Hsiu-chi Cheng | National Cheng Kung University (original) (raw)

Papers by Hsiu-chi Cheng

Research paper thumbnail of Genomic single nucleotide polymorphisms in the offspring of gastric cancer patients predispose to spasmolytic polypeptide-expressing metaplasia after H. pylori infection

Journal of Biomedical Science, 2015

Background: Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (G... more Background: Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM).

Research paper thumbnail of Helicobacter pylori Test-and-Treat Program Can Be Cost-effective to Prevent Gastric Cancer in Taiwanese Adults: Referred to the Nationwide Reimbursement Database

Helicobacter, 2015

Helicobacter pylori infection increases the risk of gastric cancer. The study aimed to compare co... more Helicobacter pylori infection increases the risk of gastric cancer. The study aimed to compare cost-effectiveness ratios of H. pylori test-and-treat programs to prevent gastric cancer in Taiwan, referring to the nationwide reimbursement database and expected years of life lost. During 1998-2009, there were 12,857 females and 24,945 males with gastric adenocarcinoma in Taiwan National Cancer Registry. They were followed up to 2010 and linked to the reimbursement database of National Health Insurance and the national mortality registry to determine lifetime health expenditures and expected years of life lost. Cost-effectiveness ratios of H. pylori test-and-treat programs for prevention of gastric adenocarcinoma were compared between screenings with (13) C-urea breath test and with anti-H. pylori IgG. The test-and-treat program with anti-H. pylori IgG to prevent gastric adenocarcinoma had lower incremental cost-effectiveness ratios than that with (13) C-urea breath test in both sexes (...

Research paper thumbnail of Expressions of MMPs and TIMP-1 in gastric ulcers may differentiate H. pylori-infected from NSAID-related ulcers

TheScientificWorldJournal, 2012

Two major causes of gastric ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal... more Two major causes of gastric ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) use. This study aimed to determine if there were different expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) between H. pylori-infected and NSAID-related ulcers. The 126 gastric ulcer patients (H. pylori infected n = 46; NSAID related n = 30; combined with two factors n = 50) provided ulcer and nonulcer tissues for assessment of MMP-3, -7, and -9 and TIMP-1 expression by immunohistochemical staining. Gastric ulcer tissues had significantly higher MMP-3, -7, and -9 and TIMP-1 expressions than nonulcer tissues (P < 0.05). H. pylori-infected gastric ulcers had even higher MMP-7, MMP-9, and TIMP-1 expressions in epithelial cells than NSAID-related gastric ulcers (P < 0.05). In patients with the two combined factors, gastric ulcers expressed similar proportions of antral ulcers and MMP-7 and MMP-9 ...

Research paper thumbnail of Supplementation of Los Angeles classification with esophageal mucosa index of hemoglobin can predict the treatment response of erosive reflux esophagitis

Surgical endoscopy, 2011

We assessed whether the esophageal mucosa index of hemoglobin (IHb) could assist the Los Angeles ... more We assessed whether the esophageal mucosa index of hemoglobin (IHb) could assist the Los Angeles (LA) classification in defining the severity of erosive reflux esophagitis (RE) and predicting the treatment response by esomeprazole. Five hundred twenty-four subjects (424 RE and 100 controls) with normal body mass index and hemoglobin had undergone endoscopy to confirm the RE grade by LA classification and to check the series of IHb values at every centimeter of the esophageal mucosa while withdrawing the endoscope to above the esophageal-gastric junction (EGJ). The RE cases had received esomeprazole for 8 weeks (40 mg/day) to assess the cumulative proportions of sustained symptomatic response (SSR). The IHb value at the EGJ was higher in RE patients than in controls (P < 0.001). Selecting 70 as the cutoff IHb value at the EGJ, the efficacy to define RE achieved 95.8% (406/424) sensitivity and 94% (94/100) specificity. For the patients with same the LA grade, the length of IHb valu...

Research paper thumbnail of The impact of body mass index on the application of on-demand therapy for Los Angeles grades A and B reflux esophagitis

The American journal of gastroenterology, 2007

Patients with Los Angeles grade A or B reflux esophagitis (RE-AB) can potentially be switched fro... more Patients with Los Angeles grade A or B reflux esophagitis (RE-AB) can potentially be switched from active-phase therapy to on-demand esomeprazole as maintenance therapy. Body mass index (BMI) correlates significantly with reflux symptoms. We investigated whether BMI affects the efficacy of esomeprazole in active-phase or subsequent on-demand therapy. Three hundred fifty patients with RE-AB were prospectively enrolled to receive an 8-wk course of esomeprazole (40 mg/day) as active-phase therapy. Based on the daily severity of acid regurgitation and heartburn, the cumulative proportions of patients with sustained symptomatic response (SSR), defined as free from symptoms for the last 7 days, were compared among different BMI groups (control: BMI <25 kg/m2, overweight: BMI 25-30 kg/m2, obese: BMI >30 kg/m2). In patients who had achieved SSR by week 8, on-demand therapy for 2 months was started. The number of 40-mg esomeprazole tablets used per 4-wk period was recorded. SSR rates w...

Research paper thumbnail of Increased risk of rebleeding of peptic ulcer bleeding in patients with comorbid illness receiving omeprazole infusion

Hepato-gastroenterology

The study aimed to evaluate whether administration of intravenous omeprazole has different reblee... more The study aimed to evaluate whether administration of intravenous omeprazole has different rebleeding rates for peptic ulcer bleeding of patients with and without comorbid illness. A total of 80 patients with peptic ulcer bleeding were enrolled after therapeutic endoscopy to achieve hemostasis. Each patient had received omeprazole 80 mg bolus loading and 40 mg twice daily for three days (total dosage of 320 mg within 3 days). Two subgroups were divided, based on the absence (Group A) or presence (Group B) of one or more comorbid illnesses, such as chronic obstructive pulmonary disease, congestive heart failure, uremia, cirrhosis, diabetes mellitus, and old stroke. The 7-day and 28-day rebleeding rates were recorded. The presence of comorbid illness had a higher rebleeding rate than those without comorbid illness (7-day: 32.5 vs. 2.5%, p < 0.05; 28-day: 37.5 vs. 5.0%, p < 0.05). Patients with two or more comorbid diseases had an even higher risk of rebleeding than those with a ...

