Paolo Pazzi

Validation of the 13C-urea breath test for the diagnosis of Helicobacter pylori infection in children: a multicenter study.

OBJECTIVE:The 13C-urea breath test (13C-UBT) is a safe, noninvasive, and accurate test for the detection of Helicobacter pylori (H. pylori) infection in adults. The aim of this study was to evaluate sensitivity and specificity of 13C-UBT in children using different types of test meal, doses of 13C-urea and breath sampling intervals. As yet, a validated, standardized 13C-UBT protocol for children has not been formulated.METHODS:13C-UBT was performed in 115 children and repeated within 3 days, modifying the test meal or the dose of 13C-urea. H. pylori status was assessed by histology and rapid urease test. 13C-UBT was performed using 100 mg or 50 mg of 13C-urea and a fatty test meal (100 FA; 50 FA), 50 mg of 13C-urea, and a carbohydrate test meal (50 CA). Breath samples were collected every 10 min for 60 min.RESULTS:The 13C-UBT in children was highly sensitive and specific with all three protocols used. The best combination of sensitivity (97.92%) and specificity (97.96%) was obtained with Protocol 50 FA at 30 min with a cut-off of 3.5 per mil.CONCLUSIONS:The 13C-UBT is an accurate test for the detection of H. pylori infection also in children. Administration of 50 mg of 13C-urea, a fatty test meal, and breath sampling at 30 min appears to be the most convenient protocol.

Natural history of gallstone disease: Expectant management or active treatment? Results from a population-based cohort study

Background and Aims:  The knowledge of natural history is essential for disease management. We evaluated the natural history (e.g. frequency and characteristics of symptoms and clinical outcome) of gallstones (GS) in a population‐based cohort study.

Increased arterial stiffness in nonalcoholic fatty liver disease: the Cardio-GOOSE study

Objective Nonalcoholic fatty liver disease (NAFLD) is a very frequent disease in Western countries. NAFLD shares with metabolic syndrome the same etiologic factors, such as obesity, diabetes, and dyslipidemia, which are also major cardiovascular risk factors. Cardio-GOOSE (Cardio-Gambettola ObservatOry liver Steatosis Estimation) is a population-based cohort study finalized to evaluate the relationship between NAFLD, subclinical vascular damage, and arterial stiffness. Methods The study population consisted of 220 participants (123 women), aged between 30 and 70 years, who participated in the GOOSE study. Arterial stiffness was determined by measuring the carotid-femoral pulse wave velocity (PWV) by means of the PulsePen device. Preclinical atherosclerosis was detected by carotid intima–media thickness (IMT) measurement. Results NAFLD was associated with metabolic syndrome in 48% of cases. IMT values were strongly related to metabolic syndrome factors. No significant differences in IMT were found between controls and patients with isolated NAFLD (0.77 ± 0.15 mm versus 0.76 ± 0.14 mm). Conversely, in patients with NAFLD associated with metabolic syndrome, IMT values were significantly higher than in patients with NAFLD alone (0.85 ± 0.16 mm, P < 0.005). PWV values were significantly lower in controls compared to patients with isolated NAFLD (7.40 ± 1.47 versus 7.98 ± 1.51 m/s, P < 0.05) as well as patients with both NAFLD and metabolic syndrome (8.29 ± 2.2 m/s, P < 0.001). The prevalence in NAFLD was increased in patients with the highest PWV values, and persisted after adjustment for factors determining metabolic syndrome (P < 0.05). Conclusions This study has shown a possible independent role of NAFLD in determining arterial stiffness.

Biliary sludge: the sluggish gallbladder.

Biliary sludge is a mixture of particulate matter which has precipitated from bile. It generally consists of cholesterol monohydrate crystals, calcium bilirubinate or other calcium salts. In a clinical setting, biliary sludge is almost always an ultrasonographic diagnosis. Although it is less clinically applicable, direct microscopic examination of gallbladder bile is far more sensitive than ultrasonography into sludge detection, and has to be regarded as the diagnostic gold standard. The overall prevalence of sludge in the general population is relatively low. However, several clinical conditions are associated with a particularly high prevalence of biliary sludge, including pregnancy, rapid weight loss, total parenteral nutrition, octreotide therapy, bone marrow or solid organ transplantation. The clinical course of biliary sludge varies, and complete resolution, a waxing and waning course, and progression to gallstones are all possible outcomes. It may cause complications usually associated with gallstones, such as biliary colic, acute cholecystitis, and acute pancreatitis. The main pathogenic mechanism involved in sludge formation is probably gallbladder dismotility, and in selected patients measures aimed to maintain adequate gallbladder contractions has been shown to effectively prevent sludge development.

