Phase III Clinical Trial of Revaprazan (Revanex(R)) for Gastric Ulcer / 대한소화기내시경학회지

BACKGROUND/AIMS: This randomized, double-blind, phase III, multicenter trial was carried out to compare the efficacy and safety of revaprazan, a novel acid pump antagonist, with that of omeprazole in patients with more than one of gastric ulcers. METHODS: Two hundred and ninety two subjects were randomized to 4~8 weeks of treatment with either revaprazan 200 mg or omeprazole 20 mg. The primary efficacy parameter was the cumulative healing rate determined by endoscopy after 4 and 8 weeks of treatment, and the secondary efficacy parameter was an improvement rate of pain. RESULTS: The intention-to-treat analysis revealed revaprazan and omeprazole to have similar cumulative healing rates (93.0% and 89.6%, respectively; p=0.3038). The per-protocol analysis revealed revaprazan and omeprazole to also have similar cumulative healing rates (99.1% and 100%, respectively; p= 0.3229). In both analyses, there were no significant differences in an improvement rate of pain between the two groups. Both drugs were well tolerated. CONCLUSIONS: Revaprazan has similar efficacy to omeprazole in the treatment of patients with gastric ulcer with a once a day application of revaprazan 200 mg or omeprazole 20 mg over a 4 to 8-week period. In terms of safety, revaprazan was well tolerated.

Phase III Clinical Trial of Revaprazan (Revanex(R)) for Gastritis / 대한소화기내시경학회지

BACKGROUND/AIMS: We performed a randomized, double-blind, phase III, multicenter trial to assess the comparative efficacy and safety of revaprazan, which is a novel acid pump antagonist in comparison with ranitidine for treating patients suffering with acute gastritis and acute aggravation of chronic gastritis. METHODS: Five hundred and twelve subjects were randomized to 2 weeks of treatment with either revaprazan 200 mg q.d. or ranitidine 150 mg b.i.d. The primary efficacy parameter was the estimated improvement rate according to endoscopy, and the secondary efficacy parameter was the improvement rate for the subjects' symptoms. RESULTS: The estimated improvement rates at 2 weeks (intention-to-treat analysis) were 79.9% with revaprazan and 60.5% with ranitidine; a significant difference was found between the two groups (p<0.0001). On the per-protocol analysis, the estimated improvement rates for revaprazan and ranitidine were 79.4% and 60.2%, respectively. There was a significant difference in the estimated improvement rates between the two groups (p<0.0001). On both analyses, there were no significant differences between the two groups for the improvement rates of the subjects' symptoms. Both drugs were well tolerated. CONCLUSIONS: The efficacy of revaprazan was higher than that of ranitidine for the estimated improvement rate according to endoscopy and also for the symptomatological improvement rate, and revaprazan was well tolerated by the subjects suffering with gastritis.

Revaprazan (Revanex(R)), a Novel Acid Pump Antagonist, for Duodenal Ulcer: Results of a Double-Blind, Randomized, Parallel, Multi-Center Phase III Clinical Trial / 대한소화기내시경학회지

BACKGROUND/AIMS: To assess the comparative efficacy and safety of revaprazan, a novel acid pump antagonist, versus omeprazole in patients with duodenal ulcer, we performed a randomized, double-blind, phase III, multicenter trial. METHODS: Two hundred and twenty eight patients were randomized to 4 weeks of treatment with either revaprazan 200 mg or omeprazole 20 mg once daily. Primary efficacy parameter was complete ulcer healing by endoscopy, and secondary parameter was the improvement in the severity of daytime and nighttime pain. RESULTS: Healing rates at 4 weeks (intention-to-treat analysis) were 91.7% with revaprazan 200 mg and 91.3% with omeprazole 20 mg; there were no significant differences between two groups (p=0.9228). In per-protocol analysis, healing rates of revaprazan 200 mg and omeprazole 20 mg were 94.4% and 92.3%, respectively. There was no significant difference in healing rate between two groups (p=0.5666). There was no significant difference between two groups in improvement rates of daytime and nighttime pain. Both drugs were well tolerated. CONCLUSIONS: Revaprazan 200 mg was equivalent to omeprazole 20 mg for both ulcer healing and symptom relief, and was well tolerated in patients with duodenal ulcer.

