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放射性心脏损伤的研究进展

刘志飞, 王颖杰

刘志飞, 王颖杰. 放射性心脏损伤的研究进展[J]. 肿瘤防治研究, 2018, 45(11): 852-857. DOI: 10.3971/j.issn.1000-8578.2018.18.0893
引用本文: 刘志飞, 王颖杰. 放射性心脏损伤的研究进展[J]. 肿瘤防治研究, 2018, 45(11): 852-857. DOI: 10.3971/j.issn.1000-8578.2018.18.0893
LIU Zhifei, WANG Yingjie. Research Progress of Radiation-indnced Heart Disease[J]. Cancer Research on Prevention and Treatment, 2018, 45(11): 852-857. DOI: 10.3971/j.issn.1000-8578.2018.18.0893
Citation: LIU Zhifei, WANG Yingjie. Research Progress of Radiation-indnced Heart Disease[J]. Cancer Research on Prevention and Treatment, 2018, 45(11): 852-857. DOI: 10.3971/j.issn.1000-8578.2018.18.0893

放射性心脏损伤的研究进展

详细信息
    作者简介:

    刘志飞(1987-),男,硕士在读,主要从事肿瘤的放射治疗临床工作

    通讯作者:

    王颖杰,E-mail:wangyj9999@163.com

  • 中图分类号: R730.6

Research Progress of Radiation-indnced Heart Disease

More Information
  • 摘要:

    放射治疗可以提高许多恶性肿瘤患者的生存率,但辐射诱发的副作用,特别是胸部照射可能引发的心脏、血管和肺的损伤,导致组织重塑,这个复杂的过程是由大量相互作用的分子信号组成,包括细胞因子、趋化因子和生长因子。而炎性反应、内皮细胞功能障碍、血栓形成、器官功能障碍以及最终的心脏衰竭是一种病理实体“放射性心脏损伤”,与纵隔淋巴瘤、乳腺癌、肺癌和食管癌等放射治疗有关,是胸部肿瘤放疗后发病率和死亡率的主要来源之一。而长期潜伏期是RIHD不被广泛研究的原因,但随着肿瘤患者生存时间延长,放疗所致的迟发性心脏损伤的问题越发突出。除了老年患者,年轻患者治疗后RIHD发生率也在逐渐增高,因此RIHD越来越受到关注和重视。本文将对放射性心脏损伤的类型、发病机制、影响因素的相关研究进行综述。

     

    Abstract:

    Radiotherapy(RT) improves the survival of many cancer patients, but there are some adverse effects of radiation. One of them is radiation-induced heart disease(RIHD). In case of chest irradiation, RIHD can affect the heart, blood vessels and lungs, with consequent tissue remodelation. This complex process is composed of a large number of interacting molecular signals, including cytokines, chemokines and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction and ultimate failing of the heart occur as the pathological entity-RIHD which is associated with radiation therapy for mediastinal lymphoma, breast, lung and oesophageal cancers, etc. And is the major source of morbidity and mortality. The long latent period is the reason why RHID is not extensively studied. With the prolonged survival of cancer patients, RIHD is growing concerned, especially in younger patients. In this review article, we discuss the pathogenesis, the type of injury and influencing factors.

     

  • 目前经胸腔镜肺叶切除、淋巴结清扫已成为早中期肺癌的标准手术方式,其手术的安全性及有效性也越来越被认可。中国人民解放军海军总医院自2009年8月至2015年8月对116例非小细胞肺癌患者采用电视胸腔镜肺叶切除(video-assisted thoracoscopic lobectomy)及系统淋巴结清扫术(systematic lymph node dissection, SLND),获得了满意的疗效。现对本组手术资料及随访数据进行总结分析,探讨胸腔镜下肺叶切除术的安全性、可靠性以及患者的并发症和生存率。

    本组共116例,男62例、女54例;中位年龄:(59.5±11.9)(范围35~82)岁,其中35~69岁81例(69.8%)、70~82岁高龄患者35例(30.2%)。患者病变位于左上肺33例、左下肺21例、右上肺30例、右中肺叶8例、右下肺24例。术前经穿刺确诊59例(鳞癌21例、腺癌38例),PET-CT诊断22例并术中冰冻确诊(鳞癌7例、腺癌15例),其余35例为术中冰冻确诊(鳞癌10例、腺癌22例、3例术后确诊腺鳞癌2例及大细胞癌1例)。本组患者不包括同期中转开胸患者。

