Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

Administration of oral prednisolone to prevent esophageal stricture after balloon-type radiofrequency ablation for ultralong-segment esophageal neoplasia.

BACKGROUND AND AIMS: Endoscopic radiofrequency ablation (RFA) has shown good efficacy and safety in eradicating flat-type early esophageal squamous cell neoplasia (ESCN). However, post-RFA stricture is still a major concern, especially when treating ultralong-segment ESCNs. The aim of this study was to investigate the efficacy and safety of oral prednisolone to prevent post-RFA stricture. METHODS: We prospectively enrolled 48 patients treated with balloon-type RFA who had Lugol-unstained or mosaic-like flat-type ESCNs with an expected treatment area more than 10 cm. Oral prednisolone was started at a dose of 30 mg/day on the third day after RFA and continued for 4 weeks. The results were compared to a historical control group of 25 patients who received RFA without oral steroids. The primary endpoint was the frequency of post-RFA stricture. Secondary endpoints were the number of balloon dilation sessions and adverse event rate. RESULTS: There were no significant differences in the worst pathology grade at baseline, length of unstained lesions between the two groups. The complete response rates after 1 session of RFA were 73% and 72%, respectively. Compared to the control group, the oral prednisolone group had a significantly lower stricture rate (4%, 2/48 patients vs. 44%, 11/25 patients; P<0.0001) and a lower number of balloon dilation sessions (median 0, range 0-4 vs. median 6, range 0-10). There were two cases of asymptomatic candida esophagitis in the study group, and no severe adverse effects. CONCLUSIONS: Oral prednisolone may offer a useful and safe preventive option for post-RFA stricture in ultralong ESCNs. CLINICAL TRIAL REGISTRATION NUMBER: NCT05768282.

Inhibition of Viral Replication Reduces Transcriptionally Active Distinct Hepatitis B Virus Integrations With Implications on Host Gene Dysregulation.

BACKGROUND & AIMS: Hepatocellular carcinogenesis of hepatitis B virus (HBV) infection may arise from integration of viral DNA into the host genome. We aimed to gauge the effect of viral inhibition on transcriptionally active HBV-host integration events and explore the correlation of viral integrations with host gene dysregulation. METHODS: We leveraged data and biospecimens from an interventional trial, in which patients with HBV viremia above 2000 IU/mL and minimally raised serum liver enzyme were randomized to receive tenofovir disoproxil fumarate (TDF) or placebo for 3 years. Total RNA-sequencing was performed on paired liver biopsies taken before and after the 3-year intervention in 119 patients. Virus-host chimeric reads were captured to quantify the number of distinct viral integrations. Dysregulation of a host gene disrupted by viral integration was defined by aberrant expression >2 standard deviations away from samples without viral integration. RESULTS: The TDF (n = 64) and placebo groups (n = 55) were comparable at baseline. Expressed viral integrations were detected in all pre- and posttreatment samples. The number of distinct viral integrations significantly correlated with circulatory biomarkers indicative of viral activities including HBV DNA, RNA, and viral antigens (P < .0003 for all correlations). Moreover, TDF vs placebo achieved a significantly greater reduction in distinct viral integrations, with 3.28-fold and 1.81-fold decreases in the expressed integrations per million reads, respectively (analysis of covariance, P = .037). Besides, viral integrations significantly correlated with host gene dysregulation. CONCLUSION: Inhibition of viral replication reduces the number of transcriptionally active distinct HBV-host DNA integrations in patients with substantial viremia. Given the mutagenic potentials of viral integrations, such treatment effects should be considered in patient management.

Association between residential exposure to petrochemical industrial complexes and pancreatic cancer: a systematic review and meta-analysis.

