Role of 3D high resolution anorectal manometry compared to conventional technique in management of constipation and fecal incontinence in children.

BACKGROUND: Anorectal manometry is a valuable tool for objective assessment of motility motor and sensory function of the anorectum. The aim of this study was to investigate role of water-perfused (WP) three dimensional high-resolution anorectal manometry (3D-HRARM) compared to WP conventional manometry (CM) in the management of chronic idiopathic constipation (CIC) and faecal incontinence (FI) in children. METHODS: This was a retrospective review of 122 consecutive children, who had WP 8-channel CM or 24 channel 3D-HRARM and endosonography under ketamine anaesthesia from September 2012 to February 2019. All patients had a validated symptom severity score questionnaire ranging from 0 (best) to 65 (worst). Mann-Whitney-U test and Spearman rank test were used and p<0.05 was considered significant. RESULTS: Subjects were divided according to investigation: CM group (n = 75) and 3D-HRAM (n = 47), who were otherwise comparable. Median anal resting pressure was 50 mmHg and rectoanal inhibitory reflex (RAIR) threshold volume was 10mls across the entire cohort. There were no significant differences in resting pressure or RAIR threshold when using conventional or 3D-HRARM. Rectal capacity was significantly higher in the CM group (p = 0.002). Rectal capacity and internal anal sphincter (IAS) thickness positively correlated with symptom severity, duration and patient age. 3D-HRARM provided a more detailed depiction of the anorectal pressure profile. Botulinum toxin was injected into the external anal sphincter (EAS) muscle (n = 75, 61%) and an anterograde colonic enema (ACE) stoma was needed subsequently in 19 (16%) to treat recurrent constipation and soiling symptoms. Rectal biopsy was done in 43(35%) patients, if RAIR was absent or inconclusive. CONCLUSION: CM and 3D-HRARM are comparable in terms of resting pressure and RAIR threshold. 3D-HRAM is safe and provides detailed functional morphology of anal sphincters and it is useful to understand underlying pathophysiology of constipation and faecal incontinence in children and plan further treatment. LEVEL OF EVIDENCE: Level I.

Long term outcome of antegrade colonic enema (ACE) stoma for treatment of constipation and fecal incontinence in children.

AIM: To determine the long term outcome of antegrade colonic enema (ACE) stoma for treatment of chronic constipation and soiling in children. METHOD: We reviewed patients prospectively who underwent formation of ACE stoma after failure of maximum medical treatment of chronic constipation and soiling from September 2008 to October 2020. All patients had anorectal manometry, endosonography and colonic transit study. A validated symptom severity (SS) score questionnaire was used pre operatively and during follow up. The sum of SS score ranged between 0 (best) and 65 (worst). Data was expressed as median(range) and Wilcoxon rank sum test was used and p value < 0.05 was considered significant. RESULTS: 58 patients had formation of ACE stoma, laparoscopic appendicostomy 56, cecostomy 1, and open procedure 1. The main indications for the ACE stoma were chronic functional constipation (FC) 50(86%), anorectal malformations (ARM) 6(11%) and Hirschsprung disease (HD) 2(3%). 41(71%) of patients had previous intrasphincteric botulinum toxin (BT) treatment. Age at operation was 11(range 4-15) years and follow up was 36(3-84) months. 47(81%) patients were continent of stool within three months postoperatively. The preoperative SS score improved from 34/65 (26-47) to 8/65 (4-12) at 12 months and 5/65 (2-11) at 24 months follow up, p ≤ 0.05. OVERALL: complication rate was 15(26%), wound infection 5, granulation tissue 4, stoma prolapse 4, retraction 1, abscess formation and fistula 1. 15 (26%) adolescents had transition of their care to adult services. CONCLUSION: There is a significant improvement of constipation, soiling and general health of patients following formation of ACE stoma. Adolescents benefits an orderly transition of their care to adult services. LEVEL OF EVIDENCE: Level 2, Therapeutic study.

Functional outcomes in Hirschsprung disease: A single institution's 12-year experience.

