A population-based, complete follow-up of 146 consecutive patients after transanal mucosectomy for Hirschsprung disease

doi:10.1016/j.jpedsurg.2015.02.006

Journal of Pediatric Surgery

Volume 50, Issue 10, October 2015, Pages 1653-1658

https://doi.org/10.1016/j.jpedsurg.2015.02.006 Get rights and content

Abstract

Objective

The objective of the study is to define the population-based bowel functional outcomes and enterocolitis following transanal endorectal pull-through (TEPT) in patients with Hirschsprung disease (HD) treated at our institution between 1986 and 2011.

Methods

146 consecutive patients who had undergone primary surgical treatment for HD were included. The median follow-up time was 15 (3–33) years. The clinical details and prevalence of enterocolitis were evaluated in all patients, and bowel function in patients > 3 years of age with functional intestino-anal continuity.

Results

No patients were lost to follow-up. Overall survival was 98%. The level of disease was rectosigmoid in 83%, long segment in 7%, total colonic in 4%, and extending up to the small bowel in 6%. 29% had an associated syndrome. 22% had a preoperative stoma. Operations included TEPT (89%), proctocolectomy with ileoanal anastomosis in 9%, and 3% had a permanent endostomy owing to small intestinal aganglionosis. One patient underwent intestinal transplantation. At the latest follow-up, 42% had occasional soiling, 12% had frequent soiling and 46% had no soiling.

Constipation occurred in 9%. An associated syndrome was the only predictor for soiling or constipation (OR 4.3, 95% CI 1.5–12). 44% developed recurrent postoperative enterocolitis, which was predicted by extended aganglionosis (OR 6.9, 95% CI 2.4–20) and syndromatic disease (OR 2.4, 95% CI 1.2–5.0).

Conclusion

The major functional sequelae following TEPT were recurrent enterocolitis and fecal soiling, which was mostly occasional. An associated syndrome was a predictor of a reduced bowel functional outcome, and alongside extended aganglionosis were significant risk factors for recurrent postoperative enterocolitis.

Section snippets

Patients

A total of 146 consecutive patients who had undergone primary surgical treatment by the same surgical team for HD at Children's Hospital, University of Helsinki, between the years of 1987 and 2011, were included in the study. Patients referred from other institutions for redo surgery were excluded. Patient records were retrospectively reviewed for clinical details. Demographic data included gestational age, birth weight, family history, associated syndromes, anomalies and other illnesses.

Patients

The main patient characteristics and distribution of aganglionosis is shown in Table 1. Overall survival was 98% (n = 143). The median age at the last outpatient visit was 15 (range 3–33) years. Two patients had died of central venous catheter-derived sepsis, and one of enterocolitis in another hospital. Two of these patients had small intestinal aganglionosis and one had rectosigmoid aganglionosis. All patients had been followed up from birth by a senior pediatric colorectal surgeon at regular

Discussion

Here, we describe 146 consecutive patients who have been treated in our center for HD with a median follow-up time of 15 years (range 3–33 years), without any patients lost to follow-up. Compared to previous studies, the strengths of this study include the complete and population-based set up, long follow-up period, and one of the largest patient populations reported thus far.

Fecal continence and constipation are the most essential measures in evaluating the outcomes of HD surgery. Recurrent

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Cited by (48)