A Case of Ascites by Pseudomembranous Colitis, Initially Diagnosed Malignant Asites / 대한소화기내시경학회지

Pseudomembranous colitis (PMC) is mostly related with the antibiotics and it presents with diarrhea, abdominal pain, fever, hypoalbuminemia and hypovolemia. In the clinical course of pseudomembranous colitis (PMC), ascites is a rare presentation, and high elevation of carcinoembryonic antigen (CEA) associated with PMC is also a very rare presentation. We experienced a case taken cephalosporin group antibiotics for six weeks and presented with fever, abdominal pain, severe diarrhea, and massive ascites. During evaluation, we found low serum-ascites albumin gradient and high level of CEA in both ascites and plasma. With the impression of hidden malignancy, the special studies were done, but PMC was only found without malignancy. After vancomycin therapy, all symptoms were relieved and CEA level declined.

The LDH to AST ratio as an indicator of pancreatic necrosis in acute biliary and alcoholic pancreatitis / 대한내과학회지

BACKGROUND: Lactate dehydrogenase (LDH) has been reported to be a sensitive indicator of pancreatic necrosis (PN), and some studies suggested that an elevation of the ratio of LDH to AST (LDH/AST ratio) woud be more accurate indicator of PN in acute biliary pncreatitis (BP). However, there were no studies in alcoholic pancreatitis (AP). The aim of this study was to assess the clinical usefulness of LDH/AST ratio in alcoholic pancreatitis (AP) as a indicator of PN. METHODS: On the basis of CT scan findings, the patients were categorized into two groups as having PN or non-PN. The plasma levels of the LDH, AST and LDH/AST ratio over two weeks postadmission period were evaluated and compared with in two groups of patients with BP (consiting of 12 PN and 34 non-PN patients), and with AP (consisting of 14 PN and 38 non-PN patients). RESULTS: In acute BP, on post-admission days 1 and 2, the LDH/AST ratio were low in both groups without significant difference. In the group with PN, thereafter, the LDH/AST ratio increased gradually, reached peak values at the 7th days and decreased. In the non-PN patients, the LDH/AST ratio increased gradually, but remained below the control range. The LDH/AST ratios were significantly higher from post-admission day 3 in the group with PN than in the non-PN group. In acute AP, the LDH levels were significantly higher over two weeks from admission day in the PN patients. The LDH/AST ratios were remained within or below the control range in both groups, though with statistically significnat difference. CONCLUSION: The LDH/AST ratio could be used as an indicator of PN in acute BP. In acute AP, however, LDH was a more useful indicator from the early stage in the course.

A Case of Gastric Adenocarcinoma Appearing as Skin Metastasis / 대한소화기내시경학회지

The skin is an uncommon site of distant metastasis from any internal malignancy, and the incidence of metastatic skin lesions as the first symptom of disease is only 0.8% in patients with all systemic malignancies. Furthermore, cutaneous metastasis from adenocarcinoma of the stomach has been found to be extremely rare. A 35-year-old female patient was admitted due to multiple cutaneous nodules in her chest, abdomen, and back. A gastroendoscopic examination and biopsy was made according to the results of skin pathologic findings. Stomach and skin biopsy results revealed a signet ring cell type of adenocarcinoma. A case of gastric adenocarcinoma in which metastatic skin nodules appeared as the first sign of disease, is here in reported with a review of related literature.

