Application of indocyanine green lymphography in the diagnosis and treatment of secondary upper extremity lymphedema: a systematic review
DOI:
https://doi.org/10.2340/jphs.v60.44582Keywords:
ICG lymphography, near-infrared fluorescence imaging, secondary lymphedema, upper extremity lymphedema, lymphaticovenous anastomosisAbstract
Background: Lymphedema is a chronic progressive disease that impairs patients’ physical and psychological health. This study aimed to conduct a systematic review of the application of indocyanine green (ICG) lymphography for the diagnosis and treatment of secondary upper extremity lymphedema.
Methods: We searched PubMed for studies on ICG lymphography for secondary upper extremity lymphedema that were published until April 2024. The quality of included studies was assessed according to the Joanna Briggs Institute Review’s Manual. Qualitative synthesis using only descriptive statistics was performed.
Results: Of the 523 articles screened, 32 met the eligibility criteria. Most of the studies were observational (4 cohort studies and 28 case series). For this review, 1,869 patients with secondary lymphedema and 112 volunteers were identified. ICG lymphography for diagnostic imaging of secondary lymphedema was reported to have a sensitivity of 89.5% and a specificity of 85.7% and was particularly useful for the diagnosis of early lymphedema. A severity staging system based on ICG lymphography images for secondary lymphedema was also reported. In the lymphaticovenous anastomosis (LVA) surgery, ICG lymphography was helpful in detecting functional lymphatic vessels preoperatively and in localizing lymphatic vessels and assessing LVA patency intraoperatively, thereby facilitating smaller skin incision and shorter operating time.
Conclusions: ICG lymphography has a great value in the diagnosis and treatment of secondary upper extremity lymphedema.
Downloads
References
Maclellan RA, Greene AK. Lymphedema. Semin Pediatr Surg. 2014;23(4):191–197. https://doi.org/10.1053/j.sempedsurg.2014.07.004 DOI: https://doi.org/10.1053/j.sempedsurg.2014.07.004
Yüksel A, Gürbüz O, Velioğlu Y, et al. Management of lymphoedema. VASA. 2016;45(4):283–291. https://doi.org/10.1024/0301-1526/a000539 DOI: https://doi.org/10.1024/0301-1526/a000539
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. https://doi.org/10.1016/S1470-2045(13)70076-7 DOI: https://doi.org/10.1016/S1470-2045(13)70076-7
Shah C, Arthur DW, Wazer D, et al. The impact of early detection and intervention of breast cancer-related lymphedema: a systematic review. Cancer Med. 2016;5(6):1154–1162. https://doi.org/10.1002/cam4.691 DOI: https://doi.org/10.1002/cam4.691
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. https://doi.org/10.1016/j.jvs.2007.01.023 DOI: https://doi.org/10.1016/j.jvs.2007.01.023
Yamamoto T, Matsuda N, Doi K, et al. The earliest finding of indocyanine green lymphography in asymptomatic limbs of lower extremity lymphedema patients secondary to cancer treatment: the modified dermal backflow stage and concept of subclinical lymphedema. Plastic Reconstr Surg. 2011;128(4):314e–321e. https://doi.org/10.1097/PRS.0b013e3182268da8 DOI: https://doi.org/10.1097/PRS.0b013e3182268da8
Mihara M, Hara H, Narushima M, et al. Indocyanine green lymphography is superior to lymphoscintigraphy in imaging diagnosis of secondary lymphedema of the lower limbs. J Vasc Surg. 2013;1(2):194–201. https://doi.org/10.1016/j.jvsv.2012.07.011 DOI: https://doi.org/10.1016/j.jvsv.2012.07.011
Ogata F, Narushima M, Mihara M, et al. Intraoperative lymphography using indocyanine green dye for near-infrared fluorescence labeling in lymphedema. Ann Plastic Surg. 2007;59(2):180–184. https://doi.org/10.1097/01.sap.0000253341.70866.54 DOI: https://doi.org/10.1097/01.sap.0000253341.70866.54
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. https://doi.org/10.1136/bmj.b2700 DOI: https://doi.org/10.1136/bmj.b2700
Moola S, Munn Z, Tufanaru C, et al. Joanna Briggs Institute review’s mannul. The Joanna Briggs Institute, Adelaide, Australia; 2017.