Research paper thumbnail of Double-Dosed Pantoprazole Accelerates the Sustained Symptomatic Response in Overweight and Obese Patients With Reflux Esophagitis in Los Angeles Grades A and B

The American Journal of Gastroenterology, 2009

Body mass index (BMI) in the range defined as overweight or obese adversely decreases the sustain... more Body mass index (BMI) in the range defined as overweight or obese adversely decreases the sustained symptomatic response (SSR) to proton pump inhibitors for patients with reflux esophagitis of Los Angeles grade A or B (RE-AB). We thus investigated whether double-dosed pantoprazole can accelerate SSR in such patients. A total of 200 overweight or obese patients with RE-AB were evenly randomized into a double-dosed group (receiving 8-week pantoprazole 40 mg twice daily) or a standard-dosed control group (receiving 8-week pantoprazole 40 mg per day and one blank tablet at night). In each patient, demographic factors and the genotype of S-mephenytoin 4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-hydroxylase (CYP2C19) were checked and defined as poor metabolizer (PM), or homologous extensive metabolizer (HomoEM), or heterologous extensive metabolizer (HeteroEM). The cumulative proportions of patients with SSR were compared during the 8-week period. Both intention-to-treat and per-protocol analyses disclosed that the rates of SSR were higher in the double-dosed group than in the standard-dosed group from week 4 (P=0.005) until week 8 (P=0.01). While using standard-dosed pantoprazole, PMs had better rates of SSR during the 8-week period than both HomoEMs and HeteroEMs (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). By using double-dosed pantoprazole, the cumulative rates of SSR were improved as early as week 4 for both HomoEMs and HeteroEMs (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.005, log-rank test). For RE-AB in overweight and obese patients, double-dosed pantoprazole effectively accelerates the SSR, especially for those with CYP2C19 genotypes as HeteroEM or HomoEM. Accordingly, it offers an earlier shift into on-demand pantoprazole for RE-AB patients with high BMI.

Research paper thumbnail of Intravenous proton pump inhibitors for peptic ulcer bleeding: Clinical benefits and limits Hsiu-Chi Cheng, Bor-Shyang Sheu

World Journal of Gastrointestinal Endoscopy, 2011

Peptic ulcer bleeding is a common disease and recurrent bleeding is an independent risk factor of... more Peptic ulcer bleeding is a common disease and recurrent bleeding is an independent risk factor of mortality. Infusion with proton pump inhibitors (PPIs) prevents recurrent bleeding after successful endoscopic therapy. A gastric acidic environment of less than pH 5.4 alters coagulation function and activates pepsin to disaggregate platelet plugs. Gastric acid is secreted by H + , K + -ATPase, naming the proton pump. This update review focuses on the mechanism and the role of PPIs in the clinical management of patients with peptic ulcer bleeding. An intravenous omeprazole bolus followed by high-dose continuous infusion for 72 h after successful endoscopic therapy can prevent the recurrent bleeding. In the Asian, however, the infusion dosage can possibly be diminished whilst preserving favorable control of the intragastric pH and thereby still decreasing rates of recurrent bleeding. Irrespective of the infusion dosage of PPIs, rates of recurrent bleeding remain high in patients with co-morbidities. Because recurrent peptic ulcer bleeding may be prolonged in those with co-morbidities, a lowdose infusion of IV PPIs for up to 7-day may result in better control of recurrent bleeding of peptic ulcers. Due to the inter-patient variability in CYP2C19 genotypes, the infusion form of new generation PPIs, such as esomeprazole, should be promising for the prevention of recurrent bleeding. This article offers a comprehensive review of clinical practice, highlighting the indication, the optimal dosage, the duration, and the potential limitation of PPIs infusion for peptic ulcer bleeding.

Research paper thumbnail of Consensus on Control of Risky Nonvariceal Upper Gastrointestinal Bleeding in Taiwan with National Health Insurance

BioMed Research International, 2014

To compose upper gastrointestinal bleeding (UGIB) consensus from a nationwide scale to improve th... more To compose upper gastrointestinal bleeding (UGIB) consensus from a nationwide scale to improve the control of UGIB, especially for the high-risk comorbidity group. The steering committee defined the consensus scope to cover preendoscopy, endoscopy, postendoscopy, and overview from Taiwan National Health Insurance Research Database (NHIRD) assessments for UGIB. The expert group comprised thirty-two Taiwan experts of UGIB to conduct the consensus conference by a modified Delphi process through two separate iterations to modify the draft statements and to vote anonymously to reach consensus with an agreement ≥80% for each statement and to set the recommendation grade. The consensus included 17 statements to highlight that patients with comorbidities, including liver cirrhosis, end-stage renal disease, probable chronic obstructive pulmonary disease, and diabetes, are at high risk of peptic ulcer bleeding and rebleeding. Special considerations are recommended for such risky patients, including raising hematocrit to 30% in uremia or acute myocardial infarction, aggressive acid secretory control in high Rockall scores, monitoring delayed rebleeding in uremia or cirrhosis, considering cycloxygenase-2 inhibitors plus PPI for pain control, and early resumption of antiplatelets plus PPI in coronary artery disease or stroke. The consensus comprises recommendations to improve care of UGIB, especially for high-risk comorbidities.

Research paper thumbnail of Usefulness of Fatty-meal Stimulated Gallbladder Contractility by Ultrasonography in the Diagnosis of Acute Cholecystitis

Journal of Medical Ultrasound, 2005

ABSTRACT Address correspondence to: Dr. Chiao-Hsiung Chuang, Department of Internal Medicine, Col... more ABSTRACT Address correspondence to: Dr. Chiao-Hsiung Chuang, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 704, Taiwan, R.O.C

Research paper thumbnail of Posttreatment 13C-urea breath test is predictive of antimicrobial resistance to H. pylori after failed therapy

Journal of General Internal Medicine, 2005

OBJECTIVE: We tested whether a 13 C-urea breath test can predict antimicrobial resistance of Heli... more OBJECTIVE: We tested whether a 13 C-urea breath test can predict antimicrobial resistance of Helicobacter pylori (H. pylori).

