[Association of neuromuscular diseases of the cardia (cardiospasm and achalasia of the cardia) with gastroduodenal ulcers].
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BACKGROUND AND AIM: Presence of intestinal metaplasia in the gastric cardia (cardia intestinal metaplasia, CIM) has been reported in 5-34% of patients undergoing upper endoscopy and is a topic of interest given the rising incidence of cancer in this location. The aim of this article is to determine the prevalence of CIM in biopsies obtained from two separate locations within the gastric cardia. METHODS: Patients presenting to the endoscopy unit for upper endoscopy for any symptoms were invited to participate in the study. The biopsy protocol included: eight biopsies from the gastric cardia, four from upper cardia (forceps across the squamocolumnar junction), four from lower cardia (within 1 cm of upper cardia), and four each from the gastric body and antrum. All cardia biopsies were stained with hematoxylin and eosin (H&E) and alcian blue at pH 2.5 for the presence of goblet cells and the body/antrum biopsies were stained with Steiner silver stain for Helicobacter pylori detection. In patients testing negative for H. pylori by histology, a serology test was performed. RESULTS: Sixty-five patients have been evaluated by this protocol; median age 54 yr (range: 34-81 yr), 63 males, 53 Caucasians, and 12 African Americans. The detection of CIM was as follows: upper cardia only, 7, both upper and lower cardia, 5, and lower cardia only, 7. Thus, CIM was detected in 12 patients (18%) in the upper cardia biopsies, in 12 patients (18%) in the lower cardia; overall prevalence of CIM was 29% (19 patients). Fifty-eight percent of CIM patients tested positive for H. pylori by either histology or serology. The addition of serology allowed for the detection of eight additional H. pylori-positive CIM patients. CONCLUSIONS: The prevalence of CIM in this study was similar (18%, four biopsies) at each location; however, if both locations were considered (eight biopsies), the prevalence increased to 29%. Thus, CIM prevalence may vary depending on the number of biopsies obtained as well as on the location of biopsies. Use of additional testing detects more patients who are H. pylori positive and should be performed if association of CIM with H. pylori is contemplated. Future endoscopic studies of the gastric cardia should specify the location of biopsies, the number of biopsies obtained, and the tests used to diagnose H. pylori.
OBJECTIVE: Little is known about the normal anatomical patterns of acid exposure at the gastric cardia and its relationship to acid refluxed into the esophagus. In this study, pH patterns of the gastric cardia at baseline and during esophageal reflux were determined using ambulatory pH monitoring in normal volunteers. METHODS: Ten volunteers with normal distal esophageal acid exposure underwent 18-h ambulatory pH monitoring studies with pH leads placed 5 cm proximal, 5 cm distal, and 10 cm distal to the proximal border of the LES. RESULTS: Median LES length and pressure were 3.5 cm (range 2.5-4.5) and 28 mm Hg (18-48), respectively. Total cardia acid exposure was 45.2% with a wide range (1.0-76.1%) and was significantly different from esophagus (1.6; 0.2-5.9%) and stomach (87.5; 76.0-95.4%) (p < 0.001). Upright (49.8; 1.5-77.0%) and recumbent (31.4; 0-75.1%) cardia acid exposure were not different. Patterns of baseline cardia acid exposure were characterized by: 1) prolonged periods of no acid exposure; 2) isolated brief episodes of acid exposure with stepwise clearances similar to the esophagus; 3) sustained repetitive vacillations between low and neutral pH; or 4) prolonged periods with pH <4 in the cardia. The majority (86.4%) of cardia acid exposures were < 1 min. in duration most consistent with patterns B and C. Esophageal reflux occurred during sustained repetitive vacillations in cardia pH (48%), prolonged periods of cardia acid exposure (33%), or with single transient exposures of acid reflux into the cardia then the esophagus (19%) with stepwise clearance in both. CONCLUSION: 1) Cardia acid exposure is present at a level intermediate between that of the esophagus and stomach; it is most commonly transient but may be continuous, similar to the stomach. 2) Refluxed esophageal acid originates from a pool of acid distal to the cardia that then bathes the cardia in sustained, repetitive, or single acid exposures and occasionally travels into the esophagus.
