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Kwak JH, Yang A, Jung HL, Kim HJ, Kim DS, Shim JY, Shim JW. Cardiac Evaluation before and after Oral Propranolol Treatment for Infantile Hemangiomas. J Clin Med 2024; 13:3332. [PMID: 38893043 PMCID: PMC11172932 DOI: 10.3390/jcm13113332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 05/26/2024] [Accepted: 06/03/2024] [Indexed: 06/21/2024] Open
Abstract
Background: Most recent clinical practice guidelines addressing the management of infantile hemangiomas (IHs) recommend oral propranolol, a non-selective beta-adrenergic antagonist, as first-line treatment. However, few reports have provided continuous follow-up data regarding cardiac evaluations. Methods: Sixty-four patients diagnosed with IHs and treated with oral propranolol before 2 years of age at the Department of Pediatrics, Kangbuk Samsung Hospital (Seoul, Republic of Korea), with regular examinations between 2017 and 2021, were included. Cardiac evaluations, including electrocardiography, Holter monitoring, chest X-ray, and echocardiography, were performed. Results: Sixty-four patients with IHs successfully underwent continuous follow-up cardiac evaluations. The median age at diagnosis was 2 weeks (1 day to 34.3 weeks). The median age at treatment initiation was 13.6 weeks (2.4-87.9 weeks), the mean longitudinal diameter of hemangioma at diagnosis was 2.8 ± 2.1 cm (0.3-12.0 cm), and the mean percentage of size decrease after 1 year of oral propranolol treatment was 71.8%. None of the 64 patients experienced severe adverse side effects during propranolol treatment. There was no statistically significant differences in echocardiographic function and electrocardiographic data after treatment. Conclusions: Propranolol treatment ≥6 months was effective and safe without significant cardiac toxicity in the treatment of patients with infantile hemangiomas.
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Affiliation(s)
| | | | - Hye Lim Jung
- Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea; (J.H.K.); (A.Y.); (D.S.K.); (J.W.S.)
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Abstract
Infantile hemangiomas (IHs) are common vascular lesions which are benign but can cause significant functional and cosmetic morbidity. Since the fortuitous discovery of propranolol being effective to treat IH over a decade ago, the therapy and prognosis for children with IH have improved dramatically. Oral propranolol (as well as other oral beta-blockers and topical timolol) are safe and effective treatments, and have now supplanted other therapies. Making the correct diagnosis is crucial, because other vascular lesions can mimic IH. In addition, IH can be the first manifestation of an underlying syndrome. For IH requiring treatment, initiating treatment early is key to optimizing success. Therefore, early recognition and referral, if necessary, are important. Continued research on IH, both basic science and clinical, should result in continued advances.
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Affiliation(s)
- Kristy S Pahl
- Department of Pediatrics, Duke University School of Medicine, Durham
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Püttgen KB, Hansen LM, Lauren C, Stefanko N, Mathes E, Olsen GM, Tollefson MM, Adams D, Baselga E, Chamlin S, Corey K, Frascari FF, Frieden IJ, Galligan ER, Gupta D, Haggstrom A, Horii K, Hornik CP, Klajn J, Liberman L, Mancini A, Mannschreck D, McGinness A, McCuaig C, Newell B, Nguyen H, Nopper A, Oyesanya T, Powell J, Reynolds M, Rios M, Siegel DH, Ward K, Garzon MC, Frommelt P, Drolet BA. Limited utility of repeated vital sign monitoring during initiation of oral propranolol for complicated infantile hemangioma. J Am Acad Dermatol 2021; 85:345-352. [PMID: 32289387 DOI: 10.1016/j.jaad.2020.04.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 04/03/2020] [Accepted: 04/04/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND Initial propranolol recommendations for infantile hemangioma published in 2013 were intended as provisional best practices to be updated as evidence-based data emerged. METHODS A retrospective multicenter study was performed to evaluate utility of prolonged monitoring after first propranolol dose and escalation(s). Inclusion criteria included diagnosis of hemangioma requiring propranolol of greater than or equal to 0.3 mg/kg per dose, younger than 2 years, and heart rate monitoring for greater than or equal to 1 hour. Data collected included demographics, dose, vital signs, and adverse events. RESULTS A total of 783 subjects met inclusion criteria; median age at initiation was 112 days. None of the 1148 episodes of prolonged monitoring warranted immediate intervention or drug discontinuation. No symptomatic bradycardia or hypotension occurred during monitoring. Mean heart rate change from baseline to 1 hour was -8.19/min (±15.54/min) and baseline to 2 hours was -9.24/min (±15.84/min). Three preterm subjects had dose adjustments because of prescriber concerns about asymptomatic vital sign changes. No significant difference existed in pretreatment heart rate or in heart rate change between individuals with later adverse events during treatment and those without. CONCLUSION Prolonged monitoring for initiation and escalation of oral propranolol rarely changed management and did not predict future adverse events. Few serious adverse events occurred during therapy; none were cardiovascular.
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Affiliation(s)
| | | | | | | | - Erin Mathes
- University of California-San Francisco, San Francisco, California
| | | | | | | | | | - Sarah Chamlin
- Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | - Flora F Frascari
- University of California-San Francisco, San Francisco, California
| | - Ilona J Frieden
- University of California-San Francisco, San Francisco, California
| | | | - Deepti Gupta
- Seattle Children's Hospital/University of Washington School of Medicine, Seattle, Washington
| | | | | | | | - Justyna Klajn
- University of California-San Francisco, San Francisco, California
| | | | - Anthony Mancini
- Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | - Anelah McGinness
- University of California-San Francisco, San Francisco, California
| | | | | | | | - Amy Nopper
- University of Missouri, Kansas City, Missouri
| | - Tola Oyesanya
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Julie Powell
- Sainte-Justine University Hospital Center, Montreal, Quebec, Canada
| | - Megan Reynolds
- Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Monica Rios
- Universitat Autonoma de Barcelona, Barcelona, Spain
| | | | - Kendra Ward
- Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | | | - Beth A Drolet
- School of Medicine and Public Health, University of Wisconsin, Milwaukee, Wisconsin.
