| BACKGROUNDS:Intrahepatic cholangiocarcinoma(ICC)is a relatively rare and highly invasive malignant tumor of the liver.It mainly comes from the epithelial cells of the secondary bile duct and its branches,accounting for about 5%-30%of the primary malignant tumors of the liver.According to epidemiological investigations,the morbidity and mortality of ICC have increased by 20%and 30%in the past 30 years.The incidence of ICC in China is the second compared to Thailand.Among the pathological forms included in ICC,mass type is the most common type,accounting for about 80%of ICC.With the progress of diagnosis and treatment,the improvement of clinical technology and the deepening of scientific research,more and more evidence about the risk factors of ICC has been confirmed by clinical workers.The more common factors included infectious factors(hepatitis B,hepatitis C,liver schistosomiasis),biliary system diseases(PSC,hepatolithiasis,congenital biliary cystic diseases),metabolic syndrome(dyslipidemia,hypertension,hyperuricemia,etc.)which are widely studied at present,and others included smoking,drinking,toxic substances or occupational exposure.At present,there are a variety of treatment methods for ICC,including traditional surgical treatment and local treatment,as well as emerging targeting and immunotherapy,but radical resection is the most thorough treatment for ICC.In view of the clinical characteristics of the disease itself,the initial symptoms are not typical,lack of effective monitoring means,so that most of the patients have been in the clinical advanced or distant metastasis state,and can only be treated conservatively.However,even after surgery,the 5-year survival rate is only 30%-35%and the prognosis is very poor.Nowadays,many factors that can affect the prognosis of ICC patients after radical resection have been confirmed by clinical workers,but there is no consensus on the prognostic factors that can significantly and independently affect the survival rate and recurrence rate of ICC.Therefore,the purpose of this study is to comprehensively analyze the general clinicopathological data and survival data of patients through a retrospective cohort study,to explore the prognostic factors affecting the overall survival(OS)and recurrence free survival(RFS),and this study makes a nomogram model that can predict the overall survival after ICC,To deepen the clinical workers’ understanding of this disease,so that clinical workers can make a scientific evaluation of the postoperative survival rate and recurrence rate of ICC,so as to better serve the clinical practice.OBJECTIVE:This retrospective cohort study was performed to explore the relationship between clinical and pathological data and postoperative survival factors in patients with intrahepatic cholangiocarcinoma after radical resection,and to establish a nomogram model which can predict the total survival time after operation.METHODS:This study comprehensively collected the clinical and pathological data and complete follow-up data of 79 patients from the Department of General Surgery of Qilu Hospital of Shandong University who were diagnosed as ICC by postoperative pathology from July 1,2009 to October 31,2017.The general indicators included the following(name,gender,age,history of hypertension,history of diabetes,history of hepatitis B infection,history of hepatolithiasis,liver cirrhosis).The laboratory tests that included ALT,ALT,ALP,CEA,CA19-9,PA,NLR,GGT.The surgical and pathological indexes included the following(hepatic portal occlusion,blood transfusion,tumor size and number,lymph node dissection and lymph node metastasis,vascular invasion,lymphovascular invasion,degree of pathological differentiation,postoperative overall survival time and postoperative recurrence time).SPSS 24.0 software was used to analyze the clinical data.Kaplan Meier method was used to calculate the cumulative overall survival rate and recurrence free survival rate,and then the survival curve was drawn.Log rank test was used to screen the clinical and pathological indicators,the Cox regression model was used to analyze multiple factors.The nomogram model was constructed by R software.The consistency index,calibration curve and area under ROC curve(AUC)were used to verify the predictive effectiveness of nomogram.The difference was statistically significant(P<0.05).RESULTS:By collecting the complete medical records of ICC patients who were admitted to Qilu Hospital of Shandong University from July 1,2009 to October 31,2017,a total of 104 cases were collected,including 87cases(83.7%)with R0 resection,7 cases(6.7%)with RI resection and 10 cases(9.6%)with R2 resection.A total of 8 cases(92.0%)who underwent R0 resection