The Diagnostic lymphangiography with therapeutic effect: Since more than 70 years Lipiodol is used as an off-label standard of care for chylothorax - why not convert to on-label use?
DOI:
https://doi.org/10.59667/sjoranm.v1i.14Keywords:
Lipiodol therapeutic agent, Lipiodol® ultra-fluid, theranostics, chylothorax, chylascos, minimal invasive therapy, conversion from off-label use to approved therapeutic agent, on-label useAbstract
Purpose: The use of Lipiodol as a diagnostic agent and off-label therapeutic agent has been investigated in well over 395 publications listed in Pubmed under the key words: lymphangiography and chylothorax in the time period between 1921-2021.
While Lipiodol® ultra-fluid has been approved for use as a diagnostic agent in most countries, it can only be used off-label as a therapeutic agent for chylothorax, cholascos, and lymphatic leaks and fistulas. The therapeutic effects in chylothorax and the question why Lipiodol® ultra-fluid is still not approved for on-label use in the treatment of chylothorax are reviewed.
Background: Lipiodol was synthesized as iodized poppy seed oil by the French pharmacist Marcel Guerbet and first described by him in 1901. Over the past 12 decades, it has proven to be a reliable and versatile clinical theranostic agent. Lipiodol® ultra-fluid has been used (a) as a diagnostic contrast agent alone in the clarification and (b) so far only in off-label use as a therapeutic agent for chylothorax or cholascos, e.g. in cases of postoperative lymph leakages. Lipiodol® ultra-fluid has, to our knowledge, only very limited approvals as a therapeutic agent, in Switzerland only for transarterial chemo-embolization (TACE) for liver cancer. For decades and in numerous countries, Lipiodol® ultra-fluid has been in use as first-line treatment of chylothorax, cholascos, lymphatic leakage or lymphatic fistulae, avoiding additional interventions or surgery.
This review aims to assess in which countries Lipiodol® ultra-fluid is approved (a) as a primary diagnostic tool and (b) as a first line therapeutic agent. This review wants to reassess why the general therapeutic approval still lacks, and what could be done to achieve it.
References
Sicard J, Forestier J. Methode radiographique d’exploration de la cavite epidurale par le lipiodol. Rev Neurol 1921;37:1264-1266.
Kinmonth JB. Lymphangiography in man; a method of outlining lymphatic trunks at operation. Clin Sci 1952;11:13-20.
Abbes M, Paschetta V, Pellegrino A, et al. [Lipiodol Lymphography of the Upper Extremity for Breast Cancer]. J Radiol Electrol Med Nucl 1963;44:680-681.
Papillon J, Chassard JL. [Lymphography with ultrafluid lipiodol in primary malignant lymph node diseases]. Nouv Rev Fr Hematol 1963;3:524-527.
Papillon J, Dargent M, Chassard JL. [Value of Lymphography with Ultra-Fluid Lipiodol in Tumors of the Testicle]. J Urol Nephrol (Paris) 1963;69:512-518.
Papillon J, Dargent M, Chassard JL. [Ultra-fluid lipiodol lymphography in cancerology (apropos of 62 cases)]. J Radiol Electrol Med Nucl 1963;44:397-406.
Pujol H, Balmes M, Lamarque JL. [Lymphography with Ultra-Fluid Lipiodol in the Diagnosis of Malignant Blood Diseases]. J Radiol Electrol Med Nucl 1963;44:690-695.
Dolan PA. Lymphography. Br J Radiol 1964;37:405-415.
Pattillo RA, Foley DV, Mattingly RF. Internal Pelvic Lymphography. Am J Obstet Gynecol 1964;88:110-122.
Suzuki S, Takano T, Okujima J. [Contrast Visualization of Lymphatic System with Lipiodol Ultra-Fluide (Ethiodol)]. Nihon Igaku Hoshasen Gakkai Zasshi 1964;24:275-283.
Love L, Kim SE. Clinical aspects of lymphangiography. Med Clin North Am 1967;51:227-248.
Norman A. Diagnostic lymphography. Geriatrics 1967;22:149-156.
Strickstrock KH, Weissleder H. [Lymphographic diagnosis and differential diagnosis of sarcoidosis]. Fortschr Geb Rontgenstr Nuklearmed 1968;108:576-586.
Gregl A, Kienle J, Eydt M. Second- and third-look lymphography: its diagnostic and therapeutic value. Radiology 1970;95:149-156.
