Clinical outcomes and predictors of bleomycin polidocanol foam sclerotherapy treatment response in venous malformations

Abstract

Objective

To evaluate the safety and efficacy of bleomycin polidocanol foam (BPF) sclerotherapy for venous malformations (VMs) and analyze the associated clinical outcomes and predictors.

Methods

We retrospectively assessed BPF sclerotherapy outcomes in 138 patients with VMs. We analyzed pain levels, lesion volume reduction, and subjective perception of response. Logistic regression analysis was performed to identify potential predictors of treatment outcome. Additionally, we carefully monitored and recorded complications.

Results

There was a notable average reduction in lesion volume by 78.50% ± 15.71%. The pain numerical rating scale (NRS) score decreased from 4.17 ± 2.63 prior to treatment to 1.05 ± 1.54 afterward, and 70.3% of the patients experienced effective relief after a single BPF treatment. Multivariate analysis revealed that a high baseline NRS (odds ratio [OR]: 4.026) and elevated activated partial thromboplastin time (APTT, OR: 1.200) were positive predictors of pain reduction. Additionally, a high baseline NRS score (OR: 1.992) and elevated thrombocytocrit (PCT, OR: 2.543) were positive predictors of incomplete postoperative pain relief. Minor complications occurred in 31 (22.46%) patients.

Conclusion

BPF sclerotherapy is safe and effective for VMs, resulting in significant reduction in lesion volume, improved symptoms, and minimal complications. APTT and PCT levels are important predictors of pain outcomes following BPF treatment.

Keywords

Bleomycin polidocanol venous malformation pain thrombocytocrit activated partial thromboplastin time predictor complication

Introduction

Venous malformations (VMs) account for 70% of vascular malformations and are the most prevalent among such pathologies.^1,2 VMs are congenital conditions that can manifest at various ages, even in later stages of life. Patients with VMs commonly experience symptoms such as swelling, pain, and cosmetic disfigurement, which significantly impact their quality of life.³ These malformations consist of abnormally connected tortuous dilated veins and can occur in any part of the body, with a higher incidence in the lower extremities.^1,4,5 Treatment options for VMs comprise surgery, sclerotherapy, laser therapy, electrochemotherapy, and drug therapy.^6–8 Traditional surgical resection is limited to cases where complete removal of the lesion is feasible; however, this option is associated with potential complications, such as postoperative bleeding or dysfunction.⁹ Percutaneous sclerotherapy, involving the injection of a sclerosing agent into the lesion, is the preferred first-line treatment for VMs.³ This approach induces local vascular endothelial dysfunction and an immune response, leading to regression of the malformed vessels.¹⁰ Sclerotherapy offers significant advantages in controlling pain and swelling as well as being minimally invasive, cost-effective, and associated with minimal complications.^11,12

Currently, there is no consensus on the ideal sclerosing agent, with common agents including absolute ethanol, polidocanol foam, bleomycin, and foam sodium tetradecyl sulfate (STS).^13–16 While anhydrous ethanol has been considered the most effective sclerosing agent for reducing VMs volume, its use is associated with serious complications, such as bleeding and ulcers.¹² Recently, bleomycin polidocanol foam (BPF) has gained widespread acceptance in the treatment of VMs.^17,18

Unfortunately, the evaluation of treatment efficacy has focused on changes in lesion size, with a lack of emphasis on subjective findings, such as symptom improvement and appearance. Additionally, many studies of BPF have been limited by small sample sizes, leading to biased results. In this retrospective study, we collected data on subjective efficacy, imaging results, laboratory tests, and complications from a relatively large sample population to comprehensively evaluate the efficacy and safety of BPF in treating VMs.

