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Biomedical subjects

R Fiocca

Publications and source records attributed to R Fiocca.

At least 37 records · Page 2Linked to original sources
PubMed2001

Morphometric assessment of gastric antral atrophy: comparison with visual evaluation.

AIMS: As part of a multinational effort to reach a consensus in the definition and evaluation of atrophic gastritis, we applied morphometric techniques to 22 antral biopsy specimens examined visually by 12 experienced gastrointestinal pathologists. METHODS AND RESULTS: Atrophy was defined as loss of glands. Each pathologist graded atrophy with both non-standardized and standardized approaches. Discriminant function analyses of morphometric measurements were conducted to validate and grade atrophy. Kappa statistics were used to compare the performance of each pathologist against the group mode and against the discriminant functions' grading of atrophy. Three morphometric indexes showed significant differences among categories of atrophy utilizing non-standardized as well as standardized visual atrophy grades: (i) the ratio of glandular length to total mucosal thickness; (ii) the proportion of the secretory compartment area occupied by glands; and (iii) the number of glandular cross sections per 40x microscopic field. The discriminant function analyses verified all cases classified visually as either non-atrophic, or moderately/severely atrophic; it verified as mildly atrophic 40% of the cases classified visually as mildly atrophic; and classified the remaining 60% as moderately or severely atrophic. The kappa statistics were good or excellent for the majority of pathologists. CONCLUSIONS: The evaluation of antral atrophy, simply defined as loss of glands, can be reliable and reproducible. The visual grading of atrophy as absent, moderate and severe is entirely consistent with objective morphometric observations.

Atrophy↗
PubMed2000

Gastric endocrine cells: types, function and growth.

The history of gastric endocrine cells identification and functional characterization is briefly outlined. An up to date classification of such cells is given. Present status of histopathological, histochemical, ultrastructural and molecular investigations on gastric endocrine hyperplasia and neoplasia is summarized and briefly discussed.

Animals↗
PubMed2000

Altered intercellular glycoconjugates and dilated intercellular spaces of esophageal epithelium in reflux disease.

BACKGROUND AND AIMS: The usefulness of histological diagnosis of gastroesophageal reflux disease (GERD) is limited by poor specificity or sensitivity of available diagnostic tools. Recently, ultrastructural morphometry showed interstitial space dilation (ISD) to be a reliable sign of reflux disease. Aims of this study were to (a) search for a light microscopy equivalent of ISD, (b) test its diagnostic value, and (c) look for a possible role of intercellular glycoconjugates in its genesis. METHODS: Esophageal grasp biopsies were taken during endoscopy, 2-3 cm and 6-7 cm above the squamocolumnar junction, from patients under investigation for GERD symptoms. The biopsies were fixed in aldehyde solutions and embedded in resin for electron microscopy or in paraffin for routine histology, and the glycoconjugates underwent immunohistochemistry using 3-fucosyl-N-acetylactosamine antibodies. RESULTS: Irregular intercellular space dilation was detected in the basal and prickle layers using both light and electron microscopy. Hematoxylin-eosin preparations showed ISD in 20 of 22 (90%) erosive esophagitis cases, 30 of 44 (68%) endoscopy negative GERD cases, and 1 of 12 (8%) controls, with good interobserver (K = 0.75) and bioptic site reproducibility. ISD correlated with loss or rearrangement of intercellular glycoconjugates of the overlying layers and with granulocyte (eosinophil and/or neutrophil) infiltration. CONCLUSIONS: Light microscopy ISD is a suitable index of GERD. Alterations of intercellular glycoconjugates are likely to have a role in the genesis of ISD and GERD.

Esophagus↗
PubMed2000

Vesicular monoamine transporter 2 as a marker of gastric enterochromaffin-like cell tumors.

