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Background Hyperbilirubinemia is a predictor of severe drug-induced liver injury (DILI). Hepatobiliary ATP-binding cassette (ABC) transporters play an important role in the transportation of many drugs and bilirubin; however, little is known about these transporters and the risk of DILI. The aim of this study was to explore associations between genetic variations in important ABC transporters and susceptibility to DILI, with a particular focus on hyperbilirubinemia. Methods A total of 200 patients with DILI and 200 healthy controls were enrolled as the training dataset. Another 106 patients with DILI were recruited as the validation dataset. They were genotyped for ABCB11 (BSEP) rs2287622, ABCB1 (MDR1) rs1128503, rs1045642, ABCB4 (MDR3) rs2230028, ABCC2 (MRP2) rs1885301, rs717620, rs2273697, rs3740066 and rs8187710 using polymerase chain reaction-based TaqMan genotyping assays. Results There were no statistical differences in any of the nine ABC transporter single nucleotide polymorphisms between the DILI and control groups. However, in the DILI group, the patients with hyperbilirubinemia had a higher frequency of the ABCC2 rs717620 C/T and T/T genotypes than those without hyperbilirubinemia (44.2% vs 20.2%, p = 0.001). After adjusting for other confounding factors, the ABCC2 rs717620 T variant was still associated with an increased risk of hyperbilirubinemia (adjusted odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.73-8.48, p = 0.001). This association was confirmed by the validation dataset (adjusted OR: 3.92, 95% CI: 1.42-10.81, p = 0.015). We also found that the mortality group had higher frequencies of the ABCC2 (MRP2) rs717620 C/T and T/T genotypes than the survival group (50.0% vs 27.9%, p = 0.048). Conclusion Carriage of the ABCC2 (MRP2) rs717620 T variant may increase the risk of hyperbilirubinemia and mortality in patients with DILI. Screening for this variant may help to prevent and mitigate drug-induced hyperbilirubinemia.

Background Nonalcoholic steatohepatitis (NASH) is closely related to reactive oxygen species (ROS). Superoxide anion radicals, the main product of ROS, can be reduced by manganese superoxide dismutase (SOD2) to hydrogen peroxide, which is further reduced by catalase (CAT) and glutathione peroxidase (GPX) to water. We aimed to investigate the association between the most important genetic variants of SOD2, CAT, and GPX1 and susceptibility to NASH. Methods A total of 126 adults with liver tissue-verified NASH, 56 patients with liver tissue-verified nonalcoholic fatty liver (NAFL), and 153 healthy controls were enrolled. Their DNA profiles were retrieved for genotype assessment of SOD2 47T>C (rs4880), CAT -262C>T (rs1001179), and GPX1 593C>T (rs1050450) variation. Results There were statistical differences between the SOD2 and CAT genotypes across the NASH, NAFL, and control groups, but not GPX1. The NASH group had a significantly higher frequency of subjects with SOD2 C allele (38.8%) compared with the NASL group (25.0%) and the controls (22.9%, p = 0.010). Similarly, the NASH group had a significantly higher percentage of subjects with CAT T allele (23.0%) compared with the NAFL group (10.7%) and the controls (7.2%, p = 0.001). For subjects with both the SOD2 C allele and CAT T allele, 88.2% were in the NASH group. After adjusting for confounders, the CAT mutant T allele and SOD2 mutant C allele were still the highest independent risk factors for NASH (odds ratio [OR] 3.10 and 2.36, respectively). In addition, there was a synergistic effect for those two alleles and the occurrence of NASH with an adjusted OR of 8.57 (p = 0.030). Conclusion The genetic variations of CAT and SOD2 may increase the risk of NASH, which may aid in the screening of patients who are at high risk of NASH, and offer a potential anti-oxidant targeting route for the treatment of NASH.

BACKGROUND The mainstay therapy for latent tuberculosis infection is a 9-month regimen of daily isoniazid (9H) and a 3-month regimen of 12 once-weekly doses of isoniazid and rifapentine (3HP). We performed this updated meta-analysis to compare hepatotoxicity, efficacy and completion rate between these two regimens. METHODS We searched all literature in the major medical databases using the subject search terms "isoniazid" and "rifapentine", and performed a systemic review and meta-analysis. RESULTS A total of 14 studies were eligible for the meta-analysis, which included 5600 (49%) patients who received the 3HP regimen and 5919 (51%) patients who received the 9H regimen. A total of 202 (2%) patients had a drug-induced liver injury (DILI) and 11 317 (98%) did not. The pooled odds ratio (OR) of DILI in the 3HP regimen was 0.18 (95% confidence interval [CI], 0.12-0.26; p < 0.0001), compared with the 9H regimen. This result remained consistent in subgroup analyses of ethnicity and study design. The 3HP regimen was superior to the 9H regimen in the prevention of active tuberculosis (OR, 0.38, 95% CI, 0.18-0.80, p = 0.01). Furthermore, the 3HP regimen was associated with a better completion rate than the 9H regimen (OR: 2.30, 95% CI, 2.10-2.53, p < 0.0001). CONCLUSION The 3HP regimen is superior to the 9H regimen, with less hepatotoxicity, and better efficacy and completion rate in treating latent tuberculosis infection.

BACKGROUND Worldwide, proton pump inhibitors (PPIs) are commonly used for the treatment of peptic ulcer and gastro-esophageal reflux disease. Recently, concern has arisen over the potential association between PPIs and hepatocellular carcinoma (HCC). The aim of the current study was to evaluate the influence of PPI use on the risk of HCC, through a systematic review and meta-analysis. METHODS A review of all English-language literature was conducted, using the subject search terms: "hepatocellular carcinoma", "liver cancer", "hepatic tumor", and "proton pump inhibitor" in the major medical databases. A meta-analysis of the qualifying publications was then performed. RESULTS A total of five studies, which had shown that PPIs were associated with HCC (crude risk ratio [RR] = 2.27, 95% confidence interval [CI]: 1.44-3.57; p < 0.01) when an unadjusted RR were adopted, were eligible for meta-analysis. It was observed that the cumulative dose of PPIs may increase the risk of HCC in a linear model (p < 0.01). However, when using data that were adjusted by comorbidities and concurrent medications, the association between PPIs and HCC became insignificant (adjusted RR = 1.62, 95% CI: 0.89-2.93; p = 0.11) and this result was consistent in the sensitivity analysis. CONCLUSION The current meta-analysis has shown that PPI use does not significantly increase the risk of HCC after adjusting for confounding factors. However, further studies are warranted to verify the association between PPIs and HCC in special populations, such as viral or alcoholic liver diseases.

BACKGROUND Antituberculosis (TB) drug-induced liver injury (ATLI) is a common adverse effect of anti-TB drugs. Whether regular monitoring of liver function can ameliorate ATLI has been widely debated. The current study aimed to investigate the liver test monitoring status of patients receiving anti-TB treatment in Taiwan, as well as the impact of scheduled liver function monitoring on the risk of ATLI. METHODS Patients who received anti-TB treatment at our hospital between 2009 and 2017 were enrolled for retrospective analysis. RESULTS A total of 1062 patients were included, and of them 469 (44.2%) received regular liver function monitoring (good monitoring group). ATLI was recognized in 100 (9.4%) patients. The good monitoring group detected more ATLI cases early compared with the poor monitoring group (14.7% vs 5.2%, and 21.4 vs 61.6 days, p < 0.01), with a lower peak serum alanine aminotransferase (276.1 vs 507.1 IU/L, p = 0.05). CONCLUSION In the current study, less than half of all patients who received anti-TB drugs had their liver function monitored regularly. Scheduled monitoring of liver function could facilitate the early identification of more ATLI cases, thus leading to less liver injury. The implementation of periodic liver function monitoring tests in patients receiving anti-TB treatment should be re-emphasized and encouraged.