Materials and methods

Study design

This retrospective study was performed at the China-Japan Friendship Hospital and aimed to collect clinical data on VMs diagnosed between January 2018 and December 2022. The study protocol was approved by the Institutional Review Board of the China-Japan Friendship Hospital (approval number: 2019-25-1), and all patients provided written informed consent before the treatment. All methods were performed in accordance with the Declaration of Helsinki of 1975 as revised in 2013. This study comprised a single-center design and involved the collection of clinical medical records’ data, imaging data, and follow-up survey data. All patient details have been de-identified. The reporting of this study conforms to the STROBE guidelines.¹⁹

Patients

Patients with suspected VMs were screened on the basis of clinical manifestations and subsequently diagnosed using imaging. The inclusion criteria were the presence of a local mass in the body, swelling or pain at the lesion site exacerbated by movement, abnormal skin color in the affected area, and limb dysfunction. A confirmed diagnosis was achieved through magnetic resonance imaging (MRI), with lesion volume calculated from the MRI images. Patients were distinguished by Puig classification, and sclerotherapy was performed for type I and type II VMs.²⁰ The exclusion criteria were as follows: (1) cases diagnosed as Klippel–Trenaunay syndrome (KTS), port-wine stain (PWS), Bean syndrome, or Maffucci syndrome; (2) missing clinical data, including patients who did not complete the MRI examination within 6 months after treatment; (3) previous electrochemical therapy, surgery, or sclerosing agent injection within 6 months prior to surgery; and (4) refusal to participate in the study.

Data collection

Data were obtained from the hospital’s electronic medical record system and recorded using a standardized protocol. The collected information comprised demographic data (age, sex, body mass index), clinical manifestations (preoperative symptoms, lesion location, age at onset), treatment process details (Puig classification, operation time, number of lesion punctures, sclerosing agent dose, length of hospital stay), and laboratory test results (white blood cell count, neutrophil count, hemoglobin, platelet count, plateletcrit, prothrombin time, activated partial thromboplastin time, D-dimer).

Lesion volumes were determined manually and independently by two experienced radiologists using the MR images. The two radiologists were blinded to the patients’ clinical features. One month later, reader 1 repeated the volume measurements for all patients. The average of the three separate volume measurements were recorded for each patient.

Treatment process

First, BPF was produced using the Tessari method by dissolving bleomycin powder (Nippon Kayaku, Tokyo, Japan) at a concentration of 0.15% in 2 mL of 3% polidocanol solution (Aethoxysklerol; Kreussler Pharm, Wiesbaden, Germany) at a polidocanol to air ratio of 1:4. The bleomycin polidocanol solution was fully mixed with air to generate BPF by connecting two syringes through a three-way stopcock and pushing and pulling the plunger at least 20 times. The polidocanol volumes were in accordance with the manufacturer’s recommendations, with a maximum dose of 2 mg of polidocanol per kilogram of body weight. Bleomycin dosage is limited to 400 mg or 5 mg/kg to reduce the risk of pulmonary fibrosis.²¹

The lesion location was determined using preoperative MRI, ultrasonography, and clinical signs and symptoms. BPF treatment was typically performed under local anesthesia, but general anesthesia was used for patients with specific lesions or severe symptoms. Punctures were performed using a 20-G needle under ultrasound guidance or direct vision. The number of injection sites and the type of needle used were determined on the basis of lesion depth and size. Double or multiple needle techniques were used to avoid extravasation. Confirmation of the lesion cavity was achieved by observing dark red blood flow. BPF was then injected into the lesion at a constant rate until the lesion was filled and no blood was observed. Following sclerotherapy, local compression bandaging was applied to the lesion for 3 to 5 days.

Therapeutic effect evaluation

All patients were followed-up 1 week, 1 month, and 6 months after surgery. At the 6-month follow-up, MRI was performed to evaluate the treatment outcome. The treatment effect was evaluated on the basis of the degree of symptom improvement and the reduction in lesion volume determined from imaging findings. A subjective symptom improvement survey was completed by the follow-up physician and comprised assessments of VMs improvement, changes in pain level before and after treatment, changes in skin color, and improvement in dysfunction. Pain was assessed using a numerical rating scale (NRS), with scores ranging from 0 to 10, where 0 indicated no pain and 10 indicated severe pain. The NRS score at the 6-month follow-up was used as an outcome, for the analysis. A reduction in the NRS score by more than 3 points was considered noticeable pain relief. Subjective improvement in VMs was categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), with CR and PR classified as effective responses. The degree of lesion volume reduction was calculated using the MRI results, with the ellipsoidal sphere volume formula (4/3π1/8abc, where a, b, and c represent the long diameter of the three axes of the lesion, respectively) used to estimate the lesion volume. A volume reduction of >60% was considered excellent. Furthermore, all postoperative complications were comprehensively analyzed, namely postoperative abnormal pain, swelling at the injection site, blisters, skin pigmentation, persistent bleeding, and ulcers.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics 22.0 software (IBM Corp., Armonk, NY, USA). Categorical variables are presented as frequencies and percentages, while continuous variables are reported as means and standard deviations. Continuous variables were compared between groups using Student’s t-test, and categorical variables were compared using the chi-squared test. Logistic multivariate stepwise regression analysis was performed to identify predictors of BPF efficacy, incorporating measures of pain assessment, subjective improvement in VMs, and reduction in lesion volume. Independent variables comprised demographic factors (sex, age, length of time from initial onset to treatment, body mass index), clinical parameters (lesion location, Puig classification, number of previous treatments, pretreatment volume, pretreatment NRS score), and preoperative laboratory parameters (white blood cell count, neutrophil count, hemoglobin, platelet count, plateletcrit, prothrombin time, activated partial thromboplastin time, D-Dimer). P < 0.05 indicated statistical significance.