The vesicular monoamine transporter 2 (VMAT2) facilitates the ATP-dependent accumulation of biogenic amine inside the secretory granules of endocrine cells and neurons and was demonstrated in the histamine-producing enterochromaffin-like (ECL) cells of the stomach. In the present investigation, VMAT2 immunohistochemistry was tested in 85 endocrine tumors, of which 60 were well differentiated gastrointestinal and pancreatic growths, 5 poorly differentiated (neuro)endocrine carcinomas (PDEC) and 1 mixed PDEC/ECL cell carcinoma of the stomach, 12 pheochromocytomas/paragangliomas, 3 adrenocortical lesions, 2 parathyroid and 2 lung neuroendocrine tumors. Extensive and intense VMAT2 immunoreactivity was observed in 16 of 16 gastric ECL cell tumors, 6 of 6 adrenal pheochromocytomas, 2 of 2 chromaffin paragangliomas and in 3 of the 4 carotid body paragangliomas investigated. Rare VMAT2-positive cells were observed in 12 of 21 intestinal enterochromaffin (EC) cell tumors, in 9 of 11 pancreatic neuroendocrine tumors, and in the mixed PDEC/ ECL cell carcinoma of the stomach (differentiated cells only). No VMAT2 immunoreactivity was observed in five gastrin, four somatostatin and three enteroglucagon/peptideYY tumors of the gastrointestinal tract, in six gastric PDECs, in three adrenocortical growths, and two parathyroid and two lung neuroendocrine tumors. These data support VMAT2 immunohistochemistry as being a useful tool for the diagnosis of gastric ECL cell tumors, separating them from all other endocrine tumors arising in the gastroduodenal area i.e., gastrin, somatostatin, EC cell and PDEC tumors, all of which proved essentially negative.

Biomarkers, Tumor↗
PubMed2000

Comparison of tests for assessment of Helicobacter pylori eradication: results of a multi-centre study using centralized facility testing.

BACKGROUND: The accuracy of diagnostic tests to assess Helicobacter pylori eradication has rarely been performed. AIM: To compare the tests most commonly used for this purpose, i.e. histology, culture and (13)C urea breath test performed in centralized facilities. METHODS: Prospective study where patients were included in four centres and diagnostic tests performed centrally by biologists experienced in the field. Gastric biopsies were obtained from antrum and corpus (two for histology, two for culture from each site) 4-6 weeks after an eradication treatment. The definition of a gold standard for H. pylori-positive patients was either a positive culture or both positive histology and urea breath test results. RESULTS: Ninety-seven patients for whom data on histology, culture and (13)C urea breath test were available were included. The majority were females (60%) suffering from non-ulcer dyspepsia (52%) and having received proton-pump inhibitor-based triple therapy (62%). Forty-one per cent of the patients were H. pylori-positive according to the gold standard. The sensitivities were 90%, 95% and 92.5% and the specificities 100%, 98.2% and 100% for culture, histology and (13)C urea breath test, respectively. CONCLUSION: All the methods had excellent specificity but the sensitivity ranged between 90 and 95%. The combination of two techniques which increases the sensitivity to virtually 100% is recommended in situations where the eradication treatment requires a precise evaluation such as in clinical trials.

Breath Tests↗
PubMed1999

Release of Helicobacter pylori vacuolating cytotoxin by both a specific secretion pathway and budding of outer membrane vesicles. Uptake of released toxin and vesicles by gastric epithelium.

The mechanisms by which Helicobacter pylori releases its virulence factors are poorly known. Active secretion has been proposed for some products, including a vacuolating toxin (VacA). Outer membrane vesicles represent another mechanism by which some Gram-negative bacteria may release virulence factors. This study sought to localize VacA by immunocytochemistry in H. pylori cells, to determine whether H. pylori produces outer membrane vesicles, and to investigate whether such vesicles might constitute a vehicle for the delivery of bacterial virulence factors to the gastric mucosa. Small (50-300 nm) membrane vesicles were found in H. pylori culture media from both H. pylori strain 60190 and strain CCUG 17874. These vesicles appeared to originate from blebs arising on the bacterial outer membrane. VacA was immunolocalized in the periplasm and outer membrane of intact bacteria and also in outer membrane blebs and vesicles. Both soluble secreted VacA and VacA-containing vesicles bound to, and were internalized by, MKN28 cells and were detectable in the gastric mucosa from H. pylori-infected humans. The release of outer membrane vesicles by H. pylori may represent a mechanism, additional to secretory pathways, for the delivery of bacterial toxins and antigens to the gastric mucosa.

