Eosinophilia - associated basal plasmacytosis: an early and sensitive histologic feature of inflammatory bowel disease.

Basal plasmacytosis is an early-onset and highly predictive feature of inflammatory bowel disease (IBD), but may have several restrictions in routine histology. Considering evidences about cooperation between eosinophils and plasma cells in IBD pathogenesis, we investigated immunostain of these two cells as a marker of disease. 343 samplings from 83 patients (52 IBD, 31 non-IBD colitis) were evaluated. The sections were stained with monoclonal antibodies against plasma cells (CD138 and MUM1), and eosinophils (CD193). Eosinophilia-associated basal plasmacytosis (EBP) was related with the histologic diagnosis of IBD (90.3% IBD and 35.4% non-IBD colitides, p < 0.005, sensitivity 90.4%). A strong relation was detected between the occurrence of EBP and (i) the achieving of a complete endoscopic mapping; (ii) the presence of other characteristic lesions of IBD in single segmental sampling, although EBP was evident in more than 40% of samples without other IBD-related lesions. EBP is a sensitive histologic feature of IBD, especially at the first endoscopic sampling, even in the absence of the other characteristic histologic lesions, and may help in formulating a more precise diagnosis in this setting.

The diagnosis of inflammatory bowel disease is often unsupported in clinical practice.

BACKGROUND: The diagnosis of inflammatory bowel disease can be challenging and requires the efforts of a multidisciplinary team. We performed a retrospective analysis with the aim of evaluating the adequacy of the prerequisites for arriving at an accurate histological diagnosis. METHODS: The following parameters were considered as prerequisites for a diagnosis of inflammatory bowel disease: clinical and endoscopic data; proper sampling and handling of biopsies; and elementary microscopic lesions. We collected 345 cases from 13 centres. RESULTS: The date of onset and treatment were available for 13% and 16% of the cases, respectively. Endoscopy information was accessible for 77% of the cases. Endoscopic mapping was completed in 13% of the cases. In no cases were the biopsies oriented on acetate strips. The diagnosis was conclusive in 47% of the cases. Activity, epithelial disruption and crypt distortion were described in 35% of the reports with a conclusive diagnosis. CONCLUSION: Our study showed that the diagnostic prerequisites were widely unfulfilled, although approximately half of the diagnoses were conclusive for inflammatory bowel disease. Thus, in our assessment of clinical practice: (1) clinicians seldom provide suitable clinical and/or endoscopic information for a histological diagnosis and (2) histopathological diagnoses of inflammatory bowel disease are often not supported by morphology.

Global DNA hypomethylation is an early event in Helicobacter pylori-related gastric carcinogenesis.

AIM: Cancer, particularly gastric cancer (GC), is prevalently an epigenetic phenomenon that is dependent on an altered DNA methylation pattern. In gastric carcinogenesis, many genes show aberrant methylation; however, none of them may be used as a biomarker of cancer risk and progression. The authors aimed to evaluate the global DNA methylation of gastric mucosa in Helicobacter pylori (Hp)-related chronic gastritis, in GC and in 10 patients with preneoplastic lesions (ie, atrophy and intestinal metaplasia) followed up for 10 years. METHODS: The authors analysed 93 dyspeptic patients who underwent upper endoscopy, 41 surgical GC samples and 10 patients with preneoplastic gastric lesions followed up for 10 years after successful Hp eradication therapy. Global DNA methylation status and surrogate markers of cell proliferation and apoptosis were evaluated by immunohistochemistry using the anti-5-methylcytosine (5-MC), anti-Ki-67 and anti-p53 (anti-apoptotic marker)-specific antibodies, respectively. RESULTS: Global DNA methylation of gastric mucosa gradually decreased from normal mucosa to Hp-positive gastritis, Hp-positive chronic atrophic gastritis, independent of Cag-A status and GC; however, the variation was significant (p<0.05) only between Hp-negative subjects and Hp-positive chronic gastritis. Interestingly, the 5-MC immunostaining was absent in areas of intestinal metaplasia. In the 10 patients with preneoplastic lesions, global DNA methylation decreased over time despite the eradication of Hp infection, but reached significance only at 10 years versus baseline. The 5-MC immunostaining negatively correlated with Ki-67 and p53 expression in all groups. CONCLUSION: Global DNA hypomethylation is an early molecular event in Hp-related gastric carcinogenesis. Further studies with more cases and a longer follow-up are needed to establish the potential GC predictive role of DNA hypomethylation.

