Mortality in Swedish patients with Hirschsprung disease.

PURPOSE: Hirschsprung disease (HSCR) has previously been associated with increased mortality. The aim of this study was to assess mortality in patients with Hirschsprung disease in a population-based cohort. METHODS: This was a nationwide, population-based cohort study. The study exposure was HSCR and the study outcome was death. The cohort included all individuals with HSCR registered in the Swedish National Patient Register between 1964 and 2013 and ten age- and sex-matched controls per patient, randomly selected from the Population Register. Mortality and cause of death were assessed using the Swedish National Causes of Death Register. RESULTS: The cohort comprised 739 individuals with HSCR (565 male) and 7390 controls (5650 male). Median age of the cohort was 19 years (range 2-49). Twenty-two (3.0%) individuals with HSCR had died at median age 2.5 years (range 0-35) compared to 49 (0.7%) controls at median age 20 years (0-44), p < 0.001. Hazard ratio for death in HSCR patients compared to healthy controls was 4.77 (confidence interval (CI) 95% 2.87-7.91), and when adjusted for Down syndrome, the hazard ratio was 3.6 (CI 95% 2.04-6.37). CONCLUSIONS: The mortality rate in the HSCR cohort was 3%, which was higher than in controls also when data were adjusted for Down syndrome.

Early jejunostomy creation in cases of isolated hypoganglionosis: verification of our own experience based on a national survey.

PURPOSE: Isolated hypoganglionosis (IH) is a rare disease, with few well-established therapeutic strategies. This study aims to verify our preliminary therapeutic strategies developed to date in a comparison with data obtained from a nationwide survey of congenital-type IH. METHODS: Of the 90 registered IH cases assessed in a survey of Japanese pediatric surgical departments, 40 patients who had initially undergone jejunostomy (JE) and 41 treated with ileostomy (IL) were analyzed. Thirteen patients with JE sites located less than 50 cm from the ligament of Treitz were defined as having undergone upper jejunostomy (UJE). Postsurgical plain abdominal X-ray findings and survival rates, estimated using the Kaplan-Meier method, were used to evaluate improvements following stoma creation. RESULTS: Improvements in bowel obstruction were observed in significantly more UJE patients (9/13) than non-UJE patients [20/63 (22 JE and 41 IL cases); p = 0.01]. Furthermore, the JE patients demonstrated a significantly higher survival rate than the IL patients (p = 0.01). Following the completion of the 10-year follow-up period, three JE patients died after undergoing massive bowel resection. CONCLUSIONS: To manage IH successfully, patients should undergo JE less than 50 cm from the ligament of Treitz during the neonatal period. Properly managing the distal intestines is important for achieving long-term survival.

Hirschsprung's disease prevalence in Europe: a register based study.

BACKGROUND: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age. METHODS: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series. Prevalence rates and 95% confidence intervals were calculated as the number of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. RESULTS: There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence interval, 1.03-1.15) per 10,000 births and there was a small but significant increase in prevalence over time (relative risk = 1.01; 95% credible interval, 1.00-1.02; p = 0.004). There was evidence of geographical heterogeneity in prevalence (p < 0.001). Excluding 146 (11.0%) cases with chromosomal anomalies or genetic syndromes, there were 1,176 cases (prevalence = 0.97; 95% confidence interval, 0.91-1.03 per 10,000 births), of which 137 (11.6%) had major structural anomalies. There was no evidence of a significant increased risk of Hirschsprung's disease in cases born to women aged ≥35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible interval, 0.91-1.31; p = 0.355). CONCLUSION: This large population-based study found evidence of a small increasing trend in Hirschsprung's disease and differences in prevalence by geographic location. There was also no evidence of an association with maternal age.

Hirschsprung's disease associated with Down syndrome: a meta-analysis of incidence, functional outcomes and mortality.

