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Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi.
2019 Dec; 33(12): 1589–1592.
Language:
Chinese
|
English
吲哚菁绿造影在淋巴水肿中的应用进展
Application progress of indocyanine green angiography in lymphedema
and
*
玉杰 陈
北京大学人民医院整形美容科(北京 100044),
Plastic and Aesthetic Surgery Department, Peking University People’s Hospital, Beijing, 100044, P.R.China
籣 穆
北京大学人民医院整形美容科(北京 100044),
Plastic and Aesthetic Surgery Department, Peking University People’s Hospital, Beijing, 100044, P.R.China
北京大学人民医院整形美容科(北京 100044),
Plastic and Aesthetic Surgery Department, Peking University People’s Hospital, Beijing, 100044, P.R.China
1. ICG 造影在淋巴水肿中应用的历史沿革
2007 年,Unno 等
[
4
]
首次报道 ICG 造影可用于淋巴水肿的诊治,皮下注射 ICG 后通过红外摄像仪等装置实时获取荧光图像,他们在注射后 30 min 内观察到了继发性淋巴水肿患者的几种典型淋巴引流模式。同年,Ogata 等
[
5
]
进一步验证了在没有皮肤切口情况下,利用 ICG 造影技术可以实时动态识别皮下正常及异常的淋巴管,并且能观察到直径仅 0.1 mm 的淋巴管;同时,该技术甚至可以检测亚临床期淋巴水肿。2011 年,Yamamoto 等
[
6
]
提出可以利用 ICG 造影动态成像对淋巴水肿严重程度进行分级,这种分级方法能更直观反应皮下淋巴循环,这种基于解剖结构的分级与病因学联系更密切,为指导后续淋巴外科的发展奠定了基础。2015 年,Yamamoto 等
[
7
]
首次将 ICG 造影用于诊断原发性淋巴水肿患者,结果显示其诊断特异性、敏感性均达 100%, 同时他们指出 ICG 造影可以提示原发性淋巴水肿发生机制,并判断预后。
2. ICG 造影在诊断淋巴水肿中的应用
2.1. 淋巴水肿诊断方法
目前,临床诊断淋巴水肿方法有多种,包括肢体测量、临床检测、生物阻抗谱(bioimpedance spectroscopy,BIS)、动态成像(淋巴核素显像和 ICG 动态荧光成像)
[
8
]
。其中,肢体测量只能进行大体估算,准确性较低,尤其对于早期淋巴水肿患者,存在极大误差。临床检测主要采用磁共振淋巴造影及多普勒超声,均为安全、无创技术。其中,前者是利用造影剂联合 T2 抑脂像清晰显示淋巴结及淋巴管,甚至畸形的淋巴通路,是观察淋巴循环较好方式。但核磁仪器使用成本较高,难以反复摄像进行实时动态监测。后者观察范围有限,往往只能观察探头以下局部组织,且皮下组织层次不清,常难以区分淋巴管、静脉管及神经
[
9
-
10
]
。BIS 是一种新的诊断方式,通过评估组织对电流流动阻力来测量肢体液体含量,假阴性率高,而且无法显示早期淋巴水肿在压迫或活动后发生改变的原因,因此 BIS 诊断早期淋巴水肿的有效性尚存在争议
[
8
]
。淋巴核素显像可用于监测整个肢体淋巴流动,但存在辐射暴露及淋巴系统显影不清等问题。ICG 动态荧光成像无辐射暴露问题,操作简便,能实时动态观测
[
8
,
9
-
11
]
;相比淋巴核素显像,其具有更高灵敏度和特异性,可实时快速显示浅表淋巴流动
[
12
]
。
2.2. ICG 造影在淋巴水肿诊断中的应用
目前,临床对于淋巴水肿的诊断主要采用皮下注射 0.2 mL ICG 进行示踪观察。ICG 注入体内后通过淋巴管回吸收,与淋巴管中相应蛋白结合,进入静脉系统,在红外光激发下发出荧光,利用红外摄像仪获取实时动态淋巴引流图像
[
9
,
13
]
。随着淋巴水肿的进展,ICG 回流逐渐减慢,流动时间延长,因此 ICG 造影不仅能准确诊断淋巴水肿,还能对严重程度进行分期
[
