Human Monoclonal Antibody Inhibiting Reverse Transcriptase Activity of Hepatitis B Virus Polymerase Protein / 대한소화기학회지

BACKGROUND/AIMS: To develop a novel treatment method for hepatitis B virus (HBV) infection, we aimed to make a human monoclonal antibody inhibiting reverse transcriptase (RT) activity of P protein which was important in HBV replication by using phage display technique. Therefore, we analysed the usability of human monoclonal antibody as a protein based gene therapy. METHODS: Reverse transcriptase/polymerase (RT/POL) functional motif of P protein of HBV was cloned in pMAL-c vector and expressed as maltose binding fusion protein form. The RT/POL recombinant protein (pMRT/POL) was purified by amylose resin column. Using human single chain Fv phage antibody library with 1.1x10(10) size, human antibody against pMRT/POL was selected with BIAcore panning. Selected antibody fragments were analyzed for the activity of RT inhibition. Finally, they were analyzed for the affinity with BIAcore and the complementarity determining regions with nucleotide sequencing. RESULTS: pMRT/POL recombinant protein expressed in E. coli showed RT activity, 1microgram of recombinant protein had an activity equivalent to 5 unit of MMLV RT. By BIAcore panning, we could select 3 clones; POL-A5, POL-B8 and POL-B12. Each clone's RT inhibiting activity were 52-82%, affinity against antigen were 8.15x10(-8) M to 1.75x10(-6) M. CONCLUSIONS: Human monoclonal antibodies produced in this study showed low affinity, but efficiently inhibited the activity of RT in vitro. If POL-A5, POL-B8, and POL-B12 can be converted to intracellular antibody form, it can be used for protein-based gene therapy by inhibiting the replication through the neutralization of polymerase protein of HBV.

A Case of Secondary Amyloidosis Presenting as Massive Gastrointestinal Bleeding / 대한소화기학회지

Amyloidosis is a disorder characterized by extracellular deposition of amyloid in various tissues and organs. Gastrointestinal manifestations including gastroparesis, constipation, malabsorption, intestinal pseudo-obstruction, and bleeding are common. GI bleeding is a rare initial symptom which can be fatal in some cases. Absence of systemic symptoms and nonspecific endoscopic findings in amyloidosis may make diagnosis difficult. Therefore, amyloidosis-induced GI bleeding should be considered in patients with an obscure hemorrhage. Recently, we experienced a 65-year-old woman who presented with massive hematochezia as a manifestations of amyloidosis. Colonoscopy and SMA angiography showed massive bleeding in the small and large intestine. Colonoscopic biopsy established amyloidosis. We report this case with a review of the relevant literatures.

Controlled Comparison of Endoscopic Epinephrine Injection and Endoscopic Argon Plasma Coagulation for the Treatment of Acute Peptic Ulcer Bleeding / 대한소화기내시경학회지

BACKGROUND/AIMS: Endoscopic injection therapy with hypertonic saline Epinephrine (HSE) is the easiest and most widely used procedure for the management of peptic ulcer bleeding. Argon plasma coagulation (APC) is a recently introduced endoscopic hemostatic procedure. Thus, we performed a prospective trial to compare the hemostatic efficacy of APC and HSE. METHODS: Forty patients with the diagnosis of bleeding ulcer were randomly assigned to receive either HSE (n=20) or APC (n=20) treatment during the period of September 2003 to April 2004. The two groups were matched for gender, age, site of bleeding, the endoscopic findings and the initial hemoglobin at the study baseline. RESULTS: The bleeding was initially controlled in 18 patients (90%) of the APC group, and in 20 patients (100%) of the HSE group. Rebeeding occurred in one patient (5%) of the APC group and in 3 patients (15.5%) of the HSE group. The lengths of stay in the hospital were 11.7 days in the APC group and 10.7 days in the HSE group. Death occurred in 1 case in the APC group and in 1 case in the HSE group. The initial hemostatic efficacy showed no difference between the two groups. CONCLUSIONS: Argon plasma coagulation is as effective as hypertonic saline epinephrine injection for the initial management of acute peptic ulcer bleeding.