PURPOSE: Down syndrome (DS) is the most frequent chromosomal abnormality associated with Hirschsprung's disease (HD). It has often been suggested that this association results in poorer outcomes with regard to postoperative complications, continence and mortality. On the other hand, the results after surgical treatment of HD in patients with DS are reportedly similar to those in cases with HD alone. The objective of this study was to determine the incidence of DS in cohorts with HD, and to compare pre-/postoperative complications, functional outcome and mortality between cohorts with and without coexisting DS. METHODS: A systematic literature-based search for relevant cohorts was conducted using multiple online databases. The number of DS cases in HD cohorts was recorded and data on pre-/postoperative complications, functional outcome and mortality were extracted. Pooled odds ratios with 95% confidence intervals were calculated using meta-analysis methodology. RESULTS: Sixty-one articles met defined inclusion criteria, comprising data from 16,497 patients with HD. The overall incidence of DS among them was 7.32%. Vice versa, the incidence of HD in 29,418 patients with DS was 2.62%. There were no significant differences regarding the male-to-female ratio between cohorts with and without coexisting DS (4:1 vs. 3:1 respectively; P = 0.5376). The rate of additional comorbidities was significantly higher in HD associated with DS (P < 0.0001). Recto-sigmoid HD was in both cohorts the most common type of HD (P = 0.8231). Long-segment HD was significantly more frequent in HD with coexisting DS (P = 0.0267), while total colonic aganglionosis occurred significantly more often in HD without DS (P = 0.0003). There were no significant differences in preoperative constipation/obstruction (P = 0.5967), but the rate of preoperative enterocolitis was significantly higher in HD associated with DS (P = 0.0486). Postoperative complications such as recurrent enterocolitis (P = 0.0112) and soiling (P = 0.0002) were significantly more frequent in HD with coexisting DS. Although not statistically significant, fecal incontinence (P = 0.1014) and persistent constipation (P = 0.1670) occurred more often after surgical treatment of HD with DS. The mortality rate was significantly higher in HD associated with DS (P < 0.0001). CONCLUSIONS: The association of HD with DS is well-recognized with an incidence of 7.32%. A large number of patients with DS continue to have persistent bowel dysfunction after surgical treatment of HD. Our data provide strong evidence that the coexistence of HD and DS is associated with higher rates of pre-/postoperative enterocolitis, poorer functional outcomes and increased mortality.

Hirschsprung's disease in the North of England: prevalence, associated anomalies, and survival.

INTRODUCTION: Hirschsprung's disease is the commonest congenital gut motility disorder, characterized by the absence of the enteric ganglion cells along the distal gut, which causes intestinal obstruction. Few publications report its epidemiology and temporal trends. METHODS: Cases of Hirschsprung's disease delivered during 1990 to 2008 in the North of England reported to the Northern Congenital Abnormality Survey (NorCAS) formed this population-based case series. RESULTS: Of 612,916 live births, 105 cases were reported to NorCAS. After excluding one diabetic and four multiple pregnancies, the live birth prevalence was 1.63 (95% confidence interval [CI], 1.33-1.98) per 10,000 live births. There was a significant temporal increase in the prevalence of Hirschsprung's disease (p = 0.020), from 1.26 (95% CI, 0.80-1.89) in 1990 to 1994 to 2.29 (95% CI, 1.53-3.29) in 2005 to 2008. The ratio of male to female cases was 2:1. Ten (10.0%) cases occurred with Down syndrome, one with Smith-Lemli-Opitz Syndrome, and six (6.0%) with associated structural anomalies. The remaining 83 (83.0%) cases were isolated. All cases were live born, but nine (9.0%) died in the first year of life. Hirschsprung's disease was not prenatally suspected in any case. Half the cases were diagnosed within 5 days postpartum, but time of diagnosis ranged from birth to 5 years of age. CONCLUSION: This study confirmed a male predominance and an association with Down syndrome, but also found a temporal increase in Hirschsprung's disease prevalence. No cases were suspected prenatally, but half were diagnosed within 5 days of life.

Total colonic aganglionosis: a systematic review and meta-analysis of long-term clinical outcome.

