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p53 abnormalities in adenocarcinoma of the gastric cardia and antrum.

AIM: To compare the frequency and type of p53 alterations (gene mutation and/or protein overexpression) in a consecutive series of surgically resected adenocarcinomas arising in the gastric cardia and gastric antrum, and to evaluate associations with clinicopathological findings (age, sex, and tumour histology, grade, and stage). METHODS: The series comprised 50 patients with adenocarcinoma of the cardia and 20 patients with adenocarcinoma of the antrum. p53 gene mutations (exons 5-8) were detected by denaturing gradient gel analysis and DNA sequencing. Nuclear p53 overexpression was detected by immunohistochemistry with the DO7 antibody. RESULTS: p53 gene mutations were found in 21 of 50 and five of 20 adenocarcinomas of the cardia and the antrum, respectively. Base transitions occurring at CpG dinucleotides were frequent in both types of tumour. p53 protein overexpression was seen in 32 of 50 and seven of 20 adenocarcinomas of the cardia and of the antrum, respectively. p53 gene mutation and/or protein overexpression were significantly more frequent in adenocarcinomas of the cardia (37 of 50) than in adenocarcinomas of the antrum (seven of 20). There were no differences in the clinicopathological characteristics of the tumours between p53 positive and p53 negative cases in both types of cancer. CONCLUSIONS: This study shows that p53 alterations are more frequent in adenocarcinoma of the cardia than in adenocarcinoma of the antrum. This feature is consistent with the clinical and epidemiological characteristics of these cancers, which suggest that adenocarcinoma arising in the gastric cardia might be related to oesophageal adenocarcinoma, and unrelated to adenocarcinomas of the gastric body and antrum.

Adenocarcinoma↗

No changing trends in incidence of gastric cardia cancer in Korea.

Although there is a controversy, several reports have shown that gastric cardia cancer has tended upwards in recent years. The aim of this study was to investigate the changing trend of stomach cancer according to the location of cancer and histologic type in Korea, where is known to be one of the most prevalent areas for gastric cancer. All the patients newly diagnosed as gastric cancer from 1991 through 2000 were recruited in Hallym University Medical Center. The periods were divided into the first (1991 through 1995) and the second (1996 through 2000) period. We analyzed the characteristics of cancer in the aspects of age, sex, tumor locations (cardia and non-cardia), and tumor grade of differentiation (well, moderate, and poor differentiated type). The number of cases was 2,395 and that of cardia cancer was 158 (6.6%). There was no evidence about the changes in the incidence of cardia cancer and histologic differentiation between two periods. The development of cardia cancer was not associated with the factors of age and sex with having no difference in the point of tumor grade. We could not find an upward tendency of cardia cancer development in recent 10 yr in Korea.

Adenocarcinoma↗

[Comparison of the endoscopic aspect of the cardia, manometry and 24 hours pH measurement in patients with chronic gastroesophageal reflux].

BACKGROUND: The endoscopic view of the gastric cardia could be related with the manometric competence of the lower esophageal sphincter (LES) and with pathological gastroesophageal reflux. AIM: To compare the endoscopic aspect of the cardia with the results from esophageal manometry and 24 h esophageal pH monitoring. MATERIALS AND METHODS: The cardia of a group of 150 patients (aged 19 to 72 years, 89 women) with gastroesophageal reflux symptoms was classified as normal or open, during upper gastrointestinal endoscopy. All subjects were subjected to a manometric study to measure LES pressure and determine LES incompetence and to a 24 h esophageal pH measurement. RESULTS: LES pressure was 14.7+/-6.2 and 8.7+/-4.2 mmHg in patients with normal and open cardia, respectvively (p <0.001). Likewise, 43 and 79% of patients with normal and open cardia had an incompetent LES, respectively (p <0.001). Pathological acid reflux was present in 43 and 71% of patients with normal or open cardia, respectively (p <0.001). CONCLUSIONS: The endoscopic appearance of the cardia can identify patients with pathological gastroesophageal reflux.

Adult↗

Clinical significance of p53 mutations in adenocarcinoma of the esophagus and cardia.

