Anorectal electromanometrical patterns in children with isolated neuronal intestinal dysplasia.

BACKGROUND: The aim of this study was to report our new findings on anorectal electromanometrical patterns in patients with isolated neuronal intestinal dysplasia (IND) type B. METHODS: We reviewed and analyzed the records of preoperative anorectal electromanometric examinations in 17 patients (10 male and 7 female) with IND. The diagnosis of IND was made based on a pathological examination. RESULTS: Mean age of the patients was 6.3 years (range 4 months to 16 years). In the preoperative barium enema study, a narrowed distal segment with proximal dilatation was noted in 8 patients, dilatation of the sigmoid or rectum without a narrowed distal segment was observed in 4 patients, and no specific findings were found in 5 patients. Out of 17 patients, only 5 patients showed positive staining for AChE in the rectal suction specimens. The electromanometric examination showed no significant difference in anal resting pressure and the length of the high pressure zone between the IND and the functional constipation (FC) groups. The frequency of anal peristalsis in the IND group, however, was significantly lower than that in the FC group. Sixteen IND patients showed an internal relaxation. However, the threshold value to evoke the relaxation in the IND group was significantly higher than that in the FC group. Moreover, the latent period of reflex and the duration of a relaxation in the IND group were longer than those in the FC group. Finally, two specific shapes of reflex wave ("W" or "U" shape) were observed in 10 patients with isolated IND type B, while no such shapes were noted in the FC group. CONCLUSION: These new findings support the notion that anorectal electromanometry is a safe and useful screening examination for IND patients.     

Laparoscopic extensive colectomy with transanal Soave pull-through for intestinal neuronal dysplasia in 17 children

Background  

Open colectomy has been preferred for intestinal neuronal dysplasia type B (IND) due to its low morbidity rate and good functional results. The aim of this study was to investigate the feasibility and results of laparoscopic colectomy with transanal Soave pull-through for the treatment of IND in children.     

Management of intractable constipation with antegrade enemas in neurologically intact children

OBJECTIVES: To assess the benefit of antegrade enemas in children with severe constipation who were referred to a tertiary care center. METHODS: From 1997 to 1999, 12 children (9 male, aged 8.7 +/- 4.4 years) underwent cecostomy placement. All children were neurologically normal and had been extensively examined to rule out organic causes of constipation. Follow-up included a questionnaire to interview caregivers 13.1 +/- 8.5 months after cecostomy placement. RESULTS: For all children, antegrade enemas led to improvement in the number of bowel movements / week (7.1 versus 1.4, P < 0.005), number of soiling accidents / week (1.0 versus 4.7, P < 0.01), abdominal pain score (0.9 versus 2.9, P < 0.005), emotional health score (3.6 versus 1.9, P < 0.005), overall health score (3.6 versus 1.7, P < 0.005), number of medications used for constipation (0.8 versus 4.0, P < 0.005), number of missed school days / month (1.5 versus 7.5, P < 0.02), and number of physician office visits / year (9.2 versus 24.0, P < 0.05). Irrigation solutions used for the antegrade enemas included polyethylene glycol (67%), saline and glycerin solution (25%), and phosphate enema (8%), administered everyday in seven children and every other day in five children. Adverse events included skin breakdown and granulation tissue in one patient, leakage of irrigation solution in one patient, and dislodging of the tube in two patients. Five patients discontinued the use of antegrade enemas within a mean of 14.6 +/- 9.1 months after beginning treatment. CONCLUSION: Antegrade enemas through a cecostomy are a safe and satisfactory option for children who are neurologically intact and who have severe constipation that does not respond to medical treatment.     

Variability of clinical symptoms in neuronal intestinal dysplasia

Neuronal intestinal dysplasia is defined as a structural disorder of the innervation of the gut which clinically resembles Hirschsprung's disease. Between 1977 and 1988 12 patients were diagnosed by enzyme histochemistry. In 3 of these patients Hirschsprung's disease was associated. Constipation was the main symptom in 6 patients with neuronal intestinal disease and in all three patients with associated Hirschsprung's disease. The other patients firstly presented with an enterocolitis, a congenital atresia of the jejunum and a chronic enteritis with malabsorption. The wide clinical variability and the lack of a clear therapeutic management valid for all patients is conspicuous.     