Bacterial Proteins↗
PubMed1999

Lansoprazole versus omeprazole for duodenal ulcer healing and prevention of relapse: a randomized, multicenter, double-masked trial.

The aim of this randomized, multicenter, double-masked, parallel-group study was to compare the efficacy of lansoprazole with that of omeprazole monotherapy in duodenal ulcer healing and prevention of relapse. A total of 251 patients with duodenal ulcer were treated with either lansoprazole 30 mg/d (n = 167) or omeprazole 40 mg/d (n = 84). Patients with healed ulcers were then randomly allocated to 12 months of maintenance therapy with lansoprazole 15 mg/d (n = 74), lansoprazole 30 mg/d (n = 71), or omeprazole 20 mg/d (n = 73). Healing rates at 4 weeks (intent-to-treat analysis) were 93.9% (95% confidence interval [CI], 90.2% to 97.6%) with lansoprazole and 97.5% (95% CI, 93.7% to 100%) with omeprazole; there were no significant differences between groups. Endoscopic relapse rates after 6 months were 4.5% (95% CI, 0% to 10.6%) with lansoprazole 15 mg, 0% with lansoprazole 30 mg, and 6.3% (95% CI, 1.5% to 12.5%) with omeprazole 20 mg, compared with 3.3% (95% CI, 0% to 8.2%), 0%, and 3.5% (95% CI, 0% to 8.8%), respectively, at 12 months. Again, there were no significant differences between groups. The incidence of adverse events during acute treatment was 6.0% and 7.1% in the lansoprazole and omeprazole groups, respectively; during maintenance therapy, the incidences were 12.2% (lansoprazole 15 mg), 5.6% (lansoprazole 30 mg), and 11.0% (omeprazole 20 mg). Within treatment groups, pain was significantly ameliorated after the acute phase but not after maintenance therapy (P < 0.05); no differences were observed between groups. Gastrin values increased significantly after acute therapy (P < 0.05), persisted at these increased levels during maintenance therapy, and returned to normal after 6-month follow-up. Both lansoprazole and omeprazole were highly effective and well tolerated in the treatment of duodenal ulcer; relapse rates were similar for all doses studied. Thus no additional benefit is to be gained from using a proton-pump inhibitor at a dose > 15 mg lansoprazole to prevent relapse.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Early onset of gastric carcinoma and constitutional deletion of 18p.

We report on the association of a gastric carcinoma and a constitutional deletion of the short arm of chromosome 18 in a 14-year-old patient. The phenotype of the patient, including microcephaly, ptosis, micrognathia, tetralogy of Fallot, and mental retardation, fits well with previously reported cases of del(18p); she also showed a positive serology against Helicobacter pylori. The comparison of the alleles of polymorphic loci located on the short arm of chromosome 18 between the patient and her parents showed a maternal origin of the abnormal chromosome. Loss of heterozygosity (LOH) for loci located in the long arm of chromosome 18 is a frequent event in gastric carcinomas; it was observed in the tumoral mass of our patient and again, the alleles lost were of maternal origin. We postulate that the constitutional chromosomal abnormality may have favored the loss of the abnormal chromosome in some cells and that the loss of the deleted chromosome 18 (demonstrated by LOH for this chromosome in the tumoral mass) has been an early step in the pathogenesis of the gastric carcinoma of our patient with Helicobacter pylori infection acting as a cofactor.

Abnormalities, Multiple↗
PubMed1999

Observer agreement on the grading of gastric atrophy.

