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Bravo capsule placement in the gastric cardia: a novel method for analysis of proximal stomach acid environment.

BACKGROUND: Intragastric pH monitoring is currently done using catheter-based pH systems. This study assessed the feasibility of proximal intragastric pH recording with the Bravo wireless pH monitoring system using novel methodology. METHODS: Nine asymptomatic volunteers and 9 symptomatic patients were studied. One pH capsule was positioned under direct endoscopic visualization so that the device straddled the squamocolumnar junction (SCJ) with the attachment well positioned on squamous mucosa and the pH electrode 1.5-2 cm distal to the SCJ. A second capsule was placed 6 cm proximal to the SCJ. The signal from each capsule was recorded by a separate receiver synchronized for time. RESULTS: Successful placement and interpretable recording for >42 h from both pH capsules was achieved in 16 (88%) of 18 subjects. Data capture were 98.3% in the cardia and 97.7% in the esophagus. Two failures occurred due to premature capsule detachment (one esophageal and one gastric). The acid environment in the cardia was similar in asymptomatic controls and symptomatic patients and exhibited less meal-related buffering than is typical of more distal intragastric recordings. In addition, nadir gastric cardia pH was almost always less than nadir esophageal pH during reflux events. CONCLUSIONS: Twenty-four hour gastric cardia pH monitoring is feasible with the Bravo system and can be added to esophageal pH monitoring to assess concomitant cardia acidity. Instantaneous cardia pH defines the potential nadir esophageal pH during reflux events.

Cardia↗

High incidence of adenocarcinoma arising from the right side of the gastric cardia in NW Iran.

BACKGROUND: In the West, the subsite incidence of gastric cancer has changed in recent decades, with cancer of the cardia increasing in incidence and that of the more distal stomach decreasing. NW Iran has a very high incidence of upper gastrointestinal cancer and we have examined the anatomical site specific incidence in this geographical region. METHOD AND MATERIALS: Of 33 718 patients who visited our clinic from March 2000 to Jan 2003, 3119 (9.3%) with persistent upper gastrointestinal symptoms underwent upper gastrointestinal fibreoptic endoscopy. Exact tumour site, subsite, and axial view were determined. Demographic data including age, sex, and place of residence were assessed. Using matched data from the cancer registry and endoscopic survey, age standardised rates (ASR) for all subsites were calculated. RESULTS: Upper gastrointestinal cancer was diagnosed histologically in 499 patients (16.0%). The most frequent site was the gastric cardia (126 (25.3%)) followed by the oesophageal body (90 (18.0%)), antrum (82 (16.4%)), corpus (74 (14.8%)), distal oesophagus (57 (11.4%)), gastro-oesophageal junction (47 (9.4%)), and proximal oesophagus (22 (4.4%)). From axial views of the cardia, 51.4% and 6.8% of tumours were found to originate from the lesser and greater curve, respectively. ASR for gastric cancer were 51.2 in males and 15.4 in females. Cardia cancer with ASR of 26.4 in males and 8.6 in females was the major component of gastric cancer. CONCLUSION: NW Iran is a geographical region with a very high incidence of cardia cancer and with the great majority originating from the right side of the cardia. This suggests a locally acting luminal carcinogen. Studying the aetiology of this cancer in NW Iran is likely to increase our understanding of the rising incidence of this cancer throughout the Western world.

Adenocarcinoma↗

Conditions for acid catalysed luminal nitrosation are maximal at the gastric cardia.