Research paper thumbnail of Resistance to metronidazole, clarithromycin and levofloxacin of Helicobacter pylori before and after clarithromycin-based therapy in Taiwan

Journal of Gastroenterology and Hepatology, 2009

Clarithromycin-based triple therapy has been commonly applied as the first-line therapy for Helic... more 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. Methods: The study collected the H. pylori isolates from 180 naive patients and 47 patients with a failed clarithromycin-based triple therapy. Their in vitro antimicrobial resistance was determined by E-test. Results: The naive H. pylori isolates had resistance rates for amoxicillin, levofloxacin, clarithromycin and metronidazole of 0%, 9.4%, 10.6% and 26.7%, respectively. An evolutional increase of the primary levofloxacin resistance was observed in isolates collected after 2004, as compared to isolates collected before 2004 (16.3% vs 3.2%, P = 0.003). There was no evolutional increment of the primary clarithromycin resistance. The clarithromycin resistance elevated significantly after a failed clarithromycin-based triple therapy (78.7% vs 10.6%, P < 0.001). The post-treatment isolates remained to have a levofloxacin resistance rate of near 17%, but the levofloxacin-resistant isolates were correlated with a higher incidence of metronidazole resistance (P = 0.023). No strain was found to be resistant to amoxicillin even after eradication failure. Conclusion: The levofloxacin resistance of naive H. pylori remains less than 10% in Taiwan. With relatively lower resistance to levofloxacin than to metronidazole of the H. pylori isolates collected after a failed clarithromycin-based therapy, proton pump inhibitorlevofloxacin-amoxicillin may be an alternative choice to serve as the second-line therapy.

Research paper thumbnail of Erythrocyte Lewis (A+B-) host phenotype is a factor with familial clustering for increased risk of Helicobacter pylori-related non-cardiac gastric cancer

Journal of Gastroenterology and Hepatology, 2006

The purpose of the present study was to test whether host erythrocyte Lewis phenotypes correlated... more The purpose of the present study was to test whether host erythrocyte Lewis phenotypes correlated with the risk of gastric cancers. Because of the association of gastric cancer with familial clustering, cancer relatives were investigated as to whether they had unique distribution of Lewis phenotypes. The study prospectively enrolled 74 Helicobacter pylori-positive gastric cancer patients and 100 H. pylori-positive duodenal ulcer patients to serve as non-cancer controls after panendoscopy. In addition, 433 family members from the 74 index cancer and 100 non-cancer control patients were enrolled. All enrolled cases were checked for their H. pylori status and erythrocyte Lewis phenotypes, defined as Le(a-b-), Le(a-b+), Le(a+b-), and Le(a+b+) subtypes by the anti-Le(a) and anti-Le(b) monoclonal antibodies. These H. pylori-infected patients with gastric cancer had a higher rate of Le(a+b-) phenotype and a lower rate of Le(a-b+) phenotype than the non-cancer duodenal ulcer controls (20.3% vs 9%; 51.4% vs 72%, P &amp;amp;amp;amp;amp;amp;lt; 0.05). Among these H. pylori-infected patients, the risk of the patients with Le(a+b-) phenotype having gastric cancer was 3.15-fold higher as compared with those with the Le(a-b+) phenotype (P = 0.02, 95% confidence interval: 1.26-7.87). The offspring and cousins of the cancer patients had a higher rate of Le(a+b-) phenotype as compared to either that of the spouses of cancer index patients or to that of the family members of the non-cancer control (P &amp;amp;amp;amp;amp;amp;lt; 0.05). Le(a+b-) phenotype of the H. pylori-infected host could be a risk factor (with familial clustering) for gastric carcinogenesis.

Research paper thumbnail of CYP2C19 genotypes determine the efficacy of on-demand therapy of pantoprazole for reflux esophagitis as Los-Angeles grades C and D

Journal of Gastroenterology and Hepatology, 2012

The present study determined whether the genotypes of S-mephenytoin 4′-hydroxylase (CYP2C19) coul... more The present study determined whether the genotypes of S-mephenytoin 4′-hydroxylase (CYP2C19) could serve as an indicator to assess the success of long-term on-demand therapy (ODT) with pantoprazole for the patients with severe reflux esophagitis as Los Angles grade C or D (RE-CD). Methods: A total of 240 patients with RE-CD were prospectively enrolled to receive continuous pantoprazole, 40 mg daily for 6 months. The patients, who achieved complete healing and were free from acid reflux-related symptoms during follow up, were included to receive ODT with a 40 mg pantoprazole tablet up to 1 year. Each patient was followed to assess the monthly tablet number of 40 mg pantoprazole and the cumulative rate of failure of ODT. The CYP2C19 genotype of each included patient was defined as homologous extensive metabolizer (HomoEM), heterologous extensive metabolizer (HeteroEM), and poor metabolizer (PM). Results: Two-hundred patients were included to receive ODT, including 51 as HomoEM, 108 as HeteroEM, and 41 as PM. There were no differences in demographic and endoscopic features among patients with different CYP2C19 genotypes (P > 0.05). The 1-year cumulative failure rate of ODT was significantly higher in HomoEM than in HeteroEM and PM (P < 0.05, by log-rank test). For those with successful ODT during the 1-year follow up, the mean monthly tablet number of pantoprazole was lower in PM than in HeteroEM and HomoEM (11.5 vs 16.3 and 18.6, P < 0.05). Conclusion: For RE-CD with complete healing after continuous pantoprazole, the successful shift to ODT is determined by the CYP2C19 genotypes of the patients.

Research paper thumbnail of Long-term Outcome of Pyogenic Liver Abscess

Journal of Clinical Gastroenterology, 2008

Long-term surveillance of pyogenic liver abscess remains unavailable. We thus aimed to identify t... more Long-term surveillance of pyogenic liver abscess remains unavailable. We thus aimed to identify the recurrence rates of pyogenic liver abscess among various etiologies and pathogens, and to elucidate the factors related with this recurrence. Six-hundred and one patients with pyogenic liver abscess were prospectively enrolled to observe abscess recurrence during a mean follow-up period of up to 6.06 years. On the basis of the etiology of the initial abscess, patients were divided into different subgroups as follows: there were 152 (25.3%) patients classified as cryptogenic, 229 (38.1%) with diabetes mellitus, 144 (24%) with underlying biliary tract disease, and 76 (12.6%) with other organic diseases or mixed subgroups. The cumulative recurrence rates of pyogenic liver abscess were lower in both the cryptogenic (2.0%) and diabetic (4.4%) groups than in the underlying biliary tract disease (23.8%) group (log-rank test, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The diabetic group had a higher rate of Klebsiella pneumoniae infection and a lower rate of Escherichia coli infection than the biliary tract group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). For patients infected with K. pneumoniae, the recurrence rate of pyogenic liver abscess was as low as that of the diabetes and the cryptogenic groups (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). Pyogenic liver abscess is more commonly recurrent in patients with underlying biliary tract disease. Irrespective of diabetic status or cryptogenic etiology, the recurrence of K. pneumoniae-infected liver abscess is low in the long-term.

