Colonic Aganglionosis Research Articles

Variability in proliferative and migratory defects in Hirschsprung disease-associated RET pathogenic variants.

Despite the extensive genetic heterogeneity of Hirschsprung disease (HSCR; congenital colonic aganglionosis) 72% of patients harbor pathogenic variants in 10 genes that form a gene regulatory network (GRN) controlling the development of the enteric nervous system (ENS). Among these genes, the receptor tyrosine kinase gene RET is the most significant contributor, accounting for pathogenic variants in 12%-50% of patients depending on phenotype. RET plays a critical role in the proliferation and migration of ENS precursors, and defects in these processes lead to HSCR. However, despite the gene's importance in HSCR, the functional consequences of RET pathogenic variants and their mechanism of disease remain poorly understood. To address this, we investigated the proliferative and migratory phenotypes in a RET-dependent neural crest-derived cell line harboring one of five missense (L56M, E178Q, Y791F, S922Y, F998L) or three nonsense (Y204X, R770X, Y981X) pathogenic heterozygous variants. Using a combination of cDNA-based and CRISPR-based PRIME editing coupled with quantitative proliferation and migration assays, we detected significant losses in cell proliferation and migration in three missense (E178Q, S922Y, F998L) and all nonsense variants. Our data suggests that the Y791F variant, whose pathogenicity has been debated, is likely not pathogenic. Importantly, the severity of migration loss did not consistently correlate with proliferation defects, and the phenotypic severity of nonsense variants was independent of their position within the RET protein. This study highlights the necessity and feasibility of targeted functional assays to accurately assess the pathogenicity of HSCR-associated variants, rather than relying solely on machine learning predictions, which could themselves be refined by incorporating such functional data.

Influence of Diet on Bowel Function and Abdominal Symptoms in Children and Adolescents with Hirschsprung Disease-A Multinational Patient-Reported Outcome Survey.

Introduction: This study aimed to understand the influence of diet and nutrition items on gastrointestinal symptoms in patients with Hirschsprung Disease (HD). Method: An online questionnaire was created to obtain patient-reported outcomes using the multinational Holistic Care in Hirschsprung Disease Network. This was distributed in Dutch, English, German, Italian, Polish, and Swedish via patient associations. Information on demographics, the extension of disease, current diet, and the influence of food ingredients on bowel function were obtained. Results: In total, 563 questionnaires were answered by parents or patients themselves. The length of the aganglionic segment was short in 33%, long in 45%, total colonic aganglionosis (TCA) in 11%, and involved the small intestine in 10%. Overall, 90% reported following a mixed diet, and 31% reported taking probiotics, with twice as many patients taking probiotics in the TCA group compared to standard HD. Mealtimes and behaviours around eating were affected by 61%, while 77% had established food items that worsened symptoms, and of these, 80% stated that they had worked these items out themselves. A high-fibre diet was followed by 24% and 18% a low-fibre diet. Symptoms were reported, particularly from dairy in 30%, fruits in 39%, pulses in 54%, and sugar in 48%. Conclusions: This first multinational survey on diet and bowel function in HD reports an association between certain dietary items with gastrointestinal symptoms. This study can support an improved understanding of the interaction between food items and bowel function in children with HD. We suggest a multidisciplinary approach to balance dietary exclusions and support adequate growth, preventing nutrition deficiencies and enhancing quality of life.

Surgical Strategies in Total Colonic Aganglionosis: Primary Pullthrough-Pathway of Care.

