Length Of Aganglionic Segment Research Articles

Prognostic factors for persistent obstructive symptoms in patients with Hirschsprung disease following pull-through.

Although most patients with Hirschsprung disease (HSCR) improve after pull-through, some patients still have persistent obstructive symptoms. Most previous studies reported persistent obstructive symptoms after pull-through in HSCR patients from developed countries. Our study determined the prognostic factors of persistent obstructive symptoms in patients with HSCR following pull-through from a particular developing country. A cross-sectional study was conducted using medical records of patients with HSCR at our institution from January 2017 to January 2022. We ascertained 114 patients with HSCR: 79 males and 35 females. Most of them (90.4%) showed a short aganglionosis and underwent transanal endorectal pull-through (55.3%). Twenty-two percent of patients showed persistent obstructive symptoms following pull-through. Operative technique and age at definitive surgery were significantly associated with the persistent obstructive symptoms after pull-through (p = 0.011 and 0.019, respectively), while sex, aganglionic segment length, presence of global developmental delay, and Down syndrome were not (p = 0.873, 0.525, 0.647, and 0.301, respectively). Multivariate analysis revealed that age at pull-through was a significant independent factor for persistent obstructive symptoms after pull-through, with an odds ratio of 3.41 (95% CI = 1.18-9.91; p = 0.02). Our study shows a moderate frequency of persistent obstructive symptoms after pull-through in our institution. In addition, patients who underwent pull-throughs at a younger age might have persistent obstructive symptoms following a definitive surgery. Our study provides new data on persistent obstructive symptoms after pull-through from a particular population that might be beneficial for pediatric surgeons' consideration before performing definitive surgery on patients with HSCR.

Modified Duhamel Retrorectal Pull-Through for Hirschsprung’s Disease

Objectives: To evaluate the post-operative complications and short-term outcomes of modified Duhamel retrorectal pull-through procedure for Hirschsprung’s disease. Design: Prospective descriptive study Place and Duration of Study: Department of Paediatric Surgery Sahiwal Teaching Hospital Sahiwal from 1stJanuary 2018 to 31st December 2020. Methodology: Thirty seven histologically confirmed cases of Hirschsprung’sdisease having previous decompressing colostomy/stoma age between 1 to 12 years of agewere included. Children under one year of age, with sever comorbidities like Down syndrome and cardiac abnormalities, and those who require re-do pull through procedure were excluded. Modified Duhamel retrorectal pull-through procedure was performed in all cases. The demographic information included age, sex, proximal level of aganglinosis, complications of definite procedure, length of hospitalization andmortality. Other information recorded included long term complications like obstructive symptoms, enterocolitis, incontinence and soiling at follow up. Krickenbeck classification was used to evaluate faecal incontinence and constipation. Kelly’s clinical score was used to assess the anal sphincter. Bowel habits were assessed only in children above three years of age. Results: Twenty six (70.27%) were males and 11 (29.72%) females with male to female ratio 2.3:1 and mean age at operation was 2.89±1-9 years. Twenty nine (78.37%) children were ≤3 years of age and 8 (21.62%) were >3 years. Mean weight was 12.91 kgs, operation time was 126.81 time, fasting time was 6.67 days and hospital stay was 11.91 days. Length of aganglionic segment was short segment 27 (72.97%), long segment 9 (24.32%) and total colonic 1 (2.7%). Hirschsprung associated enterocolitis 7 (18.91%) and wound infection 6(16.21%) were most common reported complications. Constipation in 5(13.51) and soiling with retentive constipation was present in 3 (8.10%) patients. Out of total 31 patients who reached toilet training age, 28 (90.32%) developed satisfactory voluntary bowel habits. Conclusion: Modified Duhamel pull-through procedure was found to be safe, applicable and with lower associated complications and satisfactory short term functional outcomes in our settings. Key words: Hirschsprung’s disease, Modified Duhamel pull-through procedure, Complications, Outcomes

Laparoscopic histological mapping for the determination of the length of aganglionic segment in children with Hirschsprung disease.