Comparison of clinical outcomes after total transanal and laparoscopic assisted endorectal pull-through in patients with rectosigmoid Hirschsprung disease
2022, Journal of Pediatric Surgery
Total transanal (TERPT) and laparoscopic endorectal pull-through (LERPT) are the most common procedures to treat rectosigmoid Hirschsprung's disease (HD). Since few studies have compared the two methods, we aimed to assess clinical outcomes after TERPT and LERPT in this cross-sectional study.
All patients with rectosigmoid HD operated with TERPT and LERPT between 2001 and 2018 were eligible. Peri-operative data were registered from patients’ records, and bowel function was assessed according to the Krickenbeck classification.
91/97 (94%) patients were included; 46 operated with TERPT and 45 with LERPT. Bowel function was assessed in 80 patients at median seven (4–17) years. There was no difference in functional outcome between the procedures. Unplanned procedures under general anesthesia were frequent; 28% after TERPT and 49% after LERPT (p = 0.04). 11% of TERPT and 29% of LERPT patients got botulinum toxin injections (p = 0.03). In the TERPT group, patients operated in the neonatal period had poorer outcome (78%) than those operated later (24%) (p = 0.005). No difference in operative time, length of hospital stay, and rate of early and late complications was found between the procedures.
There was no difference in long-term bowel function in patients with rectosigmoid HD operated with TERPT or LERPT. More LERPT patients had an unplanned procedure under general anesthesia, mostly due to obstructive symptoms.
III.
The science of Hirschsprung disease: What we know and where we are headed
2022, Seminars in Pediatric Surgery
Citation Excerpt :
The primary treatment of HSCR is surgical removal of the aganglionic segment, which includes removal of the functionally important rectum and puts pelvic innervation and anal sphincters at risk.88,89 Unfortunately, many patients experience persistent bowel dysfunction after surgery, including constipation, incontinence, and enterocolitis.90–95 Transplanting ENS cells to replace the missing neurons and glia in the aganglionic segment would address the underlying pathology of Hirschsprung disease and obviate the need for surgery and is therefore an active area of current research.
The enteric nervous system (ENS) is a rich network of neurons and glial cells that comprise the gastrointestinal tract's intrinsic nervous system and are responsible for controlling numerous complex functions, including digestion, transit, secretion, barrier function, and maintenance of a healthy microbiome. Development of a functional ENS relies on the coordinated interaction between enteric neural crest-derived cells and their environment as the neural crest-derived cells migrate rostrocaudally along the embryonic gut mesenchyme. Congenital or acquired disruption of ENS development leads to various neurointestinal diseases. Hirschsprung disease is a congenital neurocristopathy, a disease of the neural crest. It is characterized by a variable length of distal colonic aganglionosis due to a failure in enteric neural crest-derived cell proliferation, migration, differentiation, and/or survival. In this review, we will review the science of Hirschsprung disease, targeting an audience of pediatric surgeons. We will discuss the basic biology of normal ENS development, as well as what goes awry in ENS development in Hirschsprung disease. We will review animal models that have been integral to studying this disease, as well as current hot topics and future research, including genetic risk profiling, stem cell therapy, non-invasive diagnostic techniques, single-cell sequencing techniques, and genotype-phenotype correlation.
Long-term surgical and patient-reported outcomes of Hirschsprung Disease
2021, Journal of Pediatric Surgery
Information is needed regarding the complex relationships between long-term functional outcomes and health-related quality of life (HRQoL) in Hirschsprung's Disease (HSCR). We describe long-term outcomes across multiple domains, completing a core outcome set through to adulthood.
HSCR patients operated at a single center over a 35-year period (1978–2013) were studied. Patients completed detailed questionnaires on bowel and urologic function, and HRQOL. Patients with learning disability (LD) were excluded. Outcomes were compared to normative data. Data are reported as median [IQR] or mean (SD).
186 patients (median age 28 [18–32] years; 135 males) completed surveys. Bowel function was reduced (BFS 17 [14–19] vs. 19 [19–20], p < 0•0001; $η$ ² = 0•22). Prevalence and severity of fecal soiling and fecal awareness improved with age (p < 0•05 for both). Urinary incontinence was more frequent than controls, most of all in 13–26y females (65% vs. 31%,p = 0•003). In adults, this correlated independently with constipation symptoms (OR 3.18 [1.4–7.5],p = 0.008). HRQoL outcomes strongly correlated with functional outcome: 42% of children demonstrated clinically significant reductions in overall PedsQL score, and poor bowel outcome was strongly associated with impaired QOL (B = 22•7 [12•7–32•7],p < 0•001). In adults, GIQLI scores were more often impacted in patients with extended segment disease. SF-36 scores were reduced relative to population level data in most domains, with large effect sizes noted for females in General Health (g = 1.19) and Social Wellbeing (g = 0.8).
Functional impairment is common after pull-through, but bowel function improves with age. Clustering of poor functional outcomes across multiple domains identifies a need for early recognition and long-term support for these patients.
What should be the treatment for intestinal neuronal dysplasia type B? A comparative long-term follow-up study
2021, Journal of Pediatric Surgery
To present the long-term follow-up outcomes of patients with intestinal neuronal dysplasia type B (IND-B) managed either conservatively or surgically.
We conducted an ambispective, observational, longitudinal, and comparative study. Clinical data were reviewed at the start of treatment. After a minimum period of five years, the patients participated in semi-structured interviews in which the bowel function score (BFS) was applied to assess intestinal function, a proposed intestinal symptom index (ISI) to assess clinical symptoms, and a classification of clinical prognosis to assess treatment success. Comparisons between the two types of treatment were performed by evaluating pre- and post-treatment criteria.
