Redo pull-through in total colonic aganglionosis due to residual aganglionosis:a single center’s experience

Background Reoperation for total colonic aganglionosis(TCA)may be required for residual aganglionosis after an initial radical operation.We aimed to investigate the symptoms,management,and outcomes of patients who required a redo pullthrough(Redo PT).Methods Nine TCA patients underwent Redo PT at our center between 2007 and 2017.Their medical records were reviewed.Parental telephone interviews that included disease-specific clinical outcomes were conducted,and post-operative complications and long-termoutcomes(including height-for-age/weight-for-age and bowel-function score)were compared to those of single-pull-through(Single PT)patients(n=21).Results All the nine Redo PT patients suffered obstruction within 1 month after the initial operation that could not be alleviated by conservative treatment.All abdominal X-ray/contrast barium enemas showed proximal bowel dilatation,indicating residual aganglionosis.The median ages at the initial operation and Redo PT were 200 and 509 days,respectively.Reoperation consisted of an intraoperative frozen biopsy and a modified laparotomic Soave procedure in all patients.Postoperative complications included perianal excoriation(n=3),intestinal obstruction(n=2),enterocolitis(n=2),and rectovestibular fistula(n=1).Seven Redo PT patients were followed up for a mean time of 7.162.3 years;six(85.7%)had good growth and four(57.1%)had good bowel-function recovery.Post-operative complications and long-term outcomes were almost equal between the Redo PT and Single PT groups(all P>0.05).Conclusion TCA patients with recurrent obstructive symptoms and dilated proximal bowel may have residual aganglionosis after an initial operation.Redo PT is effective and provides good long-termoutcomes comparable to those of patients who benefited from Single PT.

Genetic interactions and modifi er genes in Hirschsprung's disease

Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.

Deficiency of platelet-derived growth factor receptor-α-positive cells in Hirschsprung's disease colon

AIM: To investigate whether the expression of platelet-derived growth factor receptor-α-positive (PDGFRα+)-cells is altered in Hirschsprung’s disease (HD).METHODS: HD tissue specimens (n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). Immunolabelling of PDGFRα+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein expression.RESULTS: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD colon.CONCLUSION: These findings suggest that the altered distribution of PDGFRα+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.

Persistent bowel dysfunction after surgery for Hirschsprung’s disease:A neuropathological perspective

Hirschsprung’s disease(HD)is a congenital disorder,characterized by aganglionosis in the distal part of the gastrointestinal tract.Despite complete surgical resection of the aganglionic segment,both constipation and fecal incontinence persist in a considerable number of patients with limited treatment options.There is growing evidence for structural abnormalities in the ganglionic bowel proximal to the aganglionosis in both humans and animals with HD,which may play a role in persistent bowel dysfunction.These abnormalities include:(1)Histopathological abnormalities of enteric neural cells;(2)Imbalanced expression of neurotransmitters and neuroproteins;(3)Abnormal expression of enteric pacemaker cells;(4)Abnormalities of smooth muscle cells;and(5)Abnormalities within the extracellular matrix.Hence,a better understanding of these previously unrecognized neuropathological abnormalities may improve follow-up and treatment in patients with HD suffering from persistent bowel dysfunction following surgical correction.In the long term,further combination of clinical and neuropathological data will hopefully enable a translational step towards more individual treatment for HD.