Modern approach to the surgical treatment of Hirschsprung's disease (HD) consists in the earliest possible repair and reduction of the number of surgical interventions. Primary one-stage transanal endorectal pull-through (TEPT) technique requires preoperative determination of the length of aganglionic segment. The efficacy of the standard method - contrast enema - is questionable in patients with a poorly defined transitional zone. To present the proposed laparoscopic method for the management pathway in patients with HD, in whom the determination of the length of aganglionic segment with contrast enema was not possible. A retrospective analysis of the diagnostic and therapeutic management employed in 14 patients, from 2 weeks to 55 months of age, with diagnosed HD, treated between January 2013 and May 2020. Laparoscopic histological mapping was performed with the use of 3 laparoscopic ports of 3-5 mm diameter. In all patients, laparoscopic mapping allowed for the determination of the length of aganglionic segment and the mode of surgical treatment. Four children with determined short-segment disease underwent TEPT, while 2 underwent temporary colostomy formation using the Duhamel-Martin-Ikeda method. Five patients with long-segment HD underwent laparoscopic-assisted TEPT. One patient with long-segment disease was treated with a temporary double-barrel colostomy and definitive surgery was performed 3 months later using the Duhamel-Martin-Ikeda method. In 2 patients with an initial diagnosis of HD established using current diagnostic pathway, HD pathology was later excluded based on the results of laparoscopic mapping and repeat rectal suction biopsy. No complications related to the laparoscopic procedure were identified. The method of laparoscopic mapping is effective in the determination of the length of aganglionic segment in children with diagnosed HD. In doubtful cases, it can be the preferred option in establishing the final mode of surgical treatment.

Initial experience with per-rectal endoscopic myotomy for Hirschsprung's disease: medium and long term outcomes of the first case series of a novel third-space endoscopy procedure.

Hirschsprung's disease (HSCR) is congenital aganglionosis affecting the hindgut and presents with constipation. Surgical pull-through is the current standard treatment but causes morbidity. Per-rectal endoscopic myotomy is a novel third-space endoscopy technique for treating short-segment (SS)-HSCR. Retrospective study of SS-HSCR patients diagnosed on history, contrast enema, rectal biopsies, and anorectal manometry, and treated by PREM. The aganglionic segment was mapped before PREM was performed using third-space endoscopy principles. Stool frequency and laxative usage before and after PREM were compared. Nine patients (age 7.5 [± 5.2] years; 7 male) underwent PREM during a 4-year period. Mean aganglionic segment length was 6.3 cm, mean procedure time 96.1 minutes, and mean length of hospital stay 2.5 days. Median follow-up was 17 months (range 9-58 months). Stool frequency was 1/4.4 days before vs. 1/1.2 days after PREM (P = 0.0004). Mean laxative usage was 5.4 units of laxative (UL) before vs. 0.4 UL after PREM (P = 0.0002). No laxatives were used by 6/9 patients after PREM. The single adverse effect seen (anal stenosis) was treated with dilatation. PREM is a safe and effective minimally invasive procedure to treat SS-HSCR and results in long-term response.

Hirschsprung Hastalığı Tanısıyla Transanal Endorektal Pull Through Yapılan Çocuklarda Uzun Dönemde Bağırsak İşlevlerinin Değerlendirilmesi

Objective: The most preferred surgical method in the treatment of Hirschsprung’s disease (HD) recently is the transanal endorectal pull through (TERP) operation. In our study, we aim to evaluate the postoperative long- term follow up results of the patients. Method: The files of patients who had TERP between 2009 and 2019 in our center and were >3 years old after surgery were reviewed retrospectively. The patients were evaluated for bowel functions, continence and quality of life in outpatient clinic postoperatively. The information of patients who could not come to control was obtained by contacting their relatives over the phone. Parents were asked to fill Rintala intestinal functions questionnaire. Results: Forty-six patients were boys and 8 were girls. The mean age at diagnosis and surgery were 26.4 and 35.5 months respectively. The mean operation time was 140 minutes, and the mean aganglionic segment length was 21.5 cm. In the early postoperative period, anastomotic stricture was observed in 3 (5.5%), and enterocolitis in 2 (3.7%) patients. Constipation occured in 13 (24%) and soiling in 7 (13%) patients. Partial fecal incontinence was observed in 2 (3.7%) patients. Statistically significant difference was found between the height and weight percentile values of patients before and after surgery. The mean score was 19.05 in bowel function questionnaire. Conclusion: Our study showed that TERP can be applied with low complication rates. Patients have bowel movements and sphincter functions near to normal in the long term. With these advantages, TERP is an effective and reliable method for all HD age groups.