Rigas A, Chrysanthakopoulos S, Tsardakas E. Diagnostic and therapeutic applications of lymphangiography in clinical medicine. Am J Surg 1970;120:66-72.
Weissleder H, Peters PE. [Lymphographic differential diagnosis in lymph node diseases]. Fortschr Geb Rontgenstr Nuklearmed 1971;114:517-525.
Nakamura H, Hashimoto T, Oi H, et al. Transcatheter oily chemoembolization of hepatocellular carcinoma. Radiology 1989;170:783-786.
Cope C, Salem R, Kaiser LR. Management of chylothorax by percutaneous catheterization and embolization of the thoracic duct: prospective trial. J Vasc Interv Radiol 1999;10:1248-1254.
Ho S, Lau WY, Leung WT. In vitro assessment of Lipiodol-targeted radiotherapy for liver and colorectal cancer cell lines. Br J Cancer 2000;82:497-498.
Wolff J. Physiology and pharmacology of iodized oil in goiter prophylaxis. Medicine (Baltimore) 2001;80:20-36.
Binkert CA, Yucel EK, Davison BD, et al. Percutaneous treatment of high-output chylothorax with embolization or needle disruption technique. J Vasc Interv Radiol 2005;16:1257-1262.
Chan EH, Russell JL, Williams WG, et al. Postoperative chylothorax after cardiothoracic surgery in children. Ann Thorac Surg 2005;80:1864-1870.
Chan SY, Lau W, Wong WH, et al. Chylothorax in children after congenital heart surgery. Ann Thorac Surg 2006;82:1650-1656.
Kos S, Haueisen H, Lachmund U, et al. Lymphangiography: forgotten tool or rising star in the diagnosis and therapy of postoperative lymphatic vessel leakage. Cardiovasc Intervent Radiol 2007;30:968-973.
Syed LH, Georgiades CS, Hart VL. Lymphangiography: a case study. Semin Intervent Radiol 2007;24:106-110.
Ginat DT, Sahler LG, Patel N, et al. Post-lymphangiographic computed tomography in chylothorax after esophagogastrectomy: a case report. Lymphology 2009;42:130-133.
Matsumoto T, Yamagami T, Kato T, et al. The effectiveness of lymphangiography as a treatment method for various chyle leakages. Br J Radiol 2009;82:286-290.
Paul S, Altorki NK, Port JL, et al. Surgical management of chylothorax. Thorac Cardiovasc Surg 2009;57:226-228.
Itkin M, Kucharczuk JC, Kwak A, et al. Nonoperative thoracic duct embolization for traumatic thoracic duct leak: experience in 109 patients. J Thorac Cardiovasc Surg 2010;139:584-590.
Alejandre-Lafont E, Krompiec C, Rau WS, et al. Effectiveness of therapeutic lymphography on lymphatic leakage. Acta Radiol 2011;52:305-311.
Itkin M, Krishnamurthy G, Naim MY, et al. Percutaneous thoracic duct embolization as a treatment for intrathoracic chyle leaks in infants. Pediatrics 2011;128:e237-241.
Rajebi MR, Chaudry G, Padua HM, et al. Intranodal lymphangiography: feasibility and preliminary experience in children. J Vasc Interv Radiol 2011;22:1300-1305.
Safar K, Aouaifia A, Oudjit A, et al. [Value of CT lymphangiography in the detection of lymphatic leakage: a report of nine cases]. J Radiol 2011;92:25-31.
Deso S, Ludwig B, Kabutey NK, et al. Lymphangiography in the diagnosis and localization of various chyle leaks. Cardiovasc Intervent Radiol 2012;35:117-126.
Nadolski GJ, Itkin M. Feasibility of ultrasound-guided intranodal lymphangiogram for thoracic duct embolization. J Vasc Interv Radiol 2012;23:613-616.
Juszczyk K, Waugh R, Sandroussi C. Lymphangiography as therapeutic management of chylothorax. J Med Imaging Radiat Oncol 2013;57:460-461.
Kawasaki R, Sugimoto K, Fujii M, et al. Therapeutic effectiveness of diagnostic lymphangiography for refractory postoperative chylothorax and chylous ascites: correlation with radiologic findings and preceding medical treatment. AJR Am J Roentgenol 2013;201:659-666.
Nadolski G, Itkin M. Thoracic duct embolization for the management of chylothoraces. Curr Opin Pulm Med 2013;19:380-386.
