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Published in Samar Razaq, Difficult Cases in Primary Care, 2021
Hirschsprung’s disease is a congenital neuropathic condition of the intestine characterised by the absence of ganglion cells in the myenteric plexuses of the distal bowel. The aganglionic bowel extends proximally from the rectum for a variable distance, and hence may be classified as short segment (affecting the rectum and/or the sigmoid colon) or long segment (extending beyond the sigmoid). Rarely total colonic aganglionosis may occur affecting the small bowel or even the entire alimentary canal. The exact mechanism of disease is unclear, although some have postulated towards a defect in the migration of ganglion cells from the neural crest between the seventh and eighth week of intrauterine development. Failure or delay in passing meconium (beyond 24 hours), vomiting, abdominal distension and poor feeding are suggestive of Hirschsprung’s disease. The presence of diarrhoea may represent Hirschsprung’s enterocolitis, a critical complication carrying high rates of mortality. Abdominal radiography and barium enemas are employed in making the diagnosis, although definitive diagnosis is by rectal biopsy. Treatment involves bowel rest, rectal dilation and irrigation, antibiotics and surgery to remove the aganglionic bowel.
Paediatric Surgery: What the Adult Surgeon Needs to Know
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Marc A. Levitt, Richard J. Wood
The aetiology of Hirschsprung disease relates to a failure of ganglion cells, derived from the neural crest, to migrate or properly differentiate through the gastrointestinal tract from proximal to distal. It appears that mutations in a variety of genes might be the cause with the most commonly identified being the Ret proto-oncogene and the endothelin family of genes. The mechanisms by which these mutations result in aganglionosis are currently under active investigation.
Principles of paediatric surgery
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
Hirschsprung's disease is characterised by the congenital absence of intramural ganglion cells (aganglionosis) and the presence of hypertrophic nerves in the distal large bowel. The absence of ganglion cells is due to a failure of migration of vagal neural crest cells into the developing gut. The affected gut is in spasm, causing a functional bowel obstruction. The aganglionosis is restricted to the rectum and sigmoid colon in 75% of patients (short segment), involves the proximal colon in 15% (long segment) and affects the entire colon and a portion of terminal ileum in 10% (total colonic agangliono- sis). A transition zone exists between the dilated, proximal, normally innervated bowel and the narrow, distal aganglionic segment.
Advances in the molecular biology and pathogenesis of congenital central hypoventilation syndrome—implications for new therapeutic targets
Published in Expert Opinion on Orphan Drugs, 2018
Simona Di Lascio, Roberta Benfante, Silvia Cardani, Diego Fornasari
Locus coeruleus (LC) defects have recently been reported in two CCHS patients with confirmed PHOX2B mutations (one PARM and one NPARM), and these findings were confirmed in a murine experimental model generated by introducing the same NPARM mutation [82]. The mice also showed intestinal aganglionosis and the loss of the RTN and facial nerve nucleus. Importantly, the authors found that the abnormal formation of the RTN and facial nerve nucleus were due to the failure of precursors migration, whereas locus coeruleus precursors were present but failed to differentiate and express normal levels of the catecholamine synthetizing enzymes DBH and TH, thus indicating LC and noradrenergic synthesis dysfunction. PHOX2B mutations therefore affect neuronal subpopulations at different stages (from complete loss to incomplete differentiation), and it is likely that defects in both RTN and LC neurons contribute to the respiratory abnormalities of CCHS patients. Locus coeruleus defects have also been reported in experimental models of Rett syndrome [87], a condition that is characterized by respiratory disturbances that are more severe during wakefulness than during sleep [88].
Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients
Published in Gut Microbes, 2020
Weibing Tang, Yang Su, Chen Yuan, Yuqing Zhang, Lingling Zhou, Lei Peng, Pin Wang, Guanglin Chen, Yang Li, Hongxing Li, Zhengke Zhi, Hang Chang, Bo Hang, Jian-Hua Mao, Antoine M. Snijders, Yankai Xia
At the pull-through surgery, the cutting edge of dilated segments of HSCR patients was collected and immediately stored at −80°C. Our standard of excision is to find mature ganglion cells on the cutting edge of the dilated segment based on fast pathology during surgery. Generally, the distance between the cutting edge of the dilated segment and the transitional segment is more than 10 cm. For classical segment HSCR, the cutting edge was usually located in the proximal sigmoid colon or the descending colon. For long-segment HSCR, the cutting edge reached the descending colon, the transverse colon, and sometimes the ascending colon. In the case of total colonic aganglionosis, the cutting edge reached the small intestine. We collected the enteric mucosa in the cutting edge of the dilated segment for sequencing, which is adjacent to normal tissue and thus better represents the characteristics of normal enteric tissues and anastomotic stoma after surgery. DNA in the enteric mucosa was extracted and purified by the QIAamp DNA Mini Kit (QIAGEN). The 16S rRNA gene was amplified by the polymerase chain reaction (PCR), using primers 515F (5′-GTGCCAGCMGCCGCGGTAA-3′) and 806R (5′-GGACTACHVGGGTWTCTAAT-3′), which target the V4 hypervariable region. PCR products were purified by the GeneJET Gel Extraction Kit (Thermo Scientific). Libraries were prepared by the TruSeq DNA PCR-Free Sample Preparation Kit. The library quality was assessed by the Qubit 2.0 Fluorometer (Thermo Scientific) and Agilent Bioanalyzer 2100 system. PCR products were sequenced by the Illumina HiSeq 2500 System, generating 250-bp paired-end reads. All sequences are available under the NCBI Sequence Read Archive BioProject ID PRJNA578412.
Distal rectal skip segment Hirschsprung disease: Case report and review of literature
Published in Fetal and Pediatric Pathology, 2019
Archana Shenoy, Yanel De Los Santos, Kevin Neil Johnson, Robin Petroze
The patient was taken to the operating room on DOL 18. Diagnostic laparoscopy did not reveal any obvious visual transition zone. The sigmoid colon appeared redundant but decompressed. In order to take full-thickness biopsies, a periumbilical incision was made and the sigmoid colon extruded through this. On palpation, there did appear to be a transition in the mid to lower sigmoid. Full thickness rectal biopsies were taken at the peritoneal reflection, 3 cm proximal to the peritoneal reflection, and again about 5 cm proximal to the palpable transition. Frozen section biopsies revealed no ganglion cells at the peritoneal reflection, ganglion cells at the 3 cm biopsy, and normal ganglionated bowel at the most proximal biopsy site. Confirming a diagnosis of rectosigmoid HD, a laparoscopic-assisted proctectomy with endorectal pull-through in the Swenson plane was then completed without complication. Prior to completing the anastomosis, a circumferential margin was sent for frozen section, confirming normal ganglionated bowel. The 25 cm Swenson pull-through specimen was sent for permanent section and processed as depicted in Figure 2. No mucosal sleeve was present distally, confirmed on microscopic examination. Initially, the proximal circumferential resection margin and a longitudinal strip along the entire length of the specimen were processed for histologic examination. Approximately 0.5 cm of bowel at the distal end demonstrated numerous clusters of deep submucosal and myenteric ganglion cells. Ganglion cells were also noted in the mid submucosa, with no ganglion cells noted in the superficial submucosa (underneath the muscularis mucosa). No ectopic ganglion cells were noted. This was flanked by 6 cm of proximal aganglionosis and submucosal nerve hypertrophy, proximal to which was approximately 18 cm of ganglionic bowel. Transition between the ganglionic and aganglionic segments was abrupt both proximally and distally. There were no tongues of ganglion cells extending into the aganglionic segment. Calretinin highlighted lamina propria nerve fibers and ganglion cells in ganglionic segments. In the distal end, only occasional lamina propria nerve fibers were seen in the ganglionated mucosa with no extension into the aganglionic segment. At the proximal ganglionic-aganglionic transition lamina propria expression of calretinin extended 6 mm beyond the last cluster of submucosal ganglion cells. Subsequently, circumferential serial sections were submitted from the distal 10 cm of bowel that confirmed submucosal and myenteric ganglion cells seen in the distal <1 cm of rectum (Fig. 2B) preceded by 6 cm of circumferential aganglionosis (Fig. 2A). Thus, a diagnosis of SSHD was confirmed.