Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making ...regarding diagnostics and management.
This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders.
Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted.
Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion.
In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.
Background Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT₄ agonist and enterokinetic with strong clinical data in chronic ...constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC. Methods A phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of ≥1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints proportion of patients with ≥3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment, adverse events (AEs), and safety parameters were also monitored. Results More patients had an increase from baseline of ≥1 SCBM per week (weeks 1-4) in the prucalopride groups 35.9% (2 mg) and 40.3% (4 mg) versus placebo (23.4%), reaching statistical significance in week 1. Over weeks 1-4, more patients in the prucalopride groups achieved an average of ≥3 SBM per week versus placebo (60.7% and 69.0% versus 43.3%), reaching significance at week 1. Prucalopride 4 mg significantly improved patient-rated severity of constipation and effectiveness of treatment versus placebo. Patient Assessment of Constipation-Symptom (PAC-SYM) total scores and Patient Assessment of Constipation-Quality of Life (PAC-QOL) total and satisfaction subscale scores were improved. The most common AEs were abdominal pain and nausea. There were no clinically relevant differences between groups in vital signs, laboratory measures or electrocardiogram parameters. Conclusion In this population with OIC, prucalopride improved bowel function and was safe and well tolerated.
Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare ...coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo.
Efficient isolation of neurons and glia from the human enteric nervous system (ENS) is challenging because of their rare and fragile nature. Here, we describe a staining panel to enrich ENS cells ...from the human intestine by fluorescence‐activated cell sorting (FACS). We find that CD56/CD90/CD24 co‐expression labels ENS cells with higher specificity and resolution than previous methods. Surprisingly, neuronal (CD24, TUBB3) and glial (SOX10) selective markers appear co‐expressed by all ENS cells. We demonstrate that this contradictory staining pattern is mainly driven by neuronal fragments, either free or attached to glial cells, which are the most abundant cell types. Live neurons can be enriched by the highest CD24 and CD90 levels. By applying our protocol to isolate ENS cells for single‐cell RNA sequencing, we show that these cells can be obtained with high quality, enabling interrogation of the human ENS transcriptome. Taken together, we present a selective FACS protocol that allows enrichment and discrimination of human ENS cells, opening up new avenues to study this complex system in health and disease.
Synopsis
This study describes flow‐cytometry based enrichment of human enteric neurons and glia using a combination of cell surface markers (CD56/CD90/CD24), which enables studies of the human ENS.
Based on CD56/CD90/CD24 co‐expression, enteric nervous system cells can be enriched by flow cytometry with higher specificity and resolution than previous methods.
Enteric neurons representing a minority of the ENS cluster can be resolved from enteric glial cells based on CD24 levels.
CD56/CD90/CD24‐positive cells can be further processed for downstream analysis, such as scRNAseq, enabling interrogation of the human ENS transcriptome.
This study describes flow cytometry‐based enrichment of human enteric neurons and glia using a combination of cell surface markers (CD56/CD90/CD24), which enables studies of the human ENS.
Constipation and fecal incontinence are common problems in children after repair of an anorectal malformation (ARM). While many children can be effectively managed with an oral laxative regimen, ...others require a mechanical colonic washout to achieve social continence. Appendicostomy and cecostomy are two techniques which permit antegrade access to the colon for the purpose of enema delivery, which improves compliance and quality of life for patients and families. The purpose of this article is to review, using a case-based approach, the indications for placement of a channel for antegrade enema access, clinical scenarios in which one technique would be preferred over another, common complications following each procedure.
Objective
To compare MRI and colostography/fistulography in neonates with anorectal malformations (ARM), using surgery as reference standard.
Methods
Thirty-three neonates (22 boys) with ARM were ...included. All patients underwent both preoperative high-resolution MRI (without sedation or contrast instillation) and colostography/fistulography. The Krickenbeck classification was used to classify anorectal malformations, and the level of the rectal ending in relation to the levator muscle was evaluated.
Results
Subjects included nine patients with a bulbar recto-urethral fistula, six with a prostatic recto-urethral fistula, five with a vestibular fistula, five with a cloacal malformation, four without fistula, one with a H-type fistula, one with anal stenosis, one with a rectoperineal fistula and one with a bladderneck fistula. MRI and colostography/fistulography predicted anatomy in 88 % (29/33) and 61 % (20/33) of cases, respectively (
p
= 0.012). The distal end of the rectal pouch was correctly predicted in 88 % (29/33) and 67 % (22/33) of cases, respectively (
p
= 0.065). The length of the common channel in cloacal malformation was predicted with MRI in all (100 %, 5/5) and in 80 % of cases (4/5) with colostography/fistulography. Two bowel perforations occurred during colostography/fistulography.
Conclusions
MRI provides the most accurate evaluation of ARM and should be considered a serious alternative to colostography/fistulography during preoperative work-up.
