The pathogenesis of HAEC, a common complication of congenital megacolon (Hirschsprung’s disease, HD), is unclear and may be related to mechanical dilatation of the proximal intestine, increased prostaglandin E1 activity, infection, defective mucosal barrier mechanisms, altered mucin, reduced number of neuroendocrine cells in the mucosa, defective leukocyte function, and abnormal gene expression. It can occur preoperatively or after radical surgery or enterostomy and is one of the major causes of death in children with HD.
I. High-risk factors for HAEC
Risk factors for HAEC have been found to include: family history of HD, co-morbid developmental delays such as trisomy 21 or Bardet-Biedl syndrome, long-segment HD, previous HAEC, and delayed diagnosis of HD. The prevalence of HAEC in children with and without a family history of HD was 35% and 16%, respectively; the prevalence of HAEC in children with combined congenital dysmorphic HD was 50%, significantly higher than the 25% in the general population; and the preoperative prevalence of HAEC in children with long-segment HD was 56%, also significantly higher than the 16% in children with short-segment HD.
In addition, the age of the child at the time of HD diagnosis also has an impact on the incidence of HAEC: delayed diagnosis is an independent risk factor for preoperative HAEC, and in neonates, children older than 1 week of age at the time of HD diagnosis are 13 times more likely to develop HAEC than those diagnosed within 1 week of age. Preterm infants were more likely to develop HAEC compared to full-term infants (45.8% vs. 24.0%). In addition to the risk factors for postoperative HAEC, anastomotic fistula, stricture, or adhesive bowel obstruction also increase the risk of postoperative HAEC threefold.
Diagnosis
HAEC is an umbrella term for a series of clinical symptoms such as abdominal distension, explosive watery diarrhea, and fever, and there is no exact definition. In view of this, Pastor et al. proposed a scoring system for the clinical diagnosis of HAEC with a total score: HAEC ≥ 10 points. In this scoring system, the accuracy of colonic dilatation on standing abdominal films for the diagnosis of HAEC was 90%, but the specificity was only 24%.
The accuracy is limited by the difficulty in determining whether the dilated bowel is small or colonic on neonatal abdominal plain films. Pneumatization of the intestine combined with truncation has a sensitivity of 74% and a specificity of 86% for the diagnosis of HAEC. The diagnosis of HAEC by CT has been reported in some cases, but is not particularly advantageous over abdominal radiographs and is not routinely performed in clinical practice. This scoring system helps clinicians to standardize the diagnosis of HAEC, but there is no more clinical medical evidence to determine the accuracy of this scoring system, and further research is needed.
2. Differential diagnosis
Inflammatory bowel disease (IBS) and HAEC have similar symptoms, and their common symptoms include abdominal pain, fever, diarrhea, and increased stool frequency. Authors have reported 10 case reports of IBS after HD surgery in which the clinical symptoms did not improve when the child was treated with HAEC because of the similarity of the symptoms, but resolved when the child was adjusted to a treatment regimen for IBS. Rectal biopsy showed chronic inflammation with eosinophilic infiltration and abscesses in the intestinal crypts.
The presence of anemia, growth retardation, rectovaginal fistula, perianal or perifistular abscess is more suggestive of IBD than HAEC, and upper and lower gastrointestinal endoscopy, biopsy, and serum markers of IBS should be performed; rectal biopsy should also be performed to rule out the presence or absence of residual ganglion cell segments and to find the diagnosis of IBS. If there is no improvement of clinical symptoms in children treated with HAEC, IBS can be treated experimentally, and mucosal immune abnormalities may play an important role in the occurrence of IBD after HD surgery.
Treatment of HAEC
The severity of the HAEC attack determines the choice of antibiotics. Metronidazole should be given at an early stage to treat anaerobic bacteria associated with HAEC (including Clostridium difficile), and broad-spectrum antibiotics, such as vancomycin if necessary, should be given for severe symptoms. Warm saline cleansing enemas should be started as early as possible, 2-4 times a day, with a rubber hose of as large a diameter as possible according to the age of the child, with multiple lateral holes to facilitate the drainage of the irrigation material.
The first lavage should be done until the irrigation fluid is clear, and the next day the lavage should be continued until the symptoms improve. For those with severe symptoms, the initial few lavage is usually not done to retain the enema, especially in neonates with weak intestinal wall, and retaining the enema increases the chance of perforation. Dilation can prevent early stenosis of the anastomosis from developing into late stenosis, and can also play a role in decompression.
2, probiotics on Ednrb(-/-) receptor-deficient HD model mice found that the colon without ganglion cell segment lacks the microorganisms contained in the stool in early normal colon, HAEC is the result of imbalance of bacterial species from harmless flora to harmful flora, therefore, if the surgical specimen or rectal biopsy reveals pathological grading of grade 3 or higher lesions in children with HAEC, regardless of the clinical manifestations Therefore, postoperative antibiotics should be used prophylactically to prevent the progression of HAEC, regardless of clinical manifestations.
However, the effectiveness of probiotics in HAEC is controversial, and a prospective double-blind randomized controlled study abroad found that probiotics did not reduce the incidence of postoperative HAEC. Children with constipation without HD did not develop enterocolitis, suggesting that a single bacterium does not explain HAEC in all cases and that the complex link between pathogenic bacteria and probiotics cannot be resolved by simple oral probiotics.
