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R M Genta

Publications and source records attributed to R M Genta.

At least 37 records · Page 2Linked to original sources
PubMed2000

Molecular identification of main cellular lineages as a tool for the classification of gastric cancer.

Gastric carcinomas (GC) are heterogeneous tumors comprising variable amounts of cells of different lineage phenotype, including gastric mucous cells (surface--SMC or gland--GMC) and intestinal cells (IC). The evaluation of tumor behavior has classically depended on strictly morphological classifications of tumors. Microsatellite instability (MSI) is frequently detected in GC, but whether MSI affects all gastric cellular lineages or exclusively occurs in unique cellular lineages in GC is not known. The aims of this study were to test a combination of anti-mucin antibodies to classify gastric cancer into predominant cell lineage phenotype and to determine whether MSI in GC is associated with particular cellular tumor phenotypes. Fifty-five GC were immunophenotyped with antibodies specific for SMC, GMC, or IC. DNA was extracted from tumor and non-neoplastic gastric tissues and amplified with 5 microsatellite markers. A mixed cellular pattern was the most frequent phenotype of GC (61%) and was seen in both glandular (63%) and diffuse (58%)-type tumors. No significant difference in the rate of MSI was found in tumors with predominant gastric, intestinal or mixed phenotype. However, tumors with null or low-level expression of cellular lineage differentiation markers displayed MSI more frequently than tumors with high-level expression (40% v 20%). In conclusion, different gastric carcinoma cell lineage patterns can be easily identified with the 3 immunohistochemical markers used in this study. The 3 main cellular lineage components of gastric cancer can be similarly affected by microsatellite instability, consistent with the notion that MSI is an early event in gastric carcinogenesis.

Adult↗
PubMed2000

Sustained increase in gastric antral epithelial cell proliferation despite cure of Helicobacter pylori infection.

OBJECTIVE: Studies of the effect of Helicobacter pylori treatment on gastric mucosa proliferation have yielded inconsistent results. We compared gastric mucosa cell proliferation posttherapy and in uninfected controls. METHODS: Biopsies were obtained from patients with H. pylori infection before treatment and at intervals for up to 33 months. Epithelial cell proliferation was determined using Ki-67 immunostaining. The labeling index (LI) is the proportion of positively labeled cells with respect to the total number of cells. The proliferative index was calculated by multiplying the labeling index (LI) and the proliferation zone PZ (PZ = length of the area between the uppermost and lowest labeled cells). RESULTS: The study included 27 patients with H. pylori gastritis and 35 controls. Epithelial cell proliferation (LI) was greater with H. pylori infection than without in both the antrum and corpus (65+/-5 vs 91+/-8 in the antrum and 44+/-4 vs 72+/-8 in the corpus, for uninfected controls vs H. pylori gastritis, respectively) (p = 0.0001). In the antrum there was no significant decrease in epithelial cell proliferation after cure of the H. pylori infection despite follow-up for >2 yr (labeling index = 83+/-10). In contrast, epithelial cell proliferation decreased in the corpus and became similar to that in controls after 7-13 months. CONCLUSIONS: Patients with H. pylori infection have sustained high epithelial cell proliferation in the antrum compared to that in uninfected subjects. A continued increase in proliferation in the antrum after cure of H. pylori infection suggests continuing damage.

Anti-Ulcer Agents↗
PubMed2000

Topographic patterns of intestinal metaplasia and gastric cancer.