Clinical Significance of Low Junction of the Cystic Duct / 대한소화기내시경학회지

BACKGROUND AND AIMS: Recently, similar to the anomalous union of the pancreatobiliary duct (AUPBD), a low junction of the cystic duct (LJCD) was reported to be associated with the carcinogenesis of the gall bladder (GB) and other pancreatobiliary diseases. This study was designed to evaluate the clinical significance of the LJCD. METHODS: In this study all cases were performed ERCP. Three hundred and twenty two cases were selected due to their clear identification of the union area between the bile duct and the pancreatic duct, inserted area of the cystic duct, and the duodenal opening of the bile duct. The LJCD was defined that the cystic duct joins the distal bile duct between the upper margin of the pancreas and the duodenal opening of the bile duct. AUPBD was defined as a common channel greater than 15 mm in length. The clinical data was divided into four groups-normal biliary anatomy (Group 1), AUPBD (Group 2), LJCD (Group 3), and combined with AUPBD and LJCD (Group 4), and then analyzed. RESULTS: The mean age of the subjects was 56.6 with 183 male and 139 female cases. Among 322 cases, there were 7.1% (23 of 322) of AUPBD, 11.2% (36 of 322) of LJCD and 0.6% (2 of 322) of combined with AUPBD and LJCD. The clinical symptoms and the laboratory findings of the subjects were no statistical significance among the groups. The incidence of CBD stones was 27.3% (88 of 322) of the patients; 25.3% (66 of 261) of Group 1, 21.7% (5 of 23) of Group 2, 47.2% (17 of 36) of Group 3, and were significantly higher in Group 3 than Group 1 & Group 3 (p=0.038). However, the incidence of GB stones and cystic duct stones was no statistical significance among the groups. Malignant diseases of the biliary trees were 9.65% (31 of 322) of the patients; 6.8% (18 of 261) of Group 1, 26% (6 of 23) of Group 2, 13.8% (5 of 36) of Group 3, and were closely correlated with AUPBD (p<0.001) and LJCD (p=0.017). CONCLUSIONS: LJCD is relatively common in patients undergoing ERCP and closely correlated with the CBD stones and the malignacies of the biliary system. However its role in these condition is uncertain and needs to be further investigated.

A Case of Choledochocolonic Fistula Combined with Absence of Gallbladder / 대한소화기내시경학회지

The enterobiliary fistulas are mostly spontaneous and are caused by biliary disease associated with calculi. Review of many series shows that the most common variety of enterobiliary fistulas is a cholecystoduodenal fistula followed by cholecystocolic, cholecystogastric and choledochoduodenal fistula in that order. But very few cases of choledochocolonic fistulae have been reported. We report a case of choledocholithiasis combined with the absence of gallbladder leading to a choledochocolonic fistula, which was confirmed by endoscopic retrograde cholangiography and abdominal exploration in a 63- year-old male patient with complaint of right upper abdominal pain.

A Case of Double Primary Cancer Associated with a Low Junction of the Cystic Duct / 대한소화기내시경학회지

Recently it has been discovered that anomalous union of pancreaticobiliary duct (AUPBD) may play an important role in the pathogenesis of bile duct cancer. Similar to this fact, there were a few reports on the clinical significance of the low junction of the cystic duct (LJCD). LJCD refers to the situation whereby the cystic duct enters the common duct at a low position between the upper margin of the pancreas and the duodenal opening of the bile duct. The pathogenetic mechanism in LJCD is similar to AUPBD in that the pancreatic juice refluxes to the bile duct, mixes with biles, and then generates the mutagens, which act as inflammatory substances and carcinogens on the epithelium of the bile duct. A 51-year-old male who experienced dyspepsia was hospitalized due to his abnormally functioning liver and dilated common bile duct. We confirmed primary cholangiocarcinoma on the common hepatic duct and gallbladder carcinoma associated with LJCD by ERCP and pathologic review of surgical specimen. We report a case of synchronous type double primary cancer associated with LJCD with a brief review of the literatures.

Immunogenicity and Safety of Recombinant Hepatitis B Vaccine(Engerix B) / 감염

BACKGROUND: Several studies on the efficacy and safety of the hepatitis B vaccine have shown variable immunogenicity. In this study we reexamined the immunogenicity and safety of recombinant hepatitis B vaccine, Engerix B which have currently been administered to the children in Korea. METHODS: Serum samples were collected from 126 children and 111 adults who were immunized according to the 0, 1, 2-month and 0, 1, 6-month vaccination schedule. Anti-HBs antibody titers were measured by ELISA in sera obtained after each immunization, and compared by immunization schedules. RESULTS: In 62 children with 0, 1, 2-month immunization schedule seroconversion rate was 83.9% after 1st vaccination, 96.8% after 2nd, and 98.4% after 3rd. In 64 children with 0, 1, 6-month immunization schedule seroconversion rates was 78.1% after 1st vaccination, 87.5% after 2nd and 100% after 3rd. In 50 adults immunized with 0, 1, 2-month schedule seroconversionrates was 48.0% after 1st vaccination, 74.0% after 2nd and 90.0% after 3rd. In 61 adults immunized with 0, 1, 6-month schedule seroconversion rate was 44.3% after 1st vaccination, 65.6% after 2nd and 93.4% after 3rd. Seroconversion rate after 0, 1, 2- month vaccination schedule were 98.4% in children and 90.0% in adults. Seroconversion rate after 0, 1, 6-month schedule were 100% in children and 93.4% in adults. There were no significant local and systemic untoward reactions among vaccinees. CONCLUSION: The recombinant Engerix B is excellent in immunogenicity with 93.4% and 100% seroconversion rates in adults and children, respectively. There is no significant difference in seroconversion rate between two vaccination schedule. The vaccine is safe.