BACKGROUND: Saliva has a high nitrite concentration, derived from the enterosalivary recirculation of dietary nitrate, and is the main source of nitrite entering the acidic stomach. Acidification of nitrite in the presence of secondary amines or amides generates potentially carcinogenic N-nitroso compounds. The reaction is inhibited by ascorbic acid and catalysed by thiocyanate. AIM: To determine whether there is intragastric regional variation in the chemical conditions promoting luminal nitrosation following nitrate ingestion. METHODS: Using microdialysis probes, we measured concentrations of nitrite, ascorbic acid, total vitamin C, and thiocyanate simultaneously in saliva, the distal oesophagus, cardia, and the proximal and distal stomach of 17 healthy volunteers before and following intragastric nitrate (2 mmol) administration. RESULTS: The median pH in the distal oesophagus, cardia, and proximal and distal stomach were 7, 2.6, 1.9, and 1.7, respectively, before, and were similar following nitrate administration. Mean nitrite concentration in the distal oesophagus was similar to that of saliva, being 29.1 micro M and 36.7 micro M, respectively, before nitrate and increasing to 181.6 micro M and 203.3 micro M after nitrate ingestion. Within the stomach, mean (SEM) nitrite concentration following nitrate was higher in the cardia (45.5 (12.7) micro M) than in the mid (7.8 (3.1)) (p<0.01) or distal (0.8 (0.6)) (p<0.1) stomach, and ascorbic acid concentration was lower at the cardia (13.0 (6.1)) than in the mid (51 (19.2)) (p<0.02) or distal (86 (29)) (p<0.01) stomach. Consequently, the median ascorbic acid to nitrite ratio was lowest at the cardia (0.3) (p<0.01) versus the mid (7.8) or distal (40) stomach. Thiocyanate concentration was similar throughout the stomach. CONCLUSIONS: The conditions favouring luminal generation of N-nitroso compounds from dietary nitrate are maximal at the most proximal cardia region of the acidic stomach and may contribute to the high incidence of mutagenesis at this site.

Adolescent↗

Airborne occupational exposures and risk of oesophageal and cardia adenocarcinoma.

BACKGROUND: The reasons for the increasing incidence of and strong male predominance in patients with oesophageal and cardia adenocarcinoma remain unclear. The authors hypothesised that airborne occupational exposures in male dominated industries might contribute. METHODS: In a nationwide Swedish population based case control study, 189 and 262 cases of oesophageal and cardia adenocarcinoma respectively, 167 cases of oesophageal squamous cell carcinoma, and 820 frequency matched controls underwent personal interviews. Based on each study participant's lifetime occupational history the authors assessed cumulative airborne occupational exposure for 10 agents, analysed individually and combined, by a deterministic additive model including probability, frequency, and intensity. Furthermore, occupations and industries of longest duration were analysed. Relative risks were estimated by odds ratios (OR), with 95% confidence intervals (CI), using conditional logistic regression, adjusted for potential confounders. RESULTS: Tendencies of positive associations were found between high exposure to pesticides and risk of oesophageal (OR 2.3 (95% CI 0.9 to 5.7)) and cardia adenocarcinoma (OR 2.1 (95% CI 1.0 to 4.6)). Among workers highly exposed to particular agents, a tendency of an increased risk of oesophageal squamous cell carcinoma was found. There was a twofold increased risk of oesophageal squamous cell carcinoma among concrete and construction workers (OR 2.2 (95% CI 1.1 to 4.2)) and a nearly fourfold increased risk of cardia adenocarcinoma among workers within the motor vehicle industry (OR 3.9 (95% CI 1.5 to 10.4)). An increased risk of oesophageal squamous cell carcinoma (OR 3.9 (95% CI 1.2 to 12.5)), and a tendency of an increased risk of cardia adenocarcinoma (OR 2.8 (95% CI 0.9 to 8.5)), were identified among hotel and restaurant workers. CONCLUSIONS: Specific airborne occupational exposures do not seem to be of major importance in the aetiology of oesophageal or cardia adenocarcinoma and are unlikely to contribute to the increasing incidence or the male predominance.

Adenocarcinoma↗

Body mass index and adenocarcinomas of the esophagus or gastric cardia: a systematic review and meta-analysis.