Results

Patients’ demographic and baseline data

A total of 138 patients were included in this study, and their baseline data are presented in Table 1. The average injected bleomycin dosage/kg of body weight was 0.31 mg/kg. Among the patients, 58 were male and 80 were female. The age range was 3 to 65 years, with a mean age of 27.86 years and a mean age at onset of 14.10 years. The majority of the patients had lower limb VMs, followed by upper limbs, head and neck, body, and pelvis and genitalia. Common symptoms were pain, swelling, abnormal skin color, and functional limitation, with bleeding occurring in a relatively small proportion of the patients. Most patients underwent treatment for the first time, while 11 had received three or more treatments.

Table 1.

Baseline patient characteristics.

Characteristic	Value
Sex: male/female, n	58/80
Age, years	27.86 ± 13.02
Age at lesion onset, years	14.10 ± 14.13
BMI, kg/m²	22.56 ± 4.48
Lesion site
Upper limb(s)	26 (18.8%)
Lower limb(s)	77 (55.8%)
Trunk	10 (7.2%)
Head and neck	16 (11.6%)
Pelvis and genitals	9 (6.5%)
Puig Classification
I	63 (45.65%)
II	75 (54.35%)
Symptom
Pain	106 (76.81%)
Swelling	59 (42.75%)
Bleeding	2 (1.45%)
Abnormal skin color	31 (22.46%)
Limb dysfunction	8 (5.80%)
No. of previous treatments
0	77 (55.8%)
1	39 (28.3%)
2	11 (8.0%)
≥3	11 (8.0%)
Laboratory tests
WBC (×10⁹/L)	5.86 ± 1.31
NEUT (×10⁹/L)	3.27 ± 1.06
HGB (g/L)	135.43 ± 16.95
PLT (×10⁹/L)	244.30 ± 57.46
PCT (%)	0.21 ± 0.05
PT (s)	13.31 ± 0.55
APTT (s)	36.53 ± 5.41
D-Dimer (mg/L FEU)	1.35 ± 2.67

Results are shown as mean ± standard deviation or number (percent).

BMI, body mass index; WBC, white blood cell count; NEUT, neutrophil count; HGB, hemoglobin; PLT, platelet count; PCT, plateletcrit; PT, prothrombin time; APTT, activated thromboplastin time.

Clinical efficacy

Table 2 presents the effect of BPF treatment on VMs. Following BPF treatment, the pain score decreased from 4.17 ± 2.63 to 1.05 ± 1.54 (preoperative to 6 months postoperative; P < 0.001), and the VMs lesion volume decreased from 20.73 ± 28.11 mL to 4.17 ± 7.17 mL (P < 0.001), corresponding to a percentage reduction of 78.50% ± 15.71%. The average reduction in pain NRS scores was 3.12 points, with 39 of 106 patients experiencing complete relief; 70.3% of the patients achieved effective subjective relief. Additionally, 97.8% of the patients achieved >50% lesion volume reduction after treatment. Among the 31 patients with abnormal skin color, 21 (67.7%) showed improvement after sclerotherapy. Of the patients with limb dysfunction, 7/8 (87.5%) experienced resolution of their symptoms after treatment.

Table 2.

Overall clinical efficacy of bleomycin polidocanol foam (BPF).