Ileocolic intussusception: an unusual complication in a newborn with intestinal neuronal dysplasia

Intestinal neuronal dysplasia type B (IND B) represents a congenital malformation of the enteric nervous system causing disorders of intestinal motility, e. g., chronic constipation. We report a newborn who primarily suffered from intussusception and peritonitis. He required a subtotal colectomy for gangrene, but since IND B had not been expected at this time, no specific immunhistochemical workup for IND was initiated. Following recurrent episodes of ileus and subileus within the next years, colonic biopsies were taken and histotopochemical staining revealed IND B. The remaining colon required resection; an ileorectostomy was performed and the patient is now asymptomatic. This case report discusses the causality of IND B for intussusception and stresses that in newborn patients the clinical presentation may be misleading, and adequate histochemical evaluation is essential for early detection.     

Distributions of substance P- and VIP-immunoreactive nerve fibres in the colonic circular muscle in children

In children with severe chronic constipation, abnormal distribution of substance P (SP) and vasoactive intestinal peptide (VIP), which represent excitatory and inhibitory nerves, respectively, has been reported. The normal distribution of these neuropeptides, however, is not well known. The aim of this study was to determine the populations of SP- and VIP-immunoreactive nerve fibres in the circular muscle of the colon in children. Surgically resected specimens were collected from a 6-year-old girl with familial polyposis coli (total colon) and nine patients with anorectal malformations aged 0–4 years (sigmoid colon). Double-labelling immunofluorescence was employed using neuron-specific enolase (NSE) with SP and NSE with VIP to count the percentage of SP- or VIP-labelled nerve fibres. These specimens showed normal submucous and myenteric plexuses stained with NSE. The population of SP- immunoreactive fibres was 15%–21% throughout the colon, and VIP was 39% in the caecum and 63%–65% in the transverse, descending, and sigmoid colon. In the four neonatal specimens (day 1 to 4), the SP population was only 1%–6% and the VIP population was also low (22%–33%). After 3 weeks of age, the populations had stabilised at 18%–26% for SP and 52%–62% for VIP. SP-immunoreactive nerve fibres were scarce in the neonatal period, and showed a rapid increase by 3 weeks and a similar though less dramatic increase in VIP-immunoreactive fibres. VIP-immunoreactive fibres were fewer in the caecum that at other colonic levels, where they accounted for 60% of NSE-labelled fibres; the SP population, however, was comparable at all levels of the colon at about 20% of NSE-labelled fibres. Accepted: 28 April 1998     

Cisapride for intractable constipation in children: observations from an open trial

Twelve patients with chronic constipation refractory to the vigorous use of emollients, enemas, and/or laxatives were chosen for study of the investigational prokinetic agent, Cisapride. The patients included 8 boys and 4 girls with diagnoses of functional constipation. Ages ranged from 2 to 13 years; duration of symptoms before Cisapride use ranged from 1.5 to 9.75 years; duration of previous treatment ranged from 0.75 to 6 years. The mean number of doses of anticonstipation agents employed per week was 14. Of the 12 patients, 10 had persistent encopresis, while 11 required hospitalization for disimpaction an average of 1.6 times in the year prior to Cisapride use. Three had chronic urinary tract complaints. Anal manometry suggested a sensory deficit in 8 of 10 patients tested. Ganglion cells were identified by rectal biopsy in all 12 patients. Cisapride treatment (0.14-0.3 mg/kg/dose) spanned 26-72 weeks (61 +/- 12). Stool frequency per week was not significantly changed, but five of seven patients who had reported hard stools had softer stools on the drug (p less than 0.05). Encopresis ceased in 8 of 10 cases, while the number of episodes decreased substantially in the other 2 cases (p less than 0.05). All alternate forms of anticonstipation therapy were withdrawn in 8 of 12 cases (p less than 0.001). Urinary problems improved in two of the three patients reporting symptoms. One patient showed no improvement in any parameter while on the agent, despite 26 weeks of administration. Side effects were infrequent, generally occurred early, and were limited to cramping, nausea, mild vomiting, anorexia, and headaches. One patient ceased use of the drug for persistent headaches.(ABSTRACT TRUNCATED AT 250 WORDS)     