PURPOSE: Total colonic aganglionosis (TCA) is a severe form of Hirschsprung's disease (HD), occurring in less than 10 % of the cases. It is a challenging surgical condition and outcomes of pull-through (PT) surgery are reported to be inferior to those in patients with recto-sigmoid HD. As even large centres only see a few patients with TCA, there is little information on the long-term outcome of patients after PT operation for TCA. The aim of this meta-analysis was to investigate the long-term clinical outcome in patients with TCA. METHODS: MEDLINE(®) and EMBASE(®) databases were searched for relevant articles that reported the outcomes of patients with TCA published between 1980 and 2011. The search terms were "Hirschsprung's disease", "Total colonic aganglionosis" AND "Outcome". All published studies containing adequate clinical data for a mean follow-up period of not less than 4 years were included. Reference lists of retrieved articles were reviewed for additional cases. Detailed records of morbidity and mortality were extracted and analysed. RESULTS: This search yielded 225 articles reporting on outcomes in TCA. Of these, 189 were excluded for having too short a follow-up period, small or single case series, inadequate clinical data and duplicated patient groups. Ultimately, 36 articles from 37 centres containing useful clinical information on the outcomes of TCA in 969 patients were identified. There were 152 early deaths prior to PT (15.7 %). Of 817 survivors, 739 underwent PT. The mortality rate for TCA post-PT was 5.7 %. The most frequently reported post-operative complication was enterocolitis in 42 % of the cases. 17.5 % of patients underwent subsequent major surgery including redo PT, stoma reformation or other laparotomy. Long-term follow-up data were available in 396 patients. Satisfactory or normal bowel control was reported in 60 % of the patients. Soiling, faecal incontinence or other poor outcome was reported in 33.5 % of the cases and 6.5 % of the patients had undergone conversion to a permanent ileostomy for post-operative complications. CONCLUSION: This meta-analysis reveals that a large number of patients with TCA have long-term problems with bowel control.

Hirschsprung's disease: what about mortality?

PURPOSE: Although significantly decreased during last decades, mortality rate for Hirschsprung's disease still ranges between 1 and 10%. The authors reviewed the main features of patients with Hirschsprung's disease treated in our Institution who died in the period between 1993 and 2010 in order to detect possible risk factors or prevention strategies. METHODS: The notes of all patients with Hirschsprung's disease admitted to our Institution between January 1993 and January 2010 were reviewed. All families were interviewed and possible unknown deaths were recorded. We reported demographic data, length of aganglionosis, type and number of associated anomalies, age and type of onset, age and cause of death, chronological relationship between death and pull-through, and all other significant details. RESULTS: Eight out of a series of 313 patients with Hirschsprung's disease died during the study period (mortality rate = 2.56%). Six patients were male for a male to female ratio of 3:1. Eleven associated anomalies were detected in five patients, including four congenital anomalies of the kidney and urinary tract, four heart, two central nervous system, and one skeletal malformations. One patient had Down Syndrome and one Cat Eye Syndrome. Two patients were born preterm. All patients had neonatal onset with delayed meconium passage. Five patients had aganglionosis confined to rectosigmoid colon (classic forms), two had total colonic aganglionosis and one had total intestinal aganglionosis. Enterostomy was performed in five patients. Median age at death was 75 days (range 30 days-8 years). The cause of death was enterocolitis in four patients, heart failure in three, and intestinal failure in one. Six patients died before the pull-through. Two patients died postoperatively. All patients but two died at home. CONCLUSIONS: Onset and clinical features do correlate with severity. Newborns and infants seem to be more likely to develop serious life-threatening complications, particularly in case of associated cardiovascular malformations. Although enterostomies do not have protective effects over cardiovascular issues, prophylactic stoma should be considered in high-risk patients. Radical treatment (pull-through) should be performed as soon as possible. Alternatively, protected and cautious discharge of newborns with associated heart anomalies is strongly recommended in order to prevent serious and uncontrolled complications, regardless of the presence of a protective enterostomy. Postoperatively, close follow-up appointments are recommended. Families should be acknowledged and educated for prompt recognition and treatment of severe life-threatening complications.

Total colonic aganglionosis: multicentre study of surgical treatment and patient-reported outcomes up to adulthood.

