Hirschsprung disease.

Hirschsprung disease (HSCR) is a rare congenital intestinal disease that occurs in 1 in 5,000 live births. HSCR is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Most patients present during the neonatal period with the first meconium passage delayed beyond 24 h, abdominal distension and vomiting. Syndromes associated with HSCR include trisomy 21, Mowat-Wilson syndrome, congenital central hypoventilation syndrome, Shah-Waardenburg syndrome and cartilage-hair hypoplasia. Multiple putative genes are involved in familial and isolated HSCR, of which the most common are the RET proto-oncogene and EDNRB. Diagnosis consists of visualization of a transition zone on contrast enema and confirmation via rectal biopsy. HSCR is typically managed by surgical removal of the aganglionic bowel and reconstruction of the intestinal tract by connecting the normally innervated bowel down to the anus while preserving normal sphincter function. Several procedures, namely Swenson, Soave and Duhamel procedures, can be undertaken and may include a laparoscopically assisted approach. Short-term and long-term comorbidities include persistent obstructive symptoms, enterocolitis and soiling. Continued research and innovation to better understand disease mechanisms holds promise for developing novel techniques for diagnosis and therapy, and improving outcomes in patients.

Study on the application of optical coherence microscopy in Hirschsprung's disease.

To explore the clinical application value of optical coherence microscopy (OCM) in Hirschsprung's disease. 109 HSCR patients were recuited in a Chinese hospital from January 2018 to July 2021. All the recruited patients underwent barium enema angiography preoperatively and the resected diseased intestinal tubes were evaluated intraoperatively. The OCM and the histopathological examination were performed successively on the surgical specimens, and the OCM images were compared with the relevant tissue sections to characterize different lesions. 10 non-HSCR fetal colorectal tissues at the same period were retained for OCM, the characteristics of which with and without HSCR under OCM imaging were analyzed. In the OCM images of in vitro tissue, it can be clearly observed that the scattering degree of HSCR narrow segment mucosal is high, glands and crypt structures are reduced or even atrophy, and the scattering degree of submucosal and intermuscular is low; In the dilated segment, the low scattering and high scattering are complex, and the muscle layer is obviously hypertrophy and structural disorder. Compared with the pathological findings, the OCM sensitivity, Kappa value, and AUC area reached 92.66%, 0.63, and 0.91, respectively. OCM can quickly and clearly display the structure of all layers of colorectal tissue, which is highly consistent with the corresponding histopathological examination results and has high sensitivity. which will provide a more reliable basis for OCM diagnosis of early HSCR, targeted biopsy and location of operative treatment, and has a certain potential for clinical application.

The Somatic Mutation Paradigm in Congenital Malformations: Hirschsprung Disease as a Model.

Patients with Hirschsprung disease (HSCR) do not always receive a genetic diagnosis after routine screening in clinical practice. One of the reasons for this could be that the causal mutation is not present in the cell types that are usually tested-whole blood, dermal fibroblasts or saliva-but is only in the affected tissue. Such mutations are called somatic, and can occur in a given cell at any stage of development after conception. They will then be present in all subsequent daughter cells. Here, we investigated the presence of somatic mutations in HSCR patients. For this, whole-exome sequencing and copy number analysis were performed in DNA isolated from purified enteric neural crest cells (ENCCs) and blood or fibroblasts of the same patient. Variants identified were subsequently validated by Sanger sequencing. Several somatic variants were identified in all patients, but causative mutations for HSCR were not specifically identified in the ENCCs of these patients. Larger copy number variants were also not found to be specific to ENCCs. Therefore, we believe that somatic mutations are unlikely to be identified, if causative for HSCR. Here, we postulate various modes of development following the occurrence of a somatic mutation, to describe the challenges in detecting such mutations, and hypothesize how somatic mutations may contribute to 'missing heritability' in developmental defects.

Thyroid Hormone in the Pathogenesis of Congenital Intestinal Dysganglionosis.