Increased in the global demand-expansion of the petrochemical industry is a possible environmental risk factor pancreatic cancer among residents living close to petrochemical complexes. This meta-analysis aimed to estimate the pooled risk of pancreatic cancer among residents living near petrochemical industrial complexes. We systematically searched and reviewed published studies in six databases based on the inclusion criteria derived from the population, exposure, comparator, and outcomes framework (population: general population; exposure: residence near petrochemical industrial complexes/living in cities with petrochemical industrial complexes; comparators: residents living farther away from petrochemical industrial complexes/living in cities without petrochemical industrial complexes; outcome: pancreatic cancer). We identified seven studies, covering 1,605,568 residents. Pooled analysis showed a significantly higher risk of pancreatic cancer among residents living near petrochemical industrial complexes (relative risk [RR] = 1.31, 95% confidence interval [CI] = 1.21-1.42) than those living farther away from petrochemical industrial complexes. Such effect was higher in female residents (RR = 1.34, 95% CI = 1.18-1.53) than in male residents (RR = 1.26, 95% CI = 1.12-1.41). This study suggests that exposure to petrochemical industry-related activities should be recognized as a risk factor for pancreatic cancer among residents living near petrochemical industrial complexes.

Declining trends of prevalence of Helicobacter pylori infection and incidence of gastric cancer in Taiwan: An updated cross-sectional survey and meta-analysis.

BACKGROUND: We aimed to assess the latest prevalence and secular trend of Helicobacter pylori infection and its association with the incidence and mortality of gastric cancer in Taiwan. MATERIALS AND METHODS: Adults naive to H. pylori eradication received 13 C-urea breath test (13 C-UBT), H. pylori stool antigen test, and serology test during 2019-2020 in this prospective screening program. Children and adolescent aged between 7 and 19 years received 13 C-UBT for H. pylori screening. We also conducted a systematic review and meta-analysis to assess the secular trend of prevalence of H. pylori from 1990 to 2020 in Taiwan. The secular trends of age-standardized incidence and mortality of gastric cancer were obtained from the Taiwan Cancer Registry. RESULTS: A total of 1494 participants were enrolled, including 294 children or adolescents and 1200 adults. The overall prevalence of active H. pylori infection by 13 C-UBT was 26.6% (397/1494), which was 30.8% in adults and 9.5% in adolescents/children. The age-standardized prevalence of active H. pylori infection was 32.3% in adults after adjustment of the population structure in Taiwan. Of the 29 studies including 38,597 subjects eligible for the meta-analysis, the pooled prevalence of H. pylori infection decreased from 63.8% (95% CI: 55.9%-71%) in 1990-2000 to 28.2% (95% CI:21.8%-35.6%) in 2016-2020. The age-standardized incidence and mortality of gastric cancer have also declined from 15.2 to 10.75 per 100,000, respectively, in 1999 to 9.29 and 5.4 per 100,000, respectively, in 2019. CONCLUSIONS: The prevalence of H. pylori infection has declined in Taiwan, which correlates with the declining trends of age-standardized incidence and mortality of gastric cancer in Taiwan.

Risk factors related to age at diagnosis of pancreatic cancer: a retrospective cohort pilot study.

BACKGROUND: Increased pancreatic cancer incidence has been observed among younger than in older adults. This pilot study aimed to determine the feasibility of a large study that would compare the age at diagnosis of pancreatic cancer among patients with different risk factors. METHODS: We compared the age at diagnosis of pancreatic cancer between groups of pancreatic cancer patients exposed and not exposed to the identified risk factors. We estimated the age at which exposure started, average exposure quantity, and total years of exposure and investigated their relationships with age at diagnosis of pancreatic cancer. RESULTS: Sixteen out of 24 (67%) subjects carried known genetic factors and/or had smoking and/or drinking habits; however, an earlier age of pancreatic cancer diagnosis was not observed. Conversely, we found a significant correlation between the age at which alcohol consumption was started and the age at diagnosis of pancreatic cancer (r = 0.8124, P = 0.0043). CONCLUSIONS: Our pilot study suggested that a large study following this study design is feasible and that the following should be conducted in a large study: mediation analysis for disease-related factors, advanced genomic analysis for new candidate genes, and the correlation between age of first exposure to risk factors and pancreatic cancer onset.

Brand interchangeability of pepsinogen tests in the real-world setting after eradication of Helicobacter pylori: a community-based study.

