Ken N. Kuo

Early Helicobacter pylori Eradication Decreases Risk of Gastric Cancer in Patients With Peptic Ulcer Disease

BACKGROUND & AIMSnHelicobacter pylori (H pylori) is a risk factor for gastric cancer. We investigated whether early H pylori eradication is associated with gastric cancer risk in patients with peptic ulcer diseases.nnnMETHODSnThis nationwide cohort study was based on the Taiwan National Health Insurance Database (NHID), which provided data on 80,255 patients who were hospitalized for the first time between 1997 and 2004 with a primary diagnosis of peptic ulcer diseases and received H pylori eradication therapy. The patient population was divided into early (within 1 year) and late (after 1 year) eradication cohorts; standardized incidence ratios (SIRs) and hazards ratios (HRs) were determined.nnnRESULTSnThere was no significant difference in gastric cancer risk between patients who received early H pylori eradication and the general population (SIR, 1.05; 95% confidence interval [CI]: 0.96-1.14), but late eradication was associated with an increased risk (SIR, 1.36; 95% CI: 1.24-1.49). In gastric ulcer patients who received early eradication, SIRs of gastric cancer decreased from 1.60 at 3-4 years to 1.05 at 7-10 years after hospitalization; the SIRs decreased from 0.57 to 0.33 for duodenal ulcer patients over the same period. Among patients who received late eradication, SIRs decreased from 2.14 to 1.32 for those with gastric ulcers and from 0.90 to 0.66 for those with duodenal ulcers. Early H pylori eradication (HR, 0.77) and frequent aspirin or nonsteroidal anti-inflammatory drug use (HR, 0.65) were independent protective factors for gastric cancer.nnnCONCLUSIONSnEarly H pylori eradication is associated with decreased risk of gastric cancer in patients with peptic ulcer diseases.

Histamine2-Receptor Antagonists Are an Alternative to Proton Pump Inhibitor in Patients Receiving Clopidogrel

BACKGROUND & AIMSnPrevious observational studies reported that concomitant use of clopidogrel and proton pump inhibitors (PPIs) in patients with prior acute coronary syndrome (ACS) was associated with adverse cardiovascular outcomes. We investigated whether H(2)-receptor antagonist (H(2)RA) is an alternative to PPI in patients with ACS.nnnMETHODSnWe conducted a population-based retrospective cohort study of 6552 patients in Taiwan discharged for ACS between 2002 and 2005. Patients were divided into 5 cohorts: clopidogrel plus H(2)RA (n = 252), clopidogrel plus PPI (n = 311), clopidogrel alone (n = 5551), H(2)RA alone (n = 235), and PPI alone (n = 203). The primary outcome was rehospitalization for ACS or all-cause mortality within 3 month of rehospitalization.nnnRESULTSnThe 1-year cumulative incidence of the primary outcome was 26.8% (95% CI: 21.5%-33.0%) in the clopidogrel plus H(2)RA cohort and 33.2% (95% CI: 27.8%-39.4%) in the clopidogrel plus PPI cohort, compared with 11.6% (95% CI: 10.8%-12.5%) in the clopidogrel alone cohort (P < .0001). No significant difference was observed between the PPI alone cohort (11.0%; 95% CI: 7.1%-16.8%), the H(2)RA alone cohort (11.8%; 95% CI: 8.2%-16.8%), and the clopidogrel alone cohort in terms of the primary outcome. The number needed to harm was 7 with concomitant H(2)RA and 5 with concomitant PPI. On multivariate analysis, concomitant H(2)RA and PPI were independent risk factors predicting adverse outcomes (adjusted hazard ratios, 2.48 and 3.20, respectively; P < .0001).nnnCONCLUSIONSnConcomitant use of clopidogrel and H(2)RA or PPI after hospital discharge for ACS is associated with increased risk of adverse outcomes.