AIMS: Assessment of lesser or doubtful degrees of gastric atrophy can be difficult, especially in the antrum, since well established criteria are lacking. At the Houston Working Party on Gastritis in 1994 a visual analogue scale was designed for the grading of histopathological parameters. This was done to promote uniformity in grading by acting as a reference. The purpose of the present study was to measure interobserver variation between pathologists familiar with the Houston visual analogue scale in a specifically selected set of biopsies from patients with lesser or doubtful degrees of atrophy. METHODS AND RESULTS: Thirty cases with biopsies of the antrum and corpus from a long-term follow-up study on Helicobacter pylori gastritis comprised the current study material. The cases were selected from that study because there had been uncertainty or disagreement on the presence of gastric atrophy. The study set of haematoxylin and eosin (H & E) slides was circulated amongst gastrointestinal pathologists familiar with the visual analogue scale who were unaware of the source of the study set nor had any other clinical information. Interobserver variability was analysed using kappa statistics. The overall agreement for the grade of atrophy in antral biopsies was 0.461; the kappa value was 0.18 (95% confidence limits 0.12-0.24), which is considered poor agreement. The kappa value was nevertheless statistically significant (P < 0. 01). The overall agreement on the grade of atrophy in the corpus biopsies was apparently good (0.833), but the kappa which adjusts for chance agreement was only moderate (0.48; 95% confidence limits 0.42-0.55; P < 0.001). CONCLUSION: The studied series comprised a self-selected sample in which there was doubt about the grade of atrophy and such a sample will produce lower kappa values than a random sample of gastric biopsies. The results nevertheless confirm that better guidelines and firm criteria are needed to properly diagnose and grade gastric atrophy. It is suggested that the use of two grades, low- and high-grade atrophy, akin to that in use for grading inflammatory bowel disorder (IBD)- associated dysplasia, could improve agreement. Furthermore optimal biopsy quality with full thickness mucosa and proper orientation appears important for grading gastric atrophy.

Atrophy↗
PubMed1999

Clinicopathological profile as a basis for classification of the endocrine tumours of the gastroenteropancreatic tract.

Recent developments in the field of endocrine cell biology and pathology, at both morphologic and molecular levels, are briefly outlined and discussed as a basis for endocrine tumour characterization. The main clinicopathological tools available for the identification and characterization of endocrine tumours are discussed. Based on this, classifications of endocrine tumours of the pancreas and gastrointestinal tract are developed covering most clinical (hyperfunctional syndromes included), pathologic and biological patterns and with special emphasis on tumour prognosis.

Endocrine Gland Neoplasms↗
PubMed1999

Risk indicators of organic diseases in uninvestigated dyspepsia: a one-week survey in 246 Italian endoscopy units.

OBJECTIVE: To evaluate the predictive value of demographic and clinical features and of the results of an office-based test for Helicobacter pylori antibodies, in the presence of organic dyspepsia. DESIGN: Over a 1-week period, 2206 consecutive patients first referred for endoscopy in 246 Italian centres were included. METHODS: Demographic and clinical features, endoscopy findings, and histological diagnosis of H. pylori infection were recorded for all patients. IgG antibodies to H. pylori were determined in 2128 cases by a rapid, immunochromatographic method (Flex Sure HP, S.K.D., San Jose, CA). RESULTS: Endoscopic abnormalities were found in 939 patients (42.6%). Histologically assessed H. pylori infection was predictive for duodenal ulcer (odds ratio (OR), 6.79; 95% confidence interval (CI), 4.4-10.5). Being male (OR, 1.97; 95% CI, 1.7-2.3), older than 40 years (OR, 1.81; 95% CI, 1.5-2.2), a smoker (OR, 1.88; 95% CI, 1.6-2.3), and presenting nocturnal awakening (OR, 1.62; 95% CI, 1.3-2.0) were independently associated with secondary dyspepsia. Epigastric (OR, 1.50; 95% CI, 1.2-1.9) and retrosternal pain (OR, 1.39; 95% CI, 1.1 -1.8) severe enough to affect the usual activities were predictive of organic diseases. The results of the Flex Sure HP test correlated poorly with histological findings. CONCLUSIONS: Male gender, older age, cigarette smoking, a family history of peptic ulcer, symptoms severe enough to induce awakening, epigastric/retrosternal pain severe enough to influence the usual activities are all independently (although weakly) associated with organic dyspepsia. H. pylori infection is strongly associated with duodenal ulcer, but the rapid test we used was not sensitive enough to achieve clinical utility.

