Altered gut microbiota in Taiwanese A97S predominant transthyretin amyloidosis with polyneuropathy.

Increasing evidence suggests that gut microbiota alterations are related to development and phenotypes of many neuropsychiatric diseases. Here, we evaluated the fecal microbiota and its clinical correlates in patients with hereditary transthyretin amyloidosis (ATTRv) and polyneuropathy. Fecal microbiota from 38 ATTRv patients and 39 age-matched controls was analyzed by sequencing 16S V3-V4 ribosomal RNA, and its relationships with clinical characteristics of polyneuropathy and cardiomyopathy were explored. The familial amyloidotic polyneuropathy stage was stage I, II, and III in 13, 18, and 7 patients. 99mTc-PYP SPECT showed a visual score of 2 in 15 and 3 in 21 patients. The gut microbiota of ATTRv patients showed higher alpha diversity (ASV richness and Shannon effective numbers) and dissimilar beta diversity compared to controls. Relative abundance of microbiota was dominated by Firmicutes and decreased in Bacteroidetes in ATTRv patients than in controls. Patients with more myocardial amyloid deposition were associated with increased alpha diversity, and the abundance of Clostridia was significantly correlated with pathophysiology of polyneuropathy in ATTRv patients. These findings demonstrated alterations in the gut microbiota, especially Firmicutes, in ATTRv. The association between altered microbiota and phenotypes of cardiomyopathy and polyneuropathy might suggest potential contributions of gut microbiota to ATTRv pathogenesis.

Eradicating Helicobacter pylori via 13C-urea breath screening to prevent gastric cancer in indigenous communities: a population-based study and development of a family index-case method.

OBJECTIVE: Screening and eradication of Helicobacter pylori help reduce disparities in the incidence of gastric cancer. We aimed to evaluate its acceptability and feasibility in the indigenous communities and develop a family index-case method to roll out this programme. DESIGN: We enrolled residents aged 20-60 years from Taiwanese indigenous communities to receive a course of test, treat, retest and re-treat initial treatment failures with the 13C-urea breath tests and four-drug antibiotic treatments. We also invited the family members of a participant (constituting an index case) to join the programme and evaluated whether the infection rate would be higher in the positive index cases. RESULTS: Between 24 September 2018 and 31 December 2021, 15 057 participants (8852 indigenous and 6205 non-indigenous) were enrolled, with a participation rate of 80.0% (15 057 of 18 821 invitees). The positivity rate was 44.1% (95% CI 43.3% to 44.9%). In the proof-of-concept study with 72 indigenous families (258 participants), family members of a positive index case had 1.98 times (95% CI 1.03 to 3.80) higher prevalence of H. pylori than those of a negative index case. The results were replicated in the mass screening setting (1.95 times, 95% CI 1.61 to 2.36) when 1115 indigenous and 555 non-indigenous families were included (4157 participants). Of the 6643 testing positive, 5493 (82.6%) received treatment. According to intention-to-treat and per-protocol analyses, the eradication rates were 91.7% (89.1% to 94.3%) and 92.1% (89.2% to 95.0%), respectively, after one to two courses of treatment. The rate of adverse effects leading to treatment discontinuation was low at 1.2% (0.9% to 1.5%). CONCLUSION: A high participation rate, a high eradication rate of H. pylori and an efficient rollout method indicate that a primary prevention strategy is acceptable and feasible in indigenous communities. TRIAL REGISTRATION NUMBER: NCT03900910.

Mass screening and eradication of Helicobacter pylori as the policy recommendations for gastric cancer prevention.

Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. Such a paradigm shift follows a three-tier architecture. First, healthcare policy-makers determine the most feasible and applicable eligibility, invitation, testing, referral, treatment, and evaluation methods for an organized screening program to maximize the population benefits and cost-effectiveness. Second, provision of knowledge and effective feedback to frontline general practitioners, including choice of diagnostic tests, selection of eradication regimens, and the indication of endoscopic examination, ensures the quality of care and increases the likelihood of desired treatment responses. Third, initiatives to raise population awareness are designed regarding the impact of H. pylori infection and risky lifestyle habits on the stomach health. These programs, with increased accessibility and geographic coverage in progress, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy.

