胆道纤维化的发生发展与治疗

胆道纤维化(BF)是病理性胆道损伤修复的结果,主要表现为胆管壁的增厚硬化和管腔的进行性狭窄,最终可能导致胆道梗阻、胆汁性肝硬化、肝衰竭、肝胆恶性肿瘤等严重不良结局。目前的研究将BF描述为某些胆管病的病理特征,对其病因、病理生理、分子机制和治疗缺乏系统总结。BF是胆道系统普遍存在但容易被忽略的疾病状态,可能通过病理性胆道损伤后的异常修复机制促进肝胆疾病的发生和进展,笔者结合国内外最新研究进展,综述BF的概念、临床表现、病因、发病机制和治疗策略,为临床医师提供参考。

Clinical significance of different periampullary diverticulum classifications for endoscopic retrograde cholangiopancreatography cannulation

BACKGROUND Different types of periampullary diverticulum(PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography(ERCP) cannulation,but the clinical significance of the two current PAD classifications for cannulation is limited.AIM To verify the clinical value of our newly proposed PAD classification.METHODS A new PAD classification(Li-Tanaka classification) was proposed at our center.All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared.RESULTS A total of 3564 patients with native papillae were enrolled, including 967(27.13%)PAD patients and 2597(72.87%) non-PAD patients. In the Li-Tanaka classification, type Ⅰ PAD patients exhibited the highest difficult cannulation rate(23.1%, P = 0.01), and type Ⅱ and Ⅳ patients had the highest cannulation success rates(99.4% in type Ⅱ and 99.3% in type Ⅳ, P < 0.001). In a multivariableadjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio(OR) = 1.87, 95% confidence interval(CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group,the difficulty of cannulation in the type Ⅰ PAD group according to the Li-Tanaka classification was greater(OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower(OR = 0.27, 95%CI: 0.11-0.66, P < 0.001),while it was higher in the type Ⅱ PAD group(OR = 4.44, 95%CI: 1.61-12.29, P <0.01).CONCLUSION Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.

Choledocholithiasis characteristics with periampullary diverticulum and endoscopic retrograde cholangiopancreatography procedures:Comparison between two centers from Lanzhou and Kyoto

BACKGROUND Most of study regarding periampullary diverticulum(PAD)impact on endoscopic retrograde cholangiopancreatography(ERCP)therapy for choledocholithiasis based on data from one endoscopy center and lacked to compare the clinical characteristic of choledocholithiasis with PAD from different geographical patients.AIM To compare the choledocholithiasis clinical characteristics between two regional endoscopy centers and analyze impacts of clinical characteristics on ERCP methods for choledocholithiasis patients with PAD.METHODS Patients seen in two endoscopy centers(The First Hospital of Lanzhou University,Lanzhou,Gansu Province,China,and Kyoto Second Red Cross Hospital,Kyoto,Japan)underwent ERCP treatment for the first time between January 2012 and December 2017.The characteristics of choledocholithiasis with PAD were compared between the two centers,and their ERCP procedures and therapeutic outcomes were analyzed.RESULTS A total of 829 out of 3608 patients in the Lanzhou center and 241 out of 1198 in the Kyoto center had choledocholithiasis with PAD.Lots of clinical characteristics were significantly different between the two centers.The common bile duct(CBD)diameter was wider,choledocholithiasis size was lager and multiple CBD stones were more in the Lanzhou center patients than those in the Kyoto center patients(14.8±5.2 mm vs 11.6±4.2 mm,12.2±6.5 mm vs 8.2±5.3 mm,45.3%vs 20.3%,P<0.001 for all).In addition,concomitant diseases,such as acute cholangitis,gallbladder stones,obstructive jaundice,cholecystectomy,and acute pancreatitis,were significantly different between the two centers(P=0.03 to<0.001).In the Lanzhou center,CBD diameter and choledocholithiasis size were lower,and multiple CBD stones and acute cholangitis were less in non-PAD patients than those in PAD patients(13.4±5.1 mm vs 14.8±5.2 mm,10.3±5.4 mm vs 12.2±6.5,39%vs 45.3%,13.9%vs 18.5%,P=0.002 to<0.001).But all these characteristics were not significantly different in the Kyoto center.The proportions of endoscopic sphincterotomy(EST),endoscopic balloon dilatation(EPBD),and EST+EPBD were 50.5%,1.7%,and 42.5%in the Lanzhou center and 90.0%,0.0%,and 0.4%in the Kyoto center,respectively.However,the overall post-ERCP complication rate was not significantly different between the two centers(8.9%in the Lanzhou and 5.8%in the Kyoto.P=0.12).In the Lanzhou center,the difficulty rate in removing CBD stones in PAD was higher than in non-PAD group(35.3%vs 26.0%,P<0.001).But the rate was no significant difference between the two groups in Kyoto center.The residual rates of choledocholithiasis were not significantly different between the two groups in both centers.Post-ERCP complications occurred in 8.9%of the PAD patients and 8.1%of the non-PAD patients in the Lanzhou Center,and it occurred in 5.8%in PAD patients and 10.0%in non-PAD patients in the Kyoto center,all P>0.05.CONCLUSION Many clinical characteristics of choledocholithiasis patients with PAD were significantly different between the Lanzhou and Kyoto centers.The patients had larger and multiple stones,wider CBD diameter,and more possibility of acute cholangitis and obstructive jaundice in the Lanzhou center than those in the Kyoto center.The ERCP procedures to manage native duodenal papilla were different depending on the different clinical characteristics while the overall post-ERCP complications were not significantly different between the two centers.The stone residual rate and post-ERCP complications were not significantly different between choledocholithiasis patients with PAD and without PAD in each center.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography:A single-blind,multicenter,randomized controlled trial

