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Biomedical subjects

R Fiocca

Publications and source records attributed to R Fiocca.

At least 91 records · Page 5Linked to original sources

Gastric argyrophil carcinoidosis in patients with Zollinger-Ellison syndrome due to type 1 multiple endocrine neoplasia. A newly recognized association.

We report four cases of gastric argyrophil carcinoidosis arising in the oxyntic mucosa of patients with Zollinger-Ellison syndrome as part of type 1 multiple endocrine neoplasia (MEN) syndrome. Multiple mucosal and submucosal carcinoids were seen in combination with innumerable hyperplastic and dysplastic growths of argyrophil endocrine cells disseminated in the entire acidopeptic mucosa. Histochemical and ultrastructural investigation indicated that the argyrophil enterochromaffin-like (ECL) cell, a type of endocrine cell normally restricted to the oxyntic mucosa and very sensitive to gastrin stimulation, was a major component of the carcinoidosis. Five similar cases were found in the literature. Because argyrophil ECL cell carcinoid or carcinoidosis is unusual in patients who have the Zollinger-Ellison syndrome but do not have MEN, we believe that the genetic trait of the MEN syndrome has an important permissive role in the promotion of gastric carcinoids through the hypergastrinemia inherent to Zollinger-Ellison syndrome.

Adult↗

Helicobacter pylori infection and chronic gastritis: clinical, serological, and histologic correlations in children treated with amoxicillin and colloidal bismuth subcitrate.

Twenty-three children with Helicobacter (Campylobacter) pylori-associated chronic gastritis are reported. Family history of peptic disease, previous digestive procedures, and nonspecific epigastric pain were the most frequently encountered clinical features. Antral nodularity at endoscopy and histologic evidence of follicular gastritis were characteristic morphological aspects. Rapid urease tests suggested the diagnosis in 90% of patients. Significant increases of serum IgG and IgA against Helicobacter pylori allowed the identification of infected children with 95% cumulative sensitivity. Treatment with amoxicillin and bismuth subcitrate eradicated the infection and improved gastritis in 13 of 19 children. These findings provide further evidence for the etiologic role of Helicobacter pylori in chronic antral gastritis in children.

Adolescent↗

Immunocytochemical detection of proliferating cells in the rat tooth germ by monoclonal antibodies against 5-bromo-2'-deoxyuridine.

5-Bromo-2'-deoxyuridine incorporated into DNA synthesizing cells in vivo is detected by a monoclonal antibody. The results are similar to those obtained with cytoautoradiography, but show variance with data from some past autoradiographic studies. This immunocytochemical technique may be a useful tool for study of cell kinetics in the oral tissues.

Animals↗

Prognostic significance of DNA content in large bowel carcinoma: a retrospective flow cytometric study.

Flow cytometric (FCM) determination of DNA content was performed on surgical specimens from 44 patients with previously untreated colonic carcinoma. For each tumor, cell suspensions were prepared from 2-4 40-microns thick sections obtained from formalin-fixed and paraffin embedded tissue samples. Aneuploidy was found in 47.2% of all the tumors and the aneuploid clone had a median DNA index of 1.49 (range: 1.24-1.93). Aneuploidy was found in 26.7% of highly differentiated tumors (WHO histologic classification), in 53.8% of moderately differentiated tumors and in 100% of poorly differentiated tumors (P = 0.04). The 33.3% of stages 1 + 2 (TNM) and the 70.6% of stages 3 + 4 tumors were aneuploid (P = 0.002). Median survival from surgery was 46.4 months for all patients. It was 18.8 months for patients with aneuploid tumors and 85.7 months for those with diploid tumors (P = 0.0002). FCM determination of DNA in colon carcinomas can easily be performed on archival histological material and provides prognostic information.

Adult↗

The gastroenteropancreatic endocrine system and related tumors.

Up to 16 types of endocrine cells have been characterized morphologically (and most of them also functionally) in the gastroenteropancreatic area. Four main groups of pancreatic endocrine tumors (with several subtypes) have been identified: islet cell, ectopic, nonfunctioning, and poorly differentiated tumors. A detailed classification system that combines cytologic and clinicopathologic patterns has been developed for the study of 132 pancreatic tumors. Among a large series (more than 120 cases) of endocrine tumors arising in the gastrointestinal tract, serotonin-producing argentaffin carcinoids have been separated from hindgut trabecular carcinoids, producing glucagon- and pancreatic polypeptide-related peptides, paragangliomas, somatostatin cell tumors, gastrinomas, and argyrophil ECL cell carcinoids. The clinicopathologic profile of the various pancreatic and gastrointestinal tumor entities has been delineated and involvement in the multiple endocrine neoplasia syndrome has been analyzed in detail.