DNase, RNase, & RNase Inhibitors as Markers for Hepatocellular Carcinoma / 대한내과학회지

OBJECTIVE: Activities of nucleases (acid DNase and neutral RNase) and RNase inhibitor known to be involved in carcinogenesis and suppression of cancer were determined in cancer tissue, serum and ascitic fluid of patients with hepatocellular carcinoma and were compared with those of the controls. Also studied were nucleases and RNase inhibitor isolated from hepatocellular carcinoma tissue and ascitic fluid of the cancer patients to evaluate the properties and interactions between them. METHOD: Activities of nucleases and RNase inhibitor were measured in cancer tissue, serum and ascitic fluid of patients with hepatocellular carcinoma by ultraviolet spectrophotometry. Nucleases and RNase inhibitor were isolated from hepatocellular carcinoma tissue and ascitic fluid of the cancer patients by DEAE-cellulose column chromatography. As controls, normal tissue of the cancer patients, serum of healthy persons and ascitic fluid of cirrhotic patients were used. RESULT: Activities of DNase, RNase and RNase inhibitor were significantly increased in hepatocellular carcinoma tissue. DNase activity was not detected, RNase activity was increased and RNase inhibitor activity was unchanged in both serum and ascitic fluid of the hepatocellular carcinoma patients. DNase was isolated as a single enzyme and RNase as seven isozymes from the hepatocellular carcinoma tissue. The DNase isolated preferentially cleaved ds DNA over ss DNA and was endonuclease in nature (majority of hydrolytic products of DNA by the DNase were oligodeoxyribonucleotides). Of seven RNase isozymes isolated from the hepatocellular carcinoma tissue, isozyme I exhibited nonsecretory nature of RNase and other six isozymes secretory nature of the enzyme. Activity of RNase isozyme V was greatly increased and the activity of inhibitor complexed with the isozyme V was also increased. RNase in ascitic fluid of the cancer patient was separated into four isozymes, of which isozyme I exhibited mixed form of secretory and nonseretory nature and greatly increased in its activity. RNase isozyme V isolated in the hepatocellular carcinoma tissue was not detected in the ascitic fluid. CONCLUSION: The use of the nucleases and the inhibitor in the cancer tissue as biochemical markers for the hepatocellular carcinoma was suggested. RNase was released into the body fluid from the cancer tissue and could be used as a diagnostic marker for the hepatocellular carcinoma. An important role of the DNase in carcinogenesis of the liver was suggested. RNase isozyme V was limited in the cancer tissue and RNase isozyme I and V and inhibitors associated with these isozymes might be involved in carcinogenesis processes, suppression of cancer and maintenance of hepatocellular carcinoma through their interactions.

A Case of a Papillary Cystic Neoplasm of the Pancreas, Communicated by Main Pancreatic Duct / 대한소화기내시경학회지

Papillary cystic neoplasms of the pancreas are uncommon. They occurs almost entirely in young women. Generally, the lesion averages 10 cm 17 size and are usually located in the pancreatic tail, resulting in displacement of the pancreatic duct. A varialbe amount of hemorrhage and liquefaction necrosis occurs, resulting in pseudopapillae cysts. Resection of the tumor is usually associated with a excellent prognosis because of the lack of metastases and rare recurrences. In this report present a case of a papillary cystic neoplasm of the pancreas with a review of references. Unlike most, the neoplasm we discovered was small (about 1.5 x 1.5 cm), and, occured in the pancreatic head of eldcrly woman. Moreover it was communicated by the main pancreatic duct via a side branch.

