Ultrasound-guided percutaneous portal transplantation of peripheral blood monocytes in patients with liver cirrhosis

BACKGROUND/AIMS: Liver transplantation offers the only definite cure for cirrhosis but lacking donors is problem. Stem cell therapy is attractive in this setting. In this study, we aimed to explore the safety and efficacy of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell (PBMC) in cirrhotic patients. METHODS: A total of nine decompensated cirrhotic patients were randomized into three groups: group 1 (n = 3) was control group, group 2 (n = 3) received granulocyte-colony stimulating factor (G-CSF) mobilization for 3 days, and group 3 (n = 3) received G-CSF mobilized PBMCs by leukapheresis and PBMC transplantation through ultrasound-guided percutaneous portal vein puncture. Liver function and clinical features were evaluated. RESULTS: At baseline, the Child-Turcotte-Pugh and the model for end-stage liver disease scores were comparable in study groups. Compared with group 1, there was a tendency to improve liver function in group 3 at 6 months after treatment. Treatment was tolerable and no complications were encountered related to the G-CSF mobilization or percutaneous portal administration of PBMCs. Imaging studies showed patent portal veins at the end of the study period. CONCLUSIONS: Autologous PBMC transplantation through ultrasound-guided percutaneous portal vein puncture could be considered as a safe alternative treatment for decompensated cirrhotic patients.

Fucoidan protects hepatocytes from apoptosis and inhibits invasion of hepatocellular carcinoma by up-regulating p42/44 MAPK-dependent NDRG-1/CAP43

Fucoidan is a traditional Chinese medicine suggested to possess anti-tumor effects. In this study the anti-metastatic effects of fucoidan were investigated in vitro in human hepatocellular carcinoma (HCC) cells (Huh-7 and SNU-761) under normoxic and hypoxic conditions and in vivo using a distant liver metastasis model involving injection of MH134 cells into spleen via the portal vein. Its ability to protect hepatocytes against bile acid (BA)-induced apoptosis was investigated in primary hepatocytes. Fucoidan was found to suppress the invasion of HCC cells through up-regulation of p42/44 MAPK-dependent NDRG-1/CAP43 and partly, under normoxic conditions, through up-regulation of p42/44 MAPK-dependent VMP-1 expression. It also significantly decreased liver metastasis in vivo. As regards its hepatoprotective effect, fucoidan decreased BA-induced hepatocyte apoptosis as shown by the attenuation of caspase-8, and -7 cleavages and suppression of the mobilization of caspase-8 and Fas associated death domain (FADD) into the death-inducing signaling complex. In summary, fucoidan displays inhibitory effects on proliferation of HCC cells and protective effects on hepatocytes. The results suggest fucoidan is a potent suppressor of tumor invasion with hepatoprotective effects.

Transarterial Chemoembolization versus Radiofrequency Ablation for Small Hepatocellular Carcinomas with Discrepant Features on Computed Tomography and Magnetic Resonance Imaging

BACKGROUND/AIMS: This study compared the outcomes of patients with small hepatocellular carcinomas (HCCs) who were treated using transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). METHODS: This was a post-hoc analysis of a prospective study that evaluated the diagnostic efficacy of magnetic resonance imaging (MRI) and computed tomography (CT). We analyzed 41 small hepatic nodules in 32 patients that showed typical radiologic hallmarks on both CT and gadoxate-enhanced MRI (typical nodules) and 25 small hepatic nodules from 22 patients that showed atypical radiologic hallmarks on CT and typical radiologic hallmarks on MRI (discrepant nodules). RESULTS: There were no significant differences in the baseline characteristics of the patients with typical and discrepant nodules. Complete response rates 1 month after TACE or RFA were 75.0% (18/24) and 94.1% (16/17; P=0.20), respectively, for the patients with typical nodules and 58.8% (10/17) and 100% (8/8; P=0.05), respectively, for the patients with discrepant nodules. Treatment failure rates after TACE or RFA were 33.3% (8/24) and 5.8% (1/17; P=0.15), respectively, for the patients with typical nodules and 47.0% (8/17) and 0.0% (0/8; P=0.02), respectively, for the patients with discrepant nodules. Among patients achieving complete response, there were no significant differences in the risk of marginal recurrence. CONCLUSIONS: RFA provided higher complete response rates and significantly lower treatment failure rates than TACE for patients with discrepant nodules of HCC. Therefore, a treatment modality such as RFA may be preferable for small HCCs which show discrepancy on two imaging modalities.