3. Enterostomies In children presenting with sepsis and severe HAEC, enterostomies should be considered, especially in neonates presenting with initial symptoms of sepsis and severe HAEC. However, in the presence of some risk factors, such as co-morbid developmental delay disorders, non-remission of HAEC after treatment, and multiple preoperative risk factors for HAEC, enterostomy is still required. It is important to note that enterostomy will certainly improve the child’s symptoms, but it does not remove HAEC in all cases, and children with HD who have a comorbid developmental disorder may have recurrent HAEC even after enterostomy.
Treatment of recurrent HAEC after surgery
The incidence of recurrent HAEC after surgery is 2%, and conservative treatment is effective in 81.5% of children, but surgery is required in 18.5% of children. For recurrent HAEC, the standard treatment at some foreign institutions is a dregs less, lactic acid free diet to reduce the substrate for bacterial overproliferation. Enteric antibiotics are given when symptoms worsen. It is also important to consider the possibility of organic pathology.
Physical examination focuses on the presence of anastomotic stricture, especially after transanal drag-out, as its most common complication is anastomotic stricture. Colonography should be performed to evaluate for strictures after tow-out, giant pouch after Duhamel, Soave valve obstruction, residual dilated ganglion cell-free segments, and torsion of the pull-down tube. Any twisting of the pull-down intestine should be reoperated promptly.
Early stenosis may be the result of an anastomotic fistula that does not show appropriate symptoms at the time, whereas distant stenosis is attributed to ischemia of the anastomosis leading to fibrosis and subsequent stenosis. In children with anastomotic stenosis, dilatation is recommended, followed by re-dragging if this fails. The literature reports that twice daily dilation increases the diameter of the anastomotic apparatus to an appropriate size, after which the frequency of dilation is gradually reduced until dilation is discontinued, and all stenoses, including recurrent stenoses, are cured by this method.
A Meta-analysis also showed that residual ganglion cell-free segments and residual migrated segments were present in approximately 1/3 of children who underwent reoperation after HD.
It is now recognized that complete resection of ganglion cell dysplasia minimizes the incidence and severity of postoperative constipation and HAEC, and combined with preoperative barium enema for 24 h and improved AChE LDH staining during radical surgery for HD, a rapid diagnosis and accurate determination of the extent of the diseased intestinal segment can be made, allowing complete resection of the diseased intestinal tube without There were no recurrence cases.
A rectal biopsy should be performed in children with recurrent HAEC after lower towing, and a full rectal biopsy should be taken to assess the presence of ganglion cells and the coarseness of the nerve trunk, but rectal biopsy is not recommended in the acute phase of HAEC to avoid perforation. Dickie et al. analyzed 36 cases of reoperation after transanal soavectomy and found that 10 cases had recurrent HAEC due to soave flap obstruction and no HAEC at 1-17 months of follow-up after removal of the soave flap and proximal dilatation of the colon.
If the above anatomical and pathological lesions are excluded, the following treatments can be used for recurrent HAEC.
1.Sodium cromoglycate (SCG) SCG is widely used in respiratory allergy, food allergy and inflammatory bowel disease. The aim is to inhibit the inflammatory activity of the colonic mucosa. The clinical symptoms of chronic and recurrent HAEC are similar to those of IBD, especially ulcerative colitis.
The method is 100 mg/dose 4 times daily, increasing to 200 mg/dose if the initial dose does not respond to SCG for 6 weeks. At 6 months after initiation of oral administration, the dose was re-evaluated and discontinued if there was no improvement in symptoms, and gradually reduced to the minimum effective dose level (300-4 mg/d) for effective children. The authors reported significant improvement in 6 out of 8 cases and concluded that anti-inflammatory drugs effective in IBD can reduce recurrent HAEC symptoms.
2.Botulinum toxin injection was reported in China by injecting botulinum toxin A into the internal anal sphincter and rectal musculature at 3, 6, and 9 o’clock positions in the amputation position with a total dose of 1.5 U/kg, and no abdominal distension or constipation was found. Botulinum toxin injection also significantly reduced the length of hospital stay due to obstruction after HD tow-out surgery, and the use of botulinum toxin should be considered in children with postoperative obstruction in HD, but the long-term results remain to be further observed.
3, Posterior myotomy/myectomy ( posterior myotomy, POMM) recurrent HAEC even 1-2 years after drag-out surgery should be considered after excluding pathological factors. POMM is effective in treating chronic constipation or recurrent HAEC after drag-out surgery, but is not appropriate for constipation due to residual ganglion cells without. Wildhaber et al. reported that POMM was performed in 32 out of 348 children after drag-out surgery and was effective in 75% of children with recurrent HAE.
The symptoms disappeared in 75% of the children with recurrent HAE, none of the children required a repeat drag-out procedure, and there was no correlation between the POMM approach and the overall function of the anus.
The efficacy of internal sphincter myectomy (ISM) is questionable because most children have social problems related to anal fecal contamination, but the risk of anal incontinence is very clear. The procedure should be performed with caution.
The cure rate of HAEC is higher than that of conservative treatment, and timely enterostomy is an effective way to save the life of the child, because congenitally stupid children have poor intestinal dynamics and living ability, and it is difficult to obtain normal intestinal function, so some authors recommend direct enterostomy.
In conclusion, although the understanding of the pathogenesis and risk factors of HAEC is gradually improving, the occurrence of HAEC cannot be completely avoided before and after surgery. Intestinal tube decompression, antibiotics, and colonic irrigation remain the core of treatment for acute HAEC, and surgical interventions such as POMM and botulinum toxin injection can be considered for recurrent HAEC on the basis of excluding organic pathology. However, if HAEC fails to respond to both pharmacologic and surgical interventions, only enterostomy is eventually performed. In terms of treatment, vigilance is needed to differentiate it from IBS, although this comorbidity is rare.