Effective Reduction of Gastric Cancer Risk With Regular Use of Nonsteroidal Anti-Inflammatory Drugs in Helicobacter Pylori–Infected Patients

PURPOSEnNonsteroidal anti-inflammatory drugs (NSAIDs) play protective roles in gastric carcinogenesis. However, the interaction between NSAIDs and Helicobacter pylori (H pylori) infection and the number needed to treat to prevent gastric cancer remains unclear.nnnPATIENTS AND METHODSnWe conducted a nationwide retrospective cohort study based on data from the Taiwan National Health Insurance Database. Hospitalized patients with a primary diagnosis of peptic ulcer disease were selected. Overall, 52,161 patients were divided into non-NSAID user and regular NSAID user cohorts. Standardized incidence ratios (SIRs), cumulative incidences, and hazard ratios (HRs) were calculated.nnnRESULTSnPatients with peptic ulcers who never used NSAIDs had higher risk of gastric cancer compared with the general population (SIR, 2.11; 95% CI, 2.07 to 2.15), but regular NSAID use conferred lower risk (SIR, 0.79; 95% CI, 0.77 to 0.81). The protective role of NSAID use was observed in patients with gastric ulcer, but not in patients with non-H pylori-associated duodenal ulcer. On multivariate analysis, regular NSAID use was an independent protective factor for gastric cancer development (HR, 0.79 for each incremental year; P < .001), especially in H pylori-associated patients (HR, 0.52 for each incremental year; P < .001). Among patients with H pylori-infected gastric ulcers, the NNT to prevent a gastric cancer was 50.nnnCONCLUSIONnRegular NSAID use may be a feasible way to prevent gastric cancer, at least in patients with gastric ulcers, and especially in H pylori-infected subjects.

Long-term peptic ulcer rebleeding risk estimation in patients undergoing haemodialysis: a 10-year nationwide cohort study

Objective We aimed to study 1-, 5- and 10-year risks of peptic ulcer rebleeding among end-stage renal disease (ESRD) patients with regular haemodialysis, to identify the high-risk subpopulation, and to estimate the number needed to harm (NNH) to increase a peptic ulcer rebleeding in different periods. Design A nationwide cohort study. Setting Data from the Taiwan National Health Insurance Research Database. Patients Uraemic cohort and matched controls were selected from among hospitalised patients with a primary diagnosis of peptic ulcer bleeding. In total, 6447 uraemic patients and 25u2008788 age-, gender- and gastroprotective agent use-matched controls were selected. Intervention No. Main outcome measures Cumulative incidences and HRs. Results The cumulative incidences of ESRD patients were significantly higher than the cumulative incidences of matched controls (1u2005year: 18.8% vs 14.2%; 5u2005years: 38.5% vs 31.4%; and 10u2005years: 46.3% vs 39.4%; all p<0.001). The NNH to increase a peptic ulcer rebleeding by ESRD at 1, 5 and 10u2005years were 22, 15 and 15, respectively. On multivariate analysis, ESRD (HR=1.38, p<0.0001) was an independent risk factor for rebleeding. Compared with matched controls, ESRD was associated with higher risk of rebleeding especially in patients using ulcerogenic agents (HR=1.33–1.45), indication to prescribe gastroprotective agents (HR=1.44) and with liver cirrhosis (HR=1.45). Conclusions ESRD patients had higher long-term risk of peptic ulcer rebleeding, especially in certain populations. The enhanced risk gradually decreased after the first year and stabilised after the fifth year.

A Nationwide Population-Based Cohort Study Shows Reduced Hospitalization for Peptic Ulcer Disease Associated With H pylori Eradication and Proton Pump Inhibitor Use

BACKGROUND & AIMSnThe incidence of peptic ulcer diseases has decreased significantly during past decades. Despite several significant population-based studies in Western countries, studies of Asian populations are lacking. We therefore investigated the incidence of hospital admissions for peptic ulcer disease in Taiwan during a 10-year period.nnnMETHODSnThis nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Database (a population of 23 million). In total, 403,567 patients with peptic ulcer diseases were recruited for the study. Standardized incidences of admissions were calculated to estimate changes.nnnRESULTSnHospitalization for peptic ulcer diseases decreased significantly between 1997 and 2006 in Taiwan. The incidences of admissions decreased from 68.3 to 39.6 per 100,000 for uncomplicated gastric ulcer, from 116.9 to 61.1 for bleeding gastric ulcer, and from 11.0 to 6.3 for perforated gastric ulcer. The incidences decreased from 46.4 to 13.6 per 100,000 for uncomplicated duodenal ulcer, from 108.0 to 40.1 for bleeding duodenal ulcer, and from 9.8 to 5.8 for perforated duodenal ulcer. The declines were observed in both genders, in all age groups, and at all hospital levels. Significant increases in Helicobacter pylori eradication therapy (202% increase) and proton pump inhibitor use (1071% increase) might have contributed to these decreases.nnnCONCLUSIONSnThe incidences of gastric and duodenal ulcer diseases decreased 42%-48% and 41%-71%, respectively, in Taiwan between 1997 and 2006.