    双腔气管内插管静脉复合全身麻醉,健侧单肺通气,健侧90°卧位。手术采用单操作孔45例:第7或8肋间腋后线作为观察孔长约1 cm;操作孔在腋前线与锁骨中线间第4或第5肋间,长约3~5 cm;两操作孔71例,在肩胛下角线,第8或9肋间加一长约辅助操作孔1 cm。电视胸腔镜采用史塞克30°镜,使用电凝钩、超声刀进行分离、解剖肺门结构,内镜直线切割缝合器处理血管、支气管和叶间裂,完成解剖性肺叶切除,使用电凝钩、超声刀行系统淋巴结清扫术。完成左上肺切除33例(其中1例为左上肺叶切除并左下肺叶局部切除)、左下肺切除21例、右上肺切除30例、右中肺叶切除8例、右下肺切除24例。

    入组患者术后建立完整资料档案。对术后分期Ⅰb期以上患者给予第3代铂类药物为基础的化疗方案,治疗4周期。术后一年每3月复查一次,以后每6月复查一次,随访方式采取来院复查、电话或信件进行。

    所有资料采用SPSS17.0软件进行统计学处理,数据采用百分率、均数±标准差(x±s)表示。采用Kaplan-Meier生存曲线对生存率进行分析。P < 0.05为差异有统计学意义。

    本组无围术期死亡。手术时间64~276 min。出血量60~560 ml,2例肺血管分支出血,经纱布压迫、镜下缝合止血。11例患者围术期发生并发症,其中肺漏气2例、肺部感染1例、肺膨胀不全和肺不张4例、心律失常1例、皮下气肿3例,均经对症治疗后治愈。术后住院时间5~12天。清扫各组淋巴结12~31枚,淋巴结站数(5.6±1.2),主要为第4、5、6、7、10、11组淋巴结。术后病理诊断,见表 1

    表  1  术后病理诊断及分期
    Table  1  Postoperative pathological diagnosis and stage
    下载: 导出CSV 
    | 显示表格

    随访截至2015年8月,平均随访时间4~69月,随访期间共死亡11例,4例失访(失访计入死亡)。Kaplan-Meier生存统计分析,Ⅰ、Ⅱ、Ⅲ期非小细胞肺癌患者术后5年生存率分别为77.6%、42.4%、20.8%,见图 1

    图  1  116例Ⅰ期到Ⅲa期非小细胞肺癌患者术后生存率
    Figure  1  Post-operative survival of 116 NSCLC patients from stage Ⅰ to stage Ⅲa

    鉴于传统开胸术式给患者造成极大的痛苦[1],电视胸腔镜肺叶切除术肺癌根治术自20世纪90年代以来发展迅速,随着经验积累和技术进步已在全世界范围内得到广泛应用,其诸多优势已经充分得到肯定,是安全、可靠的手术方式之一。我们对116例非小细胞肺癌患者采用电视胸腔镜肺叶切除术及系统淋巴结清扫术(SLND)治疗,效果良好,平均住院时间缩短、术中出血量少、炎性反应轻、术后并发症少、术后疼痛发生率低。当然,开展初期,手术时间相对较长,随着手术例数的增多及对该技术的熟练掌握,目前平均手术时间(123.1±51.0)min(64~276 min),而且手术方式也从三孔逐步过渡到两孔(单操作孔)。目前,国内外许多学者已进行单孔肺叶切除及淋巴结清扫,Feng等[2]报道一组54例单孔胸腔镜肺叶切除,认为单孔胸腔镜肺叶切除肺癌根治、淋巴结清扫是一种安全有效的手术技术,而手术器械的进步和外科技术的改良有助于该技术的提高。

    胸腔镜手术并发症发生率较低。本组患者术后常见并发症有肺漏气、出血、肺部感染、肺不张、心律失常和皮下气肿等,共11例,占9.48%,经对症处理全部治愈。Wang[3]报道一组胸腔镜手术结果,总的术后30日内并发症发生率,胸腔镜组较开放组显著降低,而术后30日并发症发生率较开放组有下降趋势但无显著性差异,胸腔镜组住院时间明显缩短,Kaplan-Meier生存分析显示5年的无疾病生存和总生存率相似。

    胸腔镜肺叶切除术的患者机体功能恢复快[4]、术后辅助化疗耐受性好[5]。日本一项比较胸腔镜与开胸手术预后及化疗耐受性的研究结果提示,胸腔镜术后并发症较低并且更有益于患者接受全程足量的化疗(腔镜组和开胸组的化疗率:(84.2% vs. 65.8%, P=0.032))[6],本组对术后分期Ⅰb期以上的患者给予第3代铂类药物为基础的化疗方案,治疗4周期,耐受性好。

