| Research background and purpose:Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor derived from the subbranches of the intrahepatic bile duct,and has been recognized as the two types of primary carcinoma of liver with hepatocellular carcinoma(HCC).But now more and more studies have found that ICC has its own characteristics in origin,growth,invasion,metastasis tendency,imaging findings,treatment and prognosis,which lead to treating ICC as an independent disease.AJCC(American Joint Committee On Cancer)version 7 has set the independent TNM stage for ICC,and models for predicting the prognosis has also been preliminary explored,these are all meet the understanding of treat the disease independently.At present,the main treatment methods of ICC include surgical resection,local treatment,systemic chemotherapy and radiotherapy.The surgical resection includes: radical resection,laparoscopic surgery;The local treatment includes: Transarterial chemoembolization(TACE),Radiofrequency ablation(RFA)and Microwave ablation(MWA).Because of the low sensitivity,radiotherapy and systemic chemotherapy are often used as an adjuvant or palliative treatment in ICC.Surgical resection is recognized as the most effective way to improve the prognosis.But,unlike HCC,ICC is prone to metastasize,especially to the lymph nodes around the liver.A large number of studies have reported that lymph node metastasis is an independent risk factor for early postoperative recurrence and metastasis in patients with ICC.Thus,it is clear that patients whose tumor can be resected radically,and without lymph node metastasis can benefit from the operation.However,there still have no methods with high accuracy and sensitivity in the diagnosis of lymph node metastasis.Therefore,in the course of surgical treatment of ICC,in addition to the resection of the tumor itself,more and more attention has been paid to the exploration and dissection of lymph nodes in the relevant areas.But lymph node enlargement can be caused by inflammation,and lymph node with cancer cells is not necessarily to be a swollen state.So according to the exploration results during operation to decide whether the lymph node should be cut out for biopsy or routine cleaned is not reliable,which has the risk of left lymph node with tumor cells in the patients.So,it is worthy of further study to evaluate the feasibility of routine lymph node dissection in patients undergoing R0 resection.Many studies have shown that routine lymph node dissection can provide valuable information for prognosis and staging of disease,but the point is whether routine lymph node dissection can improve the prognosis of patients.So in this study,patients with ICC whose tumor got R0 resected were retrospectively analyzed.The main purpose is to observe the prognosis related factors,the significance of routine lymphadenectomy and the influencing factors of lymph node metastasis.Research methodThis study retrospectively collected cases from January 2010 to December 2015 in Eastern Hepatobiliary Surgery Hospital-affiliated Hospital of Second Military Medical University.All of these cases were clinical diagnosed as ICC and has underwent surgical treatment.Inclusion criteria:(1)preoperative examination have no clear evidence of lymph node metastasis,and radical resection has been done(2)ICC was confirmed by postoperative pathology(3)Routine lymphadenectomy has been done when the suspicious lymph node was found.Exclusion critera:(1)patients hasn’t underwent radical resection(palliative resection or positive pathological margin)(2)patients only suspicious lymph node was get out for biopsy(3)cases with operation data missing or follow-up data missing(4)the cause of death has nothing to do with the disease itself.Finally,265 patients were included in the study(routine lymphadenectomy has been done in 132 cases).Collect the clinical data of all cases before surgery(including gender,age,history of hepatitis B,hepatitis C,history of biliary surgery history,history of diabetes,hypertension,preoperative AFP level,preoperative CEA level,preoperative CA-199 level,preoperative TB value and ALT value);intraoperative conditions(tumor size,sub foci surrounding the tumor and hepatic portal occlusion time,intraoperative bleeding value)and postoperative pathological data(tumor characterization,differentiation and tumor margin,lymph node metastasis)and postoperative follow-up data.Cox single factor analysis was used to analyze all the prognostic factors of the patients first.The factors whose P<0.05 were included into the multivariate analysis,and the risk ratio(HR)was used to express a factor as a risk or protective one.Kaplan-Meier survival analysis and PSM analysis were used to analyze and compare the survival condition between groups,and the survival curve was drawn.The survival rate was checked by log-rank method,the factors whose P<0.05 was statistically significant.Chi-square test was used to analyze the difference of postoperative complications,P<0.05 was statistically significant.Logistic regression analysis was used to analyze the influencing factors of lymph node metastasis,P<0.05 was statistically significant.Research resultsUp to December 2015,there were 196 cases with recurrence and metastasis in the total of 265 patients(74.0 %),151 cases died(57.0%).The median follow-up time is 33.5 months.Of all the cases,the disease-free