AIMS: Hirschsprung disease (HD) is a chronic condition associated with long-term morbidity. We assessed the short and long-term functional outcomes of operated patients in a single institution over a 12-year period. MATERIALS AND METHODS: We conducted a retrospective review of all children operated for HD between 2002 and 2014. Postoperative functional outcomes were assessed using the Rintala Bowel Function Score (BFS, 0-20, 20=best score). We assessed hospital admissions, complications including Hirschsprung associated enterocolitis (HAEC) and the need for further surgical procedures. RESULTS: 72 (52 male) patients were studied, of whom, 6 (8%) had a positive family history, 5 (7%) had Trisomy 21 and 5 (7%) had total colonic HD. The median age at diagnosis was 6.5days (2 days-6.7 years) and median follow-up was 6years (1-12years). All patients except two underwent a Duhamel pull-through procedure. The median age at surgery was 4months (6days-90months). 37 (51%) procedures were performed single-stage and 7 (10%) were laparoscopically assisted. Our early complication rate was 15%; 11 (15%) patients were treated for HAEC and 43 (60%) did not require any further surgery. 12 (17%) underwent injection of botulinum toxin, 7 (10%) needed residual spur division and 4 (5%) required an unplanned, post pull-through enterostomy for obstructive defecation symptoms and HAEC. Two (3%) patients underwent an Antegrade Colonic Enema (ACE) stoma. The median BFS was 17 (5-20). There were two deaths both out of hospital. CONCLUSIONS: Long-term functional outcomes following Duhamel Pull-Through surgery are satisfactory although 40% of patients needed some form of further surgical intervention. The management of anal sphincter achalasia has improved with the use of botulinum toxin and we advocate aggressive and early management of this condition for symptoms of obstructive defecation and HAEC. LEVEL OF EVIDENCE: III.

Pathophysiology of chronic childhood constipation: functional and morphological evaluation by anorectal manometry and endosonography and colonic transit study.

BACKGROUND: Chronic idiopathic constipation (IC) is a common problem in children. We hypothesised that hypertonicity and overactivity of the internal anal sphincter (IAS) contributed to childhood IC. METHOD: This was a prospective study of children who were admitted for investigation and treatment of chronic constipation at the gastrointestinal motility clinic in Guy's and St. Thomas' Hospital, NHS Foundation Trust, London. All children had a colonic transit marker study followed by anorectal manometry and anal endosonography under ketamine anesthesia. We used a validated symptom severity (SS) score questionnaire for assessment of constipation and fecal incontinence on admission to hospital and during follow-up for 12months. The SS score of 0 was the best and 65 the worst. RESULTS: Of 92 children, 57 were male and median (range) age was 8.46years (3.35-14.97). Duration of symptoms was 4.7years (0.3-13). Soiling was present in 88 (96%) patients, delay in defecation of once every 2 to 3days or less frequently in 86 (93%) and a palpable fecaloma (megarectum) on abdominal examination in 76 (83%). 42 children had 'fecal impaction' requiring disimpaction of stool from the rectum under general anesthesia and 50 had 'no impaction'. The median IAS resting pressure was within the normal range measuring 55mm Hg (25-107) and median amplitude and frequency of the IAS contractions were 10mm Hg (2.0-58) and 17cycles per min (5.0-34), respectively. The median IAS thickness was 0.93mm (0.5-2.0). There was no correlation between amplitude and frequency of anorectal contractions and anal sphincter resting pressure. The mean right colonic transit time was 8.55 (standard deviation ±13.22) h, left colonic transit time was 11.51h (±13.21), rectosigmoid transit time was 25.91h (±18.89) and total colonic transit time was 45.97h (±17.69). CONCLUSION: The anal sphincter resting pressure is normal in children with chronic IC. Increased frequency and amplitude of IAS contractions seen in these patients do not cause raised anal sphincter resting pressure or obstructive defecation. Further studies should be done to investigate the role of external anal sphincter dysfunction in pathophysiology of childhood constipation and fecal incontinence.

Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature.

