Long-term outcomes after endoscopic treatment for Barrett's neoplasia with radiofrequency ablation ± endoscopic resection: results from the national Dutch database in a 10-year period.

OBJECTIVE: Radiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett's oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting. DESIGN: Endoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included. RESULTS: After ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0-1; 1-2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22-69) and 4 endoscopies (1-5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk. CONCLUSION: In a setting of centralised care, RFA±ER is effective for eradication of Barrett's related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value. NETHERLANDS TRIAL REGISTER NUMBER: NL7039.

The SpaTemp cohort: 168 nondysplastic Barrett's esophagus surveillance patients with and without progression to early neoplasia to evaluate the distribution of biomarkers over space and time.

The ReBus cohort is a matched nested case-control cohort of patients with nondysplastic (ND) Barrett's esophagus (BE) at baseline who progressed (progressors) or did not progress (nonprogressors) to high-grade dysplasia (HGD) or cancer. This cohort is constructed using the most stringent inclusion criteria to optimize explorative studies on biomarkers predicting malignant progression in NDBE. These explorative studies may benefit from expanding the number of cases and by incorporating samples that allow assessment of the biomarker over space (spatial variability) and over time (temporal variability). To (i) update the ReBus cohort by identifying new progressors and (ii) identify progressors and nonprogressors within the updated ReBus cohort containing spatial and temporal information. The ReBus cohort was updated by identifying Barrett's patients referred for endoscopic work-up of neoplasia at 4 tertiary referral centers. Progressors and nonprogressors with a multilevel (spatial) endoscopy and additional prior (temporal) endoscopies were identified to evaluate biomarkers over space and over time. The original ReBus cohort consisted of 165 progressors and 723 nonprogressors. We identified 65 new progressors meeting the same strict selection criteria, resulting in a total number of 230 progressors and 723 matched nonprogressors in the updated ReBus cohort. Within the updated cohort, 61 progressors and 107 nonprogressors (mean age 61 ± 10 years) with a spatial endoscopy (median level 3 [2-4]) were identified. 33/61 progressors and 50/107 nonprogressors had a median of 3 (2-4) additional temporal endoscopies. Our updated ReBus cohort consists of 230 progressors and 723 matched nonprogressors using the most strict selection criteria. In a subgroup of 168 Barrett's patients (the SpaTemp cohort), multiple levels have been sampled at baseline and during follow-up providing a unique platform to study spatial and temporal distribution of biomarkers in BE.

Endoscopic Resection Without Subsequent Ablation Therapy for Early Barrett's Neoplasia: Endoscopic Findings and Long-Term Mortality.

INTRODUCTION: After endoscopic resection (ER) of neoplasia in Barrett's esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status. METHODS: Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality. RESULTS: Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11-51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC. CONCLUSION: In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation.

Safety of endoscopic mucosal resection (EMR) of large non-pedunculated colorectal adenomas in the elderly.

BACKGROUND: Endoscopic mucosal resection (EMR) has been proven to be safe and effective for the treatment of colorectal adenomas. However, data are limited on the safety of this technique for large polyps and in elderly patients. Aims of our study were to examine the bleeding and perforation rates in patients with large non-pedunculated adenomas (≥20mm) and to evaluate the influence of size (≥40mm) and age (≥75 years) on the complication rates. METHODS: In this multicenter retrospective study, patients who underwent EMR of non-pedunculated adenomas ≥20mm between January 2012 and March 2016 were included. The demographics of the patients, the use of antithrombotic drugs, size of the polyps, type of resection, pathology report, occurrence of post-polypectomy bleeding, and perforation- and recurrence rate were collected. RESULTS: In 343 patients, 412 adenomas were removed. Eighty patients (23.3%) were ≥75 years of age, 138 polyps (33.5%) were ≥40mm. Bleeding complications were observed in 28 cases (6.8%) and were found significantly more frequent in adenomas ≥40mm, independent of the use of antithrombotic therapy. Five perforations (1.2%) were described, not related to the size of the polyp. There was no significant difference in complication rates between patients <75 years and patients ≥75 years. Bleeding complications rates were significantly higher in patients receiving double antithrombotic therapy. CONCLUSION: EMR is safe in elderly patients. EMR of adenomas of ≥40mm was associated with more bleeding complications. Future studies should address how the bleeding rates can be reduced in these patients, especially in those who use double antithrombotic treatment.

