{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:17:18Z","timestamp":1766067438718,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Sarcomas are characterized by a high metastatic potential and aggressive growth. Despite surgery, chemotherapy plays an important role in the treatment of these tumors. Optimal anti-cancer therapy with maximized local efficacy and minimized systemic side effects has been the object of many studies for a long time. To improve the local efficacy of anti-tumor therapy, isolated limb perfusion with high-dose cytostatic agents has been introduced in surgical oncology. In order to control the local distribution of substances, radiolabeled cytostatic drugs or perfusion solutions have been applied but often require the presence of specialized personnel and result in a certain exposure to radiation. In this study, we present a novel strategy using indocyanine green to track tumor perfusion with high-dose cytostatic therapy. In a rat cadaver model, the femoral vessels were cannulated and connected to a peristaltic pump to provide circulation within the selected limb. The perfusion solution contained indocyanine green and high-dose doxorubicin. An infrared camera enabled the visualization of indocyanine green during limb perfusion, and subsequent leakage control was successfully performed. Histologic analysis of sections derived proximally from the injection site excluded systemic drug dispersion. In this study, the application of indocyanine green was proven to be a safe and cost- and time-efficient method for precise leakage control in isolated limb perfusion with a high-dose cytostatic agent.<\/jats:p>","DOI":"10.3390\/jpm11111152","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T10:33:09Z","timestamp":1636108389000},"page":"1152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Indocyanine Green for Leakage Control in Isolated Limb Perfusion"],"prefix":"10.3390","volume":"11","author":[{"given":"Isabel","family":"Zucal","sequence":"first","affiliation":[{"name":"Centre of Plastic, Aesthetic, Hand and Reconstructive Surgery, University Clinic of Regensburg, 93053 Regensburg, Germany"},{"name":"Institute for Molecular and Cellular Anatomy, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Geis","sequence":"additional","affiliation":[{"name":"Centre of Plastic, Aesthetic, Hand and Reconstructive Surgery, University Clinic of Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2454-2499","authenticated-orcid":false,"given":"Lukas","family":"Prantl","sequence":"additional","affiliation":[{"name":"Centre of Plastic, Aesthetic, Hand and Reconstructive Surgery, University Clinic of Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9440-3307","authenticated-orcid":false,"given":"Silke","family":"Haerteis","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Cellular Anatomy, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiha","family":"Aung","sequence":"additional","affiliation":[{"name":"Centre of Plastic, Aesthetic, Hand and Reconstructive Surgery, University Clinic of Regensburg, 93053 Regensburg, Germany"},{"name":"Institute for Molecular and Cellular Anatomy, University of Regensburg, 93053 Regensburg, Germany"},{"name":"Faculty of Applied Healthcare Science, Deggendorf Institute of Technology, 94469 Deggendorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.4103\/ortho.IJOrtho_220_17","article-title":"Soft-tissue Sarcomas","volume":"52","author":"Vodanovich","year":"2018","journal-title":"Indian J. Orthop."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.4065\/82.11.1409","article-title":"Sarcoma","volume":"82","author":"Skubitz","year":"2007","journal-title":"Mayo Clin. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.2147\/CMAR.S159641","article-title":"A review of soft-tissue sarcomas: Translation of biological advances into treatment measures","volume":"10","author":"Hoang","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1053\/j.seminoncol.2007.09.010","article-title":"Surgery and sentinel lymph node biopsy","volume":"34","author":"Faries","year":"2007","journal-title":"Semin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.suc.2008.03.005","article-title":"The role of radiation therapy in the management of sarcomas","volume":"88","author":"Kaushal","year":"2008","journal-title":"Surg. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"596","DOI":"10.21037\/gs.2020.03.20","article-title":"The impact of radiation on lymphedema: A review of the literature","volume":"9","author":"Allam","year":"2020","journal-title":"Gland Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1093\/jjco\/hyy151","article-title":"Risk factors for lymphatic complications following lymphadenectomy in patients with cervical cancer","volume":"48","author":"Togami","year":"2018","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.3892\/ol.2014.1935","article-title":"Molecular mechanisms of chemoresistance in osteosarcoma (Review)","volume":"7","author":"He","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1097\/00000658-199612000-00011","article-title":"Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience","volume":"224","author":"Eggermont","year":"1996","journal-title":"Ann. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1634\/theoncologist.2009-0325","article-title":"Isolated limb perfusion for malignant melanoma: Systematic review on effectiveness and safety","volume":"15","author":"Ferrandiz","year":"2010","journal-title":"Oncologist"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.6061\/clinics\/2012(03)06","article-title":"Isolated limb perfusion with hyperthermia and chemotherapy: Predictive factors for regional toxicity","volume":"67","author":"Oliveira","year":"2012","journal-title":"Clinics"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Teras, J., Carr, M.J., Zager, J.S., and Kroon, H.M. (2021). Molecular Aspects of the Isolated Limb Infusion Procedure. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020163"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/jso.21280","article-title":"Isolated limb infusion: A review","volume":"100","author":"Kroon","year":"2009","journal-title":"J. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1245\/ASO.2006.05.003","article-title":"A phase II trial of isolated limb infusion with melphalan and dactinomycin for regional melanoma and soft tissue sarcoma of the extremity","volume":"13","author":"Brady","year":"2006","journal-title":"Ann. Surg. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102058","DOI":"10.1016\/j.ctrv.2020.102058","article-title":"Isolated limb perfusion for soft tissue sarcoma: Current practices and future directions. A survey of experts and a review of literature","volume":"88","author":"Colombo","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_16","first-page":"248","article-title":"Quantitative radionuclide leakage control during isolated limb perfusion","volume":"33","author":"Sprenger","year":"1994","journal-title":"Nuklearmedizin"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/cpf.12164","article-title":"Radionuclide leakage monitoring during hyperthermic isolated limb perfusion for treatment of local melanoma metastasis in an extremity","volume":"35","author":"Paulsen","year":"2015","journal-title":"Clin. Physiol. Funct. Imaging"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3109\/02656736.2015.1101170","article-title":"Hyperthermic isolated limb perfusion in locally advanced limb soft tissue sarcoma: A 24-year single-centre experience","volume":"32","author":"Rastrelli","year":"2016","journal-title":"Int. J. Hyperth."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/13623699908409425","article-title":"Is technetium-99 (Tc-99) radiologically significant?","volume":"15","author":"Barnaby","year":"1999","journal-title":"Med. Confl. Surviv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1097\/MAJ.0b013e318216ee86","article-title":"Pitfalls with radiopharmaceuticals","volume":"342","author":"Machado","year":"2011","journal-title":"Am. J. Med. Sci."},{"key":"ref_21","unstructured":"Johnson-Arbor, K., and Dubey, R. (2020). Doxorubicin. StatPearls, StatPearls Publishing."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1245\/s10434-006-9138-1","article-title":"Preoperative isolated limb infusion of Doxorubicin and external irradiation for limb-threatening soft tissue sarcomas","volume":"14","author":"Hegazy","year":"2007","journal-title":"Ann. Surg. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"289673","DOI":"10.1155\/2011\/289673","article-title":"Incidence and Severity of Lymphoedema following Limb Salvage of Extremity Soft Tissue Sarcoma","volume":"2011","author":"Friedmann","year":"2011","journal-title":"Sarcoma"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1245\/s10434-013-3408-5","article-title":"Risk factors associated with breast lymphedema","volume":"21","author":"Boughey","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S1470-2045(13)70076-7","article-title":"Incidence of unilateral arm lymphoedema after breast cancer: A systematic review and meta-analysis","volume":"14","author":"DiSipio","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.jamcollsurg.2012.11.004","article-title":"Trends in risk reduction practices for the prevention of lymphedema in the first 12 months after breast cancer surgery","volume":"216","author":"McLaughlin","year":"2013","journal-title":"J. Am. Coll. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e2912","DOI":"10.1097\/GOX.0000000000002912","article-title":"Risk Factors for Lymphedema after Thigh Sarcoma Resection and Reconstruction","volume":"8","author":"Wu","year":"2020","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"373","DOI":"10.20892\/j.issn.2095-3941.2016.0028","article-title":"The role of radiotherapy in the management of localized soft tissue sarcomas","volume":"13","author":"Tiong","year":"2016","journal-title":"Cancer Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/micr.30246","article-title":"Systematic review of lymphovenous anastomosis (LVA) for the treatment of lymphedema","volume":"37","author":"Scaglioni","year":"2017","journal-title":"Microsurgery"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1055\/s-2008-1040054","article-title":"The Borggreve rotation-plasty. A surgical method in therapy of malignant bone tumors and functional results","volume":"131","author":"Heise","year":"1993","journal-title":"Z. Orthop. Ihre Grenzgeb."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/BF02581614","article-title":"Kniegelenkersatz durch das in der Beinl\u00e4ngsachse um 180 Grad gedrehte Fu\u00dfgelenk","volume":"28","author":"Borggreve","year":"1930","journal-title":"Arch. F\u00fcr Orthop\u00e4dische Und Unf.-Chir."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1055\/s-2008-1040138","article-title":"Clavicula pro humero\u2014a new surgical method for malignant tumors of the proximal humerus","volume":"130","author":"Winkelmann","year":"1992","journal-title":"Z. Orthop. Ihre Grenzgeb."