Adult↗
PubMed1998

Genetic pattern, histological structure, and cellular phenotype in early and advanced gastric cancers: evidence for structure-related genetic subsets and for loss of glandular structure during progression of some tumors.

Gastric cancer shows remarkable heterogeneity in histological pattern, cellular phenotype, and genotype. Tumor subsets identified by varying procedures have shown limited reciprocal correlation and have failed to provide a sound rationale for the characterization and classification of all tumors. Based on a case series of 130 gastric cancers that covered both early (70 cases) and advanced (60 cases) stages and that represented most histological types and structural patterns, this study investigated (1) microsatellite instability and p53 gene mutation by means of PCR-based molecular techniques and (2) p53 protein accumulation or tumor cell immunophenotype by means of immunoperoxidase procedures. It was found that microsatellite instability and p53 gene mutation involve two distinct subsets of both early and advanced-stage glandular (intestinal) cancer, and that, contrastingly, they leave purely diffuse cancers unaffected. Mixed cancers, namely, those in which glandular admixed with diffuse growths, showed scarce microsatellite instability at all stages, whereas prominent p53 gene mutation and p53 protein accumulation was limited to the advanced stage alone. No significant correlation was found between tumor cell immunophenotype and either genotype or histotype, although some correlation with particular structural patterns was detected. Comparison of intramucosal with invasive growths within any given tumor suggested that invasive cancers with diffuse-type growth arise in part from mucosal cancers of glandular or mixed structure through progressive loss of intercellular junctional systems. It is concluded that at least two genetically distinct subsets of glandular cancer, one with microsatellite instability and the other with p53 lesions, should be separated both from purely diffuse cancer and, at least in the advanced stage, from mixed cancer. Available evidence suggests distinct clinicopathologic profiles for such tumor entities.

Aged↗
PubMed1998

Persistence of Helicobacter pylori VacA toxin and vacuolating potential in cultured gastric epithelial cells.

The vacuolating toxin A (VacA) is one of the most important virulence factors in Helicobacter pylori-induced damage to human gastric epithelium. Using human gastric epithelial cells in culture and broth culture filtrate from a VacA-producing H. pylori strain, we studied 1) the delivery of VacA to cells, 2) the localization and fate of internalized toxin, and 3) the persistence of toxin inside the cell. The investigative techniques used were neutral red dye uptake, ultrastructural immunocytochemistry, quantitative immunofluorescence, and immunoblotting. We found that VacA 1) is delivered to cells in both free and membrane-bound form (i.e., as vesicles formed by the bacterial outer membrane), 2) localizes inside the endosomal-lysosomal compartment, in both free and membrane-bound form, 3) persists within the cell for at least 72 h, without loss of vacuolating power, which, however, becomes evident only when NH4Cl is added, and 4) generally does not degrade into fragments smaller than approximately 90 kDa. Our findings suggest that, while accumulating inside the endosomal-lysosomal compartment, a large amount of VacA avoids the main lysosomal degradative processes and retains its apparent molecular integrity.

Adenocarcinoma↗
PubMed1998

Analysis of gastroduodenitis and oesophagitis in relation to dyspeptic/reflux symptoms.

