Functional defecation disorders in children: Associated comorbidity and advances in management - Chapter 10: Surgical decision-making in the management of children with intractable functional constipation: what are we doing

(1)

UvA-DARE (Digital Academic Repository)

Functional defecation disorders in children

Associated comorbidity and advances in management Kuizenga-Wessel, S. Publication date 2017 Document Version Other version License Other Link to publication

Citation for published version (APA):

Kuizenga-Wessel, S. (2017). Functional defecation disorders in children: Associated comorbidity and advances in management.

General rights

It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons).

Disclaimer/Complaints regulations

If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.

(2)

(3)

Chapt%r

_tß

SURGICAL

DECISION-MAKING IN

THE MANAGEMENT OF

CHILDREN WITH

INTRACTABLE FUNCTIONAL

CONSTIPATION

What are we doing

and are we doing it right?

I.J.N. Koppen, S. Kuizenga-Wessel,

P.L. Lu, M.A. Benninga, C. Di Lorenzo, V.A. Lane, M.A. Levitt, R.J. Wood, D. Yacob

J Pediatr Surg. 2016;51(10):1607-1612

(4)

ABSTRACT

Background

Children with intractable functional constipation (FC) may eventually require surgery, often guided by motility testing. However, there are no evidence-based guidelines for the surgical management of intractable FC in children.

Aim

To assess the diagnostic and surgical approach of pediatric surgeons and pediatric gastroenterologists towards children with intractable FC.

Methods

A survey was administered to physicians attending an international conference held simultaneously in Columbus (Ohio, USA) and Nijmegen (the Netherlands). The survey included 4 questions based on cases with anorectal and colonic manometry results.

Results

74 physicians completed the questionnaire. Anorectal manometry was used by 70%; 52% of them would consider anal sphincter botulinum toxin injections for anal achalasia and 21% would use this to treat dyssynergia. Colonic manom-etry was used by 38%; 57% of them reported to use this to guide surgical deci-sion-making. The surgical approach varied considerably among responders answering the case questions based on motility test results; the most commonly chosen treatmentswere antegrade continence enemas and anal botulinum injections.

Conclusion

Surgical decision-making for children with intractable FC diﬀers among physi-cians. There is a need for clinical guidelines regarding the role of anorectal and colonic manometry in surgical decision-making in children with intractable FC.

(5)

Su rg ic al d ec isi on -m ak in g 10

INTRODUCTION

Childhood constipation is a common problem in pediatric healthcare. It is char-acterized by infrequent bowel movements (b3 per week), hard and/or large stools, painful defecation and it is often accompanied by abdominal pain1_.

Approximately 75–90% of children with chronic constipation seen by a pediatric gastroenterologist suﬀer from fecal incontinence, caused by the leakage of soft stools around a large and hard fecal mass accumulated in the rectum2_{. In}

most cases, an organic cause for constipation is not found and aﬀected chil-dren are diagnosed with functional constipation (FC). The reported prevalence of FC among children ranges from 0.7% to 29.6% with a mean female/male ratio of 2.1:13_{. A subset of patients with FC experience severe and long-lasting}

symptoms that respond poorly to conventional behavioral, dietary and phar-macological management, these children are considered to have intractable FC1_{. In tertiary care centers, 50% of children referred to a pediatric}

gastroen-terologist are still symptomatic after 5 years, and 20% still struggle with symp-toms after 10 years1_{. Symptoms can even persist into adulthood despite}

inten-sive laxative treatment4_{. Persistent FC symptoms negatively aﬀect quality of life}

in multiple ways (e.g., social interactions, school achievements, self-esteem) and account for significant associated healthcare costs5-7_.

Children with intractable FC may eventually require alternative therapeutic interventions including surgery. The most recent joint guidelines from the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) state that colonic manometry may be indicated in children with intractable FC because evaluation of colonic motility may help guide surgical management1_{. This recommendation is mostly based}

on expert opinion and relies on the results of few retrospective studies that reported that normal colonic manometry predicts a successful response to antegrade continence enemas (ACE)8_{and abnormal manometry was}

associ-ated with successful surgical interventions9_{. However, there are no guidelines}

that clearly recommend which surgical treatment should be performed based on manometry results. Without such guidelines, it is likely that the surgical approach towards children with severe FC diﬀers among centers and among individual surgeons. Surgery is usually considered a treatment of last resort and is generally performed with a step-up approach, beginning with the least invasive treatment and progressing to more invasive interventions only if needed. The choice of what type of surgery to perform is usually determined based on a comprehensive evaluation of the colonic and anorectal anatomy

(6)

and physiology, although this evaluation may diﬀer among centers. Generally, medical care for children with intractable FC is a joint venture, where both pediatric gastroenterology and pediatric surgery are involved. Intrasphinc-teric botulinum toxin injections and ACE are considered to be less invasive surgical strategies and are commonly employed in the treatment of intractable FC10_{. More invasive surgical interventions include colonic resection and}

diver-sion of the colon via an ostomy, either an ileostomy or a colostomy10,11_{. In their}

recent systematic review, Siminas et al. concluded that the evidence to support surgical interventions for intractable FC in children is mostly of low quality10_.