A Case of Cytomegalovirus Infection associated with Simultaneous Gastric, Duodenal and Colonic Ulcers / 대한소화기내시경학회지

Although cytomegalovirus (CMV) infection of the gastrointestinal tract can occur in persons with normal immune function, it almost exclusively affects the immunocompromised host such as transplant recipients and AIDS patients, and it can cause significant clinical illness. CMV remains the single most important pathogen that affects solid organ transplant recipients. While CMV can affect any segment of the gastrointestinal tract, the colon is the most common site of infection, and this is followed by the upper gastrointestinal tract. However, CMV infection associated with simultaneous gastric and colonic ulcer is very rare and this has been reported in only one case, and a case of simultaneous gastric, duodenal and colonic ulcer associated with CMV infection has not yet been reported in Korea. We report here on a case of simultaneous gastric, duodenal and colonic ulcer associated with CMV infection that showed the characteristic histologic findings seen for CMV infection in renal transplant recipients.

The Analysis of Appendiceal Mucocele with Emphasis on the Colonoscopic Findings / 대한소화기내시경학회지

BACKGROUND/AIMS: Appendiceal mucocele is relatively rare disease, however early diagnosis and adequate treatment is important because the rupture of mucocele during operation may results in pseudomyxoma peritonei which is fatal. Colonoscopy is very important tool to diagnose the mucocele of appendix earlier period. METHODS: We retrospectively analysed the medical records of ten cases of appendiceal mucoceles which were suspected by colonoscopy and surgically confirmed from January 1997 to March 2004. RESULTS: There was no gender difference and mean age was 55 years old. The colonoscopic findings of appendiceal mucocele were a type of submucosal tumor and the orifice of appendix was not seen in all the cases. The size was variable from 2.5 cm to 5.0 cm and the shape was spherical in majority, but one case of appendiceal mucocele lately diagnosed as mucinous cystadenocarcinoma had elongated, oval shape. The histologic diagnosis after resection were as follows: mucosal hyperplasia 4 cases (40%), mucinous cystadenoma 5 cases (50%) and mucinous cystadenocarcinoma 1 case (10%). CONCLUSIONS: Colonoscopy is an important diagnostic tool for suspecting appendiceal mucocele. It is important to confirm by surgical resection of appendiceal mucocele which is found even incidentally by colonoscopy.

A Case of Strangulated Intussusception Caused by the Small Intestinal Lipoma in Adult / 대한소화기내시경학회지

An intussusception in adulthood is an unusual cause of bowel obstruction. It accounts for up to 5% of all intussusception. Approximately 90% of cases are secondary to a definite lesion such as malignancy or lipoma. Most patients are asymptomatic and the lesion is often detected incidentally at colonoscopy, operation and autopsy. Strangulated intussuscetion is a rare case and also requires emergency operation. A 32-year-old woman visited our emergency room because of severe epigastric pain. Abdominal CT revealed a low density mass in bowel loop and distended small bowel loops filled with fluid. Colonoscopic finding showed huge purple-colored coil-spring lesion in the ascending colon. From this findings, we diagnosed a strangulated intussusception. Surgically removed specimen revealed a small intestinal lipoma.

A Case of Ileal Diverticulitis Causing Small Bowel Stenosis / 대한소화기내시경학회지

Diverticuli may be either congenital or acquired and may affect either the small or large intestines. Recently, the incidence of colonic diverticular disease is increasing in Korea but that of the small bowel, especially ileum, is very rare. We experienced a case of ileal diverticulitis causing small bowel stenosis. A 62-year-old woman was referred to our hospital because of diffuse abdominal pain for several months. Abdominal CT and small bowel series showed thickening of mucosal folds in the distal ileum. Colonoscopic findings revealed edema, mucosal thickening, blood clots, irregular dimpling, and stenosis in the distal ileum. The lesion was resected surgically and diagnosed as diverticulitis with microperforation.

