Total Colonic Aganglionosis Research Articles

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.

Interstitial cells of Cajal reduce in number in recto-sigmoid Hirschsprung's disease and total colonic aganglionosis

Interstitial cells of Cajal (ICCs) play a key role in regulating gastrointestinal tract motility. The pathophysiological basis of colonic aperistalsis in Hirschsprung's disease (HD) is still not fully understood. Many studies reported that decreased numbers or disrupted networks of ICCs were associated with HD. Little information is available on the distribution of different subtypes of ICCs in HD. The aim of this study was to determine the alterations in density of different subtypes of ICC in colonic specimens of patients with total colonic and recto-sigmoid HD. Full thickness colonic specimens were obtained from five children with total colonic aganglionosis (TCA), sixteen with recto-sigmoid HD and seven controls. ICCs were visualized in frozen sections by c-Kit (CD117) fluorescent staining. In the control colon, c-Kit positive ICCs formed a dense network surrounding the myenteric plexus (IC-MY), along the submucosal surface of the circular muscle layer (IC-SM) and in the circular and longitudinal muscle layer (IC-IM). In the aganglionic region of the colon of the patients affected by HD, the number of ICCs (especially IC-IM and IC-SM) was markedly reduced and IC-MY networks were disrupted. Nearly total lack of three subtypes of ICCs was observed in the TCA specimens. This study demonstrated the altered distribution of different subtypes of ICCs in the resected colon of patients with recto-sigmoid HD and TCA. These findings suggest that the reduction of each subtype of ICCs may play an important role in the etiology of HD.

Mosaic trisomy 22 associated with total colonic aganglionosis and malrotation

Aims Abnormalities of chromosome 22 karyotype have been reported to be associated with both malrotation and aganglionosis. However, although malrotation has been reported to occur in the rare mosaic trisomy 22, Hirschsprung's disease has not. We present a case of mosaic trisomy 22 that presented during the neonatal period with malrotation and total colonic aganglionosis, and we discuss the possible pathogenesis of both conditions in the light of this rare genetic abnormality. The association of total colonic aganglionosis and mosaic trisomy 22 has not previously been reported. Results A male neonate with an antenatal diagnosis of de novo mosaic trisomy 22 underwent a laparotomy with correction of malrotation and midgut volvulus on day 3 of life. Rectal biopsy was performed because he had not passed meconium. This revealed Hirschsprung's disease; an ileostomy was formed, and histology confirmed aganglionosis as far as the terminal ileum. At 6 months, a modified Lester Martin Duhamel pull-through was performed. He is showing normal development at follow-up. Conclusions We recommend an increased index of suspicion of Hirschsprung's disease and malrotation in patients with mosaic trisomy 22 until further evidence can establish or exclude a meaningful relationship.

Total colonic aganglionosis with or without small bowel involvement: a 30-year retrospective nationwide survey in Japan

Purpose We conducted a nationwide survey in Japan, to identify recent trends in the diagnosis and treatment of patients who had total colonic aganglionosis with or without small bowel involvement (TCSA). These data were compared with 2 similar studies conducted within the last 30 years. Methods Patient data were collected in 3 phases; phase I included 135 patients between 1978 and 1982; phase II, 107 patients between 1988 and 1992; and phase III, 101 patients between 1998 and 2002. Results The incidence of TCSA was 1:59,059, 1:58,084, and 1:58,375, and the male-female ratios were 1.5:1, 1.5:1, and 2.2:1 in each phase, respectively. Patients with associated anomalies increased from 15.2% (phase I) to 22.8% (phase III). The incidence of preoperative enterocolitis decreased over time. For treatment, Duhamel's procedure and ascending colon patch methods have increased over time, whereas Martin's procedure has decreased. The mortality rate dropped from 40.9% to 15.8%; however, a high mortality rate persists in those cases with small bowel involvement (35.5%). Conclusions A marked decrease in the overall mortality rate was observed during the study period. However, further efforts are still required especially in cases involving aganglionosis extending orally to 75 cm from Treitz's band.

