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阑尾切除术对实验性溃疡性结肠炎结肠炎症和肿瘤的影响。

Effect of appendicectomy on colonic inflammation and neoplasia in experimental ulcerative colitis.

机构信息

Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1149, Centre de Recherche sur l'Inflammation, Paris, France.

Laboratory of Excellence INFLAMEX (Institute of Inflammatory Diseases), Pôle de Recherche et d'Enseignement Supérieur, Sorbonne Paris Cité, Paris, France.

出版信息

Br J Surg. 2016 Oct;103(11):1530-8. doi: 10.1002/bjs.10209. Epub 2016 Aug 8.

Abstract

BACKGROUND

Ulcerative colitis (UC) promotes cancer, and can be ameliorated by early appendicectomy for appendicitis. The aim of the study was to explore the effect of appendicectomy on colitis and colonic neoplasia in an animal model of colitis and a cohort of patients with UC.

METHODS

Five-week old IL10/Nox1(DKO) mice with nascent colitis and 8-week-old IL10/Nox1(DKO) mice with established colitis underwent appendicectomy (for experimental appendicitis or no appendicitis) or sham laparotomy. The severity and extent of colitis was assessed by histopathological examination, and a clinical disease activity score was given. From a cohort of consecutive patients with UC who underwent colectomy, the prevalence of appendicectomy and pathological findings were collected from two institutional databases.

RESULTS

Appendicectomy for appendicitis ameliorated experimental colitis in the mice; the effect was more pronounced in the 5-week-old animals. Appendicectomy in the no-appendicitis group was associated with an increased rate of colonic high-grade dysplasia (HGD) or cancer compared with rates in sham and appendicitis groups (13 of 20 versus 0 of 20 and 0 of 20 respectively; P < 0·001). Fifteen of 232 patients who underwent colectomy for UC had previously had an appendicectomy, and nine of these had colonic cancer or HGD. Thirty (13·8 per cent) of 217 patients with the appendix in situ had colonic neoplastic lesions. Multivariable analysis showed that previous appendicectomy was associated with colorectal neoplasia (odds ratio 16·88, 95 per cent c.i. 3·32 to 112·69).

CONCLUSION

Appendicectomy for experimental appendicitis ameliorated colitis. The risk of colorectal neoplasia appeared to increase following appendicectomy without induced appendicitis in a mouse model of colitis, and in patients with UC who had undergone appendicectomy. Surgical relevance Appendicectomy for appendicitis protects against UC. In this murine model of colitis, appendicectomy for experimental appendicitis protected against colitis, but appendicectomy without appendicitis promoted colorectal carcinogenesis. In patients with ulcerative colitis who underwent colectomy, absence of the appendix (proof of previous appendicectomy) in the resection specimen was independently associated with colorectal neoplasia. Although patients with UC and a history of appendicectomy represent a small subset, they may need closer monitoring for colorectal neoplasia.

摘要

背景

溃疡性结肠炎(UC)可促进癌症的发生,早期行阑尾切除术治疗阑尾炎可改善其预后。本研究旨在探讨阑尾切除术对结肠炎和结直肠肿瘤的影响,该研究在结肠炎动物模型和 UC 患者队列中进行。

方法

5 周龄新生结肠炎的 IL10/Nox1(DKO) 小鼠和 8 周龄已建立结肠炎的 IL10/Nox1(DKO) 小鼠接受阑尾切除术(用于实验性阑尾炎或非阑尾炎)或假手术。通过组织病理学检查评估结肠炎的严重程度和范围,并给予临床疾病活动评分。从连续接受结肠切除术的 UC 患者队列中,从两个机构数据库中收集阑尾切除术和病理发现的患病率。

结果

阑尾切除术治疗阑尾炎可改善小鼠的实验性结肠炎;该效果在 5 周龄动物中更为明显。非阑尾炎组的阑尾切除术与结肠高级别异型增生(HGD)或癌症的发生率增加有关,与假手术组和阑尾炎组相比(分别为 13/20 与 0/20 和 0/20;P<0.001)。232 例接受结肠切除术治疗 UC 的患者中,15 例曾行阑尾切除术,其中 9 例患有结直肠癌或 HGD。217 例保留阑尾的患者中有 30 例(13.8%)有结肠肿瘤病变。多变量分析显示,既往阑尾切除术与结直肠肿瘤有关(比值比 16.88,95%置信区间 3.32 至 112.69)。

结论

阑尾切除术治疗阑尾炎可改善结肠炎。在结肠炎动物模型和接受阑尾切除术的 UC 患者中,无诱导性阑尾炎的阑尾切除术似乎会增加结直肠肿瘤的风险。

临床相关性

阑尾炎切除术治疗阑尾炎可预防 UC。在这种结肠炎动物模型中,阑尾切除术治疗阑尾炎可预防结肠炎,但阑尾炎切除术无阑尾炎可促进结直肠癌变。在接受结肠切除术的 UC 患者中,切除标本中阑尾缺失(既往阑尾切除术的证据)与结直肠肿瘤独立相关。尽管 UC 合并阑尾切除术的患者占一小部分,但他们可能需要更密切监测结直肠肿瘤。

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