BACKGROUND: Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. METHODS: An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. RESULTS: Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age. CONCLUSION: Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.

ANTECEDENTES: La cirugía de la aganglionosis colónica total (total colonic aganglionosis, TCA) está diseñada para preservar la continencia y lograr una calidad de vida satisfactoria. Este estudio evaluó un gran número de resultados clínicos y sociales. MÉTODOS: Se realizó un estudio internacional multicéntrico en ocho hospitales nórdicos en el que se incluyeron las historias clínicas de todos los pacientes nacidos con TCA entre 1987 y 2006. Se invitó a los pacientes y a sus cuidadores a responder una encuesta sobre la función intestinal, el crecimiento y las necesidades nutricionales, así como la repercusión social de la enfermedad a largo plazo. RESULTADOS: De un total de 116 pacientes, 5 (4,3%) habían fallecido y 102 respondieron la encuesta. Con una mediana de seguimiento de 12 años (rango 0,5-33), se había restablecido la continuidad intestinal en 75/102 (74%) a una mediana de edad de 11 meses (0,5-156). La mucosectomía con un manguito muscular corto y anastomosis ileoanal directa (short muscular cuff and straight ileo-anal anastomosis, SIAA) n = 29 o con reservorio en J (JIAA) n = 26 (55/72, 76%) fueron las reconstrucciones más habituales. Las complicaciones postoperatorias precoces que precisaron una intervención quirúrgica fueron muy poco frecuentes, pero se presentaron en 4/72 (5%) pacientes. Los síntomas a largo plazo relacionados con la función intestinal tras la reconstrucción, valorados en 57 niños mayores de cuatro años, fueron la dificultad para retener la defecación en 14 (25%), la encopresis en 21 (37%), las pérdidas fecales > 1/semana en 9 (16%) y el aumento de la frecuencia de defecación en 51 (89%). A largo plazo, se desarrolló una enterocolitis en 35/72 (47%) pacientes. Se precisó de nutrición enteral y/o parenteral suplementaria en algún momento del período de seguimiento en 51/93 (55%) pacientes. En los pacientes que respondieron a la encuesta entre 2 y 20 años (n = 56) de edad, se detectó un índice de masa corporal menor en 20 (35%) y una altura baja en 13 (23%) para su edad. En 35/57 (61%) pacientes mayores de 4 años con restauración del tránsito intestinal había restricciones sociales debido a los síntomas intestinales, de los que en 10 (17%) casos fueron moderadas o graves. CONCLUSIÓN: La reconstrucción de una TCA se asocia con síntomas intestinales persistentes y la enterocolitis sigue siendo frecuente. Un seguimiento multidisciplinario, incluso en la edad adulta, podría mejorar los resultados en la cirugía de la TCA.

Outcomes of Primary versus Multiple-Staged Repair in Hirschsprung's Disease in England.

INTRODUCTION: The study aimed to compare 1-year outcomes for primary versus multiple-staged (three operations with colostomy) repairs in Hirschsprung's disease (HD). MATERIALS AND METHODS: Retrospective analysis of a large national administrative database (Hospital Episode Statistics) including all the neonates born with HD in England between 2003 and 2015. Main outcomes were: 1-year mortality, postoperative readmissions, and reoperations. SECONDARY OUTCOMES: cumulative length of hospital stay (cLOS) and hospital volume-outcome relationship. RESULTS: A total of 1,333 neonates with HD were treated in 21 specialist pediatric surgical centers; 874 (65.5%) patients had a primary repair for HD. One-year mortality was 2.8%. The overall readmission rate was 70.2%, with a significant difference between primary and multiple-staged repair (79.9 vs. 90.1%, p < 0.01). There was no difference in reoperation. Primary pull-through was associated with a significantly lower probability of postoperative readmission (odds ratio [OR] = 0.08, 95% confidence interval [CI] = 0.06-0.11, p < 0.001) and cLOS (OR = 0.38, 95% CI = 0.28-0.52, p < 0.001) compared with multiple-staged repair. There were no significant difference in outcomes between patients treated in low-volume (<37 cases/year) and high-volume (> 55 cases/year) specialist centers. CONCLUSION: Whenever clinically indicated, primary repair should be used in HD as this is associated with fewer readmissions and shorter time spent in the hospital.