Learning endoscopic resection in the esophagus.

BACKGROUND: Endoscopic resection is the cornerstone of endoscopic management of esophageal early neoplasia. However, endoscopic resection is a complex technique requiring knowledge and expertise. Our aims were to identify the most important learning points in performing endoscopic resection in a training setting and to provide information on how to improve endoscopic resection technique. METHODS: Six gastroenterologists at centers with multidisciplinary expertise in upper gastrointestinal oncology participated in a structured endoscopic resection training program, consisting of four training days with lectures and hands-on training on live pigs, further one-to-one hands-on training days, and written feedback (by an expert) on videos of unsupervised endoscopic resection procedures. The first 20 endoscopic resections of each participant were prospectively registered. Ninety learning points were independently identified by participants using a standardized questionnaire and by an expert providing written feedback on 33 unsupervised endoscopic resection videos. Three expert endoscopists selected and ranked the most important learning points in a consensus meeting. Results. The top 10 tips (illustrated by unique videos of three perforations) were: (1) allow time for inspection and use a high-definition endoscope; (2) create a preprocedural plan by placing electrocoagulation markings; (3) know the management of bleeding; (4) optimize the endoscopic view by repeatedly cleaning out stomach and target area; (5) use a therapeutic endoscope during resection; (6) always perform a test suction; (7) keep instruments close to the tip; (8) lift edges in piecemeal endoscopic cap resections; (9) know the management of perforation; (10) pin specimens down. CONCLUSIONS: This study summarized the most important learning points for performing endoscopic resection encountered during a structured endoscopic resection training program.

Predictive factors for initial treatment response after circumferential radiofrequency ablation for Barrett's esophagus with early neoplasia: a prospective multicenter study.

BACKGROUND AND STUDY AIMS: Radiofrequency ablation (RFA) is safe and effective for the eradication of neoplastic Barrett's esophagus; however, occasionally there is minimal regression after initial circumferential balloon-based RFA (c-RFA). This study aimed to identify predictive factors for a poor response 3 months after c-RFA, and to relate the percentage regression at 3 months to the final treatment outcome. METHODS: We included consecutive patients from 14 centers who underwent c-RFA for high grade dysplasia at worst. Patient and treatment characteristics were registered prospectively. "Poor initial response" was defined as < 50 % regression of the Barrett's esophagus 3 months after c-RFA, graded by two expert endoscopists using endoscopic images. Predictors of initial response were identified through logistic regression analysis. RESULTS: There were 278 patients included (median Barrett's segment C4M6). In poor initial responders (n = 36; 13 %), complete response for neoplasia (CR-neoplasia) was ultimately achieved in 86 % (vs. 98 % in good responders; P < 0.01) and complete response for intestinal metaplasia (CR-IM) in 66 % (vs. 95 %; P < 0.01). Poor responders required 13 months treatment (vs. 7 months; P < 0.01) for a median of four RFA sessions (vs. three; P < 0.01). We identified four independent baseline predictors of poor response: active reflux esophagitis (odds ratio [OR] 37.4; 95 % confidence interval [CI] 3.2 - 433.2); endoscopic resection scar regeneration with Barrett's epithelium (OR 4.7; 95 %CI 1.1 - 20.0); esophageal narrowing pre-RFA (OR 3.9; 95 %CI 1.0 - 15.1); and years of neoplasia pre-RFA (OR 1.2; 95 %CI 1.0 - 1.4). CONCLUSIONS: Patients with a poor initial response to c-RFA have a lower ultimate success rate for CR-neoplasia/CR-IM, require more treatment sessions, and a longer treatment period. A poor initial response to c-RFA occurs more frequently in patients who regenerate their endoscopic resection scar with Barrett's epithelium, and those with ongoing reflux esophagitis, neoplasia in Barrett's esophagus for a longer time, or a narrow esophagus.