Gastrointestinal Stromal Tumors: Clinical, Pathologic Features and Effectiveness of New Diagnostic Criteria / 대한소화기학회지

BACKGROUND/AIMS: The effective and reproducible diagnostic parameters for differentiating benign from malignant gastrointestinal stromal tumors (GISTs) are still not clear. In this study, GISTs were diagnosed and classified by immunohistochemistry and their clinical and pathologic features were investigated. GISTs were re-evaluated by Amin's and NIH's criteria, and prognostic relevance of these two criteria were compared. METHODS: Fifty cases of gastrointestinal mesenchymal tumor diagnosed from May 1990 to February 2000, were evaluated by immunohistochemical staining for CD117, CD34, smooth muscle actin, and S-100 protein. GISTs were diagnosed according to Amin's and NIH's criteria. The relationship between the prognosis and diagnosis based on Amin's or NIH's classification were analyzed. RESULTS: Thirty cases of gastrointestinal mesenchymal tumors were diagnosed as GISTs. The stomach (40%) and small bowel (40%) were the most common origin for GISTs. Immunophenotypically, null, myoid, neural, combined type were 70.0%, 10.0%, 16.7% and 3.3%, respectively. Seven cases showed metastasis and one case showed recurrence. According to Amin's criteria, 5 benign, 8 borderline and 17 malignant tumors were diagnosed. The NIH's criteria showed 2 very low risk, 6 low risk, 7 intermediate risk, and 15 high risk tumors. Metastasis or recurrence of GISTs had no significant relationship with malignancy according to Amin's criteria (p=0.4069) but had significant correlation with high risk tumor based on NIH's criteria. (p=0.0352). CONCLUSIONS: GISTs showing local invasion, distant metastasis or recurrence were related with high risk tumors based on NIH's criteria. NIH's criteria might be better reliable scheme than Amin's for predicting the prognosis of GISTs.

A Case of Colonic Muco-Submucosal Elongated Polyp / 대한소화기내시경학회지

Colonic muco-submucosal elongated polyp (CMSEP) is a rare disease which has been firstly reported by Matake. Only 21 cases have been reported since 1994. Although the mechanism of generation of such polyps remains unknown, their elongation may be caused by intestinal motion for a long period. The occurrence sites were distributed throughout the colon, excluding the rectum. CMSEP is coverd with normal mucosa and consisted of edematous, loose, fibrous, connective tissue and dense, fibrous submucosal layer, often dilatation of blood vessels and lymphatics. We present a case of CMSEP diagnosed by a colonoscopic polypectomy.

A Case of Idiopathic Granulomatous Pancreatitis / 대한소화기내시경학회지

Granulomatous pancreatitis is a rare disorder and recognized rarely during life or non-operatively. Noncaseating granulomas in the pancreas, histologically indistinguishable from sarcoidosis, can be seen in a variety of diseases such as tuberculosis, fungal infection, berylliosis, Hodgkin's disease, non-Hodgkin's lymphoma and Crohn's disease. Therefore, as with other granulomatous diseases, a tissue biopsy is essential for the diagnosis. Its clinical presentation is often similar to pancreatic cancer, with common presenting symptoms including abdominal pain, weight loss, jaundice, and anorexia. We report a case of idiopathic granulomatous pancreatitis in a 56-year-old women whose clinical and radiographic findings were suggestive of pancreatic cancer.

A Case of Anomalous Union of Pancreaticobiliary Drain with Choledochal Cyst and Adenomyomatosis of the Gallbladder / 대한소화기내시경학회지

Anomalous union of pancraeticobiliary drain (AUPBD) is uncommon anomaly of the pancreaticobiliary ductal union system. Usually, this anomaly is confirmed by long common channel (>15 mm) at ERCP and is divided into according to relationship between pancreatic duct and common bile duct. Recently several reports showed that AUPBD may be associated with congenital choledochal cyst and gallbladder carcinoma. A 33-year old man was admitted with RUQ pain and jaundice. Ultrasonography, Abdominal CT, ERCP, and PTBD cholangiography showed type I choledochal cyst, AUPBD and focal adenomyomatosis on the gallbladder. Whipple's operation with excision of the choledochal cyst and chloecystectomy were performed for treatment. This clinical experience suggests that high incidence of choledochal cyst in patients with AUPBD and gallbladder adenomyomatosis are may be closely related to the carcinogenesis of gallbladder cancer in patients with AUPBD.