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Clinical Significance of Screening Electrocardiograms for the Administration of Propranolol for Problematic Infantile Hemangiomas. Int J Pediatr 2021; 2021:6657796. [PMID: 33679994 PMCID: PMC7929670 DOI: 10.1155/2021/6657796] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 02/09/2021] [Accepted: 02/13/2021] [Indexed: 11/18/2022] Open
Abstract
Objective Low-dose nonselective β blockade is an effective treatment for problematic infantile hemangioma (PIH). Screening electrocardiograms (ECG) are performed prior to the initiation of propranolol to minimize the risk of exacerbating undiagnosed heart block. How ECG results affect subsequent propranolol usage and patient management remains unclear. We examined the value of ECG prior to propranolol therapy in a quaternary pediatric hospital. Methods A retrospective chart review was performed on all infants who received propranolol (2 mg/kg/day divided three times daily) to treat PIH at Arkansas Children's Hospital from Sept. 2008 to Sept. 2015. All available demographic, historical, and clinical data were obtained. ECGs and echocardiographic data were reviewed and summarized. A pediatric cardiologist read all ECGs. Results A total of 333 patients (75% female) received propranolol therapy. ECG information was available for 317 (95%). Abnormal findings were present on 44/317 (13.9%) of study ECGs. The most common abnormal finding was "voltage criteria for ventricular hypertrophy" (n = 35, 76.1%). Two patients had abnormal rhythms; one had first-degree atrioventricular (AV) block, and one had occasional premature atrial contractions. Of the 31 patients who underwent echocardiograms, 20 (35%) were abnormal. 2.9% of infants with PIH treated with propranolol required a follow-up with a cardiologist. No patient was precluded from taking propranolol due to the findings on screening ECG. Conclusions Screening ECGs prior to propranolol therapy are abnormal in nearly 14% of patients with PIH but are unlikely to preclude therapy. In the absence of prior cardiac history, this cohort offers further evidence suggesting that screening ECGs may be of limited value in determining the safety of propranolol in otherwise healthy infants with PIH.
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Koh SP, Leadbitter P, Smithers F, Tan ST. β-blocker therapy for infantile hemangioma. Expert Rev Clin Pharmacol 2021; 13:899-915. [PMID: 32662682 DOI: 10.1080/17512433.2020.1788938] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Fifteen percent of proliferating infantile hemangioma (IH) require intervention because of the threat to function or life, ulceration, or tissue distortion. Propranolol is the mainstay treatment for problematic proliferating IH. Other β-blockers and angiotensin-converting enzyme (ACE) inhibitors have been explored as alternative treatments. AREAS COVERED The demonstration of a hemogenic endothelium origin of IH, with a neural crest phenotype and multi-lineage differentiation capacity, regulated by the renin-angiotensin system, underscores its programmed biologic behavior and accelerated involution induced by propranolol, other β-blockers and ACE inhibitors. We review the indications, dosing regimens, duration of treatment, efficacy and adverse effects of propranolol, and therapeutic alternatives including oral atenolol, acebutolol, nadolol, intralesional propranolol injections, topical propranolol and timolol, and oral captopril. EXPERT OPINION Improved understanding of the biology of IH provides insights into the mechanism of action underscoring its accelerated involution induced by propranolol, other β-blockers and ACE inhibitors. More research is required to understand the optimal dosing and duration, efficacy and safety of these alternative therapies. Recent demonstration of propranolol's actions mediated by non-β-adrenergic isomer R-propranolol on stem cells, offers an immense opportunity to harness the efficacy of β-blockers to induce accelerated involution of IH, while mitigating their β-adrenergic receptor-mediated adverse effects.
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Affiliation(s)
- Sabrina P Koh
- Gillies McIndoe Research Institute , Wellington, New Zealand
| | - Philip Leadbitter
- Gillies McIndoe Research Institute , Wellington, New Zealand.,Centre for the Study & Treatment for Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital , Wellington, New Zealand.,Department of Paediatrics, Hutt Hospital , Wellington, New Zealand
| | - Fiona Smithers
- Centre for the Study & Treatment for Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital , Wellington, New Zealand
| | - Swee T Tan
- Gillies McIndoe Research Institute , Wellington, New Zealand.,Centre for the Study & Treatment for Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital , Wellington, New Zealand.,Department of Surgery, The University of Melbourne , Parkville, Victoria, Australia
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Socchi F, Bigorre M, Normandin M, Captier G, Bessis D, Mondain M, Blanchet C, Akkari M, Amedro P, Gavotto A. Hemangiol in infantile haemangioma: A paediatric post-marketing surveillance drug study. Br J Clin Pharmacol 2020; 87:1970-1980. [PMID: 33118199 DOI: 10.1111/bcp.14593] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 09/21/2020] [Accepted: 09/24/2020] [Indexed: 01/06/2023] Open
Abstract
AIM Infantile haemangioma (IH) is the most common benign tumour in children. Since 2014, propranolol has become the first-choice therapy and currently Hemangiol is the only approved drug for complicated haemangioma. This post-marketing study reports the use of Hemangiol for IH in paediatric practice. METHOD AND RESULTS From January 2014 to November 2018, 94 children (median age 4 [0; 21] months; 75% female) treated with Hemangiol for proliferative IH were enrolled in the study. The systematic paediatric cardiology consultation never contraindicated beta-blockers. Two Hemangiol initiation protocols were used: a conventional ambulatory 3-week titration phase protocol (n = 76, 80.9%), and a rapid initiation protocol with a 48-hour dose escalation in conventional hospitalization for severe proliferative or ulcerated IH (n = 18, 19.1%). In both protocols, the haemodynamic tolerance was good. The mean maintenance dose of Hemangiol was 2.7 ± 0.8 mg/kg/day, with a median treatment duration of 7 [1.5; 19] months. Adverse events (AEs) have been found in 25 (26,6%) patients, including 8 (8.5%) patients with serious AEs (uncontrolled bronchial hyperreactivity, n = 5; serious hypoglycaemia, n = 3). Some patients had one or more AEs, a total of 24 nonserious AEs was reported in 19 patients (sleep disturbances, n = 9; respiratory disorders, n = 5; digestive disorders, n = 6). No cardiac adverse event was reported. CONCLUSION This post-marketing surveillance drug study supports the good tolerance of Hemangiol in children with IH. A rapid initiation protocol is of interest when treatment is urgent. The pretherapeutic paediatric cardiology consultation should not be systematic but only indicated for specific patients. CLINICALTRIALS.GOV: NCT04105517.