Long-Term Results of the Treatment of Total Colonic Aganglionosis with Two Different Techniques

Aim of this study was to assess the long-term results of the treatment of total colonic aganglionosis (TCA) with 2 different techniques in terms of growth, continence and quality of life (QOL). Forty-one patients treated for TCA between 1972 and 2007 were reviewed retrospectively with special attention paid to the length of aganglionosis, complications, growth, continence and QOL. Until 1992, patients underwent subtotal colonic resection and side-to-side ileosigmoid anastomosis (modified Martin). Since 1992, straight ileo-anal pull-through was preferred. At the end of follow-up (median 18 years, range 1-35), the height and weight, continence and QOL (scoring feeding habits, school/work performance, family life and professional development) were assessed by clinical visit or phone interview. Twenty-eight patients were male and 13 female. Six had total intestinal aganglionosis and were excluded from this review together with the 2 who died before definitive treatment. The 33/41 persons in whom aganglionosis had involved less than 50 cm above the ileocecal valve and who had been considered suitable for the reestablishment of transanal fecal flow were included. Eighteen children underwent a modified Martin and 15 straight ileo-anal pull-through. Postoperative intestinal obstruction occurred in 4 cases, prolapse and prolonged TPN requirement in 2, and wound disruption and fistula in 1. Thirteen patients (39 %) had postoperative enterocolitis. Two children died after operation (1 wound disruption with sepsis and 1 pneumonia). Out of 31 survivors, 57 % and 53 % were > p50 with regard to height and weight whereas only 15 % and 19 % were <p3 respectively. Only half the patients had more than 3 bowel movements per day and the median Wildhaber continence score (normal = 14) was 11 (range 6-14). Both types of operations resulted in comparable defecation and continence patterns. QOL was rated as good in all cases but one. All patients but 2 attended high school, 8 attend university, 4 are employed and 1 is married and has 2 daughters. Social life is normal except for 1 patient who perceives his disease as a burden. Patients with TCA amenable to reestablishment of the transanal fecal flow can have adequate growth, normal feeding, reasonably good continence and satisfactory QOL. However, complications and enterocolitis are frequent. A modified Martin's procedure was performed as well as straight ileo-anal pull-through with little influence on the long-term outcome.

Long-Term Outcome of Total Colonic Aganglionosis

No single surgical procedure for total colonic aganglionosis has clearly been proven to be superior. We present our experience and the long-term results of a standard Duhamel's pull-through procedure in the management of this rare form of Hirschsprung's disease. A retrospective study of all cases with Hirschsprung's disease diagnosed in our institute from November 1983 to December 2004 was conducted. All operated patients with total colonic aganglionosis (TCA) had a diversion in the first week of life. Duhamel's pull-through was the definitive procedure for all operated patients and was performed between 6 months and 1 year of age. All patients and their parents were contacted for an extended follow-up, ranging between 30 months and 21 years. Incontinence was assessed on the basis of soiling in the diaper between two consecutive defecations in the younger group of patients and the need for a diaper in the older age group. Hirschsprung's enteritis was regarded as severe if the patient's condition did not improve on conservative management and the patient needed an ileostomy post-pull-through. Thirty-six cases with Hirschsprung's disease were diagnosed during the study period. Twelve patients (31.4 %) had total colonic aganglionosis, confirmed at laparotomy, and underwent a diversion. Eight underwent definitive surgery during the first year of life. All operated patients had a standard Duhamel's pull-through as the definitive procedure. Four cases were not operated: two had Waardenburg syndrome with lethal total aganglionosis, one had multiple anomalies, and the last patient with mid-jejunal involvement died while awaiting a definitive procedure. Familial incidence was apparent in two sets of siblings. Leakage followed by stricture occurred in one patient. Hirschsprung's enteritis was diagnosed in three patients. In two, the enteritis was mild, while one patient required an ileostomy which was performed elsewhere. Half of our patients have an almost normal number of daily bowel movements (1 - 2 times). The long-term results of a standard Duhamel's pull-through for TCA are good in terms of continence, bowel motion, and physical development.