Appropriateness of colonoscopy in a digestive endoscopy unit: a prospective study using ASGE guidelines.

RATIONALE, AIMS AND OBJECTIVES: Appropriate indications for colonoscopy (C) are essential for a rational use of resources. The aim of this study is to evaluate the appropriateness of indication for C according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines and to evaluate whether appropriate use was correlated with the diagnostic yield of C. METHODS: We analysed 677 consecutive C performed over an 11-month period in a digestive endoscopy unit with an open access system. RESULTS: The rate of 'generally indicated' C was 77% and 'generally not indicated' C was 18%. The rate of indication not listed in the ASGE guidelines was 5%. The percentage of generally not indicated C requested by gastroenterologists for outpatients was lower than that requested by primary care surgeons or doctors (9.5%, 29%, 25.3%, respectively). In 38 (7.3%) and in 111 (21.3%) of 520 patients with appropriate C, cancer and polyps larger than 5 mm were found, respectively. Twenty polyps greater than 5 mm were detected in 15 cases (12%) of 122 inappropriate C, with only one case of intramucosal carcinoma; four (12%) polyps measuring over 5 mm were found in C not listed in ASGE guidelines. No advanced stage cancer was detected in the inappropriate group and in C not listed in ASGE guidelines. CONCLUSIONS: Our results showed the high rate of inappropriate procedures, according to ASGE guidelines, requested by surgeons, internists and primary care doctors for both outpatients and inpatients. The proportion of not indicated endoscopic procedures requested by gastroenterologists must be reduced through more carefully application of ASGE guidelines. Endoscopic findings were more stringent in appropriate C.

Type III intestinal metaplasia, Helicobacter pylori infection and gastric carcinoma risk index in an Italian series of 1750 patients.

BACKGROUND/AIMS: To evaluate the utility of 2 biopsies of antrum and gastric body on routine endoscopy for the assessment of type III intestinal metaplasia (IM-3) and Helicobacter pylori (Hp), 1750 patients (pts) (895 males; 855 females) were considered from June'98 to June'00. METHODOLOGY: Specimens were graded 0 to 3 for atrophy, IM-3 and Hp. 610 pts treated previously with antibiotics or not eligible for biopsy were excluded from initial 2360 pts. RESULTS: IM-3 was found in 118 pts (6.7%), 100 pts (5.7%) only in the antrum. 10 of 355 pts (2.8%) with normal endoscopy and 47 of 702 (6.6%) with non-erosive endoscopic gastritis resulted IM-3 positive in the antrum. 709 pts (40.5%) were positive for Hp in antrum and/or corpus. The presence of Hp and IM-3 in the antrum was not correlated (p=0.99; Spearman test). A positive correlation (p=0.000) between duodenal ulcer and Hp was found when antral Hp positivity was taken into account. The gastric carcinoma risk index (GCRI) was found in 358 pts (20.4%); in this group 131 pts (36.6%) were Hp positive, 81 pts (22.65%) had IM-3 only in the antrum, 184 pts (51.4%) had atrophy. CONCLUSIONS: The incidence of IM-3 is low (6.7%) in routine endoscopy. Normal endoscopy doesn't exclude the presence of IM-3. Biopsy is necessary to discover IM-3 in the antrum in 5.3% of pts with normal or aspecific endoscopic gastritis. Application of the GCRI might be useful for identifying a group of patients carrying a higher risk for gastric carcinoma.

Effect of Helicobacter pylori eradication on bulbitis and duodenal gastric metaplasia.