Characteristic	Value
Reduction in NRS score	3.12 ± 2.44
Reduction in percentage lesion volume, %	78.50 ± 15.71
Subjective VMs improvement
CR	23 (16.7%)
PR	74 (53.6%)
PD	3 (2.2%)
SD	38 (27.5%)
Abnormal skin color resolved	21 (67.7%)
Limb dysfunction resolved	7 (87.5%)

Results are shown as mean ± standard deviation or number (percent).

NRS, pain numerical rating scale; VMs, venous malformations; CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease.

The affected areas in this study comprised 26 upper limbs, 77 lower limbs, 10 trunks, 16 heads and neck, and 9 pelvises and genitalia. Treatment effects at different sites are summarized in Table 3. Among the affected areas, trunk lesions had the highest baseline NRS scores and NRS score reductions, while head and neck lesions had the lowest baseline NRS scores. Additionally, trunk lesions exhibited the largest pretreatment volume, whereas head and neck lesions had the smallest pretreatment volume among the regions. Upper limb VMs demonstrated the greatest reduction in lesion volume post-treatment, while pelvic and genital lesions showed the least reduction among the regions. For all patients, we observed a mean reduction in lesion volume of 78.50% after a single BPF treatment. Patients with pelvic and genital VMs achieved CR or PR more frequently compared with lesions in other areas, while VMs in the upper limbs had the lowest proportion of patients who achieved CR or PR. There was no statistically significant differences in pain relief, lesion volume reduction, or subjective improvement between type I and type II VMs.

Table 3.

Clinical presentation and outcome by the location of the venous malformations.

Characteristic	Upper limb (n = 26)	Lower limb (n = 77)	Trunk (n = 10)	Head and neck (n = 16)	Pelvis and genitals (n = 9)	P-value
NRS score
Pretreatment	4.85 ± 2.26	4.43 ± 2.45	6.40 ± 1.17	1.56 ± 2.34	2.11 ± 2.57	<0.001*
Posttreatment	0.77 ± 0.95	1.21 ± 1.69	1.80 ± 1.99	0.50 ± 1.32	0.67 ± 1.12	0.157
Reduction in NRS	4.08 ± 2.17	3.22 ± 2.40	4.60 ± 2.17	1.06 ± 1.77	1.44 ± 1.94	<0.001*
VMs lesion volume
Pretreatment, mL	16.37 ± 19.11	22.76 ± 27.41	32.31 ± 55.88	9.39 ± 12.50	23.30 ± 30.25	0.249
Posttreatment, mL	3.27 ± 4.33	4.02 ± 4.81	5.43 ± 7.13	2.24 ± 2.62	10.05 ± 21.92	0.091
Reduction in volume, %	81.93 ± 13.34	78.26 ± 17.65	77.74 ± 6.74	77.42 ± 12.12	73.47 ± 17.68	0.691
Subjective VMs improvement						0.888
CR	5 (19.2%)	11 (14.3%)	1 (10.0%)	3 (18.8%)	3 (33.3%)
PR	13 (50.0%)	43 (55.8%)	5 (50.0%)	9 (56.3%)	4 (44.4%)
PD	0	3 (3.9%)	0	0	0
SD	8 (30.8%)	20 (26.0%)	4 (40.0%)	4 (25.0%)	2 (22.2%)

Results are shown as mean ± standard deviation or number (percent).

NRS, numerical rating scale; VMs, venous malformations; CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease.

*P < 0.05 represents statistical significance.

Complications

Table 4 presents the data for the postoperative complications. The overall complication rate was 22.5%. Swelling (10.14%), pain (7.25%), and skin hyperpigmentation at the puncture site (4.35%) were the most frequently reported complications following BPF injection therapy. Other rare complications comprised local bleeding (3.62%), blisters (0.72%), nerve injury (0.72%), and thromboembolism (1.45%). Pain, swelling, and local bleeding resolved within a few weeks after surgery, and skin hyperpigmentation had improved dramatically at the 6-month follow-up compared with the early postoperative period. No patients experienced recurrence within 6 months after treatment. The one case of nerve injury (0.72%) occurred in the patient’s treated hand, and the symptoms resolved with functional exercise.

Table 4.

Complications of bleomycin polidocanol foam (BPF) in VMs treatment.

