Journal of Pediatric Surgery 49 (2014) 570–574
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Restorative proctocolectomy with J-pouch ileoanal anastomosis for total colonic aganglionosis among neonates and infants☆ Maria Hukkinen ⁎, Antti Koivusalo, Risto J. Rintala, Mikko P. Pakarinen Section of Pediatric Surgery, Hospital for Children and Adolescents, University of Helsinki, Finland
a r t i c l e
i n f o
Article history: Received 25 June 2013 Received in revised form 26 July 2013 Accepted 30 July 2013 Key words: Hirschsprung disease Total colonic aganglionosis Restorative proctocolectomy
a b s t r a c t Background: No consensus exists on the optimal surgical management of total colonic aganglionosis (TCA). Outcomes after restorative proctocolectomy (RPC) as the initial reconstructive procedure among neonatal and infant TCA patients have not been evaluated previously. Methods: Medical records of patients with Hirschsprung disease (HD) who underwent RPC during infancy between 1997 and 2012 (n = 8) were reviewed. Bowel function and satisfaction with operative results were assessed in a follow-up interview. Results: Median age at RPC was 1.1 months, and covering loop ileostomies were closed 3.7 months later. No operative complications occurred. Hospitalizations for enterocolitis and obstruction occurred each in 50% of patients postoperatively. Enterocolitis-associated outlet obstruction occurred in one third of patients, most of whom responded well to intersphincteric botulinum toxin (botox) injections. No pouchitis or elevated fecal calprotectin levels (median 51 μg/g) were observed. At last follow-up 3.2 years after ileostomy closure, the median 24-hour stooling frequency was 3.5. None had socially limiting fecal incontinence or problems in holding back defecation. Parent satisfaction with operative results was high. Conclusions: The rate of postoperative enterocolitis was similar to other procedures, but a better functional outcome was achieved. Botox injections were effective for postoperative functional outlet obstruction. Shortterm results following RPC among neonates and infants are promising. © 2014 Elsevier Inc. All rights reserved.
Total colonic aganglionosis (TCA) is a rare and severe form of Hirschsprung disease (HD), occurring in less than 10% of cases, with the average incidence of 1 in 50,000 individuals [1,2]. TCA is characterized by the absence of ganglion cells in the entire colon, whereas the majority of HD affects only the rectosigmoid region [3]. Treatment of TCA is challenging and postoperative results have been clearly inferior to short-segment HD. Daily stooling frequency and incontinence rates are higher, with more than one third being incontinent and over 10% using diapers at night [1,4–7]. Over 6% end up with a permanent ileostomy, compared to 1% in short-segment HD [1,4]. Severe perianal excoriations, metabolic problems and growth retardation are not uncommon [1,4–7]. The major complication and cause of death, however, is enterocolitis, affecting up to 50% of TCA patients postoperatively [2,3,6,7]. Although TCA-related morbidity and mortality rates have decreased during recent decades, they remain clearly higher than for rectosigmoid disease [6,7]. Various surgical techniques have been described for the definitive treatment of TCA. These include different methods for a straight ileoanal pull-through [8–10], as well as side-to-side ☆ This study was supported by a research grant from the Sigrid Juselius Foundation. ⁎ Corresponding author. Department of Pediatric Surgery, University of Helsinki, Hospital for Children and Adolescents, P.O. Box 281, 00029 HUS, Finland. E-mail address: maria.hukkinen@helsinki.fi (M. Hukkinen). 0022-3468/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.07.021
anastomoses between ganglionic and aganglionic intestine and the use of colon patches in order to preserve better absorptive capacity [11–13]. Higher morbidity and complication rates have been associated with the Martin procedure, where a long segment of colon is preserved [2,7,7,14]. No operation, however, has proven superior to others with regard to morbidity, mortality, or functional outcomes [2]. Postoperative complications are very common and many require reoperations [15]. Restorative proctocolectomy (RPC) with J-pouch ileoanal anastomosis (IAA) is a well-established procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP) also in the pediatric population. Owing to better continence rates and decreased stooling frequency, creation of an ileal reservoir seems to be a superior procedure when compared to straight IAA [16,17]. The most important postoperative complication is pouchitis, occurring in about half of UC, but significantly less frequently among FAP patients [17–19]. RPC with an ileal pouch has been performed also for a limited number of TCA patients. In addition to 10 older patients operated on previously in our hospital with RPC either as an initial reconstruction (n = 6) or as a redo-operation (n = 4) [16], we found two reports describing RPC for TCA: 9 of 11 procedures were redo-operations [20,21]. Reported postoperative complications were uncommon and functional outcome comparable to post-pull-through results [16,20,21]. No long-term follow-up studies describing results after
M. Hukkinen et al. / Journal of Pediatric Surgery 49 (2014) 570–574
RPC for TCA exist. Further, outcomes after RPC as the initial reconstruction among neonatal and infant TCA patients have not been described.
