By Yeon Myung Shin, Bridget R. Southwell, Michael P. Stanton, and John M. Hutson. Kosin, Korea and Melbourne, Australia. Background/Purpose: Slow-transit ...
Signs and Symptoms of Slow-Transit Constipation Versus Functional Retention By Yeon Myung Shin, Bridget R. Southwell, Michael P. Stanton, and John M. Hutson Kosin, Korea and Melbourne, Australia
Background/Purpose: Slow-transit constipation (STC) has been described recently in children. This retrospective study correlated symptoms, signs, transit times, and immunohistochemistry to determine the diagnostic differences between STC and functional fecal retention (FFR). Methods: One hundred eighty children with intractable constipation underwent clinical assessment, nuclear transit study (NTS), with or without laparoscopic colonic muscle biopsy. Patients were divided by NTS into those with STC and those with FFR. Parents completed questionnaires on presenting symptoms. Results: In 161 patients with STC and 19 with FFR, there were no differences in gender, gestation, or timing of symptom onset. Over 20% had the first meconium delayed more than 24 hours after birth even in FFR (4 of 19). Bloating and soiling were more common in STC. There were no differences be-
C
ONSTIPATION is extremely common in children and usually responds to simple treatment with diet, laxatives, and behavior modification. When symptoms persist, Hirschsprung’s disease may be considered, but, beyond this, why treatment fails is unknown. In our hospital, we have investigated more than 200 children with chronic constipation that have not responded to current medical treatment. Colonic peristalsis requires integration of excitatory and inhibitory motor signals, possibly coordinated by the interstitial cells of Cajal.1,2 To identify the excitatory and inhibitory motor neurones of the colonic muscle, we used immunofluorescence histochemistry for the tachykinin, substance P (SP), and vasoactive intestinal peptide (VIP), respectively.3 In 100
From the Department of Surgery, Kosin University, Kosin, Korea; and the Departments of Gastroenterology, General Surgery, and Surgical Research, Royal Children’s Hospital, and the Murdoch Children’s Research Institute, Melbourne, Australia. Presented at the 35th Annual Meeting of the Pacific Association of Pediatric Surgeons, La Jolla, California, May 12-16, 2002. Address reprint requests to Professor John M. Hutson, Department of General Surgery, Royal Children’s Hospital, Parkville 3052, Victoria, Australia. Copyright 2002, Elsevier Science (USA). All rights reserved. 0022-3468/02/3712-0030$35.00/0 doi:10.1053/jpsu.2002.36716
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tween patients with STC but different histology on biopsy. More STC patients had soft stools (39%) than FFR (16%), and a lower stool frequency of less than once a week (STC 26% compared with 11% FFR). FFR was managed more often with medication or diet alone (53%) compared with STC (29%), where enemas, lavage, or surgery were more common. Conclusions: Children with STC showed similar symptoms and signs to those with FFR, but more had bloating and soiling, softer stools, and longer intervals between bowel actions. Delayed meconium stool beyond 24 hours after birth was common in both groups. Diagnosis of STC or FFR required NTS and was not possible on symptoms alone. J Pediatr Surg 37:1762-1765. Copyright 2002, Elsevier Science (USA). All rights reserved. INDEX WORDS: Slow-transit constipation, functional fecal retention.
