Hirschsprung's disease associated enterocolitis:A comprehensive review

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.

Robotic-assisted proctosigmoidectomy for Hirschsprung’s disease:A multicenter prospective study

BACKGROUND Robotic surgery is a cutting-edge minimally invasive technique that overcomes many shortcomings of laparoscopic techniques,yet few studies have evaluated the use of robotic surgery to treat Hirschsprung’s disease(HSCR).AIM To analyze the feasibility and medium-term outcomes of robotic-assisted proctosigmoidectomy(RAPS)with sphincter-and nerve-sparing surgery in HSCR patients.METHODS From July 2015 to January 2022,156 rectosigmoid HSCR patients were enrolled in this multicenter prospective study.Their sphincters and nerves were spared by dissecting the rectum completely from the pelvic cavity outside the longitudinal muscle of the rectum and then performing transanal Soave pull-through procedures.Surgical outcomes and continence function were analyzed.RESULTS No conversions or intraoperative complications occurred.The median age at surgery was 9.50 months,and the length of the removed bowel was 15.50±5.23 cm.The total operation time,console time,and anal traction time were 155.22±16.77,58.01±7.71,and 45.28±8.15 min.There were 25 complications within 30 d and 48 post-30-d complications.For children aged≥4 years,the bowel function score(BFS)was 17.32±2.63,and 90.91%of patients showed moderate-to-good bowel function.The postoperative fecal continence(POFC)score was 10.95±1.04 at 4 years of age,11.48±0.72 at 5 years of age,and 11.94±0.81 at 6 years of age,showing a promising annual trend.There were no significant differences in postoperative complications,BFS,and POFC scores related to age at surgery being≤3 mo or>3 mo.CONCLUSION RAPS is a safe and effective alternative for treating HSCR in children of all ages;it offers the advantage of further minimizing damage to sphincters and perirectal nerves and thus providing better continence function.

Hirschsprung病肠壁中葡萄糖转运体-1和一氧化氮合酶阳性神经的变化憊

目的 观察葡萄糖转运体 1(GLUT 1)和一氧化氮合酶 (NOS)阳性神经在Hirschsprung病 (HD)肠壁中的变化并探讨二者与HD发病的关系。方法 应用还原型辅酶Ⅱ 黄递酶组织化学和免疫组织化学染色观察 9例HD及 5例对照组患儿结肠。结果 在正常结肠的肌层和粘膜下层内偶见细小的GLUT 1免疫反应性神经纤维 ,肠壁外的外源性神经纤维呈阳性染色 ;而在无神经节细胞肠段的相应区域内GLUT 1免疫反应性神经纤维数量明显增多、增粗。在正常结肠肠壁内有大量NOS阳性神经节细胞 ,环肌层内含有丰富的阳性神经纤维 ;而在无神经节细胞肠段的肠壁内缺乏NOS阳性神经元 ,肌层内阳性神经纤维明显减少。结论 肠壁内GLUT 1阳性神经可能为外源性神经 ,GLUT 1免疫组织化学染色可能对HD具有诊断价值。NOS阳性神经在病变肠壁中的分布异常可能与HD的病理生理机制有关。

成人Hirschsprung病1例

Hirschsprung病又名先天性巨结肠或结肠神经节细胞缺如症(aganglionosis),是一种少见病,发病率为1/20 000～1/30 000活产的新生儿.此病见于婴幼儿和儿童,偶见于成人[1].现报道成人病例1例.

