The Veneto Region's Barrett's Oesophagus Registry: aims, methods, preliminary results.

BACKGROUND: The natural history of Barrett's Oeosphagus is not completely clarified and Barrett's Oeosphagus Registries are considered useful tools to expand our knowledge on this disease. A Barrett's Oeosphagus Registry has been therefore established in the Veneto Region and neighbouring provinces. AIMS: The aims of the Registry are to assess the demographical, endoscopical and histological characteristics of Barrett's Oeosphagus patients; the prevalence of non-invasive neoplasia and Barrett's Adenocarcinoma and the timing and incidence of Barrett's Oeosphagus progression to malignancy. METHODS: An interdisciplinary committee of endoscopists, pathologists and information technology experts was established in 2004 to design a website-based Barrett's Oesophagus Registry for the Veneto Region and neighbouring north-eastern Italian provinces. Protocols for endoscopies and biopsies and standard reports were carefully defined. RESULTS: In the first 18 months, 397 patients with endoscopically visible and histologically proven Barrett's Oeosphagus were enrolled in the Registry; the median age of these patients was 66 years (male:female=3:1). Most patients (75%) had a Short Segment of Barrett's Oesophagus (3 cm). Long Segment of Barrett's Oesophagus patients were 5 years older than the Short Segment of Barrett's Oesophagus patients (p<0.05), suggesting a progression from Short Segment of Barrett's Oesophagus to Long Segment of Barrett's Oesophagus. Though no data are available on the incidence of non-invasive neoplasia or Barrett's Adenocarcinoma (i.e., progression to cancer at least 12 months after enrolment), the prevalence of neoplastic lesions (found within 12 months of enrolment) was 5% for Short Segment of Barrett's Oesophagus and 19% for Long Segment of Barrett's Oesophagus, indicating that a careful multiple-biopsy endoscopic protocol is needed, especially when Long Segment of Barrett's Oesophagus are suspected at endoscopy. The prevalence of Barrett's Adenocarcinoma among patients with non-invasive neoplasia was 1/17 cases of low-grade non-invasive neoplasia and 2/3 cases of high-grade non-invasive neoplasia, indicating that these patients require strict endoscopic and bioptic follow-up. CONCLUSION: A regional Barrett's Oeosphagus Registry is feasible at a relatively low cost and enables significant data to be collected in a relatively short time. The use of a standardised endoscopic nomenclature and report form, a strict biopsy protocol, a standard report for pathologists improves the quality of endoscopic and histological diagnoses.

Bovine lactoferrin for Helicobacter pylori eradication: an open, randomized, multicentre study.

BACKGROUND: Cure rates for eradication of Helicobacter pylori appear to be decreasing, thus more effective therapies must be identified. AIM: To evaluate the efficacy of bovine lactoferrin in the treatment of H. pylori infection. METHODS: In a multicentered prospective study, 402 (mean age 52.4, range 19-84 years) H. pylori-positive patients were assigned to one of three regimens: group A - esomeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for 7 days; group B - lactoferrin 200 mg b.d. for 7 days followed by the same schedule of group A; group C - esomeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. plus lactoferrin 200 mg b.d. for 7 days. RESULTS: Of the 402 patients, 389 completed the study. Six patients were discontinued due to side effects, one patient in group B died and six patients were lost to follow up. The eradication rate (intention-to-treat analysis) was 77% in group A (105/136), 73% in group B (97/132) and 90% in group C (120/134) (chi(2)-test P < 0.01). The incidence of side effects was 9.5% in group A, 9% in group B and 8.2% in group C (chi(2)-test P = 0.1). CONCLUSION: This study demonstrates that bovine lactoferrin is an effective adjuvant to 7-day triple therapy for eradication of H. pylori infection.

Capsule endoscopy findings in patients with suspected Crohn's disease and biochemical markers of inflammation.

BACKGROUND: Because it provides a direct view of superficial lesions in the small bowel, capsule endoscopy is a promising diagnostic tool for studying patients with suspected Crohn's disease undetected by conventional modalities. AIM: To assess the role of capsule endoscopy in the diagnosis of patients with suspected Crohn's disease. PATIENTS AND METHODS: Thirty-eight patients (16 males, mean age 46.2 years) with suspected Crohn's disease but negative at conventional imaging were examined using capsule endoscopy. They were divided into 2 groups: 12 patients with ongoing symptoms (Group 1), and 26 with ongoing symptoms and biochemical markers of inflammation (Group 2). Capsule endoscopy findings were classified as diagnostic (multiple erosions/ulcerations), suspicious (

Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. Interdisciplinary Group on Gastric Epithelial Dysplasia.

