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Cyclic Cystography: Diagnostic Yield in Selected Pediatric Populations¹

¹ From the Department of Radiology, Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039 (M.J.G., B.L.K., A.H.E., V.M.G.M., C.L.T.), and the Division of Biostatistics, University of Cincinnati Medical Center (P.S.G.). Received October 5, 1998; revision requested November 11; revision received January 6, 1999; accepted March 2. Address reprint requests to M.J.G. (e-mail: gelfand.mj@chmcc.org).

	Abstract

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PURPOSE: To test the hypothesis that the diagnostic yield of cyclic cystography is related to the prevalence of vesicoureteral reflux (VUR) in the population being evaluated.

MATERIALS AND METHODS: Two groups of children were examined prospectively: 124 with severe urinary tract infection, defined as patient hospitalization or a maximum temperature greater than 39.5°C, and 135 with previously diagnosed VUR. Nuclear cystography was performed in 249 patients, and fluoroscopic cystography was performed in 10. If VUR was not seen during the first cycle of bladder filling and voiding, a second cycle was performed.

RESULTS: VUR was present during cycle 1 in 40 (32%) of 124 patients with severe urinary tract infection and 90 (67%) of 135 children in the VUR follow-up group (P < .001). VUR was demonstrated during cycle 2 in seven (9%) of 76 of the severe urinary tract infection group and eight (24%) of 34 of the VUR follow-up group (P = .045). Of 15 patients with VUR during cycle 2, two had grade III VUR and 13 had grade I or II VUR.

CONCLUSION: The second cycle of cyclic cystography has a higher diagnostic yield in patients undergoing VUR follow-up than in patients with severe urinary tract infection. The decision to perform a second cycle of bladder filling and voiding should take into account the pretest probability of VUR in the child being examined.

Index terms: Bladder, radiography, 83.12177, 83.123 • Children, genitourinary system, 80.21 • Genitourinary system, infection, 80.21 • Ureter, reflux, 82.85

	Introduction

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For several years, it has been recognized that some children with vesicoureteral reflux (VUR) have intermittent reflux. When the initial cycle of bladder filling and voiding fails to demonstrate VUR, a second or third cycle of bladder filling and voiding may demonstrate reflux (1–4). However, multiple cycles of bladder filling and voiding are time-consuming and unpleasant to small children and their parents, and each cycle incrementally increases the absorbed radiation dose. Therefore, it is important to identify the groups of children who are most likely to benefit from cyclic cystography. In this study, we prospectively studied two groups of children, one that was likely to have a moderate prevalence of VUR and another likely to have a high prevalence of VUR. Children presenting for cystography with a recent, substantially febrile urinary tract infection were chosen as the group likely to have a moderate prevalence of VUR. Children who had previously documented VUR and who were undergoing follow-up cystography were chosen as the group likely to have a high prevalence of VUR. Findings in these groups were compared to determine if the diagnostic yield of cyclic cystography differed in these two groups.

	MATERIALS AND METHODS

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Two groups of children undergoing cystography were studied prospectively: 124 children (124 girls; age range, 3 weeks to 16 years) with severe urinary tract infection, defined as peak temperature greater than 39.5°C or a urinary tract infection that required hospitalization, and 135 children (127 girls, eight boys; age range, 4 months to 17 years) with VUR who were undergoing follow-up cystography 6–12 months after prior cystography had demonstrated VUR. Children were excluded from this study if they had known anatomic abnormalities at physical examination or renal ultrasonography, or if substantial voiding dysfunction was present. If VUR was not seen during the first cycle of bladder filling and voiding, a second cycle of bladder filling and voiding was performed. The second cycle was omitted if the catheter was expelled during voiding or if the child was difficult to control physically during the first cycle of bladder filling and voiding; this occurred in 19 children. At our institution (Children's Hospital Medical Center, Cincinnati, Ohio), the above protocol of cyclic filling of the bladder was already established as standard clinical practice in both groups at the time that the study was initiated. At the time that this study was performed, nuclear cystography was the recommended first examination for VUR in girls without known anatomic abnormality or substantial voiding dysfunction and the recommended follow-up examination for VUR in both boys and girls.