Background: Total colonic aganglionosis, as a rare variant of Hirschsprung Disease, still poses challenges to surgeons in terms of diagnosis and management. The optimal preparation for pullthrough is crucial for reconstructive surgery. This study aims to explore our surgical pathway for children with total colonic aganglionosis (TCA) and to describe the prehabilitation necessary to prepare for successful reconstructive pullthrough surgery. Methods: A prospective review of children with TCA receiving an abdominal surgical intervention between 1/22 and 4/24. The cohort included children receiving mapping +/- primary ileoanal pullthrough. An analysis of preoperative, perioperative, and postoperative data, and a short-term follow-up were performed. Results: A total of 18 children with TCA and no prior pullthrough received an abdominal intervention during the 29-month study period, and 5/18 (27.8%) were female. The children had a median of 4 (range 2-7) prior external surgeries; all had a stoma; 6 (33%) children received parental nutrition; 12 children underwent a mapping of the ganglia distribution and bowel length at a median age of 11 months (range 3-54), and in 10 of them, we relocated the stoma. There was a mean involvement of 15 (5-93) cm small bowel aganglionosis, with the remaining mean ganglionic small bowel having a length of 178 cm (110-254). A total of 11 children underwent straight primary ileoanal pullthrough of the stoma site at a median age of 16.7 months (10-133). Conclusions: The timely diagnosis of TCA still challenges the care team, and most children have a rough journey involving several surgeries until their diagnosis is established. The ensure bowel function with an adequate working stoma is the key to enabling enteral nutrition and growth, which are the baseline requirements to undertake a successful pullthrough procedure and restore continuity. Careful perioperative bowel management and parents' active involvement supports children with Hirschsprung Disease achieving the best possible quality of life.

Technical evaluation and fecal continence of laparoscopic-assisted procedures for total colonic aganglionosis

Total colonic aganglionosis (TCA), defined as aganglionosis extending from the anus up to the distal ileum, is a rare variant of Hirschsprung's disease. Surgery for TCA aims to remove the aganglionic colon and reconstruct the intestinal tract by bringing the normally innervated ileum down to the anus while preserving normal sphincter function. Laparoscopy with surgeries including laparoscopic-assisted Duhamel-like and Soave-like pull-through procedures have been progressively applied to the treatment of TCA over the past two decades and may become the dominant treatment for TCA in the future. Postoperative fecal continence, involving issues such as normal defecation, Hirschsprung-associated enterocolitis (HAEC), frequent stool and perianal erosion (perineal rash), soiling/fecal incontinence and constipation/obstructive symptoms, is very important to patients. These complications require nutritional support and comprehensive postoperative gastroenterological care and even require permanent ileostomy and redo pull-through. Some patients have previously seen a psychologist for frequent complaints of diarrhea and other physical symptoms. Patients with TCA postoperatively must be evaluated regularly by pediatric surgeons, enterostoma therapists, gastroenterologists, dieticians and psychologists to achieve a good nutritional status and psychological health.

Are the complications after laparo-assisted endo-rectal pull-through for Hirschsprung disease related to the change of the anal tone?

The main advantage of the laparo-assisted transanal endorectal pull-through technique (LA - TERPT) for Hirschsprung Disease (HD) is the respect to the rectal-anal anatomy. Postoperative complications have been observed recently. The present study aims to determine how often these postoperative complications occur in these patients. From January 2009 to December 2018, a retrospective analysis was conducted on 36 children (25 males) with HD who underwent LA-TERPT. Data were collected on the age of diagnosis and surgery, sex, the presence of other pathologies, and cases of enterocolitis. In all cases, anorectal manometry (ARM) was performed to evaluate the anal tone. The median age at diagnosis was 2 months and the mean age at surgery was 5 months. Nine related pathologies were identified: five cases of Down syndrome, one case of hypertrophic stenosis of the pylorus, atresia of the esophagus, polydactyly, and anorectal malformation. A patient with total colonic aganglionosis was identified through laparoscopic serummuscular biopsies. Enterocolitis was diagnosed in 7 cases before and 6 after surgery. At follow-up, the complications recorded were: 5 cases of constipation (treated with fecal softeners), one case of anal stenosis (patient with anorectal malformation), 16 cases of soiling (treated with enemas) and 1 child with fecal incontinence (treated with a transanal irrigation system). The ARM was performed in all 36 cases and showed normal anal tone, except for one case with anal hypotonia. LA-TERPT is an important surgical technique for HD. According to the literature, soiling is the most main complication after HD surgery, probably due to "pseudo-incontinence" with normal anal sphincter tone.

