ULTRASOUND AND FLUOROSCOPY GUIDED INTRALESIONAL BLEOMYCIN INJECTION (IBI) FOR TREATMENT OF SUPERFICIAL HEMANGIOMAS AND VASCULAR MALFORMATION.revised

Introduction

Hemangiomas and vascular malformations are benign lesions that can occur at any organ. Hemangiomas are vasoproliferative neoplasms that arise from the endothelial cells surrounding the blood filled cavites, they have a slightly higher female predilection. Hemangiomas divided into infantile and congenital types depending upon the age. Infantile hemangiomas are either absent or present as a precursor lesion at birth while congenital hemangiomas occur

fully grown at birth. Congenital hemangiomas can either involute rapidly over a very brief period in infancy (rapidly involuting congenital hemangioma (RICH) or never involute (non – involuting congenital hemangioma (NICH) ⁽¹⁾.

Vascular malformations usually present at birth, most of them are seen at the head and neck regions, which are divided into slow flow                (combination of capillary, venous, and lymphatic) and fast flow(has an arterial

component). Most of vascular malformations are self-limited as the child grows elder, but some of them may become larger with age ⁽²⁾.

Currently various medical and surgical options are available for the treatment of hemangiomas including intra lesional bleomycin, laser therapy, cryotherapy, corticosteroids and surgical excision ^(3,4).

Recently bleomycin injections have been used to manage hemangiomas, it is a primarily cytotoxic anti-tumor antibiotic drug which is also known as blenoxane used in the management of various types of cancer including lymphoma and squamous cell carcinoma ^(4,5). However, it can also cause sclerosis by endothelial mesenchymal transition, where endothelial cells change into fibroblast–like cells, so it is commonly used as a sclerosing agent for the treatment of vascular malformations. Compared to the surgery, intra lesional bleomycin injection is a simple, practical noninvasive method of treatment ⁽⁶⁾

Patients and Methods

This study was conducted in the interventional radiology unit, department of Radiology, Faculty of Medicine, Minia University starting from January 2022. Thirty patients presented with superficial heman-giomas and vascular malformation were referred from department of vascular surgery, at Minia University Hospital to be recruited in the study.

Inclusion criteria: Patients with superficial low flow hemangiomas and vascular malformation with no major vessel connection, No age limit.

Exclusion criteria: Deep inaccessible hemangiomas and vascular malformation, Fast (high) flow lesions with major vessel connection, Patient refusing injection, Patient with hemophilia or any blood disorder prevent the injection.

Method:

Injection of the superficial hemangioma and vascular malformation with bleomycin, the dose

of bleomycin is 0.3-0.6 mg/kg per injection not exceeding 15 units per cycle. Injection is administered under local or general anesthesia by ultrasound guidance. During injection, the needle is introduced through normal skin and under ultrasound and fluoroscopy guidance advanced into the lesion and then the bleomycin is injected. Needle is then withdrawn and the lesion is being compressed for about two minutes. Follow up of the patients is done by US and in some cases by MRI.

Statistical analysis:

The collected data was tabulated, and statistically analyzed using SPSS program (Statistical Package for Social Sciences) software version 26.0, Microsoft Excel 2016 and MedCalC program software version 19.1

Descriptive statistics were done for numerical parametric data as mean±SD (standard deviation) and minimum & maximum of the range and for numerical non parametric data as median and 1st& 3rd inter-quartile range, while they were done for categorical data as number and percentage.

Inferential analyses were done for quantitative variables using independent t-test in cases of two independent groups with parametric data and Mann Whitney U in cases of two independent groups with non- parametric data. Receiver operating characteristic (ROC curve) analysis was used to find out the overall productivity of parameter in and to find out the best cut-off value with detection of sensitivity and specificity at this cut-off value.

Inferential analyses were done for qualitative data using Chi square test for independent groups. The level of significance was taken at P value <0.05 is significant, otherwise is non- significant.

