Tipnis, Neelesh A.; El-Chammas, Khalil I.; Rudolph, Colin D.; Werlin, Steven L.; Sood, Manu R.
Objectives: The aim of the study was to compare oro-anal transit time (OTT) measured by radio-opaque markers with colon motility (CM) findings in children with chronic constipation and to assess clinical outcomes in children with chronic constipation evaluated by OTT and CM studies.
Methods: Twenty-four children with chronic constipation (12 girls; median age 12 years [3–18 years]; median symptoms 87 months [6–186 months]) who underwent OTT and CM studies were reviewed. The OTT was determined using commercially available Sitzmarks. Patients were studied for a median of 23 months (4–60 months) and outcomes reviewed.
Results: All 5 children with normal OTT had normal CM; however, only 47% (9/19) of children with slow OTT had an abnormal CM. The abnormal CM findings were total colonic pseudo-obstruction in 3 and left colonic pseudo-obstruction in 6 children. Of the 9 children with abnormal CM, 5 were managed surgically, 1 with medicine escalation, and 3 were lost to follow-up; all 6 children with known follow-up have more bowel movements and less soiling. Of the 15 children with normal CM, 10 were managed with medication escalation, 3 with behavioral intervention, and 2 surgically. Of these 15 children, 8 improved, 1 did not change, 2 worsened, and 4 were lost to follow-up.
Conclusions: OTT studies may be helpful to predict which children should be referred for CM studies. Normal OTT studies may predict normal colon manometry; however, abnormal OTT studies may not predict abnormalities in colonic manometry in children with chronic constipation. Therefore, patients with slow transit marker studies should be assessed by colon manometry to evaluate colon neuromuscular integrity.
Chronic constipation occurs commonly in children and accounts for 25% of pediatric gastroenterology referrals (1). Evaluation of colonic motility is warranted when conservative therapy such as laxatives and/or behavioral modification fails to remedy the condition and other causes of constipation have been excluded (2). Slow oro-anal transit time (OTT) (also known as slow transit constipation) has been found in up to half of children with chronic constipation (3–5) and can be assessed easily using commercially available radio-opaque markers or scintigraphy studies (6–11). Abnormalities of motor function have been identified in children with slow transit constipation using colon manometry (CM) studies (12). The availability of CM studies is limited to pediatric referral centers. Additionally, performance of CM studies subjects patients to lengthy and somewhat uncomfortable diagnostic procedures, which may require the use of general anesthesia for passage of catheters. Identification of children who would likely benefit from CM would be helpful to reduce the need for unnecessary studies. The aim of the present study was to correlate OTT studies with colon motility studies in children with chronic constipation.
The present study was approved by the human research review board at Children's Hospital of Wisconsin. Records of children with chronic constipation who underwent OTT and colon motility studies between January 2002 and November 2005 were retrospectively reviewed. Chronic constipation was defined as the passage of <3 bowel movements per week without the use of laxative therapy, painful defecation, or passage of hard-consistency stools. In these patients, colonic outlet obstruction was excluded based on anorectal manometry before colon motility testing.
The OTT study was performed using a gelatin capsule containing 24 radio-opaque single-pattern markers (Sitzmarks, Konsyl Pharmaceuticals, Easton, MD). Stimulant laxatives were withheld for 72 hours before the OTT study. Fecal impactions, when present, were cleared with a normal saline, tap water, or sodium phosphate enema(s) before capsule ingestion. If needed, the capsule was opened and the markers were ingested by embedding in a piece of banana or sprinkled on applesauce. Abdominal radiographs were obtained 3 and 5 days postingestion of the capsule. The number of radio-opaque markers was then counted in each of 3 regions: left colon, right colon, and rectosigmoid colon. Slow OTT was defined as retention of >6 markers with a distribution to include regions of the colon proximal to the rectum on the day 5 abdominal radiograph. The distributions of markers were categorized as failing to progress beyond the right colon, left colon, or as diffuse.