Key Points
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High-resolution MRI is feasible without the use of sedation or anaesthesia
.
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MRI is more accurate than colostography/fistulography in visualising the type of ARM
.
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MRI is as reliable as colostography/fistulography in predicting the level of the rectal pouch
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Colostography/fistulography can be complicated by bowel perforation
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Objective: To investigate the origin and outcome in a cohort of male and female fetuses with intra-abdominal cysts, in order to provide recommendations on management and to improve prenatal ...counselling. Methods: From 2002 to 2016, intra-abdominal cysts were detected by ultrasound in 158 fetuses. Cases with an umbilical vein varix were excluded. Fetal, neonatal, and maternal characteristics were retrieved from electronic patient files. Results: In female fetuses (n = 114), intra-abdominal cysts were diagnosed at a later gestational age compared with male fetuses (n = 44) (median 32.0 vs. 21.5 weeks, p < 0.001). The maximum prenatal cyst diameter was larger in female fetuses (median 35 vs. 17 mm, p < 0.001). Associated anomalies were less frequent in females (n = 15, 13.2%) compared with males (n = 15, 34.1%). In females (n = 114), most cysts were of ovarian origin (n = 81, 71.1%). Surgery was performed in 30 (26.3%) female and 15 (34.1%) male neonates (p = 0.33). Anorectal malformations were present in 6 cases and often not recognized prenatally. Conclusions: The differences in the origin of intra-abdominal cysts between male and female fetuses, resulting in differences in prenatal presentation and postnatal outcome should be taken into account in prenatal counseling within a multidisciplinary team. Evaluation of the fetal perianal muscular complex is indicated.
Outcome of patients operated for anorectal malformation (ARM) type rectovestibular fistula (RVF) is generally considered to be good. However, large multi-center studies are scarce, mostly describing ...pooled outcome of different ARM-types, in adult patients. Therefore, counseling parents concerning the bowel function at early age is challenging. Aim of this study was to evaluate bowel function of RVF-patients at preschool/early childhood age and determine risk factors for poor functional outcome.
A multi-center cohort study was performed. Patient characteristics, associated anomalies, sacral ratio, surgical procedures, post-reconstructive complications, one-year constipation, and Bowel Function Score (BFS) at 4–7 years of follow-up were registered. Groups with below normal (BFS < 17; subgroups ‘poor’ ≤ 11, and ‘fair’ 11 < BFS < 17) and good outcome (BFS ≥ 17) were formed. Univariable analyses were performed to detect risk factors for outcome.
The study included 111 RVF-patients. Median BFS was 16 (range 6–20). The ‘below normal’ group consisted of 61 patients (55.0%). Overall, we reported soiling, fecal accidents, and constipation in 64.9%, 35.1% and 70.3%, respectively. Bowel management was performed in 23.4% of patients. Risk factors for poor outcome were tethered cord and low sacral ratio, while sacral anomalies, low sacral ratio, prior enterostomy, post-reconstructive complications, and one-year constipation were for being on bowel management.
Although median BFS at 4–7 year follow-up is nearly normal, the majority of patients suffers from some degree of soiling and constipation, and almost 25% needs bowel management. Several factors were associated with poor bowel function outcome and bowel management.
Level III.
Introduction
A choledochal malformation (CM) is a rare entity, especially in the Western world. We aimed to determine the incidence of CM in the Netherlands and the outcome of surgery for CM in ...childhood.
Methods
All pediatric patients who underwent a surgical procedure for type I–IV CM between 1989 and 2014 were entered into the Netherlands Study group on choledochal cyst/malformation. Patients with type V CM were excluded from the present analysis. Symptoms, surgical details, short-term (<30 days) and long-term (>30 days) complications were studied retrospectively.
Results
Between January 1989 and December 2014, 91 pediatric patients underwent surgery for CM at a median age of 2.1 years (0.0–17.7 years). All patients underwent resection of the extrahepatic biliary tree with restoration of the continuity via Roux-en-Y hepaticojejunostomy. Twelve patients (12%) were operated laparoscopically. Short-term complications, mainly biliary leakage and cholangitis, occurred in 20 patients (22%), without significant correlations with weight or age at surgery or surgical approach. Long-term postoperative complications were mainly cholangitis (13%) and anastomotic stricture (4%). Eight patients (9%) required radiological intervention or additional surgery. Surgery before 1 year of age (OR 9.3) and laparoscopic surgery (OR 4.4) were associated with more postoperative long-term complications. We did not observe biliary malignancies during treatment or follow-up.
Conclusion
Surgery for CM carries a significant short- and long-term morbidity. Given the low incidence, we would suggest that (laparoscopic) hepatobiliary surgery for CM should be performed in specialized pediatric surgical centers with a wide experience in laparoscopy and hepatobiliary surgery.
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