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Affiliation(s)
- Floriane Socchi
- Department of Paediatric and Congenital Cardiology, M3C Regional Reference Centre, Clinical Investigation Centre, Montpellier University Hospital, Montpellier, France
| | - Michele Bigorre
- Department of Paediatric Plastic Surgery, Montpellier University Hospital, Montpellier, France
| | - Marion Normandin
- Department of Clinical Pharmacy, Montpellier University Hospital, Montpellier, France
| | - Guillaume Captier
- Department of Paediatric Plastic Surgery, Montpellier University Hospital, Montpellier, France
| | - Didier Bessis
- Department of Dermatology, Montpellier University Hospital, Montpellier, France
| | - Michel Mondain
- Department of Paediatric ENT, Head and Neck Surgery, Montpellier University Hospital, Montpellier, France
| | - Catherine Blanchet
- Department of Paediatric ENT, Head and Neck Surgery, Montpellier University Hospital, Montpellier, France
| | - Mohamed Akkari
- Department of Paediatric ENT, Head and Neck Surgery, Montpellier University Hospital, Montpellier, France
| | - Pascal Amedro
- Department of Paediatric and Congenital Cardiology, M3C Regional Reference Centre, Clinical Investigation Centre, Montpellier University Hospital, Montpellier, France.,PhyMedExp, INSERM, CNRS, University of Montpellier, Montpellier, France
| | - Arthur Gavotto
- Department of Paediatric and Congenital Cardiology, M3C Regional Reference Centre, Clinical Investigation Centre, Montpellier University Hospital, Montpellier, France.,PhyMedExp, INSERM, CNRS, University of Montpellier, Montpellier, France
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Mimura H, Akita S, Fujino A, Jinnin M, Ozaki M, Osuga K, Nakaoka H, Morii E, Kuramochi A, Aoki Y, Arai Y, Aramaki N, Inoue M, Iwashina Y, Iwanaka T, Ueno S, Umezawa A, Ozeki M, Ochi J, Kinoshita Y, Kurita M, Seike S, Takakura N, Takahashi M, Tachibana T, Chuman K, Nagata S, Narushima M, Niimi Y, Nosaka S, Nozaki T, Hashimoto K, Hayashi A, Hirakawa S, Fujikawa A, Hori Y, Matsuoka K, Mori H, Yamamoto Y, Yuzuriha S, Rikihisa N, Watanabe S, Watanabe S, Kuroda T, Sugawara S, Ishikawa K, Sasaki S. Japanese clinical practice guidelines for vascular anomalies 2017. Jpn J Radiol 2020; 38:287-342. [PMID: 32207066 PMCID: PMC7150662 DOI: 10.1007/s11604-019-00885-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.
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Affiliation(s)
- Hidefumi Mimura
- Department of Radiology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae, Kawasaki, Kanagawa 216-8511 Japan
| | - Sadanori Akita
- Department of Plastic Surgery, Wound Repair and Regeneration, Fukuoka University, School of Medicine, Fukuoka, Japan
| | - Akihiro Fujino
- Division of Surgery, National Center for Child Health and Development, Tokyo, Japan
| | - Masatoshi Jinnin
- Department of Dermatology, Wakayama Medical University, Wakayama, Japan
| | - Mine Ozaki
- Department of Plastic and Reconstructive, Aesthetic Surgery, Kyorin University School of Medicine, Mitaka, Japan
| | - Keigo Osuga
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hiroki Nakaoka
- Department of Plastic Surgery, Ehime University Hospital, Toon, Japan
| | - Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Akira Kuramochi
- Department of Dermatology, Saitama Medical University, Irumagun, Japan
| | - Yoko Aoki
- Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan
| | - Yasunori Arai
- Department of Radiology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae, Kawasaki, Kanagawa 216-8511 Japan
| | - Noriko Aramaki
- Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Masanori Inoue
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Yuki Iwashina
- Department of Plastic and Reconstructive, Aesthetic Surgery, Kyorin University School of Medicine, Mitaka, Japan
| | - Tadashi Iwanaka
- Department of Pediatric Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Shigeru Ueno
- Department of Pediatric Surgery, Tokai University School of Medicine, Isehara, Japan
| | - Akihiro Umezawa
- Department of Reproductive Biology, Center for Regenerative Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Michio Ozeki
- Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Junko Ochi
- Department of Diagnostic Radiology, Tohoku University, Sendai, Japan
| | - Yoshiaki Kinoshita
- Department of Pediatric Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Masakazu Kurita
- Department of Plastic and Reconstructive Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Shien Seike
- Department of Plastic Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Nobuyuki Takakura
- Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
| | - Masataka Takahashi
- Department of Reproductive Biology, Center for Regenerative Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Takao Tachibana
- Department of Dermatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Kumiko Chuman
- Department of Dermatology, Kanto Central Hospital, Tokyo, Japan
| | - Shuji Nagata
- Department of Radiology, Kurume University School of Medicine, Kurume, Japan
| | - Mitsunaga Narushima
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Yasunari Niimi
- Department of Neuroendovascular Therapy, St. Luke’s International Hospital, Tokyo, Japan
| | - Shunsuke Nosaka
- Division of Radiology, National Center for Child Health and Development, Tokyo, Japan
| | - Taiki Nozaki
- Department of Radiology, St Luke’s International Hospital, Tokyo, Japan
| | - Kazuki Hashimoto
- Department of Radiology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae, Kawasaki, Kanagawa 216-8511 Japan
| | - Ayato Hayashi
- Department of Plastic and Reconstructive Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Satoshi Hirakawa
- Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Atsuko Fujikawa
- Department of Radiology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae, Kawasaki, Kanagawa 216-8511 Japan
| | - Yumiko Hori
- Department of Pathology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kentaro Matsuoka
- Department of Pathology, Dokkyo Medical University, Saitama Medical Center, Koshigaya, Japan
| | - Hideki Mori
- Department of Plastic Surgery, Ehime University Hospital, Toon, Japan
| | - Yuki Yamamoto
- Department of Dermatology, Wakayama Medical University, Wakayama, Japan
| | - Shunsuke Yuzuriha
- Department of Plastic and Reconstructive Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Naoaki Rikihisa
- Department of Plastic and Reconstructive Surgery, Oyumino Central Hospital, Chiba, Japan
| | - Shoji Watanabe
- Department of Plastic and Reconstructive Surgery, Saitama Children’s Medical Center, Saitama, Japan
| | - Shinichi Watanabe
- Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan
| | - Tatsuo Kuroda
- Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Shunsuke Sugawara
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
| | - Kosuke Ishikawa
- Department of Plastic and Reconstructive Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Satoru Sasaki
- Department of Plastic and Reconstructive Surgery, Center for Vascular Anomalies, Tonan Hospital, Sapporo, Japan
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8
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Mimura H, Akita S, Fujino A, Jinnin M, Ozaki M, Osuga K, Nakaoka H, Morii E, Kuramochi A, Aoki Y, Arai Y, Aramaki N, Inoue M, Iwashina Y, Iwanaka T, Ueno S, Umezawa A, Ozeki M, Ochi J, Kinoshita Y, Kurita M, Seike S, Takakura N, Takahashi M, Tachibana T, Chuman K, Nagata S, Narushima M, Niimi Y, Nosaka S, Nozaki T, Hashimoto K, Hayashi A, Hirakawa S, Fujikawa A, Hori Y, Matsuoka K, Mori H, Yamamoto Y, Yuzuriha S, Rikihisa N, Watanabe S, Watanabe S, Kuroda T, Sugawara S, Ishikawa K, Sasaki S. Japanese Clinical Practice Guidelines for Vascular Anomalies 2017. J Dermatol 2020; 47:e138-e183. [PMID: 32200557 PMCID: PMC7317503 DOI: 10.1111/1346-8138.15189] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 11/20/2019] [Indexed: 01/19/2023]
Abstract
The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety and systematizing treatment, employing evidence‐based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQ) were decided based on the important clinical issues. For document retrieval, key words for published work searches were set for each CQ, and work published from 1980 to the end of September 2014 was searched in PubMed, Cochrane Library and Japana Centra Revuo Medicina databases. The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System technique. A total of 33 CQ were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence‐based guidelines for the management of vascular anomalies.
