H.J. Chun

Biliary papillary hyperplasia with clonorchiasis resembling cholangiocarcinoma.

Infection by the liver fluke Clonorchis sinensis is very common in the Far East. It causes low grade inflammatory changes and proliferation in the biliary tree. Initially there is desquamation of the biliary epithelium, followed by hyperplasia and adenomatous proliferation. Cholangiocarcinomas are potential long term complications. We present a case of biliary papillary hyperplasia with clonorchiasis resembling cholangiocarcinoma in a 69-yr-old Korean man. Early recognition of biliary hyperplasia and treatment of Clonorchis sinensis is important to prevent development of cholangiocarcinoma, especially in the Far East.

Efficacy of Helicobacter pylori eradication therapy in chronic liver disease

BACKGROUND/AIMSnPeptic ulcers occur more commonly in patients with liver cirrhosis (LC). Helicobacter pylori is recognized as the most important etiology in the pathogenesis of peptic ulcers. We investigated the efficacy of proton pump inhibitor (PPI)-based triple therapy in patients with chronic liver disease and peptic ulcer.nnnPATIENTS AND METHODSnOne hundred sixty-three patients with LC or chronic hepatitis (CH) with a peptic ulcer and proven H. pylori infection were included. The combination of PPI, amoxicillin (1.0 g), and clarithromycin (500 mg), each given twice daily, was administered for 1 or 2 weeks. The eradication of H. pylori was determined by the rapid urease test, histology, or the 13C-urea breath test at least 4 weeks after completing the treatment.nnnRESULTSnThe eradication rate of H. pylori was similar between the LC and CH groups; 82.6% and 88.1%, respectively. In addition, there were no significant differences in eradication rates between the patients with Child-Pugh class A and Child-Pugh class B/C disease. The side effects in each group were generally mild. Only the serum ALT levels showed a significant correlation with the success of H. pylori eradication in both the LC and CH groups.nnnCONCLUSIONnThe PPI-based triple therapy achieves high eradication rates for H. pylori infection, in patients with chronic liver disease, without significant side effects.

Effects of Levosulpiride in Patients with Functional Dyspepsia Accompanied by Delayed Gastric Emptying

Objectives Levosulpiride is the levo-enantiomer of sulpiride, a well-known antiemetic, antidyspeptic and antipsychotic drug. This study was undertaken to investigate the effects of levosulpiride on dyspeptic symptoms and gastric motor function in a group of patients with functional dyspepsia showing delayed gastric emptying. Method Forty two eligible patients were entered into a 3 week, double-blind randomized comparison of 25mg of levosulpiride or placebo t.i.d.. Symptom assessment and gastric scintigraphy following the intake of scrambled egg sandwich, were performed in each patient before and after treatment. Results The improvement of symptom score in levosulpiride group was higher than the placebo group (p<0.05). We assessed global efficacy, which was excellent in 1 (6%), good 11 (65%), fair 4 (24%), nil 1 (6%) of those receiving levosulpiride, and fair 9(60%), nil 5 (33%), poor 1 (6%) of those receiving placebo. Levosulpiride tended to be more effective than placebo in relieving the dyspeptic symptoms especially in the subgroups of dysmotility-like (p<0.05) and nonspecific (p<0.05) as compared to other subgroups (p=0.16). The reduction of gastric emptying time after levosulpiride treatment was more marked than Placebo group (p<0.05). We found a significant correlation between changes of symptom score and gastric emptying time (r=0.47, p=0.01. No serious adverse effects were reported after administration of either levosulpiride or placebo. Only two patients reported mild somnolence during levosulpiride administration. Conclusions Levosulpiride is effective and well tolerated in patients with functional dyspepsia accompanied by delayed gastric emptying. Its efficacy may be related to its action on the gastric motor function by improving the delayed gastric emptying.