Characteristic	Value
Pain	7 (7.25%)
Swelling	10 (10.14%)
Local bleeding	4 (3.62%)
Skin hyperpigmentation	6 (4.35%)
Blister	1 (0.72%)
Fever	0 (0.00)
Infection	0 (0.00)
Nerve injury	1 (0.72%)
Thromboembolism	2 (1.45%)
Recurrence	0

BPF, bleomycin polidocanol foam; VMs, venous malformations.

Logistic stepwise regression analysis

The results of the logistic multivariate stepwise regression analysis are presented in Table 5 and revealed that a high preoperative NRS score was a positive predictor of both reduced pain score and complete pain relief after surgery. Furthermore, APTT was a positive predictor of pain score reduction, while PCT was a positive predictor of complete pain relief after surgery. High initial NRS scores and high APTT values were associated with significant pain relief after sclerotherapy. In contrast, high initial NRS scores and high PCT values were associated with a likelihood of incomplete postoperative pain relief. The analysis did not identify any positive predictors of lesion volume reduction or subjective improvement in VMs.

Table 5.

Logistic stepwise regression analysis of the efficacy of BPF for VMs.

Variable	OR
Variable	Reduction in NRS score of >3 points	Postoperative NRSscore >0	Reduction in lesion volume >60%	Subjective VMs effective relief
Baseline NRS	4.026 (P = 0.000)	1.992 (P < 0.001)	–	–
APTT	1.200 (P = 0.005)	–	–	–
PCT	–	2.543 (P = 0.032)	–	–

BPF, bleomycin polidocanol foam; VMs, venous malformations; OR, odds ratio; NRS, numerical rating scale; APTT, activated partial thromboplastin time; PCT: plateletcrit.

Discussion

VMs are considered common congenital vascular malformations that can be detected in infancy or early childhood.²² However, some patients may initially present with palpable surface masses that are not initially noticed or for which no medical attention is sought. Previous studies of BPF treatment often focused on the reduction of VMs volume on MRI as an outcome measure. However, many patients seek treatment to alleviate pain or improve cosmetic appearance, and solely assessing volume changes overlooks the subjective improvements experienced by patients. Thus, in this study, we included subjective VMs improvement and changes in pain as additional measures to comprehensively analyze the therapeutic effect of BPF on VMs.

Percutaneous sclerotherapy is the preferred minimally invasive treatment for VMs, and various sclerosing agents have been used, including absolute ethanol, polidocanol foam, bleomycin, STS, and their combinations.¹² Although absolute ethanol is considered the most effective sclerosing agent owing to its ability to completely occlude vascular lumens and inhibit endothelial cell regeneration, its use is associated with serious complications, such as permanent nerve damage, thrombophlebitis, and deep venous thrombosis. These complications outweigh the benefits for patients with VMs.^23,24

BPF, which contains bleomycin and polidocanol, has emerged as a promising alternative for VMs treatment. Bleomycin, commonly used in cancer treatment, exerts its effects by inhibiting DNA synthesis.²⁵ In the context of sclerotherapy, bleomycin damages endothelial cells and triggers a non-specific inflammatory response, leading to vascular occlusion.²⁶ However, bleomycin carries the risk of pulmonary fibrosis, limiting its dosage to <450 mg to mitigate the associated complications.²⁷ In VMs, the primary aim is to alleviate symptoms, which are non-life-threatening, and the risk of pulmonary fibrosis with BPF therapy should not be disregarded. To optimize the therapeutic effect of BPF and minimize the risk of systemic complications, it is beneficial to reduce bleomycin washout and achieve high drug concentrations within the local area surrounding the VMs. Foamy bleomycin slows drug washout, enhances effectiveness compared with liquid bleomycin, and reduces the risk of systemic toxicity compared with non-foamy formulations.²⁸ Polidocanol, a detergent sclerosing agent, induces vascular endothelial cell death, followed by fibrosis and sclerosis of the blood vessels.²⁹ Recent studies have proposed BPF to slow the elution rate of the sclerosing agents, increase the contact area between the drugs and the vascular endothelium, harness the synergistic effect of the two agents, and enhance the therapeutic effect of sclerotherapy.^18,21