Siminas et al. provided a comprehensive overview of the literature and showed that there is no consensus regarding the diagnostic-work up that is required for surgical decision-making10_{. Therefore, the aim of this study was to assess}

the diagnostic and therapeutic approach of pediatric surgeons and pediatric gastroenterologists towards pediatric patients with intractable FC.

MATERIAL & METHODS

We developed a survey and administered it to physicians attending the 2015 Pediatric Colorectal, Motility and Pelvic Reconstruction Conference, held simultaneously in Columbus, Ohio (USA) and Nijmegen (the Netherlands) in November 2015. In total, 265 physicians from diﬀerent specialties (pediatric and adult surgery, gastroenterology, urology and radiology) attended the confer-ence at both locations; 147 in Columbus and 118 in Nijmegen. In Columbus, the attendees included 71 physicians from pediatric surgery (36 faculty members, 35 fellows/residents) and 29 from pediatric gastroenterology (21 faculty members, 8 fellows/residents). In Nijmegen, the distribution of physicians according to their specialties was unknown (89 faculty members, 29 fellows/residents). The questionnaire involved 19 multiple choice questions on work experience, routine diagnostic workup in children with FC, use of nonpharmacological and phar-macological treatment for FC and use of surgery in intractable FC (Appendix). In addition, the survey included multiple choice questions on 4 theoretical cases of children with intractable FC; anorectal and colonic manometry results were given and responders were asked which surgical treatment they would choose. For each question, responders had the option to an open answer in case the multiple choice answers were insuﬀicient. For this study, only surveys answered by physicians from pediatric surgery and pediatric gastroenterology were included. The results are represented as percentages of the total number of responders unless otherwise specified.

(7)

RESULTS

The survey was completed by 74 physicians working in pediatric surgery or gastroenterology in 16 diﬀerent countries: 55 (74%) worked in pediatric surgery (29 faculty members, 23 fellows, 3 residents) and 19 (26%) in pediatric gastro-enterology (14 faculty members, 5 fellows). The experience of these physicians was reported as follows: 0–5 years (43%), 5–10 years (25%), 10–15 years (8%) and N15 years (25%). Results are presented separately for pediatric surgery (surgery) and pediatric gastroenterology (GI) in all tables.

Diagnostic work-up

Table 1 summarizes the data from the questions related to the diagnostic approach. Most responders utilized digital rectal examination in the evalua-tion of children with FC. Plain abdominal X-rays were obtained by the majority of physicians. In total, 62/69 of responders who used plain abdominal X-rays did not use a scoring system (e.g., Barr, Leech or Blethyn (12)) to score the radiographs. Colonic transit studies were used infrequently, whereas the use of contrast enemas was reported to be more common.

Anorectal manometry

Anorectal manometrywas used routinely by 15 responders while 37 responders used it occasionally (Table 1). These responders (n=52) utilized this test to rule out Hirschsprung’s disease (65%; 83% in GI and 56% in surgery), to diagnose anal achalasia (58%; 78% in GI and 47% in surgery), to detect dyssynergia (56%; 67% in GI and 50% in surgery), to assess sphincter integrity (50%; 50% in GI and 50% in surgery) and for guidance prior to possible pelvic floor surgery (27%; 22% in GI and 29% in surgery). Out of the 52 physicians utilizing anorectal manometry, 52% (67% in GI and 44% in surgery) would consider anal sphincter botulinum toxin injections for anal achalasia and 21% (28% in GI and 18% in surgery) would use it to treat dyssynergia.

Colonic manometry

Colonic manometry was used routinely by 8 and occasionally by 20 responders (Table 1). Among these responders (n = 28), 61% (91% in GI and 41% in surgery) employed it to diﬀerentiate neuropathic from myopathic dysmotility, 57% (64% in GI and 53% in surgery) to guide surgical decision-making, 54% (55% in GI and 53% in surgery) to diﬀerentiate an underlying organic disease from a functional disorder and 36% (73% in GI and 12% in surgery) to assess disease severity.

(8)

Table 1 Diagnostic tools and frequency of use: n (%). Total number of

responders: 74

Routinely Occasionally Never Not

available Missing Digital rectal examination 50 (68) 21 (28) 1 (1) - 2 (3)

GI 12 (63) 7 (37) 0 - 0 surgery 38 (69) 14 (26) 1 (2) - 2 (4) Abdominal X-ray (plain) 40 (54) 29 (39) 5 (7) 0 0