Research paper thumbnail of Higher Motility Enhances Bacterial Density and Inflammatory Response in Dyspeptic Patients Infected with Helicobacter pylori

Helicobacter, 2012

Background: Motility mediated by the flagella of Helicobacter pylori is important for the cells t... more Background: Motility mediated by the flagella of Helicobacter pylori is important for the cells to move toward the gastric mucus in niches adjacent to the epithelium; then, H. pylori uses the adhesin SabA to interact with sialyl-Le x on inflammatory host cells for persistent infection. Here, we reveal the clinical association of bacterial motility, SabA expression, and pathological outcomes. Methods: Ninety-six clinical isolates were screened for bacterial motility, and the expression of SabA of each isolate was confirmed by Western blotting. H. pylori-infected patients were assessed for their bacterial density, sialyl-Le x expression, inflammatory scores, and clinical diseases. Results: The mean diameter in the motility assay was 17 mm, and eight (8.3%) of the strains had impaired motility, with a diameter <5 mm. H. pylori density in cardia, the acute inflammatory score in the body locus, and the prevalence rate of gastric atrophy were increased in patients infected with higher-motility strains (p = .023, <.001, or <.001, respectively). The total inflammatory scores (both acute and chronic) and bacterial density dramatically increased in patients expressing the sialyl-Le x antigen and infected with higher-motility, SabA-positive H. pylori (p = .016, .01, or .005, respectively). Conclusion: These results suggest that the higher motility of H. pylori enhances pathological outcomes, and the SabA-sialyl-Le x interaction has a synergistic effect on virulence of the higher-motility strains.

Research paper thumbnail of Levofloxacin-Containing Triple Therapy to Eradicate the Persistent H.�pylori after a Failed Conventional Triple Therapy

Helicobacter, 2007

To identify the optimal dosage of levofloxacin to eradicate persistent Helicobacter pylori when t... more To identify the optimal dosage of levofloxacin to eradicate persistent Helicobacter pylori when triple therapy with amoxicillin, clarithromycin, and omeprazole fails. We investigated 124 patients whose triple therapy including clarithromycin had failed. Clarithromycin resistance was indirectly assessed by the (13)C-urea breath test, with a post-treatment value cut-off point at 15. All patients were randomly divided into two groups, to receive 1-week amoxicillin 1 g and lansoprazole 30 mg twice daily, plus either levofloxacin 500 mg once (ALL-500 group) or twice daily (ALL-1000 group). Six weeks later, the (13)C-urea breath test was repeated to assess whether H. pylori was eradicated. Intention-to-treat (ITT) and per-protocol (PP) analysis showed no difference in H. pylori eradication rates in both the ALL-500 and ALL-1000 groups (ITT: 79% vs. 80.6%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05; PP: 86% vs. 87.5%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05). For both groups, the per-protocol H. pylori eradication rates were also similarly high between patients with a post-treatment value of (13)C-urea breath test &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 15 and those with a value &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 15 (ALL-500: 85% vs. 86.5%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05; ALL-1000: 88.9% vs. 86.8%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05). One-week levofloxacin 500 mg daily-based triple therapy is effective for eradicating the persistent H. pylori after a failed triple therapy with amoxicillin, clarithromycin, and omeprazole.

Research paper thumbnail of Gender Difference of Circulating Ghrelin and Leptin Concentrations in Chronic Helicobacter pylori Infection

Helicobacter, 2009

Both ghrelin and leptin are important appetite hormones secreted from the stomach. We examined wh... more Both ghrelin and leptin are important appetite hormones secreted from the stomach. We examined whether demographic background, Helicobacter pylori infection, or its related gastritis severity could be associated with circulating ghrelin and leptin levels. This study prospectively enrolled 341 dyspeptic patients (196 females, 145 males), who had received endoscopy to provide the gastric specimens over both antrum and corpus for histology reviewed by the updated Sydney&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s system. The fasting blood sample of each patient was obtained for total ghrelin and leptin analysis. Without H. pylori infection, there were similar ghrelin levels between female and male patients. In the H. pylori-infected patients, the males had lower plasma ghrelin levels than females (1053 vs. 1419 pg/mL, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Only in males, not in females, the H. pylori infection and its related acute and chronic inflammation scores were significantly associated with a lower ghrelin level (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = .04). The multivariate regression disclosed that only the chronic inflammation score independently related to a lower ghrelin level. Only in males, the ghrelin levels ranked in a downward trend for the gastritis feature as with limited-gastritis, with antrum-predominant gastritis, and with corpus-gastritis (1236, 1101, and 977 pg/mL). Leptin level was not related to H. pylori-related gastritis, but positively related to body mass index. There should be a gender difference to circulating total ghrelin levels, but not leptin levels, in response to H. pylori infection and its related chronic gastritis.

Research paper thumbnail of Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study

Gut, 2014

Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazol... more Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions. To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores. We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily, respectively. The patients with Rockall scores &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 served as controls (n=89); they received 11 days of oral esomeprazole 40 mg once daily. Thereafter, all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period. The primary end point was peptic ulcer rebleeding. Among patients with Rockall scores ≥6, the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group (p=0.02, log-rank test). The proportion of patients free from recurrent bleeding during the 4th-28th day in the oral double-dose group remained lower than that of the group with Rockall scores &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 (p=0.03, log-rank test). Among patients with Rockall scores ≥6, the rebleeding rate was lower in the oral double-dose group than in the oral standard-dose group (4th-28th day: 10.8% vs 28.7%, p=0.002). Double oral esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6. NCT01591083.

Research paper thumbnail of Psychotic disorder induced by a combination of sorafenib and BAY86-9766

General Hospital Psychiatry, 2014

The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (... more The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK cascade is important in the intra-cellular transduction of neurotransmitters, such as dopamine and glutamate. Sorafenib (Nexavar), a multi-kinase inhibitor targeting Raf kinase, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor, has shown promising results in the treatment of malignancies. BAY86-9766, a novel selective MEK 1/2 inhibitor, is being evaluated in clinical trials as an anticancer drug. We describe herein a hepatocellular carcinoma patient presenting with recurrent psychotic symptoms in the course of the BASIL trial (assessing BAY86-9766 plus sorafenib for the treatment of liver cancer). In this case, VEGFR inhibition caused by sorafenib alone may have contributed to the development of psychosis. A change in ERK activity might also have been involved. However, whether single or combination use of the two drugs is responsible for inducing the psychotic symptoms remains unclear. In summary, the role of the ERK pathway in psychosis is still vague. Further investigation of the ERK activity in patients with psychotic disorders may disclose its role in the pathophysiology of psychosis.

