射频消融

目 录 肝肿瘤射频消融质量改进指南………………………………………………………………1 Quality Improvement Guidelines for Radiofrequency Ablation of Liver Tumours ………………………………………………………………………………………………11 介入放射学会关于经皮射频消融治疗肝肿瘤的建议……………………………………27 Society of Interventional Radiology PositionStatement on Percutaneous Radiofrequency Ablation for the Treatment of Liver Tumors…………………………………………………34 1.5 T MR导向下肝脏恶性肿瘤射频消融治疗技术初探…………………………………40 Preliminary study of 1.5T MRI-guided radio-frequency ablation for hepatic malignant tumor…………………………………………………………………………………………44 射 一、 引言 影像引导下的经皮肿瘤消融技术的发展已经使之成为治疗肝脏恶性肿瘤的重 要技术进展之一。在这些消融技术中，射频（RF）消融目前作为主要的消融手段 被大多数机构采用。在早期肝细胞癌（HCC）的病人，如果肝移植或外科切除不 适用的时候，射频消融被认为是最好的治疗方法（1,2）。另外，此外，对于那些局 灶性肝转移瘤的病人，射频消融术是除手术之外的一种可行的替代治疗方法，尤 其是对于结直肠癌肝转移病人来说，由于原发病灶和转移灶同时存在或合并有其 它疾病并不适合手术切除的方式（3）。 本指南用于评估射频消融治疗 HCC 和肝转移癌的质量改进项目。最值得关注的过 程如下：1）病人选择，2）操作程序，3）监测病人。过程的评价指标包括适应症， 成功率和并发症发生率。 二、 定义 1. 安全边缘：超越肿瘤边缘的消融区域，以实现肿瘤完全灭活。理论的消融 边缘宽 0.5 -1.0mm。 2. 完全消融：在增强影像中的无增强区域，包括肿瘤及安全边缘。 3. 并发症：根据 SIR 格，可将并发症分成不同等级。主要并发症造成： 需要住院治疗（门诊操作），提高护理等级，住院时间延长，留下永久后 遗症，甚至死亡。次要并发症不产生后遗症，可能需要的名义治疗或短时 1Cardiovascular and Interventional Radiological Society of Europe 2010 年 留院观察（一般过夜）。主要和次要并发症和副作用，应当根据消融病灶 的数目和每次消融本身来。 4. 电极：射频治疗仪（applicator）。一个或多个电极必须直接插入肿瘤以释 放射频能量电流。电极可单极或双极，可以有不同的（多极扩展电极， 内部冷却电极，灌注电极）。 -单极电极：有一个 active 的电极，通过一个或多个接地垫使电流消散。 -双极电极：有两个 active 的电极接头，必须被放置在近端 -多极扩展电极：电极多齿针从一个大套管中扩张开。 -内部冷却电极：电极有一个内腔，注满不与病人组织直接接触的生理盐水。 -灌注电极：电极的尖端有小孔，允许液体（通常为盐水）与组织接触。 5. 热沉效应：消融组织被加热时，相邻的直径 3 毫米或更大的血管会通过对 流带走热量使组织冷却。它会对射频消融产生负面影响，因为它可能在肿 瘤到达完全消融之前将热量带走。 6. 水/气隔离：在消融区域和易于受热损伤的组织（通常是肠道）之间导入液 体（葡萄糖 5％，无菌水）或气体（空气，二氧化碳） 7. 不完全消融：未消融的残留肿瘤病灶，在增强影像学上表现为周围不规则 增强。它通常呈散在、结节状或或不规则生长。 8. 局部肿瘤进展：在既往完全消融的肿瘤病灶旁边出现新的病灶。 9. 总体生存：从入选研究到死亡的时间。随访终止时仍然存活的病人纳入计 算。 10. 射频消融：凝固感应来自所有频率低于 30MHz 的电磁感应能源。用于肿 瘤消融目的的频率一般在 375 -500 kHz 之间。 2Cardiovascular and Interventional Radiological Society of Europe 2010 年 11. 技术的成功：肿瘤治疗根据计划进行，术中或术后立评估消融范围。 12. 一过性高回声区：消融过程中和消融后，超声下可见在肿瘤内部和周边出 现一过性（长达 30-90 分钟）回声增高区。 三、 适应症 1. 肝癌：根据巴塞罗那临床肝癌（BCLC）分类（表 1），当极早期或早期肝 癌患者不适合进行肝切除术或移植时，射频消融是首选疗法。患者应满足 如下条件：单发肿瘤直径或 3 个肿瘤直径小于 3cm，无血管侵犯或肝外转 移；分期为 0，肝硬化分期为 Child-Pugh A 或 B。 表 1 HCC 的 BCLC 分期 极早期 PS 0, Child-Pugh A, 单个 HCC < 2 cm 早期 PS 0, Child-Pugh A-B, 单个 HCC or 3 个结节 < 3 cm 中期 PS 0, Child-Pugh A-B, 多个 HCC 进展期 PS 1-2, Child-Pugh A-B, 肿瘤门静脉侵犯, 淋巴结转移, 远处转移 终末期 PS>2, Child-Pugh C PS：肿瘤分期 2. 肝转移： - 原发肿瘤组织学类型：射频消融通常适用于结直肠癌仅有限转移到肝脏、不 宜手术切除的病人。然而，对于某些肝和肺均有有限转移灶的病人，也适用经皮 治疗，如果认为肝外病灶可以治愈的话。关于其它器官来源的肝转移癌的射频消 融，可信的初步结果已经报告在乳腺肿瘤和内分泌肿瘤。 - 病灶数量：如果所有转移病灶都可成功完成治疗，病灶数目就不应视为是射 频消融的绝对禁忌征。不过，许多中心倾向于选择治疗有五个或更少的病灶的病 人。 3Cardiovascular and Interventional Radiological Society of Europe 2010 年 - 肿瘤大小：目标肿瘤最长径不应超过 3 厘米，以能够利用现有可用设备达到最 佳的完全完全消融率。 3. 肿瘤位置： 术前影像检查必须明确每个病灶的位置及其与周围组织的关系： - 对病变位于肝脏表面可考虑射频消融，虽然他们的治疗需要足够的专 业知识，并可能出现较高的并发症风险。 - 应该避免对任一部分消化管相邻的表面病灶进行热消融，因其有致胃 肠壁热损伤的风险。结肠出现热相关穿孔的风险比胃或小肠要大得多。胃 的并发症罕见，最可能是由于胃壁相对较厚或罕见的沿肝胃韧带形成手术 粘连。与相对固定的结肠相比，小肠的蠕动可以提供更好的保护作用。使 用特殊技术-如腹腔内注射葡萄糖隔离肠管-在此种情况下可以考虑。 - 治疗肝门附近的病灶增加了热损伤胆道的风险。