Learning to perform endoscopic resection of esophageal neoplasia is associated with significant complications even within a structured training program.

BACKGROUND AND STUDY AIMS: Endoscopic resection is the cornerstone of endoscopic treatment of esophageal high grade dysplasia or early cancer. Endoscopic resection is, however, a technically demanding procedure, which requires training and expertise. The aim of the current study was to prospectively evaluate efficacy and safety of the first 120 endoscopic resection procedures of early esophageal neoplasia performed by six endoscopists (20 endoscopic resections each) who were participating in an endoscopic resection training program. PATIENTS AND METHODS: The program consisted of four tri-monthly 1-day courses with lectures, live-demonstrations, hands-on training on anesthetized pigs, and one-on-one hands-on training days. Gastroenterologists from centers with multidisciplinary expertise in upper gastrointestinal oncology participated, together with an endoscopy nurse and a pathologist. Outcome measures were complete endoscopic removal of the target area and acute complications. RESULTS: A total of 120 consecutive esophageal endoscopic resection procedures (85 ER-cap, 35 multiband mucosectomy [MBM]) were performed by six endoscopists: 109 in Barrett's esophagus, 11 for squamous neoplasia; 85 piecemeal endoscopic resections (median 3 specimens, interquartile range 2 - 4 specimens). Complete endoscopic removal was achieved in 111 /120 cases (92.5 %). Six perforations occurred (5.0 %): five were effectively treated endoscopically (clips, covered stent), and one patient underwent esophagectomy. There were 11 acute mild bleedings (9.2 %), which were managed endoscopically. Perforations occurred in ER-cap procedures performed by four participants (7.1 % ER-cap vs. 0 % MBM; P = 0.18), and in 1.7 % of the first 10 endoscopic resections and 8.3 % of the second 10 endoscopic resections per endoscopist (P = 0.26). CONCLUSION: In this intense, structured training program, the first 120 esophageal endoscopic resections performed by six participants were associated with a 5.0 % perforation rate. Although perforations were adequately managed, performing 20 endoscopic resections may not be sufficient to reach the peak of the learning curve in endoscopic resection.

Detection of a nosocomial outbreak of salmonellosis may be delayed by application of a protocol for rejection of stool cultures.

In October 2001 an outbreak of Salmonella enterica serovar enteritidis phage-type 6 occurred in a hospital and a nursing home, both served by the same hospital kitchen. Five nursing home residents died during the outbreak. S. enteritidis was isolated from three of them. Of 231 stool samples from nursing home residents, hospital patients and employees, 82 were culture-positive. All symptomatic patients were treated with oral ciprofloxacin. Inspection of the kitchen showed that during preparation of the desserts implicated in causing the outbreak, temperatures were not measured and storage temperatures were too high. No left-over food samples were available for analysis. According to the 'four-day rule' in use in this hospital, the stool samples related to the first outbreak were not cultured for Salmonella spp., whereas culturing afterwards from both stored specimens and repeats, showed that some of these samples would have been positive for S. enteritidis. Thus without the application of stool culture rejection criteria the outbreak would have been detected one day earlier. With the four-day rule in effect, the outbreak might have been detected much later, if an unusually high number of nursing home residents with gastroenteritis had not been noticed by nursing home physicians. The rule was revised to prevent a possible delay in the future. As a result of this outbreak, the government has announced legislation forbidding the sale of Salmonella-contaminated eggs. An official ban on the use of raw eggs will be included in several hygiene codes.

Parietal cell protrusions and fundic gland cysts during omeprazole maintenance treatment.

