| BackgroundBeing the fifth most common cancer worldwide,Primary liver cancer (PLC) is one of the most common malignant tumors in clinical practices. Its early symptoms are so obscure that most patients were diagnosed with terminal-stage tumor when they came for the treatment.It has been the second cancer killer with its merely 9 percent of the five-year’s survival rate,which has being caused approximately 600,000 to 1,000,000 deaths annually in china since 1990s.Surgical resection and liver transplantation are the only potentially curative therapies for PLC since it presenting obscure symptoms and usually being associating with viral hepatitis or alcoholic cirrhosis in the early stage.However,only few patients (11.9%-30.1%) at clinical presentation of tumors are suitable candidates for surgery because of multicentricity or poor hepatic functional reserve due to pre-existing cirrhosis.Dhir reports that the recurrence rate in 2 years and 5 years after the resection of liver cancer is 35-50%and 61.8% respectively. Further, even if small liver cancer, the recurrence of postoperative liver cancer is also as high as about 40%. Therefore,in clinical practices,Non-surgical treatment is mostly used to the patients with intermediate or advanced cancer. Currently,the primary indicator of curative effect are AFP and imaging examination, while for the AFP negative cases or small lesions in the liver, there are lack of effective monitoring indicators.Currently it is universally acknowledged that TACE is the preferred method for the treatment of intermediate and advanced cancer for those patients who are inoperable. The percentage for liver cancer patients who received interventional treatment has reached 61.9% in China. Transcatheter arterial chemoembolization(TACE) has been the main non-radical treatment for it can, by transporting the chemotherapeutic drugs of high concentrations to the location of lesions,alleviate the illness and prolong survival time with the progression of the tumor is slowed,the vascular invasion is delayed and the systemic exposure is reduced. However, according to researches, repeatedly TACE may exacerbate liver injury and develop compensatory collateral circulation and hence to increase the possibility of recurrence or metastasis of liver cancer. This is because TACE,instead of inducing cancerous tissue necrosis, usually results in ischemia and hypoxia of local tissue and further triggers the expressions of VEGF or HIF. In addition, during the process of treatment, TACE would induce hypoxia in liver cancer tissue and its surrounding normal liver tissue and up-regulate VEGF expression, which may further cause residual carcinoma tissue growth and transfer or new tumor formation. Therefore blocking the expression of VEGF may be the effective means to optimize TACE.Being a kind of secreted protein that widely exists in eukaryotes, VEGF is the key factor to regulate tumor blood vessels and tumor growth and to induce recurrence, metastasis and invasion, and it’s also identified as the strongest angiogenesis promoting factor in body. Recent researches show that VEGF has a close relationship with the occurrence and development of tumor. The VEGF actively expressed in many tumors.It is noteworthy that it has a generally significant rise in liver cancer. The high expression of VEGF is significantly related with the decrease of overall survival rate and tumor-free survival rate of liver cancer patients. There are overseas and domestic literature confirmed that hypoxia resulted from the TACE, is the central node to induce the tumor angiogenesis. After the TACE, the change of VEGF level in serum can reflect the tumor hypoxia to some degree and indirectly reflect the tendency of tumor angiogenesis,metastasis or recurrence.This research detected the expression difference of VEGF of serum in the patients with mid-early liver cancer using double antibody sandwich enzyme-linked immunosorbent assay (ELISA) to predict the relationship between the expression of serum VEGF and curative effect.PurposeBy observing the change of VEGF levels in serum, our research is to discuss its influence factor before and after the first TACE and its correlation between clinical index, and its relationship with the curative effect after the tumor thrombosis.Materials and MethodsFrom June 2015 to January 2016,56 patients with early-middle primary liver cancer in our hospital were included in this study,who were diagnosing after angiography, serology, imaging and pathological examination.Of these,44 were male and 12 were female,33-77years,with a median age of 53 years including BCLC-A 15cases,BCLC-B 41 cases.All the patients were treated with first TACE.Indications were:(1)First treatment, without surgical resection,no other treatment, no extrahepatic metastasis,no thrombosis with Hepatic vein and portal vein,without lymph node metastasis;(2)Confirmed by pathological biopsy or the combination of increased alpha-fetoprotein(AFP,≥400ng/ml)and the typical vascular pattern on angiography or dy-namic imaging(3)KPS score≥90 points;(4)Liver function score Child-Pugh for class A or class B or class C turn into class B after treatment;(5)without ascites;(6)normal renal function with a serum creatinine level of ≤1.5 mg/dl;(7)Expected survival in more than 3 monthsExclusions were:(1)KPS score< 90 points;(2)Severe liver and kidney dysfunction;(3)Suffering from other malignancies, and no effective control;(4)There are clinical signs and symptoms of