Trends in Colectomies for Colorectal Neoplasms in Ulcerative Colitis: a National Inpatient Sample Database Analysis over Two Decades
溃疡性结肠炎结直肠肿瘤结肠切除术的趋势: 20 年来的全国住院患者样本数据库分析
- 作者列表："Ni, Alexander","Al-Qahtani, Mohammed","Salama, Ebram","Marinescu, Daniel","Khalil, Maria Abou","Faria, Julio","Morin, Nancy","Ghitulescu, Gabriela","Vasilevsky, Carol-Ann","Boutros, Marylise
Background Rates of colectomy for ulcerative colitis have been decreasing, particularly since the advent of biologics, but the subsequent impact of reduced colectomy rates on the development of neoplasms in chronically treated ulcerative colitis colons is unknown. Purpose To determine trends in colectomy for colorectal neoplasms in adult patients with ulcerative colitis. Methods Adult admissions with ulcerative colitis were identified from the National Inpatient Sample from 1993 to 2015. The rate of colectomy with concurrent colorectal neoplasm served as the primary outcome and was evaluated using time trend linear and multivariable regression. Results There were 366,286 admissions with ulcerative colitis including 16,556 (4.5%) total colectomies. Of those undergoing colectomy, 2018 (12.2%) had a concurrent diagnosis of colorectal neoplasm. The proportion of colectomies for ulcerative colitis with concurrent colorectal neoplasm increased from 10.3 to 12.5% ( p _Trend = 0.004). Specifically, the proportion of colectomies performed for dysplasia/benign neoplasm and rectal cancer increased from 3.5 to 5.6% ( p _Trend < 0.001) and from 2.6 to 3.0% ( p _Trend = 0.028) respectively, and those for colon cancer remained stable (4.5 to 3.9%, p _Trend = 0.423). On multivariate regression, year of colectomy was a significant predictor of colectomy for colorectal neoplasm (OR = 1.044, 95% CI = 1.025–1.062). Discussion Operative management of ulcerative colitis appears to be slowly increasing in oncological indications. The rising proportions of colectomies performed for colorectal neoplasms suggest the need for continued screening in these patients, including rectal surveillance.
背景溃疡性结肠炎的结肠切除术率一直在下降，特别是自生物制剂问世以来，但结肠切除术率降低对慢性治疗溃疡性结肠炎结肠肿瘤发展的影响尚不清楚。目的确定成年溃疡性结肠炎患者结肠切除术治疗结直肠肿瘤的趋势。方法从 1993-2015 年全国住院患者样本中确定患有溃疡性结肠炎的成人住院患者。结肠切除术并发结直肠肿瘤的发生率作为主要结局，采用时间趋势线性和多变量回归进行评价。结果溃疡性结肠炎患者 366,286 例，全结肠切除术 16,556 例 (4.5%)。在接受结肠切除术的患者中，2018 (12.2%) 同时诊断为结直肠肿瘤。溃疡性结肠炎并发结直肠肿瘤行结肠切除术的比例从 10.3 上升到 12.5% ( p _ Trend = 0.004)。具体来说，对异型增生/良性肿瘤和直肠癌进行结肠切除术的比例从 3.5 增加到 5.6% ( p _ 趋势 <0.001)，从 2.6 增加到 3.0% ( p _ 趋势 = 0.028) 分别保持稳定 (4.5 ~ 3.9%，p _ Trend = 0.423)。在多变量回归中，结肠切除术年份是结直肠肿瘤结肠切除术的显著预测因子 (OR = 1.044，95% CI = 1.025-1.062)。讨论溃疡性结肠炎的手术治疗在肿瘤学适应症方面似乎正在缓慢增加。结直肠肿瘤行结肠切除术的比例上升，提示这些患者需要继续筛查，包括直肠监测。
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.