Patterns of postoperative enterocolitis in children with Hirschsprung's disease combined with hypoganglionosis

Objective

The relationship between postoperative enterocolitis (EC) and Hirschsprung's disease (HD) combined with hypoganglionosis (HYP) has not been thoroughly reported elsewhere. The aim of this study was to investigate the incidence of EC after operation in children with HD combined with HYP and to identify new strategies to prevent postoperative EC.

Methods

From 1998 to 2005, 97 children with HD underwent the modified Swenson's procedure in this institute. They were classified into 2 groups based on pathologic investigation as follows: group A contained 70 patients with HD and group B contained 27 patients with HD complicated with HYP. The mean follow-up time from the time of the operation was 3.4 years (range, 1.5-8 years). The incidence of postoperative EC and anorectal functions were evaluated and compared between these 2 groups.

Results

Eight cases (11.4%) in group A developed postoperative EC, whereas 11 (40.7%) in group B did so. The incidence of postoperative EC in group A was significantly lower than that in group B (P < .005). According to the Rintala scoring system, the percentage of patients with an excellent score in group A (85.7%) was significantly higher than that in group B (P < .05). The recurrence rate of constipation in group B was 14.8% (4/27), whereas it was 2.8% (2/70) in group A.

Conclusions

Postoperative EC is associated with retained proximal HYP, which suggests that HYP could be, at minimum, a predictive marker for this complication. Complete resection of HYP segment could potentially minimize the incidence of postoperative EC and alleviate the severity of EC.     

An approach to minimize postoperative enterocolitis in Hirschsprung's disease

Background/Purpose

Enterocolitis (EC) is a common and severe complication after pull-through for Hirschsprung's disease; its pathogenesis remains unclear, but the role of coexistent intestinal neuronal dysplasia (IND) in the proximal colon may be relevant. This study evaluated the relationship between postoperative EC and IND and assessed whether a surgical protocol including resection of coexistent IND could prevent postoperative EC.

Methods

Between June 1993 and June 2002, 36 patients with aganglionosis were submitted to definitive surgical treatment. There were 2 sequential sets of patients: group I (n = 17), in whom the resection was confined to the aganglionic colon, and group II (n = 19), who were additionally submitted to resection of the coexistent IND segment; excision was restricted to the hepatic flexure in long segmental IND. The prevalence of postoperative EC and anorectal function were evaluated and compared between the 2 groups.

Results

There was no mortality. Fifteen patients had isolated aganglionosis, and 21 presented with aganglionosis plus proximal IND. All 6 children who developed postoperative EC had coexistent IND. In group I, 9 patients had coexistent IND and 5 developed postoperative EC (5/17, 29%). In group II, 12 patients had coexistent IND but only 1 patient, with long segmental IND, developed postoperative EC (1/19, 5%). Among the patients with proximal IND, the prevalence of postoperative EC was 29%; but it was significantly lower in group II than in group I (1/12 or 8% vs 5/9 or 56%; P = .02). Anorectal function was excellent or good in more than 80% of the patients in both groups.

Conclusions

Postoperative EC was associated with retained proximal IND, suggesting that coexisting IND may be, at least, a predictive marker for this complication. Histochemical characterization of the proximal colon with no radical resection of the IND segment seems to be an effective and safe approach to minimize the prevalence of postoperative EC.     