BACKGROUND: The incidence of esophageal adenocarcinoma has increased markedly in recent decades in many countries. Obesity is a potential risk factor, although the results of individual studies differ. We did a systematic review and statistical synthesis of studies that evaluated the association between body mass index (BMI) and the risk of esophageal adenocarcinoma or the adjacent gastric cardia adenocarcinoma. METHODS: We identified potential studies using Medline, the Web of Science database, a manual review of the literature and expert bibliographies. Studies were included if they reported (a) a measure of body mass; (b) the occurrence of esophageal or cardia adenocarcinoma diagnosis; and (c) a relative risk or odds ratio (OR) with confidence intervals (CI) or provided sufficient data to permit their calculation. RESULTS: We identified 14 studies (2 cohort, 12 case-control; 2,488 esophageal and 2,509 cardia adenocarcinomas). A high BMI (>25) was associated with an increased risk of esophageal adenocarcinoma (males, OR, 2.2; 95% CI, 1.7-2.7; females, OR, 2.0; 95% CI, 1.4-2.9). Higher levels of BMI were associated with increased risk (overweight males, OR, 1.8; 95% CI, 1.5-2.2; obese males, OR, 2.4; 95% CI, 1.9-3.2). The overall associations with cardia cancer were heterogeneous, although stratification by study location provided homogeneous results for populations from the United States or Europe. A high BMI was weakly associated with the risk of cardia adenocarcinoma (OR, 1.5; 95% CI, 1.3-1.8; P(heterogeneity) = 0.38). CONCLUSIONS: Pooled results from observational studies support a positive association between high BMI and the risk for esophageal and possibly for cardia adenocarcinoma.

Adenocarcinoma↗

Carcinoma of the gastric cardia in young people.

Carcinoma of the gastric cardia is usually considered a disease of middle-aged or elderly patients and is rarely suspected in young individuals. However, six cases are reported in patients under 45 years of age. The youngest was 26. A review of patient records revealed no obvious predisposing factor to account for the development of cancer at an early age. In four cases, double-contrast upper gastrointestinal examinations revealed a polypoid mass at the cardia. In two cases, however, the true origin of a tumor arising at the cardia was only recognized by obliteration of the normal anatomic landmarks at the cardia associated with irregular areas of ulceration. In all six cases, the tumor extended into the distal esophagus. Five patients presented with dysphagia. Careful radiographic evaluation of the cardia and fundus is therefore essential to rule out an underlying carcinoma of the cardia in all patients with dysphagia, regardless of age.

Adenocarcinoma↗

Expression of p53 protein in Barrett's adenocarcinoma and adenocarcinoma of the gastric cardia and antrum.

BACKGROUND/AIM: Most studies of esophageal and gastric adenocarcinomas have shown a very high rate of p53 gene mutation and/or protein overexpression, but the influence of the tumour site upon the frequency of p53 protein expression has not been evaluated (gastroesophageal junction, Barret's esophagus, and antrum). The aim of our study was to analyze the correlation between the selected clinico-pathological parameters, and p53 protein overexpression in regards to the particular tumour location. METHODS: The material comprised 66 surgical specimens; 10 were Barrett's carcinomas, 25 adenocarcinomas of the gastric cardia (type II adenocarcinoma of the esophagogastric junction - EGJ), and 31 adenocarcinomas of the antrum. Immunostaining for p53 protein was performed on formalin-fixed, paraffin-embedded tissue sections, using the alkaline phosphatase antialkaline phosphatase (APAAP) method. The cases were considered positive for p53 if at least 5% of the tumour cells expressed this protein by immunostaining. RESULTS: There was no significant difference observed between the studied groups in regards to age, sex, Lauren's classification and tumour differentiation. There was, however, a significant difference observed in the depth of tumour invasion between Barrett's adenocarcinoma and adenocarcinoma of the cardia compared with the adenocarcinoma of the antrum. Namely, at the time of surgery, both Barrett's adenocarcinomas and adenocarcinomas of the cardia, were significantly more advanced comparing with the adenocarcinomas of the antrum. Overexpression of p53 was found in 40% (4/10) of Barrett's adenocarcinomas, 72% (18/25) of adenocarcinoma of the cardia and 65% (20/31) of adenocarcinoma of the antrum. No significant differences in p53 expression in relation to sex, type (Lauren) of tumour, depth of invasion, lymph node involvement, or tumour differentiation were observed in any of the analyzed groups of tumours. Patients with more advanced Barrett's adenocarcinoma and in the cases of lymph node invasion revealed tendency for the greater p53 positivity compared with the early forms and lymph node-negative cases; however, this difference was not significant according to the statistical analysis. With regard to adenocarcinoma of the cardia, higher rates of p53 positivity were recorded in poorly differentiated, more advanced cases with lymph node invasion. Nevertheless, none of these differences was statistically significant. On the contrary, in the patients with adenocarcinoma of the antrum, greater p53 positivity was revealed in early forms without lymph node involvement, but the observed difference was not statistically significant. CONCLUSION: No significant differences in p53 protein expression in terms of sex, type (Lauren) of tumour, depth of invasion, lymph node involvement, or tumour differentiation were observed in any of the analyzed groups of tumours (Barrett's adenocarcinoma, adenocarcinoma of the cardia and adenocarcinoma of the antrum).