Outcomes following endorectal pull-through for Hirschsprung disease: a retrospective study

PurposeTo share our experience in the surgical management of patients with Hirschsprung disease (HD) using the trans-anal endorectal pull-through “Soave” technique.MethodsThe study included cases diagnosed as HD who were operated during the period 2008 through 2018. Cases of total colonic aganglionosis were excluded to be discussed in a separate report.ResultsThe study included 67 consecutive cases of HD. All included cases underwent trans-anal endorectal pull-through which was purely trans-anal in 31 (46%), while abdominal-assisted trans-anal endorectal pull-through was applied in the remaining (54%). Early postoperative complications included 2 cases of partial dehiscence at the colo-anal anastomosis; 1 of them deteriorated after re-exploration and unfortunately died. Twenty-six cases were available to assess functional outcomes after corrective surgery. Their age at follow-up ranged between 44 months and 17 years (mean = 78.8 months; median = 72 months). All cases achieved voluntary defecation. However, fecal soiling was a common finding after surgery for HD (69%). Constipation was another common postoperative finding (73%). Lastly, a history of attacks of postoperative enterocolitis was prevalent in 19 cases (73%), which ranged between 1 and 7 attacks usually in the first 2 years after the operation.ConclusionThe trans-anal endorectal pull-through provides an effective surgical treatment for Hirschsprung disease. The high prevalence of fecal soiling after surgery highlights the importance of long-term follow-up to provide the required support for these patients during adolescence and transition into adulthood.

Extended total colonic aganglionosis and total intestinal aganglionosis: Challenging enemies.

Extended total colonic aganglionosis (ETCA) represents uncommon forms of Hirschsprung disease (HD), with aganglionosis extending into the proximal small bowel. ETCA management is challenging and associated with poor outcomes and high mortality. This study compares management and outcomes of ETCA to more common HD forms. A retrospective cohort of HD patients (2012-2023) from two institutions. Three HD forms were compared: short-segment HD (SSHD, n = 19), long-segment HD or total colonic aganglionosis (LS/TCA, n = 9) and ETCA (n = 7). Normally innervated segments in ETCA patients ranged 0-70 cm. Median times to first surgery were; ETCA = 3 days versus TCA = 21 days (p = 0.017) and SSHD = 95 days (p < 0.001), respectively. Median number of surgeries were; ETCA = 4, versus TCA = 2 (p = 0.17) and SSHD = 1 (p = 0.002), respectively. All the patients underwent a definitive pull-through procedure, except four ETCA patients with a permanent jejunostomy and residual aganglionic segment of 57-130 cm. ETCA patients had 92% lower odds of enterocolitis (14%) compared to TCA patients (67%, p = 0.054), and comparable odds to SSHD patients (16%, p = 0.92). ETCA mortality was 14%. Extended total colonic aganglionosis patients require earlier and multiple interventions. Leaving an aganglionic segment may be advantageous, without increasing risk for enterocolitis. Tailored surgical treatment and rehabilitation programmes may prevent mortality and need for transplantation.

Ernica Clinical Consensus Statements on Total Colonic and Intestinal Aganglionosis

BackgroundHirschsprung disease is a congenital intestinal motility disorder characterized by an absence of enteric ganglion cells. Total colonic aganglionosis and near total or total intestinal aganglionosis, defined as absence of ganglion cells in the entire colon and with variable length of small bowel involved, are life-threatening conditions which affect less than 10 % of all patients with Hirschsprung disease. The aim of this project was to develop clinical consensus statements within ERNICA, the European Reference Network for rare congenital digestive diseases, on four major topics: Surgical treatment of total colonic aganglionosis, surgical treatment of total intestinal aganglionosis, management of poor bowel function in total colonic and/or intestinal aganglionosis and long-term management in total colonic and or intestinal aganglionosis. MethodsA multidisciplinary panel of representatives from ERNICA centers was invited to participate. Literature was searched, using specified search terms, in Medline (ALL), Embase and Google Scholar. Abstracts were screened and full text publications were selected. The panel was divided in four groups that extracted data from the full text publications and suggested draft statements for each of the major topics. A modified Delphi process was used to refine and agree on the statements. ResultsThe consensus statement was conducted by a multidisciplinary panel of 24 participants from 10 European countries, 45 statements reached consensus after 3 Delphi-rounds. The availability of high-quality clinical evidence was limited, and most statements were based on expert opinion. Another 25 statements did not reach consensus. ConclusionsTotal colonic and total intestinal aganglionosis are rare variants of Hirschsprung disease, with very limited availability of high-quality clinical evidence. This consensus statement provides statements on the surgical treatment, management of poor bowel function and long-term management for these rare patients. The expert panel agreed that patients benefit from multidisciplinary and personalized care, preferably in an expert center. Type of StudyClinical consensus statement. Level of Evidence3a.