A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase

BACKGROUND/AIMS: Protein disulfide isomerase (PDI) has been implicated in the survival and progression of some cancer cells, by compensating for endoplasmic reticulum stress by upregulating the protein-folding capacity. However, its prognostic role in patients with hepatocellular carcinoma (HCC) has not been investigated. METHODS: We collected HCC tissues from 83 HCC patients who underwent surgical resection for an immunohistochemical study of PDI. Overall survival (OS) was measured from the date of surgical resection until the date of death from any cause. Radiological progression was evaluated using the modified Response Evaluation Criteria in Solid Tumors in an independent radiological assessment. RESULTS: PDI expression was found to be increased in human HCC compared to adjacent nontumor tissues. Increased immunopositivity for PDI was associated with a high Edmondson-Steiner grade (p = 0.028). Univariate analysis of patients who had undergone surgical resection for HCC showed that tumor PDI upregulation is a significant risk factor for poor OS (p = 0.016; hazard ratio [HR], 1.980) and time to progression (TTP; p = 0.007; HR, 1.971). Multivariate analyses revealed that high PDI expression was an independent predictor of a shorter TTP (p = 0.015; HR, 1.865) and poor OS (p = 0.012; HR, 2.069). CONCLUSIONS: Upregulated PDI expression is associated with aggressive clinicopathological features of HCC; thus, PDI might serve as an independent prognostic factor and a potential therapeutic target for HCC patients.

Treatment and clinical outcome of needle-track seeding from hepatocellular carcinoma / 대한간학회지

BACKGROUND/AIMS: Needle-track seeding is a rare but important complication of diagnostic and therapeutic ultrasound (US)-guided procedures in hepatocellular carcinoma (HCC). We examined the frequency of needle-track seeding after US-guided percutaneous ethanol injection (PEI), fine-needle aspiration biopsy (FNAB), and percutaneous transhepatic biliary drainage (PTBD) in order to determine the appropriate treatment for needle-track seeding and its clinical outcome. METHODS: We analyzed the clinical characteristics and treatment outcomes in eight patients who experienced needle-track seeding from HCC after an US-guided procedure (FNAB, PEI, or PTBD) between January 1990 and July 2004. RESULTS: Seven (0.14%) of 5,092 patients who experienced needle-track seeding (2 after PEI, 4 after FNAB, and 1 after PTBD) during the study period and 1 other patient who experienced needle-track seeding recently were recruited for this study. Two of the eight patients underwent mass excision and the other six patients underwent en-bloc wide excision for the needle-track seeding. Tumors recurred in the needle-tracks in both patients who underwent mass excision but not in the six patients who underwent en-bloc wide excision. Mortality occurred in three patients who experienced the recurrence and progression of intrahepatic HCC. CONCLUSIONS: The incidence of needle-track seeding after US-guided procedures in HCC was 0.14%. En-bloc wide excision seems to be the optimal treatment for minimizing the probability of tumor recurrence due to needle-track seeding.