Research paper thumbnail of Genomic single nucleotide polymorphisms in the offspring of gastric cancer patients predispose to spasmolytic polypeptide-expressing metaplasia after H. pylori infection

Journal of Biomedical Science, 2015

Background: Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (G... more Background: Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM).

Research paper thumbnail of Helicobacter pylori Test-and-Treat Program Can Be Cost-effective to Prevent Gastric Cancer in Taiwanese Adults: Referred to the Nationwide Reimbursement Database

Helicobacter, 2015

Helicobacter pylori infection increases the risk of gastric cancer. The study aimed to compare co... more Helicobacter pylori infection increases the risk of gastric cancer. The study aimed to compare cost-effectiveness ratios of H. pylori test-and-treat programs to prevent gastric cancer in Taiwan, referring to the nationwide reimbursement database and expected years of life lost. During 1998-2009, there were 12,857 females and 24,945 males with gastric adenocarcinoma in Taiwan National Cancer Registry. They were followed up to 2010 and linked to the reimbursement database of National Health Insurance and the national mortality registry to determine lifetime health expenditures and expected years of life lost. Cost-effectiveness ratios of H. pylori test-and-treat programs for prevention of gastric adenocarcinoma were compared between screenings with (13) C-urea breath test and with anti-H. pylori IgG. The test-and-treat program with anti-H. pylori IgG to prevent gastric adenocarcinoma had lower incremental cost-effectiveness ratios than that with (13) C-urea breath test in both sexes (...

Research paper thumbnail of Expressions of MMPs and TIMP-1 in gastric ulcers may differentiate H. pylori-infected from NSAID-related ulcers

TheScientificWorldJournal, 2012

Two major causes of gastric ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal... more Two major causes of gastric ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) use. This study aimed to determine if there were different expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) between H. pylori-infected and NSAID-related ulcers. The 126 gastric ulcer patients (H. pylori infected n = 46; NSAID related n = 30; combined with two factors n = 50) provided ulcer and nonulcer tissues for assessment of MMP-3, -7, and -9 and TIMP-1 expression by immunohistochemical staining. Gastric ulcer tissues had significantly higher MMP-3, -7, and -9 and TIMP-1 expressions than nonulcer tissues (P < 0.05). H. pylori-infected gastric ulcers had even higher MMP-7, MMP-9, and TIMP-1 expressions in epithelial cells than NSAID-related gastric ulcers (P < 0.05). In patients with the two combined factors, gastric ulcers expressed similar proportions of antral ulcers and MMP-7 and MMP-9 ...

Research paper thumbnail of Supplementation of Los Angeles classification with esophageal mucosa index of hemoglobin can predict the treatment response of erosive reflux esophagitis

Surgical endoscopy, 2011

We assessed whether the esophageal mucosa index of hemoglobin (IHb) could assist the Los Angeles ... more We assessed whether the esophageal mucosa index of hemoglobin (IHb) could assist the Los Angeles (LA) classification in defining the severity of erosive reflux esophagitis (RE) and predicting the treatment response by esomeprazole. Five hundred twenty-four subjects (424 RE and 100 controls) with normal body mass index and hemoglobin had undergone endoscopy to confirm the RE grade by LA classification and to check the series of IHb values at every centimeter of the esophageal mucosa while withdrawing the endoscope to above the esophageal-gastric junction (EGJ). The RE cases had received esomeprazole for 8 weeks (40 mg/day) to assess the cumulative proportions of sustained symptomatic response (SSR). The IHb value at the EGJ was higher in RE patients than in controls (P < 0.001). Selecting 70 as the cutoff IHb value at the EGJ, the efficacy to define RE achieved 95.8% (406/424) sensitivity and 94% (94/100) specificity. For the patients with same the LA grade, the length of IHb valu...

Research paper thumbnail of The impact of body mass index on the application of on-demand therapy for Los Angeles grades A and B reflux esophagitis

The American journal of gastroenterology, 2007

Patients with Los Angeles grade A or B reflux esophagitis (RE-AB) can potentially be switched fro... more Patients with Los Angeles grade A or B reflux esophagitis (RE-AB) can potentially be switched from active-phase therapy to on-demand esomeprazole as maintenance therapy. Body mass index (BMI) correlates significantly with reflux symptoms. We investigated whether BMI affects the efficacy of esomeprazole in active-phase or subsequent on-demand therapy. Three hundred fifty patients with RE-AB were prospectively enrolled to receive an 8-wk course of esomeprazole (40 mg/day) as active-phase therapy. Based on the daily severity of acid regurgitation and heartburn, the cumulative proportions of patients with sustained symptomatic response (SSR), defined as free from symptoms for the last 7 days, were compared among different BMI groups (control: BMI <25 kg/m2, overweight: BMI 25-30 kg/m2, obese: BMI >30 kg/m2). In patients who had achieved SSR by week 8, on-demand therapy for 2 months was started. The number of 40-mg esomeprazole tablets used per 4-wk period was recorded. SSR rates w...

Research paper thumbnail of Increased risk of rebleeding of peptic ulcer bleeding in patients with comorbid illness receiving omeprazole infusion

Hepato-gastroenterology

The study aimed to evaluate whether administration of intravenous omeprazole has different reblee... more The study aimed to evaluate whether administration of intravenous omeprazole has different rebleeding rates for peptic ulcer bleeding of patients with and without comorbid illness. A total of 80 patients with peptic ulcer bleeding were enrolled after therapeutic endoscopy to achieve hemostasis. Each patient had received omeprazole 80 mg bolus loading and 40 mg twice daily for three days (total dosage of 320 mg within 3 days). Two subgroups were divided, based on the absence (Group A) or presence (Group B) of one or more comorbid illnesses, such as chronic obstructive pulmonary disease, congestive heart failure, uremia, cirrhosis, diabetes mellitus, and old stroke. The 7-day and 28-day rebleeding rates were recorded. The presence of comorbid illness had a higher rebleeding rate than those without comorbid illness (7-day: 32.5 vs. 2.5%, p < 0.05; 28-day: 37.5 vs. 5.0%, p < 0.05). Patients with two or more comorbid diseases had an even higher risk of rebleeding than those with a ...

