Annemarie C. de Vries

Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands.

BACKGROUND & AIMS A cascade of precursor lesions (eg, atrophic gastritis, intestinal metaplasia, and dysplasia) precedes most gastric adenocarcinomas. Quantification of gastric cancer risk in patients with premalignant gastric lesions is unclear, however. Consequently, endoscopic surveillance is controversial, especially in Western populations. METHODS To analyze current surveillance practice and gastric cancer risk in patients with premalignant gastric lesions, all patients with a first diagnosis between 1991 and 2004 were identified in the Dutch nationwide histopathology registry (PALGA); follow-up data were evaluated until December 2005. RESULTS In total, 22,365 (24%) patients were diagnosed with atrophic gastritis, 61,707 (67%) with intestinal metaplasia, 7616 (8%) with mild-to-moderate dysplasia, and 562 (0.6%) with severe dysplasia. Patients with a diagnosis of atrophic gastritis, intestinal metaplasia, or mild-to-moderate dysplasia received re-evaluation in 26%, 28%, and 38% of cases, respectively, compared with 61% after a diagnosis of severe dysplasia (P < .001). The annual incidence of gastric cancer was 0.1% for patients with atrophic gastritis, 0.25% for intestinal metaplasia, 0.6% for mild-to-moderate dysplasia, and 6% for severe dysplasia within 5 years after diagnosis. Risk factors for gastric cancer development were increasing severity of premalignant gastric lesions at initial diagnosis (eg, severe dysplasia, hazard ratio 40.14, 95% confidence interval 32.2-50.1), increased age (eg, 75-84 years, hazard ratio 3.75, 95% confidence interval 2.8-5.1), and male gender (hazard ratio 1.50, 95% CI 1.3-1.7). CONCLUSIONS Patients with premalignant gastric lesions are at considerable risk of gastric cancer. As current surveillance of these patients is inconsistent with their cancer risk, development of guidelines is indicated.

The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis.

BACKGROUND The OLGA (operative link on gastritis assessment) staging system is based on severity of atrophic gastritis (AG). AG remains a difficult histopathologic diagnosis with low interobserver agreement, whereas intestinal metaplasia (IM) is associated with high interobserver agreement. OBJECTIVE The aim of this study was to evaluate whether a staging system based on IM is preferable to estimate gastric cancer risk. DESIGN AND SETTING Prospective multicenter study. PATIENTS A total of 125 patients previously diagnosed with gastric IM or dysplasia. INTERVENTIONS Surveillance endoscopy with extensive biopsy sampling. MAIN OUTCOME MEASUREMENTS Three pathologists graded biopsy specimens according to the Sydney classification. Interobserver agreement was analyzed by kappa statistics. In the OLGA, AG was replaced by IM, creating the OLGIM. RESULTS Interobserver agreement was fair for dysplasia (kappa = 0.4), substantial for AG (kappa = 0.6), almost perfect for IM (kappa = 0.9), and improved for all stages of OLGIM compared with OLGA. Overall, 84 (67%) and 79 (63%) patients were classified as stage I-IV according to OLGA and OLGIM, respectively. Of the dysplasia patients, 5 (71%) and 6 (86%) clustered in stage III-IV of OLGA and OLGIM, respectively. LIMITATION Prospective studies should confirm the correlation between gastric cancer risk and OLGIM stages. CONCLUSION Replacement of AG by IM in the staging of gastritis considerably increases interobserver agreement. The correlation with the severity of gastritis remains at least as strong. Therefore, the OLGIM may be preferred over the OLGA for the prediction of gastric cancer risk in patients with premalignant lesions.