In this single-center retrospective study, we assessed the efficacy and safety of BPF for VMs treatment. Previous studies have used varying evaluation indicators to assess the efficacy of sclerosing agent therapy. To measure changes in lesion volume, response rates and degree of reduction are often reported. In this study, we observed a mean reduction in lesion volume of 78.50% after a single BPF treatment. Although this differs from Yang et al.’s report of an 84.6% reduction, it is important to note that the average number of treatments in Yang et al.’s study was two.¹⁸

Repeat sclerotherapy is effective for patients who have undergone previous treatments. STS therapy has been reported to result in a volume reduction relative to the preoperative volume of only 41.7%.³⁰ Su et al. demonstrated that treatment with absolute ethanol led to >50% volume reduction in >93.33% of lesions, with 68.33% showing >90% regression.³¹ In our study, 97.8% of the patients achieved >50% volume reduction after treatment, comparable to the efficacy of absolute ethanol treatment in Su et al.’s study.

Regarding pain relief, the average reduction in pain NRS scores in this study was 3.12 points, with 39 of 106 patients experiencing complete relief. Most postoperative pain occurred during prolonged exercise but was significantly alleviated compared with preoperative levels. Complete remission was achieved at rest in these patients, with pain during exercise possibly due to impaired local venous return. Previous reports have demonstrated the effectiveness of absolute ethanol, STS, and bleomycin in improving pain associated with VMs.^15,30 Sclerotherapy using injectable agents is considered the first-line treatment to alleviate VMs symptoms. In our study, 70.3% of the patients achieved effective subjective relief. During the follow-up, some patients reported no change in lesion volume but noted hardened injection sites, suggesting local tissue fibrosis following sclerotherapy. Patients with abnormal skin color showed improvement after a single treatment in 67.7% of the cases, and 87.5% of the patients with limb dysfunction experienced relief.

In this study, we found that patients with VMs in the head and neck, pelvis, and genitalia had less pain relief after therapy compared with patients with lesions in other sites. Patients with VMs in head and neck, pelvis, and genitalia were primarily concerned about cosmetic issues and had lower baseline pain scores compared with patients with VMS in other sites. This finding aligns with those of Park et al., who investigated the effects of STS treatment for VMs.³⁰ Moreover, compared with other regions, pelvic and genital lesions showed a lower reduction in volume after therapy, which may be attributed to the deeper location of pelvic lesions and the reported need for multiple sclerotherapy treatments to achieve remission.¹⁴ It is important to note that the small sample size of lesions at these sites may have introduced bias. The Puig classification of the VMs showed no significant influence on the clinical efficacy, which is consistent with findings in a previous report.³² The effect of sclerotherapy on low-flow VMS is better compared with high-flow VMs.²⁰

Regarding complications, postoperative swelling and high postoperative pain levels were observed but resolved markedly within 1 month. Six patients developed skin hyperpigmentation after BPF treatment, which had improved significantly by 6 months postoperatively compared with the early postoperative period. However, the postoperative skin color still differed from the normal skin color, which can be attributed to the sclerotherapy procedure.³³ One case of nerve injury occurred and was localized to the patient's hand, possibly caused by local diffusion of the injected sclerosing agent. The patient’s hand function returned to normal after functional exercise. Including swelling and pain that could be relieved after surgery, the overall complication rate (22.5%) was slightly lower than that reported for ethanol treatment (23.5%).³⁴ However, there is no consensus on whether these very short-term abnormal symptoms should be considered complications.³⁴ No recurrence of VMs was detected within the 6-month follow-up period, although the possibility of a short follow-up duration and time to recurrence that had not been reached cannot be ruled out.

