Role of early ultrasound in detecting inflammatory intestinal disorders and identifying their anatomical location within the bowel.

BACKGROUND: Although bowel ultrasound is a widely accepted diagnostic tool in bowel diseases, its value as the primary imaging procedure in patients with symptoms/signs suggestive of inflammatory bowel disorders is still unclear. AIM: To investigate the accuracy of bowel ultrasound compared with barium X-ray studies, computed tomography, endoscopy and bowel surgery in the initial assessment of inflammatory bowel disorders. METHODS: Four hundred and eighty-seven patients hospitalized consecutively for symptoms or signs suggestive of a bowel disorder between December 1999 and March 2002 were initially enrolled in the study. All patients underwent bowel ultrasound as the first imaging procedure within 36 h of admission; radiographic evaluations, endoscopy and/or surgery were then performed as appropriate and the results of these investigations were used as the gold standard. RESULTS: Three hundred and thirty-six patients had pathological findings of the bowel detectable at ultrasound as the final diagnosis. The main organic disorders found were Crohn's disease (56%), ulcerative/indeterminate colitis (30%), bowel tumours (5%), appendicitis/diverticulitis (2%) and other inflammatory conditions (8%). The overall sensitivity and specificity of bowel ultrasound were 85% and 95%, respectively, whereas the positive and negative predictive values were 98% and 75%, respectively. Comparisons of ultrasound with X-ray or endoscopic results by disease localization showed that the diagnostic performance of ultrasound was higher for inflammatory conditions of the ileum and sigmoid/descending colon (sensitivity of 92% and 87%, respectively), whereas abnormalities localized in the rectum, duodenum and proximal jejunum were often missed by ultrasound. CONCLUSIONS: In expert hands, bowel ultrasound is highly predictive of inflammatory disease localized in the ileum or colon, and may well be used as the primary imaging method when Crohn's disease or ulcerative colitis is suspected on a clinical basis.

Treatment options for patients with Helicobacter pylori infection resistant to one or more eradication attempts.

Proton pump inhibitor-based triple regimens fail to cure Helicobacter pylori infection in at least 10-23% of treated patients. Re-treatment strategies after initial failure remain poorly defined. Of the factors leading to eradication failure, patients' compliance, gender, primary resistance to clarithromycin and metronidazole, and intragastric bacterial load appear to be the most important in determining treatment outcome. Empirical re-treatment should depend mainly upon the antibiotics initially used, as re-administration of the same compound (namely, metronidazole and clarithromycin) is not recommended. Quadruple therapy is usually suggested in this situation, but there is some reluctance to use it in clinical practice on account of the high number of tablets to be taken and concern about side-effects. The use of ranitidine bismuth citrate instead of a proton pump inhibitor plus a bismuth compound in triple second-line regimens has recently proven to be highly effective. Finally, rifabutin-based triple therapies have been shown to be a promising rescue strategy in patients who have failed two or more eradication attempts.

Treatment of Helicobacter pylori infection using a novel antiadhesion compound (3'sialyllactose sodium salt). A double blind, placebo-controlled clinical study.

BACKGROUND AND AIM: 3' sialyllactose sodium salt (3'SL) is an oligosaccharide that occurs naturally in human and bovine milk. It can inhibit the adhesion of H. pylori to human epithelial cells in vitro. The aim of this study was to test whether this oligosaccharide can suppress or cure H. pylori colonization in vivo and to determine its safety in humans. METHODS: Seventy-one consecutive dyspeptic patients with H. pylori infection documented by histology and 13C-Urea Breath Test (UBT) were initially recruited to this study. Patients with UBT values <15 were excluded, thus reducing the enrollment to 65 patients. They were given two different dosages of 3'SL (10 g or 20 g/day) in three daily administrations before meals or placebo for 4 weeks, according to a randomised double-blind protocol. A standardized 13C-UBT (using 100 mg of 13C labelled urea) was repeated in all patients at fixed intervals during treatment (at the end of weeks 1, 2 and 4) and 4 weeks after treatment withdrawal. Patients compliance and side-effects were evaluated at each weekly visit. RESULTS: Five patients were excluded from the PP analysis due to violation of the protocol (noncompliance, lost to follow-up), whereas 61 patients completed correctly the study: 17 received 3'SL 10 g/day, 22 were treated with 3'SL 20 g/day and 21 were given placebo. The three treatment groups did not significantly differ in demographic or clinical patient characteristics. No serious adverse events were observed during therapy in any of the three groups. No patients became UBT negative (<4) during or after treatment but UBT values decreased significantly during the study period in both treatment groups and placebo. CONCLUSIONS: Antiadhesive therapy was safe and well tolerated but did not suppress or cure H. pylori colonization in humans. The observed decrease in UBT values could be explained by a regression towards the mean effect.