OBJECTIVES Sulfamethoxazole-trimethoprim (SMX-TMP) is one of the most frequently used antibiotics. SMX is metabolized by N-acetyltransferase (NAT) and cytochrome P450 2C9 (CYP2C9) to nontoxic or toxic intermediates. Little is known about the association between genetic variations of these enzymes and SMX-TMP-induced liver injury (SILI). The aim of this study was to explore the genetic polymorphisms of NAT2 and CYP2C9 and the susceptibility to SILI in a Han Chinese population. METHODS A total of 158 patients with SILI and 145 controls were recruited in this study. PCR-based genotyping with matrix-assisted laser desorption ionization-time of flight was used to assay the major NAT2 and CYP2C9 genotypes including NAT2 rs1495741, rs1041983, rs1801280, CYP2C9 rs1799853, rs1057910 and rs4918758. RESULTS The SILI group had a higher frequency of the NAT2 rs1495741 variant AA genotype and rs1041983 variant TT genotype than the controls (42.4 vs. 25.5%; P = 0.008, and 40.5 vs. 25.5%; P = 0.022, respectively). The SILI group had more slow acetylators than the controls (43.7 vs. 25.5%; P = 0.001). There were no significant differences in the genetic variations of CYP2C9 between the SILI and control groups. After adjusting for confounding factors, the NAT2 slow acetylators still had an increased risk of SILI (adjusted OR: 2.49; 95% confidence interval: 1.46-4.24; P = 0.001), especially in those with hepatocellular and mixed type SILI. CONCLUSIONS NAT2 slow acetylators are associated with a higher risk of SILI in the Han Chinese population. However, CYP2C9 genetic polymorphisms are not associated with the susceptibility to SILI.

Background N -Acetyltransferase (NAT) is an important enzyme with the capacity to metabolize carcinogenic aromatic amines. However, it remains controversial whether the encoded functional NAT2 genetic polymorphism is related to the risk of gastric adenocarcinoma (GA). The aim of this study was to evaluate the association between NAT2 genetic variation and gastric adenocarcinoma (GA), with special reference to the gastric noncardiac adenocarcinoma (GNA). Methods Peripheral white blood cell DNA from 368 GA patients and 368 age- and sex-matched controls were genotyped for NAT2 by a polymerase chain reaction method. The lifestyle habits of the participants were assessed using a semiquantitative food–frequency questionnaire. NAT2 genotype, interaction with lifestyle habits, and the risk of GA and GNA were analyzed by logistic regression. Results GA patients were more likely to have a smoking habit, ate more salted foods, and consumed more well-done meat than the controls. There was no association between the NAT2 genotypes and susceptibility to GA. However, if patients with gastric cardiac adenocarcinoma (GCA; n = 42) were excluded, the NAT2 slow acetylators (without rapid acetylator allele) had a higher risk of GA than intermediate and rapid acetylators (odds ratio = 1.53; 95% confidence interval, 1.05–2.23, p = 0.027). In addition, there was a synergic effect of NAT2 slow acetylator and well-done meat intake to the development of GNA (odds ratio = 3.83; 95% confidence interval, 1.68–8.76, p = 0.001). Conclusion NAT2 slow acetylators have a higher risk of GNA than intermediate and rapid acetylators have in a Taiwanese population. The intake of well-done meat, an additive to the acetylator status, may contribute to the incidence of gastric carcinogenesis.

Background Recent studies have shown that the peripheral inflammation may cause the up-regulation of central nervous system inflammation and therefore possibly plays a vital role in the pathophysiology of subsequent psychiatric disorders. Objective We explored the relationship between gastroesophageal reflux disease (GERD) and the subsequent development of psychiatric disorders including schizophrenia as well as bipolar, depressive, anxiety, and sleep disorders. Methods We investigated patients who were diagnosed with GERD according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort comprised patients without GERD who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of subsequent new-onset psychiatric disorders were calculated for both cohorts, based on the diagnoses of psychiatrists. Results The GERD cohort consisted of 3813 patients, and the comparison cohort comprised 15,252 matched control patients without GERD. The risks of depressive disorder (HR = 3.37, 95% confidence interval [CI] = 2.49–4.57), anxiety disorder (HR = 2.99, 95% CI = 2.12–4.22), and sleep disorder (HR = 2.69, 95% CI = 1.83–3.94), were higher in the GERD cohort than in the comparison cohort. In addition, the incidence of newly diagnosed depressive, anxiety, and sleep disorders remained significantly increased in all of the stratified follow-up durations (0–1, ≥ 1 year). Conclusions GERD may increase the risks of subsequent depressive, anxiety, and sleep disorders. These psychiatric disorders have a negative effect on people's quality of life. Clinicians should pay a particular attention to psychiatric comorbidities in GERD patients.

Background: The immunochemical fecal occult blood test (iFOBT) is an alternative method to colonoscopy that can be used for colorectal cancer (CRC) screening. If the iFOBT result is positive, a colonoscopy is recommended. In this retrospective study, we identify factors associated with negative colonoscopy and positive iFOBT results obtained during CRC screening. Methods: We collected data for subjects who received a colonoscopy at Taipei Veterans General Hospital after receiving a positive iFOBT result during CRC screening from January 2015 to December 2015. Subjects' baseline data, medications, and co-morbidities as well as colonoscopy and histological findings were recorded. A negative colonoscopy result was defined as no detection of any colorectal neoplasia including non-advanced adenoma, advanced adenoma, and adenocarciona. Multivariate logistic regression analysis was conducted to identify the associated factors in screening subjects with positive iFOBT but negative colonoscopy results. Results: 559 (46.3%) out of 1207 eligible study subjects received a colonoscopy with a negative result. Multivariate logistic regression analysis revealed that the use of antiplatelets [odds ratio (OR) = 0.654; 95% confidence interval (CI), 0.434–0.986], occurrence of hemorrhoid (OR = 0.595; 95% CI, 0.460–0.768), and the existence of colitis/ulcer (OR = 0.358; 95% CI, 0.162–0.789) were independent factors associated with negative colonoscopy but positive iFOBT results during CRC screening. The colon clean level, underlying diseases of gastrointestinal bleeding tendency (e.g., chronic kidney disease, cirrhosis), and the use of anticoagulant or nonsteroidal anti-inflammatory agents were not associated with negative colonoscopy and positive iFOBT results. Conclusion: The use of antiplatelet agents and the presence of hemorrhoids and colitis/ulcers were factors associated with negative colonoscopy and positive iFOBT results. Keywords: Antiplatelet agents, Colonoscopy, Colorectal neoplasia, Hemorrhoid, Immunochemical fecal occult blood test

Background Anti-tuberculosis drug-induced liver injury (ATDILI) is a major safety concern in the treatment of tuberculosis (TB). The impact of chronic hepatitis C (CHC) infection on the risk of ATDILI is still controversial. We aimed to assess the influence of CHC infection on ATDILI through a systematic review and meta-analysis. Methods We systemically reviewed all English-language literature in the major medical databases with the subject search terms “anti-tuberculosis drug-induced liver injury” and “anti-tuberculosis drug-induced hepatotoxicity”. We then performed a systematic review and meta-analysis of the papers relevant to hepatitis C in qualified publications. Results A total of 14 studies were eligible for analysis, which included 516 cases with ATDILI and 4301 controls without ATDILI. The pooled odds ratio (OR) of all studies for CHC infection to ATDILI was 3.21 (95% confidence interval (CI): 2.30–4.49). Subgroup analysis revealed that the CHC carriers had a higher risk of ATDILI than those without CHC both in Asians (OR = 2.96, 95% CI: 1.79–4.90) and Caucasians (OR = 4.07, 95% CI: 2.70–6.14), in those receiving standard four combination anti-TB therapy (OR = 2.94, 95% CI: 1.95–4.41) and isoniazid monotherapy (OR = 4.18, 95% CI: 2.36–7.40), in those with a strict definition of DILI (serum alanine aminotransferase [ALT] > 5 upper limit of normal value [ULN], OR = 2.59, 95% CI: 1.58–4.25) and a loose definition of DILI (ALT > 2 or 3 ULN, OR = 4.34, 95% CI: 2.96–6.37), and in prospective studies (OR = 4.16, 95% CI: 2.93–5.90) and case–control studies (OR = 2.43, 95% CI: 1.29–4.58). Conclusion This meta-analysis suggests that CHC infection may increase the risk of ATDILI. Regular liver tests are mandatory for CHC carriers under anti-TB therapy.

