Archive for the ‘gastroenterology UPDATE’ category

Gastroesophageal reflux leads to esophageal cancer in a surgical model with mice

July 29th, 2009

Background:
Esophago-gastroduodenal anastomosis with rats mimics the development of human Barrett’s esophagus and esophageal adenocarcinoma by introducing mixed reflux of gastric and duodenal contents into the esophagus. However, use of this rat model for mechanistic and chemopreventive studies is limited due to lack of genetically modified rat strains. Therefore, a mouse model of esophageal adenocarcinoma is needed.
Methods:
We performed reflux surgery on wild-type, p53A135V transgenic, and INK4a/Arf+/- mice of A/J strain. Some mice were also treated with omeprazole (1,400 ppm in diet), iron (50 mg/kg/m, i.p.), or gastrectomy plus iron. Mouse esophagi were harvested at 20, 40 or 80 weeks after surgery for histopathological analysis.
Results:
At week 20, we observed metaplasia in wild-type mice (5%, 1/20) and p53A135V mice (5.3%, 1/19). At week 40, metaplasia was found in wild-type mice (16.2%, 6/37), p53A135V mice (4.8%, 2/42), and wild-type mice also receiving gastrectomy and iron (6.7%, 1/15). Esophageal squamous cell carcinoma developed in INK4a/Arf+/- mice (7.1%, 1/14), and wild-type mice receiving gastrectomy and iron (21.4%, 3/14). Among 13 wild-type mice which were given iron from week 40 to 80, twelve (92.3%) developed squamous cell carcinoma at week 80. None of these mice developed esophageal adenocarcinoma.
Conclusion:
Surgically induced gastroesophageal reflux produced esophageal squamous cell carcinoma, but not esophageal adenocarcinoma, in mice. Dominant negative p53 mutation, heterozygous loss of INK4a/Arf, antacid treatment, iron supplementation, or gastrectomy failed to promote esophageal adenocarcinoma in these mice. Further studies are needed in order to develop a mouse model of esophageal adenocarcinoma.

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Physical Activity and Diet Behaviour in Colorectal Cancer Patients Receiving Chemotherapy: Associations with Quality of Life

July 29th, 2009

Background:
The relationship between colorectal cancer (CRC) risk and physical activity and dietary habits has been well-established, but less is known about this relationship in terms of quality of life (QOL) post-diagnosis. Moreover, it is unknown whether this relationship is consistent across cancer stage or treatment setting. Thus, the purpose of this study was to assess current diet and physical activity behaviour in CRC survivors receiving systemic chemotherapy, and to examine potential associations between these behaviours, quality of life, and social support.
Methods:
Using a cross-sectional survey, 67 CRC survivors currently receiving chemotherapy in Calgary, Alberta completed the survey package. Measures included demographic and medical data, physical activity levels, diet behaviour, QOL, and social support.
Results:
In a largely metastatic sample (63%), over half were meeting national diet guidelines (58%), few were meeting national physical activity guidelines (26%), and a small number were meeting both (17%). However, exploratory analysis revealed that an impressive 88% (n=57) were physically active at some level. Neither behaviour was significantly associated with QOL or perceived social support. Furthermore, there were no significant QOL differences between those treated with palliative intent or adjuvant therapy. Important group differences emerged between those meeting and not meeting the guidelines, and associations between QOL, age, BMI, and provisions of social support.
Conclusions:
These findings provide insight into lifestyle behaviours of CRC survivors currently receiving systemic chemotherapy, and the differences in perceived QOL as affected by severity of disease and treatment setting. Prospective studies in a larger sample of CRC survivors on chemotherapy are needed to confirm lifestyle behaviour patterns and identify factors related to quality of life that are unique to this population, especially receiving metastatic treatment. Furthermore, the appropriateness of national diet and exercise guidelines for survivors being treated with palliative intent needs to be addressed.

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Visceral obesity and the risk of Barrett’s esophagus in Japanese patients with non-alcoholic fatty liver disease

July 29th, 2009

Background:
The association between obesity and the risk of Barrett’s esophagus (BE) is unclear. Furthermore, the association between visceral obesity and the risk of BE is entirely unknown.
Methods:
We conducted a retrospective study in 163 patients with non-alcoholic fatty liver disease (NAFLD) who underwent both endoscopy and abdominal CT at an interval of less than a year at our institution. BE was endoscopically diagnosed based on the Prague C & M Criteria. The surface areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated from CT images at the level of the umbilicus. The correlations between the BMI, VAT, and SAT and the risk of BE were examined by univariate and multivariate analyses.
Results:
Sixty-nine of the 163 study participants (42.3 %) were diagnosed to have endoscopic BE, which was classified as short-segment BE (SSBE) in almost all of the cases. There were no significant differences in the age or gender distribution between the groups with and without BE. According to the results of the univariate analysis, VAT was significantly associated with the risk of BE; the BMI tended to be higher in the group with BE than in the group without BE, but this relation did not reach statistical significance. VAT was independently associated with the risk of BE even after adjustment for the BMI.
Conclusions:
In Japanese patients with NAFLD, obesity tended to be associated with the risk of BE, and this risk appeared to be mediated for the most part by abdominal visceral adiposity.

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Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa

July 29th, 2009

Background:
Antibody serology is an important tool in the investigation of celiac disease (CD), but does not always correlate with mucosal appearance in the small intestine. Patients with positive CD serology but normal mucosa (Marsh 0) are at increased risk of future CD. In this study we describe a model for identifying and characterizing individuals with normal mucosa but positive CD serology. Such individuals are sometimes referred to as having latent CD.
Methods:
The records of ten Swedish pathology departments were used to identify individuals with biopsies indicating normal duodenal/jejunal mucosa. Using the national personal identification number, these data were linked with CD serology data (antigliadin, antiendomysial and tissue transglutaminase antibodies); and we thereby identified 3,736 individuals with normal mucosa but positive CD serology. Two independent reviewers then manually reviewed their biopsy reports to estimate comorbidity. We also randomly selected 112 individuals for validation through patient chart review.
Results:
The majority of the 3,736 individuals were females (62%). Children (0-15 years) made up 21.4%. The median number of biopsy specimen was 3. Our review of biopsy reports found that other gastrointestinal comorbidity was rare (inflammatory bowel disease: 0.4%; helicobacter pylori infection: 0.2%). Some 22% individuals selected for patient chart review had a relative with CD. The most common symptoms among these individuals were diarrhea (46%) and abdominal pain (45%), while 26% had anemia. Although 27% of the individuals selected for validation had been informed about gluten-free diet, only 13% were adhering to a gluten-free diet at the end of follow-up.
Conclusion:
Individuals with positive CD serology but normal mucosa often have CD-like symptoms and a family history of CD.

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