Decreased expression of hyperpolarisation-activated cyclic nucleotide-gated channel 3 in Hirschsprung's disease

AIM: To determine if hyperpolarisation-activated nucleotide-gated(HCN) channels exist in human colon, and to investigate the expression of HCN channels in Hirschsprung's disease.METHODS:We investigated HCN1,HCN2,HCN3 and HCN4 protein expression in pull-through specimens from patients with Hirschsprung’s disease(HSCR,n=10)using the proximal-most ganglionic segment and distalmost aganglionic segment,as well as in healthy control specimens obtained at the time of sigmoid colostomy closure in children who had undergone anorectoplasty for imperforate anus(n=10).Fluorescent immunohistochemistry was performed to assess protein distribution,which was then visualized using confocal microscopy.RESULTS:No HCN1 channel expression was observed in any of the tissues studied.Both HCN2 and HCN4proteins were found to be equally expressed in the aganglionic and ganglionic bowel in HSCR and controls.HCN3 channel expression was found to be markedly decreased in the aganglionic colon vs ganglionic colon and controls.HCN2-4 channels were seen to be expressed within neurons of the myenteric and submucosal plexus of the ganglionic bowel and normal controls,and also co-localised to interstitial cells of Cajal in all tissues studied.CONCLUSION:We demonstrate HCN channel expression in human colon for the first time.Reduced HCN3expression in aganglionic bowel suggests its potential role in HSCR pathophysiology.

Botulinum toxin injections after surgery for Hirschsprung disease:Systematic review and meta-analysis

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.

The development of colon innervation in trisomy 16 mice and Hirschsprung’s disease

AIM To study the colon innervation of trisomy 16 mouse, an animal model for Downs syndrome, and the expression of protein gene product 9.5 (PGP 9.5) in the stenosed segment of colon in Hirschsprungs disease (HD). METHODS Trisomy 16 mouse breeding; cytogenetic analysis of trisomy 16 mice; and PGP 9.5 immunohistochemistry of colons of trisomy 16 mice and HD were carried out. RESULTS Compared with their normal littermates, the nervous system of colon in trisomy 16 mice was abnormally developed. There existed developmental delay of muscular plexuses of colon, no submucosal plexus was found in the colon, and there was 5mm aganglionic bowel aparting from the anus in trisomy 16 mice. The mesentery nerve fibers were as well developed as shown in their normal littermates. Abundant proliferation of PGP 9.5 positive nerve fibers was revealed in the stenosed segment of HD colon. CONCLUSION Trisomy 16 mice could serve as an animal model for Hirschsprung s disease for aganglionic bowel in the distal part of colon. Abundant proliferation of PGP 9.5 positive fibers resulted from extrinsic nerve compensation, since no ganglionic cells were observed in the stenosed segment of the colon in HD. HD has a genetic tendency.

经肛门改良Soave术在Hirschsprung病(HD)治疗中的临床效果分析

目的研究对比经肛门改良Sovae术在治疗Hirschsprung病(HD)的效果。方法选取2003年1月至2015年12月我科接受治疗的77例先天巨结肠的患儿,按治疗方法的不同将其分为观察组和对照组,观察组选取患者为2008年1月至2015年12月我科开始采用经肛门改良Soave术进行治疗的患儿48例,对照组选取2003年1月至2007年12月采用开腹手术进行治疗的患儿29例,观察两组的治疗效果、术中出血量和住院时间。结果经治疗后发现观察组患儿复发1例,复发率为8.00%;对照组患儿复发1例,复发率为16.00%,两组比较差异显著P<0.05,具有统计学意义,观察组患儿的术中出血量明显少于对照组,住院时间短于对照组,两组比较差异显著P<0.05,具有统计学意义。结论经肛门改良Soave术治疗Hirschsprung病具有良好的效果,可以减少患儿的出血量,缩短患儿的住院时间,值得临床推广使用。

Genetic interactions and modifi er genes in Hirschsprung's disease

Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.

Depletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype

AIM:To investigate the role of IKBKAP(inhibitor of kappa light polypeptide gene enhancer in B-cells,kinase complexassociated protein)in the development of enteric nervous system(ENS)and Hirschsprung disease(HSCR).METHODS:In this study,we injected a morpholino that blocked the translation of ikbkap protein to 1-cell stage zebrafish embryos.The phenotype in the ENS was analysed by antibody staining of the pan-neuronal marker Hu C/D followed by enteric neuron counting.The mean numbers of enteric neurons were compared between the morphant and the control.We also studied the expressions of ret and phox2bb,which are involved in ENS development,in the ikbkap morpholino injected embryos by quantitative reverse transcriptase polymerase chain reaction and compared them with the control.RESULTS:We observed aganglionosis(χ2,P<0.01)and a reduced number of enteric neurons(38.8±9.9 vs50.2±17.3,P<0.05)in the zebrafish embryos injected with ikbkap translation-blocking morpholino(morphant)when compared with the control embryos.Specificity of the morpholino was confirmed by similar results obtained using a second non-overlapping morpholino that blocked the translation of ikbkap.We further studied the morphant by analysing the expression levels of genes involved in ENS development such as ret,phox2bb and sox10,and found that phox2bb,the ortholog of human PHOX2B,was significantly down-regulated(0.51±0.15 vs 1.00±0,P<0.05).Although we also observed a reduction in theexpression of ret,the difference was not significant.CONCLUSION:Loss of IKBKAP contributed to HSCR as demonstrated by functional analysis in zebrafish embryos.

Clinical outcomes and ergonomics analysis of three laparoscopic techniques for Hirschsprung's disease

AIM: To report the clinical outcomes and ergonomics analysis of three laparoscopic approaches in the management of Hirschsprung's disease(HD).METHODS: There were 90 pediatric patients(63 boys, 27 girls; mean age: 3.6 ± 2.7 mo; range: 1.0-90.2 mo) who underwent laparoscopic endorectal pull-through Soave procedures for short- and long-segment HD in our hospital. Three laparoscopic approaches were used: conventional laparoscopic pull-through(CLP) in 30 patients between 2009 and 2013, single-incision laparoscopic pull-through(SILP) in 28 patients between 2010 and 2013, and hybrid single-incision laparoscopic pull-through(H-SILP) in 32 patients between 2011 and 2013. We applied the hybrid version of the single-incision approach in 2011 to preserve the cosmetic advantage of SILP and the ergonomic advantage of CLP. We retrospectively analyzed the clinical data, cosmetic results, and ergonomics of these three approaches to have a better understanding of the selection of one approach over another. RESULTS: The CLP, SILP, and H-SILP groups were similar in regard to age, sex, transition zone, blood loss, hospital stay, and intraoperative complications. Early and late postoperative results were not different, with equal daily defecation frequency and postoperative complications. No conversion to open technique was needed and none of the patients had recurrent constipation. With proper training, the ergonomics challenges were overcome and similar operative times were registered for the general operative time in the patients < 1 year of age and the short-segment HD patients. However, significantly shorter operative times were registered compared to SILP for patients > 1 year of age(CLP and H-SILP: 120 ± 15 min and 119 ± 12 min, respectively, vs 140 ± 7 min; P < 0.05) and for long-segment HD patients(152 ± 3.5 min and 154 ± 3.6 min, respectively, vs 176 ± 2.3 min; P < 0.05). The best cosmetic result was registered with the SILP(scarless), followed by the H-SILP(near scarless appearance) and the CLP(visible scars) procedures. CONCLUSION: Based on the results, we believed that the laparoscopic approach should be selected according to the age, transition zone, and desired cosmetic result.

Megacolon in adulthood after surgical treatment of Hirschsprung's disease in early childhood

Hirschsprung＇s disease （HD） is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowel, However, patients often do not obtain complete functional improvement after surgical treatment. We present the case of a 25-year-old woman who had surgical treatment of lid in early childhood. After that procedure she had clinical features of constipation for years in the end, passing of stool once a week, requiring laxatives and enemas. We diagnosed an incomplete resection of the aganglionic bowel via rectal biopsy and resected the remaining aganglionic segment. Two months after surgery the patient＇s bowel function improved to a frequency of 1-4 stools per day. We conclude that regular follow-up is required to identify lid patients with persistent alterations of bowel function after surgery. In patients presenting with constipation, recognition of a remaining aganglionic segment or other alterations of the enteric nervous system should be aimed at in an early stage. 2005 The WJG Press and Elsevier Inc. All rights reserved

Hirschsprung's disease:Is there a relationship between mast cells and nerve fibers?

