超声造影对兔肝VX2肿瘤转移机制与肿瘤原位消融靶点相关性的研究

Liver cancer is the most common malignant tumors of the digestive system , with a high morbidity and mortality.Liver cancer is latent, and found mostly late. As often associated with micrometastases, surgical resection is less than 1/4. With the development of in situ inactivation and ablation techniques, patients with liver cancer have more opportunities of being treatment. Early diagnosis and comprehensive assessment of the growth pattern of the liver cancer are important for choosing the right treatment, prolong survival and improve prognosis. Liver tumor angiogenesis and microvessel density are correlated with tumor metastasis and recurrence, that it is a research focus of transfer mechanism and tumor invasion in recent years. But another important way circulation of liver tissue has not yet made a breakthrough,which the research of lymphatic circulation include liver tumor lymphangiogenesis and lymphatic invasion and metastasis of liver cancer relationship. In this study, using contrast enhanced ultrasound techniques to explore the differences of the liver tumor blood and lymphatic growth, and build relationship CEUS parameters and mechanisms of lymph metastasis, and selecte the specific indicators of blood and lymphatic metastasis. Further according to the different mechanisms of blood and lymphatic invasion and metastasis, to develop in situ inactivation ablation program, and determine the ablation target.Thus,to provide an objective basis for the diagnosis of the invasion and metastasis of various transfer mechanisms, and achieve goals of optimize liver cancer treatment strategies.

肝癌是消化系统最常见的恶性肿瘤之一，发病率和病死率高。肝癌发病较隐匿，发现时多为晚期，并常合并微小转移灶，可行手术切除者不足1/4。随着原位灭活及消融技术的发展，给肝癌患者提供更多的救治机会。肝癌的早期诊断和生长方式的全面评估对选择合适的治疗方案、延长生存期及改善预后具有重要意义。肝肿瘤微血管生成、微血管密度与肿瘤浸润转移和复发的相关性是近年来肿瘤浸润、转移机制研究的热点，但肝组织的另一重要循环途径-淋巴循环（肝肿瘤的淋巴管生成和肝肿瘤淋巴侵袭与转移关系）的研究尚未取得突破性进展。本研究拟应用超声造影技术探索肝肿瘤血行及淋巴管生长的差异性，构建超声造影参数与肝肿瘤淋巴转移机制的关系，筛选出血行和淋巴侵袭及转移的特异性超声造影指标，进而根据血行及淋巴侵袭及转移的不同机制指导原位灭活消融方案并确定消融靶点，从而为肝癌不同转移机制的侵袭和转移情况提供客观的诊断依据，实现优化肝肿瘤治疗策略的目标。

肝癌是消化系统最常见的恶性肿瘤之一，发病率和病死率高，且发病较隐匿，发现时多为晚期，并常合并微小转移灶，可行手术切除者不足1/4。随着原位灭活及消融技术的发展，给肝癌患者提供更多的治疗手段。肝癌的早期诊断和生长方式的全面评估对选择合适的治疗方案、延长生存期及改善预后具有重要意义。本研究主要采用超声造影观察肝肿瘤微血管和淋巴管显像的差异性，筛选出血行和淋巴侵袭及转移的特异性指标，进而根据血行及淋巴侵袭及转移的不同表现指导原位灭活消融方案，为肝癌不同生长和转移的情况提供客观的诊断依据，从而实现优化肝肿瘤治疗策略的目标。通过动物实验和临床实验两部分，获得原发性肝癌与淋巴转移灶的造影参数，确定肝肿瘤血行及淋巴生长的特征性。通过对比分析肝肿瘤组织学微血管密度、淋巴管密度与超声造影参数，发现微血管密度与造影剂达峰时间、峰值强度成正相关，淋巴管密度与达峰时间和峰值强度无相关性。经皮直接注射较经静脉注射达峰时间短，且前者峰值强度明显高于后者。根据超声造影显示肝肿瘤滋养动脉、微血管及淋巴管的特点，制定优先消融供血动脉的方案，扩大消融微血管及淋巴管走行区。并综合肝脏脂肪浸润程度、热沉效应（肿瘤供血血管分布、病灶位置及临近血管）、病灶本身成分等影响消融效率的关键因素，制定个体化消融方案。超声造影剂在淋巴内皮细胞间隙的出入胞作用，进入毛细淋巴管，回流至淋巴结，其引流过程经增强影像技术捕捉，从而清晰的呈现组织的毛细淋巴管、集合管及前哨淋巴结。淋巴结转移是影响肝癌病人临床疗效和生存期的重要因素之一。研究肝癌淋巴生长及转移的途径，在术前超声造影观察肝癌的淋巴引流途径及淋巴管密度，确定原发性肝癌淋巴结有否转移对选择合适的治疗策略至关重要。术后提示淋巴结转移、判断预后、以及对选择进一步治疗方案具有指导意义。