1. Materials and methods This retrospective study aimed to describe outcomes after RPC with J-pouch IAA among neonates and infants with TCA. Medical records of all consecutive HD patients who underwent RPC as the initial reconstructive procedure during infancy between 1997 and 2012 in Helsinki University Hospital for Children and Adolescents were reviewed (n = 8). HD was diagnosed by preoperative fullthickness (n = 1) or suction (n = 4) rectal biopsies, or by intraoperative seromuscular biopsies (n = 3). The length of aganglionosis was defined at laparotomy by pathologic examination of multiple leveling colon biopsies. Aganglionosis extended to the ascending colon (n = 1), cecum (n = 3), or distal ileum (n = 4). A preoperative ileostomy was placed in five patients. Proctocolectomy and IAA were performed primarily in all patients during the same surgery. After histological determination of the transition zone, a transabdominal colectomy was performed. If the transition zone extended to ileum, the aganglionic segment of distal ileum was resected. A circumferential rectal mucosectomy was performed either transabdominally (n = 4) or transanally (n = 4), leaving a short muscular cuff extending cranially from above the dentate line. A 3.5- to 5-cm-long stapled J-pouch was formed from the distal ileum and its apex was hand-sewn to the anal canal 1–2 cm above the dentate line. A covering loop ileostomy to ensure healing was performed in seven patients. Three experienced pediatric surgeons operated on all the patients. The medical patient records were reviewed for presentation, diagnostic studies, operative details, postoperative complications, and functional outcome. Pouch biopsies and fecal calprotectin were assessed as described previously [22]. The diagnosis of enterocolitis was based on clinical symptoms, including fever, diarrhea, and abdominal pain and distension. Follow-up data collection was completed by an interview about the functional outcome and satisfaction to surgery, performed by a researcher not involved with patient care. Parents of one patient refused the interview, and fecal calprotectin measurement was obtained in seven patients. We used a bowel function questionnaire, previously validated for bowel function evaluation in healthy children and patients with anorectal malformations and HD [23–25]. In addition, the age at weaning from diapers, occurrence of urinary incontinence, stool consistency, flatulence and abdominal distension, as well as parent satisfaction with functional and cosmetic results were asked. The hospital ethical committee approved the study protocol.
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Table 1 Patient demographics (total n = 8). Median gestational age (weeks) Median birth weight (grams) Positive family history (n) Meconium b24 h 24–48 h N48 h Median age of presenting symptoms (d) Delayed meconium (n) Obstruction (n) Enterocolitis (n) Median age of contrast study (d) False transition zone (n) Histologic transition zone Ascending colon (n) Cecum (n) Distal ileum (n) Acetylcholinesterase staining Increased Indeterminate Weak/Negative
40 (40, 41) 3710 (3535, 3783) 2 1 1 6 2 (1.8, 45) 1 5 2 2.5 (2, 6) 3 1 3 4 4 1 2
d = days. Interquartile ranges given for median values.
2.2. Operative characteristics Preoperative ileostomy (n = 5) was performed at a median age of 11 (interquartile range 6, 165) days. One patient had a wound infection and stomal prolapse requiring revision. Four were given preoperative antibiotics for enterocolitis before RPC, which was performed at a median age of 1.1 (0.5, 11) months. The aganglionosis extended to the ileum in four patients, of which three underwent 6-, 15-, and 50-cm resections of distal ileum. In one patient, the permanent sections later confirmed the pulled-through unresected terminal ileum to be hypoganglionic in contrast to the intraoperative frozen-section finding. All patients were given intravenous antibiotics and parenteral nutrition postoperatively. Median stay in the ICU was 2 days. No early operative complications occurred. Patients were discharged after a median hospital stay of 13 (11, 19) days without any regular medications. Supplemental enteral sodium chloride (4 mmol/kg/day) was given to all patients, and highenergy dietary supplements were given to three patients. The patient who underwent an ileal resection of 50 cm developed short bowel syndrome (SBS) and required parenteral nutrition for 20 months. Others were discharged with full enteral feedings. Covering loop ileostomy (n = 7) was closed 3.7 (1.8, 4.9) months later after a pouch endoscopy. Prolonged used of a nasogastric tube was necessary in two patients because of poor nutritional intake. One was weaned off the tube soon after stoma closure, whereas the other eventually underwent percutaneous endoscopic gastrostomy (PEG).
2. Results
2.3. Postoperative complications
2.1. Preoperative characteristics
Postoperative complications requiring hospitalization included episodes of enterocolitis or obstructive symptoms with or without enterocolitis. Two patients had no postoperative complications, whereas the others had been hospitalized at least once. One patient required a temporary rediversion 1 week after stoma closure because of bowel obstruction. The ileostomy was eventually closed 11 months after RPC without further complications. An additional three patients were treated conservatively for acute ileus. Four (50%) were hospitalized 1–4 times because of enterocolitis, and in three, at least one episode was associated with symptomatic outlet obstruction. Conservative treatment included intravenous antibiotics and rectal tube decompression if needed. In addition, clostridium botulinum toxin (botox) injections were used for outlet obstruction-associated enterocolitis (n = 3) and for recurrent enterocolitis (n = 1). The
All patients were male, with positive family history in two. No associated anomalies were diagnosed. Primary symptoms presented at a median age of 2 days; however, in two patients symptoms presented after the neonatal period (age of 5 and 9 months). Although six patients passed meconium N48 hours after birth, only one was admitted to a hospital for this reason; primary symptoms among others included intestinal obstruction and enterocolitis. Contrast enema was performed in six patients, falsely suggesting the transition zone in the left colon in three. Acetylcholine (AChE) histochemistry on colonic biopsies (n = 7) was weak or absent in three. No calretinin immunoreactivity (n = 3) was observed. Patient characteristics are summarized in Table 1.
