CO2 or air cholangiography reduces the risk of post-ERCP cholangitis in patients with Bismuth type IV hilar biliary obstruction.
CO2 或空气胆管造影可降低铋剂 IV 型肝门部胆道梗阻患者 ERCP 术后胆管炎的风险。
- 作者列表："Zhang WH","Ding PP","Liu L","Wang YL","Lai WH","Han JJ","Han J","Li HW
BACKGROUND:Endoscopic biliary stenting by endoscopic retrograde cholangiopancreatography (ERCP) is the most common form of palliation for malignant hilar obstruction. However, ERCP in such cases is associated with a risk of cholangitis. The incidence of post-ERCP cholangitis is particularly high in Bismuth type IV hilar obstruction, and this risk is further increased when the contrast injected for cholangiography is not drained. The present study aims to compare the incidence of cholangitis associated with the use of a contrast agent, air and CO2 for cholangiography in type IV hilar biliary lesions. METHODS:The clinical data of consecutive 70 patients with type IV hilar obstruction, who underwent ERCP from October 2013 to November 2017, were retrospectively analyzed. These patients were divided into three groups based on the agent used for cholangiography: group A, contrast (n = 22); group B, air (n = 18); group C, CO2 (n = 30). These three methods of cholangiography were chronologically separated. Prior to the ERCP, MRCP was obtained from all patients to guide the endoscopic intervention. RESULTS:At baseline, there was no significant difference in terms of the patient's age, gender, symptoms and liver function tests among the three groups (P > 0.05). The complication rates were significantly higher in group A than in groups B and C (63.6% vs. 26.7 and 27.8%, P < 0.05). The incidence of post-ERCP cholangitis was significantly higher in group A (P < 0.05), while the incidence of post-ERCP pancreatitis and bleeding were similar in the three groups. After the ERCP, the mean hospital stay was shorter in groups B and C, when compared to group A (P < 0.05). However, there was no significant difference in the 30-day mortality rate among the three groups (P > 0.05). Furthermore, there was no significant difference between groups B and C in terms of primary end points. CONCLUSION:CO2 or air cholangiography during ERCP for type IV hilar obstruction is associated with reduced risk of post-ERCP cholangitis, when compared to conventional contrast agents.
背景: 内镜下逆行胰胆管造影术 (ERCP) 的胆道支架置入术是恶性肝门部梗阻最常见的姑息治疗方式。然而，在这种情况下，ERCP 与胆管炎的风险相关。在铋 IV 型肝门部梗阻中，ERCP 后胆管炎的发生率特别高，当胆管造影注射的造影剂未引流时，这种风险进一步增加。本研究旨在比较 IV 型肝门部胆管病变中使用造影剂、空气和 CO2 行胆道造影相关胆管炎的发生率。 方法: 回顾性分析 2013 年 10 月至 2017 年 11 月连续 70 例行 ERCP 的 IV 型肝门部梗阻患者的临床资料。根据胆道造影所用药物分为三组: A 组，造影剂 (n = 22); B 组，空气 (n = 18); C 组,CO2 (n = 30)。这三种胆道造影方法按时间顺序分离。ERCP 前，所有患者均获得 MRCP，以指导内镜介入治疗。 结果: 基线时，三组患者的年龄、性别、症状和肝功能检查差异无统计学意义 (p> 0.05)。A 组并发症发生率明显高于 B 组和 C 组 (63.6% vs. 26.7 和 27.8%，p <0.05)。A 组 ERCP 术后胆管炎的发生率明显高于 A 组 (p <0.05)，而三组 ERCP 术后胰腺炎和出血的发生率相似。ERCP 术后 B 、 C 组平均住院时间明显短于 A 组 (p <0.05)。但三组间 30d 死亡率差异无统计学意义 (p> 0.05)。此外，B 组和 C 组在主要终点方面无显著差异。 结论: 与传统造影剂相比，ERCP 治疗 IV 型肝门部梗阻时 CO2 或空气胆管造影可降低 ERCP 术后胆管炎的风险。
METHODS:BACKGROUND & AIMS:Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) exceeds 20% and BTC is currently the leading cause of death in PSC patients. To open new avenues for management, we aimed to delineate novel and clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC). APPROACH & RESULTS:We analysed formalin fixed, paraffin embedded tumor tissue from 186 PSC-BTC patients from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations and copy number variations, along with histomorphological and immunohistochemical characterization. Irrespective of the anatomical localization, PSC-BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, e.g. TP53 (35.5%), KRAS (28.0%), CDKN2A (14.5%), and SMAD4 (11.3%), as well as potentially druggable mutations (e.g. HER2/ERBB2). We found a high frequency of non-typical/non-ductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%) CONCLUSION: Genomic alterations in PSC-BTC include a significant number of putative actionable therapeutic targets. Notably, PSC-BTC show a distinct extrahepatic morpho-molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC-associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome-based personalized treatment strategies in PSC-BTC.
