Resection margin histology may predict intermediate-term outcomes in children with rectosigmoid Hirschsprung disease

Abstract

Introduction

Recent studies suggest that some of the post-surgical morbidity in Hirschsprung disease (HSCR) is due to enteric nervous system structural defects in the proximal, ganglionated bowel that remains after surgery. We hypothesized that resection margin histology would predict intermediate-term outcomes in HSCR patients.

Methods

Following IRB approval, HSCR patients with rectosigmoid disease born between 2009 and 2016 were reviewed and tissue blocks were obtained for new analyses. Proximal resection margins were analyzed for ganglion size, Hu + neurons/ganglion, and % nitric oxide synthase (NOS) neurons/ganglion as compared to control (non-HSCR) patient samples. Chart reviews were performed for 1- and 2-year outcomes. Patients were contacted for survey to determine Rintala bowel function score.

Results

45 patients had recto-sigmoid disease and were further analyzed. HSCR patients had significantly smaller individual ganglion size (4533 μm2, range 1744–16,287 vs. 6492 μm2, range 1932–30,838, p = 0.0192) and fewer HuC/D + neurons per ganglion (15, range 5.2–34 vs. 21, range 5.2–6.7, p = 0.0214). HSCR patients demonstrated a markedly increased percentage of NOS (relaxation neurotransmitter) neurons (50, range 22–85 vs. 37, range 16–80, p = 0.0266). None of the histology measures correlated with presence/absence of constipation at 1–2 year follow-up (p = NS). However, smaller ganglion size and higher percentage of NOS neurons correlated with decreased patient-reported quality of life (r = 0.3838, r =  − 0.1809).

Conclusion

1–2 year follow-up may be insufficient to determine if resection margin histology correlates with outcomes. Patient-reported quality of life surveys, although limited in number, suggest that neurotransmitter imbalance at the resection margin may predict poor outcomes in HSCR patients. This study supports the concept that the ganglionated portion of the remaining colon post-surgery may not sustain normal bowel function.

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Acknowledgements

The authors would like to thank Cindy Lazar (Histology Manager, Methodist Le Bonheur Healthcare, Memphis, TN) for her assistance in obtaining archived specimens for our analysis.

Funding

This work was supported by grants from the National Institutes of Health, USA (K08DK098271 to AG, R03DK114543 to AG, R01DK125047 to AG, T35DK113964 to LB and KLF), American College of Surgeons, USA (George H.A. Clowes Career Development Award to AG), and the Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship (to KLF).

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Authors

Contributions

Conception and design of the study: LVV, MF, AG; Acquisition of data: LB, KLF, LVV, MF; Analysis and interpretation of data: LB, KLF, LVV, MF, AG; Drafting/Revision the article: LB, KLF, AG; Final approval: all authors.

Corresponding author

Correspondence to Ankush Gosain.

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The authors have no conflicts of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of Tennessee Health Science Center Institutional Review Board approval (16-04806-XP) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

The University of Tennessee Health Science Center Institutional Review Board granted waiver of informed consent and HIPAA authorization for the collection of data for the study in accord with the criteria and review procedures specified at 45 CFR 164.512(i)(2).

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Brooks, L.A., Fowler, K.L., Veras, L.V. et al. Resection margin histology may predict intermediate-term outcomes in children with rectosigmoid Hirschsprung disease. Pediatr Surg Int 36, 875–882 (2020). https://doi.org/10.1007/s00383-020-04689-x

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Keywords

  • Hirschsprung
  • Aganglionosis
  • Neurotransmitter
  • Enteric nervous system
  • Quality of life