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11,0 10,0 9,0 8,0 7,0 6,0 5,0 4,0 3,0 2,0 6 months
12 months
24 months
Time after ileostomy closure Fig. 1. Total number of hospitalizations because of enterocolitis or obstruction during first, second, and third year after RPC (n = 8).
response was good in three patients, and two were given repeated injections. The incidence of hospitalizations because of obstruction and enterocolitis was highest during the first year after RPC (Fig. 1). Mild symptoms of enterocolitis occurred occasionally in five patients (63%) and were controlled with short courses of per oral metronidazole or ciprofloxacin. During the year before the last follow-up, two patients had been hospitalized for enterocolitis, three had had short courses of per oral antibiotics, and four had been asymptomatic. The patient with SBS took regular antibiotics (metronidazole and ciprofloxacin) to control for bacterial overgrowth as well as antidiarrheal medications (loperamide and psyllium). One required daily metronidazole whereas others had no regular medications. Sodium chloride supplement was still in use in three patients, all aged b3 years, and the patient with a gastrostomy was fed partly via the PEG tube. Median weight-forage and height-for-age z-scores at last follow-up were − 0.2 (− 1.2, − 0.1) and − 0.5 (− 0.9, − 0.1), respectively. Pouchitis was screened for during follow-up by pouch endoscopies. No strictures, leaks or sinuses were found. Histologic examination of pouch biopsies at the last endoscopy (median 2.0 [1.3, 5.4] years after RPC) revealed mild pouchitis in two patients. In the absence of clinical symptoms and macroscopic inflammation, antibiotics were not used. For several postoperative months five patients had perianal excoriations, which responded well to local care and had not recurred by the last follow-up. The median fecal calprotectin level was well in the normal range at last follow-up.
Table 2 The incidence of enterocolitis and intestinal obstruction, pouch histology at last endoscopy, and fecal calprotectin levels at last follow-up. n Enterocolitis Per oral antibiotics Hospitalizations Associated outlet obstruction Botox treatment Acute intestinal obstruction Recurrent episodes Temporary rediversion Pouch histology at last endoscopy Normal Reactive changes Mild pouchitis F-calprotectin N100 μg/g b100 μg/g Median
5 5 4 3 4 4 1 1 3 3 2 2 5 51 (8, 93)
Fig. 2. Median 24-hour bowel movement frequencies with interquartile ranges 6, 12, and 24 months after ileostomy closure (n = 8).
Slightly elevated levels (b 160 μg/g) were detected in two patients. The postoperative complications are summarized in Table 2. 2.4. Functional results The 24-hour bowel movement frequencies 6, 12, and 24 months after ileostomy closure are presented in Fig. 2. At last follow-up at a median age of 3.2 (2.3, 7.7) years, the median stooling frequency for a 24-hour period was 3.5 (3, 4.3). Apart from one (aged 3.3 years), all Table 3 Functional outcome at last follow-up at median age of 3.2 (2.3, 7.7) years. n Ability to hold back defecation Always Most of the time Uncertain Absent Feels/reports the urge to defecate Always Problems b1/wk Weekly problems No voluntary control Soiling Never Staining b1/wk, no change of underwear required Frequent staining, change of underwear often required Daily soiling, requires protective aids Accidents Never Fewer than 1/wk Weekly, requires protective aids Daily, requires protective aids day and night Nighttime bowel movements Never Fewer than 1/wk Weekly Every night Disturbing flatulence Never Fewer than 1/wk Weekly Daily Abdominal distension Never Fewer than 1/wk Weekly Daily
4 0 0 0 3 0 1 0 2 1 0 1 3 0 1 0 2 1 1 0 3 3 0 1 4 3 0 0
Continence including nighttime bowel movements reported for those weaned from diapers and aged ≥3 years (n = 4). Data on flatulence and abdominal distension were missing in one patient.
