AIM: To determine if expression of colonic tryptophan hydroxylase-2(TPH2), a surrogate marker of neuronal 5-hydroxytryptamine, is altered in Hirschsprung's-associated enterocolitis. METHODS: Entire resected coloni...AIM: To determine if expression of colonic tryptophan hydroxylase-2(TPH2), a surrogate marker of neuronal 5-hydroxytryptamine, is altered in Hirschsprung's-associated enterocolitis. METHODS: Entire resected colonic specimens were collected at the time of pull-through operation in children with Hirschsprung's disease(HSCR, n = 12). Five of these patients had a history of pre-operative Hirschsprung's-associated enterocolitis(HAEC). Controls were collected at colostomy closure in children with anorectal malformation(n = 10). The distribution of expression of TPH2 was evaluated using immunofluorescence and confocal microscopy. Protein expression of TPH2 was quantified using western blot analysis in the deep smooth muscle layers. RESULTS: TPH2 was co-expressed in nitrergic and cholinergic ganglia in the myenteric and submucosal plexuses in ganglionic colon in HSCR and healthy controls. Co-expression was also seen in submucosal interstitial cells of Cajal and PDGFRα+ cells. The density of TPH2 immuno-positive fibers decreased incrementally from ganglionic bowel to transition zonebowel to aganglionic bowel in the myenteric plexus. Expression of TPH2 was reduced in ganglionic bowel in those affected by pre-operative HAEC compared to those without HAEC and healthy controls. However, expression of TPH2 was similar or high compared to controls in the colons of children who had undergone diverting colostomy for medically refractory HAEC.CONCLUSION: Altered TPH2 expression in colonic serotonergic nerves of patients with HSCR complicated by HAEC may contribute to intestinal secretory and motor disturbances, including recurrent HAEC.展开更多
Hirschsprung’s disease(HSCR)is a congenital disorder characterized by failure of the neural crest cells to migrate and populate the distal bowel during gestation affecting different lengths of intestine leading to a ...Hirschsprung’s disease(HSCR)is a congenital disorder characterized by failure of the neural crest cells to migrate and populate the distal bowel during gestation affecting different lengths of intestine leading to a distal functional obstruction.Surgical treatment is needed to correct HSCR once the diagnosis is confirmed by demonstrating the absence of ganglion cells or aganglionosis of the affected bowel segment.Hirschsprung’s disease associated enterocolitis(HAEC)is an inflammatory complication associated with HSCR that can present either in the pre-or postoperative period and associated with increased morbidity and mortality.The pathogenesis of HAEC remains poorly understood,but intestinal dysmotility,dysbiosis and impaired mucosal defense and intestinal barrier function appear to play a significant role.There is no clear definition for HAEC,but the diagnosis is primarily clinical,and treatment is guided based on severity.Here,we aim to provide a comprehensive review of the clinical presentation,etiology,pathophysiology,and current therapeutic options for HAEC.展开更多
Objective： To 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 ...Objective： To 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 Sources： Our 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 Selection： Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded. Results： Several 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. Conclusions： The 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.展开更多
BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into...BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis,a potential life-threatening condition.Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.AIM To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.METHODS A systematic review and meta-analysis was done by searching PubMed,EMBASE and the Cochrane Library,using entry terms related to:(1)Hirschsprung disease;and(2)Botulinum toxin injections.14 studies representing 278 patients met eligibility criteria.Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection,proportion of patients with adverse effects and data on type botulinum toxin,mean dose,average age at first injection and patients with associated syndromes.Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.RESULTS Botulinum toxin injections are effective in treating obstructive symptoms in on average 66%of patients[event rate(ER)=0.66,P=0.004,I2=49.5,n=278 patients].Type of botulinum toxin,average dose,average age at first injections and proportion of patients with associated syndromes were not predictive for this effect.Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures.There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections(ER=0.79,vs ER=0.46,Q=19.37,P<0.001).Botulinum toxin injections were not effective in treating enterocolitis(ER 0.58,P=0.65,I2=71.0,n=52 patients).There were adverse effects in on average 17%of patients(ER=0.17,P<0.001,I2=52.1,n=187 patients),varying from temporary incontinence to mild anal pain.CONCLUSION Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present,but mild and temporary.展开更多
