Persistent elevation of serum CA 19-9 with no evidence of malignant disease.

BACKGROUND: Serum CA 19-9 is the mainstay marker for the diagnosis of biliopancreatic malignancies, though a persistent elevation can also be observed in various benign diseases. AIMS: In this study, a marked increase of serum CA 19-9 was seen in 10 patients who had no evidence of malignant disease. The possible causes of this finding are discussed. PATIENTS: Nine women and one man were studied, whose admitting diagnoses were as follows: pulmonary fibrosis in two, diabetes in two, non-ulcer dyspepsia in two, obesity in one, acute diarrhoea in one, colon diverticula in one and gastric ulcer in one. METHODS: Routine blood tests, tumour marker determinations, imaging studies and endoscopy were carried out at admission. RESULTS: Serum CA 19-9 levels ranged from 112 to 1338 IU/ml (mean 517 IU/ml). Abdominal ultrasonography, CT-scan, upper gastrointestinal X-ray series and gastrointestinal endoscopies were negative for malignancy. During the follow-up period (range 2-7 years) serum CA 19-9 values were persistently elevated in all patients. CONCLUSIONS: Our study shows that persistent and significant elevation of serum CA 19-9 can be found in non-malignant and non-cholestatic disease.

Capsule endoscopy for the detection of bleeding Meckel's diverticulum. A case report.

The case of a 59-year-old man with a history of recurrent severe gastrointestinal bleeding due to Meckel's diverticulum is described. The diagnosis was achieved by means of capsule endoscopy. The histological examination revealed the presence of Meckel's diverticulum with ectopic gastric mucosa. The use of capsule endoscopy for the detection of Meckel's diverticulum is discussed.

Measuring dyspepsia: a new severity index validated in Bologna.

BACKGROUND: Measurement of the severity of dyspepsia symptoms before and after treatment and determining what is a significant change is a major problem in designing dyspepsia treatment studies. OBJECTIVES: To assess the reproducibility, validity and responsiveness to treatment of a dyspepsia questionnaire to be used in clinical and population-based studies. METHODS: Seventy-three dyspeptic patients (35 male, 38 female; mean age 52 years) and 75 healthy volunteers (32 male, 43 female; mean age 52 years) were included. Subjects were interviewed for the presence/absence and severity/frequency of 19 gastrointestinal symptoms. Severity was measured on a 5-point scale. Frequency was also recorded on a 5-point scale. A global symptom index (severity x frequency) was calculated for the eight most severe symptoms; a mean global symptom index (8-MGSI) was considered for the evaluation of the instrument. To evaluate intra-observer variation, one author interviewed subjects (T0) and then repeated the interview 1 week later (T1). For inter-observer variation, two authors interviewed patients. VALIDITY was measured by comparing 8-MGSI of the dyspepsia patients to those of healthy volunteers. Responsiveness was assessed by comparing mean global symptom index before and 1 month after appropriate therapy. RESULTS: Reproducibility: The mean 8-MGSI was 4.5 at T0 and 3.7 at T1 with a correlation coefficient of 0.62. As for inter-observer variation, the average 8-MGSI was 4.8 by the first author and 3.9 by the second with a correlation coefficient of 0.60. VALIDITY: The mean 8-MGSI was, respectively, 1.4 in healthy volunteers and 4.8 in dyspeptic patients (p = 0.001). Responsiveness: After treatment, a significant improvement in 8-MGSI was detected (p = 0.001). CONCLUSIONS: This questionnaire is a reliable, valid and responsive instrument for measuring the presence, severity and frequency of dyspepsia.

Helicobacter pylori and functional dyspepsia: review of previous studies and commentary on new data.

Many studies have attempted to prove a link between Helicobacter pylori infection and functional dyspepsia but the results have been conflicting. Several mechanisms have been postulated for how H pylori associated inflammation disturbs antral and duodenal function but no pathophysiological explanation of how H pylori may cause dyspeptic symptoms is presently available.

Low-dose lansoprazole and clarithromycin plus metronidazole vs. full-dose lansoprazole and clarithromycin plus amoxicillin for eradication of Helicobacter pylori infection.