Parietal cell protrusion (PCP), swelling and bulging of parietal cells, has been observed in the oxyntic mucosa of patients receiving omeprazole. The frequency of this event and the underlying mechanisms remain to be clarified. As such, it is unknown whether there is a relation with either serum gastrin or Helicobacter pylori infection, and whether PCP predisposes to the development of fundic gland cysts (FGC). We therefore investigated the development of PCP and FGC in gastroesophageal reflux disease (GERD) patients treated with omeprazole and correlated findings to duration of therapy, gastrin, and H pylori infection. In a randomized, double-blinded study, GERD patients were evaluated by endoscopy with biopsy sampling for histology and culture at baseline, and after 3 and 12 months' therapy with omeprazole 40 mg daily. H pylori-positive patients were randomized to additional eradication therapy or placebo antibiotics at baseline. All histological slides were scored blinded for time and outcome of culture for the presence of PCP and FGC. Fasting serum samples from all visits were used for gastrin measurements. The prevalence of PCP increased during omeprazole therapy from 18% at baseline to 79% and 86% at 3 and 12 months (P < .001, baseline v both 3 and 12 months). The prevalence of FGC increased from 8% to 17% and 35% (P < .05, baseline v 12 months). The prevalence of PCP and FGC did not differ among the H pylori-positive and H pylori-negative patients at baseline (PCP 16% v 20% and FGC 7% v 8%, respectively). Whereas H pylori eradication did not significantly affect development of PCP (P = .7), FGC developed significantly more often in the H pylori-eradicated patients when compared with persistent H pylori-positive patients (P < .05). PCP development was related to serum gastrin rise during therapy. In conclusion, PCP occurs in most patients within the first months of omeprazole treatment and is related to increased gastrin levels. FGC develops more gradually and is enhanced by H pylori eradication.

Effect of Helicobacter pylori eradication on chronic gastritis during omeprazole therapy.

BACKGROUND: We have previously observed that profound acid suppressive therapy in Helicobacter pylori positive patients with gastro-oesophageal reflux disease is associated with increased corpus inflammation and accelerated development of atrophic gastritis. AIM: To investigate if H pylori eradication at the start of acid suppressive therapy prevents the development of these histological changes. PATIENTS/METHODS: In a prospective randomised case control study, patients with reflux oesophagitis were treated with omeprazole 40 mg once daily for 12 months. H pylori positive patients were randomised to additional double blind treatment with omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily or placebo for one week. Biopsy sampling for histology, scored according to the updated Sydney classification, and culture were performed at baseline, and at three and 12 months. RESULTS: In the persistently H pylori positive group (n=24), active inflammation increased in the corpus and decreased in the antrum during therapy (p=0.032 and p=0.002, respectively). In contrast, in the H pylori positive group that became H pylori negative as a result of treatment (n=33), active and chronic inflammation in both the corpus and antrum decreased (p

Atrophic gastritis during long-term omeprazole therapy affects serum vitamin B12 levels.

BACKGROUND: Omeprazole maintenance therapy for gastro-oesophageal reflux disease (GERD) has been associated with an increased incidence of atrophic gastritis in H. pylori-infected patients and with a decreased absorption of protein-bound, but not of unbound cobalamin. AIM: : To test the hypothesis that the combination of decreased cobalamin absorption and atrophic gastritis decreases serum cobalamin levels during omeprazole therapy. METHODS: Forty-nine H. pylori-positive GERD patients were treated with omeprazole for a mean (+/- s.d.) period of 61 (25) months. At the start of omeprazole treatment (T0) and at the latest follow-up visit (T1), serum was obtained for measurement of cobalamin. Corpus biopsy specimens were obtained at entry and follow-up for histopathological scoring according to the updated Sydney classification. RESULTS: At inclusion, none of the 49 patients had signs of atrophic gastritis. During follow-up, 15 patients (33%) developed atrophic gastritis, nine of whom had moderate to severe atrophy. These 15 patients did not differ from the other 34 patients with respect to age, serum cobalamin at T0 or the duration of follow-up. During follow-up, no change was observed in the median serum cobalamin level in the 34 patients without atrophy; (T0) 312 (136-716) vs. (T1) 341 (136-839) pmol/L (P=0.1). In the 15 patients who developed atrophy, a decrease in cobalamin was seen from 340 (171 to 787) at baseline to 285 (156-716) at latest follow-up (P < 0.01). CONCLUSIONS: The development of atrophic gastritis during omeprazole treatment in H. pylori-positive GERD patients is associated with a decrease of serum vitamin B12 levels.