Hara H, Mihara M, Seki Y, et al. Comparison of indocyanine green lymphographic findings with the conditions of collecting lymphatic vessels of limbs in patients with lymphedema. Plastic Reconstr Surg. 2013;132(6):1612–1618. https://doi.org/10.1097/PRS.0b013e3182a97edc DOI: https://doi.org/10.1097/PRS.0b013e3182a97edc
Yamamoto T, Yamamoto N, Doi K, et al. Indocyanine green–enhanced lymphography for upper extremity lymphedema: a novel severity staging system using dermal backflow patterns. Plastic Reconstr Surg. 2011;128(4):941–947. https://doi.org/10.1097/PRS.0b013e3182268cd9 DOI: https://doi.org/10.1097/PRS.0b013e3182268cd9
Jørgensen MG, Toyserkani NM, Hansen FCG, et al. Prospective validation of indocyanine green lymphangiography staging of breast cancer-related lymphedema. Cancers. 2021;13(7):1540. https://doi.org/10.3390/cancers13071540 DOI: https://doi.org/10.3390/cancers13071540
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. https://doi.org/10.1089/lrb.2018.0014 DOI: https://doi.org/10.1089/lrb.2018.0014
Jørgensen MG, Hermann AP, Madsen AR, et al. Indocyanine green lymphangiography is superior to clinical staging in breast cancer-related lymphedema. Sci Rep. 2021;11(1):21103. https://doi.org/10.1038/s41598-021-00396-2 DOI: https://doi.org/10.1038/s41598-021-00396-2
Liu M, Liu S, Zhao Q, et al. Using the indocyanine green (ICG) lymphography to screen breast cancer patients at high risk for lymphedema. Diagnostics. 2022;12(4):983. https://doi.org/10.3390/diagnostics12040983 DOI: https://doi.org/10.3390/diagnostics12040983
Tokumoto H, Akita S, Kubota Y, et al. Relationship between the circumference difference and findings of indocyanine green lymphography in breast cancer-related lymphedema. Ann Plastic Surg. 2022;88(1):114–117. https://doi.org/10.1097/SAP.0000000000002918 DOI: https://doi.org/10.1097/SAP.0000000000002918
Akita S, Nakamura R, Yamamoto N, et al. Early detection of lymphatic disorder and treatment for lymphedema following breast cancer. Plastic Reconstr Surg. 2016;138(2):192e–202e. https://doi.org/10.1097/PRS.0000000000002337 DOI: https://doi.org/10.1097/PRS.0000000000002337
Tashiro K, Yamashita S, Koshima I, et al. Visualization of accessory lymphatic pathways in secondary upper extremity lymphedema using indocyanine green lymphography. Ann Plastic Surg. 2017;79(4):393–396. https://doi.org/10.1097/SAP.0000000000001120 DOI: https://doi.org/10.1097/SAP.0000000000001120
Yoon JA, Shin MJ, Shin YB, et al. Correlation of ICG lymphography and lymphoscintigraphy severity stage in secondary upper limb lymphedema. J Plastic Reconstr Aesth Surg. 2020;73(11):1982–1988. https://doi.org/10.1016/j.bjps.2020.08.055 DOI: https://doi.org/10.1016/j.bjps.2020.08.055
Mihara M, Hara H, Araki J, et al. Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs. PLoS One. 2012;7(6):e38182. https://doi.org/10.1371/journal.pone. 0038182 DOI: https://doi.org/10.1371/journal.pone.0038182
Granoff MD, Johnson AR, Lee BT, et al. A novel approach to quantifying lymphatic contractility during indocyanine green lymphangiography. Plastic Reconstr Surg. 2019;144(5): 1197–1201. https://doi.org/10.1097/PRS.0000000000006176 DOI: https://doi.org/10.1097/PRS.0000000000006176
Rasmussen JC, Tan IC, Marshall MV, et al. Human lymphatic architecture and dynamic transport imaged using near-infrared fluorescence. Transl Oncol. 2010;3(6):362–372. https://doi.org/10.1593/tlo.10190 DOI: https://doi.org/10.1593/tlo.10190
Yamamoto T, Narushima M, Yoshimatsu H, et al. Dynamic indocyanine green (ICG) lymphography for breast cancer-related arm lymphedema. Ann Plastic Surg. 2014;73(6):706–709. https://doi.org/10.1097/SAP.0b013e318285875f DOI: https://doi.org/10.1097/SAP.0b013e318285875f
Chang DW, Suami H, Skoracki R. A prospective analysis of 100 consecutive lymphovenous bypass cases for treatment of extremity lymphedema. Plastic Reconstr Surg. 2013;132(5):1305–1314. https://doi.org/10.1097/PRS.0b013e3182a4d626 DOI: https://doi.org/10.1097/PRS.0b013e3182a4d626
Yamamoto T, Yamamoto N, Numahata T, et al. Navigation lymphatic supermicrosurgery for the treatment of cancer-related peripheral lymphedema. Vasc Endovasc Surg. 2014;48(2):139–143. https://doi.org/10.1177/1538574413510979 DOI: https://doi.org/10.1177/1538574413510979
Furukawa H, Osawa M, Saito A, et al. Microsurgical lymphaticovenous implantation targeting dermal lymphatic backflow using indocyanine green fluorescence lymphography in the treatment of postmastectomy lymphedema. Plastic Reconstr Surg. 2011;127(5):1804–1811. https://doi.org/10.1097/PRS.0b013e31820cf2e2 DOI: https://doi.org/10.1097/PRS.0b013e31820cf2e2