Clinical features of hepatic tuberculosis in biopsy-proven cases / 대한간학회지

BACKGROUNDS/AIMS: Hepatic involvement is frequently observed in patients with miliary tuberculosis, but primary hepatic tuberculosis with no clinical extrahepatic manifestations of tuberculosis is uncommon. With the ever-increasing number of immunocompromised patients, it is expected that hepatic tuberculosis will occur more frequently. The aim of the present study was to establish the clinical manifestations and course of the disease. METHODS: From January 1989 to September 2008, 12 patients were diagnosed with hepatic tuberculosis by liver biopsy at Seoul National University Hospital. We retrospectively evaluated their clinical, laboratory, and imaging findings by medical record review. RESULTS: Four patients had primary hepatic tuberculosis, and eight patients had hepatic tuberculosis secondary to pulmonary or miliary tuberculosis. Three patients were immunocompromised, and six patients had no previous medical problem. An elevated serum level of alkaline phosphatase was the most frequently observed finding in laboratory tests. Imaging studies showed variable findings, including hepatosplenomegaly, multiple hepatic nodules, abscess formation, and even normal findings. Ten patients responded to antituberculosis drugs, and two cases with tuberculous liver abscess had persistent disease despite prolonged therapy. CONCLUSIONS: In patients with a protracted illness, hepatosplenomegaly and/or abnormal liver function tests, hepatic tuberculosis should be suspected, even in healthy young patients or patients with normal imaging findings. Patients with tuberculous abscess formation tend to respond poorly to antituberculosis therapy, and surgery could be considered in these patients.

Cationic Trypsinogen Gene Mutation in Patients with Chronic Idiopathic Pancreatitis / 대한소화기학회지

BACKGROUND/AIMS: Mutation of Cationic trypsinogen gene is clearly associated with hereditary pancreatitis and plays an important role in the pathogenesis of pancreatitis. According to literature, this mutation is occasionally occurred in patients with pancreatitis in Western countries and Japan. The aim of this study was to find out whether the mutation was observed in Korean patients with chronic idiopathic pancreatitis. METHODS: Peripheral blood samples of 11 patients with chronic idiopathic pancreatitis were collected consecutively, and DNA was extracted from the samples. Polymerase chain reaction was performed in exon 2 and 3 of cationic trypsinogen gene. Then, DNA products were purified and sequenced. RESULTS: The mutation was not found in exon 2 and 3 of cationic trypsinogen gene in these patients. CONCLUSIONS: There was no cationic trypsinogen mutation in Korean patients with chronic idiopathic pancreatitis. Further large sampled cohort study is needed.

Mutations of SPINK1 and PRSS1 Gene in Korean Patients with Chronic Pancreatitis / 대한소화기학회지

BACKGROUND/AIMS: It has been found that mutations of cationic trypsinogen gene (PRSS1) and serine protease inhibitor, Kazal type 1 gene (SPINK1) increase the susceptibility of chronic pancreatitis (CP). Specifically, mutations in the PRSS1 gene are related to the occurrences of hereditary and idiopathic pancreatitis while SPINK1 mutations are known to act as a disease modifier and are associated with idiopathic CP. However, the association of SPINK1 mutations with alcoholic CP is still controversial. We investigated the prevalence of PRSS1 and SPINK1 mutations in idiopathic and alcoholic CP in Korea. METHODS: Seventy-one Korean patients with CP (alcoholic: 47, idiopathic: 22 and familial: 2) and 19 controls were included in this studies. Genomic DNA was extracted from peripheral blood of the patients. Mutations of SPINK1 (exon 3: N34S) and PRSS1 (exon 2: N29I, exon 3: R122H) genes were detected by PCR-RFLP methods. For the detection of SPINK1 mutation, restriction endonuclease PstI and BsrDI were used, while Sau3A and AflIII were used for the defection of PRSS1 mutation. RESUTLS: Only one patient (2.1%) with alcoholic CP was a heterozygote for SPINK1 (N34S) mutation. Mutation in the PRSS1 (N29I, R122H) gene was not found in any group of CP patients. Additionally, we could not find any mutations of SPINK1 or PRSS1 in the control group. CONCLUSIONS: SPINK1 and PRSS1 mutations are not related to the development of CP in Korea.