Inadequate Use of Acid-Suppressive Therapy in Hospitalized Patients and Its Implications for General Practice

Acid-suppressive therapy (AST) is largely prescribed in both hospital and general practice setting but few data are available on appropriateness of AST use in hospitalized patients and its fallout on prescribing in general practice. We assessed AST in patients consecutively admitted to an internal medicine department to determine the type and timing of prescription and indication for use according to widely accepted guidelines. Prescriptions were rated as indicated, acceptable, or not indicated. Overall, 58.7% of 834 admitted patients received AST, mainly proton pump inhibitors. The prescriptions were indicated in 50.1% of patients, not indicated in 41.5%, and acceptable in 6.5%. The main reason for inappropriate use was prophylaxis in low-risk patients (64.8%). On admission, 35.7% of 112 patients already on AST were judged to receive inappropriate prescription; of 348 patients discharged on AST, overuse was identified in 38.5%. No significant difference was observed for inappropriate use at admission, during hospitalization, and at discharge. In 64 inpatients (7.7%) AST, although indicated, mainly for ulcer prophylaxis in high-risk patients, was not prescribed. In conclusion, AST is substantially overused in both hospital and general practice settings, mainly for ulcer prophylaxis in low-risk patients. On the other hand, AST is underused in a small, but not negligible proportion of high-risk patients.

Risk factors for the development of gallstone recurrence following medical dissolution

Objective To assess risk factors for gallstone recurrence following non‐surgical treatment. Design A prospective follow‐up of a multicentre cohort of post‐dissolution gallstone patients. Setting Six gastroenterology units in the UK and Italy. Participants One hundred and sixty‐three patients with confirmed gallstone dissolution following non‐surgical therapy (bile acids or lithotripsy plus bile acids), followed up by ultrasound scan and clinical assessment at 6‐monthly intervals for up to 6 years (median, 25 months; range, 6‐70 months). Outcome measures Subject‐related variables (sex, age, height, weight, body mass index), gallstone‐related variables (number, diameter, presence of symptoms, months to complete stone clearance), treatment modalities (bile acid therapy, extracorporeal shock wave lithotripsy) and follow‐up related variables (weight change, use of non‐steroidal anti‐inflammatory agents, statins, pregnancies and/or use of oestrogens) were assessed by univariate and multivariate analysis as putative risk factors for gallstone recurrence. Results Forty‐five gallstone recurrences were observed during the follow‐up period. Multiple primary gallstones and length of time to achieve gallstone dissolution were the only variables associated with a significant increase in the recurrence rate. Appearance of biliary sludge during follow‐up was also significantly related to development of gallstone recurrence. Use of statins or non‐steroidal antiinflammatory agents did not confer protection against recurrence. Conclusions Patients with primary single stones are the best candidates for non‐surgical treatment of gallstones, because of a low risk of gallstone recurrence. The positive association of recurrence with biliary sludge formation and time to dissolution of primary stones may provide indirect confirmation for the role of impaired gallbladder motility in the pathogenesis of this condition. Eur J Gastroenterol Hepatol 12:695‐700

Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in-vitro study in perifused rat hepatocytes

Objectives: Membrane toxicity induced by hydrophobic bile salts may be important in liver diseases. Administration of ursodeoxycholate reduces serum liver enzymes in chronic liver diseases, but the nature of this effect is still unclear. We aimed at establishing a convenient in‐vitro system for investigating the hepatotoxic properties of hydrophobic bile salts and the putative hepatoprotective effect of ursodeoxycholate. Methods: About 100mg of freshly isolated rat hepatocytes were suspended on a resin column (Bio‐Gel P4 fine) and perifused with different concentrations of bile salts. The effluent was collected at 5‐min intervals and assayed for lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity. Enzyme leakage induced by bile salts was compared with that induced by Triton X‐100 (Union Carbide, Danbury, CT, USA) at different concentrations. After perifusion, hepatocytes were collected for electron microscopic observation. Results: Cytotoxicity of individual bile salts, assessed by enzyme release, was time and concentration dependent and corresponded to their hydrophilic‐hydrophobic balance. Perifusion with hydrophilic bile salts, cholate and ursodeoxycholate, did not result in a significant enzyme release in concentrations up to 5mmol/l, whereas hydrophobic bile salts, chenodeoxycholate and deoxycholate, induced significant enzyme leakage even in low concentrations, 0.5 and 0.1 mmol/l, respectively. Addition of ursodeoxycholate significantly reduced the hepatotoxic effect of deoxycholate. This protective effect was evident within minutes. The ultrastructural appearance of hepatocytes exposed to hydrophobic bile salts was very similar to the nonspecific cellular lysis observed after exposition to Triton X‐100, suggesting that they act mainly in a detergent‐like fashion. Conclusion: Perifused rat hepatocytes seem a convenient in‐vitro system for investigating the hepatotoxic properties of bile salts and hepatoprotective effect of ursodeoxycholate, offering the opportunity to investigate the effects of bile salts under dynamic conditions, mimicking the in‐vivo situation, and allowing continuous enzyme release monitoring. Hydrophobic bile salts seem to act mainly in a detergent‐like fashion; ursodeoxycholate‐related hepatoprotection could be due not only to a dilution effect of toxic bile salts, but also to a direct cytoprotective effect.