Discussion

Hemangiomas and vascular malformations are benign lesions that can occur at any organ. Intra-lesional Bleomycin injection (IBI) is an effective treatment  in  haemangiomas  and vascular malformation lesions, avoiding the need for invasive primary surgery or systemic treatment regimens in 80% of cases, and allowing for limited need of secondary surgical or adjunctive procedures in cases with a moderate result ⁽⁷⁾

In our study, demographic characteristics of the studied patients showed that the age of patients ranged from two years to 35 years with mean age ±SD was 12.9± 11.66 years. There were 18 (60%) females and 12 (40%) males with male to female ratio was 0.67:1. Regmi et al., 3 underwent a study aimed to determine the efficacy and safety of intralesional Bleomycin sclerotherapy for head and neck haemangioma and slow flow vascular malformation including thirty-six patients (¹²⁾

males and 24 females) with their ages ranged from five years to 54 years with a mean age of 25 years.

In our study, the clinical characteristics of studied patients showed   that face   was   the   most common site of hemangiomas that found in nine (30%) cases followed by hand in six

(20%) cases then neck in three (10%) cases, foot in three (10%) cases, chest wall in three (10%) cases, nape in three (10%) cases, and forearm in three (10%) cases. the mean size of lesions was 4.22± 1.34 cm and ranged from 2 cm to 6 cm. while in a Regmi et al., 3 study, commonest site of these lesions were face, oral cavity and oropharynx in 12 (33.3%) followed by neck in five (13%), cheek in six (16%), lip in five (13%), parotid in four (11%), ear in two (5%) and nose in two (5%). In   another study by Garzon et al. 8 who reported that, vascular malformations are among the most common congenital and neonatal abnormalities, head and neck is the most common site of occurrence of these lesions (60%) followed by the trunk (25%) and    the    extremities (15%) Redkar et al., 9 found that, sixteen children (94%) had lesions in the head, neck, and chest region and one had (6%) lesion on the hand.

In this study, radiological (US & Doppler) findings observed that, most (80%) cases revealed slow flow, while medium flow was seen in six (20%) cases. 

Regmi et al., 3 found that, most of their study cases were slow flow   vascular   malformations (86%) and only five cases of haemangioma (14%) were high flow.

In this    study, according to number of sessions we found that, 70% of cases received two sessions; six (20%) cases received one session while 10 % of cases received three sessions. While Redkar et al., 9 observed  that,     three  patients (hemangiomas:   17%)   required   only one injection, two patients required (cystic hygroma: 11%) two sessions of injections, four patients (hemangiomas: 23%) required three sessions of injections, (one had 80% resolution  who  is  under  follow‑up) two  patients  (one  hemangiomas  and one  cystic  hygroma:  11%)  required five   injections,   and   four   patients (cystic hygroma: 23%) required six injections with 4 weeks gap in between each  injection.  Also, Regmi et al., 3 found that, mean number of injections required in 15 patients of lymphangioma (Group 1) and equal number of slow flow vascular malformation (Group 2) were 3 and 5 respectively.

In this   study, complete response was observed in 15 (50%) cases, moderate response was observed in 9 (30%) cases, mild response was observed in 6 (20%) cases, and no significant response was observed in three (10%) cases. In a study by   Regmi et al., 3   ten patients (28%) had complete resolution (cured), 19 had marked improvement (53%), five had mild improvement (14%) and two had no response (6%). Muir et al., 7 showed that, complete response was obtained in 40 (42%) of patients, Significant improvement of the treated lesion   occurred   in   38 (38%) of patients, Moderate improvement in 16 (17%) and only one (1%) had no response. There was an overall significant effect seen in a total of 80 patients (80%), 1–3 years post IBI treatment. All patients were regularly followed up at 4- to 6-month intervals, showing the same good results.

In this study, the relation between response with Doppler findings observed that, there was statistically significant relation between response with Doppler findings (p<0.001) as complete and moderate response was significantly higher in patients had low flow in Doppler. This was in the same ^{(10 )}

response was statistically higher in line with Eivazi et al., demonstrated the significant   positive   correlation between response and low flow in Doppler findings.

In our study, we found that relation between response and number of sessions showed that, there was statistically significant relation between response with number of sessions (p<0.001) as complete and moderate response was significantly higher in patients who received     one     session.     This     in agreement with   Regmi et al., 11 that found that the number of injections required ranged from 2-7 which was similar to pienaaret et al., ⁽¹²⁾ .