A Case of Gastritis Cystica Profunda Suspiciously Caused by Gastric Foreign Body / 대한소화기내시경학회지

Gasritis cystica profunda (GCP) is a rare disease in which hyperplasia of mature glandular epithelium extends into the tissues beneath the submucosa. It shows multiple small cysts in the mucosa and submucosa of the stomach. It was firstly reported by Littler and Gleibermann on 1972. GCP is mainly observed at the site of gastroenterostomy but, it may occur in the stomach without a previous history of surgery. The proposed pathogenesis of the these abnormalities are related to ischemia, chronic inflammation and the presence of a foreign body. GCP may present not only as a submucosal tumor or as solitary or diffuse polyps but also as a giant gastric mucosal fold rarely. It should be differentiated from Menetrier's disease, Zollinger-Ellison syndrome, inflammatory disease and malignancy. We present a case of gastritis cystica profunda without having had any previous surgery, suspiciously caused by gastric foreign body. We made a diagnosis based on findings from the esophagogastroduodenoscopy, endoscopic ultrasonography and histologic findings after surgery.

A clinical study on the eradication therapy on multiple gastric polyposis associated with H. pylori infection / 대한내과학회지

BACKGROUND: Little has been known about the incidence, the relationship with H. pylori infection and the prognosis of the multiple gastric polyposis. Recently, it was suggested that the eradication of H. pylori infection led the disappearance of the gastric polyps associated with H. pylori. We carried out a prospective study to determine the effect of H. pylori eradication on multiple gastric polyposis associated with H. pylori. METHODS: From July 1997 through August 2000, 13 patients who had multiple gastric polyposis on upper gastrointestinal endoscopy were recruited for this study. After eradication of H. pylori, we performed follow-up endoscopy at 2-3 months and 5-6 months later. RESULTS: The topographical distributions of gastric polyps were as following : antrum only in 7 cases, antrum and lower body in 4 cases, antrum and fundus area in 1 case, and entire stomach in 1 cases, respectively. The histopathological findings were as following : 13 cases showed chronic active gastritis, 2 cases with hyperplastic polyps, and 1 case with adenomatous polyps. After eradication of H. pylori infection, regression of multiple gastric polyps occurred in 7 cases (53.8%). In 7 cases with regression, regression was observed in 5 cases with chronic active gastritis alone, 1 case with hyperplastic polyps, and 1 case with adenomatous polyps. The re-biopsy specimens in 7 cases with regression revealed that the grade of inflammation decreased from 2.2 to 1.5 by the histological index of the updated Sydney system. CONCLUSION: With these results, we may conclude that the development of multiple gastric polyposis might be closely related with chronic H. pylori infection, and the eradication of H. pylori could lead to the regression of polyposis.

Retrospective Study of 125 Cases Colon Polyp Patients Who Underwent Colonoscopic Polypectomy / 대한소화기내시경학회지