BACKGROUND: Serum pepsinogen (PG) is recommended as a screening test for premalignant gastric lesions. However, real-world evidence demonstrating its applicability and equivalence between different test brands is limited. METHODS: Mass screening began in 2018 in a high-risk Taiwanese population after eradication of Helicobacter pylori, with the first stage of two PG tests (GastroPanel®, Helsinki, Finland and LZ-Test®, Tokyo, Japan) and the second stage of endoscopy. A positive test was defined as PG-I < 30 ng/mL or PG-I/II ratio < 3 for GastroPanel® and PG-I ≤ 70 ng/mL and PG-I/II ratio ≤ 3 for LZ-Test®. Index lesions included atrophic gastritis and intestinal metaplasia. Test performance was evaluated based on the participation rate, positivity rate, referral rate, positive predictive value (PPV), and the detection rate. RESULTS: Among 7616 eligible participants, 5117 (67.2%) received PG tests and 284 (5.6%) tested positive. Of those who tested positive, 105 (37.0%) underwent endoscopy. Overall PPVs for atrophic gastritis and intestinal metaplasia were 12.4% and 18.9%, respectively, with detection rates of 2.5 and 3.9 per 1000, respectively. Correlations of numerical measures between tests were high and the agreements of test results were substantial. The PPVs (16.3% vs. 16.3% and 23.8% vs. 21.3%, P = 1.00 and 0.71, respectively), detection rates (2.5 vs. 2.5 and 3.7 vs. 3.3 per 1000, P = 1.00 and 0.27, respectively), and the stage distributions of gastritis were all comparable, which were confirmed by multiple regression analyses. CONCLUSIONS: PG testing is effective for mass screening after eradication of H. pylori. Tests from different manufacturers, even using different analytical methods and cutoff criteria, can perform equivalently.

Establishing the blood reference interval of pancreatic elastase-1: A prospective study.

BACKGROUND AND AIM: Pancreatic elastase-1 (PE-1) has been investigated in pancreatic disorders. However, the reference interval (RI) of PE-1 in blood remains unconfirmed. We aimed to establish the blood RI of PE-1 in an adult population. METHODS: In this prospective cross-sectional study, we enrolled 400 adults who had received the whole-body physical check-up program between May 1, 2019 and November 20, 2019. The serum and plasma PE-1 levels were measured by latex turbidimetric immunoassay in different storage conditions (fresh, refrigerated, and frozen). The 95% and 99% RI of PE-1 were calculated according to the Clinical & Laboratory Standards Institute guidelines. The correlations between PE-1 and other parameters were analyzed using multivariable regression models. Ultimately, 38 patients with acute pancreatitis were prospectively recruited as the validation cohort. RESULTS: The PE-1 levels in fresh serum were highly correlated with those in refrigerated (R2  = 0.998) or frozen (R2  = 0.942) samples; however, plasma should not be suggested in frozen conditions (plasma vs serum: R2  = 0.185). In the RI study population (202 male & 198 female participants), the median age was 52.6 (25-75% interquartile range: 43.1-61.0). The 95% and 99% RIs of PE-1 were 30.0-221.0 and 22.0-359.0 ng/dL, respectively. Triglycerides (ß = 0.106, P = 0.033), lipase (ß = 0.154, P = 0.007), and CA19-9 (ß = 0.130, P = 0.008) were independent factors associated with PE-1. In the pancreatitis validation cohort, with a cut-off value of 359.0 ng/dL, the sensitivity and specificity were 100% and 99.8%, respectively. CONCLUSION: The RI of PE-1 established in this study can be used for further applications. Serum is the suggested form for frozen sample storage.

