The use of non-invasive stool tests for verification of Helicobacter pylori eradication and clarithromycin resistance.

BACKGROUND: Clarithromycin resistance of Helicobacter pylori (H. pylori) represents a major challenge in eradication therapy. In this study, we assessed if non-invasive stool tests can be used to verify successful H. pylori eradication and determine clarithromycin resistance. MATERIALS AND METHODS: In this prospective study, patients undergoing urea breath testing (UBT) for confirmation of H. pylori eradication were asked to collect the stool as both a dry fecal sample and fecal immunochemical test (FIT). Stool H. pylori antigen testing (SAT) was performed on these samples and assessed for its accuracy in eradication verification. Type and duration of antibiotic treatment were retrospectively collected from patient records and compared with clarithromycin resistance determined by PCR of stool samples. RESULTS: H. pylori eradication information was available for a total of 145 patients (42.7% male, median age: 51.2). Successful eradication was achieved in 68.1% of patients. SAT on FIT samples had similar accuracy for eradication assessment compared to dry fecal samples, 72.1% [95% CI 61.4-81.2] versus 72.2% [95% CI 60.9-81.7]. Clarithromycin resistance rate was 13.4%. CONCLUSION: H. pylori antigen testing on FIT stool samples to verify H. pylori eradication is feasible and has similar accuracy as H. pylori antigen testing on dry stool samples. Dry stool, but not FIT, was suitable for non-invasive identification of H. pylori clarithromycin resistance by rt-PCR personalizing antibiotic treatment strategies without the need for invasive diagnostics is desirable, as the cure rate of first-line empirical H. pylori treatment remains low.

Fully vs. partially covered selfexpandable metal stent for palliation of malignant esophageal strictures: a randomized trial (the COPAC study).

BACKGROUND: Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis. METHODS: In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first. RESULTS: Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs (P = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively (P = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events. CONCLUSIONS: Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia.

Yield of routine molecular analyses in colorectal cancer patients ≤70 years to detect underlying Lynch syndrome.

Although early detection of Lynch syndrome (LS) is important, a considerable proportion of patients with LS remains unrecognized. We aimed to study the yield of LS detection by routine molecular analyses in colorectal cancer (CRC) patients until 70 years of age. We prospectively included consecutive CRC patients ≤70 years. Tumour specimens were analysed for microsatellite instability (MSI), immunohistochemical mismatch-repair protein expression and MLH1-promoter methylation. Tumours were classified as either: (a) likely caused by LS; (b) sporadic microsatellite-unstable (MSI-H); or (c) microsatellite-stable (MSS). Predictors of LS were determined by multivariable logistic regression. A total of 1117 CRC patients (57% males, median age 61 years) were included. Fifty patients (4.5%, 95% CI 3.4-5.9) were likely to have LS, and 71 had a sporadic MSI-H tumour (6.4%, 95% CI 5.1-8.0). Thirty-five patients likely to have LS (70%) were aged > 50 years. A molecular profile compatible with LS was detected in 10% (15/144) of patients aged ≤50, in 4% (15/377) of those aged 51-60 and in 3% (20/596) of patients > 61 years. Compared to MSS cases, patients likely to have LS were significantly younger (OR 3.9, 95% CI 1.7-8.7) and more often had right-sided CRCs (OR 14, 95% CI 6.0-34). In conclusion, molecular screening for LS in CRC patients ≤70 years leads to identification of a molecular profile compatible with LS in 4.5% of patients, with most of them not fulfilling the age criterion (≤50 years) routinely used for LS assessment. Routine use of MSI testing may be considered in CRC patients up to the age of 70 years, with a central role for the pathologist in the selection of patients.

Risk factors for the development of esophageal adenocarcinoma in Barrett's esophagus.

OBJECTIVE: To identify risk factors for esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). METHODS: A hospital-based case-control study was performed in which 91 cases with EAC and 244 controls with histologically confirmed BE (>2 cm) with no dysplasia or low-grade dysplasia were included. Information on demographic, anthropometric, and lifestyle characteristics, physical activity levels, working posture, family history, gastroesophageal reflux disease (GERD) symptoms, and medication use was collected by questionnaire. RESULTS: Cases more often were current smokers (odds ratio 3.7, 95% confidence interval 1.4-9.9), more often had a body mass index >25 assessed at age 20 (2.6, 1.2-5.5), and more frequently had been working in a stooped posture at age 20 (2.0, 1.1-3.9), compared to controls. In addition, cases less often experienced symptoms of heartburn (0.3, 0.2-0.5) and less frequently used proton pump inhibitors (0.1, 0.05-0.2), compared to controls, whereas use of nonsteroidal anti-inflammatory drugs/aspirin was more common among cases (1.8, 1.1-3.2). Cases more often were men, compared to controls (91%vs 67%, p < 0.001). CONCLUSION: In patients with BE, the risk of EAC is related to risk factors for GERD, which is, however, asymptomatic. As these risk factors are common in Western countries, they are probably not helpful in individualization of surveillance intervals.