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Affiliation(s)
- Hidefumi Mimura
- Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Sadanori Akita
- Department of Plastic Surgery, Wound Repair and Regeneration, Fukuoka University, School of Medicine, Fukuoka, Japan
| | - Akihiro Fujino
- Division of Surgery, National Center for Child Health and Development, Tokyo, Japan
| | - Masatoshi Jinnin
- Department of Dermatology, Wakayama Medical University, Wakayama, Japan
| | - Mine Ozaki
- Department of Plastic, Reconstructive and Aesthetic Surgery, Kyorin University School of Medicine, Mitaka, Japan
| | - Keigo Osuga
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hiroki Nakaoka
- Department of Plastic Surgery, Ehime University Hospital, Toon, Japan
| | - Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Akira Kuramochi
- Department of Dermatology, Saitama Medical University, Iruma-gun, Japan
| | - Yoko Aoki
- Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan
| | - Yasunori Arai
- Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Noriko Aramaki
- Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Masanori Inoue
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Yuki Iwashina
- Department of Plastic, Reconstructive and Aesthetic Surgery, Kyorin University School of Medicine, Mitaka, Japan
| | - Tadashi Iwanaka
- Department of Pediatric Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Shigeru Ueno
- Department of Pediatric Surgery, Tokai University School of Medicine, Isehara, Japan
| | - Akihiro Umezawa
- Department of Reproductive Biology, Center for Regenerative Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Michio Ozeki
- Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Junko Ochi
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yoshiaki Kinoshita
- Department of Pediatric Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Masakazu Kurita
- Department of Plastic and Reconstructive Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Shien Seike
- Department of Plastic Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Nobuyuki Takakura
- Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
| | - Masataka Takahashi
- Department of Reproductive Biology, Center for Regenerative Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Takao Tachibana
- Department of Dermatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Kumiko Chuman
- Department of Dermatology, Kanto Central Hospital, Tokyo, Japan
| | - Shuji Nagata
- Department of Radiology, Kurume University School of Medicine, Kurume, Japan
| | - Mitsunaga Narushima
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Yasunari Niimi
- Department of Neuroendovascular Therapy, St. Luke's International Hospital, Tokyo, Japan
| | - Shunsuke Nosaka
- Division of Radiology, National Center for Child Health and Development, Tokyo, Japan
| | - Taiki Nozaki
- Department of Radiology, St. Luke's International Hospital, Tokyo, Japan
| | - Kazuki Hashimoto
- Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Ayato Hayashi
- Department of Plastic and Reconstructive Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Satoshi Hirakawa
- Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Atsuko Fujikawa
- Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Yumiko Hori
- Department of Pathology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kentaro Matsuoka
- Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | - Hideki Mori
- Department of Plastic Surgery, Ehime University Hospital, Toon, Japan
| | - Yuki Yamamoto
- Department of Dermatology, Wakayama Medical University, Wakayama, Japan
| | - Shunsuke Yuzuriha
- Department of Plastic and Reconstructive Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Naoaki Rikihisa
- Department of Plastic and Reconstructive Surgery, Oyumino Central Hospital, Chiba, Japan
| | - Shoji Watanabe
- Department of Plastic and Reconstructive Surgery, Saitama Children's Medical Center, Saitama, Japan
| | - Shinichi Watanabe
- Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan
| | - Tatsuo Kuroda
- Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Shunsuke Sugawara
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
| | - Kosuke Ishikawa
- Department of Plastic and Reconstructive Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Satoru Sasaki
- Department of Plastic and Reconstructive Surgery, Center for Vascular Anomalies, Tonan Hospital, Sapporo, Japan
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9
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Mimura H, Akita S, Fujino A, Jinnin M, Ozaki M, Osuga K, Nakaoka H, Morii E, Kuramochi A, Aoki Y, Arai Y, Aramaki N, Inoue M, Iwashina Y, Iwanaka T, Ueno S, Umezawa A, Ozeki M, Ochi J, Kinoshita Y, Kurita M, Seike S, Takakura N, Takahashi M, Tachibana T, Chuman K, Nagata S, Narushima M, Niimi Y, Nosaka S, Nozaki T, Hashimoto K, Hayashi A, Hirakawa S, Fujikawa A, Hori Y, Matsuoka K, Mori H, Yamamoto Y, Yuzuriha S, Rikihisa N, Watanabe S, Watanabe S, Kuroda T, Sugawara S, Ishikawa K, Sasaki S. Japanese clinical practice guidelines for vascular anomalies 2017. Pediatr Int 2020; 62:257-304. [PMID: 32202048 PMCID: PMC7232443 DOI: 10.1111/ped.14077] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 11/20/2019] [Indexed: 01/19/2023]
Abstract
The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.