Mo1736 INITIAL EXPERIENCE WITH PER-RECTAL ENDOSCOPIC MYOTOMY (PREM) FOR HIRSCHSPRUNG’S DISEASE: MEDIUM AND LONG-TERM OUTCOMES OF THE FIRST CASE SERIES OF A NOVEL THIRD SPACE ENDOSCOPIC PROCEDURE

Standard treatment forHirschsprung’s disease (HD) has been single or multi-stage pull-through surgery.These procedures are associated with significant morbidity. We have previously reported per-rectal endoscopic myotomy (PREM)for successful treatment of short segment HD. This case series reports safety & medium to long-term outcomes after PREM. Retrospective analysis of prospectively maintained database of patientsundergoing PREM for HD at a single center over 4-years (2015-19). HD was diagnosed by barium enema, anorectal manometry (ARM) & sigmoidoscopic cap EMR biopsieswhich also mappedextent of aganglionic segment. Unit laxative use was calculated as product of the ‘times standard dose’ and ‘number of laxatives used’. Additional units given for rectal enema use. All patients underwent standard PREM procedure with myotomy extending beyond predetermined length of aganglionic segment. Abstracted parameters includeddemographics, length of aganglionic segment, procedure data(myotomylength, procedureduration, use of clip and line method for access into tunnel, adverse events [AE]), time to post-PREM1st bowel movement & follow-up (stool frequency, fecal incontinence, laxative use). Eightpatients (6 males [75%], Meanage –7.12 ± 5.24 years [Range 1- 24])underwent PREM. All had short segment (rectosigmoid) HD.Mean length of aganglionic segment –6.8 ± 3.0 cm (Range 2 – 15).PREM was technically successful in all. Meanlength of myotomy –11.3 ± 2.9cm (Range 8 – 20). Clip-and-line technique used to enter submucosal tunnel in 6(75%). Medianprocedure time–80min (IQR70 – 120). No immediate adverse events encountered.All patients started on oral feeds after 24 hours. Mean post-PREM1st bowel movement after2 days (Range 1 – 3). Longest post PREM follow-up – 48 months; median follow-up – 15months (IQR2.5 – 30). Stool frequency significantly improved post-PREM (1 in 4.5 [± 1.1] days to 1 in 1.2 [±0.3] days [p= 0.0004, paired ‘t’ test]). Laxative use reduced from mean 6.62 units (Range 4 – 11) pre-PREM to mean 0.25 (Range 0 – 2) post-PREM (p = 0.0002).Six (75%) patients did not require any laxative. No new onset incontinence post PREM noted. Post PREM high-resolution ARMin 3/8 patients revealed normal basal and squeeze pressures. First PREM patient developed mild anal stenosis 8 months post procedure requiring single session digital anal dilatation.No other delayed adverse eventsencountered. PREM is a safe and feasible procedure. Results of this case series demonstrate excellent medium and long-term clinical outcomes after PREM. PREM could be considered as a minimally invasive therapeutic option for patients with HD. Studies with larger sample size are required to confirm these findings.

Results of Transanal Endorrectal Descent in Hirschprung's Disease

ObjectiveTo present our experience of patients with Hirschsprung disease (HD) operated by transanal endorrectal descent (TED). MethodsA retrospective study performed of TEDs. We correlate fundamentally the aganglionic segment length with: complications, need for colostomy and surgical approach. ResultsBetween 2003 and 2012 we performed 73 TED (57 men), 78.6% diagnosed in the neonatal period. The aganglionic segment length evidenced in the enema was correlated with surgical findings in 68.9% of cases, being higher in the short forms than in the long segments (80.9 vs 44%, P<.001). Four patients required preoperative colostomy. The mean age of surgery was 6.3 months (4.5–33.7). Short forms represented 64.4% of cases. The abdominal approach was necessary in 10 patients, nine of these were long/total colonic aganglionic segment. Postoperative enterocolitis presented in 10.9% (nine patients), with no relation with the length of aganglionic or the existence of residual dysplasia. Obstructions occurred in 19.2% of the long form or pancolonic forms. Currently, of the evaluable patients, five present constipation and 12 present occasional leakage. ConclusionsTED is the surgery of choice for patients with HD. The majority can be handled by preoperative “nursing” without colostomy. The diagnostic tests of choice are manometry with suction biopsy. No significant correlation was found between enterocolitis and length of aganglionic segment, although we observed a drastic reduction of postoperative enterocolitis, since the introduction of technical changes, such as the use of postoperative rectal tubes and the posterior section of the cuff muscles.