巨噬细胞表型改变在先天性巨结肠相关性小肠结肠炎中的研究

目的通过检测先天性巨结肠患儿结肠组织中巨噬细胞表型的改变,探讨巨噬细胞活化与巨结肠相关性肠炎发病之间的关系。方法收集先天性巨结肠患儿(肠炎组4例,非肠炎组6例)结肠远段及近段标本,行HE染色、评估各段肠管炎症损伤程度,CD68和iNOS免疫荧光双染法评估M1型巨噬细胞活化状况,CD68和Arg-1免疫荧光双染法评估M2型巨噬细胞活化状况,RTqPCR检测各组肠管iNOS及Arg-1的mRNA表达水平。结果免疫荧光染色显示,肠炎组近段结肠iNOS/C/D68阳性细胞的百分比(73.12±2.48)%明显高于肠炎组远段结肠(54.19±1.98)%、非肠炎组近段结肠(49.35±2.70)%及远段结肠(43.18±4.21)%;而肠炎组近段结肠Arg-1/CD68阳性细胞的百分比(33.15±4.81)%明显低于远段结肠(49.32±3.98)%;非肠炎组近段结肠Arg-1/CD68阳性细胞的百分比(45.23±1.95)%亦低于远段结肠(56.52±2.79)%,差异有统计学意义(P0.05)。RT-qPCR结果显示,肠炎组近段结肠iNOS表达明显升高,而Arg-1表达则在肠炎组及非肠炎组的远段结肠升高(P0.05)。结论先天性巨结肠相关性小肠结肠炎的发生可能与巨噬细胞向M1型转化有关。     

Postoperative Hirschsprung's enterocolitis after minimally invasive Swenson's procedure

Background/Purpose

Our preferred minimally invasive technique of Swenson's procedure has evolved from laparoscopic (LapSwen) to Swenson's transanal pullthrough (SWAP). We studied the incidence of postoperative Hirschsprung's enterocolitis (HEC) over the past decade.

Methods and Materials

We retrospectively reviewed the charts of 52 children who had a primary Swenson's pullthrough procedure between 1995 and 2006. Two cohorts (25 LapSwen [1995-2000] and 27 SWAP [1998-2006]) were compared.

Results

Median ages of diagnosis were 13 days for LapSwen and 4 days for SWAP. Median age at surgery was 4.1 months for LapSwen and 3.3 months for SWAP. Postoperative HEC occurred in 12% (16% LapSwen, 7.4% SWAP). The incidence of Down's syndrome and preoperative HEC did not differ between the 2 cohorts. Three children with HEC were Clostridium difficile-positive. Long-term function in the 36 children older than 4 years was excellent in 22%, good in 50%, fair in 11% and poor in 17%.

Conclusion

Our incidence of postoperative HEC is low, and we have seen a trend toward fewer cases after the SWAP procedure. Early diagnosis, preoperative rectal irrigations, and routine postoperative anal dilatation may be contributing to the elimination of HEC as a significant risk after surgery for Hirschsprung's disease.     

The ITGB2 immunomodulatory gene (CD18), enterocolitis, and Hirschsprung's disease

Hirschsprung's disease (HSCR)–associated enterocolitis (HAEC) remains a major contributor to morbidity and mortality associated with HSCR, being sometimes difficult to diagnose in its subclinical form. Its pathogenesis appears to include impaired local defense mechanisms as well as dysfunctional immune response and leukocyte function. In this context, the ITGB2 (CD18) immunomodulation-related gene is a possible candidate in HAEC pathogenesis as it codes for the β-subunit of leukocyte adhesion molecule lymphocyte function-associated antigen 1, which has an established role in T-cell development and function. ITGB2/CD18 has also been linked to chronic colitis in both human and animal models involving defense mechanisms within colonic mucosa. There is therefore a fairly compelling case for the potential involvement of the ITGB2 (CD18) in HAEC pathogenesis.

Aim

The aim of this study was to investigate the ITGB2 immunomodulatory gene (CD18) in a cohort of patients with HSCR and explore its correlation with enterocolitis.

Patients and methods

Screening for mutations of the ITGB2 (CD18) gene was performed on DNA extracted from colonic tissue samples and whole blood of 33 HSCR patients controlled by analysis of 60 unaffected individuals from the diverse South African population. Polymerase chain reaction amplification was performed, followed by heteroduplex single-strand conformation polymorphism analysis and bidirectional semiautomated DNA sequencing analysis.