BACKGROUND: Although the incidence of adenocarcinoma of the stomach has decreased over the past several decades, gastric cardia carcinoma has increased over the same period. METHODS: The clinicopathologic characteristics and immunohistochemical staining results of 21 proteins were investigated in 165 patients with cardia carcinoma, including 74 patients with true cardia carcinoma and 91 patients with subcardia carcinoma, and the results were compared with the results from 564 patients with noncardia carcinoma. RESULTS: In the clinicopathologic analysis, patients who had cardia carcinoma tended to have tumors with poorly differentiated histology according to the World Health Organization classification system (P = 0.012), diffuse type according to the Lauren classification system (P = 0.049), and advanced pathologic TNM stage (P < 0.001). On immunohistochemical staining, loss of the p16 (P = 0.038) and smad4 (P < 0.001) tumor suppressor genes was more frequent in cardia carcinoma than in noncardia carcinoma. Carcinoembryonic antigen and CD44 overexpression were more frequent in patients with cardia carcinoma (P < 0.05). Conversely, patients who had cardia carcinoma exhibited less frequent expression of MUC1 (P = 0.008) and MUC5AC (P = 0.006) compared with patients who had noncardia carcinoma. Epstein-Barr virus infection was more common in patients with cardia carcinoma (P < 0.001). In the survival analysis, the patients with cardia carcinoma had a poorer prognosis. In the multivariate analysis, tumor location in the cardia was confirmed as an independent, poor prognostic factor in patients with gastric carcinoma. CONCLUSION: Cardia carcinoma and noncardia carcinoma differed in their clinicopathologic characteristics and in their alterations of gene expression, as evaluated by immunohistochemistry. The current results support the hypothesis that cardia carcinoma forms a specific category of gastric carcinoma that is distinct from noncardia carcinoma.
BACKGROUND: Adverse events associated with the thermal ablation of Barrett's esophagus (BE) include the generation of gastric mucosa buried beneath the neosquamous regrowth, and unrecognized development and growth of adenocarcinomas. No reports exist regarding the endoscopic appearance and histology of the cardia before and after BE ablation. The aim of our study was to assess the relative frequency of the occurrence of visible endoscopic and histologic changes in the cardia, before and after complete BE ablation. METHODS: A subset analysis of patients with uncomplicated BE, BE with dysplasia, or early carcinoma, who had been enrolled into one of 4 ongoing prospective studies of mucosal ablation, was examined. Eighty-two patients were identified who entered a BE ablation study, with 75 of these completing BE mucosal ablation. Cardia biopsy specimens were taken in all patients before ablation and serially after BE ablation. Cardia histology was graded by using the modified Sydney System for gastritis. RESULTS: Before ablation, cardia nodules were noted in 3, cardia intestinal metaplasia (IM) in 7 (8.5%), and none harbored cardia dysplasia. Postablation surveillance ranged from 3 to 75 months (mean 31.1 months [19.5]). Six subjects (8%) developed cardia nodules during surveillance; cardia IM was found in 21(28%), with 17 of these being a new finding (incidence of 25%). Cardia low-grade dysplasia incidence was 1.3% and high-grade dysplasia was 4% after BE ablation. CONCLUSIONS: The pathophysiology of the abnormal cardia histology and the endoscopic lesions (nodules) is unclear, but endoscopic surveillance of not only the neosquamous epithelium but also the cardia should be considered after ablation, especially in those high-grade dysplasia and early adenocarcinoma BE patients.
