Hsiao Bai Yang

Expression of vascular endothelial growth factor in normal liver and hepatocellular carcinoma: An immunohistochemical study

Angiogenesis is of vital importance during the development and progression of solid tumors. To examine the role of vascular endothelial growth factor (VEGF) in hepatocarcinogenesis, we evaluated the expression of peptide in normal human liver (n = 6) and in 36 cases of hepatocellular carcinoma (HCC). Immunoreactivity for VEGF was present in the extracellular matrix of the portal tracts in the normal and nontumor part of liver, but not in hepatocytes and bile duct epithelium. For HCC, variable amounts of VEGF were expressed in 13 cases (36.1%) of tumor cells. Using a logistic regression model, expression of VEGF was significantly associated with a higher proliferative index (P = .01) and sonographic portal vein thrombosis (P = .05). However, VEGF expression did not correlate with a biochemical liver profile, alpha-fetoprotein levels, histological grading, gender, or clinical stage of cirrhosis (P > 0.1, respectively). Log-rank test showed that evaluation of VEGF did not provide more prognostic information (P > .5) than that from tumor volume and portal vein thrombosis (P < .01, respectively). In addition, VEGF was always present in the fibrovascular stroma or pericellular matrix of HCC, although no strong relationship was observed with the expression of VEGF in tumor cells (P > .5). Our data suggested that expression of VEGF may characterize a progression toward higher proliferation in hepatocarcinogenesis in vivo. The relevance of VEGF existing in the extracellular matrix of the normal liver and HCC remains to be clarified.

Resistance to metronidazole, clarithromycin and levofloxacin of Helicobacter pylori before and after clarithromycin‐based therapy in Taiwan

Background and Aim:  Clarithromycin‐based triple therapy has been commonly applied as the first‐line therapy for Helicobacter pylori eradication. Levofloxacin could serve as an alternative in either first‐line or second‐line regimens. This study surveyed the prevalence of levofloxacin resistance of H. pylori isolates in naive patients and in patients with a failed clarithromycin‐based triple therapy.

Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in Taiwanese

NPC is an epithelial tumor that is highly prevalent among the southern Chinese. Numerous studies have indicated that specific HLA haplotypes and genes within the HLA complex are associated with NPC. As a first effort to localize the gene responsible for susceptibility, the HLA‐A, ‐B, and ‐A2 subtypes were examined for their association to NPC. Consistent with previous reports, frequencies of HLA‐A2 [OR = 2.50, pc = 0.020 (study population); OR = 3.73, pc = 0.0030 (≥40 years old)] were significantly higher in patients with NPC than in healthy controls. Two‐locus analysis indicated that A2+B46+ individuals are at greater risk for NPC than A2−B46− individuals in both the population studied and the ≥40‐year‐old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2+B38+ individuals were at higher risk than A2−B38− individuals in both the population studied and the ≥40‐year‐old group; A2 and B38 are not genetically linked. These findings suggest that B38 or B46 alone cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46 positivity greatly increases risk. None of 5 A2 subtypes identified from studied populations was significantly associated with NPC. Microsatellite marker D6S211, located 97 kb telomeric to HLA‐A, was analyzed for its association with NPC. Allele 4 of D6S211 was significantly associated with NPC (OR = 3.97, pc = 0.0042). These results strongly support the hypothesis that genes associated with susceptibility to NPC in the HLA region are within the HLA‐A locus.

Quadruple therapy containing amoxicillin and tetracycline is an effective regimen to rescue failed triple therapy by overcoming the antimicrobial resistance of Helicobacter pylori

Aim : To identify optimal antibiotics for second‐line quadruple therapy of Helicobacter pylori after failed 1‐week triple therapy.

Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways.

BackgroundH. pylori infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways.ResultsChallenge with H. pylori increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after H. pylori infection in a dose-dependent manner. A higher dose (MOI 100) of L. acidophilus pre-treatment attenuated the H. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting.ConclusionsH. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of L. acidophilus pre-treatment reduce H. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.

Children of Helicobacter pylori-infected dyspeptic mothers are predisposed to H. pylori acquisition with subsequent iron deficiency and growth retardation

Background.  We tested whether Helicobacter pylori‐infected dyspeptic mothers had a higher rate of H. pylori infection in their children, and whether such H. pylori‐infected children were predisposed to iron deficiency or growth retardation.

H. pylori eradication prevents the progression of gastric intestinal metaplasia in reflux esophagitis patients using long-term esomeprazole.