AIM:To define the topography of mast cells and their numbers in cases of Hirschsprung's disease(HD)and non-HD,assess neural hypertrophy using imaging software and to study the relationship between mast cells and nerve fibers.METHODS:HE stained sections of 32 cases of chronic constipation in the age group of 0-14 years were reviewed for ganglion cells.AChE staining was performed on frozen sections of colonic and rectal biopsies.Based on their findings cases were divided into HD and non-HD and mast cells stained by toluidine blue were evaluated.Image analysis by computerized software was applied to S-100 stained sections for assessment of neural hypertrophy.RESULTS:Difference between number of mast cells in HD group(mean=36.44)and in non-HD group(mean =14.79)was statistically significant.Image analysis morphometry on S-100 stained sections served as a useful adjunct.The difference between number,size,and perimeter of the nerve fibers between HD and non-HD group was statistically significant.CONCLUSION:Mast cells are significantly increased in HD and their base line values are much higher in Indian children than that reported in Western literature.Their role in HD needs further research.Morphometry of S-100 stained nerve fibers is a useful adjunct to conventional methods for diagnosis of HD.

Genetic polymorphism of UL144 open reading frame of human cytomegalovirus DNA detected in colon samples from infants with Hirschsprung's disease

AIM： To explore the genetic diversities of UL144 open reading frame （ORF） of cytomegalovirus DNA detected in colon tissue from infants with Hirschsprung＇s disease （HD） by sequencing UL144 DNA in 23 aganglionic colon tissue and 4 urine samples from 25 HD infants. METHODS： Nest PCR was performed for amplification of the UL144 gene. The UL144 gene was analyzed with soffwares, such as DNAclub, BioEdit, PROSITE database, and DNAstar. RESULTS： The strains from HD patients were distributed among three genotypes of UL144： group 1A （64%）, group 2 （24%）, and group 3 （12%）. The UL144 genotypes between strains from HD and control group were compared by chi square test （x^2 = 1.870, P = 0.393）. Strains from the colon were sporadically distributed in UL144 genotypes. CONCLUSION： There are genetic diversities of UL144 ORF in colon tissue of infants with HD. However, cytomegalovirus UL144 genotypes are not associated with clinical manifestations of HD.

Deficiency of platelet-derived growth factor receptor-α-positive cells in Hirschsprung's disease colon

AIM: To investigate whether the expression of platelet-derived growth factor receptor-α-positive (PDGFRα+)-cells is altered in Hirschsprung’s disease (HD).METHODS: HD tissue specimens (n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). Immunolabelling of PDGFRα+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein expression.RESULTS: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD colon.CONCLUSION: These findings suggest that the altered distribution of PDGFRα+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.

Transumbilical enterostomy for Hirschsprung’s disease with a two-stage laparoscopy-assisted pull-through procedure