GI 5 (26) 12 (63) 2 (11) 0 0 surgery 35 (64) 17 (31) 3 (6) 0 0 CTT (radiopaque markers) 10 (14) 36 (49) 19 (26) 5 (7) 4 (5) GI 1 (5) 16 (84) 2 (11) 0 0 surgery 9 (16) 20 (36) 17 (31) 5 (9) 4 (7) CTT (scintigraphy) 2 (3) 7 (10) 37 (50) 20 (27) 8 (11) GI 0 2 (11) 13 (68) 4 (21) 0 surgery 2 (4) 5 (9) 24 (44) 16 (29) 8 (15) Anorectal manometry 15 (20) 37 (50) 11 (15) 10 (14) 1 (1) GI 4 (21) 14 (74) 0 1 (5) 0 surgery 11 (20) 23 (42) 11 (20) 9 (16) 1 (2) Colonic manometry 8 (11) 20 (27) 22 (30) 18 (24) 6 (8) GI 3 (16) 8 (42) 4 (21) 4 (21) 0 surgery 5 (9) 12 (22) 18 (33) 14 (26) 6 (11) Contrast enema 26 (35) 38 (51) 7 (10) 1 (1) 2 (3) GI 2 (11) 15 (79) 2 (11) 0 0 surgery 24 (44) 23 (42) 5 (9) 1 (2) 2 (4) Defecography 5 (7) 28 (38) 24 (32) 12 (16) 5 (7) GI 0 5 (26) 10 (53) 4 (21) 0 surgery 5 (9) 23 (42) 14 (26) 8 (15) 5 (9) Transabdominal ultrasound 7 (10) 18 (24) 37 (50) 5 (7) 7 (10) GI 0 1 (5) 16 (84) 2 (11) 0 surgery 7 (13) 17 (31) 21 (38) 3 (6) 7 (13) Transrectal ultrasound 0 10 (14) 37 (50) 10 (14) 17 (23) GI 0 1 (5) 13 (68) 3 (16) 2 (11) surgery 0 9 (16) 24 (44) 7 (13) 15 (27) CTT, colonic transit time; GI, gastroenterology. The boldface entries represent the total number of responders who preferred a certain treatment for the specific case.

(9)

Non-pharmacological treatment n (%)1 _{Pharmacological treatment} _{n (%)}2

Bowel diary GI Surgery 52 (70) 13 (68) 39 (71)

Osmotic laxatives (e.g. PEG) GI Surgery 65 (88) 19 (100) 46 (84) Reward system GI Surgery 27 (37) 14 (74) 13 (24)

Stimulant laxatives (e.g. bisacodyl) GI Surgery 57 (77) 18 (95) 39 (71) Toilet program GI Surgery 56 (76) 19 (100) 37 (67) Lubricants GI Surgery 25 (34) 8 (42) 17 (31) Dietarty advice GI Surgery 61 (82) 11 (58) 50 (91)

Serotonergic drugs (e.g. prucalopride) GI Surgery 1 (1) 1 (5) 0 Referral psychology GI Surgery 31 (42) 13 (68) 18 (33)

Prosecretory drugs (e.g. lubiprostone) GI Surgery 8 (11) 7 (37) 1 (2) Biofeedback GI Surgery 23 (32) 4 (21) 20 (36) Enemas GI Surgery 53 (72) 12 (63) 41 (75) Pre-, pro-, synbiotics

GI Surgery

13 (18) 1 (5) 12 (22) Transanal irrigation (e.g. Peristeen)

GI Surgery

30 (41) 4 (21) 26 (47) Transcutaneous electrical nerve

stimulation3 GI Surgery 1 (1) 1 (5) 0

GI: gastroenterology; PEG: polyethylene glycol. The boldface entries represent the total number of responders who preferred a certain treatment for the specific case. 1_{1 missing value for all}

non-phar-macological answers (surgery). 2_{4 missing values for all pharmacological answers (all surgery).}3 _This

answer was not provided on the questionnaire, it was added by a responder.

Table 2 Non-pharmacological and pharmacological treatments and

(10)

Table 3 Answers to case-based questions by 28 responders using AMAN and

CM (11 from GI, 17 from surgery); n (%). Responders were asked to select their preferred initial treatment based on the case.

CASE 1 CASE 2 CASE 3 CASE 4

A M A N : no rm al CM : no rm al A M A N : ab se nt R A IR 1 CM : no rm al AM AN : hi gh R P CM : no rm al A M A N : no rm al C M : ab no rm al 2

Anal botulinum toxin injections 2 (7) 13 (46) 18 (64) 0 GI 1 (9) 7 (64) 9 (82) 0 surgery 1 (6) 6 (35) 9 (53) 0 Anal sphincter myectomy 0 1 (4) 1 (4) 1 (4)

GI 0 0 0 0

surgery 0 1 (6) 1 (6) 1 (6) Anal dilation 2 (7) 1 (4) 3 (11) 0

GI 1 (9) 1 (9) 1 (9) 0 surgery 1 (6) 0 2 (12) 0 Antegrade continence enemas 17 (61) 4 (14) 0 12 (43)

GI 9 (82) 2 (18) 0 6 (55) surgery 8 (47) 2 (12) 0 6 (35) Sacral nerve stimulation 1 (4) 2 (7) 0 1 (4)

GI 0 0 0 1 (9) surgery 1 (6) 2 (12) 0 0 Diverting ileostomy 1 (4) 0 0 0

GI 0 0 0 0

surgery 1 (6) 0 0 0 (Segmental) colonic resection 0 0 0 3 (11)