AIM: To compare, in a randomized controlled trial, the efficacy and tolerability of two 1-week triple therapies for Helicobacter pylori eradication. METHODS: One hundred and thirty-four consecutive patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive lansoprazole 30 mg once daily, clarithromycin 250 mg twice daily, and metronidazole 500 mg twice daily (LCM group), or lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily (LCA group). H. pylori status was assessed by rapid urease test, histology and 13C-urea breath test before and after therapy. RESULTS: At 3 months, H. pylori eradication (intention- to-treat/per protocol analysis) was 92.4%/93.8% in the LCM group and 83.1%/85.7% in the LCA group (P=N.S.). Side-effects were more frequently reported in the LCA group (37.9%) than in the LCM group (19.7%) (P < 0.05). CONCLUSIONS: In this open, randomized controlled trial, eradication of H. pylori by low-dose lansoprazole and clarithromycin plus metronidazole was higher with significantly less side-effects than by full-dose lansoprazole and clarithromycin plus amoxicillin. This finding may be related to the stronger synergism of clarithromycin plus metronidazole, even at lower doses, than of clarithromycin plus amoxicillin. Considering the lower cost as well, LCM should be preferred to LCA in the eradication of H. pylori.

Endoscopic surveillance in Barrett's esophagus.

Barrett's esophagus (BE), a complication of chronic gastroesophageal reflux disease (GORD), is a condition that is premalignant for adenocarcinoma of the esophagus and esophagogastric junction. Esophageal adenocarcinoma, once an uncommon entity, has been growing rapidly in incidence over the last two decades in several parts of the world. Barrett's esophagus is a change in the esophageal epithelium of any length that can be recognized at endoscopy and is confirmed to have intestinal metaplasia by biopsy (American College of Gastroenterology guidelines). Because of its premalignant nature, it is recommended that patients with BE undergo regular endoscopic surveillance. The recommendation for endoscopic surveillance is based on unproved and controversial assumptions including: 1) the assumption that Barrett's esophagus adversely influences survival; 2) the assumption that endoscopic surveillance can reliably detect early, curable neoplasia in the columnar lined esophagus. Moreover, the low incidence of adenocarcinoma (reported cancer incidence rates in prospective studies on BE range between 0.5% and 1.9%) is used to support an approach of not surveying patients with Barrett's esophagus. Despite these not convincing data, endoscopic surveillance is considered ''reasonable'' and ''desirable'' by the gastroenterological associations and consensus meetings. Endoscopic surveillance for cancer in Barrett's esophagus (BE) is performed primarily to seek dysplasia, to prevent the progression to invasive malignancy; however, one of the limitations of using dysplasia is a lack of understanding of its natural history. The efficacy of endoscopic surveillance for Barrett's esophagus is likely to remain unclear for a long time. The American College of Gastroenterology has recommended the following practice guidelines: a) for patients with no dysplasia, surveillance endoscopy is recommended at an interval of every 2 to 3 years; b) for patients with low grade dysplasia, surveillance endoscopy every 6 months for the first year is recommended, followed by yearly endoscopy if the dysplasia has not progressed in severity; c) for patients with high grade dysplasia, two alternatives are proposed after the diagnosis has been confirmed by an expert gastrointestinal pathologist. One alternative is intensive endoscopic surveillance until intramucosal cancer is detected at an interval of every 3-6 months. The other alternative is esophageal resection. In the situation of indeterminate dysplasia, whereas the pathologist can not come to definite diagnosis, control biopsies are proposed after 2 months of adequate acid suppression by means of proton pump inhibition. In all cases, the technique of random, four quadrant biopsies taken every 2 cm in the columnar-lined esophagus for standard histologic evaluation is recommended. Any grossly abnormal areas may be biopsied too. One can expect however that during the next future these protocol will change considering new data on dysplasia detection (biochemical markers, flow cytometry), new techniques to identify dysplasia (chromoendoscopy, endosonography, coherence optical tomography, fluorescence techniques) and development of better ablative techniques. At present a marker other than dysplasia identifying a high risk group for cancer on which to focus endoscopic surveillance has not yet been established.

The Loiano-Monghidoro population-based study of Helicobacter pylori infection: prevalence by 13C-urea breath test and associated factors.

OBJECTIVES: As part of a cross-sectional study on cholelithiasis, 1533 out of 1840 residents in Loiano/Monghidoro, a rural area in Northern Italy (792 men, 741 women, age range 28-80 years), agreed to be further evaluated in relation to their Helicobacter pylori status. METHODS: Each participant performed a 13C-urea breath test (13C-UBT) and provided information on sociodemographic, lifestyle and clinical characteristics. RESULTS: The 13C-UBT was positive in 1041 subjects (67.9%; men: 69%; women: 67%) and was positively associated with increasing age (P < 0.001), alcohol consumption (P < 0.01), a higher number of siblings (P < 0.001) and a personal history of peptic ulcer (P < 0.01), but inversely with a nonmanual occupation (P < 0.001). Overall, H. pylori infection was unrelated to smoking, house pets, and a family history of gastroduodenal diseases. The prevalence of H. pylori infection was 72% in subjects reporting one or more dyspeptic symptoms and 65% among asymptomatic participants (P < 0.001); a multivariate analysis showed that only epigastric pain was significantly, although weakly, associated with 13C-UBT positivity. CONCLUSIONS: This large population-based study showed a prevalence of H. pylori infection higher than that reported by serologic surveys in urban areas. Current H. pylori infection was strongly associated with indicators of lower socioeconomic status, alcohol consumption and increasing age. A role of H. pylori infection in determining epigastric pain was suggested.

