OBJECTIVETo systematically summary the updated results about the pathogenesis of Hirschsprung's-associated enterocolitis (HAEC). Besides, we discussed the research key and direction based on these results.

DATA SOURCESOur data cited in this review were obtained mainly from PubMed from 1975 to 2015, with keywords "Hirschsprung enterocolitis", "Hirschsprung's enterocolitis", "Hirschsprung's-associated enterocolitis", "Hirschsprung-associated enterocolitis", "HAEC", and "EC".

STUDY SELECTIONArticles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded.

RESULTSSeveral factors, mainly including mucus barrier, intestinal microbiota, and immune function, as well as some other factors such as genetic variations and surgical reasons, have been found to be related to the pathogenesis of HAEC. Changed quantity and barrier property of mucus, different composition of microbiota, and an abnormal immune state work together or separately trigger HAEC.

CONCLUSIONSThe maintenance of intestinal homeostasis is due to a well cooperation of microbiota, mucus barrier, and immune system. If any part presents abnormal, intestinal homeostasis will be broken. Meanwhile, for patients with Hirschsprung's disease or HAEC, dysfunction of these parts has been found. Thus, the happening of HAEC may be mainly attributed to the disorders of intestinal microbiota, mucus barrier, and immune system.

Animals ; Enterocolitis ; etiology ; pathology ; Hirschsprung Disease ; complications ; pathology ; Humans ; Intestines ; microbiology ; pathology

PURPOSE: The single stage transanal pull-through (SSPT) for Hirschsprung’s disease is becoming the most popular procedure. This single center study compared the result of single stage operation with two-stage operation for Hirschsprung’s disease in neonates. METHODS: We retrospectively reviewed medical records of all patients who were diagnosed as Hirschsprung’s disease and underwent SSPT or two-stage operation operation in Asan Medical Center between January 2003 and July 2014. RESULTS: There were 17 SSPT and 28 two-stage operation. The mean age of SSPT group was 14.2±7.1 days, and the mean age of two-stage operation group was 15.4±8.6 days for stomy formation, and 188.6±36.3 days for Duhamel operation. The operation time of SSPT was shorter than Duhamel operation (145.0±37.0 minutes vs. 193.0±36.0 minutes, p<0.001). The mean follow-up period of SSPT and two-stage operation was 35.5±34.9 months (range, 2-132 months) and 56.6±35.5 months (range, 1-121 months), respectively. Defecation problem rate such as fecal soiling or fecal impaction showed no significant difference between the two groups (p=0.719). Two SSPT patients required botulinum toxin injection due to rectal stenosis. Three patients of SSPT group underwent re-do endorectal pull-through due to remnant aganglionic or hypoganglionic bowel. CONCLUSION: The SSPT showed shorter hospital days. However, few patients experienced rectal stenosis, but were manageable with botulinum toxin injection. The SSPT requires experienced-pathologist, as well as surgeon, because intra-operation pathology reading is critical for appropriate SSPT. SSPT is a feasible and reasonable option to treat Hirschsprung’s disease.
Botulinum Toxins ; Chungcheongnam-do ; Constriction, Pathologic ; Defecation ; Fecal Impaction ; Follow-Up Studies ; Hirschsprung Disease ; Humans ; Infant, Newborn* ; Medical Records ; Pathology ; Retrospective Studies ; Soil

PURPOSE: The term benign transient non-organic ileus of neonates (BTNIN) is applied to neonates who present symptoms and plain radiographic findings of Hirschsprung's disease, but do not have aganglionic bowel and are managed well by conservative treatment. It can often be difficult to diagnose BTNIN because its initial symptoms are similar to those of Hirschsprung's disease. The aim of this study is to evaluate the clinical characteristics and proper treatment of BTNIN. MATERIALS AND METHODS: A retrospective review was made on the clinical data of 19 neonates who were treated for BTNIN between January 2008 and December 2011 at a single facility. RESULTS: Abdominal distension occurred in every patient (19/19). Other common symptoms included emesis (5/19), explosive defecation (5/19), and constipation (4/19). The vast majority of patients (15/19) experienced the onset of symptoms between 2 and 4 weeks of age. Radiograph findings from all of the patients were similar to Hirschsprung's disease. A barium study showed a transition zone in 33.4% (6/18) of the patients. However, rectal biopsy revealed ganglion cells in the distal rectum in 88.2% (15/17) of the patients, and anorectal manometry showed a normal rectoanal inhibitory reflex in 90% (9/10). All patients responded well to conservative treatment. Symptoms disappeared at the mean age of 4.9+/-1.0 months, and the abdominal radiographs normalized. CONCLUSION: BTNIN had an excellent outcome with conservative treatment, and must be differentiated from Hirschsprung's disease. A rectal biopsy and anorectal manometry were useful diagnostic tools in the differential diagnosis.
Female ; Hirschsprung Disease/diagnosis/pathology ; Humans ; Ileus/*diagnosis/pathology ; Infant, Newborn ; Male ; Rectum/pathology ; Retrospective Studies