Adenoma, Islet Cell↗

Expression of pepsinogen II in gastric cancer. Its relationship to local invasion and lymph node metastases.

We have determined the prevalence of pepsinogen II (PG II) immunoreactive cells in a large series of early and advanced gastric cancers and relationships among PG II-positivity, tumor histologic type, extent of gastric wall invasion, and presence of lymph node metastases. Of the 316 cancers evaluated, 150 (47%) expressed PG II. The prevalence by histologic type was 55% in 146 glandular tumors, 43% in 83 diffuse tumors, 16% in 25 mucoid tumors, and 51% in 59 mixed-type cancers. Two parietal cell cancers and one undifferentiated cancer were PG II-negative. In glandular and diffuse cancers, but not mucoid and mixed tumors, both the extent of gastric wall invasion and incidence of lymph node metastases were associated positively with PG II expression by the primary tumor. In particular, PG II-reactive cells were found significantly more often in advanced than in early diffuse cancers (P less than 0.05) and significantly more often in submucosal early cancers than in intramucosal early cancers (P less than 0.01). The prevalence of PG II expression also was higher significantly in metastatic cancers than in nonmetastatic cancers. This was true for advanced gastric cancers as a whole (P less than 0.01), advanced glandular-type cancer alone (P less than 0.01), advanced glandular- and diffuse- type cancers together (P less than 0.001), and early diffuse-type cancer (P less than 0.05). Only four (3%) of 145 cancers evaluated for pepsinogen I (PG I) were positive, and each also was positive for PG II. The results suggest that the expression of PG II by glandular and diffuse types of gastric cancer may be a marker of increased malignancy.

Humans↗

In vivo bromodeoxyuridine incorporation in human gastric cancer: a study on formalin-fixed and paraffin-embedded sections.

Bromodeoxyuridine (BUDR) is a non-radioactive thymidine analogue which is incorporated into the DNA of proliferating cells. This allows evaluation of the size of the S-phase as the BUDR labelling index (BUDR-LI) not only in vitro but also in vivo, since BUDR is not toxic at the doses needed to label cells. To ascertain whether in vivo BUDR incorporation can be detected on routine histological material we tested several different procedures prior to immunoperoxidase staining, on formalin-fixed, paraffin-embedded sections from five patients with gastric cancer, who received BUDR (250 mg m-2, intravenous) 4 h before surgery. To determine the optimal conditions for detecting BUDR in formalin-fixed tissues, immunohistochemical testing for BUDR was performed simultaneously on duplicate sections fixed with 70% ethanol. It was found that hydrolysis with 3N HCl at 37 degrees C for 30 min and digestion with 0.5% in at 37 degrees C for 30 min were sufficient to detect BUDR immunoreactivity in formalin-fixed sections. The method presented extends the range of applications of the in vivo BUDR technique for cell kinetics studies in human neoplasms because it can be used on routinely fixed archival material, with the advantage of correlating the kinetic data with histopathological characters.

Adenocarcinoma↗

Widespread expression of intestinal markers in gastric carcinoma: a light and electron microscopic study using BD-5 monoclonal antibody.

BD-5 monoclonal antibody reacted with tumour cells in 262 of 316 cases of gastric cancers, including 121 of 134 early, 141 of 182 advanced tumours (p less than 0.01), and 113 of 146 glandular, 72 of 83 diffuse, 22 of 25 mucoid, and 55 of 59 mixed tumours. No difference in reactivity was observed between metastatic and non-metastatic advanced tumours. Immunocytochemical techniques applied to light and electron microscopical specimens of colorectal mucosa and gastric cancer showed that BD-5 immunoreactive material occurred in the Golgi complex, in small clear, to dense cored, cytoplasmic vesicles, and in the glycocalix of the luminal and lateral membranes of normal and neoplastic cells in the glands, as well as in the peripheral membrane of dispersed neoplastic cells. Mucin granules stored in the cytoplasm of goblet cells were unreactive or poorly reactive. Ultrastructural features consistent with colorectal type differentiation were observed in many reactive tumours. Unreactive tumours showing ultrastructural patterns consistent with intestinal differentiation, especially of small bowel type, were also observed. Signs of intestinal differentiation, including BD-5 immunoreactivity, often occur in gastric cancer, irrespective of histological type and stage of disease.

