Laryngeal Carcinoma in Patients With Inflammatory Bowel Disease: Clinical Outcomes and Risk Factors.
- 作者列表："van de Ven SEM","Derikx LAAP","Nagtegaal ID","van Herpen CM","Takes RP","Melchers WJG","Pierik M","van den Heuvel T","Verhoeven RHA","Hoentjen F","Nissen LHC
BACKGROUND:Inflammatory bowel disease (IBD) patients are at increased risk for developing extra-intestinal malignancies, mainly due to immunosuppressive medication. The risk of developing head and neck cancer in immunosuppressed transplant patients is increased. The relation between IBD patients and laryngeal cancer (LC) remains unclear. We aimed (1) to identify risk factors in IBD patients for LC development and (2) to compare clinical characteristics, outcome, and survival of LC in IBD patients with the general population. METHODS:All IBD patients with LC (1993-2011) were retrospectively identified using the Dutch Pathology Database. We performed 2 case-control studies: (1) to identify risk factors, we compared patients with IBD and LC (cases) with the general IBD population; (2) to analyze LC survival, we compared cases with controls from the general LC population. RESULTS:We included 55 cases, 1800 IBD controls, and 2018 LC controls. Cases were more frequently male compared with IBD controls (P < 0.001). For ulcerative colitis (UC), cases were older at IBD diagnosis (P < 0.001). Crohn's disease (CD) cases were more frequently tobacco users (P < 0.001) and more often had stricturing (P = 0.006) and penetrating (P = 0.008) disease. We found no survival difference. Immunosuppressive medication had no impact on survival. CONCLUSIONS:Male sex was a risk factor for LC in IBD patients. Older age at IBD diagnosis was a risk factor for UC to develop LC. Tobacco use and stricturing and penetrating disease were risk factors for LC development in CD patients. Inflammatory bowel disease was not associated with impaired survival of LC. Immunosuppressive medication had no influence on survival.
背景: 炎症性肠病 (IBD) 患者发生肠外恶性肿瘤的风险增加，主要是由于免疫抑制药物。免疫抑制移植患者发生头颈部癌症的风险增加。IBD 患者与喉癌 (LC) 的关系仍不清楚。我们的目的是 (1) 确定 IBD 患者发生 LC 的危险因素，(2) 比较 IBD 患者与普通人群 LC 的临床特征、结局和生存率。 方法: 采用荷兰病理学数据库回顾性鉴定所有 IBD LC 患者 (1993-2011)。我们进行了 2 项病例对照研究 :( 1) 为了确定危险因素，我们将 IBD 和 LC 患者 (病例) 与普通 IBD 人群进行了比较; (2) 分析 LC 生存率,我们比较了来自普通 LC 人群的病例与对照。 结果: 我们纳入了 55 例病例，1800 例 IBD 对照，2018 例 LC 对照。与 IBD 对照组相比，病例为男性更常见 (P <0.001)。对于溃疡性结肠炎 (UC)，IBD 诊断时病例年龄较大 (P <0.001)。克罗恩病 (CD) 病例更经常吸烟 (P <0.001)，更经常发生狭窄 (P = 0.006) 和穿透性 (P = 0.008) 疾病。我们没有发现生存差异。免疫抑制药物对生存率无影响。 结论: 男性是 IBD 患者发生 LC 的危险因素。IBD 诊断时年龄较大是 UC 发生 LC 的危险因素。烟草使用、狭窄和穿透病是 CD 患者发生 LC 的危险因素。炎症性肠病与 LC 的生存率受损无关。免疫抑制药物对生存率无影响。
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.