Hospital use of acid-suppressive medications and its fall-out on prescribing in general practice: a 1-month survey.

BACKGROUND: Acid-suppressive medications are commonly used in hospitalized patients, but, to date, little is known about the overall use of these drugs in the hospital setting. AIM: To evaluate the appropriateness of acid-suppressive therapy in a large teaching hospital in northern Italy, and the fall-out of hospital prescription in general practice. METHODS: The use of antisecretory agents was monitored for 1 month in adult patients consecutively admitted to L. Sacco University Hospital by reviewing their clinical charts. The appropriateness of each prescription was reviewed jointly by two consultant gastroenterologists. RESULTS: A total of 46.8% of 799 hospitalized patients received acid-suppressive therapy. Ranitidine was the most frequently used drug (44.4%), followed by pantoprazole (31.8%) and omeprazole (23.0%). Stress ulcer prophylaxis and the prevention of non-steroidal anti-inflammatory drug-induced ulcer accounted for 60.4% of the indications for use. Overall, 68% of prescriptions were not appropriate as determined by consensus review; 56.4% of patients receiving unnecessary prophylactic treatment whilst in hospital were discharged on therapy, and 46% were still receiving the treatment 3 months later. CONCLUSIONS: Acid-suppressive agents are over-used in hospitalized patients. Most of the inappropriate hospital prescriptions are for ulcer prophylaxis in low-risk patients. This unnecessary use may also induce inappropriate drug consumption in general practice.

Cause of death in patients with inflammatory bowel disease.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) can both result in disease-related mortality. The aim of the present study was to analyze the comorbid medical conditions that contribute to death of patients with inflammatory disease. METHODS: The United States' vital statistics offer the opportunity to study causes of death broken down by primary and contributing secondary conditions. Deaths from UC and CD were retrieved from the 1991-1996 data files of the National Center for Health Statistics. The strengths of individual associations between each comorbid condition and UC or CD were expressed as proportional mortality ratios, adjusted to the age-, gender-, and race-distribution of the general population. RESULTS: Deaths from UC and CD were found to be associated with a similar set of comorbid conditions and complications. Shock, volume depletion, protein/calorie malnutrition, and anemia were the most frequent comorbid conditions in the group of nutritional, fluid, and electrolyte disturbances. Both diseases were frequently associated with peritonitis and septicemia. Lastly, a large number of deaths were associated with complications following medical and surgical interventions. CONCLUSIONS: Deaths due to inflammatory bowel disease appear to be related to complications from multiple medical interventions and surgical procedures. In managing inflammatory bowel disease, the physician must keep in mind the potential for complications that may be associated with aggressive treatment.

The comorbid occurrence of other diagnoses in patients with ulcerative colitis and Crohn's disease.

OBJECTIVES: The comorbidity between inflammatory bowel disease (IBD) and other diagnoses may help to shed light on the etiology and pathophysiology of IBD. The US Vital Statistics offer the opportunity to study causes of death broken down by comorbid disease associations. The aim of this study was to analyze the presence of comorbid conditions in persons who died from ulcerative colitis or Crohn's disease. METHODS: The numbers of deaths from ulcerative colitis and Crohn's disease were retrieved from the computerized 1991-1996 data files of the National Center for Health Statistics. Comorbid associations between other diagnosis and ulcerative colitis or Crohn's disease were expressed as age-, gender-, and race-standardized proportional mortality ratios. RESULTS: Ulcerative colitis and Crohn's disease showed, in general, similar patterns of comorbidity. Both diseases were associated with similar sets of GI complications, such as intestinal obstruction and stasis, mucosal inflammation and infection, vascular complications, and complications related to fistula and abscess formation. Extraintestinal complications of both IBD involved disorders of the hepatobiliary system, urinary system, and various coagulopathies. Ulcerative colitis alone was found to be associated with Hirschsprung's disease and schizophrenia, whereas Crohn's disease alone was found to be related with osteoporosis and amyloidosis. CONCLUSIONS: No completely unexplained or hitherto undescribed association was revealed. The numerous intestinal and extraintestinal complications associated with IBD serve as a reminder of the systemic nature and the resultant clinical severity of both ulcerative colitis and Crohn's disease.