BACKGROUND/AIMS: Adenomatous polyp was a precancerous lesion and it's removal was the secondary prevention of colorectal cancer. So we evaluated: age, sex, gross findings (Yamada type, size, number), histologic types, the incidence of coexisting cancers. METHODS: We analyzed the 125 patients with colon polyps who underwent colonoscopic polypectomy from March 1993 to Febrary 1998 in Pusan Paik hospital Inje university. RESULTS: The male to female ratio was 1:0.43, and the polyps were most common in sixth decade. Abdominal pain was the most common symptom (34.4%). On occult blood examination, 25.5% of the patients with colorectal polyp had positive finding. According to Yamada classification, type IV is 49 patients (39.2%) and type III is 47 patients (37.6%). The most common size was 0.5 cm to 1.0 cm, and single polyp was noted in 68 cases (54.4%). Among patients with colon polyps, 6 cases had coexisting colon cancers, and 1 case was diagnosed as adenocarcinoma. Histologically, the numbers of adenomatous polyp and hyperplastic polyp were 74 (59.2%) and 17 (13.6%). Retention polyps were commom under the age of 20 years, but adenomatous polyps were common over the age of 40 years. Five cases diagnosed as adenomatous polyps on forceps biopsy were proven as nonadenomatous polyps on polypectomy sections. CONCLUSIONS: Among patients with colon polyps, 6 cases had coexisting colon cancers and 1 case was diagnosed adenocarcinoma but, did not reach statistical significance. The result of this study suggested that forceps biopsy results were different with polypectomy biopsy results, so we therefore recommands polypectomy as primary treatment for all colonic polyps.

Mutations of the Pre-S Region in HBV-Associated Liver Cirrhosis and Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: According to the recent research, mutations in the HBV pre-S region may have an impact on the progression of hepatitis B virus(HBV)-related liver disease. The aim of this study was to clarify the frequency and location of naturally occurring mutations in the pre-S region of HBV, and their possible effects on the clinical course of HBV-associated chronic liver diseases. METHODS: HBV DNA was extracted from the sera of 15 patients (8 with liver cirrhosis and 7 with hepatocellular carcinoma). The pre-S sequence was amplified via polymerase chain reaction, subcloning and sequenced. RESULTS: All patients had point mutations in the pre-S region. Nine of 10 mutation sites (90%) in the pre-S1 region, and 4 of 5 mutation sites (80%) in the pre-S2 region were identical in both liver cirrhosis and hepatocellular carcinoma. Deletions were detected in seven patients (4 with liver cirrhosis and 3 with hepatocellular carcinoma). Among the 4 patients with liver cirrhosis, three had deletion in 5'-end of the pre-S2 region and one spanning the 3'-end of the pre-S1 to 5'-end of the pre-S2 region. All 3 patients with hepatocellular carcinoma had deletions in 5'-end of the pre-S1 region, and two patients had simultaneous deletion spanning the 3'-end of the pre-S1 to the 5'-end of the pre-S2. CONCLUSION: The pre-S mutants were frequently detected in HBV-associated liver cirrhosis or hepatocellular carcinoma and the point mutations or deletions in the pre-S gene were clustered in specific regions.

The characteristics of the five cases of hepatic eosinophilic abscess / 대한내과학회지

Hepatic eosinophilic abscess is a very rare disease which has been reported in fascioliasis, and some gastrointestinal malignancy. We experienced 5 cases with hepatic eosinophilic abscesses which were caused by unknown etiology, confirmed by liver biopsy, from 1990 to 1994. The chracteristics of the cases including clinical menifestations, serologic findings, ultrasonography and abdominal computerizes tomogram(CT) were summerized. They had no characteristic findings except eosinophilia in clinical menifestations and they showed various ultrasonographic and CT findings which are different from the radiologic findings of liver abscesses by bacterial or amebic infection. We think that hepatic eosinophilic abscess must be included in differential diagnosis of all hepatic tumors.

A Case of Primary Antiphospholipid Syndrome associated with Chronic Hepatitis C / 대한내과학회지

Hepatitis C was known to be associated with many autoimmune disease, but the pathophysiology was not well understood. Antiphospholipid antibodies, which are autoantibodies detected to negatively charged phospholipids, are sometimes detected in infectious diseases, including sypilis and autoimmun diseases, such as systemic lupus erythematosus and unknown etiology. A few reports suggested that there is a relation between primary antiphospholipid syndrome and hepatitis C. We recently experienced a case of primary antiphospholipid syndrome with chronic hepatitis C in 20 years old womam who developed cerebral infartion. A brief review of related literature is presented.

