include the decline in Helicobacter pylori infection and the widespread use of proton pump inhibitors, although these have rarely been controlled for in case-control and cohort studies investigating associations between obesity and cardia cancer. We review these epidemiological trends and discuss proposed mechanisms for the association, drawing attention to controversies over the difficulty of defining cardia cancer. The relative paucity of high-quality epidemiological studies from other regions of the world should prompt further investigation of this issue, especially in populations undergoing rapid socioeconomic change.

Ultrasonographic characteristics of the abdominal esophagus and cardia in dogs.

Differential diagnoses for regurgitation and vomiting in dogs include diseases of the gastroesophageal junction. The purpose of this cross-sectional study was to describe ultrasonographic characteristics of the abdominal esophagus and gastric cardia in normal dogs and dogs with clinical disease involving this region. A total of 126 dogs with no clinical signs of gastrointestinal disease and six dogs with clinical diseases involving the gastroesophageal junction were included. For seven euthanized dogs, ultrasonographic features were also compared with gross pathology and histopathology. Cardial and abdominal esophageal wall thicknesses were measured ultrasonographically for all normal dogs and effects of weight, sex, age, and stomach filling were tested. Five layers could be identified in normal esophageal and cardial walls. The inner esophageal layer was echogenic, corresponding to the cornified mucosa and glandular portion of the submucosa. The cardia was characterized by a thick muscularis, and a transitional zone between echogenic esophageal and hypoechoic gastric mucosal layers. Mean (±SD) cardial wall thicknesses for normal dogs were 7.6 mm (±1.6), 9.7 mm (±1.8), 10.8 mm (±1.6), 13.3 mm (±2.5) for dogs in the <10 kg, 10-19.9 kg, 20-29.9 kg and ≥30 kg weight groups, respectively. Mean (±SD) esophageal wall thicknesses were: 4.1 mm (±0.6), 5.1 mm (±1.3), 5.6 mm (±1), and 6.4 mm (±1.1) for the same weight groups, respectively. Measurements of wall thickness were significantly correlated with dog weight group. Ultrasonography assisted diagnosis in all six clinically affected dogs. Findings supported the use of transabdominal ultrasonography as a diagnostic test for dogs with suspected gastroesophageal disease.

Gastroesophageal junction of Anatolian shepherd dog; a study by topographic anatomy, scanning electron and light microscopy.

The aim of this study was to cast a spotlight on the topography and to point out the clinical importance of the gastroesophageal junction (GEJ) in Anatolian Shepherd dogs. Nine Anatolian Shepherd dogs were used to study the morphology of the GEJ. The esophagus was appeared has a portion within the thoracic cavity while no portion of the esophagus presented within the abdominal cavity that documented the absence of the intra-abdominal portion in all studied dogs. The topographic anatomy, scanning electron and light microscopic examinations revealed that the gastroesophageal junction was located at the level of the phrenico-esophageal ligament (PEL) inside the esophageal hiatus. Our results were distinguished the morphology of the esophageal and gastric cardiac mucosa at the level of the gastroesophageal junction by the scanning electron micrographs. The light microscopical examination was explained the PEL attached to the esophageal side in one dog and to the gastric cardiac side in three dogs.

Ultrasonographic characterization of the feline cardia and pylorus in 34 healthy cats and three abnormal cats.

A prospective study was performed in 34 fasted healthy cats to describe the normal ultrasonographic anatomy of the cardia and pylorus. Measurements were obtained for the caudal esophageal wall thickness (Ew), cardia wall thickness (Cw), pyloric wall thickness (Pw), thickness of the pyloric muscularis (Mp), length of the thicker part of the proximal duodenal submucosa (Dl). Among the 34 cats, 24 were examined using a linear transducer, and 10 with a microconvex transducer. Ew and Cw could be measured in 70% of the cats when a linear transducer was used, in 100% of the cats when a microconvex probe was used, Pw and Mp could be measured in 100% of the cats whatever probe was used. The submucosa of the most proximal part of the duodenum was thicker in half of the cats in longitudinal section. The muscularis layer of the pylorus was triangular in longitudinal section and thicker than the muscularis of the proximal duodenum. The mean for Ew, Cw, Pw, Mp, and DI was 4.9 mm (SD = 1.1), 5 mm (SD = 0.6), 4.4 mm (SD = 0.6), 2.5 mm (SD = 0.5), and 4.7 mm (SD = 2.38), respectively. Three cats with abnormalities of the cardia and pylorus are also described to illustrate clinical implications.

The cardia: esophageal or gastric? Critical reviewing the anatomy and histopathology of the esophagogastric junction.

