Francesco Di Mario

Gastric epithelial dysplasia in the natural history of gastric cancer: A multicenter prospective follow-up study

BACKGROUND/AIMS Because the precancerous significance of gastric epithelial dysplasia (GED) is still under debate, this study attempts to ascertain whether a prospective follow-up of GED can contribute to clarifying its clinical and pathological relationships with gastric cancer (GC). METHODS One hundred twelve patients with mild (G1), moderate (G2), and severe (G3) GED or diagnosed as indefinite for dysplasia were prospectively followed up with a standardized endoscopic and bioptic protocol. RESULTS Evaluation of GED outcome refers only to 93 patients with a follow-up period longer than 12 months. Regression of dysplasia was documented in 36%, 27%, and 0% of G1, G2, and G3 GED cases, respectively. Progression to more severe dysplasia or evolution into GC was detected in 21%, 33%, and 57% of G1, G2, and G3 GED cases, respectively. Evolution into GC was documented for all grades of dysplasia and correlated significantly with high-grade atrophic gastritis. A high prevalence of early GC (86.9%) was also observed. CONCLUSIONS GED is a pre-invasive lesion, and carcinomatous evolution increases proportionally with its histological grade. Bioptical follow-up is mandatory for all histological grades of GED and significantly increases the likelihood of GC being detected in its early stages.

Helicobacter pylori in promotion of gastric carcinogenesis

Gastric atrophy and intestinal metaplasia are considered the earliest phenotypic changes in the cascade of events leading from normal mucosa to intestinal-type gastric cancer, and epidemiological evidence linksHelicobacter pylori to gastric epithelial malignancies. To evaluate any causal relationship between bacterial infection and atrophic metaplastic lesions, gastric pathology was histologically and histochemically evaluated in 267 consecutive, nonulcerous, untreated subjects, with attention given to the phenotypes of intestinal metaplasia. The prevalence ofHelicobacter pylori infection was 61%. Intestinal metaplasia (particularly types II and III) was significantly associated with bothHelicobacter pylori detection (xLR2:P<0.002) and increasing age (xLR2:P<0.002). Using logistic regression analysis, the development of intestinal metaplasia proved more significantly linked withHelicobacter pylori infection [odds ratio=4.55 (95% confidence interval: 1.51–13.7)], than with age [odds ratio =1.03 (95% CI: 1.01–1.06)], with no interaction. In conclusion,Helicobacter pylori can be considered among the major causal agents of mucosal lesions involved in the multistep process of gastric carcinogenesis, justifying any attempt to eradicate this bacterial infection.

Prevention of acute NSAID-related gastroduodenal damage: a meta-analysis of controlled clinical trials.

No consensus exists as to whether cotherapy is effective in the short-term prevention of severe NSAID-related gastroduodenal damage. The aim of this study was to provide a quantitative systematic review of the efficacy of gastroprotective drugs, such as misoprostol, H2-blockers, and proton pump inhibitors (PPI) in preventing the severe acute NSAID-related gastroduodenal damage. Placebo-controlled randomized clinical trials on the use of misoprostol, H2-blockers, and PPIs as preventative agents published between January 1986 and May 1999 were identified through Medline and reference lists from clinical reviews. Studies on patients or healthy subjects were considered to be eligible for data pooling if they were performed in acute NSAID users (not longer than 30 days) and with at least one endoscopic evaluation during therapy that reported results specifically for gastric and duodenal damage. Risk difference (RD), heterogeneity χ2 test, publication bias assessment and number needed to treat (NnT) were calculated for each meta-analysis by a customized program. Twenty-one trials met the inclusion criteria evaluating a total of 636 healthy subjects and 1904 patients with arthritis randomized to active drug or placebo. The baseline risk of NSAID-related gastric (68% vs 16.6%, P < 0.001) and duodenal (22% vs 8.5%, P < 0.001) damage was higher in healthy subjects compared to patients with arthritis. Meta-analysis demonstrated a significant heterogeneity between trials performed in the two populations (P < 0.0001). In healthy subjects the active drug treatment induced a significant prevention of severe gastric (misoprostol RD = 69%, 95% CI = 60.3–77.7, H2-blocker RD = 38.3%, 95% CI = 17.8–58.9 and PPI RD = 43%, 95% CI = 28.2–57.7) and duodenal damage (misoprostol RD = 22.3%, 95% CI = 13.6–31, H2-blocker RD = 13.2%, 95% CI = 5.2–21.3 and PPI RD = 17.7%, 95% CI = 3.5–31.8). NnT values were, respectively, 1, 3, and 2 for gastric and 4, 8, and 6 for duodenal damage. In patients with arthritis lower RD and higher NnT values were found compared to healthy subjects. In conclusions, cotreatment with gastroprotective drugs for short-term prevention of severe gastroduodenal NSAID-related damage was more effective in healthy subjects than in patients with arthritis; misoprostol and PPIs were more effective than H2-blockers in the prevention of both gastric and duodenal severe damage; more studies need to evaluate the role of short-term prevention in patients with arthritis who require acute NSAID treatment.

Efficacy of 7 day lansoprazole-based triple therapy for Helicobacter pylori infection in elderly patients.

Background: The prevalence of Helicobacter pylori increases with age. However, data regarding the effects of anti‐H. pylori treatments in the elderly are very scarce.