OBJECTIVES:This study aimed to determine whether Helicobacter pylori eradication limits the progression of precancerous changes, manifested as intestinal metaplasia (IM), in patients with reflux esophagitis using long-term esomeprazole.METHODS:Three hundred twenty-five reflux esophagitis patients were enrolled and randomly assigned to (i) the H. pylori–positive eradication group receiving 1-week triple therapy (n=105); (ii) H. pylori–positive non-eradication controls (n=105); and (iii) H. pylori–negative controls (n=115). All the patients received continuous esomeprazole until sustained symptomatic response, and when possible, shifted to on-demand therapy (ODT) thereafter. Serial gastroscopy was scheduled on enrollment and at the end of the first and second years to assess the prevalence and progression or regression of gastric atrophy (AT) and IM.RESULTS:There were 93 patients in the H. pylori–eradication group, 83 in the non-eradication controls, and 100 in the negative controls to complete the study. The negative controls had no progression of AT and IM during follow-up. For the H. pylori–positive eradication group, there was significant regression of AT and IM during follow-up (P<0.05). In the H. pylori–positive non-treated controls, the prevalence rates of AT and IM were significantly greater on the second year than on enrollment (P<0.05). During the second-year follow-up, the patients in the eradication group achieved more regression and less development of AT and IM than did the non-eradication controls (P<0.001).CONCLUSIONS:In patients using long-term esomeprazole for reflux esophagitis, screening for and eradicating H. pylori infection are necessary in order to limit the progression or cause the regression of gastric precancerous changes.

Host TNF-α -1031 and -863 promoter single nucleotide polymorphisms determine the risk of benign ulceration after H. pylori infection

OBJECTIVES:This study tested whether host genotypes of the tumor necrosis factor-alpha (TNF-α) promoter single nucleotide polymorphism (SNP) could determine clinical and histological outcomes after Helicobacter pylori infection.METHODS:A total of 524 dyspeptic patients, 424 with and 100 without H. pylori infection, were checked for TNF-α promoter SNP over the locus on −1031(T/C), −863(C/A), −857(C/T), −806(C/T), and −308(G/A) by sequence-specific oligonucleotide probe. Each patient received panendoscopy to take gastric biopsy to detect H. pylori infection and its related histology using the updated Sydneys system. Gastric TNF-α expressions were stained by immunohistochemistry.RESULTS:In H. pylori-infected patients, −1031C or −863A carriers of TNF-α promoter had more severe gastric neutrophil infiltration and TNF-α gastric staining than individuals with −1031TT or −863CC genotype, respectively (p < 0.05). The multivariate logistic regression verified both −1031C and −863A carriers were independent risk factors to have duodenal ulcers and gastric ulcer without IM in the H. pylori-infected hosts (p < 0.05). As compared to −863CC and −1031TT genotype combinations, the ulcer risk after H. pylori infection was 2.46 (95% CI: 1.32–4.59, p≤ 0.00001) for the carriers with either −1031C or −863A allele, and even elevated to 6.06 (95% CI: 3.57–10.21, p≤ 0.00001) for the individuals harboring both −863A and −1031C alleles. For patients with gastric ulcer, the 863CC genotype had a higher rate to have intestinal metaplasia than −863A carrier (p≤ 0.005).CONCLUSIONS:TNF-α−1031 and −863 promoter SNP should be novel host factors to determine the gastric inflammation and risk of peptic ulceration upon H. pylori infection.

Fatao coxsackievirus B infection in early infancy characterized by fulminant hepatitis

OBJECTIVES to clarify the major features of fatal coxsackievirus B infection characterized by fulminant hepatitis in early infancy. METHODS clinical manifestations and laboratory investigations concerning five consecutive young infants with overwhelming coxsackievirus B fulminant hepatitis between 1994 and 1997 were retrospectively reviewed. Aetiological diagnosis was made by viral cultures and confirmed by a neutralization test with a type-specific antiserum. RESULTS all five had a deteriorating clinical course of severe hepatitis complicated by disseminated intravascular coagulopathy (DIC). Coxsackievirus B1 infection was established in four patients and coxsackievirus B3 in one. The pathological findings of the two cases illustrated extensive hepatocellular necrosis. Fulminant hepatitis can occur as a leading presentation of disseminated coxsackievirus B infections and dominant the clinical features in neonates and young infants. CONCLUSIONS the liver was the target organ of fatal coxsackievirus B infection in our patients. Hepatic involvement progressed rapidly to jaundice and coagulopathy, and was considered to be indicative of poor prognosis. Coxsackievirus B hepatitis may be serious in early infancy.

Chronic celecoxib users more often show regression of gastric intestinal metaplasia after Helicobacter pylori eradication

To test whether the chronic users of celecoxib, a selective cyclo‐oxygenase‐2 inhibitor, had less Helicobacter pylori‐related intestinal metaplasia or if such users’ intestinal metaplasia could be prone to disappear after H. pylori eradication.