Long-term clinical outcome in patients with total colonic aganglionosis: a 31-year review

Background The purpose of this study is to review the long-term clinical outcome in patients surgically treated for total colonic aganglionosis (TCA). Methods The hospital records of 58 patients with TCA from 2 centers were retrospectively analyzed. These patients were then followed up by personal or telephonic interviews using a standardized questionnaire. Results Of the 58 patients, 36 were male and 22 were female. Thirty-eight patients presented in the neonatal period. A total of 13 (22.4%) presented with enterocolitis, 43 (74.1%) with intestinal obstruction, and 2 (3.5%) with severe constipation. All patients had disease involving the entire colon up to at least the terminal ileum. Two patients had total intestinal aganglionosis and died after ileostomy. Various pull-through procedures performed in 56 patients included Soave in 16, Swenson in 5, and Duhamel in 35 patients. Postoperatively, 31 (55.4%) patients had enterocolitis. At long-term follow-up (2-31 years), 3 patients had opted for permanent ileostomies because of intractable incontinenece or recurrent enterocolitis. Eleven patients were too young to assess bowel function or unavailable for follow-up. Of the remaining 42 patients, 22 had normal bowel control and 20 were soiling. At 5 years, patients had an average of 5.2 bowel movements per day, which reduced to a mean of 3.4 per day at the age of 15 years. Conclusion Patients with TCA continue to have long-term problems with bowel control, although many improve with time.

Variability of Acetylcholinesterase Hyperinnervation Patterns in Distal Rectal Suction Biopsy Specimens in Hirschsprung Disease

Variability in cholinergic innervation may contribute to false-negative and false-positive evaluations for Hirschsprung disease (HD). We compared intraspecimen variability of histochemical acetylcholinesterase (ACE) activity in 62 distal rectal mucosal biopsy specimens from 33 patients with short-segment HD (SSHD), 14 patients with short-segment HD/Down syndrome (SSHD/DS), 10 patients with total colonic aganglionosis (HDTC), and 45 ganglionated control specimens obtained because of clinical suspicion for HD. Specimens were evaluated in 1-mm linear segments for abnormal distribution and abnormal intensity of staining reaction in the lamina propria (LP), muscularis mucosae (MM), numerical excess of small submucosal nerves (SSN), and presence or absence of large submucosal nerves (LSN) defined as >35 microns in diameter. Patients with HD and controls were predominantly infant males. Aggregate length of specimens was 186 mm in HD and 136 mm in controls. We defined multiple patterns and relative frequencies of normal and abnormal ACE reactivity in the muscularis mucosae, submucosal nerves, and innervation in the lamina propria. We verified a hyperinnervation pattern more common in neonates within each subset of HD. Large submucosal nerves >35 microns in diameter are relatively less common in SSHD/DS and HDTC. Eleven of 57 patients with HD had at least 1 mm of normal muscularis mucosae accounting for 19/186 mm examined. Ten percent of control mm had at least 1 submucosal nerve >35 microns in diameter. Intraspecimen variability in ACE patterns, when extreme, can usually be resolved by findings elsewhere in an adequate specimen, minimizing the need for repeat procedures.

Hirschsprung's Disease, One of the Most Difficult Diagnoses in Pediatric Surgery: A Review of the Problems from Clinical Practice to the Bench

The diagnosis of Hirschsprung's disease (HSCR) should take place early in the neonatal period, because without an effective diagnosis and appropriate treatment, a considerable proportion of infants will go on to develop serious complications such as acute enterocolitis or toxic megacolon. Because no more than 10 % of HSCR cases have a late presentation with classical chronic constipation and megacolon, the clinician has to make a difficult, early diagnosis, which is the crux of the clinical problem. The aim of this review paper is to present all tools currently available to make a clear HSCR diagnosis and to discuss the problems facing the clinician and the pediatric surgeon in the correct identification of HSCR and of other intestinal dysganglionoses. Based on the current state of knowledge and 24 years' personal experience in clinical practice and basic research in this field, I describe an algorithmic approach that enables clinicians and surgeons to rationalize and maximize the clarity of diagnosis through a complementary set of procedures and enzyme-histochemical reactions. Two innovative techniques, added to the protocol in the last four years, are described: the lyophilized HSCR diagnostic kit, and the one-trocar transumbilical laparoscopic intestinal full-thickness biopsy technique (OTTLB). The rational, algorithmic diagnostic pathway proposed in this review paper aims to optimize every diagnosis by the stepwise application of a complementary set of procedures and enzyme-histochemical reactions as they become appropriate. In the interests of simplifying genetic molecular diagnosis, I suggest the following guidelines: 1) only in cases of total colonic aganglionosis (TCA) is it advisable to carry out full RET mutation screening (the mutation rate is up to 70 %); and 2) all HSCR patients should be tested only for standard MEN2A and MTC mutations. If these are present, the patients should be followed up carefully with proper surveillance and biochemical testing of other susceptible family members as they are at risk of developing neuroendocrine tumors.