Accuracy of simultaneous measurement of serum biomarkers: Carbohydrate antigen 19-9, pancreatic elastase-1, amylase, and lipase for diagnosing pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic cancer is difficult to diagnose early since tumor markers have low sensitivity and specificity. We simultaneously measured serum carbohydrate antigen (CA) 19-9, pancreatic elastase-1, lipase, and amylase, and evaluated the accuracy of a single marker or a combination of two, three, or four markers in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). METHODS: Seventy-six patients with PDAC were included, and 75 patients with non-PDAC diseases were enrolled as the control group. Blood specimens were collected and analyzed for pancreatic elatase-1, CA19-9, amylase and lipase. Sensitivity, specificity, and accuracy for each individual marker and in combination were determined. RESULTS: In PDAC subjects, abnormal CA19-9 was seen most frequently at 80.3%, followed by pancreatic elastase-1 at 57.9%, lipase at 53.9%, and amylase at 51.3%. In non-PDAC subjects, the percentage of abnormal serum pancreatic elastase-1, CA19-9, lipase, and amylase were 50.7%, 41.3%, 40.0%, and 28.0%, respectively. The accuracy rate of amylase and CA19-9 results combined was 64.9% and was higher than the combination of other markers in the intersection set. In the union set, the group of amylase and CA19-9 combined and the group of lipase and CA19-9 combined had the highest accuracy at 66.2%. In the intersection and union set, the area under the curve of CA19-9 was the highest at 0.695. CONCLUSION: CA19-9 as a single marker is the most accurate in the clinical diagnosis of PDAC. Combination of lipase, amylase, or pancreatic elastase-1 results does not significantly increase the accuracy of PDAC diagnosis.

Deciphering Genetic Alterations of Taiwanese Patients with Pancreatic Adenocarcinoma through Targeted Sequencing.

Pancreatic adenocarcinoma (PAC) is the 8th leading cause of cancer-related deaths in Taiwan, and its incidence is increasing. The development of PAC involves successive accumulation of multiple genetic alterations. Understanding the molecular pathogenesis and heterogeneity of PAC may facilitate personalized treatment for PAC and identify therapeutic agents. We performed tumor-only next-generation sequencing (NGS) with targeted panels to explore the molecular changes underlying PAC patients in Taiwan. The Ion Torrent Oncomine Comprehensive Panel (OCP) was used for PAC metastatic lesions, and more PAC samples were sequenced with the Ion AmpliSeq Cancer Hot Spot (CHP) v2 panel. Five formalin-fixed paraffin-embedded (FFPE) metastatic PAC specimens were successfully assayed with OCP, and KRAS was the most prevalent alteration, which might contraindicate the use of anti-EGFR therapy. One PAC patient harbored a FGFR2 p. C382R mutation, which might benefit from FGFR tyrosine kinase inhibitors. An additional 38 samples assayed with CHP v2 showed 100 hotspot variants, collapsing to 54 COSMID IDs. The most frequently mutated genes were TP53, KRAS, and PDGFRA (29, 23, 10 hotspot variants), impacting 11, 23, and 10 PAC patients. Highly pathogenic variants, including COSM22413 (PDGFRA, FATHMM predicted score: 0.88), COSM520, COSM521, and COSM518 (KRAS, FATHMM predicted score: 0.98), were reported. By using NGS with targeted panels, somatic mutations with therapeutic potential were identified. The combination of clinical and genetic information is useful for decision making and precise selection of targeted medicine.

Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands.

OBJECTIVE: Although mass eradication of Helicobacter pylori has been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear. DESIGN: Mass eradication of H. pylori infection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalent H. pylori infection. Test positives for the 13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively. RESULTS: After six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates of H. pylori fell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, p<0.001) and 25% (95% CI -14% to 51%, p=0.18), respectively. No significant changes were noted in the incidence rates of other digestive tract cancers or the antibiotic resistance rate of H. pylori. CONCLUSION: Population-based eradication of H. pylori has significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period. TRIAL REGISTRATION NUMBER: NCT00155389.

Risk stratification for gastric cancer after Helicobacter pylori eradication: A population-based study on Matsu Islands.

BACKGROUND AND AIM: The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal. METHODS: Mass eradication of H. pylori began in 2004 in a high-risk population. After eradication, a screening program involving first-stage serological tests (pepsinogen-I, pepsinogen-II, H. pylori immunoglobin G, and gastrin-17) and second-stage endoscopic examination was launched in 2015-2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to "rule in" and "rule out" the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA-124a-3 in the stomach were measured to indicate genetic damage. RESULTS: Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin-17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin-17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non-atrophic-appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 [95% confidence interval: 2.92-5.77]; negative likelihood ratio: 0.14 [0.10-0.19]). Gastrin-17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 [1.21-3.42] and 0.57 [0.34-0.95]). DNA methylation levels in the post-eradication mucosa were more discriminative for predicting index lesions (3.89 [2.32-6.54] and 0.25 [0.15-0.42]). CONCLUSIONS: After eradication, pepsinogen false-negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.

