Intest Res.  2024 Jul;22(3):297-309. 10.5217/ir.2023.00129.

Intestinal ultrasound for intestinal Behçet disease reflects endoscopic activity and histopathological findings

• Yaguchi K
• Kunisaki R
• Sato S
• Hirai K
• Izumi M
• Fukuno Y
• Tanaka M
• Okazaki M
• Wu R
• Nishikawa Y
• Matsune Y
• Shibui S
• Nakamori Y
• Nishio M
• Matsubayashi M
• Ogashiwa T
• Fujii A
• Toritani K
• Kimura H
• Kumagai E
• Sasahara Y
• Inayama Y
• Fujii S
• Ebina T
• Numata K
• Maeda S

• KMID: 2558190
• DOI: http://doi.org/10.5217/ir.2023.00129

Abstract

Background/Aims
Intestinal Behçet disease is typically associated with ileocecal punched-out ulcers and significant morbidity and mortality. Intestinal ultrasound is a noninvasive imaging technique for disease monitoring. However, no previous reports have compared intestinal ultrasound with endoscopic ulcer activity or histopathological findings for intestinal Behçet disease. We evaluated the usefulness of intestinal ultrasound for assessing the activity of ileocecal ulcers in intestinal Behçet disease.
Methods
We retrospectively compared intestinal ultrasound findings with 73 corresponding endoscopic images and 6 resected specimens. The intestinal ultrasound findings were assessed for 7 parameters (bowel wall thickness, vascularity [evaluated using the modified Limberg score with color Doppler], bowel wall stratification, white-plaque sign [strong hyperechogenic lines or spots], mesenteric lymphadenopathy, extramural phlegmons, and fistulas), and endoscopic ulcer activity was classified into active, healing, and scar stages. Histopathological findings were evaluated by consensus among experienced pathologists.
Results
Bowel wall thickness (P< 0.001), vascularity (P< 0.001), loss of bowel wall stratification (P= 0.015), and white-plague sign (P= 0.013) were significantly exacerbated in the endoscopic active ulcer stage. Receiver operating characteristic curve analysis revealed that a bowel wall thickness of > 5.5 mm (sensitivity 89.7%, specificity 85.3%) was potentially useful for detecting active lesions. When compared with histopathological findings, an increase in bowel wall thickness reflected the ulcer marginal ridge, and the white-plaque sign reflected the ulcer bottom.
Conclusions
Intestinal ultrasound is useful for monitoring intestinal ulcer activity in intestinal Behçet disease.

Keyword

Behçet disease; Intestinal diseases; Ultrasonography; Ulcer; Endoscopy

Figure

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  Fig. 1. Endoscopic classification of ileocecal ulcers in intestinal Behçet disease. (A) Active stage: ulcers accompanied by edema, with white plaques adhering to the ulcer bottom and/or exposed blood vessels. (B) Healing stage: regenerative epithelium appearing around the ulcer and a shallower ulcer bottom. (C) Scar stage: ulcers with scarring.