Current significance of meconium plug syndrome

BackgroundThe significance of meconium plug syndrome is dependent on the underlying diagnosis. The incidence of pathologic finding, particularly Hirschsprung's disease, contributing to the presence of these plugs, has been debated. However, there are little recent data in the literature. Therefore, we reviewed our experience with meconium plugs as a cause of abdominal distension to evaluate the associated conditions and incidence of Hirschsprung's disease. MethodsWe reviewed the records of newborns with meconium plugs found in the distal colon on contrast enema from 1994 to 2007. Demographics, radiologic findings, histologic findings, operative findings, and clinical courses were reviewed. ResultsDuring the study period, 77 patients were identified. Mean gestational age was 37.4 weeks and birth weight, 2977 g. Hirschsprung's disease was found in 10 patients (13%). One had ultrashort segment disease and another had total colonic aganglionosis. Maternal diabetes was identified in 6 patients. No patients were diagnosed with cystic fibrosis, meconium ileus, malrotation, or intestinal atresia. ConclusionMeconium plugs found on contrast enema are associated with a 13% incidence of Hirschsprung's disease in our experience. Although all patients with plugs and persistent abnormal stooling patterns should prompt a rectal biopsy and genetic probe, the incidence of Hirschsprung's and cystic fibrosis may not be as high as previously reported.

Study of acetylcholinesterase activity in rectal suction biopsy for diagnosis of intestinal dysganglionoses: 17-year experience of a single center

Although the utility of the acetylcholinesterase (AChE) histochemistry on rectal suction biopsy in diagnosing Hirschsprung's disease (HD) has been documented, few reports address a great number of biopsies and patients. Our aim is to present a 17-year experience on the method of rectal suction biopsy and AChE histochemical staining for diagnosis of intestinal dysganglionoses. Between August 1989 and July 2006, 297 children suspected of having HD were submitted to rectal suction biopsies that were evaluated by the same two surgeons. There were 18 complications (6.0%), namely one self-limited rectal bleeding and 17 (5.7%) inadequate procedures that were repeated. A total of 157 patients (52.8%) showed no increased AChE activity and the remaining patients (140-47.2.0%) presented patterns of increased AChE activity confirming the diagnosis of HD or neuronal intestinal dysplasia. Among the 140 cases suspected as having HD, in 131 children the diagnosis of HD was confirmed and they were operated on. The histological studies showed that 111 children presented the classic form of HD or a long spastic segment. Sixteen children presented total colonic aganglionosis and four children proved to have intestinal neuronal dysplasia, according to histological and radiological criteria. Nine (6.6%) newborns were identified as false-positives and no false-negative results were verified. The rectal suction biopsy combined with AChE staining is advantageous for the differentiation between normal bowel and intestinal dysganglionoses. The rectal suction method is simple and can easily be performed by experienced surgeons. The histological evaluation is very objective and can be performed by a non-pathologist.

Hirschsprung disease: do risk factors of poor surgical outcome exist?

Introduction Long-term results after surgical treatment of Hirschsprung disease (HSCR) are not always as good as a surgeon may perceive. Several studies have tried to correlate preoperative features to the surgical outcome of HSCR, but none came to definitive conclusions. Our study is aimed at identifying risk factors of poorer long-term outcome after surgery for HSCR. Materials and Methods One hundred two patients with HSCR were included. Eighty had rectosigmoid aganglionosis and 22 had total colonic aganglionosis (TCSA). Preoperative variables were sex, associated anomalies, delayed meconium passage, preoperative enterocolitis, preoperative bowel obstruction, age at surgery, and number of pull-through procedures performed. Outcome measures were surgical complications, postoperative enterocolitis, perineal excoriations, constipation, continence, psychological self acceptance, and patients' perspectives. These were evaluated with regard to preoperative features and length of aganglionosis. Results Results of patients with TCSA proved to be significantly worse than those of patients with classic HSCR (constipation and poor continence excluded). Male patients with TCSA proved to have a significantly higher incidence of complications (100% vs 38.5%) and poor psychological self acceptance (100% vs 46.2%). Patients with associated anomalies (central nervous system) experienced a significantly higher incidence of postoperative constipation (43% vs 13%). Patients who described failure or delayed meconium passage complained of significantly worse continence (28.3% vs 7.1% of fair to poor continence). Preoperative enterocolitis proved to be significantly correlated to postoperative enterocolitis (16.4% vs 37.1%) and perineal excoriations (13.7% vs 30.9%). Patients with preoperative intestinal obstructions complained of significantly worse psychological self acceptance (37.8% vs 12.5%). Conclusions Length of aganglionosis has the greatest impact on overall surgical outcome of HSCR. Other minor risk factors have been identified, namely, male sex, associated central nervous system anomalies, failure to pass meconium, and preoperative enterocolitis occurrences. Age at surgery and redo procedures proved not to significantly interfere with the outcome. Our study provides comprehensive and useful data to inform parents and families of a baby with HSCR with regard to expected results and long-term outcomes of surgery basing on preoperative features. Further studies on larger series are strongly recommended.