GI 0 0 0 1 (9) surgery 0 0 0 2 (12) Colostomy 0 0 0 1 (4) GI 0 0 0 1 (9) surgery 0 0 0 0 Ileo-anal anastomosis 0 0 0 0 GI 0 0 0 0 surgery 0 0 0 0 I don’t know 3 (11) 4 (14) 2 (7) 5 (18) GI 0 0 0 0 surgery 3 (18) 4 (24) 2 (12) 5 (29) Missing 2 (7) 3 (11) 4 (14) 5 (18) GI 0 1 (9) 1 (9) 2 (18) surgery 2 (12) 2 (12) 3 (18) 3 (18)

(11)

Non-pharmacological and pharmacological treatment

The non-pharmacological and pharmacological approach towards children with FC among responders is shown in Table 2.Most commonly employed non-pharmacological interventions included a bowel diary (70%), a toilet program (76%) and dietary advice (82%). Osmotic laxatives (88%), stimulant laxatives (77%) and enemas (72%) were the most commonly used pharmaco-logical treatments.

Case-based questions

The case-based questions (Attachment 1) resulted in a variety of approaches among the 28 responders (16 faculty, 11 fellows and 1 resident) who reported using both anorectal manometry and colonic manometry. For each case, responders were asked to choose their initial therapeutic option for a child with intractable FC and specific manometry findings. The first case was a child who had normal colonic and anorectal manometry. The second case had an absent rectoanal inhibitory reflex (RAIR) on anorectal manometry in the pres-ence of normal rectal biopsy results and a normal colonic manometry. The third case had a high anal canal resting pressure on anorectal manometry and a normal colonic manometry. The fourth case described a child who had a normal anorectal manometry and an abnormal colonic manometry showing absence of high amplitude propagating contractions in the colon distal to the transverse colon. The answers to these case-based questions are shown in Table 3. There was a considerable variety in the answers to each question. In the first case, the majority (61%) chose ACE. In the second and third case, most responders preferred anal botulinum toxin injections (respectively 46% and 64%). In the fourth case, ACE was selected most often (43%), although this question was also left unanswered by a considerable amount of responders (32%).

<< AMAN: anorectal manometry; CM: colonic manometry; GI: gastroenterology; RAIR: rectoanal inhibitory reflex; RP: resting pressure. The boldface entries represent the total number of responders who preferred a certain treatment for the specific case. 1_{Normal rectal biopsy.}2

(12)

DISCUSSION

Our survey results show that the diagnostic and therapeutic approach towards children with intractable FC diﬀers considerably even among physicians with interest and expertise in the fields of pediatric surgery and pediatric gastro-enterology. This emphasizes the need for more studies on this topic and the development of evidence-based guidelines for children who respond poorly to optimal pharmacological management. Furthermore, it is necessary to assess why the available guidelines are poorly adhered to, a problem that has been described before13,14_{, and how to improve guideline adherence.}

Diagnostic work-up

It has been reported that many physicians are reluctant to perform a digital rectal examination in children15_{. However, a digital rectal examination can}

provide valuable information on the presence of a rectal fecal mass (one of the six diagnostic Rome III criteria for FC) and be helpful in the assessment of anorectal sensation and sphincter tone16-18 _{. Among the responders of this}

survey, the vast majority of physicians performed digital rectal examination routinely or occasionally. This result may be related to the fact that the majority of responders worked in pediatric surgery, where patients are often referred for suspected anatomical problems and with severe long-lasting symptoms, which makes it essential to rule out organic causes of constipation. An interesting finding was that the vast majority of responders (93%) used abdominal X-rays either routinely or occasionally. Multiple studies have shown that there is insuf-ficient evidence to support the use of plain abdominal X-rays as a diagnostic tool in children with functional defecation disorders 1,12,19-22_{. There is no clear}

association between clinical symptoms of constipation and fecal loading as determined by abdominal X-ray22,23_{. Moreover, the sensitivity and specificity of}

the diﬀerent scoring systems used to evaluate fecal loading based on abdom-inal X-rays (Barr, Leech, Blethyn) are unsatisfactory, with low inter- and intraob-server reliability22_{. The finding that none of these scoring systems was used by}

the responders is likely a consequence of the low reliability of this diagnostic tool in clinical practice. However, if this modality is to have clinical value, a novel reliable and objective method for evaluation is needed, since the lack of a standardized method to assess these radiologic images may lead to inaccuracy and substantial diﬀerences in interpretation. In this survey, contrast enemas were commonly used in the diagnostic work-up of children with FC. Although contrast enemas are not a valid alternative to rectal biopsy or anorectal manometry to exclude or diagnose Hirschsprung’s disease1_{, they can}

(13)

be helpful to identify anatomical abnormalities in children with constipation (e.g., megarectum or megasigmoid). It has been postulated that development of these abnormalities may make FC particularly diﬀicult to treat and that patients with significant dilation of the distal colon may benefit from surgery24_.