BACKGROUND/AIMS: Because the precancerous significance of gastric epithelial dysplasia (GED) is still under debate, this study attempts to ascertain whether a prospective follow-up of GED can contribute to clarifying its clinical and pathological relationships with gastric cancer (GC). METHODS: One hundred twelve patients with mild (G1), moderate (G2), and severe (G3) GED or diagnosed as indefinite for dysplasia were prospectively followed up with a standardized endoscopic and bioptic protocol. RESULTS: Evaluation of GED outcome refers only to 93 patients with a follow-up period longer than 12 months. Regression of dysplasia was documented in 36%, 27%, and 0% of G1, G2, and G3 GED cases, respectively. Progression to more severe dysplasia or evolution into GC was detected in 21%, 33%, and 57% of G1, G2, and G3 GED cases, respectively. Evolution into GC was documented for all grades of dysplasia and correlated significantly with high-grade atrophic gastritis. A high prevalence of early GC (86.9%) was also observed. CONCLUSIONS: GED is a pre-invasive lesion, and carcinomatous evolution increases proportionally with its histological grade. Bioptical follow-up is mandatory for all histological grades of GED and significantly increases the likelihood of GC being detected in its early stages.

Prevalence of Helicobacter pylori infection in patients with precancerous changes and gastric cancer.

Several papers suggested a role for H. pylori infection in gastric cancer. We evaluated the prevalence of H. pylori infection in an endoscopic population of patients with gastric precancerous conditions and lesions by studying biopsies from 252 patients and recording the presence and degree of H. pylori infection. Patients were subgrouped as follows: chronic non-atrophic gastritis (CG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), epithelial dysplasia (ED) and gastric cancer (K). As control populations, patients with duodenal ulcer (DU) and patients with no endoscopic and histologic damage (CO) were investigated. H. pylori infection rate increased with age, but became significantly lower (P < 0.001) with the progression of gastric mucosal damage: DU 85%, CG 72%, CAG 58%, particularly in the antral type (39%), IM 63% overall, ED 44% and K 35%. The density of colonization showed the same trend (P < 0.001). Of the K patients, only 36% were H. pylori positive in the adjacent mucosa. Anti-H. pylori antibodies (IgG, IgA and IgM) were also tested. A concordance in the diagnosis between histology and serology was obtained in 82% of the cases. In our experience, H. pylori infection correlates inversely with the presence of gastric precancerous changes and cancer. A cautious interpretation of the epidemiological data regarding H. pylori infection and gastric cancer is therefore, in our opinion, mandatory.

Early and advanced gastric cancer in the follow-up of moderate and severe gastric dysplasia patients. A prospective study. I.G.G.E.D.--Interdisciplinary Group on Gastric Epithelial Dysplasia.

The role of gastric epithelial dysplasia (GED) as a biological and morphological precursor of gastric cancer has been widely investigated, but few studies have prospectively evaluated the risk of its evolution into gastric cancer. In 1985, a prospective multicenter follow-up study was undertaken on patients with high-grade (moderate or severe) GED. The study involved 49 patients, with a follow-up currently averaging 18.8 months (range: 1-70) and a mean number of 4 endoscopies (range: 2-10). Follow-up was abandoned when 2 subsequent control endoscopies and a 1-year period were negative for GED, or when neoplasia was detected. Gastric cancer was diagnosed in 16 cases (33%). The cancer was detected at an early stage in 10 patients (62%). Eleven cases (59%) were diagnosed within 1 year of follow-up and 5 cases after 13, 18, 21, 24 and 39 months, respectively. Cancer was associated with 36% of moderate GED cases and with 80% of severe cases. Dysplastic changes were no longer detectable at follow-up in 27% of the moderate cases and in 10% of the severe cases. The relative risks for the two lesions being associated with or evolving into gastric cancer were 26 and 132, respectively. In conclusion, high-grade (moderate or severe) GED is frequently associated with or evolves into gastric cancer. The follow-up of patients considerably enhances the chances of diagnosing gastric cancer in its early stages, thus making such an approach mandatory.

Changes in parietal and mucous cell mass in the gastric mucosa of normal subjects with age: a morphometric study.

Whether or not the gastric mucosa undergoes significant changes in normal aging subjects is still open to debate. In 51 subjects undergoing endoscopy and lacking any significant endoscopic or histologic modification we evaluated mucosal thickness, gland number, numbers of parietal, chief and mucous cells at the fundus and of mucopeptic cells at the antrum, with a morphometric method, subgrouping the patients according to their age class. Our findings demonstrate that the number of parietal cells tends to increase with age and, on the other hand, the number of mucous cells is reduced in elderly subjects (p < 0.05). When considering the parietal-to-mucous cell ratio, this is significantly increased (p = 0.0005) with age. Acid secretion being an offensive factor and mucus a fundamental component of the gastric mucosal barrier, these findings suggest an increased susceptibility of the gastric mucosa to damage in the elderly.