sepsis;(5)Affect the ability of the patients with brain metastases, severe brain disease or mental illness;(6)Pregnancy or breast-feeding women;(7)Participated in other clinical subjects within 4 weeks;(8)Blood platelet count<50×109/L,WBC<3×109/L.Elimination criteria:(1)Patients volunteered to exit, which cannot complete blood plan according to the rules;(2)Died of liver failure 2 weeks after interventional therapy;(3)Lost to follow.Peripheral venous blood samples were taken from the patients with HCC patients early in the morning after fasting before initial treatment, on 1 day,3 day and 4—6 weeks after first TACE treatment.All samples were allowed to stand at room temperature 1-2 hours,drawn into serum separator tubes and centrifuged at 3,500r/min for 15 min,taken the upper serum moving to 1.5 ml nonenzymatic EP tube,then stored at-800C until analysis.The levels of serum VEGF concentrations were measured quantitatively using an enzyme-linked immunosor-bent assay kit(Germany IBM company)according to the manufacturer,instructions on a microplate reader at 450 nm.All samples and standard adopts were assayed in duplicate, concentrations of sample VEGF obtained from VEGF standard curve. Liver enhancement CT imaging 1 week pre-and 4-6 weeks post—TACE were observed.Finally, the relationship between serum VEGF levels and liver biochemistry, AFP and prognosis were investigated.All analyses were performed using the SPSS version 19.0 statistical software(SPSS; Chicago, IL, USA). Continuous variables are reported as means ± standard deviation, whereas categorical variables are shown as frequencies and percentages. Demographic characteristics were compared between cases and controls with the χ2 and Student t-tests.Parameters using spearman method to calculate the correlation coefficient. All tests take two-sided test.Results were considered statistically significant at P<0.05.Results1.Comparison of serum levels of VEGF before and after the intervention therapy:Serum VEGF levels have obvious dynamic changes pre-and post-TACE.The expression levels of serum VEGF in PHC patients were(278.59±72.39)pg/ml lday pre—TACE,1 day and 3 day after TACE serum VEGF levels increased to(544.04±55.00)Pg/ml and (401.52±47.11) pg/ml respectively,4-6 weeks post-TACE. expression levels of them were decreased to(278.48 ± 76.32)pg/ ml.The serum VEGF levels pre-and-post-TACE showed a trend of increasing at first and then declining,There were significant difference between the VEGF levels on lday,3day after TACE and 1day before TACE(P<0.05).whereas There was no significant difference between the patients 4-6 weeks after TACE and 1day before TACE(t=0.008, P=0.994).2.Modified Response Evaluation Criteria In Solid Tumors (mRECIST)was employed to assess the tumor response. Tumor response included complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD)..According to the mRECIST,The effective rate was 78.57% with 3 cases CR(5.4%),41 cases PR (73.21%),7 cases SD (12.5%) and 5 cases PD (8.93%).44 patients were divided into effective group (complete response and partial response)and 12 invalid group(stable disease and progressive disease),the difference are statistically significant (260.31±70.22pg/ml vs.345.08±60. 72 pg/ml, t=3.805, P< 0.001)3.Relationship between VEGF level before interventional therapy and lesions characteristics and biochemical indicators:The serum VEGF of the 5 Patients (AFP<8.2/ul) were 279.80±33.42 pg/ml, and 51 patients (AFP≥8.2/ul)(295.05 ±70.00pg/ml,t=0.479, p=0.634). The serum VEGF of the 13 Patients with tumour capsule were 292.61±46.70pg/ml, and 43 patients without tumour capsule(294.04±74.57pg/ml,t=0.083, p=0.934).The serum VEGF of the 7 Patients with intrahepatic arteriovenous shunts were 349.28±57.24 pg/ml, significantly higher than that of 49 patients without intrahepatic arteriovenous shunts ((275.38 ±67.85) pg/ml,t=2.74, p=0.008).The serum VEGF of the 22 Patients (Platelet<150,000/ul) were 245.04±67.52 pg/ml, significantly lower than that of 34 patients (Platelet≥150,000/ul)((300.29±67.79) pg/ml,t=2.983, p=0.004).4.The serum VEGF is associated with blood platelet count (r=0.460, p<0.001)5.The comparison of liver function pre-and post-TACE:The Child-Pugh score, AST, ALT, TBIL, ALB and PT 3 day after TACE compared lday pre—TACE had statistical differences. The Child-Pugh score, AST, ALT, TBIL and PT were on the rise while ALB showed a downward trend (p< 0.05).4-6weeks later, they all returned to pre-operation level. Follow-up to February 1,2016,56 patients lost 1 cases (8.9%), of which 2 cases have been death due to esophagogastric variceal bleeding (EGVB) and tumor recurrence or metastasisConclusions1.The serum VEGF levels pre-and-post-TACE showed a trend of increasing rapidly at first and then declining gradually,peaking on lday after TACE.There were significant difference between the VEGF levels on 1day,3day after TACE and lday before TACE(P<0.05).whereas There was no significant difference between the patients 4-6 weeks after TACE and 1day before TACE(t=0.008, P=0.994).2.The serum VEGF level before interventional therapy was associated with Platelet and intrahepatic arteriovenous shunts3.The serum VEGF level predicting the occurrence and development of primary hepatic carcinoma and evaluating the poor prognosis by the high level of VEGF can act as an early—stage, sensitive, efficient and AFP—independent marker on evaluation of therapeutic effect of intervention. |
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