The CM study was performed using a water-perfused system (Medical Measurement Systems, Enschede, The Netherlands) using a 3.9-mm 8-lumen catheter with side-hole openings spaced 10 cm apart for small children and 15-cm apart for older children. Patients were admitted 1 day before the testing procedure for colonic lavage with a polyethylene glycol bowel preparation solution. The following morning, while under general anesthesia, colonoscopy was performed to place a guidewire to the cecum. No muscle relaxants were permitted during anesthesia induction. The motility catheter was then threaded over the guidewire by a radiologist such that the tip of the motility catheter was resting beyond the hepatic flexure and the proximal site resting in the rectum. After a recovery period of 2 to 3 hours, the motility catheter was perfused with 0.45% saline at 0.15 mL/minute and colonic contractions were recorded continuously. After a 1-hour fasting baseline, patients were fed an age-appropriate mixed solid-liquid meal. Recordings were obtained for a 1-hour postprandial period. Following the postprandial period, bisacodyl enema solution (5 or 10 mg) was infused via catheter into the proximal colon and recordings continued for an additional hour to assess the effect of stimulant laxative. Results of CM were classified as normal CM by the presence of high-amplitude propagating contractions (HAPCs), in which colonic contraction amplitudes of at least 60 mmHg for 10 seconds propagated in an aboral pattern over at least 30 cm of bowel (13). CM testing was classified as colonic pseudo-obstruction (CPO) if the contractions were nonpropagative (neuropathic CPO) or absent/low amplitude (myopathic CPO) in a nondilated colon. To determine the presence of a gastrocolonic response, a 20% increase in the postprandial motility index compared baseline was considered adequate (14).
Clinical Characteristics and Outcomes
Clinical characteristics including sex, age at time of CM testing, duration of symptoms, and symptoms (soiling, abdominal pain, bloating, nausea, and vomiting) were recorded. Investigator notes were reviewed to assess clinical outcomes including post-therapy management (medication escalation, addition of behavioral modification, or referral for surgical management) and treatment response (improved/resolved or no change/worsened).
OTT results were categorized as slow or normal. CM studies were categorized as normal or abnormal based on HAPC response. Patients with abnormal CM studies were further categorized as having total colonic or segmental abnormalities. Gastrocolic response was categorized as normal or abnormal. Outcomes were categorized based on poststudy treatment selection (medication escalation, surgery) and by stooling response (improved, unchanged, worsened, or unknown). Where appropriate, χ2 analysis was performed using either Yates continuity correction or Fisher exact test.
The clinical characteristics of the children sorted by OTT results are listed in Table 1. There were no statistical differences in clinical characteristics between slow and normal children with OTT.
Findings of OTT Testing
Five children had normal OTT. Of the 19 children with slow OTT, 5 (26%) had markers that failed to progress beyond the right colon, 7 (37%) had markers that failed to pass beyond the left colon, and 7 (37%) had a diffuse distribution of markers. Of the 5 children with normal OTT, 4 had no visible markers on the abdominal radiograph 3 days postmarker ingestion and the other had 3 markers rectum. In this child, the day 5 abdominal radiograph had no markers. All of the children with slow OTT had an abnormal number and distribution of markers on both the day 3 and 5 post-capsule ingestion radiographs.
Findings of CM Testing
Fifteen (62%) children had normal CM studies and 9 (38%) had abnormal CM studies. The abnormal CM study findings were no HAPCs in response to bisacodyl (3), segmental arrest of the HAPCs at the right colon (4), and segmental arrest of HAPCs at the splenic flexure (2). The gastrocolonic response to the meal was normal in 8 (33%) and abnormal in 16 (67%) children with chronic constipation.
Correlation of OTT and CM Studies
Figure 1 illustrates the correlation of the results of OTT testing in a subject with slow OTT and with CM testing. Figure 2 illustrates the distribution of OTT and CM testing results. All 5 children with normal OTT had normal CM studies; however, the results of CM testing in the 19 children with slow OTT were equally divided between normal (10) and abnormal (9). The gastrocolonic response to the meal was absent in 2 of 5 (40%) children with normal OTT and absent in 14 of 19 (74%) children with slow OTT (P = 0.186).
Follow-up data were available in 17 children, whereas the remainders were lost to follow-up. Three children had normal OTT and 14 had slow OTT. Of the 14 children with slow OTT, CM testing was normal in 8 and abnormal in 6 children.
Figure 3 illustrates the distribution of clinical outcome in children with slow OTT and normal OTT constipation. Overall, those children managed with surgery (3 cecostomy, 4 subtotal colectomy) and behavioral modification (3) improved, whereas only 3 of 7 children managed with medication improved following OTT and CM testing.
In the present study, we correlate the OTT with colonic manometry testing in children with refractory constipation. The Sitzmarks study, as described here, is a simple office-based test that may help providers categorize patients into those with normal OTT or slow OTT. In this small retrospective study, the OTT results corresponded well with colon manometry results. We found that all of the children with normal OTT had normal colon manometry studies, whereas only children with slow OTT had an abnormal colon manometry study. Thus, although sensitive, the OTT study was not specific for predicting whether the whole colon or a segment of the colon was affected by either a neuropathic or myopathic disease process. Therefore, manometric testing remains an important step in the evaluation of children with slow OTT.