INTRODUCTION: The objective of this study is to investigate the role of thyroid hormone (TH) in the pathogenesis of intestinal dysganglionosis (ID). METHODS: A zebrafish model of congenital hypothyroidism (CH) was created by exposing the larvae to the 6-propyl-2-thiouracil (PTU). The enteric neurons were labeled with anti-HuC/D antibodies. The number of enteric neurons was counted. The larval intestine was dissociated and stained with anti-p75 and anti-α4 integrin antibodies. Mitosis and apoptosis of the p75+ α4 integrin+ enteric neural crest cells (ENCCs) were studied using flow cytometry. Intestinal motility was studied by analyzing the transit of fluorescent tracers. RESULTS: PTU (25 mg/L) significantly reduced TH production at 6- and 9-days post fertilization without changing the body length, body weight, and intestinal length of the larvae. Furthermore, PTU inhibited mitosis of ENCCs and reduced the number of enteric neurons throughout the larval zebrafish intestine. Importantly, PTU inhibited intestinal transit of fluorescent tracers. Finally, thyroxine supplementation restored ENCC mitosis, increased the number of enteric neurons, and recovered intestinal motility in the PTU-treated larvae. CONCLUSIONS: PTU inhibited TH production, reduced the number of enteric neurons, impaired intestinal motility, and impeded ENCC mitosis in zebrafish, suggesting a possible role of CH in the pathogenesis of ID.

Diagnosis of Hirschsprung Disease.

Diagnosis or exclusion of Hirschsprung disease (HSCR) is a frequent exercise in any pediatric hospital. Although HSCR may present at different ages and with varied clinical findings, the most common presentation is a neonate with severe constipation or signs of intestinal obstruction. A variety of diagnostic tests including contrast enema and anorectal manometry may be used as diagnostic screens, but diagnosis ultimately rests upon histopathological evaluation of a rectal biopsy. For the experienced pathologist, conventional hematoxylin-and-eosin-stained sections often suffice to exclude HSCR or establish the diagnosis. However, ancillary diagnostic tests such as acetylcholinesterase histochemistry or calretinin immunohistochemistry are complementary and extremely helpful in some cases. In this Perspectives article, we review the clinical and pathological features of HSCR, highlight those that are found in most patients, and discuss how to address particularly challenging aspects of the diagnostic workup.

Intestinal organoids in infants and children.

Recent advances in culturing of intestinal stem cells and pluripotent stem cells have led to the development of intestinal organoids. These are self-organizing 3D structures, which recapitulate the characteristics and physiological features of in vivo intestinal epithelium. Intestinal organoids have allowed the development of novel in vitro models to study various gastrointestinal diseases expanding our understanding of the pathophysiology of diseases and leading to the development of innovative therapies. This article aims to summarize the current usage of intestinal organoids as a model of gastrointestinal diseases and the potential applications of intestinal organoids in infants and children. Intestinal organoids allow the study of intestinal epithelium responses to stress factors. Mimicking intestinal injury such as necrotizing enterocolitis, intestinal organoids increases the expression of pro-inflammatory cytokine genes and shows disruption of tight junctions after they are injured by lipopolysaccharide and hypoxia. In cystic fibrosis, intestinal organoids derived from rectal biopsies have provided benefits in genetic studies and development of novel therapeutic gene modulation. Transplantation of intestinal organoids via enema has been shown to rescue damaged colonic epithelium in mice. In addition, tissue-engineered small intestine derived from intestinal organoids have been successfully established providing a potential novel treatment and a new hope for children with short bowel syndrome.

Should we look for Hirschsprung disease in all children with meconium plug syndrome?