Acetylcholinesterase ; analysis ; Antibodies, Monoclonal, Murine-Derived ; metabolism ; Australia ; Biopsy ; Calbindin 2 ; analysis ; Child ; Diagnosis, Differential ; Endoscopy, Gastrointestinal ; Eosinophilic Esophagitis ; pathology ; Hirschsprung Disease ; metabolism ; pathology ; Humans ; Intestinal Diseases ; pathology ; Lymphangiectasis, Intestinal ; immunology ; pathology ; Multiple Endocrine Neoplasia Type 2b ; pathology ; Nervous System Diseases ; pathology ; Quality Control

BACKGROUND/AIMS: Calprotectin is a 36.5 kD calcium and zinc binding protein in the S100 protein family. Fecal calprotectin levels are elevated in patients with inflammatory bowel disease and some other gastrointestinal disorders such as colorectal carcinoma. We decided to evaluate the fecal calprotectin level to see if it was able to distinguish between functional and organic causes of constipation. METHODS: Seventy-six children aged 1 to 120 months that all underwent deep rectal mucosa biopsies at Children Medical Center from November 2010 till September 2011 were recruited. Nineteen cases were diagnosed as Hirschsprung's disease and 57 of the patients had nerve ganglion cells in their biopsies. Calprotectin concentration was analyzed by the ELISA method. RESULTS: Although there was a significant difference between the median of the two groups (p=0.036), the median was not above the predetermined cutoff value of 50 microg/g. CONCLUSIONS: We propose that fecal calprotectin, using the above cutoff value, has limited value in differentiating functional constipation from Hirschsprung's disease.
Age Factors ; Child ; Child, Preschool ; Constipation/*diagnosis ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Feces/chemistry ; Female ; Hirschsprung Disease/*diagnosis/metabolism/pathology ; Humans ; Infant ; Infant, Newborn ; Intestinal Mucosa/pathology ; Leukocyte L1 Antigen Complex/*analysis ; Male ; Sex Factors

Congenital central hypoventilation syndrome with Hirschsprung's disease, also known as Haddad syndrome, is an extremely rare disorder with variable symptoms. Recent studies described that congenital central hypoventilation syndrome had deep relation to the mutation of the PHOX2B gene in its diagnosis and phenotype. We report a newborn male infant with clinical manifestations of recurrent hypoventilation with hypercapnea and bowel obstruction. These clinical manifestations were compatible with congenital central hypoventilation syndrome and Hirschsprung's disease, and polyalanine 26 repeats in the PHOX2B gene supported the diagnosis of congenital central hypoventilation. We described a first case of Haddad syndrome in Korean and its clinical and genetic characteristics were discussed.
Asian Continental Ancestry Group ; Base Sequence ; DNA Mutational Analysis ; Hirschsprung Disease/diagnosis/genetics/pathology ; Homeodomain Proteins/*genetics ; Humans ; Hypoventilation/congenital/diagnosis/genetics ; Infant, Newborn ; Male ; Molecular Sequence Data ; *Mutation ; Sleep Apnea, Central/diagnosis/genetics ; Transcription Factors/*genetics

OBJECTIVETo investigate the distribution of connexin 43 (Cx43) and interstitial cells of Cajal (ICC) in bowels of children with Hirschsprung's disease (HD) and explore their roles in the pathogenesis of HD.

METHODSForty-two children with HD diagnosed by histopathology (33 males and 9 females) aged from 2 months to 10 years were enrolled. Expression of Cx43 and ICC in the bowels was detected using immunohistochemistry. These cases were all sporadic, including 30 cases of common type and 12 cases of short segment type. Five samples from the children with intussusception (aged from 1 month to 8 years) were used as controls.