OBJECTIVE: The role of intestinal metaplasia in gastric oncogenesis has been demonstrated by both cross-sectional and longitudinal studies. This study was designed to determine whether, in a population at high risk for gastric cancer, different topographical patterns and phenotypes of intestinal metaplasia were associated with different degrees of cancer risk. METHODS: A total of 68 Colombian patients with gastric cancer and 67 controls with nonulcer dyspepsia were studied by an extensive biopsy protocol. Intestinal metaplasia was assessed semiquantitatively by histology and was characterized histochemically. In both patients and controls, the Spearman's correlation test was applied to the test if the gastric distribution of metaplastic lesions resulted in specific topographical patterns associated with different risks for cancer. RESULTS: Four topographical patterns of intestinalization emerged: 1) "Focal," in 14 cancer patients and 16 controls; 2) "Antrum-predominant," in seven cancer patients and six controls; 3) "Magenstrasse" (involving the lesser curvature from cardia to pylorus) in 25 cancer patients and four controls. This pattern was associated with higher cancer risk (OR = 5.7; 95% CI: 1.3-26) than were the two less extensive patterns; and 4) "Diffuse," involving essentially the entire gastric mucosa with the exception of the fundus, was unique to 13 cancer patients. The OR for cancer was 12.2; 95% CI: 2.0-72.9. Incomplete-type metaplasia significantly correlated with the extent of total metaplasia and was also associated with greater cancer risk. CONCLUSIONS: In a population with high risk for gastric cancer, the extension of intestinal metaplasia correlates with the extent of its "incomplete" phenotype and is significantly associated with increased cancer risk. Both the extent and location of intestinal metaplasia along the lesser curvature (from the cardia to the prepyloric zones) identify patients with the highest cancer risk.

Adenocarcinoma↗
PubMed1999

Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue. An uncontrolled trial.

BACKGROUND: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is related to Helicobacter pylori infection and may depend on this infection for growth. OBJECTIVE: To determine the response of gastric MALT lymphoma to antibiotic treatment. DESIGN: Prospective, uncontrolled treatment trial. SETTING: University hospital referral center and three collaborating university and community hospitals. PATIENTS: 34 patients with stage I or stage II N1 gastric MALT lymphoma. INTERVENTION: Two of three oral antibiotic regimens--1) amoxicillin, 750 mg three times daily, and clarithromycin, 500 mg three times daily; 2)tetracycline, 500 mg four times daily, and clarithromycin, 500 mg three times daily; or 3) tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times daily--were administered sequentially (usually in the order written) for 21 days at baseline and at 8 weeks, along with a proton-pump inhibitor (lansoprazole or omeprazole) and bismuth subsalicylate. MEASUREMENTS: Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsy. Partial remission was defined as a reduction in endoscopic tumor stage or 50% reduction in the size of large tumors. RESULTS: 34 patients were followed for a mean (+/-SD) of 41 +/- 16 months (range, 18 to 70 months) after antibiotic treatment. Of 28 H. pylori-positive patients, 14 (50% [95% CI, 31% to 69%]) achieved complete remission, 8 (29%) achieved partial remission (treatment eventually failed in 4 of the 8), and 10 (36% [CI, 19% to 56%]) did not respond to treatment. Treatment failed in all 6 (100% [CI, 54% to 100%]) H. pylori-negative patients. Patients with endoscopic appearance of gastritis (stage I T1 disease) were most likely to achieve complete remission within 18 months. Tumors in the distal stomach were associated with more favorable response than tumors in the proximal stomach. CONCLUSIONS: A subset of H. pylori-positive gastric MALT lymphomas, including infiltrative tumors, may respond to antibiotics. The likelihood of early complete remission seems to be greatest for superficial and distal tumors.

Anti-Bacterial Agents↗
PubMed1999

Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and gastric ulcer in Mongolian gerbils.

The establishment of persisting Helicobacter pylori infection in laboratory animals has been difficult, but in 1996 Hirayama reported the development of a successful Mongolian gerbil model. The present study was undertaken with two aims: to better characterize the normal histological structure and histochemical properties of the gastric mucosa of the Mongolian gerbil; and to evaluate the progression of the histopathological features of H. pylori-induced gastritis in this animal model for one year after the experimental infection. Seventy-five Mongolian gerbils were used. Mongolian gerbils were sacrificed at 2, 4, 8, 12, 26, 38, and 52 weeks after H. pylori inoculation. Sections prepared from stomachs immediately fixed in Carnoy's solution were stained with hematoxylin and eosin and Alcian blue at pH 2.5/periodic acid-Schiff, a dual staining consisting of the galactose oxidase-cold thionin Schiff reaction and paradoxical Concanavalin A staining, and with immunostaining for H. pylori and BrdU. H. pylori infection induced in the Mongolian gerbil a chronic active gastritis, in which a marked mucosal infiltration of neutrophils on a background of chronic inflammation became detectable 4 weeks after inoculation and continued up to 52 weeks. Intestinal metaplasia and gastric ulcers appeared after 26 weeks in some of the animals, whereas others developed multiple hyperplastic polyps. The Mongolian gerbil represents a novel and useful model for the study of H. pylori-induced chronic active gastritis and may lend itself to the investigation of the epithelial alterations that lead to intestinal metaplasia and gastric neoplasia.