OBJECTIVE: To compare the frequency and spectrum of p53 gene mutations in adenocarcinomas of the esophagus and cardia and to compare clinical and pathologic features in patients with p53 mutant and nonmutant cancers. SUMMARY BACKGROUND DATA: The p53 gene is commonly mutated in human cancers, and a p53 mutation is reported to be present in more than 50% of esophageal adenocarcinomas. Although many studies have investigated the frequency of p53 protein overexpression in adenocarcinomas of the esophagus or esophagogastric junction, few studies have assessed the frequency and clinical significance of p53 mutations in these tumors. In particular, the prognostic importance of p53 mutation is uncertain. Adenocarcinomas of the esophagus and cardia share many epidemiologic and pathologic features, but it is controversial whether they represent the same tumor. A comparison of the frequency and spectrum of mutations in adenocarcinomas of the esophagus and cardia would test whether these tumors are also similar at the molecular level. METHODS: DNA was isolated from microdissected paraffin-embedded tumor tissues of patients who underwent esophagogastrectomy for adenocarcinoma of the esophagus (n = 19), cardia (esophagogastric junction, n = 12), or subcardia (n = 6). Exons 5 to 8 of the p53 gene were analyzed for the presence of mutations using the polymerase chain reaction with single-strand conformation polymorphism and DNA sequencing of bands showing abnormal mobility. The presence of mutation was confirmed by selective hybridization of a mutant-specific oligonucleotide to DNA isolated from the tumor. RESULTS: p53 mutations were identified in 18 of 37 (48.6%) tumors. Patients with p53 mutant tumors were significantly younger and had a significantly poorer prognosis. There was a similar prevalence of p53 mutations in adenocarcinomas of the esophagus (53%) and cardia (58%). In contrast, mutations were relatively uncommon in subcardia adenocarcinomas (one mutant tumor [17%]). The types of mutations found in the esophageal and the cardia cancers were also similar. CONCLUSIONS: Adenocarcinomas of the esophagus and cardia have a similar frequency and spectrum of p53 gene mutations, suggesting that these tumors have a common pathogenesis. Patients with mutations are younger, have signs of more advanced disease, and have a poorer prognosis than patients without mutations.

Adenocarcinoma↗

Cardia carcinoma considered as a distinct clinical entity.

From 1 January 1969 until 31 December 1985, gastric resections were performed in 937 patients with carcinoma of the stomach and 422 patients with carcinoma of the cardia. During this period, the general frequency of cardia carcinoma increased continuously from 6.6 per cent (1969-71) to 37.5 per cent (1984-85) and a corresponding decrease of carcinomas in other sites was observed. Early carcinomas (pT1) of the oesophageal margin (n = 10, 2.4 per cent) were diagnosed less often than early carcinomas in other sites (n = 177, 18.9 per cent). Whereas 51.4 per cent of all resected carcinomas of the stomach showed no lymph node metastases (pN0), only 14.1 per cent of cardia carcinomas belonged to this category. With respect to operative treatment, Laurén's classification which defines the required margin of clearance according to diffuse type (frequency in cardia carcinoma 43 per cent, in other stomach sites 51 per cent), is of great significance. We believe that extensive oesophageal resection is necessary for patients with such difficult tumours. The pattern of metastasis in cardia carcinoma is similar to that of cancer in other stomach sites, the preferred area is the regional lymph nodes on the lesser curve (83 per cent). Histological classification and metastasis pattern show that cardia carcinoma is a type of carcinoma of the stomach which must be treated according to the criteria of stomach cancer surgery.

Adenocarcinoma↗

Marked regional variation in adenocarcinomas of the esophagus and the gastric cardia in the United States.

