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.

Digestive cancer management in Asia: position statements: a report on GI Oncology Summit in 2011.

BACKGROUND AND AIM: With the rising incidence of digestive cancers in the Asia Pacific region and the advancement in diagnosis, management and palliation in these conditions, the clinical burden on oncologists is ever increasing. This Summit meeting was called to discuss the optimal management of digestive cancers and the role of Gastroenterologists. METHOD: Experts from Asia Pacific countries in the fields of medical, oncologic, surgical and endoscopic management of cancers in the esophagus, stomach, colon/rectum and the liver reviewed the literature and their practice. 18 position statements were drafted, debated and voted. RESULTS: It was agreed that the burden on GI cancer is increasing. More research will be warranted on chemotherapy, chemoprevention, cost-effectiveness of treatment and nutrition. Cancer management guidelines should be developed in this region when more clinical data are available. In order to improve care to patients, a multi-disciplinary team coordinated by a "cancer therapist" is proposed. This cancer therapist can be a gastroenterologist, a surgeon or any related discipline who have acquired core competence training. This training should include an attachment in a center-of-excellence in cancer management for no less than 12 months. CONCLUSION: The management of GI cancer should be an integrated multi-disciplinary approach and training for GI cancer therapists should be provided for.

Revisit of field cancerization in squamous cell carcinoma of upper aerodigestive tract: better risk assessment with epigenetic markers.

We quantified field cancerization of squamous cell carcinoma in the upper aerodigestive tract with epigenetic markers and evaluated their performance for risk assessment. Methylation levels were analyzed by quantitative methylation-specific PCR of biopsied specimens from a training set of 255 patients and a validation set of 224 patients. We also measured traditional risk factors based on demographics, lifestyle, serology, genetic polymorphisms, and endoscopy. The methylation levels of four markers increased stepwise, with the lowest levels in normal esophageal mucosae from healthy subjects without carcinogen exposure, then normal mucosae from healthy subjects with carcinogen exposure, then normal mucosae from cancer patients, and the highest levels were in cancerous mucosae (P < 0.05). Cumulative exposure to alcohol increased methylation of homeobox A9 in normal mucosae (P < 0.01). Drinkers had higher methylation of ubiquitin carboxyl-terminal esterase L1 and metallothionein 1M (P < 0.05), and users of betel quid had higher methylation of homeobox A9 (P = 0.01). Smokers had increased methylation of all four markers (P < 0.05). Traditional risk factors allowed us to discriminate between patients with and without cancers with 74% sensitivity (95% CI: 67%-81%), 74% specificity (66%-82%), and 80% area under the curve (67%-91%); epigenetic markers in normal esophageal mucosa had values of 74% (69%-79%), 75% (67%-83%), and 83% (79%-87%); and both together had values of 82% (76%-88%), 81% (74%-88%), and 91% (88%-94%). Epigenetic markers done well in the validation set with 80% area under the curve (73%-85%). We concluded that epigenetics could improve the accuracies of risk assessment.

Gastric plasma biomarkers and Operative Link for Gastritis Assessment gastritis stage.

INTRODUCTION: The Operative Link for Gastritis Assessment (OLGA) staging system has been proposed as a histopathological reporting system of gastric atrophy. Noninvasive methods for indirect evaluation of gastric mucosal atrophy by biomarkers are also being introduced. OBJECTIVES: To analyze gastric mucosal atrophy by biomarkers, pepsinogen I (PgI), pepsinogen II (PgII), PgI/PgII ratio, fasting gastrin-17 (G-17), stimulated gastrin-17 (sG-17), in relation to OLGA gastritis stage. PATIENTS AND METHODS: Gastric biopsies were taken from 269 prospective patients referred for upper endoscopy because of dyspeptic problems and evaluated by two expert pathologists (D.J. and P.S.). Atrophy was assessed according to the OLGA staging system. Pg I, PgII, Pg I/II, G-17, sG-17 were determined in a plasma sample. RESULTS: The mean levels of PgI and PgI/PgII decreased significantly from 90.8 µg/l and 7.6 in stage 0 gastritis to 64.3 µg/l and 4.3 in high-stage gastritis. The mean values of G-17 and sG-17 were significantly higher among patients with stage II gastritis compared with stage 0 and high-stage gastritis.The proportion of patients with normal mucosa and nonatrophic gastritis according to biomarkers decreased from 78% in stage 0 to 22% in high-stage (III-IV) gastritis. Among the latter no case with normal mucosa, according to biomarkers, was observed. CONCLUSIONS: A significant inverse correlation between the mean levels of PgI, PgI/II ratio and the OLGA stage was observed. Percentage of dyspeptic patients with normal mucosa, by blood biomarkers, decreased with increasing OLGA gastritis stages. OLGA staging system provides a good frame for scientific analysis of gastric mucosal atrophy.

A prospective evaluation of the feasibility of primary screening with unsedated colonoscopy.