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patients aged ≥ 3 years had weaned from diapers at a median age of 2.6 (2.3, 3.0) years. Among them, all were able to hold back defecation. Any type soiling or fecal accidents occurred in one patient (aged 5 years), and associated with history of recurrent enterocolitis, stool withholding behavior, and difficulties in recognizing the urge to defecate requiring occasional use of protective pads. Nighttime bowel movements occurred occasionally in two patients. One had constipation, which was manageable with diet. Stools were loose in all patients. None reported urinary incontinence or voiding difficulties. The data on bowel function are summarized in Table 3. The overall satisfaction with operative outcome among parents was high. On a scale of 1–5, with 5 being very satisfied, median rating was 4 (3, 5) for bowel function and 4 (3.5, 5) for cosmesis. None of the families experienced any social problems related to bowel function. 3. Discussion This is the first study describing results of RPC as the initial reconstruction for HD among neonates and infants. RPC has been earlier shown to be safe and effective for older children with UC and FAP. Investigator not involved with patient care interviewed the parents to reassure truthful description of functional outcomes. Our results strongly suggest that RPC offers good results also for TCA even during the neonatal period. Early functional outcome seems promising, with median daily bowel movement frequency of 3, and low rates of fecal incontinence. No operative complications occurred. Apart from one stoma revision and one rediversion, no reoperations were needed. The most important, but manageable late postoperative complications were enterocolitis, obstructive symptoms, and perianal rash, which are commonly encountered following any surgery for TCA. No endoscopic pouchitis was observed and fecal calprotectin levels were normal or near normal. Enterocolitis is a nonpreventable complication, affecting approximately half of TCA patients postoperatively [1–3,6,7,15]. Higher incidence rates have been observed after the Martin operation [2,7], whereas other procedures show no difference in relation to postoperative enterocolitis episodes. The rate of enterocolitis among our patients was slightly higher than reported previously in long-term studies [5,6]. Most episodes were mild and controlled with per oral antibiotics. Severe enterocolitis episodes were almost exclusively associated with symptoms of outlet obstruction responding well to intersphincteric injections of botox. The number of hospitalizations was highest during the first year after ileostomy closure; however, a longer follow-up would be needed to demonstrate whether the incidence of enterocolitis actually decreases with time. Obstructive symptoms are a common postoperative complication after RPC [18,20,26], but occur in only about 10% of HD patients after pull-through [27]. Wide abdominal and pelvic dissection at time of RPC predisposes patients to adhesive obstruction [26]. Functional outlet obstruction in HD patients, instead, can be caused by persistent aganglionosis, internal sphincter achalasia, or intestinal dysmotility, which seems to be more common among those with a long segment disease [27]. Although the innervation of the internal sphincter muscle is defective in all HD patients, only some suffer from persistent obstruction [28]. In our sample, half of patients had an acute ileus without mechanical obstruction within 2 years of RPC. In addition, one third had episodes of outlet obstruction associated with enterocolitis. Intersphincteric botox injections can be used to relax the sphincter in a reversible fashion [28], and had good effect in three of four of our patients. Interestingly, the patient with hypoganglionic pulled-through region had no obstructive symptoms. Fecal calprotectin levels have been shown to correlate positively with the frequency of pouchitis in UC patients after RPC [22]. In our patients, no pouchitis was observed in endoscopies during follow-up. Median fecal calprotectin concentration was in the normal range and only two patients had slightly increased levels, however, well below
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those observed in conjunction with pouchitis [22]. Two patients with histological mild pouchitis were free of enterocolitis/pouchitis symptoms during follow-up. The incidence of postoperative pouchitis is known to be lower among FAP patients than among UC patients [16,17,20], and our results suggest that HD patients also represent a low-risk group. Use of a short J-pouch, as in here, appears advisable in this respect. The cumulative risk for symptomatic pouchitis, however, increases in long-term follow-up [19,29]. Moreover, as the correlation between endoscopic and clinical findings is variable [30], regular follow-up using fecal calprotectin determinations and endoscopies seems necessary. In addition to pouchitis, an important and potentially very disabling problem after RPC is high frequency of bowel movements [18,19]. Both children and adults commonly have 5 to 6 bowel movements per day and 1 to 2 per night postoperatively [17–19,29]. In our study, the observed median 24-hour bowel movement frequency of 3.5 at 3.2 years can be considered as an excellent result. Moreover, none had regular nighttime bowel movements. Typically, the daily stooling frequency in TCA patients decreases from 5 to 6 in childhood to 3 to 4 in adolescence [4–6]. Considering that the prevalence of soiling among healthy preschool children is as high as 50% and fecal accidents occur in 10% [25], the postoperative bowel function of our patients seems comparable to general pediatric population. A very good functional outcome was achieved in a small group of TCA patients undergoing RPC during infancy. The observed rate of postoperative enterocolitis was similar to what is observed after other pull-through procedures, although it often presented with obstructive symptoms necessitating hospitalization in half of patients. Despite these postoperative complications, the overall satisfaction with operative results was high. Although no pouchitis was observed, patients require regular endoscopic follow-ups. These short-term results are promising; however, longer follow-ups in larger study samples are needed to better define the role of RPC in the treatment of HD.