Adenocarcinoma↗

Invisible cardia cancer metastasis to the diaphragm.

The best surgical procedure to treat a carcinoma in the gastric cardia remains a controversy because the carcinoma is often advanced and there are other unknown factors. In this article the incidence of invisible metastasis from cardia cancer to the diaphragm will be analyzed using an experimental cardia cancer model and clinical studies. An experimental cardia cancer was induced by an endoscopic injection of VX2 cancer cells into the submucosal layer of the esophago-gastric junction in rabbits using a 27G needle and an Olympus BF-4B2 bronchofiberscope. A total of 26 cardia cancer models for Borrmann type 2 or 3 were produced. Of these, six (23%) had visible cancer metastases in the diaphragm, including 4 cases with direct invasion and 2 cases with peritoneal dissemination on the surface of the diaphragm. Four (20%) of the remaining 20 were histologically found to have macroscopically-invisible cancer metastases mainly in the lymph vessels of the left hemidiaphragm. From 1985 to 1988, 22 clinical cases of cardia cancer were managed by a combined total gastrectomy with a partial diaphragm resection through a left thoracoabdominal approach. When widely resected, reconstruction was performed using a latissimus dorsi muscle flap. Six (27%) of these 22 were also histologically found to have macroscopically-invisible cancer metastases to the diaphragm, including 1 (11%) of the 9 well-differentiated type and 5 (39%) of 13 poorly-differentiated type adenocarcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Esophageal and gastric cardia epithelial cell proliferation in northern Chinese subjects living in a high-incidence area.

Linxian and the nearby county Huixian, in the Henan province in Northern China, have a very high incidence of esophageal squamous cell carcinoma (SCC). Previous studies from these counties have suggested that increased proliferation of esophageal epithelial cells, morphologically manifested as basal cell hyperplasia (BCH) and dysplasia (DYS), is an early indicator of abnormality in persons predisposed to SCC. A high incidence of gastric cardia adenocarcinoma (AC) was also found in these areas. To determine proliferation patterns of esophageal and gastric cardia epithelia with normal and different severities of precancerous lesions, we measured proliferating cell nuclear antigen (PCNA), Ki-67, and bromodeoxyuridine (BrdU) incorporation and compared the results. Esophageal biopsies (175) and gastric cardia biopsies (41) were collected from symptom-free subjects in Huixian. Of these, 23 esophageal biopsies were incubated with BrdU. The avidin-biotin-peroxidase complex (ABC) method was used to detect PCNA, Ki-67, and BrdU. The number of immunostain-positive cells was counted manually. Intense immunostaining for PCNA, Ki-67, and BrdU was observed in the cell nuclei of tissues with normal and different severities of precancerous lesions. With esophageal biopsies, both PCNA and Ki-67 increased significantly as the epithelia progressed from normal to BCH and to DYS. The number of PCNA- and Ki-67-positive cells was three times higher than that of BrdU incorporation in the same category of BCH. With cardia biopsies, the number of Ki-67 positive cells was lower in normal tissue and increased significantly from chronic superficial gastritis to chronic atrophic gastritis to DYS. Staining patterns for PCNA and Ki-67 were correlated with the histopathology of the esophagus. The correlation was not as clear with gastric cardia. BrdU studies appear to be more complicated. The PCNA and Ki-67 methods may be useful for screening high-risk esophageal and gastric cardia cancer subjects, and for monitoring chemoprevention effects.