Several studies have evaluated OTT using solid marker studies using either a single bolus or serial marker ingestion strategies. No single strategy for the determination of OTT has emerged, and variation in normal values exists based on methodology and geographic regions (10). In these studies, the upper limit of normal transit ranged between 32 and 84 hours. We chose a single bolus marker ingestion strategy based on ease of administration and compliance with marker ingestion; however, this method may be challenging in very young children, children with dysphagia, and/or children with neurological impairment. The strategy of obtaining the abdominal radiograph at 72 hours postmarker ingestion and again at 120 hours, if needed, was chosen to ease compliance with the transit time protocol and limit radiation exposure. The timing of the radiographs was based on an aggregate of the published pediatric studies (3–5,7,9,10). The number of markers used for transit cutoff values was based on the number of markers in the commercially available capsule. In the present study, all of the children with slow colonic transit had an abnormal transit marker study at both 3 and 5 days postmarker ingestion, and children with normal transit constipation had a normal transit study at both 3 and 5 days. Therefore, our group has recently modified the transit marker study to obtain a single x-ray 3 to 5 days postmarker ingestion with an ideal interval of 5 days. Segmental colonic transit can be determined (Metcalf method) by ingesting a capsule of different marker types on 3 consecutive days, and an abdominal x-ray is obtained on day 4 and 7 postingestion. Based on the number and location of retained markers, segmental delays can be identified. Correlation of segmental colonic transit and colon manometry has not been evaluated in children. Recently, Southwell et al (15) reported normal values for scintigraphic evaluation of colon transit in adults and children and compared these results with the transit marker studies. The authors note good reliability of these techniques in adult patients; however, comparison of scintigraphy and transit marker studies for the evaluation of constipation in children has not been completed.
The manometric abnormalities found in the present study included segmental and total colonic aperistalsis. Colon manometry findings have been noted in children and have been useful in identifying the cause of refractory constipation. As part of a larger study, 62% of the children with chronic constipation refractory to medical management had abnormal colon motility: distal colonic low-amplitude simultaneous contractions in 45%, proximal colon motility abnormality in 1%, and pancolonic abnormality in 16% (16). Twenty-four -hour colon manometry studies may provide additional clues to the cause of slow transit constipation. Children with slow transit constipation were also found to have fewer numbers of antegrade propagating contractions compared with children with normal transit constipation and normal adults (12). In addition, high-amplitude propagating sequences (defined as propagating sequence with at least 1 wave contraction amplitude >116 mmHg) were absent in 22% of children with slow transit constipation but present in all of the children with normal transit constipation and adult controls in the present study.
The addition of colonic manometry to the evaluation of children with slow transit constipation is clinically beneficial. In the present study, CM testing identified a region of abnormal colonic contractions in 9 children. A surgical intervention was chosen in two-thirds of these individuals, all of whom improved. In a study of children receiving antegrade enemas via cecostomy tube, van den Berg et al (17) found that in children undergoing cecostomy tube placement, the presence of HAPCs was predictive of a successful outcome in between 88% of children compared with a successful outcome in only 56% of children in whom HAPCs were completely absent. Colon motility testing was also helpful in clinical decision making in children undergoing colonic diversion for intractable constipation. Villarreal et al (18) identified 12 children undergoing colonic diversion for intractable constipation. Seven were diagnosed with visceral neuropathy or myopathy based on histologic evaluation of full-thickness colon biopsies and the remaining 5 were normal. CM testing revealed abnormalities in all 12 children including no contractions, absent HAPC, and absent gastrocolonic response. Following diversion, 4 children had no improvement, 4 had persistent segmental abnormalities, and 4 had normal findings when colon manometry was repeated 5 to 30 months later. Ten of the 12 children experienced reversal of the diversion. Six of the 10 children also had resection of the dysmotile colon based on the repeat manometry findings. Stooling improved in these 10 children including all 5 with no findings of visceral neuropathy or myopathy. Youssef et al (19) reviewed 19 patients who received colonic resection after abnormal colon motility studies. No evidence of visceral neuropathy was found in these children based on histologic evaluation of the resected specimen. Following surgery, 89% of the children's parents reported their child's health as excellent and all of the 19 children reported improvement in symptoms within 3 months.
We conclude that assessment of the OTT is important to the evaluation of children with chronic constipation. Our study suggests that an OTT should be performed in children with refractory constipation. Determining the OTT is simple using commercially available markers and can be used as a guide to determine which children would benefit from additional colon motility testing. Determination of OTT may help predict which children would benefit from further testing such colon motility testing. A normal OTT study may preclude the need for additional testing, particularly if a larger prospective study generates similar results. However, until a larger prospective study is completed, colon motility study should be considered in treatment of refractory patients with normal OTT. Additionally, the OTT is not a substitute for colon motility testing to determine the integrity of the neuromuscular function of the colon.
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