Randomized controlled trials of antibiotic prophylaxis in severe acute pancreatitis: Relationship between methodological quality and outcome

Aim: To evaluate the methodological quality of randomized controlled trials (RCTs) of systemic antibiotic prophylaxis in severe acute pancreatitis in relation to outcome. Methods: The MEDLINE, EMBASE and Cochrane databases were searched for RCTs that studied the effectiveness of systemic antibiotic prophylaxis in severe acute pancreatitis. A meta-analysis was performed with a random effects model. Methodological quality was quantified by a previously published scoring system (range 0–17 points). Results: Six studies, with a total of 397 participants, obtained a methodological score of at least 5 points and were included. Systemic antibiotic prophylaxis had no significant effect on infection of pancreatic necrosis (absolute risk reduction (ARR) 0.055; 95% CI –0.084 to 0.194) and mortality (ARR 0.058, 95% CI –0.017 to 0.134). Spearman correlation showed an inverse association between methodological quality and ARR for mortality (correlation coefficient –0.841, p = 0.036). Conclusions: The inverse relationship between methodological quality and impact of antibiotic prophylaxis on mortality emphasizes the importance of high-quality RCTs. At present, adequate evidence for the routine use of antibiotic prophylaxis in severe acute pancreatitis is lacking.

Identification of genetic loci associated with Helicobacter pylori serologic status.

IMPORTANCE Helicobacter pylori is a major cause of gastritis and gastroduodenal ulcer disease and can cause cancer. H. pylori prevalence is as high as 90% in some developing countries but 10% of a given population is never colonized, regardless of exposure. Genetic factors are hypothesized to confer H. pylori susceptibility. OBJECTIVE To identify genetic loci associated with H. pylori seroprevalence in 2 independent population-based cohorts and to determine their putative pathophysiological role by whole-blood RNA gene expression profiling. DESIGN, SETTING, AND PARTICIPANTS Two independent genome-wide association studies (GWASs) and a subsequent meta-analysis were conducted for anti-H. pylori IgG serology in the Study of Health in Pomerania (SHIP) (recruitment, 1997-2001 [n = 3830]) as well as the Rotterdam Study (RS-I) (recruitment, 1990-1993) and RS-II (recruitment, 2000-2001 [n = 7108]) populations. Whole-blood RNA gene expression profiles were analyzed in RS-III (recruitment, 2006-2008 [n = 762]) and SHIP-TREND (recruitment, 2008-2012 [n = 991]), and fecal H. pylori antigen in SHIP-TREND (n = 961). MAIN OUTCOMES AND MEASURES H. pylori seroprevalence. RESULTS Of 10,938 participants, 6160 (56.3%) were seropositive for H. pylori. GWASs identified the toll-like receptor (TLR) locus (4p14; top-ranked single-nucleotide polymorphism (SNP), rs10004195; P = 1.4 × 10(-18); odds ratio, 0.70 [95% CI, 0.65 to 0.76]) and the FCGR2A locus (1q23.3; top-ranked SNP, rs368433; P = 2.1 × 10(-8); odds ratio, 0.73 [95% CI, 0.65 to 0.81]) as associated with H. pylori seroprevalence. Among the 3 TLR genes at 4p14, only TLR1 was differentially expressed per copy number of the minor rs10004195-A allele (β = -0.23 [95% CI, -0.34 to -0.11]; P = 2.1 × 10(-4)). Individuals with high fecal H. pylori antigen titers (optical density >1) also exhibited the highest 25% of TLR1 expression levels (P = .01 by χ2 test). Furthermore, TLR1 exhibited an Asn248Ser substitution in the extracellular domain strongly linked to the rs10004195 SNP. CONCLUSIONS AND RELEVANCE GWAS meta-analysis identified an association between TLR1 and H. pylori seroprevalence, a finding that requires replication in nonwhite populations. If confirmed, genetic variations in TLR1 may help explain some of the observed variation in individual risk for H. pylori infection.