Association of transforming growth factor-b1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection

Transforming growth factor-b1 (TGF-beta 1) can act as both a tumor suppressor and a stimulator of tumor progression. We have examined the relationship between polymorphisms of the TGF-beta 1 gene and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. A total of 1,237 Korean subjects were prospectively enrolled; 1,046 patients with chronic HBV infection and 191 healthy controls with no evidence of recent or remote HBV infection. The patients were divided into two groups: those without (n=809) and those with HCC (n=237). Single nucleotide polymorphisms (SNPs) of TGF-beta 1 were searched for and genotyped using the single base extension method. In Korean subjects, only two SNPs were found among the seven known polymorphisms of TGF-beta 1, at position -509 and in codon 10. The risk of HCC was significantly lower in patients with the T/T or C/T genotypes than in those with the C/C genotypes at position -509 (PT; L10P] conferred a decreased likelihood of HCC (OR=0.74; 95% CI, 0.59-0.93; P=0.008). In conclusion, the presence of the TGF-beta 1 -509C>T promoter or of the L10P polymorphism, and the combination of both [-509C>T; L10P] as a haplotype were strongly associated with a reduced risk of HCC in patients with chronic HBV infection.

A Case of Acute Hepatitis E / 대한간학회지

Hepatitis E is an infectious viral disease with clinical and morphologic features of acute hepatitis. Although HEV infection is endemic in the Indian subcontinent, Southeast and Central Asia, a large outbreak of hepatitis E was identified in China. Smaller outbreaks have been observed in the Middle East, northern and western parts of Africa, and Mexico. Sporadic hepatitis E also has been observed in several countries. In nonendemic regions, the sporadic cases of hepatitis E are almost always associated with travel to HEV-endemic regions. In Korea, there has been no report on hepatitis E. Recently, we experienced a case of acute icteric hepatitis in which serologic study showed seroconversion of IgM anti-HEV. The patient did not have any travel history to an HEV-endemic area. We report this as an initial case of acute hepatitis E in Korea.

Cyclooxygenase-2 expression and apoptosis in Helicobacter pylori-infected human gastric epithelial cells / 대한내과학회지

BACKGROUND: Helicobacter pylori induces apoptosis and alters the proliferation of gastric mucosal epithelial cells. Cyclooxygenase-2 (COX-2) is an inducible form of COX for prostaglandin (PG) synthesis, which has been known to cause alteration in epithelial cell growth. In this study, we examined whether COX-2 gene expression by H. pylori infection could influence gastric epithelial cell apoptosis. METHODS: Human gastric epithelial cells were infected with H. pylori, after which COX-2 gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (RT-PCR). The level of PGE2 was determined in culture supernatants by radioimmunoassay. Apoptosis and caspase-3 activation were also measured in H. pylori-infected gastric epithelial cells. RESULTS: Expression of COX-2 mRNA and proteins was upregulated in Hs746T gastric epithelial cell lines infected with H. pylori, when assessed by quantitative RT-PCR and Western blot. However, COX-1 mRNA expression in H. pylori-infected Hs746T cells did not change. The extent of COX-2 mRNA expression and PGE2 production was similar in cagA-positive and cagA-negative strains and was not correlated with the presence of vacuolating cytotoxin. H. pylori infection resulted in apoptosis of gastric epithelial cell lines such as Hs746T. However, inhibition of COX-2 expression by NS-398, a specific COX-2 inhibitor, showed a significant increase of apoptosis and caspase-3 activation in Hs746T cells infected with H. pylori compared with H. pylori-infected cells without NS-398 treatment. In contrast, valerylsalicylate, an inhibitor that is relatively specific to COX-1, did not change the apoptosis levels of H. pylori-infected gastric epithelial cells. CONCLUSION: These results suggest that upregulated COX-2 expression by H. pylori infection can inhibit apoptosis of gastric epithelial cells.