483 IL28B POLYMORPHISM IS ASSOCIATED WITH NECROINFLAMMATORY ACTIVITY AND ADVANCED FIBROSIS IN PATIENTS INFECTED WITH CHRONIC HEPATITIS DUE TO GENOTYPE NON-1 HCV

482 IS LIVER FIBROSIS PROGRESSION FASTER IN HUMAN IMMUNODEFICIENCY VIRUS/HEPATITIS C VIRUS COINFECTED PATIENTS ON ANTIRETROVIRAL THAN IN HCV ONLY INFECTED PATIENTS? F.H.D.L. Pace, M.L.G. Ferraz, A.E.B. Silva. Internal Medicine – Gastroenterology and Hepatology, Universidade Federal Juiz de Fora, Juiz de Fora, Internal Medicine – Gastroenterology and Hepatology, Universidade Federal de Sao Paulo, Sao Paulo, Brazil E-mail: fpace@oi.com.br

493 CLINICAL SIGNIFICANCE OF PRECORE AND CORE PROMOTER MUTATIONS IN KOREAN CHRONIC HEPATITIS B PATIENTS

Background and Aims: The clinical significance of precore/core promoter mutations of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients is controversial. We aimed to clarify the relationships between precore (G1896A) and core promoter (A1762T, G1764A) variants and serum HBV DNA levels, hepatic inflammation, and liver fibrosis in Korean CHB patients. Methods: A total of 226 treatment-naive CHB patients were studied. Mutations in the precore/core promoter regions were detected by RFMP. Liver biopsies were performed to assess fibrosis in 186 patients, while 40 patients had imaging findings compatible with cirrhosis. Serum alanine aminotransferase (ALT) levels were used as surrogate markers for hepatic inflammation. Results: Ninety patients (39.8%) showed eAg seroconversion. Core promoter and precore mutations were found in 87.2% and 52.2% of patients, respectively. Both types of mutations were more frequent in HBeAg negative patients than in HBeAg positive patients (P < 0.001). HBeAg negative patients were older with more advanced liver fibrosis but had lower serum ALT and HBV DNA levels compared to HBeAg positive patients (all P < 0.001). HBeAg positive patients with core promoter variants did not differ from those without such variants in serum HBV DNA levels, but were older with higher ALT levels and advanced fibrosis (all P < 0.01). HBeAg positive patients with precore variants had lower serum HBV DNA levels than those without mutations (P =0.023). Advanced fibrosis was associated with older age in both HBeAg positive and negative patients (P < 0.05), while core promoter variants were independently associated with disease progression (≥F2) in HBeAg positive patients (P =0.007). ALT levels showed independent correlations with viral load in both groups (P < 0.05). Precore variants showed inverse correlations with HBV DNA levels in HBeAg positive patients (P =0.015). Neither type of variant was correlated with fibrosis, serum ALT and HBV DNA levels in HBeAg negative patients. Conclusion: A1762T/G1764A and G1896A variants are closely associated with HBeAg seroconversion in persistently viremic Korean CHB patients. In HBeAg positive patients, precore variants are associated with enhanced host immune response and are capable of decreasing serum HBV DNA levels, while core promoter variants are associated with liver damage and progression of liver fibrosis.

Successfully cured primary esophageal lymphoma in a patient with acquired immune deficiency syndrome (AIDS).

primary presentation of human immunodeficiency virus (HIV)-associated extranodal non-Hodgkin’s lymphoma (NHL) [1]. Although rare, this disease should be suspected in patients with acquired immunodeficiency syndrome (AIDS) who have recurrent esophageal symptoms and esophageal ulcerations or a mass not responding to antiviral or antifungal therapy [2]. Endoscopy is essential to pathologic diagnosis, serving as a useful tool for differential diagnosis of esophageal diseases seen in AIDS patients. We report a completely healed case of esophageal NHL in an HIV-seropositive patient. A 39-year-old man diagnosed as having AIDS 6 years ago presented with odynophagia and dysphagia since 2 months for both solids and liquids. Esophagogastroduodenoscopy (EGD) revealed two lesions (l Fig. 1): the lesion in the upper esophagus showed mild inflammatory changes around an ulcer with a dirty base, whereas the mid-esophageal lesion, which was protruding into the lumen, consisted of an ulcer with irregular margins and a whitish layer on the top. Pathologic examination confirmed these lesions as NHL of diffuse large B-cell type (l Fig. 2). There was no notable abnormality in the thorax, abdomen, or pelvis, except for suspected mild wall thickening in the upper and mid-esophagus on computed tomography. Bone marrow biopsy showed normocellular marrow and normal karyotype, resulting in a definitive diagnosis of primary malignant lymphoma confined to the esophagus. Combination chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) was administered every 3 weeks, in conjunction with highly active antiretroviral therapy (HAART) (zidovudine, lamivudine, and indinavir). After 6 cycles of chemotherapy, the patient has been in a state of complete remission for nearly 3 years. A follow-up EGD 4 years after diagnosis (l Fig. 3) showed completely healed lesions with a minute persistent deformity. The endoscopic findings of HIV-seropositive primary esophageal lymphoma are variable, with no proven pathognomonic features. Histologic diagnosis is challenging; therefore, repeated endoscopic biopsies followed by empirical therapy and follow-up examinations are important and required for confirmation of diagnosis [3]. Successfully cured primary esophageal lymphoma in a patient with acquired immune deficiency syndrome (AIDS)

