Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma.
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BACKGROUND: The causes of adenocarcinomas of the esophagus and gastric cardia are poorly understood. We conducted an epidemiologic investigation of the possible association between gastroesophageal reflux and these tumors. METHODS: We performed a nationwide, population-based, case-control study in Sweden. Case ascertainment was rapid, and all cases were classified uniformly. Information on the subjects' history of gastroesophageal reflux was collected in personal interviews. The odds ratios were calculated by logistic regression, with multivariate adjustment for potentially confounding variables. RESULTS: Of the patients interviewed, the 189 with esophageal adenocarcinoma and the 262 with adenocarcinoma of the cardia constituted 85 percent of the 529 patients in Sweden who were eligible for the study during the period from 1995 through 1997. For comparison, we interviewed 820 control subjects from the general population and 167 patients with esophageal squamous-cell carcinoma. Among persons with recurrent symptoms of reflux, as compared with persons without such symptoms, the odds ratios were 7.7 (95 percent confidence interval, 5.3 to 11.4) for esophageal adenocarcinoma and 2.0 (95 percent confidence interval, 1.4 to 2.9) for adenocarcinoma of the cardia. The more frequent, more severe, and longer-lasting the symptoms of reflux, the greater the risk. Among persons with long-standing and severe symptoms of reflux, the odds ratios were 43.5 (95 percent confidence interval, 18.3 to 103.5) for esophageal adenocarcinoma and 4.4 (95 percent confidence interval, 1.7 to 11.0) for adenocarcinoma of the cardia. The risk of esophageal squamous-cell carcinoma was not associated with reflux (odds ratio, 1.1; 95 percent confidence interval, 0.7 to 1.9). CONCLUSIONS: There is a strong and probably causal relation between gastroesophageal reflux and esophageal adenocarcinoma. The relation between reflux and adenocarcinoma of the gastric cardia is relatively weak. (+info)
Evaluating gastric cancer misclassification: a potential explanation for the rise in cardia cancer incidence.
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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. (+info)
Mortality trend from cancer of the gastric cardia in The Netherlands, 1969-1994.
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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). (+info)
Expression of nm23 in the primary tumor and the metastatic regional lymph nodes of patients with gastric cardiac cancer.
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Tumor recurrence and distant metastasis are major causes of treatment failure in gastric cardiac cancer (GCC). Rapid growth of tumor cells and reduced expression of nm23, a metastatic suppressor gene, in tumor cells have been suggested as two important mechanisms for disease progression of GCC. Therefore, to determine the prognostic value of nm23 expression in GCC, we used immunohistochemistry to examine the expression of nm23 in the pathological sections of both gastric cancer and metastatic lymph nodes from 24 stage III patients. Twenty-two patients had total gastrectomy, and two patients had proximal subtotal gastrectomy with a D2 dissection. Postoperative adjuvant therapy was provided, and the clinical responses were followed routinely. Clinical correlation was evaluated by chi2 with Fisher's exact test and survival by log-rank test. Our results show that the reduced nm23 expression in the primary tumor and in the nodal metastasis is the most useful marker for the poor prognosis of GCC following surgery. (+info)
Inflammation of the gastro-oesophageal junction (carditis) in patients with symptomatic gastro-oesophageal reflux disease: a prospective study.
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BACKGROUND: Recent data have suggested that cardia biopsy specimens may be more reflective of gastro-oesophageal reflux disease (GORD) than squamous biopsy specimens. AIMS: To assess the distribution, severity, and types of mucosal injury in GORD. PATIENTS: Thirty patients with symptomatic GORD with no or minimal erosions. METHODS: Biopsies were performed at the squamocolumnar junction (Z-line) and 1-2 cm below the Z-line. Injury to the columnar mucosa was scored for inflammatory cells, epithelial cell abnormalities, and for the presence of intestinal metaplasia and Helicobacter pylori. A carditis score above 2 was considered positive (maximum score = 9). RESULTS: Mean carditis scores and percentages of patients with a positive carditis score were higher in Z-line biopsy specimens containing both squamous and columnar mucosa than in those with just columnar mucosa or in specimens taken 1-2 cm below the Z-line. Carditis at the Z-line was focal in 49% of the specimens and was always present adjacent to the squamous epithelium. Goblet cells were present more frequently in the specimens immediately at the Z-line than in those 1-2 cm below the Z-line. H pylori was present in only four patients. The mean carditis scores of specimens 1-2 cm below the Z-line in these patients was significantly higher than in those patients without H pylori. CONCLUSIONS: Mucosal injury at the gastric cardia is highly localised to the region adjacent to the squamocolumnar junction in patients with GORD. Morphological studies of the cardia in GORD should focus on tissue samples that contain both squamous and columnar epithelium in order to obtain an accurate picture of the spectrum of injury. (+info)
Patterns of gastritis in patients with gastro-oesophageal reflux disease.