Non-pharmacological and pharmacological treatment

The non-pharmacological treatments used by our responders usually consisted of a toilet program (behavioral intervention) and a bowel diary, in compliance with the ESPGHAN NASPGHAN recommendations1_{. Although use of a reward}

system has been shown to improve therapy compliance, this measure was only used by a minority of responders25_{. Furthermore, pre-, pro- or synbiotics were}

used as a non-pharmacological intervention by one-fifth of responders. This is surprising, since there is insuﬀicient evidence to support this practice26_{. The}

pharmacological management of FC mainly consisted of osmotic laxatives, stimulant laxatives and enemas, in agreement with the ESPGHAN-NASPGHAN guidelines1_{. The regular use of enemas is not recommended in these guidelines,}

but these guidelines were developed for FC in general, and do not address intractable FC specifically. Prosecretory agents (e.g., lubiprostone and lina-clotide) were also reported to be used by a substantial amount of responders despite the fact that neither has been tested and approved for use in children yet. It could be that a large proportion of these children with severe symptoms participate in clinical trials, as lubiprostone is currently being investigated in a multicenter randomized controlled trial, or it could be that these medications are being prescribed oﬀ-label to patients who have failed conventional phar-macological management.

Anorectal manometry and surgery

Anorectal manometry is most commonly used to diﬀerentiate between FC and Hirschsprung’s disease, but it is also useful in detecting anal achalasia and dyssynergia27_{. In cases of intractable FC with abnormal anal sphincter pressure}

or function (after Hirschsprung’s disease had been ruled out), most responding physicians opted for intra-anal botulinum toxin injections. Several studies, both retrospective and prospective, have shown that injection of botulinum toxin into the internal anal sphincter can be an eﬀective treatment for these patients28-31_.

Although less commonly described, there have also been reports of successful outcomes after injection of botulinum toxin into the external anal sphincter32,33_.

Botulinum toxin causes a temporary chemical paralysis of smooth and striated muscle fibers by blocking the release of acetylcholine from neurons. The eﬀect of botulinum toxin usually lasts for 3 to 6 months and, if necessary, repeated

(14)

injections can be administered after the initial effect wears off. Other common answers to this case-based question included anal dilation and anal sphincter myectomy. Unlike botulinum toxin injections, these procedures usually have a permanent effect. The major risk of these two procedures is that the basal pressure of the anal sphincter can be weakened to the point of causing fecal incontinence. Therefore, in cases of intractable FC with high sphincter pressure or a non-relaxing sphincter, after ruling out Hirschsprung’s disease, it seems sensible to opt for internal anal sphincter botulinum injections. Subsequent symptomatic improvement would confirm that the anal sphincter dysfunction is contributing to the problem. There have been reports of symptom improvement after botulinum toxin injections lasting longer than 6 months28,31_{, which suggests}

that the pathophysiology of the nonrelaxing anal sphincter is complex and that breaking the vicious cycle of painful defecation and withholding behavior could be an important additional benefit of this treatment.

Colonic manometry and surgery

The responses to our case-based questions highlight the complexity of ther-apeutic decision making and the broad variance in interpretation of colonic manometry results with regards to the surgical management of intractable FC. Colonic manometry is used to diﬀerentiate between myopathic and neuro-pathic motility disorders and to identify dysmotile colonic segments amenable for surgery27,34,35_{. Dysmotility of the colon is usually defined by the absence}

of high amplitude propagating contractions (HAPCs) and in severe cases this abnormality can be used to justify a total or partial colonic resection and/ or diversion of the dysmotile colonic segment by means of an ostomy11,36-38_.

However, it has also been shown that findings of dysmotility are potentially reversible and that motility as measured by colonic manometry can improve after decompression of the colon36-38_{. An improvement in colonic motility has}

also been demonstrated to occur in patients after using ACE39_{. This suggests}

that colonic dysmotility may not only contribute to the severity of the consti-pation but may also be a consequence of long-standing consticonsti-pation, possibly because of fecal stasis and colonic distension which in turn may lead to suboptimal motor function. Although total or partial colonic resection may lead to symptom improvement40_{, it has never been investigated whether this}

is necessary or if temporary decompression through diversion alone might be equally eﬀective. Furthermore, with the development of high-resolution colonic manometry, there is an increasing body of evidence suggesting that colonic dysmotility is more complex than just an evaluation of the presence and morphology of HAPCs and that there are other motor abnormalities that may

(15)

be of clinical importance27,41_{. Future studies are needed to further evaluate the}

utility of high-resolution colonic manometry in surgical decision-making in the management of children with intractable FC.

