Chan Sik Won

Histological subclassification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical stage and grade of portal hypertension

BACKGROUND & AIMS Further histological subclassification of cirrhosis may be useful because of heterogeneity of severity within cirrhosis. We aimed to determine the relationship between histological subclassification and clinical stage of cirrhosis as well as grade of portal hypertension. METHODS One hundred-twenty-three biopsy-proven cirrhosis patients, whose clinical stage of cirrhosis and hepatic venous pressure gradient (HVPG) could be estimated, were included in this prospective study. Histology of cirrhosis was blindly subclassified using the Laennec fibrosis scoring system semi-quantitatively without knowledge of the clinical stage or the HVPG results. The Laennec system subclassifies cirrhosis as mild - thin septa, moderate - at least two broad septa, and severe - at least one very broad septum or many minute nodules. Clinical stages were determined by the presence or absence of varices, ascites, and variceal hemorrhage. Biological and laboratory data were also collected. RESULTS Alcohol intake was the most common cause of cirrhosis in this cohort (87, 70.7%). Histology of cirrhosis subclassified using the Laennec scoring system significantly correlated with both the clinical stage of cirrhosis (p < 0.001) and HVPG (mild: 8.1 ± 2.6 mm Hg, moderate: 12.4 ± 3.3mm Hg, severe: 16.3 ± 4.0 mm Hg, p < 0.001). With higher grades of histological subclassification of cirrhosis, increased frequency in both severe portal hypertension (HVPG ≥ 12 mm Hg) and episodes of variceal hemorrhage were observed (p < 0.001). CONCLUSIONS Histological subclassification of cirrhosis by the Laennec fibrosis scoring system is tightly correlated with both the clinical stage of cirrhosis and grade of portal hypertension. This suggests that cirrhosis should be subclassified into different stages according to its histological severity.

Upgrade of Lesions Initially Diagnosed as Low-Grade Gastric Dysplasia upon Forceps Biopsy Following Endoscopic Resection

Background/Aims Gastric dysplasia is generally accepted to be the precursor lesion of gastric carcinoma. Approximately 25% to 35% of histological diagnoses based on endoscopic forcep biopsies for gastric dysplastic lesions change following endoscopic resection (ER). The aim of this study was to determine the predictive endoscopic features of high-grade gastric dysplasia (HGD) or early gastric cancer (EGC) following ER for lesions initially diagnosed as low-grade dysplasia (LGD) by a forceps biopsy. Methods To determine predictive variables for upgraded histology (LGD to HGD or EGC). The lesion size, gross endoscopic appearance, location, and surface nodularity or redness as well as the presence of a depressed portion, Helicobacter pylori infection, and intestinal metaplasia were retrospectively investigated. Results Among 251 LGDs diagnosed by an initial forceps biopsy, the diagnoses of 100 lesions (39.8%) changed following the ER; 56 of 251 LGDs (22.3%) were diagnosed as HGD, 39 (15.5%) as adenocarcinoma, and 5 (2.0%) as chronic gastritis. In a univariate analysis, large lesions (>15 mm), those with a depressed portion, and those with surface nodularity were significantly correlated with a upgraded histology classification following ER. In a multivariate analysis, a large size (>15 mm; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.46 to 5.43) and a depressed portion in the lesion (OR, 2.7; 95% CI, 1.44 to 5.03) were predictive factors for upgraded histology following ER. Conclusions Our study shows that a substantial proportion of diagnoses of low-grade gastric dysplasias based on forceps biopsies were not representative of the entire lesion. We recommend ER for lesions with a depressed portion and for those larger than 15 mm.

