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Gastric cardia inflammation and intestinal metaplasia: associations with reflux esophagitis and Helicobacter pylori.

Gastric cardia inflammation and intestinal metaplasia are the subjects of recent investigation. Some authors have found associations with gastroesophageal reflux disease, whereas others have identified relationships with Helicobacter pylori (HP). We studied 150 consecutive patients who underwent upper endoscopy, had normal gastroesophageal anatomy, and had biopsies of the antrum, cardia, and lower esophagus, to evaluate relationships between reflux esophagitis, cardia inflammation, intestinal metaplasia, and HP gastritis. Forty-two patients had HP infection. Cardia inflammation was significantly related to esophageal squamous inflammation in the non-HP-infected patient group and to antral inflammation and cardia HP infection in the HP-infected patient group. The differences between the patient groups was most apparent in the patients with moderate or marked inflammation. Twenty-seven percent of patients had cardia intestinal metaplasia that was related to cardia inflammation. Cardia inflammation and intestinal metaplasia probably have multiple causes. Pathologists should refrain from applying the term Barrett's esophagus for biopsies procured from the cardia that show intestinal metaplasia in patients with a normal squamocolumnar junction.

Adolescent↗

Clinicopathologic characteristics and outcome of adenocarcinoma of the human gastric cardia in comparison with carcinoma of other regions of the stomach.

BACKGROUND: Carcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. This study was done to analyze the biologic characteristics of carcinoma of the gastric cardia compared with other gastric carcinomas. STUDY DESIGN: Clinicopathologic features and postoperative prognosis of 68 cases of carcinoma of the cardia were evaluated, in comparison with findings of tumors in other regions of the stomach. RESULTS: From 1975 to 1992, 68 (6.5 percent) of 1,042 patients with carcinoma of the stomach had adenocarcinoma of the cardia. Carcinoma of the cardia was characterized by a more advanced stage compared with carcinoma of other regions of the stomach. The incidence of early stage carcinoma (limited to the submucosal layer) was 11.8 percent in the cardia, 15.8 percent in the upper one-third, and 42.2 percent in the remaining middle and lower thirds of the stomach. When compared to carcinoma in other regions of the stomach, tumors of the cardia had a significantly poorer prognosis and there was a higher incidence of lymph node and hepatic metastasis. The five-year survival rates in patients with adenocarcinoma in the cardia, the upper one-third, and the remaining middle and lower thirds of the stomach were 35.3, 43.7, and 61.9 percent, respectively. Especially for patients with stage II and stage III disease, the prognosis was significantly worse with adenocarcinoma of the cardia than with carcinomas of the other regions of the stomach. CONCLUSIONS: Early detection is crucial to improve the survival of patients with carcinoma of the gastric cardia. Extended dissection of lymph nodes and aggressive postoperative chemotherapy in an attempt to prevent hepatic metastasis are highly recommended.

Adenocarcinoma↗

Adenocarcinomas of the esophagus and gastric cardia: medical conditions, tobacco, alcohol, and socioeconomic factors.

Adenocarcinomas of the esophagus and gastric cardia have increased in incidence over the past 10-15 years in Western countries. The cause for this increase in incidence is still unknown. Our study was designed to investigate potential risk factors for adenocarcinomas of the esophagus and gastric cardia and to compare the risk profiles of a group of patients with this cancer with those having distal stomach cancer. We studied 95 incident cases with the pathological diagnosis of adenocarcinomas of the esophagus and gastric cardia, 67 patients with adenocarcinomas of the distal stomach, and 132 cancerfree controls. Patients were seen at Memorial Sloan-Kettering Cancer Center from November 1, 1992 to November 1, 1994. Epidemiological data were collected by a modified National Cancer Institute Health Habits History Questionnaire. Risk factors were analyzed using Mantel-Haenszel methods and a logistic regression model. Hypertension was associated with a 2-fold increased risk of adenocarcinomas of esophagus and gastric cardia after controlling for age, sex, race, education, pack-years of smoking, alcohol use, body mass index, and total dietary intake of calories. Increased risk of adenocarcinomas of esophagus and gastric cardia was associated with age, male gender, and Caucasian race. Tobacco smoking was related to a modest risk of adenocarcinomas of esophagus and gastric cardia. In contrast, the risk of distal stomach cancer was associated with stomach ulcers and pack-years of cigarette smoking. Iron deficiency was significantly associated with increased risk of both adenocarcinomas of the esophagus and gastric cardia and adenocarcinomas of the distal stomach. No obvious associations were identified for occupational exposures, family history of cancer, and physical activities. This study suggests that medical conditions such as hypertension and iron deficiency may be related to the risk of adenocarcinomas of esophagus and gastric cardia and confirms the moderate risk associated with tobacco smoking. Our results indicated an etiological heterogeneity with respect to risk factors identified between adenocarcinomas of esophagus and gastric cardia and those of the distal stomach.

