Clinical Research On The Establishment Of Preoperative Safety Evaluation System For Radical Resection Of Bismuth Type Ⅱ-Ⅳ Hilar Cholangiocarcinoma With Cumulative Damage Effect Of Jaundice As The Predictive Factor

Objective:Because most of the patients with radical resection of Bismuth type II-IV hilar cholangiocarcinoma had obstructive jaundice before operation and required partial hepatectomy,the incidence of postoperative complications and mortality remained high.There is still a lack of a safety assessment system to systematically predict the short-term postoperative outcomes.This study aims to establish a safety evaluation system of radical resection of Bismuth type II-IV hilar cholangiocarcinoma by quantifying the severity of preoperative obstructive jaundice.Materials and Methods:The data of 171 patients undergoing radical resection of Bismuth type II-IV hilar cholangiocarcinoma in West China Hospital of Sichuan University ranging from January 2011 to June 2018 were analyzed.In order to quantify the severity of preoperative obstructive jaundice,CDEJ was established and by logistic regression analysis and nomogram method,the predictive model and risk scoring system were constructed with the different aspects of postoperative outcomes as dependent variables.The clinical medical records of 31 patients who underwent radical resection of Bismuth type II-IV hilar cholangiocarcinoma in Sichuan Provincial People’s Hospital from August 2018 to June 2021 were collected as the validation data set to externally validate the established risk scoring system.The non tumor liver tissues of patients with obstructive jaundice who need partial hepatectomy were collected and detected by H.E staining,Ki67 immunohistoch-emical staining and TUNEL fluorescence staining,respectively,to observe the differences of liver pathological changes and hepatocyte proliferation and apoptosis under different CDEJ grades;at the same time,RNAseq detection was performed to find the differences of liver tissues under different CDEJ grades Gene expression pathway.Results:Clinical research: totally 171 patients’ complete data were collected,and 13 prediction models and 3 risk scoring systems were successfully established.Among them,CDEJ not only determines the occurrence of complications(P < 0.05,OR=1.0001;95% CI: 1.000027-1.000239)and the severity(complication grade;total score of complications)(P< 0.05,OR=1.0002;95% CI: 1.00013-1.00028;P< 0.05,OR=1.0003;95% CI: 1.00013-1.0004),but also determines the occurrence of liver dysfunction(P<0.05,OR=1.0001;95%CI:1.00001-1.00019)and its severity(P<0.05,OR=1.00004;95%CI:1.00003-1.00019),and intraoperative blood loss grade(P<0.05,OR=1.00004;95% CI: 1.00005-1.00021).The validation results of the three risk scoring systems showed that the prediction accuracy rates of complications,liver dysfunction and infection were 83.87%,67.74% and 77.42% respectively.Basic experiment: the degree of H.E staining inflammation and hepatocyte necrosis in group C with the highest CDEJ were significantly higher than those in group B and group A,while the degree of fibrous hyperplasia in group B was the highest.The average OD value of Ki67 immunohistochemical staining in group B and group C was significantly higher than that in group A(0.2410 ± 0.0563,0.2276 ± 0.0217 vs0.1929 ± 0.0164;P< 0.05),but there was no significant difference between group B and group C(0.2410 ± 0.0563 vs 0.2276 ± 0.0217;P> 0.05);the positive cell rate of TUNEL fluorescence staining in group A and group B was significantly lower than that in group C(10.57 ± 3.15,25.90 ± 3.27 vs 56.75 ± 18.87;P< 0.05),but the positive cell rate of TUNEL fluorescence staining in group A and group B was significantly lower than that in group C(10.57 ± 3.15,25.90 ± 3.27 vs 56.75,There was no significant difference between group A and group B(10.57 ± 3.15 vs 25.90 ±3.27;P> 0.05).RNAseq results showed that with the increase of CDEJ level,there were 4 aspects and 7 related gene pathways were significantly expressed,among which,Cell Cycle pathway and Apoptosis pathway were positively correlated(P <0.05),DNA replication pathway was negatively correlated(P< 0.05);liver fibrosis:CAMs pathway were positively correlated(P < 0.05),while NKC pathway was negatively correlated(P < 0.05);mitochondrial injury: OPpathway was negatively correlated(P< 0.05);immune function: INIg A pathway was positively correlated(P< 0.05).Conclusion:CDEJ is related to the degree of hepatocyte damage caused by obstructive jaundice,and is an independent risk factor for intraoperative blood loss,post-operative complications and HIF.The radical resection of Bismuth type II-IV hilar cholangiocarcinoma safety prediction system established in this study still needs to be confirmed by large sample prospective studies.