BACKGROUND/AIMS: The pathogenesis of dyspeptic/reflux symptoms and the clinico-pathologic profile of affected patients are still poorly understood. To improve our knowledge in this field we carried out a systematic, comparative analysis of symptom profiles and histopathologic patterns of oesophagogastroduodenal mucosa in a series of 221 subjects, 140 with and 81 without endoscopic evidence of hiatal hernia. Of these, 190 showed reflux and/or dyspeptic symptoms. METHODS: Before endoscopy, all the subjects were questioned about the presence and severity of 12 individual symptoms. Biopsies were taken from the distal oesophagus, cardia, corpus, angulus, antrum and duodenal bulb, and were scored in accordance with the Sydney system. RESULTS: Patient groups with a distinct clinico-pathologic profile were better identified when symptoms of adequate severity were compared with histopathologic parameters. A correlation between gastroesophageal reflux disease (GORD) symptoms and histologic signs of oesophagitis was mostly restricted to patients endoscopically positive for oesophagitis. Retroxiphoid pyrosis correlated with cardial gastritis but not with oesophagitis, either endoscopic or histologic, while ulcer-like epigastric pain correlated with active duodenitis and distal gastritis. No definite histopathologic background was detected in patients with putative dysmotility-like symptoms, endoscopy-negative GORD and low score or mixed symptoms. CONCLUSION: A contribution of Helicobacter pylori gastroduodenitis to the pathogenesis of some dyspeptic symptoms seems likely. However, the identification of specific histologic changes causing individual symptoms remains rather elusive, with the exception of active antroduodenitis in patients with ulcer-like pain and of active proximal gastritis in patients with severe retroxiphoid pyrosis.

Biopsy↗
PubMed1997

Microsatellite instability in intestinal- and diffuse-type gastric carcinoma.

To investigate the role of genetic instability in the development of intestinal- and diffuse-type gastric cancers, six microsatellite loci were analysed in 98 carcinomas of the two main histotypes, at both early and advanced stages of progression, and in five preneoplastic lesions. RER+ phenotype frequency proved to be significantly higher (P = 0.013) in intestinal (23 per cent) than in diffuse cancers (5 per cent) and slightly higher in advanced (19 per cent) than in early (12 per cent) tumours. When comparing early and advanced tumours of the same histotype, a similar frequency was found for diffuse tumours (4 per cent vs. 6 per cent), and an increase from 19 to 30 per cent for intestinal cancers. Instability at more than one locus was limited to intestinal tumours and replication errors were also detected in an intestinal dysplasia. On the whole, these data suggest that genetic instability has an important and early role in gastric carcinogenesis of the intestinal type and a less important role in gastric carcinogenesis of the diffuse type. Most tumours of this panel had previously been characterized for p53 gene mutations. p53 screening was extended to all samples, to investigate the possible association between gene mutations and microsatellite instability. Analysis showed a trend (P = 0.07, Fisher's exact test) towards a negative association between these two genetic lesions in tumours of the intestinal type.

Adenocarcinoma↗
PubMed1997

Helicobacter pylori vacuolating toxin accumulates within the endosomal-vacuolar compartment of cultured gastric cells and potentiates the vacuolating activity of ammonia.

This study explored the relationship between vacuolating toxin and ammonia in the genesis of Helicobacter pylori-induced vacuolation in cultured human gastric cells and investigated the intracellular sites of toxin accumulation. Neutral red dye uptake and electron microscopy were used in the investigation of the respective roles of, and of the reciprocal interaction between, toxin and ammonia in cell vacuolation and ultrastructural immunocytochemistry was used for the identification of the intracellular sites of internalized toxin. Toxin was found to cause an expansion of the endosomal compartment, where it accumulates after cellular internalization. However, toxin does not form large, neutral red-positive vacuoles unless combined with ammonia, whose moderate vacuolating activity is markedly potentiated by the toxin. It is concluded that the toxin accumulated within the endosomal compartment alters the morphology and function of this organelle and plays a permissive role towards cell vacuolation, possibly by increasing the accumulation of protonated ammonia within endosomes. In turn, ammonia induces excessive dilatation of the endosomes with reciprocal fusion of their membranes, thus causing cytoplasmic vacuolation.

Ammonia↗