Adenocarcinoma↗

Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of 14Q31-32.1 discriminates between esophageal (Barrett's) and gastric cardia adenocarcinomas.

Incidence rates have risen rapidly for esophageal and gastric cardia adenocarcinomas. These cancers, arising at and around the gastroesophageal junction (GEJ), share a poor prognosis. In contrast, there is no consensus with respect to clinical staging resulting in possible adverse effects on treatment and survival. The goal of this study was to provide more insight into the genetic changes underlying esophageal and gastric cardia adenocarcinomas. We have used comparative genomic hybridization for a genetic analysis of 28 adenocarcinomas of the GEJ. Eleven tumors were localized in the distal esophagus and related to Barrett's esophagus, and 10 tumors were situated in the gastric cardia. The remaining seven tumors were located at the junction and could not be classified as either Barrett-related, or gastric cardia. We found alterations in all 28 neoplasms. Gains and losses were distinguished in comparable numbers. Frequent loss (> or = 25% of all tumors) was detected, in decreasing order of frequency, on 4pq (54%), 14q (46%), 18q (43%), 5q (36%), 16q (36%), 9p (29%), 17p (29%), and 21q (29%). Frequent gain (> or = 25% of all tumors) was observed, in decreasing order of frequency, on 20pq (86%), 8q (79%), 7p (61%), 13q (46%), 12q (39%), 15q (39%), 1q (36%), 3q (32%), 5p (32%), 6p (32%), 19q (32%), Xpq (32%), 17q (29%), and 18p (25%). Nearly all patients were male, and loss of chromosome Y was frequently noted (64%). Recurrent high-level amplifications (> 10% of all tumors) were seen at 8q23-24.1, 15q25, 17q12-21, and 19q13.1. Minimal overlapping regions could be determined at multiple locations (candidate genes are in parentheses): minimal regions of overlap for deletions were assigned to 3p14 (FHIT, RCA1), 5q14-21 (APC, MCC), 9p21 (MTS1/CDKN2), 14q31-32.1 (TSHR), 16q23, 18q21 (DCC, P15) and 21q21. Minimal overlapping amplified sites could be seen at 5p14 (MLVI2), 6p12-21.1 (NRASL3), 7p12 (EGFR), 8q23-24.1 (MYC), 12q21.1, 15q25 (IGF1R), 17q12-21 (ERBB2/HER2-neu), 19q13.1 (TGFB1, BCL3, AKT2), 20p12 (PCNA), 20q12-13 (MYBL2, PTPN1), and Xq25. The distribution of the imbalances revealed similar genetic patterns in the three GEJ tumor groups. However, loss of 14q31-32.1 occurred significantly more frequent in Barrett-related adenocarcinomas of the distal esophagus, than in gastric cardia cancers (P = 0.02). The unclassified, "pure junction" group displayed an intermediate position, suggesting that these may be in part gastric cardia tumors, whereas the others may be related to (short-segment) Barrett's esophagus. In conclusion, this study has, fist, provided a detailed comparative genomic hybridization-map of GEJ adenocarcinomas documenting new genetic changes, as well as candidate genes involved. Second, genetic divergence was revealed in this poorly understood group of cancers.

Adenocarcinoma↗

Esophageal balloon cytology and subsequent risk of esophageal and gastric-cardia cancer in a high-risk Chinese population.

Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world. In 1983, esophageal balloon cytology screening was performed in 3 communes in northern Linxian. Of the participants, 10,066 with no evidence of cancer were followed prospectively for 7 1/2 years to evaluate the ability of the initial cytologic diagnoses to identify individuals at increased risk for developing cancer of the esophagus or gastric cardia. A total of 747 incident cases of esophageal or cardia cancer and 322 deaths due to these tumors were identified during the follow-up period and used in this analysis. The risks for esophageal or cardia cancer incidence and mortality increased in parallel with the presumed severity of the 1983 Chinese cytologic diagnoses. After adjusting for potential confounding factors, relative risks for esophageal or cardia cancer incidence, by initial cytologic diagnosis, were normal = 1.00 (reference), hyperplasia = 1.25, dysplasia 1 = 2.20, dysplasia 2 = 4.22 and near-cancer = 5.96. Our results suggest that esophageal balloon cytology, as performed and interpreted in Linxian in 1983, successfully identified individuals at increased risk for developing cancer of the esophagus or gastric cardia.

Age Factors↗

Tooth loss is associated with increased risk of gastric non-cardia adenocarcinoma in a cohort of Finnish smokers.

OBJECTIVE: Tooth loss has been associated with upper gastrointestinal cancer in several studies, but only one previous study used prospectively collected data. The importance of confounding by Helicobacter pylori has not previously been addressed. The objective was to determine the association between tooth loss and upper gastrointestinal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort and to determine the importance of potentially confounding dietary factors or H. pylori seropositivity. MATERIAL AND METHODS: A prospective cohort study with 29,124 subjects included 49 esophageal squamous cell carcinomas, 66 esophageal/gastric cardia adenocarcinomas, and 179 gastric non-cardia adenocarcinomas occurring between 1985 and 1999. Cox proportional hazards models adjusted for age and education were used to estimate hazard ratios (HRs) and 95% CIs. Odds ratios and 95% CIs were calculated with and without adjustment for H. pylori seropositivity in a nested case-control group to determine whether H. pylori confounded the association between tooth loss and gastric cancer. RESULTS: Tooth loss significantly increased the hazard ratio for gastric non-cardia cancer, the HR (95% CI) for edentulous subjects versus those with < 10 teeth lost was 1.65 (1.09, 2.49, respectively). No statistically significant associations were found between tooth loss and esophageal squamous cell carcinoma or esophageal/gastric cardia adenocarcinoma. Confounding by dietary factors, tobacco smoking, or H. pylori did not explain these results. CONCLUSIONS: Tooth loss was associated with increased risk of gastric non-cardia cancer, but not esophageal squamous cell carcinoma or esophageal/gastric cardia adenocarcinoma in this Finnish cohort.

Adenocarcinoma↗

Disparities in the classification of esophageal and cardia adenocarcinomas and their influence on reported incidence rates.

OBJECTIVE: To evaluate the diagnostic accuracy of esophageal and cardia adenocarcinoma in the Swedish Cancer Register. SUMMARY BACKGROUND DATA: Based on cancer registers, a rising incidence of esophageal and cardia adenocarcinoma has been reported in several populations, but possible influence of differences in tumor classification has not been evaluated. METHODS: In a nationwide study in 1995 through 1997, all Swedish patients, born in Sweden and younger than 80 years with esophageal or cardia adenocarcinoma and half of all patients with esophageal squamous cell carcinoma, were prospectively, uniformly, and thoroughly classified. This study classification was compared with the tumor classification in the Swedish Cancer Register, which is based on routine clinical practice. RESULTS: The overall completeness of the Cancer Register was high (98.3%), whereas the site-specific completeness of the Register was 63% for esophageal adenocarcinoma, 74% for cardia adenocarcinoma, and 91% for esophageal squamous cell carcinoma. The incidence of esophageal adenocarcinomas was 16% higher in the study classification compared with that of the Register during the study period, whereas the incidence of cardia adenocarcinoma was 2% lower in the study classification. CONCLUSIONS: There is a diagnostic mismatch between esophageal and cardia adenocarcinoma in the clinical setting and, therefore, also in Cancer Registers. In etiologic and therapeutic research, this problem needs consideration, since these tumors have distinct risk factor profiles and could be subjected to different treatment strategies. The increasing incidence rate of esophageal adenocarcinoma in Sweden is unlikely to be explained by such differences in tumor classification, however.