BACKGROUND: Adenocarcinomas of the esophagus and the gastric cardia recently have experienced rapidly increasing incidence rates. Although these sites frequently are combined, they may have different risk factors. METHODS: The authors compared regional incidence rates of esophageal adenocarcinoma, gastric cardia adenocarcinoma, and esophageal squamous cell carcinoma within the U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registry for the years 1973-1998. RESULTS: Regional incidence rates varied considerably. The Seattle-Puget Sound registry's recent average esophageal adenocarcinoma rates were over twice as high as those of the Utah registry (5.3 vs. 2.4 per 100,000 persons per year; P < 0.01); gastric cardia rates also differed (4.0 vs. 2.8 per 100,000 persons per year; P < 0.01). The incidence rate increase also varied markedly between regions. Since 1974, white male esophageal adenocarcinoma rates increased by 800% in Seattle compared with an increase of only 300% in Utah. In contrast, white male cardia adenocarcinoma rates increased by only 16% in Seattle (from 3.1 per 100,000 persons per year in 1974 to 3.6 per 100,000 persons per year in 1998) compared with 300% in Utah (from 0.7 to 2.2 per 100,000 persons per year). Both types of adenocarcinoma were more common in males and in the white population in all regions, but recent esophageal adenocarcinoma rates for black males in Connecticut were significantly higher than the U.S. black male average (3.1 vs. 0.8 per 100,000 persons per year; P < 0.01) and equaled the rates for the white population in some areas. Esophageal adenocarcinoma rates continued rising for white males through 1998, whereas cardia adenocarcinoma rates stabilized after 1988. CONCLUSIONS: There are substantial regional, temporal, and ethnic differences between esophageal adenocarcinoma incidence rates and gastric cardia adenocarcinoma incidence rates within a single cancer registry system. Thus, these malignancies may differ in important ways and should not be combined routinely in research studies. Individual-level studies are needed to explain these substantial regional and ethnic differences.

Adenocarcinoma↗

Gastroesophageal reflux symptoms in patients with adenocarcinoma of the esophagus or cardia.

BACKGROUND: The efficacy of endoscopic screening for chronic gastroesophageal reflux symptoms of heartburn and regurgitation in adult subjects depends on the sensitivity of this strategy for detecting Barrett esophagus in subjects before the development of adenocarcinoma of the esophagus or cardia. The aim of the current study was to determine what proportion of patients with cancer of the esophagus or cardia would have been candidates for a screening endoscopy before their cancer diagnosis based on the presence and duration of preceding reflux symptoms. METHODS: All patients with adenocarcinoma of the esophagus, adenocarcinoma of the cardia, or long-segment Barrett esophagus presenting for endoscopy at 4 tertiary care and 2 Veterans Affairs (VA) hospitals were given a previously validated questionnaire to determine their recall of common gastroesophageal reflux symptoms. RESULTS: The study population of 375 subjects consisted primarily of 294 (78%) white men. Only 67 of 110 patients (61%) with adenocarcinoma of the esophagus and 8 of 21 patients (38%) with adenocarcinoma of the cardia recalled symptoms of heartburn or regurgitation being present for >5 years before their diagnosis of cancer. Only 40 of 110 patients (36%) with adenocarcinoma of the esophagus and 5 of 21 patients (24%) with adenocarcinoma of the cardia recalled weekly symptoms being present for >5 years before their cancer diagnosis. Of the 244 patients with Barrett esophagus, 170 (70%) recalled heartburn or regurgitation for >5 years and 89 patients (37%) recalled weekly symptoms for >5 years. CONCLUSIONS: Current practice, which uses a screening strategy of performing endoscopy in patients with >5 years of heartburn or regurgitation, can detect Barrett epithelium in only a limited proportion of those patients at risk for developing adenocarcinoma of the esophagus or adenocarcinoma of the cardia.

Adenocarcinoma↗

Localization of TFF3 peptide in human esophageal submucosal glands and gastric cardia: differentiation of two types of gastric pit cells along the rostro-caudal axis.

TFF3 (trefoil factor family 3), which is a major secretory product of the gastric antrum and the intestine, but which is nearly absent in the gastric corpus, plays a key role in the maintenance of mucosal integrity. Here, we have systematically investigated TFF3 expression in the esophagus and gastric cardia by the use of reverse transcription/polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Synthesis of TFF3, but not TFF1 or TFF2, is detectable in esophageal submucosal glands. The stratified squamous epithelium is devoid of TFF synthesis. Prominent TFF3 expression starts at the Z-line with a sharply decreasing gradient toward the cardia. Immunohistochemistry has localized TFF3 to surface mucous cells of the proximal cardia. TFF3 distribution differs characteristically from that of TFF1 (secreted primarily by superficial surface mucous cells), whereas TFF3, together with the mucin MUC5AC, is also found in deeper lying cells toward the isthmus. This is the first report of TFF3 as a typical secretory peptide of esophageal submucosal glands and gastric cardia. The different expression patterns of TFF3 and TFF1 in the cardia suggest a stepwise maturation of surface mucous cells from TFF3/MUC5AC-positive cells close to the isthmus to TFF1/TFF3/MUC5AC-positive cells at the pit. The gradient of TFF3 expression along the gastric rostro-caudal axis defines two types of gastric pit cells: those secreting TFF3 in the cardia and the antrum and those nearly devoid of TFF3 synthesis in the corpus. This indicates the special requirement, particularly of the esophagogastric junction, for TFF3-triggered protection and repair.

