To compare radiological findings with the histological diagnosis of Hirschsprung disease (HD) to establish the usefulness of contrast enema as an initial screening and diagnostic tool. To correlate accuracy of radiological diagnosis at Grey’s Hospital with international standards.
Systematic searches were conducted through the Picture Archiving and Communication System and the National Health Laboratory Service records for patients aged 0–12 years, with clinically suspected HD, for whom both contrast enemas and rectal biopsies were performed between 01 January 2011 and 31 August 2015 in a tertiary-level hospital. A total of 54 such patients were identified. Diagnostic accuracy levels were calculated by comparing radiological results with histology results, which is the gold standard.
Diagnostic accuracy of contrast enema was 78%, sensitivity was 94.4% and the negative predictive value was 95.7%. Specificity (68.8%) and positive predictive values (63%) were considerably lower. A lower false-negative rate of 5.6% was obtained at Grey’s Hospital as compared with the international reports of up to 30%.
Contrast enema remains useful as an initial screening and diagnostic test for HD. Results of this South African tertiary referral hospital were consistent with the best international results for sensitivity of the contrast enema (approximately 80% – 88% in excluding the disease).
Hirschsprung disease (HD), also known as colonic aganglionosis, is a rare cause of constipation. It is defined as a functional obstruction of bowel caused by the lack of distal enteric ganglion cells with a reported incidence of 1:5000–7200 in newborns.
A retrospective audit was undertaken of all contrast enemas and rectal biopsies performed on patients aged 0–12 years between 01 January 2011 and 31 August 2015 inclusive. Only children investigated with both contrast enema and full-thickness rectal biopsy for the clinical suspicion of HD were included in the study.
A systematic search was conducted through the Picture Archiving and Communication System (PACS) for patients aged 0–12 years who had been referred for contrast enemas between 01 January 2011 and 31 August 2015 inclusive. A total of 185 patients were identified. The request forms for these patients were reviewed to identify the patients who were specifically referred for the diagnosis or exclusion of HD (history of constipation or changed bowel habits). The total number of patients identified was 97. A concurrent search for rectal biopsy results was conducted through the National Health Laboratory Service (NHLS) website, and ultimately a total of 54 patients were identified who had undergone both contrast enema and biopsy. The remaining 43 patients were excluded from the study because they did not meet the selection criteria and were not investigated further for the purposes of our study.
Enemas were performed at our tertiary institution mostly by trainee radiologists and occasionally by specialist radiologists, while the images were predominantly examined by the performing trainee radiologist in conjunction with a specialist radiologist; on a few occasions, images were examined by a radiology registrar alone. Only water-soluble contrast enemas (WSCEs) are performed at Grey’s Hospital using gastrografin, omnipaque or ultravist as contrast agents. For the procedure, a Foley’s catheter is inserted into the lower rectum and the catheter bulb is not inflated. Contrast is passed as far as possible, in most cases until the terminal ileum is opacified. For our study, positive enema results were based mainly on the presence of a transition zone (TZ) or calibre change, reversed recto-sigmoid ratio (RRSR) and other ancillary findings such as delayed post-contrast evacuation of bowel, saw-tooth mucosal pattern or mucosal irregularity.
Full-thickness rectal biopsies were performed under general anaesthesia by a specialist paediatric surgeon at 15 mm above the dentate line, posteriorly, and sent for haematoxylin and eosin (H&E) staining and, occasionally, for calretinin staining. (Suction biopsy equipment was not available during the study period but has since been acquired.) Specimens were examined by a specialist histopathologist, who looked for the presence or absence of ganglion cells in Meissner’s submucosal plexus and Auerbach’s intermyenteric plexus, at times with the additional finding of neuronal hyperplasia.
Related symptoms such as constipation, abdominal distension, vomiting and delayed passage of meconium (where present) were recorded for each patient to ascertain any statistical significance.
A data sheet was used to collect the relevant data. The study was approved by the Biomedical Research Ethics Committee (BE475/15), the Provincial Department of Health and the management of Grey’s Hospital.
This is a blind, retrospective, descriptive study, focusing on the analysis of radiological and histopathological records. Patients’ identities are protected and no consent was necessary.
Data were collected and entered into a computerised database program (Microsoft Excel). A codebook which included variable names, descriptions and formats was developed. Sensitivity and specificity rates for contrast enemas within 95% CIs (confidence intervals) were calculated with the method of Wilson. The single inconclusive enema result was excluded from this calculation. Risk factors associated with a positive histology result were identified using Fisher’s exact test. Factors associated with a significant
Of the 54 patients included in the study, 28 had positive contrast enemas, 25 had negative enemas and 1 had an inconclusive enema result (
Screening test evaluation: Single table analysis.
Contrast enema result | Histology result | ||
---|---|---|---|
Positive | Negative | Total | |
Positive | 17 | 10 | 27 |
Negative | 1 | 22 | 23 |
Diagnostic evaluation of the contrast enema compared to rectal biopsy as the gold standard.
Parameter | Estimated % | 95% confidence interval |
---|---|---|
Sensitivity | 94.4 | 74.2–99.0 |
Specificity | 68.8 | 51.4–82.1 |
Positive predictive value | 63.0 | 44.2–78.5 |
Negative predictive value | 95.7 | 79.0–99.2 |
Diagnostic accuracy | 78.0 | 64.8–87.3 |
In terms of risk factors for the disease, with adjustments for age and sex, children who were less than 1 month had a greater chance of testing positive on histology for the disease than children over 1 month of age (
Risk factors for the disease adjusted for age and sex.