BACKGROUND: Meconium plug syndrome (MPS) is associated with Hirschsprung disease (HD) in 13-38% of cases. This study sought to assess institutional variation in utilization of rectal biopsy in children with MPS and the likelihood of diagnosing HD in this population. METHODS: Patients with MPS on contrast enema in the first 30 days of life from the Pediatric Health Information System database in 2016-2017 were included. Institutional rates of rectal biopsies performed during the initial admission were calculated and then used to predict institutional rates of early HD diagnoses using Poisson regression. RESULTS: Of 373 newborns with MPS, 106 (28.4%) underwent early rectal biopsy, of whom 43 (40.5%) had HD. Fifty-seven (15.3%) were ultimately diagnosed with HD. Eight (14%) of these patients had a delayed diagnosis. HD rates between institutions did not differ significantly (range 0-50%, p=0.52), but usage of early rectal biopsy did (range 0-80%, p=0.03). Each additional early biopsy increased the early HD diagnosis rate by 35% (ß=0.30, 95% CI 0.15-0.45, p<0.0001). CONCLUSION: The incidence of HD is increased in children with MPS. There is significant hospital variability in the utilization of early rectal biopsy, and opportunity exists to standardize practice. TYPE OF STUDY: Study of Diagnostic test Level of Evidence: Level III.

Optimal time for single-stage pull-through colectomy in infants with short-segment Hirschsprung disease.

OBJECTIVE: Short-segment Hirschsprung disease (HSCR) is the predominant type of HSCR that affects approximately 75% of patients. Whether single-stage endorectal pull-through (ERPT) surgery is appropriate for neonatal patients with HSCR has not been definitively determined. This retrospective cohort study concerning infants with short-segment HSCR investigated the optimal age for single-stage ERPT surgery, regardless of the operative approach. METHODS: The 198 patients were stratified by operative age ≤ 3 or > 3 months (groups A or B, respectively, n = 62 and 136, respectively). Diagnoses of short-segment HSCR were conducted by preoperative contrast enema and rectal suction biopsy with acetylcholinesterase immunohistochemical staining. The perioperative clinical course for all patients was reviewed and the accuracy rate of the preoperative diagnoses and postoperative short- and midterm outcomes were assessed. RESULTS: The rates of diagnostic accuracy, according to the results of the preoperative contrast enema or rectal suction biopsy, were lower in group A (67.2 and 93.5%, respectively) than in group B (81.4 and 94.9%, respectively). In groups A and B, 49 (79.1%) and 108 (79.4%) infants, respectively, completed follow-up examinations. The short-term outcomes were postoperative HSCR-associated enterocolitis, adhesive bowel obstruction, anastomosis leakage, and anal stenosis during the first 12 months after surgery. The midterm outcomes were incontinence and constipation at ~24 months after surgery. Compared with group B, group A experienced more incidences of anastomotic leakage in the short-term and more soiling in the midterm. In groups A and B, the rates of constipation recurrence were nil and 1.9%, respectively. CONCLUSION: Infants with HSCR ≤3 months old at the time of single-stage ERPT surgery showed lower rates of accurate and conclusive diagnostic results and poorer postoperative outcomes. Waiting to perform this surgery until infants are older might be more beneficial.

Pathological changes of interstitial cells of Cajal and ganglion cells in the segment of resected bowel in Hirschsprung's disease.

OBJECTIVES: This study was conducted to investigate the pathological changes which occur in interstitial cells of Cajal (ICCs) and ganglion cells found in segments of resected bowel obtained from patients with Hirschsprung's disease (HD), as well as to explore the benefits of using a contrast enema (CE) with 24-h delayed X-ray films to predict the length of resected bowel. METHODS: We performed a retrospective analysis of 58 children with HD who had undergone the pull-through procedure. After each operation, the ICCs and ganglion cells present in the proximal ends of the barium residue (Level A) and resected proximal bowel segment (Level B) were analyzed using immunohistochemical staining methods. Each patient was followed up for 1 year to record their stool frequency, defecation control ability, and post-surgical complications which may have occurred. RESULTS: Immunohistochemical staining detected fewer ICCs in Level A than in Level B (p < 0.05). However, the density of ganglion cells in the two levels was not significantly different (p > 0.05). One patient had anastomotic stricture, and five patients suffered from enterocolitis. CONCLUSIONS: The density of ICCs was significantly lower in the bowel segments that displayed barium retention. A CE may be a valuable tool for predicting the length of bowel resection in patients with HD.

