Percutaneous Sclerotherapy with Bleomycin and Ethiodized Oil: A Welcomed Minimally Invasive Treatment for Giant Liver Hemangiomas

HomeRadiologyVol. 301, No. 2 PreviousNext Reviews and CommentaryFree AccessEditorialPercutaneous Sclerotherapy with Bleomycin and Ethiodized Oil: A Welcomed Minimally Invasive Treatment for Giant Liver HemangiomasJohn P. McGahan , Roger E. GoldmanJohn P. McGahan , Roger E. GoldmanAuthor AffiliationsFrom the Department of Radiology, UC Davis Health, 4860 Y St, Suite 3100, Sacramento, CA 95817.Address correspondence to J.P.M. (e-mail: [email protected]).John P. McGahan Roger E. GoldmanPublished Online:Aug 17 2021https://doi.org/10.1148/radiol.2021211594MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In See also the article by Ayoobi Yazdi et al in this issue.Dr John McGahan is the professor and vice chair within the Department of Radiology at the University of California, Davis Medical Center located in Sacramento, Calif. Much of his research focuses on the development of new minimally invasive interventional techniques. He has recently received lifetime achievement awards from the Society of Abdominal Radiology and the Society of Radiologists in Ultrasound for his contributions to research.Download as PowerPointOpen in Image Viewer Dr Roger Goldman is an assistant professor in the Division of Vascular and Interventional Radiology at the University of California, Davis Medical Center. His clinical work consists of interventional oncology, venous thromboembolic disease intervention, and diagnostic sampling for endocrine disorders. His research focuses on novel technologic and engineering solutions to complex problems in diagnostic and interventional radiology and surgery.Download as PowerPointOpen in Image Viewer Hemangiomas are the most common benign tumors of the liver, with an estimated incidence of 0.3%–20% in autopsy studies (1). The International Society for the Study of Vascular Anomalies has classified adult hemangiomas as venous malformations (2). Most hemangiomas are detected at imaging performed for other reasons. These lesions are usually small and are not treated, as they have no malignant potential, cause no biochemical or hormonal disturbances, and do not produce mass effect on adjacent organs or vascular structures. As hemangiomas grow, they may be defined as giant hemangiomas. Giant liver hemangiomas (GLHs) are usually considered hemangiomas greater than 5 cm, although some authors define giant hemangiomas as being greater than 10 cm (3). In this issue of Radiology, Ayoobi Yazdi et al (4) defined giant hemangiomas as lesions greater than 5 cm.As these GLHs enlarge, the lesions may cause emergent symptoms requiring intervention. There are no consensus guidelines on the treatment of GLH, with most therapeutic options supported by a combination of retrospective case series and expert consensus. Rarely, emergency surgery is needed for ruptured giant hemangioma or for those patients who develop Kasabach-Merritt syndrome. This syndrome consists of hypofibrinogenemia, anemia, thrombocytopenia, and prolonged prothrombin time that can develop with giant hemangiomas and is life-threatening.Enlargement of GLH may produce symptoms or disease sequelae. Pain is hypothesized to be the result of infarct and necrosis of the tumor or mass effect on the liver capsule or adjacent organs. Mass effect of large hemangiomas may lead to organ or vessel compression, producing gastric or bowel obstruction, Budd-Chiari syndrome, portal hypertension, inferior vena cava thrombosis or occlusion, or obstructive jaundice (5). Surgical treatment of symptomatic GLH was traditionally considered the standard of care, either through resection, enucleation, or transplantation. A growing body of evidence points to the utility, efficacy, and safety of minimally invasive approaches to management. To our knowledge, no studies have prospectively evaluated modern minimally invasive percutaneous image-guided techniques. Ayoobi Yazdi et al (4) concisely review these minimally invasive approaches, which include transarterial embolization, percutaneous transabdominal radiofrequency or microwave ablation, and percutaneous transabdominal sclerotherapy. These approaches have shown promise in reducing both size and symptoms related to GLH. The authors describe and prospectively evaluate a percutaneous transabdominal approach to symptomatic GLH with excellent medium-term efficacy and minimal complications (4). These data provide additional compelling evidence for the minimally invasive management of symptomatic GLH. The article contextualizes the results of percutaneous transabdominal sclerotherapy, highlighting similar clinical efficacy and lower rates of complications.In this study, Ayoobi Yazdi and colleagues investigate the safety and medium-term (12-month) efficacy of percutaneous injection of bleomycin mixed with ethiodized oil for treatment of symptomatic GLH. They