Adenocarcinoma↗

Comparative studies on epithelial lesions at gastric cardia and pyloric antrum in subjects from a high incidence area for esophageal cancer in Henan, China.

AIM:To investigate the pathogenesis of gastric cardia and the distal part of stomach cancer and to further characterize the histopathogenesis model for gastric cardia cancer from the high-risk population for esophageal cancer.METHODS:Mass survey with endoscopic mucosa biopsy and histopathological examination were carried out on 226 subjects aged above 30 years. Three biopsies were collected one each from the middle part of the esophagus, the gastric cardia and the pyloric antrum. The biopsy tissue was fixed with 85% alcohol and paraffin-embedded.RESULTS:The incidence of intestinal metaplasia and dysplasia at gastric cardia epithelium was higher than that at the pyloric antrum from the subjects in the same area. And there were high incidences of both esophageal and gastric cardia cancer, but a low incidence of gastric cancer at the distal part of the stomach.CONCLUSION:There might be different etiology and pathogenesis of gastric cardia and pyloric cancer at the distal part of the stomach.

Journal Article↗

Increasing incidence of carcinoma of the gastric cardia in Sweden from 1970 to 1985.

Several American, Japanese and European centres have reported an increase in carcinoma of the gastric cardia, contrary to the general trend in the incidence of gastric cancer. The aim of this nationwide population-based study was to describe trends in the incidence of tumours of the gastric cardia in Sweden over the 16-year period from 1970 to 1985. The Swedish cancer register, which is more than 95 per cent complete, was used to identify cases. There were 1514 men and 481 women with cancer of the gastric cardia. The age-standardized rates increased in men from 1.9 per 10(5) population in 1970-1973 to 3.0 per 10(5) in 1982-1985, corresponding to a mean annual increase of 2.5 per cent (95 per cent confidence interval (c.i.) 1.6-3.4 per cent). In women, the age-standardized rates increased from 0.5 per 10(5) in 1970-1973 to 0.8 per 10(5) in 1982-1985, the mean annual increase being 0.9 per cent (95 per cent c.i. 0.0-1.8 per cent). The highest incidences were found in southern Sweden, contrary to the geographical distribution of gastric cancer in general, which shows a south-to-north gradient. The disparate epidemiological features of cancer of the cardia and gastric cancer at other sites suggest that the aetiologies may also be different. Since little is known about the aetiology of cancer of the cardia, and the incidence seems to be rising rapidly, analytical studies are urgently needed.

Adult↗

Association of prediagnosis endoscopy with stage and survival in adenocarcinoma of the esophagus and gastric cardia.

BACKGROUND: Barrett esophagus, a consequence of chronic gastroesophageal reflux disease, is a premalignant condition for adenocarcinoma of the esophagus and, possibly, the gastric cardia. However, the actual use and clinical impact of upper gastrointestinal endoscopy in screening and surveillance for Barrett esophagus are unknown. METHODS: A cohort included 1633 patients with adenocarcinoma (777 esophagus, 856 cardia) who were 70 years or older. They were diagnosed between 1993 and 1996 and were identified from the Surveillance, Epidemiology and End Results program registry. All claims for upper endoscopy and a diagnosis of Barrett esophagus from 1991 through 1 year before diagnosis were identified from linked Medicare files. RESULTS: One or more upper endoscopies before diagnosis were performed in 9.7% of patients (13.0% esophagus, 6.8% cardia) and a diagnosis of Barrett esophagus was present in only 3.7% of patients. A shift toward earlier stage at diagnosis was observed in patients with previous endoscopy or Barrett diagnosis. For example, 62% of patients with esophageal and 49% of patients with cardia tumors who underwent previous endoscopy presented with in situ or local stage carcinoma, compared with 35% and 27% of other patients, respectively. Receipt of endoscopy was also associated with a reduced risk of death for esophageal adenocarcinoma (relative hazard 0.73, 95% confidence interval 0.57-0.93; P = 0.01), but not for adenocarcinoma of the cardia. CONCLUSIONS: Receipt of upper endoscopy at least 1 year before diagnosis of adenocarcinoma, which may reflect prediagnosis screening, was associated with an earlier tumor stage and improved survival. These data support the role of endoscopic screening and surveillance for Barrett esophagus and highlight the underdiagnosis of populations at risk.