Association Between Polymorphisms of Ethanol-Metabolizing Enzymes and Susceptibility to Alcoholic Cirrhosis in a Korean Male Population

Alcohol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH) and cytochrome P-4502E1 (CYP2E1), and then to acetate by aldehyde dehydrogenase (ALDH). Polymorphisms of these ethanol-metabolizing enzymes may be associated with inter-individual difference in alcohol metabolism and susceptibility to alcoholic liver disease. We determined genotype and allele frequencies of ALDH2, CYP2E1, ADH2, and ADH3 in male Korean patients with alcoholic cirrhosis (n=56), alcoholics without evidence of liver disease (n=52), and nondrinkers (n=64) by using PCR or PCR-directed mutagenesis followed by restriction enzyme digestion. The prevalences of heterozygous ALDH2*1/*2 plus homozygous ALDH2*2/*2 in patients with alcoholic cirrhosis (7.1%) and alcoholics without evidence of liver disease (3.8%) were significantly lower than that in nondrinkers (45.3%). The c2 allele frequencies of the CYP2E1 in alcoholic cirrhosis, alcoholics without evidence of liver disease, and nondrinkers were 0.21, 0.20, and 0.20, respectively. Allele frequencies of ADH2*2 in the three groups were 0.78, 0.74, and 0.77 and those of ADH3*1 were 0.94, 0.98, and 0.95. Therefore, we confirmed the observation that the ALDH2*2 gene protects against the development of alcoholism. However, the development of cirrhosis in Korean alcoholic patients was not associated with polymorphisms of ethanol-metabolizing enzymes.

Hepatopulmonary Syndrome in Poorly Compensated Postnecrotic Liver Cirrhosis by Hepatitis B Virus in Korea

BACKGROUND: Hepatopulmonary syndrome (HPS) refers to the association of hypoxemia, intrapulmonary shunting and chronic liver disease. But there is no clear data about the prevalence of HPS in postnecrotic liver cirrhosis by hepatitis B virus(HBV), the most common cause of liver disease in Korea. The aim of this study was to investigate the prevalence of HPS in poorly compensated postnecrotic liver cirrhosis by HBV, and the correlation of the hepatopulmonary syndrome with clinical aspects of postnecrotic liver cirrhosis by HBV. METHODS: Thirty-five patients underwent pulmonary function test, arterial blood gas analysis and contrast-enhanced echocadiography. All patients were diagnosed as HBV-induced Child class C liver cirrhosis and had no evidence of intrinsic cardiopulmonary disease. RESULTS: Intrapulmonary shunt was detected in 6/35 (17.1%) by contrast- enhanced echocariography. Two of six patients with intrahepatic shunts had significant hypoxemia (PaO2 < 70 mmHg) and four showed increased alveolar- arterial oxygen gradient over 20 mmHg. Only cyanosis could reliably distinguish between shunt positive and negative patients. CONCLUSIONS: The prevalence of intrapulmonary shunt in poorly compensated postnecrotic liver cirrhosis by HBV was 17.1% and the frequency of hepatopulmonary syndrome was relatively low (5.7%). 'Subclinical' hepatopulmonary syndrome (echocardiographically postive intrapulmonary shunt but without profound hypoxemia) exists in 11.4% of cases with poorly compensated postnecrotic liver cirrhosis by HBV. Cyanosis is the only reliable clinical indicator of HPS of HBV- induced poorly compensated liver cirrhosis. Further studies are required to determine if the prevalence and clinical manifestations of HPS varies with etiology or with geographical and racial differences.