Limitations

This survey was intended to acquire more information on the current diagnostic and therapeutic approach towards children with FC, especially with regard to manometry and surgical interventions, and was therefore administered to physicians from both pediatric surgery and pediatric gastroenterology. Since the questionnaire was administered during a conference, it was kept brief to increase the response rate. Although we tried to be comprehensive, it would have been interesting to obtain more detailed information (e.g., regarding the specific dietary advice given or the maximum dosage of medication used). In addition, it would have been interesting to explore why physicians chose certain answers. To assess this, an interview-based study would be necessary. Furthermore, this survey was administered to physicians attending a confer-ence on colorectal diseases and disorders, likely representing physicians with a special interest in this topic. It is unknown whether this sample is a fair repre-sentation of pediatric surgeons and gastroenterologists in general. However, since manometry and surgery in the management of intractable FC are usually performed in specialized centers and by specialized physicians, we assume that this is a reliable representation of the population that we wanted to study and in fact may even underestimate the inconsistencies that exist in clin-ical practice. Additionally, our study is at risk for selection bias. We could not specify the specialty of the physicians attending the conference in Nijmegen (the Netherlands), therefore we were unable to provide an exact response rate. However, if all physicians attending the conference in Nijmegen were from pediatric surgery or gastroenterology, the response rate for this survey would have been 74/(100 + 118) = 31%. If the distribution of physicians in Nijmegen was similar to that in Columbus (68% of attending physicians from pediatric surgery/ gastroenterology), the response rate would have been 74/(100 +(0.68*118)) =41%. Finally, the group of responders consisted of staﬀ members and fellows. It is possible that the fellows were less experienced in the field of motility studies, which may have influenced the results. However, for each question responders could indicate if they did not know the answer or if the question

was not applicable to them. Therefore, we assume that responders who answered the questions indeed gave answers that reflect their true personal approach.

(16)

CONCLUSION

Surgical decision-making for children with intractable FC diﬀers among physi-cians worldwide. Anorectal and colonic manometry are often used to guide surgical decision making. However, since there are no guidelines for surgical management of FC in children, the application and interpretation of manom-etry vary among physicians, resulting in diﬀerent surgical approaches. This survey demonstrates the need for clinical guidelines regarding the role of anorectal and colonic manometry in surgical decision-making in children with intractable FC.

Acknowledgements

(17)

REFERENCES

1 Tabbers MM, DiLorenzo C, Berger MY, et al.

Evaluation and treatment of functional consti-pation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr 2014;58:258–74.

2 Tabbers MM, Boluyt N, BergerMY, et al. Clinical

practice: Diagnosis and treatment of functional constipation. Eur J Pediatr 2011;170:955–63.

3 Mugie SM, Benninga MA, Di Lorenzo C.

Epidemiology of constipation in children and adults: A systematic review. Best Pract Res Clin Gastroenterol 2011;25:3–18.

4 Bongers MEJ, vanWijk MP, Reitsma JB, et al.

Long-term prognosis for childhood constipa-tion: Clinical outcomes in adulthood. Pediat-rics 2010;126:e156–62.

5 Choung RS, Shah ND, Chitkara D, et al. Direct

medical costs of constipation from childhood to early adulthood: A population-based birth cohort study. J Pediatr Gastroenterol Nutr 2011;52:47–54.

6 Liem O, Harman J, BenningaM, et al. Health

utilization and cost impact of childhood constipation in the United States. J Pediatr 2009;154:258–62.

7 Belsey J, Greenfield S, Candy D, et al.

System-atic review: Impact of constipation on quality of life in adults and children. Aliment Phar-macol Ther 2010;31:938–49.

8 van den Berg MM, Hogan M, Caniano DA, et

al. Colonic manometry as predictor of cecos-tomy success in children with defecation disor-ders. J Pediatr Surg 2006;41: 730–6 [discussion 730–6].

9 Pensabene L, Youssef NN, Griﬀiths JM, et al.

Colonic manometry in children with defeca-tory disorders. Role in diagnosis and manage-ment. Am J Gastroenterol 2003;98:1052–7.

10 Siminas S, Losty PD. Current Surgical

Manage-ment of Pediatric Idiopathic Constipation: A systematic review of published studies. Ann Surg 2015;262:925–33.

11 Youssef NN, Pensabene L, Barksdale E, et al. Is

there a role for surgery beyond colonic agan-glionosis and anorectal malformations in chil-dren with intractable constipation? J Pediatr Surg 2004;39:73–7.

12 Berger MY, Tabbers MM, Kurver MJ, et al. Value

of abdominal radiography, colonictransit time, and rectal ultrasound scanning in the diag-nosis of idiopathic constipation in children: A systematic review. J Pediatr 2012;161:44–50.e1–2.

13 Yang CH, Punati J. Practice patterns of

pedi-atricians and trainees for the management of functional constipation compared with 2006 NASPGHAN guidelines. J Pediatr Gastroenterol Nutr 2015;60:308–11.

14 HasosahM, Telmesani A, Al-Binali A, et al.

Knowledge and practice styles of pedia-tricians in Saudi Arabia regarding child-hood constipation. J Pediatr Gastroenterol Nutr2013;57:85–92.

15 Safder S, Rewalt M, Elitsur Y. Digital rectal

examination and the primary care physicians: A lost art? Clin Pediatr (Phila) 2006;45:411–4.

16 Burgers R, de Jong TPVM, Benninga MA. Rectal

examination in children: Digital versus trans-abdominal ultrasound. J Urol 2013;190:667–72.

17 Soh JS, Lee HJ, Jung KW, et al. The

diag-nostic value of a digital rectal examination compared with high-resolution anorectal manometry in patients with chronic constipa-tion and fecal incontinence. Am J Gastroen-terol 2015;110:1197–204.

18 Tantiphlachiva K, Rao P, Attaluri A, et al.

Digital rectal examination is a useful tool for identifying patients with dyssynergia. Clin Gastroenterol Hepatol 2010;8:955–60.