Incidence and recurrence rates of colorectal adenomas in first-degree asymptomatic relatives of patients with colon cancer.

OBJECTIVES: Subjects with one first-degree relative affected with colorectal cancer are considered to be at increased risk of colorectal adenomas. We compared the recurrence and incidence rates of colorectal adenomas among subjects with one first-degree relative with colorectal cancer and those without family history. METHODS: A series of consecutive asymptomatic subjects successfully underwent a colonoscopy, were found to have either normal results or at least one adenoma, provided a detailed family history, and were offered a second colonoscopy 3 yr later; 190 out of 436 subjects accepted, 134/172 with one or more adenomas and 56/264 with no abnormalities at the initial examination. A first-degree family history was reported by 43/134 and 26/56, respectively. RESULTS: By multivariate analysis, the presence of adenomas at follow-up examination was significantly associated with a positive family history of colorectal cancer in both subgroups, those with a previously resected adenoma (odds ratio = 2.23, 95% CI = 1.04-4.79) and those without (odds ratio = 8.95, CI = 1.29-62.22). CONCLUSION: A history of one first-degree relative with colorectal cancer is associated with a significant increase in 3-yr cumulative incidence and recurrence rates of adenomas.

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.

Review article: non-invasive methods for the diagnosis of Helicobacter pylori infection.

Non-invasive tests for the diagnosis of Helicobacter pylori infection are widely used in clinical practice and the management of patients with gastrointestinal disease. The serology and 13C-urea breath test are widely available, whereas salivary and faecal assay are still being developed. The non-invasive tests represent notable savings for the patient both in terms of money and discomfort. Whilst serology is the most widespread test its use is not advised in post-treatment follow-up. The 13C-urea breath test is a simple, safe and highly accurate method ideal to evaluate, in the short-term follow-up, Helicobacter pylori eradication after treatment.

What can be learnt from the new data about antibiotic resistance? Are there any practical clinical consequences of Helicobacter pylori antibiotic resistance?

Effective treatment regimens are now available for the eradication of Helicobacter pylori, but one of the factors limiting their efficacy is antibiotic resistance. Omeprazole-based triple therapy (omeprazole plus two antibiotics) can, at present, be considered the treatment of choice for H. pylori infection; some of the best results have been achieved by combining omeprazole with either amoxycillin and clarithromycin or metronidazole and clarithromycin. However, the potential effectiveness of nitroimidazole derivatives and clarithromycin must be weighed against the possibility that resistance can develop to these agents. Eradication in metronidazole-resistant strains is lower than in sensitive strains, but is still about 75% (versus 97%). However, clarithromycin resistance is thought to have more clinical significance, reducing the eradication rate of 95% in sensitive strains to 40% in resistant strains, although the overall importance of clarithromycin resistance for H. pylori eradication is still likely to be relatively low. Recent data on secondary resistance indicate that the rate is at least 50% for both metronidazole and clarithromycin in patients in whom eradication has failed. If, in the future, a large number of H. pylori-positive individuals undergo such treatment, treatment failures may become a major issue, and the problem of antibiotic resistance will have to be overcome.

Helicobacter pylori: optimum diagnosis and test of cure.

The fact that about 50% of the world's population is infected with Helicobacter (H.) pylori and the important role that this bacterium plays in public health have been important incentives in the search for accurate diagnostic methods. A large number of invasive and non-invasive methods have been used to diagnose H. pylori infection. Each method has its advantages and disadvantages and each practitioner should choose the best diagnostic method according to the facilities available. Non-invasive tests for the diagnosis of H. pylori infection are largely used in clinical practice and in management of patients with gastroduodenal disease. Serology is the most widespread test but its use is not advised in the post-treatment follow-up. The Urea Breath Test is a simple, safe and highly accurate method ideal for evaluating the short-term follow-up of H. pylori eradication after therapy.

Efficacy of lansoprazole in eradicating Helicobacter pylori: a meta-analysis.