Results

Heteroduplex single-strand conformation polymorphism banding patterns of the ITGB2 gene showed variations in 22 HSCR patients (66%), 13 of whom had severe episodes of HAEC, and 6 others had milder symptoms. Of the 13, 6 (46%) had Down's syndrome–associated HSCR. Genetic variations included 1 mutation (D77N), 2 known (V367, V441), and 4 novel polymorphisms (−111T/C, 24G/T, 295G/A, 892A/G). Significant associations were identified in the exon 5′ untranslated promotor region (P < .0001), exon 10 (P < .0007), and the 3′ untranslated promotor region at 122G/A (P < .0001) and 370 G/T positions (P = .04). Those regions of the gene most frequently associated with HAEC and severe symptoms were those with more than 1 variant identified in the gene.

Conclusions

This study shows that impaired CD18 leukocyte and T regulatory cell regulation can probably be linked to a genetic (ITGB2) predisposition to HAEC. It furthermore provides a possible genetic link to HAEC patient selection, identifying a potential molecular target.     

Gastroschisis with Hirschsprung's disease: a therapeutic dilemma

The authors report a case of a neonate with gastroschisis, which, after repair, was further complicated by the diagnosis of Hirschsprung's disease. The authors discuss the diagnostic and management dilemmas posed by the coexistence of these two conditions for the clinician.     

The combination of Hirschsprung's disease and achalasia

The unusual combination of Hirschsprung's disease and Achalasia in one case treated by standard procedures led to the discussion about RET germ-line mutations and consequently to the speculation about higher risk for multiple endocrine neoplasia syndrome type 2-related tumors. Although a mutation could be excluded by sequence analysis in this case, the correlation of these specific diseases affords additive investigations to make sure that no further prophylactic procedures were necessary.     

中西医结合治疗脊髓损伤并发伪膜性结肠炎32例

目的:观察中西医结合治疗脊髓损伤并发伪膜性结肠炎的临床疗效.方法:将脊髓损伤并发伪膜性结肠炎的患者64例随机分成两组,每组32例.治疗组:用参苓白术散加减口服加万古霉素口服;对照组:万古霉素口服.结果:治疗组患者在止泻时间、退热时间、失水纠正时间及疗程均较对照组明显缩短,无1例死亡,停药后治疗组仅2例复发,而对照组有7例复发.两组间有差异显著性(P＜0.05).结论:中西医结合治疗脊髓损伤并发伪膜性结肠炎具有疗效好、疗程短、停药后复发率低的优点.     

Redo-endorectal pull through following various pull through procedures in Hirschsprung's disease

Background The purpose of this study was to analyse the outcome of redo-endorectal pull through in Hirschsprung's disease following different original pull through procedures. In the past, redo-endorectal pull through was mainly performed following endorectal pull through, but not following the Duhamel procedure. We present the outcome of eight patients after redo-endorectal pull through, including five who underwent Duhamel pull through as original procedure. Materials and methods Between 2002 and 2004, eight patients underwent redo-endorectal pull through following the Duhamel procedure (five), Rehbein procedure (one) and endorectal pull through (two). A retrospective study was performed to evaluate the clinical course after redo-endorectal pull through, reviewing inpatients' and outpatients' charts and performing standardised interviews. Results Four of eight patients had normal stool pattern after redo-endorectal pull through. In two patients mild and in another two patients severe chronic constipation occurred after redo-surgery. Constipation-associated incontinence was noted in four patients, which is terminated after initiation of laxative treatment in three. Enterocolitis occurred in one patient and recurrent ileitis in another child with total colonic aganglionosis. No impairment of bladder function was observed after redo-endorectal pull through. Conclusion Redo-endorectal pull through proved to be a safe technique and feasible even after prior Duhamel pull through, resulting in good clinical outcome. Parts of this study have been presented at 123. Kongress der Deutschen Gesellschaft für Chirurgie, 2–5 Mai 2006, Berlin.     

Outcomes of Hirschsprung's disease associated with Mowat-Wilson syndrome

Purpose

Mowat-Wilson syndrome (MWS) is a developmental disorder presenting with mental retardation, delayed motor development, and a wide spectrum of clinical features. Hirschsprung's disease (HD) is associated in almost 50% of cases. This report aims to analyze the course of HD and to evaluate the clinical outcomes of these patients.

