巨结肠及类缘病诊断和治疗的临床研究

目的：探讨巨结肠类缘病的病理形态学特征，提高其诊断率。方法：对97例行巨结肠根治术后的病变肠段进行常规HE染色，观察肠神经元及神经节细胞形态和数量的变化并与正常组进行比较，并21例采用NSE和S－100蛋白免疫组化染色。结果：巨结肠类缘病（allied HD）标本的神经元与神经节细胞细胞数与正常组及巨结肠症（HD）比较差异有显著性（P＜0．01）。结论：巨结肠类缘病的诊断主要根据病理特征而定，在HWE染色基础上结合NSE及S－100蛋白免疫组织化学染色提高确诊率。     

先天性巨结肠不同节段肠壁神经、平滑肌的分布及临床意义

目的 观察先天性巨结肠(HD)不同节段肠壁神经和平滑肌的病变范围,探讨先天性巨结肠根治术后肠动力功能紊乱原因及手术切除结肠范围.方法 用免疫组织化学和苏木素-伊红(HE)染色法,检测20例先天性巨结肠肠壁神经节细胞、神经纤维和平滑肌细胞病理组织学改变及分布范围.结果 巨结肠不同节段肠壁神经节细胞、神经纤维数量及突触素(Syn)、神经节细胞黏附分子(NCAM)的阳性表达,在距扩张远端8 cm虽未达到正常,但与对照组差异减小(P＞0.05).环肌层和纵肌层出现不同程度增厚,在距扩张远端8 cm仍未正常(P＜0.01).肌层出现空泡样变,与对照组比较差异无统计学意义(P＞0.05).结论 先天性巨结肠切除段肠壁神经、平滑肌层均存在病变,在距扩张段的远端8 cm处,两者病变总体缓解.在允许情况下,手术切除结肠的范围应达到或超过此范围.     

先天性巨结肠肌间神经丛形态学观察及其意义

目的观察先天性巨结肠肌间神经丛形态学并分析其意义。方法对8例先天性巨结肠患者手术标本过行苏木素伊红(HE)染色和免疫组织化学S100蛋白染色,进行形态学观察。结果先天性巨结肠狭窄部肠壁肌间神经无神经细胞,可见增多的直径增粗无髓鞘纤维,呈波浪状弯曲。雪旺氏细胞增多,结肠扩张段肌间神经丛可见神经节细胞,神经纤维无明显增粗,数量无明显增多。结论先天性巨结肠肌间神经丛形态学明显异常改变,与无神经节细胞病变肠段结肠发育障碍有关。     

先天性巨结肠突触素免疫组织化学研究

目的:采用突触素免疫组织化学方法,对先天性巨结肠神经肌肉连接进行研究,并探讨其与先天性巨结肠发病的关系。方法:应用免疫组化技术对20例先天性巨结肠病变肠段及10例正常结肠组织标本行突触素神经肌肉连接标记,光镜下观察其免疫反应。结果:对照组的结肠突触素免疫反应呈强阳性表达,先天性巨结肠组扩张肠段突触素免疫反应呈阳性或弱阳性表达,狭窄段肠壁突触素免疫反应呈阴性表达。结论:先天性巨结肠病变肠段同时缺乏内源性神经支配和外源性神经支配,处于完全失神经支配状态,导致原神经节细胞病变肠管功能障碍。     

