PO.PR02.03 · 预防研究
在家族性腺瘤性息肉病Pirc大鼠模型中,采用多用途硬质内镜的结肠镜检查与死后息肉检出的比较
Comparison of colonoscopy using a multipurpose rigid endoscope with postmortem detection of polyp in Pirc rat model of familial adenomatous polyposis
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摘要 Abstract
中文摘要
背景:家族性腺瘤性息肉病(FAP)是一种罕见病,影响约万分之一的个体,占结直肠癌病例的<1%。未经治疗的FAP具有近100%的终生结直肠癌风险,通常在40岁前显现,并在15-25岁之间通过结肠切除术治疗。FAP的Pirc(大鼠结肠息肉病,polyposis in rat colon)模型携带与人类类似的Apc基因突变。该模型随年龄增长在结肠和十二指肠中形成多发息肉,被广泛用于测试预防性干预和机制研究。对息肉数量、大小和分级的纵向监测对于预防性干预疗效的临床前测试至关重要,并可通过结肠镜检查实现。本研究中,我们比较了硬质内镜结肠镜检查与Pirc大鼠息肉的死后分析。
方法:使用硬质内镜(Small Coloview镜,10 cm,Karl Storz,德国图特林根)检查16周龄雄性和雌性Pirc大鼠(n=8)的结肠。结肠镜检查前,用异氟烷麻醉大鼠,用温水冲洗结肠以清除粪便物质。在视频回顾中,根据管腔阻塞程度对息肉进行分级:G1:几乎无法检测;G2:≥几乎无法检测至<1/8管腔;G3:≥1/8至<1/4管腔;G4:≥1/4至<1/2管腔;G5:≥1/2管腔至完全阻塞。随后处死动物,切除结肠以确定息肉数量,并用数字卡尺(General® Ultratech,美国加利福尼亚州)测量直径。使用Wilcoxon配对符号秩检验比较两种方法之间的总息肉数和可检测息肉数。报告每个息肉分级的息肉直径均值±标准差(SD)。统计分析使用GraphPad Prism v.10进行。
结果:使用内镜的息肉总数中位数为2(范围:0-5),死后为3(范围:1-12),无统计学显著差异(p= 0.09)。由于硬质内镜仅能可视化大鼠结肠远端10 cm,故比较了可检测息肉数。死后可检测息肉数中位数为2.5(范围:0-7),与结肠镜检查无显著差异(p= 0.5)。息肉直径均值±SD如下:G2:2.9±0.7 mm,G3:3.4±0.5 mm,G4:3.6±0.6 mm,G5:3.6±0.7。结肠镜检查的局限性包括无法完整可视化整个结肠、难以区分相邻息肉,以及检测直肠息肉的困难。
结论:使用硬质内镜进行息肉检测是可行的,且与死后评估相当,支持其用于临床前预防研究中的纵向监测。柔性和可延伸内镜可能增强息肉检测和监测。致谢:本研究由CPRIT RP240401资助。Rashim Singh博士由NCATS/NIH资助,奖项编号K12TR004522。
查看英文原文 English abstract
Background : Familial adenomatous polyposis (FAP) is a rare disease affecting ~1 in 10,000 individuals and accounts for <1% of colorectal cancer cases. Untreated FAP carries a nearly 100% lifetime risk of colorectal cancer, typically manifesting by age 40 and is treated by colon resection between 15-25 of age. The Pirc ( p olyposis i n r at c olon) model of FAP harbors an Apc gene mutation analogous to that in humans. This model develops multiple polyps in the colon and duodenum with age and is widely used to test preventive interventions and in mechanistic studies. Longitudinal monitoring of polyp number, size, and grade is essential for preclinical testing of efficacy of preventive interventions and can be achieved through colonoscopy. In this study, we compared rigid endoscope-enabled colonoscopy with postmortem analysis of polyps in Pirc rats.
Methods : Colons of 16-week-old male and female Pirc rats (n=8) were examined using a rigid endoscope (Small Coloview scope, 10 cm, Karl Storz, Tuttingen, Germany). Before colonoscopy, rats were anesthetized with isoflurane, colons were flushed with warm water to remove fecal matter. In the video review, polyps were graded based on the degree of lumen obstruction: G1: barely detectable; G2: ≥ barely detectable to <1/8 th of lumen; G3: ≥1/8 to <1/4 of lumen; G4: ≥1/4 to <1/2 of lumen; and G5: ≥1/2 of lumen to complete blockade. Animals were then euthanized, and colons were excised to determine polyp number and diameter measured with digital caliper (General® Ultratech, CA, USA). Total and detectable polyp counts were compared between the two methods using Wilcoxon matched-pairs signed rank test. Mean ± standard deviation (SD) of polyp diameter for each polyp grade was reported. Statistical analyses were performed using GraphPad Prism v.10.
Results : The median total polyps count was 2 (range: 0-5) using the endoscope and 3 (range: 1-12) postmortem, with no statistically significant difference (p= 0.09). Because the rigid endoscope visualizes only the distal 10 cm of rat colon, detectable polyps were compared. The median detectable polyps count was 2.5 (range: 0-7) postmortem and was not significantly different from colonoscopy (p= 0.5). The mean ± SD of the polyp diameter was as follows: G2: 2.9±0.7 mm, G3: 3.4±0.5 mm, G4: 3.6±0.6 mm, and G5: 3.6±0.7. Limitations of colonoscopy included incomplete visualization of the entire colon, difficulty distinguishing adjacent polyps, and challenges in detecting rectal polyps.
Conclusion : Polyp detection using a rigid endoscope is feasible and comparable to postmortem evaluation, supporting its use for longitudinal monitoring in preclinical prevention studies. Flexible and extendable endoscopes may enhance polyp detection and monitoring. Acknowledgements: This research was funded by CPRIT RP240401. Dr. Rashim Singh is supported by the NCATS/NIH under award number K12TR004522.
利益披露 Disclosure
I. T. Narkar, None.
V. Tumbas Saponjac,
Sanarentero LLC Employment, Independent Contractor, Patent, Other Intellectual Property.
M. Hu,
Sanarentero LLC g., Board of Directors, non-salaried role), Other Business Ownership, Patent, Other Intellectual Property.
R. Singh,
Sanarentero LLC Employment, g., Board of Directors, non-salaried role), Other Business Ownership, Patent, Other Intellectual Property.