BACKGROUND: Discrepancy exists regarding the anatomical allocation of the cardia: esophageal or gastric. With this review we aimed to clarify this issue. METHODS: Using PUB MED, Scopus and Google we analyzed the recent literature (1889-2012) regarding the "esophageal" vs. the "gastric" cardia. RESULTS: The synonymous use of the term cardia to describe the anti reflux mechanism within the distal portion of the esophagus and the proximal segment of the stomach nourished the misunderstanding, that the cardia represents a normal anatomical structure interposed between the tubular esophagus and the body of the stomach. Anatomical, histopathological and physiological studies revealed that what has been taken for gastric cardia in fact represents reflux damaged dilated distal esophagus (DDE). Since DDE is covered by columnar lined esophagus (CLE) it cannot be differentiated from the proximal stomach during regular endoscopy. However, the histopathology of multi level biopsies obtained from the endoscopically suspected esophagogastric junction (EGJ) serves to allocate the origin of the columnar lined foregut, esophageal (cardiac, oxyntocardiac mucosa, intestinal metaplasia) vs. gastric (oxyntic mucosa). CONCLUSIONS: Neither the esophagus nor the stomach contains a "cardia". The recent misconceptions regarding the foregut anatomy explain, why the innermost coverage of the reflux damaged esophagus is termed "cardiac mucosa". Thus the term should be reserved to name the histopathology of cardiac and oxyntocardiac mucosa, which develop due to gastroesophageal reflux within the distal esophagus.

Histological features of gastric cardia in adults: an autopsy study.

BACKGROUND AND AIMS: The existence, histology and origin of gastric cardiac mucosa are controversial. The aim of the present study was to determine the existence, histological characteristics and length of cardiac mucosa and to correlate these features with the patients' age and the presence of inflammation in the gastric cardia and/or esophagus. METHODS; The cardiac mucosa within the whole esophagogastric junction was histologically analyzed in 38 consecutive autopsy specimens and measured in 24 cases. RESULTS: The cardiac mucosa was identified in all specimens from all cases, with a mean length of 6.7 mm, range 0.927-19.5 mm. In the majority of cases, the length of cardiac mucosa was less than 10 mm (87.5%) and greater than 5 mm (71%). Cardiac mucosa was composed of a combination of pure mucous glands and mucous glands with parietal cells in 74% of cases, and only of mucous glands with parietal cells in 26% of cases. Carditis was recorded in 23.7% cases and reflux esophagitis in 15.8%. The length of cardiac mucosa was not significantly different between cases with and without carditis (p>0.05), between those with and without esophagitis (p>0.05), and between age groups older and younger than 60 years (p>0.05). CONCLUSION: In the adult population, a short histological segment of gastric cardia was consistently present as a normal histological structure. The type, length and circumferential presence of cardiac mucosa were not significantly associated with carditis, esophagitis or age.

Anatomical measurements of the gastric cardia in obese patients.

BACKGROUND: Currently, surgeons implant a variety of laparoscopic adjustable gastric bands. However, there is little data to guide the selection process. This study aims to determine the relationship between a patient's body mass index (BMI), height, and weight and the anatomical measurements of the gastric cardia in morbidly obese patients undergoing laparoscopic adjustable gastric band (LAGB) surgery. METHODS: A total of 67 morbidly obese patients undergoing LAGB surgery were studied. Intraoperative measurements of the gastric cardia were obtained. The relative circumference and posterior diameter of the gastric cardia were measured along with the patient's height, weight, and BMI. Pearson's correlation coefficient was used to measure the relationship between the circumference and posterior diameter of the gastric cardia and the BMI, height, and weight. A p < 0.05 was considered significant. RESULTS: No correlation exists between a patient's BMI or weight and the circumference or diameter of the gastric cardia. A correlation exists between a patient's height and the posterior diameter of the gastric cardia (p = 0.02). Of note, there is a correlation between the relative circumference and the posterior diameter of the gastric cardia for each patient (p = 0.05). CONCLUSION: Our unique data show no significant correlation between a patient's BMI and weight and the measurements of the gastric cardia. There was a correlation between a patient's height and the posterior diameter of the gastric cardia. These intraoperative measurements may help surgeons objectively select the appropriate band for each respective patient undergoing LAGB surgery. This may potentially decrease postoperative dysphagia.

Cardia: al fin de cuentas ¿qué es? / Cardia: at the end of the day, what is it?

There is no consensus about the precise definition of what the cardia is. Although this term is often utilized in the medical literature, it takes on a variety of meanings, depending on the context. For histologists and endoscopists, the cardia is a region of the stomach immediately below the gastroesophageal junction. However, the concepts of gastroesophageal junction used by histologists and endoscopists are not the same as used by anatomists. This junction is histologically defined as the abrupt transition from the nonkeratinized stratified squamous epithelium of the esophagus to simple columnar epithelium and corresponds to the endoscopically defined Z-line. Nevertheless, this epithelial change does not occur exactly in the anatomical transition between the esophagus and stomach, but is situated in the esophagus, 1 or 2 cm above the anatomical transition. Surgeons usually use the term cardia as synonymous with lower esophageal sphincter. From a strictly oncological point of view, the cardia is the region that includes the most distal 5 cm of the esophagus and the most proximal 5 cm of the stomach. Thus, it is easy to see that there is no uniform concept of the cardia. The term cardia needs to be revised as a matter of urgency.