Quality of Life of Patients with Hirschsprung's Disease at 5 - 20 Years Post Pull-Through Operations

The aim of this study was to evaluate the bowel habits and quality of life with respect to faecal continence of patients with Hirschsprung's disease (HD) who had undergone pull-through operations more than 5 years previously. Four hundred and sixty-seven patients who underwent pull-through operations for HD during the period of 1987 - 1999 were followed up for evaluation. A questionnaire including demographic data and a qualitative clinical scoring method as described by Holschneider was used for the evaluation of faecal continence. The scoring system did not require a physical examination. Outcomes of the 3 major procedures (Swenson, Duhamel and Soave technique) were analysed. The research was undertaken from October 2004 to September 2006. Patients with neurological defects and total colonic aganglionosis (TCA) were excluded from the analysis. Only patients with typical HD were evaluated, and they were divided into 3 groups based on the length of the period since surgery: 5 - 10 years in Group A; 10 - 15 years in Group B; and 15 - 20 years in Group C. Only 204 patients (male to female ratio: 169 : 35) returned to the Queen Sirikit National Institute of Child Health for evaluation. Twenty-six patients were excluded because of TCA in 13, Down's syndrome in 9 and cerebral palsy in 4. The remaining 178 patients were evaluated and divided into Group A (n = 67), Group B (n = 75) and Group C (n = 36). Excellent results (14 points), good results (10 - 13 points) and fair results (5 - 9 points) were noted in Group A in 52.2 %, 34.3 % and 7.5 % of cases respectively, in Group B in 68 %, 28 % and 4 % of cases, respectively, and in Group C in 88.9 %, 11.1 % and 0 % of cases, respectively. Five cases (7.5 %) in Group A and 3 cases (4 %) in Group B with fair results still had problems such as constant soiling and an inability to hold back defecation. They experienced marked limitations in their social life because of their dependence on diapers and frustration because of teasing by their friends. Faecal incontinence still remains a problem in some patients with HD at 5 - 15 years after surgical correction. However, nearly all patients who were operated on more than 15 years previously had nearly normal faecal continence and a normal social life.

A review of genetic mutation in familial Hirschsprung's disease in South Africa: towards genetic counseling

Hirschsprung's disease (HSCR) represents a complex disorder of signaling molecules, resulting from the effects of at least 9 known susceptibility genes. Affected families carry 200 times higher risk, but genetic counseling via pedigree analysis is difficult and the significance of genetic variations is unclear. This study evaluated a set of patients affected by HSCR with familial recurrence to evaluate factors of greatest value in genetic counseling. One hundred twenty patients with HSCR (including 18 kindreds) were screened for genetic variations of the 2 major susceptibility genes (RET and endothelin B receptor [EDNRB]) and compared with 60 control samples (20 per ethnic group). Familial recurrence patterns were studied for patient sex, pattern of recurrence, presence of associated syndromic features, and genetic features of major susceptibility genes. Polymerase chain reaction and HEX-SSCP analysis were performed on DBA extracted from blood/microdissected tissue samples. SSCP variants were validated and automated sequencing techniques performed on polymerase chain reaction products showing conformational variants in acrylamide gel. Familial cases had a male-female ratio of 1.5:1, male-to-male transmission (n = 10; 2 father to son), female-to-male transmissions (n = 4; 3 female carriers, female-to-female (n = 4; 2 mother to daughter), and 1 paternal RET deletion-female with very long segment aganglionosis. Increasing gene penetrance occurred in 3 pedigrees. An increased incidence of long segment HSCR was noted in families with recurrence and appeared important. No consistent mendelian trends or specific genetic sites were observed, but 3 suggested autosomal dominant and recessive in a further 3. Identified genetic variations included deletions, frame shifts, and missense mutations, as well as a number of significant single nucleotide polymorphism variations. Transmitted RET mutations occurred in 5 (30%) of 16 kindreds. Splice RET mutation plus variants of exon 17 (973L) affected 2 children with identical total colonic aganglionosis. In a 3-generation family, variations in RET exons 6, 13, and 18 (928) affected 3 male children with increasing penetration to recur as total intestinal aganglionosis in a grandchild. Mendelian transmission appears mediated by the RET proto-oncogene. EDNRB mutations suggest haplotypic gene-gene interaction. Genetic counseling remains a challenge in HSCR because of its multfactorial etiology.