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[17] Seetharamaiah R, West BT, Ignash SJ, et al. Outcomes in pediatric patients undergoing straight vs J pouch ileoanal anastomosis: a multicenter analysis. J Pediatr Surg 2009;44(7):1410–7. [18] Pakarinen MP, Natunen J, Ashorn M, et al. Long-term outcomes of restorative proctocolectomy in children with ulcerative colitis. Pediatrics 2009;123(5): 1377–82. [19] Hahnloser D, Pemberton JH, Wolff BG, et al. Results at up to 20 years after ileal pouch-anal anastomosis for chronic ulcerative colitis. Br J Surg 2007;94(3): 333–40. [20] Fonkalsrud EW, Thakur A, Beanes S. Ileoanal pouch procedures in children. J Pediatr Surg 2001;36(11):1689–92. [21] Lal DR, Nichol PF, Harms BA, et al. Ileo-anal S-pouch reconstruction in patients with total colonic aganglionosis after failed pull-through procedure. J Pediatr Surg 2004;39(7):e7–9. [22] Pakarinen MP, Koivusalo A, Natunen J, et al: Fecal calprotectin mirrors inflammation of the distal ileum and bowel function after restorative proctocolectomy for pediatric-onset ulcerative colitis. Inflamm Bowel Dis 2010;16(3):482486. Accessed 20100215. http://dx.doi.org/10.1002/ibd.21069. [23] Rintala RJ, Lindahl H. Is normal bowel function possible after repair of intermediate and high anorectal malformations? J Pediatr Surg 1995;30(3):491–4.
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Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Restorative proctocolectomy with J-pouch ileoanal anastomosis for total colonic aganglionosis among neonates and infants☆ Maria Hukkinen ⁎, Antti Koivusalo, Risto J. Rintala, Mikko P. Pakarinen Section of Pediatric Surgery, Hospital for Children and Adolescents, University of Helsinki, Finland
a r t i c l e
i n f o
Article history: Received 25 June 2013 Received in revised form 26 July 2013 Accepted 30 July 2013 Key words: Hirschsprung disease Total colonic aganglionosis Restorative proctocolectomy
a b s t r a c t Background: No consensus exists on the optimal surgical management of total colonic aganglionosis (TCA). Outcomes after restorative proctocolectomy (RPC) as the initial reconstructive procedure among neonatal and infant TCA patients have not been evaluated previously. Methods: Medical records of patients with Hirschsprung disease (HD) who underwent RPC during infancy between 1997 and 2012 (n = 8) were reviewed. Bowel function and satisfaction with operative results were assessed in a follow-up interview. Results: Median age at RPC was 1.1 months, and covering loop ileostomies were closed 3.7 months later. No operative complications occurred. Hospitalizations for enterocolitis and obstruction occurred each in 50% of patients postoperatively. Enterocolitis-associated outlet obstruction occurred in one third of patients, most of whom responded well to intersphincteric botulinum toxin (botox) injections. No pouchitis or elevated fecal calprotectin levels (median 51 μg/g) were observed. At last follow-up 3.2 years after ileostomy closure, the median 24-hour stooling frequency was 3.5. None had socially limiting fecal incontinence or problems in holding back defecation. Parent satisfaction with operative results was high. Conclusions: The rate of postoperative enterocolitis was similar to other procedures, but a better functional outcome was achieved. Botox injections were effective for postoperative functional outlet obstruction. Shortterm results following RPC among neonates and infants are promising. © 2014 Elsevier Inc. All rights reserved.
Total colonic aganglionosis (TCA) is a rare and severe form of Hirschsprung disease (HD), occurring in less than 10% of cases, with the average incidence of 1 in 50,000 individuals [1,2]. TCA is characterized by the absence of ganglion cells in the entire colon, whereas the majority of HD affects only the rectosigmoid region [3]. Treatment of TCA is challenging and postoperative results have been clearly inferior to short-segment HD. Daily stooling frequency and incontinence rates are higher, with more than one third being incontinent and over 10% using diapers at night [1,4–7]. Over 6% end up with a permanent ileostomy, compared to 1% in short-segment HD [1,4]. Severe perianal excoriations, metabolic problems and growth retardation are not uncommon [1,4–7]. The major complication and cause of death, however, is enterocolitis, affecting up to 50% of TCA patients postoperatively [2,3,6,7]. Although TCA-related morbidity and mortality rates have decreased during recent decades, they remain clearly higher than for rectosigmoid disease [6,7]. Various surgical techniques have been described for the definitive treatment of TCA. These include different methods for a straight ileoanal pull-through [8–10], as well as side-to-side ☆ This study was supported by a research grant from the Sigrid Juselius Foundation. ⁎ Corresponding author. Department of Pediatric Surgery, University of Helsinki, Hospital for Children and Adolescents, P.O. Box 281, 00029 HUS, Finland. E-mail address: maria.hukkinen@helsinki.fi (M. Hukkinen). 0022-3468/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.07.021
anastomoses between ganglionic and aganglionic intestine and the use of colon patches in order to preserve better absorptive capacity [11–13]. Higher morbidity and complication rates have been associated with the Martin procedure, where a long segment of colon is preserved [2,7,7,14]. No operation, however, has proven superior to others with regard to morbidity, mortality, or functional outcomes [2]. Postoperative complications are very common and many require reoperations [15]. Restorative proctocolectomy (RPC) with J-pouch ileoanal anastomosis (IAA) is a well-established procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP) also in the pediatric population. Owing to better continence rates and decreased stooling frequency, creation of an ileal reservoir seems to be a superior procedure when compared to straight IAA [16,17]. The most important postoperative complication is pouchitis, occurring in about half of UC, but significantly less frequently among FAP patients [17–19]. RPC with an ileal pouch has been performed also for a limited number of TCA patients. In addition to 10 older patients operated on previously in our hospital with RPC either as an initial reconstruction (n = 6) or as a redo-operation (n = 4) [16], we found two reports describing RPC for TCA: 9 of 11 procedures were redo-operations [20,21]. Reported postoperative complications were uncommon and functional outcome comparable to post-pull-through results [16,20,21]. No long-term follow-up studies describing results after
M. Hukkinen et al. / Journal of Pediatric Surgery 49 (2014) 570–574
RPC for TCA exist. Further, outcomes after RPC as the initial reconstruction among neonatal and infant TCA patients have not been described.