腹腔镜下结肠切除、直肠内拖出术治疗巨结肠类缘病

目的探讨腹腔镜下结肠部分或次全切除、直肠内拖出术治疗巨结肠类缘病的可行性。方法1999年10月-2006年5月，对保守治疗无效或复发的38例先天性巨结肠类缘病（Hirschsprung’s disease-allied disorder，HAD）和先天性巨结肠（Hirschsprung’s disease，HD）合并HAD的患儿在腹腔镜下行结肠部分或次全结肠切除、直肠内拖出术。分别在脐缘、右上、右下、左中腹刺入4个5mm trocar，行结肠次全切除时，左侧需建立2个操作孔，分别在左上及左中下腹。腹腔镜下分别游离降结肠、横结肠、升结肠及回盲部侧腹膜，肛门手术按改良Soave方法。结果38例均在腹腔镜下完成手术。9例行左半结肠切除，手术时问110—180min，平均135min；29例行结肠次全切除并按Deloyers法将升结肠逆时针转位270。下拖，保留的升结肠长度7—13cm，平均11．5cm，手术时间140—220min，平均175min。术中出血15～70ml，平均35ml。病理诊断肠神经元性发育异常10例，神经节细胞减少症3例，神经节细胞未成熟症4例，未分类型9例，HD合并IND6例，HD合并HG2例，HD合并IGC4例。38例术后随访6个月一7年，平均3年5个月，29例次全结肠切除患儿3个月内每日大便4—18次，6—10个月后渐转为每日2～3次，9例左半结肠切除患儿术后6个月后每13大便1—2次，无吻合口狭窄，无便秘复发。结论腹腔镜下结肠部分或次全切除经肛门拖出根治术治疗HAD安全、有效、可行，手术创伤较小，但需要一定的腹腔镜操作经验。     

先天性巨结肠的外科治疗

先天性巨结肠（Hirschsprungdisease，HD）是以便秘为主要临床表现的一种常见的消化道畸形．病因为外胚层神经嵴细胞迁移发育过程停顿．病变肠壁肌间神经丛和黏膜下神经丛的神经节细胞缺如。使肠段失去正常蠕动（即间歇性收缩和松弛的推进式运动）而处于经常的痉挛状态，造成粪便排出障碍．近端肠管则被动继发扩张，异常扩大、肥厚，形成所谓的巨结肠。     

神经元特异性烯醇化酶和银染色在先天性巨结肠类缘病诊断？…

为探讨先天性巨结肠类缘病的病理诊断,分析了２０例类缘病ＮＳＥ及银染色。结果表明,ＮＥＳ结合银染色肌间和粘膜下神经丛中神经节细胞、神经纤维有特征性表达。认为ＮＳＥ结合银染色是一种诊断先天性巨结肠类缘病有价值的诊断方法。     

神经干细胞移植治疗结肠去神经节小鼠

目的 观察神经干细胞在去神经节小鼠结肠壁内的存活分化,探讨神经干细胞移植治疗结肠无神经节细胞症的可行性.方法 0.5%苯扎氯铵(BAC)处理8周龄昆明小鼠结肠浆膜层选择性去除结肠肇神经节制作巨结肠模型,原代培养新生小鼠大脑皮质来源神经干细胞,Hoechsd3342标记传代纯化后神经干细胞.运用微量注射器将标记后的神经干细胞移植入模型鼠病变肠段,分别于术后1、2、3、4周行大体观察,苏木素-伊红(HE)染色,免疫组织荧光检测小鼠生物学特性和神经干细胞存活分化情况.结果 原代培养神经干细胞Nestin表达阳性,体外培养可分化为神经元和神经胶质细胞;BAC处理后,HE染色及免疫组织化学染色显示小鼠结肠肌间及黏膜下神经节消失;神经干细胞移植后各观测时间点可见荧光标记细胞,免疫组织荧光检测显示术后1周结肠壁存在巢蛋白(Nestin)表达阳性细胞,3周后可见神经元特异性烯醇化酶(NSE)及胶质纤维酸性蛋白(GFAP)表达阳性细胞,对照组未观察到阳性表达.结论 神经干细胞可以在去神经节小鼠结肠肇内存活并分化为神经元及胶质细胞,部分恢复肠道神经的调节作用.     