Early endoscopic retrograde cholangiopancreatography in predicted severe acute biliary pancreatitis: A prospective multicenter study

Summary Background Data:The role of early endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) remains controversial. Previous studies have included only a relatively small number of patients with predicted severe ABP. We investigated the clinical effects of early ERCP in these patients. Methods:We performed a prospective, observational multicenter study in 8 university medical centers and 7 major teaching hospitals. One hundred fifty-three patients with predicted severe ABP without cholangitis enrolled in a randomized multicenter trial on probiotic prophylaxis in acute pancreatitis were prospectively followed. Conservative treatment or ERCP within 72 hours after symptom onset (at discretion of the treating physician) were compared for complications and mortality. Patients without and with cholestasis (bilirubin: >2.3 mg/dL [40 &mgr;mol/L] and/or dilated common bile duct) were analyzed separately. Results:Of the 153 patients, 81 (53%) underwent ERCP and 72 (47%) conservative treatment. Groups were highly comparable at baseline. Seventy-eight patients (51%) had cholestasis. In patients with cholestasis, ERCP (52/78 patients: 67%), as compared with conservative treatment, was associated with fewer complications (25% vs. 54%, P = 0.020, multivariate adjusted odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.13–0.99, P= 0.049). This included fewer patients with >30% pancreatic necrosis (8% vs. 31%, P = 0.010). Mortality was nonsignificantly lower after ERCP (6% vs. 15%, P = 0.213, multivariate adjusted OR: 0.44, 95% CI: 0.08–2.28, P = 0.330). In patients without cholestasis, ERCP (29/75 patients: 39%) was not associated with reduced complications (45% vs. 41%, P = 0.814, multivariate adjusted OR: 1.36; 95% CI: 0.49–3.76; P = 0.554) or mortality (14% vs. 17%, P = 0.754, multivariate adjusted OR: 0.78; 95% CI: 0.19–3.12, P = 0.734). Conclusions:Early ERCP is associated with fewer complications in predicted severe ABP if cholestasis is present.

Epidemiology of Premalignant Gastric Lesions: Implications for the Development of Screening and Surveillance Strategies

Gastric cancer is one of the most common cancers worldwide; however, gastric cancer incidence varies greatly between different geographic areas. As gastric cancer is usually diagnosed at an advanced stage, the disease causes considerable morbidity and mortality. To detect gastric carcinomas at an early and curable stage, screening and surveillance seem necessary. Premalignant gastric lesions are well known risk factors for the development of intestinal type gastric adenocarcinomas. In a multistep cascade, chronic Helicobacter pylori‐induced gastritis progresses through premalignant stages of atrophic gastritis, intestinal metaplasia and dysplasia, to eventually gastric cancer. Therefore, this cascade may provide a basis for early detection and treatment of gastric cancer. Epidemiology of gastric cancer and premalignant gastric lesions should guide the development of screening and surveillance strategies, as distinct approaches are required in countries with low and high gastric cancer incidences.

Migrant communities constitute a possible target population for primary prevention of Helicobacter pylori-related complications in low incidence countries.

Objective. Pre-selection of individuals with epidemiological risk factors for Helicobacter pylori infection and atrophic gastritis could increase the efficiency of serologic screening to prevent peptic ulcer disease and gastric cancer in Western countries. The aim of this study was to determine the prevalence of and risk factors for H. pylori infection and atrophic gastritis in a migrant community in The Netherlands. Material and methods. Inhabitants from an urban district in Rotterdam, The Netherlands with a large proportion of immigrants were randomly selected. Information was collected on demographic factors, socio-economic status, lifestyle, history of dyspeptic symptoms and medication use. In addition, serologic H. pylori and CagA status and the presence of atrophic gastritis were evaluated. Results. In total, 288 subjects were included. Surinamese or Antillean, Turkish, Cape Verdian and Moroccan subjects were H. pylori-infected in 65%, 82%, 86% and 96% of cases, respectively, whereas the infection rate in Dutch subjects was 46% (all p<0.05). Within multivariate logistic regression analysis, ethnicity and number of persons in a household were identified as independent risk factors for H. pylori infection. In addition, mean pepsinogen I level and pepsinogen I/II ratio were significantly lower in subjects of non-Dutch origin as compared to Dutch subjects (both p<0.001). No Dutch subjects suffered from atrophic gastritis, as compared with 12 subjects of non-Dutch origin (p=0.13). Conclusions. The prevalence of H. pylori is high in migrant populations in The Netherlands. Furthermore, markers of atrophic gastritis are increased in subjects of foreign origin. Therefore, these migrant communities may constitute a target group for serologic screening to prevent H. pylori-related complications in Western countries.