SummaryBackgroundMalignant gastric outlet obstruction causes significant malnutrition and morbidity. The implantation of a metallic stent is an alternative palliative treatment to allow the intake of food in these patients.Patients and MethodsThirty-eight consecutive patients with malignant gastric outlet obstruction who had received an uncovered metallic stent placement in our department from April 2010 to April 2012 were enrolled for analysis. The mean follow-up time was 6.3 months. Food intake, measured by the Gastric Outlet Obstruction Scoring System, complications, duration of stent patency, and survival were evaluated.ResultsThe technical and clinical success rates of the procedure were 100% and 94.7%, respectively. The Gastric Outlet Obstruction Scoring System scores were significantly improved at 1 day, 7 days, and 30 days after the implantation compared with those prior to the procedure (p

Background & Aims Non-alcoholic fatty liver disease is the most prevalent liver disease in the world. However, the exact mechanisms that lead to development of advanced non-alcoholic steatohepatitis (NASH) are unknown. Oxidative stress may be an important pathogenic factor in NASH. Manganese superoxide dismutase (SOD2) is an important antioxidant phase 2 enzyme that can reduce reactive oxidative substances and protect hepatocytes. In contrast, cytochrome P450 2E1 (CYP2E1) has pro-oxidant activity and may enhance oxidative stress and counteract the effect of SOD2. Little is known regarding the associations of genetic variants of these enzymes with the risk of NASH. We aimed to investigate the association of genetic variants of SOD2 and CYP2E1 with susceptibility to NASH. Methods Data from 100 patients with NASH, 31 patients with non-alcoholic steatosis (NAS) and 90 healthy controls were analysed. Their DNA was retrieved for genotyping SOD2 47T>C and CYP2E1 −1053C>T variation by polymerase chain reaction. Results There was no statistical difference in the frequency distributions of SOD2 and CYP2E1 genotypes among the NASH, NAS and control groups. However, the frequency of the SOD2 C variant was significantly higher in the NASH group than in the NAS and control groups (22% vs. 14.5% and 11.1%, respectively; P = 0.015). After adjustment for confounders, the SOD2 C/C and C/T genotypes remained associated with the risk of NASH (odds ratio, 2.81; 95% confidence interval, 1.37–5.76; P = 0.005). Conclusions The anti-oxidative SOD2 47T>C genetic variant might increase susceptibility to NASH in Chinese. Individuals with the SOD2 C variant may have a higher risk for NASH.

Purpose To investigate the risk of cancer among patients with nonapnea sleep disorders (SDs). Methods We included newly diagnosed SD patients aged 20 years and older without antecedent cancer between 2000 and 2010 from the National Health Insurance Research Database. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of patients with SD with that of the general population. Results During the 10-year study period, 2062 cancers developed among 63,381 SD patients, who were observed for 382,826 person-years (median follow-up of 6.23 years). The SIR for all cancers was 1.19 (95% confidence interval [CI], 1.14–1.24). For specific cancer types, SD patients exhibited an increased SIR for liver and lung cancers (1.44; 95% CI, 1.28–1.61 and 1.34; 95% CI, 1.18–1.51, respectively). Conclusions We observed that overall cancer risk is increased among Asian SD patients. In terms of individual cancers, the risks of liver and lung cancers were elevated. Clinicians should be aware of the possibility of increased liver and lung cancers among SD patients in Taiwan. A prospective study is necessary to confirm these findings.

To evaluate the risk of Parkinson disease (PD) among patients with depression by using the Taiwan National Health Insurance Research Database (NHIRD).We conducted a retrospective study of a matched cohort of 23,180 participants (4,634 patients with depression and 18,544 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 10 years to determine the rates of new-onset PD, and Cox regression was used to identify the predictors of PD. We also examined the risk of PD after excluding patients who were diagnosed with PD within 2 or 5 years after their depression diagnosis. A logistic regression model was used to identify risk factors associated with PD onset in patients with depression.During the 10-year follow-up period, 66 patients with depression (1.42%) and 97 control patients (0.52%) were diagnosed with PD. After adjusting for age and sex, patients with depression were 3.24 times more likely to develop PD (95% confidence interval 2.36-4.44, p0.001) compared with the control patients. After excluding patients who were diagnosed with PD within 2 or 5 years after their depression diagnosis, patients with depression had a higher hazard ratio for developing PD than the control patients. The odds ratios for age (1.09) and difficult-to-treat depression (2.18) showed that each is an independent risk factor for PD in patients with depression.The likelihood of developing PD is greater among patients with depression than patients without depression. Depression may be an independent risk factor for PD.

Background. Thecagpathogenicity island (cag-PAI) is one of the most important virulent determinants ofHelicobacter pylori. An insertion sequence (IS) element ofcag-PAI (IS605) has been found to generateH. pyloristrains with varying virulence.Aim. To evaluate the impact of IS605 andcag-PAI onH. pyloristrains isolated from Taiwanese patients with severity of gastric diseases.Methods.H. pyloriisolates were cultured from gastric biopsies from 99 patients with peptic ulcer, chronic gastritis, and gastric carcinoma. Six distinct, well-separated colonies were isolated from each patient and analyzed by genotyping.Results.cagA,cagE,cagM,cagT,orf10, andorf13 were found to be present in 90.0%–100.0% of theH. pyloriisolates. A total deletion ofcagA,cagE,cagM,cagT,orf10, andorf13 was found in 1 isolate (1.0%). The IS605 element was found to be positive in 15.2% of the isolates. The presence of IS605 was higher inH. pyloriisolated from patients with gastric carcinoma (25.0%) than in patients with duodenal ulcer (6.5%) or chronic gastritis (6.3%) (P<0.001).Conclusions. The majority of the patients examined had intactcag-PAI. IS605 was present in 15.2% and was higher inH. pyloriisolated from patients with gastric carcinoma than in those with peptic ulcer.