7063 An immunohistochemical study of the origin and differentiation of gastric stromal tumor.

Objective: Gastrointestinal stromal tumors(GISTs), formerly known as leiomyomas and leiomyosarcomas, are the subject of much debate and controversy regarding their histogenesis, criteria of diagnosis, prognostic features, and nomenclature. These tumors have various phenotypical features and are generally divided into (1) tumors showing differentiation toward smooth muscle cells, (2) tumors showing apparent differentiation toward neural elements, (3) tumors showing dual differentiation toward smooth muscle and neural elements, (4) tumors lacking differentiation toward either cell type(uncommitted type). Some authors use the term GIST in a more restricted sense, i.e. only for the uncommitted type. This study was performed to identify a possible origin and differentiation of gastric stromal tumor. Methods: An immunohistochemical staining was performed on 38 patients who were suspected to have gastric stromal tumors on gastroscopy or endoscopic ultrasonography and who were confirmed by endoscopic resection or operation between January 1994 and June 1999 at Department of Internal Medicine, Institute Digestive Disease and Nutrition, Korea University College of Medicine. Formalin-fixed, paraffinembedded tissues from 38 patinets were immunostained for CD 34, CD 117, Vimentin, SMA, Desmin, S-100, PGP 9.5, and NSE. Results: The patients age ranged from 26 to 81, with an average age of 53.8 years. The male to female ratio was 12:26. Endoscopic resections were performed on 22 patients and operations on 16 patients. The average tumor size was 25.3mm. On immunohistochemical staining, uncommitted type was found in 18 patients(47.4%), of which 17 patients(94.4%) were CD117(+) CD34(+)Vimentin(+), a phenotype consistent with a interstitial cells of Cajal(ICC). 12 patients(31.6%) were thought to have muscular differentiation with SMA(+)S-100(-), 7 patients(18.4%) showed neural differentiation with S-100(+)PGP(+)NSE(+)Vimentin(+)SMA(-), and 1 patient(2.6%) showed dual differentiation with S-100(+)PGP (+)NSE (+)Vimentin (+)SMA(+). Conclusion: Of the 38 gastric stromal tumors, there were 12 patients with muscular differentiation, 7 patients with neural differentiation, 1 patient with dual differentiation, and 18 patients with uncommitted type. Most of uncommitted type had a phenotype of ICC, and this supports the hypothesis that uncommitted type has a origin of ICC.

7191 Electron microscopic study of association between helicobacter pylori and gsatric epithelial cells.

Backgrounds: To study pathophysiologic roles of Helicobacter pylori, we investigate the ultrastructural relation of Helicobacter pylori to the gastric epithelial cells. Subjects and Methods: Endoscopic biopsy of gastric antrum and body were performed from thirty-one patients(18men and 13women) with chronic gastritis. These specimens were processed and observed by transmission and scanning electron microscope(Hitachi H-600, Hitachi S- 450). Results: 1) Helicobacter pylori were spiral, coccoid, and intermediate or un-defined forms. 2)Most of the Helicobacter pylori were present in the mucus gel layer, on the surface of gastric epithelium and were common at the area around the junctional complexes. 3)Coccoid forms were most common in the mucosal layer. 4)The gastric epithelial cells show increased cytoplasmic electron density, few microvilli, disruption of apical membrane, presence of cell fragments in intercellular space and mucosal layer. Junctional complexes were frequently observed deep in the intercellular space between the cytoplasmic elevation filled with secretory granules. Complete destruction of junctional complex was not common. Conclusions: Helicobacter pylori had variable relations to the gastric epithelial cells in human stomach. These features may contribute to the pathogenic action of the organism.