BACKGROUND: Colonoscopy is the most effective screening tool for colorectal cancer. In Taiwan, colonoscopy is used much less than sigmoidoscopy for screening because sedation significantly increases the cost and is not readily available, and unsedated colonoscopy is considered to be poorly tolerated. However, unsedated colonoscopy has been shown to be well accepted and may improve the cost-effectiveness and access to colonoscopic screening. OBJECTIVES: To compare the feasibility of unsedated colonoscopy and sigmoidoscopy for primary screening and to analyze factors associated with acceptance of the procedures and need for sedation. DESIGN: Single center, prospective. SETTING: National Taiwan University Medical Center. POPULATION AND INTERVENTIONS: A consecutive series of 261 subjects without history of colonoscopy or sigmoidoscopy who underwent unsedated colonoscopy (n = 176) or sigmoidoscopy (n = 85) for primary screening. MAIN OUTCOME MEASUREMENTS: Pain scores, acceptance, and need for sedation. RESULTS: No significant differences in pain, acceptance, and need for sedation were found between the colonoscopy and sigmoidoscopy groups. Only 9.6% in the colonoscopy group and 10.1% in the sigmoidoscopy group considered sedation necessary. Multivariate analyses revealed that the examinee's sex and the endoscopist, but not the type of endoscopic examination, were associated with the severity of pain and need for sedation. LIMITATIONS: Nonrandomized study design. CONCLUSIONS: Unsedated colonoscopy for primary screening is well accepted in nine tenths of examinees who accept this option and is similar to sigmoidoscopy in pain, acceptance, and need for sedation. Primary screening with unsedated colonoscopy is feasible, as with sigmoidoscopy.

Is eradication of Helicobacter pylori the feasible way to prevent gastric cancer? New evidence and progress, but still a long way to go.

Epidemiological, animal and biological studies provide compelling evidence for the role of Helicobacter pylori infection in gastric carcinogenesis. The finding that H. pylori-induced chronic atrophic gastritis is the major cause of gastric cancer suggests that eradication of the bacterium may prevent this malignancy. Computer-simulation studies have confirmed the cost-effectiveness of eradication in high-risk subjects; however, unresolved issues complicate active testing for and treatment of H. pylori infection among asymptomatic carriers. Concerns include the enormous costs for developing countries to implement strategies, the inconclusiveness of data from randomized controlled studies, the potential induction of antimicrobial resistance, and the uncertain effect of eliminating this organism on the spectrum of modern disease. Although current evidence is insufficient to recommend universal testing and treatment, it is possible to identify highly susceptible individuals who are most likely to benefit from treatment. Novel biomarkers for predicting risk are under extensive investigation, including genetic, epigenetic and proteinomic factors. The emerging evidence suggests that treatment of H. pylori infection in asymptomatic carriers may decrease the burden of gastric cancer. However, confirmation of long-term benefits remains a long way off.

Screening for gastric cancer in Asia: current evidence and practice.

Gastric cancer is the second most common cause of death from cancer in Asia. Although surgery is the standard treatment for this disease, early detection and treatment is the only way to reduce mortality. This Review summarises the epidemiology of gastric cancer, and the evidence for, and current practices of, screening in Asia. Few Asian countries have implemented a national screening programme for gastric cancer; most have adopted opportunistic screening of high-risk individuals only. Although screening by endoscopy seems to be the most accurate method for detection of gastric cancer, the availability of endoscopic instruments and expertise for mass screening remains questionable--even in developed countries such as Japan. Therefore, barium studies or serum-pepsinogen testing are sometimes used as the initial screening tool in some countries, and patients with abnormal results are screened by endoscopy. Despite the strong link between infection with Helicobacter pylori and gastric cancer, more data are needed to define the role of its eradication in the prevention of gastric cancer in Asia. At present, there is a paucity of quality data from Asia to lend support for screening for gastric cancer.

Age and distal colonic findings determine the yield of advanced proximal neoplasia in Chinese patients with rectal bleeding.

BACKGROUND AND AIMS: Few data were available on the optimal diagnostic strategy for Chinese patients with hematochezia. We aimed to evaluate the impact of age and distal colonic findings on the yield of diagnostic strategies in young Chinese patients with hematochezia. METHODS: Consecutive outpatients aged less than 50 years were analyzed using a hypothesized mixed diagnostic strategy to determine the optimal cut-off age for the use of sigmoidoscopy and colonoscopy. The efficacy and cost of the diagnostic strategy and the number of colonoscopies needed to detect one advanced proximal neoplasm (APN) using different cut-off ages were assessed. RESULTS: In the hypothesized mixed diagnostic strategy for young patients, the sensitivities for the detection of APN were 100%, 92% and 75% if the cut-off ages were 30, 35 and 40 years, respectively. The cost needed to detect one APN would be $US 3155, $US 3179 and $US 3497 if the cut-off ages were 30, 35 and 40 years, respectively. Colonoscopy would be performed in 84%, 69% and 51% of patients if the cut-off ages were 30, 35 and 40 years, respectively. CONCLUSION: Colonoscopy should be considered for Chinese patients with rectal bleeding who are aged > or =35 years or those aged <35 years who have adenoma in the distal colon.

Cost-effectiveness analysis between primary and secondary preventive strategies for gastric cancer.