Neonatal sigmoid volvulus.

BACKGROUND: Neonatal sigmoid volvulus is a rare entity. It is associated with Hirschsprung's disease. Presentation is acute abdominal distention, vomiting and obstipation. Abdominal radiograph will show the "coffee bean" sign, but this is frequently missed and the diagnosis requires a high index of suspicion. Treatment options include contrast enema, colonoscopy or laparotomy, depending on the condition of the baby and local availability. POPULATION AND RESULTS: During the last 6years, 6 infants with sigmoid volvulus were treated in our department. Four presented during the first 48h since birth, and 2 presented at the age of 2 and 7weeks of age. One child was operated and 5 had primary contrast enema with radiologic de-volvulus. Rectal biopsy was performed in all cases; three children had Hirschsprung's disease. Those with normal biopsies responded well to rectal washouts. Two patients had early one stage transanal pullthrough and one had 2 further occasions of sigmoid volvulus prior to definitive surgery. All three recovered with an uneventful course. CONCLUSIONS: Neonatal sigmoid volvulus requires a high level of suspicion. Contrast enema is efficient for primary de-volvulus. Rectal biopsy should be performed and if positive for Hirschsprung's disease, surgery should be performed sooner rather than later.

Contrast Enema for Hirschsprung Disease Investigation: Diagnostic Accuracy and Validity for Subsequent Diagnostic and Surgical Planning.

INTRODUCTION: A targeted Hirschsprung disease (HD) diagnostic is necessary, as it determines a specific approach primarily based on surgical resection of the affected aganglionic colonic segment. The aim of this study was to evaluate the diagnostic accuracy of a contrast enema (CE) for HD diagnosis and to determine whether it should be performed before or after rectal biopsies (RBs). METHODS: A retrospective observational study of children undergoing RB for HD investigation was performed. In the performed CE, the occurrence and the level of a colonic caliber change (CCC) were recorded and its concordance with the histologically assessed level of aganglionosis by RB and the odds ratio were calculated. RESULTS: A total of 107 cases were included. Sensitivity and specificity for a CCC in CE were 74.1% and 94.6%. A CCC present in CE was associated with a 50-fold increased probability for a histologically proven HD. The overall concordance between a CCC and the histologically assessed level of aganglionosis was high (kappa 0.642, p = 0.003), being correct in 94.4% of cases when the CCC was located in the rectosigmoid, but only in 50% of cases when it was located in more proximal segments. By performing a CE only after HD diagnosis confirmation by RB would avoid 67.5% of CE with no loss of diagnostic accuracy. CONCLUSION: We confirm that CE is a valuable tool for HD diagnosis; however, it should only be performed for subsequent diagnostic and surgical planning following histological confirmation of HD by RB. On the basis of this, an algorithm for an optimized investigation and management of HD is presented.

Rectal biopsy for Hirschsprung's disease: a review of techniques, pathology, and complications.

BACKGROUND: Hirschsprung's disease (HD) is one of the most common congenital anomalies of colorectal function, affecting approximately 1 in 5000 live births, with a 4:1 male predominance. HD is characterized by aganglionosis that is most often limited to the rectosigmoid, but can extend proximally along the colon and, in rare instances, reach into the small intestine. A clinical history of delayed passage of meconium beyond 48 hours after birth, physical exam findings of abdominal distention and vomiting, and a contrast enema demonstrating a transition zone are highly suggestive of HD. DATA SOURCES: We searched databases including PubMed, Google Scholar, and Scopus for the following key words: Hirschsprung's disease, rectal biopsy, pathology, ganglion cell, nerve trunk hypertrophy, pediatric constipation, and selected publications written in English that were relevant to the scope of this review. RESULTS: Based on the data presented in the literature, we reviewed 1) biopsy techniques for the diagnosis of Hirschsprung's disease, addressed inadequate biopsies, and complications from rectal biopsy, and 2) pathologic and histologic interpretation of biopsy specimens for the diagnosis of Hirschsprung's disease. CONCLUSION: A well-executed rectal biopsy with expert pathologic evaluation of the specimen remains the gold standard for the diagnosis of Hirschsprung's disease and is the subject of this review.