Helicobacter pylori and the efficacy of omeprazole therapy for gastroesophageal reflux disease.

OBJECTIVE: Helicobacter pylori infection may affect gastric acid output and intragastric pH. In patients with an insufficient lower esophageal sphincter, this effect may theoretically influence the severity of reflux disease, as well as the efficacy of acid suppressive therapy. To evaluate whether the H. pylori status of patients with gastroesophageal reflux disease (GERD) affects the severity of disease and the efficacy of omeprazole therapy to maintain disease remission, we conducted this study. METHODS: Patients with GERD were prospectively studied by upper gastrointestinal endoscopy with biopsy sampling for histology and H. pylori culture before start of treatment and at annual follow-up. At endoscopy, esophagitis was graded according to the criteria of Savary-Miller, and the presence of Barrett's esophagus, hiatal herniation, or other abnormalities was recorded. Omeprazole was started at an initial dose of 20 mg daily; the dose was adjusted based on symptoms and the endoscopical findings. RESULTS: One hundred thirty-seven GERD patients were included and followed up for a mean 56.6 months; 49 (36%) of them were infected with H. pylori. H. pylori-infected and -uninfected patients did not differ with respect to age (60 +/- 13 vs 61 +/- 14 yr, p = 0.65) or duration of follow-up (54 +/- 30 vs 58 +/- 31 months, p = 0.12). H. pylori-negative patients tended to present with more severe esophagitis at baseline (median Savary-Miller score 3 vs 2, p = 0.06) and had a higher prevalence of Barrett's esophagus (39/88 vs 10/49, p = 0.006). However, no difference was found with respect to the dose of omeprazole needed for maintained relief of symptoms and endoscopical signs of esophagitis (median 40 mg in both groups, p = 0.35). CONCLUSIONS: H. pylori-negative GERD patients have a higher prevalence of Barrett's esophagus, but do not need a higher dose of omeprazole to maintain symptomatic and endoscopical disease remission.

Hypergastrinaemia during long-term omeprazole therapy: influences of vagal nerve function, gastric emptying and Helicobacter pylori infection.

AIM: elucidate the mechanisms that lead to severe hypergastrinaemia during long-term omeprazole therapy for gastro-oesophageal reflux disease (GERD). PATIENTS AND METHODS: A total of 26 GERD patients were studied during omeprazole maintenance therapy. Twelve patients with severe hypergastrinaemia (gastrin > 400 ng/L) were compared with 14 control patients (gastrin < 300 ng/L). Helicobacter pylori serology and a laboratory screen were obtained in all patients. Gastric emptying was scored by the evidence of food remnants upon endoscopy 12 h after a standardized meal. Gastric antrum and corpus biopsies were analysed for histological parameters, as well as somatostatin and gastrin concentrations. All patients underwent a meal-stimulated gastrin test and the hypergastrinaemia patients also underwent a vagal nerve integrity assessment by pancreatic polypeptide testing (PPT). RESULTS: Severe hypergastrinaemia patients had a longer duration of treatment (80 vs. 55 months; P = 0.047) and were characterized by a higher prevalence of H. pylori infection (9/12 vs. 2/14, P = 0.004), corpus mucosal inflammation and atrophic gastritis (P < 0.04). This was reflected in lower serum pepsinogen A concentrations (mean +/- S.E.M. 53.6 +/- 17.9 vs. 137 +/- 16.0 mg/L, P = 0.03), pepsinogen A/C ratio (1.8 +/- 0.3 vs. 4.1 +/- 0.6, P = 0.005) and mucosal somatostatin concentrations (2.75 +/- 0.60 vs. 4.48 +/- 1.08 mg/g protein, P = 0.038). Two patients in the hypergastrinaemia group had signs of delayed gastric emptying, but none in the normogastrinaemia group did (P = N.S.). In addition, both groups had a normal meal-stimulated gastrin response. CONCLUSION: Severe hypergastrinaemia during omeprazole maintenance therapy for GERD is associated with the duration of therapy and H. pylori infection, but not with abnormalities of gastric emptying or vagal nerve integrity.