先天性肛门直肠畸形术后便秘合并巨结肠的临床特点及处理

目的 总结先天性肛门直肠畸形术后顽固性便秘合并巨结肠的临床特点和治疗效果.方法 回顾性分析2005年8月至2010年7月收治的顽固性便秘合并巨结肠23例临床资料,男10例,女13例.首次手术年龄3 d至6岁,术前诊断均为中低位肛门直肠畸形.23例患儿均以肛门成形术后便秘就诊.下消化道气钡造影显示下端结肠及直肠扩张,无移行段,排钡延迟.本次手术年龄1岁2个月至15岁8个月.均采用Soave巨结肠根治术.结果 术前见肛门外观大致正常13例,外观正常合并直肠尿道瘘1例,肛门开口位置前移6例,瘢痕回缩2例,肛门外口狭窄1例.术中进入盆腔后即为扩张肠管,系膜增生增厚,肠壁血管增生粗大.13例单纯经会阴手术,10例经腹会阴手术,其中1例同时回肠末端造瘘.9例巨结肠切除同时,再次行肛门成形术,1例巨结肠切除同时行前矢状入路直肠尿道瘘修补术.病理检查15例切除肠管远近段,可见神经节细胞者,8例肠管远端无神经节细胞者,23例均见肌层增生肥厚,肌纤维变性,肌层排列紊乱.二次术后随诊肛门功能李氏评分5～6分.结论 先天性肛门直肠畸形术后顽固性便秘往往并发巨结肠改变,影像显示为肠管局限性扩张、僵硬和动力紊乱.采取手术治疗,切除病变肠管,做必要的肛门解剖缺陷修复,术后效果良好.

Abstract：

Objective To summarize the experience of diagnosis and treatment of intractable constipation in children with repaired anorectal malformation.Methods Between August 2005 and July 2010,23 children with a history of anorectal malformation (ARM) repair were diagnosed with intractable constipation,and underwent surgical treatment at this center.The patients,including 10 boys and 13 girls,underwent primary surgeries to repair low or intermediate type of ARMs.Their ages at the primary surgery ranged from 3 days to 6 years old.Physical examinations found normal appearance of anus on 14 children including 1 with rectourethral fistula,anus antelocation on 6,cicatricial retraction of anus on 2,and anal stricture on 1.The positive barium enema revealed the dilated distal colon and rectum without transition zones,and delayed barium transit time.The patients' age at the second surgery ranged from 1 year and 2 months to 15 years and 8 months old.Results Dilated distal colon and rectum,with increased intestinal wall and mesentery thickness as well as proliferated blood vessels,was found during surgery on all patients.However,no transition zone was observed.To remove the dilated intestine,transanal Soave procedure was performed on 13 children,and the other 10 underwent abdomino-perineal Soave procedure including 1 had additional ileostomy.Besides the megacolon resection,9 patients also underwent anoplasty,and rectourethral fistula was also repaired on 1 patient.At the distal end of the removed intestine,pathological examination revealed ganglion cells in 15 patients,and no ganglion cells in 8 patients.Hypertrophy,degeneration and derangement of the intestinal smooth muscle cells were also observed.After reoperation,patients' anal function was graded as 5 or 6 according to Lizheng's anal function scoring criteria.Conclusions Intractable constipation after ARM repair is usually caused by acquired megacolon.It can be cured by megacolon resection.     

Anorectal electromanometry in the diagnosis of neuronal intestinal dysplasia in childhood

The diagnosis of neuronal intestinal dysplasia (NID) is currently established by histochemical procedures. From October 1, 1981, until July 31, 1990, we submitted a total number of 737 patients under 15 years of age with several distinct colonic and anorectal disorders, to clinical, radiological, electromanometrical, histochemical and histological evaluation. 573 had a clinical diagnosis of chronic constipation, and in 38 of these NID could be demonstrated by histochemical examination. Motivated by our own findings with the anorectal electromanometry in these patients we performed a double-blind prospective study to find out if there are any particular and pathognomonic manometric parameters of NID in childhood. 80% of our patients with NID diagnosed prospectively since April 1st, 1986, had a relaxation of the internal anal sphincter which was not proportional to the volume of rectal distention. Anorectal hyperexcitability was also present in these patients, whereas a statistically highly significant (p less than 0.01) increase of the amplitude of anorectal fluctuations (7.27 +/- 1.12 mmHg) as compared to the values measured in our own patients with functional chronic constipation (2.87 +/- 0.33 mmHg) could be demonstrated. Considering only those patients who simultaneously presented all of the above mentioned electromanometric criteria (e.g. non-proportional relaxation of the internal anal sphincter, anorectal hyperexcitability, increased amplitude of anorectal fluctuations) without an increase of the anorectal pressure profile, we could demonstrate that the correlation between the electromanometric diagnosis of NID and the final histochemical diagnosis was 100%. Nevertheless, under these conditions, 30% (9 out of 30) of patients with NID were not recognized electromanometrically because they had been excluded as false negative cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

肠神经元性发育不良诊治进展

肠神经元性发育不良是导致儿童慢性便秘的常见疾病,属于先天性巨结肠同源病的一种。近年来,肠神经元性发育不良的诊断方法不断发展,但目前尚无统一的诊断标准。肠神经元性发育不良的治疗方式包括保守治疗及手术治疗,手术治疗时应保存肛管的完整性。另外,应用肠神经干细胞移植以及小肠移植治疗肠神经元性发育不良也日益成为关注的热点。文章就目前IND的病因、诊断及其治疗的最新进展进行了综述。     

Use of colonic manometry to differentiate causes of intractable constipation in children.

