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

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

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

OBJECTIVETo explore the UL139 gene polymorphism of human cytomegalovirus (HCMV), and the relationship between polymorphisms of HCMV UL139 ORF and Hirschsprung's disease (HD).

METHODSForty-three specimens of the aganglionic intestinal segment and 6 urine samples of HD infants were amplified by nested polymerase chain reaction (PCR) method. The amplicons were sequenced in both strands directly. The control group consisted of 10 asymptomatic HCMV infected infants, and their urine specimens were also analyzed using the same method.

RESULTSHCMV UL139 genes of 28 clinical strains from HD 1 patients were successfully amplified and sequenced. UL139 was hypervariable and was clustered into 3 major groups and 5 genotypes. The predominant genotype of HCMV in HD infants was UL139 Group 3 (48 percent). Comparison of strains distribution between the two groups did not reach statistical significance using chi square test (chi square=7.378, P=0.194). The results of correlation analysis between UL139 and UL144 genes showed a p value 0.05 by Kendall test. Clinically, strains from the rectosigmoid segment, total colon aganglionosis, and long-segment were distributed sporadically in UL139 genotypes.

CONCLUSIONUL139 gene displayed polymorphisms. No linkage was found between UL139 genotype and clinical phenotype of HD. There was no correlation between HCMV UL144 and UL139.

Cytomegalovirus ; genetics ; Female ; Genotype ; Hirschsprung Disease ; etiology ; virology ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Open Reading Frames ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Viral Proteins ; chemistry ; genetics

OBJECTIVEThe short-term efficacy of the transanal one-stage endorectal pull through operation for Hirschsprung's disease is satisfactory. However the long-term outcome of anorectal function has not been fully understood. The aim of this study was to evaluate the stooling pattern, colonic motility and anal sphincter performance after transanal one-stage pull through operation in children with Hirschsprung's disease.

METHODSFifty-eight children who underwent transanal one-stage pull through operation for Hirschsprung's disease were followed up. The mean follow-up duration was 15.8 months (range, 6-24 months). The stooling patterns of the patients were investigated by the informed questionnaire. Barium enema, defecography, total and segmental colonic transit time and the anorectal vector manometry were performed. Thirty- three healthy children were used as controls.

RESULTSMost of patients had normal stool consistency and frequency. Postoperative enterocolitis occurred in 3 patients, and constipation was found in five patients. Postoperative soiling was observed in 9 patients. None of the 58 patients had incontinence, cuff infection, anastomotic leak and mortality. The barium enema showed that the configuration of the colon recovered well in most of patients. Postopertive defecography showed the anorectal angle of all the patients was open, fixed and bigger than that of preoperation and the healthy controls (P < 0.01). Postoperatively, the mean total gastrointestinal transit time (TGITT), the left colonic transit time (LCTT) and rectosigmoid colonic transit time (RSTT) in the 58 patients were significantly shorter than preoperatively (P < 0.01) and were similar to those of the control group. The rectoanal inhibitory reflex was regained in 5 patients. The anal maximal pressure of the patients with constipation in resting and squeezing condition were significantly higher than those of the asymptomatic patients and controls (P < 0.05). The vector volume (VV) and vector symmetric index (VSI) in patients with soiling were significantly lower than those in preoperation and the controls (P < 0.05). The VSI in the patients with constipation was significantly higher compared with the controls (P < 0.05).

CONCLUSIONSThe stooling function, colonic motility and anal sphincter performance manifest well in most of the patients after the transanal endorectal pull through operation for Hirschsprung's disease. Stooling disorders in few cases are probably related to decrease or disappearance of the sigmoid loops, dysfunction of the "neorectosigmoid", an open and fixed anorectal angle and achalasia of the internal anal sphincter.