Cajal间质细胞在先天性巨结肠分布的研究

目的：通过观察cajal间质细胞（interstitial cells of cajal，ICC）在正常结肠及先天性巨结肠先天性巨结肠（hirschsprung’s disease，HD）患者痉挛段、移行段、扩张段的分布，探讨HD的发病机制。方法：收集25例HD患儿标本，于术中分别选取扩张段、移行段、痉挛段肠壁的全层组织，另取6例手术患儿的正常结肠全层组织标本，常规固定石蜡包埋组织切片备用。对标本行c-Kit免疫组织化学染色。光镜观察ICC的分布，计数并进行统计学分析。结果：正常结肠ICC主要分布在环肌内侧面与黏膜下层之间即黏膜下ICC（submucosal ICC．ICC—SM）、环肌与纵肌之间的肌间神经从周围即肌间ICC（myenteric ICC，ICC—MY）以及环肌与纵肌内。HD患儿痉挛段ICC—SM、ICC—IM细胞数较扩张段和正常对照组明显减少（P〈0．01），且ICC的细胞突起的分支亦减少，彼此之间不能形成完整的细胞网络。而扩张段ICC与正常对照组比较无明显差异（P〉0．05）。结论：HD患儿结肠ICC的异常分布，可能是HD发病、肠管蠕动障碍以及排便异常的原因之一。     

成年人先天性巨结肠同源病

先天性巨结肠同源病是在病变肠段内神经节细胞减少、未成熟、发育不全等。成年人先天性巨结肠同源病较少见。该病病史长，就医晚，多因巨结肠危象、肠梗阻、肠穿孔等急腹症就医。该病属于解剖性真性便秘，除了与假性便秘鉴别外，主要应与甲状腺功能低下的机能性巨结肠和特发性巨结肠相区别。该病多可手术治疗并可保留排便功能。本组提供5例报告，并予以讨论。     

先天性脊柱侧凸患者中的脊髓畸形和脊椎畸形

目的:探讨先天性脊柱侧凸患者的各类脊髓畸形与脊椎畸形之间的关系。方法:对我院2003年～2005年收治的211例已确诊的先天性脊柱侧凸患者的临床资料进行回顾性分析,统计先天性脊柱侧凸患者脊髓畸形、脊椎畸形的发生率及其好发部位,观察两者间的关系。结果:211例先天性脊柱侧凸患者中脊髓畸形44例(20.85%),其中脊髓空洞症25例次(11.85%),脊髓纵裂30例次(14.22%),马尾终丝栓系28例次(13.27%),低位圆锥12例次(5.69%),其他类型少见,多种畸形常并发存在;脊髓畸形好发于脊柱胸段、胸腰段、腰段、腰骶段。44例伴有脊髓畸形的先天性脊柱侧凸病例中不良分节34例(77.27%),孤立性半椎体1例(2.27%),非孤立性半椎体21例(47.73%),脊柱裂30例(68.18%),混合型41例(93.18%);脊椎畸形好发于脊柱胸段、腰段、腰骶段。结论:先天性脊椎畸形常合并脊髓畸形,总体上脊髓畸形与脊椎畸形的好发部位相似,但各种脊髓畸形、脊椎畸形间缺少显著的、特定的对应关系。     

小儿巨结肠类缘病合并畸形(附四例报告)

目的　提高对小儿巨结肠类缘病的认识。方法　对小儿巨结肠类缘病合并畸形的 4例病例临床与病理特征加以总结。结果　 4例术后病理活检均证实为巨结肠类缘病 ,其中 2例同时伴有先天性肛门直肠畸形 ,1例伴有先天性脊柱侧弯 ,1例伴有先天性白内障。 2例行升结肠造瘘 ,1例行Duhamel改良根治术 ,1例全消化道神经节细胞发育不良者行空肠造瘘。结论　巨结肠类缘病病因复杂 ,诊断困难 ,可同时存在其他先天性畸形。营养不良、电解质紊乱及顽固性肠道感染是该病常见的并发症 ,预后不良。     

Pseudomembranous enterocolitis and hemorrhagic necrotizing enterocolitis in Hirschsprung's disease