The 259 children entered in this study were examined by means of nuclear or fluoroscopic cystography; 249 underwent nuclear cystography (Orbiter 7500; Siemens Gammasonics, Des Plaines, Ill) and 10 underwent fluoroscopic cystography (Advantx; GE Medical Systems, Milwaukee, Wis), with four in the severe urinary tract infection group and six in the follow-up VUR group. Nuclear cystography was performed with technetium 99m sulfur colloid prepared with use of AN sulfur colloid (0.300–0.600 mCi [11.1–22.2 MBq]; Syncor International, Chatsworth, Calif) directly instilled into the urinary bladder via a catheter. Fluoroscopic cystography was performed with diatrizoate meglumine (Cystografin 18%; Squibb Diagnostics, Princeton, NJ) directly instilled into the urinary bladder via a catheter with the dose varying according to bladder capacity.

To control selection bias and prevent the participating physicians from enrolling only "interesting" patients in the study, the following rule was used: If any eligible cystogram was omitted from the study, all cystograms obtained on that day by using that modality (nuclear or fluoroscopic) were excluded from the study. This rule limited the number of fluoroscopic cystograms entered into the study. The patients in the two groups were not matched by age or sex.

Nuclear and fluoroscopic cystograms were obtained and graded according to previously described methods (5–7). Maximum bladder volume was recorded routinely for each cycle. Maximum bladder volumes for the first and second cycles were compared when VUR was present during the second cycle.

Data were analyzed by using the ² test, the Wilcoxon signed rank test, and the Kaplan-Meier method. Using the data from the severe urinary tract infection and VUR follow-up groups, we fit a quadratic function (y = b₀ + b₁x + b₂x²) to the data for x equal to 0, 1, and 2, where x was the number of filling cycles and y was the frequency of VUR, which was used to estimate the maximum value of y, or estimated maximal frequency of VUR, for values of x greater than 2. A P value less than .05 was considered to indicate a statistically significant difference.

	RESULTS

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The results are summarized in the Table. In the severe urinary tract infection group, the first cycle of bladder filling and voiding demonstrated VUR in 40 (32%) of 124 children. Of the remaining 84 patients without VUR during the first cycle, 76 underwent a second cycle, with the second cycle omitted in four because of technical problems (eg, expulsion of the catheter during the first void) and in four others because the child was difficult to control physically during the first cycle. Of these 76 children, seven (9%) had VUR during the second cycle, yielding a frequency of VUR of 38% after two cycles.

In the VUR follow-up group, the first cycle demonstrated VUR in 90 (67%) of 135 patients. Of the remaining 45 patients without VUR during the first cycle, 34 underwent a second cycle, with the second cycle omitted in three because of technical problems and in eight because the child was difficult to control physically during the first cycle. Of these 34 children, eight (24%) had VUR, which yielded a frequency of VUR of 73% after two cycles. When the severe urinary tract infection and VUR follow-up groups are combined, 15 (14%) of 110 children had VUR during the second cycle.

The frequency of VUR in the VUR follow-up group was significantly higher than the frequency of VUR in the severe urinary tract infection group during the first (P < .001) and second (P = .045) cycles.

The estimated maximal frequency of VUR was 39% in the severe urinary tract infection group and 80% in the VUR follow-up group. Therefore, on the basis of these estimated frequencies, approximately 82% (32% ÷ 39%) of all children with VUR in the severe urinary tract infection group were identified after one cycle. Similarly, 84% (67% ÷ 80%) of all children with VUR in the VUR follow-up group were identified during the first cycle.

The highest grade of VUR during the second cycle was grade I in one patient, grade II in 12, and grade III in two.

In the group of 15 children who had VUR during only the second cycle, the mean maximal bladder volume during the first cycle was 276 mL, and it was 281 mL during the second cycle. The maximal bladder volume achieved during the second cycle was slightly larger than that during the first cycle (P = .063), but the median increase in bladder volume between the first and second cycles was only 10 mL.

	DISCUSSION

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In the initial studies (8–13) in which nuclear cystography was compared with fluoroscopic cystography, VUR was not detected consistently when the two types of cystography were performed within a few weeks of each other. The sensitivities of nuclear and fluoroscopic cystography were equal in 453 patients in these studies, but in only 65% of paired studies was VUR present with both imaging methods. The intermittency of VUR in some patients also is supported by the observation that grade I (ureteral reflux only) VUR is an intermittent finding that is not reproducible on sequential cystograms and usually appears as grade II (VUR to the renal pelvis without dilatation) or grade 0 (absence of VUR) on the follow-up study (14,15).