Aims Statin-induced liver injury (SILI) is quite rare, but may be severe. Little is known about the impact of chronic hepatitis B infection (CHBI) on SILI. We aimed to investigate the risk factors and outcome of SILI, with special reference to its interaction with CHBI. Methods Patients with SILI were recruited from our hospital, and three-to-one drug-matched controls were randomly selected. The clinical data of the patients were then compared. Results A total of 108 patients with SILI and 324 controls were enrolled. The patients with SILI were both older and had a higher statin dose than the controls. There was no predilection of liver injury associated with the seven available statins. Among the SILI patients, there was no statistical difference between the baseline and peak liver enzyme tests, and latency and severity between hepatitis B carriers (n = 16) and non-carriers (n = 92). High dose of statin and age were the two independent risk factors of SILI (OR and 95% CI: 1.93, 1.08–3.35, P = 0.025, and 1.73, 1.07–2.80, P = 0.027, respectively). Permanent discontinuation of statin was noted in 50 (46.3%) patients with SILI due to severe SILI or recurrent hepatotoxicity after rechallenge of other statins. Conclusion High dose of statin and old age may increase patient susceptibility to SILI; however, CHBI and abnormal baseline liver tests are not risk factors of SILI. Nonetheless, SILI is still worthy of notice, because nearly half of the overt cases discontinued statin treatment due to severe hepatotoxicity in this study.

Infection with Helicobacter pylori (H. pylori) has been linked to various gastro-intestinal diseases; nevertheless it remains to be clarified why only a minority of infected individuals develop illness. Studies from the West have indicated that the cagA gene and the associated EPIYA genotype of H. pylori is closely linked to the development of severe gastritis and gastric carcinoma; however, as yet no consistent correlation has been found among the bacteria from East Asia. In addition to genotype variation, the CagA protein undergoes fragmentation; however, the functional significance of fragmentation with respect to H. pylori infection remains unknown. In this study, we isolated 594 H. pylori colonies from 99 patients and examined the fragmentation patterns of CagA protein using immunoblotting. By analyzing the ability of the isolates to induce the host cell morphological transition to the highly invasive hummingbird phenotype, we demonstrated that H. pylori colonies with substantial CagA fragmentation are less potent in terms of causing this morphological transition. Our results uncovered a functional role for CagA fragmentation with respect to H. pylori-induced hummingbird phenotype formation and these findings suggest the possibility that the post-translational processing of CagA may be involved in H. pylori infection pathogenesis.

Background: Polymorphism of N-acetyltransferase 2 gene was reported to be associated with the susceptibility of various cancers and liver diseases. However, its relationship to alcoholic liver disease is controversial and open to debate. The aim of this study was to evaluate the relationship of NAT2 genetic polymorphisms and the susceptibility to alcoholic liver cirrhosis (ALC) in Chinese, with special emphasis on the interaction of smoking. Methods: Peripheral white blood cell DNA from 148 patients with ALC, 104 patients with long-term alcoholic drinking but without cirrhosis (ANC) and 209 healthy controls were genotyped for NAT2 using a polymerase chain reaction–restriction fragment length polymorphism method. The possible confounding factors were included for analysis. Results: There was no statistical difference in the frequency of NAT2 genotype or NAT2 acetylator status among the 3 groups. However, among the chronic alcoholic drinkers, the rapid acetylators with smoking habits had higher percentage of ALC than those without smoking habit (18.9% vs. 9.5%, p = 0.002). The adjusted odds ratio for rapid acetylator smoker to have ALC was 3.45 (95% CI = 1.53 to 7.76, p = 0.003). Conclusions: The genetic factor, NAT2 polymorphism, may interact with environmental factor, smoking, to confer different susceptibilities to ALC. NAT2 rapid acetylators with smoking habit may increase the risk of ALC in Chinese.

Heat stroke is a life-threatening illness, and the disease spectrum can include the involvement of multiple organs to varying degrees. Rhabdomyolysis with renal function impairment is frequently noted in this disease. However, acute hepatic failure has been rarely reported in non-exertional heat stroke. We report a case of acute hepatic failure combined with disseminated intravascular coagulopathy, acute renal failure, and neurological deficit caused by heat stroke after bathing in a hot spring. Molecular adsorbent recirculating system (MARS) treatment was performed daily on days 10–12 of admission. As a result of progressive azotemia, hemodialysis was performed. Unfortunately, after a long course of intensive care, the patient died from septic shock and multiple organ failure. According to available evidence, MARS and hemodialysis are beneficial in treating exertional heat stroke. However, a limited number of studies have treated non-exertional heat-stroke-related acute hepatic failure. Early cooling to reduce the overwhelming heat-stress-related cytokine storm, and advanced MARS to eliminate circulating toxin might have a role in treating this rare but fatal illness.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • An adjunct to endoscopy, proton pump inhibitor (PPI) is effective pharmacotherapy in high-risk patients with peptic ulcer bleeding (PUB). • An intravenous 80-mg bolus and 192 mg day−1 successive infusion for 3 days is the currently recommended dosing modality in administering PPI. WHAT THIS STUDY ADDS • Clinical outcomes are not different in PUB patients receiving infusional pantoprazole at either 192 mg or 160 mg day−1 for 3 days. • The effective dosage of PPI may not be as high as currently recommended. • In view of cost-effectiveness, a lower dosage (160 mg day−1) of infusional PPI may be adopted in the management of PUB. AIM The optimal dosage of proton pump inhibitor in bleeding peptic ulcers remains controversial. The aim was to compare the clinical effectiveness of two doses of infusional pantoprazole in peptic ulcer bleeding. METHODS Peptic ulcer patients (n= 120) with bleeding stigmata were enrolled after successful endoscopic therapy. After an initial bolus injection of 80 mg pantoprazole, patients were randomized to receive continuously infused pantoprazole at either 192 mg day−1 or 40 mg every 6 h (i.e. 160 mg day−1) for 3 days. Clinical outcomes between the two groups within 14 days were compared, with 14-day recurrent bleeding regarded as the primary end-point. RESULTS Both groups (n= 60 each) were well matched in demographic and clinical factors upon entry. Bleeding totally recurred in 11 (9.2%) patients, with six (10%) in the 192 mg day−1 group and five (8.3%) in the 160 mg day−1 group (relative risk of bleeding recurrence between two treatments 1.2; 95% CI 0.39, 3.72). All secondary outcomes between the two groups were similar, including the amount of blood transfusion (mean 1179 ml vs. 1203 ml, P > 0.1), hospital stay (mean 9.5 days vs. 9.9 days, P > 0.1), need for surgery (n= 1 vs. n= 0, P > 0.1), and mortality (n= 1 vs. n= 0, P > 0.1). CONCLUSIONS Following endoscopic haemostasis, infusional pantoprazole at either 192 mg day−1 or 40 mg every 6 h appear similar.

Background: Interleukin (IL)-12 is a proinflammatory cytokine produced by antigen-presenting cells upon stimulation by diverse stimuli. This study aimed to explore the relationship between IL-12 serum levels and different stages of alcoholic liver disease, alcoholic intake status and abstinence from alcohol. Methods: A total of 35 healthy controls without alcohol consumption and 94 patients with alcoholic liver disease (17 with alcoholic steatosis, 37 with alcoholic hepatitis, 40 with alcoholic cirrhosis) were included. Their serum IL-12 levels were measured and followed-up at the 3 rd ,6 th and 9 th months. Data were further analyzed according to abstinence from alcohol or not. Results: Mean serum IL-12 levels were higher in the alcoholic hepatitis group (163.1 ± 57.8 pg/mL) than in the alcoholic liver cirrhosis group (110.5 ± 41.6 pg/mL) and alcoholic steatosis group (74.4 ± 26.2 pg/mL). All of these 3 alcoholic groups had higher serum IL-12 levels than the control group (39.3 ± 8.3 pg/mL; p < 0.02). Among the patients who abstained from alcohol, there was no difference in serum IL-12 levels between control and steatosis patients at the 9 th month, but the serum IL-12 levels of the hepatitis and cirrhosis groups were still higher than in the control group (p < 0.001 and p = 0.001, respectively). In addition, the patients who continued to drink alcohol had higher serum IL-12 levels than those who abstained from alcohol in the steatosis, hepatitis and cirrhosis groups. At the cut-off value of 54 pg/mL, IL-12 had good sensitivity and specificity in the diagnosis of alcoholic liver disease. Conclusion: Serum IL-12 levels reflected the different stages of alcoholic liver disease and can represent the status of continuous alcohol consumption. It has the potential to be a biomarker of alcoholic liver disease. [J Chin Med Assoc 2010;73(2):67–71]