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.

Combination of Symptom Profile, Endoscopic Findings, and Esophageal Mucosal Histopathology Helps to Differentiate Achalasia from Refractory Gastroesophageal Reflux Disease.

Achalasia, a rare primary esophageal motility disorder, is often misdiagnosed as refractory gastroesophageal reflux disease (GERD). This study is aimed to identify the clinical and histopathologic features that may help to differentiate these two entities. Patients with untreated achalasia and those with refractory reflux symptoms despite ≥8 weeks of proton-pump inhibitor treatment were enrolled prospectively. All patients underwent validated symptom questionnaires, esophagogastroduodenoscopy with biopsy, and high-resolution impedance manometry (HRIM). Histopathology of esophageal mucosa was compared based on four pre-determined histological criteria: basal cell hyperplasia or papillae elongation, eosinophilic infiltration, petechiae formation, and hypertrophy of the muscularis mucosae (MM). Compared with the GERD patients, patients with achalasia had similar reflux symptoms, but higher Eckardt scores, fewer erosive esophagitis and hiatal hernia, more esophageal food retention on endoscopy, and higher prevalence of hypertrophy of the MM and petechiae formation on histopathology. Multivariate logistic regression based on Eckardt score ≥4, normal esophagogastric junction morphology or esophageal food retention, and coexistence of petechiae formation and hypertrophy of the MM, established the best prediction model for achalasia. Therefore, combination of routinely accessible variables, including Eckardt score, endoscopic features, and histopathology obtained via esophageal mucosal biopsy, may provide an earlier identification of achalasia.

Bismuth salts with versus without acid suppression for Helicobacter pylori infection: A transmission electron microscope study.

BACKGROUND: Bismuth oxychloride produced by interaction of bismuth compounds with gastric acid is believed to damage Helicobacter pylori. The effect of bismuth salts on H. pylori in the presence of strong acid suppression is unknown. This randomized trial aimed to determine effects of bismuth subcitrate on H. pylori with and without acid suppression. METHODS: H. pylori -positive participants were allocated (1:1:1) to receive (a) no treatment (control), (b) colloidal bismuth subcitrate (CBS, 125 mg/tab), or (c) CBS plus high-dose proton-pump inhibitor (PPI), esomeprazole 40 mg q.i.d. for 3 days. In the treatment groups, CBS was given: 1 dose, 1 hour before endoscopy, 1 dose, 4 hours before endoscopy, or q.i.d. 24 hours before endoscopy. The study end-points were evaluated using transmission electron microscopy to observe the morphological changes of H. pylori in antral and corpus biopsies. RESULTS: Twenty-seven H. pylori carriers were enrolled in this trial with qualitative end-points. In the no treatment group, active budding and replication of H. pylori were observed. In the CBS group, cellular swelling, vacuolization, structural degradation, and cell wall eruption of H. pylori were observed, with no apparent association with when the CBS was given. Among those receiving high-dose PPI-plus CBS or CBS only, there were no differences in number of H. pylori present or severity of bacterial damage whether CBS was given 1, 4, or 24 hours before endoscopy. CONCLUSIONS: Based on direct morphological evaluation, the toxic effect of CBS treatment on H. pylori was demonstrated independent of acid suppression with PPI.

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.

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.

Planning mass eradication of Helicobacter pylori infection for indigenous Taiwanese peoples to reduce gastric cancer.