Hepatobiliary scintigraphy is an important diagnostic modality for work-up of neonatal cholestasis. Therefore, our objective was to evaluate the literature regarding the accuracy of hepatobiliary scintigraphy in differentiating biliary atresia from non-biliary atresia causes of cholestasis (collectively called neonatal hepatitis). Our search included Medline, SCOPUS and Google Scholar. Only studies using Tc-99 m-labeled immunodiacetic acid (IDA) derivatives were included. Overall, 81 studies were included in the meta-analysis. Pooled sensitivity and specificity were 98.7% (range 98.1-99.2%) and 70.4% (range 68.5-72.2%), respectively. Factors that increased specificity included the use of radiotracers with high hepatic extraction, administration of hepatic-inducing drugs (such as phenobarbital), use of a calculated dose/kg and administration of a booster dose in cases of non-excretion of the tracer in the bowel. SPECT imaging and duodenal fluid sampling also had high specificity; however, they need further validation because of the low number of studies. Semiquantitative imaging methods do not seem to have any incremental value. We conclude that hepatobiliary scintigraphy using IDA derivatives can be very useful for diagnostic work-up of neonatal cholestasis. To improve the specificity, several measures can be followed regarding type and dose of the radiotracer and imaging protocols. Non-imaging methods seem to be promising and warrant further validation.

Outcome of peripherally inserted central venous catheters in surgical and medical neonates.

BACKGROUND/PURPOSE: Peripherally inserted central venous catheters (PICCs) are commonly used for neonatal vascular access. The aim of this study was to look at PICC line complication rates and possible predictors of PICC infection in a neonatal intensive care unit. METHOD: This was a prospective study of 226 neonates who had PICCs on our neonatal intensive care unit between January 2006 and June 2009. Complete data was available on 218 neonates who had 294 PICC lines. Criteria for catheter-related sepsis was positive blood cultures (peripheral/central) and/or a positive catheter tip culture after removal in the presence of a clinical suspicion of line sepsis. RESULTS: Of 218 neonates, 132 (169 lines) were medical, and 86 (125 lines) were surgical. Our PICC line infection rate was 17 infections per 1000 catheter-days. Surgical neonates had infection rates of 24.8% compared with 18.3% of medical neonates (P < .18). The odds ratio for a PICC infection was 3.1 (95% confidence interval, 1.64-5.87) if the catheter was in situ for 9 days or more, P < .01. Coagulase-negative staphylococcus was isolated from 55 (89%) of 62 blood cultures. CONCLUSIONS: Our PICC infection rate was 17 per 1000 catheter-days. The length of catheter stay was the only predictor of PICC infection.

Transcutaneous needle-free injection of botulinum toxin: a novel treatment of childhood constipation and anal fissure.

