Surgery for Port-Wine Stains: A Systematic Review.

BACKGROUND: Port-wine stains (PWS) are congenital low-flow vascular malformations of the skin. PWS tend to become thicker and darker with time. Laser therapy is the gold standard and the first-line therapy for treating PWS. However, some resistant PWS, or PWS that have tissue hypertrophy, do not respond to this therapy. Our aim is to evaluate the role of surgery in the treatment of PWS birthmarks. METHODS: A literature search was performed in PubMed, Scopus, Web of Science (WOS) and Google Scholar for all papers dealing with surgery for port-wine stains, from January 2010 to December 2020 using the search strings: (capillary vascular malformation OR port-wine stains OR Sturge Weber Syndrome OR sws OR pws) AND (surgical OR surgery). RESULTS: Ten articles were identified and used for analysis. They were almost all case series with a short follow up period and lacked an objective-systematic score of evaluation. CONCLUSIONS: Delay in treatment of port wine stains may result in soft tissue and bone hypertrophy or nodules with disfiguring or destructive characteristics. The correction of PWS-related facial asymmetry often requires bone surgery followed by soft tissue corrections to achieve a more harmonious, predictable result.

Multiple General Anesthesia in Children: A Systematic Review of Its Effect on Neurodevelopment.

The effect of multiple general anesthesia (mGA) procedures administered in early life is a critical theme and has led the Food and Drug Administration (FDA) to issue an alert. This systematic review seeks to explore the potential effects on neurodevelopment of mGA on patients under 4 years. The Medline, Embase and Web of Science databases were searched for publications up to 31 March 2021. The databases were searched for publications regarding "children multiple general anesthesia OR pediatric multiple general anesthesia". Case reports, animal studies and expert opinions were excluded. Systematic reviews were not included, but they were screened to identify any possible additional information. A total of 3156 studies were identified. After removing the duplicates, screening the remaining records and analyzing the systematic reviews' bibliography, 10 studies were considered suitable for inclusion. Comprehensively, a total cohort of 264.759 unexposed children and 11.027 exposed children were assessed for neurodevelopmental outcomes. Only one paper did not find any statistically significant difference between exposed and unexposed children in terms of neurodevelopmental alterations. Controlled studies on mGA administered before 4 years of age support that there might be a greater risk of neurodevelopmental delay in children receiving mGA, warranting the need for careful risk/benefit considerations.

Sirolimus treatment for paediatric head and neck lymphatic malformations: a systematic review.

PURPOSE: This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on treatment efficacy but also on possible treatment-related adverse events, and treatment combinations with other techniques. METHODS: Search criteria were applied to MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases and included all studies published up to March 2022 reporting paediatric lymphatic malformations treated with sirolimus. We selected all original studies that included treatment outcomes. After the removal of duplicates, selection of abstracts and full-text articles, and quality assessment, we reviewed eligible articles for patient demographics, lymphatic malformation type, size or stage, site, clinical response rates, sirolimus administration route and dose, related adverse events, follow-up time, and concurrent treatments. RESULTS: Among 153 unique citations, 19 studies were considered eligible, with reported treatment data for 97 paediatric patients. Most studies (n = 9) were case reports. Clinical response was described for 89 patients, in whom 94 mild-to-moderate adverse events were reported. The most frequently administered treatment regimen was oral sirolimus 0.8 mg/m2 twice a day, with the aim of achieving a blood concentration of 10-15 ng/mL. CONCLUSION: Despite promising results for sirolimus treatment in lymphatic malformation, the efficacy and safety profile of remains unclear due to the lack of high-quality studies. Systematic reporting of known side effects, especially in younger children, should assist clinicians in minimising treatment-associated risks. At the same time, we advocate for prospective multicentre studies with minimum reporting standards to facilitate improved candidate selection.

A Retrospective Evaluation to Assess Reliability of Electrophysiological Methods for Diagnosis of Hearing Loss in Infants.

Background: An electrophysiological investigation with auditory brainstem response (ABR), round window electrocochleography (RW-ECoG), and electrical-ABR (E-ABR) was performed in children with suspected hearing loss with the purpose of early diagnosis and treatment. The effectiveness of the electrophysiological measures as diagnostic tools was assessed in this study. Methods: In this retrospective case series with chart review, 790 children below 3 years of age with suspected profound hearing loss were tested with impedance audiometry and underwent electrophysiological investigation (ABR, RW-ECoG, and E-ABR). All implanted cases underwent pure-tone audiometry (PTA) of the non-implanted ear at least 5 years after surgery for a long-term assessment of the reliability of the protocol. Results: Two hundred and fourteen children showed bilateral severe-to-profound hearing loss. In 56 children with either ABR thresholds between 70 and 90 dB nHL or no response, RW-ECoG showed thresholds below 70 dB nHL. In the 21 infants with bilateral profound sensorineural hearing loss receiving a unilateral cochlear implant, no statistically significant differences were found in auditory thresholds in the non-implanted ear between electrophysiological measures and PTA at the last follow-up (p > 0.05). Eight implanted children showed residual hearing below 2000 Hz worse than 100 dB nHL and 2 children showed pantonal residual hearing worse than 100 dB nHL (p > 0.05). Conclusion: The audiological evaluation of infants with a comprehensive protocol is highly reliable. RW-ECoG provided a better definition of hearing thresholds, while E-ABR added useful information in cases of auditory nerve deficiency.