Background: Cell migration (restitution) occurs in the early phase of gastric ulcer healing. Tumor necrosis factor (TNF)-α is overexpressed at the ulcer margin and plays a physiologic role in gastric ulcer healing. Dexamethasone, which is a potent corticosteroid, delays rat gastric ulcer healing. We evaluated whether dexamethasone inhibited TNF-α-stimulated gastric epithelial cell migration using a rat normal gastric epithelial cell line (RGM-1). Methods: An artificial wound model was employed to measure cell migration. Western blot was performed to evaluate the possible mechanisms. Intracellular prostaglandin E2 level was measured using an enzyme-linked immunosorbent assay. Results: TNF-α treatment (10 ng/mL) for 12–48 hours significantly increased RGM-1 cell migration, and TNF-α treatment increased cyclooxygenase (COX)-2 protein expression 8 hours later and prostaglandin E2 (PGE2) synthesis 12 hours later compared with control (p < 0.05). Dexamethasone (10 –6 M) significantly inhibited the stimulatory effect of TNF-α on RGM-1 cell migration, which was associated with a significant decrease in COX-2 expression and PGE2 level in cells (p < 0.05). Conclusion: TNF-α plays a regulatory role in rat gastric epithelial cell migration and dexamethasone inhibited TNF-αstimulated cell migration, which was associated with a decrease in COX-2 expression and PGE2 formation. [J Chin Med Assoc 2009;72(10):509–514]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? • Endoscopic therapy significantly reduces recurrent bleeding, surgery and mortality in patients with bleeding peptic ulcers. • Intravenous (i.v.) proton pump inhibitors (PPIs) have been found to be effective as adjuvant pharmacotherapy in preventing rebleeding in these patients. • It remains undetermined whether oral and i.v. regular-dose PPIs are equally effective. WHAT THIS STUDY ADDS? • Oral rabeprazole and i.v. regular-dose omeprazole are comparable in preventing rebleeding in patients with high-risk bleeding peptic ulcers after successful endoscopic injection with epinephrine. AIMS We aimed to assess the clinical effectiveness of oral vs. intravenous (i.v.) regular-dose proton pump inhibitor (PPI) after endoscopic injection of epinephrine in patients with peptic ulcer bleeding. METHODS Peptic ulcer patients with active bleeding, nonbleeding visible vessels, or adherent clots were enrolled after successful endoscopic haemostasis achieved by epinephrine injection. They were randomized to receive either oral rabeprazole (RAB group, 20 mg twice daily for 3 days) or i.v. omeprazole (OME group, 40 mg i.v. infusion every 12 h for 3 days). Subsequently, the enrolled patients receive oral PPI for 2 months (rabeprazole 20 mg or esomeprazole 40 mg once daily). The primary end-point was recurrent bleeding up to 14 days. The hospital stay, blood transfusion, surgery and mortality within 14 days were compared as well. RESULTS A total of 156 patients were enrolled, with 78 patients randomly allocated in each group. The two groups were well matched for factors affecting the clinical outcomes. Primary end-points (recurrent bleeding up to 14 days) were reached in 12 patients (15.4%) in the OME group and 13 patients (16.7%) in the RAB group [95% confidence interval (CI) of difference −12.82, 10.22]. All the rebleeding events occurred within 3 days of enrolment. The two groups were not different in hospital stay, volume of blood transfusion, surgery or mortality rate (1.3% of the OME group and 2.6% of the RAB group died, 95% CI of difference −5.6, 3.0). CONCLUSIONS Oral rabeprazole and i.v. regular-dose omeprazole are equally effective in preventing rebleeding in patients with high-risk bleeding peptic ulcers after successful endoscopic injection with epinephrine.

Acute pyelonephritis causes hospitalization and is a commonly-ignored cause of death in geriatric patients. It has been well studied in young-adult populations but rarely in geriatric populations. The aim of our study was to analyze the characteristics of acute pyelonephritis in geriatric patients. The electronic admission records of a community hospital in northeastern Taiwan were retrospectively screened from July 1, 2003 to June 30, 2006. The basic characteristics, laboratory findings and infectious microorganisms of all subjects were evaluated. Sixty-five subjects (mean age 71.6 +/- 4.9 years; range 65-84 years) and 73 admission records contributed by them were enrolled. These 65 subjects, including one who died in hospital, were predominantly female (52 subjects; 80%). Twenty-two subjects (33.8%) had co-existing diabetes mellitus, 9 subjects (13.8%) had co-existing tumors, and 19 subjects (29.2%) had a history of intra-abdominal surgery. The admission records revealed right kidney involvement (52.1%), co-existing urolithiasis (50.7%) and admission to wards of internal medicine (57.5%). Urological procedures were performed on 20 (27.4%) of all 73 admission records. Escherichia coli was the most common infecting microorganism (19.2% of all records; 42.4% of records with positive microorganism culture). Hemoglobin10 g/dl was a significant predictive factor for both hospital stay7 days and serum creatinine2.0 mg/dl (p = 0.003 and 0.002, respectively). Positive microorganism culture was also a significant predictive factor for hospital stays7 days (p0.001). In our geriatric patients with acute pyelonephritis, low hemoglobin levels implied co-existing renal insufficiency and prolonged hospitalization. Positive microorganism culture also implied prolonged hospitalization.

Hemoclip placement is an effective endoscopic therapy for peptic ulcer bleeding. Triclip is a novel clipping device with three prongs over the distal end. So far, there is no clinical study concerning the hemostatic effect of triclip placement.To determine the hemostatic effect of the triclip as compared with that of the hemoclip.A total of 100 peptic ulcer patients with active bleeding or nonbleeding visible vessels received endoscopic therapy with either hemoclip (N = 50) or triclip placement (N = 50). After obtaining initial hemostasis, they received omeprazole 40 mg intravenous infusion every 12 h for 3 days. The main outcome assessment was hemostatic rate and rebleeding rate at 14 days.Initial hemostasis was obtained in 47 patients (94%) of the hemoclip group and in 38 patients (76%) of the triclip group (P= 0.011). Rebleeding episodes, volume of blood transfusion, the hospital stay, numbers of patients requiring urgent operation, and mortality were not statistically different between the two groups.Hemoclip is superior to triclip in obtaining primary hemostasis in patients with high-risk peptic ulcer bleeding. In bleeders located over difficult-to-approach sites, hemoclip is more ideal than triclip.

Supplemental digital content is available in the text, The optimal timing of percutaneous cholecystostomy for severe acute cholecystitis is unclear. The aim of this study was to investigate the timing of percutaneous cholecystostomy and its relationship to clinical outcomes in patients with inoperable acute severe cholecystitis. From 2008 to 2010, 209 consecutive patients who were admitted to our hospital due to acute cholecystitis and were treated by percutaneous cholecystostomy were retrospectively reviewed. The time periods from symptom onset to when percutaneous cholecystostomy was performed and when patients were discharged were recorded. In the 209 patients, the median time period between symptom onset and percutaneous cholecystostomy was 23 hours (range, 3–95 hours). The early intervention group (≤24 hours, n = 109) had a significantly lower procedure-related bleeding rate (0.0% vs 5.0%, P = 0.018) and shorter hospital stay (15.8 ± 12.9 vs 21.0 ± 17.5 days) as compared with the late intervention group (>24 hours, n = 100). Delayed percutaneous cholecystostomy was a significant independent factor for a longer hospital stay (odds ratio 3.03, P = 0.001). In inoperable patients with acute severe cholecystitis, early percutaneous cholecystostomy reduced hospital stay and procedure-related bleeding without increasing the mortality rate.