Anatomic and clinical data suggest that the gastroesophageal junction or cardia in patients with gastroesophageal reflux disease GERD) may be dilated. We hypothesized that anatomic dilatation of the cardia induces a lower esophageal sphincter dysfunction that may be corrected by narrowing the gastroesophageal junction (i.e., calibration of the cardia). We measured the perimeter of the cardia during surgery in control subjects and patients with GERD and Barrett's esophagus. We then tested our hypothesis in a mechanical model. The model was based on a pig gastroesophageal specimen with perpendicularly placed elastic bands around the cardia simulating the action of the "sling" and "clasp" fibers. "Dilatation" of the cardia was induced by displacing the sling band laterally and decreasing its tension. "Calibration" of the cardia was performed by reapproximation of the sling band toward the esophagus but maintaining the same tension as the dilated model. In the "basal," "dilated," and "calibrated" states, the perimeter of the cardia was noted and rapid mechanized pullback manometry with a water-perfused catheter was performed. The opening pressure was determined, and three-dimensional sphincter pressure images were analyzed. The average cardia perimeter was 6.3 cm in control subjects, 8.9 cm in GERD patients, and 13.8 cm in patients with Barrett's esophagus. The arrangement of the bands in the experimental model generated a manometric high-pressure zone similar to that in the human lower esophageal sphincter. Dilatation of the cardia resulted in a decrease in the resting pressure, length, and vector volume of the high -pressure zone, and reduced the opening pressure. Calibration restored the resting and opening pressure, and normalized the three-dimensional pressure image. In patients with GERD and Barrett's esophagus, the cardia is dilated. Our model supports the hypothesis that lower esophageal sphincter function is compromised by anatomic dilatation of the cardia and can be restored by approximation of the "sling" fibers toward the lesser curvature "clasp" fibers). This provides evidence for a correlation between gastroesophageal sphincter dysfunction in reflux disease and its correction by antireflux surgery.
BACKGROUND & AIMS: Whether inflammation of the cardia indicates gastroesophageal reflux disease (GERD) and/or is a manifestation of pangastritis caused by Helicobacter pylori infection is unknown. The aim of this study was to evaluate the relationship between cardia inflammation, H. pylori infection, and cardia intestinal metaplasia in patients with and without GERD. METHODS: Patients with GERD were compared with controls undergoing endoscopy for a variety of other conditions. Endoscopic biopsy specimens from the distal esophagus and cardia, fundus, and antrum were evaluated for inflammation, H. pylori infection, and intestinal metaplasia. RESULTS: Neither the prevalence of H. pylori infection (controls, 48%; GERD, 41%) nor cardia inflammation (controls, 41%; GERD, 40%) differed between groups. All 11 controls and 22 of 23 patients with GERD (96%) and cardia inflammation had H. pylori infection. Esophagitis was more common among GERD patients (33%) than controls (7%; P = 0.01). Cardia intestinal metaplasia was more common among controls (22%) than GERD patients (3%; P = 0.01); all had cardia inflammation, 7 had H. pylori infection, and 6 had metaplasia elsewhere in the stomach. CONCLUSIONS: The prevalence of cardia inflammation is similar in patients with and without GERD and is associated with H. pylori infection (P < 0.001). Cardia intestinal metaplasia is associated with H. pylori-related cardia inflammation (P = 0.01) and intestinal metaplasia elsewhere in the stomach, indicating that it is distinct from Barrett's esophagus.
BACKGROUND: Reports of dramatic increases in gastric cardia cancer incidence warrant concern. However, the recent introduction of a separate diagnostic code, the lack of a consensus definition of the cardia area, and the accelerating interest in cardia cancer may affect classification practices. Little is known about the magnitude of cardia cancer misclassification in large cancer registries. METHODS: In a well-defined Swedish population (1.3 million), we uniformly classified all patients with newly diagnosed gastric adenocarcinoma (from 1989 through 1994) with respect to gastric subsite, and we used this patient group as our gold standard. We then evaluated the completeness of the Swedish Cancer Registry in registering gastric adenocarcinomas against this gold standard and, further, assessed the completeness of cardia cancer registration and the rate of falsely included cases to estimate the potential impact on observed incidence trends. RESULTS: Our gold standard contained 1337 case subjects with gastric adenocarcinoma. Overall, the Swedish Cancer Registry was 98% complete with regard to gastric adenocarcinomas and had a 4% rate of falsely included cases. The completeness of coding cardia cancer was only 69%, and the positive predictive value for cardia cancer was 82%, with no improvement over time. CONCLUSIONS: Although overall completeness of gastric cancer registration by the Swedish Cancer Registry was excellent, accuracy in registering cardia tumors was surprisingly low. Our estimates suggest that true cardia cancer incidence could be up to 45% higher or 15% lower than that reported in the Cancer Registry. This margin of error could accommodate the observed increase in cardia cancer in Sweden. Therefore, secular trends in cardia cancer incidence should be interpreted cautiously.