这种肿瘤位置是射频 消融的相对的禁忌。在经验丰富者，对位于胆囊附近的肿瘤进行热消融已 证明是可行的，尽管大多数病例会并发自限性的医源性胆囊炎。 - 热消融邻近肝血管的病灶术是可行的，因为通常流动的血液能够保护 血管壁免受热损伤：但是在这些情况下，由于对流产生热量损失，靠近血 管的肿瘤组织的不完全消融风险可能增加。 四、 医师资格认证 治疗前，所有计划进行射频消融治疗肝肿瘤病人都应该经由一个包含介入放 射学家、肝脏病学家、肿瘤学家、外科医生和麻醉学家在内的多学科团队进行详 细评估。介入放射学家所必需具备的核心知识包括理解肝脏解剖，肝肿瘤的诊断 及放射性和非放射性的治疗选择。 4Cardiovascular and Interventional Radiological Society of Europe 2010 年 五、 成像制导/监测 病灶可以通过超声，CT 或磁共振成像进行定位。选择引导系统要根据肿瘤的 可见性，操作者偏好以及所在机构的可用设备如 CT 透视机或开放 MR 系统。消融 中和消融后在超声下见到的瘤内和瘤周一过性高回声区域可以作为肿瘤完全消融 的粗略指标。但是这种方法不能充分评估治疗效果，后续的影像随访是必要的。 MR 是目前唯一具备实时温度监测技术的影像方法。 六、 麻醉监护 热消融治疗通常在静脉镇静或全身麻醉且有心脏、血压和氧饱和度监测的条 件下进行。在一些中心使用全身麻醉。美国麻醉医师协会（ASA）评分（附录 1） 可用于射频消融治疗前评估病人身体状况。达到 ASAIII 评分标准或以上的病人可 以进行治疗。 七、 治疗后的评估和随访 对比增强 CT 或 MR 成像是被公认为评估治疗结果的标准方法。治疗后 4-6 周，完全消融灶在 CT 和 MR 影像上表现为一个具有或不具有边缘增强环的无增强 区域。沿消融区域周围的增强环表现为一个相对向心的、对称的和同质的回声， 内缘光滑。这是一个过性现象，反映了机体对热损伤的良性生理反应过程（最初， 反应性充血；随后，纤维化和巨细胞反应）。消融灶周边的良性增强需要与局部肿 瘤残留鉴别，后者表现为在消融灶边缘出现不规则增强。与消融灶周边的良性增 强不同，局部未消融的肿瘤残留灶常呈分散状，结节状，或偏心状生长。超声造 影在消融结束后即刻进行，并可初步评估治疗效果。后续影像学随访的目的应该 是发现局部肿瘤进展，肝内新病灶，或肝外病灶。推荐的随访计划包括治疗后 3- ， 6- ，9- ，12 个月，接下来 3 年内每隔六个月进行 CT 或 MR 检查。 5Cardiovascular and Interventional Radiological Society of Europe 2010 年 禁忌症 射频消融禁忌： 1。肿瘤距主胆管<1cm，风险主要是治疗后迟发胆道狭窄 2。肝内胆管扩张 3。前外生位置的肿瘤，风险为肿瘤种植 4。胆肠吻合术 5。不可治疗/不能纠正的凝血功能障碍 1. 临床结果：HCC 技术有效性： 射频消融治疗小肝癌的效果令人满意，在肿瘤直径小于 3cm 时，完全消 融率约 90％（4-8）。来自大样本的组织学数据显示，肿瘤大小和位置邻近直 径在 3mm 或以上血管是影响射频消融疗效的重要因素。病理结果显示，直径 <3mm 的肿瘤和周围无血管的肿瘤的完全坏死率可达到 83%和 88%（9）。在 与无水酒精注射（PEI）比较的 五项随机试验（4-8）表明，射频消融比 PEI 具有更高的局部肿瘤灭活作用，从而到达更好的局部肿瘤控制（见表 2）。因 此，射频消融可以完全取代 PEI。 2. 生存： 五项随机试验比较了射频消融术与 PEI 治疗早期 HCC 的疗效（见表 2）。在 接受射频消融治疗和接受 PEI 治疗病人当中，两项欧洲的试验未能显示出两者的 整体生存率存在具有统计学意义的差异。然而，三项亚洲研究认为射频消融病人 具有生存优势（5-7）。这些数据被纳入两项独立的荟萃分析，小 HCC 病人进行射 频治疗的生存益处得到证实（10,11）。因此，基于射频消融能提供更加一致的局部 肿瘤控制结果和更好的生存结果，射频消融术是早期 HCC 病人的首选治疗方法。 最近，经射频消融治疗患者的长期生存结果已有报告（表 3）（12-17）。射频消融 病人的生存期取决于肝硬化的严重程度 和肿瘤分期。 Child A 分级的早期肝癌病 6Cardiovascular and Interventional Radiological Society of Europe 2010 年 作者 病例数 生存率（%） 1 年 3 年 5 年 Lencioni et al (12) Child A, 1 HCC < 5 cm or 3 < 3 cm 144 100 76 51 1 HCC < 5 cm 116 100 89 61 Child B, 1 HCC < 5 cm or 3 < 3 cm 42 89 46 31 Tateishi et al (13) Naive patients * 319 95 78 54 Nonnaive patients ** 345 92 62 38 Cabassa et al (14) 59 94 65 43 Choi et al (15) Child A, 1 HCC < 5 cm or 3 < 3 cm 359 NA 78 64 Child B, 1 HCC < 5 cm or 3 < 3 cm 160 NA 49 38 Takahashi et al (16) Child A, 1 HCC < 5 cm or 3 < 3 cm 171 99 91 77 Hiraoka et al (17) Child-Pugh A-B 105 NA 88 59 NA：not available *首次治疗即采用射频消融治疗的病人 **病人因为肿瘤复发接受射频治疗，此前接受过包括切除，酒精注射，微博消融和 经肝动脉栓塞治疗。 8Cardiovascular and Interventional Radiological Society of Europe 2010 年 1. 临床结果：大肠癌肝转移 技术的有效性： 许多研究探讨了射频消融治疗在不能手术的大肠癌有限肝转移的的病人中的 应用。两项早期的研究 报告的完全缓解率不超过 60％~70％（18,19）。以后， 由于在射频技术的进步以及可能由于接受治疗的肿瘤更小， 射频治疗后成功 的局部肿瘤控制率大幅度上升。在两项报告中，射频消融的肿瘤灭活率分别为 91％和 97%（20,21）。 2. 生存： 最近，非手术的肝大肠转移癌患者接受射频消融治疗后长期生存的数据已有 报告（表 4）（22-28）。特别地，在三个报告中，那些病灶在 5 个或以下，每个直 径 5cm 或以下的患者，第五年的 5 年存活率介于 24%-44%（22,23,26）。当射频 消融治疗用于治疗单发转移灶且病灶小（<4 厘米）的患者，5 年生存率可达 40％ （29）。