Occupational mortality from inflammatory bowel disease in the United States 1991-1996.

OBJECTIVE: The occupational distribution of inflammatory bowel disease (IBD) may help to shed light on its yet unknown etiology. The U.S. vital statistics offer the opportunity to study cause of death by occupation and industry. METHODS: The numbers of deaths from Crohn's disease and ulcerative colitis were retrieved from the computerized 1991-1996 data files of the National Center for Health Statistics. Deaths were grouped by gender, ethnicity, disease type, occupation, and industry. Mortality by occupation and industry were expressed as proportional mortality ratio (PMR), adjusted for gender and ethnicity. RESULTS: Between 1991 and 1996, 2399 subjects died from Crohn's disease and 2419 subjects died from ulcerative colitis. Significant correlations were found between the PMR values of ulcerative colitis and Crohn's disease regarding their distribution by occupation, r = 0.36 and p < 0.05, as well as by industry, r = 0.37, p < 0.01. IBD mortality by occupation was significantly reduced among farmers (PMR: 70, 95% confidence interval [CI]: 42-97), mining machine operators (31, 95% CI: 0-74), and laborers (71. 95% CI: 45-98). A nonsignificant increase was found among sales persons (117, 95% CI: 95-139) and secretaries (122, 95% CI: 83-161). IBD mortality by industry was significantly reduced in agricultural production of livestock (39, 95% CI: 1-78), mining (46, 95% CI: 9-83), grocery stores (55, 95% CI: 17-94), and work in private households (64, 95% CI: 30-97). A nonsignificant increase was found in food production (128, 95% CI: 74-182), investment and insurance business (137, 95% CI: 77-198), and administration (122, 95% CI: 81-163). CONCLUSIONS: IBD mortality is low in occupations associated with manual work and farming and relatively high in sedentary occupations associated with indoor work. Crohn's disease and ulcerative colitis show a similar distribution.

Focal gastric inflammatory infiltrates in inflammatory bowel diseases: prevalence, immunohistochemical characteristics, and diagnostic role.

OBJECTIVES: To date, few studies have evaluated gastric histology in patients with inflammatory bowel disease (IBD). The aim of this prospective controlled study was to establish the frequency of focal gastritis in Crohn's disease (CD) and ulcerative colitis (UC) patients, as well as to evaluate its immunohistochemical characteristics and clinicoanatomical determinants. METHODS: We evaluated 141 consecutive patients with known CD of the large and/or small bowel, 79 patients with UC, and 141 CD- and UC-free controls; all underwent upper gastrointestinal (GI) endoscopy and 13C urea-breath test. Biopsy specimens taken from the antrum, angulus, and gastric body were evaluated by histology and immunohistochemistry. A series of variables, including CD activity index, duration, extent and location of disease, intestinal resection, number of recurrences, and previous and current medical therapy, as well as the presence of dyspeptic symptoms and mucosal lesions at endoscopy, were determined in all CD patients and correlated with the presence or absence of focal gastritis. RESULTS: Helicobacter pylori-associated gastritis was found in 47 patients with CD (33%), in 37 patients with UC (47%), and in 60% of CD-/UC-free controls (p < 0.01). In H. pylori-negative CD patients focal gastritis was found in 43% of cases (40/94), compared with 12% (5/42) of UC patients and 19% (11/57) of controls (p < 0.05). Specificity and positive predictive value of focal gastritis in CD were 84% and 71%, respectively. It was characterized by a focal perifoveolar or periglandular lymphomonocytic infiltrate, with CD8+/CD4+ cells predominant both in CD and UC patients. There were no significant correlations between the occurrence of focal gastritis and any clinicoanatomical CD features. CONCLUSIONS: Focal gastritis is relatively common in CD patients although it is not exclusive to this condition. Its recognition could be useful in the diagnostic workup of any patient with suspected or indeterminate inflammatory bowel disease, as it makes a diagnosis of CD more likely.