Research paper thumbnail of Double-Dosed Pantoprazole Accelerates the Sustained Symptomatic Response in Overweight and Obese Patients With Reflux Esophagitis in Los Angeles Grades A and B

The American Journal of Gastroenterology, 2009

Body mass index (BMI) in the range defined as overweight or obese adversely decreases the sustain... more Body mass index (BMI) in the range defined as overweight or obese adversely decreases the sustained symptomatic response (SSR) to proton pump inhibitors for patients with reflux esophagitis of Los Angeles grade A or B (RE-AB). We thus investigated whether double-dosed pantoprazole can accelerate SSR in such patients. A total of 200 overweight or obese patients with RE-AB were evenly randomized into a double-dosed group (receiving 8-week pantoprazole 40 mg twice daily) or a standard-dosed control group (receiving 8-week pantoprazole 40 mg per day and one blank tablet at night). In each patient, demographic factors and the genotype of S-mephenytoin 4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-hydroxylase (CYP2C19) were checked and defined as poor metabolizer (PM), or homologous extensive metabolizer (HomoEM), or heterologous extensive metabolizer (HeteroEM). The cumulative proportions of patients with SSR were compared during the 8-week period. Both intention-to-treat and per-protocol analyses disclosed that the rates of SSR were higher in the double-dosed group than in the standard-dosed group from week 4 (P=0.005) until week 8 (P=0.01). While using standard-dosed pantoprazole, PMs had better rates of SSR during the 8-week period than both HomoEMs and HeteroEMs (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). By using double-dosed pantoprazole, the cumulative rates of SSR were improved as early as week 4 for both HomoEMs and HeteroEMs (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.005, log-rank test). For RE-AB in overweight and obese patients, double-dosed pantoprazole effectively accelerates the SSR, especially for those with CYP2C19 genotypes as HeteroEM or HomoEM. Accordingly, it offers an earlier shift into on-demand pantoprazole for RE-AB patients with high BMI.

Research paper thumbnail of Intravenous proton pump inhibitors for peptic ulcer bleeding: Clinical benefits and limits Hsiu-Chi Cheng, Bor-Shyang Sheu

World Journal of Gastrointestinal Endoscopy, 2011

Peptic ulcer bleeding is a common disease and recurrent bleeding is an independent risk factor of... more Peptic ulcer bleeding is a common disease and recurrent bleeding is an independent risk factor of mortality. Infusion with proton pump inhibitors (PPIs) prevents recurrent bleeding after successful endoscopic therapy. A gastric acidic environment of less than pH 5.4 alters coagulation function and activates pepsin to disaggregate platelet plugs. Gastric acid is secreted by H + , K + -ATPase, naming the proton pump. This update review focuses on the mechanism and the role of PPIs in the clinical management of patients with peptic ulcer bleeding. An intravenous omeprazole bolus followed by high-dose continuous infusion for 72 h after successful endoscopic therapy can prevent the recurrent bleeding. In the Asian, however, the infusion dosage can possibly be diminished whilst preserving favorable control of the intragastric pH and thereby still decreasing rates of recurrent bleeding. Irrespective of the infusion dosage of PPIs, rates of recurrent bleeding remain high in patients with co-morbidities. Because recurrent peptic ulcer bleeding may be prolonged in those with co-morbidities, a lowdose infusion of IV PPIs for up to 7-day may result in better control of recurrent bleeding of peptic ulcers. Due to the inter-patient variability in CYP2C19 genotypes, the infusion form of new generation PPIs, such as esomeprazole, should be promising for the prevention of recurrent bleeding. This article offers a comprehensive review of clinical practice, highlighting the indication, the optimal dosage, the duration, and the potential limitation of PPIs infusion for peptic ulcer bleeding.

Research paper thumbnail of Consensus on Control of Risky Nonvariceal Upper Gastrointestinal Bleeding in Taiwan with National Health Insurance

BioMed Research International, 2014

To compose upper gastrointestinal bleeding (UGIB) consensus from a nationwide scale to improve th... more To compose upper gastrointestinal bleeding (UGIB) consensus from a nationwide scale to improve the control of UGIB, especially for the high-risk comorbidity group. The steering committee defined the consensus scope to cover preendoscopy, endoscopy, postendoscopy, and overview from Taiwan National Health Insurance Research Database (NHIRD) assessments for UGIB. The expert group comprised thirty-two Taiwan experts of UGIB to conduct the consensus conference by a modified Delphi process through two separate iterations to modify the draft statements and to vote anonymously to reach consensus with an agreement ≥80% for each statement and to set the recommendation grade. The consensus included 17 statements to highlight that patients with comorbidities, including liver cirrhosis, end-stage renal disease, probable chronic obstructive pulmonary disease, and diabetes, are at high risk of peptic ulcer bleeding and rebleeding. Special considerations are recommended for such risky patients, including raising hematocrit to 30% in uremia or acute myocardial infarction, aggressive acid secretory control in high Rockall scores, monitoring delayed rebleeding in uremia or cirrhosis, considering cycloxygenase-2 inhibitors plus PPI for pain control, and early resumption of antiplatelets plus PPI in coronary artery disease or stroke. The consensus comprises recommendations to improve care of UGIB, especially for high-risk comorbidities.

Research paper thumbnail of Usefulness of Fatty-meal Stimulated Gallbladder Contractility by Ultrasonography in the Diagnosis of Acute Cholecystitis

Journal of Medical Ultrasound, 2005

ABSTRACT Address correspondence to: Dr. Chiao-Hsiung Chuang, Department of Internal Medicine, Col... more ABSTRACT Address correspondence to: Dr. Chiao-Hsiung Chuang, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 704, Taiwan, R.O.C

Research paper thumbnail of Posttreatment 13C-urea breath test is predictive of antimicrobial resistance to H. pylori after failed therapy

Journal of General Internal Medicine, 2005

OBJECTIVE: We tested whether a 13 C-urea breath test can predict antimicrobial resistance of Heli... more OBJECTIVE: We tested whether a 13 C-urea breath test can predict antimicrobial resistance of Helicobacter pylori (H. pylori).

