Role of chronic atrophic gastritis of the body-fundus and achlorhydria in the development of epithelial dysplasia and gastric carcinoma.

BACKGROUND/AIM: Chronic atrophic gastritis of the body-fundus with hypo-achlorhydria has been long since considered the precursor of gastric cancer (GC). A study has been made about the histological pattern of the body-fundic mucosa (oxyntic area) in course of preneoplastic lesions (epithelial dysplasia), associated or progressed to gastric cancer, in order to evaluate the real association with chronic atrophic gastritis and, therefore, with a reduced acid secretion. METHODOLOGY: The study of the histological condition of the body-fundic mucosa and of the acid secretion has been effected in 120 cases of epithelial dysplasia (ED) from January 1990 to November 1997. The casuistry is composed of 70 cases of low grade dysplasia (LGD) and 50 cases of high grade dysplasia (HGD). Gastric biopsy specimens were studied for dyspepsia: for each patient, at least 8 specimens were obtained from the lesion area and in surrounding areas. Besides, at least 4 biopsies have been performed in the opposite gastric region. ED diagnosis was effected according to well defined criteria. The histological study of gastric mucosa in gastritis was effected or revised in accordance with the updated Sydney system (Houston). Stimulated acid secretion was expressed as Maximal Acid Output (MAO), which is the amount of HCl produced in one hour, following stimulation with pentagastrin (6 micro-g/kg). The clinical outcome subdivision of ED was made using the criteria of Rugge et al. (12). RESULTS: HGD significantly associates with GC in comparison with LGD. The histological evaluation of the oxyntic area shows severe chronic atrophic gastritis (SCAG) in a low percentage of cases (15/120: 12.5%): LGD 9/70: 12.85% ; HGD 6/50: 12%. Complete achlorhydria has been noted in 5 cases of LGD and in 1 case of HGD only. In case of GC (43 subjects) SCAG has been evidenced in 10 cases and complete achlorhydria in 5 cases. CONCLUSIONS: From the data of the present experience emerges that the presence of SCAG of the oxyntic area in course of ED or early GC is limited to a low percentage of cases. Such concepts induce to modify some indications related to the endoscopic surveillance and, in accordance with the American Society of Gastrointestinal Endoscopy we are stating that there are no sufficient data to support subsequent endoscopic surveillance for the subjects with atrophic gastritis.

p53 and Ki-67 expression in epithelial gastric dysplasia and in gastric cancer.

BACKGROUND: The aim of this study was to examine p53 and Ki-67 expression in relation to high grade dysplasia (HGD) clinical behaviour. METHODS: A retrospective, cross sectional study was conducted on mucosal biopsies from the stomach of 38 consecutive cases of HGD (25 males, average age: 57.5). The studied samples are represented by gastric biopsies obtained in course of gastroscopy for dyspepsia (at least 8 biopsies). HGD diagnosis was done by experienced pathologists (MC, DG) according to Goldstein's criteria. There were 12 non-dysplastic controls (7 males, average age: 49.4). The immunohistochemical study has been led with the utilization of a p53-antibody. For the cell proliferation assay, the sections were incubated with the MM1 monoclonal antibody. The clinical outcome subdivision of HGD was effected using the criteria of Rugge et al. For the classification of gastric cancer (GC): UICC TNM. RESULTS: p53 positivity has been evidenced in 65.5% of cases, while hyperproliferation in 100% of cases. That independently of the clinical behaviour. CONCLUSIONS: p53 positivity has been found only in part of the HGD cases and moreover a number of HGD with low or absent p53 scores has been found associated with high proliferation indices independently of the clinical evolution. This dissociation of cell kinetics and p53 expression suggests that other genetic events contributing to unregulate cell proliferation may occur in these lesions.

Helicobacter pylori influence on gastric acid secretion in duodenal ulcer patients diagnosed for the first time.

BACKGROUND: Many experiences have hypothesised that Helicobacter pylori induced hypergastrinemia could lead to an increase of the parietal cell mass and, consequently, of acid secretion. METHODS: The parietal cell mass and maximal acid output have been studied in patients with duodenal ulcer diagnosed for the first time, not due to drugs assumption. In particular, it has been evaluated the parietal cell mass and the acid secretion subdividing duodenal ulcer patients in relation to gastrinemia values (hypergastrinemia and normogastrinemia). RESULTS: The parietal cell mass and the maximal acid output remain high independently of Helicobacter pylori presence. About 60% of the subjects in the Helicobacter pylori positive group show gastrinemia values higher than the average: neither did the study reveal in this group any variations in the parietal cell mass and acid secretion. CONCLUSIONS: It emerges from the results that the mild chronic hypergastrinemia in Helicobacter pylori positive duodenal ulcer is not important enough to induce an increase in parietal cell mass and acid secretion. Therefore, Helicobacter pylori eradication is important in relapse prevention of duodenal ulcer, but not for its repercussions on the gastric secretion.