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  Fig. 2. Typical intestinal ultrasound (IUS) images of intestinal Behçet disease ulcers. (A) Ulcer 1 is a large, shallow ulcer that straddles the ileocecal valve. The images show obscurity of the 5 layers of the bowel wall, hyperechogenic spots in the bowel wall (light blue arrow), and extramural phlegmons (light green arrow). Bowel wall thickness was noted as the average of 3 measurements in the thickest part of the lesion (double-headed arrows). (B) IUS image of ulcer 1 observed from a different angle than that in panel (A). Loss of the 5 layers of the bowel wall, hyperechogenic line in the intestinal lumen (light blue arrows), and extramural phlegmons (light green arrows) are seen. (C) Ulcer 2 is a typical circular punched-out ulcer in the terminal ileum. The intestinal tract is thickened segmentally, and the 5 layers of the bowel wall have disappeared (double-headed arrows). Hyperechogenic spots in the bowel wall can also be seen (light blue arrow). The image shows the preoperative IUS measurements of bowel wall thickness (arrow ①) and distance from the outer muscular layer to the white-plaque sign (arrow ②). (D) Vascularity was evaluated by color Doppler and graded according to the modified Limberg scoring system. Longer stretches of vascularity reaching the mesentery can be seen (grade 3). (E) Gross findings in a formalin-fixed specimen of the resected intestinal tract removed by ileocecal resection. The red dotted lines represent the resection lines. (F) Gross findings of ulcer 1 in a formalin-fixed tissue section. (G) Gross findings of ulcer 2 in a formalin-fixed tissue section. (H) Histopathological sample of ulcer 2 (hematoxylin and eosin staining, ×6.6). (I) Histopathological sample of ulcer 2 (hematoxylin and eosin staining, ×11.2). The muscular layer is the area indicated by the red bent arrow, and the subserosal fibrous layer is the area indicated by the blue bent arrow. Histopathological measurement of the distance from the top of the ulcer marginal ridge to the outside of the muscular layer (arrow ①) and the distance from the ulcer bottom to the outside of the muscular layer (arrow ②). (J) Ultrasound image of ulcer 2 with water-immersion observation after formalin fixation; the muscular layer (red bent arrow) and the subserosal fibrosis layer (blue bent arrow) are observed as distinct layers with different concentrations on ultrasound.

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  Fig. 3. Patient flow diagram showing the patient selection process. A total of 110 patients were diagnosed with intestinal Behçet disease (BD) at Yokohama City University Medical Center between 2007 and 2019. Of the 87 examinations for 59 patients with typical ileocecal intestinal BD ulcers who underwent intestinal ultrasound (IUS) and colonoscopy (CS) within 2 weeks, the findings for 73 examinations of 47 patients were included after applying the exclusion criteria. aDuplicate cases are included.

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  Fig. 4. Comparison of intestinal ultrasound (IUS) findings and endoscopic ulcer activity. (A) The mean bowel wall thickness for each endoscopic activity of intestinal ulcers in Behçet disease. The mean bowel wall thickness of the control group was 1.9 mm (n=10), scar group was 4.3 mm (n=18), healing group was 4.6 mm (n=16), and active group was 7.9 mm (n=39). There were significant differences between the active stage and the healing stage, scar stage, and healthy controls, and between the healthy controls and the healing stage and scar stage (P<0.001 for each). (B) Receiver operating characteristic curve to determine the optimal cutoff value for active lesions. Bowel wall thickness >5.5 mm was indicated to detect the active stage (sensitivity 89.7%, specificity 85.3%, area under the curve 0.90, 95% confidence interval 0.83–0.98). (C) Assessment of vascularity graded by the modified Limberg scoring system for each endoscopic activity of intestinal ulcers in Behçet disease. Vascularity was significantly different in the active stage compared with the other stages (P<0.001 for each). (D) Assessment of bowel wall stratification for each endoscopic activity of intestinal ulcers in Behçet disease. There was a significant difference only between the active stage and healthy controls (P=0.008). (E) Assessment of the white-plaque sign for each endoscopic activity of intestinal ulcers in Behçet disease. The white-plaque sign was significantly different only between the active stage and healthy controls (P=0.001).

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  Fig. 5. Comparison of endoscopic ulcer size (maximum diameter) and bowel wall thickness by intestinal ultrasound (IUS). Spearman correlation coefficient revealed that bowel wall thickness showed a weak but positive correlation with ulcer size measured by colonoscopy. CI, confidence interval.

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  Fig. 6. Comparison of wall thickness and the white-plaque sign by preoperative intestinal ultrasound (IUS) and histopathological measurement. Spearman correlation coefficient revealed that the bowel wall thickness captured by IUS reflected the distance to the peak of the ulcer margin elevation (the mean bowel wall thicknesses measured by IUS and histopathology were 10.5 mm and 8.9 mm, respectively), with a strong correlation. Additionally, the white-plaque sign reflected the ulcer bottom depending on the distance from the muscular layer (the mean values were 3.1 mm and 3.1 mm, respectively), also with a strong correlation. CI, confidence interval.

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