Resultados del descenso endorrectal transanal en la enfermedad de Hirschsprun

ObjectiveTo present our experience of patients with Hirschsprung disease (HD) operated by transanal endorrectal descent (TED). MethodsA retrospective study performed of TEDs. We correlate fundamentally the aganglionic segment length with: Complications, need for colostomy and surgical approach. ResultsBetween 2003 and 2012 we performed 73 TED (57 men), 78.6% diagnosed in the neonatal period. The aganglionic segment length evidenced in the enema was correlated with surgical findings in 68.9% of cases, being higher in the short forms than in the long segments (80.9 vs. 44%, P<.001). Four patients required preoperative colostomy. The mean age of surgery was 6.3 months (4.5 to 33.7). Short forms represented 64.4% of cases. The abdominal approach was necessary in 10 patients, 9 of these were long/total colonic aganglionic segment. Postoperative enterocolitis presented in 10,9% (9 patients), with no relation with the length of aganglionic or the existence of residual dysplasia. Obstructions occurred in 19.2% of the long form or pancolonic forms. Currently, of the evaluable patients, 5 present constipationand 12 present occasional leakage. ConclusionsTED is the surgery of choice for patients with HD. The majority can be handled by preoperative «nursing» without colostomy. The diagnostic tests of choice are manometry with suction biopsy. No significant correlation was found between enterocolitis and length of aganglionic segment, although we observed a drastic reduction of postoperative enterocolitis, since the introduction of technical changes, such as the use of postoperative rectal tubes and the posterior section of the cuff muscles.

Botulinum toxin is efficient to treat obstructive symptoms in children with Hirschsprung disease.

Obstructive symptoms are common after pull-through for Hirschsprung disease. Botulinum toxin injection treatment may improve the bowel function if internal sphincter achalasia is the cause of obstructive symptoms. The aim of this study was to review the outcome in patients treated with intrasphincteric botulinum toxin injections after pull-through for Hirschsprung disease. The operative records were used to identify children with Hirschsprung disease who were treated with botulinum toxin injections at Karolinska University Hospital, Stockholm, Sweden, from September 2007 to November 2014. Data on age, sex, associated syndromes, length of aganglionic segment, age at pull-through, type of pull-through, age at first botulinum toxin injection, indication for botulinum toxin injection, and effect of first botulinum toxin injection were retrieved from the case records. Bowel function at last follow-up visit or telephone contact was recorded. Nineteen patients were identified. All had biopsy-verified Hirschsprung disease. Eighteen (15 males and 3 females) children had undergone intrasphincteric botulinum toxin injection treatment for obstructive symptoms after pull-through, which was done at 127 (18-538) days of age. Four children had total colonic aganglionosis. The first botulinum toxin injection was given at 2.4 (0.53-6.9) years of age. Thirteen children (72 %) had a good response to the first injection treatment. The children underwent 3 (1-13) injection treatments. At follow-up four patients had improved and did not need treatment for obstruction, four were scheduled for further botulinum toxin injections, eight had persistent obstructive symptoms treated with laxatives or enemas, and two children had an ileostomy. Botulinum toxin injection treatment improves the obstructive symptoms in children after pull-through for Hirschsprung disease. The effect is reversible and a majority of patients need repeat injections. When injection treatment is not repeated, a large proportion of children need laxatives or enemas due to recurrent symptoms.