BACKGROUND AND AIM: The aim of this study is to identify gastric cancer burden in Indigenous Taiwanese peoples and conduct a project to evaluate how to reduce the disparities most effectively in Indigenous communities. METHODS: First, we quantified the health disparities in gastric cancer in Indigenous peoples using data from the cancer registries during the period of 2006-2014. Second, we identified parameters that might be associated with Helicobacter pylori infection or help identify a good eradication strategy. RESULTS: Gastric cancer incidence (24.4 vs 12.3 per 100 000 person-years) and mortality rates (15.8 vs 6.8 per 100 000 person-years) were higher in Indigenous than in non-Indigenous, with 2.19-fold (95% confidence interval [CI]: 2.06-2.33) and 2.47-fold (2.28-2.67) increased risk, respectively. In Indigenous communities, H. pylori infection was more prevalent in Indigenous than in non-Indigenous (59.4% vs 31.5%, P < 0.01). Regression analyses consistently showed that either the mountain or plain Indigenous had 1.89-fold (95% CI: 1.34-2.66) and 1.73-fold (95% CI: 1.24-2.41) increased risk for H. pylori infection, respectively, as compared with non-Indigenous, adjusting for other baseline characteristics. The high infection rates were similarly seen in young, middle-aged, and older adults. Program eradication rates using clarithromycin-based triple therapy were suboptimal (73.7%, 95% CI: 70.0-77.4%); the habits of smoking (1.70-fold, 95% CI: 1.01-2.39) and betel nut chewing (1.54-fold, 95% CI: 0.93-2.16) were associated with the higher risk of treatment failure. CONCLUSION: Gastric cancer burden is higher in Indigenous Taiwanese peoples than in their non-Indigenous counterparts. Eliminating the prevalent risk factor of H. pylori infection is a top priority to reduce this health disparity.

Early timing of single balloon enteroscopy is associated with increased diagnostic yield in patients with overt small bowel bleeding.

BACKGROUND/PURPOSE: Although performing balloon enteroscopy soon after the onset of small bowel bleeding appeared to enhance diagnostic rate, the optimal timing was unclear. METHODS: A retrospective cohort study in a single referral center. Patients with overt, suspected small bowel bleeding who underwent primary single-balloon enteroscopy (SBE) were evaluated to determine the association between procedure timing and diagnostic yield rates. RESULTS: A total of 220 patients were enrolled (47.7% males; mean age, 65.6 ± 18.1 years). They were stratified into four groups based on the timing of SBE: emergency (<24 h after onset or continued bleeding, n = 64), 24-72 h (n = 28), 3-7 days (n = 41), and >7 days (n = 87). A significant trend of decreasing diagnostic yields was observed across the groups (90.6%, 67.9%, 68.3%, and 44.8%, respectively, P < 0.0001). Diagnostic yield rates were different between emergency and 24-72 h groups (P < 0.0001), and between 3 and 7 days and >7 days groups (P < 0.05), but not between 24 and 72 h and 3-7 days groups (P = 0.97). In multivariate regression analysis, emergency, ≤ 3 days, and ≤7 days SBEs had greater yield rates than SBEs at later timings. CONCLUSION: The likelihood of diagnostic yield was highest when SBE was performed during continued bleeding or within 24 h of onset, and gradually declined as waiting time increased. We therefore recommend that SBE should be performed as soon as possible, preferably no later than seven days.

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.

Time to Colonoscopy and Risk of Colorectal Cancer in Patients With Positive Results From Fecal Immunochemical Tests.