No existe concenso sobre una definición precisa de lo que es el cardia. Aunque este término es a menudo utilizado en la literatura médica ha tomado una variedad de significados dependiendo del contexto. Para histólogos y endoscopistas, el cardia es una región del estómago inmediatamente bajo la unión gastroesofágica. Sin embargo, los conceptos de unión gastroesofágica usado por éstos es diferente al de los anatomistas. Esta unión es histológicamente definida como la abrupta transición del epitelio escamoso estratificado no queratinizada del esófago, a un epitelio columnar simple y corresponde a lo que endoscópicamente se define como línea Z. Sin embargo, este cambio epitelial no ocurre exactamente en la transición anatómica entre el esófago y el estómago, pero está situado en el esófago, 1 a 2 cm por encima de la transición anatómica. Generalmente, los cirujanos usan el término cardia como sinónimo de esfínter esofágico inferior. Desde un estricto punto de vista oncológico, el cardia es la región que incluye los más distales 5 cm del esófago y los más proximales 5 cm del estómago. Así, es fácil afirmar que no hay un concepto uniforme del cardia. El término necesita ser urgentemente revisado.

Transient lower esophageal sphincter relaxations do not result from passive opening of the cardia by gastric distention.

BACKGROUND & AIMS: Transient lower esophageal sphincter relaxation is the main mechanism for gastroesophageal reflux. Although there is evidence that transient lower esophageal sphincter relaxations are neurally mediated, another school of thought is that transient lower esophageal sphincter relaxations result from gastric distention, which shortens the sphincter to the point where it opens and the pressure decreases. We assessed the relationship of transient lower esophageal sphincter relaxation to gastroesophageal junction opening in an unsedated human model. METHODS: Seven healthy volunteers (6 men and 1 woman, aged 18-53 years) were studied while they were sitting. Manometry was performed by using a sleeve catheter passed through 1 nostril. A 5.3-mm endoscope was placed through the other nostril to obtain a retroflexed view of the cardia. The biopsy channel was connected to a barostat to distend the stomach with air at 15 mm Hg for 30 minutes. Manometric and endoscopic video-recording times were synchronized but scored independently. RESULTS: The transient lower esophageal sphincter relaxation onset invariably preceded gastroesophageal junction opening (median, 5.0 seconds; range, 0.5-20.7 seconds; P < .001). The transient lower esophageal sphincter relaxation nadir also typically occurred before gastroesophageal junction opening (median, 2.1 seconds; range, -4.2 to +19.5 seconds; P < .001). Once open, the gastroesophageal junction moved proximally for the duration of the transient lower esophageal sphincter relaxation. Termination of transient lower esophageal sphincter relaxations occurred about the time the time of gastroesophageal junction closure. CONCLUSIONS: These data refute the hypothesis that transient lower esophageal sphincter relaxations result from passive mechanical distraction of the gastroesophageal junction. Rather, transient lower esophageal sphincter relaxations must occur before the gastroesophageal junction can open.

Endoscopic measurement of cardia circumference as an indicator of GERD.

BACKGROUND: It is theorized that repeated gastric distention leads to dilatation of the cardia and the development of GERD. We hypothesize that cardia circumference correlates with the presence and the severity of GERD, and we developed software to measure cardia circumference from static endoscopic images. Our aims were to validate the software and to quantify cardia circumference along the spectrum of GERD. METHODS: Software-based measurements were compared with actual measurements in animal and mechanical models. A retrospective review of an endoscopic database and patient charts produced 273 subjects, grouped as follows: controls, GERD, < or = 3-cm Barrett's esophagus, or > 3-cm Barrett's esophagus. A blinded abstractor measured cardia circumference by using images from the database. RESULTS: Software and actual measurements correlated closely and were reproducible among observers. Median cardia circumference for each group was the following: control, 31.8 mm; GERD, 37.8 mm; < or = 3-cm Barrett's esophagus, 38.4 mm; and > 3-cm Barrett's esophagus, 45.0 mm (p < 0.001). By using 34.3 mm as a cutoff, cardia circumference was 85.3% sensitive and 89.6% specific for the diagnosis of GERD. CONCLUSIONS: There was a direct relationship between cardia circumference and the presence of GERD. This finding augments our understanding of the anatomic contributions of the esophagogastric junction in the pathogenesis of GERD. Cardia measurement may prove to be a useful diagnostic tool.