    胸腔镜肺叶切除手术对高龄、肺功能低的患者[7-8]具有显著优势。Oparka等[9]研究发现对限制性肺通气障碍患者,FEV1预计值 < 60%,胸腔镜肺部并发症明显低于开放手术(P=0.023),肺炎发生率减少(4.3% vs. 21.7%, P < 0.05),重症监护时间缩短(2天vs. 4天, P=0.05),住院时间缩短(7天vs. 10天, P=0.058);而比较FEV1 < 40%患者术后复发和生存结果显示,胸腔镜解剖性肺段切除较开胸肺段切除的住院时间缩短(8天vs. 12天, P=0.054),而5年生存率明显延长(42% vs. 18%, P=0.02)。本组年龄最大的1例患者82岁,右下肺内基底段肿物3.5 cm×3.0 cm,部分肺不张,经皮CT引导下穿刺证实鳞状细胞癌,术前FEV1仅52%(2.1升),考虑到术前局限肺不张,通气血流比有失调,术后肺功能则有可能改善,而肿物较大不能行肺段切除,故行单孔右下肺叶切除,淋巴结清扫,术后经呼吸道管理、呼吸功能锻炼等围手术期处理,恢复顺利,无明显并发症发生,氧饱和度可达95%,术后病理T2N0M0(Ⅰb期),术后未进行任何辅助治疗,目前已随访28月,未见肿瘤复发,生活质量较高。我们认为胸腔镜肺叶切除操作能够减少对健肺的揉捏,刺激少、炎性反应轻;而胸腔镜微小的创伤可减轻术后疼痛,有利于咳嗽、余肺膨胀,使肺功能快速恢复。

    关于淋巴结清扫,胸腔镜手术由于镜头能够达到胸腔内的各个部位,视野更清楚,因此对淋巴结的清扫具有独到的优势。本组清扫各组淋巴结12~31枚,淋巴结站数(5.6±1.2),符合肺癌根治标准。Zhang等[10]在一项电视辅助胸腔镜手术(video-assisted thoracoscopic surgery, VATS)和开放手术比较研究中对淋巴结清扫和淋巴结采样,全身和局部复发率和长期生存率的Meta分析提示,两组中总的淋巴结清扫或淋巴结采样与纵隔淋巴结清扫或采样数无显著性差异,但胸腔镜组的全身性或局部复发率明显降低。该研究提示在早期非小细胞肺癌中,胸腔镜在降低复发率和提高生存率上是一种可替代传统开胸手术的正确合适的选择。

    淋巴结清扫是影响术后疗效的主要因素,Merritt等[11]研究发现,开放组的淋巴结清扫平均数明显高于腔镜组,开放组中24.6%的患者淋巴结从术前的N0期升至术后的N1或N2期,而腔镜组仅占10%(P=0.05),两组Kaplan-Meier 3年生存率相似。虽然淋巴结升期并未能转化为3年生存率的提高,但笔者认为在胸腔镜手术中应该更加充分地清扫淋巴结。Licht等[12]的一项Ⅰ期NSCLC研究结果也发现腔镜组的淋巴结升期率要低于开放组,而同样多因素生存分析提示两组生存率无显著性差异。另外,淋巴结处理也是胸腔镜中转开胸主要影响因素[13],胸腔镜手术过程中处理困难淋巴结可增加手术时间、增加失血量、术后恢复时间延长,因此,选择正确及时的中转开胸可以减少以上危害。

    远期生存质量是评价一种手术方式是否合理的最重要标准。Murakawa等[14]认为,胸腔镜手术在手术时间、出血量、置管时间和住院时间上要优于开放手术,但生存期预后方面与开放手术基本相差不大。Cao等[15]报道一组标准的胸腔镜肺叶切除与传统开胸手术有相似的远期生存效果。Yamamoto等[16]报道325例电视胸腔镜肺叶切除术治疗原发性肺癌,随访时间超过5年,平均随访66月,全组患者5年总体生存率和无病生存率在各分期分别为:Ⅰa期85%和83%、Ⅰb期69%和64%、Ⅱ期48%和37%、Ⅲ期29%和19%。这些数据不次于国际公认的开胸手术生存率。本组116例非小细胞肺癌胸腔镜肺叶切除及系统淋巴结清扫术患者中,有112例完成了随访,平均随访时间4~69月,Ⅰ、Ⅱ、Ⅲ期非小细胞肺癌患者术后5年生存率分别为77.6%、42.4%、20.8%,与上述报道结果相类似。

    本组116例胸腔镜肺叶切除手术经验进一步证实了该手术是一种安全、可靠的手术方式,可完成解剖意义上的肿瘤彻底切除和淋巴结清扫,已经成为肺部肿瘤外科治疗的标准手术术式之一。相信随着手术器械的改进和技术的提高,手术适应证范围将继续扩大,并发症发生率会进一步降低,肺癌患者术后的生存率将进一步提高。

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出版历程
  • 收稿日期:  2018-07-04
  • 修回日期:  2018-10-11
  • 网络出版日期:  2024-01-12
  • 刊出日期:  2018-11-24

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