Childhood constipation, a real problem..? Marc Benninga, Emma Children s Hospital, AMC, Amsterdam, the Netherlands

Constipation

0-10% >10-20% >20-30% >30-40% Mugie SM, et al. Best Pract & Res Clin Gastroenterol 2011

Functional constipation Must include one month of at least two of the following in infants up to 4 years of age, children and adolescents: 1. Two or fewer defecations per week 2. History of excessive stool retention 3. History of painful or hard bowel movements 4. History of large diameter stools which may obstruct the toilet 5. Presence of a large fecal mass in the rectum In toilet trained children the following additional criteria may be used 6. At least 1 episode/week of incontinence after the acquisition of toileting skills 7. History of large diameter stools which may obstruct the toilet Benninga MA, et al. Gastroenterology 2016, Hyams JS, et al. Gastroenterology 2016

Behavior Mechanisms of Constipation Abuse Nerves, muscles, ICCs + Stress Food Genetics Sensation

Tabbers MM, et al. JPGN 2014

14 yr old girl referred because of fecal incontinence despite intensive laxative treatment

Medical history Meconium production unknown? Toilet trained around 3rd yr of age Since the age of 4 yrs fecal incontinence Visited general practitioner at 11 yrs of age! Referral general pediatrician Toilet training Laxatives (PEG, Lactulose), bisacodyl Biofeedback Complementary medicine

Emma Children s hospital Never defecates at the toilet > 5x/day loss of stools in her underwear No urge to defecate No withholding behavior Abdominal pain No other symptoms Good appetite (fiber and fluid intake sufficient)

SHx Highschool No bullying, no sexual/physical abuse Plays soccer Family history Sister with constipationobstipatie

Physical examination Abdomen: No palpable mass No dimple or anal wink Perianal feces, no hemorroïds or fissures Rectaal examination: normal sphincter tone, normal sphincter contraction, ampulla filled with soft fecal material, no palpable mass

Treatment pyramid for FC in children Ostomy +/- resection SNS? TES? Regular enemas/transanal irrigation/ace Novel therapeutic agents (ongoing trials) Second line pharmacological treatment (stimulants) Osmotic laxatives (PEG, Lactulose), CBT, Biofeedback Education, toilet program, reward system, bowel diary

Algorithm of fecal incontinence 10% 90% Rajindrajith S, et al. Aliment Pharmacol Ther 2013

Algorithm of functional fecal incontinence 10% 90% Rajindrajith S, et al. Aliment Pharmacol Ther 2013

Total colonic transit time 129 hours Distended rectum

Treatment pyramid for FC in children Ostomy +/- resection SNS? TES? Regular enemas/transanal irrigation/ace Novel therapeutic agents (ongoing trials) Second line pharmacological treatment (stimulants) Osmotic laxatives (PEG, Lactulose) Education, toilet program, reward system, bowel diary

Double blind placebo controlled trial Screened N = 304 89 excluded Randomized Randomized 1 early withdrawal Prucalopride n = 107 Full analysis/safety set a Placebo n = 108 Full analysis/safety set a 1 early withdrawal 10 early withdrawals Prucalopride n = 106 Completed treatment Placebo n = 107 Completed treatment 6 early withdrawals Prucalopride n = 96 Prucalopride n = 101 a Full analysis set and Safety set were the same for this study. All analyses use this population.

Primary endpoint: 3 SBMs/week AND 1 FI per 2 weeks over weeks 5 8 p = 0.90 Mugie SM, et al. Gastroenterology 2015

The Role of Chloride Channels in Intestinal Transport Lubiprostone is a bicyclic functional fatty acid Selectively activates chloride channel-2 (CIC-2) Enhance intestinal fluid secretion Facilitate increased motility FDA approved in January 2006 Lubiprostone

An Open-Label, Multicenter, Safety and Effectiveness Study of Lubiprostone for the Treatment of Functional Constipation in Children 127 patients 12 kg, 17 years, and with <3 spontaneous BMs 4 wks, once 12μg twice daily, or 24 μg Hyman PE, et al. JPGN 2014

Percentage Enemas versus oral laxatives for children with chronic constipation: RCT 80 NS E 60 40 20 CT 0 3 6 9 12 Months Bongers M, et al. Clin Gastroenterol Hepatol. 2009

Peristeen (c) transanal irrigation system for pediatric fecal incontinence (N = 33) Peristeen (C) appears a safe and effective bowel management system Improves bowel function and QoL for FI as a result of functional constipation, Hirschsprung's disease, and anorectal malformations (53-83%) of children achieve social FI High parental satisfaction Nasher O, et al. Int J Pediatr 2014 Pacilli M, et al. J Pediatr Surg 2014 Koppen IJ, et al. JPGN 2016

Follow uptreatment After 7 months, despite daily colonic irrigation still fecal incontinence Microlax, bisacodyl

Follow up Colonic irrigation too much for her Discussed next steps Malone, sacral neuromodulation She wants to get it over and done with, take my colon out!

Sacral nerve stimulation for chronic constipation

Colonic respons to sacral nerve stimulation in constipation Mid ascending colon SNS Splenic flexure sigmoid colon 60min Dinning P, et al. Br J Surg 2012

Uncoordinated motor patterns in descending colon after the meal

Colonic response to bisacodyl

Sacral Neuromodulation Therapy: A Promising Treatment for Adolescents With Refractory Functional Constipation 33 patients, 32 girls 3 patients no effect, electrode removed Median follow up 12.6 months (12.2 26.1) Re-operation in 12 patients Dislocation electrode Pain No success in 11 patients of whom 4 received an ileostoma Van Wunnik B, et al. Dis Colon Rect 2012 De Wilt A, et al. Dis Colon Rect 2016

So now you tried everything. Something has to happen now.

Dilemmas Which diagnostic tests? If and when to do a Malone? Colostoma or ileostoma? When to remove the stoma? Resection (colon, sigmoid)? Psychiatry? Factitious disorder?

Emma Children s Hospital Surgery for constipation (2011-2016 ) CHAIT 15 Ileostoma 33 (18 before colect) Subtotal colectomyt 19 Colostoma 12 Sigmoid resection 5 84 Wessel S, et al. Neurogastro Motil in press

Patient 12-2015 3-2016 Ileostomy Laparoscopic hand-assisted subtotal colectomy with ileorectal anastomosis Spontaneous defecation without leakage

Complications of surgical procedures 80% stoma problems; 40% revision Procedure failures : - CHAIT > colostomy or ileostomy - colostoma > some patients needed oral irrigation - high output stoma - subtotal colectomy and anastomosis > ileostoma Wessel S, et al. Neurogastro Motil in press

90 % parental satisfaction with the outcome of the surgical intervention!

Conclusions Functional constipation in childhood is a serious problem and should be taken seriously In a part of the children symptoms are long-lasting and are socially in acceptable and interfere with their daily activities Large RCT are necessary to evaluate the effect of different foods and new compounds in children with constipation Surgery should be reserved for selected cases only