| PART1 Study on Clinicopathological Characteristics and Possible Mechanism of hepatolithiasis Complicated with Bile Duct StrictureObjective: To explore the possible mechanism of bile duct stricture after hepatolithiasis by studying the changes of local microenvironment of cholangitis and bile duct stricture in patients with hepatolithiasis.Method: 40 cases of hepatolithiasis with bile duct stricture were collected as stricture and hyperplasia group,and 30 cases of hepatolithiasis with cholangitis underwent hepatectomy as inflammation group.Liver tissue samples of 20 patients who underwent hepatectomy due to liver injury in the same period were taken as normal group.HE staining,Masson staining and immunohistochemistry were used to detect the distribution density of fibroblasts,the infiltration grade of inflammatory cells,the proliferation of collagen fibers and the positive expression of Survivin,TGF-?1 and Caspase-3 in tissues.Results:1.There were 189 cases of abdominal pain and discomfort at admission,including 56 cases of fever,87 cases of jaundice and 34 cases of Charcot triad.Among them,74 cases had a history of previous biliary surgery,52 cases had a history of biliary surgery,and 22 cases had a history of 2 previous biliary operations.There were 76 patients with bile duct stricture,accounting for 21.11% of the collected cases.There were 40 patients with intrahepatic bile duct stones located in the right lobe of the liver,105 patients with intrahepatic bile duct stones in the left lobe of the liver,9 patients with bile duct stones in both sides of the liver,and 206 patients with intrahepatic bile duct stones complicated with extrahepatic bile duct stones.Among the 360 patients included in the study,228 patients underwent hepatectomy,including 19 cases of biliary tract infection,8 cases of residual stones,11 cases of stone recurrence and 14 cases of bile leakage.2.Pathological comparison between the stricture and hyperplasia group and the inflammation group: in the inflammation group,part of the bile duct wall showed fibrosis and began to thicken,part of the bile duct mucosa was damaged,a small amount of collagen fibers proliferated and the direction was disordered.Extensive infiltration of inflammatory cells can be seen in the microscopic visual field,mainly including lymphocytes,few neutrophils and monocytes,mainly in the submucosa and around the glands of the bile duct wall.In the stricture and hyperplasia group,severe fibrosis of bile duct wall,thickening of some bile duct wall,uneven thickness,disordered direction and proliferation of scattered collagen fibers could be seen.It can also be seen that the increased density of fibroblasts,nuclear hypertrophy,bile duct mucosal epithelium began to be damaged and exfoliated,accompanied by extensive infiltration of inflammatory cells,mainly a large number of lymphocytes,a small number of neutrophils and monocytes and so on.3.The positive expression rates of TGF-?1 in the above three groups were 52.5% in the stenosis group,30.00% in the inflammatory group and 5.0% in the normal group,respectively,and there were significant differences among the three groups(P<0.01).The positive expression rate of Survivin in the above three groups was 65.00% in the stenosis hyperplasia group,36.67% in the inflammation group and 10.00% in the normal group.There was significant difference between the stenosis group and the inflammation group,the stenosis group and the normal group(P<0.01),but there was no significant difference between the inflammation group and the normal group(P>0.05).The positive expression rates of Caspase-3 in the above three groups were 32.5%in the stenosis group,56.67% in the inflammatory group and 95.00% in the normal group.there was significant difference among the three groups(P<0.01).Conclusion:1.In this experiment,HE staining,Masson staining and immunohistochemical staining were used to find the difference between cholangitis combined with intrahepatic bile duct and bile duct stricture and hyperplasia: in the inflammation group,part of the bile duct wall showed fibrosis and began to thicken,part of the bile duct mucosa was damaged,a small amount of collagen fibers proliferated,and the direction was disordered.Extensive infiltration of inflammatory cells can be seen in the microscopic visual field,mainly including lymphocytes,few neutrophils and monocytes,mainly in the submucosa and around the glands of the bile duct wall.Severe fibrosis of bile duct wall,thickening of some bile duct wall,uneven