BACKGROUND & AIMS: In patients with positive results from a fecal immunochemical test (FIT), failure to receive a timely follow-up colonoscopy may be associated with higher risks of colorectal cancer (CRC) and advanced-stage CRC. We evaluated the prevalence of any CRC and advanced-stage CRC associated with delays in follow-up colonoscopies for patients with positive results from a FIT. METHODS: We collected data from 39,346 patients (age, 50-69 years) who participated in the Taiwanese Nationwide Screening Program from 2004 through 2012 and had completed a colonoscopy more than 1 month after a positive result from a FIT. Risks of any CRC and advanced-stage CRC (stage III-IV) were evaluated using logistic regression models and results expressed as adjusted odds ratios (aORs) and corresponding 95% CIs. RESULTS: In our cohort, 2003 patients received a diagnosis of any CRC and 445 patients were found to have advanced-stage disease. Compared with colonoscopy within 1-3 months (cases per 1000 patients: 50 for any CRC and 11 for advanced-stage disease), risks were significantly higher when colonoscopy was delayed by more than 6 months for any CRC (aOR, 1.31; 95% CI, 1.04-1.64; 68 cases per 1000 patients) and advanced-stage disease (aOR, 2.09; 95% CI, 1.43-3.06; 24 cases per 1000 patients). The risks continuously increased when colonoscopy was delayed by more than 12 months for any CRC (aOR, 2.17; 95% CI, 1.44-3.26; 98 cases per 1000 patients) and advanced-stage disease (aOR, 2.84; 95% CI, 1.43-5.64; 31 cases per 1000 patients). There were no significant differences for colonoscopy follow up at 3-6 months for risk of any CRC (aOR, 0.98; 95% CI, 0.86-1.12; 49 cases per 1000 patients) or advanced-stage disease (aOR, 0.95; 95% CI, 0.72-1.25; 10 cases per 1000 patients). CONCLUSIONS: In an analysis of data from the Taiwanese Nationwide Screening Program, we found that among patients with positive results from a FIT, risks of CRC and advanced-stage disease increase with time. These findings indicate the importance of timely colonoscopy after a positive result from a FIT.

Effects of screening and universal healthcare on long-term colorectal cancer mortality.

BACKGROUND: To evaluate the time trends of colorectal cancer (CRC) affected by a Nationwide Colorectal Cancer Screening (NCCS) programme with biennial faecal immunochemical testing (FIT) and Nationwide Healthcare Insurance (NHI). METHODS: Data from the national registries on cancer and death in Taiwan were separated into years 1984-1993, 1994-2003 and 2004-2013 based on the implementations of NHI (starting 1995) and NCCS (starting 2004). The adult population was divided into three age groups (young, 30-49; middle-aged, 50-69; and old, 70-84 years); only the middle-aged were eligible for NCCS. Crude and adjusted effects of NCCS and NHI were quantified by percentage change and 95% confidence interval (CI) with respect to CRC mortality, according to the attributions from incidence and survival. RESULTS: Within 335 million person-years of follow-up, 204 362 incident CRCs and 80 771 CRC-related deaths were identified. Increasing mortality trends were noted for 1994-2003 (post-NHI) vs 1984-1993 due to remarkable increasing incidence trends that could not be offset by improved survival as a result of NHI. During 2004-13 (post-NCCS), mortality continued to increase by 15% (95% CI: 10-21%) in young adults (30-49 years) and 8% (95% CI: 6-11%) in older adults (70-84 years), whereas middle-aged adults (50-69 years) had a reduction of 7% (95% CI: 5-9%) due to a remarkable stage shift and subsequent improvement in survival. In the middle-aged adults, increased incidence was less but survival improvement was more compared with other age groups. CONCLUSIONS: Whereas universal healthcare insurance led to improvement in CRC survival, FIT-based screening has made an even greater contribution to reducing CRC mortality.

Personalized risk assessment for dynamic transition of gastric neoplasms.

BACKGROUND: To develop an individually-tailored dynamic risk assessment model following a multistep, multifactorial process of the Correa's gastric cancer model. METHODS: First, we estimated the state-to-state transition rates following Correa's five-step carcinogenic model and assessed the effect of risk factors, including Helicobacter pylori infection, history of upper gastrointestinal disease, lifestyle, and dietary habits, on the step-by-step transition rates using data from a high-risk population in Matsu Islands, Taiwan. Second, we incorporated information on the gastric cancer carcinogenesis affected by genomic risk factors (including inherited susceptibility and irreversible genomic changes) based on literature to generate a genetic and epigenetic risk assessment model by using a simulated cohort identical to the Matsu population. The combination of conventional and genomic risk factors enables us to develop the personalized transition risk scores and composite scores. RESULTS: The state-by-state transition rates per year were 0.0053, 0.7523, 0.1750, and 0.0121 per year from normal mucosa to chronic active gastritis, chronic active gastritis to atrophic gastritis, atrophic gastritis to intestinal metaplasia, and intestinal metaplasia to gastric cancer, respectively. Compared with the median risk group, the most risky decile had a 5.22-fold risk of developing gastric cancer, and the least risky decile around one-twelfth of the risk. The median 10-year risk for gastric cancer incidence was 0.77%. The median lifetime risk for gastric cancer incidence was 5.43%. By decile, the 10-year risk ranged from 0.06 to 4.04% and the lifetime risk ranged from 0.42 to 21.04%. CONCLUSIONS: We demonstrate how to develop a personalized dynamic risk assessment model with the underpinning of Correa's cascade to stratify the population according to their risk for progression to gastric cancer. Such a risk assessment model not only facilitates the development of an individually-tailored preventive strategy with treatment for H. pylori infection and endoscopic screening but also provides short-term and long-term indicators to evaluate the program effectiveness.

