Upper gastrointestinal adenocarcinoma: associations with gastric secretory function and gender

Gastric and oesophageal cancers were responsible for more than one million deaths in 2002. Although global incidence of gastric cancer is decreasing, this malignancy is still the fourth most common cause of cancer worldwide. The incidence of oesophageal adenocarcinoma is rising rapidly, three-fold in the last two decades. The incidence of adenocarcinoma of gastric cardia is stable. In the pathogenesis of both gastric and oesophageal adenocarcinomas, the state of the gastric mucosa and its secretory function plays a central role. Non-cardia adenocarcinoma develops in subjects with H.pylori associated atrophic gastritis and hypochlorhydria. Little is known about the gastric phenotype in patients with adenocarcinoma of the cardia and gastroesophageal junction. Another important but poorly understood risk factor for upper GI adenocarcinoma is male gender. In the first study we aimed to investigate the association between the pattern of H.pylori gastritis and gastric secretory function in 255 H.pylori-infected patients with dyspepsia showing normal endoscopy. Our findings showed that maximal acid output correlates inversely with severity of corpus gastritis, corpus atrophy, and positively related to male gender and serum pepsinogen I. In the second study we compared cancers at the cardia and non-cardia subsites with respect to pre-morbid gastric mucosal atrophy and acid secretion. In a nested case-control study comprising 101,601 men and women enrolled in the Norwegian JANUS cohort, 230 cases of gastric cancer were identified. 173 cases including 144 non-cardia and 44 cardia cancer were enrolled to study. Three controls were matched to each case. Serum pepsinogen I, pepsinogen II, anti-H.pylori IgG antibody and gastrin were measured using serums which had been collected a median of 11.9 years before cancer diagnosis radioimmunoassay method. Non-cardia cancer was positively associated with H.pylori and gastric atrophy. 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, but H.pylori positive cardia cancer showed a positive association with gastric atrophy. The predominant histological subtype of cardia cancer was intestinal and it was not associated with gastric atrophy compared to the diffuse subtype. Cardia cancer in atrophic patients had an intestinal: diffuse ratio similar to non-cardia cancer, whereas cardia cancers in persons without atrophy were predominantly intestinal. 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. In the third study we extended our investigation of the aetiology of cardia cancer by examining the association of both serological evidences of gastric atrophy and gastroesophageal reflux disease (GORD) symptoms with adenocarcinoma of the oesophagus, cardia and non-cardia regions of the stomach. This has been performed for the different histological subtypes of the cancer. We have also included H.pylori status and smoking history which are other well established risk factors for upper GI cancer. This has been undertaken in a population in Northwest Iran with a high incidence of upper gastrointestinal cancer. 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 was used to subtype gastric and oesophageal adenocarcinoma. 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 and with frequent GORD symptoms though the latter was only apparent in the non-atrophic 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. 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. In the fourth study we investigated the relationship between gender and upper gastrointestinal adenocarcinoma. Male gender is a well-established risk factor for oesophageal adenocarcinoma. Male predominance of gastric cancer is related to the histological subtype of the tumour being more marked in the intestinal versus diffuse histological subtype. In addition, global data suggests that the male predominance of upper gastrointestinal cancer is related to the anatomical location, being higher for proximal and lower for distal tumours. However, the proportion of the intestinal histological subtype differs according to anatomical site and it is unclear whether it is the anatomical site or the histological subtype which is associated with the gender phenomenon. We have conducted a population-based study to investigate this. The study was based upon 3270 gastric and oesophageal cancers recorded in West of Scotland Cancer Registry between 1998 and 2002. The Lauren subtype of adenocarcinoma was determined by reviewing 1204 reports and 3241 slides in a sample of 812 cases. Logistic regression models were used to estimate relationship between male predominance and histological subtype, tumour location and age. We found that the crude incidence rate of intestinal subtype was higher in males (23.86/ 100,000 person-years) versus females (9.00/ 100,000 person-years), giving M/F of 2.65. M/F ratio of intestinal subtype cancer was 3.41 at age <50, reached a peak of 7.86 at age 50-59, and then showed a progressive decrease throughout the life. In contrast, the incidence rate of diffuse subtype adenocarcinoma was similar in both sexes (5.58 vs. 5.20 /100,000 person-years) yielding M/F of 1.07. Multivariate analyses including histological subtype, tumour location and age indicated that the male predominance was related to the histological type rather than anatomical location. Intestinal type tumour showed similar male predominance of incidence irrespective of its anatomical location (OR, 95% CI: 2.6, 1.78 – 3.9). Further analysis of the age-specific incidence curves indicated that the male predominance of intestinal subtype was due to a 17.2-year delay of development of this cancer in females

Response to Crocetti et al.

