Relationship Between The Detection Of Circulating Tumor Cells And Outcomes In Patients With Hepatocellular Carcinoma

The research background and objective:Cancer is one of the main factors leading to human death; various malignancies both serious harm to the patient’s physical and mental health. But also to the patient’s family and society very heavy financial burden. HCC (hepatocellular carcinoma HCC) is the most common malignant tumor worldwide, China’s urban areas, the incidence of liver cancer accounts for about 25% of the total incidence. Currently, the clinical treatment of hepatocellular carcinoma use of liver transplantation, surgery, interventional therapy, radiofrequency ablation, molecular targeting (sorafenib) and gene therapy treatment, the preferred treatment for the liver transplant and surgery. According to a variety of methods of treatment of hepatocellular carcinoma related literature shows:Liver transplantation 5-year survival rate was 60% to 80%, small liver cancer 5-year survival of 50% to 60%, a large liver cancer 5-year survival rate was 30%～40%, small hepatocellular carcinoma ablation 5-year survival of 30% to 40%, transcatheter arterial chemoembolization 5-year survival of 20% to 30%, but the 3- and 5-year survival rate was no significant improvement. The study found that the final bottleneck no matter what method of treatment of postoperative recurrence and metastasis are. Because the liver blood supply, blood metastasis is the main way of hepatocellular carcinoma metastasis after treatment, there is a majority of HCC patients, even if the tumor volume is very small, it may have occurred prior to surgery microvascular invasion or micrometastases:Even in primary liver cancer early growth of newly formed tumor cells can also be detached from the primary tumor and enter the bloodstream, and the distant spread, grown, under certain conditions, the formation of metastases. When cancer cells invade the portal vein tumor thrombus formed, thrombus in the liver can cause loss of multiple metastases; at the same time, you can also enter the body via the portal vein circulation, leading to liver metastasis. Therefore, postoperative metastasis in patients with hepatocellular carcinoma recurrence has become an important factor affecting the prognosis of patients with liver cancer. How to monitor, prevent postoperative recurrence and metastasis of hepatocellular carcinoma patients, become the main direction of research scholars. The present study primarily by serum markers, clinical imaging means for tumor detection, diagnosis, treatment and monitoring, but the results are not satisfactory. Clinically urgent need to find a way to effectively monitor the testing methods liver metastasis. Circulating tumor cells (circulating tumor cells CTCs) research has become a hot field of tumor recurrence and metastasis research, a large number of clinical trials abroad, CTCs with a non-invasive real-time monitoring of tumors, can effectively predict progression-free survival and overall survival, more conducive to tumor micrometastasis detection and prognosis. Therefore, CTCs can be applied to clinical treatment of primary tumors, monitoring and individualized treatment being.CTCs refers to spontaneous or because clinics operated by the primary tumor or metastases into the blood circulation system of the tumor cells, in the form of individual cells or groups of cells present in the circulatory system. Early in 1896, the Australian scholar Ashworth found blood from patients with metastatic tumors in case there is a blood cells and tumor cells are very similar, and the first to put forward the concept of CTCs. Subsequently, CTCs and gradually entered into the field of vision more scholars. Because, CTCs and more present in the peripheral circulation among various cancer patients and in healthy people or other non-neoplastic diseases of the peripheral circulation among the almost undetectable. From an objective terms, CTCs presence is not necessarily prompt the body metastatic foci have formed, into the peripheral circulation system because the vast majority of CTCs, will gradually apoptosis in the body’s immune function, only a few CTCs can He survived, and biological characteristics of the joint action of tumor cells, immune status, the host organ microenvironment, can only form metastases. Since CTCs and primary tumor have similar features and even the same nature, some scholars believe it may be CTCs as a representative of the original tumor "liquid biopsy specimens" or "marker."With the recent CTCs after the academic role in the process of tumor metastasis of a systematic and in-depth study found that, if effective way for cancer patients for accurate detection of CTCs in peripheral blood, it can help during the vicious At the same time the early diagnosis of cancer, treatment, recurrence and metastasis of monitoring, but also can effectively predict prognosis; further