Research paper thumbnail of Resistance to metronidazole, clarithromycin and levofloxacin of Helicobacter pylori before and after clarithromycin-based therapy in Taiwan

Journal of Gastroenterology and Hepatology, 2009

Clarithromycin-based triple therapy has been commonly applied as the first-line therapy for Helic... more 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. Methods: The study collected the H. pylori isolates from 180 naive patients and 47 patients with a failed clarithromycin-based triple therapy. Their in vitro antimicrobial resistance was determined by E-test. Results: The naive H. pylori isolates had resistance rates for amoxicillin, levofloxacin, clarithromycin and metronidazole of 0%, 9.4%, 10.6% and 26.7%, respectively. An evolutional increase of the primary levofloxacin resistance was observed in isolates collected after 2004, as compared to isolates collected before 2004 (16.3% vs 3.2%, P = 0.003). There was no evolutional increment of the primary clarithromycin resistance. The clarithromycin resistance elevated significantly after a failed clarithromycin-based triple therapy (78.7% vs 10.6%, P < 0.001). The post-treatment isolates remained to have a levofloxacin resistance rate of near 17%, but the levofloxacin-resistant isolates were correlated with a higher incidence of metronidazole resistance (P = 0.023). No strain was found to be resistant to amoxicillin even after eradication failure. Conclusion: The levofloxacin resistance of naive H. pylori remains less than 10% in Taiwan. With relatively lower resistance to levofloxacin than to metronidazole of the H. pylori isolates collected after a failed clarithromycin-based therapy, proton pump inhibitorlevofloxacin-amoxicillin may be an alternative choice to serve as the second-line therapy.

Research paper thumbnail of Erythrocyte Lewis (A+B-) host phenotype is a factor with familial clustering for increased risk of Helicobacter pylori-related non-cardiac gastric cancer

Journal of Gastroenterology and Hepatology, 2006

The purpose of the present study was to test whether host erythrocyte Lewis phenotypes correlated... more The purpose of the present study was to test whether host erythrocyte Lewis phenotypes correlated with the risk of gastric cancers. Because of the association of gastric cancer with familial clustering, cancer relatives were investigated as to whether they had unique distribution of Lewis phenotypes. The study prospectively enrolled 74 Helicobacter pylori-positive gastric cancer patients and 100 H. pylori-positive duodenal ulcer patients to serve as non-cancer controls after panendoscopy. In addition, 433 family members from the 74 index cancer and 100 non-cancer control patients were enrolled. All enrolled cases were checked for their H. pylori status and erythrocyte Lewis phenotypes, defined as Le(a-b-), Le(a-b+), Le(a+b-), and Le(a+b+) subtypes by the anti-Le(a) and anti-Le(b) monoclonal antibodies. These H. pylori-infected patients with gastric cancer had a higher rate of Le(a+b-) phenotype and a lower rate of Le(a-b+) phenotype than the non-cancer duodenal ulcer controls (20.3% vs 9%; 51.4% vs 72%, P &amp;amp;amp;amp;amp;amp;lt; 0.05). Among these H. pylori-infected patients, the risk of the patients with Le(a+b-) phenotype having gastric cancer was 3.15-fold higher as compared with those with the Le(a-b+) phenotype (P = 0.02, 95% confidence interval: 1.26-7.87). The offspring and cousins of the cancer patients had a higher rate of Le(a+b-) phenotype as compared to either that of the spouses of cancer index patients or to that of the family members of the non-cancer control (P &amp;amp;amp;amp;amp;amp;lt; 0.05). Le(a+b-) phenotype of the H. pylori-infected host could be a risk factor (with familial clustering) for gastric carcinogenesis.

Research paper thumbnail of CYP2C19 genotypes determine the efficacy of on-demand therapy of pantoprazole for reflux esophagitis as Los-Angeles grades C and D

Journal of Gastroenterology and Hepatology, 2012

The present study determined whether the genotypes of S-mephenytoin 4′-hydroxylase (CYP2C19) coul... more The present study determined whether the genotypes of S-mephenytoin 4′-hydroxylase (CYP2C19) could serve as an indicator to assess the success of long-term on-demand therapy (ODT) with pantoprazole for the patients with severe reflux esophagitis as Los Angles grade C or D (RE-CD). Methods: A total of 240 patients with RE-CD were prospectively enrolled to receive continuous pantoprazole, 40 mg daily for 6 months. The patients, who achieved complete healing and were free from acid reflux-related symptoms during follow up, were included to receive ODT with a 40 mg pantoprazole tablet up to 1 year. Each patient was followed to assess the monthly tablet number of 40 mg pantoprazole and the cumulative rate of failure of ODT. The CYP2C19 genotype of each included patient was defined as homologous extensive metabolizer (HomoEM), heterologous extensive metabolizer (HeteroEM), and poor metabolizer (PM). Results: Two-hundred patients were included to receive ODT, including 51 as HomoEM, 108 as HeteroEM, and 41 as PM. There were no differences in demographic and endoscopic features among patients with different CYP2C19 genotypes (P > 0.05). The 1-year cumulative failure rate of ODT was significantly higher in HomoEM than in HeteroEM and PM (P < 0.05, by log-rank test). For those with successful ODT during the 1-year follow up, the mean monthly tablet number of pantoprazole was lower in PM than in HeteroEM and HomoEM (11.5 vs 16.3 and 18.6, P < 0.05). Conclusion: For RE-CD with complete healing after continuous pantoprazole, the successful shift to ODT is determined by the CYP2C19 genotypes of the patients.

Research paper thumbnail of Long-term Outcome of Pyogenic Liver Abscess

Journal of Clinical Gastroenterology, 2008

Long-term surveillance of pyogenic liver abscess remains unavailable. We thus aimed to identify t... more Long-term surveillance of pyogenic liver abscess remains unavailable. We thus aimed to identify the recurrence rates of pyogenic liver abscess among various etiologies and pathogens, and to elucidate the factors related with this recurrence. Six-hundred and one patients with pyogenic liver abscess were prospectively enrolled to observe abscess recurrence during a mean follow-up period of up to 6.06 years. On the basis of the etiology of the initial abscess, patients were divided into different subgroups as follows: there were 152 (25.3%) patients classified as cryptogenic, 229 (38.1%) with diabetes mellitus, 144 (24%) with underlying biliary tract disease, and 76 (12.6%) with other organic diseases or mixed subgroups. The cumulative recurrence rates of pyogenic liver abscess were lower in both the cryptogenic (2.0%) and diabetic (4.4%) groups than in the underlying biliary tract disease (23.8%) group (log-rank test, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The diabetic group had a higher rate of Klebsiella pneumoniae infection and a lower rate of Escherichia coli infection than the biliary tract group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). For patients infected with K. pneumoniae, the recurrence rate of pyogenic liver abscess was as low as that of the diabetes and the cryptogenic groups (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). Pyogenic liver abscess is more commonly recurrent in patients with underlying biliary tract disease. Irrespective of diabetic status or cryptogenic etiology, the recurrence of K. pneumoniae-infected liver abscess is low in the long-term.