BACKGROUND: The combination of lansoprazole with antibiotics either as double or triple therapy has demonstrated an H. pylori eradication rate of between 80 and 90%. With the aim of providing a complete revision of the results of these clinical studies and a quantification of the efficacy of lansoprazole in eradicating H. pylori and healing peptic ulcers, we have undertaken a meta-analysis of all the controlled studies published in the literature. METHODS: This meta-analysis reviewed all randomized, controlled clinical trials published as full text articles in English between 1993 and 1996 that reported the efficacy of lansoprazole treatment as monotherapy or in combination with antibiotics in the treatment of peptic ulcer and in eradicating H. pylori. Articles were identified from the literature, which included both manual and computerized research (MEDLINE) and references provided by articles in this area. In order to compare the efficacy of triple therapy comprising lansoprazole vs. another PPI, data from abstracts (n = 5) were used, as no full text articles were located. RESULTS: This systematic review of the literature documents that lansoprazole has a high degree of efficacy in eradicating H. pylori, above all when used within treatment schemes including amoxicillin or clarithromycin, and metronidazole or tinidazole. This efficacy is comparable to that of other PPIs. CONCLUSIONS: Triple therapy allows the eradication of H. pylori in more than 85% of cases in patients with peptic ulcer. In addition, there is a substantial comparability of the efficacy of lansoprazole and omeprazole when they are used together with other anti-infective agents. Thus, lansoprazole appears to offer an option in the eradication of H. pylori.

Efficacy and safety of three 7-day Helicobacter pylori eradication regimens containing ranitidine bismuth citrate.

BACKGROUND: This multicentre, randomized study was designed to assess the clinical efficacy, safety and tolerability of three novel 7-day triple therapies containing ranitidine bismuth citrate (RBC) and two antibiotics. METHODS: We studied patients with non-ulcer dyspepsia and gastritis who were randomly assigned to one of three treatment regimens given for 7 days in a b.d. dosing schedule: RBC 400 mg plus clarithromycin 250 mg and tinidazole 500 mg (RBCCT): RBC 400 mg plus clarithromycin 500 mg and amoxycillin 1 g (RBCCA); RBC 400 mg plus tinidazole 500 mg and amoxycillin 1 g (RBCTA). H. pylori status was determined by CLO-test, histology and 13C-urea breath test. A repeat breath test was performed at least 28 days after completion of therapy to assess eradication. RESULTS: One hundred and fifty-seven patients were eligible for intention-to-treat analysis (ITT) and 140 patients completed the study and returned for assessment of eradication. Intention-to-treat cure rates were 78% with RBCCT, 71% with RBCCA and 61% with RBCTA. An all-patients-treated analysis (APT), performed on evaluable patients, demonstrated eradication rates of 85% with RBCCT, 81% with RBCCA and 70% with RBCTA. No statistically significant difference was found between treatment groups. Twenty-four patients experienced side-effects, but in only seven cases was treatment discontinued due to adverse events. CONCLUSIONS: A 7-day course of RBC, clarithromycin and either tinidazole or amoxycillin provides a good rate of H. pylori eradication. Three novel RBC-based triple therapies proved to be safe and well tolerated, with discontinuations due to side-effects occurring in less than 5% of cases.

Evaluation of short-term low-dose triple therapy for the eradication of Helicobacter pylori by factorial design in a randomized, double-blind, controlled study.

BACKGROUND: Studies demonstrating the efficacy of short-term low-dose triple therapies including omeprazole (O), clarithromycin (C) and a nitroimidazole (tinidazole, T) for Helicobacter pylori eradication have largely been open and uncontrolled, and have not assessed antibiotic sensitivity. Simpler regimens using the component drugs have not been evaluated. AIM: To evaluate the OCT regimen in a randomized, controlled trial, testing for pre- and post-treatment antibiotic resistance and comparing, in a factorial design, the OCT regimen with simpler combinations of its components. METHODS: One hundred and twenty-eight patients (68 males, 60 females, age 22-80 years, mean 53 years) with H. pylori gastritis were randomly assigned to one of the following four treatment groups: (C) clarithromycin 250 mg b.d.; (OC) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d.; (CT) clarithromycin 250 mg b.d. + tinidazole 500 mg b.d.; (OCT) omeprazole 20 mg q.d.s. + clarithromycin 250 mg b.d. + tinidazole 500 mg b.d. The drugs were administered for 1 week. Medical interview, upper gastrointestinal endoscopy (with four antral and four corpus biopsies) and the 13C-urea breath test were carried out for all patients prior to and 4 weeks after treatment. Biopsy specimens were used for the urease test, histology, and culture and sensitivities. RESULTS: All but one patient completed treatment. Side-effects were rare and mild in all groups. The eradication rate was 93.8% in group OCT, 59.4% in group CT, 31.3% in group OC and 6.3% in group C. Pre-treatment metronidazole resistance was 12.8%, clarithromycin 1.1% and, to both antibiotics, 2.1%. In patients with pre-treatment metronidazole resistance, the eradication rate was 75% in group OCT and 33% in group CT. Post-treatment resistance to clarithromycin was induced in 28.5% of the failures in group C, but in none of group OC. Resistance to both antibiotics occurred in 22.2% of the failures in group CT and in none of group OCT. CONCLUSIONS: (i) The high efficacy of the OCT regimen is proved and each of the individual components of the regimen is essential to the result, possibly via a synergistic effect. (ii) Pre-treatment metronidazole resistance is scarcely relevant to the outcome. (iii) Acquired resistance is essentially nil if omeprazole is part of the regimen.