From 1977 to 1991, we encountered 67 patients with Hirschsprung's disease and 14 of them developed enterocolitis, with 3 cases being fatal. Enterocolitis occurred preoperatively in 12 infants, as well as after ileostomy in one and after a pull-through procedure in another. Seven infants had severe enterocolitis, including three with pseudomembranous enterocolitis and four with hemorrhagic necrotizing enterocolitis. Enterocolitis in Hirschsprung's disease mainly occurs due to intestinal obstruction and ischemia; however, in some cases, Clostridium difficile overgrowth and its toxin also appears to be related to severe pseudomembranous enterocolitis. In severe enterocolitis, antibiotics and enterostomy often prove to be ineffective, and thus an early resection of the affected bowel appears to be necessary. Moreover, when the aganglionic segment extends to the small bowel, severe enterocolitis tends to occur in the aganglionic intestine even after performing an enterostomy, and a resection of the aganglionic bowel is therefore recommended to allow for adequate lavage of the segment distal to the enterostomy site.     

肠动静脉畸形诊断和标记定位问题——附38例报告

肠动静脉畸形为消化道出血重要原因。应用肠系膜动脉造影诊断并同时置标记物作为病人手术定位以减少术中盲目性。材料和方法:选择性肠系膜动脉造影,术前诊断38例小肠动静脉畸形,其中10例放置导引钢丝或造影导管,作为术中定位标记,并即刻或择期手术。结果:本组动脉造影X线表现为:(1)动静脉瘘和静脉早显21例;(2)局部染色浓密30例,(3)局部异常增多的血管丛30例;(4)肠壁内静脉扩张,迂曲27例。38例病理检查,仅2例为炎症,诊断符合正确率95％。10例置标记物者,术中顺利寻找并切除病灶。结论:选择性肠系膜动脉造影是诊断该病的最可靠方法,同时放置标记物能帮助外科医师顺利寻找并切除病变,且无并发症。该方法是一全新的定位方法,值得推广。     

Jejunoileal atresia and associated malformations: correlation with the timing of in utero insult

PURPOSE: Duodenal atresia is associated with a higher incidence of associated congenital malformations than jejunoileal atresia, supporting the hypothesis that the duodenal obstruction occurs early in fetal life. In this study, the authors analyzed the incidence of major associated malformations in jejunal atresia (JA) and ileal atresia (IA) to determine if there is a positive correlation between the proximity of the intestinal atresia and the association of other major anomalies. METHODS: Records of all patients with jejunoileal atresias treated at the authors' institution between 1980 and 1997 were examined. RESULTS: There were 83 patients with jejunoileal atresias, 38 with JA, and 45 with IA. Sixteen (42%) of the JA patients had an associated major congenital malformation, whereas only 1 (2%) of the IA patients had an associated malformation. A single atresia was found in 18 (47%) of JA patients and 41 (91%) of IA patients. Twenty (53%) of the JA patients had either multiple or apple-peel atresia. Thirteen patients (16%) died, 11 with JA, and 2 with IA. Of the 11 patients with JA who died, 6 had multiple atresias, 4 had cystic fibrosis, and 1 had small bowel volvulus. CONCLUSION: The higher incidence of associated major congenital extraintestinal malformations in JA compared with IA patients suggests that some cases of JA may arise from a malformative process.     