Dobutamine stress echocardiography for evaluating cirrhotic cardiomyopathy in liver cirrhosis

Background/Aims The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the β-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). Methods Seventy-one cirrhotic patients with normal left ventricular (LV) chamber size and ejection fraction were enrolled. The LV systolic and diastolic functions were evaluated by two-dimensional and Doppler echocardiography at rest and during peak dobutamine infusion (40 µg/kg/min). An abnormal response was defined as a decrease of less than 10% in LV end-diastolic volume, a decrease of less than 20% in end-systolic volume, and an increase of less than 10% in LV ejection fraction (EF) at peak dobutamine infusion, based on previously used criteria. The early/late diastolic flow (E/A) ratio and diastolic parameters were also measured. Results A blunted LV response to dobutamine was observed in 18 of 71 cirrhotic patients (25.4%). The baseline EF was significantly higher in 18 patients with a blunted DSE response than that of those with a normal DSE response (P<0.05). The baseline and peak E/A ratios, which are common diastolic dysfunction markers, were higher in the cirrhosis group than in the control group (P<0.001). No adverse events associated with DSE were observed. Conclusions Blunted cardiac responses to dobutamine stimulation, which are implicated in defects in the β-adrenergic signaling pathway, might contribute to the pathogenesis of CCM in patients with cirrhosis.

171 PORTAL HYPERTENSIVE GASTROPATHY CORRELATE WITH PORTAL HYPERTENSION AND PROGNOSIS IN LIVER CIRRHOSIS

2. To assess whether the acute response to oral propranolol predicts the long-term response to these drugs. Methods: Thirty-eight patients with cirrhosis and HVPG ≥12mmHg were included. The HVPG was measured at baseline and 90 minutes after an oral dose of 80mg propranolol. Following randomisation, 17 patients received propranolol (mean dose 122.4mg/day) and 21 carvedilol (mean dose 14.0mg/day) titrated according to pulse and blood pressure response. After 12 weeks, HVPG-measurements were repeated. Results: Acute HVPG-response to propranolol was significant −19.3±12.8% (p < 0.01). Long-term treatment with propranolol and carvedilol decreased HVPG −12.5±16.7% (p < 0.01) and −18.7±16.7% (p < 0.01), respectively, with no significant difference between the two treatment-regimens (p = 0.26). The frequency of long-term responders (HVPG decrease ≥20% or to <12mmHg) was 41% (propranolol) versus 62% (carvedilol) (p = 0.20). There were no significant differences in DMAP, DGFR or Dweight during treatment. Using receiver operating characteristic curve analysis, the acute decrease in HVPG could not discriminate between patients with or without long-term effect of carvedilol (area under the curve (AUC) 0.54, p = 0.8). In the propranolol group the discrimination was better but still insignificant (AUC 0.73, p = 0.13). The acute decrease in HVPG of ≥12 % after oral propranolol was the best cutoff value to predict the long-term response, with a sensitivity and specificity of 71% and 78%, respectively. Neither the threshold of 12 % nor the traditional of 20% could significantly discriminate between long-term responders or non-responders (p = 0.13 and p=0.11, respectively). Conclusion: This randomized clinical trial shows no significant difference in the portal pressure-lowering effects of carvedilol and propranolol after 12 weeks of treatment. The acute response to propranolol might be a useful diagnostic tool to predict the longterm effect of propranolol but not of carvedilol.

1038 Lesser Sensitivity and Positive Predictive Value of Fecal Immunochemical Test (FIT) in Right Advanced Colonic Neoplasia Than Left Lesions

Background: Screening for Barretts esophagus (BE) and esophageal adenocarcinoma (EAC) with an EGD remains controversial, especially with regards to its cost-effectiveness. Prior models have not considered the added benefits of identifying early gastric cancer (GCA) or esophageal squamous cell cancer (SCC). In addition, screening costs can be reduced by performing screening EGD at the same time as screening colonoscopy. Aim: To evaluate the cost effectiveness of screening the general population for UGI cancers (EAC, esophageal SCC, GCA) by performing an EGD at the time of screening colonoscopy. Methods: A Markov Model was created using a hypothetical cohort of 50 year old patients with no gastrointestinal symptoms who are already undergoing screening colonoscopy. The primary decision compared two strategies: adding and not adding a screening EGD. Options for surveillance for non-dysplastic BE (NDBE) and low grade dysplasia (LGD), non-compliance with surveillance, endoscopic eradication therapy (EET) for BE with high grade dysplasia (HGD) and mucosal EAC, and endoscopic misdiagnosis were included in the model. Transition rates and utility values were taken from the published literature and expert consensus. Costs were viewed from the perspective of a third party payor and were obtained from the Centers for Medicare and Medicaid Services. The time horizon was from age 50 to age 80 or death. The primary outcome was the incremental cost-effectiveness ratio (ICER). Results: Screening the general population at the age of 50 for UGI cancers with surveillance of NDBE and LGD required