OBJECTIVE: Barrett's esophagus has been associated with adenocarcinoma of the esophagogastric junction and gastric cardia. The purpose of this study was to determine whether patients with Barrett's esophagus have a higher prevalence of intestinal metaplasia involving the gastric cardia than those without Barrett's esophagus. METHODS: Two groups of patients were compared for the prevalence of intestinal metaplasia of the gastric cardia. Group 1 included 50 patients with well-defined Barrett's esophagus who were being followed in an endoscopic surveillance program. Group 2 consisted of 104 individuals participating in a separate study identifying the prevalence of cardia intestinal metaplasia in patients undergoing elective upper endoscopy. Both groups had biopsy specimens taken from the gastric cardia. Eleven patients in group 2 were found to have Barrett's esophagus and were excluded from the analysis. Histological evidence of intestinal metaplasia was defined as specialized columnar epithelium containing goblet cells staining with Alcian blue at pH 2.5. RESULTS: The prevalence of cardia intestinal metaplasia in the 50 patients in group 1 (Barrett's esophagus) was 22%, whereas the prevalence in the 93 patients in group 2 (no Barrett's esophagus) was 24%, which was not a statistically significant difference. A significant difference between groups still could not be identified when the results were examined with regard to equal number of biopsy specimens taken. None of the patients in either group had dysplasia identified within the cardia intestinal metaplasia. CONCLUSIONS: Patients with Barrett's esophagus do not have a higher prevalence of intestinal metaplasia of the gastric cardia than those presenting for routine endoscopy. Although intestinal metaplasia of the gastric cardia is a relatively common finding, dysplasia is uncommon. Therefore, we suggest that screening biopsy specimens of the gastric cardia in patients with Barrett's esophagus be limited to study protocols at this time. In addition, we believe that these data raise the question of whether a true association exists between Barrett's esophagus and gastric cardia cancer.
OBJECTIVES: Helicobacter pylori has a predilection for antral colonization. Local acid production is the major determinant of colonization. Because production is low in the antrum and cardia, H. pylori should also colonize the cardia. We therefore investigated the histologic pattern of gastritis and the prevalence of H. pylori in the cardia compared with the antrum and corpus. METHODS: From 135 H. pylori-infected patients with gastritis, ulcer disease, or reflux esophagitis, biopsies were obtained from the antrum, corpus, and cardia. The prevalence, topography, and histologic parameters of gastritis were examined. RESULTS: All 135 patients had active antral H. pylori gastritis: in the cardia, 132 of these patients (97.7%) showed active gastritis, and 124 patients (91.9%) had H. pylori visible on staining. Gastritis of the cardia in most patients resembled antral gastritis, but the density of bacteria and the inflammatory responses were less marked. The most striking finding in the cardia of patients with gastroesophageal reflux was a lower density of bacteria compared with antrum and corpus. Intestinal metaplasia was found in 32 patients in antral mucosa (23.7%) versus 28 patients in the cardia (20.7%), versus 11 patients in the corpus (8.1%), and was multifocal in 17 patients (12.6%). CONCLUSIONS: H. pylori gastritis commonly involves the cardia. The histologic density of the bacteria and inflammatory responses are lower than in the antrum. Intestinal metaplasia in the cardia is a common finding in H. pylori gastritis. The cause of the lower bacterial density in the cardia of patients with reflux esophagitis needs further investigation.