1. Materials and methods This retrospective study aimed to describe outcomes after RPC with J-pouch IAA among neonates and infants with TCA. Medical records of all consecutive HD patients who underwent RPC as the initial reconstructive procedure during infancy between 1997 and 2012 in Helsinki University Hospital for Children and Adolescents were reviewed (n = 8). HD was diagnosed by preoperative fullthickness (n = 1) or suction (n = 4) rectal biopsies, or by intraoperative seromuscular biopsies (n = 3). The length of aganglionosis was defined at laparotomy by pathologic examination of multiple leveling colon biopsies. Aganglionosis extended to the ascending colon (n = 1), cecum (n = 3), or distal ileum (n = 4). A preoperative ileostomy was placed in five patients. Proctocolectomy and IAA were performed primarily in all patients during the same surgery. After histological determination of the transition zone, a transabdominal colectomy was performed. If the transition zone extended to ileum, the aganglionic segment of distal ileum was resected. A circumferential rectal mucosectomy was performed either transabdominally (n = 4) or transanally (n = 4), leaving a short muscular cuff extending cranially from above the dentate line. A 3.5- to 5-cm-long stapled J-pouch was formed from the distal ileum and its apex was hand-sewn to the anal canal 1–2 cm above the dentate line. A covering loop ileostomy to ensure healing was performed in seven patients. Three experienced pediatric surgeons operated on all the patients. The medical patient records were reviewed for presentation, diagnostic studies, operative details, postoperative complications, and functional outcome. Pouch biopsies and fecal calprotectin were assessed as described previously [22]. The diagnosis of enterocolitis was based on clinical symptoms, including fever, diarrhea, and abdominal pain and distension. Follow-up data collection was completed by an interview about the functional outcome and satisfaction to surgery, performed by a researcher not involved with patient care. Parents of one patient refused the interview, and fecal calprotectin measurement was obtained in seven patients. We used a bowel function questionnaire, previously validated for bowel function evaluation in healthy children and patients with anorectal malformations and HD [23–25]. In addition, the age at weaning from diapers, occurrence of urinary incontinence, stool consistency, flatulence and abdominal distension, as well as parent satisfaction with functional and cosmetic results were asked. The hospital ethical committee approved the study protocol.
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Table 1 Patient demographics (total n = 8). Median gestational age (weeks) Median birth weight (grams) Positive family history (n) Meconium b24 h 24–48 h N48 h Median age of presenting symptoms (d) Delayed meconium (n) Obstruction (n) Enterocolitis (n) Median age of contrast study (d) False transition zone (n) Histologic transition zone Ascending colon (n) Cecum (n) Distal ileum (n) Acetylcholinesterase staining Increased Indeterminate Weak/Negative
40 (40, 41) 3710 (3535, 3783) 2 1 1 6 2 (1.8, 45) 1 5 2 2.5 (2, 6) 3 1 3 4 4 1 2
d = days. Interquartile ranges given for median values.
2.2. Operative characteristics Preoperative ileostomy (n = 5) was performed at a median age of 11 (interquartile range 6, 165) days. One patient had a wound infection and stomal prolapse requiring revision. Four were given preoperative antibiotics for enterocolitis before RPC, which was performed at a median age of 1.1 (0.5, 11) months. The aganglionosis extended to the ileum in four patients, of which three underwent 6-, 15-, and 50-cm resections of distal ileum. In one patient, the permanent sections later confirmed the pulled-through unresected terminal ileum to be hypoganglionic in contrast to the intraoperative frozen-section finding. All patients were given intravenous antibiotics and parenteral nutrition postoperatively. Median stay in the ICU was 2 days. No early operative complications occurred. Patients were discharged after a median hospital stay of 13 (11, 19) days without any regular medications. Supplemental enteral sodium chloride (4 mmol/kg/day) was given to all patients, and highenergy dietary supplements were given to three patients. The patient who underwent an ileal resection of 50 cm developed short bowel syndrome (SBS) and required parenteral nutrition for 20 months. Others were discharged with full enteral feedings. Covering loop ileostomy (n = 7) was closed 3.7 (1.8, 4.9) months later after a pouch endoscopy. Prolonged used of a nasogastric tube was necessary in two patients because of poor nutritional intake. One was weaned off the tube soon after stoma closure, whereas the other eventually underwent percutaneous endoscopic gastrostomy (PEG).