Adenocarcinoma↗

Methylene blue staining for intestinal metaplasia of the gastric cardia with follow-up for dysplasia.

BACKGROUND: Previous studies by our group have identified a 23% prevalence of intestinal metaplasia involving the gastric cardia in patients undergoing elective esophagogastroduodenoscopy (EGD). The current study evaluates the potential clinical utility of vital staining with methylene blue for detecting intestinal metaplasia of the cardia. In addition, the prevalence of Helicobacter pylori infection and incidence of dysplasia in cardia intestinal metaplasia was assessed. METHODS: Twenty-four of 104 patients undergoing elective EGD were previously identified with cardia intestinal metaplasia. Twenty-one of these 24 returned for follow-up EGD with methylene blue staining and cardia biopsies. During EGD four random biopsies were taken in the cardia. After staining with methylene blue, four targeted biopsy specimens were taken from any stained areas. H. pylori infection was assessed by rapid urease testing and serologic evaluation. RESULTS: Staining with methylene blue was positive in 16, equivocal in 4, and negative in 1. Overall, cardia intestinal metaplasia was identified in 17 of 21 patients (81%) by at least one of the 8 biopsies. The sensitivity of detecting intestinal metaplasia by targeted biopsies to stained areas was 67% as opposed to 38% for random biopsies (odds ratio 3.0: 95% CI [0.88,10.24]). The prevalence of H. pylori infection in patients with cardia intestinal metaplasia was 76%. One patient developed low-grade dysplasia, whereas the others remained negative. CONCLUSIONS: Intestinal metaplasia of the gastric cardia is associated with a high prevalence of H. pylori infection and is a reproducible finding in the majority of patients. Methylene blue staining and an increasing number of biopsies improve the sensitivity of detecting this potentially neoplastic lesion.

Aged↗

Intestinal metaplasia is the probable common precursor of adenocarcinoma in barrett esophagus and adenocarcinoma of the gastric cardia.

BACKGROUND: Intestinal metaplasia in the tubular esophagus is the recognized precancerous lesion of adenocarcinoma in Barrett esophagus. However, it is not yet clear whether adenocarcinoma of the gastric cardia arises from the same premalignant lesion, i.e., intestinal metaplasia of the gastric cardia. The purpose of this study was to compare adenocarcinomas in Barrett esophagus and adenocarcinomas of the gastric cardia at an early stage, when it was more likely that intestinal metaplasia had not been completely overgrown by the tumor. METHODS: The authors compared the epidemiologic, clinical, and pathologic features of early stage adenocarcinoma in Barrett esophagus and adenocarcinoma of the gastric cardia from 42 patients who underwent resection surgery. The presence of intestinal metaplasia was assessed in the resected specimens by using Alcian blue (pH 2.5) staining. RESULTS: Intestinal metaplasia was detected in the mucosa adjacent to neoplasia in 25 of 26 patients with adenocarcinoma in Barrett esophagus and in 11 of 16 (69%) patients with adenocarcinoma of the gastric cardia. Patient and tumor characteristics and survival were comparable in both groups. CONCLUSIONS: Intestinal metaplasia is a very common finding in the mucosa adjacent to early stage adenocarcinoma of the gastric cardia. Adenocarcinoma in Barrett esophagus and adenocarcinoma of the gastric cardia may represent the same disease; the former arises from longer segments of intestinal metaplasia and the latter from intestinal metaplasia of the cardia.

Adenocarcinoma↗

Phylogenetic diversity of cellular organization in the cardia of muscoid flies (Diptera: Schizophora).