Impact of Colorectal Nurse Specialist supervised parental administration of rectal washouts on Hirschsprung's disease outcomes: a retrospective review.

To highlight the utility of Colorectal Nurse Specialist (CNS) supervised parental administration of rectal washouts in the management of Hirschsprung's disease (HD). Retrospective case note review of HD patients treated at a tertiary children's hospital in United Kingdom from January 2011 to December 2022. Data collected included demographics, complications, enterocolitis, obstructive symptoms and stomas. Primary pull-through (PT) is done 8-12weeks after birth. Parental expertise in performing rectal washouts at home is ensured by our CNS team before and after PT. PT was completed in 69 of 74 HD patients. Rectal washouts were attempted on 63 patients before PT. Failure of rectal washout efficacy necessitated a stoma in four patients (6.4%). Of the 65 patients who had PT and stoma closed, three (4.5%) required a further stoma over a mean follow-up period of 57 months (Range 7-144 months). Two of these had intractable diarrhoea due to Total Colonic Aganglionosis (TCA). One patient (1.5%) had unmanageable obstructive symptoms requiring re-diversion. Hirschsprung-associated enterocolitis (HAEC) requiring hospital admission occurred in 14 patients (21%). Our stoma rates are lower compared to recent UK data. This could potentially be due to emphasis on parental ability to perform effective rectal washouts at home under CNS supervision.

Клінічна симптоматика агангліонозу кишечника та його ускладнень у дітей віком від 3 до 6 років

Clinical symptoms of colonic aganglionosis (CA) in children 3 to 6 years of age are difficult due to its clinical presentation which represents as the complications of this pathology, because of it the classic signs of Hirschsprung’s disease (HD) are partially eliminated or hidden, which makes it difficult for the effective diagnosis of this pathology in these children. Purpose - to study the clinical symptoms of CA and its complications in children 3 to 6 years of age and to determine the significance of clinical symptoms for the verification of HD. Materials and methods. We have done retrospective analysis of the clinical manifestations in 240 children 3 to 6 years of age with HD, considering the extent of CA, the presence of associated malformations and complications. There were 95 (39.58%) patients with the rectal form of CA, 143 (59.59%) with the rectosigmoid form, 2 (0.83%) with the subtotal form. There were no patients with total CA in this age group. There were 192 boys (80.0%), and 48 girls (20.0%). At the age of 3-4 years 71 (29.58%) patients were diagnosed with HD, at the age of 4-5 years - 79 (32.91%), and at the age of 5-6 years - 90 (37.51%) patients. Results. The diagnosis of HD can be of course considered as late for patients from 3 to 6 years of age. We found associated malformations in 45 (18.75%) patients. Associated intestinal malformations were found in 26 (10.83%) patients, of which 19 (7.92%) had malformations that significantly increased the clinical symptoms of CA and its complications: malrotation (n=17 (7.08%)) and internal abdominal hernia (2 (0.83%)). Enterocolitis (EC) was found in 98 (40.83%) patients. The 1st degree of EC was established in 9 (3.75%) children, 2nd degree - in 34 (14.16%) and 3rd degree - in 55 (22.91%) patients. Among these 55 with 3rd degree of EC the critical moment in the progression of the course of EC was toxic megacolon (TM), which occurred in 14 (25.46%). Hypotrophy was established in 18 (7.49%) patients. Anemia of various degrees was diagnosed in 35 (14.58%) children. The acute stage of the course of HD was diagnosed in 98 (40.83%) patients, subacute - in 77 (32.08%) and chronic - in 65 (27.08%) children. The clinical course of HD was correlated with the extent of the colon affected with CA and is closely related to the presence of its complications: EC, anemia and hypotrophy. Conclusions. Clinical symptoms of CA in children aged 3 to 6 years remains typical and informative upon careful evaluation of complaints, medical history, and objective and laboratory results. The severity of the course, associated developmental malformations and late diagnosis are the main reasons for the appearance of severe complications of HD in children 3 to 6 years of age - EC (40.83%), TM (25.46%), hypotrophy (7.49%) and anemia (14.58%). Variants of complications in CA are characteristic and predictable. Comparison of the clinical signs of CA and its complications contribute to the correct assessment of the patient's condition and timely establishment of the correct diagnosis. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of all institutions mentioned in the work. Informed consent of the children’s parents was obtained for the research. No conflict of interests was declared by the authors.