19 Moylan S, Armstrong J, Diaz-Saldano D, et

al. Are abdominal x-rays a reliable way to assess for constipation? J Urol 2010;184:1692–8.

20 Pensabene L, Buonomo C, Fishman L, et al.

Lack of utility of abdominal x-rays in the evaluation of children with constipation: Comparison of diﬀerent scoring methods. J

(18)

Pediatr Gastroenterol Nutr 2010;51:155–9.

21 Kokke FT, Sittig JS, de Bruijn A, et al. Starreveld

scoring method in diagnosing childhood constipation. Pediatr Radiol 2010;40:1789–93.

22 Reuchlin-Vroklage LM, Bierma-Zeinstra S,

Benninga MA, et al. Diagnostic value of abdominal radiography in constipated chil-dren: A systematic review. Arch Pediatr Adolesc Med 2005;159:671–8.

23 Bongers MEJ, Voskuijl WP, van Rijn RR, et al.

The value of the abdominal radiograph in children with functional gastrointestinal disor-ders. Eur J Radiol 2006; 59:8–13.

24 Lee SL, DuBois JJ,Montes-Garces RG, et al.

Surgicalmanagement of chronic unremitting constipation and fecal incontinence associ-ated with megarectum: A preliminary report. J Pediatr Surg 2002;37:76–9.

25 Koppen IJN, Lammers LA, Benninga MA, et

al. Management of functional constipation in children: Therapy in practice. Paediatr Drugs 2015;17:349–60.

26 Tabbers MM, Benninga MA. Constipation in

children: Fibre and probiotics. BMJ Clin Evid 2015 [pii:0303].

27 Koppen IJN, Di Lorenzo C, Saps M, et al.

Childhood constipation: Finally something is moving! Expert Rev Gastroenterol Hepatol 2016;10:141–55.

28 Chumpitazi BP, Fishman SJ, Nurko S.

Long-ter-mclinical outcome after botulinumtoxin injec-tion in children with nonrelaxing internal anal sphincter. Am J Gastroenterol 2009;104:976– 83.

29 Irani K, Rodriguez L, Doody DP, et al.

Botu-linum toxin for the treatment of chronic consti-pation in children with internal anal sphincter dysfunction. Pediatr Surg Int 2008;24:779–83.

30 Keshtgar AS, Ward HC, Sanei A, et al. Botulinum

toxin, a new treatment modality for chronic idiopathic constipation in children: Long-term follow-up of a double-blind randomized trial. J Pediatr Surg 2007;42:672–80.

31 Basson S, Charlesworth P, Healy C, et al.

Botulinum toxin use in paediatric colorectal

surgery. Pediatr Surg Int 2014;30:833–8.

32 Ahmadi J, Azary S, Ashjaei B, et al.

Intras-phincteric botulinum toxin injection in treat-ment of chronic idiopathic constipation in children. Iran J Pediatr 2013; 23:574–8.

33 Keshtgar AS,Ward HC, Clayden GS.

Trans-cutaneous needle-free injection of botu-linum toxin: A novel treatment of childhood constipation and anal fissure. J Pediatr Surg 2009;44:1791–8.

34 Giorgio V, Borrelli O, Smith VV, et al.

High-res-olution colonic manometry accurately predicts colonic neuromuscular pathological phenotype in pediatric slow transit constipa-tion. Neurogastroenterol Motil 2013;25:70–8.

35 Di Lorenzo C, Flores AF, Reddy SN, et al.

Use of colonic manometry to diﬀerentiate causes of intractable constipation in children. J Pediatr 1992;120:690–5.

36 Villarreal J, Sood M, Zangen T, et al. Colonic

diversion for intractable constipation in chil-dren: Colonic manometry helps guide clin-ical decisions. J Pediatr Gastroenterol Nutr 2001;33:588–91.

37 Christison-Lagay ER, Rodriguez L, Kurtz M, et

al. Antegrade colonic enemas and intestinal diversion are highly eﬀective in the manage-ment of children with intractable constipa-tion. J Pediatr Surg 2010;45:213–9 [discussion 219].

38 Martin MJ, Steele SR, Noel JM, et al. Total

colonic manometry as a guide for surgical management of functional colonic obstruc-tion: Preliminary results. J Pediatr Surg 2001;36:1757–63.

39 Rodriguez L, Nurko S, Flores A. Factors

asso-ciated with successful decrease and discon-tinuation of antegrade continence enemas (ACE) in children with defecation disorders: A study evaluating the eﬀect of ACE on colon motility. Neurogastroenterol Motil 2013;25:140-e81.

40 Levitt MA, Peña A. Surgery and constipation:

When, how, yes, or no? J Pediatr Gastroen-terol Nutr 2005;41(Suppl. 1):S58–60.

(19)

41 Wessel S, Koppen IJ, Wiklendt L, Costa M,

Benninga MA, Dinning PG. Characterizing colonic motility in children with chronic intrac-table constipation: a look beyond high-am-plitude propagating sequences. Neurogas-troenterol Motil 2016;28:743–57.