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

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. 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. 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. Redo-endorectal pull through proved to be a safe technique and feasible even after prior Duhamel pull through, resulting in good clinical outcome.

Polymorphisms of human cytomegalovirus UL139 open reading frame in Hirschsprung's disease

To explore the UL139 gene polymorphism of human cytomegalovirus (HCMV), and the relationship between polymorphisms of HCMV UL139 ORF and Hirschsprung's disease (HD). Forty-three specimens of the aganglionic intestinal segment and 6 urine samples of HD infants were amplified by nested polymerase chain reaction (PCR) method. The amplicons were sequenced in both strands directly. The control group consisted of 10 asymptomatic HCMV infected infants, and their urine specimens were also analyzed using the same method. HCMV UL139 genes of 28 clinical strains from HD 1 patients were successfully amplified and sequenced. UL139 was hypervariable and was clustered into 3 major groups and 5 genotypes. The predominant genotype of HCMV in HD infants was UL139 Group 3 (48 percent). Comparison of strains distribution between the two groups did not reach statistical significance using chi square test (chi square=7.378, P=0.194). The results of correlation analysis between UL139 and UL144 genes showed a p value 0.05 by Kendall test. Clinically, strains from the rectosigmoid segment, total colon aganglionosis, and long-segment were distributed sporadically in UL139 genotypes. UL139 gene displayed polymorphisms. No linkage was found between UL139 genotype and clinical phenotype of HD. There was no correlation between HCMV UL144 and UL139.

Outcomes of Surgical Management of Total Colonic Aganglionosis

The purpose of this study was to assess the long-term clinical outcomes and bowel function of patients with total colonic aganglionosis (TCA) after surgery. The hospital records of 17 TCA patients treated surgically during 1985 to 2004 were reviewed. Long-term follow-up was done by telephone interviews with the parents. Primary enterostomy was performed in 13 (76%) patients. In three (17%) patients, TCA was not suspected initially. They underwent conservative surgery primarily, which required a second operation soon after. One had transverse colectomy with ileostomy. By pathologic review, nine (53%) patients had small bowel involvement of aganglionosis. Six (35%) patients died before corrective surgery. They all had extensive small bowel involvement. Among 11 patients who had a corrective operation, 10 were treated with Martin's procedure. Long-term (mean 74 months) follow-up was available in seven patients, and the mean weight-for-age percentiles was 27.1% (range 5-50%), the frequency of defecation was three to five times a day in four patients (57%), one or two times a day in two patients (28%), and more than five times a day in one patient (15%). TCA is difficult to diagnose; but once it is diagnosed correctly and treated by corrective surgery, outcomes seem promising. Martin's operation brought about a good outcome and enabled patients to have acceptable bowel habits. The prognosis is highly dependent on the extent of aganglionosis.

Interstitial cells of Cajal in the normal gut and in intestinal motility disorders of childhood

Interstitial cells of Cajal (ICCs) are pacemaker cells which are densely distributed throughout the whole gastrointestinal tract. ICCs have important functions in neurotransmission, generation of slow waves and regulation of mechanical activities in the gastrointestinal tract, especially for the coordinated gastrointestinal peristalsis. Therefore, a loss of ICCs could result in gastrointestinal motor dysfunction. In recent years c-kit labeling has been widely used to study pathological changes of ICCs in gastrointestinal motility disorders. Paediatric gastrointestinal motility disorders such as hypertrophic pyloric stenosis, Hirschsprung's disease, total colonic aganglionosis, hypoganglionosis, intestinal neuronal dysplasia, internal anal sphincter achalasia, megacystis microcolon intestinal hypoperistalsis syndrome have been reported to be associated with loss or deficiency of ICCs networks. This review describes the distribution of ICCs in the normal gastrointestinal tract and its altered distribution in intestinal motility disorders of childhood.