Child, Preschool ; Colon ; physiopathology ; Female ; Follow-Up Studies ; Gastrointestinal Transit ; Hirschsprung Disease ; physiopathology ; surgery ; Humans ; Infant ; Male ; Postoperative Complications ; etiology ; Pressure ; Rectum ; physiopathology ; surgery

OBJECTIVETo investigate the relationship between the morphological features of different types of neuronal intestinal malformations (NIM) and their postoperative complications.

METHODSThe data of morphological and clinical features of 324 cases with NIM were analyzed retrospectively.

RESULTSIn all 324 patients, 210 cases were Hirschsprung's disease (HD), 38 intestinal neuronal dysplasia (IND), 45 mixed HD/IND, 8 hypoganglionosis, 22 combined HD/hypoganglionosis and 1 immaturity of ganglion cells. The percentages of normal neuron in bowel of different NIM were 88.1%, 24.4%, 18.4%, 4/8, 27.7% and 0/1 in HD, HD/IND, IND, hypoganglionosis, HD/hypoganglionosis and immaturity of ganglion cells respectively. There were totally 46 cases complicated with recurrent postoperative enterocolitis (EC). Incidence of recurrent postoperative EC in HD patients was 6.7% while in IND/HD and IND patients was 35.6% and 28.9%, respectively. Incidences of EC in cases with the residual IND margins and with the normal margins were 38.2% and 8.7%, respectively. Incidence of EC in cases with transanal endorectal pull-through procedure and with transabdominal procedure was 18.0% and 8.3%, respectively. Nine cases underwent another procedure because of severe persistent constipation or EC after operation, including 4 cases HD/IND, 1 case IND, 3 cases HD and 1 case HD/hypoganglionosis.

CONCLUSIONSNeuron distribution is inconsistent with pathology of NIM. Postoperative EC are rare in the patients only with isolated HD. Furthermore, margins with residual IND and transanal endorectal pull-through procedure are risk factors to recurrent EC. However, the extension of excision about IND is uncertain and need further study.

Adolescent ; Child ; Child, Preschool ; Digestive System Abnormalities ; complications ; pathology ; surgery ; Enteric Nervous System ; abnormalities ; pathology ; Female ; Hirschsprung Disease ; complications ; pathology ; surgery ; Humans ; Infant ; Male ; Postoperative Complications ; etiology ; Retrospective Studies

BACKGROUNDOne stage transanal Soave pull-through procedure (TSPP) is a recent popular operation in the treatment of Hirschsprung's disease (HD). With no visible scar and a short hospital stay, it is well accepted by surgeons and mothers. In the conventional Soave procedure, a long rectal muscular cuff left for anocolic anastomosis might increase the incidence of postoperative enterocolitis and constipation. This study presents a modified transanal Soave pull-through procedure (MTSPP) which includes an oblique mucosectomy and an oblique anastomosis with a short split muscular cuff.

METHODSA review of two groups of HD patients was made: 112 underwent conventional transanal Soave procedure from 1999 to 2001 (group 1) and 140 underwent modified transanal Soave procedure from 2002 to 2004 (group 2). A comparison was made between the two groups on operative data and postoperative complications. The data included: age at the operation, operating time, blood loss, time to feeds and hospital stay, occurrence of postoperative enterocolitis or constipation, need for anal dilatation, postoperative bowel function and perianal skin problems.

RESULTSThere was no significant difference between two groups with respect to age, gender, length of colon resected, operating time, blood loss and hospital stay. However occurrence of postoperative enterocolitis, constipation, anastomotic stricture and time needed for anal dilatation were evidently less in group 2 (MTSPP). The mean operating time in group 1 was (106 +/- 39) minutes with a range of 60 to 170 minutes; in group 2 was (101 +/- 36) minutes with a range of 66 to 190 minutes. The average length of the bowel resected in group 1 was (24 +/- 7) cm, range 15 to 58 cm; in group 2 was (26 +/- 8) cm, range 15 to 70 cm. Two patients, one in each group, required laparoscopic assistance because of long aganglionic colon. Another patient in group 2 required laparotomy because of total colonic aganglionosis. Postoperative complications in group 1 included: temporary perianal excoriation in 34 patients (26 were < 3 months of age), enterocolitis in 21, anastomotic stricture in 11, recurrent constipation in 12, cuff abscess in 1, anastomosis leak in 1, soiling in 3 and rectal prolapse in 1. In group 2 post operative complications included: transient perianal excoriation in 37 patients (30 were < 3 months of age), enterocolitis in 13, anastomotic stricture in 5, recurrent constipation in 6, anastomotic leak in 1, adhesive bowel obstruction in 1 and soiling in 4. Complete bowel continence was found in 97 children (86.6%) in group 1 and in 129 children (92.1%) in group 2 at one year followup after operation.