Analysis of the Efficacy of Medical Treatment and the Cumulative Operation Rates of Behcet's Colitis According to the Colonoscopic Classification / 대한소화기내시경학회지

BACKGROUND/AIMS: The lesions of Behcet's colitis showed aphthoid or punched-out ulceration, but the macroscopic types of lesions have not been defined. The aim of this study was to predict the clinical outcome of patients with Behcets colitis according to colonoscopic findings. METHODS: We retrospectively reviewed the medical records and colonoscopic photographs of 50 patients with Behcet's colitis. Colonoscopic findings were categorized according to three types: volcano-, geographic- and aphthous-type. The efficacy of medical treatment was assessed by follow-up colonoscopy or double-contrast barium enema 4 to 8 weeks after treatment and recurrence of the lesions was evaluated during the follow-up period. Cumulative operation rates were obtained by the Kaplan-Meier method. RESULTS: Macroscopic types of colonic ulcers revealed 25 out of 50 (50%) patients with volcano-type, 11 (22%) with geographic-type, and 14 (28%) with aphthous-type lesions. Complete remission rates by medical treatment and operation rates in volcano-type ulcerations were 6 of 25 (24%) and 13 of 25 (52%), geographic-type 8 of 11 (73%) and 1 of ll (9%), and aphthous-type 9 of 14 (64%) and 2 of 14 (14%), respectively. The recurrence rate in volcano-type ulcerations was 9 of 19 (47%), geographic-type 1 of 9 (11%) and aphthous-type 1 of 11 (9%), CONCLUSIONS: Volcano-type ulcerations in Behcets colitis showed less favorable response to medical treatment and more episodes of operation and recurrence than geographic- and aphthous-type ulcerations.

Hepatitis B Virus DNA Mutation, Pattern of Major Histocompatibility Class-I among Familial Clustered HBV Carriers in Relation to Disease Progression / 예방의학회지

OBJECTIVES: Chronic HBsAg carriers are the principal source of infection for other susceptible people, and are themselves at high risk of developing serious liver diseases. In Korea, it has been estimated that 65-75% of the HBsAg positives remained as persistent carriers. Additionally, familial clustering of HBV infection has frequently been observed among carriers. Some would become progressive, chronic hepatitis patients, and others would not. The aim of this study was to evaluate the association between various factors, such as the duration of infection, type of virus, mutation of precore/core region in HBV, major histocompatibility class-I, and developing chronic liver diseases among familial HBV carriers. METHODS: Chronic carrier status was identified by repeated serological tests for HBsAg at intervals of six months or more. A familial chronic carrier was defined when the disease was observed in a family member over two generations. Two families were recruited, among which a total of 20 chronic HBsAg carriers(11 carriers in No.1, and 9 in No.2 family) were identified. Data on the general characteristics and liver disease status were collected. Identification of the HBV-DNA was successful only for 13 subjects among the 20 carriers. Analysis of viral DNA in terms of subtype, pre-core and core region mutations was carried out. The type of major histocompatibility class-I for the 13 subjects was also analysed. RESULTS & CONCLUSIONS: Seven of 10 chronic HBV carriers of the 1st generation and one of 10 of the 2nd generation were clinical patients with chronic hepatitis, the others, three of the 1st and nine of the 2nd generation, were asymptomatic carriers. This data indicates that the duration of HBV carriage is one of the major factors for disease severity. The subtype of HBsAg analysed using HBV-DNA identified in 13 carriers were adr, and the pattern of precore nonsense mutation in HBV-DNA was identical among family members, which means that the same virus strains were transmitted between the family members. The association between the precore or core mutations in HBV-DNA and the disease severity was not observed. While it was suggested that a specific type of MHC class-I may be related to disease progression.