In this study, baseline pain scores and APTT were identified as predictors of pain reduction after therapy, while baseline pain scores and PCT were predictors of complete postoperative pain relief. However, no predictors were found for lesion volume reduction and subjective relief. Severe initial pain and high APTT values were associated with significant pain relief after sclerotherapy. Conversely, severe initial pain and high PCT values were associated with a likelihood of incomplete postoperative pain relief. Low APTT indicates a hypercoagulable state in the body. Plateletcrit is an important platelet parameter, and platelets play a crucial role in thrombosis.³⁵ Therefore, poor pain outcomes may be associated with abnormal coagulation and local thrombosis. Notably, for patients with VMs and coagulation disorders, correcting the coagulation abnormality can alleviate pain.³⁶ Furthermore, the primary mechanism of sclerotherapy for VMs encompasses vascular fibrosis and thrombosis.³⁷ Polidocanol mainly activates vascular fibrosis by destroying endothelial cells,²⁹ and the process of thrombosis is controversial. A previous study showed that low concentrations of polidocanol can initiate and enhance clot formation in vivo.³⁸ A hypercoagulable state in the body may intensify this process and cause local embolism, which leads to pain. Previous studies have also reported a positive correlation between changes in fibrinogen degradation product and D-Dimer levels and treatment outcomes.³⁹ Predictors of lesion volume change and subjective measures vary widely in previous reports, with some studies finding no predictive factors, while some factors, such as size, lesion diffusion, sex, and number of sclerotherapy sessions have been reported to impact sclerotherapy outcomes.^{16,30,40–42}

There is still no clear consensus on the definition and evaluation of treatment efficacy for VMs. The variation in lesion volume changes reported in different studies makes it challenging to compare treatments. Given that the treatment of VMs focuses primarily on palliative symptomatic measures aimed at improving patient symptoms, it is crucial to consider subjective improvement reported by patients, rather than relying solely on imaging results. Furthermore, previous studies have identified a lack of connection between imaging results and patient satisfaction.^43,44 The development of specialized scales for evaluating treatment response in VMs is warranted.

One of the limitations of this study is its retrospective, single-center design, which may have introduced selection bias. However, the results can still be considered valid for the context in which they were studied. The short follow-up period precluded the collection of postoperative recurrence data. Additionally, the evaluation of subjective efficacy relied on a single index, without using common quality of life questionnaires, such as the 36-Item Short Form Survey (SF-36). The lack of established scales to describe treatment response in this area highlights the need for the development of effective and specialized scales.

Conclusion

BPF was effective and safe as a sclerosing agent for VMs treatment, with the ability to significantly reduce lesion volume and improve symptoms, with minimal complications. APTT and PCT are important predictors of post-BPF treatment pain, and awareness of this information can help improve postoperative analgesia. Further studies are warranted to refine treatment protocols, evaluate long-term outcomes, and develop specialized scales for assessing treatment efficacy in VMs.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605231223441 - Supplemental material for Clinical outcomes and predictors of bleomycin polidocanol foam sclerotherapy treatment response in venous malformations

Supplemental material, sj-pdf-1-imr-10.1177_03000605231223441 for Clinical outcomes and predictors of bleomycin polidocanol foam sclerotherapy treatment response in venous malformations by Bin Ni, Jing-wen Liu, Xue-qiang Fan, Bin He, Qiang-qiang Nie, Zhi-dong Ye, Peng Liu and Jian-yan Wen in Journal of International Medical Research

Footnotes

Acknowledgements

The authors would like to express their sincere gratitude to all participants in this study.

Author contributions

Conceptualization, Bin Ni, Jing-wen Liu, Xue-qiang Fan and Jian-yan Wen; Methodology, Bin Ni, Jing-wen Liu; Software, Bin Ni; Validation, Jing-wen Liu; Formal analysis, Bin Ni, Jing-wen Liu; Writing—original draft preparation, Bin Ni, Jing-wen Liu; Writing—review and editing, Bin Ni, Jing-wen Liu, Qiang-qiang Nie, Bin He, Zhi-dong Ye, and Peng Liu; Supervision, Zhi-dong Ye, Peng Liu, Xue-qiang Fan, and Jian-yan Wen; Project administration, Xue-qiang Fan and Jian-yan Wen; Funding acquisition, Xue-qiang Fan and Jian-yan Wen. All authors have read and agreed to the published version of the manuscript.

Data availability statement

The datasets generated and/or analyzed during the current study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author on reasonable request.

Declaration of conflicting interests

The authors declare that there is no conflict of interest.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China [grant numbers 82270443, 82170066, 81670275, and 81670443]; National High Level Hospital Clinical Research Funding [grant number 2022-NHLHCRF-ZSYX-01]; the International S&T Cooperation Program [grant number 2013DFA31900]; and Major New Drug Creation Special Project [grant number 2020ZX09201-012].

ORCID iD

Jian-yan Wen

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