},{"key":"ref_33","first-page":"S139","article-title":"Our experience with Van Nes Rotationplasty for locally advanced lower extremity tumours","volume":"64","author":"Askari","year":"2014","journal-title":"JPMA J. Pak. Med. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1515\/jtim-2016-0011","article-title":"A little help from steroids in oncology","volume":"4","author":"Lossignol","year":"2016","journal-title":"J. Transl. Int. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nrc2843","article-title":"The colony-stimulating factors and cancer","volume":"10","author":"Metcalf","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1002\/cncr.25850","article-title":"Isolated limb perfusion for unresectable extremity sarcoma: Results of 2 single-institution phase 2 trials","volume":"117","author":"Wray","year":"2011","journal-title":"Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1177\/030089160108700314","article-title":"Deep venous thrombosis of the extremity diagnosed by color Doppler ultrasonography after isolated limb perfusion","volume":"87","author":"Ozcan","year":"2001","journal-title":"Tumori"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0277-5379(82)90235-8","article-title":"Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions","volume":"18","author":"Wieberdink","year":"1982","journal-title":"Eur. J. Cancer Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1177\/1553350615604053","article-title":"Indocyanine Green: Historical Context, Current Applications, and Future Considerations","volume":"23","author":"Reinhart","year":"2016","journal-title":"Surg. Innov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"940585","DOI":"10.1155\/2012\/940585","article-title":"A review of indocyanine green fluorescent imaging in surgery","volume":"2012","author":"Alander","year":"2012","journal-title":"Int. J. Biomed. Imaging"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.bjps.2017.01.020","article-title":"Indocyanine green applications in plastic surgery: A review of the literature","volume":"70","author":"Burnier","year":"2017","journal-title":"J. Plast. Reconstr. Aesthet. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1055\/s-0031-1281515","article-title":"The application of indocyanine green fluorescence angiography in plastic surgery","volume":"27","author":"Liu","year":"2011","journal-title":"J. Reconstr. Microsurg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fsurg.2019.00039","article-title":"Enhancing Safety in Reconstructive Microsurgery Using Intraoperative Indocyanine Green Angiography","volume":"6","author":"Ludolph","year":"2019","journal-title":"Front. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/jso.21943","article-title":"The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery","volume":"104","author":"Schaafsma","year":"2011","journal-title":"J. Surg. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/cncr.31851","article-title":"A clinical trial of intraoperative near-infrared imaging to assess tumor extent and identify residual disease during anterior mediastinal tumor resection","volume":"125","author":"Predina","year":"2019","journal-title":"Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1245\/s10434-018-07114-9","article-title":"Tumor Resection Guided by Intraoperative Indocyanine Green Dye Fluorescence Angiography Results in Negative Surgical Margins and Decreased Local Recurrence in an Orthotopic Mouse Model of Osteosarcoma","volume":"26","author":"Mahjoub","year":"2019","journal-title":"Ann. Surg. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/j.jcms.2019.07.011","article-title":"A technique for safe deep facial tissue dissection: Indocyanine green-assisted intraoperative real-time visualization of the vasa nervorum of facial nerve with a near-infrared camera","volume":"47","author":"Kwon","year":"2019","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrclinonc.2013.123","article-title":"Image-guided cancer surgery using near-infrared fluorescence","volume":"10","author":"Vahrmeijer","year":"2013","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.healun.2005.08.017","article-title":"Optimal time for post-mortem heparinization in canine lung transplantation with non-heart-beating donors","volume":"25","author":"Okazaki","year":"2006","journal-title":"J. Heart Lung Transpl."},{"key":"ref_50","first-page":"900","article-title":"Extracorporeal perfusion for obtaining postmortem homografts","volume":"54","author":"Marchioro","year":"1963","journal-title":"Surgery"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s12593-013-0089-z","article-title":"Microvascular anastomosis of submillimeter vessels-a training model in rats","volume":"5","author":"Liu","year":"2013","journal-title":"J. Hand Microsurg."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/11\/11\/1152\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:26:08Z","timestamp":1760167568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/11\/11\/1152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,5]]},"references-count":51,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["jpm11111152"],"URL":"https:\/\/doi.org\/10.3390\/jpm11111152","relation":{},"ISSN":["2075-4426"],"issn-type":[{"type":"electronic","value":"2075-4426"}],"subject":[],"published":{"date-parts":[[2021,11,5]]}}}