The Role of Plasma Endothelin-1 in Fluid-Electrolyte Balance and Renal Function in Patients with Liver Cirrhosis / 대한내과학회지

OBJECTIVES: It has been recently known that endotheUn-1 is a potent vasoconstrictor. The purpose of the present study was to clarify the possible correlation of endothelin-1 with other vasoactive neurohormonal activities and its effects on fluid-electrolyte balance and renal function in patients with liver cirrhosis. METHODS: In 35 patients of liver cirrhosis with (n=19) and without (n=16) ascites and in 12 normal controls, plasma and urine levels of endothelin-1 were measured by specific radioimmunoassay, and serum sodium, serum albumin and other blood chemistries, renal functions with creatinine clearance, urinary sodium excretion, plasma renin activity, plasma aldosterone and plasma norepinephrine were measured at the same time. RESULTS: The plasma endothelin-1 level was significantly higher in ascitic group than nonascitic group (mean +/- SD; 16.4 +/- 10.6 VS. 7.5 +/- 4.1pg/mL, p=0.0000), and there was no significant difference in plasma endothelin-1 level between nonascitic group and normal controls(4.8 +/- 1.9pg/mL). The urine endothelin-1 level also was significantly higher in ascitic group than non-ascitic group (140.3 +/- 74.3 VS. 58.5 +/- 37.4 pg/mL, p=0.0000), there was no significant difference in urine endothelin-1 level between nonascitic group and normal controls (19.5 +/- 112pg/mL). In patients with cirrhosis, the plasma endothelin-1 concentration showed significant negative correlation with creatinine clearance (r=-0.55), serum albumin (r=-0.56%) and serum sodium concentrtion (r=-0.62), and significant positive correlation with plasma renin activity (r=0.63), plasma aldosterone (r=0.68) and norepinephrine (r=0.70). The factors that influence on plasma concentration of endothelin-1 were plasma norepinephrine (p=0.0000), serum sodium (p=0.0169), plasma aldosterone (p=0.0176), serum albumin (p=0.0213) and plasma renin activity (p=0.0329) in statistically significant order. CONCLUSION: The elevated plasma endothelin-1 level along with the increased activity of other neurohormonal substances including plasma renin, aldosterone and norepinephrine induces sodium and water retention in decompensated liver cirrhosis. Thus, the plasma endothelin-1 level seems to have an important role in the development of functional renal impairment in decompensated liver cirrhosis by inducing renal vasoconstriction.

The Study on Necessity of ERCP in Patients with Symptomatic Gallhladder Stones / 대한소화기내시경학회지

BACKGROUND/AIMS: Laparoscopic cholecystectomy(LC) has become the new therapeutic gold standard in uncomplicated symptomatic gallbladder stone. However, some patients with gallstones may be associated with bile duct stones or other biliary pathology. LC is not ideal for removal and evaluation of biliary duct stones even with advocated techniques. Although ERCP is the best way to demonstrate the biliary tree, ERCP is an invasive procedure that may causes complications. The aim of this study was to predict the neeessity for ERCP and to determine the indication of ERCP before LC using noninvasive methods of biliary tree associated liver biochemistry(LB) parameters and sonography. METHODS: 270 symptomatic gallbladder stone patients were studied by both sonography and LB including total bilirubin, alkaline phophatase, gamma-glutamyltransferase and amylase. All patients were performd ERCP for evaluation of biliary tree pathology, Patients who were already found to have either tumors or bile duct stones on sonography were excluded. Patients were classified into normal and dilated biliary tree groups by sonographic findings, normal and abnormal LB groups, negative and positive ERCP groups. Positive ERCP were defined by bile duct stones, tumors, stricture and idiopathic common bile duct dilatation over 11 mm. RESULTS: 1) There were positive ERCP findings in 30.4% of all patients. 2) The male to female ratio was 1:2, and the patients of positive ERCP group (58.9 +/- 12.0) were significantly )p=0.000) older than negative group (52.7 +/- 13.1). 3) There was bile duct dilatation in 39.3% of patients by sonography. Bile duct dilatation on sonography had an 66.0% positive predictability, 85.3% sensitivity and 80.6% specificity for ductal pathology on ERCP. 4) There was abnormal LB in 53.0% of patients. A single abnormal LB equated to a 46.2% positive predictablity, 80.5% sensitivity and 59.0% specificity for ductal pathology on ERCP. 5) In patients with both normal sonography and LB, 96.0% of patients had a negative ERCP study. CONCLUSION: ERCP is not necessary before LC for patients with symptomatic gallbladder stones who have both a normal biliary tree on sonography and normal LB. But, a patient with either a dilated bile duct on sonography of an abnormal LB does require ERCP study.

