Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

肠三叶因子对新生鼠缺氧肠损伤模型白细胞介素8、丙二醛的影响及意义

目的　研究肠三叶因子 (intestinaltrefoilfactor,ITF)对坏死性小肠结肠炎 (necrotizingenterocolitis,NEC)新生大鼠的肠粘膜中白细胞介素 8(interleukin 8,IL 8)及丙二醛 (malondialdehyde,MDA)含量的影响 ,探讨ITF对NEC是否有保护作用。　方法　建立NEC模型 ,对新生 1日龄Wistar大鼠予 10 0 %二氧化碳 ,5min后再予 10 0 %氧气 ,5min后放回母鼠身边喂养 ,第 4天处死大鼠取肠道组织待检。新生鼠 32只随机分为四组 ,A组为NEC模型后腹腔注射ITF 0 .5mg ;B组为NEC模型后皮下注射ITF 0 .2mg ;C组为NEC模型组 ;D组为正常对照组。取近回盲段 1～ 2cm肠道组织固定包埋、切片、HE染色光镜下作病理学检查 ,其他肠道组织制备组织匀浆取上清液用放射性免疫法检测IL 8,用生化法检测MDA的含量。　结果　A、B组IL 8的含量 [pg (mg·pro) ]各为 2 9.72 2± 7.134、30 .5 12± 8.2 30 ,均较C组 39.379± 4 .4 2 0低 (P <0 .0 5 ) ,而与D组 2 3.92 2± 6 .16 8比较 ,差异无显著性 (P >0 .0 5 ) ;A、B组MDA的含量 [nmol (mg·pro) ]各为 2 .2 6 7± 0 .2 6 7、2 .15 4± 0 .30 1,较C组 3.378± 0 .835低 (P <0 .0 1) ,与D组 2 .2 2 5± 0 .4 4 3比较 ,差异无显著性 (P >0 .0 5 )。C组HE染色切片见肠壁的损伤轻重不一 ,有的     

新生儿坏死性小肠结肠炎肠穿孔与肠未穿孔患儿术后结局的对比研究CSCD

目的对比新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)肠穿孔与肠未穿孔患儿手术治疗后转归情况,为NEC手术时机的选择及术后治疗提供参考。方法回顾性分析2009年8月至2019年8月中国人民解放军总医院第七医学中心儿科医学部新生儿外科收治的237例经手术治疗的NEC患儿临床资料。按照是否发生肠穿孔分为肠未穿孔组(172例)与肠穿孔组(65例),收集两组患儿术中所见坏死肠管长度、手术后实施肠内及肠外营养时间、呼吸机使用时间、NICU入住时间、术后并发症以及预后情况。结果NEC肠未穿孔组172例中,治愈124例(124/172,72.1%),死亡48例(48/172,27.9%);肠穿孔组65例中,治愈48例(48/65,73.8%),死亡17例(17/65,26.2%)。两组术中所见坏死肠管长度以及术后肠外营养时间、肠内营养时间、呼吸机使用时间、NICU入住时间及术后并发症比较,差异均有统计学意义(P<0.05)。Bell分期为ⅢA与ⅢB期的患儿病死率比较,差异有统计学意义(χ^(2)=4.731,P=0.030)。结论NEC肠未穿孔的患儿可能存在更多肠管坏死,术后并发症多,康复时间长。建议对于NEC肠未穿孔患儿,可根据患儿临床实际情况探讨更合适的手术指征。     

新生儿坏死性小肠结肠炎外科诊疗进展

新生儿坏死性小肠结肠炎(NEC)是小儿外科常见的急腹症,具有发病迅速、早期诊断困难、病死率高、术后并发症多等特点。目前临床争论主要集中在两方面:第一,手术时机及方式的选择问题;第二,如何尽可能多的保留肠管,防止术后短肠综合征发生。笔者就目前NEC外科治疗研究进展做一综述,以期寻求启发与解答。     

Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis

Introduction

The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC).

Material and methods

Newborn Sprague–Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression.

Results

The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p < 0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1.

Discussion

Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease.     