Omeprazole as a diagnostic tool in gastroesophageal reflux disease.

OBJECTIVE: To determine the diagnostic value of empirical treatment with omeprazole in the diagnosis of gastroesophageal reflux disease (GERD). METHODS: Patients with symptoms suggestive of GERD underwent upper gastrointestinal endoscopy and 24-h esophageal pH monitoring. Patients with reflux esophagitis grade 0 or 1 were included in the study and were randomized to double-blind treatment with either 40 mg omeprazole or placebo o.m. The effect of treatment was evaluated after 1 and 2 wk with a symptom questionnaire with a four-grade Likert scale, and symptomatic response outcome was compared with the results of 24-h pH-metry. RESULTS: Ninety-eight patients were included; however, 13 were excluded from the final analysis because of protocol violation. Of the remaining 85 patients, 54 had no signs of esophagitis at endoscopy, and 31 had esophagitis grade 1. The pH registration showed pathological gastroesophageal reflux in 47 patients (55%). Forty-one patients were randomized to treatment with omeprazole and 44 to placebo. There was a significant correlation between the pH registration result and response to omeprazole (p = 0.04, chi2), but not to placebo (p = 0.16). With pH-metry as the gold standard, the omeprazole test had positive and negative predictive values of 68% and 63%, respectively, for the diagnosis of GERD. When the omeprazole test was used as the gold standard, the positive and negative predictive values of pH monitoring were 68 % and 63 %, respectively. Similar sensitivity was found when the pH-metry was compared with presence of esophagitis. CONCLUSION: Determination of the symptomatic response to 40 mg of omeprazole for 14 days is a simple and inexpensive tool for the diagnosis of GERD, with a sensitivity and specificity comparable to 24-h pH monitoring.

Role of Helicobacter pylori in the pathogenesis of atrophic gastritis.

BACKGROUND: Atrophic gastritis is defined as a loss of the glandular structures and a collapse of the reticulin skeleton of the stomach mucosa. It is often accompanied by intestinal metaplasia. Both conditions result from long-term persistent chronic active gastritis and significantly increase the risk for gastric cancer. METHODS: Review of the role of Helicobacter pylori in the pathogenesis of atrophic gastritis. Specific attention is given to the classifications and histologic features of atrophic gastritis, the frequency with which atrophic gastritis occurs in H. pylori-infected subjects, the factors that influence the process of development of atrophic gastritis in the presence of infection, and the various mechanisms by which this bacterial infection may induce atrophic gastritis. In addition, the possible role of H. pylori in the etiology of auto-immune atrophic gastritis and pernicious anemia is discussed. CONCLUSIONS: H. pylori infection eventually causes atrophic gastritis in a considerable number of infected subjects. In different populations, the prevalence of atrophic gastritis increases by 1 to 3% per annum. Factors that may increase the risk for atrophy are infection at an early age, cytotoxin production by the infecting strain, and lowering of acid output. The association between H. pylori infection and the development of atrophic gastritis significantly supports the role of this infection in gastric carcinogenesis.

Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin.

AIMS: To evaluate absorption of protein-bound and unbound cyanocobalamin before and during treatment with omeprazole, and cobalamin levels in patients on long-term treatment with omeprazole. METHODS: In eight former duodenal ulcer patients absorption of unbound and protein-bound cobalamin was determined by measuring 24-h urinary excretion of unbound 58Co-cyancobalamin or protein-bound 57Co-cyanocobalamin during a modified Schilling test. Tests were performed before and during treatment with 20 mg and 40 mg omeprazole daily for 9 days. Serum cobalamin levels were assessed in 25 patients with gastro-oesophageal reflux disease (GERD) before and during long-term maintenance therapy with omeprazole. Mean treatment duration was 56 months (range 36-81 months). RESULTS: Urinary excretion of unbound cobalamin was unchanged with both dosages of omeprazole. Excretion of 57Co-cyanocobalamin, however, decreased significantly during treatment with both 20 mg omeprazole (mean +/- S.E.M.: 1.31 +/- 0.20 vs. 0.54 +/- 0.17%; P < 0.02) and 40 mg omeprazole (1.25 +/- 0.26 vs. 0.29 +/- 0.06%; P < 0.02). Mean serum cobalamin levels (+/- S.E.M.) before and during therapy with omeprazole in GERD patients were 298 +/- 27 and 261 +/- 16 pg/mL (normal range 180-900 pg/mL), respectively (P = N.S.). CONCLUSIONS: Absorption of protein-bound, but not unbound, cyanocobalamin is decreased when measured by a modified Schilling test during treatment with omeprazole. However, no change in serum cobalamin levels was observed in patients with GERD after treatment with omeprazole for up to 7 years.