Biopsy Strategies for Endoscopic Surveillance of Pre-malignant Gastric Lesions

Background:  Endoscopic surveillance of pre‐malignant gastric lesions may add to gastric cancer prevention. However, the appropriate biopsy regimen for optimal detection of the most advanced lesions remains to be determined. Therefore, we evaluated the yield of endoscopic surveillance by standardized and targeted biopsy protocols.

The use of clinical, histologic, and serologic parameters to predict the intragastric extent of intestinal metaplasia: a recommendation for routine practice.

BACKGROUND Surveillance of intestinal metaplasia (IM) of the gastric mucosa should be limited to patients at high risk of gastric cancer. Patients with extensive IM are at increased cancer risk; however, the intragastric extent of IM is usually unknown at the time of the initial diagnosis. OBJECTIVE To assess the predictive value of clinical, histologic, and serologic parameters for the intragastric extent of IM. DESIGN AND SETTING Prospective, multicenter study. PATIENTS Eighty-eight patients with a previous diagnosis of IM of the gastric mucosa. INTERVENTION Surveillance gastroscopy with extensive random biopsy sampling. MAIN OUTCOME MEASUREMENTS Biopsy specimens were evaluated according to the Sydney classification system. In addition, serologic testing of Helicobacter pylori and cagA status, pepsinogens I and II, gastrin, and intrinsic factor antibodies was performed. The association between the available parameters and extensive IM was evaluated with logistic regression analysis. RESULTS In 51 patients (58%), IM was present in the biopsy specimens from at least 2 intragastric locations. The most important predictors of extensive IM were a family history of gastric cancer, alcohol use > or = 1 unit/d (1 glass, approximately 10 mL or 8 g ethanol), moderate or marked IM of the index biopsy specimen, and a pepsinogen I to II ratio < 3.0. A simple risk score based on these factors could identify extensive IM in 24 of 25 patients (sensitivity 96%). LIMITATION A prospective cohort study should confirm the proposed risk stratification. CONCLUSIONS A risk score of clinical, histologic, and serologic parameters can predict extensive intragastric IM and may serve as a practical tool to select patients for surveillance endoscopy in routine clinical practice.

Increased risk of esophageal squamous cell carcinoma in patients with gastric atrophy: Independent of the severity of atrophic changes

An association between gastric atrophy and esophageal squamous cell carcinomas (ESCC) has been described. However, the mechanism of this association is unknown. In this study, we aimed to examine this relationship in a cohort of patients with varying grades of gastric atrophy to increase the understanding about the causality of the association. Patients diagnosed with gastric atrophy between 1991 and 2005 were identified in the Dutch nationwide histopathology registry (PALGA). The incidence of ESCC and, presumably unrelated, small cell lung carcinomas (SCLC) observed in these patients was compared with that in the general Dutch population. Relative risks (RRs) and 95% confidence intervals were calculated by a Poisson model. At baseline histological examination, 97,728 patients were diagnosed with gastric atrophy, of whom 23,278 with atrophic gastritis, 65,934 with intestinal metaplasia and 8,516 with dysplasia. During follow‐up, 126 patients were diagnosed with ESCC and 263 with SCLC (overall rates 0.19, respectively 0.39/1,000 person‐years at risk). Compared with the general Dutch population, patients with gastric atrophy ran a RR of developing ESCC of 2.2 [95% CI 1.8–2.6] and of SCLC of 1.8 [95% CI 1.6–2.1]. The risk of ESCC did not increase with increasing severity of gastric atrophy (p = 0.90). In conclusion, this study found an association between gastric atrophy and both ESCC and SCLC, but the risk of ESCC did not increase with the severity of gastric atrophy. Therefore, a causal relationship seems unlikely. Confounding factors, such as smoking, may explain both associations.