Experience with gastro-intestinal duplications in childhood

BACKGROUND: Intestinal duplications are rare congenital malformations. The different locations and sizes of these duplications require a specific diagnostic and surgical approach. This study reviews our paediatric patients with intestinal duplications in order to analyse the influence of prenatal sonography and laparoscopy on the clinical course. PATIENTS AND METHODS: Thirteen duplications of the alimentary tract in 12 patients have been treated over a 10-year period from 1989 to 1999. Six of our patients were diagnosed prenatally by ultrasound and were free of symptoms until surgery, except for one patient who had meconium-ileus owing to cystic fibrosis. In another five patients, the diagnosis was made on the basis of symptoms with signs of obstruction. In one child, the duplication was found incidentally during an operation for an anorectal malformation. The location of the 13 duplications was the stomach in three cases, the duodenum in one case, the jejunum in two cases, the ileum in six cases and the rectum in one case. Laparotomy was performed in ten patients. Two cases were treated by laparoscopic-assisted resection. CONCLUSION: Early diagnosis and treatment of uncomplicated intestinal duplications by means of prenatal sonographic screening and laparoscopic-assisted resection, respectively, are desirable in this congenital malformation. Resection of the duplication with or without minimal resection of the adjacent normal intestine should be mandatory.     

Two cases of bizarre rib anomalies associated with intestinal malformation.

Two cases of bizarre skeletal anomalies associated with intestinal malformation are presented. One patient had ileal atresia and Hirschsprung's disease, and the other anorectal malformation. Abnormalities in the number and morphology of ribs and vertebrae were present. Esophageal atresia often is associated with skeletal abnormalities, including supernumerary ribs, but these usually are not severe. Despite their severe costal malformations, neither patient had any complication after surgery to correct their intestinal malformation.     

Intestinal neuronal dysplasia is a possible cause of persistent bowel symptoms after pull-through operation for Hirschsprung's disease

The proximal margin of the resected bowel specimens from 33 consecutively treated patients undergoing a definitive pull-through operation for Hirschsprung's disease (HD) and control specimens consisting of suction rectal biopsy specimens obtained from 24 age-matched patients evaluated for constipation (and proven not to have HD) were examined using conventional H&E staining and acetylcholinesterase (AChE) histochemistry. Complete resection of the aganglionic segment was confirmed in 31 patients. In one patient, the proximal margin was found to be aganglionic; in another, the proximal margin was in a transitional zone. In both patients, frozen sections at the time of surgery were interpreted as having ganglion cells. In 10 of 31 patients, intestinal neuronal dysplasia was demonstrated in the proximal margin of the resected bowel. The abnormalities included hyperplasia of the submucous plexus, giant ganglia (with > 7 ganglion cells), and ectopic ganglion cells (all 10 patients) and increased AChE activity in the lamina propria (5 patients). All ten patients with IND had persistent bowel problems after the definitive operation for HD, such as enterocolitis, soiling, or constipation. Only four of the other 21 patients had persistent bowel symptoms. This study suggests that IND is commonly associated with HD. It also emphasizes the importance of histochemical examination of the resected segment to predict postoperative bowel function in patients with HD.     

Hirschsprung's disease: catecholamine content, alpha-adrenoceptors, and the effect of electrical stimulation in aganglionic colon

In order to assess abnormalities in the adrenergic mechanism in the intestine of Hirschsprung's disease, catecholamine concentrations, alpha-adrenoceptors, and the effect of electrical field stimulation were examined in aganglionic segments of colon or rectum. The aganglionic segment had a higher concentration of norepinephrine, assayed with high performance liquid chromatography with an electrochemical detector, whereas concentrations of epinephrine or dopamine were similar in normal and pathological segments. In four patients with extensive aganglionosis, the norepinephrine concentration in aganglionic colon segments decreased progressively in descending, transverse, and ascending colon. The tissue content of alpha-adrenoceptors and their affinity assayed from the specific binding of [3H]dihydro-alpha-ergocryptine appeared similar in normal and aganglionic segments of the rectosigmoidal colon. Electrical field stimulation of normal rectosigmoidal colon segments caused relaxation at low frequencies and contraction at a very high frequency. Relaxation was not abolished by blocking concentrations of propranolol or phentolamine. In aganglionic segments, the predominant response to electrical field stimulation was contraction, which was inhibited by either atropine or tetrodotoxin. These results indicate that an alpha-adrenergic system and cholinergic innervation apparently exist in aganglionic colon segments and that dysfunction of the colon appears to result from lack of a nonadrenergic inhibitory system.