Department of Pediatric Surgery, University Children's Hospital Basel, Basel, BS, Switzerland.
Department of Pediatric Pulmonology, UKBB Ringgold Standard Institution, Basel, BS, Switzerland.
Eur J Pediatr Surg. 2023 Aug;33(4):299-309. doi: 10.1055/a-1889-6355. Epub 2022 Jul 1.
Hirschsprung's disease (HSCR) is a congenital intestinal neurodevelopmental disorder characterized by the absence of enteric ganglion cells in the distal colon. Although Hirschsprung-associated enterocolitis (HAEC) is the most frequent life-threatening complication in HSCR, to date reliable biomarkers predicting the likelihood of HAEC are yet to be established. We established a three-center retrospective study including 104 HSCR patients surgically treated between 1998 and 2019.
Patient-derived cryopreserved or paraffin-preserved colonic tissue at surgery was analyzed via βIII-tubulin immunohistochemistry. We subsequently determined extrinsic mucosal nerve fiber density in resected rectosigmoid specimens and classified HSCR patients accordingly into nerve fiber-high or fiber-low groups. We compared the distribution of clinical parameters obtained from medical records between the fiber-high ( = 36) and fiber-low ( = 68) patient groups. We assessed the association between fiber phenotype and enterocolitis using univariate and multivariate logistic regression adjusted for age at operation.
Enterocolitis was more prevalent in patients with sparse mucosal nerve fiber innervation (fiber-low phenotype, 87%) compared with the fiber-high phenotype (13%; = 0.002). In addition, patients developing enterocolitis had a younger age at surgery (3 vs. 7 months; = 0.016). In the univariate analysis, the odds for enterocolitis development in the fiber-low phenotype was 5.26 (95% confidence interval [CI], 1.67-16.59; = 0.005) and 4.01 (95% CI, 1.22-13.17; = 0.022) when adjusted for age.
Here, we showed that HSCR patients with a low mucosal nerve fiber innervation grade in the distal aganglionic colon have a higher risk of developing HAEC. Consequently, histopathologic analysis of the nerve fiber innervation grade could serve as a novel sensitive prognostic marker associated with the development of enterocolitis in HSCR patients.
先天性巨结肠（HSCR）是一种先天性肠神经发育障碍，其特征是远端结肠缺乏肠神经节细胞。尽管与巨结肠相关的结肠炎（HAEC）是 HSCR 最常见的危及生命的并发症，但迄今为止，尚无可靠的生物标志物来预测 HAEC 的可能性。我们建立了一项包括 104 例 1998 年至 2019 年手术治疗的 HSCR 患者的三中心回顾性研究。
通过 βIII-微管蛋白免疫组织化学分析手术时获得的患者来源的冷冻或石蜡保存的结肠组织。随后，我们确定了切除的直肠乙状结肠标本中粘膜外神经纤维密度，并相应地将 HSCR 患者分为神经纤维高或纤维低组。我们比较了纤维高组（n=36）和纤维低组（n=68）患者的病历记录中临床参数的分布。我们使用单变量和多变量逻辑回归分析调整手术年龄后，评估纤维表型与结肠炎之间的关联。
与神经纤维高组（13%）相比，粘膜神经纤维支配稀疏的患者（纤维低表型，87%）更易发生结肠炎（ = 0.002）。此外，发生结肠炎的患者手术年龄更小（3 个月 vs. 7 个月； = 0.016）。在单变量分析中，纤维低表型发生结肠炎的优势比为 5.26（95%置信区间 [CI]，1.67-16.59； = 0.005）和 4.01（95% CI，1.22-13.17； = 0.022），当调整年龄时。
在这里，我们表明远端无神经节细胞结肠中神经纤维支配程度低的 HSCR 患者发生 HAEC 的风险更高。因此，神经纤维支配程度的组织病理学分析可以作为一种新的与 HSCR 患者结肠炎发展相关的敏感预后标志物。