Ten-year experience in the management of total colonic aganglionosis

Purpose The aim of this study was to review the 10 years' experience in the management of patients with total colonic aganglionosis (TCA) and follow-up of their health condition. Methods Cases of 25 patients with TCA in the Children's Hospital of Fudan University from 1996 to 2005 were reviewed and analyzed. The confirmed diagnosis was established by an intraoperative frozen-section biopsy of the rectum, colon, appendix, and ileum. The data included in this study accounted for sex, age, signs of presentation, any familiar history of Hirschsprung disease (HD) or associated abnormalities, and ileal involvement. Plain x-ray films, barium enema, and anorectal manometry were provided for evaluation. The results of surgical management were analyzed for weight at definite operation, blood requirement during operation, the total parenteral nutrition duration, and the pre- and postoperative complications of these patients. Follow-up data were collected regarding growth development, stool frequency, stool consistency, fecal soiling, incontinence, enterocolitis, and anal stricture. Results Among 25 patients, 8 (32%) females and 17 (68%) males were diagnosed as having TCA. Sixteen patients (64%) were evaluated at the neonatal period, whereas 9 patients (36%) were evaluated after the neonatal period. All 25 patients received at least 1 plain abdominal radiograph or barium enema at the university hospital before operation. However, there was no specific pathognomonic finding that may provide a definite diagnosis. Nineteen (76%) patients underwent initial laparotomy at our institute and 6 patients (24%) were operated on beforehand at other hospitals. Twenty-three (92%) patients were diagnosed as having TCA and underwent ileostomy, whereas 2 (8%) patients underwent primary pull-through procedure. Eighteen (72%) patients had undergone definite surgery. Pre- and postoperative complications included enterocolitis (44.4%), perianal excoriation (77.7%), electrolyte imbalance (50%), and anastomotic leak (16.6%). Average duration of total parenteral nutrition before operation was 17.77 ± 12.54 days and after operation was 10.27 ± 5.23 days. Mean follow-up time was 27.6 ± 35.39 months. Two patients had 5 to 6 bowel movements per day. Seven had a frequency of stool ranging between 1 and 3 bowel movements per day. Their bowel movements returned to normal about 12 to 18 months after surgery. On follow-up, the height and weight development of the patients was found to be normal. Conclusions Gradual progress was observed in all the patients that took part in the study, and all patients had positive results eventually.

Developmental anomalies of the enteric nervous system in normoganglionic segments of bowel from rats with total colonic aganglionosis

Polysialyated neural cell adhesion molecule (PSA-NCAM) is a marker for immature neurons and S100 beta is a known marker for enteric glia. The aim of this study was to determine the maturation of the enteric nervous system (ENS) in normoganglionic (Ng) bowel from rats with total colonic aganglionosis (TCA). Ng ileum was obtained from TCA rats (spotting lethal: mutant, sl/sl: n = 15) at 10, 19, and 24 days of age (n = 5 for each age). Normal control Ng ileum was obtained from wild type littermates (+/+, n = 25) at 10, 19, 24, 30, and 60 days of age (n = 5 for each age). Specimens were studied with immunohistochemistry for PSA-NCAM and S100 beta. On H-E staining, normal mature ganglion cells (GC) were identified in submucus and myenteric plexuses in all specimens from TCA rats and normal controls. For PSA-NCAM, submucus and myenteric GC in control ileum were strongly positive at 10 days old, weakly positive at 19 days old, and did not stain from 24 days old and after. However, in all ileum specimens from TCA rats, both submucus and myenteric GC were strongly positive for PSA-NCAM regardless of age. For S100 beta, submucus and myenteric glial cells in control ileum were negative at 10 and 19 days old, but positive from 24 days old and after. However, in all ileum specimens from TCA rats, submucus and myenteric glial cells were S100 beta negative regardless of age. Our results suggest that GC in the Ng segment of TCA rats remain immature beyond an age when they should be mature.