Barbara Braden

The [13C]acetate breath test accurately reflects gastric emptying of liquids in both liquid and semisolid test meals

BACKGROUND/AIMS The current standard for gastric emptying studies are radioactive isotope methods. [13C]breath tests have been developed as a nonradioactive alternative. The aim of this study was to validate a [13C]acetate breath test as a measure of gastric emptying of the liquid phase both in liquid and semisolid test meals by simultaneous radioscintigraphy. METHODS Thirty-five patients with dyspeptic symptoms and 20 healthy volunteers were tested using a semisolid oatmeal or a liquid test meal. Both test meals were labeled by 150 mg sodium [13C]acetate and (in patients) by 45 MBq 99mTc-albumin colloid. Half-time of gastric emptying was calculated after curve fitting of the 13C exhalation to a modified power exponential function. 99mTc-albumin emptying was measured by conventional radioscintigraphy. RESULTS The half-emptying times for the [13C]acetate breath test closely correlated to those measured by radioscintigraphy both for semisolids (r = 0.87) and liquids (r = 0.95). The time of maximum 13CO2 exhalation was itself a reliable parameter compared with the half-emptying times obtained by scintigraphy (r = 0.85 for semisolids; r = 0.94 for liquids). CONCLUSIONS The [13C]acetate breath test is a reliable and noninvasive tool for the analysis of gastric emptying rates of liquid phases without radiation exposure.

The natural history of small-duct primary sclerosing cholangitis.

BACKGROUND & AIMS The long-term prognosis of patients with small-duct primary sclerosing cholangitis (PSC) remains incompletely characterized. We aimed at determining the natural history and long-term outcomes of a large number of patients with small-duct PSC. METHODS Data from 83 patients with well-characterized small-duct PSC from several medical institutions in Europe and the United States were combined. Each patient with small-duct PSC was randomly matched to 2 patients with large-duct PSC by age, gender, calendar year of diagnosis, and institution. RESULTS The median age at diagnosis in both groups was 38 years (61% males). Nineteen (22.9%) of the 83 patients with small-duct PSC progressed to large-duct PSC in a median of 7.4 (interquartile range [IQR], 5.1-14) years. One patient with small-duct PSC who progressed to large-duct PSC was diagnosed with cholangiocarcinoma but after progression to large-duct PSC; 20 patients with large-duct PSC developed cholangiocarcinoma. Patients with small-duct PSC had a significantly longer transplantation-free survival compared with large-duct PSC patients (13 years [IQR, 10-17] vs 10 years [IQR, 6-14], respectively; hazard ratio, 3.04; 95% confidence interval: 1.82-5.06; P < .0001). Two patients with small-duct PSC who underwent liver transplantation had recurrence of small-duct PSC in the graft 9 and 13 years, respectively, after transplantation. CONCLUSIONS Small-duct PSC is a disease of progressive potential but associated with a better long-term prognosis as compared with large-duct PSC. Small-duct PSC may recur after liver transplantation. Cholangiocarcinoma does not seem to occur in patients with small-duct PSC, unless the disease has progressed to large-duct PSC.

Improved Differentiation of Pancreatic Tumors Using Contrast-Enhanced Endoscopic Ultrasound

BACKGROUND & AIMS Endoscopic ultrasound is a widely accepted imaging method for staging of ductal adenocarcinoma and the localization of neuroendocrine tumors of the pancreas. We prospectively evaluated conventional color Doppler imaging and contrast-enhanced endoscopic Doppler ultrasound (CE-EDUS) as a new imaging technique for further characterization and differentiation of solid pancreatic tumors. METHODS From 300 patients with pancreatic lesions investigated using contrast-enhanced endoscopic ultrasound we could finally include 93 patients with an undetermined, solitary, predominantly solid, lesion 40 mm or less, and a definite histologically proven diagnosis. After bolus injection of the contrast agent SHU 508A 4 g (400 mg/dL) the vascular pattern of the lesion during the arterial phase was compared with the vascularity of the residual pancreatic parenchyma. RESULTS Color Doppler imaging did not reveal vascularity of the pancreatic parenchyma in any of the patients, and therefore tumor hypovascularity could not be determined in contrast to all CE-EDUS-examined patients revealing at least some degree of parenchymal vascularity. Fifty-seven of 62 patients with ductal adenocarcinoma of the pancreas showed a hypovascularity of the tumor using CE-EDUS. All other pancreatic lesions revealed an isovascular or hypervascular pattern using contrast-enhanced endoscopic ultrasound (20 neuroendocrine tumors, 10 serous microcystic adenomas, and 1 teratoma). Hypovascularity as a sign of malignancy in contrast-enhanced endoscopic ultrasound obtained 92% (82%-97%) sensitivity and 100% specificity (89%-100%). CONCLUSIONS Contrast-enhanced endoscopic ultrasound is effective in differentiating small solid pancreatic tumors of different origin in most cases. Hypovascularity indicates malignancy of pancreatic tumors.

