Enterocolitis in Hirschsprung's disease

During the 5 years 1985–1989, 24 (32%) of 76 patients treated for Hirschsprung's disease (HD) developed enterocolitis, this being present at the time of diagnosis in 10 (13%) infants, 7 of whom were neonates. HD presented as necrotizing enterocolitis in 5 neonates, 4 of whom were premature. The enterocolitis developed postoperatively in 14 (18%) patients, in 7 after an enterostomy and in 7 after a pull-through procedure. Recurrent episodes of enterocolitis occurred in 4 of the patients who developed postoperative enterocolitis. The risk of enterocolitis was increased in girls, in patients with associated Down's syndrome, those with a family history of HD, and those managed by an endorectal pull-through procedure. The Duhamel procedure was associated with a low (5%) incidence of postoperative enterocolitis. Long-segment aganglionosis was not associated with an increased risk of enterocolitis and preoperative enterocolitis conferred no increased risk of postoperative enterocolitis.     

icrobial studies of enterocolitis in Hirschsprung's disease

Enterocolitis in Hirschsprung's disease (HD) has been the most significant cause of morbidity and mortality in children suffering from this disorder. A variety of aetiologies have been postulated, including hypersensitivity to bacterial antigens, proximal colonic dilatation with secondary mucosal ischaemia, abnormalities of the mucosubstances within the colon, elevated prostaglandin El activity, and microbiological infections with pathogens such asClostridium difficile and rotavirus. Recent studies have shown that children with HD who are prone to the development of enterocolitis have abnormalities of their immunological status. Studies of the microbiological flora of the colon of children with HD showed no significant difference between children with uncomplicated HD, those who ran a complicated course with enterocolitis, and a control group with no gastro-intestinal pathology. Viral studies have recently implicated a rotavirus in the aetiology of this condition, thus compounding the problem of pinpointing any particular organism. Previous studies have shown that some children with HD can develop a potentially lethal pseudomembranous colitis even if there has been no previous exposure to antibiotic therapy. These are clearly the group in which otherwise commensalCl. difficile has a significant pathogenic role. In view of this multi-factorial infective aetiology, it is recommended that a high level of suspicion be kept and all children with HD who develop any of the signs or symptoms of enterocolitis should have a full microbiological infective screen, as any number of bacterial or viral organisms may be the causal factor.     

Toxic megacolon in Hirschsprung's disease is still potentially fatal

In recent years the emphasis in Hirschsprung's disease has been largely directed toward histology and histochemical findings and to the results of the surgical procedures currently practiced. However, in the individual patient with Hirschsprung's disease, of greater significance can be the occurrence of life-threatening enterocolitis. In its most severe form, this is associated with gross dilatation of the colon and profound toxemia, the combination being termed toxic megacolon. Because of its relative rarity and the need for neonatologists and pediatric surgeons to keep in mind this potentially disastrous complication, a patient with toxic megacolon is described and a therapeutic approach suggested.     

Evaluation of risk factors in the development of enterocolitis complicating Hirschsprung's disease

Enterocolitis remains a major cause of morbidity and mortality in patients with Hirschsprung's disease (HD). Forty-one (30%) of 135 patients treated for HD from 1975 to 1992 developed enterocolitis; enterocolitis occured preoperatively in 25. It was a presenting feature in 17 infants, including 11 neonates. The proportion of patients presenting with enterocolitis in the neonatal period increased with advancing age, 6 (11%) out of 56 presenting within the 1st week and 5 (24%) out of 21 after 1 week. Episodes of enterocolitis continued in 7 of these 25 patients after a pull-through procedure. Sixteen patients had a first episode of enterocolitis after surgery: 3 after a colostomy, and 13 after a pull-through procedure. The incidence of enterocolitis was 28% in patients with rectosigmoid involvement and 38% in patients with long-segment or total colonic aganglionosis (P= 0.1). Enterocolitis occured in 8 (47%) of 17 patients with trisomy 21 as compared to 33 of 118 (28%) other patients (P= 0.1). Four of the 41 patients died as a result of enterocolitis, 3 in the neonatal period after a colostomy performed at a mean age of 22 days, although the symptoms suggestive of HD were present since birth. Prompt diagnosis and expeditious management are necessary in patients with HD.     