Ranitidine bismuth citrate plus clarithromycin 7-day regimen is effective in eradicating Helicobacter pylori in patients with duodenal ulcer.

BACKGROUND: No clinical study has been performed to-date to evaluate the efficacy of the dual therapy of ranitidine bismuth citrate (RBC) plus clarithromycin (C) 500 mg b.d. given for 7 days for the eradication of H. pylori. AIM: To assess the eradication rates achieved by treatment with RBC 400 mg b.d. for 28 days combined with clarithromycin 500 mg b.d. for 7 days in H. pylori-positive duodenal ulcer patients. METHODS: One hundred and twelve H. pylori-positive patients with endoscopically proven active duodenal ulcer were included in a multicentre, open, randomized trial. H. pylori infection was initially detected by CLO-test and histology on antral and corpus biopsies, and by 13C-urea breath test (UBT). Patients were included if at least two of the tests were positive for H. pylori infection. Patients were randomized to receive RBC 400 mg b.d. for 4 weeks combined with clarithromycin 500 mg b.d. for the first 7 days (Group A) or 14 days (Group B). A second endoscopy was performed at least 28 days after the end of therapy for the assessment of ulcer healing and H. pylori infection. Eradication was assumed if all the tests (CLO-test, histology and UBT) were negative for H. pylori. RESULTS: Fifty patients in Group A and 55 in Group B were assessed for H. pylori eradication and ulcer healing. The eradication rates according to intention-to-treat analysis were 75% in Group A and 80% in Group B. Considering only those patients with evaluable data at least 28 days after the end of therapy, H. pylori eradication was achieved in 84% and 82% in Group A and B, respectively. No statistically significant difference in eradication was found between the two groups by Mantel-Haenszel test. Only one patient, in Group A, was withdrawn because of adverse events (epigastric pain and pruritus).

Diagnosis of Helicobacter pylori infection: non-invasive diagnostic tests.

The non-invasive urea breath test can demonstrate the presence of Helicobacter pylori infection with the same accuracy as invasive methods (histology, rapid urease test, culture), but with less distress and inconvenience to the patient. It is evident that this test can and should substitute invasive methods in patients with uncomplicated duodenal ulcer, in those with non-ulcer dyspepsia and in all who have gastrointestinal disorders that do not require endoscopic examination. The urea breath test has a primary role for determining the success of eradication therapy. It is ideal for short- and long-term follow-up, particularly in the case of duodenal ulcer, which is strictly related to the presence of Helicobacter pylori. In serious disease, when endoscopic examination is mandatory, such as complicated ulcer or mucose associated lymphoid tissue lymphoma, the urea breath test can still improve the diagnostic accuracy of Helicobacter pylori infection as it does not imply sampling error, to which biopsy is subject.

Urea breath tests for the detection of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori is recognized as an important human pathogen. The urea breath test, using either 13C or 14C, provides a noninvasive diagnostic method for the detection of active H. pylori infection. METHODS: We review the data regarding the utility of the urea breath test in the diagnosis and follow-up of patients with suspected H. pylori infection. RESULTS: Following its ingestion, labeled urea is hydrolyzed by H. pylori urease, producing ammonia and labeled CO2, which is absorbed and can be detected in expired breath. The urea breath test provides a semiquantitative assessment of the load of H. pylori and overcomes the problem of the sampling error due to the patchy distribution of the infection. 13C-urea breath test has an advantage over the 14C version, because the 13C isotope is a nonradioactive natural isotope; therefore, a user's license is unnecessary, making simple the handling and mailing of samples. The 13C-urea breath test is preferred in children and expectant mothers. CONCLUSION: The high sensitivity, and specificity of the 13C-urea breath test are such that it can be considered a clinical gold standard against which other diagnostic methods can be validated. This test can be used as the sole method for evaluating the effectiveness of treatment of H. pylori infection.