M1039 Prevalence and Risk Factors of Colorectal Neoplasms According to Coronary Artery Obstructive Disease

113,500 per quality-adjusted life-year (QALY) compared to no screening or surveillance. A screening only strategy (no BE surveillance) was dominated by the screening and surveillance strategy. If all patients were compliant with surveillance guidelines and all patients with HGD and mucosal EAC underwent EET (base case: 55% compliant, 50% choose EET while remaining undergo surgery), the ICER for screening and surveillance decreased to

Portal hypertensive gastropathy: correlation with portal hypertension and prognosis in cirrhosis.

92,300 per QALY compared to no screening or surveillance. In one-way sensitivity analyses, the prevalence of EAC, esophageal SCC, or GCA would have to increase by a factor of 10.3, 28.7, or 5.8, respectively to generate an ICER of less than

Risk Factors of Rebleeding Following Endoscopic Therapy for Nonvariceal Upper Gastrointestinal Hemorrhage

50,000 per QALY. Conclusion: The ICE ratio for screening the general population for UGI cancers with endoscopy remains high, despite accounting for reduced endoscopy costs and the combined benefits of detecting early EAC, esophageal SCC, and GCA. However, the ICER compares favorably to commonly performed screening strategies for other cancers.

442 Technological Assistance of Cap-Assisted Chromoendoscopy Enhances the Detection Rates of Both Colorectal Adenoma and Proximal Serrated Polyp in an Average-Risk Screening Population: Preliminary Results of a Multi-Center Randomized Controlled Trial

Background and Aim: African Americans (AA) are at higher risk for colorectal cancers than general population and the neoplastic changes could be detected if followed properly. The aim of this study was to evaluate the incidence of colon cancer in patients who have previously undergone polypectomy. Method: In a retrospective study, 4793 documented symptomatic (GI bleeding, abdominal pain, weight loss) patients aged 40-90 years with no personal or family history of familial adenomatous polyposis and inflammatory bowel disease who underwent colonoscopy were identified from pathology, surgery and colonoscopy centers of Howard University Hospital over a period of 49 years (1959-2007). Demographic characteristics and histological findings were recorded. The frequency of pathological subtypes (tubular, villous, and tubular-villus and adenomatous polyps) of colorectal polyps was determined. Logistic regression was used to assess the independent risk factor of malignancy in patients with a prior diagnosis of adenoma. Results: Among 4793 patients with colon adenoma (without cancer) diagnosed from 1959-2007. There were 1619 (34%) patients with only right sided adenomas, 2951 (62%) were left sided and 220 (4%) were had adenoma on both sides of colon. Among the adenoma cases 52% (n=74) were 64 years or younger. Half (n=48) of the patients developed cancer before 1999. During the study period colon cancer occurred in 3% of cases previously diagnosed with adenoma. Adjusting for effect of sex and age, tubular adenoma (OR:2.5, 95%CI:1.6-4.1) and right colon location (OR:5.7,95% CI:3.9-8.5) were risk factor for neoplastic changes in cases with adenoma. The median (IQR) duration between diagnosis of adenoma and subsequent colon cancer was 9 (4-15) years. Conclusion: Despite adenoma diagnosis and removal, neoplastic changes is a fairly prevalent outcome in African-American with colorectal adenoma. High risk groups includes right sided and multiple adenoma. Compliance with full colonoscopy after polypectomy will reduce the risk of neoplastic progression in this group.