Sa1600 Colonoscopy As a New Tool in Determining the Transition Zone in Endoanal Pull-Through in Hirschsprung's Disease - Preliminary Results

Colonoscopy As a New Tool in Determining the Transition Zone in Endoanal Pull-Through in Hirschsprung’s Disease Preliminary Results Erika P. Ortolan, Pedro L. Lourencao, Gisele O. Orsi, Bonifacio K. Takegawa Surgery, Botucatu Medical School UNESP Univ Estadual Paulista, Botucatu, Brazil Background: Surgical treatment of Hirschsprung’s disease (HD) has changed in recent decades, with attempts to reduce extensive surgical dissections. Independent of the technique used, the surgery consists in colectomy of the aganglionic region, beyond the transition zone. Since De la Torre & Ortega first described the exclusive transanal endorectal pull-through (TEPT) technique in 1998, it has become the technique of choice, especially in short aganglionic segments. However, recognizing the transition zone during TEPT is very difficult, leading to a procedure involving several frozen section biopsies and that requires an experienced pathologist. Kohno et al (2005) described the use of colonoscopy in determining a landmark for the location of pull-through with relatively accuracy, denominated the “shorebreak” finding, based on the principle that while normal bowel exhibits peristaltic movements, aganglionic bowel does not. He developed a retrospective study comparing the shorebreak finding in colonoscopy marked with India ink with pathological findings in frozen section biopsies. Based on this single report, our group decided to test this new approach, in a prospective study. The purpose of this work was to report our preliminary results concerning the prospective use of colonoscopy as a new tool to determine the transition zone in HD. Patients and Methods: Colonoscopy was prospectively performed on four patients with HD diagnosis, previously confirmed by anorectal manometry, contrast enema and suction biopsies. The exam was performed just prior to TEPT, using the same anesthetic and bowel prep procedure. The area marked with India ink was chosen following observation of colon motility during colonoscopy, in which the absence of motility identified the beginning of the aganglionic area. For endoscopic tattooing, physiological saline was injected locally submucosally to raise the mucosa, followed by the injection of India ink. All the exams were performed by the same pediatric surgery team member (main author), who was unaware of the contrast enema results. Informed consent to perform the exam was obtained. Results: In all patients, the shorebreak finding marked with India ink was equivalent to the aganglionic segment length and transition zone in contrast enemas. The patients were submitted to TEPT beyond this marked area. The excised colon was opened and the transition zone was macroscopically equivalent to the marked area. These results were confirmed by anatomopathological findings using HE, acetylcholinesterase and calretinin stains. Conclusion: Given these preliminary results, it is our conclusion that endoscopic marking of the shorebreak finding provides an important new tool for determining the point of TEPT in the treatment of HD, especially in hospitals that cannot depend on intraoperative frozen sections or experienced pathologists.

Does Pre-Biopsy Contrast Enema Delay the Diagnosis of Long Segment Hirschsprung's Disease?

The diagnosis of long segment Hirschsprung's disease (LSHD) is frequently delayed. Our purpose was to: 1) summarize contrast enema (CE) findings in patients with LSHD, and 2) evaluate the utility of CE by comparing LSHD patients managed with/without pre-biopsy CE. All LSHD cases (transition zone [TZ] proximal to the splenic flexure) treated between 1984 and 2009 were stratified according to whether a pre-biopsy CE was done (Group 1) or not (Group 2). CE were reviewed by a single pediatric radiologist, and the original reports were categorized as "helpful", "inconclusive" or "misleading". Group comparisons included elapsed days from admission to diagnostic rectal biopsy/first operation and initial hospitalization length of stay (LOS). 29 patients (16 in Group 1; 13 in Group 2) were identified. CE review revealed TZ in 7/16 (44%); and of these, 6 (86%) underestimated the actual aganglionic segment length. 6/16 (38%) original CE reports were "misleading". Overall, Group 1 patients experienced a significant delay in time to biopsy (p=0.047), first operation (p=0.005), and showed a trend towards prolonged LOS. Pre-biopsy CE offers little to the diagnosis of LSHD and may contribute to diagnosis/treatment delays. Even if a TZ is recognized in biopsy proven HD, the predicted aganglionic segment length should not guide the operative planning.

Comparison of Transanal One-stage Soave Procedure to Modified Duhamel Procedure in Hirschsprung's Disease