were excluded because of Follow-up failure.Finally,a total of 79 patients met the purpose of our study.1.General clinical data:Among 79 patients with ICC who underwent radical resection,46(58.2%)were male and 33(41.8%)were female.The ratio of male to female was 1.39:1;In this study,the distribution of age ranged from 40 to 75 years old,with an average of 58.94±86 years old,and a median age of 60;18 cases(22.8%)had hepatitis B,25 cases(31.6%)had hepatolithiasis,16 cases(20.1%)had hypertension and 15 cases(19.0%)had diabetes.In terms of clinical manifestations:18 cases(22.8%)were found by routine physical examination,51 cases(64.6%)had abdominal pain,10 cases(12.7%)had high fever and chills,and 6 cases(7.6%)had jaundice on the skin and sclera.2.Surgical treatment:Of the 79 patients treated with R0 resection.33 cases(41.8%)received left hemihepatectomy,11 cases(13.9%)received right hemihepatectomy,and 35 cases(44.3%)received non-hemihepatectomy because of the particularity of tumor location.combined organ resection was performed in 38 cases(48.1%),lymph node dissection was performed in 37 cases(46.8%),laparoscopic resection was performed in 11 cases(13.9%).Nodular cirrhosis was found in 17 cases(21.5%),and intraoperative blood transfusion was carried out in 28 cases(35.4%).The tumors closed the gallbladder or invaded into the adjacent organs were found in 38 cases(48.1%),lymph node dissection in 37 cases(46.8%)and laparoscopic resection in 11 cases(13.9%).Intraoperative hilar occlusion was performed in 24 cases(30.4%).3.Postoperative follow-up:Of all the patients undergoing R0 resection,a total of 8 patients were excluded because of Follow-up failure,and the final follow-up rate was 90.8%.Among them,64 cases(81.0%)appeared tumor recurrence during follow-up.The median RFS was 11 months.The cumulative recurrence free survival rates in the 1-,2-,and 3-year were 43.0%,26.6%and 20.3%respectively.The median survival time was 15 months and the OS was 4 months to 66 months.The 1-,2-,and 3-year cumulative overall survival rates were 63.3%,41.8%,and 27.8%,respectively.4.Survival analysis:Log-Rank method was used to analyze the following factors:sex,age,hypertension,diabetes,hepatitis B,history of cholelithiasis,preoperative laboratory results(ALT,AST,CA19-9,CEA,GGT,NLR,ALP,PA),blood transfusion,hilar occlusion,liver cirrhosis,lymph node dissection,lymph node metastasis,vascular invasion,vascular thrombus,pathological differentiation,tumor size and number of tumors.The final survival results showed CA19-9>39U/ml(χ2=16.614,P<0.05),GGT(χ2=5.417,P<0.05),NLR(χ2=6.065,P<0.05),lymph node metastasis(χ2=11.900,P<0.05),and vascular invasion(x2=8.647,P<0.05),the number of tumors(χ2=8.140,P<0.05),lymphovascular invasion(χ2=13.15,P<0.05),pathological differentiation(χ2=5.179,P<0.05)were risk factors affecting the total OS after ICC operation.Multivariate analysis using Cox proportional risk regression model showed that CA19-9>39U/ml(HR=2.599,95%CI=1.409-4.794),lymphovascular invasion(HR=1.623,95%CI=1.080-3.608),tumor number(HR=2.112,95%CI=1.145-3.896)were the independent risk factor affecting postoperative survival of ICC patients.The final recurrence result of the patients showed CA19-9>39U/ml(χ2=10.047,P<0.05),GGT(χ2=4.310,P<0.05),NLR(x2=4.203,P<0.05),ALP(χ2=4.347,P<0.05),lymph node metastasis(χ2=7.022,P<0.05),vascular invasion(x2=5.808,P<0.05),lymphovascular invasion(χ2=9.895,P<0.05),tumor number(χ2=4.830,P<0.05),pathological differentiation(χ2=6.443,P<0.05)were risk factors affecting postoperative recurrence.Multivariate analysis showed that CA19-9>39U/ml(HR=1.956,95%CI=1.127-3.394),tumor number(HR=1.857,95%CI=1.040-3.315),pathological differentiation(HR=1.941,95%CI=1.1 11-3.392)were independent risk factors for postoperative recurrence.5.The establishment and verification of the nomograph.The nomograph prediction model of survival was obtained by using R software.The c-index was 0.723(95%CI:0.66～0.79.The AUC of the 1-,2-,and 3-year were 0.78(95%CI:0.68～0.89),0.85(95%CI:0.77-0.93)and 0.77(95%CI:0.67～0.87),respectively.CONCLUSIONS:1.Radical resection is still the only surgical treatment to cure ICC,but the recurrence rate is high and the long-term survival is poor.2.CA19-9,lymphovascular invasion and tumor number are independent risk factors for long-term survival of patients with ICC.3.CA19-9,tumor number and pathological differentiation are independent risk factors for postoperative recurrence in patients with ICC.4.CA19-9 and tumor number are common independent risk factors for survival and recurrence.5.The result of the nomogram is good,and it can predict the survival rate during one to three year’s follow-up. |
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