PURPOSE: Constipation is a common problem in children, and when it becomes chronic fecal impaction, overflow soiling and megarectum may develop. Children with chronic idiopathic constipation (IC) may not respond to conventional treatments of laxatives, enemas, and toilet training. The aims of the study were to evaluate the long-term outcome of transcutaneous needle-free injection of botulinum toxin (TNFBT) into the external anal sphincter (EAS) and to assess the extent of the toxin penetration into the sphincter. METHOD: Children were recruited if symptomatic with chronic constipation, soiling, painful defecation, and withholding behavior requiring disimpaction of stool and rectal biopsy under general anesthesia. A total dose of 200 U of botulinum toxin (BT) (Dysport; Ipsen Limited, Slough, United Kingdom) was injected transcutaneously into the EAS at 3 and 9-o'clock positions using J-tip needle-free syringes (National Medical Products Inc, Irvine, Calif). The depth and width of toxin penetration was assessed by endosonography. Outcome was measured by a validated symptom severity (SS) score questionnaire. The total SS score ranged between 0 (best) and 65 (worst). The outcome was compared with 31 children in a comparable historical control group at 3 and 12-month follow-up. RESULTS: Sixteen children were recruited with median age of 6.11 (range, 3-14.85) years and median duration of symptoms of 3.9 years (1.6-11.5). On endosonography, the median depth and width of BT penetration was 8 (7-10) mm and 8 (6-10) mm, respectively. At 3-month follow-up, the median SS score improved in all children after TNFBT from 32.50 (5-57) to 7.50 (0-26) (Wilcoxon's P < .0001). There were significant improvements in symptoms of constipation, soiling, painful defecation, general health and behavior, and fecal impaction of rectum (P < .05). Anal fissures healed in all 4 children. The SS score in the control group improved from 33 (12-49) to 15 (0-40) (P < .0001). At 12-month follow-up, the improvement of SS score in TNFBT group was significantly more than the control group as follows: 4 (0-25) vs 15 (0-51), respectively (Mann-Whitney U P < .002). Three patients had a second TNFBT injection for relapsed symptoms. There were no complications. The transcutaneous needle-free injection of botulinum toxin eliminates the risk of intravascular injection or needlestick injury. The transcutaneous needle-free injection of botulinum toxin also has other therapeutic applications including an alternative therapy to biofeedback training for dyssynergia of the EAS, treatment of muscle limb spasticity in cerebral palsy, and cosmetic treatment of overactive facial muscles and wrinkles and hyperhydrosis. CONCLUSION: Transcutaneous needle-free injection of botulinum toxin into the external anal sphincter is a novel and safe new treatment of chronic idiopathic constipation and anal fissure in children. A second injection may be required in 20% of patients.

Solitary rectal ulcer syndrome in children.

SRUS is a rare condition in children, which usually presents with a symptom complex of rectal bleeding, passage of mucus and straining on defecation, tenesmus, perineal and abdominal pain, sensation of incomplete defecation, constipation and rectal prolapse. The underlying etiology of SRUS is not fully understood but it is likely to be secondary to ischemic changes in the rectum associated with paradoxical contraction of pelvic floor and external anal sphincter muscles and rectal prolapse. Conservative measures like high intake of fluids and fibers, laxatives, biofeedback and behavior modification therapy may be beneficial for treatment of constipation. Excision of rectal ulcer and surgery of overt rectal prolapse, however, may be required in refractory cases not responding to conservative treatments. A therapeutic role for botulinum toxin injection into the external anal sphincter for treatment of SRUS associated with constipation and paradoxical contraction of pelvic floor and external anal sphincter muscles in children, may exist.

Botulinum toxin, a new treatment modality for chronic idiopathic constipation in children: long-term follow-up of a double-blind randomized trial.

BACKGROUND: Myectomy of the internal anal sphincter (IAS) has been performed on some children after failure of medical treatment to treat idiopathic constipation. The aim of this study was to compare botulinum toxin injection with myectomy of the IAS in the treatment of chronic idiopathic constipation and soiling in children. METHODS: This was a double-blind randomized trial. Patients between 4 and 16 years old were included in the study if they had failed to respond to laxative treatment and anal dilatation for chronic idiopathic constipation. All study patients had anorectal manometry and anal endosonography under ketamine anesthesia. Outcome was measured using a validated symptom severity (SS) scoring system, with scores ranging from 0 to 65. RESULTS: Of 42 children, 21 were randomized to the botulinum group and 21 were randomized to the myectomy group. At the 3-month follow-up, the median preoperative SS score improved from 34 (range = 19-47) to 20 (range = 2-43) in the botulinum group (P < .001) and from 31 (range = 18-49) to 19 (range = 3-47) in the myectomy group (P < .002). At the 12-month follow-up, the scores were 19 (range = 0-45) and 14.5 (range = 0-41) for the botulinum group and the myectomy group, respectively (P < .0001). There was no complication in both groups. CONCLUSION: Botulinum toxin is equally effective as and less invasive than myectomy of the IAS for chronic idiopathic constipation and fecal incontinence in children.

Outcome of excision of megarectum in children with anorectal malformation.

