성인에서 발생한 거대 결장 국소 신경절세포감소증: 전향적 코호트 연구

Abstract

OBJECTIVES: It is still controversial whether adult-onset megacolon with focal stenosis is a unique disease entity. We describe a cohort of 29 patients with a putative new GI neuromuscular disease, focal hypoganglionosis adult-onset megacolon (FHAM) at our institution from 2017 to 2020. METHODS: This prospective cohort study assessed the radiologic, endoscopic, histopathologic phenotyping, and treatment outcomes of patients with FHAM. stool samples were compared with those of 13 asymptomatic volunteers using 16S rRNA gene sequencing. Data of community controls (19,948 adults aged 40-60 years undergoing health screening) were analyzed to identify the risk factors. Experts in the UK re-reviewed the clinical features and pathological specimens according to the international guidance for GI neuromuscular pathology. REUSLTS: The median age of FHAM patients at symptom onset was 59 years (range 32.0–74.9) with mean symptom onset only 1 year before diagnosis. All patients had focal stenotic regions with proximal bowel dilatation (mean diameter of 78.8 mm; 95% CI, 72–86). Comparison with community controls showed no obvious risk factors. Ten patients underwent surgery. All exhibited significant hypoganglionosis: 5.4 (IQR, 3.7–16.4) myenteric ganglion cells/cm in stenotic regions compared to proximal 278 (190–338) and distal 95 (45–213) colonic cell densities. Hypoganglionosis was associated with CD3+ T cells along the myenteric plexus. Colectomy was associated with significant symptom improvements compared to ongoing medical treatment (changes in Global Bowel Satisfaction scale score, -5.4 [surgery] vs. -0.3 [medical] points; P < 0.001). Bacterial richness and diversity were more significantly increased in patients with FHAM than in asymptomatic volunteers. Verrucomicrobia at the phylum level and Frisingicoccus, Ruthenibacterium, and Agathobaculum at the genus level were significantly more prevalent in patients with FHAM than in asymptomatic volunteers (P < 0.05). CONCLUSIONS: FHAM appears to be a new enteric neuropathy characterized by hypoganglionosis that may be secondary to inflammation. Bowel resection appears to benefit patients. FHAM is also associated with a rich and diverse fecal microbiota, with a high abundance of the genus, Verrucomicrobia and the genera, Frisingicoccus, Ruthenibacterium, and Agathobaculum.