In each of 30 dipteran species, representing 13 acalyptrate and 7 calyptrate families, the cardia is formed from specialized cells at the junction between foregut and midgut. Foregut epithelium forms the stomodeal valve; midgut epithelium envelops the valve to form the cardia's outer wall. Cytological characteristics within these epithelia differ from region to region and from species to species. Since the cardia secretes the peritrophic membrane, cardias with diverse patterns of cellular differentiation may be expected to produce peritrophic membranes with similarly diverse properties. Close relatives often share more details of cardia structure than do distantly related taxa. Within the monophyletic Calyptratae, a common pattern of cellular differentiation includes three distinct zones of columnar midgut cells enclosing a flanged stomodeal valve. Among species in the paraphyletic Acalyptratae, midgut typically includes a single zone of tall columnar cells, while the valve may be spheroidal, cylindrical, conical, or flanged. The correlation of phylogenetic distance with divergence in cardia organization implies a strong influence of ancestry upon current structure, regardless of current diet. However, at least some of the observed diversity in cardia structure is associated with dietary divergence. Calyptrate flies with derived blood-feeding behavior display cellular differentiation that is simplified from that seen in calyptrate relatives with less specialized feeding habits. This evolutionary modification suggests that cardia organization and hence peritrophic membrane structure can adapt to dietary changes, with possible significance for the spatial organization of digestive processes and interactions with ingested microorganisms.

Animals↗

Distinct recurrence pattern and outcome of adenocarcinoma of the gastric cardia in comparison with carcinoma of other regions of the stomach.

BACKGROUND: Carcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. The prognosis for adenocarcinoma of the upper stomach is considered to be relatively poorer than carcinomas of the more distal stomach. We have therefore investigated patients with carcinoma of the gastric cardia in order to evaluate the underlying cause of this poor prognosis. MATERIALS AND METHODS: Clinicopathologic features and postoperative prognosis of 101 patients with carcinoma of the cardia were evaluated and compared with findings on 1884 patients with tumors in other regions of the stomach. RESULTS: Tumors of the cardia had a mean size of 6.8 cm, which was significantly larger than the mean size of 5.9 cm for tumors found in the middle- and lower third of the stomach. The incidence of serosal invasion, lymph node metastasis, and lymphatic and blood vessel invasion was higher in association with adenocarcinoma of the cardia than with adenocarcinoma in remaining parts of the stomach. In the analysis of patients who had undergone curative resection, the 5-year survival rates were 61.6, 79.1, and 82.6% in patients with carcinoma of the cardia, upper one-third, and remaining middle- and lower one-third of the stomach, respectively, and the differences were statistically significant. Multivariate analysis indicated that adenocarcinoma of the gastric cardia is an independent prognostic factor. With regard to the site of recurrence, both lymph node and hematogenous recurrence were observed more frequently in the cardia than in the remaining parts of the stomach. CONCLUSIONS: Our data indicate that the prognosis of patients with adenocarcinoma of the gastric cardia is extremely poor. To improve their prognosis, new treatments in addition to gastrectomy with extensive lymph node dissection are needed.

Adenocarcinoma↗

The gastric cardia in Helicobacter pylori infection.

Helicobacter pylori gastritis is believed to be both more prevalent and more severe in the antrum than in the corpus. The mucosa of the cardia is architecturally similar to that of the antrum. This study was designed to test the hypothesis that intensity of H pylori infection and the associated inflammation are similar in the cardia and the antrum and are greater in these locations than in the corpus. A total of 445 gastric biopsy specimens were obtained from predetermined sites from 50 subjects (42 with demonstrated H pylori infection). Slides were stained with a combined stain to simultaneously visualize H pylori, mucosal morphology, and inflammatory infiltrate. Numbers of H pylori, inflammatory responses, and intestinal metaplasia were graded on a scale from 0 to 5. Helicobacter pylori was detected in the cardia of 40 of the 42 infected subjects (95%). Helicobacter pylori density was similar in the three gastric regions. The intensity of chronic active gastritis was similar in the antrum and the cardia, and was higher in these locations than in the corpus (P < .005). Lymphoid follicles were significantly less prevalent in the cardia and in the corpus than in the antrum (P < .05). Helicobacter pylori infection was as prevalent in the cardia as in the rest of the stomach and its density was similar in all sites of antrum, corpus, and cardia. The inflammatory responses characteristic of chronic active gastritis, except for lymphoid follicles, were similar in the antrum and the cardia and in both these locations were more intense than in the corpus. The significance of these findings is discussed with respect to the relationship between H pylori infection and the genesis of gastric adenocarcinoma and lymphoma.

Adult↗

Unchanging trend of adenocarcinoma of the esophagus and gastric cardia in Taiwan: a 15-year experience in a single center.