Purpose: Transanal one-stage Soave (TOS) procedure is the most recently reported procedure for Hirschsprung’s disease. This study was performed to compare the surgical outcomes of TOS with those of modified Duhamel procedure. Methods: The study populations were 17 consecutive patients who underwent TOS procedure between March, 2003 and February, 2008 (TOS group) and 19 consecutive patients who underwent modified Duhamel procedure between March, 1996 and February, 2001 (Duhamel group) by one pediatric surgeon. Age, gender, length of aganglionic segment, operating time, complications, duration of postoperative hospital stay, and functional results were retrospectively analyzed and compared between the two groups. Results: There was no difference in age, gender, and length of the aganglionic segment between the two groups. The operating time (195 versus 255 minutes, P<0.05) and the duration of postoperative hospital stay (7 versus 9 days, P<0.05) were significantly shorter in the TOS group. Postoperative complications occurred in 10 of 17 in the TOS group (4 perianal excoriation, 3 anastomotic stenosis, and 3 postoperative enterocolitis) and 10 of 19 in Duhamel group (2 wound infection, 1 perianal excoriation, 1 anastomotic leakage, 1 rectal bleeding, 2 intestinal obstruction, and 3 postoperative enterocolitis). Two cases in the Duhamel group required operation to treat postoperative complication, one for anastomotic leakage and one for intestinal obstruction. There was no significant difference in the functional results between both groups. Conclusion: TOS shows similar functional results and postoperative complications but has the advantage of a significantly shorter operating time and postoperative hospital stay compared with modified Duhamel procedure. (J Korean Surg Soc 2009;77:202-206)

Variations in aganglionic segment length of the enteric neural plexus in Mowat-Wilson syndrome

Background/Purpose Patients with zinc finger homeo box 1B ( ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS). In this study, we investigated variations in the enteric neural plexus abnormalities in MWS using morphometry-based histopathologic analysis. Methods Seven patients with MWS (3 with mutations in exon 8 of ZFHX1B and 4 with deletions) who had undergone modified Duhamel's operations for Hirschsprung disease were examined. Surgically resected rectosigmoid specimens were analyzed morphometrically. Results The length of the aganglionic segment was longer than 3 cm in all the patients with deletions. In 3 patients with mutations, the aganglionic region was not detected in the surgically resected specimens; however, the parameters of the ganglions and plexus were significantly smaller than those of controls (cloaca and aproctia), indicative of a transitional zone. Variation in the severity of pathological changes among the 3 patients with mutations was also noted. Conclusions The variations in myenteric plexus pathologies in MWS appear to be caused by both variations in ZFHX1B abnormalities and epigenetic factors.

Comparison of functional outcomes of duhamel and transanal endorectal coloanal anastomosis for Hirschsprung’s disease

Purpose The aim of this study was to determine the morbidity and medium-term functional outcome of the Duhamel operation and laparotomy and transanal endorectal coloanal anastomosis (TECA) for Hirschsprung’s disease (HSCR). Methods The study populations were 34 consecutive children who underwent the Duhamel operation (or Lester Martin modification) and 37 who had the TECA. Demographic details were obtained by case note review, and functional outcome was determined by a combination of outpatient interview, questionnaire, and telephone enquiry. Results There was no difference between the groups with respect to age, gender, and length of aganglionic segment. Seventy percent presented as neonates (Duhamel, 24 of 34; TECA, 26 of 37). A single-stage primary pull-through was performed in 17 of 37 children in the TECA group, and in 1 of 34 from the Duhamel group. There was a single perioperative death in the Duhamel group and an unrelated, late death in the TECA group. Postoperative enterocolitis was seen in 13 of 37 TECA children and in a single child from the Duhamel group. A stricture of the pull-through segment was seen in 7 of 37 children after TECA and required temporary diversion in 2 of 9. Late division of a rectal spur was required in 6 of 33 Duhamel children. Requirement for late myectomy was the same in both groups (Duhamel 3 of 33, TECA 4 of 37). Complications requiring stoma formation occurred in 5 of 37 after TECA and 2 of 33 after the Duhamel operation. Two children from the TECA group and 1 from the Duhamel group remain diverted. One child from each group required a re-pull-through procedure. Two patients were lost to follow-up in the TECA group, leaving 34 children in this group and 33 in the Duhamel group in whom functional outcome could be assessed. Functional outcome was similar in the 2 groups. Conclusions TECA and Duhamel procedures have similar medium-term functional outcomes. TECA has a high incidence of postoperative enterocolitis and transient stricture formation but is suitable for single-stage neonatal treatment of HSCR.

Phenotype variation in two-locus mouse models of Hirschsprung disease: tissue-specific interaction between Ret and Ednrb.