Adult↗

Prevalence of intestinal metaplasia in the distal oesophagus, oesophagogastric junction and gastric cardia in symptomatic patients in north-east Italy: a prospective, descriptive survey. The Italian Ulcer Study Group "GISU".

BACKGROUND: Incidence of adenocarcinoma of distal oesophagus and gastric cardia, probably arising from areas of intestinal metaplasia, has been increasing rapidly. AIMS: To define prevalence of intestinal metaplasia of distal oesophagus, oesophagogastric junction and gastric cardia and to evaluate potential associated factors, by means of a prospective multicentre study including University and teaching hospitals, and primary and tertiary care centres. PATIENTS: Each of 24 institutions involved in study enrolled 10 consecutive patients undergoing first-time routine endoscopy for dyspeptic symptoms. METHODS: Patients answered symptom questionnaires and underwent gastroscopy Three biopsies were taken from distal oesophagus, oesophago-gastric junction and gastric cardia, and were stained with haematoxylin and eosin. Specimens were also evaluated for Helicobacter pylori infection. RESULTS: A total of 240 patients (124 male, 116 female; median age 56 years, range 20-90) were enrolled in study. Intestinal metaplasia affected distal oesophagus in 5, oesophago-gastric junction in 19 and gastric cardia in 10 patients. Low-grade dysplasia was found at distal oesophagus and/or oesophago-gastric junction of 3/24 patients with intestinal metaplasia vs 2/216 without intestinal metaplasia (p<0.05). A significant association was found between symptoms and presence of intestinal metaplasia, regardless of location, and between Helicobacter pylori infection and intestinal metaplasia at oesophago-gastric junction. CONCLUSIONS: Intestinal metaplasia of distal oesophagus, oesophagogastric-junction and gastric cardia is found in a significant proportion of symptomatic patients undergoing gastroscopy and is associated with dysplasia in many cases. Although prevalence of dysplasia seems to decrease when specialized columnar epithelium is found in short segment, or even focally in oesophago-gastric junction, these small foci of intestinal metaplastic cells may represent source of most adenocarcinomas of cardia.

Barrett Esophagus↗

Prospective evaluation of intestinal metaplasia and dysplasia within the cardia of patients with Barrett's esophagus.

The prevalence of cardia versus noncardia gastric intestinal metaplasia in patients with Barrett's esophagus was assessed prospectively. Four-quadrant biopsies were obtained from the cardia from 119 consecutive patients with Barrett's esophagus and 64 control patients. Gastric surveillance biopsies were obtained in 108 of the Barrett's patients and 58 control patients. There was a significantly greater prevalence of cardia intestinal metaplasia in short-segment Barrett's (10.2%), but not traditional Barrett's (3.3%), compared to control patients (0%) (P = 0.009). Dysplastic changes were significantly more frequent in the metaplastic epithelium within the esophagus than in the cardia (P < 0.0001). A significantly greater prevalence of noncardia intestinal metaplasia compared to cardia intestinal metaplasia was found in each of the three groups of patients; however, the prevalence of noncardia intestinal metaplasia between short-segment, traditional, and control patients was not significantly different. Cardia intestinal metaplasia was an infrequent finding in patients with Barrett's esophagus and appears to develop independently from that in the remainder of the stomach.

Adenocarcinoma↗

Psychosocial working conditions and the risk of esophageal and gastric cardia cancers.