Aims Superoxide dismutase 2 (SOD2) is an important antioxidant phase 2 enzyme. The associations of SOD2 genetic variation and the risk of advanced alcoholic liver diseases are still debatable. We aimed to investigate the association of the main SOD2 genetic variant (47T>C) and the susceptibility to alcoholic cirrhosis. Methods A total of 80 patients with alcoholic cirrhosis (AC), 80 patients with alcoholic non-cirrhosis (ANC), 80 with viral hepatitis B-related cirrhosis (VC), and 165 healthy controls (HC) were enrolled into this study. A polymerase chain reaction was used to genotype their SOD2 47T>C (rs4880). Results There was no statistical difference in the frequency distribution of the three SOD2 47T>C genotypes among groups. However, if individuals with C variant were grouped together, the AC group had higher frequency of SOD2 C/C or C/T genotype than ANC, VC and HC groups had (38.7% vs. 21.3%, 26.3% and 21.8%, respectively, P = 0.010). After adjustment for confounders, the SOD2 C/C and C/T genotypes remained associated with the risk of AC (adjusted OR: 2.79 and 3.50, respectively, P < 0.03, compared with ANC and HC groups). In contrast, there was no significant difference of SOD2 genetic variation between VC and HC groups. Conclusions Anti-oxidative enzyme SOD2 47T>C genetic variant may increase the susceptibility to AC. This suggests that oxidative stress plays a role in the development of AC.

Background Irritable bowel syndrome (IBS) is the most common functional gastrointestinal (GI) disorder observed in patients who visit general practitioners for GI-related complaints. A high prevalence of psychiatric comorbidities, particularly anxiety and depressive disorders, has been reported in patients with IBS. However, a clear temporal relationship between IBS and psychiatric disorders has not been well established. Objective We explored the relationship between IBS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder. Methods We selected patients who were diagnosed with IBS caused by gastroenteritis, according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort was formed of patients without IBS who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of subsequent new-onset psychiatric disorders were calculated for both cohorts, based on psychiatrist diagnoses. Results The IBS cohort consisted of 4689 patients, and the comparison cohort comprised 18756 matched control patients without IBS. The risks of depressive disorder (HR = 2.71, 95% confidence interval [CI] = 2.30–3.19), anxiety disorder (HR = 2.89, 95% CI = 2.42–3.46), sleep disorder (HR = 2.47, 95% CI = 2.02–3.02), and bipolar disorder (HR = 2.44, 95% CI = 1.34–4.46) were higher in the IBS cohort than in the comparison cohort. In addition, the incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0–1, 1–5, ≥5 y). Conclusions IBS may increase the risk of subsequent depressive disorder, anxiety disorder, sleep disorder, and bipolar disorder. The risk ratios are highest for these disorders within 1 year of IBS diagnosis, but the risk remains statistically significant for more than 5 years. Clinicians should pay particular attention to psychiatric comorbidities in IBS patients.

Pantoprazole and omeprazole are irreversible proton pump inhibitors that have been found to significantly reduce intragastric acidity in patients with peptic ulcer and/or esophagitis. It has been reported that gastric acid secretion is lower in the Chinese patients compared with the Western population. Based on a MEDLINE search, no studies of the treatment of intragastric acidity with IV pantoprazole have been conducted in the Chinese population to date.This trial was performed to compare the effects of IV pantoprazole versus omeprazole on 24-hour intragastric acidity in Chinese patients with endoscopically confirmed duodenal ulcer.This single-center, randomized, pilot study was conducted at the Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan. Chinese patients aged 18 to 80 years with endoscopically confirmed duodenal ulcer were randomly assigned to receive a continuous IV infusion of pantoprazole or omeprazole 160 mg/d for 3 days. On days 4 to 14, patients received pantoprazole 40 mg/d or omeprazole 20 mg/d orally. During endoscopic examination at enrollment, an antral biopsy specimen was obtained for rapid urease test, with each patient's agreement, by a blinded investigator. The primary end point was 24-hour intragastric pH on day 3. Secondary end points were percentage of the total time during the 24-hour period (%t) pH3 and4 and proportions of patients with healed ulcers on day-14 endoscopy. Endoscopic examination for monitoring of adverse effects of both drugs was repeated 8 weeks after study completion.A total of 40 patients were enrolled (35 men, 5 women; mean age, 63.3 years; 20 per treatment group). Twenty-four-hour intragastric pH was not significantly different between the omeprazole and pantoprazole groups (mean [SD], 6.61 [1.27] vs 6.84 [0.78]). The %t pH3 (mean [SD], 8.01% [19.60%] vs 2.70% [7.18%]) and pH4 (mean [SD], 9.28% [21.41%] vs 3.87% [9.79%]) were not significantly different between the omeprazole and pantoprazole groups. On day-14 endoscopy, ulcers were found to be healed in 3 (15%) patients in each group. In the omeprazole group, 1 (5%) patient experienced mild diarrhea, and 1 (5%) experienced mild abdominal fullness. These adverse effects were considered treatment related. No adverse effects were reported in either treatment group at 8 weeks after the study.The results of this pilot study of 3-day treatment with a continuous IV infusion of pantoprazole or omeprazole 160 mg/d found that these 2 treatments had similar effects on 24-hour intragastric pH in this small population of Chinese patients with duodenal ulcer. Both treatments were well tolerated.

Background. Helicobacter pylori has been linked to chronic gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Invasive tests are less sensitive than noninvasive tests in diagnosing H. pylori infection in patients with bleeding peptic ulcers. The H. pylori stool antigen test has been useful in diagnosing H. pylori in patients with peptic ulcers before and after eradication of H. pylori. The aim of this study was to evaluate the H. pylori stool antigen test in patients with bleeding peptic ulcers. Methods. Patients with bleeding and nonbleeding peptic ulcers underwent a rapid urease test, histology, bacterial culture and H. pylori stool antigen test. Positive H. pylori infection was defined as a positive culture or both a positive histology and a positive rapid urease test. Helicobacter pylori stool antigen was assessed with a commercial kit (Diagnostec H. pylori antigen EIA Kit, Hong Kong). Results. Between October 2000 and April 2002, 93 patients with bleeding peptic ulcers (men/women: 78/15, gastric ulcer/duodenal ulcer: 58/35) and 59 patients with nonbleeding peptic ulcers (men/women: 47/12, gastric ulcer/duodenal ulcer: 30/29) were enrolled in this study. Forty-seven (50.5%) patients with bleeding peptic ulcers and 30 (50.8%) patients with nonbleeding peptic ulcers, were found to be infected with H. pylori (p > .1). Helicobacter pylori stool antigen tests were positive in 54 (58.1%) and 30 (50.8%) patients with bleeding peptic ulcers and nonbleeding peptic ulcers, respectively (p > .1). The sensitivity (82% vs. 93%), specificity (68% vs. 93%), positive predictive value (74% vs. 93%), negative predictive value (77% vs. 93%) and diagnostic accuracy (75% vs. 93%) were all lower in patients with bleeding vs. nonbleeding peptic ulcers. The specificity, positive predictive value, and diagnostic accuracy of the H. pylori stool antigen test in patients with bleeding peptic ulcers were significantly lower than those in patients with nonbleeding peptic ulcers (p = .01, p = .02 and p = .003, respectively). Conclusion. The H. pylori stool antigen test is not reliable for diagnosing H. pylori infection in patients with bleeding peptic ulcers.