Gastric epithelial dysplasia: a prospective multicenter follow-up study from the Interdisciplinary Group on Gastric Epithelial Dysplasia.

To assess the evolution of gastric epithelial dysplasia (GED), a prospective multicenter study was based on a protocol of repeated endoscopies and biopsies. To date, 134 cases (0.4% of all patients endoscopically examined in the same period) have been diagnosed as having GED and 80 of those have had an "adequate" follow-up (at least three endoscopies). Mean follow-up time was 18 months. Gastric epithelial dysplasia was mild in 59% of cases, moderate in 25%, and severe in 10%. Six percent of the patients had lesions that were "indefinite for dysplasia." Chronic atrophic gastritis (40%), gastric ulcer (32%), gastrectomy (10%), and polyps (9%) were the most frequently associated lesions. The term "regression" was adopted for GED no longer detectable during follow-up and the term "progression" was used when more severe changes or cancer was detected. Mild GED regressed in 66% of cases, persisted in 15%, and progressed in 19% (three cases to moderate, one to severe, and five to cancer). Moderate GED regressed in 30% of patients, persisted in 30%, and progressed in 40% (one to severe GED and seven to cancer). Severe GED regressed in 12.5% of patients, persisted in 12.5%, and progressed to cancer in 75%. Of the five patients with lesions indefinite for dysplasia, two had no dysplastic changes at follow-up and three had cancer diagnosed. Ten of 21 cases of cancer (48%) were at the early stage. The diagnosis was reached within the first year of follow-up in 14 cases and after 1 year in seven (13 to 39 months). Fifteen of 21 cases of cancer were diagnosed in gastric ulcer patients. In conclusion, GED is an infrequent finding and its biologically neoplastic significance is confirmed by the results of the follow-up study: (1) in its mild form, it tends to regress but adequate subsequent check-ups are mandatory as it may associate with or evolve as cancer; (2) patients with moderate GED require strict follow-up since the lesion shows a higher cancer risk; (3) surgery is indicated for severe GED because gastric cancer develops in 75% of cases; and (4) patients with lesions indefinite for dysplasia should immediately undergo repeat endoscopy and biopsy. Such an approach allows gastric cancer to be detected at an early stage in a much higher percentage of cases than may be expected.

Direct involvement of human gastric mucosa in the activation of alimentary pro-carcinogens.

Exposure to N-nitroso-compounds and aromatic amines, xenobiotics which require an activation in order to exert their genotoxic potential, is causally associated with gastric cancer. We evaluated the capacity of microsome-containing fractions from human gastric mucosa to activate two model carcinogenic compounds. A 9,000 x g supernatant (S9) was obtained from gastric mucosal specimens and, for comparison, from human liver and aroclor-induced and non induced rat liver. The capacity of the S9 to activate N-nitrosopyrrolidine (NPY) and 2-aminofluorene (2AF) to mutagenic metabolites was tested in the Ames/Salmonella reversion assay, while dimethylnitrosamine (DMN) and aminopyrine (AP) demethylation activities were spectrophotometrically evaluated by using an enzymatic assay of the amount of formaldehyde released following the enzymatic demethylation of the corresponding substrates. Results indicate that human gastric S9 fractions may activate 2AF to a genotoxic derivative and are characterized by DMN and AP demethylase activities higher (p < 0.05) than those of human liver, when expressed in mg/protein (p < 0.05). Although the parameters evaluated can only be considered as a partial measure of the general activating capacity toward dietary and environmental procarcinogens, these results suggest that human gastric mucosa may be directly involved in the metabolic activation of these compounds to mutagenic/carcinogenic species.

Pepsinogen A/pepsinogen C or pepsinogen A multiplied by gastrin in the diagnosis of gastric cancer?

Being pepsinogen A (PGA) levels generally reduced and pepsinogen C (PGC) increased in gastric cancer patients, PGA/PGC ratio has been proposed as a useful marker of the tumour. We tested PGA, PGC and Gastrin (G) levels in patients with gastric cancer (39) and, as a control, in patients with epithelial dysplasia (21), chronic atrophic gastritis (57), gastric ulcer (11) or subjects lacking major or minor endoscopic and microscopic changes at gastroscopy (48). PGA and PGA/PGC levels were significantly reduced in gastric cancer patients (p less than 0.005 and p less than 0.0001 respectively with analysis of variance). Gastrin levels were also reduced in the same patients (p less than 0.005). We therefore adopted an index number (PGA x Gastrin) which was also dramatically reduced in gastric cancer (p less than 0.005); using an arbitrarily chosen cut-off, the "marker" showed very high sensitivity (76%), specificity (96%) and overall accuracy (74%, by Youden J test). We therefore suggest the use of the index number PGA x G in the diagnosis of gastric cancer, as the most useful gastrin presently available, to our knowledge.