7
,
14
-
15
]
。Yamamoto 等
[
16
]
基于 ICG 造影提出了淋巴系统实时动态荧光示踪分级,共分为 4 级。Ⅰ 级,许多新生淋巴管,最小化真皮回流,线型;Ⅱ 级,中等新生淋巴管,节段性真皮回流,溅射型;Ⅲ 级,极少新生淋巴管,广泛真皮回流,星辰型;Ⅳ 级,没有新生淋巴管,严重真皮回流,弥漫型。该分级标准从更微观角度观察淋巴水肿,提升了诊断的准确性。
目前,ICG 造影已用于包括宫颈癌在内的许多实体器官肿瘤前哨淋巴结的定位
[
17
]
,具有检查成本低、实时显示淋巴动态循环、前哨淋巴结检出率高等优点。但基于 ICG 造影进行分级也存在不足:① 只能依据镜下成像分为线型、溅射型、星辰型及弥散型,存在一定主观性;② ICG 进入淋巴系统后需要与蛋白结合,此时形成的的 ICG-蛋白复合体较大,存在流速过慢的问题,重度淋巴水肿患者成像等待时间较长;③ ICG 与淋巴管中蛋白结合后,在近红外光激发下发出荧光,这种荧光穿透力较弱,故只能显示皮下 1.5 cm 以内的浅表淋巴回流
[
15
]
。因此,ICG 在诊断淋巴水肿方面的应用仍需进一步探究。
3. ICG 造影在淋巴水肿治疗中的应用
淋巴水肿治疗主要分为保守治疗和手术治疗。对于 ICG 造影提示为 Ⅲ、Ⅳ 级的严重淋巴水肿,因为皮下新生淋巴管极少,手术治疗常难以取得预期效果,往往不再选择手术,而采取局部压迫等保守疗法,但效果较差。因此对于有条件手术治疗患者,为达更好疗效建议选择手术治疗。由于淋巴管呈半透明及几乎分布在黄色脂肪组织中,术中难以通过肉眼识别,而 ICG 造影可以清晰显示淋巴管,在手术治疗淋巴水肿中具有极大应用价值
[
18
]
。淋巴水肿手术成功的关键因素为术前识别和定位淋巴管以及淋巴静脉吻合术(lymphaticovenular anastomosis,LVA)后检测其通畅性
[
19
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21
]
。利用 ICG 造影能显著缩短术中寻找淋巴管以及移植淋巴管所需时间,并且为精确定位切口位置以达到最小化切口提供了可能
[
18
]
。
治疗淋巴水肿的手术方式有多种,如带血运的淋巴结移植术、LVA 和减容手术等
[
22
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23
]
,其中 LVA 被认为是最理想术式。LVA 出现于 20 世纪 70 年代,主要用于治疗早期淋巴水肿。术中将淋巴管(结)与邻近小静脉吻合,使积聚的淋巴液直接引入静脉循环中,绕过淋巴管阻塞区,从而减少淋巴水肿的发生
[
24
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27
]
。
目前淋巴水肿术式主要根据其严重程度来选择,严重程度可参照传统国际淋巴协会分级和 ICG 造影分级,但两种分级标准之间无一定对应关系。有学者报道,根据传统国际淋巴协会分级结果已经失去手术时机的患者,其 ICG 造影分级可能为 Ⅰ、Ⅱ 级,即提示患肢有相对较丰富的侧支循环,按此分级结果可以选择 LVA 改善预后
[
28
]
。Yamamoto 等
[
29
]
建议 LVA 适应证及切口的选择均应基于 ICG 造影结果,当 ICG 造影显示淋巴回流呈广泛性弥漫时不宜选择 LVA,应考虑行带血运淋巴结移植术或者吸脂术。然而 Seki 等
[
30
]
认为 ICG 造影呈星辰型或弥漫型图像时,会掩盖存在的线型图像,限制了其检测进展性淋巴水肿患者淋巴管的能力,从而延误 LVA 时机。因此 ICG 造影在淋巴水肿手术治疗的应用值得更进一步研究。
综上述,ICG 造影是一种微创成像方式,不仅能评估淋巴水肿严重程度,还可以通过实时动态观察淋巴流动来确定淋巴管位置,为临床选择合适的切口及手术方式提供客观依据
[
9
]
。
4. 总结及展望
目前,亚临床期淋巴水肿往往难以检测,早期淋巴水肿难以引起临床重视,晚期又缺少理想的治疗措施,如何早期诊断并治疗淋巴水肿仍需深入研究。ICG 造影为淋巴水肿的诊治带来了新突破,从评估到治疗均能实时动态提供皮下组织中淋巴循环的状况,耗时短、无辐射及可重复性是其优点,但也存在淋巴显影速度不能量化及深部淋巴管(结)难以显影等方面的问题。
作者贡献:陈玉杰负责查阅文献及撰写文章,穆籣指导选题并协助修改文章。
利益冲突:所有作者声明,在课题研究和文章撰写过程中不存在利益冲突。
References
1.