2. Results
2.3. Postoperative complications
2.1. Preoperative characteristics
Postoperative complications requiring hospitalization included episodes of enterocolitis or obstructive symptoms with or without enterocolitis. Two patients had no postoperative complications, whereas the others had been hospitalized at least once. One patient required a temporary rediversion 1 week after stoma closure because of bowel obstruction. The ileostomy was eventually closed 11 months after RPC without further complications. An additional three patients were treated conservatively for acute ileus. Four (50%) were hospitalized 1–4 times because of enterocolitis, and in three, at least one episode was associated with symptomatic outlet obstruction. Conservative treatment included intravenous antibiotics and rectal tube decompression if needed. In addition, clostridium botulinum toxin (botox) injections were used for outlet obstruction-associated enterocolitis (n = 3) and for recurrent enterocolitis (n = 1). The
All patients were male, with positive family history in two. No associated anomalies were diagnosed. Primary symptoms presented at a median age of 2 days; however, in two patients symptoms presented after the neonatal period (age of 5 and 9 months). Although six patients passed meconium N48 hours after birth, only one was admitted to a hospital for this reason; primary symptoms among others included intestinal obstruction and enterocolitis. Contrast enema was performed in six patients, falsely suggesting the transition zone in the left colon in three. Acetylcholine (AChE) histochemistry on colonic biopsies (n = 7) was weak or absent in three. No calretinin immunoreactivity (n = 3) was observed. Patient characteristics are summarized in Table 1.
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11,0 10,0 9,0 8,0 7,0 6,0 5,0 4,0 3,0 2,0 6 months
12 months
24 months
Time after ileostomy closure Fig. 1. Total number of hospitalizations because of enterocolitis or obstruction during first, second, and third year after RPC (n = 8).
response was good in three patients, and two were given repeated injections. The incidence of hospitalizations because of obstruction and enterocolitis was highest during the first year after RPC (Fig. 1). Mild symptoms of enterocolitis occurred occasionally in five patients (63%) and were controlled with short courses of per oral metronidazole or ciprofloxacin. During the year before the last follow-up, two patients had been hospitalized for enterocolitis, three had had short courses of per oral antibiotics, and four had been asymptomatic. The patient with SBS took regular antibiotics (metronidazole and ciprofloxacin) to control for bacterial overgrowth as well as antidiarrheal medications (loperamide and psyllium). One required daily metronidazole whereas others had no regular medications. Sodium chloride supplement was still in use in three patients, all aged b3 years, and the patient with a gastrostomy was fed partly via the PEG tube. Median weight-forage and height-for-age z-scores at last follow-up were − 0.2 (− 1.2, − 0.1) and − 0.5 (− 0.9, − 0.1), respectively. Pouchitis was screened for during follow-up by pouch endoscopies. No strictures, leaks or sinuses were found. Histologic examination of pouch biopsies at the last endoscopy (median 2.0 [1.3, 5.4] years after RPC) revealed mild pouchitis in two patients. In the absence of clinical symptoms and macroscopic inflammation, antibiotics were not used. For several postoperative months five patients had perianal excoriations, which responded well to local care and had not recurred by the last follow-up. The median fecal calprotectin level was well in the normal range at last follow-up.
Table 2 The incidence of enterocolitis and intestinal obstruction, pouch histology at last endoscopy, and fecal calprotectin levels at last follow-up. n Enterocolitis Per oral antibiotics Hospitalizations Associated outlet obstruction Botox treatment Acute intestinal obstruction Recurrent episodes Temporary rediversion Pouch histology at last endoscopy Normal Reactive changes Mild pouchitis F-calprotectin N100 μg/g b100 μg/g Median
5 5 4 3 4 4 1 1 3 3 2 2 5 51 (8, 93)
Fig. 2. Median 24-hour bowel movement frequencies with interquartile ranges 6, 12, and 24 months after ileostomy closure (n = 8).
Slightly elevated levels (b 160 μg/g) were detected in two patients. The postoperative complications are summarized in Table 2. 2.4. Functional results The 24-hour bowel movement frequencies 6, 12, and 24 months after ileostomy closure are presented in Fig. 2. At last follow-up at a median age of 3.2 (2.3, 7.7) years, the median stooling frequency for a 24-hour period was 3.5 (3, 4.3). Apart from one (aged 3.3 years), all Table 3 Functional outcome at last follow-up at median age of 3.2 (2.3, 7.7) years. n Ability to hold back defecation Always Most of the time Uncertain Absent Feels/reports the urge to defecate Always Problems b1/wk Weekly problems No voluntary control Soiling Never Staining b1/wk, no change of underwear required Frequent staining, change of underwear often required Daily soiling, requires protective aids Accidents Never Fewer than 1/wk Weekly, requires protective aids Daily, requires protective aids day and night Nighttime bowel movements Never Fewer than 1/wk Weekly Every night Disturbing flatulence Never Fewer than 1/wk Weekly Daily Abdominal distension Never Fewer than 1/wk Weekly Daily
4 0 0 0 3 0 1 0 2 1 0 1 3 0 1 0 2 1 1 0 3 3 0 1 4 3 0 0
Continence including nighttime bowel movements reported for those weaned from diapers and aged ≥3 years (n = 4). Data on flatulence and abdominal distension were missing in one patient.