Adult↗

Flow cytometric analysis of paraffin-embedded material in human gastric cancer.

Flow cytometric DNa analysis was performed on formalin-fixed, paraffin-embedded samples obtained by gastroscopic biopsy from 9 patients with histologically normal gastric mucosa (36 specimens) and by radical gastrectomy from 42 cases of human gastric cancer (120 specimens). Ploidy patterns and the distribution of cells in the different cell cycle phases were estimated, and the results were correlated with the histologic and clinical features. All samples of normal mucosa showed a diploid modal DNA content whereas DNA aneuploidy was encountered in 71.4% of the gastric tumors. The correlation between aneuploidy and histologic malignancy grading was statistically significant: aneuploidy was found in 36.4% of highly differentiated (grade 1 and grade 2) tumors and in 75.0% of poorly differentiated (grade 3) tumors (P less than .05). The percentage of cells in S-phase in normal gastric mucosa (median: 5.0%) was lower than that in the tumors (median: 11.3%) (P less than .05). There was a trend for grade 3 tumors to have higher median values (median: 13.4%) than grade 1 and 2 tumors (median: 9.3%); however, this was not statistically significant. An aneuploid DNA pattern was associated with a poorer prognosis, both in early and in advanced stages of gastric tumors, while proliferative activity did not correlate with postoperative survival.

Adult↗

Glucagon, glicentin, proglucagon, PYY, PP and proPP-icosapeptide immunoreactivities of rectal carcinoid tumors and related non-tumor cells.

Glucagon/PP-related peptides were detected immunohistochemically in 18 out of 22 cases of rectal tumors investigated. The reactive tumors showed prevalence of trabecular or mixed trabecular-acinar structure and moderate staining with Grimelius' silver and lead-hematoxylin. Three of the remaining 4 cases were characterized by reactivity for 5-hydroxytryptamine only, prevalence of a solid nest structural component and intense staining with Grimelius' silver technique and lead-hematoxylin. Fifteen of the 18 glucagon/PP-reactive cases were investigated immunohistochemically with a series of 6 sera directed against different sequences of glucagon, glicentin and proglucagon, and of 7 sera directed against PP, PYY and proPP-icosapeptide. A large spectrum of glucagon-related immunoreactivities, including C-terminus and mid-portion glucagon-immunoreactivity, N- and C-terminus glicentin-immunoreactivity, GLP1- and GLP2-immunoreactivity, were detected in human rectal L cells and most rectal carcinoids. With the exception of a few scattered cells in the rectal mucosa and in 3 tumors, C-terminus glucagon-immunoreactivity was obtained only after trypsin or subtilisin treatment of tissue sections. Both PYY and PP/proPP-like peptide(s) were detected in rectal L cells and carcinoids, with prevalence of PYY in normal cells and PP/proPP-like peptides in tumor cells. It is concluded that the same or closely related hormone/prohormone sequences are synthesized and stored in rectal endocrine cells and carcinoid tumors although differences of quantitative expression, post-translational cleavage or reactivity to antibodies may occur. The usefulness of protease treatments of tissue sections to unmask immunoreactivities of uncleaved propeptides or fixative-denatured peptides is outlined.

Animals↗

Characterization of four main cell types in gastric cancer: foveolar, mucopeptic, intestinal columnar and goblet cells. An histopathologic, histochemical and ultrastructural study of "early" and "advanced" tumours.

Gastrectomy specimens of 148 gastric cancers, 40 of them being intramucosal or microinvasive, 27 penetrating the submucosa and 81 invading the muscularis propria, with or without involvement of the serosa and perigastric tissues, have been investigated with conventional histopathologic techniques, mucin histochemistry and electron microscopy to characterize the various lines of tumour cell differentiation and to correlate these with the histologic patterns of tumour growth. More or less differentiated intestinal columnar, intestinal goblet, gastric foveolar or mucopeptic cells were recognized in most tumours, of glandular, diffuse or mucoid type. Although simultaneous expression of more than one cell type into the same tumour occurred very frequently, intestinal columnar cells were more prominent in tubular adenocarcinomas, goblet cells (especially of colorectal type) in mucoid cancers, mucopeptic cells in diffuse cancers of invasive desmoplastic type and foveolar cells in diffuse cancers of intramucosal signet-ring cell type. In general, an increased tendency to foveolar cell differentiation and a reduced tendency to mucopeptic differentiation has been found in intramucosal cancers as compared to invasive cancers. It is concluded that the type of tumour cell differentiation, which might have some influence on the natural history of gastric cancer, is better related with more defined tumour subtypes than with the usually recognized glandular or diffuse patterns.