Helicobacter pylori CagA seropositivity does not influence inflammatory parameters, lipid concentrations and haemostatic factors in healthy individuals.

BACKGROUND: H. pylori CagA seropositivity has been recently associated with ischaemic heart disease. OBJECTIVE: To evaluate whether H. pylori virulence has any effect on certain circulating coagulation factors and on markers of systemic inflammation in healthy individuals. DESIGN: Prospective cohort study. SETTING: Haematology and gastroenterology unit at a university teaching hospital. SUBJECTS: A total of 494 consecutive asymptomatic blood donors attending a blood bank. MEASUREMENTS: Blood analysis for haemostatic factors, lipids concentrations, inflammatory parameters as well as determination of anti H. pylori IgG and CagA reactivity by ELISA assayes. RESULTS: The overall prevalence of H. pylori infection was 53%; 56% of H. pylori positive sera expressed CagA reactivity. CagA seropositive subjects did not differ significantly from CagA negative or H. pylori negative subjects in values for lipids, haemostatic factors, or inflammatory parameters. CONCLUSIONS: CagA seropositivity is not associated with increased systemic inflammation or with raised concentrations of haemostatic factors - predictors of ischaemic heart disease - in healthy individuals.

Prolonging proton pump inhibitor-based anti-Helicobacter pylori treatment from one to two weeks in duodenal ulcer: is it worthwhile?

AIMS: To compare the efficacy of one-week versus two-week treatment with lansoprazole, amoxycillin and clarithromycin in inducing healing of Helicobacter pylori-positive duodenal ulcers as well as to investigate the role of several factors, determinant in the ulcer healing process. PATIENTS AND METHODS: Seventy-one active duodenal ulcer patients were randomised to receive one- or two-week treatment with lansoprazole (30 mg bid), clarithromycin (500 mg bid) and amoxycillin (1 g bid), not followed by any additional acid suppressive therapy. Ulcer healing and Helicobacter pylori infection were assessed by endoscopy and urea breath test 4 weeks after the end of treatment. Before entering the trial and four weeks after the end of treatment, dyspeptic symptoms were recorded and scored by a validated questionnaire. The potential effects of a number of clinical variables on the ulcer healing process were evaluated by means of univariate and multivariate analyses. RESULTS: Duodenal ulcer was healed in 80.5% patients treated for one week and in 91.4% patients treated for 2 weeks according to intention-to-treat analysis (p=NS). Ulcer healing was more frequent in the Helicobacter pylori cured patients compared to those with persisting infection (90.9% vs 68.5%; p=0.04). Multivariate analysis did not reveal any significant predictor of duodenal ulcer healing. CONCLUSIONS: Two-week treatment with lansoprazole, amoxycillin and clarithromycin, without continuation of antisecretive therapy, is better, although the difference is not statistically significant, than one-week treatment in healing Helicobacter pylori-positive duodenal ulcer disease. The eradication of Helicobacter pylori is the most important factor related to ulcer healing.

Is routine histological evaluation an accurate test for Helicobacter pylori infection?

AIM: To compare the diagnostic accuracy of routine histology for Helicobacter pylori infection, with histology by an expert pathologist, and to compare histology with the rapid urease test (RUT), 13C-urea breath test, IgG serology and culture of antrum and corpus specimens, in a consecutive series of untreated patients presenting for upper oesophago-gastro-duodenoscopy. MATERIALS AND METHODS: One-hundred and fifteen consecutive patients underwent multiple tests for H. pylori infection: rapid urease test, 13C-urea breath test, IgG serology and histology and culture on antrum and corpus biopsy specimens. Histology was first evaluated by the pathologists in a routine examination, and then blindly reviewed by an expert pathologist with a special interest in gastrointestinal pathology. The patients were considered to be H. pylori-positive if two or more tests were positive. RESULTS: Eighty-one patients (70.4%) were found to be H. pylori positive. 13C-urea breath test and IgG serology showed the best sensitivity and specificity (100%). Both the antral and body cultures, and the rapid urease test had the highest specificity (100%). Histological diagnosis after re-evaluation by an expert pathologist showed a high sensitivity (98. 8%) and specificity (100%), and was better than routine histology (sensitivity 92.6%; specificity 90.3%). The accuracy of the rapid urease test was greater than that of routine histology, and the combination of these two tests improved the sensitivity of H. pylori detection to up to 100%. CONCLUSION: All diagnostic tests usually utilised in clinical practice have a sensitivity higher than 90%. In patients who were not pre-treated with antisecretory agents or antibiotics, the sensitivity of histological diagnosis, however, seems to be influenced by the accuracy of the histological examination. The sensitivity of routine histology, but not of revised histological diagnosis, is improved by an additional rapid urease test.