describe the participants who were followed up to ensure excellent clinical efficacy and safe injection of the sclerosant mixture. They prospectively excluded patients with hepatic impairment and other possible causes of abdominal pain at rates of 14% (five of 37) and 5% (two of 37), respectively. It should be noted that the study participant population differs from that in prior studies in the relatively low number in whom an alternate cause of pain could not be identified. Multiple prior works identify a number of patients in whom symptoms could be attributable to an alternate diagnosis to liver hemangioma, including peptic ulcer disease or cholelithiasis (6).Several portions of the technique were described to ensure safe injection of the mixture. First, the authors used a small (22-gauge) spinal or Chiba-type needle. They always placed the needle through normal liver parenchyma and near the center, avoiding hypoechoic or anechoic regions. Next, they used fluoroscopic injection of radiopaque contrast agent to check for any communication with their injection site and surrounding veins, hepatic artery, or the biliary system. It is surmised that the total fluoroscopy time, total procedural time, and requirements for intraprocedural analgesia would be equivalent or reduced as compared with transarterial intervention, though the data and comparison analysis have not been presented.The technical success, safety profile, and moderate-term clinical efficacy of their procedure were impressive. The technical success was 100% in the 28 participants enrolled in the postprocedural follow-up. Sixty-eight percent of the participants experienced moderate or severe pain controlled with intravenous medication without the need for hospitalization. There were no major complications. At 1 year, 61% of the participants had complete pain relief, and the rest had partial pain relief as documented by the widely used and validated visual analog scale for pain. The hemangioma volume was reduced by 76% at 1-year follow-up.Injectables have been used to treat GLH. There have been no case series or trials directly comparing the use of different sclerosing agents in the treatment of giant cavernous hemangiomas. However, percutaneous injection of alcohol, bleomycin, and sodium morrhuate have been comparatively studied in treatment of nonvisceral vascular malformations, predominantly of the head and neck. Alcohol is thought to cause dehydration and subsequent sloughing of the dysmorphic endothelial cells lining the venous channels. Detergent sclerosants—such as sodium morrhuate, sodium tetradecyl sulfate, polidocanol, and ethanolamine—are hypothesized, like ethanol, to cause direct damage to endothelial cells. Alternatively, bleomycin is a cytotoxic antitumor antibiotic resulting in vascular endothelial destruction through inhibition of DNA synthesis in addition to sclerosis that leads to vascular endothelial destruction. One potential adverse effect with the use of bleomycin is that it has been shown to cause pulmonary fibrosis when injected intravenously for cancer therapy. Meta-analysis of the use of intralesional bleomycin in multiple case series demonstrated no such pulmonary effect (7). The authors postulated that this was because low dosage of bleomycin was used, with little escaping into the vascular system.A systematic review and meta-analysis of bleomycin injections versus other sclerosants demonstrated statistically equivalent size reduction with a lower rate adverse events and fewer severe complications after bleomycin administration (7). Muir et al (8) showed that intralesional bleomycin injection was effective in complete resolution (42%) or partial resolution (38%) of head and neck hemangiomas, vascular malformations, or venous malformations in 95 patients.More recently, Spence et al (9) matched percutaneous treatment of facial malformations treated with alcohol with those treated with bleomycin. They showed that while alcohol required fewer sessions, it was associated with a much higher incidence of complications, and thus, they preferred bleomycin for treatment of venous malformations. Notably, comparing sclerosants in case series treating nonvisceral vascular malformations, with the overwhelming majority involving the head and neck, may not extrapolate well to the treatment of GLH.The study by Ayoobi Yazdi et al (4) has several notable limitations to broad applicability. No control or randomization was performed in their single-arm prospective study. The investigation was carried out at a single referral center with the ethnic, socioeconomic, and genetic heterogeneity of the participant population undefined. The study specifically excluded patients with hepatic impairment, narrowing the applicability of the results to this population that made up 14% of the initially screened patients. The authors stated that their inclusion criteria for percutaneous use of bleomycin were