survival rate was 50%,29% and 20% in the 1,2 and 3 years,the median disease-free survival time was 11.9 months.The overall survival rate was 77%,47% and 36% in the 1,2 and 3 years,the median overall survival time was 22.8 months.Cox multi factors analysis of prognostic factors showed that :medical history of diabetes(P=0.03,HR 1.626),preoperative CA-199 level(P=0.002,HR 1.001),tumor size≥5cm(P=0.034,HR 1.410),sub foci surrounding the tumor(P=0.012,HR 1.617),lymph node dissection(P=0.001;HR 0.451)are factors affect on disease-free survival;preoperative CA-199 level(P=0.015,HR 1.001),tumor size≥5cm(P=0.009,HR 1.639),vascular invasion(P=0.007;HR 2.526),lymph node dissection(P=0.001;HR 0.396)are factors affect on the overall survival.Results of comparison between groups :(1)Before PSM:the cleaning group has 132 cases(cases with recurrence and metastasis was 79,accounting for 59.8% of the group,accounting for 29.8% of the all,lymph node pathological diagnosis was positive in 52 cases),while the uncleaning group 133 cases(cases with recurrence and metastasis was 117,accounting for 87.9% of the group,accounting for 44.2% of the all).(1)Comparison of disease-free survival condition: 1,2 and 3 years disease-free survival rate is 65%,41%,30% in cleaning group vs 36%,18%,12% in uncleaning group,(P=0.001).The median disease-free survival time was 18.0 months in cleaning group vs 9.0 months in uncleaning group.(2)Comparison of overall survival condition: 1,2 and 3 years overall survival rate was 86%,66%,51% in cleaning group vs 69%,32%,24% in uncleaning group,(P=0.001).The median overall survival time was 42.0 months in cleaning group vs 17.0 months in uncleaning group.(2)After PSM: the cleaning group and uncleaning group has 77 cases respectively.(1)Comparison of disease-free survival condition: 1,2 and 3 years disease-free survival rate is 68%,47%,36% in cleaning group vs 31%,13%,6% in uncleaning group,(P=0.001).The median disease-free survival time was 22.2 months in cleaning group vs 9.2 months in uncleaning group.(2)Comparison of overall survival condition: 1,2 and 3 years overall survival rate was 91%,75%,56% in cleaning group vs 71%,30%,21% in uncleaning group,(P=0.001).The median overall survival time was 46.8 months in cleaning group vs 17.0 months in uncleaning group.The lymph node positive patients were removed from the cleaning group,and the survival condition of the patients with negative lymph node and uncleaning patients was compared.(1)Before PSM: the lymph node negative group has 80 cases while the uncleaning group 133.(1)Comparison of disease-free survival condition: 1,2 and 3 years disease-free survival rate is 76%,56%,44% in lymph node negative group vs 36%,18%,12% in uncleaning group,(P=0.001).The median disease-free survival time was 27.9 months in lymph node negative group vs 9.0 months in uncleaning group.(2)Comparison of overall survival condition: 1,2 and 3 years overall survival rate was 95%,78%,65% in lymph node negative group vs 69%,32%,24% in uncleaning group,(P=0.001).The median overall survival time was 48.0 months in lymph node negative group vs 17.0 months in uncleaning group.(3)There was no significant difference in postoperative complications between the two groups.(2)After PSM: the lymph node negative group and uncleaning group has 50 cases respectively.(1)Comparison of disease-free survival condition: 1,2 and 3 years disease-free survival rate is 77%,60%,52% in lymph node negative group vs 32%,22%,15% in uncleaning group,(P=0.001).The median disease-free survival time was 38.1 months in lymph node negative group vs 9.0 months in uncleaning group.(2)Comparison of overall survival condition: 1,2 and 3 years overall survival rate was 94%,82%,74% in lymph node negative group vs 68%,40%,28% in uncleaning group,(P=0.001).The median overall survival time was 54.0 months in lymph node negative group vs 18.9 months in uncleaning group.In the analysis of the influence factors of lymph node metastasis,tumor diameter ≥5cm(P=0.012,HR 1.859)and preoperative CA-199 level(P=0.002,HR 2.415)were independent risk factors affecting on lymph node metastasis.Research conclusion1.For ICC patients who underwent R0 resection,diabetes history,high level of preoperative CA-199 level,tumor size≥5cm and sub foci surrounding the tumor were independent risk factors for disease-free survival;high level of preoperative CA-199,tumor size≥5cm and vascular invasion were independent risk factors for overall survival.2.Routine lymphadenectomy was protective factor for disease-free survival and overall survival.3.According to the comparison results of the study,patients with routine lymphadenectomy had better prognosis than those who did not.Patients who got negative lymph node sertified by pathological diagnosis had better prognosis than those who haven’t underwent routine lymphadenectomy.4.The risk factors of lymph node metastasis in patients with ICC were high level of preoperative CA-199 and tumor size≥5cm.It is suggested that routine lymphadenectomy may improve the disease-free survival and overall survival of the ICC patients,getting lymph node pathology contribute to the prognosis analysis of patients.For patients who evaluated can undergo radical resection,especially with high level of preoperative CA-199 and larger tumorsize,routine lymphadenectomy is recommended. |
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