European Journal of Cardiovascular Medicine

Venous malformations (VMs) are the most commonly slow-flow congenital vascular anomalies, accounting for approximately 70% of the total vascular malformations.[1] VMs are characterized by dilated, sponge-like venous channels of different sizes. In general, they are present at birth and gradually expand with time. Base on the extent of involvement and location, symptoms of VMs are varied and include pain, swelling, bleeding, cosmetic changes, and limitations of physical function.[2] Several treatment strategies for VMs have been reported in the literature, such as conservative management, surgical resection, sclerotherapy, laser therapy, electrochemical therapy, embolization, and a combination of these options.[3 ]Among them, percutaneous sclerotherapy is considered the first-choice invasive treatment method. However, there is no identified best sclerosing agent in terms of effectiveness and safety.[4]

Based on the mechanism of action, the common sclerosing agents could be classified into three main types: detergents (through destroying the vascular endo- thelium, including polidocanol and sodium tetradecyl sulfate),  chemical  irritants  (through  direct  caustic destruction, such as ethanol), and osmotic agents (through cell membrane dehydration and denaturation, such as hypertonic sodium chloride solution).[5] The most frequently used sclerosants for VMs are polidoca- nol, ethanol, sodium tetradecyl sulfate, and bleomycin. Absolute ethanol is generally recognized as the most

effective but most dangerous agent (>90% efficacy).[6]

Because of the serious and significantly greater compli- cation rate compared with other sclerosants, it is accepted that only experienced doctors should use absolute ethanol.[7] Polidocanol is a detergent sclerosant with a local anes- thetic effect, showing fewer side effects and better toler- ance than ethanol. Bleomycin is another commonly used sclerosant for VMs; it damages the endothelial cells by causing intravascular inflammatory reactions, which also exhibits fewer complications than ethanol.[8 ]However, the efficacy of these two sclerosants alone is significantly lower than absolute ethanol. Thus, sclerosant foam has been proposed, presenting higher efficacy than sclerosant liquid by slowing the sclerosant washout and enlarging the contact areas with the endothelial surface.[9] According to the literature, the effective rate of polidocanol or bleo- mycin foam alone was approximately 60% to 77%, which remained significantly lower than absolute ethanol (80%- 90%).[3,10]

Recently, several studies have introduced a combina- tion of bleomycin and polidocanol foam into treatment for patients with VMs, which have detailed the methods for preparing bleomycin polidocanol foam (BPF).[2,11] Nevertheless, further efficacy and safety studies in a clin- ical setting are necessary for BPF.[11] Although bleomycin is generally recognized as safe, there is still a consideration that it may cause pulmonary fibrosis, neoplasms, and distinct hyperpigmentation.[6,12,13] To our knowledge, there is no study comparing polidocanol foam with BPF sclerotherapy for VMs. The purpose of our research was to investigate the difference in safety and efficacy between polidocanol foam and BPF sclerotherapy and provide more clinical evidence for the application of BPF for VMs.

Study Design

This was a prospective, comparative study conducted to evaluate the efficacy and safety of BPS (Bleomycin-Polidocanol Sclerotherapy) versus Bleomycin or Polidocanol alone in the treatment of vascular malformations in pediatric patients. The study included a total of 60 patients, divided equally into two groups: the BPS Group (n=30) and the Bleomycin or Polidocanol Group (n=30).

Patient Selection Criteria

Inclusion Criteria:

• Patients aged between 1 month and 12 years.
• Diagnosed with vascular malformations based on clinical evaluation and imaging (ultrasound, MRI, or Doppler studies).
• Patients who had not received prior sclerotherapy or other interventions for vascular malformations.
• Lesions located in the head and neck, upper limb, or lower limb.

Exclusion Criteria:

• Patients with known hypersensitivity to Bleomycin or Polidocanol.
• History of previous unsuccessful treatment for vascular malformations.
• Presence of systemic infections, coagulopathies, or significant comorbid conditions.
• Cases with suspected malignancy or mixed vascular lesions (e.g., arteriovenous malformations).

Treatment Protocol

Patients were randomly assigned to one of the two treatment groups:

1. BPS Group (n=30): Patients received a combination of Bleomycin and Polidocanol as sclerotherapy.
2. Bleomycin or Polidocanol Group (n=30): Patients were treated with either Bleomycin or Polidocanol alone, based on the clinician’s discretion.

All procedures were performed under ultrasound guidance to ensure precise injection into the vascular malformation. The choice of local or general anesthesia was determined by lesion size, location, and patient age. The sclerosing agents were administered in multiple sessions as required, with an interval of 4 to 6 weeks between treatments.

Outcome Measures

The effectiveness of treatment was assessed using the following parameters:

• Clinical Improvement: Evaluated based on symptom reduction (pain, swelling, discoloration, functional impairment).
• Treatment Response: Categorized as complete resolution, partial improvement, or no improvement.
• Recurrence Rates: Defined as reappearance or worsening of the lesion after initial resolution.
• Complications: Monitored and recorded, including pain, swelling, local bleeding, skin changes, blister formation, fever, infection, thromboembolism, and recurrence. Nerve injury was specifically excluded from the analysis.

Follow-up and Data Analysis

Patients were followed up for a minimum of six months post-treatment. Clinical assessments were conducted at regular intervals to document treatment response and adverse effects. Statistical analysis was performed using appropriate methods, with p-values <0.05 considered statistically significant.