Viral dynamics in chronic hepatitis B patients treated with lamivudine, lamivudine-famciclovir or lamivudine-ganciclovir.

BACKGROUND: Prolonged nucleoside analogue therapy has been shown to reduce viral replication and normalize serum transaminases in the majority of chronic hepatitis B patients. However, from a theoretical point of view, monotherapy with lamivudine (a cytosine nucleoside analogue) will probably not result in eradication of hepatitis B virus. A prolonged course of lamivudine therapy would be needed to clear the virus from the liver. The occurrence of mutations, in combination with continuing low-grade viral replication in a number of patients, will prevent elimination of the virus from the liver. However, combination therapy with more than one nucleoside analogue could possibly overcome the disadvantages of monotherapy. PATIENTS AND METHODS: In this study, we report on 12 patients who were evaluated by means of a mathematical model during lamivudine monotherapy and lamivudine-famciclovir and lamivudine-ganciclovir therapy. RESULTS: There was no difference in the parameters representing blocking of viral production (epsilon = 93%, 95% and 86%, respectively), turnover of free virus (half-life of 16 h, 10 h and 12 h, respectively) and turnover of infected hepatocytes (half-life of 9 days, 7 days and 4 days, respectively) between the lamivudine, lamivudine-famciclovir and lamivudine-ganciclovir treatment groups. CONCLUSIONS: Although our study group is small, we do not think the drug combinations used offer a major advantage over lamivudine monotherapy. Different combinations of nucleoside analogues need to be studied in order to obtain a major breakthrough in this treatment strategy.

The influence of baseline characteristics on viral dynamic parameters in chronic hepatitis B patients treated with lamivudine.

BACKGROUND/AIMS: Viral decline during lamivudine therapy in chronic hepatitis B patients is bi-phasic. We studied the influence of lamivudine dose and baseline characteristics on parameters obtained from a mathematical model. METHODS: Chronic hepatitis B patients were randomized to receive 150 mg (group 1; n=11) or 600 mg (group 2; n=10) lamivudine daily for 4 weeks. Hepatitis B virus DNA was measured frequently with the Digene Hybrid Capture II test and the Roche PCR assay. RESULTS: The description of viral decline in our closely monitored patients by means of the mixed-effects approach with both the bi-phasic model and a piecewise linear regression model resulted in a good fit. Baseline alanine aminotransferase (ALT) was significantly related to the slope of the second phase of viral decline. Previous lamivudine-treated patients showed a significant slower first phase than patients naive to lamivudine treatment. CONCLUSIONS: The initial observed difference in viral decline between 150 and 600 mg of lamivudine disappeared when baseline ALT was taken into account. This strengthens the hypothesis that the level of intrinsic activity is related to the turnover of infected hepatocytes. Moreover, reintroduction of lamivudine in previously lamivudine-treated patients should be considered carefully.

Viral dynamics during and after entecavir therapy in patients with chronic hepatitis B.

BACKGROUND/AIMS: Nucleoside analogues inhibit hepatitis B virus (HBV) replication. Entecavir, a new guanine nucleoside, has also been shown to reduce covalently closed circular DNA (cccDNA) to undetectable levels in woodchucks chronically infected with hepatitis virus. Mathematical description of changes in viral load during and after therapy may help to understand the several events that take place during nucleoside analogue treatment. METHODS: Ten chronic hepatitis B patients were evaluated with a mathematical model during and after withdrawal of four doses of entecavir. Blood was drawn for HBV DNA measurement at frequent intervals. Non-linear modelling was used to fit individual patient data. RESULTS: The median effectiveness in blocking viral production is 96% (n=10, range 87-98%). The median half-life of viral turn-over was 16 h (range 12-29 h). The median half-life of infected hepatocytes was 257 h (=10.7 days) (n=9, range 112-762 h). Rebound of viral replication also followed a bi-phasic return to baseline levels. CONCLUSIONS: Decay and rebound of viral concentration during and after entecavir therapy, respectively, showed a bi-phasic pattern. Both can be described with a mathematical model. Data on levels of cccDNA in the liver in these patients could be helpful in supporting the parameters as calculated with the model.