Helicobacter pylori in Dental Plaque and Saliva

BACKGROUND: About half of the world population is infected with H. pylori, but the transmission and the source of this infection are still unclear. Recently, dental plaque (DP) and saliva have been implicated as possible sources of H. pylori infection. This study was done to investigate the detection rates of H. pylori in the DP and saliva by use of PCR depending on H. pylori infection state of gastric mucosa. METHODS: In 46 subjects, gastric H. pylori colonization was evaluated with CLO test, microscopy of Gram stained mucosal smear, culture and histology after modified Giemsa staining in the antrum and body, respectively. A patient was regarded as H. pylori positive if one or more of the four aforementioned test methods demonstrated H. pylori colonization of the gastric mucosa. For detection of H. pylori in the DP and saliva, PCR assay was done with ET4-U and ET4-L primers. To estimate the sensitivity and specificity of this PCR, H. pylori positivity was evaluated in the antrum and body, separately. RESULTS: The sensitivity of mucosal PCR was 50.0% (27/54) and the specificity 86.8% (33/38). When a subject was regarded as H. pyloi positive, if either antrum or body mucosal H. pylori was is positive, the positive rate of mucosal PCR was 62.1% (18 subjects) in the 29 H. pylori-positive and 17.6% (3 subjects) in the 17 H. pylori-negative subjects. DP PCR was positive in 2 of 29 H. pylori-positive subjects (6.9%) and none in the 17 H. pylori-negative (0%). Saliva PCR was positive in 4 of 14 H. pylori-positive subjects (28.6%) and none of 6 H. pylori-negative (0%). CONCLUSION: The detection rates of H. pylori in DP and saliva by PCR were rather low, 6.9% and 28.6%, respectively, and these rates might have been underestimated by low sensitivity of the PCR method used in this study. However, the results that H. pylori was found in the DP and saliva suggest that the oral cavity can perform a role as a reservoir of H. pylori in Korea.

Increase of apoptosis in human gastric epithelial cells infected with Helicobacter pylori and possible involvement of neutrophils / 대한내과학회지

BACKGROUND: Infection with Helicobacter pylori activates a proinflammatory gene program in human gastric epithelial cells and is associated with significant epithelial cell damage. We evaluated whether immune mediators produced by neutrophils could modulate gastric epithelial cell apoptosis in response to H. pylori infection. METHODS: After human gastric epithelial cells were infected with H. pylori in the presence of immune mediators, including tumor necrosis factor (TNT)alpha and Fas ligand (FasL), apoptosis and caspase-3 activity were assessed. The neutrophils were obtained from healthy volunteers, and Western blot analysis for FasL and quantitative reverse transcription polymerase chain reaction for TNFalpha transcripts were performed. Fas expression in gastric epithelial cells was explored by flow cytometric analysis. RESULTS: Activation of caspase-3 was first apparent 12 hours after H. pylori infection, and the phenotypic expression of apoptosis was first apparent 18 hours after infection. The extent of apoptosis was similar in cases of cagA+cytotoxin+, cagA+cytotoxin-, cagA-cytotoxin- H. pylori- infected gastric epithelial cells. Approximately 20% of the Hs746T cells expressed Fas within 24 hours after H. pylori infection. The soluble FasL was upregulated in neutrophils after treatment with H. pylori-soluble proteins for 24 and 48 hours. The addition of TNFalpha and the soluble form of FasL, produced by neutrophils, significantly increased H. pylori-infected cell apoptosis and caspase-3 activation. However, the combination of these two immune mediators showed only an additive increase. CONCLUSION: These results suggest that H. pylori-induced gastric epithelial cell apoptosis and caspase-3 activation can be modulated by the immune response of neutrophils.

A case of intraductal papillary mucinous tumor of pancreas associated with liver metastasis / 대한내과학회지

Intraductal papillary mucinous tumor has been reported with increasing frequency these days. It can be malignant (adenocarcinoma) or premalignant (adenoma). This tumor, even when malignant, is often resectable and has a favorable prognosis as compared with pancreatic ductal adenocarcinoma. We report a case of intraductal papillary mucinous tumor with liver metastasis in a 63-year-old male patient. He presented with recurrent epigastric pain, which had developed 3 months ago. Abdominal computed tomography showed the diffusely dilated pancreatic duct, 3 cm-sized low-attenuated mass in the body and multiple liver metastasis. During endoscopic retrograde pancreatography, patulous orifice of papilla, mucin secretion and diffusely dilatedpancreatic duct were noted. Cytologic examination during ERCP revealed mucinous material with atypical columnar cells. Metastatic adenocarcinoma was confirmed by sono-guided liver biopsy. Only supportive care has been done and he died at 3 months after the diagnosis.