BACKGROUND: For reasons yet unknown, the incidence of esophageal and gastric cardia adenocarcinoma is increasing rapidly and moderately, respectively. These tumors occur predominantly among males. We hypothesized that stressful psychosocial working conditions might be involved in the etiology of these cancers. OBJECTIVE: To study if job strain, work pace satisfaction and coping are linked to the risk of esophageal or cardia cancers. METHODS: A nationwide Swedish population-based case-control study including 189 and 262 esophageal and cardia adenocarcinoma cases, respectively, 167 esophageal squamous-cell carcinoma cases, and 820 controls. All study subjects were interviewed. The relative risk was estimated using odds ratios, with 95% confidence intervals, adjusted for potential confounders. RESULTS: We found no statistically significant associations between two different measures of job strain and the three cancer types, except between one job strain measure and risk of cardia adenocarcinoma (OR: 2.2; 95% CI: 1.0-4.8). There was a moderately strong association between having a covert coping style, compared to an overt, and risk of both esophageal (OR: 1.8; 95% CI: 1.2-2.8) and cardia adenocarcinoma (OR: 1.5; 95% CI: 1.0-2.3). Among subjects reporting low work pace satisfaction we found an almost 4-fold increased risk of esophageal squamous-cell carcinoma (OR: 3.8; 95% CI: 1.3-11.0), and a nearly 3-fold increased risk of esophageal adenocarcinoma (OR: 2.8; 95% CI: 1.1-7.0). CONCLUSIONS: Work-related stress does not seem to be of importance in the etiology of adenocarcinoma of the esophagus or the gastric cardia. However, the interaction of a stressful work environment and the individual's responses to it may be associated with a moderately increased risk of these cancer types.

Adaptation, Psychological↗

A case-control study of cancers of the gastric cardia in Italy.

In a case-control study of gastric cancer (GC) in high-risk and low-risk areas in Italy, 923 GCs were reviewed by one pathologist and classified according to anatomic site. There were 68 (7.4%) cancers occurring in the gastric cardia. Compared to other GCs, cardia cancer tended to occur more often in males (sex ratio 2.8 vs 1.7) and as intestinal or unclassified histologic types. Nutritional factors for cardia tumours resembled those of other GCs, showing inverse associations with the consumption of raw vegetables, citrus and other fresh fruit, and ascorbic acid, and positive associations with the intake of traditional soups and meat, protein and cholesterol, and preference for salty foods. Cigarette smoking and wine consumption were unrelated to cardia cancer risk, and there was only a weak association with total alcohol intake. Cardia tumours showed a greater familial occurrence of GC than did other sites, with a 7-fold increase in risk for those reporting two first-degree relatives with GC. The authors discuss these findings in view of the rising incidence of adenocarcinomas of the cardia and lower oesophagus that has been reported in some western countries.

Adult↗

A comparative analysis by SAGE of gene expression profiles of Barrett's esophagus, normal squamous esophagus, and gastric cardia.

BACKGROUND & AIMS: The metaplastic process in which the normal squamous epithelium of the distal esophagus is replaced by columnar-lined epithelium, known as Barrett's esophagus (BE), is poorly understood. The aim of this study was to define, analyze, and compare transcription profiles of BE, normal cardia epithelium, and squamous epithelium to gain more insight into the process of metaplasia and to identify uniquely expressed genes in these epithelia. METHODS: Serial analysis of gene expression was applied for obtaining transcription libraries of biopsy specimens taken from a BE-affected patient with intestinal type of metaplasia and from normal squamous and gastric cardia epithelia. Validation of results by reverse-transcription polymerase chain reaction and immunoblotting was performed using tissues of 20 patients with BE. RESULTS: More than 120,000 tags were sequenced. Between BE and squamous 776, and between BE and gastric cardia 534 tags were significantly differentially expressed (P < .05, pairwise comparison). In contrast, squamous compared with gastric cardia epithelia showed significant differential expression of 1316 tags. The most up-regulated genes in BE compared with squamous epithelium were trefoil factors, annexin A10, and galectin-4. Each of the epithelia showed a unique cytokeratin expression profile. CONCLUSIONS: This study provides a comparison of the transcriptomes of BE, squamous epithelium, and gastric cardia epithelium. BE proves to be an incompletely differentiated type of epithelium that shows similarities to both normal squamous and gastric cardia epithelia. In addition, several uniquely expressed genes are identified. These results are a major advancement in understanding the process of metaplasia that leads to BE.

Adult↗

Mortality trend from cancer of the gastric cardia in The Netherlands, 1969-1994.