(20)

Attachment 1 Questionnaire 2015

Pediatric Colorectal, Motility and Pelvic Reconstruction Conference

QUESTIONS ON WORK EXPERIENCE 1) I work in:

pediatric surgery pediatric gastroenterology pediatric urology

adult surgery adult gastroenterology adult urology

2) I work as a:

faculty member fellow resident nurse other: _________

3) Years of experience:

0-5 5-10 10-15 >15

4) I work in: the Netherlands other country:______________________

5) I am involved in the treatment of pediatric patients with (please check all that apply):

constipation fecal incontinence I don’t treat children

6) I define functional constipation in children as:

defecation freq. < 3x/week defecation freq. <3x/week and hard/painful stools

Rome II criteria Rome III criteria other: _______________________________

7) In the diagnostic workup of children with functional constipation I use the following:

Routinely Occasionally Never Not available to me

Digital rectal examination

Abdominal X-ray (plain)

Colonic transit time (marker study) Colonic transit time (scintigraphy) Anorectal manometry Colonic manometry Contrast enema Defecography Transabdominal ultrasound of rectum Transrectal ultrasound

(21)

8) If I use plain abdominal X-rays to assess fecal load in children with constipation I use this scoring system (check all that apply):

Barr Leech Blethyn I use plain abdominal X-rays,

I don’t use plain abdominal X-rays but I don’t use a scoring system

other:_________________________________ not applicable/I don’t know

9) I use anorectal manometry in cchildren with constipation for the following reason(s) (check all that apply):

to rule out Hirschsprung’s disease to diagnose Hirschsprung’s disease

to detect dyssynergia to diagnose anal achalasia

to assess anal sphincter integrity to guide pelvic floor surgery decision-making

I never use anorectal manometry other:_________________________________

not applicable/I don’t know

10) I use colonic manometry in children with constipation for the following reason(s) (check all that apply):

to assess disease severity to diﬀerentiate functional from organic forms of constipation

to guide surgical decision-making to diﬀerentiate between neurogenic/myogenic dysmotility

I never use colonic manometry not applicable/I don’t know

other:_________________________________

11) In the non-pharmacological treatment of children with functional constipation I use the following (check all that apply):

bowel diary reward system toilet program dietary advice

referral to psychology (e.g. behavioral therapy) biofeedback

pre-/pro-/synbiotics transanal irrigation (e.g. Peristeen)

not applicable/I don’t know other:_________________________________

12) In the pharmacological treatment of children with functional constipation I routinely use the following (check all that apply):

osmotic laxatives (e.g. PEG/lactulose) stimulant laxatives (e.g. bisacodyl/senna) lubricants (e.g. mineral oil)

serotonergic drugs (e.g. prucalopride)

prosecretory drugs (e.g. linaclotide/lubiprostone) enemas

(22)

13) I usually try the following treatments, before I consider surgery in children with functional constipation (check all that apply):

osmotic laxatives stimulant laxatives Inovel laxatives (serotonergic/prosecretory agents) system intensive cleanouts (transanal irrigation/regular enemas)

I never consider surgery for functional constipation

other:_______________________________________ not applicable/I don’t know

14) In the surgical treatment of children with functional constipation over the past 5 years I used the following (check all that apply):

anal botox injections anal sphincter myectomy

anal dilatation antegrade continence enemas (ACE)

sacral neurostimulation diverting ileostomy

(segmental) colonic resection colostomy

ileo-anal anastomosis other:____________________________________

15) I consider anal botox injections in children with functional constipation and (check all that apply): severe symptoms, regardless of diagnostic assessment

young age (<4 years), regardless of diagnostic assessment signs of outlet obstruction (e.g. markers in rectum during CTT) dyssynergia at anorectal manometry

high resting pressure at anorectal manometry

anal achalasia other:____________________________________

17) For a child with functional constipation refractory to medications who has a normal anorectal and a normal colonic manometry, my initial surgical treatment would be (check one option):

sacral neurostimulation diverting ileostomy

(segmental) colonic resection colostomy

ileo-anal anastomosis other:________________________________

(23)

18) For a child with functional constipation refractory to medications who has an absent recto-anal inhibitory reflex on anorectal manometry but with normal rectal biopsy and a normal colonic manometry, my initial treatment would be (check one option):

anal botox injections anal sphincter myectomy anal dilatation

antegrade continence enemas (ACE) sacral neurostimulation

diverting ileostomy (segmental) colonic resection

colostomy ileo-anal anastomosis

19) For a child with functional constipation refractory to medications who has a high anal canal resting pressure on anorectal manometry and a normal colonic manometry, my initial treatment would be (check one option):

sacral neurostimulation diverting ileostomy (segmental) colonic resection

other:________________________________ not applicable/I don’t know

20) For a child with functional constipation refractory to medications who has a normal anorectal manometry and an abnormal colonic manometry showing absence of high amplitude propagating contractions (HAPCs) of the left colon, my initial treatment would be (check one option):

anal botox injections anal sphincter myectomy anal dilatation

antegrade continence enemas (ACE) sacral neurostimulation

diverting ileostomy (segmental) colonic resection

other:________________________________ not applicable/I don’t know