The role of plasma D-dimers concentration in the exclusion of pulmonary embolism.

OBJECTIVE: To determine the role of four ELISA D-dimer assays in the exclusion of pulmonary embolism. DESIGN: Blinded comparison using pulmonary angiography and/or lung scintigraphy as a reference method. SETTING: A secondary and tertiary referral centre. PATIENTS AND METHODS: Consecutive patients with suspected pulmonary embolism underwent lung scintigraphy, followed by angiography if a non-diagnostic result was obtained. Comorbid conditions resulting in elevated plasma D-dimer levels were defined a priori. Cut-off levels for 100% sensitivity was determined. A decision-analytic model was used to determine effectiveness and costs in the management pulmonary embolism. MAIN OUTCOME MEASURES: The exclusion efficacy of the various assays at a sensitivity of 100% and cost-effectiveness. RESULTS: A total of 179 patients were included (78 inpatients and 101 outpatients; 74 patients had comorbid conditions). Pulmonary embolism could be adequately excluded in between 8% and 18% of all patients, an in between 3% and 7% and 11% and 27% of inpatients and outpatients, respectively, depending on the assay used. D-dimer assays could exclude pulmonary embolism in <5% of patients with comorbid conditions, whereas this increased to 14-32% in outpatients without comorbid conditions. A cost-effectiveness analysis showed a cost reduction of 10% at a specificity of 30%, largely due to a 28% decrease in angiography requirements. Furthermore, for every 2% decrease to sensitivity, one per 1000 evaluated patients would die as a result of inadequately treated pulmonary embolism. CONCLUSION: D-dimer ELISA assays may have a role in the exclusion of pulmonary embolism in symptomatic outpatients, where the application may reduce angiography by 30% and costs by 10%.

A normal perfusion lung scan in patients with clinically suspected pulmonary embolism. Frequency and clinical validity.

STUDY OBJECTIVE: To assess the frequency of a normal perfusion lung scan in a consecutive series of patients with clinically suspected pulmonary embolism, to determine the complication risk of heparin therapy in those patients treated while awaiting lung scanning, and to evaluate the clinical validity of withholding anticoagulant therapy in patients with a normal lung scan result. DESIGN: Prospective cohort. SETTING: Two teaching hospitals in Amsterdam, the Netherlands. PATIENTS: Consecutive inpatients and outpatients referred for clinically suspected pulmonary embolism who underwent lung scintigraphy. INTERVENTIONS: Initiation of intravenous heparin therapy before lung scanning was left to the discretion of the attending physician. Anticoagulant therapy was withheld or withdrawn in patients with a normal lung scan. Patients were followed-up for 6 months. MEASUREMENTS AND RESULTS: A normal perfusion scan was obtained in 114 of 412 consecutive patients (28%; 95% confidence interval [CI] 23 to 32%). Major bleeding complications occurred in 2 of 30 patients (6.7%; 95% CI 0.8 to 22.1%) in whom heparin was administered while awaiting lung scintigraphy. One patient was lost to follow-up, and venous thromboembolism (0%; 95% CI 0 to 3.2%) did not develop in the remaining 113 patients. CONCLUSIONS: In a substantial proportion of patients with clinically suspected pulmonary embolism (28%) the diagnosis is excluded by lung scintigraphy. The test should be performed as soon as feasible to prevent unnecessary hospitalization and bleeding complications. Long-term anticoagulant therapy can be safely withheld in symptomatic patients with a normal perfusion lung scan.