Background: Helicobacter pylori causes chronic gastritis, peptic ulcer, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Different genotypes of H. pylori are confirmed from diverse geographical areas. Its association with clinical diseases remains controversial. The aim of the present study was to investigate the H. pylori vacuolating cytotoxin (vacA) alleles, cytotoxin-associated gene (cagA) and iceA, in patients with peptic ulcer and gastritis. Methods: We enrolled patients with peptic ulcer and chronic gastritis. Biopsy specimens were obtained from the antrum and lower body of the stomach. DNA extraction and polymerase chain reaction (PCR) were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA. Results: A total of 133 patients (57 gastric ulcer, 52 duodenal ulcer, 24 chronic gastritis) had positive PCR results from biopsy specimens. Concerning genotypes, we found cagA (79% in the antrum, 92% in the body) and iceA1 (73% in the antrum, 82.8% in the body) strains in the majority of patients. The dominant vacA subtype was s1a (74.4% in the antrum, 75% in the body), followed by s1c (51.1% in the antrum, 60.5% in the body). In the middle region, the m2 strain dominated (49.6% in the antrum, 41.4% in the body), followed by m1T (19.5% in the antrum, 9.5% in the body). Mixed infection occurred in 89 patients (67%). There was no statistical difference in genotypes among the three groups. Conclusion: In Taiwan, H. pylori with positive cagA and iceA1 was found in the majority of cases. H. pylori with vacA s1a strains was the most common vacA subtype, followed by s1c, while s1b was rare. In the middle region, the m2 subtype was predominant followed by m1T. There was no significant association between genotypes and clinical diseases.

Endoscopic heater probe thermocoagulation and hemoclip are considered to be safe and very effective in the treatment of bleeding peptic ulcer. So far, there are only few reports concerning hemostasis with endoscopic hemoclip. The aims of this study were to compare the hemostatic effects of both therapeutic modalities in patients with peptic ulcer bleeding.A total of 80 patients with active bleeding or nonbleeding visible vessels were randomized to receive endoscopic hemoclip (n = 40) or heater probe thermocoagulation (n = 40).Initial hemostasis was achieved in 34 patients (85%) in the hemoclip group and 40 patients (100%) in the heater probe group (p = 0.01277). Rebleeding occurred in three patients (8.8%) in the hemoclip group and two patients (5%) in the heater probe group (p0.1). Among patients with difficult-to-approach bleeding, we obtained a better hemostatic rate in the heater probe group (nine of 11 patients vs three of 10, p = 0.02417). The volume of blood transfused after entry into the study, duration of hospital stay, number of patients requiring urgent surgery, and the mortality rate were not statistically significantly different between the two groups.For patients with peptic ulcer bleeding, heater probe thermocoagulation offers an advantage in achieving hemostasis than hemoclip. In difficult-to-approach bleeders, heater probe is a more suitable therapeutic modality.

Background: Endoscopic injection of epinephrine in the treatment of bleeding peptic ulcer is considered highly effective, safe, inexpensive, and easy to use. However, bleeding recurs in 6% to 36% of patients. The aim of this study was to determine the optimal dose of epinephrine for endoscopic injection in the treatment of patients with bleeding peptic ulcer. Methods: One hundred fifty-six patients with active bleeding or nonbleeding visible vessels were randomized to receive small- (5-10 mL) or large-volume (13-20 mL) injections of a 1:10,000 solution of epinephrine. Results: The mean volume of epinephrine injected was 16.5 mL (95% CI [15.7, 17.3 mL]) in the large-volume group and 8.0 mL (95% CI [7.5, 8.4 mL]) in the small-volume group. Initial hemostasis was achieved in all patients studied. The number of episodes of recurrent bleeding was smaller in the large-volume group (12/78, 15.4%) compared with the small-volume group (24/78, 30.8%, p = 0.037). The volume of blood transfused after entry into the study, duration of hospital stay, numbers of patients requiring urgent surgery, and mortality rates were not statistically different between the 2 groups. Conclusions: Injection of a large volume (>13 mL) of epinephrine can reduce the rate of recurrent bleeding in patients with high-risk peptic ulcer and is superior to injection of lesser volumes of epinephrine when used to achieve sustained hemostasis. (Gastrointest Endosc 2002;55:615-9.)

BACKGROUNDPeptic ulcers with active bleeding or a non-bleeding visible vessel require aggressive endoscopic treatment.AIMSTo determine whether endoscopic adrenaline injection alone or contact probe therapy following injection is a suitable treatment for peptic ulcer bleeding.METHODSA total of 96 patients with active bleeding or non-bleeding visible vessels received adrenaline alone, bipolar electrocoagulation alone, or combined treatment (n=32 in each group).RESULTSInitial haemostasis was not achieved in one patient in the adrenaline group, two in the gold probe group, and two in the injection gold probe group (p>0.1). Rebleeding episodes were fewer in the injection gold probe group (2/30, 6.7%) than in the gold probe group (9/30, 30%, p=0.04) and in the adrenaline group (11/31, 35.5%, p=0.01). Treatment failure (other therapy required) was rarer in the injection gold probe group (4/32, 12.5%) than in the adrenaline group (12/32, 37.5%, p=0.04). The volume of blood transfused after entry of the study was less in the injection gold probe group (mean 491 ml) than in the adrenaline group (1548 ml, pCONCLUSIONSFor patients with peptic ulcer bleeding, combined adrenaline injection and gold probe treatment offers an advantage in preventing rebleeding and decreasing the need for blood transfusion.

The role of endoscopic therapy for peptic ulcer bleeding is well-documented. Nevertheless, rebleeding occurs in 10% to 30% of patients, and such patients are at high risk for death without early retreatment or definitive surgery. The aim of our study was to predict which patients would rebleed within 1 month after successful multipolar electrocoagulation of 100 patients with active peptic ulcer bleeding (spurting, oozing, or nonbleeding visible vessel). We had achieved initial hemostasis in 97 patients and carried out univariate and multivariate analyses to predict which patients would rebleed. Rebleeding occurred within 1 month in 17 (17.5%) patients. we correlated 20 clinical and endoscopic factors with rebleeding episodes. With univariate analysis, blood transfusion of 500 ml or more at entry (p < 0.0001) and use of cimetidine (p = 0.01) were statistically significant for rebleeding. With multivariate analysis, use of omeprazole was an independent factor for preventing rebleeding (odds ratio, 7.68; 95% confidence interval, 1.642-35.929). We suggest that omeprazole may help to prevent rebleeding in patients who have had hemostasis with multipolar electrocoagulation.

We previously identified four potential putative gastroduodenal disease fragments by using the interspersed repetitive extragenic palindromic DNA sequence based PCR (REP-PCR) technique. We investigated these fragments with regard to their disease specificity. The putative disease-specific REP-PCR fragments were cloned, mapped by restriction enzymes, cross-hybridized, and confirmed by Southern hybridization. The four fragments were also used as probes against REP-PCR amplicons from H. pylori isolates obtained from gastritis (N = 20), duodenal ulcer (N = 30), and gastric cancer patients (N = 30). Three of these fragments (1.4- and 0.76-kb for gastritis; 1.35 kb for duodenal ulcer) were amplified without any discrimination between any disease-specific H. pylori isolates. However, amplification following hybridization with the fourth 0.81-kb fragment was observed only from gastritis (60%) and duodenal ulcer (52%) but with none (0%) of gastric cancer patients. Nucleotide sequence analysis of the 0.81-kb fragment revealed that it was an open reading frame of the hypothetical protein HP0373 matched to the position of 380,966 to 383,068 nucleotides of the H. pylori complete genome sequence. Hence, the REP-PCR sequence was not a extragenic palindromic DNA sequence. The hypothetical protein was also present in all the tested isolates. The REP-PCR fingerprinting technique is useful to differentiate disease-specific H. pylori strains based on the interspersed repetitive extragenic palindromic DNA sequences; however, it may not be useful to identify disease-specific virulence determinant(s) without being confirmed by DNA sequence analysis and functional studies.