BACKGROUND: Time trends of cancer of the gastric cardia differ between populations and the reasons are not fully understood. The object of this study was to investigate the occurrence of cancer of the gastric cardia in descriptive relation to age at death, calendar period, birth cohort and gender in the Netherlands between 1969 and 1994. METHODS: Data on the number of people with cancer of the gastric cardia as the underlying cause of death from 1969 to 1994 were obtained from annual publications by the National Causes of Death Registry of Statistics Netherlands. To estimate the separate effects of age, calendar period and birth cohort on the trend in mortality, a simultaneous analysis of these factors was performed using a log-linear Poisson model. RESULTS: In 1969, the mortality rates from cancer of the gastric cardia for males and females per 100,000 people were 2.1 and 1.1; in 1994 the mortality rates were 1.5 and 0.7, respectively. Examination of the time trend suggested that mortality for cancer of the gastric cardia may reflect a period phenomenon, although a cohort effect may have also contributed to the observed time trend. Furthermore, more males than females died from cancer of the gastric cardia. The difference was most striking in the younger age categories. CONCLUSION: In this Dutch population, the age-period-cohort-gender analysis indicated that the mortality rates decreased after the period 1975-1979 which might be explained by a decrease in exposure to risk factor(s) or an increase in exposure to protective factor(s).

Adult↗

Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries.

BACKGROUND: In many western countries an increase in incidence of adenocarcinoma of the oesophagus and/or gastric cardia have been reported. The aim of this study was to describe and compare trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in several areas of Europe, 1968-1995, using Eurocim (a database of cancer incidence and mortality data from 95 European cancer registries). METHODS: Time-trends in age-standardized incidence rates of adenocarcinomas of the oesophagus and gastric cardia are described in 11 population-based cancer registries from 10 countries in North, South, East, West and Central Europe, 1968-1995. The statistical significance of the time-trends in incidence was assessed using Poisson regression analysis. RESULTS: An increase in incidence of adenocarcinomas of the oesophagus and gastric cardia was observed in Northern Europe (Denmark), Southern Europe (Italy, Varese), Eastern Europe (Slovakia) and Western Europe (England and Wales, Scotland). In Central Europe (Switzerland, Basel) and in the cancer registries of Iceland (Northern Europe), France, Bas-Rhin and Calvados, Southern Ireland, and the Netherlands, Eindhoven (Western Europe) no rise in incidence was observed. The increase in incidence of adenocarcinomas of the oesophagus and gastric cardia was accompanied by a decrease in incidence of both adenocarcinomas and non-adenocarcinomas of the non-cardia part of the stomach in almost all of the 11 cancer registries studied. Increased histological verification of tumours of the oesophagus and stomach and improvement in precision of histological diagnosis may partly explain the increase in incidence of adenocarcinomas in some registries. CONCLUSIONS: This study, using Eurocim data, supports the findings from other time-trend studies of population-based cancer registries in western countries.

Adenocarcinoma↗

Opposing risks of gastric cardia and noncardia gastric adenocarcinomas associated with Helicobacter pylori seropositivity.

BACKGROUND: Colonization with Helicobacter pylori is a risk factor for gastric adenocarcinoma, but the magnitude of this association and its relationship to anatomic location of the cancer, duration of follow-up, age at diagnosis, histologic subtype, and H. pylori strain differences are less clear. We conducted a prospective nested case-control study of H. pylori serology to address these questions. METHODS: Case and control subjects were selected from the 29,133 50- to 69-year-old males recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. At baseline, detailed demographic data and a serum sample were collected. From 1985 to 1999, 243 incident cases of gastric adenocarcinoma were diagnosed in cohort members. Serum samples from 234 case subjects (173 with noncardia gastric cancers and 61 with gastric cardia cancers) and 234 age-matched control subjects were assayed for antibodies against H. pylori whole-cell and CagA antigens. We fit conditional logistic regression models to estimate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of H. pylori seropositivity, defined as seropositivity to either whole-cell or CagA antigens, with noncardia gastric and gastric cardia cancers. All statistical tests were two-sided. RESULTS: H. pylori seropositivity was strongly associated with the risk of noncardia gastric cancer (adjusted OR = 7.9, 95% CI = 3.0 to 20.9) but was inversely associated with the risk of gastric cardia cancer (adjusted OR = 0.31, 95% CI = 0.11 to 0.89). H. pylori seropositivity rates did not vary statistically significantly by length of follow-up, age at diagnosis, or histologic subtype. A calculation of rates showed that the absolute risks of noncardia gastric and cardia gastric adenocarcinomas in the H. pylori-positive participants of this cohort would be 63 and 12 per 100,000 person-years, respectively, whereas corresponding rates in H. pylori-negative participants would be 8 and 37 per 100,000 person-years, respectively. CONCLUSION: H. pylori is a strong risk factor for noncardia gastric cancer but is inversely associated with the risk of gastric cardia cancer. These findings bolster the hypothesis that decreasing H. pylori prevalence during the past century may have contributed to lower rates of noncardia cancer and higher rates of cardia cancer in Western countries.