Clinical expression of Hirschsprung disease (HSCR) requires the interaction of multiple susceptibility genes. Molecular genetic analyses have revealed that interactions between mutations in the genes encoding the RET receptor tyrosine kinase and the endothelin receptor type B (EDNRB) are central to the genesis of HSCR. We have established two locus noncomplementation assays in mice, using allelic series at Ednrb in the context of Ret kinase-null heterozygotes, to understand the clinical presentation, incomplete penetrance, variation in length of aganglionic segment, and sex bias observed in human HSCR patients. Titration of Ednrb in the presence of half the genetic dose of Ret determines the presentation of an enteric phenotype in these strains, revealing or abrogating a sex bias in disease expression depending on the genotype at Ednrb. RET and EDNRB signaling pathways are also critical for the normal development of other tissues, including the kidneys and neural crest-derived melanocytes. Our data demonstrate that interaction between these genes is restricted to the enteric nervous system and does not affect renal, coat color, and retinal choroid development.

Preoperative enterocolitis is associated with poorer long-term bowel function after Soave-Boley endorectal pull-through for Hirschsprung's disease

Background/Purpose: The purpose of the investigation was to apply a semiquantitative scoring system for bowel function to patients who had undergone endorectal pull-through (ERPT) for Hirschsprung's disease (HD) and to use this to analyse the clinical factors relating to functional outcome. Methods: The case note details of 63 patients undergoing ERPT for HD were reviewed. A questionnaire using a semiquantitative scoring system for 6 aspects of bowel function was sent to parents of 55 patients. The total functional score (TFS) for each patient was calculated, and a statistical analysis was performed to determine which clinical factors were significantly related to bowel functional outcome. Results: Fifty (91%) of the parents returned the questionnaire. TFS was “good” in 45%, “fair” in 33% and “poor” in 22%. There was a statistically significant difference in the scores of those who had preoperative Hirschsprung's associated enterocolitis (HAEC) TFS = 8.0 and those who did not, TFS 12.7 (P <.01) The sex of the patient, length of aganglionic segment, timing of ERPT (early/late), staging of ERPT (1 or 2), presence/absence of anastomotic stricture, and presence or absence of Down's syndrome did not statistically significantly affect TFS. Conclusions: Preoperative HAEC was the most important factor in relation to functional outcome after ERPT for HD. The reason remains unclear. J Pediatr Surg 38:69-72. Copyright 2003, Elsevier Science (USA). All rights reserved.

Transanal endorectal coloanal surgery for Hirschsprung's disease: Experience in two centers

Background/Purpose: Transanal mucosal proctectomy with low coloanal anastomosis has been used widely in the treatment of rectal malignancies, ulcerative colitis, and familial polyposis. The use of this technique for Hirschsprung's disease is a relatively new concept. The aim of this study was to evaluate and compare the results of transanal endorectal coloanal anastomosis (TECA) for Hirschsprung's disease from 2 centers. Methods: All children who underwent TECA for Hirsch sprung's disease at Alder Hey Children's Hospital, Liverpool, England from January 1995 to December 1998 (n = 41) and the Children's Hospital, Helsinki, Finland from June 1988 to December 1998 (n = 95) were evaluated. Patient demographics, age at diagnosis, initial management, length of aganglionic segment, and age at operation were documented. Postoperative complications and functional outcome were analyzed. Results: Patient demographics were similar in the 2 centers. Age at diagnosis was less than 1 month in 71% of children at Liverpool, compared with 53% at Helsinki. Sixteen (39%) patients in Liverpool and 75 (79%) patients in Helsinki underwent primary TECA without colostomy. Postoperative enterocolitis occurred in 14 of 136 patients (10%). An ischemic stricture of the colon was documented in 4 children in the Liverpool series, 2 of whom had TECA as a salvage procedure after a previously failed Duhamel pull-through operation. Frequency of bowel movements, seen in the immediate postoperative period in most patients gradually improved with time from a median of 5 (range, 2 to 12) bowel movements a day at 3 months after TECA to 2 (range, 1 to 6) bowel movements a day at 2 years' follow-up. Assessment of continence was possible in 51 of 136 patients (37%) over the age of 4 years. Thirty-nine children had normal bowel function giving an overall success rate of 76%. Conclusions: Transanal endorectal coloanal anastomosis is a good technique for treatment of Hirschsprung's disease with few operation-related complications. Based on the data emerging from these 2 centers the functional outcome is highly satisfactory and comparable with other established procedures. J Pediatr Surg 35:1209-1213. Copyright © 2000 by W.B. Saunders Company.