CONCLUSIONSModified transanal Soave pull-through procedure for HD with oblique mucosectomy and anastomosis and a short split muscular cuff is a safe and feasible operation with low incidence of postoperative complication. It is an encouraging improvement of the conventional transanal Soave pull-through procedure. MTSPP is a preferable choice in the surgery of HD.

Adolescent ; Child ; Child, Preschool ; Digestive System Surgical Procedures ; methods ; Enterocolitis ; etiology ; Female ; Hirschsprung Disease ; surgery ; Humans ; Infant ; Infant, Newborn ; Male ; Minimally Invasive Surgical Procedures ; Postoperative Complications ; etiology

OBJECTIVETo summarize the causes and treatment experiences of postoperative constipation recurrences of Hirschsprung disease.

METHODSClinical data of 37 cases receiving operation again for postoperative constipation recurrences of Hirschsprung disease were collected. The recurrent causes, reoperation procedures and therapeutic efficacy were analyzed.

RESULTSAmong 37 cases, the recurrent causes included insufficient resection of the intestine in 14 cases, co-existent intestinal neural hypogenesis in 6, gate syndrome in 5, and others in 12 cases. There was no postoperative death. Thirty-one cases (83.8%) were followed-up from 6 months to 11 years. The defecation frequency was 1-2 times per day in 15 cases, one times per two days in 7, one times per three days in 6 cases. Two cases could defecate with the help of laxative purgatives. Nobody had incontinence.

CONCLUSIONThe main cause of postoperative constipation recurrences of Hirschsprung disease is insufficient resection of the intestine,and reoperation can get better results.

Child ; Child, Preschool ; Constipation ; etiology ; surgery ; Defecation ; Digestive System Surgical Procedures ; methods ; Female ; Hirschsprung Disease ; surgery ; Humans ; Infant ; Male ; Recurrence ; Reoperation

Abnormalities, Multiple ; physiopathology ; Bronchoscopy ; Diagnosis, Differential ; Hirschsprung Disease ; diagnosis ; physiopathology ; Humans ; Hypoventilation ; complications ; physiopathology ; Infant ; Laryngoscopy ; Male ; Respiratory Insufficiency ; complications ; diagnosis ; physiopathology ; Sleep Apnea, Central ; etiology ; Syndrome

In order to investigate the relationship between the expression of heme oxygenase-2 (HO-2) mRNA and the pathogenesis of Hirschsprung's disease (HD), total ribonucleic acid (RNA) was extracted in the aganglionic and ganglionic segments of colon respectively from 15 cases of HD. The single-stranded cDNA of HO-2 was synthesized and further amplified by reverse transcription-polymerase chain reaction (RT-PCR). The expression of HO-2 mRNA was normal in ganglionic segments, but absent in aganglionic segments. It is concluded that the absence of HO-2 mRNA expression may be an important mechanism responsible for HD.
Child ; Child, Preschool ; Colon ; enzymology ; Female ; Heme Oxygenase (Decyclizing) ; biosynthesis ; genetics ; Hirschsprung Disease ; enzymology ; etiology ; genetics ; Humans ; Infant ; Infant, Newborn ; Male ; RNA, Messenger ; biosynthesis ; genetics