Light and scanning electron microscopy of the cardiac gland region of the stomach of the babirusa (Babyrousa babyrussa--Suidae, Mammalia).

Previous studies have indicated that the gross anatomical structure of the stomach of the babirusa (Babyrousa babyrussa) differs markedly from that of all other pigs. This light and scanning electron microscopic study revealed a previously unknown, microscopic structure characterised by a 'honeycomb' pattern at the luminal surface of the tunica mucosa. The walls of the 'honeycomb' were about 0.20-0.25 mm high and appeared almost entirely composed of various types of bacteria. Underneath the bacteria the walls were formed by thin tubes composed of non-glandular squamous epithelial-like cells, extending from the tops of the ridges between each glandular pit. There is as yet no evidence of a comparable structure in the stomach of any other pig, or to our knowledge any other forestomach-fermenting mammal.

Observations on aggregated lymphoid nodules in the cardiac glandular areas of the Bactrian camel (Camelus bactrianus).

Aggregated lymphoid nodules are an important part of the gut-associated lymphoid tissue (GALT). They are mainly distributed in the ileum and appendix of animals and humans but their distribution in the cardiac glandular area has not been reported. A study of stomach histology in the Bactrian camel has revealed that the nodules are distributed as a band-like region along the ventral wall of the stomach neck, at the beginning of the cranial enlargement and on the lesser curvature. The mucous folds are thicker in these regions than where there are no aggregated lymphoid nodules. The nodules appeared similar to ileal aggregated lymphoid nodules found in other animals and consisted of typical polymorphological lymphatic nodules arranged in a single continuous row occupying the submucosa and forming mucosal folds together with the mucous membrane. The whole mucous membrane with cardiac glands, diffuse lymphatic tissue and solitary lymphoid nodules in the lamina propria were found to cover the aggregated lymphoid nodule regions, but some nodules with a typical corona extended into the lamina propria and were covered with follicle-associated epithelium devoid of cardiac glands. These findings indicate that the stomach of the Bactrian camel possesses not only a special structure of digestion but also has characteristic immunological morphology.

On the existence and location of cardiac mucosa: an autopsy study in embryos, fetuses, and infants.

BACKGROUND: The incidence of gastric cardiac adenocarcinoma has increased in the last decades. Gaining insight into the pathogenesis of this lesion is hampered by the limited knowledge of the origin and histology of cardiac mucosa (CM). Currently, the location, extent, and even the existence of CM are controversial. AIMS: We studied the development of the gastro-oesophageal junction (GOJ) in embryos, fetuses, and infants to clarify if CM is a normal structure at birth and where it is located. SUBJECTS: Twenty one autopsy cases were evaluated ranging in age from 13 weeks' gestational age (GA) to seven months. METHODS: The distal oesophagus and proximal part of the stomach were embedded entirely. Serial sections were stained with haematoxylin-eosin and alcian blue/periodic acid-Schiff. The following parameters were measured: length of abdominal oesophagus; length of columnar lined oesophagus; length of CM; and distance from CM to angle of His. RESULTS: CM was present in all evaluated sections. Its mean length varied throughout gestation. A maximum value was reached at a GA of 16 weeks (1.2 mm). After term delivery it was very short (0.3-0.6 mm). CM was proximal to, or straddled, the angle of His in all cases. During gestation, the mucin staining pattern of the CM was to a high degree similar to that of the developing pyloric mucosa. CONCLUSIONS: CM develops during pregnancy and is present at birth as a normal structure. If the angle of His is taken as a landmark for the GOJ, CM is located in the distal oesophagus.

The gastric cardia: to be or not to be?

The origin and biologic significance of cardiac gastric mucosa are controversial. Traditionally, it has been considered native mucosa and part of normal foregut development. It has been recently suggested that cardiac mucosa is present only as a metaplastic response to gastroesophageal reflux disease and therefore always abnormal. We evaluated the esophagogastric junction in 100 pediatric autopsy samples to determine the existence, characteristics, and length of pure cardiac mucosa at different ages. No patient had a history of gastroesophageal reflux disease. Cardiac mucosa immediately distal and contiguous to the esophageal squamous mucosa was identified in all 100 samples, varying in length from 0.1 to 3 mm; the mean length was 1 mm. There was an inverse correlation between patient age and length of cardiac mucosa; gender had no influence on measured length. Three patients had mild to moderate histologic esophagitis; two had gastritis. No metaplastic features or Helicobacter pylori were identified. These findings support the concept that there is a normal, variably narrow developmental zone at the esophagogastric junction covered by cardiac mucosa and is present at birth. When cardiac type mucosa is found in biopsy material, it does not necessarily represent evidence of a mucosal metaplastic response to gastroesophageal reflux disease.