BACKGROUND/AIMS: Duodenal gastric metaplasia seems to be linked to infection by Helicobacter pylori, to the extent of acid secretion and to bulbitis. An investigation was made of the relationship between bulbitis and duodenal gastric metaplasia, or whether bulbitis can arise along with duodenal gastric metaplasia after Helicobacter pylori eradication in an average of six years. METHODOLOGY: We compared 22 patients with duodenal ulcers [male/female 16/6; (mean age+/-SD) 55+/-12 years] Helicobacter pylori-negative after eradication, with 23 Helicobacter pylori-positive patients free from active duodenal ulcers [male/female 17/6; (mean age+/-SD) 59+/-12 years]. RESULTS: The bulbitis score was found to be lower in the Helicobacter pylori-negative than in the Helicobacter pylori-positive group (p=0.02). The duodenal gastric metaplasia score in the Helicobacter pylori-negative was higher than in the Helicobacter pylori-positive group (p=0.001). We failed to find any relationship between the presence of bulbitis and duodenal gastric metaplasia. We found a non-significant inverse correlation between the presence of duodenal gastric metaplasia and chronic body gastritis (p=0.07). CONCLUSIONS: Bulbitis and duodenal gastric metaplasia may depend on different causal factors not related to Helicobacter pylori infection. The extension of duodenal gastric metaplasia with time following recovery from peptic ulcer disease may represent a mucosal protection factor against acid.

Re-treatment with interferon-beta of patients with chronic hepatitis C virus infection.

OBJECTIVE: To evaluate the efficacy of interferon-beta (IFN-beta) in the re-treatment of patients with chronic hepatitis C who did not respond to IFN-alpha monotherapy. PATIENTS AND METHODS: Thirty patients (24 men and six women; mean age, 41 +/- 13 (SD) years; range, 23-62 years), with chronic hepatitis C that was non-responsive to a standard course of IFN-alpha therapy, were re-treated with recombinant human IFN-beta-1a. All patients received IFN-beta, 12 MIU subcutaneously, three times weekly for 3 months, after which time patients' responses were evaluated. Responders (normal alanine aminotransferase, and negative for serum hepatitis C virus RNA) continued to receive IFN-beta, 12 MIU, for a further 3 months. Non-responders had their dose increased to 18 MIU for the remaining 3 months of treatment. After 6 months of treatment, therapy was stopped and patients were followed-up for a further 6 months. RESULTS: Overall, six (20%) of the 30 patients exhibited a response at the end of treatment. One patient (3.3%) maintained a sustained virological response at the end of post-treatment follow-up. CONCLUSIONS: Treatment with recombinant IFN-beta, at doses of up to 18 MIU for 6 months, is safe and well tolerated. However, the results of the trial do not support the use of IFN-beta monotherapy in patients with chronic hepatitis C that is resistant to IFN-alpha.

Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: a multicenter, placebo-controlled, randomized clinical trial.

BACKGROUND: ERCP is frequently complicated by pancreatitis. The aims of this study were to assess the efficacy of somatostatin and gabexate for prevention of post-ERCP pancreatitis in high-risk patients and to determine predisposing factors for post-ERCP pancreatitis. A meta-analysis was conducted of all published studies on the use of somatostatin or gabexate for prevention of post-ERCP pancreatitis. METHODS: A double blind, multicenter, placebo-controlled trial was conducted in patients at high risk for post-ERCP pancreatitis. Patients were randomized to receive an intravenous infusion of somatostatin (750 mg), gabexate (500 mg), or placebo that was started 30 minutes before endoscopy and continued for 2 hours afterward. Patients were evaluated clinically and serum amylase levels determined at 4 and 24 hours after endoscopy. RESULTS: No significant difference in the occurrence of pancreatitis, hyperamylasemia, or abdominal pain was observed among placebo-, gabexate-, and somatostatin-treated patients. A sphincterotomy longer than 2 cm (p = 0.0001), more than 3 pancreatic injections (p = 0.0001), and unsuccessful cannulation (p = 0.008) were predictive of post-ERCP pancreatitis. Hyperamylasemia was predicted by more than 3 pancreatic injections (p = 0.0001) and sphincterotomy (p = 0.02). The meta-analysis of trials of short-term infusion of gabexate or somatostatin did not show efficacy for either drug. CONCLUSIONS: Short-term administration of gabexate or somatostatin in patients at high risk for pancreatitis is ineffective for prevention of ERCP-induced pancreatitis. Pancreatic injury is related to maneuvers used to obtain biliary access rather than to any patient characteristic or endoscopist experience.