more help scientific selection and optimization of treatment.Typically, per milliliter of peripheral blood leukocytes and red blood cells containing 5×1091×107 or so or so, with respect to the blood cells, it is present in the number of tumor cells in the peripheral blood is very small. How to enrich and identify tumor cells in peripheral blood CTCs detected become the biggest technical obstacles. Actual clinical testing found that peripheral blood CTCs there was minimal, and its precise separation there are some difficulties, and therefore further limits the CTCs application and promotion. Until the late 1990s, with the further development of modern biotechnology, and academic research on cancer deepening, CTCs detection has been fully developed. In addition, due to the possible presence of primary tumor after some of the clinical treatment of minimal residual disease can not be effectively detected by high-resolution imaging technology to detect, but it can be associated with high sensitivity and specificity to detect the patient’s lymph nodes, bones, blood circulation out; and detecting CTCs in peripheral blood can not hit multiple, repetitive inspections, which also provide effective detection and management of cancer patients for clinical outcomes. With the treatment of cancer has entered the era of individualized treatment, many oncologists rely tumor molecules or phenotype cancer treatment decisions, and continue to develop CTCs detection technology advances, more scholars began to take advantage of its non-invasive "liquid biopsy" Check advantage detect metastatic cancer prognosis.MethodIn this study, the Guangzhou Yi Shan developed CanPatrolTMCTCs detection technology, selected in July 2013 to January 2015 Nanfang Hospital hepatobiliary surgery treated 296 cases of hepatocellular carcinoma were enrolled, and choose 39 cases of non-tumor or benign tumor as the control group. After collecting more than the peripheral blood of patients admitted to hospital two days 10ml; whole-blood filtration enrichment technique detection of peripheral blood CTCs, analyze it with sex, age, AFP level, cirrhosis, hepatitis B surface antigen, a number of tumors, tumor size, BCLC stage, TMN stage, degree of differentiation, with or without vascular thrombosis, with or without intrahepatic metastasis, liver metastasis and recurrence with or without clinical pathology relations; to further explore the CTCs detected in the clinical diagnosis and treatment of primary liver cancer application. This method is the use of RNA in situ hybridization and nanofiltration technology combine principles, without reliance specific biomarker, is the only way to achieve synchronization CTCs form type, cell differentiation and molecular typing of advanced detection technology. Just gathering was seized by 5～10ml peripheral blood, at any stage of cancer treatment will be, to earlier and more accurately reflects the tumor status than other conventional means of inspection and does not cause any side effects would be subject.Result(1)HCC therapy in patients with positive CTCs and CTCs count the number of cases analyzed.296 cases of hepatocellular carcinoma in patients with liver cell CTCs positive 211 cases, the positive rate of 71.43%(211/296), CTCs quantity distributed between 0-47 months/5ml, with a median value of 14/5ml, with an average of 7.549±11.508 a. CTCs positive control group,39 cases 0 cases, the positive rate was 0%(0/39).(2) 127 surgical patients detected 89 cases of CTCs positie, positive rate was 70.07%, cells of detection of CTCs detection of parting, type of epithelial CTCs have 52 cases, interstitial type CTCs in 73 patients, epithelial/interstitial hybrid CTCs in 70 patients.(3)The number of CTCs in patients with serum AFP level, tumor BCLC staging, TMN stage, portal vein thrombosis, microvascular thrombosis, intrahepatic metastasis, liver metastasis, recurrence was statistically associated (p<0.05); but with sex, age, hepatic cirrhosis, hepatitis B surface antigen, number of tumors, tumor size, tumor differentiation degree (P> 0.05).(4) Surgery in patients with preoperative CTCs test results positive group (CTC 3/5 ml) or the risk of tumor recurrence after surgery was significantly higher than that of CTCs negative total CTC (< 3) group, CTCs in positive disease-free surial CTCs negative groups significantly shortened (χ2= 5.034, P= 5.034).Conclusions(1)CanPatrolTM system has a high sensitivity and specificity in patients with hepatocellular carcinoma detection of CTCs.(2) CTCs quantity and HCC patients with AFP, BCLC staging, TNM staging, portal venous tumor emboli, intrahepatic metastasis, distant metastasis, capillary tumor emboli and recurrence were positively correlated.(3)Before the operation of CTCs positive patients risk of tumor recurrence after a significant rise in CTCs negative patients, disease-free survival time of CTCs negative patients significantly reduced.