Adenocarcinoma↗

Comparative study of intestinal metaplasia and mucin staining at the cardia and esophagogastric junction in 225 symptomatic patients presenting for diagnostic open-access gastroscopy.

OBJECTIVE: Adenocarcinoma around the esophagogastric junction (EGJ) is increasing in incidence, and is frequently associated with areas of macroscopic or microscopic intestinal metaplasia (IM). The aim of this study was to define the incidence and type of metaplastic changes in the cardia and at the EGJ in symptomatic patients in whom there was no endoscopic columnar segment. METHODS: Patients attending for open-access gastroscopy had three sets of endoscopic biopsies taken at 3-cm intervals, from cardia, EGJ, and distal esophagus. Hematoxylin and eosin, Alcian blue/PAS (AB/PAS), and high-iron diamine/Alcian blue (AB/HID) were used to define and characterize IM. RESULTS: Of 225 patients, eight (4%) had carcinoma, eight (4%) had conventional long-segment Barrett's esophagus, 15 (7%) showed endoscopic short-segment Barrett's change, with no endoscopic Barrett's in 194 (86.2%). Of the latter, 34 (17.5%) had IM at the EGJ, and nine (4.6%) had IM at the cardia on hematoxylin and eosin. Acid mucin stains were positive at the EGJ in 135 (69.6%) and at the cardia in 75 (38.7%). Metaplasia at the EGJ was associated with sulphomucins (p < 0.0001) and involved the surface glandular epithelium (p < 0.0001) more frequently than the cardia. Metaplasia was not related to reflux symptoms, hiatus hernia, or endoscopic esophageal inflammation. Ninety percent of those with IM detectable by hematoxylin and eosin were taking acid suppression, compared with 72.8% overall. CONCLUSIONS: Intestinal metaplasia is very common at the esophagogastric junction and gastric cardia, with marked differences in incidence and characteristics of mucin staining between the two sites. The relationship of intestinal metaplasia to the development of carcinoma is yet to be determined.

Adolescent↗

Gastric cardia inflammation: role of Helicobacter pylori infection and symptoms of gastroesophageal reflux disease.

OBJECTIVE: Although high prevalences of both chronic inflammation (carditis) and intestinal metaplasia at the gastric cardia have been reported, the pathogenesis is still unclear. This study assesses the role of Helicobacter pylori (H. pylori) infection and symptoms of gastroesophageal reflux disease (GERD) in these histological alterations. METHODS: Consecutive patients who underwent upper endoscopy were enrolled in the study, irrespective of their symptoms. Patients previously treated for H. pylori infection and those using proton pump inhibitors were excluded. Two biopsies were performed in the antrum, two in the gastric body, and two at the gastric cardia. All biopsies were used to look for H. pylori and for histological assessment. RESULTS: A total of 133 patients were enrolled. Carditis and intestinal metaplasia at the cardia were detected in 100 (75.2%) and in 18 (13.5%) patients, respectively. The H. pylori infection rate was significantly higher in patients with carditis than in those without it (87/100 vs 7/33; p < 0.0001), and was higher in those with intestinal metaplasia at the cardia than in those without it (17/94 vs 1/39; p = 0.03). Conversely, the prevalence of GERD symptoms was not significantly different between patients with and without carditis (34/100 vs 16/33; p = NS), and between those with and without intestinal metaplasia (5/50 vs 13/83; p = NS). Interestingly, the prevalence of both H. pylori (64/94 vs 39/94; p = 0.0005) and intestinal metaplasia (18/133 vs 4/133; p = 0.0042) in the gastric cardia was significantly higher than that in gastric body. CONCLUSION: According to our study data, the gastric cardia is frequently infected with H. pylori with consequent development of both carditis and intestinal metaplasia, whereas GERD does not seem to be involved in these histological changes.

Cardia↗