Persistence of enterocolitis following diversion of faecal stream in Hirschsprung's disease

Mucosal defence mechanisms of the excluded bowel were studied in 12 patients with Hirschsprung's disease. The entire resected segment of colon obtained following Swenson's operation was cut at 0.5-cm intervals and serially examined by routine haematoxylin and eosin staining, immunocytochemistry, and mucin histochemistry. Seven patients who had clinical evidence of enterocolitis prior to defunctioning colostomy showed histological and immunological evidence of enterocolitis (crypt abscesses, ulceration, leucocyte aggregation, Paneth cell metaplasia, and marked immunocyte responses) in the excluded bowel even several months after diversion of the faecal stream. Mucin histochemistry showed marked depletion of neutral mucins and sulphomucins in the excluded bowel with inflammatory changes and reversal of the sialo- to sulphomucin ratio. These results indicate that patients with enterocolitis complicating Hirschsprung's disease have persistent inflammatory changes in the excluded large bowel after diversion of the faecal stream by colostomy. Environmental factors such as bacterial stimulation and proliferation probably cause inhibition of cell renewal, resulting in abnormalities of mucin fractions. Changes in mucin composition, which is an important mechanical and chemical factor of the mucosal defence mechanism, may lead to altered susceptibility to bacterial degradation and hence may be important in the pathogenesis of enterocolitis. Offprint requests to: P. Puri     

Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of enterocolitis complicating Hirschsprung's disease

Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein that is necessary for the transendothelial migration of leucocytes. This study was undertaken to elucidate the role of ICAM-1 in the pathophysiology of Hirschsprung's disease (HD)-related enterocolitis. Ganglionic and aganglionic portions of bowel from 18 patients with HD who did not have clinical or histological evidence of enterocolitis and 5 patients with HD who developed enterocolitis before or after a pull-through operation were stained using monoclonal antibody against ICAM-1. The bowel specimens obtained from 2 children with imperforate anus at the time of colostomy closure and 3 children at the time of bladder augmentation were similarly stained to act as controls. The ganglionic portion of bowel from patients with HD without enterocolitis and controls showed either no ICAM-I staining or occasional staining of the endothelial lining of submucosal vessels with no staining of the glandular crypt epithelium. In contrast, both ganglionic and aganglionic bowel from patients with enterocolitis complicating HD demonstrated strong ICAM-1 staining in the endothelium of submucosal vessels. Strong expression of ICAM-1 in the glandular crypt epithelium was seen in only 2 patients who had developed enterocolitis before pull-through operations. This study illustrates the importance of endothelial cell activation in the pathogenesis of HD-related enterocolitis.     

The expression and significance of calretinin in the colon of patients with Hirschsprung's disease

目的 本研究应用免疫组织化学染色方法,观察对照组肠壁、先天性巨结肠症(Hirschsprung's disease,HD)患儿有神经节细胞段和无神经节细胞段肠壁神经组织中钙视网膜蛋白(Calretinin,CR)的表达结果,目的在于了解HD的病理生理改变以及寻找诊断先天性巨结肠的简便有效的方法.方法 收集苏州大学附属儿童医院小儿外科2005至2008年手术切除HD标本54例,包括HD扩张段与痉挛段.以15例年龄与之相符的无HD患儿的手术切除结肠标本作为对照组.分别对HD痉挛段、扩张段、对照组肠壁组织切片进行CR的免疫组织化学染色和HE染色,计算机成像系统照相存盘,用图像分析软件(Image-Pro-Plus)分别判定CR在HD扩张段与痉挛段神经丛中阳性染色面积百分比.所得数据用SPSS 12.0统计软件包进行处理分析.结果 ①无论是HE或免疫组化染色HD的扩张段神经节细胞皆存在,肌层神经纤维有不同程度的排列改变,神经节细胞大小不等;痉挛段均未见神经节细胞;②在正常结肠及HD扩张段肠壁免疫组化染色可见钙视网膜蛋白在肌间及黏膜下神经丛中对神经节细胞呈强阳性表达,神经纤维也呈阳性反应;而HD痉挛段肠壁的免疫组化染色则可见钙视网膜蛋白在肌间神经丛及黏膜下神经丛大多表达阴性(90.7％),仅少量呈弱阳性表达(9.3％);③定量分析:CR分别在HD痉挛段之间神经丛中阳性染色面积百分率(0.00665±().00387)与其在HD扩张段神经丛中阳性染色面积百分率(0.26483±0.14626)存在差异,有显著统计学意义(P＜0.01).结论 钙视网膜蛋白免疫组化染色可很好的显示正常结肠及HD扩张段肠壁的神经节细胞及神经纤维,而在HD痉挛段该指标免疫组化染色结果呈阴性或弱阳性表达.钙视网膜蛋白可能作为诊断HD的神经标志物之一.     