这些数据大大超过任何化疗方案获得的数据，并提供间接的证据表明，射 频消融治疗可以改善有限 肝脏转移癌患者的生存期。这一结论得到了一项随机对 照实验中期分析结果（34）的支持。该随机对照试验旨在比较化疗联合射频消融 与单纯化疗治疗大肠癌肝转移的疗效。 表 4. 研究报道的经皮射频消融治疗大肠肝转移癌的长期生存结果 作者 病例数 生存率（%） 1 年 3 年 5 年 Solbiati et al (22) 117 93 46 Lencioni et al (23) 423 86 47 24 Gillams et al (24) 73 91 28 25 Machi et al (25) 100 90 42 30 Jackobs et al (26) 68 96 68 9Cardiovascular and Interventional Radiological Society of Europe 2010 年 Sorensen et al (27) 102 87 46 26* Veltri et al (28) 122 79 38 22 *4 年生存率 3. 并发症 与射频消融相关的早期主要并发症发生在 2.2%-3.1％的患者，包括腹腔内出 血，肝脓肿，肠穿孔，气/血胸，胆管狭窄和肿瘤种植（0.5％）;相关的死亡率是 0.1〜0.5％（见表 5）。次要并发症的发生率在 5％~8.9％。最常见的死亡原因是败 血症，肝衰竭，结肠穿孔以及门静脉血栓，而最常见的并发症为腹腔出血，肝脓 肿，胆道损伤，肝失代偿，接地垫灼伤。次要并发症和副作用通常是一过性和自 限性的（31-33）。一种罕见的射频消融治疗晚期并发症是肿瘤沿针道种植。在 HCC 病人，一项多中心调查报告 1610 例中有 8 例（0.5%）发生肿瘤种植（31），另一 个机构报告 187 例中有 1 例（0.5%）发生种植（12）。肿瘤位于包膜下和肿瘤的 侵袭性生长方式（表现为分化程度很低），似乎是发生上述并发症的高风险因素 （39）。 表 5 已报道的和可接受的主要并发症发生率 每次治疗的并发症 报道的发生率 建议上限 需要输血治疗的出血 1% 2% 肠穿孔 0.3% 0.6% 脓肿 0.3% 0.6% 血胸 0.1% 0.2% 肿瘤种植 0.5% 1% 肝失代偿 0.3% 0.6% 胆管损伤 0.5% 1% 接地垫烫伤 0.1% 0.2% 死亡 0.5% 1% 10 CIRSE | Cardiovascular and Interventional Radiological Society of Europe - 1 - Quality Improvement Guidelines for Radiofrequency Ablation of Liver Tumours Laura Crocetti, MD, PhD Thierry de Baere, MD Riccardo Lencioni, MD Introduction The development of image-guided percutaneous techniques for local tumour ablation has been one of the major advances in the treatment of liver malignancies. Among these methods, radiofrequency (RF) ablation is currently established as the primary ablative modality at most institutions. RF ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when liver transplantation or surgical resection are not suitable options (1,2). In addition, RF ablation is considered as a viable alternate to surgery for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer, in patients deemed ineligible for surgical resection, because of extent and location of the disease or concurrent medical conditions (3). These guidelines are written to be used in quality improvement programs to assess RF ablation of HCC and liver metastases. The most important processes of care are 1) patient selection, 2) performing the procedure, and 3) monitoring the patient. The outcome measures or indicators for these processes are indications, success rates, and complication rates. Definitions Ablative margin: the region ablated beyond the borders of the tumour, to achieve complete tumour destruction. It should be ideally 0.5–1.0-cm wide. Complete ablation: Non-enhancing area at contrast-enhanced imaging modalities, including the tumour and the ablative margin. Complications: Complications can be stratified on the basis of outcome by using the SIR standard table. Major complications result in: admission to a hospital for therapy (for outpatient procedures), an unplanned increase in the level of care, prolonged hospitalization, permanent 11 CIRSE | Cardiovascular and Interventional