A 30-Year Prospective Follow-Up Study Reveals Risk Factors for Early Death in Cartilage-Hair Hypoplasia.

Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia with combined immunodeficiency, variable clinical course and increased risk of malignancy. Management of CHH is complicated by a paucity of long-term follow-up data, as well as knowledge on prognostic factors. We assessed clinical course and risk factors for mortality in a prospective cohort study of 80 patients with CHH recruited in 1985-1991 and followed up until 2016. For all patients we collected additional health information from health records and from the national Medical Databases and Cause-of-death Registry. The primary outcome was immunodeficiency-related death, including death from infections, lung disease and malignancy. Standardized mortality ratios (SMRs) were calculated using national mortality rates as reference. Half of the patients (57%, n = 46) manifested no symptoms of immunodeficiency during follow-up while 19% (n = 15) and 24% (n = 19) demonstrated symptoms of humoral or combined immunodeficiency, including six cases of adult-onset immunodeficiency. In a significant proportion of patients (17/79, 22%), clinical features of immunodeficiency progressed over time. Of the 15 patients with non-skin cancer, eight had no preceding clinical symptoms of immunodeficiency. Altogether 20 patients had deceased (SMR = 7.0, 95%CI = 4.3-11); most commonly from malignancy (n = 7, SMR = 10, 95%CI = 4.1-21) and lung disease (n = 4, SMR = 46, 95%CI = 9.5-130). Mortality associated with birth length below -4 standard deviation (compared to normal, SMR/SMR ratio = 5.4, 95%CI = 1.5-20), symptoms of combined immunodeficiency (compared to asymptomatic, SMR/SMR ratio = 3.9, 95%CI = 1.3-11), Hirschsprung disease (odds ratio (OR) 7.2, 95%CI = 1.04-55), pneumonia in the first year of life or recurrently in adulthood (OR = 7.6/19, 95%CI = 1.3-43/2.6-140) and autoimmunity in adulthood (OR = 39, 95%CI = 3.5-430). In conclusion, patients with CHH may develop adult-onset immunodeficiency or malignancy without preceding clinical symptoms of immune defect, warranting careful follow-up. Variable disease course and risk factors for mortality should be acknowledged.

Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.

The spotting lethal rat, a naturally occurring rodent model of Hirschsprung disease, carries a deletion in the endothelin-B receptor (EDNRB) gene that abrogates expression of functional EDNRB receptors. Rats homozygous for this mutation (sl) exhibit coat color spotting and congenital intestinal aganglionosis. These deficits result from failure of the neural crest-derived epidermal melanoblasts and enteric nervous system (ENS) precursors to completely colonize the skin and intestine, respectively. We demonstrate that during normal rat development, the EDNRB mRNA expression pattern is consistent with expression by ENS precursors throughout gut colonization. We used the human dopamine-beta-hydroxylase (DbetaH) promoter to direct transgenic expression of EDNRB to colonizing ENS precursors in the sl/sl rat. The DbetaH-EDNRB transgene compensates for deficient endogenous EDNRB in these rats and prevents the intestinal defect. The transgene has no effect on coat color spotting, indicating the critical time for EDNRB expression in enteric nervous system development begins after separation of the melanocyte lineage from the ENS lineage and their common precursor. The transgene dosage affects both the incidence and severity of the congenital intestinal defect, suggesting dosage-dependent events downstream of EDNRB activation in ENS development.

Postoperative outcome and survival in relation to small intestinal involvement of total colonic aganglionosis.

