Two distinct aetiologies of cardia cancer, evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status

Background: Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear. Aim: To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach. Methods: Nested case–control study. To each of 129 non-cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori antibodies, pepsinogen I:II and gastrin. Results: Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II ,2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non-cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1). Conclusion: These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer

Relationship between p53 expression and gastric cancers in cardia and antrum

Background: The mutations in p53 gene and accumulation of p53 protein are the most common genetic events in gastric carcinomas. The present study was conducted to compare the frequency of p53 gene overexpression in a consecutive series of adenocarcinomas arising from the cardia and the antrum. This study also evaluates the associations of this gene expression with demographic and clinicopathologic findings (age, sex, histology, and grade of tumor). Methods: Retrospective analysis was performed on 111 patients with gastric cancer who had undergone upper gastrointestinal endoscopies in 5th Azar Medical Center (northeastern, Iran), during 1998-2005. The series comprised of 25 patients with cardia adenocarcinoma and 86 patients with antral adenocarcinoma. p53 alteration (nuclear p53 overexpression) was detected by immunohistochemistry. Results: Nuclear p53 overexpression was found in 14 (56%) out of the 25 and 27 (31.3%) out of the 86 patients with cardia and antral adenocarcinomas, respectively. p53 gene overexpression was significantly more frequent in adenocarcinomas of the cardia than the antrum. There were no differences in the clinicopathologic characteristics of the tumors between p53-positive and p53-negative cases in both types of the cancer. Conclusion: This study shows that p53 alterations correlate well with gastric location, and they are more frequent in adenocarcinoma of the cardia than the antrum. This result reinforce the hypothesis that the cancers of the lower esophagus and upper stomach have distinct epidemiologic, pathogenesis, and molecular characteristics from that observed in cancers of the lower part of the stomach

Combination of gastric atrophy, reflux symptoms and histological subtype indicates two distinct aetiologies of gatric cardia cancer.

<b>INTRODUCTION</b> Atrophic gastritis is a risk factor for non-cardia gastric cancer, and gastro-oesophageal reflux disease (GORD) for oesophageal adenocarcinoma. The role of atrophic gastritis and GORD in the aetiology of adenocarcinoma of the cardia remains unclear. We have investigated the association between adenocarcinoma of the different regions of the upper gastrointestinal tract and atrophic gastritis and GORD symptoms. <b>METHODS</b> 138 patients with upper GI adenocarcinoma and age and sex matched controls were studied. Serum pepsinogen I/II was used as a marker of atrophic gastritis and categorised to five quintiles. History of GORD symptoms, smoking and H.pylori infection was incorporated in logistic regression analysis. Lauren classification of gastric cancer was used to subtype gastric and oesophageal adenocarcinoma. <b>RESULTS</b> Non-cardia cancer was associated with atrophic gastritis but not with GORD symptoms; 55% of these cancers were intestinal subtype. Oesophageal adenocarcinoma was associated with GORD symptoms, but not with atrophic gastritis; 84% were intestinal subtype. Cardia cancer was positively associated with both severe gastric atrophy [OR, 95% CI: 3.92 (1.77 – 8.67)] and with frequent GORD symptoms [OR, 95% CI: 10.08 (2.29 – 44.36)] though the latter was only apparent in the nonatrophic subgroup and in the intestinal subtype. The association of cardia cancer with atrophy was stronger for the diffuse versus intestinal subtype and this was the converse of the association observed with non-cardia cancer. <b>CONCLUSION</b> These findings indicate two distinct aetiologies of cardia cancer, one arising from severe atrophic gastritis and being of intestinal or diffuse subtype similar to non-cardia cancer, and one related to GORD and intestinal in subtype, similar to oesophageal adenocarcinoma. Gastric atrophy, GORD symptoms and histological subtype may distinguish between gastric versus oesophageal origin of cardia cancer

Peculiar and Unusual Drowning in Waste Oil from Motor Vehicles: Case Report

Drowning is one of the most frequent causes of accidental or suicidal death, and more rarely it is associated with a homicide. Cases of drowning in water or in the sea are common. The authors report an unusual and peculiar case of drowning, that of a woman who accidentally fell inside a collection tank of waste oil of motor vehicles

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

Pleiotropic and Novel Phenotypes in The \u3cem\u3eDrosophila\u3c/em\u3e Gut Caused by Mutation of \u3cem\u3eDrop-Dead\u3c/em\u3e

Normal gut function is vital for animal survival, and deviations from such function can contribute to malnutrition, inflammation, increased susceptibility to pathogens, diabetes, neurodegenerative diseases, and cancer. In the fruit fly Drosophila melanogaster, mutation of the gene drop-dead (drd) results in defective gut function, as measured by enlargement of the crop and reduced food movement through the gut, and drd mutation also causes the unrelated phenotypes of neurodegeneration, early adult lethality and female sterility. In the current work, adult drd mutant flies are also shown to lack the peritrophic matrix (PM), an extracellular barrier that lines the lumen of the midgut and is found in many insects including flies, mosquitos and termites. The use of a drd-gal4 construct to drive a GFP reporter in late pupae and adults revealed drd expression in the anterior cardia, which is the site of PM synthesis in Drosophila. Moreover, the ability of drd knockdown or rescue with several gal4 drivers to recapitulate or rescue the gut phenotypes (lack of a PM, reduced defecation, and reduced adult survival 10–40 days post-eclosion) was correlated to the level of expression of each driver in the anterior cardia. Surprisingly, however, knocking down drd expression only in adult flies, which has previously been shown not to affect survival, eliminated the PM without reducing defecation rate. These results demonstrate that drd mutant flies have a novel phenotype, the absence of a PM, which is functionally separable from the previously described gut dysfunction observed in these flies. As the first mutant Drosophila strain reported to lack a PM, drd mutants will be a useful tool for studying the synthesis of this structure

Surgical approaches to adenocarcinoma of the gastroesophageal junction: the Siewert II conundrum.

BACKGROUND: The Siewert classification system for gastroesophageal junction adenocarcinoma has provided morphological and topographical information to help guide surgical decision-making. Evidence has shown that Siewert I and III tumors are distinct entities with differing epidemiologic and histologic characteristics and distinct patterns of disease progression, requiring different treatment. Siewert II tumors share some of the characteristics of type I and III lesions, and the surgical approach is not universally agreed upon. Appropriate surgical options include transthoracic esophagogastrectomy, transhiatal esophagectomy, and transabdominal extended total gastrectomy. PURPOSE: A review of the available evidence of the surgical management of Siewert II tumors is presented. CONCLUSIONS: Careful review of the data appear to support the fact that a satisfactory oncologic resection can be achieved via a transabdominal extended total gastrectomy with a slight advantage in terms of perioperative complications, and overall postoperative quality of life. Overall and disease-free survival compares favorably to the transthoracic approach. These results can be achieved with careful selection of patients balancing more than just the Siewert type in the decision-making but considering also preoperative T and N stages, histological type (diffuse type requiring longer margins that are not always achievable via gastrectomy), and the presence of Barrett\u27s esophagus