We evaluated colon manometry as a means of differentiating causes of intractable constipation in children. We studied pressure changes in the transverse, descending, and rectosigmoid colons of 23 children with intractable constipation. All patients had a history of less than one bowel movement per week for longer than 2 years without resolution after conventional medical management. The possibility of Hirschsprung disease was excluded in all. On the basis of pathologic and manometric studies of the upper gastrointestinal tract, 10 patients had a diagnosis of gastrointestinal neuropathy and two had a diagnosis of myopathy. The other 11 patients had functional fecal retention; this diagnosis was based on history and outcome of therapy. On the day of study we used endoscopy to place a manometry catheter into the transverse colon and recorded intraluminal pressure for longer than 4 hours. After obtaining a baseline recording, we gave the patient a meal to assess gastrocolonic response. Colonic contractions were recorded in 21 of 23 children. Children with functional fecal retention could be differentiated from those with neuropathy by examination of the postprandial record. After a meal children with functional fecal retention had (1) an increase in motility index (3.4 +/- 0.5 while fasting vs 9.1 +/- 1.3 postprandially; p less than 0.001), and (2) at least one high-amplitude propagated contraction (in 10 of 11 children). The patients with neuropathy had no high-amplitude propagated contractions (p less than 0.001 vs group with functional fecal retention) and motility index in these children did not increase significantly after a meal (2.7 +/- 1.0 while fasting vs 2.9 +/- 1.3 postprandially). The two children with hollow visceral myopathy had no contractions. We conclude that in children with severe chronic constipation the colonic results of manometry differentiate patients with functional fecal retention from those with neuropathy or myopathy of the colon.     

Colonic diversion for intractable constipation in children: colonic manometry helps guide clinical decisions.

BACKGROUND: Colonic manometry helps discriminate functional and behavioral causes for childhood constipation from colonic neuromuscular disease. METHODS: Of 375 colonic manometries performed for clinical indications, 12 could not be interpreted because of chronic colonic dilation. Based on colonic manometries that showed either no contractions or an absence of the gastrocolonic response or an absence of high-amplitude propagating contractions, the authors recommended diverting colostomies or ileostomies in 12 chronically constipated children (mean age, 4 years; range, 2-14 years, 5 boys). Before study, medical treatment was ineffective in all children. These children had persistently dilated colons with pathologic diagnoses of intestinal neuronal dysplasia (n = 4), hypoganglionosis (n = 2), hollow visceral myopathy (n = 1), and normal (n = 5). RESULTS: Six to 30 months after diversion, the authors restudied all the children. Eleven of 12 diverted colons were no longer dilated. In two patients, abnormal motility involving the entire colon was unchanged from the initial study, small bowel motility was abnormal, and we recommended no further surgery. In two cases, the colon remained abnormal but small bowel motility was normal, and we recommended subtotal colectomy and ileoproctostomy. In four cases, the left colon remained abnormal, but the right colon was normal, and we recommended reanastomosis after left hemicolectomy. In four cases, motility in the diverted colons was normal, including a gastrocolonic response and high-amplitude propagating contractions, and the authors recommended reanastomosis. Defecation problems resolved in 10 of 12 when followed up 5 to 30 months after treatment. CONCLUSION: These data suggest that in some cases of intractable childhood constipation associated with colonic distention, temporary diversion improved colonic motility. Colonic manometry may be used to predict which patients will benefit from resection or reanastomosis.     

Gender differences in reduced substance P (SP) in children with slow-transit constipation

Purpose  

Adult slow-transit constipation (STC) occurs predominantly in females and is associated with low numbers of substance P (SP)-containing nerves in colonic circular muscle.     

Incidence of spinal cord lesions in patients with intractable constipation

Abstract Spinal magnetic resonance imaging of children with intractable constipation was reviewed. Nine percent of patients had spinal cord abnormalities. Tethered cord was the most common lesion in 75% of patients. Magnetic resonance imaging is a useful tool to evaluate children with intractable constipation.     