Influence of bacterial CagA status on gastritis, gastric function indices, and pattern of symptoms in H. pylori-positive dyspeptic patients.

OBJECTIVE: To date, little is known about a possible relationship between H. pylori-related disturbances of gastric function and the bacterial virulence. The aim of this study was to assess whether certain gastric function indices as well as the pattern of symptoms in nonulcer dyspepsia (NUD) are related to CagA status. METHODS: A total of 56 consecutive patients with NUD (38 H. pylori-positive and 18 H. pylori-negative) were studied. Dyspeptic symptoms were categorized according to the predominant complaints and scored for severity and frequency. In all subjects, basal and pentagastrin-stimulated acid secretion, fasting and meal-induced gastrin release, fasting serum pepsinogen I (PG I) levels, and gastric emptying of solids were determined. CagA status was determined by assaying serum CagA IgG antibodies by western blotting. RESULTS: Eighteen of 38 (47%) H. pylori-positive dyspeptics were CagA seropositive. Type and severity of dyspeptic symptoms did not significantly differ between CagA-positive and CagA-negative dyspeptics nor between H. pylori-positive and negative patients. Among the gastric function indices studied, only meal-stimulated gastrin was significantly influenced by CagA status (peak gastrin 129.9 [44.1] vs 99.1 [48.6] pg/ml in CagA-positive and negative NUD, respectively), but this was not accompanied by any significant modification of basal or stimulated acid secretion or gastric emptying of solids. The activities of both antral and corpus gastritis in NUD harboring CagA-positive strains were significantly higher than those of CagA-negative NUD. Accordingly, serum PG I levels were significantly higher in CagA-positive than CagA-negative or H. pylori-negative dyspeptics. CONCLUSIONS: These findings support a role for CagA status in influencing the activity and perhaps the distribution of gastritis in NUD, as well as the degree of gastrin response to a meal; however, this is not accompanied by disturbances of acid secretion or gastric emptying or by differences in the type and severity of symptoms.

Effects of Helicobacter pylori eradication on gastric function indices in functional dyspepsia. A prospective controlled study.

BACKGROUND: To date, it is unclear whether Helicobacter pylori infection is associated with disturbances of gastric emptying or acid secretion in patients with functional dyspepsia (FD). Our aim was to investigate whether, in the long run, cure of H. pylori infection significantly influences gastric emptying of solids, acid secretion, and gastrin and pepsinogen I (PGI) release in patients with FD. METHODS: Thirty-eight consecutive H. pylori-positive patients with FD, whose complaints were scored for severity and frequency on the basis of a validated symptom questionnaire, were initially enrolled in the study. They were randomized to receive an eradicating regimen consisting of omeprazole plus clarithromycin and tinidazole for 1 week or full-dose ranitidine for 3 weeks. In 33 patients (18 H. pylori-cured and 15 with persistent infection) basal and pentagastrin-stimulated acid secretion, fasting and meal-induced gastrin concentrations, fasting serum PGI levels, and gastric emptying of solids were determined before and 6 months after therapy. RESULTS: In the 18 H. pylori-cured patients meal-induced gastrin and fasting PGI levels were significantly reduced after 6 months as compared with pretreatment values (peak serum gastrin, 76.0 +/- 23.4 versus 111.9+/-37.4 pg/ml; PGI, 57.1+/-23.4 versus 72.9+/-29.1 ng/ml), whereas they remained virtually unchanged in the 15 patients with persistent infection. In contrast, both basal and stimulated acid secretion and gastric emptying time of solids remained unmodified over time in both groups of patients. CONCLUSIONS: We confirm that also in patients with functional dyspepsia H. pylori eradication in the long run significantly reduces gastrin and PGI release as a result of improvement in the underlying antral gastritis, but this is not accompanied by modifications of gastric emptying of solids or acid secretion.