Radiological Society of Europe - 2 - adverse sequelae, or death. Minor complications result in no sequelae; they may require nominal therapy or a short hospital stay for observation (generally overnight). Major and minor complications and side effects should be reported on the basis of the number of ablation sessions on a per-session basis. Electrode: RF applicator. One or multiple eletrodes have to be insertered directly into the tumour to deliver RF energy current. Electrodes can be monopolar or bipolar and thay can have different designs (multitined expandable, internally cooled, perfused). - Monopolar electrode: there is a single active electrode, with current dissipated at one or several return grounding pads. - Bipolar electrode: there are two active electrode applicators, which have to be placed in proximity - Multitined expandable electrode: multiple electrode tines that expand from a larger needle cannula. - Internally cooled electrode: the electrode has an internal lumen which is perfused by saline without coming into direct contact with patient tissues - Perfused electrode: the tip of the electrode has small apertures that allows the fluid (usually saline) to come in contact with the tissue Heat sink effect: convective cooling by adjacent blood vessels usually 3 mm or larger when ablated tissues are heated. It can negatively affect the results of RF ablation because it can potentially remove heat before complete tumour ablation is achieved Hydro/Gas dissection : instillation of liquid (dextrose 5%, sterile water) or gas (air, CO2) between the area of ablation and the structure vulnerable to heating damage (usually the bowel) Incomplete ablation: Presence of residual unablated tumour that is seen as peripheral irregular enhancement at imaging. It often grows in scattered, nodular, or eccentric pattern. Local tumour progression: Appearance at follow-up of foci of untreated disease in tumours that 12 CIRSE | Cardiovascular and Interventional Radiological Society of Europe - 3 - were previously considered to be completely ablated. Overall survival: Time from inclusion in the study to death. Patients alive at the end of follow-up are censored. Radiofrequency Ablation: coagulation induction from all electromagnetic energy sources with frequencies less than 30 MHz. For tumour ablation purposes the frequency is usually in the 375– 500 kHz range. Technical success: The treatment of the tumour was perfomed according to protocol and the complete tumour coverage is assessed, either during or immediately after the procedure. Transient hyperechoic zone: transient (up to 30–90 minutes) zone of increased echogenicity seen at US within and surrounding a tumour during and immediatelyafter RF ablation Indications HCC: RF ablation is the therapy of choice in very early and early HCC according to the Barcelona Clinic Liver Cancer (BCLC) classification (Table 1) when patients are not