The role of histological investigation in prognostic evaluation of advanced gastric cancer. Analysis of histological structure and molecular changes compared with invasive pattern and stage.

The relative contribution of tumour histology or molecular changes, compared with invasion pattern or stage, to prognostic assessment of gastric cancer was investigated in a series of 185 advanced (T2 to T4, stage IB to IV) cancers that had undergone intentionally curative surgery at Varese General Hospital. Survival analysis of the histological types considered in commonly used classifications, such as Lauren, Kubo, the World Health Organization (WHO) and related classifications, allowed separation of a small high-grade (Hg, 12 cases) group of adenosquamous, anaplastic and small cell endocrine carcinomas from a large cohesive group (C, 86 glandular or solid cancers) and from another large (87 cases) group of tumours with dissociated cells [29 diffuse (D) and 58 mixed (M) tumours]. Univariate and multivariate analysis showed the independent prognostic value of this C/M+D/Hg classification approach, which proved superior to other classifications and to cell dissociation at the growing front or angio, lympho and neuro-invasion. Expression of sialyl Lewis(c), the DUPAN-2 antigen, proved to be an independent predictor of worse survival among tumours beyond stage I, showing an exclusively or predominantly cohesive structure. Microsatellite instability (MSI) predicted favourable survival in purely cohesive tumours of intermediate (II) stage, especially of solid/medullary and lymphoid stroma/lympho-epithelioma-like structure, among which two distinct tumour subsets were characterised, one MSI-positive and the other Epstein-Barr virus positive. T2NOM0 (stage IB) tumours showed mostly favourable survival independently from histological type, invasive pattern, DUPAN-2 or MSI status. It is concluded that an appropriate histological evaluation, coupled with sialylated glycoproteins histochemistry and, for stage-II tumours, MSI tests may contribute significantly to prognostic assessment of tumours beyond stage I. However, the stage itself, with special reference to lymph-node metastases and invasion level beyond subserosa, remains the most important prognostic clue for gastric cancer.

[Endoscopic surveillance of precancerous changes in the stomach]. / Sorveglianza endoscopica delle modificazioni precancerose dello stomaco.

Undoubtedly, one of the most important achievements of gastroenterology is the demonstration that, for many pathological conditions with future neoplastic degeneration risk, a periodical endoscopic surveillance is a determining element for the restraining of possible evolutive complications. Nonetheless, it is to be considered how, during the last years, the prevention and follow-up procedures for the stomach disease have been sometimes emphasized. In fact, various recent evidences originated from precise scientific evaluations have contained same prevention strategic attitudes so as to reach the best cost-benefit ratio. In this survey the various gastric preneoplastic modifications, subdivided in precancerous conditions and lesions are examined and guidelines are proposed in order to offer quick and easily applicable solutions.

[Gastric epithelial dysplasia]. / La displasia epiteliale gastrica.

Gastric epithelial dysplasia represents the only true histological marker of gastric cancer. In this bringing up to date, such subject is reproposed in consideration of taking into account the most recent acquisitions, subdividing gastric dysplasia into two degrees only: moderate and severe. For the first time an immunophenotypic study is made by means of the evaluation of gastric-entero-pancreatic antigens, which better identify the evolutive potential of the two degrees of gastric dysplasia and, furthermore, the clinical development is evaluated, thus showing the necessity of a strict endoscopic surveillance of such lesion.

Mixed endocrine-exocrine tumors of the gastrointestinal tract.

Mixed endocrine-exocrine tumors of the gastrointestinal tract are rare neoplasms, which have been reported in the literature mainly as case reports and have been designated with a various and rather confusing terminology. In this review, on the basis of personally studied cases and of the analysis of cases reported in the literature, we have tried to identify types of mixed endocrine-exocrine tumors showing different clinicopathologic and biological characteristics. We have also tried to group the different clinicopathologic entities in prognostic classes which include: benign, low-grade, intermediate grade, and high-grade malignant mixed endocrine-exocrine tumors. The criteria for identifying the various types of mixed endocrine-exocrine tumors are extensively discussed.

[The physiopathological aspects of chronic gastritis, Helicobacter pylori and precancerous gastric changes]. / Aspetti fisiopatologici della gastrite cronica, Helicobacter pylori e modificazioni precancerose gastriche.

Chronic gastritis represents the paradigmatic histological condition by means of which the various clinical displays develop. Among the several etiologic factors, Helicobacter pylori (Hp) certainly represents a determining element for the promotion of such condition. Several morpho-functional evaluations (parietal cells, peptic cells, acid secretion, peptic secretion, gastrinemia) point out how Hp has on the mucosa a mainly direct action, without any substantial modifications of the gastric milieu. Certainly, the bacteria help the bodyfundic atrophic gastritis, but seldom this condition contributes to the modification of the gastric pH in such a relevant way so as to prime the fall of events which lead to the preneoplastic/neoplastic modifications. Metaplastic, dysplastic and neoplastic clones may arise, in the course of Hp infection, even in conditions of normochloridria. Such bacterium behaves as a cofactor of various other damaging or predisposing agents, contributing to modulate the risk by acting on host genetic susceptibility.