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BACKGROUND: The cause of inflammation in cardiac mucosa at the gastro-oesophageal junction (GOJ) is unclear, both gastro-oesophageal reflux disease (GORD) and Helicobacter pylori having been implicated. AIMS: To describe patterns of gastritis in patients with symptomatic GORD. METHODS: In 150 patients (126 normally located Z-line, 24 Barrett's oesophagus) with symptoms of GORD, biopsies were taken of the GOJ, corpus, and antrum. Inflammation was assessed using the updated Sydney System. RESULTS: For the 126 patients with a normally located Z-line, biopsies of the GOJ revealed cardiac mucosa in 96, fundic mucosa in 29, and squamous mucosa in one. Inflammation in glandular mucosa at the GOJ was present in 99/125 specimens (79%), including 87/96 (91%) with cardiac mucosa and 12/29 (41%) with fundic mucosa. Inflammation in fundic mucosa was closely related to H pylori and active inflammation was only seen in its presence. Inflammation in cardiac mucosa was less closely linked to H pylori. When H pylori was present in cardiac mucosa (28/96, 29%) active inflammation was usually present (25/28, 89%). However, active inflammation was also found in 34/68 (50%) cardiac mucosa specimens without H pylori. Overall, 28/87 (32%) biopsies with carditis were colonised with H pylori and 59/87 (68%) were not. In H pylori colonised patients, inflammation was seen throughout the stomach, while in non-colonised patients, it was confined to cardiac mucosa. CONCLUSIONS: Patients with symptomatic GORD had a high prevalence of carditis. This was of two types, H pylori associated and unassociated. Except on Giemsa staining, the two were morphologically identical, suggesting mediation by a similar immunological mechanism. (+info)
Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia.
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BACKGROUND: Biopsy specimens obtained from the gastro-oesophageal junction can reveal intestinal metaplasia in patients presenting for routine upper endoscopy. The site of biopsy may play a critical role in determining the dysplasia risk of a patient. AIMS: To evaluate prospectively the dysplasia risk in patients with intestinal metaplasia of the distal oesophagus or within the gastric cardia. METHODS: Patients with short segment Barrett's oesophagus (SSBO) and cardia intestinal metaplasia (CIM) were followed prospectively. RESULTS: 177 patients with SSBO were identified (mean age 62 years, range 38-82; 91% whites). Twenty prevalence cases of dysplasia in SSBO were detected: 17 low grade dysplasia (LGD), three high grade dysplasia (HGD). Seventy six patients with CIM were identified (mean age 67 years, range 37-81; 81% whites). A single prevalence case of LGD in CIM was detected. During follow up of 78 SSBO and 34 CIM patients, dysplasia developed in nine (seven LGD, two HGD) with SSBO and in one (LGD) with CIM. There were significant differences between the two groups with respect to age, ethnicity, dysplasia prevalence, and incidence. Time to dysplasia progression was significantly longer in CIM compared with SSBO patients. Of the five patients with SSBO and HGD, one developed adenocarcinoma of the oesophagus on follow up. No HGD or cancers have been detected over this time period in CIM patients. CONCLUSIONS: The dysplasia risk is significantly greater in SSBO than in CIM patients, indicating two potentially different clinical processes. Future studies should separate SSBO from CIM in order to enhance the understanding of the pathophysiology and malignant potential of each entity. (+info)
Columnar mucosa and intestinal metaplasia of the esophagus: fifty years of controversy.
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OBJECTIVE: To outline current concepts regarding etiology, diagnosis, and treatment of intestinal metaplasia of the esophagus and cardia. SUMMARY BACKGROUND DATA: Previously, endoscopic visualization of columnar mucosa extending a minimum of 3 cm into the esophagus was sufficient for the diagnosis of Barrett's esophagus, but subsequently the importance of intestinal metaplasia and the premalignant nature of Barrett's have been recognized. It is now apparent that shorter lengths of intestinal metaplasia are common, and share many features of traditional 3-cm Barrett's esophagus. METHODS: Themes and concepts pertaining to intestinal metaplasia of the esophagus and cardia are developed based on a review of the literature published between 1950 and 1999. RESULTS: Cardiac mucosa is the precursor of intestinal metaplasia of the esophagus. Both develop as a consequence of gastroesophageal reflux. Intestinal metaplasia, even a short length, is premalignant, and the presence of dysplasia indicates progression on the pathway to adenocarcinoma. Antireflux surgery, as opposed to medical therapy, may induce regression or halt progression of intestinal metaplasia. The presence of high-grade dysplasia is frequently associated with an unrecognized focus of adenocarcinoma. Vagal-sparing esophagectomy removes the diseased esophagus and is curative in patients with high-grade dysplasia. Invasion beyond the mucosa is associated with a high likelihood of lymph node metastases and requires lymphadenectomy. CONCLUSIONS: Despite improved understanding of this disease, controversy about the definition and best treatment of Barrett's esophagus continues, but new molecular insights, coupled with careful patient follow-up, should further enhance knowledge of this disease. (+info)