基金supported by grants from the National Children’s Research Centre/Children’s Medical and Research Foundation and from the Temple Street Foundation
文摘AIM: To determine if expression of colonic tryptophan hydroxylase-2(TPH2), a surrogate marker of neuronal 5-hydroxytryptamine, is altered in Hirschsprung's-associated enterocolitis. METHODS: Entire resected colonic specimens were collected at the time of pull-through operation in children with Hirschsprung's disease(HSCR, n = 12). Five of these patients had a history of pre-operative Hirschsprung's-associated enterocolitis(HAEC). Controls were collected at colostomy closure in children with anorectal malformation(n = 10). The distribution of expression of TPH2 was evaluated using immunofluorescence and confocal microscopy. Protein expression of TPH2 was quantified using western blot analysis in the deep smooth muscle layers. RESULTS: TPH2 was co-expressed in nitrergic and cholinergic ganglia in the myenteric and submucosal plexuses in ganglionic colon in HSCR and healthy controls. Co-expression was also seen in submucosal interstitial cells of Cajal and PDGFRα+ cells. The density of TPH2 immuno-positive fibers decreased incrementally from ganglionic bowel to transition zonebowel to aganglionic bowel in the myenteric plexus. Expression of TPH2 was reduced in ganglionic bowel in those affected by pre-operative HAEC compared to those without HAEC and healthy controls. However, expression of TPH2 was similar or high compared to controls in the colons of children who had undergone diverting colostomy for medically refractory HAEC.CONCLUSION: Altered TPH2 expression in colonic serotonergic nerves of patients with HSCR complicated by HAEC may contribute to intestinal secretory and motor disturbances, including recurrent HAEC.
文摘Hirschsprung’s disease(HSCR)is a congenital disorder characterized by failure of the neural crest cells to migrate and populate the distal bowel during gestation affecting different lengths of intestine leading to a distal functional obstruction.Surgical treatment is needed to correct HSCR once the diagnosis is confirmed by demonstrating the absence of ganglion cells or aganglionosis of the affected bowel segment.Hirschsprung’s disease associated enterocolitis(HAEC)is an inflammatory complication associated with HSCR that can present either in the pre-or postoperative period and associated with increased morbidity and mortality.The pathogenesis of HAEC remains poorly understood,but intestinal dysmotility,dysbiosis and impaired mucosal defense and intestinal barrier function appear to play a significant role.There is no clear definition for HAEC,but the diagnosis is primarily clinical,and treatment is guided based on severity.Here,we aim to provide a comprehensive review of the clinical presentation,etiology,pathophysiology,and current therapeutic options for HAEC.
基金This study was supported by a grant from National Natural Science Foundation of China
文摘Objective： To 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 Sources： Our 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 Selection： Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded. Results： Several 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. Conclusions： The 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.
文摘BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis,a potential life-threatening condition.Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.AIM To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.METHODS A systematic review and meta-analysis was done by searching PubMed,EMBASE and the Cochrane Library,using entry terms related to:(1)Hirschsprung disease;and(2)Botulinum toxin injections.14 studies representing 278 patients met eligibility criteria.Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection,proportion of patients with adverse effects and data on type botulinum toxin,mean dose,average age at first injection and patients with associated syndromes.Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.RESULTS Botulinum toxin injections are effective in treating obstructive symptoms in on average 66%of patients[event rate(ER)=0.66,P=0.004,I2=49.5,n=278 patients].Type of botulinum toxin,average dose,average age at first injections and proportion of patients with associated syndromes were not predictive for this effect.Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures.There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections(ER=0.79,vs ER=0.46,Q=19.37,P<0.001).Botulinum toxin injections were not effective in treating enterocolitis(ER 0.58,P=0.65,I2=71.0,n=52 patients).There were adverse effects in on average 17%of patients(ER=0.17,P<0.001,I2=52.1,n=187 patients),varying from temporary incontinence to mild anal pain.CONCLUSION Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present,but mild and temporary.