The risk of cancer in patients with rheumatoid arthritis taking tumor necrosis factor antagonists: a nationwide cohort study.

IntroductionThe association between cancer and use of biologic therapy among rheumatoid arthritis (RA) patients remains controversial. We aimed to compare the relative risk of cancer development between RA patients taking tumor necrosis factor α (TNFα) antagonists and those taking nonbiologic disease-modifying anti-rheumatic drugs (nbDMARDs).MethodsWe conducted a nationwide cohort study between 1997 and 2011 using the Taiwan National Health Insurance Research Database. The risk of newly diagnosed cancer was compared between patients starting TNF-α antagonists (biologics cohort) and matched subjects taking nbDMARDs only (nbDMARDs cohort). Cumulative incidences and hazard ratios (HR) were calculated after adjusting for competing mortality. Standardized incidence ratio (SIR) was calculated for cancer risk. Multivariate analyses were performed using Cox proportional hazards model.ResultsWe compared 4426 new users of TNF-α antagonists and 17704 users of nbDMARDs with similar baseline covariate characteristics. The incidence rates of cancer among biologics and nbDMARDs cohorts were 5.35 (95% confidence interval (CI) 4.23 to 6.46) and 7.41 (95% CI 6.75 to 8.07) per 1000 person-years, respectively. On modified Cox proportional hazards analysis, the risk of cancer was significantly reduced in subjects in biologics cohort (adjusted HR 0.63, 95% CI 0.49 to 0.80, Pu2009<u2009.001), after adjusting for age, gender, disease duration, major co-morbidities, and prior use of DMARDs and corticosteroids. However, there was an increased risk for hematologic cancers in biologics cohort, yet without statistical significance. The effect of biologics was consistent across all multivariate stratified analyses and the association between biologics use and cancer risk was independent of dosage of concomitant nbDMARDs.ConclusionThese findings suggested that RA patients taking TNF-α antagonist are associated with a lower risk of cancer, but not for hematologic cancers, than RA patients taking nbDMARDs alone.

A Tool to Predict Risk for Gastric Cancer in Patients With Peptic Ulcer Disease on the Basis of a Nationwide Cohort

BACKGROUND & AIMSnPatients with gastric ulcers have significantly higher risk of gastric cancer, especially within 2xa0years after diagnosis. We used data from a national database to develop a personalized risk prediction model for patients with peptic ulcer diseases.nnnMETHODSnWe collected data from Taiwans National Health Insurance Research Database on 278,898 patients admitted for the first time with a primary diagnosis of peptic ulcer disease. We used the data to develop a nomogram, which we validated by discrimination and calibration, and in a test cohort. Cumulative incidences of study subjects predicted by the nomogram were examined.nnnRESULTSnIn total, 1269 subjects developed gastric cancer. Age, sex, peptic ulcer sites, peptic ulcer complications, Helicobacter pylori eradication, nonsteroidal anti-inflammatory drug use, and surveillance endoscopy were independent factors associated with risk of gastric cancer (all Pxa0<xa0.001). The concordance index for the nomogram developed on the basis of these factors was 0.78. Study subjects were divided into quartiles of predicted risk scores; from lowest score quartile to highest, cumulative incidences at 1 year were 7.4/10,000 people, 14.2/10,000 people, 25.5/10,000 people, and 86.6/10,000 people. The cumulative incidences at 2 years were 9.3/10,000 people, 20.9/10,000 people, 38.0/10,000 people, and 135.7/10,000 people for the same quartiles of risk scores. The nomogram was validated in an independent cohort, and similar incidence values were determined.nnnCONCLUSIONSnWe developed and validated a nomogram to predict risk for gastric cancer 1 and 2 years after diagnosis of peptic ulcer disease. The nomogram provides a prognostic tool that can be easily used for individuals and can help physicians explain risk levels to patients.

Nonsteroidal anti-inflammatory drugs are associated with reduced risk of early hepatocellular carcinoma recurrence after curative liver resection: a nationwide cohort study.