[Primary gastric lymphomas. Clinico-pathological study and evaluation of prognostic factors in 65 cases treated surgically]. / Linfomi gastrici primitivi. Studio clinico-patologico e valutazione dei fattori prognostici in 65 casi trattati chirurgicamente.

Based on the histological criteria proposed by the REAL and adopted by the WHO Classification, 30 cases of MALT type lymphoma, 18 cases of diffuse large B cell lymphoma (DLCL), and 17 cases of DLCLs, associated with a MALT type, were identified in a series of 65 surgically treated primary gastric lymphomas. The clinical records of the patients were analyzed retrospectively and the resected specimens were immunostained for bcl-2, p53 and Ki-67. Primary gastric DLBCLs, with or without a MALT type component, disclosed a higher stage of local extension, a more frequent nodal involvement and a significantly worse survival than pure MALT types. High p53 expression and high proliferation rate correlated with the presence of a large cell component and appeared useful for its identification in mixed forms. Low bcl-2 expression discriminated DLCL from DLCL/MALT. Tumor size, stage and Mib-1 index revealed a value in predicting prognosis.

Low incidence of hereditary nonpolyposis colorectal cancer syndrome in a selected area of the Lombardy Cancer Registry.

AIMS AND BACKGROUND: Epidemiological investigations on the frequency of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are few and have shown a variable worldwide incidence ranging from 1% to 7% of all colorectal cancers (CRCs). In Italy, relevant differences have been observed: 2.8-3% of all CRCs in northern regions and less than 1% in southern regions. The aim of the present study was to investigate the HNPCC incidence in a selected area of northern Italy belonging to the Lombardy Cancer Registry. METHODS AND STUDY DESIGN: We analyzed 197 consecutive patients with newly diagnosed CRCs, histologically verified, and resident in two areas of the Lombardy Cancer Registry. For each case, genetic counseling with at least three generations pedigree reconstruction, HNPCC classification according to Amsterdam criteria, molecular analysis for microsatellite instability and immunohistochemistry for hMLH1 and hMSH2 were performed. RESULTS: A very low frequency (0.5%) of HNPCC fulfilling the Amsterdam criteria was found in comparison to the other Italian areas. Such an incidence seems to be due to actual population differences and reflects a genetic heterogeneity. CONCLUSIONS: The data underline the importance of a precise knowledge of actual HNPCC incidence in different populations in order to optimize effectiveness and efficiency of screening programs for the disease.

Primary malignant duodenal tumours: a point of view and a proposal of classification.

To date, malignant duodenal tumours have remained obscure subject-matter although they were first described in the eighteenth century. Recent development in technology and in anatomohistopathology makes it necessary to review the duodenal tumours classification, especially in relation to the progressive development of stromal and neuroendocrine forms. In the literature, precise epidemiological data are not reported and, as regards some duodenal tumours, simply do not exist. Series are generally either surgical, anatomopathological or gastroenterological. Hospital centres need to establish a collaboration which gathers new observed cases to avoid the dispersion of case series. Thus, a European Register will be established to report the real incidence by analyzing the specific differential elements.

Gastric cyto-secretory correlations in peptic ulcer.

BACKGROUND/AIMS: Maximal acid output, parietal cell mass, serum pepsinogen A (PGA) and total peptic activity (TPA) in gastric juice were studied and compared in duodenal ulcer and in different gastric ulcer sites. METHODOLOGY: 152 peptic ulcer patients were studied. 64 cases of gastric ulcer (GU) were subdivided according to Johnsons's classification and compared with 88 duodenal ulcer (DU) patients diagnosed for the first time. 40 normal subjects were studied as controls. RESULTS: Duodenal ulcer is characterized by normo-hyperparietalism, normo-hyperchloridria and an increase in peptic activity. In cases of GU, such correlation is not only conditioned by the topographic seat of the ulcer, but by the histological condition of the gastric mucosa too. Body GU is characterized by hypoparietalism, hypochloridria, hyper-PGA and hyper-TPA. Pre-pyloric GU is characterized by normo-hyperparietalism, normo-hyperchloridria, hyper-PGA and hyper-TPA. In GU the cyto-secretory behavior is characterized by the histology of the body mucosa with prevalence of preatrophic-atrophic gastritis in case of body GU and prevalence of superficial gastritis in case of GU type II and III. CONCLUSIONS: The results confirm the anatomic-functional analogy between DU and type II and III GU. If considered from the functional point of view, these conditions differ considerably from those that are characteristic of type I GU (as they closely follow the chronic gastritis pattern).