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Affiliation(s)
- Hidefumi Mimura
- Department of Radiology, St Marianna University School of Medicine, Kawasaki, Japan
| | - Sadanori Akita
- Department of Plastic Surgery, Wound Repair and Regeneration, School of Medicine, Fukuoka University, Fukuoka, Japan
| | - Akihiro Fujino
- Division of Surgery, National Center for Child Health and Development, Tokyo, Japan
| | - Masatoshi Jinnin
- Department of Dermatology, Wakayama Medical University, Wakayama, Japan
| | - Mine Ozaki
- Department of Plastic and Reconstructive, Aesthetic Surgery, Kyorin University School of Medicine, Mitaka, Japan
| | - Keigo Osuga
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hiroki Nakaoka
- Department of Plastic Surgery, Ehime University Hospital, Toon, Japan
| | - Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Akira Kuramochi
- Department of Dermatology, Saitama Medical University, Irumagun, Japan
| | - Yoko Aoki
- Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan
| | - Yasunori Arai
- Department of Radiology, St Marianna University School of Medicine, Kawasaki, Japan
| | - Noriko Aramaki
- Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Masanori Inoue
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Yuki Iwashina
- Department of Plastic and Reconstructive, Aesthetic Surgery, Kyorin University School of Medicine, Mitaka, Japan
| | - Tadashi Iwanaka
- Department of Pediatric Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Shigeru Ueno
- Department of Pediatric Surgery, Tokai University School of Medicine, Isehara, Japan
| | - Akihiro Umezawa
- Department of Reproductive Biology, Center for Regenerative Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Michio Ozeki
- Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Junko Ochi
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yoshiaki Kinoshita
- Department of Department of Pediatric Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Masakazu Kurita
- Department of Plastic and Reconstructive Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Shien Seike
- Department of Plastic Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Nobuyuki Takakura
- Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
| | - Masataka Takahashi
- Department of Reproductive Biology, Center for Regenerative Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Takao Tachibana
- Department of Dermatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Kumiko Chuman
- Department of Dermatology, Kanto Central Hospital, Tokyo, Japan
| | - Shuji Nagata
- Department of Radiology, Kurume University School of Medicine, Kurume, Japan
| | - Mitsunaga Narushima
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Yasunari Niimi
- Department of Neuroendovascular Therapy, St Luke's International Hospital, Tokyo, Japan
| | - Shunsuke Nosaka
- Division of Radiology, National Center for Child Health and Development, Tokyo, Japan
| | - Taiki Nozaki
- Department of Radiology, St Luke's International Hospital, Tokyo, Japan
| | - Kazuki Hashimoto
- Department of Radiology, St Marianna University School of Medicine, Kawasaki, Japan
| | - Ayato Hayashi
- Department of Plastic and Reconstructive Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan
| | - Satoshi Hirakawa
- Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Atsuko Fujikawa
- Department of Radiology, St Marianna University School of Medicine, Kawasaki, Japan
| | - Yumiko Hori
- Department of Pathology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kentaro Matsuoka
- Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | - Hideki Mori
- Department of Plastic Surgery, Ehime University Hospital, Toon, Japan
| | - Yuki Yamamoto
- Department of Dermatology, Wakayama Medical University, Wakayama, Japan
| | - Shunsuke Yuzuriha
- Department of Plastic and Reconstructive Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Naoaki Rikihisa
- Department of Plastic and Reconstructive Surgery, Oyumino Central Hospital, Chiba, Japan
| | - Shoji Watanabe
- Department of Plastic and Reconstructive Surgery, Saitama Children's Medical Center, Saitama, Japan
| | - Shinichi Watanabe
- Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan
| | - Tatsuo Kuroda
- Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Shunsuke Sugawara
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
| | - Kosuke Ishikawa
- Department of Plastic and Reconstructive Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Satoru Sasaki
- Department of Plastic and Reconstructive Surgery, Center for Vascular Anomalies, Tonan Hospital, Sapporo, Japan
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10
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Abstract
Infantile hemangiomas (IH) are a common benign tumor of infancy, most being uncomplicated and not requiring therapy. Some IH may require treatment; the pediatric provider must be familiar with morphology, distribution, natural history, and associations of IH. Several treatment options are available for IH: current standard of care, oral propranolol. Other therapies include wound care; topical beta-blocker therapy for small, superficial, and uncomplicated IH; treatment of IH residua. In addition to functional compromise and other complications, potential for permanent deformity and eventual psychosocial stigmatization are important when considering the need for treatment of IH in a neonate or infant.
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11
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Krowchuk DP, Frieden IJ, Mancini AJ, Darrow DH, Blei F, Greene AK, Annam A, Baker CN, Frommelt PC, Hodak A, Pate BM, Pelletier JL, Sandrock D, Weinberg ST, Whelan MA. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics 2019; 143:peds.2018-3475. [PMID: 30584062 DOI: 10.1542/peds.2018-3475] [Citation(s) in RCA: 244] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Infantile hemangiomas (IHs) occur in as many as 5% of infants, making them the most common benign tumor of infancy. Most IHs are small, innocuous, self-resolving, and require no treatment. However, because of their size or location, a significant minority of IHs are potentially problematic. These include IHs that may cause permanent scarring and disfigurement (eg, facial IHs), hepatic or airway IHs, and IHs with the potential for functional impairment (eg, periorbital IHs), ulceration (that may cause pain or scarring), and associated underlying abnormalities (eg, intracranial and aortic arch vascular abnormalities accompanying a large facial IH). This clinical practice guideline for the management of IHs emphasizes several key concepts. It defines those IHs that are potentially higher risk and should prompt concern, and emphasizes increased vigilance, consideration of active treatment and, when appropriate, specialty consultation. It discusses the specific growth characteristics of IHs, that is, that the most rapid and significant growth occurs between 1 and 3 months of age and that growth is completed by 5 months of age in most cases. Because many IHs leave behind permanent skin changes, there is a window of opportunity to treat higher-risk IHs and optimize outcomes. Early intervention and/or referral (ideally by 1 month of age) is recommended for infants who have potentially problematic IHs. When systemic treatment is indicated, propranolol is the drug of choice at a dose of 2 to 3 mg/kg per day. Treatment typically is continued for at least 6 months and often is maintained until 12 months of age (occasionally longer). Topical timolol may be used to treat select small, thin, superficial IHs. Surgery and/or laser treatment are most useful for the treatment of residual skin changes after involution and, less commonly, may be considered earlier to treat some IHs.
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Affiliation(s)
- Daniel P Krowchuk
- Departments of Pediatrics and Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
| | - Ilona J Frieden
- Departments of Dermatology and Pediatrics, School of Medicine, University of California, San Francisco, San Francisco, California
| | - Anthony J Mancini
- Departments of Pediatrics and Dermatology, Feinberg School of Medicine, Northwestern University and Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois
| | - David H Darrow
- Departments of Otolaryngology and Pediatrics, Eastern Virginia Medical School and Children's Hospital of the King's Daughters, Norfolk, Virginia
| | - Francine Blei
- Donald and Barbara Zucker School of Medicine, Northwell Health, New York City, New York
| | - Arin K Greene
- Department of Plastic and Oral Surgery, Boston Children's Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts
| | - Aparna Annam
- Department of Radiology, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado
| | - Cynthia N Baker
- Department of Pediatrics, Kaiser Permanente Medical Center, Los Angeles, California
| | - Peter C Frommelt
- Department of Pediatrics, Cardiology, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin
| | - Amy Hodak
- American Board of Pediatrics, Chapel Hill, North Carolina
| | - Brian M Pate
- Department of Pediatrics, University of Kansas School of Medicine-Wichita, Wichita, Kansas
| | | | - Deborah Sandrock
- St Christopher's Hospital for Children and College of Medicine, Drexel University, Philadelphia, Pennsylvania
| | - Stuart T Weinberg
- Departments of Biomedical Informatics and Pediatrics, School of Medicine, Vanderbilt University, Nashville, Tennessee; and
| | - Mary Anne Whelan
- College of Physicians and Surgeons, Columbia University, New York City, New York
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12
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Lund EB, Chamlin SL, Mancini AJ. Utility of routine electrocardiographic screening before initiation of propranolol for infantile hemangiomas. Pediatr Dermatol 2018; 35:e233-e234. [PMID: 29683225 DOI: 10.1111/pde.13508] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Screening electrocardiography (ECG) before initiation of propranolol for treatment of infantile hemangiomas (IH) is controversial. A retrospective chart review was conducted to assess the utility of pretreatment ECG in infants with IH starting propranolol. Although nearly half of the ECGs were abnormal, no contraindications to treatment were identified from screening ECG, and no association was found between any of the reported side effects and abnormal ECG. These results support previously published data, and in a larger cohort, providing further confirmation that pretreatment ECG is not necessary in most infants with IH.