PURPOSEnThe efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in reducing the risk of various de novo cancers has been reported; however, its role in reducing hepatocellular carcinoma (HCC) recurrence after liver resection still remains unknown.nnnMETHODSnWe have conducted a nationwide cohort study by recruiting all patients with a newly diagnosed HCC who had received curative liver resection as their initial treatment. The use of NSAIDs and the risk of early HCC recurrence have been examined by multivariate and stratified analyses. To avoid immortal time bias, the use of NSAIDs has been treated as a time-dependent variable in Cox proportional hazard ratio models.nnnRESULTSnBetween January 1997 and December 2010, a total of 15,574 HCC patients who had received liver resection were enrolled in this study. The 1-, 3-, and 5-year overall survival rates were 90.4%, 73.2%, and 59.8%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 80.5%, 59.4%, and 50.2%, respectively. NSAID use (hazard ratio, 0.81; 95% confidence interval, 0.73-0.90) and minor liver resection (hazard ratio, 0.83; 95% confidence interval, 0.78-0.89) were independently associated with a reduced risk of early HCC recurrence after liver resection. In the stratified analyses, NSAID usage was universally associated with reduced risks in most subgroups, particularly for those aged younger than 65 years, male, with underlying diabetes mellitus and receiving major liver resection.nnnCONCLUSIONSnThe use of NSAIDs can be associated with a reduced risk of early HCC recurrence within 2 years after curative liver resection, regardless of patients age, extent of liver resection, viral hepatitis status, underlying diabetes, and liver cirrhosis.

Hepatic Resection for Hepatocellular Carcinoma Patients on Hemodialysis for Uremia: A Nationwide Cohort Study

BackgroundThe association between uremia and survival outcomes of patients undergoing hepatic resection for hepatocellular carcinoma (HCC) has not been well investigated, particularly for perioperative complications. This nationwide cohort study aimed to compare survival outcomes as well as perioperative mortality and complications between uremia-HCC patients and non-uremia-HCC patients who underwent hepatic resection.MethodsUsing Taiwan’s National Health Institute Research Database, 149 uremia-HCC patients who underwent hepatic resection between 1996 and 2008 were enrolled. The control group comprised 596 HCC patients who also received hepatic resection during the same time period. The two groups were matched for age, gender, viral hepatitis status, and underlying liver cirrhosis. Disease-free survival, overall survival, and perioperative complications were compared between the two groups.ResultsFor the uremia-HCC cohort, the 1-, 5-, and 10-year overall and disease-free survival rates were 86, 52, and 38xa0%, as well as 77, 27, and 18xa0%, respectively. The survival outcomes were comparable between uremia-HCC cohort and the HCC cohort, regardless of extent of hepatic resection. As for perioperative complications, the uremia-HCC cohort had a higher risk of postoperative infections requiring invasive interventions as well as an increased risk of life-threatening heart-associated complications, compared to the HCC cohort.ConclusionsUremia did not influence survival outcomes between the uremia-HCC and the HCC cohorts, irrespective of extent of hepatic resection. This study urges a better perioperative care strategy to avoid potential cardiac and infectious complications in uremia-HCC patients.

A nationwide population-based study shows increasing incidence of cholangiocarcinoma

PurposeAn increasing incidence of cholangiocarcinoma (CCA) has been reported in Western countries, but evidence is lacking in Asia. We investigated the incidence of CCA in a nationwide cohort.Patients and methodsWe conducted a nationwide cohort study based on data from the Taiwan National Health Insurance Research Database (NHIRD) between 1998 and 2008. A total of 6,491 CCA patients were recruited. Adjusted incidences, cumulative incidences, and stratified analyses were used to detect trends regarding CCA incidence in Taiwan.ResultsThe incidence of CCA increased by 2.01-fold, from 1.79 in 1998 to 3.60 in 2008 per 100,000 persons. For extrahepatic CCA, the incidence increased by 1.5-fold from 0.48 to 0.73 per 100,000. Intrahepatic CCA increased by 3.0-fold from 0.72 to 2.19 per 100,000. The rising incidence of CCA was observed across all sexes and ages, especially in those older than 65xa0years of age. The proportion of CCA patients who underwent surgery and the overall survival rates remained stable.ConclusionsThe incidence of both intrahepatic and extrahepatic CCA increased significantly between 1998 and 2008. Rising trends were observed among different ages and sexes, especially in the elderly population.