Reoperation for Hirschsprung's disease

目的 分析先天性巨结肠根治术后再次手术的病例,分析再次手术的原因,讨论手术指征和再次手术方式的选择.方法 回顾分析1999年至2011年间先天性巨结肠根治术后再次手术19例临床资料.再次手术原因:吻合口狭窄5例,残留无神经节细胞症5例,直肠皮肤瘘6例,直肠阴道瘘1例,复杂瘘2例.再次手术方式:经腹联合后矢状入路术式7例,Soave术式7例,Duhamel术式1例,Rehbein术式3例,经腹修补直肠阴道瘘1例.随访患儿术后不同时期排便次数、粪便性状、便秘、失禁、污粪以及小肠结肠炎等内容.结果 84.2％(16/19)患儿有便意,能自行排便,2例偶有污粪,1例直肠骶部瘘未愈.结论 先天性巨结肠根治术后出现严重并发症,通过合理选择再次手术方式,可以达到满意的临床效果.     

肥大细胞检测在先天性巨结肠小肠结肠炎中的临床意义

目的 探讨肥大细胞在先天性巨结肠小肠结肠炎发病机制的作用,为临床治疗提供依据.方法 2004年5月～2006年5月在上海交通大学医学院附属新华医院行先天性巨结肠根治术中切除的狭窄段、移行段和扩张段肠管黏膜层标本,共30例.男23例,女7例,年龄1个月～7岁,平均1.2岁.短段型5例,普通型18例,长段型6例,全结肠型1例.根据术前有无小肠结肠炎临床症状将患儿分为巨结肠肠炎组(n=12)和非肠炎组(n=18).肥大细胞采用甲苯胺蓝染色和免疫组织化学染色(chymase)染色.结果 巨结肠肠炎组狭窄段、移行段和扩张段肥大细胞在黏膜,黏膜下及扩张的血管周围聚集,脱颗粒现象明显.非肠炎组结肠组织中肥大细胞在黏膜下,黏膜明显减少,脱颗粒现象轻微.结论 肥大细胞在肠炎的发生中起一定的作用,采用肥大细胞抑制剂是一种新的临床治疗先天性巨结肠小肠结肠炎途径.     

Hirschsprung's disease in the newborn

The records of all patients with Hirschsprung's disease diagnosed and treated at our institution between 1 July 1974 and 31 August 1985 were reviewed. Of these 99 patients, 35 (35%) presented and were diagnosed within the first 30 days of life and constitute the basis of the present study group. Twenty-two infants (63%) had standard rectosigmoid disease with a male-to-female ratio of 2.2:1. Only one infant was premature. The spectrum of presenting signs included abdominal distension in 19 (54%), failure to pass meconium within the first 48 h of life in 16 (46%), constipation in 12 (34%), and vomiting in 9 (26%). Intestinal perforation was a presenting sign in 2 patients (6%) and enterocolitis occurred preoperatively in 4 (12%). Evaluation was facilitated by diagnostic barium enema in 60% of the patients. In those infants able to undergo elective evaluation, the definitive diagnosis was made by suction rectal biopsy, which was accurate in all cases. In addition to the high proportion of patients with long-segment disease (13 patients, 37%), there was a significant incidence of associated congenital anomalies (26%), including Down's syndrome in 5 (14%). Thirty-three of the 35 patients have undergone definitive treatment using the endorectal pull-through procedure, performed at an average age of 12 months, with no mortality related to the operation. In addition to highlighting the high incidence of congenital anomalies, the large proportion of neonates with long-segment disease, and the reliability of the diagnostic barium enema, this subgroup of patients with Hirschsprung's disease emphasizes the special diagnostic and management considerations required in the newborn infant who presents with sepsis of unknown etiology, intestinal obstruction, or constipation. A high index of suspicion, liberal use of suction rectal biopsy, early leveling colostomy, and definitive treatment by endorectal pull-through are important in achieving 0% operative mortality and excellent functional results.     