BACKGROUND: The prognosis and treatment of total colonic aganglionosis (TCA) vary according to the presence and extent of small bowel involvement. METHODS: Medical records of TCA patients treated in Helsinki University Children's Hospital during 1984-2013 (n=21) were reviewed. RESULTS: The aganglionosis extended up to cecum or distal ileum (n=12), mid small bowel (n=4), or duodenojejunal flexure (n=5). Patients underwent resection of distal aganglionic bowel with ileoanal (IAA) or jejunoanal anastomosis (JAA) with (n=9) or without J-pouch (n=5), Lester-Martin pull-through (n=1), or were left with an end-jejunostomy (n=6). Further procedures included autologous intestinal reconstruction (n=3) and ITx/listing for ITx (n=2). Compared to distal ileum aganglionosis, patients with more proximal disease required parenteral nutrition (PN) more often (100% vs. 25%) and weaned off PN less frequently (p=0.001). At last follow-up 6.5 (interquartile range 2.5-14.5) years postoperatively, all patients with distal ileum aganglionosis were off PN and alive compared to 78% on PN (p<0.001) and 67% alive (p=0.063) of those with more proximal disease. All had normal plasma bilirubin and patients with preserved intestinal continuity (n=13) were continent. CONCLUSIONS: Outcomes following restorative proctocolectomy for aganglionosis extending up to mid small bowel are promising, whereas long-term outlook in proximal small intestinal disease is dismal without ITx.

Hirschsprung's disease. Evaluation of mortality and long-term function in 260 cases.

This report describes 260 patients treated for Hirschsprung's disease. There were 213 boys (82%) and 47 girls (18%). Age at diagnosis was younger than 30 days in 106 patients (41%), 1 month to 1 year in 90 patients (35%), and older than 1 year in 64 patients (25%). Diagnosis was achieved with barium enema and rectal biopsy. Aganglionosis involved the rectum or rectosigmoid in 174 patients (67%), the left colon in 38 patients (15%), and the proximal colon in 23 patients (9%); 25 patients (9%) had total colonic aganglionosis. Enterocolitis occurred in 47 cases (18%). Following an initial colostomy or ileostomy, a definitive pull-through procedure was performed in 247 patients (95%) (modified Duhamel in 185, Soave in 25, Swenson procedure in 15, and anomyectomy/sphincterotomy in 22); the overall survival rate was 93.8% (244 of 260 patients). An increased mortality was associated with Down syndrome, total colonic aganglionosis, and enterocolitis. Long-term follow-up (mean, 6 years 10 months) was available in 103 patients who underwent a Duhamel procedure. Sixty-seven (65%) had normal bowel function, 28 (27%) occasionally used enemas or stool softeners, and eight (8%) had severe constipation or soiling. Bowel habits improved with time and were considered normal in 58% of patients at less than 5 years of follow-up and in 88% of patients at more than 15 years of follow-up. The Duhamel operation is a very effective definitive procedure for Hirschsprung's disease. Long-term follow-up is an important component of patient care.

Management of Hirschsprung's disease in children with trisomy 21.

Thirteen infants and children with trisomy 21 have been treated for Hirschsprung's disease since 1975. Clinical presentation of Hirschsprung's disease included constipation (five); neonatal intestinal obstruction (four); enterocolitis (three); and meconium plug syndrome (one). Additional associated congenital anomalies occurred in 10 patients, of which complex cardiac disease accounted for 25% of the defects. Seven children underwent definitive operation: Duhamel pull-through (four); Soave pull-through (two); and anal myectomy (one). Satisfactory continence occurred in all but one child. Enterocolitis developed in seven patients (54%): two at diagnosis of Hirschsprung's disease; three after colostomy; and two after pull-through. Five children died (38%): one from enterocolitis, two from cardiorespiratory failure after recovery from enterocolitis, and two from end-stage cardiac disease. Children with trisomy 21 can safely undergo definitive operation for Hirschsprung's disease but are at high risk for developing enterocolitis and complications of associated cardiac disease.

Intestinal transplantation for total/near-total aganglionosis and intestinal pseudo-obstruction.