Patients and methods

Between 1997 and 2007, 110 patients presenting with HD were diagnosed and managed in our institution. Five of them presented the association of HD and MWS. Their records were reviewed retrospectively.

Results

All of the 5 patients have a genetic disorder specific of MWS (nonsense mutation or deletion on SIP1 gene, locus 2q22). Two patients underwent transanal endorectal pull-through procedure for classic rectosigmoid HD. Three patients were operated on for total colonic aganglionosis using Duhamel procedure. The median follow-up was 4 (range, 0.3-7) years. Only one patient is doing well (rectosigmoid HD). Two patients have a stoma diversion for severe motility disorders. Of the 3 total colonic aganglionosis, one still has repeated episodes of obstruction requiring total parenteral nutrition (TPN). The 2 others still have repeated episodes of enterocolitis. All patients required a prolonged TPN (32.5 months in average).

Conclusion

Hirschsprung's disease associated with MWS is a severe condition. Even in case of short segment HD, patients can present motility disorder requiring a prolonged TPN. Physician and surgeon should be aware about the evolution of this rare condition.     

Duhamel手术治疗成人先天性巨结肠

目的　了解Ｄｕｈａｍｅｌ 手术治疗成人先天性巨结肠的效果,探讨其术后结直肠间隔的再手术处理。方法　回顾性分析５ 例经病理证实为成人先天性巨结肠患者行Ｄｕｈａｍｅｌ 手术治疗和长期随诊的结果。结果　３例排便情况良好;２ 例因结直肠间隔过长引起排便困难,应用侧侧吻合器（ＧＩＡｏｒ ＴＬＣ） 行结直肠间隔切开术,再手术后其排便功能良好。结论　Ｄｕｈａｍｅｌ 手术是治疗成人先天性巨结肠的有效方法;术后出现排便困难的原因之一是结直肠间隔过长,可应用侧侧吻合器（ＧＩＡｏｒ ＴＬＣ） 行结直肠间隔切开术处理。     

Total colonic Hirschsprung's disease: a 28-year experience

Purpose

The aim of this study was to review outcomes after surgical treatment of total colonic Hirschsprung's disease (TCH).

Methods

Twenty-five records of patients with TCH treated between 1974 and 2002 were reviewed. Follow-up data were collected using a standardized questionnaire. Objective functional outcome was assessed using a scoring system.

Results

Twenty patients had aganglionosis of the colon and distal ileum, 5 of whom had a more extensive condition. One of these 5 patients underwent an endorectal pull-through (ERPT), 1 underwent intestinal transplantation, and 3 died. Four of the remaining 20 patients underwent a primary ERPT, 16 received a stoma as neonates followed by ERPT in 12, and a Martin-Duhamel procedure or Swenson's operation in 3 (median age, 10.5 months); 1 remains with an ostomy. Postoperative complications included enterocolitis (55%), anal stricture (25%), and perineal excoriation (20%). Mean follow-up were 17.5 years (±11.1 years). Eighty-nine percent were free of recurrent enterocolitis. Frequency of bowel movements is 1 to 5 per day in 82% of the patients, 18% have 6 or more bowel movements per day. Occasional soiling is noted in 40% (one third of those requiring nighttime diapers). Overall functional outcome was good in 83%. Those patients with the longest follow-up periods had the best stooling scores (P = .04).

Conclusions

Surgical treatment of TCH is associated with a number of complications including recurrent enterocolitis and anal strictures. Long-term outcome is quite favorable.     

Hirschsprung's disease in Arab siblings with Bardet-Biedl syndrome

Hirschsprung's disease (HSCR) is a developmental disorder characterized by the absence of enteric neurons in distal segments of the gut. Though HSCR is isolated (nonsyndromic) in most cases, its association with chromosomal aberrations, some congenital anomalies, and a few syndromes has been documented. We report the association of HSCR with Bardet-Biedl syndrome in 2 siblings born to consanguineous Saudi Arabian parents. Both cases were diagnosed during the neonatal period. The first patient had the severe variety of the disease with aganglionosis involving the entire colon and terminal ileum. He died of postoperative complications. The second child had a limited short segment variety of HSCR. For social reasons, the surgical intervention was done only at 5 years of age with no documented complications.     