RESULTSCx43 and ICC were not expressed in the muscle layers of the aganglionic segment in children with HD, which was significantly different from the Cx43 and ICC expression in the ganglionic segment of HD patients and the control bowels. Moderate expression of Cx43 and ICC were observed in the migratory segment, which was significantly different from that in the ganglionic and aganglionic segments in patients with HD. Moderate or strong expression of Cx43 and ICC was observed in the circular muscle and the region between the circular and longitudinal layer in the ganglionic segment from patients with HD. There were no significant differences in the Cx43 and ICC expression between the ganglionic segment of HD patients and control bowels.

CONCLUSIONSThe absence of Cx43 and ICC expression in the aganglionic bowel and the destruction of the gap junction may induce the dysfunctions of intercellular substance exchange and communication transmission, which might partly be responsible for the pathogenesis of HD.

Child ; Child, Preschool ; Connexin 43 ; analysis ; physiology ; Female ; Hirschsprung Disease ; etiology ; metabolism ; pathology ; Humans ; Infant ; Intestines ; chemistry ; pathology ; Male ; Myocytes, Smooth Muscle ; chemistry ; Proto-Oncogene Proteins c-kit ; analysis

OBJECTIVETo investigate the distribution of mast cells (MC) in colon tissue of Hirschsprung disease (HD) and explore the role of mast cells in the pathogenesis of HD.

METHODSForty-one cases of HD (male 23, female 18), age from 2 months to 15 years, and eight age-matched normal cases were enrolled in this study. The distribution of MC in all layers of colon was examined by immunohistochemistry with mouse antihuman mast cell tryptase monoclonal antibody.

RESULTSThe count of MC in all layers of colon aganglionic segments of HD was significantly higher as compared with colon ganglionic segments of HD and normal controls (21.47+/-3.59 vs 3.18+/-0.87, 2.75+/-0.51). The average optical density values(A) of MC in aganglionic and ganglionic segments significantly decreased as compared to normal control (0.38+/-0.10,0.31+/-0.11 vs 0.51+/-0.08).

CONCLUSIONMast cells may play an important role in the pathogenesis of HD.

Adolescent ; Child ; Child, Preschool ; Female ; Hirschsprung Disease ; metabolism ; pathology ; Humans ; Infant ; Intestinal Mucosa ; pathology ; Male ; Mast Cells ; cytology ; metabolism ; pathology ; Tryptases ; metabolism

Hirschsprung's disease is one of the most common causes of intestinal obstruction in neonates and infants. The underlying pathology of this disease is the absence of the ganglion cells in both the myenteric (Auerbach's) plexus and the submucosal (Meissner's) plexus. Since Hirschsprung's report in 1886, there have been thousands of papers on Hirschsprung's disease but the cause of the absence of the ganglion cells has not been identified. Hirschsprung's disease can be successfully treated with the Swenson, the Duhamel, and the Soave operations even though the pathogenesis is unknown. With the recent progress of molecular biology and genetics, a more detailed approach to the pathogenesis of Hirschsprung's disease can be undertaken. In addition, there have been recent developments in the surgical approach. In this review, recent advances in surgery for Hirschsprung's disease are presented.
Ganglion Cysts ; Genetics ; Hirschsprung Disease* ; Humans ; Infant ; Infant, Newborn ; Intestinal Obstruction ; Molecular Biology ; Pathology

Intestinal neuronal dysplasia (IND) type B is a disease of the submucosal plexus of intestine manifesting chronic intestinal obstruction or severe chronic constipation. IND is one of intestinal dysganglionoses and clinically closely associated with Hirschsprung's disease. Until recently, it is not fully clear whether IND is a congenital malformation or an acquired secondary condition related to some gastrointestinal problems. However, recently published data and consensus reports have enhanced our understanding of the pathogenesis and management of IND. The aim of this paper was to review the current state of knowledge regarding the controversial issues of IND including the etiology, classification, diagnostic criteria, and available therapeutic intervention.
Child ; Colon/*innervation/radiography ; Constipation/etiology ; Enteric Nervous System/*abnormalities ; Ganglia/pathology ; Gastrointestinal Motility ; Hirschsprung Disease/pathology ; Humans ; Immunohistochemistry ; Intestinal Diseases/*diagnosis/pathology ; Intestinal Mucosa/pathology