Hirschsprung-Associated Congenital Anomalies

Between 1976-1993, 302 patients were diagnosed to have Hirschsprung's disease (HD) in Hacettepe University Children's Hospital. All patients have been searched for the occurrence of associated anomalies and other parameters including 1) sex, 2) gestational age, 3) birth weight, 4) length of aganglionic segment, 5) familial occurrence, 6) consanguinity. Forty-nine of 302 patients were proved to have 83 associated congenital anomalies together with HD. Distribution of anomalies was as follows; central nervous system and special senses 28.92%, genitourinary system 26.51%, skeletal 24.09%, gastrointestinal 12.05%, cardiovascular 8.43%. In eleven patients more than one anomaly involving different systems were detected; only one of these patients was female and six of them have shown short segment disease. Down's syndrome was present in 5 patients. Female: male ratio was 1:4.2 for the whole series and 1:6 for the patients with Hirschsprung associated congenital anomalies (HACA). In the HACA group the percentage increased in favor of long-segment and extensive aganglionosis without statistical significance (p>0.05). The majority of patients were term babies and their birth weights were between 2500g < 3500g. Consanguinity was present in 36 families. No affected parents were detected but two sisters and four brothers were proved to have HD. Three pairs of twins, one of which was monozygotic, and all showing discordance were detected. There was no difference between HACA group and HD without HACA in terms of sex, birth weight, length of aganglionic segment and consanguinity. Although HD seemed to be genetically heterogeneous HACA did not have a genetically different origin from that of HD.

Clinical outcome and long-term quality of life after surgical correction of Hirschsprung's disease

One hundred seventy-eight of 330 patients were recalled after undergoing surgery for histologically proven Hirschsprung's disease (HD). One hundred fifteen were older than 4 years at interview (Mean age, 10 years). This sample appeared to be representative of the whole in terms of demographic features such as ethnic group, sex, length of aganglionic segment, timing of presentation and surgery performed. Anthropomorphic indices for weight and height were comparable to norms, but many younger patients were below expected weight for age. In general, weight and height for age was regained with time. Nine patients had delayed developmental milestones, which were owing to specific causes in four. Nine patients had a poor functional outcome, of which two had neurological impairment. Satisfactory school performance was achieved in all but 19 (26%) of the remaining patients. Long-term functional results were comparable for the Soave and Duhamel procedures with less favorable results noted following the Swenson procedure. Assessment of complications demonstrated a significantly ( P < .01) lower incidence of constipation, sexual dysfunction, and micturition disturbance following the Soave procedure when compared with the Duhamel and Swenson procedures. Neurological impairment and length of aganglionic segment beyond the rectosigmoid area appeared to influence functional outcome, as did persisting enterocolitis. Enterocolitis was observed in 16.6% of patients on presentation, but continued in only 6%. Constipation was particularly associated with the Duhamel procedure, and a higher incidence of micturition disturbance, abdominal distension, and cuff stricture was noted following the Swenson procedure. Functional assessment by three different scoring methods showed that 86 (74.7%) of the 115 patients over the age of 4 had excellent anorectal function and appeared to be well adjusted. Twenty-two patients (19.2%) had relatively minor long-term problems but seven (6.1%) had persistent fecal soiling with resulting psychosocial maladjustment.

Histochemical acetylcholinesterase activity in the mucosa of the resected bowel in Hirschsprung's disease. An analysis of 30 cases.

Resected bowels from 30 patients with Hirschsprung's disease were consecutively investigated as to the length of the aganglionic segment and the extent of the increased mucosal acetylcholinesterase (AChE) activity. The latter was not always in accord with the length of aganglionic segment. The increased AChE activity not only did not reach the normal ganglionic segment proximally, but, in almost all cases also extended for less than 5 cm from the distal end of the resected bowels. In two cases with the ultra-short type of segment and in four with the short type of segment increased mucosal AChE activity extended for a short length only into the normal bowel segment. The more advanced the patient's age at the time of operation, and the more intense the AChE activity in rectal suction biopsy, the more proximal was the extent of increased AChE activity. Proximal extension of the mucosal AChE activity showed no clear relationship to the creation of a colostomy or to the occurrence of preoperative enterocolitis.