The efficacy and acceptability of classical bismuth triple therapy may be limited by poor patient compliance and adverse effects. It is widely agreed that improved, simpler, and reliable therapies are needed to cure Helicobacter pylori infection and foster patient compliance. We evaluated the efficacy and side effects of a Bazzoli triple therapy substituting lansoprazole for omeprazole for H. pylori infection in active peptic ulcer in Korea (30 mg of lansoprazole, 250 mg of clarithromycin, and 400 mg of metronidazole, all twice daily). H. pylori status was evaluated by rapid urease test, histology, and culture at entry and four or more weeks after ending antimicrobial therapy. Fifty-eight patients (mean age: 43 years) with gastric (N = 30) or duodenal ulcer (N = 28) and H. pylori infection were studied. H. pylori was cured in 47 (81%, 95% CI = 69-90%). Mild side effects, including vomiting, diarrhea, and itching, were observed in four patients (7%). Compliance averaged 95%. Fifty-five ulcers (95%) were healed. Pretreatment pylorobulbar deformity was observed in 49 patients (85%), and in 43 (88%) the deformity disappeared after treatment. Pretreatment metronidazole and clarithromycin resistance was observed in 87% and 2% of patients, respectively. The cure rate of H. pylori infection was significantly higher in patients >50 years of age than those

BACKGROUND & AIMS: To evaluate the risk of depressive disorders among non-alcoholic patients by using the Taiwan National Health Insurance Research Database (NHIRD). METHODS: We conducted a retrospective study of a matched cohort of 52 725 participants (10 545 non-alcoholic cirrhotic patients and 42 180 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 11 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in cirrhotic patients. RESULTS: During the 11-year follow-up period, 395 (3.75%) non-alcoholic cirrhotic patients and 1 183 (2.80%) control patients were diagnosed with depressive disorders. The incidence risk ratio of depressive disorders between non-alcoholic cirrhotic patients and control patients was 1.76 (95% CI, 1.57-1.98, P

Background To evaluate the risk of cancer among Taiwanese female registered nurses (RNs) using a nationwide population-based dataset. Methods We recruited female RNs without antecedent cancer from the Taiwan National Health Insurance Research database during 2000–2010. Standardized incidence ratios (SIRs) of cancer were calculated. We also compared rates of Papanicolaou (Pap) smear use between the RNs and the general population matched by age and sex. Results A total of 2,077 cancers developed among 184,809 female RNs, with a follow-up of 1,371,910 person-years (median follow-up of 7.86 years), leading to an increased SIR of 1.10 [95% confidence interval (CI) 1.05–1.15]. RNs aged between 40–59 years also had a significantly increased SIR (1.14, 95% CI 1.08–1.21). For specific cancer types, RNs had an increased SIR for breast (1.28, 95% CI 1.19–1.37), thyroid (1.26, 95% CI 1.10–1.43), lung and mediastinum (1.36, 95% CI 1.13–1.62), and uterine cancers (1.23, 95% CI 1.01–1.49). A decreased SIR was found for cervix (0.48, 95% CI 0.37–0.61) and liver and biliary tract cancers (0.68, 95% CI 0.50–0.90). Pap smear use averaged 5.80 times per person among female RNs aged 35 years or older and 5.50 times per person in the age-matched control group (p = 0.009). Conclusion This study found that overall cancer risk was higher among female RNs than general population. For individual cancers, the risks of breast, lung, thyroid and uterine cancer were higher and the risks of cervix and liver cancer were lower than general population. The lower risk of cervical cancer might be partially explained by the increased use of Pap smears in the RNs group. Further large, unbiased population-based prospective studies are needed to investigate the association between nurses and cancer risk and identify the risk factors of cancer in nurses.

The role of gastric secretion has been controversial in patients with cirrhosis. Except for studies of gastric secretion in cirrhotic patients who underwent a shunt operation, there is no report correlating gastric secretion with portal pressure in patients with cirrhosis. In this study, we evaluated gastric secretion in cirrhotic patients and correlated it with hemodynamic parameters. Within 12 months, 20 normal volunteers and 16 cirrhotic patients were enrolled. Gastric secretion was assessed in all patients, but portal pressure hemodynamic studies were performed only in cirrhotic patients. We found that the median basal acid output, maximal acid output, and basal pepsin output in the controls (1.41 mmol/h, 9.2 mmol/h, and 0.02 mg/h, respectively) and in the cirrhotic patients (0.6 mmol/h, 7.84 mmol/h, and 1.5 mg/h, respectively) were not statistically different. However, maximal pepsin output was lower in the cirrhotic patients (1.5 mg/h) than in the normal subjects (5.14 mg/h) (p0.05). Gastric secretion correlated poorly with hepatic venous pressure gradient (HVPG) and the presence of congestive gastropathy in cirrhotic patients. The severity of congestive gastropathy correlated poorly with HVPG. Helicobacter pylori has difficulty replicating in the stomach when HVPG is14 mm Hg. We conclude that patients with cirrhosis have a lower maximal pepsin output than that of the healthy subjects. Gastric secretion correlates poorly with HVPG and the presence of congestive gastropathy in patients with cirrhosis.

Background : The natural history of a bleeding peptic ulcer with a tightly adherent blood clot remains uncertain. Controversy exists concerning removal of such blood clots at the bleeding ulcer base. This article presents the natural history of a bleeding peptic ulcer with a tightly adherent clot and defines the characteristics of those requiring aggressive management. Methods : Clinical parameters were analyzed to determine the independent predictors of rebleeding in these patients. One hundred one patients with bleeding peptic ulcers and tightly adherent blood clots were enrolled during a period of 12 months. Results : Twenty-five patients (25%) rebled within 1 month. With a multivariate analysis, we found comorbid illness (odds ratio, 3.41), shock (odds ratio, 3.65), and initial hemoglobin at or below 10 gm/dL (odds ratio, 2.99) to be independent predictors of rebleeding. Conclusions : Most patients with a tightly adherent clot in an ulcer have an uneventful course. However, endoscopic therapy may prove to be beneficial in the subset of patients with independent predictors of rebleeding. (Gastrointest Endosc 1996;43:470-3.)

We carried out a prospective, randomized, controlled trial over a 7-month period to assay the hemostatic effects of octreotide and heater probe thermocoagulation (HPT) in 54 patients with active peptic ulcer bleeding or nonbleeding visible vessels at the ulcer base. Nineteen patients received octreotide 100 micrograms bolus i.v. followed by 25 micrograms/h i.v. for 3 days. Twenty patients received HPT. Fifteen patients received ranitidine 100 mg i.v. every 12 h. The three groups were matched for sex, age, location of bleeders, endoscopic findings, shock, and initial hemoglobin. Ultimate hemostasis was obtained in 11 (58%) of the octreotide group, 18 (90%) of the heater probe group, and 8 (53%) of the control group (p < 0.05). Volume of blood transfused, number of patients receiving operation, hospital stay, and number of deaths were not statistically significant among the three groups. We conclude that HPT is more effective than octreotide in the arrest of peptic ulcer bleeding.