Gian Maria Paganelli

Helicobacter pylori infection and gastric function in patients with chronic idiopathic dyspepsia

Helicobacter pylori infection, histological features of the gastric mucosa, and gastric motor and secretory functions were evaluated in 45 consecutive patients with chronic idiopathic dyspepsia. H. pylori infection was found in 60% of dyspeptic patients, compared with 33% of 15 healthy controls (P = 0.1). No difference was detected in basal or stimulated gastric acid secretion between dyspeptic patients and healthy controls. Gastric emptying was significantly (P less than 0.01) delayed in dyspeptic patients compared with healthy controls when standardized for age and sex. Delayed gastric emptying was associated with a low frequency of H. pylori infection, female gender, and young age. Epigastric pain or burning and postprandial fullness were, respectively, more severe in patients with H. pylori infection (P less than 0.02) and in those with delayed gastric emptying (P less than 0.01). These findings support the existence of separate subsets of patients with chronic idiopathic dyspepsia. Despite the presence of overlaps, there appear to be partially different functional derangements and clinical features in different subgroups of dyspeptic patients.

Morphologic and cytoproliferative patterns of duodenal mucosa in two patients after long-term total parenteral nutrition: changes with oral refeeding and relation to intestinal resection.

The morphologic and cytoproliferative patterns of the duodenal mucosa of two adult patients, one of whom had a short bowel, were evaluated after more than 2 months of postoperative total parenteral nutrition and 2 and 12 months after the resumption of oral alimentation. Morphometric analysis was performed on routinely processed duodenal biopsies. Cell proliferation was evaluated by means of in vitro bromodeoxyuridine uptake. The results were compared with those obtained in five healthy controls. After parenteral nutrition, patients showed significantly lower villus height and crypt depth than those of controls and a normal bromodeoxyuridine labeling index. After 2 months of refeeding, villus and crypt returned to normal, and the labeling index was increased. After 12 months of oral refeeding, labeling index, villus height, and crypt depth were similar to those of controls. The patient with the short bowel showed a number of cells per unit length of villus and crypt significantly greater than those of the controls and of the patient who underwent shorter intestinal resection. In human duodenal mucosa, (1) hypoplasia develops after long-term total parenteral nutrition; (2) mucosal recovery occurs through an increased cell proliferation after oral refeeding; and (3) extensive small bowel resection determines the development of relative hyperplasia.

Rectal cell proliferation and colon cancer risk in patients with hypergastrinaemia

Background—The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating effect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development. Aims—To evaluate the effect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics. Patients and controls—Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p<0.001). Methods—Immunohistochemistry was performed on 3 μm sections of rectal biopsy specimens incubated with 5′-bromodeoxyuridine. Results—The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (φh value) was significantly higher in patients with CAG or ZES compared with controls (p<0.01 in both patient groups versus controls). Conclusions—Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The effect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.

Endoscopic assessment of acute inflammation of the ileal reservoir after restorative ileo-anal anastomosis

Forty-seven patients, undergoing ileo-anal anastomosis for ulcerative colitis (42) or familial polyposis (5), were endoscopically examined after protective ileostomy or after restorative ileo-anal anastomosis. The neorectum and the ileum above were examined in all cases and multiple biopsies were taken. No symptoms of pouch inflammation were found in 41 subjects; 80.5% of these had non-macroscopic lesions and 19.5% had focal lesions such as congestion, petechiae, mucous hypersecretion (5), or single ulcers (3). None of these developed pouchitis. Pouchitis was observed in the other six subjects, who all underwent surgery for ulcerative colitis and developed 14 clinical episodes of pouchitis during the follow-up. In these cases the entire neorectum mucosa was always affected by the lesions which, in 50%, also extended to the ileum above. The most common endoscopic features (71.4%) were congestion, potechiae, oozing areas, mucous hypersecretion, and multiple superficial ulcers. In half the remaining cases (14.3%) the neorectum showed the features, described above, while the upper ileum was affected by deep round or irregular ulcers within normal mucosa; Crohns disease was excluded in these cases. In the remaining 14.3%, pouchitis showed a pseudomembranous feature. In our experience, the endoscopic pattern of pouchitis is polymorphic. Although an ulcerative colitis-like feature prevails, pseudomembranous and Crohns ileitis-like features may also be present.

Early Gastric Cancer in Italy Clinical and Pathological Observations on 80 Cases

Of 542 gastric cancer patients operated in the period between 1976 and 1982, we found early gastric cancer (EGC) in 80 cases (15.3%). Patients with EGC did not show specific symptoms if compared with patients affected by gastric or duodenal peptic ulcer, gallstones, functional disorders of the upper gastrointestinal tract, or advanced gastric cancer (AGC). Single-contrast radiology showed a low sensitivity, especially in the depressed lesions. In contrast, endoscopy alone diagnosed 64 EGCs (80.0%) as malignant lesions. The five-year overall survival rate of the EGC patients was 85.9% and that of AGC patients was 43.8%. From a pathological point of view, our results confirm the usefulness of the studies on EGC for the comprehension of gastric carcinogenesis. The clinical relevance of EGC is linked to the good prognosis; however, the absence of clear symptoms and lack of alternative diagnostic methods to the endoscopy cast some doubts on the feasibility of mass detection programs.