Current clinical features in diagnosis and treatment for immaturity of ganglia in Japan: analysis from 10-year nationwide survey.

BACKGROUND: To identify the current clinical features in diagnosis and treatment for immaturity of ganglia (IG) in Japan, we retrospectively analyzed data for patients with IG from the nationwide surveys in Japan. This survey was performed by Japanese Study Group of allied disorders of Hirschsprung's disease (ADHD). METHODS: In primary research, data on totally 355 cases of ADHD were collected for 10 years (2001-2010). Fifteen patients were IG. All IG patients were confirmed by pathological examination. In secondary research, detail questionnaires were sent and collected. RESULTS: Male/female ratio was 9/6 and mean birth weight was 2474 g. All cases (100 %) were onset in neonatal period. Primary symptoms were abdominal distention (86.7 %), vomiting (53.3 %), and late egestion of meconium (26.7 %). An abnormal distention of intestine was recognized in 86.7 % on X-ray, and microcolon was recognized in 58.3 % on contrast enema. Caliber change was recognized in 58.3 % on laparotomy. An enterostomy was made in 13 patients (86.7 %), and an ileostomy was made in 69.2 %. Pathological diagnosis was performed in 100 %. Enterostomy was closed in 100 %. CONCLUSIONS: Totally, 15 definitive cases of IG in 10 years were collected and analyzed. All cases were onset in the neonatal period and almost all underwent enterostomy, but no mortalities occurred.

The utility of the contrast enema in neonates with suspected Hirschsprung disease.

BACKGROUND/PURPOSE: The contrast enema (CE) is commonly utilized for suspected Hirschsprung disease (HD) patients. We set out to determine the utility of the CE in the newborn for clinically suspicious HD. METHODS: All CEs performed for suspicion of HD in neonates from January 2004 to December 2013 were reviewed by two pediatric radiologists who were blinded to the original interpretations and final diagnoses. A standardized scoring sheet was utilized to document essential radiographic findings. Definitive diagnoses were determined by pathology. Descriptive statistics, likelihood ratios, and interrater agreement were determined. RESULTS: 158 CEs were reviewed. Interrater agreement was 89% with kappa (95% CI) of 0.63 (0.47-0.76). Common indications for CE were similar between non-HD and HD groups. The positive, inconclusive, and negative likelihood ratios (95% CI) were 38 (10-172), 3.2 (1.3-9.1), and 0.15 (0.06-0.47), respectively, leading to posttest probabilities for positive, inconclusive, and negative tests of 83%, 32%, and 2.5%, respectively. CONCLUSIONS: Although radiographic positive CE for HD portends a high probability of HD, inconclusive studies still represent a significant increased risk. In clinically suspicious infants for HD, those with inconclusive studies may benefit from a lower threshold to perform follow-up rectal biopsy.

Laboratory procedures update on Hirschsprung disease.