Esophagus, Stomach & Intestine; A Case of Carcinosarcoma of Esophagus / 대한소화기내시경학회지

More than 17 different terms, including carcinosatcoma and pseudosarcoma, have been applied to the rare polypoid tumors of the esophagus that demonstrate both carcinomatous and sarcomatous components. The multiplicity in terminology seems related to the uncertain histogenesis of these tumors. A demonstration of the ultrastructure of the spindle cells (containing desmosomes and tonofilaments) is consistent with an epithelial origin. The patient was a 53 year-old man who had suffered from dysphagia and foreign body sensation in larynx. Endoscopic finding was a large polypiod mass with ulceroinfiltrative lesion at the level of 27cm from the incisor. Pathologic findings were that the covering epithelium showed well differentiated squamous carcinoma with invasive pattern and the stroma contained islands of sarcoma and squamousl cell carcinoma. Immunoreactivity to cytokeratin was not observed. Partial esophagectomy and esophagogastrostomy was done. We report a case of rare malignant esophageal carcinosarcoma.

Clinical Analysis of Choledochal Cyst / 대한소화기내시경학회지

We studied and analyzed 66 cases of choledochal cyst in a 9 year period from March, 1985 to December, l993 at Hangang, Kangnam and Chuncheon Sacred Heart Hospital. The results were as follows; 1) Age ranged from 1 year to 82 years and ll of 66 cases were below 10 years. The ratio of men to women was 1: 1.9. 2) The frequency of the triad of symptoms and signs were in order of abdominal pain 53 cases(80.3%), jaundice 12 cases(18.2%) and abdominal mass 9 cases(13.6%). The classical triad of pain, mass and jaundice was present in only 2 cases(3.0%). 3) Alkaline phosphatase was elevated in 42 cases(63.6%), hyperbilirubinemia in 29 cases(43.9%) and hyperamylasemia in 9 cases(13.6%). 4) Performed diagnostic procedures were ultrasonogram in 57 cases(86.4%), endo- scopic retrograde cholangiopancreatogram in 32 cases(48.5%), DISIDA scan in 18 cases(27.3%), computed tomogram in 14 cases(21.2%) and percutaneous transhepatic cholangiagram in 6 cases(9.1%). 5) Among 38 cases which ERCP or PTC were performed, according to the Todani's classification, Type I was seen in 28 cases(73.7%), Type IVA in 7 cases(18. 4%), Type II in 2 cases(5.3%) and Type V in I case(2.6%). 6) The associated diseases were cholangitis in 15 cases(22.7%), choledocholithiasis in 12 cases(18.2%) and cholangiocarcinoma in 2 cases(3.0%). 7) Operative procedures were performed in 22 of 66 cases, excision of cyst with Roux-en-Y c~holedochojejunostomy in 17 cases, choledochocystojejunostomy in 2 cases and external drainage in 3 cases.

One Case of Menetrier's Disease / 대한소화기내시경학회지

Menetrier's disease is a rare disease characterized by the presence of large rugal folds involving part or all of the stomach. Patients with hypertrophic gastropathy often have distressing abdominal symptoms, weight loss and edema due to gastric protein loss. The 48-year-old male patient was admitted to the Hangang Sacred Heart Hospital with cheif complaints of indigestion and epigastric pain. The diagnosis of Menetriers disease is established by radiologic, endoscopic, and pathologic examination. He was treated with soft diet, antacid, H2- receptor antagonist, and IV albumin. We report a case of Menetriers disease with brief review of literatures.

The Long Term Therapeutic Effects of Endoscopic Injection Sclerotherapy in Esophageal Varices Bleeding / 대한소화기내시경학회지

Chronic progressive liver diseases, such as liver cirrhosis, eventually cause portal hypertension & hepatic coma, and among the cause of death from UGI bleeding variceal bleeding secondary to portal hypertension is the most common, over 50%. Clinical management for variceal bleeding includes IV vasopressin injection, insertion of Balloon tamponade administration of somatosatin or propranolol, and shunt operation, but the effect has not been promising. (continue...)