4728 Classification of gastric stromal tumor according to immunohistochemical phenotype.

Backgrounds: Gastrointestinal stromal tumor(GIST) is a mesenchymal tumor which originates from the GI tracts. Although recent immunohistochemical study has helped classifying mesenchymal tumor and forming diagnostic criteria for benign and malignant tumors according to cells origin and differentiation, it is yet to be settled. This study has classified gastric stromal tumor by using immunohistochemical staining. Materials and Methods: Immunohistochemical staining was performed on the gastric stromal tumor specimens attained by endoscopic resection and surgery. Smooth muscle actin, Desmin, Neuron-specific enolase, S-100, CD 34 and Vimentin has been used as immunohistochemical antibodies and the guideline for Ackermans surgical pathology has been used as criteria for diagnosing malignancy(Ackermans surgical pathology 8th ed, 1996). Smooth muscle type was classified as benign, borderline and malignant according to the size and number of mitosis. Neural type was classified as malignant, and combined smooth muscle-neural type and uncommitted type were classified as either potentially malignant or malignant. Results: Subjects consisted of 12 males and 26 females with average age being 53 ± 12.8 years old. 22 cases has been endoscopically resected, 16 surgically removed, with the mean length of tumor being 25.3 ± 18.1 mm. The results of immunohistochemical staining showed 12 cases(31.6%) of smooth muscle type, 7 cases(18.4%) of neural type, 1 case(2.6%) of combined smooth muscle-neural type and 18 cases(47.4%) of uncommitted type. On the basis of above immunohistochemical results and histologic findings, 12 cases(31.6%) were regarded as benign, 17 cases(44.7%) as potentially malignant or malignant, and 9 cases(23.7%) as malignant(Table). Conclusion: When classified by immunohistochemical staining, 68.4% of gastric stromal tumor proved to be potentially malignant or malignant.

⁎4727 Reassessment of usefulness of eus in differentiation of benign and malignant gastric stromal tumors which were diagnosed according to pathologic guidelines of ackerman's surgical pathology.

Backgrounds: GISTs originate from mesenchymal tissue within the GI tract, and it is difficult to differentiate between benign and malignancy by endoscopy. Although recent development of EUS allows a trial of differentiation from benign and malignant stromal tumors, its diagnostic accuracy is controversial. The aim of this study is to determine whether EUS can differentiate between benign and malignant gastric stromal tumors. Materials and Methods: EUS was performed prior to endoscopic resection or surgical resection of 38 gastric stromal tumors. EUS features such as tumor size(diameter>4 cm), irregular extraluminal border, echogenic foci, and cystic spaces, which were proposed by Chak A et al. as EUS findings of malignant GISTs(Gastrointest Endosc 1997) were evaluated. Pathologic diagnosis was based on guidelines of Ackermans surgical pathology (Ackermans surgical pathology 8th ed, 1996). Results: Subjects consisted of 12 males and 26 females. 22 cases has been endoscopically resected, 16 cases surgically removed. The results of immunohistochemical staining showed 12 cases of smooth muscle type, 7 cases of neural type, 1 case of mixed type and 18 cases of uncommitted type. On the basis of above immunohistochemical results and histologic findings, 12 cases were regarded as benign, 17 cases as potentially malignant or malignant, and 9 cases as malignant. Analyses of EUS features according to the criteria of Chak et al. are shown in the following table. Conclusion: When gastric stromal tumors were diagnosed with criteria from Ackermans surgical pathology, EUS features, which were proposed by Chak et al, were assessed to be less useful in differentiating between benign and malignant stromal tumors.