BACKGROUND AND AIMS: Intestinal metaplasia (IM) at the cardia is likely to be a precursor of cardia cancer. Previous work has shown that it is associated with chronic inflammation attributable to either gastro-oesophageal reflux disease (GORD) or Helicobacter pylori infection. An alternative aetiological factor is bile reflux. Duodenogastric reflux brings about histological changes in the gastric mucosa that can be graded and used to calculate a bile reflux index (BRI). We used the BRI to assess whether reflux of bile plays a part in the development of cardia IM. METHODS: Histological changes in simultaneous gastric antrum and cardia biopsies from 267 dyspeptic patients were independently graded by two pathologists. The association between cardia IM and age, sex, clinical group, H pylori status, increased BRI (>14), and inflammation at the cardia were evaluated using logistic regression. RESULTS: A total of 226 patients had adequate cardia and antral biopsies; 149 had GORD and 77 had non-ulcer dyspepsia. Cardia IM was present in 66 (29%) patients, of whom 28 (42%) had complete IM. Increasing age, male sex, chronic inflammation, and a high BRI emerged as significant independent associations with cardia IM. Clinical group and H pylori status were not independent risk factors. CONCLUSIONS: Histological evidence of bile reflux into the stomach is associated with cardia IM. This could have an important bearing on carcinogenesis at this site.
AIM: The incidence of gastric cardia cancer has greatly increased in the past 2-3 decades, however, the risk factors for the disease are still not clearly understood. The investigations among Chinese population on the risk factors of gastric cardia cancer were also scarcely reported. We therefore conducted a case-control study in Fujian province, China, to investigate the potential risk and protective factors of this disease. METHODS: 191 cardia and 190 non-cardia gastric cancer cases, and a total of 222 control cases were included in this study. Standard questionnaires were used in collecting epidemiological factors and the data were then analyzed by the unconditional logistic regression model. RESULTS: As the factors such as age, gender, smoking, alcohol consumption, and family history of gastric cancer were controlled, a multivariable analysis was conducted, which revealed that there was a significant correlation between the dietary habits such as irregular meal, over and fast eating, and the gastric cardia cancer with the odds ratios (ORs) of 4.2 (95 % confidence interval: 2.3-7.7), 4.7 (2.1-10.8), and 2.7 (1.3-5.3) respectively. Other correlations were also observed between the gastric cardia cancer and the consumption of salty fish or pickled vegetable, smoking, and the family cancer history with the ORs of 5.5 (1.4-19.5), 1.8 (1.0-3.0), 2.1 (1.3-3.5), and 3.8 (2.3-6.2) respectively. In contrast, the negative correlations were found existing between the intake of fresh vegetables and fruits, the use of refrigerator, and the gastric cardia cancer, with the ORs of 0.4 (0.2-0.9), 0.2 (0.1-0.5), and 0.2 (0.1-0.4), respectively. However, dietary habits were associated less with non-cardia gastric cancer compared with its cardia counterpart. CONCLUSION: Dietary habits might be one of the risk factors for the cardia carcinogenesis among Chinese population.