Struk S, Honart JF, Qassemyar Q, et al Use of indocyanine green angiography in oncological and reconstructive breast surgery.
Annales de Chirurgie Plastique Esthétique.
2018;
63
(1):54–61. doi: 10.1016/j.anplas.2017.09.008.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
3.
Ietto G, Amico F, Soldini G, et al Real-time intraoperative fluorescent lymphography: A new technique for lymphatic sparing surgery.
Transplant Proc.
2016;
48
(9):3073–3078. doi: 10.1016/j.transproceed.2016.08.017.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
4.
Unno N, Inuzuka K, Suzuki M, et al Preliminary experience with a novel fluorescence lymphography using indocyanine green in patients with secondary lymphedema.
J Vasc Surg.
2007;
45
(5):1016–1021. doi: 10.1016/j.jvs.2007.01.023.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
5.
Ogata F, Azuma R, Kikuchi M, et al Novel lymphography using indocyanine green dye for near-infrared fluorescence labeling.
Ann Plast Surg.
2007;
58
(6):652–655. doi: 10.1097/01.sap.0000250896.42800.a2.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
6.
Yamamoto T, Narushima M, Doi K, et al Characteristic indocyanine green lymphography findings in lower extremity lymphedema: the generation of a novel lymphedema severity staging system using dermal backflow patterns.
Plast Reconstr Surg.
2011;
127
(5):1979–1986. doi: 10.1097/PRS.0b013e31820cf5df.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
7.
Yamamoto T, Yoshimatsu H, Narushima M, et al Indocyanine green lymphography findings in primary leg lymphedema.
Eur J Vasc Endovasc Surg.
2015;
49
(1):95–102. doi: 10.1016/j.ejvs.2014.10.023.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
8.
Qin ES, Bowen MJ, Chen WF Diagnostic accuracy of bioimpedance spectroscopy in patients with lymphedema: A retrospective cohort analysis.
J Plast Reconstr Aesthet Surg.
2018;
71
(7):1041–1050. doi: 10.1016/j.bjps.2018.02.012.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
9.
Hayashi A, Hayashi N, Yoshimatsu H, et al Effective and efficient lymphaticovenular anastomosis using preoperative ultrasound detection technique of lymphatic vessels in lower extremity lymphedema.
J Surg Oncol.
2018;
117
(2):290–298. doi: 10.1002/jso.24812.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
10.
Zaleska MT, Olszewski WL The effectiveness of intermittent pneumatic compression in therapy of lymphedema of lower limbs: methods of evaluation and results.
Lymphatic Research and Biology.
2019;
17
(1):60–69. doi: 10.1089/lrb.2018.0005.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
11.
Tashiro K, Yamashita S, Koshima I, et al Visualization of accessory lymphatic pathways in secondary upper extremity lymphedema using indocyanine green lymphography.
Ann Plast Surg.
2017;
79
(4):393–396. doi: 10.1097/SAP.0000000000001120.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
12.
Hara H, Mihara M Indocyanine green lymphographic and lymphoscintigraphic findings in genital lymphedema—genital pathway score.
Lymphat Res Biol.
2017;
15
(4):356–359. doi: 10.1089/lrb.2017.0025.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
13.
Miranda Garcé M, Pons G, Mirapeix R, et al Intratissue lymphovenous communications in the mechanism of action of vascularized lymph node transfer.
J Surg Oncol.
2017;
115
(1):27–31. doi: 10.1002/jso.24413.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
14.
Chen WF, Zhao H, Yamamoto T, et al Indocyanine green lymphographic evidence of surgical efficacy following microsurgical and supermicrosurgical lymphedema reconstructions.
J Reconstr Microsurgery.
2016;
32
(9):688–698. doi: 10.1055/s-0036-1586254.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
15.
Yamamoto T, Narushima M, Yoshimatsu H, et al Dynamic indocyanine green (ICG) lymphography for breast cancer-related arm lymphedema.