Yoshimatsu R, Yamagami T, Miura H, et al. Prediction of therapeutic effectiveness according to CT findings after therapeutic lymphangiography for lymphatic leakage. Jpn J Radiol 2013;31:797-802.
Dori Y, Keller MS, Rychik J, et al. Successful treatment of plastic bronchitis by selective lymphatic embolization in a Fontan patient. Pediatrics 2014;134:e590-595.
Gruber-Rouh T, Naguib NNN, Lehnert T, et al. Direct lymphangiography as treatment option of lymphatic leakage: indications, outcomes and role in patient's management. Eur J Radiol 2014;83:2167-2171.
Kortes N, Radeleff B, Sommer CM, et al. Therapeutic lymphangiography and CT-guided sclerotherapy for the treatment of refractory lymphatic leakage. J Vasc Interv Radiol 2014;25:127-132.
Lee EW, Shin JH, Ko HK, et al. Lymphangiography to treat postoperative lymphatic leakage: a technical review. Korean J Radiol 2014;15:724-732.
Liu DY, Shao Y, Shi JX. Unilateral pedal lymphangiography with non-contrast computerized tomography is valuable in the location and treatment decision of idiopathic chylothorax. J Cardiothorac Surg 2014;9:8.
Parvinian A, Mohan GC, Gaba RC, et al. Ultrasound-guided intranodal lymphangiography followed by thoracic duct embolization for treatment of postoperative bilateral chylothorax. Head Neck 2014;36:E21-24.
Snow AL, Uller W, Kim HB, et al. Percutaneous embolization of a chylous leak from thoracic duct injury in a child. Cardiovasc Intervent Radiol 2014;37:1111-1113.
Courtney M, Ayyagari RR. Idiopathic chylopericardium treated by percutaneous thoracic duct embolization after failed surgical thoracic duct ligation. Pediatr Radiol 2015;45:927-930.
Hsu MC, Itkin M. Lymphatic Anatomy. Tech Vasc Interv Radiol 2016;19:247-254.
Hur S, Shin JH, Lee IJ, et al. Early Experience in the Management of Postoperative Lymphatic Leakage Using Lipiodol Lymphangiography and Adjunctive Glue Embolization. J Vasc Interv Radiol 2016;27:1177-1186 e1171.
Zhang C, Chen X, Wen T, et al. Computed tomography lymphangiography findings in 27 cases of lymphangioleiomyomatosis. Acta Radiol 2017;58:1342-1348.
Dong J, Xin J, Shen W, et al. Unipedal Diagnostic Lymphangiography Followed by Sequential CT Examinations in Patients With Idiopathic Chyluria: A Retrospective Study. AJR Am J Roentgenol 2018;210:792-798.
Kim PH, Tsauo J, Shin JH. Lymphatic Interventions for Chylothorax: A Systematic Review and Meta-Analysis. J Vasc Interv Radiol 2018;29:194-202.
Majdalany BS, Saad WA, Chick JFB, et al. Pediatric lymphangiography, thoracic duct embolization and thoracic duct disruption: a single-institution experience in 11 children with chylothorax. Pediatr Radiol 2018;48:235-240.
Seeliger B, Alesina PF, Walz MK. Posterior retroperitoneoscopic thoracic duct ligation: a novel surgical approach. Surg Endosc 2018;32:3732-3737.
Kuetting D, Schild HH, Pieper CC. In Vitro Evaluation of the Polymerization Properties of N-Butyl Cyanoacrylate/Iodized Oil Mixtures for Lymphatic Interventions. J Vasc Interv Radiol 2019;30:110-117.
Pieper CC, Hur S, Sommer CM, et al. Back to the Future: Lipiodol in Lymphography-From Diagnostics to Theranostics. Invest Radiol 2019;54:600-615.
Sommer CM, Pieper CC, Itkin M, et al. Conventional Lymphangiography (CL) in the Management of Postoperative Lymphatic Leakage (PLL): A Systematic Review. Rofo 2020;192:1025-1035.
Jardinet T, Veer HV, Nafteux P, et al. Intranodal Lymphangiography With High-Dose Ethiodized Oil Shows Efficient Results in Patients With Refractory, High-Output Postsurgical Chylothorax: A Retrospective Study. AJR Am J Roentgenol 2021;217:433-438.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Frank Mosler
This work is licensed under a Creative Commons Attribution 4.0 International License.
This license requires that reusers give credit to the creator. It allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, even for commercial purposes.