Contrast-enhanced ultrasound of histologically proven liver hemangiomas.

Differentiation of small and atypical hemangiomas from other hepatic masses using imaging methods can be difficult, especially in patients with underlying malignant disease. Therefore, contrast‐enhanced ultrasound was assessed in patients with histologically confirmed hemangiomas with respect to contrast‐enhancing kinetics and tumor characteristics. In 58 patients with indeterminate hepatic lesions demonstrated with at least 2 imaging methods (ultrasound/computed tomography/magnetic resonance imaging), ultrasound‐guided liver biopsy revealed hemangioma. In all patients a hepatic neoplasm had been suspected because of underlying malignant disease (n = 41), liver cirrhosis (n = 15), or growth of the lesion (n = 2). All patients underwent nonlinear, low mechanical index real‐time contrast‐enhanced ultrasound scanning with bolus injections of SonoVue. Peripheral nodular arterial enhancement was detected in 43 patients (74%), whereas the typical metastatic peripheral rim‐like enhancement was not observed at all. Strong homogenous arterial enhancement was found in 9 of 58 (16%) patients. In 6 patients (10%), the arterial contrast enhancement pattern could not be determined because of the very small size of the lesions or fibrotic nodules. Forty‐five (78%) of the hemangiomas showed homogenous centripetal filling within 180 seconds. Conclusion: Contrast‐enhanced ultrasound demonstrates typical hemangioma imaging characteristics, that is, peripheral nodular contrast enhancement and iris‐diaphragm sign in a high percentage of patients with undetermined lesions. This technique may therefore improve noninvasive functional characterization and differentiation of hemangiomas. (HEPATOLOGY 2007;45:1139–1145.)

New Immunoassay in Stool Provides an Accurate Noninvasive Diagnostic Method for Helicobacter pylori Screening in Children

Objective. The noninvasive13C-urea breath test (UBT) is a reliable diagnostic method for detection of Helicobacter pylori infection in children, and it avoids invasive gastrointestinal endoscopy. In this study, we compared a noninvasive, newly developed fecal H pylori antigen test with the UBT. Methodology. One hundred sixty-two children (76 girls and 86 boys) were tested for H pylori infection using the UBT and a new antigen test in stool samples. The H pylori stool test is based on a sandwich enzyme immunoassay with antigen detection. Results. Twenty-four of the children (14.8%) with dyspepsia tested positive for H pylori according to the breath test results. In 22 of the 24 patients, H pyloriantigen could be detected in the stool (sensitivity: 91.6%). Of 138 patients with negative UBT results, 136 were H pylori-negative in the stool test (specificity: 98.6%). Conclusions. The new, noninvasive, low-cost H pylori antigen test in stool can replace the UBT for detection of H pylori infection in children with comparable reliability and accuracy.

Methods and functions: Breath tests

Breath tests provide a valuable non-invasive diagnostic strategy to in vivo assess a variety of enzyme activities, organ functions or transport processes. Both the hydrogen breath tests and the (13)C-breath tests using the stable isotope (13)C as tracer are non-radioactive and safe, also in children and pregnancy. Hydrogen breath tests are widely used in clinical practice to explore gastrointestinal disorders. They are applied for diagnosing carbohydrate malassimilation, small intestinal bacterial overgrowth and for measuring the orocecal transit time. (13)C-breath tests non-invasively monitor the metabolisation of a (13)C-labelled substrate. Depending on the choice of the substrate they enable the assessment of gastric bacterial Helicobacter pylori infection, gastric emptying, liver and pancreatic function as well as measurements of many other enzyme activities. The knowledge of potential pitfalls and influencing factors are important for correct interpretation of breath test results before drawing clinical conclusions.