Taiwan nutritional consensus on the nutrition management for gastric cancer patients receiving gastrectomy.

Currently, consensus reports on the nutritional management for gastric cancer patients receiving gastric resection are lacking. The Gastroenterological Society of Taiwan therefore organized the Taiwan Gastric Cancer Nutritional Consensus Team to provide an overview of evidence and recommendations on nutritional support for gastric cancer patients undergoing gastrectomy. This consensus statement on the nutritional support for gastric cancer patients has two major sections:(1)perioperative nutritional support; and (2)long-term postoperative nutritional care. Thirty Taiwan medical experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. The key statements included that preoperative nutritional status affects the incidence of operative complications and disease-specific survival in gastric cancer patients undergoing gastrectomy. Following gastrectomy, both early oral and enteral tube feeding can result in a shorter stay than total parenteral nutrition. Compared to late oral feeding, early oral feeding can reduce hospital stay in gastric cancer patients receiving gastrectomy without an increase in complication rate. Routine supplementation with vitamin B12 is indicated for gastric cancer patients undergoing a total gastrectomy. Both high-dose oral vitamin B12 supplementation and intramuscular administration of vitamin B12 are equally effective in the treatment of vitamin B12 deficiency.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Association of Daily Aspirin Therapy With Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis C Virus Infection.

BACKGROUND & AIMS: Aspirin therapy has been associated with reduced risk of colon cancer, but there is only limited evidence for its effects on risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We aimed to investigate the association of daily aspirin therapy with HCV-related HCC risk. METHODS: In this cohort study, based on Taiwan's National Health Insurance Research Database, we screened 237,963 patients with chronic HCV infection for the period of 1997 through 2011. We excluded patients with confounding conditions and 2478 patients who continuously received daily aspirin therapy for 90 days or more (treated group) were randomly matched 1:2 with 4956 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores. Cumulative incidence of, and hazard ratio (HR) for, HCC development were analyzed after we adjusted for patient mortality as a competing risk event. RESULTS: The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group over 5 years (4.67%; 95% CI, 3.74%-5.59% vs 7.32%; 95% CI, 6.33%-8.30%; P<.001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.78, 95% CI, 0.64-0.95; P = .011), after adjustment for age per year, male sex, cirrhosis, liver decompensation, hyperlipidemia, statin use, and interferon therapy. Sensitivity subgroup analyses also verified this association (all HRs<1.0). In addition, older age (HR, 1.03 per year; 95% CI, 1.02-1.04), male sex (HR, 1.46; 95% CI, 1.21-1.77), and cirrhosis (HR, 3.13; 95% CI, 2.55-3.84) were independently associated with an increased HCC risk. CONCLUSIONS: In a nationwide cohort study in Taiwan, we found aspirin therapy to be significantly associated with a reduced risk of HCV-related HCC.

Exploring health and well-being in Taiwan: what we can learn from individuals' narratives.

BACKGROUND: Our aim was to explore the concepts of health and well-being from the point of view of the people experiencing them. Most of the efforts to understand these concepts have focused on disease prevention and treatment. Less is known about how individuals achieve health and well-being, and their roles in the pursuit of a good life. We hoped to identify important components of these concepts that may provide new targets and messages to strengthen existing public health programs. An improved understanding of health and well-being - or what it means to be well - can guide interventions that help people lead healthier, more fulfilling lives. METHODS: Using a grounded qualitative approach drawing from narrative inquiry, we interviewed 24 Taiwanese adults. Thematic inductive coding was employed to explore the nature of health and well-being. RESULTS: Eight constituent domains emerged regarding well-being and health. While the same domains were found for both constructs, important frequency differences were found when participants discussed health versus well-being. Physical health and lifestyle behaviors emerged as key domains for health. Disease-related comments were the most frequently mentioned sub-category within the physical health domain, along with health care use and aging-related changes. For well-being, family and finances emerged as key domains. Family appears to be a cornerstone element of well-being in this sample, with participants often describing their personal well-being as closely tied to - and often indistinguishable from - their family. Other domains included work-life, sense of self, resilience, and religion/spirituality. CONCLUSIONS: Health and well-being are complex and multifaceted constructs, with participants discussing their constituent domains in a very interconnected manner. Programs and policies intended to promote health and well-being may benefit from considering these domains as culturally-appropriate leverage points to bring about change. Additionally, while the domains identified in this study are person-centered (i.e., reflecting the personal experiences of participants), the stories that participants offered provided insights into how well-being and health are influenced by structural, societal and cultural factors. Our findings also offer an opportunity for future refinement and rethinking of existing measurement tools surrounding these constructs.

Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection.

BACKGROUND & AIMS: We aimed to compare the efficacy of genotypic resistance-guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. METHODS: We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance-guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. RESULTS: H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance-guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P = .181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance-guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P = .170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. CONCLUSIONS: Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance-guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.

Serum Pepsinogen as a Predictor for Gastric Cancer Death: A 16-Year Community-based Cohort Study.

GOALS: The purpose of this article is to validate the long-term association between initial serum pepsinogen (PG) measurements and subsequent gastric cancer-specific deaths from a long-term longitudinal cohort. BACKGROUND: Endoscopic surveillance can be effective and efficient in reducing gastric cancer mortality if a biomarker such as serum PG is available to identify high-risk individuals and if the biomarker also is specific to gastric cancer risk. STUDY: Between 1995 and 1998, a gastric cancer-screening program was conducted in a high-risk population: The first stage involved PG testing, and the second stage involved upper endoscopy. The outcome was gastric cancer death, which was monitored until December 31, 2010; results were expressed as the hazard ratio (HR) and corresponding 95% confidence interval (CI) using the Cox proportional hazards regression model. Other causes of death were used as comparators. RESULTS: Among participants (n=3514) aged ≥30 years, 1682 (47.9%) were screened to determine serum PG levels. After 16 years of follow-up, 14 deaths from gastric cancer were documented. Multivariate analyses adjusted for age, sex, and Helicobacter pylori serological positivity showed that PG-I <30 µg/L and PG-I <30 µg/L or PG-I/II ratio <3 were significantly associated with the risk of gastric cancer death (HR, 3.27; 95% CI, 1.11-9.61 and HR, 3.45; 95% CI, 1.18-10.12, respectively). In contrast, there were no significant associations between PG and other causes of death, including neoplastic and non-neoplastic diseases. CONCLUSION: This long-term cohort study shows the usefulness of PG measurement as a biomarker that is specific to the risk of gastric cancer death.

Systematic review and network meta-analysis: Comparative effectiveness of therapies for second-line Helicobacter pylori eradication.

BACKGROUND AND AIM: The eradication rate of Helicobacter pylori (H. pylori) has been declining over the past decades. A rescue plan is needed for increasing populations with treatment failure. However, the optimum second-line eradication regimen remains inconclusive. We conducted a network meta-analysis to assess the comparative effectiveness of second-line H. pylori eradication therapies and determine the optimum regimen. METHODS: We searched electronic databases from January 2005 to February 2018 for randomized controlled trials assessing the effectiveness of second-line regimens in patients with persistent H. pylori infection after first-line treatment. Bayesian network meta-analysis was performed to combine the direct and indirect evidence and to investigate the rank order of second-line therapies. We also appraised the quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation guidance. RESULTS: Twenty-six trials with 3628 participants who received second-line eradication therapy were identified. All regimens showed pooled eradication rates < 90%. Compared with 7-day triple therapy, quinolone-based (odds ratio [OR] 4.29, 95% credible interval [CrI] 1.67-12.12, surface under the cumulative ranking [SUCRA] 0.95), non-quinolone-based bismuth-containing quadruple therapies for 10 days or more (OR 2.25, 95% CrI 1.10-4.62, SUCRA 0.78), and sequential therapy (OR 2.91, 95% CrI 1.16-7.65, SUCRA 0.66) showed significantly higher effectiveness. Overall, regimens with longer duration demonstrated higher eradication rates but higher rates of adverse events. More adverse events were reported in those patients treated with concomitant therapy. CONCLUSIONS: Quinolone-based bismuth-containing quadruple therapies for 10 days or more are the optimum second-line regimens for H. pylori eradication.