Chronic gastroesophageal reflux disease is closely associated with esophageal adenocarcinoma and gastric cardia carcinoma, and esophageal adenocarcinoma and gastric cardia carcinoma have both been increasing in Western countries recently. Gastroesophageal reflux disease is not rare in Taiwan, but the frequency of occurrence of esophageal adenocarcinoma or gastric cardia carcinoma has not been studied here to date. Patients diagnosed with esophageal and gastric cancers at this hospital between 1981 and 1995 were recruited using the hospital tumor registry database. There were 45, 1546, 970, and 4167 patients diagnosed with esophageal adenocarcinoma, esophageal squamous cell carcinoma, gastric cardia carcinoma, and gastric noncardia adenocarcinoma, respectively. The ratios of esophageal adenocarcinoma versus esophageal squamous cell carcinoma among the three cohorts were 0.030, 0.016, and 0.041, respectively (trend, P = 0.086). The corresponding values for gastric cardia carcinoma versus gastric noncardia adenocarcinoma were 0.252, 0.232, and 0.218, respectively (trend, P = 0.256). The ratios of esophageal adenocarcinoma versus esophageal squamous cell carcinoma and of gastric cardia carcinoma versus gastric noncardia adenocarcinoma have not risen in the three cohorts. Unlike the situation in Western countries, the incidence of esophageal adenocarcinoma and gastric cardia carcinoma versus esophageal squamous cell carcinoma and gastric noncardia adenocarcinoma have not increased over the past 15 years among the Chinese in Taiwan. Although gastroesophageal reflux disease is common here, its definite pathogenesis leading to esophageal adenocarcinoma or gastric cardia carcinoma remains unresolved.

Adenocarcinoma↗

Inflammation of the gastric cardia in children with symptoms of acid peptic disease.

OBJECTIVES: To assess the severity and causes of inflammation of the gastric cardia in children undergoing endoscopy for symptoms of acid peptic disease. STUDY DESIGN: Patients undergoing upper gastrointestinal endoscopy for symptoms of acid peptic disease had biopsies from gastric cardia, gastric, and esophageal sites, and 24-hour intraesophageal pH monitoring. Gastric cardia was defined at endoscopy as the anatomic zone from the squamocolumnar junction to 0.5 cm below it. Severity of gastric cardia inflammation was scored 0 to 9 according to densities of inflammatory cells and epithelial abnormalities in surface and pit epithelium. A score > or =2 was considered positive. RESULTS: Forty-seven children (median age, 6.5 years; range, 3-15) had Helicobacter pylori infection, gastroesophageal reflux disease (GERD), or both. In 22 patients, H pylori was detected in cardiac biopsies by rapid urease test and histology; it was detected also in the corpus and antrum in only seven of the 22. No patient had H pylori in gastric corpus/antrum without having the organism at the cardia as well. In 12 H pylori-positive patients, GERD was also diagnosed. Twenty-five patients had GERD and no H. pylori infection. Severity score was 3.8+/-0.8 in the H pylori group and 2.08+/-0.9 in the GERD alone group (P<.001); however, there was no difference in reflux index (24-hour % of gastroesophageal reflux) between the two groups. In neither group was correlation found between reflux index and severity score (H pylori, r=0.22; GERD alone, r=0.31; NS) nor between cardia inflammation and esophagitis grade (H pylori, r=0.37; GERD alone, r=0.22; NS). CONCLUSIONS: In children with symptoms of acid peptic disease, inflammation of the gastric cardia does occur. It is more severe when the cardiac zone is infected with H pylori than in its absence. Of major practical significance is the finding that the gastric cardia is a highly sensitive site for the detection of H pylori infection.

Adolescent↗

Recent time trends in cancer of the oesophagus and gastric cardia in the region of Calvados in France, 1978-1995: a population based study.