Xiaoming L, Wei T, Yi’nan J, et al. Application of combined preoperative indocyanine green lymphography and ultrasonography for low-pressure vein localization in secondary lymphedema surgery for breast cancer. Asian J Surg. 2024;47(1):289–295. https://doi.org/10.1016/j.asjsur.2023.08.121 DOI: https://doi.org/10.1016/j.asjsur.2023.08.121
Liu HL, Pang SY, Chan YW. The use of a microscope with near-infrared imaging function in indocyanine green lymphography and lymphaticovenous anastomosis. J Plastic Reconstr Aesth Surg. 2014;67(2):231–236. https://doi.org/10.1016/j.bjps.2013.10.039 DOI: https://doi.org/10.1016/j.bjps.2013.10.039
Gentileschi S, Servillo M, Albanese R, et al. Lymphatic mapping of the upper limb with lymphedema before lymphatic supermicrosurgery by mirroring of the healthy limb. Microsurgery. 2017;37(8):881–889. https://doi.org/10.1002/micr.30247 DOI: https://doi.org/10.1002/micr.30247
Lin CH, Yamamoto T. Identification of lymph vessels using an indocyanine green camera-integrated operative microscope for lymphovenous anastomosis in the treatment of secondary lymphedema. J Vasc Surg. 2023;11(1):161–166. https://doi.org/10.1016/j.jvsv.2022.06.012 DOI: https://doi.org/10.1016/j.jvsv.2022.06.012
Yamamoto T, Narushima M, Yoshimatsu H, et al. Minimally invasive lymphatic supermicrosurgery (MILS): indocyanine green lymphography-guided simultaneous multisite lymphaticovenular anastomoses via millimeter skin incisions. Ann Plastic Surg. 2014;72(1):67–70. https://doi.org/10.1097/SAP.0b013e3182605580 DOI: https://doi.org/10.1097/SAP.0b013e3182605580
Akita S, Unno N, Maegawa J, et al. A phase III, multicenter, single-arm study to assess the utility of indocyanine green fluorescent lymphography in the treatment of secondary lymphedema. J Vasc Surg. 2022;10(3):728–737.e3. https://doi.org/10.1016/j.jvsv.2021.09.006 DOI: https://doi.org/10.1016/j.jvsv.2021.09.006
Brebant V, Heine N, Lamby P, et al. Augmented reality of indocyanine green fluorescence in simplified lymphovenous anastomosis in lymphatic surgery. Clin Hemorheol Microcircul. 2019;73(1):125–133. https://doi.org/10.3233/CH-199220 DOI: https://doi.org/10.3233/CH-199220
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. https://doi.org/10.1007/s10549-017-4335-0 DOI: https://doi.org/10.1007/s10549-017-4335-0
Chung JH, Baek SO, Park HJ, et al. Efficacy and patient satisfaction regarding lymphovenous bypass with sleeve-in anastomosis for extremity lymphedema. Arch Plastic Surg. 2019;46(1):46–56. https://doi.org/10.5999/aps.2018.00773 DOI: https://doi.org/10.5999/aps.2018.00773
Khan AA, Hernan I, Adamthwaite JA, et al. Feasibility study of combined dynamic imaging and lymphaticovenous anastomosis surgery for breast cancer-related lymphoedema. Br J Surg. 2019;106(1):100–110. https://doi.org/10.1002/bjs.10983 DOI: https://doi.org/10.1002/bjs.10983
Seki Y, Kajikawa A, Yamamoto T, et al. Real-time indocyanine green videolymphography navigation for lymphaticovenular anastomosis. Plastic Reconstr Surg. 2019;7(5):e2253. https://doi.org/10.1097/GOX.0000000000002253 DOI: https://doi.org/10.1097/GOX.0000000000002253
Yang JC, Wu S, Chiang M, 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. https://doi.org/10.1002/jso.25014 DOI: https://doi.org/10.1002/jso.25014
Visconti G, Hayashi A, Bianchi A, et al. Lymphaticovenular anastomosis for advanced-stage peripheral lymphedema: expanding indication and introducing the hand/foot sign. J Plastic Reconstr Aesth Surg. 2022;75(7):2153–2163. https://doi.org/10.1016/j.bjps.2022.02.012 DOI: https://doi.org/10.1016/j.bjps.2022.02.012
Hara H, Mihara M. Multi-area lymphaticovenous anastomosis with multi-lymphosome injection in indocyanine green lymphography: a prospective study. Microsurgery. 2019;39(2): 167–173. https://doi.org/10.1002/micr.30398 DOI: https://doi.org/10.1002/micr.30398
Lasso JM, Alonso-Farto JC. Indocyanine green-guided liposuction for patients presenting with residual nonpitting edema after lymphovenous anastomosis. J Plastic Reconstr Aesth Surg. 2022;75(8):2482–2492. https://doi.org/10.1016/j.bjps.2022.02.081 DOI: https://doi.org/10.1016/j.bjps.2022.02.081
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Youlei Qian, Zixuan Yao, Chao Wang, Chao Dong, Song Xia, Yuguang Sun, Wenbin Shen, Jianfeng Xin

This work is licensed under a Creative Commons Attribution 4.0 International License.
Acta Chirurgica Scandinavica Society owns the copyright for all material published until Volume 57 (2023) unless otherwise specified. As from 2024 all published articles, unless otherwise specified, are published under CC-BY licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, with the condition of proper attribution to the original work.