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Affiliation(s)
- Emily B Lund
- Section of Dermatology, University of Chicago Pritzker School of Medicine, Chicago, IL, USA
| | - Sarah L Chamlin
- Departments of Pediatrics and Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
| | - Anthony J Mancini
- Departments of Pediatrics and Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
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13
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Fogel I, Ollech A, Zvulunov A, Valdman‐Greenshpon Y, Atar Snir V, Friedland R, Lapidoth M, Ben‐Amitai D. Safety profile during initiation of propranolol for treatment of infantile haemangiomas in an ambulatory day‐care hospitalization setting. J Eur Acad Dermatol Venereol 2018; 32:2004-2009. [DOI: 10.1111/jdv.14955] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 02/26/2018] [Indexed: 12/01/2022]
Affiliation(s)
- I. Fogel
- Department of Dermatology Northwestern University Chicago IL USA
| | - A. Ollech
- Department of Dermatology Northwestern University Chicago IL USA
| | - A. Zvulunov
- Pediatric Dermatology Unit Schneider Children's Medical Center of Israel Petach Tikva Israel
- Ben Gurion University of the Negev Be'er Sheva Israel
| | - Y. Valdman‐Greenshpon
- Dermatology Unit Kaplan Hospital Rehovot Israel
- Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - V. Atar Snir
- Pediatric Dermatology Unit Schneider Children's Medical Center of Israel Petach Tikva Israel
- Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - R. Friedland
- Pediatric Dermatology Unit Schneider Children's Medical Center of Israel Petach Tikva Israel
- Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - M. Lapidoth
- Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
- Laser Unit Rabin Medical Center ‐ Hasharon Hospital Petach Tikva Israel
| | - D. Ben‐Amitai
- Pediatric Dermatology Unit Schneider Children's Medical Center of Israel Petach Tikva Israel
- Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
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14
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Frongia G, Byeon JO, Arnold R, Mehrabi A, Günther P. Cardiac diagnostics before oral propranolol therapy in infantile hemangioma: retrospective evaluation of 234 infants. World J Pediatr 2018; 14:254-258. [PMID: 29796952 DOI: 10.1007/s12519-018-0137-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 06/07/2017] [Accepted: 06/07/2017] [Indexed: 12/30/2022]
Abstract
BACKGROUND The indication and extent of cardiac screening before oral propranolol therapy (OPT) in patients with infantile hemangioma (IH) has been challenged. In this study, we evaluated pre-OPT cardiac diagnostics in a pediatric IH cohort in our department. METHODS Retrospective chart review of infants ≤ 12 months old with IH undergoing OPT. The diagnostics prior to OPT, occurrence of complications, and outcome were recorded. RESULTS A total of 234 patients were evaluated. The mean age at the onset of OPT was 4.2 ± 0.3 months, the average duration of OPT was 6.1 ± 0.1 months, and the average follow-up was 12.3 ± 0.7 months. Echocardiograms and electrocardiograms were performed prior to OPT in all patients. One hundred and three (44.0%) echocardiograms revealed pathological findings, 19 (8.1%) of which were minor (including atrial septal defects, pulmonary stenosis, and patent ductus arteriosus). Pathological findings were observed in 17 (7.3%) of electrocardiograms, only one (0.4%) of which was minor (suspected cardiac arrhythmia, subsequently excluded by long-term electrocardiogram analysis). These findings did not contraindicate OPT and no severe adverse events associated with OPT occurred during the follow-up period. CONCLUSIONS Routine cardiac screening by electrocardiogram and echocardiogram before OPT is debatable and not routinely indicated in children with IH. Further studies are necessary to draw definite conclusions on the reasonable indication and extent of this diagnostic approach.
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Affiliation(s)
- Giovanni Frongia
- Division of Pediatric Surgery, Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
| | - Ji-Oun Byeon
- Division of Pediatric Surgery, Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Raoul Arnold
- Department of Pediatric Cardiology, Center for Pediatrics and Adolescent Medicine, University Hospital of Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany
| | - Patrick Günther
- Division of Pediatric Surgery, Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
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15
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16
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Bayart CB, Tamburro JE, Vidimos AT, Wang L, Golden AB. Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study. Pediatr Dermatol 2017; 34:413-421. [PMID: 28556385 DOI: 10.1111/pde.13177] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND/OBJECTIVES The nonselective beta-blocker propranolol is the current criterion standard for treatment of infantile hemangiomas (IHs) and the first therapy that the U.S. Food and Drug Administration has approved for the condition, but concern about adverse effects, such as bronchospasm, hypoglycemia, and sleep disturbances, has sparked interest in the use of alternative agents such as the selective β1 antagonist atenolol. Our aim was to compare the efficacy and adverse effect profiles of atenolol with those of propranolol in the treatment of IHs in a retrospective noninferiority trial. METHODS Twenty-seven children with IHs treated with atenolol according to the Cleveland Clinic foundation's standardized clinical assessment and management plan (SCAMP) met inclusion criteria and were compared with a matched group of 53 children with IHs treated with propranolol. Three reviewers assessed response to therapy using a modified version of the previously validated Hemangioma Activity Score (HAS). RESULTS The mean change in HAS was -2.94 ± 1.20 for patients treated with atenolol and -2.96 ± 1.42 for those treated with propranolol. There was no statistically significant difference in pre- and posttreatment modified HAS scores between the two groups (p = 0.60). There was no significant difference in the overall rate of adverse effects (p = 0.10), although 11% of patients treated with propranolol experienced reactive airway symptoms, whereas this was not seen in any of the patients treated with atenolol. CONCLUSION Our study supports previous findings that atenolol is at least as effective as propranolol for treatment of IHs and poses less risk of bronchospasm. Our SCAMP proposes guidelines for dosing and monitoring parameters.