Jequier and Jequier (1) and other investigators (2–4) demonstrated that a second cycle of bladder filling and voiding demonstrated VUR in a number of patients in whom the first cycle was normal. In the combined studies of Jequier and Jequier (1), Pozderac et al (2), Fettich and Kenda (3), and Paltiel et al (4), 14% of patients had VUR during the second cycle.

In this study, a group of patients with a 32% frequency of VUR during the first cycle (severe urinary tract infection group) had only a 9% yield of VUR during the second cycle. In contrast, a second group with a 67% frequency of VUR during the first cycle (VUR follow-up group) had a significantly greater yield of 24% during the second study (P = .045 for the second cycle).

The severe urinary tract infection group most likely is composed of three subgroups: children who have VUR with every void, children who have VUR intermittently, and children in whom VUR will never be demonstrated, even if the bladder is filled repeatedly. In the VUR follow-up group, every child had detectable VUR in the past, and the number in whom VUR is always or intermittently present can be expected to be larger than in the severe urinary tract infection group. Studies (16–20) have demonstrated that slightly less than half of children with acute pyelonephritis detected at cortical scintigraphy have VUR. This may be compared with an unselected population undergoing cystography in which about 33% of the children will have VUR (5,7).

With this protocol, those who demonstrated VUR during the first cycle underwent no further examination. In the severe urinary tract infection group, however, after the first cycle there remained a relatively large number of children for whom a second cycle was necessary to look for VUR but only a small number of children who actually had intermittent VUR. This pattern was reversed in the VUR follow-up group, which had approximately the same number of children with intermittent VUR but a much smaller number of children without reflux during the first cycle.

In previous studies (1–4) of cyclic cystography, no attempt was made to subdivide children undergoing cystography into subpopulations with differing pretest probabilities of VUR. When this is done, the yield of VUR from a second cycle of bladder filling and voiding is significantly higher in a population with a high prevalence of VUR than in a population with a moderate prevalence of VUR. These data suggest that cyclic cystography should not be performed in all children who may have VUR but rather in subpopulations in which the diagnostic yield is high enough to justify the additional time, discomfort, fright, and radiation exposure associated with the additional cycle of bladder filling and voiding.

Groups of children with VUR differ in the frequency with which VUR is found during a single cycle of bladder filling and voiding. When cyclic cystography was performed in a population of children with a high frequency of VUR, the frequency with which VUR was detected during the second cycle was relatively high. However, the yield of VUR during the second cycle was significantly lower in a group of patients who had only a moderate frequency of VUR during the first cycle. Cyclic cystography is indicated in children who are undergoing follow-up cystography for previously documented VUR. Cyclic cystography also should be considered in other groups of children who have moderate to high pretest probabilities of VUR during the first cycle of bladder filling and voiding.

	Acknowledgments

 
The authors thank Pamela R. Masters, CNMT, and Laura Gehling, CNMT, for their technical efforts in performing the cystographic studies and Kathleen B. Umberg for aid in manuscript preparation.

	Footnotes

 
² Current address: Department of Nuclear Medicine, Kuwait University, Safat, Kuwait.

³ Current address: Department of Environmental Health, University of Cincinnati.

⁴ Current address: Department of Radiology, Children's Hospital, Birmingham, Ala.

Abbreviation: VUR = vesicoureteral reflux

Author contributions: Guarantor of integrity of entire study, M.J.G.; study concepts and design, M.J.G.; definition of intellectual content, M.J.G.; literature research, M.J.G.; clinical studies, M.J.G., A.H.E., V.M.G.M., B.L.K.; data acquisition, M.J.G., A.H.E., V.M.G.M., C.L.T., B.L.K.; data analysis, M.J.G., P.S.G.; statistical analysis, M.J.G., P.S.G.; manuscript preparation, M.J.G.; manuscript editing and review, M.J.G., V.M.G.M., A.H.E., B.L.K.