The incidence of oesophageal cancer differs from country to country, and even between areas of the same country. Many studies in recent years have shown an upward trend of a particular histologic type: adenocarcinoma of the oesophagus. It is difficult to precisely locate adenocarcinomas situated at the junction between the oesophagus and the gastric cardia. Clear criteria to define and classify such tumours are essential in order to analyse their evolution. The present study describes the changing incidence of cancers of the oesophagus and gastric cardia according to histologic type from 1978 to 1995 in Calvados, the highest-risk French region with two different topographic classifications of adenocarcinomas: one based on Misumi's criteria and the other based on local extension of cancer. In total, 1835 cancers of the oesophagus and gastric cardia were diagnosed in this period. Incidence rates for oesophageal and gastric cardia cancers standardized on the world population were 24.4/10(5) and 2.4/10(5) in men and 1.4/10(5) and 0.4/10(5) in women, respectively. The time trend in the incidence of squamous cell cancers was downward in men -0.74 (P < 10(-6)) and stable in women +0.04 (P = 0.65). Regarding adenocarcinomas, with the classification based on Misumi's categories, there was a slight but significant upward trend for oesophageal adenocarcinoma in men [mean annual variation of +0.09 (P < 10(-5))] while the tendency was downward and significant for gastric cardia adenocarcinoma [mean annual variation of -0.09 (P < 10(-4))]. When adenocarcinomas of the oesophagus and those of the gastric cardia with oesophageal involvement are taken together (second classification), there was an upward trend which was not significant in men and was significant in women. There was no such upward trend in adenocarcinomas limited to the gastric cardia and/or involving the stomach. Because of the difficulties in determining accurate localization routinely in population-based studies, it seems sensible to preclude classification biases in recommending the grouping together of gastric cardia adenocarcinomas with oesophageal adenocarcinomas, at least with those among the latter occurring in the lower third of the oesophagus.

Adenocarcinoma↗

Long-term follow-up of intestinal metaplasia of the gastric cardia.

OBJECTIVE: Recent studies have found a relatively high prevalence of gastric cardia intestinal metaplasia in individuals presenting for elective upper endoscopy. It has been hypothesized that this lesion may be a precursor of gastric cardia cancer. Our objective was to identify the incidence of dysplasia in patients with gastric cardia intestinal metaplasia. METHODS: Twenty-eight patients who had previously been identified with cardia intestinal metaplasia had follow-up examinations performed. None of the patients had dysplasia at the time of diagnosis. All had an examination at 1 yr, and 20 patients had an examination at 3 yr after diagnosis. During follow-up examinations all patients underwent vital staining with methylene blue to help identify areas of intestinal metaplasia in the cardia. Two to four biopsies were taken from blue-stained mucosa. Histological specimens were stained using a combination of hematoxylin and eosin with Alcian blue at pH 2.5. RESULTS: There were 27 men and one woman with a mean age of 69.8 yr (range, 48-83 yr). The mean length of follow-up was 2.5 yr (range, 12-46 months). Only one patient was diagnosed with dysplasia (low-grade) during the study, for an incidence of 1.4% per yr. CONCLUSIONS: The prevalence (0%) and incidence (1.4%/yr) of dysplasia in cardia intestinal metaplasia are low. Although further studies are needed, screening and surveillance for gastric cardia intestinal metaplasia is unlikely to be clinically useful for the prevention of gastric cardia cancer.

Aged↗

The gastric cardia in gastro-oesophageal disease.

BACKGROUND: There have been conflicting reports concerning the use of cardia biopsies in screening patients for gastro-oesophageal disease. AIM: To define the histopathological changes in the gastric cardia of patients with and without gastro-oesophageal disease. METHODS: Topographically mapped gastric biopsy specimens were obtained from patients with gastro-oesophageal disease and from controls. Biopsies were scored on a visual analogue scale of 0 to 5 for Helicobacter pylori, intestinal metaplasia, pancreatic metaplasia, foveolar hyperplasia, and active inflammation. The presence or absence of cardiac glands was recorded. RESULTS: Sixty-five patients with gastro-oesophageal disease and 71 controls were examined. Intestinal metaplasia was present in cardia biopsies of 10 patients with gastro-oesophageal disease and 11 controls. Only two patients with gastro-oesophageal disease and intestinal metaplasia in the cardia had no evidence of exposure to H pylori. Intestinal metaplasia was not found in the cardia of those with long segment Barrett's oesophagus. Carditis was strongly associated with active H pylori infection (p = 0.000) and resolved after treatment of the infection. A negative association was present between gastro-oesophageal disease and the presence of cardiac glands in cardiac biopsies (p = 0.003). Pancreatic metaplasia was found in 15 of 65 and foveolar hyperplasia in 19 of 65 cases but neither was related to gastro-oesophageal disease. CONCLUSION: Intestinal metaplasia in the cardia is uncommon in gastro-oesophageal disease in the absence of H pylori infection. With chronic H pylori infection the junction between the cardia and corpus expands in a cardia-corpal direction.