Research paper thumbnail of Higher Motility Enhances Bacterial Density and Inflammatory Response in Dyspeptic Patients Infected with Helicobacter pylori

Helicobacter, 2012

Background: Motility mediated by the flagella of Helicobacter pylori is important for the cells t... more Background: Motility mediated by the flagella of Helicobacter pylori is important for the cells to move toward the gastric mucus in niches adjacent to the epithelium; then, H. pylori uses the adhesin SabA to interact with sialyl-Le x on inflammatory host cells for persistent infection. Here, we reveal the clinical association of bacterial motility, SabA expression, and pathological outcomes. Methods: Ninety-six clinical isolates were screened for bacterial motility, and the expression of SabA of each isolate was confirmed by Western blotting. H. pylori-infected patients were assessed for their bacterial density, sialyl-Le x expression, inflammatory scores, and clinical diseases. Results: The mean diameter in the motility assay was 17 mm, and eight (8.3%) of the strains had impaired motility, with a diameter <5 mm. H. pylori density in cardia, the acute inflammatory score in the body locus, and the prevalence rate of gastric atrophy were increased in patients infected with higher-motility strains (p = .023, <.001, or <.001, respectively). The total inflammatory scores (both acute and chronic) and bacterial density dramatically increased in patients expressing the sialyl-Le x antigen and infected with higher-motility, SabA-positive H. pylori (p = .016, .01, or .005, respectively). Conclusion: These results suggest that the higher motility of H. pylori enhances pathological outcomes, and the SabA-sialyl-Le x interaction has a synergistic effect on virulence of the higher-motility strains.

Research paper thumbnail of Levofloxacin-Containing Triple Therapy to Eradicate the Persistent H.�pylori after a Failed Conventional Triple Therapy

Helicobacter, 2007

To identify the optimal dosage of levofloxacin to eradicate persistent Helicobacter pylori when t... more To identify the optimal dosage of levofloxacin to eradicate persistent Helicobacter pylori when triple therapy with amoxicillin, clarithromycin, and omeprazole fails. We investigated 124 patients whose triple therapy including clarithromycin had failed. Clarithromycin resistance was indirectly assessed by the (13)C-urea breath test, with a post-treatment value cut-off point at 15. All patients were randomly divided into two groups, to receive 1-week amoxicillin 1 g and lansoprazole 30 mg twice daily, plus either levofloxacin 500 mg once (ALL-500 group) or twice daily (ALL-1000 group). Six weeks later, the (13)C-urea breath test was repeated to assess whether H. pylori was eradicated. Intention-to-treat (ITT) and per-protocol (PP) analysis showed no difference in H. pylori eradication rates in both the ALL-500 and ALL-1000 groups (ITT: 79% vs. 80.6%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05; PP: 86% vs. 87.5%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05). For both groups, the per-protocol H. pylori eradication rates were also similarly high between patients with a post-treatment value of (13)C-urea breath test &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 15 and those with a value &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 15 (ALL-500: 85% vs. 86.5%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05; ALL-1000: 88.9% vs. 86.8%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05). One-week levofloxacin 500 mg daily-based triple therapy is effective for eradicating the persistent H. pylori after a failed triple therapy with amoxicillin, clarithromycin, and omeprazole.

Research paper thumbnail of Gender Difference of Circulating Ghrelin and Leptin Concentrations in Chronic Helicobacter pylori Infection

Helicobacter, 2009

Both ghrelin and leptin are important appetite hormones secreted from the stomach. We examined wh... more Both ghrelin and leptin are important appetite hormones secreted from the stomach. We examined whether demographic background, Helicobacter pylori infection, or its related gastritis severity could be associated with circulating ghrelin and leptin levels. This study prospectively enrolled 341 dyspeptic patients (196 females, 145 males), who had received endoscopy to provide the gastric specimens over both antrum and corpus for histology reviewed by the updated Sydney&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s system. The fasting blood sample of each patient was obtained for total ghrelin and leptin analysis. Without H. pylori infection, there were similar ghrelin levels between female and male patients. In the H. pylori-infected patients, the males had lower plasma ghrelin levels than females (1053 vs. 1419 pg/mL, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Only in males, not in females, the H. pylori infection and its related acute and chronic inflammation scores were significantly associated with a lower ghrelin level (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = .04). The multivariate regression disclosed that only the chronic inflammation score independently related to a lower ghrelin level. Only in males, the ghrelin levels ranked in a downward trend for the gastritis feature as with limited-gastritis, with antrum-predominant gastritis, and with corpus-gastritis (1236, 1101, and 977 pg/mL). Leptin level was not related to H. pylori-related gastritis, but positively related to body mass index. There should be a gender difference to circulating total ghrelin levels, but not leptin levels, in response to H. pylori infection and its related chronic gastritis.

Research paper thumbnail of Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study

Gut, 2014

Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazol... more Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions. To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores. We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily, respectively. The patients with Rockall scores &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 served as controls (n=89); they received 11 days of oral esomeprazole 40 mg once daily. Thereafter, all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period. The primary end point was peptic ulcer rebleeding. Among patients with Rockall scores ≥6, the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group (p=0.02, log-rank test). The proportion of patients free from recurrent bleeding during the 4th-28th day in the oral double-dose group remained lower than that of the group with Rockall scores &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 (p=0.03, log-rank test). Among patients with Rockall scores ≥6, the rebleeding rate was lower in the oral double-dose group than in the oral standard-dose group (4th-28th day: 10.8% vs 28.7%, p=0.002). Double oral esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6. NCT01591083.

Research paper thumbnail of Psychotic disorder induced by a combination of sorafenib and BAY86-9766

General Hospital Psychiatry, 2014

The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (... more The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK cascade is important in the intra-cellular transduction of neurotransmitters, such as dopamine and glutamate. Sorafenib (Nexavar), a multi-kinase inhibitor targeting Raf kinase, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor, has shown promising results in the treatment of malignancies. BAY86-9766, a novel selective MEK 1/2 inhibitor, is being evaluated in clinical trials as an anticancer drug. We describe herein a hepatocellular carcinoma patient presenting with recurrent psychotic symptoms in the course of the BASIL trial (assessing BAY86-9766 plus sorafenib for the treatment of liver cancer). In this case, VEGFR inhibition caused by sorafenib alone may have contributed to the development of psychosis. A change in ERK activity might also have been involved. However, whether single or combination use of the two drugs is responsible for inducing the psychotic symptoms remains unclear. In summary, the role of the ERK pathway in psychosis is still vague. Further investigation of the ERK activity in patients with psychotic disorders may disclose its role in the pathophysiology of psychosis.