Long-term clinical outcome in patients with Hirschsprung's disease and associated Down's syndrome

Background/Purpose

Down's syndrome (DS) is the most common chromosomal abnormality associated with Hirschsprung's disease (HD). The purpose of this study was to review the long-term clinical outcome in patients with HD and associated DS.

Methods

Between 1975 and 2003, 39 (15%) of the 259 patients with HD had been associated with DS. Follow-up was carried out by means of examination of patient's records and personal/telephone interviews with the patient's parents or guardians.

Results

Twenty-six (67%) patients presented in the newborn period and 13 (33%) after the neonatal period. Twenty-eight (72%) patients had rectosigmoid HD, 10 long segment, and 1 total colonic aganglionosis. Thirty-two patients had other associated anomalies, 24 of these having cardiac anomalies. Definitive pull-through operation was performed in 33 patients. Parents of 1 child refused surgical intervention and parents of 2 children decided against pull-through operation after colostomy. Three children died before pull through. Thirteen patients had one or more episodes of enterocolitis after pull-through operation. At the time of follow-up (6 months to 28 years), 3 patients were found to have reverted to stoma because of poor bowel control or recurrent enterocolitis. Of the remaining 30 patients, 3 were lost to follow-up and 4 were too young to be assessed for bowel control. Assessment of bowel function in 23 patients revealed normal control in 8 (4 of these soiled for 6-17 years after definitive surgery), soiling in 8, and constipation requiring enemas or laxatives in 7.

Conclusions

The vast majority of patients with HD associated with DS continue to have disturbances of bowel function after definitive pull-through operation.     

双吻合器在先天性巨结肠症一期切除吻合术的应用

目的探讨双吻合器在先天性巨结肠症一期切除术中应用的可行性和临床效果。方法回顾性分析总结2003年6月至2009年6月用双吻合器为30例先天性巨结肠症患儿实施一期根治性切除术的治疗情况。结果30例手术均获成功,无手术死亡。平均手术时间120 min,吻合器中心杆近远结直肠圈,病检均找到神经节细胞。并发吻合口瘘2例,均非手术治愈。切口裂开1例,肺部感染2例,均治愈,平均住院8 d,平均随访时间28个月,术后排便次数2~3次/d,腹胀消失,进食情况良好。结论应用双吻合器行先天性巨结肠症一期根治切除吻合术,操作简单,术时短,恢复快,并发症发生率低,临床疗效满意。     

Fast evaluation of intraoperative biopsies for ganglia in Hirschsprung's disease

Purpose

The most important diagnostic features of Hirschsprung's disease (HD) are the combination of aganglionosis and hypertrophic nerve bundles. Acetylcholinesterase staining is widely used for diagnosis of HD as it identifies hypertrophic nerves in both diagnostic and intraoperative biopsies. The main drawback of this method is in the identification of ganglia. It has been suggested that the combination of this method together with another histochemical marker would be a superior diagnostic tool. Hematoxylin and eosin is still the diagnostic measure of choice for identifying ganglia in many centers, although it presents a persistent diagnostic challenge for pathologists trying to rapidly and accurately interpret the frozen biopsies that guide intraoperative decision making.

Methods

Therefore, we sought to develop a fast, intraoperative immunohistochemical protocol for visualization of ganglia and nerves in HD specimens that can be used in conjunction with these other tools.

Results

With the use of acetone fixation and immunofluorescence staining with antibodies to neurofilament 68 and tubulin, ganglia in sections of full thickness and suction biopsies could be visualized in only 10 minutes. This protocol facilitated the identification of ganglia in hematoxylin and eosin-stained adjacent sections and also identified hypertrophic nerve trunks.

Conclusion

This method should significantly enable the identification of ganglia in suction and full thickness biopsies.