Clinical features of the course of Hirschsprung’s disease in newborns and infants with consideration of the extent of colonic aganglionosis

The clinical course of Hirschsprung’s disease (HD) in newborns and infants depends on the extent of сolonic aganglionosis, the age of patient, the presence of associated malformations and complications. The aim - to study the peculiarities of the clinical course of HD in newborns and infants. Materials and methods. An analysis of the clinical course of HD in 483 in newborns and infants. There were 100 (20.71%) patients with the rectal, 192 (39.75%) with rectosigmoid, 150 (31.05%) with subtotal, and 41 (8.49%) with total form of HD. 98 (20.29%) patients were found to have associated malformations. Results. 64 (13.25%) patients with a rectal form, 72 (14.91%) - with rectosigmoid, 150 (31.05%) - with subtotal, and 41 (8.49%) with total form had an acute clinical course and subacute clinical course was observed in 36 (7.45%) patients with rectal and 120 (24.85%) with rectosigmoid forms of HD. 327 (67.70%) infants with HD were diagnosed with varying degrees of hypotrophy, 315 (65.22%) had HD-associated enterocolitis, 16 (3.31%) had toxic megacolon, and 241 (49.89%) patients had varying degrees of anemia. Conclusions. In the presence of associated malformations in newborns and infants, in 8.07% of cases, clinical symptoms may prevail over the classic signs of HD. The severity of the course and late diagnosis are the main reasons for the appearance of severe complications of HD in newborns and infants - hypotrophy (67.70%), HD-associated enterocolitis (65.22%), toxic megacolon (3.31%) and anemia (49.89%). The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of all institutions mentioned in the work. Informed consent of the children’s parents was obtained for the research. No conflict of interests was declared by the authors.

Autologous cell transplantation for treatment of colorectal aganglionosis in mice

Neurointestinal diseases cause significant morbidity and effective treatments are lacking. This study aimes to test the feasibility of transplanting autologous enteric neural stem cells (ENSCs) to rescue the enteric nervous system (ENS) in a model of colonic aganglionosis. ENSCs are isolated from a segment of small intestine from Wnt1::Cre;R26iDTR mice in which focal colonic aganglionosis is simultaneously created by diphtheria toxin injection. Autologous ENSCs are isolated, expanded, labeled with lentiviral-GFP, and transplanted into the aganglionic segment in vivo. ENSCs differentiate into neurons and glia, cluster to form neo-ganglia, and restore colonic contractile activity as shown by electrical field stimulation and optogenetics. Using a non-lethal model of colonic aganglionosis, our results demonstrate the potential of autologous ENSC therapy to improve functional outcomes in neurointestinal disease, laying the groundwork for clinical application of this regenerative cell-based approach.

Клінічні прояви хвороби Гіршпрунга в дітей віком від 1 до 3 років

Clinical manifestations of Hirschsprung's disease (HD) in children aged 1 to 3 years depend on many factors, namely the extent of colonic aganglionosis (CA), the age of patients, the presence of associated congenital malformations and severe complications. Purpose - to study the features of the clinical manifestations of HD in children aged 1 to 3 years for the early detection and verification of this pathology. Materials and methods. We conducted a retrospective analysis of the clinical manifestations of HD in 268 children aged 1 to 3 years: 74 (27.62%) children with the rectal form of HD, 187 (69.77%) with rectosigmoid form and 7 (2.61%) with subtotal form. Associated malformations were found in 50 (18.66%). To study the clinical course, we considered the anamnesis, physical examination, data of general clinical laboratory indicators of blood, urine and feces, electrocardiography, neurosonography, echocardiography, ultrasound and X-ray dianostics. Results. Hypotrophy was found in 54 (20.15%) children: the first degree in 9 (3.36%) children, the second degree in 34 (12.69%) and the third degree in 11 (4.1%) patients. Laboratory tests revealed mild anemia in 4 (1.49%), moderate anemia in 11 (4.1%), and severe anemia in 31 (11.57%) children. The HD course was complicated by enterocolitis in 25 (33.78%) of 74 patients with rectal, in 86 (46.52%) of 187 children with rectosigmoidal and in 7 (100%) of 7 children with subtotal CA. Toxic megacolon was diagnosed in 6 (3.21%) patients. Conclusions. Associated malformations and late diagnosis are the main causes of severe complications of HD in children aged 1 to 3 years: enterocolitis (44.03%), toxic megacolon (4.85%), hypotrophy (20.15%) and anemia (17.16%). The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of all institutions mentioned in the work. Informed consent of the children’s parents was obtained for the research. No conflict of interests was declared by the authors.

