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| Discussion |
This study shows that the new, practical
Heliprobe 14C-UBT system is highly accurate for the
diagnosis of HP infection. Results obtained using the Heliprobe
method are comparable to those using standard method [6, 7,
8], and a strong correlation between the methods was found in
the present study.
Five patients with the standard method and six with the Heliprobe
method had positive results despite negative histology. Since
we validated our results against histology, these results were
classified as false positive. But owing to the patchy distribution
of HP in gastric mucosa, the biopsy-based tests may suffer from
sampling over [10, 11]. Furthermore, histological examination
is highly dependent on the experience of the pathologist, and
high inter-observer variation has been reported [11, 12]. Thus
it is likely that these patients were HP positive despite a
negative histology. Sources of urease other than HP, such as
bacterial overgrowth in the oropharynx, stomach or upper intestine,
may rarely cause false-positive test results [6]. However, the
reason for differences between the methods is not clear. Capsule
dissolution may be slower in some patients, causing relatively
lower radioactivity in early breath samples. If this is the
case, Heliprobe breath samples may contain lower activity than
standard samples, giving rise to a Heliprobe-negative, standard
method-positive result.
The CLO test had low sensitivity and specificity in this study.
Besides suffering from biopsy sampling error, the CLO test depends
greatly on the pH of the media and the amount of the urea in
the medium. These factors may vary in different products and
thereby influence the results obtained with other tests [5,
10].
Various factors affect the results of the UBT. Several different
methodological approaches have been suggested in order to simplify
and increase the accuracy of the UBT. The differences concern
doses and forms of 14C-urea, patient preparation
before the test, the time and number of breath samples, and
modes of quantification. Our results showed that most of these
steps can be omitted without prejudicing accuracy.
The original 14C-UBT system used relatively high
activities (200-400 kBq) and multiple breath sampling. Later
studies showed that the diagnostic accuracy of 14C-UBT
is maintained even with low doses and single breath samples
[6, 7].
The UBT indirectly detects gastric HP be measuring urease activity.
However, urease-producing bacteria are also present in the oropharynx
and may cause false-positive results, especially in early breath
samples. Late breath sampling may result in false-negative results
because of emptying of urea from the stomach. Several procedures
to avoid contamination of breath by the oropharyngeal flora
have been suggested, including mouth washing, simultaneous meal
to delay gastric emptying, and performance of multiple breath
sampling. Another more simple and effective method is use of
14C-urea in a gelatin capsule, thus bypassing the
oropharynx. Hamlet et al reported that when the 14C-urea
is supplied in a capsule, a single 10-min breath sample is highly
accurate (100% sensitivity and specificity) for the diagnosis
of HP infection. They compared the capsule method with the urea
drink method and found the former to be more reliable because
no overlapping in activity occurred between HP-positive and
–negative patients; by contrast, conventional breath testing
showed overlapping during the whole 30-min test period. Their
study also showed that a fatty test meal lowers the 14CO2
excretion during the first 20 min and may adversely affect the
accuracy of a rapid UBT [8]. Other advantages of the capsule
form include commercial availability, no risk of spills, shorter
test duration and a lower radiation dose.
The expression of results of UBT varies between investigators.
Henze et al. and Veldhuyzen van Zanten et al. have used CPM
[14, 15]. Because CPM is affected by chemical or colour quenching,
chemical changes of the cocktail and methods of sample preparation,
Pathak et al. strongly suggested the use of DPM counts [16].
For these reasons we preferred to use DPM counts in the standard
method.
Some authors have used formulas to correct for body weight or
body surface to account for differences in endogenous CO2
production, the results being expressed as recovery standard
units [(% of administered dose recovered/mmol CO2
trapped) x body weight (kg)] [1,7]. However, neither of these
factors has been proved to influence the results of the breath
test. Indeed, it has even been reported that uncorrected counts
result in better distinction between HP-positive and –negative
patients [8, 15, 16]. For this reason and to simplify the test,
we omitted all such calculations. Both tests gave excellent
results and a high correlation was found between DPM values
of the standard method and CPM values of the Heliprobe method.
Adequate patient preparation is important if accurate results
are to be obtained with 14C-UBT. A large number of
investigators have reported that the UBT becomes false negative
during therapy with proton pump inhibitors. Iansoprazole, bismuth
compounds, antibiotics and ranitidine [17, 18, 19]. Preliminary
reports indicated that addition of citric acid to the urea solution/capsule
may diminish the negative effect of acid-inhibitory drugs on
the accuracy of UBT [20]. Although we used an acidified 14C-urea
capsule, we preferred to discontinue medications before the
test for a certain period of time. The exact value of acidified
urea needs further verification.