OBJECTIVE: The present study is done to assess the relative cost-effectiveness, optimal initial age, and interscreening interval between primary and secondary prevention strategies for gastric cancer. METHODS: Base-case estimates, including variables of natural history, efficacy of intervention, and relevant cost, were derived from two preventive programs targeting a high-risk population. Cost-effectiveness was compared between chemoprevention with (13)C urea breath testing followed by Helicobacter pylori (H. pylori) eradication and high-risk surveillance based on serum pepsinogen measurement and confirmed by endoscopy. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The incremental cost-effectiveness ratio (ICER) for once-only chemoprevention at age 30 years versus no screening was U.S. $17,044 per life-year gained. Eradication of H. pylori at later age or with a periodic scheme yielded a less favorable result. Annual high-risk screening at age of 50 years versus no screening resulted in an ICER of U.S. $29,741 per life-year gained. The ICERs of surveillance did not substantially vary with different initial ages or interscreening intervals. Chemoprevention could be dominated by high-risk surveillance when the initial age was older than 44 years. Otherwise, chemoprevention was more cost-effective than high-risk surveillance, either at ceiling ratios of U.S. $15,762 or up to U.S. $50,000. The relative cost-effectiveness was most sensitive to the infection rate of H. pylori and proportion of early gastric cancer in all detectable cases. CONCLUSIONS: Early H. pylori eradication once in lifetime seems more cost-effective than surveillance strategy. However, the choice is still subject to the risk of infection, detectability of early gastric cancer, and timing of intervention.

A community-based study of Helicobacter pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures.

BACKGROUND: Although eradication of Helicobacter pylori infection can decrease the risk of gastric cancer, the optimal regimen for treating the general population remains unclear. We report the eradication rate (intention-to-treat and per protocol) of a community-based H. pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures. MATERIALS AND METHODS: In 2004, a total of 2658 residents were recruited for 13C-urea breath testing. Participants with positive results for infection received a standard 7-day triple therapy (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily), and a 10-day re-treatment (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) if the follow-up tests remained positive. Both H. pylori status and side-effects were assessed 6 weeks after treatment. RESULTS: Among 886 valid reporters, eradication rates with initial therapy were 86.9% (95% confidence interval [CI]: 84.7-89.1%) and 88.7% (95%CI: 86.5-90.9%) by intention-to-treat and per protocol analysis, respectively. Re-treatment eradicated infection in 91.4% (95%CI: 86-96.8%) of 105 nonresponders. Adequate compliance was achieved in 798 (90.1%) of 886 subjects receiving the initial treatment and in all 105 re-treated subjects. Mild side-effects occurred in 24% of subjects. Overall intention-to-treat and per protocol eradication rates were 97.7% (95%CI: 96.7-98.7%) and 98.8% (95%CI: 98.5-99.3%), respectively, which were only affected by poor compliance (odds ratio, 3.3; 95%CI, 1.99-5.48; p < .0001). CONCLUSIONS: A comprehensive plan using drugs in which the resistance rate is low in a population combined with the strategy of test, treat, retest, and re-treat of needed can result in virtual eradication of H. pylori from a population. This provides a model for planning country- or region-wide eradication programs.

Multistate and multifactorial progression of gastric cancer: results from community-based mass screening for gastric cancer.

Although multistate progression models for gastric cancer have been proposed, estimation of quantitative parameters of such models is yet to be done. The present study was conducted to elucidate risk factors for gastric cancer and its precursors, and to model the progression rates from superficial gastritis to gastric cancer. Data were derived from a community-based screening programme for gastric cancer in the Matzu region of Taiwan. A total of 2184 residents participated in a two-stage screening project. Subjects testing positive for Helicobacter pylori infection or pepsinogen (PGI or PII/PGII ratio) and immunoglobulin G (IgG), and subjects with a history of peptic ulcer or other upper gastrointestinal disease or with a family history of gastric cancer were referred to endoscopy. We identified 325 biopsy-proven precursors and gastric cancers, including 148 superficial gastritis (SG), 42 atrophic gastritis (AG), 117 intestinal metaplasia (IM) and two gastric cancers. Three further cancers were diagnosed on endoscopy alone and 14 were later diagnosed in those who did not comply with referral to endoscopy. A Markov process model was used to estimate the progression rates from superficial gastritis through to gastric cancer, with exponential regression to assess the effect of covariates on progression rates. The annual progression rate from SG to AG was 0.0670 (95% confidence interval [CI] 0.0446-0.0895). Annual progression rates from AG to IM and from IM to gastric cancer were 0.2775 (0.1665-0.3884) and 0.2265 (0.1315-0.3214), respectively. This gives average dwelling times in AG and IM of 3.60 years and 4.42 years, respectively. Progression from no disease to SG was significantly accelerated in those testing positive for H. pylori, those testing positive for PGI and in subjects with a family history of gastric cancer or a personal history of upper gastrointestinal disease. Further progression to AG and IM was significantly accelerated in those testing positive for PGI and in those with a history of upper gastrointestinal disease.