Hirschsprung disease with recurrent obscure gastrointestinal bleeding

Hirschsprung Disease (HD) is a form of colonic aganglionosis with an incidence of 1 in 5000 liver births. It presents as constipation since birth with other intestinal and extraintestinal disorders [1]. Here we present a case of a 22-year-old female who presented

Concurrence of Hirschsprung disease and annular pancreas: a rare case report

Hirschsprung’s disease (HD) and annular pancreas are both uncommon congenital gastrointestinal malformations. Although additional abnormalities are associated with 18% of HD cases, there is limited evidence of concomitant HD and annular pancreas. We present a full-term, two-day-old male with abdominal distended, and failure to pass first stool after 3 days of observation and rectal washout the abdominal X-rays showed a double bubble appearance. Intraoperative finding, the patient had pancreas annulare (PA). Colonic aganglionosis was discovered using full-thickness rectal biopsies (FTRB). At the age of seven months, a transanal endorectal pull-through was performed without complications. Although the diagnosis of these conditions might be difficult due to their clinical similarities, appropriate diagnosis, and surgical management are possible and can dramatically minimize morbidity and death in the newborn.

Long-Term Functional Outcomes and Multidisciplinary Management after Ileorectal Duhamel Pull-Through for Total Colonic Aganglionosis-20-Year Experience in a Tertiary Surgical Center.

Management of patients with total colonic aganglionosis (TCA) is challenging for pediatric surgeons. The purpose of this study was to review our institution's 20-year experience regarding long-term outcomes and multidisciplinary team management of these patients after an ileorectal Duhamel pull-through procedure. Retrospective review was conducted for all patients diagnosed with TCA in our tertiary institution. Data were collected on demographics, clinical presentation, complications, need for additional surgery, and long-term effects on bowel function. Of a total of 202 patients with Hirschsprung's disease, 13 were diagnosed with TCA (6.4%). Clinical presentation was variable. Eleven presented in neonatal period with distal bowel obstruction and two presented with constipation in early infancy. Ileorectal Duhamel pull-through was performed in all patients. Median follow-up was 13 years. Eleven are toilet trained, of whom five are fully continent. Six continue to have problems with bowel continence or constipation. One developed recurrent episode of Hirschsprung's associated enterocolitis. Two patients had stoma re-established. Patients experiencing difficulties in bowel function are jointly managed by a multidisciplinary team consisting of surgeons, gastroenterologists, pediatric psychologists, and clinical nurse specialists. TCA can be associated with significant long-term morbidity. Nearly half of the patients in this series have ongoing problems with bowel continence requiring a permanent stoma in some. Diligent follow-up coupled with inputs of a multidisciplinary team has greatly helped manage these complex patients in our institution.

Postoperative Hirschsprung’s associated enterocolitis (HAEC): transition zone as putative histopathological predictive factor

AimsHirschsprung’s-associated enterocolitis (HAEC) is the most severe complication of Hirschsprung disease (HD), and its pathogenesis is still unknown. Length of transition zone (TZ) interposed between aganglionic and normal bowel has...

Preoperative management comprising tube irrigation using a trans-anal indwelling tube for infants with hirschsprung disease can allow single-stage radical surgery

BackgroundPreoperative management of Hirschsprung’s disease (HD) is currently being conducted with the goal of performing single-stage radical surgery without ileostomy.MethodsWe retrospectively reviewed HD cases between 2013 and 2022, as well as their outcomes related to preoperative management.ResultsThirty-nine patients with HD were included in this study, including short-segment HD (30 cases), long-segment HD (4 cases), and total colonic aganglionosis (5 cases). Among these 39 patients, 95% (37 of 39 patients) underwent single-stage radical surgery after management with glycerin enema use (n = 13), irrigation with tube insertion each time irrigation was performed (n = 13), and irrigation using a tube placed in the bowel (n = 11).ConclusionsPreoperative management of patients with HD allowed for single-stage surgery of long-segment HD and total colonic aganglionosis. Cases that could be managed without performing an emergency enterostomy during the neonatal period were managed with irrigation until radical surgery was performed.