OBJECTIVES: The detection of ganglion cells in rectal biopsies of infants or toddlers with severe constipation is routinely performed by pediatric pathologists in many institutions. Hirschsprung disease (HD) is defined by the lack of ganglion cells (aganglionosis). The early recognition and the prompt implementation of surgical procedures obviously protect infants affected with HD from potential life-threatening conditions, including enterocolitis and debilitating constipation. Image-based and non-image-based clinical techniques and some laboratory tests have been reevaluated along the years, but often fragmentarily. Immunohistochemical markers have been increasingly used in pathology laboratories to detect ganglion cells and nerve fibers. Recently, calretinin, a vitamin D-dependent calcium-binding protein with expression in ganglion cells and nerves, has been described as an adjunctive or primary diagnostic test in HD. The aim of the present study was to systematically summarize and update laboratory procedures targeting ganglion cells in rectal biopsies. METHODS: Procedures and tests have been reviewed and values of specificity and sensitivity have been calculated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Contrast enema has the lowest sensitivity and specificity of all of the 3-index investigations under the lens: contrast enema, anorectal manometry, and biopsy with histology. The latter procedure seems to have the highest sensitivity and specificity. Acetylcholinesterase staining on fresh-frozen material has been found to have slightly higher rates of sensitivity and specificity when compared with hematoxylin and eosin only. Calretinin staining may be supportive for the diagnosis, although some cases with false-positivity may be of some concern. CONCLUSIONS: Hematoxylin and eosin with or without acetylcholinesterase remains the criterion standard according to our PRISMA-based data. In our opinion, the number of false-positive results with potential overtreatment may limit the increasing advocacy for calretinin staining. Both the "primum non nocere" dictum and the "loss aversion heuristic" need to be satisfied harmoniously by preventing harm from unnecessary surgery.

How to manage low gut obstruction in neonates with immature ganglion cells in the colonic wall?

BACKGROUND: Neonates with immature ganglion cells in the colonic wall may have the clinical picture similar to Hirschsprung's disease, especially total colonic aganglionosis. Management of this entity depends on the judgment of each clinician. OBJECTIVE: The aim of this study was to review management of clinical low gut obstruction in neonates with presence of immature ganglion cells in the colon. MATERIAL AND METHOD: A retrospective study of neonates with clinical low gut obstruction due to presence of immature ganglion cells treated between 2007 and 2012 was reviewed. RESULTS: Six patients, one term and 5 pre-term neonates, were proven to have immature ganglion cells in the colonic wall. They presented with delay or failure to pass meconium, progressive abdominal distension and bilious vomiting after birth. Abdominal films showed generalized small bowel dilatation and barium enemas revealed a microcolon in 4 of them. They underwent laparotomy between 4 and 11 days of life. A microcolon with a transitional zone (Tz) was seen at the terminal ileum, 30-75 cm proximal to the ileocecal valve. Colonic biopsy and the appendix revealed presence of immature ganglion cells and ileal biopsy at the Tz showed presence of normal ganglion cells. An ileostomy was performed at the Tz in all of the 5 premature neonates, while an enterostomy was not done in term infant. Closure of the enterostomy in the 5 premature cases was performed after they had been proven to have mature ganglion cells in the colonic wall by a rectal biopsy after the age of 3 months. All of the 6 cases were doing well on the last follow-up between 1 and 3 years. CONCLUSION: Functional low gut obstruction in neonates caused by immaturity of the colonic ganglion cells should be managed by laparotomy including biopsies of the colon, appendix and terminal ileum with enterostomy at the Tz. Closure of the enterostomy is done after presence of mature ganglion cells proven by a rectal biopsy after 3 months of age. Full-term neonates with immature ganglion cells in the colonic wall may be successfully managed conservatively without enterostomy.

A survey of current practices in management of Hirschsprung's disease in Nigeria.

BACKGROUND: Although there are several modalities of treatment for Hirschsprung's disease (HD), there are presently no clear guidelines on treatment of the condition by paediatric surgeons in Nigeria. This survey determines the current approach to treatment among Nigerian paediatric surgeons and should help in establishing a consensus and guidelines for care in this and similar setting. MATERIALS AND METHODS: An online questionnaire was designed using survey Monkey ® to determine current clinical and operative management of patients with HD by consultant paediatric surgeons practicing in the Nigeria. The paediatric surgeons were notified by E-mail, which included a link to the survey on survey Monkey ® . The survey was also administered at the 12 th annual meeting of Association of Paediatric Surgeons of Nigeria in September, 2013, to capture those who did not complete the online survey. Thirty-one paediatric surgeons from 21 different tertiary paediatric surgery centres completed the survey. RESULTS: Sixteen (52%) respondents see up to 20% of their patients with HD in the neonatal period. Twenty-six (84%) respondents do routine barium enema. Twenty six (84%) respondents do full thickness rectal biopsy under general anaesthesia (GA). There was no consistency in operative techniques, with transabominal Swenson's operation being practiced by 17 (57%) respondents and 11 (37%) transanal endorectal pull through. 14 (45%) do pull through at any age. 12 (39%) respondents do more than half of their patient as primary pull through. CONCLUSION: Full thickness rectal biopsy under GA is still the vogue with variations in the surgical technique for management of Hirshsprung's disease in Nigeria. Primary pull through procedures is becoming increasingly popular. There's a need for Paediatric Surgeons in Nigeria to come up with a guideline on management of HD, to guide trainees and other surgeons in the care of these patients.