Background:Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography(ERCP),the benefits and safety of high-carbohydrate fluid diet(CFD)intake 2 h before ERCP remain unclear.This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’recovery.Methods:This prospective,multicenter,randomized controlled trial involved 15 tertiary ERCP centers.A total of 1330 patients were randomized into CFD group(n=665)and fasting group(n=665).The CFD group received 400 mL of maltodextrin orally 2 h before ERCP,while the control group abstained from food/water overnight(>6 h)before ERCP.All ERCP procedures were performed using deep sedation with intravenous propofol.The investigators were blinded but not the patients.The primary outcomes included postoperative fatigue and abdominal pain score,and the secondary outcomes included complications and changes in metabolic indicators.The outcomes were analyzed according to a modified intention-to-treat principle.Results:The post-ERCP fatigue scores were significantly lower at 4 h(4.1±2.6 vs.4.8±2.8,t=4.23,P<0.001)and 20 h(2.4±2.1 vs.3.4±2.4,t=7.94,P<0.001)in the CFD group,with least-squares mean differences of 0.48(95%confidence interval[CI]:0.26-0.71,P<0.001)and 0.76(95%CI:0.57-0.95,P<0.001),respectively.The 4-h pain scores(2.1±1.7 vs.2.2±1.7,t=2.60,P=0.009,with a least-squares mean difference of 0.21[95%CI:0.05-0.37])and positive urine ketone levels(7.7%[39/509]vs.15.4%[82/533],χ^(2)=15.13,P<0.001)were lower in the CFD group.The CFD group had significantly less cholangitis(2.1%[13/634]vs.4.0%[26/658],χ^(2)=3.99,P=0.046)but not pancreatitis(5.5%[35/634]vs.6.5%[43/658],χ^(2)=0.59,P=0.444).Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla(odds ratio[OR]:0.61,95%CI:0.39-0.95,P=0.028)in the multivariable models.Conclusion:Ingesting 400 mL of CFD 2 h before ERCP is safe,with a reduction in post-ERCP fatigue,abdominal pain,and cholangitis during recovery.Trail Registration:ClinicalTrials.gov,No.NCT03075280.

Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders:from molecular mechanisms to clinical implications

Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality.Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders,which may promote the development and progression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries.Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases.In this review,we emphasized the importance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations,epidemiology,and aberrant cellular composition involving the biliary ductules,cholangiocytes,immune system,fibroblasts,and the microbiome.We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies.This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.