Most venous malformations (VMs) present in the head and neck region. Many sclerosing agents have been documented in the literature, but Bleomycin is a new promising sclerosing agent of facial venous malformations.
this study was conducted to evaluate the clinical outcome and safety of Bleomycin (BL) intralesional injections in management of maxillofacial venous malformation in pediatric patients.
15 patients of both sexes and of age up to 12 years having VMs in the maxillofacial region were randomly selected from the vascular anomalies clinic in Cairo University Specialized Pediatric Hospital. All patients were treated by BLM intralesional injections with the safe pediatric dose of 0.5 IU/kg, at 4 weeks intervals with maximum dose of 15 IU\session. All cases were performed by the same operator, and patients were followed up over 12 months after last injection.
Twelve patients had complete response (>90% improvement), and 3 patients had marked improvement response. Eleven patients were injected under topical local anaesthesia, and 4 patients had regional local anaesthesia. All patients had post-operative swelling that lasted for 3–5 days. There was no pain during or after injections, no ulceration, no weight loss, no hair loss and no signs of pulmonary fibrosis throughout the follow up time. Recurrence occurred only in 2 patients due to noncompliance with sessions, and they were re-injected with BLM.
this study has shown that Bleomycin is safe, effective and an excellent therapy for treating VMs in the maxillofacial region. No systemic or local complications had occurred.
Venous malformations (VMs) present in the head and neck region, particularly the face, causing many functional and esthetic problems in pediatric patients.
Sclerotherapy is the first-line treatment for VMs, many sclerosing agents have been mentioned in the literature, but various complications had been reported in the face, such as facial nerve injury, ulceration, and scarring.
Bleomycin (BLM) is a cytotoxic antibiotic anti-cancer agent with sclerosing effect that has recently proved its effectiveness and safety in treatment of facial VMs.
Most venous malformations (VMs) present in the head and neck region, particularly the face, causing many functional and esthetic problems in pediatric patients [ ]. Sclerotherapy is the first-line treatment for VMs, many sclerosing agents have been mentioned in the literature, but various complications had been reported in the face, such as facial nerve injury, ulceration, and scarring [ ].
Bleomycin (BLM) is a cytotoxic antibiotic anti-cancer agent with sclerosing effect that has recently proved its effectiveness and safety in treatment of facial VMs [ ].
Patients and methods
This prospective study has been approved by the Research Ethics Committee of faculty of Dentistry in Suez Canal University (No. 157\2018). Fifteen patients of age up to 12 years, of both sexes, and having VMs in the maxillofacial region were selected from the vascular anomalies clinic in Cairo University Specialized Pediatric Hospital (CUSPH). This study was performed from March 2019 till March 2020. Patients were followed up for 12 months after last injection.
Diagnosis as VMs was done by taking clinical examination, confirmed by ultrasonography (USG) and magnetic resonance imaging (MRI) for deep lesions.
Parents of all the children signed informed written consents containing treatment benefits, potential risks, and the procedure was explained in a simple clear language to the parents before the study. Patients were treated according to the principles of Helsinki Declaration.
Colored photographs were taken with a standardized 16-megapixel digital camera on first visit, in treatment sessions, and after treatment. Demographic data of each patient, and lesion anatomical site and size, BLM dose, timing of each injection, clinical response, and complications were documented in each patient file.
Bleomycin is available in 15 IU vials (Bleocel®, CELON Labs, India). BLM must be stored in temperature 2–8 °C, and should be freshly prepared; 15 mg powdered BLM dissolved in 15 ml of 0/9% normal saline (1 IU BLM is equivalent to 1 mg/ml BLM). The safe pediatric dose of BLM is 0.5 IU\kg; with maximum dose of 15 IU\session, and at 4 weeks interval. BLM dose was calculated according to infant or child weight and lesion size that were measured on each session. Then, BLM was slowly injected into the lesion; with multiple punctures from different directions to distribute the sclerosing solution homogenously inside the lesion. The number of sessions was decided according to each lesion response [ , ]. All cases were injected by the same operator (first author) under completely aseptic conditions. BLM timing of each injection and doses were documented in each patient follow-up card.
Paracetamol 100 mg/ml as CETAL® drops or 250 mg/5 ml as CETAL® suspension (EPICO, Egypt), according to infant\child weight, and B.B.C® topical spray (AMOUN, Egypt) were prescribed for 1–3 days to reduce post-operative pain. Parents were instructed to do cold fomentations on the first day after intralesional injection to reduce post-operative swelling.
Colored photographs, USG, and MRI (for deep lesions) were obtained after the last intralesional injection to evaluate lesion response to treatment.
Clinical response was categorized by Sainsbury et al. as: complete response (>90% reduction of lesion), marked improvement (>70% reduction of lesion), moderate improvement (40–70% reduction of lesion), slight improvement (<40% reduction of lesion), and no response (<10% reduction of lesion) [ ].
This study included 15 patients, 8 males and 7 females; their mean age was 5.1 years, (age range: 2-months to 11-years old).
Regarding clinical response, 12\15 patients had complete response (>90% improvement), and 3\15 patients had marked improvement response.
Regarding anaesthesia, 11\15 patients were injected under topical local anaesthesia, and 4\15 patients had nerve block local anaesthesia; 2 VMs in the tongue, one VM in upper lip, and one VM in the lower lip.
Regarding complications, there was no post-operative pain, no ulceration, and no scarring. Facial nerve and muscles of facial expression were not affected. There were no clinical signs of pulmonary fibrosis (central cyanosis – dyspnea – tachypnea), throughout the follow up time. Pulmonary Function Tests were not performed during COVID-19 pandemic.
All patients had post-operative swelling that lasted for 3–5 days. Fig. 1 shows post-operative swelling after BLM injection of VM in the lower lip of an 8-years old boy.
Treatment duration ranged between 2 and 8 months; BLM was injected at 4 weeks interval; 6\15 patients required 8 sessions (8 months), 6\15 patients required 6 sessions (6 months), and 2\15 patients required 4 sessions (4 months), and 1\15 patient required 2 sessions (2 months).
Recurrence occurred only in 2\15 patients, due non-compliance of parents with treatment sessions; lesions were re-injected with BLM.
Table 1 summarizes demographics and clinical response of patients, Fig. 2 -A shows VM in the right side of face of a 2 months female infant, Fig. 2 -B shows complete response after 8 BLM injections. Fig. 3 -A shows VM in middle third of left side of tongue in a 10 years old girl, and Fig. 3 -B shows complete response after 4 BLM injections; taste sensation and tongue movement were not affected.