Impact Factors For Micro-invasion In Patients With Intrahepatic Cholangicocarcinoma: Application Of Defining Target Volume (GTV To CTV)

Objective To study the correlation between clinical factors and pathologic findings of micro-invasion in intrahepatic cholangiocarcinomas(IHC),and estimate its potential value in application of defining target volume(GTV to CTV).Methods From January 2004 to July 2008,IHC patients who underwent surgical resection and diagnosed as IHC in pathologic in our hospital were reviewed.They should not received any preoperative treatment for solitary liver carcinoma.The distance from the cutting edge to the tumor margin should be more than 1 cm.The satellite sites were not found both in preoperative radiation examination and intraoperative exploration.We collected their pathologic slices and clinical data,including the tumor size,tumor border,TNM stage,histological grade,the degree of liver cirrhosis,serum alpha-fetoprotein(AFP),serum carcino-embryonic antigen(CEA), serum carbohydrate antigen 19-9(CA199),serum HbsAg,serum platelet count,serum total bilirubin(TB),alanine aminotransferase(ALT),aspartate aminotransferase (AST),γ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP) and so on.The correlation between pathologic findings and clinical factors of microscopic invasion in IHC was collected from pathological diagnosis and surgical records.The distance of micro-invasion in intrahepatic cholangiocarcinomas(IHC) was measured in microscopic examination.The correlations between radiation examination,specimens and slices were also measured.SPSS 15.0 was used for statistic analysis.Results There were 65%(65/100) IHC patients with micro-invasion,ranged from 0.4 mm to 8 mm.The mean distance was(2.69±0.24)mm.Expansion of 5.5mm, 7.5mm and 8.0mm was required to provide a 95%,99%and 100%chance of obtaining clear resection margins under a microscope.Micro-invasion was positively correlated to tumor edge,TNM stage,histological grade,serum CA199,serum ALT,AST,γ-GT and ALP.A score system was established according to six predictors:tumor edge,serum CA199,serum ALT,AST,γ-GT and ALP.For the patients with scores between 0-1.5,the microscopic invasive distance was below 4mm in 96.4%patients.If the score was great than 1.5,only 78.0%patients present the invasion distance below 4 mm,and 6.5mm was more reasonable in 95.1 patients.We also verified these results using CT and MRI replacing surgical specimens in 22 and 24 patients.The average contraction rate between specimens and radiation examination was(89±4.2)%和(90±3.2)%in CT and MRI,and from specimens to slices was(90.1±3.61)%.The total rate from CT or MRI to slices was about 80%.So in the CT or MRI imaging we should add 7mm,9.5mm and 10mm from GTV to CTV to satisfy 95%,99%and 100%patients.For the patients with scores between 0-1.5,the invasive distance was below 5mm in 96%patients in CT or MRI.If the score was more than 1.5,from GTV to CTV 8mm was in 95.1%IHC patients and more reasonable in CT or MRI imaging.The intrahepatic recurrence rate was 44.6%(29/65) and 40.0%(14/35) for those with and without micro-invasion,p=0.678.The median hepatic recurrent time was 965 days and 374 days.Their intrahepatic non-recurrent survival for the patients without micro-invasion was better than those with micro-invasion.Two-and three-year survival in patients with and without micro-invasion were 22.1%vs 53.5%,12.9%vs 43.8%,(Log-rank p=0.001).Univariate analysis suggested liver disease(such as intrahepatic calculi or liver fluke),preoperative jaundice,serum ALT,AST,γ-GT and ALP,serum CA199,tumor size,intrahepatic micro-invasion,post-operate treatment, lymphatic metastasis,histological grade,TNM stage were significant prognostic factors for survival.The higher score showed more intra-hepatic recurrent and poor suvival.Multivariate analysis showed that micro-invasion,lymphatic etastasis, preoperative jaundice,intrahepatic calculi or liver fluke and serum CA19-9 were significant prognostic factors.Conclusion There were 65%(65/100) IHC patients with micro-invasion,ranged from 0.4 mm to 8 mm.The shrinkage from CT or MRI was about 80%.From GTV to CTV 5.5mm,7.5mm and 8.0mm was required to provide a 95%,99%and 100%chance of obtaining clear resection margins under a microscope and 7.0mm,9.5mm and 10mm in CT or MRI.The micro-invasion degree was related to tumor edge,TNM stage,tumor grade,serum CA199,serum ALT,AST,γ-GT and ALP.We can get marks by ALT,ASTγ-GT,ALP,CA199 and tumor edge to evaluate the arrangements of tumor invasion(GTV to CTV).For IHC patients,their intrahepatic recurrent survival and prognosis were positively relative to the present of the hepatic micro-invasion.Micro-invasion was an independent prognosis factor for IHC.The score was also important for intrahepatic recurrent and survival.