candidates for either liver resection or transplantation. Patients are required to have a single tumour smaller or as many as three nodules smaller than 3 cm each, no evidence of vascular invasion or extrahepatic spread, performance status test of 0, and liver cirrhosis in Child-Pugh class A or B. Table 1: BCLC classification in patients diagnosed with HCC ___________________________________________________________________________ Very Early Stage: PS 0, Child-Pugh A, single HCC < 2 cm Early Stage: PS 0, Child-Pugh A-B, single HCC or 3 nodules < 3 cm Intermediate Stage: PS 0, Child-Pugh A-B, multinodular HCC Advanced Stage: PS 1-2, Child-Pugh A-B, portal neoplastic invasion, nodal metastases, 13 CIRSE | Cardiovascular and Interventional Radiological Society of Europe - 4 - distant metastases Terminal Stage: PS>2, Child-Pugh C _____________________________________________________________________________ PS: performance status Liver metastases: - Primary tumour histotype: RF ablation is generally indicated for nonsurgical patients with colorectal cancer oligometastases isolated to the liver. Selected patients with limited hepatic and pulmonary colorectal metastatic disease, however, may qualify for percutaneous treatment provided that extrahepatic disease is deemed curable. In patients with hepatic metastases from other primary cancers, promising initial results have been reported in the treatment of breast and endocrine tumours. - Number of lesions: The number of lesions should not be considered an absolute contraindication to RF ablation if successful treatment of all metastatic deposits can be accomplished. Nevertheless, most centres preferentially treat patients with five or fewer lesions. - Tumour size: The target tumour should not exceed 3 cm in longest axis to achieve best rates of complete ablation with most of the currently available devices. Tumour location: Pretreatment imaging must carefully define the location of each lesion with respect to surrounding structures: - Lesions located on the surface of the liver can be considered for RF ablation, although their treatment requires adequate expertise and may be associated with a higher risk of complications. - Thermal ablation of superficial lesions that are adjacent to any part of the gastrointestinal tract must be avoided because of the risk of thermal injury of the gastric or bowel wall. The colon appears to be at greater risk than the stomach or small bowel for thermally mediated perforation. Gastric complications are rare, most likely owing to the relatively greater wall thickness of the stomach or the rarity of surgical adhesions along the gastrohepatic ligament. The mobility of the small bowel may also provide the bowel with greater protection compared with the 14 CIRSE | Cardiovascular and Interventional Radiological Society of Europe - 5 - relatively fixed colon. The use of special techniques - such as intraperitoneal