Ann Plast Surg.
2014;
73
(6):706–709. doi: 10.1097/SAP.0b013e318285875f.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
16.
Yamamoto T, Iida T, Matsuda N, et al Indocyanine green (ICG)-enhanced lymphography for evaluation of facial lymphoedema.
J Plast Reconstr Aesthet Surg.
2011;
64
(11):1541–1544. doi: 10.1016/j.bjps.2011.05.025.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
17.
Brar H, Hogen L, Covens A Cost-effectiveness of sentinel node biopsy and pathological ultrastaging in patients with early-stage cervical cancer.
Cancer.
2017;
123
(10):1751–1759. doi: 10.1002/cncr.30509.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
18.
Aung T, Taeger C, Geis S, et al. The use of integrated indocyanine green fluorescence microscope camera for intraoperative lymphography of supermicrosurgery. Clin Hemorheol Microcirc, 2018. [Epub ahead of print]
19.
Yang JC, Wu SC, Chiang MH, et al Intraoperative identification and definition of “functional” lymphatic collecting vessels for supermicrosurgical lymphatico-venous anastomosis in treating lymphedema patients.
J Surg Oncol.
2018;
117
(5):994–1000. doi: 10.1002/jso.25014.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
20.
李广学, 穆籣, 刘岩, 等 吲哚菁绿淋巴造影在超显微淋巴管静脉吻合中的应用
中华整形外科杂志
2018;
34
(4):271–273. doi: 10.3760/cma.j.issn.1009-4598.2018.04.006.
[
CrossRef
]
[
Google Scholar
]
21.
Mu L, Peng Z, Zang H, et al Operating microscope with near infrared imaging function for indocyanine green lymphography in prevention of lymphedema with lymphaticovenous anastomosis immediately after mastectomy and axillary dissection.
Microsurgery.
2017;
37
(4):354–355.
[
PubMed
]
[
Google Scholar
]
22.
Campisi CC, Larcher L, Lavagno R, et al Microsurgical primary prevention of lymphatic injuries following breast cancer treatment.
Plast Reconstr Surg.
2012;
130
(5):749e–750e. doi: 10.1097/PRS.0b013e318267d906.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
23.
杨锴, 穆籣, 刘岩, 等 吲哚菁绿血管造影在皮瓣手术中的应用价值
中国修复重建外科杂志
2015;
29
(9):1113–1116.
[
Google Scholar
]
24.
DiSipio T, Rye S, Newman B, et al Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis.
Lancet Oncol.
2013;
14
(6):500–515. doi: 10.1016/S1470-2045(13)70076-7.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
25.
Yamamoto T, Yoshimatsu H, Narushima M, et al A modified side-to-end lymphaticovenular anastomosis.
Microsurgery.
2013;
33
(2):130–133. doi: 10.1002/micr.22040.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
26.
Winters H, Tielemans HJP, Hameeteman M, et al The efficacy of lymphaticovenular anastomosis in breast cancer-related lymphedema.
Breast Cancer Res Treat.
2017;
165
(2):321–327. doi: 10.1007/s10549-017-4335-0.
[
PMC free article
]
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
27.
Granzow JW, Soderberg JM, Kaji AH, et al Review of current surgical treatments for lymphedema.
Ann Surg Oncol.
2014;
21
(4):1195–1201. doi: 10.1245/s10434-014-3518-8.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
28.
Garza RM, Ooi ASH, Falk J, et al The relationship between clinical and indocyanine green staging in lymphedema.
Lymphat Res Biol.
2019;
17
(3):329–333. doi: 10.1089/lrb.2018.0014.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
29.
Yamamoto T, Narushima M, Koshima I Lymphatic vessel diameter in female pelvic cancer‐related lower extremity lymphedematous limbs.
J Surg Oncol.
2018;
117
(6):1157–1163. doi: 10.1002/jso.24974.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
30.
Seki Y, Kajikawa A, Yamamoto T, et al The dynamic-lymphaticovenular anastomosis method for breast cancer treatment-related lymphedema: creation of functional lymphaticovenular anastomoses with use of preoperative dynamic ultrasonography.
J Plast Reconstr Aesthet Surg.
2019;
72
(1):62–70. doi: 10.1016/j.bjps.2018.09.005.
[
PubMed
] [
CrossRef
]
[
Google Scholar
]
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