	References

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1. Jequier S, Jequier JC. Reliability of voiding cystography to detect vesicoureteral reflux. AJR 1989; 153:807-810.[Abstract/Free Full Text]
2. Pozderac RV, Becker CJ, Reitelman C, Kuhns LR. Comparison of single and two-stage radionuclide cystography (RNC) for the evaluation of reflux (abstr). J Nucl Med 1990; 31:893.
3. Fettich JJ, Kenda RB. Cyclic direct radionuclide voiding cystography: increasing reliability in detecting vesicoureteral reflux in children. Pediatr Radiol 1992; 22:337-338.[Medline]
4. Paltiel HJ, Rupich RC, Kiruluta HG. Enhanced detection of vesicoureteral reflux in infants and children with use of cyclic voiding cystourethrography. Radiology 1992; 184:753-755.[Abstract/Free Full Text]
5. Strife JL, Bisset GS, III, Kirks , et al. Nuclear cystography and renal sonography: findings in girls with urinary tract infection. AJR 1989; 153:115-119.[Abstract/Free Full Text]
6. Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Mobius TE, for the International Reflux Study in Children. International system of radiographic grading of vesicoureteric reflux. Pediatr Radiol 1985; 15:105-109.[Medline]
7. Bisset GS, III, Strife JL, Dunbar JS. Urography and voiding cystourethrography: findings in children with urinary tract infection. AJR 1987; 148:479-482.[Abstract/Free Full Text]
8. Conway JJ, King LR, Belman AB, Thorson T, Jr. Detection of vesicoureteral reflux with radionuclide cystography: comparison with roentgenographic cystography. AJR 1972; 115:720-727.[Abstract]
9. Servadio C, Nissenkorn I, Baron J. Radioisotope cystography using ^99mTc-sulfur colloid for the detection and study of vesicoureteral reflux. J Urol 1974; 113:750-754.
10. Bailey RR, Stapleton P, Turner JG, Brownlie BEW. Detection of vesicoureteric reflux using radionuclide micturating cystography. Aust N Z J Med 1976; 6:542-546.[Medline]
11. Rothwell DL, Constable HR, Albrecht M. Radionuclide cystography in the investigation of vesicoureteric reflux in children. Lancet 1977; 8021:1072-1075.
12. Nasrallah PF, Nara S, Crawford J. Clinical applications of nuclear cystography. J Urol 1982; 128:550-553.[Medline]
13. Guillet J, Basses-Cathalinat B, Christophe E, et al. La cystographique isotopique rétrograde: son application dans le diagnostic des reflux vésico-uréteraux de l'enfant. Nouv Presse Med 1982; 11:3831-3834.[Medline]
14. Fretzayas A, Karpathios T, Dimitriou P, Nicolaidou P, Matsaniotis N. Grading of vesicoureteral reflux by radionuclide cystography. Pediatr Radiol 1984; 14:148-150.[Medline]
15. Gelfand MJ, Strife JL, Hertzberg VS. Low-grade vesicoureteral reflux: variability in grade on sequential radiographic and nuclear cystograms. Clin Nucl Med 1991; 16:243-246.[Medline]
16. Traisman ES, Conway JJ, Traisman HS, et al. The localization of urinary tract infection with ^99mTc glucoheptonate scintigraphy. Pediatr Radiol 1986; 16:403-406.[Medline]
17. Björgvinsson E, Majd M, Eggli KD. Diagnosis of acute pyelonephritis in children: comparison of sonography and ^99mTc DMSA scintigraphy. AJR 1991; 157:539-543.[Abstract/Free Full Text]
18. Ditchfield MR, DaCampo JF, Cook DJ, et al. Vesicoureteral reflux: an accurate predictor of acute pyelonephritis in childhood urinary tract infection. AJR 1994; 190:413-415.
19. Benador D, Benador N, Slosman DO, Nussle D, Mermillod B, Girardin E. Cortical scintigraphy in the evaluation of renal parenchymal changes in children with pyelonephritis. J Pediatr 1994; 124:17-20.[Medline]
20. Stokland E, Hellström M, Jacobsson B, Jodal U, Sixt R. Renal damage one year after first urinary tract infection: role of dimercaptosuccinic acid scintigraphy. J Pediatr 1996; 129:815-820.[Medline]

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