Anatomically identical short-segment Hirschsprung's disease in three male siblings

Three male children with identical short-segment Hirschsprung's disease born to a young married couple are reported. There was no positive family history despite an extensive search. There were no associated abnormalities. Although sex-modified multifactorial inheritance, with males having a lower threshold of genes for expression of Hirschsprung's disease, is accepted, the identical expression of the disorder in the three siblings presented suggests a dominant, possibly X-linked gene with variable penetrance. Another possibility is that an identical micro-environmental factor was present prenatally resulting in all three boys having Hirschsprung's disease. This is the first report of three siblings with identical short-segment Hirschsprung's disease. Offprint requests to: S. Z. Rubin     

Abnormal distribution of nerve terminals in the normoganglionic bowel of Hirschsprung's disease: a causative factor of failed pull-through operations?

The aim of this study was to examine the innervation pattern of the muscle layers of normoganglionic pulled-through bowel in patients with Hirschsprung's disease (HD) by observing the distribution of nerve terminals comprising neuromuscular junctions and synapses. As a marker for nerve terminals, monoclonal antibody (MAb) 171B5 was used. Pulled-through normoganglionic bowel from 12 patients with HD that was either biopsied or resected at operation and normal bowel specimens from 7 age-matched controls were labelled using an immuno-histochemical technique with MAb 171B5. In all specimens of the control group and 9 patients of the HD group, numerous neuromuscular junctions were demonstrated in the muscle layers of the normoganglionic bowel and numerous synapses in the myenteric plexuses. However, in the specimens of 3 patients of the HD group abnormal distribution of nerve terminals was seen in the normoganglionic bowel. Two of these 3 patients had abnormal postoperative defecation. Based on our study, there appears to be a small number of HD patients who have an innervation disorder of the muscle layers in the proximal, normoganglionic bowel pulled through at surgery, which hitherto have been thought to be normal.     

Neonatal intestinal perforation in Hirschsprung's disease

Over a period of 18 years, 77 of 135 patients treated for Hirschsprung's disease (HD) presented in the neonatal period. Of these 77 patients, 8 had gastrointestinal (GI) perforations. Seven patients were born at full term and 1 at 32 weeks of gestation. Three patients had associated trisomy 21. The site of perforation included rectum in 1 patient, sigmoid in 1, descending colon in 1, transverse colon in 2, caecum in 2, and jejunum in 1. Perforations occurred in ganglionic bowel in 7 patients and in the aganglionic segment in 1. One patient died in the newborn period of overwhelming sepsis secondary to enterocolitis, and histology of the bowel confirmed HD. In 6 patients HD was confirmed on barium enema and suction rectal biopsy, and they subsequently underwent a definitive pull-through operation. The 1 patient in whom the initial barium enema was normal continued to suffer from constipation until the age of 7 years, when the diagnosis of HD was established. He then underwent a pull-through procedure with no further problems. An association between neonatal intestinal perforation and HD must therefore be recognised to avoid delay in the management. Correspondence to: P. Puri     