Animals↗
PubMed1999

Influence of endoscopic biopsy forceps characteristics on tissue specimens: results of a prospective randomized study.

BACKGROUND: A large variety of endoscopic biopsy forceps are commercially available. However, little is known regarding the influence of forceps characteristics such as disposability, size, shape, and presence of a needle on the adequacy of the specimens for histologic diagnosis. Our aim was to analyze in a prospective, randomized, pathologist-blinded study the performance of different biopsy forceps. METHODS: Twelve biopsy forceps were tested, 6 each at upper endoscopy and colonoscopy. Two biopsy specimens were obtained with each forceps, for a total of 12 specimens per patient. The tissue samples were examined for the following parameters: weight (mg), size (mm3), depth, crush artifact, sheering effect, and adequacy of the specimens for histologic information (0 = inadequate, 1 = suboptimal, and 2 = adequate). RESULTS: Fifty-five patients undergoing routine upper or lower gastrointestinal endoscopy were included in the study, and a total of 624 tissue samples were available for analysis. Overall, disposable forceps provided specimens of greater size and depth. At upper endoscopy, alligator-shaped forceps improved the depth of the sample as did the absence of a needle within the cup. These factors, however, had no impact on the specimens obtained at colonoscopy. When the adequacy of the specimens was assessed for histologic diagnosis, no significant difference was noted between any of the individual forceps, although collectively oval-shaped forceps were superior to alligator-shaped forceps at colonoscopy. CONCLUSIONS: The biopsy forceps currently available in the market are equally efficient in providing histologic diagnosis. The primary consideration when selecting an endoscopic biopsy forceps, therefore, should be the cost and ease of use and not any perceived advantage in performance.

Adult↗
PubMed1999

The dark side of the gastric biopsy.

Based on the assumption that both sides of a gastric biopsy sample have a similar appearance, the choice of which side of a specimen is to be sectioned is usually random. We tested the hypothesis that the diagnosis reached by examining the two sides of a gastric biopsy may differ. Eighty-one antral biopsy specimens from patients with neither focal lesions nor previous gastric surgery were evaluated. After preparing 8-10 sections from each of the two opposite faces of each biopsy, sections were scored for Helicobacter pylori, activity, atrophy, intestinal metaplasia, lymphoid follicles. The presence of other lesions was also noted. Intrabiopsy agreement (the consistency in the identification of histological lesions on the opposite sides of the same sample) was calculated by using kappa statistics. A kappa value lower than 0.5 was considered "poor"; between 0.51 and 1.00 "moderate to excellent." The intrabiopsy agreement kappa values were: activity = 0.83, atrophy = 0.54, intestinal metaplasia = 0.51 and lymphoid follicles = 0.19. A mean of 42 serial sections (ranging from a mean of 22 for lymphoid follicles to a mean of 81 for xanthogranulomata) was needed to achieve an excellent (ie, kappa > or = 0.75) intrabiopsy agreement between the features showed at the opposite sides of a biopsy specimen. Intrabiopsy variability may represent a hitherto unrecognized source of error, and it should be minimized or avoided. In a research context information about the number of sections examined from a biopsy would provide a crucial element necessary to evaluate the accuracy of the histological data.

Atrophy↗
PubMed1999

Atrophy, acid suppression and Helicobacter pylori infection: a tale of two studies.

Much of what is currently accepted regarding Helicobacter pylori-associated gastritis and its relationship with gastric adenocarcinoma rests on the assumption that atrophic gastritis can be correctly identified and reproducibly recognized. Several studies have indicated that pathologists have a low level of agreement on this topic, and the terms 'gastric atrophy' and 'atrophic gastritis' remain imprecisely defined and poorly understood. Furthermore, the genesis and progression of the atrophic changes that take place in the gastric mucosa of some individuals infected with H. pylori are incompletely characterized. The lack of a strict definition of atrophic gastritis is at least partially responsible for recent concerns regarding the effects of prolonged pharmacological gastric acid inhibition in patients with H. pylori infection. One recent paper concluded that patients with reflux oesophagitis and H. pylori infection who are treated with longterm acid inhibition have an increased risk of atrophic gastritis. As this term evokes associations with an increased risk of gastric cancer, the possibility was subsequently raised that anti-secretory maintenance therapy might increase the risk of cancer in H. pylori-positive patients. A second report, however, concluded that long-term acid-inhibitory therapy for an average of three years is no different from fundoplication in the development of gastric atrophy. Also, because no intestinal metaplasia developed in any of the patients, and only atrophic gastritis associated with intestinal metaplasia is considered a precursor of gastric cancer, there is no evidence to support the hypothesis that long-term acid inhibition in individuals with H. pylori infection increases the risk of gastric cancer.