BACKGROUND A one-stage laparoscopic operation has recently been considered a favorable option for the management of patients with Hirschsprung's disease(HD)due to its superior cosmetic results.One-stage transanal endorectal pull-through for the treatment of rectosigmoid HD has been widely used in newborns without complications.However,enterostomy is required in some HD cases for enterocolitis and dilated colon.Our transumbilical enterostomy(TUE)and twostage laparoscopy-assisted anorectoplasty were effective and achieved a similar cosmetic effect to one-stage laparoscopy on the abdominal wall in patients with anorectal malformation,but the effect in patients with HD is unclear.AIM To evaluate the safety,efficacy and cosmetic results of TUE in two-stage laparoscopy-assisted pull-through for HD.METHODS From June 2013 to June 2018,53 patients(40 boys,13 girls;mean age at enterostomy:5.5±2.2 mo)who underwent enterostomy and two-stage laparoscopy-assisted pull-through for HD with stoma closure were reviewed at our institution.Two enterostomy approaches were used:TUE in 24 patients,and conventional abdominal enterostomy(CAE)in 29 patients.Eleven patients with rectosigmoid HD had severe preoperative enterocolitis or a dilated colon.26 patients had long-segment HD,and 16 patients had total colonic aganglionosis(TCA).The patients with left-sided HD underwent the two-stage laparoscopic Soave procedure,and the patients with right-sided HD and TCA underwent the laparoscopic Duhamel procedure.Demographics,enterostomy operative time,complications and cosmetic results were respectively evaluated.RESULTS There were no differences between the groups with respect to gender,age at enterostomy,weight and clinical type(P>0.05).No conversion to open technique was required.Two patients experienced episodes of stomal mucosal prolapse in the TUE group and 1 patient in the CAE group(8.33%vs 3.45%,P>0.05).No parastomal hernia was observed in either of the two groups.Wound infection at the stoma was seen in 1 case in the TUE group,and 2 cases in the CAE group(4.17%vs 6.90%,P>0.05).No obstruction was noted in any of the patients in the TUE group,whereas obstruction was found in 1 patient in the CAE group.Enterocolitis was observed in 3 and 5 patients in the TUE and CAE group,respectively(12.50%vs 17.24%,P>0.05).There was no significant difference between the TUE group and CAE group in terms of the incidence of soiling and constipation(P>0.05).The cosmetic result using the scar score in the TUE group was better than that in the CAE group(6.83±0.96 vs 13.32±1.57,P<0.05).CONCLUSION TUE is a safe and feasible method for the treatment of HD,and the staged enterostomy and two-stage laparoscopy-assisted pull-through achieved a similar cosmetic effect to the one-stage laparoscopic procedure.

Generic and disease-specific health-related quality of life in patients with Hirschsprung disease:A systematic review and meta-analysis

BACKGROUND Patients with Hirschsprung disease(HD)are at risk of persistent constipation,fecal incontinence or recurrent enterocolitis after surgical treatment,which in turn may impact physical and psychosocial functioning.Generic health-related quality of life(HRQoL)and disease-specific health-related quality of life are relevant outcome measures to assess the impact of HD on the QoL of these patients.AIM To summarize all available evidence on HRQoL of patients with HD after surgery and the impact of possible moderating factors.METHODS Pubmed,Web of Sciences,Psyc Info and Embase were searched with search terms related to’Hirschsprung disease’,’Pediatrics’and’Quality of life’.Mean and standard deviation of generic HRQoL overall and domain scores were extracted from each study,as well as data describing potential factors associated with QoL.Random effect models were used for meta-analytic aggregation of generic HRQoL scores.Meta-regression was used to assess the relationship between patient and clinical characteristics and generic HRQoL.Disease-specific HRQoL outcomes of patients with HD were systematically reviewed.RESULTS Seventeen articles were included in the systematic review(n=1137 patients)and 15 in the quantitative meta-analysis(n=1024 patients).Four studies reported disease-specific HRQoL.Patient’s age ranged between 0 and 21 years.Meta-analytic aggregation showed a nonsignificantly impaired generic HRQoL(d=-0.168[95%CI:-0.481;0.145],P=0.293,I^(2)=94.9)in patients with HD compared to healthy controls.Physical(d=-0.042[95%CI:-0.419;0.335],P=0.829,I^(2)=95.1),psychosocial(d=-0.159[95%CI:-0.458;0.141],P=0.299,I^(2)=93.6)and social HRQoL(d=-0.092[95%CI:-0.642;0.457],P=0.742,I^(2)=92.3)were also not significantly lower compared to healthy controls.There was no relation between health-related outcomes and the sex of the patients and whether generic HRQoL was measured by parental proxy or self-report.Disease-specific complaints of patients with HD impaired physical HRQoL,but not psychosocial and social HRQoL.CONCLUSION In this systematic review and meta-analysis,no evidence was found for impaired generic HRQoL in patients with HD compared to healthy controls,neither for moderating effects of sex,parental proxy or self-report.