Adenocarcinoma↗

Changes in p53 and cyclin D1 protein levels and cell proliferation in different stages of human esophageal and gastric-cardia carcinogenesis.

The objective of this study was to quantify the changes in p53 and cyclin D1 protein levels in different stages of human esophageal and gastric cardia carcinogenesis in a high-risk population in Henan, China. Immunoreactivity of p53, cyclin D1 and proliferating-cell nuclear antigen (PCNA) was observed in the cell nuclei of esophageal and gastric cardia biopsies. The number of p53-immunostaining-positive cells was low in normal epithelia, slightly increased in basal-cell hyperplasia (BCH), markedly increased in dysplasia (DYS) (10-fold), and further increased in squamous-cell carcinoma (SCC) (40-fold). This pattern of change was similar to that of cell proliferation as indicated by PCNA immunostaining. On the other hand, the number of cyclin D1-immunostaining-positive cells did not increase from BCH to DYS, although a slight increase from DYS to SCC was noted. In the gastric cardia, again, the pattern of change of p53-positive cells in different stages of lesions paralleled the pattern of cell proliferation. The number of p53-positive cells was very low, much lower than that of PCNA-positive cells, in normal, chronic superficial gastritis (CSG) and chronic atrophic gastritis (CAG); therefore, the increase of p53-positive cells from CAG to DYS was more dramatic (100-fold). From DYS to adenocarcinoma (AC), the p53-positive and the PCNA-positive cells increased 4-fold. On the other hand, the number of cyclin D1-positive cells did not increase in pre-cancerous lesions, but increased slightly in AC. This study demonstrates that p53 protein accumulation increased with the progression of pre-cancerous lesions, especially in the genesis of dysplasia, both in the esophagus and in the gastric cardia. Our approach of quantitative immunohistochemistry sheds light on the mechanisms of genesis of esophageal and gastric-cardia cancers, which frequently occur together in many high-incidence areas.

Adenocarcinoma↗

Palliative and curative surgical therapy of malignant stenoses of the esophagus and cardia.

Between January 1967 and July 1986, 171 patients with malignant stenosis of the esophagus and cardia were subjected to curative or palliative surgical treatment. Specifically, there were 84 primary esophageal carcinomas, 5 cases of malignant esophageal stenosis caused by an extra-esophageal malignant tumor (inter alia bronchial carcinoma), and 82 primary carcinomas of the cardia. The average age of the patients as a whole was 63.7 years, and the sex ratio (male:female) was 4.0:1. In 18 esophageal carcinoma patients and 21 patients with carcinoma of the cardia curative resection was possible, but in 132 patients merely palliative surgery was performed, most frequently esophageal intubation and gastrostomy. The specific operations with a curative objective performed upon the esophageal carcinoma patients were abdominothoracic esophageal resection with upward displacement of the stomach (n = 16) or interposition of a colonic segment (n = 2), whereas in the patients with carcinoma of the cardia, proximal resection was performed in 13 cases, either subtotally or as a cardiofundectomy, and total gastrectomy in 8 cases. For the subsequent reconstruction of the passage the interposition of a jejunal segment was most frequently used. The clinical mortality for the curative resections was 33% for the 18 esophageal carcinoma patients and 9.5% for the 20 patients with carcinoma of the cardia. The long-term survival rates are depressing: of the patients who underwent curative resection 47.6% were still alive after one year, 28.6% after 2 years and 14.3% after 5 years. Of the patients treated only palliatively on account of an already advanced stage of the tumor, 91.5% died within the first year; only 4.9% of patients from this group were still alive after 2 years.

Adult↗