胰腺神经内分泌肿瘤复杂肝转移的介入及药物治疗策略
The Management Strategies of Interventional Therapy and Drug Therapy of Complicated Pancreatic Neuroendocrine Neoplasms with Liver Metastases
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摘要: 胰腺神经内分泌肿瘤(pancreatic neuroendocrine neoplasm, pNEN)初诊时已有60%以上患者出现远处转移, 最常见转移部位是肝脏, 其中65.5%肝转移无法手术切除, 严重影响预后。pNEN复杂肝转移的治疗基础是全身用药, 包括生长抑素类似物、靶向药物及化疗, 可抗激素分泌和抗增殖, 但其总体客观反应率(objective response ratio, ORR)并不高。经肝动脉途径介入治疗可安全、快速降低肝肿瘤负荷和激素分泌, 显著提高ORR, 其治疗方式包括肝动脉栓塞术(trans-arterial embolization, TAE)、肝动脉灌注化疗栓塞术(trans-arterial chemoembolization, TACE)和放射性微球栓塞术, 三者在疗效上并无显著差异。但TAE的ORR相对较高, 且无TACE的化疗副作用, 应用较广泛。多肽-受体介导的放射性核素治疗对高表达生长抑素受体、肝转移瘤负荷小的低级别肿瘤疗效颇佳, 但亦需注意其骨髓抑制及放射性肾损伤等并发症。pNEN复杂肝转移需采取多种手段综合治疗, 总体策略为先尽可能通过药物和介入治疗减小肝转移瘤负荷, 创造条件行胰腺原发病灶切除术。Abstract: Pancreatic neuroendocrine neoplasms (pNENs) are the most common type of gastro-entero-pancreatic neuroendocrine tumor. Over 60% of patients were detected with distant metastases after the initial diagnosis. Liver is the most common metastatic site, 65.5% of liver metastases are unresectable. The basic treatment strategy is system therapy, mainly including somatostatin analogues, target therapy, and chemotherapy with the effect of anti-hormone secretion and anti-proliferation. But the objective response ratio (ORR) of system therapy is mild. Hepatic artery direct therapies, including trans-arterial embolization (TAE), trans-arterial chemoembolization (TACE), and trans-arterial radioembolization (TARE) can reduce the hepatic tumor burden fast and safely. The ORR can be improved too. There is no significant difference in the efficacy of the three methods. TAE has the highest ORR among the three methods but no side effect of chemotherapy of TACE, so that it is widely used in clinical practice. The outcome of peptide receptor radionuclide therapy (PRRT) was proved to be satisfactory in the low-grade or intermediate grade pNENs that expressed high levels of somatostatin receptor or had a moderately metastatic hepatic tumor burden. The severe complications from PRRT are myelo-suppression and radiation nephrotoxicity. The combined therapy should be applied to the treatment of complicated pNENs with liver metastases. The general strategies are reducing the hepatic tumor burden as soon as possible by firstly applying system drugs and interventional therapy, and then the primary tumor should be resected in elective surgery.