The Usefulness of Monitoring of Transtubular Potassium Gradient and Spot Urine Na/K Ratio in the management of Cirrhotic Ascites / 대한간학회지

BACKGROUND/AIMS: Transtubular potassium gradient(TTKG) is known as the most accurate indicator of aldosterone activity. TTKG may be used to monitor the effectiveness of aldosterone antagonist which is prescribed generally for the management of cirrhotic ascites. Spot urine [Na]/[K] ratio may also be used for the same purpose. METHODS: After measuring TTKG, spot urine [Na]/[K] ratio, and plasma aldosterone concentration in each of the 23 patients all who had cirrhotic ascites, 100 mg of spiron-olactone was prescribed to be taken daily for 5 days. When no diuretic response occurred and TTKG was more than 3.5 at the end of 5 days, the dose of spironolactone was increased by 100 mg/day at the interval of 5 days until TTKG decreased to below 3.5. Furosemide was added to the non-responders if their TTKG had dropped to below 3.5. RESULTS: Basal plasma concentration of aldosterone was higher than upper normal limit in 13(57%) patients, and correlated with TTKG significantly(r=0.60, p=0.002). TTKG was calculated to be 3.5+/-0.67 when assuming the aldosterone activity has been completely blocked. Spot urine [Na]/[K] ratio had significant negative correlation with TTKG before and after the administration of spironolactone. In most patients, diuretic response appeared with the fall of TTKG (especially below 3.5) and with the rise of spot urine [Na]/[K] ratio. In patients who did not respond to a low dose spironolactone, further treatment plan (to increase dose of spironolactone or to add furosemide) was guided by TTKG, and all were successful. CONCLUSIONS: TTKG and spot urine [Na]/[K] ratio are good indicators of aldosterone activity, and might be used as useful guidelines in the diuretic management of cirrhotic ascites.

Lactose intolerance in lactase - deficient subjects and patients with inflammatory bowel disease after drinking common doses of milk / 대한내과학회지

OBJECTIVE: To define whether lactase-deficient subjects are intolerable to even a pack of milk(200ml) and whether milk intolerance in the patients with IBD is only due to lactose malabsorption, we performed this study. METHODS: We evaluated 32 healthy adults and 12 patients with active stage of inflammatory bowel disease(IBD) who had not received antibiotics therapy within the previous 3 weeks. Thirty-two healthy adults underwent H2-breath test with 200, 400, 600 and 800ml of milk at 1st, 2nd, 3rd and 4th day of study, respectively. We measured their end-expiratory hydrogen concentrations and asked them to record the gastrointestinal symptoms. Twelve patients with IBD were tested only with 200ml of milk. Lactose malabsorption was defined as the increase of 20ppm over basal H2 concentration and lactose intolerance as having two or more of the following symptoms; abdominal pain, diarrhea, borborygmus and flatus. RESULTS: The prevalence of lactase deficiency was 72%(23 of 32 subjects) at 800ml of milk(lactose 40g). Among the lactase-deficient subjects, lactose intolerance at 200ml of milk(lactose 10g) was noticed only in 13%(3 of 23 subjects). In the patients with active stage of IBD, the frequency of milk intolerance at 200ml of milk was 50%(6 of 12 subjects), which was higher than in the healthy adults(9%). But the prevalence of lactose malabsorber in the patients with IBD at 200ml of milk(17%) was not higher than in the healthy adults(16%). CONCLUSION: Most of lactase-deficient subjects(87%) can ingest one pack of milk without lactose intolerance. The increased prevalence of lactose intolerance in the patients with IBD at 200ml of milk is not originated from lactose malabsorption, but probably from incomplete colonic compensation salvage.