Adult↗

Early carcinoma of the gastric cardia in Japan: is it different from that in the West?

BACKGROUND: The incidence of adenocarcinoma of the gastric cardia has increased recently in the West. However, in Japan, most patients with gastric carcinoma have disease that is situated in the body and the distal stomach. The objectives of this study were to compare the clinicopathologic findings of patients with early gastric carcinoma (EGC) arising at the cardia and those with carcinoma in more distal parts of the stomach, then comparing the findings with those from patients with carcinoma of the gastric cardia in the West. METHODS: Three thousand one hundred forty-four patients with EGC who underwent surgical resection between 1962 and 1997 at the National Cancer Center Hospital in Tokyo were studied. Seventy patients with EGC at the cardia were compared with those who had lesions in the middle and lower parts of the stomach. The body mass index (BMI), smoking, and drinking were evaluated using all patients with cardia EGC and 344 patients in a matched cohort in the latter group. RESULTS: Seventy patients had an EGC located just at the cardia, whereas 2796 patients had lesions in the lower two-thirds of the stomach. The former lesions were different from those in the distal two-thirds of the stomach: More often, they were of an elevated type (34% vs. 14%, respectively, they were histologically well differentiated in 89% (vs. 59%), and there were more submucosal tumors (53% vs. 41%). The BMI, smoking, and drinking in the two groups were not different. The incidence of Barrett esophagus and gastroesophageal reflux disease (GERD) in patients with EGC were 2. 9% (2 of 70 patients) and 5.7% (4 of 70 patients), respectively. CONCLUSIONS: There were many significant differences in clinicopathologic characteristics between patients with carcinoma of the cardia and patients with carcinoma of the distal stomach in Japan. The incidence of early cardia carcinoma was very low in Japan, and obesity, smoking, drinking, Barrett esophagus, or GERD were not related to its occurrence, in contrast to reports in the West.

Adenocarcinoma↗

Adenocarcinoma of the esophagus and/or gastric cardia.

One hundred twenty-nine adenocarcinomas involving the esophagus and/or gastric cardia differed significantly from 212 cancers of the rest of the stomach as follows: male-female ratio, 6:1 versus 2:1, birth outside Canada, US or UK, 12% versus 34%; parent or sibling with gastric cancer, 5% versus 13%; previous duodenal ulcer, 23% versus 9%; chronic reflux symptoms, 25% versus 3%; hiatal hernia, 51% versus 11%. Of the 129 esophagocardia cancers, 24 involved the esophagus alone, 48 the cardia and esophagus, 33 the cardia alone or cardia and fundus, and 24 the upper stomach and lower esophagus extensively. Thirty-four were associated with Barrett's esophagus. The 72 patients with involvement of both the upper stomach and lower esophagus (48 cardia and esophagus, 24 extensive) were identical with the esophagocardia group as a whole. The 24 patients with esophageal cancer and the 34 with Barrett's epithelium were the same clinically as the whole esophagocardia group except more had chronic reflux and hiatal hernia. The 33 patients with cancer confined to the cardia or cardia and fundus resembled the whole esophagocardia group but did not have Barrett's esophagus. Adenocarcinoma of the esophagocardia region is probably a different disease from cancer of the rest of the stomach.

Adenocarcinoma↗

Detection of Barrett's adenocarcinoma of the gastric cardia with sucrase isomaltase and p53.

BACKGROUND: Routine surveillance for dysplastic epithelium in patients with Barrett's esophagus has markedly improved prognosis. Many patients with short segments of Barrett's mucosa near the esophagogastric junction remain undiagnosed and at risk for the development of Barrett's adenocarcinomas (BA). Sucrase isomaltase (SI), an intestinal enzyme, is highly expressed in intestinal-type Barrett's mucosa and frequently expressed in dysplastic Barrett's mucosa and BA. Sucrose isomaltase is not expressed in normal esophageal or gastric mucosa. Alterations in the p53 tumor suppressor gene are frequent events in dysplastic Barrett's mucosa and BA and result in nuclear protein accumulation. The purpose of this study was to determine the presence or absence of these markers of Barrett's mucosa in adenocarcinoma of the esophagogastric junction or cardia. METHODS: Expression of SI and p53 were examined in 40 BAs and 25 cardia adenocarcinomas using immunohistochemical techniques. RESULTS: Sucrose isomaltase analysis revealed positive staining in 55% (22/40) of the BAs and 44% (11/25) of the cardia adenocarcinomas. Of 14 cardia adenocarcinomas that were SI negative, 100% (14/14) had no associated Barrett's mucosa. However, in 21 cardia adenocarcinomas with no associated Barrett's mucosa, 7/21 (33%) were SI positive. This suggests that SI-positive tumors may represent BA without the standard definition of Barrett's esophagus being met. P53 was present in 65% of BAs and 64% of cardia adenocarcinomas, demonstrating the importance and similarity of this gene alteration in both tumor types. Staining was positive for SI or p53 in 77% (50/65) of all tumors. Tumors of lower stage expressed SI more often than higher stage tumors. CONCLUSIONS: These data suggest that a subset of cardia adenocarcinomas represent BAs. Surveillance endoscopy incorporating additional esophagogastric junction biopsies and assessment of SI or p53 may improve detection of intestinalized Barrett's mucosa and early dysplastic changes.

