ABSTRACT
BACKGROUND AND AIM: Barrett's esophagus (BE) is a premalignant condition for esophageal adenocarcinoma. Although risk factors exist for screening patients in the West, we aimed to determine the factors in terms of demographics and symptoms for patients in an Asian setting. METHODS: We recruited 1378 patients over a 7-year period as part of an ongoing gastric cancer screening program. An appropriately designed questionnaire was utilized to determine the necessary risk factors and symptoms with endoscopic analysis and subsequent histological confirmation as the gold standard. We utilized the existence of intestinal metaplasia of the distal esophagus as the primary diagnostic pathology. RESULTS: We demonstrated that no symptoms were indicative of BE in an Asian setting. Age (odds ratio 1.081, 95% confidence interval 1.022-1.143) and male gender (odds ratio 4.808, 95% confidence interval 1.727-13.33) proved significant demographic factors for the presence of intestinal metaplasia (P 0.007, 0.003, respectively). CONCLUSIONS: We advocate the utilization of increasing age and male gender as the primary risk factors for patients at risk of BE. We also recommend astute examination of the distal esophagus whilst patients undergo simultaneous gastric cancer screening.
ABSTRACT
OBJECTIVES: We hypothesized that RUNX3 inactivation by promoter hypermethylation in colorectal polyps is an early molecular event in colorectal carcinogenesis. METHODS: RUNX3 protein expression was analyzed immunohistochemically in 50 sporadic colorectal polyps comprising 19 hyperplastic polyps (HPs), 14 traditional serrated adenomas (TSAs), and 17 sporadic traditional adenomas (sTAs) as well as in 19 familial adenomatous polyposis (FAP) samples from 10 patients showing aberrant crypt foci (ACF) (n=91), small adenomas (SmAds) (n=40), and large adenomas (LAds) (n=13). In addition, we assessed the frequency of promoter hypermethylation of RUNX3 by methylation-specific PCR (MSP) in all the 50 sporadic polyps as well as 38 microdissected FAP polyps comprising ACF, SmAds, and LAds obtained from 7 FAP samples. A total of 12 normal colon samples were also included for RUNX3 MSP analysis. RESULTS: Compared to normal colon (2 of 12, 16%) and sTAs (3 of 17, 18%), HPs (15 of 19, 79%) and TSAs (8 of 14, 57%) displayed significant inactivation of RUNX3 (P<0.05). In FAP, RUNX3 inactivation was more frequently seen in ACF (78 of 91, 86%), SmAds (25 of 40, 62%), and LAds (6 of 13, 46%) compared to normal mucosa (0 of 19, 0%) in the same samples (all P<0.05). Promoter hypermethylation of RUNX3 was significantly higher in colorectal polyps (64 of 87, 74%) compared to normal colon (2 of 12, 16%) (P=0.001). Serrated polyps such as HPs (17 of 19, 89%) and TSAs (12 of 14, 86%) were significantly more methylated than sTAs (7 of 17, 44%) (P=0.004). RUNX3 hypermethylation was observed in 28 of the total 38 (74%) FAP polyps. Overall, RUNX3 promoter methylation correlated with inactivation of RUNX3 expression in sporadic (27 of 36, 75%) (P=0.022) and FAP (21 of 28, 75%) (P=0.021) polyps. CONCLUSIONS: Our data suggest that RUNX3 inactivation due to promoter hypermethylation in colorectal polyps represents an early event in colorectal cancer (CRC) progression. In addition, epigenetic RUNX3 inactivation is a frequent event in the serrated colonic polyps as well as in the ACF of FAP polyps.
Subject(s)
Adenomatous Polyposis Coli/genetics , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colonic Polyps/genetics , Colonic Polyps/pathology , Core Binding Factor Alpha 3 Subunit/genetics , Adenomatous Polyposis Coli/metabolism , Adenomatous Polyposis Coli/pathology , Case-Control Studies , Colonic Neoplasms/metabolism , Colonic Polyps/metabolism , Core Binding Factor Alpha 3 Subunit/metabolism , DNA Methylation/physiology , Epigenesis, Genetic/physiology , Humans , Hyperplasia , Promoter Regions, GeneticABSTRACT
GOALS: To estimate and compare the direct medical cost in the management of chronic hepatitis B (CHB) infection and its complications from the perspective of public health organizations in Hong Kong and Singapore. BACKGROUND: Hong Kong and Singapore are endemic hepatitis B virus areas with about 10% and 5%, respectively, of the population estimated as hepatitis B virus infected. STUDY: The medical histories of 660 patients with CHB who received medical services over 5 years from three major public hospitals in Hong Kong and Singapore were studied retrospectively. Costs were analyzed according to the five disease states and estimated in Hong Kong dollars (HKD) and Singapore dollars (SGD). RESULTS: In both Hong Kong and Singapore, the per-patient total annual cost increased with the severity of the disease. CHB cost HKD 6318 (US 810 dollars) in Hong Kong and SGD 718.15 (US 410.37 dollars) in Singapore. Compensated cirrhosis cost HKD 10,304 (US 1321 dollars) in Hong Kong and SGD 1,175.34 (US 671.62 dollars) in Singapore. Decompensated cirrhosis cost HKD 58,428 (US 7490 dollars) in Hong Kong and SGD 15,389.84 (US 8794.19 dollars) in Singapore. Hepatocellular carcinoma cost HKD 121,822 (US 15,618 dollars) in Hong Kong and SGD 12314.04 (US 7036.59 dollars) in Singapore. Each case of liver transplant was estimated to cost HKD 514,498 (US 65,961 dollars) in Hong Kong and SGD 86,369.28 (US 49,353.87 dollars) in Singapore. CHB in Hong Kong accounted for about 4% of the healthcare expenditure. CONCLUSION: This study confirms that CHB and its liver disease complications are a significant economic burden to the healthcare budgets of Hong Kong and Singapore, and indicates that effective therapy that arrests or reverses the progression of liver disease would be highly cost-effective.