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Affiliation(s)
- Cheryl B Bayart
- Department of Dermatology, Cleveland Clinic Foundation, Cleveland, Ohio.,Department of Pediatrics, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Joan E Tamburro
- Department of Dermatology, Cleveland Clinic Foundation, Cleveland, Ohio.,Department of Pediatrics, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Allison T Vidimos
- Department of Dermatology, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Lu Wang
- Department of Biostatistics, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Alex B Golden
- Department of Cardiology, Connecticut Children's Medical Center, Hartford, Connecticut
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17
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Smithson SL, Rademaker M, Adams S, Bade S, Bekhor P, Davidson S, Dore A, Drummond C, Fischer G, Gin A, Grills C, Halbert A, Lokmic Z, McCahon E, Morgan VA, Murrell DF, Orchard D, Penington A, Purvis D, Relic J, Robertson S, Robinson AJ, Scardamaglia L, Su J, Tan S, Wargon O, Warren L, Wong LC, Zappala T, Phillips R. Consensus statement for the treatment of infantile haemangiomas with propranolol. Australas J Dermatol 2017; 58:155-159. [DOI: 10.1111/ajd.12600] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 11/12/2016] [Indexed: 11/28/2022]
Affiliation(s)
| | | | - Susan Adams
- University of New South Wales School of Women's and Children's Health; Randwick New South Wales Australia
| | - Stuart Bade
- The Lady Cilentro Children's Hospital; Brisbane Queensland Australia
| | - Philip Bekhor
- Royal Children's Hospital; Melbourne Victoria Australia
| | - Samantha Davidson
- The Lady Cilentro Children's Hospital; Brisbane Queensland Australia
| | - Amanda Dore
- The Lady Cilentro Children's Hospital; Brisbane Queensland Australia
| | | | - Gayle Fischer
- University of Sydney; Sydney New South Wales Australia
| | - Alexander Gin
- Royal Children's Hospital; Melbourne Victoria Australia
| | - Claire Grills
- Royal Children's Hospital; Melbourne Victoria Australia
| | - Anne Halbert
- Princess Margaret Hospital for Children; Perth Western Australia Australia
| | - Zerina Lokmic
- Murdoch Childrens Research Institute; Melbourne Victoria Australia
| | - Emma McCahon
- Children's Hospital at Westmead; Sydney Australia
| | | | | | - David Orchard
- Royal Children's Hospital; Melbourne Victoria Australia
| | | | - Diana Purvis
- Starship Children's Hospital; Auckland New Zealand
| | - John Relic
- John Hunter Children's Hospital; Newcastle New South Wales Australia
| | | | | | | | - John Su
- Royal Children's Hospital; Melbourne Victoria Australia
| | - Swee Tan
- Gillies McIndoe Research Institute; Wellington New Zealand
| | - Orli Wargon
- Sydney Children's Hospital; Sydney New South Wales Australia
| | - Lachlan Warren
- Women's and Children's Hospital; Adelaide South Australia Australia
| | | | - Tania Zappala
- The Lady Cilentro Children's Hospital; Brisbane Queensland Australia
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18
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Yarbrough KB, Tollefson MM, Krol AL, Leitenberger SL, Mann JA, MacArthur CJ. Is Routine Electrocardiography Necessary Before Initiation of Propranolol for Treatment of Infantile Hemangiomas? Pediatr Dermatol 2016; 33:615-620. [PMID: 27599450 DOI: 10.1111/pde.12972] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND In recent years propranolol has become the treatment of choice for infantile hemangiomas (IHs). There is broad variation in the approach to propranolol initiation in clinical practice. This retrospective study explored the effectiveness of routine pre-treatment ECG in screening infants being considered for systemic treatment with propranolol. METHODS All patients seen in the outpatient pediatric dermatology clinics at Oregon Health and Sciences University (OHSU) and The Mayo Clinic Rochester (MCR), as well as those seen in multidisciplinary vascular anomalies clinics, who had ECGs obtained prior to planned initiation of propranolol for treatment of IH from 2008 to 2013, were identified. A total of 162 patients were included in the study. RESULTS We found that 43% (69) of routine ECGs were read as abnormal, leading to 28 formal consultation appointments with pediatric cardiologists. After either formal consultation or informal discussion with cardiology, no patients with initially "abnormal" ECGs were ultimately excluded from treatment with propranolol based on routine ECG findings. Additionally no patients in our cohort experienced an adverse effect during treatment that could have been predicted or prevented by ECG prior to initiation of the propranolol. CONCLUSION Our findings suggest that routine ECG may not be necessary or helpful in the vast majority of patients treated with propranolol for IHs.
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Affiliation(s)
- Kevin B Yarbrough
- Phoenix Children's Hospital, Phoenix, AZ.,Oregon Health and Science University, Portland, OR
| | | | | | | | - Julianne A Mann
- Oregon Health and Science University, Portland, OR.,Dartmouth-Hitchcock Medical Center, Lebanon, NH
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19
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Léaute-Labrèze C, Boccara O, Degrugillier-Chopinet C, Mazereeuw-Hautier J, Prey S, Lebbé G, Gautier S, Ortis V, Lafon M, Montagne A, Delarue A, Voisard JJ. Safety of Oral Propranolol for the Treatment of Infantile Hemangioma: A Systematic Review. Pediatrics 2016; 138:peds.2016-0353. [PMID: 27688361 DOI: 10.1542/peds.2016-0353] [Citation(s) in RCA: 126] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/01/2016] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Given the widespread use of propranolol in infantile hemangioma (IH) it was considered essential to perform a systematic review of its safety. The objectives of this review were to evaluate the safety profile of oral propranolol in the treatment of IH. METHODS We searched Embase and Medline databases (2007-July 2014) and unpublished data from the manufacturer of Hemangiol/Hemangeol (marketed pediatric formulation of oral propranolol; Pierre Fabre Dermatologie, Lavaur, France). Selected studies included ≥10 patients treated with oral propranolol for IH and that either reported ≥1 adverse event or effect (AE) or planned to capture AEs. Data capture was standardized and extracted study design, demographic characteristics, IH characteristics, intervention, and safety outcomes. AEs were assigned a system organ class and preferred term. RESULTS A total of 83 of 398 identified literature records met the inclusion criteria, covering 3766 propranolol-treated patients. The manufacturer's data for 3 pooled clinical trials (435 propranolol-treated patients) and 1 Compassionate Use Program (1661 patients) were included. AE data were reported for 1945 of 5862 propranolol-treated patients. The most frequently reported AEs included a range of sleep disturbances, peripheral coldness, and agitation. The most serious AEs (atrioventricular block, bradycardia, hypotension, bronchospasm/bronchial hyperreactivity, and hypoglycemia-related seizures) were managed by decreasing doses or temporary/permanent discontinuation of propranolol. Limitations included the variety of included study designs; monitoring, collection, and reporting of AE data; small sample sizes for some articles; and the wide scope of review. CONCLUSIONS Oral propranolol is well tolerated if appropriate pretreatment assessments and within-treatment monitoring are performed to exclude patients with contraindications and to minimize serious side effects during treatment.