BACKGROUND/PURPOSE: Megarectum in association with anorectal malformation contributes to chronic constipation and fecal incontinence. Resection of megarectum in anorectal malformation improves bowel function, but neuropathy and poor sphincter quality may affect the outcome of fecal continence adversely. The aim of this study was to evaluate the benefits of resection of megarectum in anorectal malformation and to ascertain the impact of anal sphincter quality and neuropathy on the outcome. METHODS: We studied 62 children with intractable fecal incontinence after repair of anorectal malformation between January 1991 and January 2005. All patients were investigated with anorectal manometry and anal endosonography under ketamine anesthesia. On endosonography, an intact or scarred internal anal sphincter (IAS) was classified as good and a fragmented or absent IAS as poor. On manometry, a resting anal sphincter pressure equal to or more than 30 mm Hg was classified as good and a lower pressure as poor. Functional assessment of fecal continence was done before and after excision of megarectum using a modified Wingfield scores. RESULTS: Sixteen children had excision of megarectum with median age of 9 years (range, 2-15 years) and postoperative follow-up of 5 years (range, 1-10 years). Seven had formation of antegrade continent enema stoma before excision of megarectum. Children were classified into three groups of anomalies: low (n = 6), intermediate (n = 4), and high (n = 6). All children were incontinent of feces. After excision of megarectum, of the 9 children with good IAS and no neuropathy, 7 became continent of feces. Of the remaining 7 children, 4 had poor IAS and 3 had neuropathy, 5 of whom required an antegrade continent enema stoma to be clean. CONCLUSION: Excision of megarectum in children who had previous repair of anorectal malformation results in fecal continence in the presence of a good IAS and absence of neuropathy. Patients with a poor IAS or neuropathy will often require artificial means of fecal continence.

Role of anal dilatation in treatment of idiopathic constipation in children: long-term follow-up of a double-blind randomized controlled study.

Constipation in childhood is a common symptom, with an estimated incidence between 0.3% and 8%. Most of the evidence for the current management of constipation and fecal soiling in children is based on reports of nonrandomized retrospective trials. Anal dilatation has had an established role in the management of idiopathic constipation but has never been evaluated by a randomized study. A double-blind randomized controlled trial was done of children who failed to respond to medical treatment and were admitted for investigation and treatment of idiopathic constipation to Guy's Hospital, London, between April 2001 and April 2003. All children had intestinal transit study on admission. They were randomized, using a computer-generated allocation in sealed envelopes, to receive no anal dilatation (control group) or anal dilatation (anal dilatation group). Anorectal manometry and endosonography were done under ketamine anesthesia followed by anal dilatation if necessary under the same anesthesia. Disimpaction of feces from the rectum was done at the end of the procedure under general anesthesia using propofol muscle relaxant to minimize stretching of anal sphincter muscles in the control group. All children had intensification of medical treatment, toilet training, and monitoring of their response to treatment during their hospital stay, which ranged from 3 to 5 days. Outcome was measured using a parent's questionnaire of symptom severity at 3 and 12 months of follow-up by one of the authors, who was blinded to randomization. The symptom severity score ranged between 0 and 65 and consisted of scores for the following: delay in defecation (score range 0-10), difficulty and pain with passing stool (0-5), soiling problem (0-10), intensity of laxative treatment (0-10), child's general health (0-5), behavior related to the bowel problem (0-5), overall improvement of symptoms (0-12,) and assessment of megarectum on abdominal examination (0-8). Of 60 neurologically normal children, 31 (19 males) were randomized in the control group and 29 (18 males) in the anal dilatation group. All children had findings consistent with idiopathic constipation and positive anorectal reflex on manometry, no anal sphincter damage on endosonography, and no anal fissure on examination under anesthesia. The median age for control and anal dilatation groups was 7.97 (range 4.1-14.25) years and 7.78 (4-13.25) years, respectively. Both groups were also comparable with regard to median of duration of laxative treatment (32 months vs. 31.5 months), internal anal sphincter thickness on endosonography (0.90 mm vs. 0.80 mm), resting anal sphincter pressure on manometry (51 mmHg vs. 51 mmHg), total rectal capacity on manometry (260 mmHg vs. 260 mmHg), and total symptom severity score before admission (33 vs. 29), respectively. At 12-month follow-up, the median pre-admission symptom severity score had improved significantly, from 33 (range 12-49) in the control group and 29 (16-51) in the dilatation group to 15 (0-51, p < 0.0001) and 19 (1-46, p < 0.0001), respectively. There was no significant difference between the two groups with regard to symptom severity score improvement at 12-month follow-up (p < 0.92). We found a significant correlation between total rectal capacity measured on manometry and symptom severity score before admission and at 12-month follow-up (r = 0.30, p < 0.01 and r = 0.25, p < 0.05, respectively). Our results indicate that anal dilatation does not contribute to the management of school-aged children with idiopathic constipation. Admission to hospital for clarification of diagnosis and intensification of medical treatment with disimpaction of stool from the rectum is beneficial.