腹腔镜下结肠切除Soave直肠内拖出术在肠神经元发育不良症中的应用

目的探讨腹腔镜下结肠切除、Soave直肠内拖出术治疗肠神经元发育不良症（IND）的可行性和中期随访结果。方法对25例IND和先天性巨结肠合并IND（HaIND）的患儿在腹腔镜下行Soave、结肠切除术,其中IND17例,HaIND8例。所有病例通过钡灌肠及延迟拍片、直肠黏膜活检、直肠肛管测压、腹腔镜浆肌层或全层活检明确诊断及病变范围。采用一个观察孔,2～4个操作孔。根据病变范围在腹腔镜下分别游离降结肠、横结肠、升结肠及系膜,会阴部手术按改良Soave方法。对患者手术方法、病变范围的确定、术后并发症和临床结果进行评估。结果25例中,10例行左半结肠切除,15例行结肠次全切除,按Deloyers法将升结肠逆时针转位270°下拖。行左半结肠切除术的患儿术前24h钡剂残留部位均在降结肠远端以远肠管,行结肠次全切除术的患儿术前24h钡剂残留在降结肠近端以近的肠管。平均手术时间分别为145min和188min,平均失血40ml。术后并发症：吻合口瘘2例,重度肛周皮肤红肿、糜烂11例,肠粘连1例,小肠结肠炎2例。术后平均随访4年,行左半结肠切除术的患儿,术后3个月内排便恢复正常;行结肠次全切除术的患儿术后3个月大便每日4～10次,12～24个月每日大便2～3次。2例出现污粪,无便秘复发和大便失禁病例。结论腹腔镜下结肠切除、Soave术治疗IND和HaIND安全、可行,创伤较小,术后并发症少,术后中期随访疗效满意。术前钡灌肠24h延迟拍片钡剂残留部位可以预测结肠切除的近端位置。     

Intestinal transit time in children with intestinal neuronal malformations mimicking Hirschsprung's disease.

A total of 106 consecutive children with intestinal neuronal malformations were included in a prospective study. The intestinal transit time was assessed using a modification of Hinton's method. The results of transit time studies, the associated specific histochemical findings, therapeutic procedures, and the clinical course on follow-up assessments over a mean period of 2.4 years were analysed. The intestinal transit time was prolonged in all 53 patients with aganglionosis and in 37 (69.8%) out of 53 children with other intestinal malformations. Eight out of 16 children with IND type B had an abnormal transit time, 1 underwent anterior resection, and 2 had a temporary colostomy. In 7 out of 8 children with hypoganglionosis and 9 out of 10 children with a reduced parasympathetic tone the transit time was prolonged. A resection was performed in 7 and 2 of these children respectively. Both patients with heterotopia of the myenteric plexus had a prolonged bowel transit and parts of the large bowel had to be resected. Only 11 out of 17 children with heterotopia of the submucous plexus, dysganglionosis, or immature ganglia had a prolonged transit time, 2 underwent sphincteromyotomy. At follow-up, all patients with malformations other than aganglionosis stated that symptoms had improved and they were willing to tolerate their complaints. However, 25 reported on persistent constipation, 6 on overflow encopresis. All children who required surgery had a prolonged intestinal transit time, but also 21 (56.8%) of 37 children who were successfully treated without surgery. None of the 16 children with normal transit had to be operated. It is concluded that specific histochemical findings do not always correlate with delayed intestinal transport. The determination of the intestinal transit time represents an important tool to identify the clinical relevance of histochemical findings in the individual patient.     

Isolated intestinal neuronal dysplasia Type B (IND-B) in Japan: results from a nationwide survey

Purpose

Intestinal neuronal dysplasia Type B (IND-B) has been proposed to be an allied disorder of Hirschsprung’s disease (ADHD). The original histological criteria included hyperganglionosis, giant ganglia, ectopic ganglion cells and an increased AChE activity in the lamina propria. The criteria for IND-B have been gradually revised. The present diagnostic criteria are [1] more than 20 % of the submucosal ganglia contain nine or more ganglion cells and [2] the patient is older than 1 year. To clarify the current status of IND-B in Japan, a nationwide retrospective cohort study was performed.

Methods

Questionnaires were sent to 161 major institutes of pediatric surgery and gastroenterology in Japan.

Results

A total of 355 cases of ADHD were collected, including 18 cases of IND-B (5 %). Based on original criteria, 13 out of 18 cases were diagnosed as IND-B. However, only four cases met the current criteria. Three of the four patients (75 %) required pull-through operation. All of the patients exhibited giant ganglia and ganglioneuromatosis-like hyperplasia of the myenteric plexus.

Conclusions

IND-B cases matching the current criteria are thought to be quite rare and they are associated with marked hyperplasia of the myenteric plexus. “True” IND-B is a rare and intractable disease.