Gastric Mucosa↗

High incidence of Campylobacter-like organisms in endoscopic biopsies from patients with gastritis, with or without peptic ulcer.

Campylobacter-like organisms (CLOs) were histologically detected in 230 (74.5%) of 310 patients undergoing endoscopy with multiple gastric biopsies for symptoms suggestive of upper digestive disease. CLOs were found in 78.6% of nonulcerous dyspeptic patients, 82.2% of healed ulcers, 88.2% of duodenal or pyloric ulcers and 90.0% of gastric ulcers but only in 46.9% of gastric stumps and 47.6% of nonulcerous patients without dyspepsia. Among 274 subjects with gastritis, CLOs were found in 83.9%, while none of the 36 gastritis-free stomachs harbored CLOs. Severe atrophic gastritis was less frequently infected with CLO (55.5%) as compared with superficial, interstitial or preatrophic gastritis (84.4%). CLOs were only slightly more frequent in the presence of intraepithelial granulocytes and were never found in areas of complete intestinal metaplasia. Foveolar and superficial epithelia heavily infected with CLOs showed peculiar ultrastructural changes (micropapillary hyperplasia with luminal bulging of mucous cells, cytoplasmic vacuolization and edema, etc.) suggesting a direct link between CLO infection and epithelial damage, which in turn may have a role in the genesis of mucosal inflammation.

Adolescent↗

Ploidy and proliferative activity of human gastric carcinoma: a cytofluorometric study on fresh and on paraffin embedded material.

Flow cytometric DNA analysis was performed on both fresh and on paraffin embedded samples obtained by gastroscopic biopsies in 5 patients with histologically normal gastric mucosa (20 specimens) and by radical gastrectomies in 9 cases of human gastric cancer (36 specimens). Ploidy and the distribution of cells in the different cell cycle phases were estimated. Results from fresh tissue were compared with those from paraffin embedded material. All the samples of normal mucosa showed a diploid modal DNA content. Unimodal DNA distribution was found both in fresh and paraffin embedded material of 3 well differentiated gastric adenocarcinomas, whereas the remaining 6 tumors (1 moderately differentiated, 4 poorly differentiated and 1 undifferentiated adenocarcinomas) showed aneuploidy. The percentage of cells in S phase in normal tissue and in tumors were respectively 9.0% and 11.9% in the fresh material, and 10.0% and 15.0% in the paraffin embedded material. No statistically significant differences were found between fresh and paraffin embedded samples, whereas the proliferative activity was, in both cases, statistically higher in tumors than in normal mucosa (p less than .01 and p less than .001 respectively). The quality of DNA flow cytometry from paraffin embedded material was comparable with that from fresh samples.

Aged↗

Glucagon- and PP-related peptides of intestinal L cells and pancreatic/gastric A or PP cells. Possible interrelationships of peptides and cells during evolution, fetal development and tumor growth.

The immunohistochemical detection of six distinct sequences of proglucagon and its derivatives (GRPP, glicentin, glucagon-37, glucagon-29, GLP1, GLP2 and MPGF) in both intestinal L cells and pancreatic or gastric A cells of some mammals (dog, man, guinea pig) confirms that the two cell types produce the same proglucagon molecule, although the final step of its post-translational processing differs in the two cells. Immunohistochemical and ultrastructural patterns of glucagon/glicentin cells in the pancreas of lower vertebrates and early human fetuses, as well as tumor cell studies, suggest an evolution of gastropancreatic A cells from L cells. On the contrary, the PP-related peptide PYY of intestinal L cells, and PP with its C-terminal icosapeptide extension of pancreatic PP cells, likely originate from different prohormones. Although intermediate patterns of peptide expression can be observed, including some F-type PP cells of the dog pancreas (uncinate process) and pyloric mucosa showing PYY immunoreactivity or rare PYY and/or HPP immunoreactive cells of the human rectum lacking glicentin reactivity, no obvious relationship can be established between L cells and pancreatic (F-type) PP cells. However, some evolutionary, embryogenetic and oncogenetic link may exist between L cells and human D1-type PP cells, a minor population of PP cells scattered in the pancreatic tissue of dorsal pouch origin and a major fraction of tumor PP cells.

Animals↗