Abundance and significance of neuroligin-1 and glutamate in Hirschsprung's disease

AIM: To investigate the abundance and potential diagnostic significance of neuroligin-1 and glutamate(Glu) in Hirschsprung's disease(HSCR).METHODS: Ninety children with HSCR and 50 children without HSCR matched for similar nutritional status, age and basal metabolic index were studied. The expression and localization of neuroligin-1 and Glu were assessed using double-labeling immunofluorescence staining of longitudinal muscles with adherent myenteric plexus from the surgically excised colon of children with HSCR. Western blot analysis, quantitative real-time PCR(q RT-PCR) and immunohistochemistry were performed to evaluate the abundance of neuroligin-1 and Glu in different HSCR-affected segments(ganglionic, transitional, and aganglionic segments). Enzyme-linked immunosorbent assay(ELISA) was used to detect and compare serum Glu levels in the long-segment HSCR, short-segment HSCR and non-HSCR samples.RESULTS: Neuroligin-1 and Glu were co-expressed highest to lowest in the ganglionic, transi tional and aganglionic segments based on Western blot(neuroligin-1: 0.177 ± 0.008 vs 0.101 ± 0.006, 0.177 ± 0.008 vs 0.035 ± 0.005, and 0.101 ± 0.006 vs 0.035 ±0.005, P < 0.005; Glu: 0.198 ± 0.006 vs 0.115 ± 0.008, 0.198 ± 0.006 vs 0.040 ± 0.003, and 0.115 ± 0.008 vs 0.040 ± 0.003, P < 0.005) and q RT-PCR(neuroligin-1: 9.58 × 10-5 ± 9.94 × 10-6 vs 2.49 × 10-5 ± 1.38 × 10-6, 9.58 × 10-5 ± 9.94 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, and 2.49 × 10-5 ± 1.38 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, P < 0.005). Serum Glu level was the highest to lowest in the non-HSCR, short-type HSCR and long-type HSCR samples based on ELISA(in nmol/μL, 0.93 ± 0.31 vs 0.57 ± 0.25, 0.93 ± 0.31 vs 0.23 ± 0.16, and 0.57 ± 0.25 vs 0.23 ± 0.16, P < 0.005).CONCLUSION: Neuroligin-1 and Glu may represent new markers of ganglion cells, whose expression may correlate with the pathogenesis, diagnosis, differential diagnosis or classification of HSCR.

Persistent bowel dysfunction after surgery for Hirschsprung’s disease:A neuropathological perspective

Hirschsprung’s disease(HD)is a congenital disorder,characterized by aganglionosis in the distal part of the gastrointestinal tract.Despite complete surgical resection of the aganglionic segment,both constipation and fecal incontinence persist in a considerable number of patients with limited treatment options.There is growing evidence for structural abnormalities in the ganglionic bowel proximal to the aganglionosis in both humans and animals with HD,which may play a role in persistent bowel dysfunction.These abnormalities include:(1)Histopathological abnormalities of enteric neural cells;(2)Imbalanced expression of neurotransmitters and neuroproteins;(3)Abnormal expression of enteric pacemaker cells;(4)Abnormalities of smooth muscle cells;and(5)Abnormalities within the extracellular matrix.Hence,a better understanding of these previously unrecognized neuropathological abnormalities may improve follow-up and treatment in patients with HD suffering from persistent bowel dysfunction following surgical correction.In the long term,further combination of clinical and neuropathological data will hopefully enable a translational step towards more individual treatment for HD.

成人先天性Hirschsprungs病并桶状胸、肠梗阻,中毒性巨结肠1例

成人先天性Hirschsprungs病是一种多因素引起,并经长期演变而来的特发性疾病,发病率较低。常见并发症包括肠梗阻、营养不良、小肠结肠炎及中毒性巨结肠,中毒性巨结肠的发生率较低,但危及生命。本文报道1例合并桶状胸病例。1病例资料男性,51岁,已婚,农民,因'顽固性便秘、腹胀腹痛36年,加重1月'以'成人先天性巨结肠'入吉林大学第一医院胃肠外科。患者幼年起病,长期便秘,未规律治疗。