Adult Hirschsprung's disease: report of four cases.

Adult Hirschsprung's disease (HD) is a rare motor disorder of the gut that is frequently misdiagnosed as refractory constipation. The primary pathogenic defect in adult HD is identical to that seen in infancy or childhood, and is characterized by the total absence of intramural ganglion cells of the submucosal (Meissner) and myenteric (Auerbach) neural plexuses in the affected segment of the bowel. Ninety-four percent of HD cases are diagnosed before the patient reaches 5 years of age, however, on rare occasion, mild cases of HD may go undiagnosed until he or she reaches adulthood. In this study, we describe four cases of adult HD with a history of longstanding recurrent constipation, relieved by laxatives, and presenting to the Department of Gastrointestinal Surgery with progressive abdominal distention, colicky pain or acute intestinal obstruction. Barium enema or computed tomography revealed a grossly distended proximal large colon with fecal retention. Intraoperative frozen section biopsy was performed in all cases and showed aganglionosis of the stenotic segment and a normal distal rectum. In all cases, patient symptoms were completely resolved and there were no complications arising immediately post-surgery or at one-year follow-up. Adult HD should be considered in the differential diagnosis of cases where adult patients present with chronic constipation or even acute intestinal obstruction. The modified one-stage Martin-Duhamel or Rehbein's procedure is a feasible surgical option for treating cases of adult HD involving a segment or the entire bowel.

Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice: implications for Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital condition in which enteric ganglia, formed from neural crest cells (NCC), are absent from the terminal bowel. Dysmotility and constipation are common features of HSCR that persist following surgical intervention. This persistence suggests that the portion of the colon that remains postoperatively is not able to support normal bowel function. To elucidate the defects that underlie this condition, we utilized a murine model of HSCR. METHODS: Mice with NCC-specific deletion of Ednrb were used to measure the neuronal density and neurotransmitter expression in ganglia. KEY RESULTS: At the site located proximal to the aganglionic region of P21 Ednrb null mice, the neuronal density is significantly decreased and the expression of neurotransmitters is altered compared with het animals. The ganglia in this colonic region are smaller and more isolated while the size of neuronal cell bodies is increased. The percentage of neurons expressing neuronal nNOS and VIP is significantly increased in Ednrb nulls. Conversely, the percentage of choline acetyltransferase (ChAT) expressing neurons is decreased, while Substance P is unchanged between the two genotypes. These changes are limited to the colon and are not detected in the ileum. CONCLUSIONS & INFERENCES: We demonstrate changes in neuronal density and alterations in the balance of expression of neurotransmitters in the colon proximal to the aganglionic region in Ednrb null mice. The reduced neuronal density and complementary changes in nNOS and ChAT expression may account for the dysmotility seen in HSCR.

Total colonic aganglionosis--a diagnostic intricacy.

Total colonic aganglionosis (TCA) is an unusual variety of aganglionosis. Although appearing to be an extension of Hirschprung's disease (HD), it may differ from it in many ways and thus is difficult to diagnose on the basis of features applied for HD. The aim of this case report is to discuss the difficulties encountered in recognition of TCA and identification of features which can help in early diagnosis.