Innovative Diagnostic Modalities in Paediatric Urology
also for the initial investigation in girls, a classic VCUG is still the preferred method of choice for many investigators. On the other hand, the downside is a much higher dose of ionising radiation to the patient.
Although recent improvements such as the introduction of low-dose fluoroscopy techniques and pulse fluoroscopy with the addition of digital enhancing modalities, have dramatically decreased the radiation dose to the patient,3–5
primarily due to more reflux episodes being detected solely by sonocystography and that these reflux episodes are of a higher grade and, consequently, may be clinically more relevant than the predominantely low-grade reflux found only on VCUG. Finally, the high negative predictive value of sonocystography may have practical consequences as it demonstrates that sonocystography may be suitable for screening purposes.12
a VCUG still exposes the patient to almost 100
times the radiation of an RNC. A particular concern is the quite high gonadal radiation dose, particularly with multiple fluoroscopic monitoring studies.6
Gonadal shielding in males and careful imaging coning help to decrease the patient’s radiation exposure. Moreover, with the use of a low-dose fluoroscopic system in conjunction with a computer-based video frame grabber, the ovarian radiation dose may become similar to that of RNC.3
A VCUG performed with an optimised
pulsed fluoroscope can achieve ‘as low as reasonably achievable’ (ALARA) levels and of course maintain diagnostic image quality. In such a setting, radiation dosage can be reduced to 10% that of continuous fluoroscopy, resulting in dosages about 10 times that of RNC. Therefore, pulsed fluoroscopy is currently the recommended standard.7,8
On the other hand, a direct RNC allows continuous monitoring for VUR throughout the whole examination time without introducing any additional radiation. Therefore, some authors consider RNC to be more sensitive in the diagnosis of VUR,9
although precise grading is
impossible. However, this probably makes it an ideal methodology for conservative follow-up after any antireflux intervention.
The sensitivity of RNC for detecting reflux is equal to or even greater than that of VCUG; however, the spatial resolution and anatomic detail seen on an RNC are ultimately inferior to those seen on a VCUG.10
The main advantage of RNC over fluoroscopic VCUG is definitively decreased radiation exposure for the patient. The average effective radiation dose of a VCUG using low-dose fluoroscopy is around 3mrem compared with 0.5mrem for an RNC. Of course, the average effective dose of the VCUG is variable and depends on the patient size, operator and machinery.8
Conclusion and Future Modalities We must demand an accurate, safe, radiation-free and non-invasive method for reflux examination as the ideal method for reflux screening. Additionally, since all of these studies can be quite stressful for children and their families, a specially designed and equipped environment is obligatory for the comfort of all involved. Preparation and education of the families helps to reduce discomfort. If needed, sedation with the use of midazolam can be beneficial without any negative influence on the outcome of the examination.13
Contrast-enhanced ultrasound allows an accurate and safe diagnosis and, in contrast to VCUG and RNC, is radiation-free, but unfortunately it is still an invasive procedure with the insertion of a catheter. A future prospective procedure might be an exogenous bubble generated to fulfil one of the most important criteria in reflux diagnosis: being non-invasive. Efforts are already under way to achieve this goal. Until then, nuclear medicine studies and contrast studies will remain essential for the evaluation of VUR.
An absolutely ideal modality in the diagnosis of VUR would be a certain marker in serum or urine that could identify children with VUR. Basic research is ongoing to investigate different markers that have been found to be elevated in children with VUR.14
Measured levels of microproteinuria, urine retinol-binding protein, urinary prostaglandine
E2, urinary β2-microglobulin, urinary interleukin levels and serum endothelium leukocyte adhesion molecules have been shown to be elevated in patients with VUR compared with controls. So far, none of these methods can identify which kidney is affected by reflux, nor can they assess the grade, but they offer the potential advantage of rapid screening for VUR.
Sonocystography is a very sensitive tool in the detection of a possible VUR, especially since the introduction of various ultrasound echo-enhancing agents.11
First attempts with this technology were
made in 1976. The capability of echo-enhanced reflux sonography extends further in that the method may enable the complete elimination of any radiation exposure. This may justify the longer examination time compared with VCUG. Using an X-ray contrast agent (a certain concentration at a given time is necessary to be able to see the contrast), even a single microbubble can be visualised using the ultrasound method. Together with the duration of the ultrasound examination, this may be responsible for the detection of some low-grade refluxes that might be missed using VCUG and RNC. Moreover, this method allows for cyclic fillings without any additional radiation. On the other hand, similar to RNC, the lack of diagnostic visualisation of anatomical details, in particular the urethra, represents a disadvantage of the ultrasound methodology. Additionally, interobserver variability might be quite high and a specially trained examiner is obligatory. In summary, from the available literature on this issue, the comparative aggregated data between sonocystography and VCUG indicate that reflux exclusion and diagnosis between the two methods are highly concordant, that the discordant findings are
EUROPEAN UROLOGICAL REVIEW
Another marker, β-hexosaminidase, has been shown to be higher in patients with VUR and renal scarring.15
Tamm-Horsefall protein (THP)
is another high-molecular-weight glycoprotein that is exclusively present in the kidney and not secreted elsewhere. In children with intrarenal reflux is it also detectable in blood vessels and lymph nodes. It is believed to accumulate from the leakage of adjacent ruptured tubules.16
Interestingly, in a study on children with
A great deal of research must be undertaken to minimise or hopefully relieve the burden of one of the widest used imaging modalities in paediatric urology. n
surgically corrected VUR but no improvement in renal function post-operatively, THP levels remained elevated before and after surgery.17
Christian Radmayr is a Professor of Urology and Head of the Paediatric Urology Unit at Innsbruck University Hospital. He has been a member of the European Society for Paediatric Urology (ESPU) Educational Committee, the Joint Committee on Paediatric Urology (JCPU) and the ESPU/European Association of Urology (EAU) guidelines committee.
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