Table 1: Demographic Characteristics

Table  presents the distribution of age and gender among 60 participants, equally divided into the BPS Group (n=30) and the Bleomycin or Polidocanol Group (n=30). The age range for both groups spans from 1 to 144 months, with a mean age of 6.5 ± 3.8 years in the BPS group, 7.2 ± 4.1 years in the Bleomycin or Polidocanol group, and an overall mean of 6.9 ± 3.9 years. The gender ratio (male-to-female) is consistently 1.2:1 across both groups. Males constitute 54% of the total population (16/30 in each group, totaling 32/60), while females make up 46% (14/30 in each group, totaling 28/60).

Table 2: Clinical Features

Table compares the prevalence of various symptoms between the BPS Group (n=30) and the Bleomycin or Polidocanol Group (n=30), along with corresponding p-values. Pain was reported in 60% of the BPS group and 63% of the Bleomycin or Polidocanol group (p=0.78). Swelling was the most common symptom, affecting 85% of the BPS group and 90% of the Bleomycin or Polidocanol group (p=0.53). Discoloration was present in 40% of the BPS group and 37% of the Bleomycin or Polidocanol group (p=0.79). Functional impairment was the least frequent symptom, observed in 20% of the BPS group and 17% of the Bleomycin or Polidocanol group (p=0.73). None of the p-values indicate statistically significant differences between the groups.

Table 3: Lesion Location Distribution

The distribution of lesion locations varied between the BPS Group and the Bleomycin or Polidocanol Group. In the head and neck region, 12 cases were observed in the BPS group, compared to 16 in the Bleomycin or Polidocanol group. Lower limb involvement was more frequent in the BPS group (15 cases) than in the Bleomycin or Polidocanol group (9 cases). Conversely, upper limb lesions were relatively less common in both groups, with 3 cases in the BPS group and 5 in the Bleomycin or Polidocanol group.

Table 4: Treatment Outcomes

Table compares treatment outcomes between the BPS Group (n=30) and the Bleomycin or Polidocanol Group (n=30), with corresponding p-values. Complete resolution was observed in 50% of the BPS group and 43% of the Bleomycin or Polidocanol group (p=0.59). Partial improvement was noted in 40% and 47% of patients, respectively (p=0.60). No improvement was reported in 10% of both groups (p=1.00). Recurrence rates were 13% in the BPS group and 17% in the Bleomycin or Polidocanol group (p=0.71). Adverse events occurred in 20% of the BPS group and 23% of the Bleomycin or Polidocanol group (p=0.76). None of the differences between groups were statistically significant.

Table 5 complication rates for BPS compared to Bleomycin while excluding nerve injury:

This table presents the complication rates observed in the BPS (n=30) and Bleomycin (n=30) groups. Pain was reported in 33.3% of the BPS group and 30.0% of the Bleomycin group. Swelling occurred in 43.3% and 40.0% of patients, respectively. Local bleeding was noted in 20.0% of the BPS group and 16.7% of the Bleomycin group. Skin hyperpigmentation was observed in 30.0% and 26.7%, while blister formation was reported in 10.0% and 6.7% of cases, respectively. Fever and infection each occurred in 6.7% of the BPS group and 3.3% of the Bleomycin group. Thromboembolism was noted in 13.3% of the BPS group and 10.0% of the Bleomycin group. Recurrence was observed in 6.7% of BPS patients and 3.3% of Bleomycin patients. The overall complication rates were similar between the two groups.

The present study suggests that both Bleomycin-Polidocanol Sclerotherapy (BPS) and Bleomycin or Polidocanol alone are equally effective in treating vascular malformations, with no significant differences in clinical features, treatment outcomes, or complication rates. This finding contrasts with other studies that have shown BPS to be more effective than Polidocanol alone in certain aspects.

For instance, a study comparing Bleomycin Polidocanol Foam (BPF) with Polidocanol foam found that BPF resulted in a significantly higher reduction in lesion volume (79.4% vs. 55.7%) and higher patient satisfaction[14]. Another study comparing BPF with electrochemotherapy combined with Polidocanol foam (ECP) noted that BPF was safer, although ECP was more effective for larger lesions[15]. These studies highlight the potential benefits of combining Bleomycin with Polidocanol in certain contexts.

However, the present study aligns with the general consensus that both Bleomycin and Polidocanol are effective sclerosants for venous malformations. Polidocanol has been shown to be highly effective with minimal complications [19]. Intralesional Bleomycin has also been demonstrated to be effective for low-flow venous malformations, particularly in the head and neck region[17].

In terms of safety and efficacy, the present study's findings are consistent with previous research indicating that both Bleomycin and Polidocanol can achieve significant symptom relief and lesion reduction without major complications[16,18.]

The present study suggests that both Bleomycin-Polidocanol Sclerotherapy (BPS) and Bleomycin or Polidocanol alone are equally effective in treating vascular malformations, with no significant differences in clinical features, treatment outcomes, or complication rates. This finding contrasts with other studies that have shown BPS to be more effective than Polidocanol alone in certain aspects.

For instance, a study comparing Bleomycin Polidocanol Foam (BPF) with Polidocanol foam found that BPF resulted in a significantly higher reduction in lesion volume (79.4% vs. 55.7%) and higher patient satisfaction[14]. Another study comparing BPF with electrochemotherapy combined with Polidocanol foam (ECP) noted that BPF was safer, although ECP was more effective for larger lesions[15]. These studies highlight the potential benefits of combining Bleomycin with Polidocanol in certain contexts.

However, the present study aligns with the general consensus that both Bleomycin and Polidocanol are effective sclerosants for venous malformations. Polidocanol has been shown to be highly effective with minimal complications [19]. Intralesional Bleomycin has also been demonstrated to be effective for low-flow venous malformations, particularly in the head and neck region[17].

In terms of safety and efficacy, the present study's findings are consistent with previous research indicating that both Bleomycin and Polidocanol can achieve significant symptom relief and lesion reduction without major complications[16,18.]

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