Treatment of Hirschsprung's disease without colostomy

The authors report 21 cases of Hirschsprung's disease with severe neonatal symptoms: intestinal obstruction, enterocolitis, and necrotizing enterocolitis. The goal of the approach was to avoid colostomy. After the diagnosis was established, prompt treatment was begun usually with total parenteral nutrition (TPN) via a central catheter. In the first 11 patients surgery was performed at an average age of 8 months, starting preoperatively with an elemental diet. From 1987,to 1990, 10 patients were treated. After a period,of TPN and complete resolution of intestinal symptoms, an early Soave pull-through was performed at an average age of 34 days. Follow-up varied from 16 months to 8 years. The results were excellent: there were no anastomotic leaks or infections and stenosis was prevented by means of periodic calibrations and/or dilitations. Evacuations were regular in all cases. Correspondence to: C. Del Rossi     

Neonatal one-stage repair of Hirschsprung's disease

In this series of 13 patients a one-stage repair, suitable for use in the 1st postnatal week, was developed. The endorectal technique was utilised for the pelvic dissection and an end-to-end anastomosis was then constructed. Modification of adult instruments assisted dissecting in the neonatal pelvis as well as allowing for a precise colo-anal anastomosis. There were no associated deaths and the complication rate was low. Although the technique is a variation of established methods, there are features that should stimulate theoretical discussion and further consideration of neonatal treatment of Hirschsprung's disease.     

Management of Hirschsprung's disease — an alternate approach

Management of neonatal Hirschsprung's disease based on diagnosis by histologic techniques and frozen acceptable method. However, the non-availability of histologic and histochemical techniques often necessitates alternate approaches. In 376 infants below the age of 2 months who were admitted with the presumptive diagnosis of Hirschsprung's disease, a barium enema was the key investigation. Histologic confirmation could be obtained after a colostomy was established. Manometry allowed the detection of any diagnostic errors. The overall error rate was approximately 4%. An alternate algorithm is suggested for the management of Hirschsprung's Disease, particularly in less well-developed centers. Correspondence to: K. K. Varma     

The electrorectogram in Hirschsprung's disease

The electrorectographic pattern of Hirschsprung's disease (HD) was studied in 14 HD patients with a mean age of 4.6 ± 1.5 years; 7 healthy children acted as controls. Monpolar recordings were made from a silver-silver chloride electrode situated 1 cm from the tip of a 4 F catheter attached to the rectal mucosa by suction. At least four 120-min recording sessions were performed for each subject. No complications were encountered. Regular and reproducible triphasic pacesetter potentials (PP) were recorded from all healthy children, followed randomly by bursts of action potentials (AP). No PP or AP were recorded from patients with HD; the silent electrorectogram (ERG) was reproducible. Since numerous difficulties in histopathologic interpretation affect the reliability of rectal biopsy for the diagnosis of HD, the ERG may play a role in this respect. The ERG is noninvasive and nonradiologic; however, until this investigati tool is substantiated by the work of other investigators, a histologic diagnosis needs to be made before undertaking a pull-through procedure.     

先天性巨结肠DNA甲基化的研究进展

先天性巨结肠(Hirschsprung's disease,HSCR)是一种多基因与环境共同作用的复杂疾病,遗传易感性和胚胎期肠道微环境紊乱是其发病的两大主要原因,但其病因及发病机制仍不明确。随着对HSCR发病机制不断深入的研究,发现DNA甲基化异常可能参与神经嵴细胞的增殖、成熟、分化和迁移等过程,从而导致HSCR发生。     

Hirschsprung's disease coexisting with colonic atresia

A case is presented to emphasize the potential coexistence of Hirschsprung's disease and intestinal atresia.     

先天性巨结肠RET基因突变及相关疾病分析

先天性巨结肠（Hirschsprung‘s disease,HD)是常见的先天性消化道畸形。其病因尚未明了,最近研究表明原癌基因RET的突变在HD发病中起主要作用。方法：采集30例散发性先天性巨结肠和30例正常儿童的全血标本,提取基因组;采用聚合酶链反应（PCR）和单链构象多态（SSCP）技术分析RET基因的第6、10、16外显子。结果：2例患儿存在第10外显子的突变。其中1例家庭中有MEN2A患者;1例患儿存在第16外显子的突变。结论：RET基因突变可能是导致先天性巨结肠发生的重要原因之一。MEN2A和先天性巨结肠的发生可能有一定联系。