Adenocarcinoma↗

Epidemiological characteristics of adenocarcinoma of the gastric cardia and distal stomach in the United States, 1973-1982.

Data from the Surveillance, Epidemiology, and End Results (SEER) programme of the National Cancer Institute were utilized to estimate the incidence of adenocarcinoma of the gastric cardia and distal stomach in the US in order to determine whether the epidemiological features of these diseases differ. Based upon 12,562 histologically confirmed cases identified, the annual incidence of gastric cardia adenocarcinoma was 1.1 per 100,000 people and for the distal stomach 3.8 per 100,000. The male-to-female ratio for adenocarcinoma arising in the cardia was 7.0, versus 2.2 for that arising in the distal stomach. The sex ratio shifted across age groups for the gastric cardia and was highest for the 50-59 year age group, but remained relatively stable across age groups for cancers of the distal stomach. Over the decade studied, the sex ratio decreased from 8.0 to 4.6 for gastric cardia tumours, but remained constant for adenocarcinoma of the distal stomach. Blacks were 2.5 times more likely to develop adenocarcinoma of the distal stomach than whites, but had a 50% lower risk of gastric cardia tumours than whites. These results support an emerging concept that adenocarcinoma of the gastric cardia, gastro-oesophageal junction and distal oesophagus may comprise a group of disease which is aetiologically distinct from distal gastric tumours.

Adenocarcinoma↗

Morphology of the cardia and significance of carditis in pediatric patients.

The morphology of the gastric cardia in children and the significance of inflammation in this region are unknown. Some investigators propose that the cardia is comprised of mucous glands at birth, whereas others suggest that mucous glands, when present, represent a metaplastic response to gastroesophageal reflux disease. The aim of this study was to evaluate the morphologic features of the cardia in a pediatric population and to determine the significance of inflammation in this region by correlating the pathologic features with clinical and endoscopic data. Routinely processed hematoxylin and eosin-stained mucosal biopsies of the cardia from 74 pediatric patients (age range 0.1-18 years; male/female ratio 0.76:1) without endoscopic evidence of Barrett's esophagus were examined for a variety of histologic features, such as the type of glandular epithelium (mucous, mixed mucous/oxyntic, oxyntic), and the amount and type of inflammation both within 1.0 mm and >1.0 mm from the squamocolumnar junction. The results were correlated with the patients' clinical symptoms and with other histologic features, such as esophagitis, gastritis, Helicobacter pylori, and the presence of goblet cells. Our results show that either pure mucous glands (81%) or mixed mucous/oxyntic-type glands (19%) were present within 1 mm of the squamocolumnar junction in all of the patients (100%) in this study. Patients with mixed mucous/oxyntic glands located <1 mm from the squamocolumnar junction were more likely to have goblet cells than were patients with mucous glands alone, but they did not differ with respect to any other feature, including patient age. However, both active esophagitis and increased inflammation in the cardia correlated positively with a longer length of pure mucous glands in the gastroesophageal junction region. Of the cases with inflammation (carditis), eosinophils correlated with the presence of active esophagitis (a histologic manifestation of gastroesophageal reflux disease), whereas increased lymphocytes correlated with chronic H. pylori gastritis. In summary, a small amount of pure mucous-type glands is present in the cardia in most pediatric patients, a finding that supports a congenital origin for this type of epithelium. However, our finding of an association between length of mucosa occupied by pure mucous glands and active esophagitis suggests that injury and repair related to gastroesophageal reflux disease may contribute to expansion of the zone occupied by cardia-type mucous glands.

Adolescent↗