thickness,disordered direction and proliferation of scattered collagen fibers could be seen in the stricture and hyperplasia group.It can also be seen that the increased density of fibroblasts,nuclear hypertrophy,bile duct mucosal epithelium began to be damaged and exfoliated,accompanied by extensive infiltration of inflammatory cells,mainly a large number of lymphocytes,a small number of neutrophils and monocytes and so on.2.The positive expression rates of TGF-?1 and Survivin were higher in intrahepatic bile duct stricture and hyperplasia tissues,and there was a positive correlation between them.The positive expression rate of Caspase-3 in intrahepatic bile duct stricture and hyperplasia tissues was lower,and negatively correlated with the former two,suggesting that the expression and interaction of the three may play a role in promoting the occurrence and development of hepatolithiasis-associated bile duct strictures.PART2 Expression and Clinical Significance of TGF-?1,Survivin and Caspase-3 in Intrahepatic Cholangiocarcinoma Associated with Intrahepatic CholelithiasisObjective: To study the pathological changes of intrahepatic bile duct in patients with hepatolithiasis complicated with intrahepatic cholangiocarcinoma,and to explore the correlation between the expression of TGF-?1,Survivin and Caspase-3 and intrahepatic cholangiocarcinoma.Methods: The expressions of TGF-?1,Survivin and Caspase-3 in intrahepatic bile duct tissues of 52 patients with intrahepatic cholangiocarcinoma(tumor group),30 patients with hepatolithiasis complicated with chronic inflammation(inflammatory hyperplasia group)and 30 normal intrahepatic bile duct tissues(normal group)were detected by immunohistochemical method.The relationship between the expression of three markers and the clinicopathological features and prognosis of patients with intrahepatic cholangiocarcinoma was analyzed.Results:1.A total of 52 cases of intrahepatic cholangiocarcinoma diagnosed by pathology in our hospital from 2013 to 2019 were collected and classified into tumor group.In the tumor group,there were 8 cases of liver cirrhosis,15 cases of cholelithiasis,15 cases of Hbs Ag positive,22 cases of lymph node metastasis and 12 cases of vascular invasion.Univariate analysis showed that the postoperative prognosis of patients with intrahepatic cholangiocarcinoma was related to lymph node metastasis,tumor differentiation,vascular invasion,tumor maximum diameter,R0 resection,CA199,AFP,TGF-?1,Survivin and Caspase-3 expression(all P<0.05),but not with age,sex,liver cirrhosis,choledocholithiasis and Hbs Ag expression(all P>0.05).Cox proportional hazard model analysis showed that R0 resection,tumor differentiation,TGF-?1,Survivin and Caspase-3 expression were independent prognostic factors for postoperative survival of patients with intrahepatic cholangiocarcinoma.2.The positive expression rates of TGF-?1 in tumor group,inflammatory group and normal group were 73.08%,40.0% and 16.67%,respectively.there was significant difference among the three groups(P<0.01).3.The positive expression rates of Survivin in tumor group,inflammatory group and normal group were 69.23%,43.33% and normal,respectively.Group B(16.67%),the difference between groups was statistically significant(P<0.01).4.The positive expression rates of Caspase-3 in tumor group,inflammatory group and normal group were 42.31%,66.67% and 90.0% respectively(P<0.01),and the expression of TGF-?1 in bile duct tissue of patients with intrahepatic cholangiocarcinoma was significantly higher than that of normal group(P<0.01).5.It was negatively correlated with Caspase-3 protein(r=0.890,P<0.01)and positively correlated with Survivin(r=0.917,P<0.01),Survivin),and negatively correlated with Caspase-3(r=0.894,P<0.01).Conclusions1.The positive expression rate of Caspase-3-? 1 and Survivin is higher in intrahepatic cholangiocarcinoma,and there is a positive correlation between them,while the positive expression rate of TGF-?1 is lower,which is negatively correlated with the former two.They interact with each other to promote the occurrence and development of intrahepatic cholangiocarcinoma.2.The positive expressions of TGF-?1,Survivin and Caspase-3 are independent factors affecting the postoperative survival time of patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma.Monitoring the levels of TGF-?1,Survivin and Caspase-3 in intrahepatic cholangiocarcinoma is helpful to judge the prognosis of patients. |
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