Epithelial dysplasia in atrophic gastritis. Bioptical follow-up study.

Fifty-nine cases of gastric dysplasia (46 of which were mild, 11 moderate and 2 severe) were studied in relation to their association with atrophic gastritis and intestinal metaplasia. Atrophic gastritis was found in 39 cases (28 of which were mild, 10 moderate and 1 severe). Dysplasia was considered "persistent" when found of the same degree in at least two consecutive check-ups after initial diagnosis (13 cases); it was considered "progressive" if found more severe or evolving as cancer (5 cases) or "regressive" if detected in a lesser degree or no longer detected (13 cases). Sixteen of the 18 persistent or progressive cases of dysplasia were associated with atrophic gastritis, whereas 10 of the 13 cases with regressive dysplasia revealed no concomitant pattern of gastric mucosa atrophy (p less than 0.005). These findings suggest that dysplasia represents a truly pre-neoplastic change particularly when associated with atrophic gastritis and which must therefore be more carefully monitored.

CA 50 determination in body fluids: can we screen patients at risk for gastric cancer?

CA 50 (a tumor-associated gangliosidic antigen) levels have been determined by an RIA test in serum, gastric juice and urine of patients undergoing upper gastrointestinal tract endoscopy: 22 control subjects (no macroscopic or microscopic lesions), 29 patients with chronic atrophic gastritis, 20 with epithelial dysplasia and 16 with gastric cancer entered the study. Gastric juices were also tested for pH, protein concentration and specific gravity, urines for protein concentration and osmolarity. Serum and gastric juices were also tested for CEA levels and the results obtained with the two markers compared. In patients with gastric cancer, CA 50 gastric juice levels were statistically higher than in controls; a wide overlap was however present among groups, and sensitivity and specificity were respectively 38% and 85% for serum and 69% and 82% for gastric juice. Sensitivity and specificity were respectively 23% and 89% for CA 50 determination in urines. In this case, no statistically significant difference was observed between gastric cancer and control patients. A trend toward higher median values was observed in advanced with respect to early gastric cancer. A correlation was found between gastric juice and serum CA 50 levels, as well as between serum and urine levels of the marker. A correlation was also observed between CA 50 values and protein concentration in gastric juice and with osmolarity in urines. Overall, CA 50 levels were statistically higher in patients with intestinal metaplasia than in those who did not present the lesion. Increased CA 50 gastric juice levels are also observed in patients with chronic atrophic gastritis and epithelial dysplasia. CA 50 gastric juice and urine levels appear to be dependent, at least in part, on the concentration of the fluid.

[Intragastric pH determination as a screening test in the diagnosis of chronic atrophic gastritis]. / Il pH intragastrico come test di screening per la diagnosi di gastrite cronica atrofica.

A simple routine endoscopic screening test has been sought for the diagnosis of chronic atrophic gastritis. An endoscopic-bioptic study was therefore carried out on 850 subjects presenting consecutively at a Digestive Endoscopy Department with dyspeptic-pain symptomatology. In a first sample of 389 patients, 2 biopsies of the gastric body and 2 of the gastric antrum were carried out, independently of the endoscopically documented macroscopic picture. Atrophic changes were in this way encountered in 65 patients (16.7%). In a second group of 461 patients, intragastric pH was determined extemporaneously during endoscopy. pH was = or greater than the chosen threshold value (3.5) in 117 patients and less than this value in 344. In all subjects with pH greater than 3.5 and, by comparison, in 130 with pH less than 3.5 biopsy was carried out on the gastric mucosa, 2 biopsies of the body and 2 of the antrum. Using this approach it was possible to determine the presence of atrophic changes in the gastric mucosa in 57 of 117 (48%) and in 25 of 130 (20%) respectively. In total, chronic atrophic gastritis was diagnosed in 83 of 461 subjects (18%). This percentage is comparable to that observed in the frequency of chronic atrophic gastritis using the more demanding and less selective test of bioptic sampling indiscriminately for all patient. So, the straight-forward determination of intragastric pH in a sample of gastric juice taken during digestive endoscopy would appear to meet the criteria demanded for a screening test and its wider use is recommended in routine endoscopic practice.