Anti-Ulcer Agents↗
PubMed1999

Molecular relationships of Helicobacter pylori strains in a family with gastroduodenal disease.

OBJECTIVE: Few studies have examined the genetic relationships of Helicobacter pylori strains affecting family members. Our aim was to do so. METHODS: We characterized H. pylori isolates obtained from members of a single family presenting with various gastroduodenal diseases to examine H. pylori bacterial genetic similarity. Endoscopic evaluation with gastric mapping was performed on each individual to establish clinical and histological disease. Genomic DNA extracted from each H. pylori isolate was used to generate DNA fingerprints for each strain by REP-PCR. vacA genotypes and cagA presence were established by PCR. RESULTS: Gastrointestinal diseases among the five members of this family included gastric adenocarcinoma in a 52-yr-old man (index patient), gastric MALT-lymphoma in the 73-yr-old mother; intestinal metaplasia (IV) and atrophic gastritis in the 48-yr-old brother; intestinal metaplasia (I-III) in the 47-yr-old brother, and a duodenal ulcer scar in the 42-yr-old sister. REP-PCR DNA fingerprints of H. pylori isolates from the index patient, his mother, and both of his brothers were identical or highly similar. By contrast, the H. pylori DNA fingerprint from the sister was markedly different from the H. pylori DNA fingerprints from the other family members. All isolates had the genotype cagA-positive and vacA slb/ml mosaic genotype. CONCLUSIONS: The DNA fingerprints of H. pylori strains obtained from members of this family with malignancy or premalignant histological disease were identical or highly similar and markedly different from the H. pylori DNA fingerprint from the sibling with duodenal ulcer disease. All H. pylori isolates within the family possessed genetic markers of enhanced virulence (presence of the cagA gene and vacA sl/ml mosaicism). In addition to host genetics and environmental factors, these findings suggest that infection with genetically similar H. pylori strains is a significant factor in determining the clinical outcome of an infection with H. pylori.

Adenocarcinoma↗
PubMed1999

Proinflammatory activation of neutrophils and monocytes by Helicobacter pylori in patients with different clinical presentations.

Chronic Helicobacter pylori infection is associated with mucosal inflammation. The aim of the present study was to assess human neutrophil and monocyte activation by H. pylori strains obtained from patients with different clinical presentations. Bacterial sonicates from 12 strains were used to stimulate phagocyte upregulation of CD11b/CD18 adherence molecules assessed by fluorescence flow cytometry and oxidative burst responses assessed by chemiluminescence. A dose-dependent activation of CD11b/CD18 adherence molecules was observed with all strains on both neutrophils and monocytes. The activities were similar for strains from patients with duodenal ulceration and for strains from asymptomatic volunteers irrespective of histopathologic grades of the biopsy specimens from the antral mucosa. The neutrophil chemiluminescence response correlated with histopathologic severity. We conclude that upregulation of neutrophil and monocyte adherence molecules by H. pylori sonicates is not associated with clinical presentation of the infection.

CD18 Antigens↗
PubMed1999

Gastric precancerous lesions: heading for an international consensus.