The dry, practical and ready-to-use breath cartridge is an important
advantage of this new system. Besides the simple and easy collection
of breath, this system prevents accidental ingestion of hazardous
organic CO2 absorber solutions during breath sampling.
Carbon-13 is a no-radioactive isotope, but 13C-UBT
is more expensive because it requires mass spectrometry. 14C
has a physical half-life of about 5,000 years, raising the question
of the risks of radiation exposure. Because nearly the entire
ingested isotope is rapidly excreted in urine or breath over
the following 72 h and only a small amount of isotope is used,
the test actually entails low radiation exposure (3 µSv)
[21, 22]. In fact, the dose is less than the natural background
radiation in one day. As mentioned by Boivin et al., the debate
on safety has revolved only around the radiation does received
from 14C-UBT, and it has been generally accepted
that there is no or a lower risk with the 13C alternative.
On the other hand, 13C-UBT contains more than 30,000
times as much urea as 14C-UBT, and the safety of
this amount of urea is also questionable [23]. For this reason,
in 1997 the Nuclear Regulatory Commission permitted in vivo
diagnostic use of capsules containing 1µCi of 14C-urea
without a license [24].
Additional advantages of the Heliprobe system are the shorter
test time and the low cost. Breath samples are analysed with
a ß-scintillation counter in 14C-UBT and with
a mass spectrometer in 13C-UBT. Because both items
of equipment are expensive, analysis can be done in an external
laboratory by mail order and results are usually obtained a
few days later. In contrast, with the Heliprobe system the results
are obtained in half an hour on-site and the analyzer is much
cheaper than either a ß-scintillation counter or a mass
spectrometer.
In conclusion, the new Heliprobe 14C-UBT is a simple,
rapid, practical, safe, cheap and highly accurate system for
the diagnosis of HP infection. The main advantages of the system
are commercial availability, no risk of spills, reduced interference
by oropharyngeal flora, shorter test duration, low radiation
dose, simple and safe breath collection, and a practical and
cheap counting system.
Acknowledgements. The authors are grateful to Assoc. Prof. Muhittin
Scrdar for help with statistical analysis of the data. |
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Hamlet AK, Erlandsson KI.
Olbe L, Svennerholm AM, Backman VE, Pettersson AB. A simple,
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Henze E, Malfertheiner
P. Clausen M, Burkhardt H, Adam WE. Validation of a simplified
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JM, Nostrant TT. DelValle J. Lansoprazole and ranitidine
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Stubbs JB, Marshall B.
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K, Olofsson M. Mattsson S. Nilsson LE. Nosslin B, Pau
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| 23. |
Boivin C. 13C-urea versus
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|
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Vienna Academy of Postgraduate
Medical Education and Research
Conference and Association Management |
| |
| EHSG 2003- European Helicobacter
Study Group – XVIth International Workshop, September
3 – 6, 2003, Stockholm, Sweden |
Validation of a new portable near patient
urea breath test; Heliprobe system W. A. de Boer1,
C. van Alfen1, J. Ryden2;
1Ziekenhuis
Bernhoven, dept of Internal Medicine, Oss, Netherlands, 2Noster
System AB, Stockholm, Sweden. |
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| Background: |
| Test & Treat is the evidence-based
optimal strategy for the dyspepsia in primary care. According
to the Maastricht guidelines urea breath tests (UBT) are the
preferred non-invasive initial Helicobacter test. Usually breath
samples need to be mailed to a central facility. We tested a
new portable “near patient” 14C-UBT designed
for primary care, thus obviating the need to refer the patient. |
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| Methods: |
| Between April 2000 – January
2002 endoscoped patients in whom biopsies were taken for Helicobacter
were asked to return for UBT. They received 1µCi (37kBq)
of 14C-urea (Helicap capsule) with citric acid. After
10 minutes the patients exhaled into a breathcard. After saturation
it was inserted into the Heliprobe machine. Results take 5 minutes.
Infection status was based on number of detected 14C
counts per measurement (d): infected if d=50, not-infected if
d=25, and indeterminate for d-values in-between. |
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| Results: |
| 107 pts participated, 1 was excluded
due to indeterminate result. In all pts 7 biopsies were taken
(antrum: 2 histology, 1 culture, 1 CLO. Corpus: 2 histology,
1 CLO). Combined biopsy results served as gold standard. Prevalence
was 39%. The Heliprobe System was easy to use and results were
obtained within 20 minutes. Results: Sensitivity 95% (40/42)
(95%CI 84-99), and specificity 100%(64/64) (95%CI 94-100). There
were no adverse events. |
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| Conclusion: |
| The Heliprobe 14C-UBT system
is a very reliable, easy to use, near patient Helicobacter test
which can be used for test & treat in primary health care.
It is extremely reliable in patients not taking acid suppressants. |
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