A unicentric cross-sectional observational study on chronic intestinal inflammation in total colonic aganglionosis: beware of an underestimated condition

BackgroundInflammatory Bowel Diseases (IBD) are known to occur in association with Hirschsprung disease (HSCR). Most of cases are represented by Crohn Disease (CD) occurring in patients with Total Colonic Aganglionosis (TCSA) with an estimated prevalence of around 2%. Based on these considerations and on a number of provisional data belonging to our Center for Digestive Diseases, we developed a unicentric cross-sectional observational study aimed at describing phenotype, genotype, pathology and metagenomics of all patients with TCSA and Crohn-like lesions.ResultsOut of a series of 62 eligible TCSA patients, 48 fulfilled inclusion criteria and were enrolled in the study. Ten patients did not complete the study due to non-compliance or withdrawal of consent and were subsequently dropped out. A total of 38 patients completed the study. All patients were tested for chronic intestinal inflammation by a combination of fecal calprotectine (FC) or occult fecal blood (OFB) and underwent fecal metagenomics. Nineteen (50%) tested positive for FC, OFB, or both and subsequently underwent retrograde ileoscopy. Fourteen patients (36.8%) presented Crohn-like lesions, occurring after a median of 11.5 years after surgery (range 8 months − 21.5 years). No statistically significant differences regarding demographic, phenotype and genotype were observed comparing patients with and without lesions, except for need for blood transfusion that was more frequent in those with lesions. Faecal microbiome of patients with lesions (not that of caregivers) was less biodiverse and characterized by a reduction of Bacteroidetes, and an overabundance of Proteobacteria. FC tested negative in 3/14 patients with lesions (21%).ConclusionsOur study demonstrated an impressive 10-folds higher incidence of chronic inflammation in TCSA. Up to 50% of patients may develop IBD-like lesions postoperatively. Nonetheless, we failed in identifying specific risk factors to be used to implement prevention strategies. Based on the results of our study, we suggest screening all TCSA patients with retrograde ileoscopy regardless of FC/OFB values. The frequency of endoscopic assessments and the role of FC/OFB screening in prompting endoscopy is yet to be determined.

Late Diagnosis of Hirschsprung Disease: Clinical Presentation and Long-Term Functional Outcomes

PurposeHirschsprung Disease (HD) is typically diagnosed in the neonatal period. A small subset of patients have a prolonged course of abdominal distention and constipation prior to diagnosis. Late HD is defined as having been diagnosed at greater than or equal to one year of age. The literature is limited and offers conflicting data on the implications of a late diagnosis. We aim to investigate the presentation, operative approach, and functional outcomes of a large cohort of patients with a late HD diagnosis. MethodsAll patients with a late diagnosis of HD (after 1 year of age) at our institution between 1997 and 2021 were included. ResultsTwenty-eight patients were diagnosed with HD at a median age of 3.4 years. Chronic constipation, failure to thrive, and enterocolitis occurred in 100 %, 31 %, and 14 %, respectively. All patients underwent contrast enema and biopsies during their workup, identifying primarily rectosigmoid disease (n = 27) and total colonic aganglionosis (n = 1). Surgical intervention was performed in 27 patients, with 4 patients (15 %) needing a stoma (3 with plan for staged pull-through, 1 long-term stoma) and 23 patients (85 %) undergoing a single-stage pull-through. Postoperative complications included Hirschsprung-associated enterocolitis (n = 5), ostomy prolapse and revision (n = 2), abdominal distention requiring ileostomy creation (n = 2), redo pull-through (n = 2), retroperitoneal hematoma (n = 1), and cecostomy tube placement (n = 1). At a median follow-up of 5.4 years, 83 % of eligible patients achieved fecal continence with 43 % needing laxatives for persistent constipation. ConclusionRecognizing a late presentation of HD requires a high index of suspicion. Patients with a late diagnosis did not experience an increased rate of permanent stoma, complications, or redo surgery compared to rates reported for the larger HD population. Similar long-term functional outcomes were achieved compared to the larger HD population. Level of EvidenceIV.