Natural history of gallstones in non-insulin-dependent diabetes mellitus : a prospective 5-year follow-up

This prospective study was undertaken to assess the natural history of gallstones in patients with non-insulin-dependent diabetes. Four hundred forty outpatients with diabetes mellitus were studied; 81 of these had gallstones diagnosed by ultrasound. On the basis of the information they gave, they were divided into two groups: A, asymptomatic; and B, symptomatic (previous episode(s) of biliary pain) at recruitment. Five years after diagnosis, the patients were recalled and questioned about their symptoms. Three of 81 could not be traced and eight had died from diseases not related to gallstones. Seventy were finally evaluated, 47 belonging to group A, 23 to group B. The cumulative percentage of initially asymptomatic patients who presented with biliary pain or complications during the follow-up was 14.9% (4.2% for complications). Of group A patients, 17% underwent cholecystectomy (one prophylactic, six elective and two emergency). One patient (2.1%) died after operation of obstructive jaundice. Of group B patients, 47.8% had biliary symptoms or complications (8.7% cholecystitis); 21.7% were operated (17.4% elective, 4.3% emergency cholecystectomy). Since few patients with asymptomatic gallstones and non-insulin-dependent diabetes mellitus develop pain or complications over time, prophylactic cholecystectomy is probably not advisable.

Gastric juice polymerase chain reaction: an alternative to histology in the diagnosis of Helicobacter pylori infection.

Background.Infection from Helicobacter pylori plays a role in several gastroduodenal diseases. The recent availability of molecular techniques, particularly the polymerase chain reaction (PCR), allows us to detect small amounts of this bacterium. The aims of this study were to compare PCR and histological findings and to ascertain the clinical usefulness of H. pylori PCR identification in different biological samples.

The Clinical Usefulness of Serum Pepsinogens, Specific IgG Anti-HP Antibodies and Gastrin for Monitoring Helicobacter pylori Treatment in Older People

OBJECTIVE: to evaluate the clinical usefulness of Pepsinogen A (PGA) and C (PGC), PGA/PGC ratio, gastrin, and specific IgG anti‐HP antibodies (anti‐HP Ab) in monitoring the effect of cure for Helicobacter pylori (HP) infection in older people.

Effect of Age on Gastric Acid, Pepsin, Pepsinogen Group A and Gastrin Secretion in Peptic Ulcer Patients

To verify the effect of age on gastric secretions in gastric (GU) and duodenal ulcer (DU) patients, we carried out a retrospective study evaluating basal and stimulated gastric acid secretion in 427 peptic ulcer subjects aged between 12 and 73 years (GU = 74, DU = 353) in addition to studying gastric juice pepsin, serum pepsinogen group A (PGA) and gastrin in 175 patients (GU = 28, DU = 147). All subjects were then divided into groups according to their sex and age (< 30, 30-39, 40-49, 50-59 and > 60 years). Basal, maximal and peak acid outputs (BAO, MAO, PAO) were unchanged in the various age groups, though MAO and PAO were higher in males than females and in DU than in those with GU, even in the elderly (> 60 years). Pepsin and gastrin levels were unchanged at the various ages in GU and DU, while PGA was higher in males with DU aged 50 or over. This demonstrates that acid, pepsin and gastrin secretions do not change with age in ulcer patients. Acid secretion retains its typical distribution according to pathology (DU > GU) and sex (males > females), and also appears to have a fundamental pathogenetic role in peptic ulcer in the elderly.

Short-term treatment of gastric ulcer : A meta-analytical evaluation of blind trials

Gastric ulcer is relatively infrequent, and clinical trials are often based on small-sized samples. The aim of this study was to define the “gold standard” therapy of active gastric ulcer. We included all single- or double-blind clinical trials on the short-term treatment of gastric ulcer. All the articles published over the period 1977–1994 were reviewed. Meta-analysis was done with both fixed and random effect models; results were shown using Galbraiths radial plot. Forty-eight papers comprising 52 studies were evaluated. Cimetidine, ranitidine, and famotidine proved significantly better than placebo [odds ratio (OR) and 95% confidence interval (CI 95%) at four to six weeks were: 2.67 (2.03–3.52), 3.94 (2.28–6.80), 1.76 (1.08–2.88), respectively]. Cimetidine and ranitidine had results comparable with the newer H2 blockers [OR (CI 95%) at four weeks: 1.16 (0.91–1.47), 1.11 (0.80–1.55), respectively]. H2 blockers were proved comparable with either sucralfate [OR (CI 95%) at eight weeks: 0.81 (0.37–1.79)] or bismuth [OR (CI 95%) at four to six weeks: 0.67 (0.37–1.20)]. Omeprazole is more effective than H2 blockers [OR (CI 95%) at four weeks: 2.00 (1.57–2.55)]. It is concluded that H2 blockers are preferred to either a placebo or sucralfate for short-term gastric ulcer treatment; the newer H2 blockers do not have significant advantages over the older types; omeprazole can be regarded as the “gold standard” for active gastric ulcer treatment.

Nuclear DNA content and pathology in radically treated pancreatic carcinoma: The prognostic significance of DNA ploidy, histology and nuclear grade

Nuclear DNA content and pathology are considered to be prognostically relevant in several solid tumors, but controversial findings have emerged in pancreatic carcinoma (PC). Histopathology and DNA ploidy were each correlated with survival in radically treated PC to ascertain the hierarchy of their prognostic significance.