Nondispersive Isotope-Selective Infrared Spectroscopy: A New Analytical Method for 13C-Urea Breath Tests

BACKGROUND Currently, stable isotope techniques in breath tests using 13C-labeled substrates are limited to a few centers equipped with expensive and complex isotope ratio mass spectrometry (IRMS). Although breath samples can be mailed to these centers, widespread application of 13C breath tests would be more feasible with a cheaper and more practicable analysis system at hand. METHODS We therefore tested the newly developed nondispersive isotope-selective infrared spectrometer (NDIRS) with reference to IRMS in a clinical setting comparing the results of both techniques in 538 consecutive 13C-urea breath tests performed for the detection of Helicobacter pylori infection. RESULTS With NDIRS five false-positive and three false-negative results were observed; that is, the sensitivity of NDIRS was 98.3%, and the specificity was 98.6%. The delta over base-line values of both devices correlated linearly (Y = 0.87 +/- 0.01 X + 0.29 +/- 1.5; r = 0.95; p < 0.0001; n = 538). CONCLUSIONS When running this large number of breath tests in 3 days, the NDIRS proved to be a reliable, stable, and easy-to-operate analytical tool, which is well qualified for gastroenterologic application in the diagnostic routine. Both the price and the easy handling of NDIRS will facilitate the widespread use of the noninvasive stable isotope technique for 13C breath tests.

Comparison of new faecal antigen test with 13C-urea breath test for detecting Helicobacter pylori infection and monitoring eradication treatment: prospective clinical evaluation

The 13C-urea breath test is currently regarded as the best non-invasive diagnostic method for detecting Helicobacter pylori infection, even when monitoring efficacy of treatment.1–2 Serological methods are not appropriate for such monitoring as antibodies stay for months after successful eradication.3 A newly developed immunoassay that detects bacterial antigens in a faeces specimen might constitute a non-invasive technique for evaluating the efficacy of eradication regimens shortly after treatment is stopped. In this prospective study we compared a new antigen test for H pylori in faeces4 with the reference method of monitoring treatment, the 13C-urea breath test. We intended to evaluate the clinical validity of the test for first diagnosis of H pylori infection and for monitoring efficacy of eradication treatment. Ninety participants (46 men, 44 women; age range 18-82 years) complaining about dyspeptic symptoms were screened for H pylori infection with …

Improved characterisation of solitary solid pancreatic tumours using contrast enhanced transabdominal ultrasound

BackgroundContrast enhanced ultrasound (CEUS) is a new imaging method for detection and characterisation of liver tumours. The role of CEUS in pancreatic disease is less obvious. We prospectively evaluated CEUS for characterization of undetermined solid pancreatic lesions (gold standard histology).Patients and methodsA total of 112 solitary undetermined pancreatic masses (70 ductal adenocarcinoma and 42 neoplastic nodules of other origin) were prospectively examined in patients without metastatic disease using transabdominal ultrasound. Tumour enhancing features were analyzed in comparison to the surrounding pancreatic parenchyma in patients with adequate visualisation.ResultsThe sign of iso-hypervascularity as a sign of non-ductal adenocarcinoma showed a sensitivity of 100%, specifity of 90% and accuracy of 93.8%. The sign of hypovascularity as a sign of ductal adenocarcinoma showed a sensitivity of 90%, specifity of 100% and an accuracy of 93.8%.ConclusionCEUS allows differential diagnosis of ductal adenocarcinoma and non-ductal adenocarcinoma (mainly neuroendocrine tumours and (microcystic) serous pancreatic adenoma) in the most of cases.

Influence of cisapride on gastric emptying of solids and liquids monitored by13C breath tests

Abstract[13C]Acetate and [13C]octanoate breath tests were used to analyze the gastric emptying of liquids and solids in healthy controls and patients with functional dyspepsia both with and without cisapride. A standard test meal was labeled with either 150 mg [13C]acetate (liquid phase labeled in the water) or with 100 mg [13C]octanoate (solid phase labeled in the egg yolk). Six patients with dyspepsia and six healthy controls underwent a 4-hr breath test four times, ie, both the [13C]acetate and [13C]octanoate test with and without cisapride. Duplicate [13C]acetate or [13C]octanoate breath tests were performed in another 12 healthy controls in order to assess day-to-day variability of gastric emptying for liquids and solids. The mass spectrometric data were fitted to a power exponential function allowing mathematical analysis of half-emptying times and lag times. In patients with dyspepsia, gastric half emptying times of solids were significantly delayed as compared to the emptying of solids in the controls (203±41 vs 148±35 min;P<0.05). With cisapride, gastric emptying of solids was significantly accelerated (P<0.05) both in the patients (166±58 min) and in the controls (117±27 min). The gastric emptying of liquids did not differ in patients and controls, and cisapride had no effect on the emptying of liquids within the normal range. In the healthy controls, half emptying times both for liquids and solids were reproducible on the two different days (CVintra: 5.58% for liquis, 20.01% for solids). We conclude that as an entirely noninvasive and nonradioactive tool13C-labeled breath tests are well reproducible and allow assessment of the effect of cisapride on the characteristics of gastric emptying.