Appropriateness of Upper Gastrointestinal Endoscopy: A Hospital-Based Study

Aims of this study were to evaluate: (1) whether upper gastrointestinal endoscopy (UGE) is used appropriately according to the American Society for Gastrointestinal Endoscopy (ASGE) and British Society of Gastroenterology (BSG) guidelines in a hospital setting and (2) whether there is any relationship between appropriateness of UGE and the presence of lesions detected by endoscopy. %Indications and endoscopic findings for 734 consecutive UGE performed in 697 inpatients were retrospectively evaluated using ASGE and BSG guidelines to determine appropriateness of referrals. UGE showing endoscopic findings that had direct therapeutic or prognostic consequences were classified as “positive”; the other UGEs were classified as “negative.” In all, 46% of UGEs were “positive,” 54% “negative,” and 61.7% and 23.2% of UGEs were inappropriate according to ASGE and BSG guidelines, respectively (P < 0.001). The probability of finding a positive endoscopy was significantly higher in UGE rated as appropriate than in those rated as inappropriate on the basis of ASGE guidelines (P < 0.001), but not on the basis of BSG guidelines. Endoscopies rated as inappropriate according to ASGE and BSG criteria showed a positive finding in 37.3% and 42.3% of cases, respectively (not significant difference). Multivariate analysis showed that the positive finding is directly related to age (P < 0.05), male gender (P < 0.001), prior UGE (P < 0.05), hematemesis (P < 0.001), and inversely related with upper abdominal pain (P < 0.01) and dyspepsia (P < 0.05). In hospitalized patients, UGE is frequently used for inappropriate indications, according to both ASGE and BSG guidelines. However, the actual clinical usefulness of appropriateness criteria, such as those proposed by ASGE and BSG, is questionable, as their strict observance could lead to missing a large number of significant endoscopic findings.

Brush cytology : A reliable method to detect Helicobacter pylori

This study was conducted to verify the reliability of brush cytology in detecting Helicobacter pylori in an unselected group of patients with duodenal ulcer (DU) and nonulcer dyspepsia (NUD). Endoscopy was performed on 416 consecutive patients: group A, 94 with active DU; group B, 176 patients with DU after omeprazole (n = 78), ranitidine (n = 43), or triple anti-H. pylori therapy (n = 55); and group C, 146 patients with NUD. During endoscopy, the gastric mucosa was brushed and two biopsy samples from the antrum and body were obtained for histology. In 65 patients, culture of the brush-collected materials also was performed as was that from of biopsy samples. The overall frequency of H. pylori presence detected by brush cytology was significantly higher compared with that of histology (p < 0.001), particularly in group A (p < 0.05), group C (p < 0.05), and in patients with DU after omeprazole treatment (p < 0.01), but not in patients with DU after ranitidine or anti-H. pylori treatment. The overall frequency of H. pylori-positive cultures from the brush-collected material was higher compared with cultures from the biopsy samples (38.5% vs. 24.6%), particularly in the NUD group (32.6% vs. 16.3%). Brush cytology is more sensitive than histology, besides being faster and cheaper, for the assessment of H. pylori infection, particularly when the density of the bacteria is low.

Postprandial refilling and turnover: specific gallbladder motor function defects in patients with gallstone recurrence.

Background and aims Impaired gallbladder motor functions are important in the pathogenesis of primary cholesterol gallstones, and possibly in the pathogenesis of recurrent gallstones. By using ultrasonography and cholescintigraphy simultaneously, we recently defined new parameters of gallbladder motor function (postprandial refilling and turnover in addition to emptying), which were markedly impaired in gallstone patients. The aim of this study was to assess the value of these new parameters in distinguishing patients with from those without gallstone recurrence. Methods We studied 11 patients with gallstone recurrence, 11 without gallstone recurrence (at least 40 months after complete dissolution by oral bile acids) and 11 healthy controls. Simultaneous measurements of gallbladder volume (ultrasound) and gallbladder counts (&ggr;‐camera scintigraphy) were carried out in the fasting state and at 10 min intervals following meal ingestion, for a period of 90 min. Gallbladder refilling, turnover of bile and turnover index were calculated, as well as gallbladder emptying by both cholescintigraphy and ultrasound. Results Patients with gallstone recurrence had reductions in gallbladder emptying, postprandial refilling and gallbladder bile turnover. They also had a significant reduction in the turnover index (1.7 ± 1.4) compared to controls (3.5 ± 0.3, P< 0.01) and to patients without gallstone recurrence (3.1 ± 1.5, P< 0.05). Patients without gallstone recurrence had only a small reduction in emptying and no reduction in postprandial refilling or turnover compared to controls. Conclusions We conclude that impairment of gallbladder emptying persists in all patients after gallstone dissolution, albeit to a more pronounced extent in patients with recurrence; but that impairment of postprandial refilling and turnover are specific defects in patients with recurrence. Eur J Gastroenterol Hepatol 12:787‐794