Post-colonoscopy Colorectal Cancer in Sweden 2003-2012: Survival, Tumor Characteristics, and Risk Factors.
瑞典结肠镜检查后结直肠癌 2003-2012: 生存率、肿瘤特征和危险因素。
- 作者列表："Forsberg A","Widman L","Sc D MB","Ekbom A","Hultcrantz R
BACKGROUND & AIMS:Rate of post-colonoscopy colorectal cancer (PCCRC) is a measure of colonoscopy quality, but there are conflicting results from studies of survival times of patients with PCCRC. We assessed survival times of patients with PCCRC and characterize microscopic and macroscopic features of post-colonoscopy colorectal tumors. METHODS:We performed a population-based cohort study using data from a database in Sweden, on 458,937 colonoscopies (54.0% women patients) performed from 2003 through 2012. Rates of colorectal cancer within 3 years of a colonoscopy were calculated based on the World Endoscopy Organization guidelines. Risk factors were evaluated using Poisson regression analysis. We used Cox regression models and Kaplan-Meier analyses, stratified by sex, to assess conditional survival. Logistic regression models were used to evaluate features of post-colonoscopy colorectal tumors, including stage location (right, left, or rectum) differentiation grade (high or low), synchronous tumors, perineural growth, resection margins, and mucinous and vessel characteristics. RESULTS:Within 36 months after a colonoscopy, there were 19,184 individuals who had received a diagnosis of CRC; 1384 of these PCCRCs (7.2%). The proportion of individuals with PCCRC decreased from 9.4% in 2003 to 6.1% in 2012. The highest risk factors for PCCRC were prior diagnosis of CRC (relative risk [RR], 3.31; 95% CI, 2.71-4.04), ulcerative colitis (RR, 5.44; 95% CI, 4.75-6.23), Crohn's disease (RR, 3.81; 95% CI, 2.98-4.87), and prior polypectomy (RR, 2.32; 95% CI, 1.97-2.72). Individuals with PCCRCs had shorter survival times than individuals with CRCs detected during the index colonoscopy. Multivariate hazard ratios for PCCRC were 2.75 for men (95% CI, 2.21-3.42) and 2.00 for women (95% CI, 1.59-2.52), respectively. Individuals with left-side PCCRC had shorter survival times that patients with CRC detected during index colonoscopy. Post-colonoscopy colorectal tumors had increased odds of low differentiation grade (odds ratio, 1.27; 95% CI, 1.09-1.49) compared colorectal tumors detected during index colonoscopy. CONCLUSIONS:In analysis of colonoscopies in Sweden, the rate of PCCRCs decreased from 9.4% in 2003 to 6.1% in 2012. Diseases that require surveillance (such as prior colorectal neoplasms and inflammatory bowel diseases) are largest risk factors for PCCRC. Patients with PCCRC have shorter times of survival patients with CRC detected during their initial colonoscopy-especially women and patients with left-side tumors.
背景与目的: 结肠镜检查后结直肠癌 (PCCRC) 的发生率是衡量结肠镜检查质量的指标，但对 PCCRC 患者生存时间的研究结果存在矛盾。我们评估了 PCCRC 患者的生存时间，并表征了结肠镜检查后结直肠肿瘤的微观和宏观特征。 方法: 我们使用来自瑞典数据库的数据进行了一项基于人群的队列研究，从 2003 年到 2012 年进行了 458,937 次结肠镜检查 (54.0% 例女性患者)。根据世界内镜组织指南计算结肠镜检查后 3 年内结直肠癌的发生率。使用 Poisson 回归分析评估危险因素。我们采用 Cox 回归模型和 Kaplan-Meier 分析，按性别分层，评估条件生存率。Logistic 回归模型被用来评估结肠镜检查后结直肠肿瘤的特征，包括分期位置 (右、左或直肠) 分化分级 (高或低) 、同步肿瘤、神经生长、切缘，以及粘液和血管特征。 结果: 结肠镜检查后 36 个月内，有 19,184 例个体接受了 CRC 诊断; 其中 1384 例 pccrc (7.2%)。PCCRC 个体比例从 2003 年的 9.4% 下降到 2012 年的 6.1%。PCCRC 的最高危险因素为既往诊断为 CRC (相对危险度 [RR]，3.31; 95% CI，2.71-4.04) 、溃疡性结肠炎 (RR，5.44; 95% CI, 4.75-6.23) 、克罗恩病 (RR，3.81; 95% CI，2.98-4.87) 和既往息肉切除术 (RR，2.32; 95% CI，1.97-2.72)。与指数结肠镜检查中检测到的 crc 个体相比，pccrc 个体的生存时间较短。PCCRC 的多变量风险比男性为 2.75 (95% CI，2.21-3.42)，女性为 2.00 (95% CI，1.59-2.52)。左侧 PCCRC 个体的生存时间比索引结肠镜检查时检测到的 CRC 患者短。结肠镜检查后结直肠肿瘤与指数结肠镜检查时检测到的结直肠肿瘤相比，低分化分级的几率增加 (比值比，1.27; 95% CI，1.09-1.49)。 结论: 在瑞典结肠镜检查的分析中，pccrc 率从 2003 年的 9.4% 下降到 2012 年的 6.1%。需要监测的疾病 (如既往结直肠肿瘤和炎症性肠病) 是 PCCRC 的最大危险因素。PCCRC 患者在初次结肠镜检查中检测到 CRC 患者的生存时间较短，尤其是女性和左侧肿瘤患者。
METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.
METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.
METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.