injection of dextrose to displace the bowel - can be considered in such instances. - Treatment of lesions adjacent to the hepatic hilum increases the risk of thermal injury of the biliary tract. This tumour location represents a relative contraindication to RF ablation. In experienced hands, thermal ablation of tumours located in the vicinity of the gall-bladder has been shown to be feasible, although associated in most cases with self-limited iatrogenic cholecystitis. - Thermal ablation of lesions adjacent to hepatic vessels is possible, since flowing blood usually protects the vascular wall from thermal injury: in these cases, however, the risk of incomplete treatment of the neoplastic tissue close to the vessel may increase because of the heat loss by convection. Physician Credentialling Prior to treatment, all patients with liver tumours who are considered for RF ablation should undergo a thorough clinical evaluation by a multidisciplinary team including interventional radiologist, hepatologist, oncologist, surgeon, and anesthesiologist. The body? core of knowledge required for the interventional radiologist includes understanding of liver anatomy, liver tumour diagnosis and radiological and non radiological treatment options . Imaging guidance/monitoring Targeting of the lesion can be performed with ultrasound, CT, or MR imaging. The guidance system is chosen largely on the basis of tumour visibility,operator preference and local availability of dedicated equipment such as CT fluoroscopy or open MR systems. The transient hyperechoic zone that is seen at ultrasound within and surrounding a tumour during and immediately after RF ablation can be used as a rough guide to the extent of tumour destruction. It is not sufficient to evaluate treatment effectiveness and follow-up imaging is mandatory. MR is currently the only imaging modality with validated techniques for real-time temperature monitoring. Anesthesiology care 15 CIRSE | Cardiovascular and Interventional Radiological Society of Europe - 6 - Thermal ablation is usually performed under intravenous sedation or general anesthesia with standard cardiac, pressure, and oxygen monitoring. In some centres ( American spelling- suggest centre if this is a CIRSE doc) general anesthesia is used. ( similarly tumour is American spelling- tumour is preferable if this doc is not a combined SIR doc) American Society of Anesthesiologists (ASA) score (Appendix 1) can be used to assess patient physical status prior to RF ablation. Patients up to ASA III score can be treated. Post-treatment assessment and follow-up Contrast-enhanced CT or MR imaging are recognized as the standard modalities to assess treatment outcome. CT and MR images obtained 4-6 weeks after treatment show successful ablation as a nonenhancing area with or without peripheral enhancing rim. The enhancing rim that may be observed along the periphery of the abla