Risk factor | Odds ratio | 95% confidence interval | |
---|---|---|---|
Age < 1 month | 6.9 | 0.07 | 0.9–54.5 |
Male sex | 9.3 | 0.05 | 1.1–82.7 |
Transition zone | 4.5 | 0.07 | 09–22.3 |
Reversed recto-sigmoid ratio | 3.4 | 0.2 | 0.6–18.4 |
, all values as calculated by chi-square and Fisher’s exact tests.
, The transition zone and reversed recto-sigmoid ratio were the only radiological features that were statistically significant after adjusting for age and sex. None of the symptoms were statistically significant when adjusted for age and sex. Although vomiting was significantly associated with the disease [OR: 3.7; 95% CI 1.1 – 12.9;
Results of the Grey’s Hospital were comparable with the best international results for sensitivity of the contrast enema (approximately 80% – 88%) for excluding HD.
The high negative predictive value (NPV) of 95.7% was consistent with those reported in literature and suggests that very few positive cases are missed, which supports the usefulness of the contrast enema.
A study by O’Donovan et al. assessed the validity of using low osmolality WSCE instead of barium enemas in neonates and infants for the investigation of HD.
Lateral (a) and frontal (b) views demonstrating long segment Hirschsprung disease involving the rectum and distal sigmoid colon, with a transition zone (white arrows) seen in the sigmoid colon.
Lateral (a), oblique (b) and frontal (c) views demonstrating a zone of transition in the region of the recto-sigmoid junction (white arrows) in a patient with Hirschsprung disease. A reversed recto-sigmoid ratio is also seen.
Lateral (a) and frontal (b) views in a patient with Hirschsprung disease. The lateral view demonstrates a reversed recto-sigmoid ratio.
In this study, we did not assess for any correlation between the TZs at contrast enema and at surgery.
The most common presenting symptoms for HD are delayed passage of meconium (60% – 90%), abdominal distension (63% – 91%) and bilious vomiting (19% – 37%).
Diamond et al. reported that on a univariate analysis, age below 30 days, female sex, absence of a TZ and presence of another finding were all statistically, at the 0.05 level, associated with an increased risk of an FP contrast enema result. The presence of bilious emesis or the passage of meconium beyond the first day of life was associated with a decreased risk of an FP result.
Our study showed that females are more than three times as likely to be FP as compared to males; 30% of males are FP versus 60% of females (OR 3.4, 95% CI 0.5–25,
According to our study, age above 30 days is an indication of an FP enema result, which contradicts the finding of the report by Diamond et al. There was only one reported case of delayed passage of meconium in our study, so no comparison could be made concerning this feature.
Factors associated with a TP result in our study include age less than 30 days, male sex and children presenting with vomiting (
Risk factors associated with true-positives.
Risk factor | Odds ratio | 95% confidence interval | |
---|---|---|---|
Age < 1 month | 7.2 | 0.1 | 0.7–69.4 |
Male sex | 3.4 | 0.3 | 0.5–25.3 |
Transition zone | 1.3 | 0.9 | 0.3–6.6 |
Reversed Recto-Sigmoid ratio | 0.3 | 0.4 | 0.03–2.9 |
Other | 1.2 | 0.9 | 0.2–6.2 |
Unrelated | n/a | 0.9 | n/a |
Vomiting | 2.3 | 0.4 | 0.5–12.0 |
Constipation | 1.3 | 0.9 | 0.3–5.9 |
Abdominal distention | 1.0 | 0.9 | 0.2–4.7 |
Delayed passage of Meconium | n/a | 0.9 | n/a |
Dysmorphic features | n/a | 0.5 | n/a |
, all values as calculated by Fisher’s exact test.
Other, delayed post-contrast evaluation of bowel, serrated outline if lower mucosal wall, saw-tooth mucosal pattern, mucosal irregularity, corrugated convoluted rectum and sigmoid; Unrelated, features not related to Hirschsprung disease; n/a, not applicable (cannot be calculated due to 0 false-positive).
Note: None of the values are statistically significant, but the high OR associated with patients aged less than one month (neonates), male patients and with vomiting suggest a strong association with true positive finding.
Lastly, a note about ARM. This is a non-invasive diagnostic test, easy to perform in children older than 1 year and has often been suggested as an ideal screening tool.
The study is limited to a certain age group. The correct histopathological diagnosis is dependent on the technique of rectal biopsy. Radiological interpretation is dependent on the degree of experience of the interpreting radiologist, as well as the study technique and quality of images, which are in turn influenced by the degree of experience of the performing radiologists who in certain instances were junior trainees. Patient factors such as lack of co-operation as can be seen with younger patients may also influence the quality of the study or images. The sample size is reduced.
The contrast enema remains useful as a screening test for HD. Results of this South African tertiary referral hospital were consistent with the best international results for sensitivity of the contrast enema (approximately 80% – 88% in excluding the disease). However, full-thickness rectal biopsy remains the gold standard for diagnosis of HD.
The authors would like to thank Catherine Connolly for her assistance with data analysis and Dr Matthew Goodier for his assistance with data analysis and suggested revisions for this article.
The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.
M.S.M. performed literature review, prepared research proposal protocol for ethics board approval, gathered data for analysis, and prepared the primary write-up of the research manuscript. H.M. was the co-investigator of the research project, assisted with data collection for analysis and helped with manuscript editing. V.d.P. supervised the research project and helped with the manuscript editing.