Rectal cell proliferation and colorectal cancer risk level in patients with nonfamilial adenomatous polyps of the large bowel

The authors evaluated cell kinetics of apparently normal rectal mucosa in the following subjects: 25 with single small adenoma (smaller than 10 mm) of the large bowel, 12 with multiple small adenomas, 28 with a single large adenoma (larger than 10 mm), 22 bearing multiple adenomas among which at least one was larger than 10 mm, 32 with cancer of the large intestine, and 32 controls without colorectal diseases. The study was performed by means of incubation of biopsy specimens with tritiated thymidine and autoradiography. The labeling index was similar in all of the groups. However, patients with one or more large adenomas showed a shift of the proliferative compartment toward the top of the crypts similar to that observed in patients with cancer. This abnormal proliferative pattern was not noticed in patients with one or more small adenomas and was not related to the number of adenomas of each subject. The presence of defects of cell growth in the normal rectal mucosa of patients with large adenomas may indicate that subjects with this abnormality are at high risk of adenoma growth and progression to cancer. 68:2451‐2454, 1991.

Serum pepsinogen I and II concentrations and IgG antibody to Helicobacter pylori in dyspeptic patients

AIMS--To investigate the association between histologically confirmed gastritis, carriage of Helicobacter pylori and pepsinogen (PG) I and PG II concentrations. METHODS--Prospective study of 81 dyspeptic patients undergoing upper gastrointestinal endoscopy was made. The extent of gastric mucosal inflammation and the presence of H pylori was determined, and serology to evaluate PG I and II concentrations and IgG titres to H pylori was carried out. RESULTS--The presence of H pylori was strongly correlated with high IgG antibody titres to H pylori and gastritis. Patients who were H pylori positive had significantly higher PG I and PG II concentrations and a significantly lower PG I:PG II ratio than patients who were negative for H pylori. In 13 patients with duodenal ulcer and H pylori positive gastritis serum PG I concentrations were significantly higher than in H pylori positive patients without duodenal ulcer. Significant correlations were found between the age of patients and serum PG II, the PG I:PG II ratio, IgG antibodies to H pylori, the severity of body gastritis and H pylori infection, and between the degree of gastritis in the body of the stomach and the PG II concentration. CONCLUSIONS--Serum PG I and II concentrations, together with a fall in the PG I:PG II ratio, could be used as predictors of H pylori infection as well as serum IgG antibody response to H pylori.

European Trials on Dietary Supplementation for Cancer Prevention

ABSTRACT European institutions aimed at cancer research and control are spending sizable resources to develop preclinical and clinical chemoprevention trials. Pilot studies showed positive effect on colorectal cell proliferation from supplementation with calcium; vitamins A, C, and E; Ω‐3 fatty acids; and folic acid. A significant reduction in adenoma recurrence after polypectomy was found in patients randomly assigned to take vitamin A, C, and E supplementation or, to a lesser extent, lactulose. Although first reports showed a disquieting higher incidence of lung cancer in male smokers who took β‐carotene supplementation, the European Organization of Research and Treatment of Cancer (EORTC) planned a chemoprevention study on the prevention of second primary tumors in patients with curatively treated head and neck or lung cancer (EUROSCAN). Retinol palmitate or N‐acetylcysteine or both are given for two years. The European Cancer Prevention Organization (ECP) is carrying out a clinical trial in patients with previous adenomas of the large bowel, to test the efficacy of calcium or fiber supplementation on adenoma recurrence. ECP in collaboration with EURONUT has also started a multinational intervention study of the effect of H. pylori eradication and/or dietary supplementation with vitamin C on intestinal metaplasia.

Effect of sex and age on rectal cell renewal in humans

We evaluated the influence of age and sex on rectal cell proliferation of 69 hospital controls and 66 patients with colorectal adenomas, by means of incubation of rectal biopsies with tritiated thymidine and autoradiography. In particular, we evaluated the labeling frequency in the upper 40% of rectal crypts (0 h), actually considered as a reliable kinetic marker of colon cancer risk. A direct correlation between 0h and age was found in control subjects (P less than 0.02) but not in adenomas patients (P = NS). Moreover, control subjects over 65 years of age showed a shift of the proliferative compartment similar to that observed in the adenomas group. After adjusting for the age, we did not observe any significant effect of the sex of patients or controls on their cell kinetics parameters. Our results are in agreement with those previously reported on smaller series and with epidemiological studies which indicate a high risk for developing colorectal neoplasia in the elderly subjects.

Cell-Kinetic Alterations Induced by Aspirin in Human Gastric Mucosa and Their Prevention by a Cytoprotective Agent

The effect on gastric epithelial cell proliferation of a short-term, low-dose treatment with aspirin was evaluated in 9 healthy volunteers. Nine days before and during aspirin administration, the subjects assumed sulglycotide, a sulfated glycopeptide with cytoprotective properties. Endoscopic biopsies were collected in each subject from the gastric body and antrum before and after treatment. The specimens were incubated in a culture medium containing bromodeoxyuridine (BrdU). The proliferative activity was evaluated by immunohistochemical detection of BrdU uptake. A decrease in BrdU-labelled cells together with a shortening of the length of gastric columns were observed after treatment with aspirin and placebo in biopsies of both body and antrum (p less than 0.05). On the contrary, no modifications were observed after treatment with aspirin and sulglycotide. We conclude that a decrease in the proliferative activity of the epithelial cells could be one of the mechanisms by which aspirin affects the defensive properties of gastric mucosa. The treatment with a cytoprotective drug seems to be effective in preventing this alteration.