severely constipated patients investigated with colonic biopsy, early onset and delayed colonic transit correlated with reduced SP-labelled axons in the circular muscle.4 More recently, we have used a nuclear transit study (NTS) to determine the rate of transit through the small and large bowel and identify if transit slows in the colon (slow colonic transit, SCT) or anorectally (functional fecal retention, FFR). This has resulted in the identification of slow-transit constipation in children.5,6 Patients identified with slow colonic transit have laparoscopic biopsy of colonic muscle3,4 to allow immunohistochemical analysis of nerve fibers in the circular muscle. This report presents a retrospective study of 180 children with chronic constipation caused by delay of anorectal release (FFR) or by slow transit through the colon (slow-transit constipation, STC). We compared the symptoms of patients and examined whether patients with slow colonic transit had different symptoms from those with anorectal retention. We also determined the incidence of colonic dysfunction in newborns or a family history of bowel dysfunction, factors that might suggest a congenital aetiology. We report on 161 patients with slow colonic transit (SCT) and 19 with severe FFR. MATERIALS AND METHODS Children with severe, intractable constipation were referred to one of the authors over a 6-year period from 1995 to 2001. All children in this
Journal of Pediatric Surgery, Vol 37, No 12 (December), 2002: pp 1762-1765
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Table 1. Timing of First Medical Contact STC
Constipation Soiling Diarrhea Vomiting Bloating Pain Anal bleeding Failed toilet training Poor appetite Unknown
FFR
Before 2 yr
After 2 yr
Before 2 yr
After 2 yr
81 4 4 4 7 0 0
8 16 2 0 2 0 0
9 0 0 1 0 1 2
1 3 0
1 1
16 0 5
0 0
1 0 5
0 0 0
study had not responded to at least 6 months of medical therapy instituted by a general practitioner or pediatrician, and many patients had undergone years of treatment. Clinical histories were augmented by interview or questionnaire. Information was collected on gender, gestation, onset of symptoms, timing of first meconium stool, first medical contact, stool volume, stool consistency, stool frequency, family history, and treatment used. Abdominal examination suggested soft stools throughout the colon in many patients and hard fecal mass in the rectosigmoid in some patients. Overall, using clinical examination alone, it was not possible to distinguish the site of defect in children with severe intractable constipation. Since 1997, scintigraphy6 (also called nuclear transit study, NTS) has been introduced at our hospital to follow transit through the small and large intestine and to distinguish children with normal transit, FFR or STC. A similar protocol to that described by Notghi was used,7 with normal values derived from several studies of transit time in healthy children.8-10 The studies were carried out using oral radio-labelled Technetium 99m (dose according to weight, based on adult dose of 250 MBq). Images of the whole trunk were collected at 0 to 2, 6, 24, 30, and 48 hours. Normal colonic transit was defined as the presence of tracer in the cecum by 6 hours, in the rectosigmoid by 30 hours, and passed in the feces by 48 hours. Slow colonic transit was defined as global colonic delay with hold-up of tracer proximal to the rectosigmoid at 30 and 48 hours (with no rectal fecaloma). FFR was identified by hold-up of tracer in the rectosigmoid at 48 hours preceded by normal transit. Visual inspection of collected radiographic images was augmented by use of a “colonic transit index” (sum of the geometric centers of radioactivity at 6, 24, 30, and 48 hours). Barium enema was not performed routinely for these patients. Laparoscopic seromuscular biopsy of the colonic muscle was only collected from children with scintigraphic STC. Sections were treated for immunofluorescence staining of tachykinins and vasoactive intestinal peptide (VIP) as previously described.3,4 Tachykinin nerve fiber density in the colonic circular muscle from children with STC was compared with colon from children with familial adenomatous polyposis, the ganglionated region of Hirschsprung’s colon, and adult colon resected for carcinoma. (Colonic biopsy was approved by the Ethicsin-Human-Research Committee at our institution). Statistical analysis to compare STC and FFR by patient questionnaire information was carried out using unpaired t tests.
RESULTS
A total of 180 questionnaires were returned, 161 from children diagnosed with STC on NTS, and from 19 children with FFR on NTS. Children from both groups
reported a similar incidence of major symptoms: constipation (FFR-STC:89% to 91%), soiling (42% to 64%), abdominal pain (42% to 51%), bloating (26% to 46%), anal pain (16% to 19%), vomiting (7% to 16%), poor appetite (42% to 22%) and behavioral problems (21% to 22%). There were no gender differences within the group (M:F ⫽ 82:79 for SCT and 10:9 for FFR), mean ages were 10.5 years for STC and 6 years for FFR. A total of 89 of 161 (55%) STC patients had reduced density of tachykinin nerve fibers, whereas 72 of 161 had normal density of tachykinins. The analysis of signs and symptoms in these 2 STC groups showed no differences in any characteristic, so they are amalgamated for this report. The frequency of prematurity was similar—STC (10 of 161; 6%) and FFR (1 of 19; 5%). First meconium stool was known to be delayed beyond 24 hours after birth in 44 of 104 (41%) of STC children, and 4 of 12 (33%) of FFR children. In 35% of STC and FFR patients the timing was unknown. More than half of all children had a family history of constipation— 84 of 161; (52%) for STC, and 11 of 18 (61%) for FFR. Constipation began early in both groups (Table 1) and was present at birth in 42 of 161 (26%) of STC children and 2 of 18 (11%) with FFR (difference not statistically significant; P ⫽ .17). By 6 weeks of age, 56% of STC and 44% of FFR patients were symptomatic. Three fourths of both STC and FFR patients presented before 2 years of age. Of these, 81 of 161 (52%) of SCT and 9 of 18(50%) of FFR children presented with constipation. Bloating, diarrhea, and vomiting were more common before 2 years of age. After 2 years, failure to toilet train or fecal soiling became more common reasons to seek medical advice. Characteristics of stool differed between the 2 groups (Table 2), with 52% of STC having large stools compared with 26% FFR. More patients with STC had soft stools (39%) than those with FFR (16%, P ⬍ .001). Responses to treatment methods varied, with FFR Table 2. Stool Characteristics
