P1179 - Evaluation of the Diagnostic Accuracy of Submucosal Nerve Trunk Diameter for Diagnosis of Hirschsprung Disease

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Lili Miles, MD

Nemours Children's Health, Florida
Orlando, Florida

Lili Miles, MD¹, Roberto Gomez Suarez, MD², Amanda Jenkins, MS², Matthew Robinson, MS³, Stephanie Sutton, MPH⁴, Michael V. Miles, PharmD⁵
¹Nemours Children's Health, Florida, Orlando, FL; ²Nemours Children's Hospital, Orlando, FL; ³University of Central Florida, Orlando, FL; ⁴University of Central Florida College of Medicine, Orlando, FL; ⁵UCF, Orlando, FL

Introduction: Important histopathological features of Hirschsprung disease (HD), i.e. aganglionosis and submucosal nerve hypertrophy, can be identified by rectal suction biopsy (RSB). Although studies have suggested that micrometric determination of submucosal nerve trunk diameter (SND) >40µm correlates with aganglionosis, reports often cite that age-related factors limit the reliability of SND. We hypothesize that 1) the reliability of SND by RSB may be significantly improved by using a more accurate SND cut-off, and 2) that age-related variability is minimal. The purpose of this study is to evaluate the diagnostic reliability of SND as a biomarker for HD in consecutive patients using an optimized SND cut-off, and an improved method for diagnostic assessment of HD in RSB tissues.

Methods: This retrospective 2-phase study was approved by the institutional review board. Electronic medical record data were collected for all study patients. Patients with history of HD post pull-through surgery or inadequate RSB tissue for pathology evaluation were excluded. In phase I (predictive cohort) all patients who received RSB in our institution for diagnosis of HD between 10/2012-10/2020 were identified. SND was evaluated using receiver operator characteristic (ROC) analysis to determine the cutoff for maximum sensitivity and specificity for HD diagnosis. In phase II (temporal validation cohort) data were collected from all patients with RSB for HD diagnosis between 11/2020-2/2023. The SND of this cohort was evaluated by an experienced pathologist without knowledge of the final diagnosis. Using the SND cut-off from phase I, phase II subjects were unblinded as HD or non-HD. The diagnostic accuracy was then determined.

Results: In phase I 96 subjects (median age 24mo; range 2d-18y) were identified, including 11 with HD. SND was significantly increased in HD subjects (Table). A total of 17 subjects (median age 4mo; range 2d-6y) were identified in phase II, including 4 with HD. ROC analysis indicated an optimized cut-off of 45.5µm (AUC=1.0). Using the 45.5µm cut-off and the true diagnosis, again the diagnostic accuracy was 100%. No statistically significant relationship (p >0.2) was found between age and SND in either cohort (ANOVA).

Discussion: Using an optimized cut-off and improved methodology, our results indicate that SND should be considered an important factor for the histopathological diagnosis of HD, and that age has minimal effect on diagnostic accuracy of SND. Further validation of these results is needed.

Figure: Comparison of RSB slides showing submucosan nerve diameter measurements for (A) a 5 year-old non-HD control, (B) a 2 day-old HD male, and (C) a 5 year-old HD male.

	Age < 1 mo Mean(SD)/Median		Age 1 mo - 60 mos Mean(SD)/Median		p-value (non-HD vs HD)
	non-HD	HD	non-HD	HD	p-value (non-HD vs HD)
Phase I: N	7	7	54	4
Submucosal Depth Max (µm)	^a540(339)/ 660	^a779(546)/ 800	^b877(531)/ 725	^b988(392)/ 950	^a0.34/ ^b0.41
Nerve Diameter Max (µm)	^c20(5)/ 20	^c65(22)/ 55	^d28(7)/ 28	^d66(15)/ 65	^c0.002/ ^d0.001
Muscularis Mucosa Thickness Max (µm)	^e73(32)/ 55	^e86(58)/ 80	^f238(199)/ 200	^f233(89)/ 215	^e0.85/ ^f0.72
Phase II: N	3	2	10	2
Submucosal Depth Max (µm)	^g628(216)/ 650	^g870(325) 870	^h709(216/ 685	^h1178(279)/ 1178	^g0.56/ ^h1.0
Nerve Diameter Max (µm)	ⁱ20(9)/ 25	ⁱ81(46)/ 81	^j26(23)/ 27	^j58(0) 58	ⁱ0.076/ ^j0.03
Muscularis Mucosa Thickness Max (µm)	^k68(51)/ 55	^k58(25)/ 58	^l191(171)/ 123	^l863(902)/ 863	^k0.053/ ^l0.16

Table: Comparison of phase I and phase II micrometric results for younger (<1 mo) and older (1mo-60mos) subjects with and without Hirschsprung disease (HD) diagnosis. (Mann-Whitney test)

Disclosures:

Lili Miles indicated no relevant financial relationships.

Roberto Gomez Suarez indicated no relevant financial relationships.

Amanda Jenkins indicated no relevant financial relationships.

Matthew Robinson indicated no relevant financial relationships.

Stephanie Sutton indicated no relevant financial relationships.

Michael Miles indicated no relevant financial relationships.

Lili Miles, MD¹, Roberto Gomez Suarez, MD², Amanda Jenkins, MS², Matthew Robinson, MS³, Stephanie Sutton, MPH⁴, Michael V. Miles, PharmD⁵. P1179 - Evaluation of the Diagnostic Accuracy of Submucosal Nerve Trunk Diameter for Diagnosis of Hirschsprung Disease, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.