METHODS:BACKGROUND:The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes. METHODS:One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patients were classified as having moderate to severe IBD if they met at least 1 of 3 criteria: (i) Mayo 2 or 3 colitis or Simple Endoscopic Score-Crohn's Disease ≥7 on endoscopy; (ii) acute flare of IBD necessitating steroid rescue therapy; or (iii) post-LT colectomy for medically refractory IBD. RESULTS:Moderate to severe IBD at any time post-transplant was associated with a higher risk of Clostridium difficile infection (27% vs 8% mild IBD vs 8% no IBD; P = 0.02), colorectal cancer/high-grade dysplasia (21% vs 3% both groups; P = 0.004), post-LT colectomy (33% vs 3% vs 0%) and rPSC (64% vs 18% vs 20%; P < 0.001). Multivariate analysis revealed that moderate to severe IBD increased the risk of both rPSC (relative risk [RR], 8.80; 95% confidence interval [CI], 2.81-27.59; P < 0.001) and colorectal cancer/high-grade dysplasia (RR, 10.45; 95% CI, 3.55-22.74; P < 0.001). CONCLUSIONS:Moderate to severe IBD at any time post-LT is associated with a higher risk of rPSC and colorectal neoplasia compared with mild IBD and no IBD. Patients with no IBD and mild IBD have similar post-LT outcomes. Future prospective studies are needed to determine if more intensive treatment of moderate to severe IBD improves long-term outcomes in patients undergoing LT for PSC.
METHODS::T cells from patients with primary sclerosing cholangitis (PSC) show a prominent IL-17 response upon stimulation with bacteria or fungi, yet the reasons for this dominant TH17 response in PSC are not clear. Here, we analyzed the potential role of monocytes in microbial recognition and in skewing the T cell response towards Th17. Monocytes and T cells from blood and livers of PSC patients and controls were analyzed ex vivo and in vitro using trans-well experiments with cholangiocytes. Cytokine production was measured using flow cytometry, ELISA, RNA in situ hybridization and quantitative real time PCR. Genetic polymorphisms were obtained from Immunochip analysis. Following ex vivo stimulation with PMA/Ionomycin, PSC patients showed significantly increased numbers of IL-17A-producing peripheral blood CD4+ T cells compared to PBC patients and healthy controls, indicating increased Th17 differentiation in vivo. Upon stimulation with microbes, monocytes from PSC patients produced significantly more IL-1β and IL-6, cytokines known to drive Th17 cell differentiation. Moreover, microbe-activated monocytes induced the secretion of Th17 and monocyte-recruiting chemokines CCL-20 and CCL-2 in human primary cholangiocytes. In livers of patients with PSC cirrhosis, CD14hi CD16int and CD14lo CD16hi monocytes/macrophages were increased compared to alcoholic cirrhosis and monocytes were found to be located around bile ducts. Conclusion: PSC patients show increased Th17 differentiation already in vivo. Microbe-stimulated monocytes drive Th17 differentiation in vitro and induce cholangiocytes to produce chemokines mediating recruitment of Th17 cells and more monocytes into portal tracts. Taken together, these results point to a pathogenic role of monocytes in patients with PSC.