patients who declined surgery for giant cavernous hemangiomas. This could have been an opportunity to compare the results of patients with giant cavernous hemangiomas treated with surgery versus percutaneous bleomycin therapy.In summary, Ayoobi Yazdi et al provide compelling prospective evidence for single-session percutaneous image-guided sclerotherapy of GLH using a combination of bleomycin and ethiodized oil. The study used a fixed dose of bleomycin and ethiodized oil regardless of participant or lesion size. They cogently note the optimal pharmacotherapy of the intralesional sclerosant is yet to be resolved. The dose dependence of both bleomycin and ethiodized oil, and the injectable form—such as liquid versus foam—need further investigation. The study discussion highlights a substantial minority of participants (21%) with increased visual analog scale pain scores at 12 months after the procedure as compared with 6 months, without demonstration or suggestion of concomitant increase in lesion size. The subcohort raises the question of the long-term efficacy of sclerotherapy and natural history of sclerosed GLHs. These lesions were shown to have significantly decreased in size, though they remained identifiable in all participants at 12 months and may begin to enlarge. The indications, technique, and safety of repeat intervention in the treated patient population need further investigation. However, we believe this technology is a promising treatment for GLH.Disclosures of Conflicts of Interest: J.P.M. disclosed no relevant relationships. R.E.G. disclosed no relevant relationships.References1. Choi BY, Nguyen MH. The diagnosis and management of benign hepatic tumors. J Clin Gastroenterol 2005;39(5):401–412. Crossref, Medline, Google Scholar2. Merrow AC, Gupta A, Patel MN, Adams DM. 2014 revised classification of vascular lesions from the International Society for the Study of Vascular Anomalies: radiologic-pathologic update. RadioGraphics 2016;36(5):1494–1516. Link, Google Scholar3. van Tilborg AA, Nielsen K, Scheffer HJ, et al. Bipolar radiofrequency ablation for symptomatic giant (>10 cm) hepatic cavernous haemangiomas: initial clinical experience. Clin Radiol 2013;68(1):e9–e14. Crossref, Medline, Google Scholar4. Ayoobi Yazdi N, Mehrabinejad MM, Dashti H, Pourghorban R, Nassiri Toosi M, Rokni Yazdi H. Percutaneous sclerotherapy with bleomycin and ethiodized oil: a promising treatment in symptomatic giant liver hemangioma. Radiology 2021.https://doi.org/10.1148/radiol.2021204444. Published online August 17, 2021. Google Scholar5. Liu X, Yang Z, Tan H, et al. Characteristics and operative treatment of extremely giant liver hemangioma >20 cm. Surgery 2017;161(6):1514–1524. Crossref, Medline, Google Scholar6. Herman P, Costa MLV, Machado MAC, et al. Management of hepatic hemangiomas: a 14-year experience. J Gastrointest Surg 2005;9(6):853–859. Crossref, Medline, Google Scholar7. Horbach SER, Rigter IM, Smitt JHS, Reekers JA, Spuls PI, van der Horst CMAM. Intralesional bleomycin injections for vascular malformations: a systematic review and meta-analysis. Plast Reconstr Surg 2016;137(1):244–256. Crossref, Medline, Google Scholar8. Muir T, Kirsten M, Fourie P, Dippenaar N, Ionescu GO. Intralesional bleomycin injection (IBI) treatment for haemangiomas and congenital vascular malformations. Pediatr Surg Int 2004;19(12):766–773. Crossref, Medline, Google Scholar9. Spence J, Krings T, TerBrugge KG, Agid R. Percutaneous treatment of facial venous malformations: a matched comparison of alcohol and bleomycin sclerotherapy. Head Neck 2011;33(1):125–130. Crossref, Medline, Google ScholarArticle HistoryReceived: June 24 2021Revision requested: July 12 2021Revision received: July 13 2021Accepted: July 16 2021Published online: Aug 17 2021Published in print: Nov 2021 FiguresReferencesRelatedDetailsCited ByConsiderations Regarding Image-guided Treatment of Liver HemangiomaPooya Torkian, Shahram Akhlaghpoor, 17 May 2022 | Radiology, Vol. 304, No. 2Accompanying This ArticlePercutaneous Sclerotherapy with Bleomycin and Ethiodized Oil: A Promising Treatment in Symptomatic Giant Liver HemangiomaAug 17 2021RadiologyRecommended Articles Percutaneous Sclerotherapy with Bleomycin and Ethiodized Oil: A Promising Treatment in Symptomatic Giant Liver HemangiomaRadiology2021Volume: 301Issue: 2pp. 464-471Vascular Anomaly Syndromes in the ISSVA Classification System: Imaging Findings and Role of Interventional Radiology in ManagementRadioGraphics2022Volume: 42Issue: 6pp. 1598-1620Considerations Regarding Image-guided Treatment of Liver HemangiomaRadiology2022Volume: 304Issue: 2pp. E45Update on Pediatric Interventional RadiologyRadioGraphics2022Volume: 42Issue: 6pp. 1580-1597One Step Closer to Precision Medicine for Transarterial Therapy of HCCRadiology2020Volume: 297Issue: 1pp. 235-236See More RSNA Education Exhibits Not Just "Hemangiomas"! 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