No abstract available

Contributing factors to extreme tendencies to internet in students of Shahrekord University of Medical Sciences and providing preventive strategies to deal with it

Background and aims: Internet seems to be increasingly involved a major part of the daily lives of population. In recent years, many reports have confirmed the huge number of internet users worldwide. This article is seeking to explore the factors contributing to the tendency to internet in students of Shahrekord University of Medical Sciences (SKUMS) and aimed to recommend some preventive strategies to deal with their extreme tendencies to the internet usage. Methods: This descriptive study was conducted among 378 students and teachers of SKUMS, randomly enrolled using stratified random sampling from different faculties. To measure the variables, a questionnaire was used. Results: The results showed that the factors such as the tendency to make temporary friends, more attention to the opposite sex, and the loneliness were the most important determinants of extreme tendency to the internet usage. The designing some courses in different educational periods in order to make them more familiar with various online crimes as well as ways of self-protection was one of the most important preventive strategies to deal with extreme tendency to internet. Conclusion: Several factors could contribute into extreme tendency to internet among university students, which have to be identified, and effective strategies should also be exploited to deal with the extreme tendency to internet

The gastric acid pocket is attenuated in H. pylori infected subjects

Objective Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in Helicobacter pylori positive and negative volunteers in a Western population. Design We studied 31 H. pylori positive and 28 H. pylori negative volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetermined locations from the gastro-oesophageal junction and stomach. Combined high-resolution pH metry (12 sensors) and manometry (36 sensors) was performed for 20 min fasted and 90 min postprandially. The squamocolumnar junction was marked with radio-opaque clips and visualised radiologically. Biopsies were scored for inflammation and density of parietal, chief and G cells immunohistochemically. Results Under fasting conditions, the H. pylori positives had less intragastric acidity compared with negatives at all sensors &gt;1.1 cm distal to the peak lower oesophageal sphincter (LES) pressure (p&lt;0.01). Postprandially, intragastric acidity was less in H. pylori positives at sensors 2.2, 3.3 and 4.4 cm distal to the peak LES pressure (p&lt;0.05), but there were no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H. pylori positives. The H. pylori positives had a lower density of parietal and chief cells compared with H. pylori negatives in 10 of the 11 gastric locations (p&lt;0.05). 17/31 of the H. pylori positives were CagA-seropositive and showed a more marked reduction in intragastric acidity and increased mucosal inflammation. Conclusions In population volunteers, H. pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket

Equivalent frame modelling of an unreinforced masonry building with flexible diaphragms - a case study

A case study was conducted to investigate the applicability of the equivalent frame modelling for the nonlinear time-history analysis of unreinforced masonry buildings with flexible diaphragms. The dynamic responses calculated from the equivalent frame models were compared against shake table test results of a full-scale two-storey stone masonry building. The investigated modelling approach reflected the simplifications commonly assumed for the global analysis of buildings; namely, considering the diaphragms to behave elastically and neglecting the stiffness and strength contributions of the out-of-plane responding walls. The sensitivity of the analysis to different idealisations of the equivalent frame, as well as to the diaphragm stiffness values, were also investigated. Discussions are provided on the accuracies and limitations of the investigated modelling approach, which may serve as a useful guidance for practical application.Yasuto Nakamura, Hossein Derakhshan, Abdul H. Sheikh, Jason M. Ingham, and Michael C. Griffit

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

&lt;b&gt;INTRODUCTION&lt;/b&gt; 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. &lt;b&gt;METHODS&lt;/b&gt; 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. &lt;b&gt;RESULTS&lt;/b&gt; 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. &lt;b&gt;CONCLUSION&lt;/b&gt; 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

Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns:Results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis

OBJECTIVES: Extra-articular manifestations (EAMs) are important systemic features of axial spondyloarthritis (axSpA), which may influence the choice of tumour necrosis factor-inhibitor (TNFi). We examined the cumulative incidence and predictors of EAMs and the influence of these on first TNFi choice in a 'real-world' cohort of patients with axSpA. METHODS: Clinical and patient-reported outcomes of 2420 patients with axSpA from 83 centres were collected by the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis. Lifestyle factors for EAMs (acute anterior uveitis (AAU), inflammatory bowel diseases (IBD), psoriasis) were compared with those without EAMs. Also, the association between pretreatment EAMs and choice of first TNFi (adalimumab, etanercept, certolizumab) was analysed. RESULTS: AAU was directly associated with human leukocyte antigen (HLA)-B27 (incidence rate ratio (IRR) 1.95, 95% CI 1.40 to 2.73) and inversely associated with ever-smoking (IRR=0.71, 95% CI 0.55 to 0.92). For both psoriasis and IBD, there was an inverse relationship with HLA-B27 (IRR 0.54, 95% CI 0.36 to 0.79 and IRR 0.63, 95% CI 0.43 to 0.91, respectively). A diagnosis of either AAU (OR 3.79, 95% CI 2.11 to 6.80) or IBD (OR 5.50, 95% CI 2.09 to 14.46) was associated with preference for adalimumab versus others. In contrast, a diagnosis of either AAU (OR 0.14, 95% CI 0.06 to 0.33) or IBD (OR 0.17, 95% CI 0.05 to 0.57) was associated with less preference for etanercept over other TNFi. CONCLUSION: The higher occurrence of AAU and lower occurrence of psoriasis and IBD in HLA-B27-positive patients with axSpA are consistent with current pathophysiology. Patients with previous AAU and IBD are more likely to be prescribed adalimumab and less likely to receive etanercept, consistent with the superior efficacy of monoclonal TNFi for these indications. Future work will determine whether EAMs influence TNFi survival, or effectiveness, and whether this varies between agents

A suggested prototype for assessing bone health

Background- Osteoporosis is becoming a health concern worldwide. Considering the fact that prevention plays an important role in reducing the burden of this silent disease and in view of the limited resources available, many countries have adopted certain programs to fight osteoporosis through shifting their attention towards at-risk individuals. The Iranian Multicenter Osteoporosis Study (IMOS) is one of these programs. The program aims to assess bone health and the prevalence of vitamin D deficiency in different parts of Iran with various altitudes, latitudes and lifestyle habits in a way that the results could be generalized to the country. Method- The present article presents the protocol used in the third phase of the study. It was designed based on the experiences gathered in the previous phases to overcome the shortcomings particularly subject loss. The questionnaire applied in this study was developed based on a thorough literature review of the risk factors and secondary causes of osteoporosis and was approved by an expert panel. It should be added that while the majority of the existing studies aim to study a certain aspect of osteoporosis, the present protocol provides the information needed for policy makers and researchers to study different osteoporosis-related issues. Conclusion- The authors believe the protocol, to be implemented with small modifications, can help policymakers in different parts of the world, particularly developing countries, gather accurate information on different aspects of bone health at the national level. © 2015, Academy of Medical Sciences of I.R. Iran. All rights reserved

Characterization and prognostic value of mutations in exons 5 and 6 of the p53 gene in patients with colorectal cancers in central Iran

Background/Aims: We aimed to investigate the relation-ships among various mutations of the p53 gene and their protein products, histological characteristics, and disease prognosis of primary colorectal cancer in Isfahan, central Iran. Methods: Sixty-one patients with colorectal adenocarcinoma were enrolled in the study. Mutations of the p53 gene were detected by single-stranded conformation polymorphism and DNA sequencing. The protein stability was evaluated by immunohistochemistry. Patients were followed up to 48 months. Results: Twenty-one point mutations in exons 5 and 6 were detected in the tumor specimens of 14 patients (23%). Of those, 81% and 9.5% were missense and nonsense mutations, respectively. There were also two novel mutations in the intronic region between exons 5 and 6. In 11 mutated specimens, protein stability and protein accumulation were identified. There was a relationship between the type of mutation and protein accumulation in exons 5 and 6 of the p53 gene. The presence of the mutation was associated with an advanced stage of cancer (trend, p&#60;0.009). Patients with mutated p53 genes had significantly lower survival rates than those with wild type p53 genes (p&#60;0.01). Conclusions: Mutations in exons 5 and 6 of the p53 gene are common genetic alterations in colorectal adenocarcinoma in central Iran and are associated with a poor prognosis of the disease

Out-of-plane seismic response of vertically spanning URM connected to flexible diaphragms

Version of Record online: 22 OCT 2015Abstract not availableHossein Derakhshan, Michael C. Griffith and Jason M. Ingha