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Affiliation(s)
- Christine Léaute-Labrèze
- Unité de Dermatologie Pédiatrique et Centre d'Investigation Clinque Pédiatrique 1401, Hôpital Pellegrin-Enfants, Bordeaux, France;
| | - Olivia Boccara
- Service de Dermatologie, Hôpital Necker Enfants Malades, Paris, France
| | - Caroline Degrugillier-Chopinet
- Service Explorations Cardiovasculaires et de Cardiologie Pédiatrique, Centre Hospitalier Régional Universitaire de Lille, Lille, France
| | - Juliette Mazereeuw-Hautier
- Service de Dermatologie et Centre de Référence des Maladies Rares de la Peau, Hôpital Larrey, Toulouse, France
| | - Sorilla Prey
- Unité de Dermatologie Pédiatrique et Centre d'Investigation Clinque Pédiatrique 1401, Hôpital Pellegrin-Enfants, Bordeaux, France
| | | | | | | | - Martine Lafon
- Institut de Recherche Pierre Fabre, Toulouse, France; and
| | - Agnès Montagne
- Institut de Recherche Pierre Fabre, Toulouse, France; and
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Fernandez-Pineda I, Williams R, Ortega-Laureano L, Jones R. Cardiovascular drugs in the treatment of infantile hemangioma. World J Cardiol 2016; 8:74-80. [PMID: 26839658 PMCID: PMC4728108 DOI: 10.4330/wjc.v8.i1.74] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 09/04/2015] [Accepted: 10/28/2015] [Indexed: 02/06/2023] Open
Abstract
Since the introduction of propranolol in the treatment of complicated infantile hemangiomas (IH) in 2008, other different beta-blockers, including timolol, acetabutolol, nadolol and atenolol, have been successfully used for the same purpose. Various hypotheses including vasoconstriction, inhibition of angiogenesis and the induction of apoptosis in proliferating endothelial cells have been advanced as the potential beta-blocker-induced effect on the accelerated IH involution, although the exact mechanism of action of beta-blockers remains unknown. This has generated an extraordinary interest in IH research and has led to the discovery of the role of the renin-angiotensin system (RAS) in the biology of IH, providing a plausible explanation for the beta-blocker induced effect on IH involution and the development of new potential indications for RAS drugs such as angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in the treatment of IH. This review is focused on the current use of cardiovascular drugs in the treatment of IH.
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Janmohamed SR, Chandran NS, Oranje AP. Controversies in the Treatment of Infantile Haemangiomas with β-Blockers. PRACTICAL PEDIATRIC DERMATOLOGY 2016:69-78. [DOI: 10.1007/978-3-319-32159-2_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Wedgeworth E, Glover M, Irvine A, Neri I, Baselga E, Clayton T, Beattie P, Bjerre J, Burrows N, Foelster-Holst R, Hedelund L, Hernandez-Martin A, Audrain H, Bhate K, Brown S, Baryschpolec S, Darne S, Durack A, Dvorakova V, Gach J, Goldstraw N, Goodyear H, Grabczynska S, Greenblatt D, Halpern J, Hearn R, Hoey S, Hughes B, Jayaraj R, Johansson E, Lam M, Leech S, O'Regan G, Morrison D, Porter W, Ramesh R, Schill T, Shaw L, Taylor A, Taylor R, Thomson J, Tiffin P, Tsakok M, Janmohamed S, Laguda B, McPherson T, Oranje A, Patrizi A, Ravenscroft J, Shahidullah H, Solman L, Svensson A, Wahlgren C, Hoeger P, Flohr C. Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey. Br J Dermatol 2015; 174:594-601. [DOI: 10.1111/bjd.14233] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2015] [Indexed: 12/25/2022]
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Tang LYH, Hing JWG, Tang JYM, Nishikawa H, Shahidullah H, Browne F, Chikermane A, Parulekar M. Predicting complications with pretreatment testing in infantile haemangioma treated with oral propranolol. Br J Ophthalmol 2015; 100:902-906. [DOI: 10.1136/bjophthalmol-2015-307284] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 09/14/2015] [Accepted: 10/01/2015] [Indexed: 12/17/2022]
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Abstract
Infantile hemangiomas (IHs) are the most common tumors of childhood. Unlike other tumors, they have the unique ability to involute after proliferation, often leading primary care providers to assume they will resolve without intervention or consequence. Unfortunately, a subset of IHs rapidly develop complications, resulting in pain, functional impairment, or permanent disfigurement. As a result, the primary clinician has the task of determining which lesions require early consultation with a specialist. Although several recent reviews have been published, this clinical report is the first based on input from individuals representing the many specialties involved in the treatment of IH. Its purpose is to update the pediatric community regarding recent discoveries in IH pathogenesis, treatment, and clinical associations and to provide a basis for clinical decision-making in the management of IH.
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Abstract
PURPOSE OF REVIEW Since 2008, beta-blockers have become first-line treatment for infantile hemangiomas, the most common tumor of infancy. Their role is also being explored in the treatment of other childhood vascular tumors. RECENT FINDINGS Recent research has demonstrated that propranolol is a more effective and safer treatment for infantile hemangiomas than previous therapeutic options. It is most effective when initiated during the tumor's proliferative phase. Other oral beta-blockers such as atenolol and nadolol are less studied, but may offer similar efficacy. Topical beta-blockers such as timolol appear to be effective in treating small, superficial infantile hemangiomas. Beta-blockers have shown variable results for the treatment of other vascular tumors of childhood, such as pyogenic granulomas, kaposiform hemangioendotheliomas, and tufted angiomas. SUMMARY Propranolol has revolutionized the treatment of infantile hemangiomas, and other beta-blockers provide promising alternatives. Unanswered questions remain about the optimal choice of agent, delivery mechanism, dosage, need for pretreatment evaluation or ongoing monitoring, and duration of therapy. The role of beta-blockers in treating other types of vascular tumors requires further study.
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