Association Between Colorectal Cancer Mortality and Gradient Fecal Hemoglobin Concentration in Colonoscopy Noncompliers.

Background: To what extent the risk for colorectal cancer (CRC) death among noncompliers of colonoscopy is elevated following positive fecal immunological testing and whether the elevated risk varies with the fecal hemoglobin concentration (f-Hb) and location of CRC have not been researched. Methods: We used data on 59 389 individuals (4.0%) among 1 489 937 Taiwanese screenees age 50 to 69 years with f-Hb 20 µg hemoglobin or more per gram of feces from 2004 to 2009. They were classified into 41 995 who received colonoscopy and 10 778 who received no confirmatory examination; the latter was categorized into three risk groups according to f-Hb (20-49, 50-99, and 100+). Mortality from CRC as the primary end point was monitored until December 31, 2012. Results: A 1.64-fold (95% confidence interval [CI] = 1.32 to 2.04) increased risk for CRC death for the noncolonoscopy group as opposed to the colonoscopy group adjusting for differences in baseline characteristics. A gradient relationship was noted between cumulative mortality and age- and sex-adjusted f-Hb categories with 1.31-fold (95% CI = 1.04 to 1.71), 2.21-fold (95% CI = 1.55 to 3.34), and 2.53-fold (95% CI = 1.95 to 3.43) increased risk, respectively, for the 20-49, 50-99, and 100+ risk groups in the noncolonoscopy group compared with the colonoscopy group. The noncolonoscopy group led to a statistically significant 1.75-fold increased risk (95% CI = 1.35 to 2.33) for CRC of the distal colon but a statistically nonsignificant 1.11-fold increased risk (95% CI = 0.70 to 1.75) for the proximal colon, compared with the colonoscopy group. When the comparator was limited to subjects whose colonoscopy was completed to the cecum, the statistically significantly elevated risk for CRC mortality was seen for both distal and proximal colon in the noncolonoscopy group. Conclusions: After a positive fecal immunochemical test, colonoscopy can reduce by about half the number of deaths from CRC. Among colonoscopy noncompliers, higher f-Hb is associated with an increased risk of mortality from CRC in a dose-response manner.

Outreach and Inreach Organized Service Screening Programs for Colorectal Cancer.

BACKGROUND: Outreach (i.e., to invite those who do not use, or who under use screening services) and inreach (i.e., to invite an existing population who have already accessed the medical system) approaches may influence people to increase their use of screening test; however, whether their outcomes would be equivalent remains unclear. METHODS: A total of 3,363,896 subjects, 50-69 years of age, participated in a colorectal cancer (CRC) screening program using biennial fecal immunochemical tests; 34.5% participated during 2004-2009 when the outreach approach alone was used, and 65.5% participated from 2010-2013 when outreach was integrated with an inreach approach. We compared the outcomes of the two approaches in delivery of screening services. RESULTS: Coverage rates increased from 21.4% to 36.9% and the positivity rate increased from 4.0% to 7.9%, while referral for confirmatory diagnostic examinations declined from 80.0% to 53.3%. The first period detected CRC in 0.20% of subjects screened, with a positive predictive value (PPV) of 6.1%, and the second detected CRC in 0.34% of subjects, with a PPV of 8.0%. After adjusting for confounders, differences were observed in the PPV for CRC (adjusted relative risk, 1.50; 95% confidence interval [CI], 1.41-1.60), cancer detection rate (1.20; 95% CI, 1.13-1.27), and interval cancer rate (0.72; 95% CI, 0.65-0.80). When we focused on the comparison between two approaches during the same study period of 2010-2013, the positivity rate of fecal testing (8.2% vs. 7.6%) and the PPV for CRC detection remained higher (1.07; 95% CI, 1.01-1.12) in subjects who were recruited from the inreach approach. CONCLUSIONS: Outcomes of screening were equivalent or better after integration of outreach and inreach approaches. IMPACT: The results will encourage makers of health-care policy to adopt the integration approach to deliver screening services.

Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of benefit of H pylori eradication in populations with different levels of gastric cancer risk and in different clinical scenarios is unclear. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies to investigate the effects of H pylori eradication on the incidence of gastric cancer. METHODS: We searched PubMed, Cochrane Library, and ClinicalTrials.gov, reviewing titles and abstracts of studies of the effects of eradication of H pylori infection on risk of gastric cancer, through May 2015. We also searched bibliographies of included studies, related reviews, and abstracts presented at Digestive Disease Week. Twenty-four eligible studies (22 research manuscripts and 2 abstracts) were included in our meta-analysis (715 incident gastric cancers among a total of 48,064 individuals/340,255 person-years). We assessed the effects, as well as their modification by baseline gastric cancer incidence, study design (randomized trial vs observational study), clinical scenario (asymptomatic infected individuals vs individuals after endoscopic resection of early gastric cancer), demographic characteristics of patients (age and sex), and duration of follow-up. RESULTS: After adjustment for baseline gastric cancer incidence, individuals with eradication of H pylori infection had a lower incidence of gastric cancer than those who did not receive eradication therapy (pooled incidence rate ratio = 0.53; 95% confidence interval: 0.44-0.64). There was little heterogeneity among studies. Baseline gastric cancer incidence modified the benefit of H pylori eradication (P = .037 for interaction); the incidence rate ratio of gastric cancer decreased in a nonlinear fashion with increasing baseline incidence of gastric cancer (P = .018, in comparison with the linear model). The benefit also modestly increased with age (P = .023 for interaction), but this might be due to correlation between age and baseline gastric cancer incidence. Eradication provided significant benefit for asymptomatic infected individuals (pooled incidence rate ratio, 0.62; 95% CI: 0.49-0.79) and individuals after endoscopic resection of gastric cancers (pooled incidence rate ratio, 0.46; 95% CI: 0.35-0.60). The benefits of H pylori eradication did not differ with study design, sex, or follow-up period. CONCLUSIONS: In a systematic review and meta-analysis, we associated eradication of H pylori infection with a reduced incidence of gastric cancer. The benefits of eradication vary with baseline gastric cancer incidence, but apply to all levels of baseline risk.

Mass Eradication of Helicobacter pylorito Prevent Gastric Cancer: Theoretical and Practical Considerations.

Although the age-adjusted incidence of gastric cancer is declining, the absolute number of new cases of gastric cancer is increasing due to population growth and aging. An effective strategy is needed to prevent this deadly cancer. Among the available strategies, screen-and-treat for Helicobacter pylori infection appears to be the best approach to decrease cancer risk; however, implementation of this strategy on the population level requires a systematic approach. The program also must be integrated into national healthcare priorities to allow the limited resources to be most effectively allocated. Implementation will require adoption of an appropriate screening strategy, an efficient delivery system with a timely referral for a positive test, and standardized treatment regimens based on clinical efficacy, side effects, simplicity, duration, and cost. Within the population, there are subpopulations that vary in risk such that a "one size fits all" approach is unlikely to be ideal. Sensitivity analyses will be required to identify whether the programs can be utilized by heterogeneous populations and will likely require adjustments to accommodate the needs of subpopulations.