Interferon Treatment on HBeAg Positive Chronic Hepatitis B with HBV Precore Mutant in Liver Tissue / 대한내과학회지

BACKGROUND: This study investigates the prevalance of HBV precore mutant in chronic B hepatitis patients and whether HBV precore mutants affect hepatic inflammation and response to interferon alfa. METHODS: HBV DNA in liver tissue from 48 chronic hepatitis patients was amplified by polymerase chain reaction. The HBV precore mutants were detected by direct sequencing of amplified PCR products. Thirty-three HBeAg-positive patients (Group 1: wild- type, Group 2: mixed) were received 3-6 MU INF three times a week for 4-6 months. We did follow-ups for at least six months(mean : Group 1-11.3, Group 2- 13.7 months). A complete responder was defined as persistent(>6 months) normalization of transaminase and loss of HBeAg and/or seroconversion. RESULTS: The HBV precore mutants were found in 15 cases(31.2%) among 48 patients: 7 cases(21.2%) in 33 HBeAg-positive patients and 8 cases(53.3%) in 15 HBeAg-negative patients. The HBV precore mutants were more frequently found in HBeAg-negative patients(p= 0.043). Differences in severity of hepatic pathology were not observed in the wild-type versus mutant-type chronic hepatitis B patients(p =1.00). Initial response rate was not significantly different between two Groups(p= 0.228), but complete response rate had a lower tendency in Group 2 (p=0.073). CONCLUSION: There is a tendency for HBV precore mutants to be less responsive to INF therapy than wild type. Therefore the patients with chronic hepatitis B should be treated as early as possible in natural history of their liver disease before the emergence of HBV precore mutants.

A case of CMV Gastrointestinal Disease / 대한소화기내시경학회지

Cytomegalovirus(CMV) commonly infects immunocompromised patient, including those with malignant disease, immunosuppression (particularly that induced by steroid therapy), organ transplantation AIDS. Involvement of the gastrointestinal tract is often associated with disseminated infection. Enteric involvement is expressed by inflammation, hemorhage, and ulceration. CMV is postulated to cause submucosal capillary and arteriolor vasculitis that can result in ischemic injury. CMV induced gastritic and colonic ulcers have not previously been reported in Korea. We report a patient of malignancy who had gastric and colonic ulcers assoicated with CMV infection whieh showed chracteristic histological finding of CMV infection in biopsed specimen.

Comparison of Endoscopic Injection with Hypertonic Saline-Epinephrine(HSE) and Absolute Ethanol for Bleeding Peptic Ulcers / 대한소화기내시경학회지

BACKGROUND/AIMS: The endoscopic injection therapy with hypertonic saline-epinephrine(HSE) and absolute ethanol are the most widely and easily used procedure in the management of patients with bleeding peptic ulcers. We performed a prospective, randomized trial to compare the hemostatic efficacy between HSE and absolute ethanol injection therapy. METHODS: During the period of 1993 to 1996, 60 patients who were identified as active bleeding or visible vessel were enrolled for this trial. The 60 patients were randomly divided into two groups(HSE group, 30 cases: ethhnol group, 30 cases). We performed endoscopic injection therapy with 3% saline and 1:10,000 epinephrine solution in HSE group, and with 99.5% absolute ethanol in ethanol group. The two groups were matched for sex, age, site of bleeding, endoscopic findings, initial hemoglobin, and concomitant illness at randomization. RESULTS: Bleeding was initially controlled in 21(70%) of the HSE group and in 29(96.7%) of the ethanol group(p < 0.05). Rebleeding occurred in 4(19%) of the HSE group and in 2(6.9%) of the ethanol group(p < 0.1). The ethanl group achieved a better hemostatic effect for spurting hemorrhage(3/13 vs 9/10, p < 0.05). The emergent operations were undergone in 10(33.3%) and 2(6.7%) for HSE group and ethanol group respectively(p < 0.01). The stay in hospital were less than in ethanol group(mean 9.5 vs 16.3, p < 0.01). The death were noticed in 6 cases(20%) in HSE group and 1 case(3.3%) in ethanol group(p < 0.05). CONCLUSIONS: This study shows that absolute ethanol injection is more efficaceous and better satisfactory method in peptic ulcer bleeding.