Volume Small/Moderate Large Not known Consistency Hard/firm Soft/variably soft Not Known Frequency ⬎ 1 wk 1/wk ⬍ 1/wk Not known
STC
FFR
75 (47%) 83 (52%) 3 (2%)
13 (68%) 5 (26%) 1 (5%)
94 (58%) 63 (39%) 4 (3%)
14 (78%) 3 (16%) 1 (5%)
69 (40%) 35 (22%) 43 (28%) 15 (10%)
10 (56%) 5 (26%) 1 (11%) 1 (5%)
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responding to medication with or without diet/behavior modification in 9 of 18 (50%) of the patients, and to enema/lavage in 4 of 19(21%). Only 46 of 161 (29%) of those with STC responded to medication and diet, whereas 96 of 161 (60%) required invasive therapies— enemas, rectal lavages, or antegrade colonic enemas (via appendicostomy, 29 of 161). No patients with FFR had surgical intervention, other than manual evacuation/anal stretch for fecaloma (5 of 19, 26%). A total of 19 of 161 (12%) STC patients had partial colectomy (n ⫽ 11) or colostomy (n ⫽ 8) formation. DISCUSSION
Severe intractable constipation can be classified on scintigraphy (NTS) into STC, normal colonic transit, and FFR. This retrospective study confirms that these groups have similar overt symptoms, but respond to different treatments. Clark11 documented the timing of first meconium in 500 consecutive healthy, full-term newborns, and reported that 99% passed meconium within 24 hours. Delayed passage of meconium is a cardinal symptom of Hirschsprung’s disease, occurring in over 90% of cases.12 These findings suggest that STC and severe FFR also may have poor colonic function at birth with passage of meconium delayed in about one third of both groups. However, about a further one third of parents were unable to recall or had no record of the time of first stool. To have accurate and long-term data on the timing of first meconium, this could usefully be recorded in baby health care books. Infants (⬍2 years) from both groups initially presented with constipation, bloating, and vomiting. Later presentations were because of soiling or failure to toilet train. We found that FFR children passed hard, infrequent stools, whereas STC children were more likely to have softer stools. This correlated with initial abdominal examination in which, in many of the children with chronic constipation, soft stools were palpated throughout the colon (despite infrequent evacuation). This asso-
ciation of soft stools with slow-colonic transit suggests an abnormality in colonic water secretion/absorption. Whereas half of the STC children have an identified reduction in tachykinin-labelled nerve fiber density in the circular muscle, they had similar symptoms to STC children with normal density of tachykinins. It is unknown whether reduced tachykinin nerve fiber density in colonic circular muscle is a primary or secondary phenomenon. The equal numbers of patients identified with or without tachykinin anomalies, despite similar levels of intervention, suggests that this is unlikely to be secondary to treatment. The recent proposed role for tachykinins in excitation/contraction13 implies that STC may be the result of a primary deficiency. Patients with STC, but without tachykinin anomalies, may harbour other, as yet unrecognized, functional anomalies of innervation (for example, reduced interstitial cells of Cajal1,2). Surgical intervention was required in some children with STC, but not in patients with FFR. Although in the past, some STC children had partial colectomy or colostomy, currently, the surgical treatment of choice for STC is appendicostomy for antegrade colonic washouts. We recently reported a 70% successful outcome rate by using antegrade colonic washouts (via appendicostomy) to treat children with STC.14 Providing there is no rectosigmoid obstructing fecaloma, children with FFR are able to have relatively normal bowel habits if diet/ medication is controlled. NTS showed normal proximal colonic motility in FFR; therefore, resection/appendicostomy should be unnecessary except in extreme cases. We report on 161 children with scintigraphic STC and 19 children with FFR and show subtle differences between these groups with respect to characteristics of constipation and significant differences in subsequent surgical interventions required. The identification of slow-transit constipation (STC) in children5,6 has opened up new possibilities for both diagnosis and treatment. The next step will be to investigate colonic motility (both in vivo and in vitro), to identify the defects underlying STC.
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schneider AM, Puri P (eds): Hirschsprung’s disease and allied disorders. Harwood Academic Publishers, 2000, pp 129-135 13. Mitolo-Chieppa D, Mansi G, Nacci N, et al: Idiopathic chronic constipation: Tachykinis as cotransmitters in colonic contraction. Eur J Clin Invest 31:349-355, 2001 14. Marshall J, Hutson JM, Anticich N, et al: Antegrade continence enemas in the treatment of slow-transit constipation. J Pediatr Surg 36:1227-1230, 2001