Whether from anatomical short gut (such as after resection of extensive intestinal aganglionosis) or from a functional cause (such as intestinal pseudoobstruction), intestinal failure is a devastating disease process with profound morbidity and mortality. These patients require total parenteral nutrition (TPN) and are at risk of developing complications such as liver failure, catheter-related sepsis and loss of venous access. Intestinal transplantation, which has advanced markedly over the last 14 years, is now the accepted standard of care for patients failing TPN. Survival outcomes have improved significantly, infectious complications are better controlled, and new immunosuppressive therapies offer great hope for the future. In particular, the results of intestinal transplantation achieved with the motility disorders are equivalent to those experienced with other causes of intestinal failure. In themselves, the motility disorders present their own set of complicating factors, including determining the extent of the disease process (which may involve any part of the gastrointestinal tract), associated urological anomalies, and the type of organ transplantation required. Extensive workup and careful consideration is required before transplantation is undertaken. However, early referral is desirable once complications arise if these patients are to be offered optimal medical care before the chance of transplantation is lost.

Evidence of secondary neuronal intestinal dysplasia in a rat model of chronic intestinal obstruction.

The etiology of neuronal intestinal dysplasia remains largely unknown. There is, however, supporting evidence of the existence of Hirschprung's disease or chronic intestinal obstruction associated with neuronal intestinal dysplasia. With the aim of investigating the possible development of neuronal intestinal dysplasia linked to chronic intestinal obstruction, we have examined the enteric nervous system response to long-term obstruction in a rat model. Three different surgical techniques were tested in Wistar male rats. In animals that survived longer than the cutoff chronic intestinal obstruction point (6 weeks), full-thickness biopsies and acetylcholinesterase (AChE), NADH, hematoxylin-eosin, and anti-S100 protein stainings were performed. The results of our model indicate that chronic intestinal obstruction induced different degrees of enteric nervous system dysplasia, including histological features of neuronal intestinal dysplasia. The relationship between chronic intestinal obstruction and anomalies of the enteric nervous system, including neuronal intestinal dysplasia, needs to be further studied.

A 40-year multinational retrospective study of 880 Swenson procedures.

This report reviews the experience of pediatric surgeons in seven cities in North American and Western Europe where the Swenson procedure was performed on 880 patients. Information on the diagnosis, treatment, complications, and long-term results was collected by reviewing the hospital records, the treating physicians' office records, and by interviewing the patients in person or by telephone. A follow-up evaluation was obtained on 814 patients. The patients' ages at the time of the resection ranged from four days to 50 years. The length of follow-up averaged 10.3 years, while the longest follow-up was 39.5 years. The overall postoperative mortality was 2.4% during the entire 40 years of the study. The postoperative mortality has decreased to 1.25% for the last 20 years. Significant factors influencing postoperative mortality included Down's syndrome, the patient's age at the time of the operation, and leak of the distal colonic anastomosis. Most of the patients followed for over 5 years have normal bowel habits, report one to three bowel movements per day, and have no soiling. No patient has urinary incontinence or impotence.

Problems and pitfalls in the management of Hirschsprung's disease.

A study of 126 patients with histologically proven Hirschsprung's disease revealed various problems associated with the surgical management of these cases. Complications such as prolapse, stricture, and cuff abscess were noted in patients undergoing endorectal pull-through (ERPT). These complications were not always obvious, and in some cases, the diagnosis became apparent only several years after definitive surgery. Specific technical aspects of the procedure probably play an important role in the pathogenesis of these problems. Ultrashort-segment Hirschsprung's disease remains a problem in treatment. Rectal myectomy gives good results in some cases and unsatisfactory results in others.

Familial Hirschsprung's disease--a report of 22 affected siblings in four families.

Twenty-two infants, belonging to four families from Gaza, presenting with typical features of Hirschsprung's disease are reported. Eight patients died at home shortly after birth, prior to 1974, due to low intestinal obstruction. Fourteen patients were referred to Hadassah University Hospital after 1974 and diagnosed, by rectal biopsy, as having Hirschsprung's disease. Thirteen underwent laparotomy and multiple intestinal biopsies. Ten had total intestinal aganglionosis, two had total or near total aganglionosis, and in only one patient was the common rectosigmoid aganglionosis found. One patient died prior to surgery. This unusual familial disease, involving very long aganglionic segments, raises the possibility that these infants suffered from a unique variant of Hirschsprung's disease.