As pathological criteria lie at the foundation for the classification of many diseases, a crucial requisite for such classifications to be valid is that their morphological basis be standardised. Inadequately standardised diagnostic criteria result in unacceptable interobserver variation, a factor that may influence both individual patient care and the evaluation of clinical protocols. One of the most important goals in gastric diseases today is to establish whether cure of Helicobacter pylori is an effective preventive measure against gastric cancer. To tackle this issue it is necessary to measure reliably intermediate outcomes, specifically gastric atrophy and dysplasia. However, there is little agreement on what gastric atrophy and atrophic gastritis are, and treatment and follow up results obtained at one clinical centre are often radically different from those obtained at another. Similarly, studies that examine the fate of dysplastic lesions in the stomach show a great divergence of outcomes between Europe and North America and Japan, where the concept of dysplasia has different connotations. To reach a consensus on the definitions and diagnostic criteria for atrophy and atrophic gastritis, a group of gastrointestinal pathologists and gastroenterologists met in Houston, Texas, USA, in February 1998. Substantive progress was made, but several problems remained, and a study aimed at resolving the issues that seem to stand in the way of an international agreement is currently underway. To fulfil the need for a broad discussion on the diagnostic differences of gastric dysplasia and cancer between East and West, an international group of pathologists gathered in Padova, Italy, in the spring of 1998. Their main objectives were: (1) to agree on the definitions of the spectrum of gastric preneoplastic lesions; (2) to establish an international glossary for gastric precancerous lesions; and (3) to test the consensus and eventually generate guidelines useful to clinicians for the development of management strategies. A consensus was achieved on the definition of gastric dysplasia as preinvasive neoplasia. Other validation studies are underway. The experiences achieved in the search for an international consensus on the phenotypes of atrophic gastritis and gastric dysplasia may represent a model in dealing with the new scenario of a modern evidence-based pathology.

Atrophy↗
PubMed1999

The sad NSAID colon.

The condensed article reports the results of the histopathologic evaluation of the colorectal biopsy specimens from 14 patients who developed abdominal pain and bloody stools or diarrhea while receiving nonsteroidal anti-inflammatory drugs (NSAIDs). All patients had a mixed inflammatory infiltrate (predominantly neutrophilic in four patients and lymphocytic in two) and about one-half also had minimal crypt disarray. The intestinal symptoms resolved in all patients after NSAIDs were discontinued, but there was no histopathologic verification that the inflammatory changes had subsided. Nonspecific changes ("focal colitis"), similar to those described in this group, are present in most patients who undergo a colonoscopy for the investigation of diarrhea. This article calls attention on one of the possible and neglected causes for nonspecific colitis. However, larger controlled studies are needed to firmly establish a cause-and-effect relationship with NSAID intake.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Helicobacter pylori infection produces reversible glycosylation changes to gastric mucins.

The protective ability of gastric mucins may depend largely on their oligosaccharide chains. We evaluated the effects of H. pylori infection on the glycosylation of gastric mucins. Gastric biopsy specimens from 20 H. pylori-infected patients before and after cure of the H. pylori infection and 8 normal uninfected volunteers were examined by immunostaining for simple mucin-type glycoproteins and blood-group-related antigens bearing type 1 chain backbone. The immunoreactivity in different gastric compartments was evaluated. Simple mucin-type glycoproteins and blood-group-related antigens were expressed in surface mucous cells. Simple mucin-type glycoproteins showed antrum-predominant expression in normal volunteers and were found in significantly fewer surface mucous cells in infected patients than in normal volunteers; their expression was restored after eradication of H. pylori. Sialyl Lewis(a) and Lewis(b) were expressed in fewer surface mucous cells after than before eradication. The patterns of glycosylation of gastric mucins vary in different gastric compartments and are reversibly altered by H. pylori infection. These alterations may affect the protective functions of gastric mucins.

Adult↗
PubMed1998

Intestinal metaplasia with adherent Helicobacter pylori: a hybrid epithelium with both gastric and intestinal features.

Helicobacter pylori seem to avoid areas of intestinal metaplasia in the gastric mucosa, but attachment of these bacteria to epithelium with the appearance of incomplete intestinal metaplasia has been documented. To characterize the nature of the epithelium to which H pylori was attached, we carried out an immunohistochemical study using monoclonal antibodies against gastric surface mucous cell mucins (M1), blood group-related carbohydrates antigens (Le(a), sialyl Le(a), Le(b), type 1H, and type 2H) and sialyl Tn antigen. The results of this study suggest that these areas of H pylori attachment represent a hybrid epithelium whose cells share characteristics of both gastric surface mucous cells and intestinal metaplastic cells. Whether all areas of incomplete intestinal metaplasia represent an intermediate stage between the normal gastric epithelium and the fully developed complete type of metaplasia remains to be determined.

ABO Blood-Group System↗