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patients aged ≥ 3 years had weaned from diapers at a median age of 2.6 (2.3, 3.0) years. Among them, all were able to hold back defecation. Any type soiling or fecal accidents occurred in one patient (aged 5 years), and associated with history of recurrent enterocolitis, stool withholding behavior, and difficulties in recognizing the urge to defecate requiring occasional use of protective pads. Nighttime bowel movements occurred occasionally in two patients. One had constipation, which was manageable with diet. Stools were loose in all patients. None reported urinary incontinence or voiding difficulties. The data on bowel function are summarized in Table 3. The overall satisfaction with operative outcome among parents was high. On a scale of 1–5, with 5 being very satisfied, median rating was 4 (3, 5) for bowel function and 4 (3.5, 5) for cosmesis. None of the families experienced any social problems related to bowel function. 3. Discussion This is the first study describing results of RPC as the initial reconstruction for HD among neonates and infants. RPC has been earlier shown to be safe and effective for older children with UC and FAP. Investigator not involved with patient care interviewed the parents to reassure truthful description of functional outcomes. Our results strongly suggest that RPC offers good results also for TCA even during the neonatal period. Early functional outcome seems promising, with median daily bowel movement frequency of 3, and low rates of fecal incontinence. No operative complications occurred. Apart from one stoma revision and one rediversion, no reoperations were needed. The most important, but manageable late postoperative complications were enterocolitis, obstructive symptoms, and perianal rash, which are commonly encountered following any surgery for TCA. No endoscopic pouchitis was observed and fecal calprotectin levels were normal or near normal. Enterocolitis is a nonpreventable complication, affecting approximately half of TCA patients postoperatively [1–3,6,7,15]. Higher incidence rates have been observed after the Martin operation [2,7], whereas other procedures show no difference in relation to postoperative enterocolitis episodes. The rate of enterocolitis among our patients was slightly higher than reported previously in long-term studies [5,6]. Most episodes were mild and controlled with per oral antibiotics. Severe enterocolitis episodes were almost exclusively associated with symptoms of outlet obstruction responding well to intersphincteric injections of botox. The number of hospitalizations was highest during the first year after ileostomy closure; however, a longer follow-up would be needed to demonstrate whether the incidence of enterocolitis actually decreases with time. Obstructive symptoms are a common postoperative complication after RPC [18,20,26], but occur in only about 10% of HD patients after pull-through [27]. Wide abdominal and pelvic dissection at time of RPC predisposes patients to adhesive obstruction [26]. Functional outlet obstruction in HD patients, instead, can be caused by persistent aganglionosis, internal sphincter achalasia, or intestinal dysmotility, which seems to be more common among those with a long segment disease [27]. Although the innervation of the internal sphincter muscle is defective in all HD patients, only some suffer from persistent obstruction [28]. In our sample, half of patients had an acute ileus without mechanical obstruction within 2 years of RPC. In addition, one third had episodes of outlet obstruction associated with enterocolitis. Intersphincteric botox injections can be used to relax the sphincter in a reversible fashion [28], and had good effect in three of four of our patients. Interestingly, the patient with hypoganglionic pulled-through region had no obstructive symptoms. Fecal calprotectin levels have been shown to correlate positively with the frequency of pouchitis in UC patients after RPC [22]. In our patients, no pouchitis was observed in endoscopies during follow-up. Median fecal calprotectin concentration was in the normal range and only two patients had slightly increased levels, however, well below
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those observed in conjunction with pouchitis [22]. Two patients with histological mild pouchitis were free of enterocolitis/pouchitis symptoms during follow-up. The incidence of postoperative pouchitis is known to be lower among FAP patients than among UC patients [16,17,20], and our results suggest that HD patients also represent a low-risk group. Use of a short J-pouch, as in here, appears advisable in this respect. The cumulative risk for symptomatic pouchitis, however, increases in long-term follow-up [19,29]. Moreover, as the correlation between endoscopic and clinical findings is variable [30], regular follow-up using fecal calprotectin determinations and endoscopies seems necessary. In addition to pouchitis, an important and potentially very disabling problem after RPC is high frequency of bowel movements [18,19]. Both children and adults commonly have 5 to 6 bowel movements per day and 1 to 2 per night postoperatively [17–19,29]. In our study, the observed median 24-hour bowel movement frequency of 3.5 at 3.2 years can be considered as an excellent result. Moreover, none had regular nighttime bowel movements. Typically, the daily stooling frequency in TCA patients decreases from 5 to 6 in childhood to 3 to 4 in adolescence [4–6]. Considering that the prevalence of soiling among healthy preschool children is as high as 50% and fecal accidents occur in 10% [25], the postoperative bowel function of our patients seems comparable to general pediatric population. A very good functional outcome was achieved in a small group of TCA patients undergoing RPC during infancy. The observed rate of postoperative enterocolitis was similar to what is observed after other pull-through procedures, although it often presented with obstructive symptoms necessitating hospitalization in half of patients. Despite these postoperative complications, the overall satisfaction with operative results was high. Although no pouchitis was observed, patients require regular endoscopic follow-ups. These short-term results are promising; however, longer follow-ups in larger study samples are needed to better define the role of RPC in the treatment of HD.
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