22例伪膜性结肠炎临床特征分析

背景:我国不合理使用抗生素的现象严重,抗生素相关性腹泻如伪膜性结肠炎(PMC)的发病率呈上升趋势。目的:综合分析PMC的临床特征以提高其诊治水平。方法:收集2007年6月～2012年2月于湖南省人民医院住院治疗,经结肠镜检查确诊的PMC患者,对其病史资料进行回顾性分析。结果:共22例PMC患者纳入研究,其中70岁以上者18例(81.8%),18例患者存在基础疾病。所有患者均于使用抗生素过程中出现腹泻,并可伴有不同程度的腹痛、发热、血便等其他症状。使用头孢菌素类抗生素者最多见(14例),20例患者联合使用两种或两种以上抗生素。21例接受结肠镜检查者均可见典型伪膜样病灶,内镜分型轻度9例,中度7例,重度5例。经停用原有抗生素以及使用甲硝唑、万古霉素、益生菌制剂等治疗后,21例患者好转出院。结论:PMC多发生于有基础疾病的老年人,病程早期缺乏特异性临床表现。结肠镜检查是诊断PMC的重要手段之一,确诊后应尽早停用原有抗生素,使用足量、足疗程的甲硝唑和万古霉素以及益生菌制剂。     

低出生体质量儿坏死性小肠结肠炎的影响因素及手术疗效分析

目的 探讨低出生体质量儿坏死性小肠结肠炎(NEC)的影响因素、手术疗效与预后。 方法 以2006年1月至2015年12月收治的146例低出生体质量NEC患儿为病例组,另采用随机数字表法选取同期在新生儿重症监护室(NICU) 住院治疗的146例非NEC低出生体质量儿为对照组。分析两组患儿的临床资料,采用单因素和多因素分析探讨NEC的影响因素,并分析NEC患儿中手术组与保守治疗组疗效的差异。 结果 多因素logistic回归分析显示,母乳喂养与喂服益生菌为NEC的保护性因素,先天性心脏病、败血症与输血是NEC的危险因素。手术组的好转率(95.45%)明显高于保守治疗组(85.00%)(P<0.05)。 结论 低出生体质量儿NEC的发病受多种因素影响,应针对其影响因素进行综合干预。适合的手术疗法能提高疗效,改善患儿的预后。     

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.     

Redo pullthrough for Hirschsprung disease: A single surgical group's experience

Introduction

This study presents our surgical experience for redo-pullthrough (RedoPT) for Hirschsprung disease (HD). It reviews the patient's clinical outcomes and assesses stooling patterns after RedoPT.

Methods

A retrospective review of our institution's RedoPTs as well as one author's overseas cases was performed. Stooling scores were tabulated using an established survey tool and compared to primary PT matched patients.

Results

Between 1974 and 2012, 46 individuals (52% males) underwent RedoPT, representing 3 percent of all HD pullthroughs. Median age at primary PT and RedoPT was 1 year (range 1 week–18 years) and 3.5 years (range 8 weeks–41 years), respectively. Indications for RedoPT were predominately for aganglionosis/transition zone pathology (71%); followed by stricture or an obstructing Duhamel pouch (19%), tight cuff (8%) and a twisted PT (4%). None were performed for an isolated clinical diagnosis of repeated bouts of enterocolitis. RedoPT surgical approach depended upon the initial pullthrough technique and any previous complications. Stooling scores were significantly (P < 0.05) worse in the RedoPT patients compared to the historically-matched group of children undergoing a primary PT for HD (5.5 ± 1.2 vs. 12.2 ± 1.4, primary PT versus RedoPT, respectively). When breaking down this total score into individual parameters, stooling pattern scores (1.0 ± 0.2 vs. 4.1 ± 0.4, P = 0.001) and enterocolitis scores (2.0 ± 0.4 vs. 4.2 ± 0.4, P = 0.001) were statistically worse in the RedoPT group. Patients in both groups had similar overall continence rates.

Conclusion

Appropriately selected children undergoing a RedoPT can achieve good results, with comparable continence rates to those undergoing a primary PT.     

坏死性小肠结肠炎的影像诊断

目的:探讨X线平片对坏死性小肠结肠炎(NEC)的诊断价值以及早期诊断的重要性.方法:搜集15例经保守治疗或手术证实的NEC患儿的病例资料.其中男9例,女6例,早产儿10例,发病时间为生后2小时～8月.所有病例均摄腹部仰卧正位片和水平侧位或站立位片,对其X线平片进行回顾性分析.结果:15例中病变发生于胃1例,肠道14例;其中早期7例,主要X线表现为肠道动力性梗阻,肠管充气不均匀,部分肠管充气减少、部分肠管选择性充气扩张,肠壁间隔增宽;进展期8例,主要X线表现为肠管形态不规则、僵直固定、呈管状改变,腹腔内渗液增多,出现肠壁壁间积气5例,门静脉积气3例,形成气腹2例.结论:肠壁壁间积气和门静脉积气是NEC的特征性征象,腹部仰卧正位和水平侧位片及随访观察是诊断NEC最有价值的检查方法.