BACKGROUND/AIMS: We aimed to investigate the prevalence of intestinal metaplasia in the cardia of a patient group with high incidence of Helicobacter pylori infection presenting for elective upper endoscopy. We also re-evaluated the relation between intestinal metaplasia in the cardia and gastroesophageal reflux disease, smoking, alcohol history, H. pylori infection, Barrett's esophagus and intestinal metaplasia elsewhere in the stomach. METHODOLOGY: Sixty patients presenting for elective upper endoscopy were included in this study. Prior to undergoing endoscopy each patient was questioned with regard to the clinical indication and symptoms including heartburn, regurgitation, and dysphagia. In addition, a smoking and alcohol history were recorded. Endoscopic biopsies: 1) one from the midantrum on the lesser curvature, 2) one from the incisura angularis, 3) one from the mid-corpus on the lesser curvature, 4) one from the columnar side of the squamocolumnar junction, 5) one from the squamous side of the squamocolumnar junction, 6) one from 2 cm distal to the esophagogastric junction, 7) one from across the squamocolumnar junction. Slides were stained using a combination of hematoxylin-eosin with Alcian blue at pH 2.5 for intestinal metaplasia. Each specimen was examined for the presence of H. pylori. RESULTS: The prevalence of H. pylori infection was 63%. Prevalence of the H. pylori infection was significantly lower in the patients with intestinal metaplasia of the cardia than in the patients without intestinal metaplasia of the cardia (P = 0.025). There was a positive correlation between the age of the patients and having intestinal metaplasia of the cardia (r = 0.286, P = 0.008). There was no relationship between intestinal metaplasia of the cardia and pyrozis, regurgitation, dysphagia, history of alcohol and smoking esophagitis determined by endoscopy or histopathology, sex, intestinal metaplasia elsewhere in the stomach (P > 0.05). CONCLUSIONS: The incidence of the intestinal metaplasia of the gastric cardia in Turkey is less than that of western countries. Intestinal metaplasia of the gastric cardia negatively correlates with H. pylori infection. And there was no relationship between gastric cardia intestinal metaplasia and reflux disease. Further investigations are needed for determining the premalign lesion and etiologic factors for cancer of the gastric cardia.
OBJECTIVE: Although the incidence of gastric adenocarcinoma in the U. S. is declining, the incidence of cancer localized to the gastric cardia has risen dramatically. It is not yet clear whether cancer of the gastric cardia arises from a premalignant lesion such as intestinal metaplasia (IM). The purpose of this study was to determine the prevalence of IM involving the cardia in patients presenting for elective EGD, and evaluate potential associated factors. METHODS: During a 7 month period patients referred for elective EGD at the Tucson VA Medical Center were invited to participate in the study. Prior to EGD each patient was surveyed with regard to GERD symptoms and smoking and alcohol history. During EGD note was made of the presence of esophagitis, hiatus hernia, and Barrett's-appearing mucosa. The esophagogastric junction (EGJ) was defined as the end of the tubular esophagus coinciding with the proximal heads of the gastric folds. Seven biopsies were taken from specific sites in the antrum, angularis, cardia, and EGJ. Biopsy specimens were stained with a combination of H & E and Alcian blue at a pH of 2.5. Histologic evidence of IM was defined as columnar-type epithelium including goblet cells staining with Alcian blue. Patients were also evaluated for H. pylori infection by histologic and serologic examinations. RESULTS: There were 104 patients (99 male, 5 female) with a mean age of 61.6 years. Twenty-four (23%) were found to have IM involving the gastric cardia, although none of these had dysplasia. Eleven patients (11%) had Barrett's esophagus; however, only 2 of these had concomitant IM of the cardia. On the other hand, 9 of the 24 with IM of the cardia had concomitant IM elsewhere in the stomach. Forty-nine patients (47%) were found to be positive for H. pylori infection and there was a significant association between H. pylori infection and IM of the gastric cardia (p = 0.03). CONCLUSIONS: These data show that IM of the gastric cardia is a relatively common finding and is associated with H. pylori infection. Although dysplasia was not identified, long-term follow-up studies will be necessary to determine the incidence of dysplasia or adenocarcinoma developing from IM of the cardia.
The incidence rates of gastric cardia and esophageal adenocarcinomas are increasing, but data suggest that carriage of cagA(+) Helicobacter pylori strains may protect against development of Barrett's esophagus and esophageal adenocarcinoma. Our aims were to examine the relationship between pre-malignant and malignant lesions in the gastric cardia and serum antibodies to H. pylori antigens in patients with and without complications of Barrett's esophagus. The prevalence of carditis was 40% in controls compared with 13% in patients with complicated or uncomplicated Barrett's esophagus and cardia adenocarcinoma (p < 0.001). Cardia intestinal metaplasia (IM) and atrophy were present and concordant in 28% of controls but less frequent in patients with Barrett's alone or with dysplasia/adenocarcinoma (0% for each, p < 0.001). Carriage of cagA(+) strains was present in 34% of patients with carditis and significantly associated with increased frequency and severity of cardia inflammation, IM, and atrophy but not with adenocarcinoma. IgA and HspA seropositivity were significantly increased in H. pylori-colonized patients with carditis compared to persons with normal cardia histology (p </= 0.005) but not in persons with esophageal disease or cardia adenocarcinoma. We conclude that carriage of cagA(+) H. pylori strains and induction of particular serological responses are significantly associated with marked histological findings in the gastric cardia but not with adenocarcinoma of either the gastric cardia or esophagus.
