Sophie E.R. Horbach

Sclerotherapy for low-flow vascular malformations of the head and neck: A systematic review of sclerosing agents.

BACKGROUND Sclerotherapy has become the gold standard for the first-line therapy of most venous (VMs) and lymphatic malformations (LMs) of the head and neck. Numerous sclerosing agents are used to treat these low-flow vascular malformations; however, to date, it remains unclear which sclerosing agent is superior in terms of effectiveness and safety. METHODS In a systematic review of the literature (1995-present), we compare the effectiveness and complications of the sclerosing agents most commonly used for cervicocraniofacial VMs and LMs. RESULTS The literature search yielded 1155 articles, among which 36 (1552 patients) were included in the systematic review. The quality of evidence was low. Pingyangmycin, absolute ethanol, OK-432, ethanolamine oleate, bleomycin, polidocanol, doxycycline, and sodium tetradecyl sulfate (STS) were the most reported sclerosing agents. All agents seem effective, and the mean overall response varies from 71% to 100%. Complications occurred more frequently after ethanol sclerotherapy (18%), compared to other sclerosing agents (0-6%). Cellulitis and ulceration were encountered following sclerotherapy with most sclerosing agents, but skin necrosis was particularly observed after ethanol. Facial nerve paralysis occurred only after OK-432 (0.05%) and ethanol sclerotherapy (6%). CONCLUSIONS This systematic review could not identify a significantly superior sclerosing agent in terms of effectiveness, due to the low quality of the available evidence. Until stronger evidence is available, the difference in complication rates is potentially the deciding factor in the choice between sclerosing agents. As a significantly higher complication rate and more severe local complications were encountered after using absolute ethanol, we cannot recommend this agent for sclerotherapy of cervicofacial vascular malformations.

Intralesional Bleomycin Injections for Vascular Malformations: A Systematic Review and Meta-Analysis.

Background: Vascular malformations are congenital anomalies of the vascular system. Intralesional bleomycin injections are commonly used to treat vascular malformations. However, pulmonary fibrosis could potentially be a severe complication, known from systemic bleomycin therapy for malignancies. In this study, the authors investigate the effectiveness and safety of bleomycin (A2, B2, and A5) injections for vascular malformations, when possible relative to other sclerosants. Methods: The authors performed a PubMed, Embase, Cochrane Central Register of Controlled Trials, and gray literature search for studies (1995 to the present) reporting outcome of intralesional bleomycin injections in patients with vascular malformations (n ≥ 10). Predefined outcome measures of interest were size reduction, symptom relief, quality of life, adverse events (including pulmonary fibrosis), and patient satisfaction. Results: Twenty-seven studies enrolling 1325 patients were included. Quality of evidence was generally low. Good to excellent size reduction was reported in 84 percent of lymphatic and 87 percent of venous malformations. Pulmonary fibrosis was never encountered. Meta-analysis of four studies on venous malformations treated with bleomycin versus other sclerosants showed similar size reduction (OR, 0.67; 95 percent CI, 0.24 to 1.88) but a significantly lower adverse event rate (OR, 0.1; 95 percent CI, 0.03 to 0.39) and fewer severe complications after bleomycin. Symptom relief, quality of life, and patient satisfaction were reported inadequately. Conclusions: The authors’ data suggest that bleomycin is effective in reducing the size of lymphatic and venous malformations, and leads to a lower adverse event rate and fewer severe complications than other sclerosants. The included literature does not provide evidence that pulmonary fibrosis is a complication of intralesional bleomycin injections. This study represents the “best available” evidence; however, only low- to moderate-quality studies were available. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Oral sildenafil as a treatment option for lymphatic malformations in PIK3CA-related tissue overgrowth syndromes.

Patients with extensive lymphatic malformations associated with tissue overgrowth syndromes (such as Klippel‐Trenaunay syndrome and CLOVES) often pose a therapeutic challenge for physicians. In recent years, it has been suggested that oral sildenafil therapy might be used to treat congenital lymphatic malformations. However, this possible new therapy has not yet been used in patients with lymphatic malformations associated with tissue overgrowth syndromes. A 30‐year‐old man with extensive capillary‐lymphatic malformations of the right leg and thorax, and a tissue overgrowth syndrome caused by a somatic mutation in the PIK3CA gene, was treated with oral sildenafil due to symptoms of pain, dyspnea, and functional impairment. Several weeks after the start of the treatment, the patient reported softening of the lymphatic malformation and a significant improvement of his symptoms and physical condition. So far, sildenafil is still considered a last resort in the treatment of complex treatment‐resistant lymphatic malformations. With this case report, we demonstrate that sildenafil could also be an alternative treatment option for lymphatic malformations in patients with syndromes belonging to the PIK3CA‐related overgrowth spectrum.

Development of an international core outcome set for peripheral vascular malformations: the OVAMA project

An important limitation in vascular malformation research is the heterogeneity in outcome measures used for the evaluation of treatment outcome.

