Kirti Shetty

The risk for cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis.

ObjectiveRecent studies have implicated primary sclerosing cholangitis (PSC) as a risk factor for colorectal cancer (CRC) in ulcerative colitis (UC). Our study was designed to define both the risk and the risk factors for CRC or dysplasia in a large UC cohort with PSC.MethodsPatients with UC and PSC were compared with a random sample of UC controls without PSC. Patients were analyzed from the inception of disease until an outcome or censor.ResultsThirty-three (25%) of 132 UC patients with PSC developed CRC or dysplasia compared with 11 (5.6%) of 196 controls (adjusted relative risk 3.15, 95% confidence interval 1.37–7.27). Possible risk factors were chronic disease activity and lack of folate supplementation. Of 17 CRCs in the PSC group, 76% occurred proximal to the splenic flexure and 35% presented at an advanced stage, compared with one of five (20%) CRCs in controls being proximal and none being advanced. Six (4.5%) PSC patients, and no controls, died of CRC (p < 0.01).ConclusionsUC patients with PSC are at increased risk of developing CRC or dysplasia. Chronically active disease may be a risk factor, whereas folate could have a protective effect. CRCs associated with PSC are more likely to be proximal, to be diagnosed at a more advanced stage, and to be fatal.

Sa1851 Prognostic Significance of TGF-β Signaling in Human Hepatocellular Carcinoma

A S L D A b st ra ct s (LCD) including the variants small cell change (SCC), and large cell change (LCC), HCC, and NLC control tissues using Vectra® automated multispectral imaging system, and to evaluate any differential staining features between groups.Design: FOXM1 immunohistochemistry was performed on a liver cancer progression tissue array consisting of 85 paired liver tissue cores representing 20 NDC, 40 LCD consisting of 20 SCC and 20 LCC, 20 HCC, and 5 NLC control tissues in optical density by Vectra® automated multispectral imaging system. Staining was statistically compared between sample groups using a 2 tailed p-value derived from Welchs T Test. Results: The mean FOXM1 nuclear staining in OD was NLC 0.0318 ±0.0107, SCC 0.0741 ±0.0239, NDC 0.0717 ±0.0216, LCC 0.1103 ±0.1210, and HCC 0.1134 ±0.0378. Nuclear staining features by FOXM1 had three distinct groups with the highest staining seen in HCC and LCC, followed by SCC and NDC, and the least in NLC. The nuclear staining features of FOXM1 in HCC and LCC were similar (p=0.9158), as were those seen in SCC and NDC (p=0.7437). NLC showed markedly less staining (p <0.0088) than all other sample groups. SCC and NDC had statistically less staining than HCC (p<0.0003). SCC and NDC did not have statistically different nuclear staining from LCC (p=0.1961 for SCC, and p=0.1677 for NDC). Conclusions: Here, we provide evidence that the hepatocyte nuclear expression of the protein product of human proto-oncogene FOXM1 shows a stepwise increase in NLC and paired liver tissue samples of NDC and SCC, and LCC and HCC by Vectra®automated multispectral imaging system. Further, FOXM1 nuclear expression rises in LCC, before the development of HCCduring hepatocarcinogenesis. Additionally, the FOXM1 nuclear immunolevels did not differ in LCC and HCC.

Tu1175 The Protective Influence of Vitamin D in Hepatocellular Carcinoma

Backgrounds: Green tea catechins (GTCs) have been shown to provide anti-carcinogenic effects in several laboratory studies. Although the effect of green tea consumption on the risk of gastric cancer has been studied in epidemiological studies, the results remain controversial. The anti-carcinogenic mechanisms of GTCs have not been fully evaluated in rodent models of gastric cancer. Previous reports indicate that transgenic INS-GASmice are hypergastrinemic and induced corpus gastritis and eventually developed gastric cancer at over 20 months old. Aim: The aim of our study was to investigate the molecular effects of GTCs on gastritis and premalignant lesions in INS-GAS mice. Methods: Thirty eight, male INSGAS mice on a FVB background were used in this study. Mice were divided into two groups: A GTCs group and control. Mice in the GTCs group were allowed free access to drinking water containing 2000ppm of GTCs from the age of 9 weeks. Mice were euthanized at the age of 13 or 37 weeks. Histological scores (inflammation and dysplasia) were graded on a blinded basis by pathologist on a scale from 0 to 4. The mRNA expressions of IFN-gamma and TNF-alpha in the corpus of stomachs were evaluated using quantitative PCR. Statistical analysis was performed using a Mann-Whitney U test. Results: Body weights in mice supplemented with GTCs were significantly lower than that of controls at both 13 and 37 weeks of age (p < 0.05). Treated and control mice developed minimal to mild corpus gastritis, although dysplasia was evident. The histological score of dysplasia in mice supplemented with GTCs was significantly lower than that in controls at 37 weeks of age (p < 0.05). GTCs supplementation did not affect the inflammation score. The mRNA level of IFN-gamma in mice administrated GTCs was significantly lower than that of controls at 13 weeks of age (p < 0.05), although it did not reach statistical significance at 34 weeks of age (p = 0.056). GTCs supplementation did not alter TNF-alpha mRNA expression levels between both groups. Conclusions: Administration of GTCs attenuated progression of gastric dysplasia in INS-GAS male mice. These results demonstrated that IFN-gamma dependent mechanisms may be involved in the protective role of GTCs in development of gastritis and premalignant lesions in this rodent model.