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.
BACKGROUND: The incidence of adenocarcinoma of the proximal stomach (cardia) is increasing. The pathophysiological processes underlying this trend are unclear. Normal cell turnover depends on cell proliferation being in balance with programmed cell death or apoptosis. It has been well documented that excessive proliferation potentiates the effects of any carcinogen that targets DNA. It is therefore accepted that excessive proliferation is a risk factor for subsequent neoplasia development. AIMS: To compare apoptosis and proliferation in normal cardia tissue, carditis, and cardia intestinal metaplasia, and to determine the effect of Helicobacter pylori infection and gastro-oesophageal reflux disease. METHODS: Biopsies from the cardia were obtained from consecutive dyspeptic patients and asymptomatic controls at the time of gastroscopy. Samples were assessed histologically and classified as normal, carditis, or cardia tissue with intestinal metaplasia. All samples were then examined, employing immunohistochemical techniques, for the presence of proliferating and apoptotic cells. RESULTS: A total of 76 histological specimens were examined. There was a statistical significant difference in the proliferation index between controls and both carditis and cardia intestinal metaplasia, and also between carditis and cardia intestinal metaplasia. In contrast, there was a significant increase in the apoptotic index for carditis compared with controls, while that of intestinal metaplasia did not differ from controls. As a result, comparison of the apoptotic/proliferation ratios for each group revealed that, for both carditis and cardia intestinal metaplasia, the apoptotic index/proliferation index ratio is reduced significantly compared with controls, but as a result of different mechanisms. CONCLUSION: This study demonstrates that individuals with carditis and cardia intestinal metaplasia have alterations in epithelial cell kinetics. In particular, it shows that there is a persistent imbalance between proliferation and apoptosis, which may represent malignant potential.
BACKGROUND/AIMS: The putative influence of tumor location on the biologic behavior of gastric carcinomas remains controversial. The aim of this study was to investigate if carcinomas arising in the three types of gastric mucosa (cardia, fundus/body and antrum) have different clinical and pathologic profiles and carry a different prognosis. METHODS: Three hundred and two patients with cardia or gastric carcinoma resected between 1984 and 1996 were retrospectively studied. Cases were divided in three groups according to tumor location: cardia (n = 80); fundus/body (n = 60); antrum (n = 162). The three groups were crosstabulated with clinic and pathologic parameters, such as age, sex, macroscopy, histology, desmoplasia, tumor size, depth of tumor wall penetration, nodal status, venous invasion and stage. Survival rates were calculated for the three locations according to the aforementioned parameters. Univariate survival analysis and Cox regression were performed for each location. RESULTS: Cases from the cardia and fundus/body were similar and distinct from antrum cases according to macroscopy, tumor size, depth of wall penetration, venous invasion, nodal status and stage. Cases from fundus/body were similar to antrum cases and distinct from cardia cases according to gender and Laurén's classification. An overall difference in survival between the three locations was observed (p = 0.006). Cumulative survival was better for patients with carcinomas in the antrum than in the cardia (p = 0.04) and in the fundus/body (p = 0.003); no significant differences were observed in survival between cardia and fundus/body carcinoma cases. Cox regression identified stage and venous invasion as prognostic factors for patients with carcinomas in the three locations. In the group of cardia tumors, older patients had a worse outcome and in the group of fundus/body carcinomas, large tumors were associated with a poorer survival. CONCLUSIONS: Our results show that cardia carcinoma and antrum carcinoma are distinct gastric carcinoma entities whereas fundus/body carcinoma shares some characteristics from both entities.