Shared Decision-Making in the Management of Congenital Vascular Malformations

Background: In shared decision-making, clinicians and patients arrive at a joint treatment decision, by incorporating best available evidence and the patients’ personal values and preferences. Little is known about the role of shared decision-making in managing patients with congenital vascular malformations, for which preference-sensitive decision-making seems obvious. The authors investigated preferences regarding decision-making and current shared decision-making behavior during physician-patient encounters. Methods: In two Dutch university hospitals, adults and children with congenital vascular malformations facing a treatment-related decision were enrolled. Before the consultation, patients (or parents of children) expressed their preference regarding decision-making (Control Preferences Scale). Afterward, participants completed shared decision-making–specific questionnaires (nine-item Shared Decision-Making Questionnaire, CollaboRATE, and satisfaction), and physicians completed the Shared Decision-Making Questionnaire–Physician questionnaire. Consultations were audiotaped and patient involvement was scored by two independent researchers using the five-item Observing Patient Involvement instrument. All questionnaire results were expressed on a scale of 0 to 100 (optimum shared decision-making). Results: Fifty-five participants (24 parents and 31 adult patients) were included. Two-thirds preferred the shared decision-making approach (Control Preferences Scale). Objective five-item Observing Patient Involvement scores were low (mean ± SD, 31 ± 15), whereas patient and physician Shared Decision-Making Questionnaire scores were high, with means of 68 ± 18 and 68 ± 19, respectively. The median CollaboRATE score was 93. There was no clear relationship between shared decision-making and satisfaction scores. Conclusions: Although adults and parents of children with vascular malformations express a strong desire for shared decision-making, objective shared decision-making behavior is still lacking, most likely because of poor awareness of the shared decision-making concept among patients, parents, and physicians. To improve shared decision-making practice, targeted interventions (e.g., decision aids, staff training) are essential.

Compression therapy for congenital low-flow vascular malformations of the extremities: A systematic review

Introduction Low-flow vascular malformations are congenital abnormalities of the veins, capillaries or lymphatic vessels or a combination of the previous. Compressive garments are frequently used as a first-line treatment option for low-flow vascular malformations of the extremities with the purpose of relieving symptoms. Yet, the benefits and harms of compression stockings remain unclear. Methods A systematic search was performed in MEDLINE, Embase, Cochrane Central Register of Controlled Trials including a hand search for studies measuring the benefits and harms of compression garments in treating low-flow vascular malformations. Two investigators performed study selection, quality assessment and data extraction independently. Results Of the 565 studies found, eventually five (totalling 101 patients with venous malformations or Klippel–Trenaunay syndrome receiving compression therapy) observational studies were included in the systematic review. Although the overall quality of these studies was poor, results suggest that compression garments might lessen intravascular coagulation, improve symptoms and appearance, diminish oedema, and protect against minor trauma. None of the studies quantified any harms of compression therapy. Conclusion Even though compression therapy is commonly used in the treatment of low-flow vascular malformations, available literature does not provide high-quality evidence to validate its use. We therefore advocate the need for prospective comparative trials with standardised outcome measures to study the benefits and harms of this treatment option.

Discrepancy between the clinical and histopathologic diagnosis of soft tissue vascular malformations

Background: Soft tissue vascular malformations are generally diagnosed clinically, according to the International Society for the Study of Vascular Anomalies (ISSVA) classification. Diagnostic histopathologic examination is rarely performed. Objective: We sought to evaluate the validity of the current diagnostic workup without routinely performed diagnostic histopathology. Methods: We retrospectively determined whether there were discrepancies between clinical and histopathologic diagnoses of patients with clinically diagnosed vascular malformations undergoing therapeutic surgical resections in our center (2000–2015). Beforehand, a pathologist revised the histopathologic diagnoses according to the ISSVA classification. Results: Clinical and histopathologic diagnoses were discrepant in 57% of 142 cases. In these cases, the pathologist indicated the diagnosis was not at all a vascular malformation (n = 24; 17%), a completely different type of vascular malformation (n = 26; 18%), or a partially different type with regard to the combination of vessel‐types involved (n = 31; 22%). Possible factors associated with the discrepancies were both clinician‐related (eg, diagnostic uncertainty) and pathology‐related (eg, lack of immunostaining). Limitations: Retrospective analysis of a subgroup of patients undergoing surgery. Conclusion: The large discrepancy between clinical and histopathologic diagnoses raises doubt about the validity of the current diagnostic workup for vascular malformations. Clear clinical and histopathologic diagnostic criteria might be essential for a uniform diagnosis.

Complications of pregnancy and labour in women with Klippel–Trénaunay syndrome: a nationwide cross-sectional study

To evaluate complications of pregnancy, including thromboembolism, in women with extensive vascular malformations associated with Klippel–Trénaunay syndrome (KTS).

Electrosclerotherapy for capillary malformations: study protocol for a randomised within-patient controlled pilot trial

Introduction The current state-of-the-art treatment modality for hypertrophic capillary malformations (CMs), laser therapy, has a considerable rate of non-responders and recurrence. Intralesional bleomycin injections (or ‘sclerotherapy’) are commonly used to treat venous and lymphatic malformations with an excellent effect, but these intravascular injections are not possible in CMs due to the small diameter of the vessels. Electroporation—an electric field applied to the tissue—could increase the permeability of endothelial cells, which could theoretically facilitate targeted localised bleomycin delivery. We therefore hypothesise that bleomycin injections in combination with electroporation—‘electrosclerotherapy’ (EST), also known as ‘electrochemotherapy’—could potentially be a novel alternative treatment option for CMs. Methods and analysis In this randomised within-patient controlled pilot trial, 20 patients with hypertrophic CMs will be enrolled. Three regions of interest (ROIs) within the CM will be randomly allocated for treatment with (A) EST, (B) bleomycin sclerotherapy without electroporation and (C) no treatment. Patients and outcome assessors are blinded for the treatment allocation. Treatment outcome for each ROI will be measured approximately 7 weeks after the treatment procedure, using patient-reported and physician-reported global assessment scores, colorimetry, laser speckle imaging and reporting of adverse events. Ethics and dissemination The study protocol is approved by the ethics review committee of the Academic Medical Center, Amsterdam. Results will be published in peer-reviewed medical journals and will be presented at international conferences and scientific meetings. Study results will be fed back to the patient population through website and social media notifications. Trial registration number NCT02883023;Pre-results. NTR6169.