Fifty patients diagnosed with IND-B were included in the study. Thirty-eight patients underwent surgical treatment (26 elective surgical treatment for primary colorectal resection and 12 emergency colostomies for intestinal obstruction or enterocolitis). Twelve patients were managed conservatively. With the exception of the patients who required an emergency operation (n = 12), the two groups were composed of patients with severe constipation who had similar clinical and functional characteristics at the time of IND-B diagnosis. A better clinical response was observed in patients submitted to conservative treatment, with a greater increase in the BFS (16.5 [-4/+18] versus 4 [-15/+17]; p = 0.001), indicating better bowel function and a more pronounced drop in ISI (-6 [-7/-4] versus -4 [-6/+1]; p = 0.015), suggesting fewer symptoms. The percentage of patients who had a successful treatment was higher in the group treated conservatively (72.7% versus 42.3%; p = 0.03).
Conservative management showed better long-term outcomes than surgical management in children with IND-B.
Functional outcome, quality of life, and ‘failures’ following pull-through surgery for hirschsprung's disease: A review of practice at a single-center
2020, Journal of Pediatric Surgery
Citation Excerpt :
Contradicting this finding is a study [8] based on the same population which concludes that bowel function deteriorates with age and demonstrates persistence of constipation and soiling with age. While some studies have found that fecal incontinence [22] and constipation [27,35] do not change with age, other studies showed an improvement with age [3,7,27,36,37]. Our results suggest that as patients age their bowel function is neither improving nor deteriorating.
The purpose of this study was to assess bowel function and quality of life (QoL) in patients with Hirschsprung's disease (HD) and identify patients who have ‘failed’ treatment.
A review of a single-center HD cohort treated with pull-through surgery from 2004 to 2017 was completed. Bowel function of patients five years and above and QoL of all patients were assessed using validated questionnaires. Patients who ‘failed’ treatment were defined as above five years with one or more of: a) long-term stoma, b) needing an antegrade continence enema or transanal irrigation, c) severe soiling, or d) severe constipation. Statistical analysis was performed with P < 0.05 deemed significant. Data are given as mean [range].
Seventy-one patients presented with HD within the study period. Mean follow-up was 5.4 years [0.7–13.3]. Of 38 eligible patients, bowel function was assessed in 24 patients (nine had a stoma, five lost to follow-up). The mean incontinence score was 17 [0–28)], and the mean constipation score was 17 [5–25]. Incontinence and constipation scores were worse than healthy controls (P < 0.001 and P = 0.001, respectively) and did not improve with age. Fifty-six patients had QoL assessed with no difference between our cohort (81 [25–100]) and healthy controls (81 [unknown]); (P = 0.85). Thirty-three patients were assessed for ‘failure’ (bowel function score n = 24; stoma n = 9). Thirty of 33 (91%) children older than five years can be considered to have ‘failed’ treatment.
Patients have worse bowel function than healthy children, which does not improve with age. QoL is comparable to healthy controls. A significant proportion of patients have poor outcomes and have ‘failed’ treatment.
Level III.
Reduced expression of the NLRP6 inflammasome in the colon of patients with Hirschsprung's disease
2019, Journal of Pediatric Surgery
Hirschsprung's associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung's Disease (HSCR). The pathogenesis of HAEC remains unsatisfactorily understood. Mounting evidence of an altered microbiome in patients with HSCR adds a new angle to the pathogenesis of HAEC. NLRP6 is a member of the nucleotide-binding domain, leucine-rich-repeat-containing (NLR) innate immune receptor family, a multiprotein complex that functions as a sensor of damage-associated molecular patterns. Known as inflammasomes they have been implicated in the regulation of colonic microbial ecology and by alteration, regulators of inflammation. We designed this study to test the hypothesis that NLRP6 expression is altered in the colon of patients with HSCR.
We investigated NLPR6 protein expression in both the aganglionic and ganglionic regions of HSCR patients (n = 10) versus healthy control colon (n = 10). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expressions were quantified using quantitative real-time polymerase chain reaction (qPCR), Western blot analysis, and densitometry.
qPCR and Western blot analysis revealed that NLRP6 is expressed in the colon of patients with HSCR. NLRP6 expression was significantly decreased (p < 0.003) in the ganglionic and aganglionic bowel in HSCR compared to controls. Confocal microscopy revealed that NLRP6 expression in colonic epithelium was markedly decreased in HSCR specimens compared to controls.
We demonstrate for the first time the expression and distribution of NLRP6 in patients with HSCR. The observed decreased expression of NLRP6 may contribute to an altered colonic microbiome in patients with HSCR and increases the susceptibility to develop HAEC.

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^☆: Sources of funding: This research was supported by grants from the Foundation for Pediatric Research (Finland), Päivikki and Sakari Sohlberg Foundation and the Sigrid Jeselius Foundation.

^☆☆: Reprints: Reprints will not be available from the authors.

^★: The paper is not based on a previous communication to a society or meeting.

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Original ArticleA population-based, complete follow-up of 146 consecutive patients after transanal mucosectomy for Hirschsprung disease☆,☆☆,★

Abstract

Objective

Methods

Results

Conclusion

Section snippets

Patients

Patients

Discussion

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Lancet

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Original Article
A population-based, complete follow-up of 146 consecutive patients after transanal mucosectomy for Hirschsprung disease☆,☆☆,★