Thickening of the internal anal sphincter in idiopathic constipation in children.

Thickening of the internal anal sphincter (IAS) is observed in chronic idiopathic constipation (IC) and solitary rectal ulcer syndrome (SRUS), where it has been correlated with the presence and severity of rectal intussusception. Alternatively, thickened IAS may be a feature of the obstructed megarectum in a similar way to the hypertrophy of bladder neck seen in dyssynergic bladders. The aim of this study was to investigate the significance of thickening of the IAS in children with chronic IC and to determine any association between the thickened IAS and anorectal manometry findings and patient's symptoms. A total of 144 children were admitted for investigations and treatment of chronic IC and evaluated prospectively between April 2001 and April 2003. IAS thickness was measured by endosonography using B&K axial endosonic probe type 1850 with a 10-MHz rotating transducer. The thickness of IAS was measured at 3, 6, and 9 o'clock, and the mean value of the three measurements was used for analysis. Functional assessment was done by anorectal manometry pressure studies under ketamine anaesthesia. A validated symptom score (SS) was used to assess the severity of symptoms. The sum of SS ranged between 0 and 65. Spearman's rho two-tailed test was used to correlate the thickness of IAS with patients' symptoms and anorectal manometry findings. Results were expressed as median and range and p-value of less than 0.05 was considered significant. Of 144 children, 84 were boys, median age 8.1 years (range 3.1-15). Soiling was present in 137 (94%) patients, delay in defecation in 132 (91%), and a palpable megarectum on abdominal examination in 117 (80%). The median duration of symptoms and duration of laxative treatment were 4 years (range 0.3-14.5) and 3.3 years (0.2-13.5), respectively. The average severity score for soiling, delay in defecation, palpable megarectum, and the total SS were 8 (range 0-10), 5 (0-10), 2 (0-12), and 33 (11-51), respectively. The median thickness of IAS was 0.9 mm (range 0.3-2.8) and the median resting anal sphincter pressure was 54 mmHg (19-107). The median amplitudes of rectal and anal sphincter contraction were 3 mmHg (1-25) and 9 mmHg (1-35), respectively. The thickness of IAS correlated significantly with total symptom severity score (r=0.31, p=0.0001), soiling score (r=0.28, p=0.001), megarectum score on abdominal palpation (r=0.29, p=0.001), size of megarectum on manometry (r=0.36, p=0.0001), amplitude of rectal contraction (r=0.23, p=0.007), and age of patient (r=0.55, p=0.0001). There was also a significant correlation between the amplitude of rectal and anal sphincter contraction (r=0.32, p=0.0001). There was no correlation between thickness of IAS and resting anal sphincter pressure and amplitude of anal sphincter contraction on anorectal manometry study. A total of 24 children had myectomy of thickened and overactive IAS in addition to the medical treatment of their chronic IC. The histology examination of myectomy specimen with eosin and haematoxylin staining and histochemical acetylcholine esterase staining showed smooth muscle fibres and ganglion cells. Thickening of IAS correlates significantly with duration and severity of symptoms, size of megarectum, and amplitude of rectal contraction. The pathogenesis is secondary to the continuous presence of faeces in the rectum, resulting in chronic abnormal stimulus to the IAS, which leads to hypertrophic changes in the rectum wall and IAS.