Prevention of postoperative persistent bowel symptoms in patients with Hirschsprung's Disease

Hirschsprung's disease (HD) is a relatively common cause of intestinal obstruction in the new-born, occurring in 1 in 4,000 live births. It is characterised by abnormal development of the nerve supply to varying lengths of the large bowel prior to birth. The gold standard treatment for HD is an operation to remove the diseased bowel from the anal canal until healthy bowel is reached with a normal nerve supply, which is then joined to the anal canal to restore normal bowel function. Despite a properly performed operation, a substantial proportion (35-48%) of patients suffer from persisting bowel symptoms such as constipation, soiling and an inflammatory condition of the bowel known as enterocolitis.
Gastrointestinal motility is controlled by four groups of cells, the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), Platelet-derived growth factor receptor alpha-positive cells (PDGFR?+ cells), and smooth muscle cells (SMCs). Together, these four networks of cells regulate secretory activities and peristalsis of the bowel. The mechanisms underlying persistent symptoms post-surgery are poorly understood and understudied. We hypothesise that the ganglionic pulled-through bowel in HD is abnormal and therefore propose to investigate the morphological and molecular characteristics of the entire resected bowel specimens from patients with HD, with particular emphasis on the expression of ion channels within the smooth muscle layer, and PDG?+ cells.

Award Date

23 October 2015

Award Value

€301,869

Principal Investigator

Professor Prem Puri

Host Institution

The Children's Medical and Research Foundation

Scheme

Health Research Awards