Bleomycin Sclerotherapy for Extensive Lympho-Venous Malformation. A Retrospective Analysis of A Patient's Death

Introduction

Lympho-venous malformations (LVM) in children may be localized everywhere in a child's body as limited or extensive malformations, including a few anatomical regions representing errors in vascular and lymphatic development. LVM are classified as combined malformations [1]. A radical surgical excision of the malformation reported to be the best treatment, however in extensive LVM complete resection of the malformation is impossible. Incomplete resection of the malformation leads to recurrence and over-resection leads to tissue and organ damage [2] [3] [4]. Thus, the search for a non-surgical form of treatment for LVM continues. Direct injection sclerotherapy has been proposed with few side-effects, but the effectiveness of direct sclerotherapy was poor.

Yura and co-workers in 1997 reported good results with bleomycin sclerotherapy of lymphatic malformations (LM) after unsuccessful surgical treatment [5]. Other centers have been skeptical of this treatment due to the unclear therapeutic mechanism of bleomycin and high risk of post therapeutic pulmonary complications [6] [7].

An early toxic effect on pulmonary tissue was observed in 10% of all oncologic patients who received i. v. bleomycin therapy and presented with fever, dry cough, dyspnea at rest and cyanosis. Permanent damage to pulmonary tissue causing pulmonary fibrosis after bleomycin therapy was described as occurring some weeks or even months after treatment. In patients who underwent bleomycin therapy, spirometric restrictive changes were described. Vital capacity (VC), total lung capacity (TLC) and diffusion lung capacity for carbon monoxide (DLCO) have been shown to decrease. A DLCO below 40% of initial values is a simple contraindication to bleomycin therapy. Early as well as late pulmonary toxicity of bleomycin with progressive pulmonary fibrosis causes death in 1–2% of patients [8] [9].

A combined treatment of a patient with extensive LVM who died at the age of 20 years is presented.

References

• 1 Mulliken JB, Głowacki J. Haemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics.  Plast Reconstr Surg. 1982;  69 412-420
• 2 Kennedy TL, Whitaker M, Pellitteri P. et al . Cystis hygroma/lymphangioma: a rational approach to management.  Laryngoscope. 2001;  111 1929-1937
• 3 Okazaki T, Iwatani S, Yanai T. et al . Treatment of lymphangioma in children: our experience of 128 cases.  J Pediatr Surg. 2007;  42 386-389
• 4 Padwa BL, Hayward PG, Ferraro NF. et al . Cervicofacial lymphatic malformation: clinical course, surgical intervention and pathogenesis of skeletal hypertrophy.  Plast Reconstr Surg. 1995;  95 951-960
• 5 Yura J, Hashimoto T, Ustruga T. Bleomycin treatment for cystic hygroma in children.  Arch Jpn Chir. 1977;  46 607-614
• 6 Okada A, Kubota A, Fukuzawa M. et al . Injection of bleomycin as a primary therapy of cystic lymphangioma.  J Pediatr Surg. 1992;  27 440-443
• 7 Orford J, Barkar A, Thonell S. et al . Bleomycin therapy for cystichygroma.  J Pediatr Surg. 1995;  30 1267-1282
• 8 Abid SH, Malhotra V, Perry MC. Radiation-induced and chemotherapy induced pulmonary injury.  Curr Opin Oncol. 2001;  13 242-248
• 9 Sleijfer S. Bleomycin-induced pneumonitis.  Chest. 2001;  120 617-624
• 10 Szymik-Kantorowicz S, Grochowska E, Bysiek A. et al . Odległe wyniki skleroterapii bleomycyną malformacji limfatycznych.  Przeg Chirurg Dziec. 2008;  3 149-152
• 11 Scheule RK, Perkins RC, Hamilton R. et al . Bleomycin stimulation of cytokine secretion by the human alveolar macrophage.  Am J Physiol. 1992;  262 386-391
• 12 Emran MA, Dubois J, Laberge L. et al . Alcoholic solution of zein (Ethibloc) sclerotherapy for treatment of lymphangiomas in children.  J Pediatr Surg. 2006;  41 975-979
• 13 Nehra D, Jacobson L, Barnes P. et al . Doxycycline sclerotherapy as primary treatment of head and neck lymphatic malformations in children.  J Pediatr Surg. 2008;  43 451-460
• 14 Acevedo JL, Shah RK, Brietzke SE. Nonsurgical therapies for lymphangiomas: A systematic review.  Otolaryngol Head Neck Surg. 2008;  138 418-424
• 15 Kim KH, Sung MW, Roh JL. et al . Sclerotherapy for congenital lesions in the head and neck.  Otolaryngol Head Neck Surg. 2004;  131 307-316
• 16 Sung MW, Chang SO, Choi JH. et al . Bleomycin sclerotherapy in patients with congenital lymphatic malformation in the head and neck.  Am J Otolaryngol. 1995;  16 236-241
• 17 Atwa K, Abuhasna S, Shihab Z. et al . Acute pulmonary toxicity following intralesional administration of bleomycin for a lymphovenous malformation.  Pediatr Pulmonol. 2010;  45 192-196

Correspondence