Successful treatment of a recurrent large cystic hygroma in a child with intracystic injection of OK-432

Sir" The treatment of a large cystic hygroma remains controversial. We report a case of a lymphangioma at the right neck that recurred after surgical resection and intracystic injection of bleomycin (BLM), but which responded remarkably to intracystic injection of OK-432 (group A Streptococcus pyogenes of human origin). A 4-month-old male with a cystic hygroma was referred to our hospital because of respiratory difficulty. Total resection of the tumour had been attempted at another hospital 3 months earlier. Because of recurrence, intracystic injection of BLM had been applied after aspiration of lymphatic fluid, but with no significant effect. During a brief visit home, the child stopped breathing whilst being fed via a nasogastric tube. He was resuscitated and referred to us. After insertion of an endotracheal tube and cardiorespiratory resuscitation, heart beat recovered to 152 beats/min.; SBP was 77 mmHg. Physical examination disclosed an elastic soft lymphangioma, approximately 12 cm in diameter on the right side of the neck, causing his neck to bend to the left. Ultrasound and CT scan demonstrated a multicystic lesion that displaced the trachea to the left and invaded the mediastinum. On the 4th day of admission, the first intracystic injection of OK-432 (0.1 mg/20 ml saline) was given, after aspiration of 25 ml of clear, yellowish intracystic fluid. Within 2 months, four more injections were performed, up to a total dosage of 0.5 mg. After the fourth injection, the tumour began to regress, the neck position straightened, and the child was extubated. Body temperature rose to a peak of 40.0 ~ C and leucocytes increased to 19.9 x 10 ~, after each injection, but body temperature returned to normal within 1-2 days without specific therapy. After 5 months, the neck appeared straight and the tumour could be palpated as a subtle cystic lesion. CT scan showed hardly and substantial lesion around the trachea and mediastinum. It is estimated that 50%-60% of lymphangiomas are present at birth, and 90% are manifest by the end of the 2nd year of life [1]. The most common site is the neck. Larger lymphangiomas invade the mediastinum, oral cavity, and pharynx, and they may compromise the airway. Insertion of an endotracheal tube may become difficult. Aggressive treatment early in life for large lymphangiomas that threaten the airways has been recommended [3]. However, surgical therapy i s often associated with adverse effects, such as facial nerve palsy, shortening of the tongue, and large scars. Sclerotherapy with intracystic injection of BLM was reported by Tanigawa et al. [5], with favourable results. However, the therapy may lead to pulmonary fibrosis that is unpredictable and occasionally fatal. Sclerosing therapy with OK-432, produced from the Su strain of type HI, Group A Streptococcus pyrogenes of human origin (Picibanil; Chugai Pharmaceutical Co., Tokyo, Japan), was introduced by Ogita et al. [4]. It resulted in complete regression in eight of ten cystic hygromas without serious side-effects, except fever of 2-3 days duration, local tenderness, and swelling. The mechanism by which the inflammation induces tissue fibrosis and regression of lymphangioma remains unclear. Possibly, anaphylatoxins and chemotactic factors are released, causing an inflammatory reaction. Recently, Gagliardini et al. [2] suggested that an interleukinconverting enzyme, interleukin-1 [3 synthetase, induces not only inflammation but also apoptosis (programmed cell death). The hypothesis that OK-432 causes regression by inducing apoptosis of lymphatic endothelium is in accord with the clinical findings that local inflammatory reaction does not damage overlying skin or induce scar formation. Moreover, the hypothesis suggests that the origin of lymphangioma is stasis of the apoptotic rearrangement in lymphatic vessels. OK-432 therapy seems to provide a clue to the aetiology of lymphangioma.