Stop Calling Me Cavernous Hemangioma! A Literature Review on Misdiagnosed Bony Vascular Anomalies.

Vascular malformations of the bone most often involve the cranio-facial area. Even in relevant peer reviewed journals, venous malformations are often misdiagnosed as "hemangiomas" or "angiomas" of the bone. By reviewing literature from the past 5 years (2013-2018), we found many reports of vascular malformations of the bone where the diagnosis was incorrect. Unfortunately, there is still much confusion in understanding and/or diagnosing vascular malformations, despite the fact that in recent years many papers tried to clarify this topic. The purpose of this article is to make a review of the scientific literature concerning vascular malformations of the bone which have been reported as angioma, hemangioma, or hemangioendothelioma, and have been published between January 2013 to October 2018. Clinical features, imaging and histologic reports contained in the papers were reviewed. Subsequently, after reviewing every single paper we reclassified the diagnosis according to the 2018 ISSVA classification. Almost all of the vascular anomalies presented in the reviewed papers as angiomas, hemangiomas, or hemangioendotheliomas were venous (mostly) or arteriovenous malformations. Therefore, only 8 out of 58 papers (14.7%) had an accurate diagnosis. Interestingly, all of the papers reporting cavernous or capillary hemangiomas were actually presenting venous malformations. Making a correct diagnosis is of primary importance because depending on the type of vascular anomaly, the treatment and the prognosis for the patient are very different. Everyone who approaches or describes a vascular anomaly of the bone should know and should adopt a correct and updated nosography.

SECg Staging System: A New Approach to the Management of Arteriovenous Malformations of the Head and Neck.

OBJECTIVES: Arteriovenous malformations (AVM) are the most troublesome vascular malformations to deal with. They tend to behave like low-grade malignancies with infiltrative and disruptive growth. Crucially, the clinical course of an AVM that has been improperly managed is usually characterized by a recurrence that is much more aggressive than the original disease. As in oncology, a comprehensive staging system is highly desirable and is to date lacking in the literature. The authors present a new comprehensive staging system. METHODS: A multicentric multidisciplinary team of experts in the field of vascular anomalies has created this new staging system. The SECg staging system defines the local extension of the disease (S1-S4), the vascular architecture of the malformation (E1, E2, E3), the severity of the symptoms (C0-C3) and the presence or absence of growth of the AVM (g+, g-). RESULTS: This staging system allows to address all the aspects of AVMs and, more importantly, to help building an appropriate, individualized treatment plan for affected patients. After being staged an AVM can be defined as (a) healable, (b) healable with predicted sequelae, or (c) unhealable. Then, the SECg system allows to outline (a) absolute indications, (b) relative indications, and (c) no indications for treatment. The purpose of the treatment (radical, palliative) is furthermore taken into consideration. CONCLUSIONS: This multicentric, the SECg staging system that this multidisciplinary group of Authors has defined allows for a comprehensive staging of the disease which in turn has enabled to outline an algorithm to properly manage AVMs.

CD10 and CD34 as markers in vascular malformations with PIK3CA and TEK mutations.

AIMS: Vascular malformations (vMs) encompass a wide range of diseases often associated with somatic or, more rarely, germinal genetic mutations. A mutation in the PIK3Ca/mTOR pathway is more often involved in various vMs. CD10 and CD34 are cellular markers that may play a role in mesenchymal differentiation and proliferation. The aim of our study was to find a possible link between the immunohistochemical expression of CD10 and CD34 in vMs and their relationship with mutations in the PIK3CA/mTOR signaling pathway. METHODS AND RESULTS: Our study on 58 samples of vMs showed that in endothelial cells, CD10 was significantly expressed in PIK3CA-mutated samples compared with samples without any mutation (p < 0.05), especially and even more consistently when compared with samples with mutation in other pathways (p < 0.0001). Conversely, in the same PIK3CA-mutated samples, CD34 expression in endothelial cells was significantly reduced compared with samples either without any mutation or mutations in other pathways (p < 0.05 and p < 0.0005). Compared with samples with mutations in other pathways, a significant overexpression of endothelial CD10 was also found in samples with TEK/TIE2 mutation, a gene linked to the PIK3CA/mTOR pathway (p < 0.01). However, CD34 expression was not altered. In samples with PIK3CA mutation, the CD10 expression was significantly increased in the stroma compared with samples with TEK/TIE2 gene or other gene mutations (p < 0.05). CONCLUSION: Therefore, the CD10 and CD34 immunohistochemical profile could suggest/support the presence of mutations in the PIK3CA/mTOR pathway in samples of vMs.

Basal Cell Carcinoma Arising over a Venous Malformation of the Forehead Communicating with the Endocranial Veins.

INTRODUCTION: An increasing number of skin cancer arising over vascular anomaly has been reported in literature. In such cases, the oncologic radicality required to threat skin malignancies may be in contrast with the safety needed when dealing with vascular malformation. As a result, treatment of this association may be insidious and treacherous and imposes a sound knowledge and carefulness. MATERIALS AND METHODS: The authors report on a case of a 77-years-old woman affected by a basal cell carcinoma (BCC) arising over a vascular malformation of forehead. Preoperative radiological imaging revealed an underlying venous malformation (VM) communicating with intracranial district. Patient underwent sclerotherapy of the VM with gelified ethanol in order to reduce potentially fatal bleeding during surgery and, on the other hand, any leakage of the sclerosant in the intracranial veins. Excision of the BCC was then performed without complications. RESULTS: Neither intra-operative nor post-operative complications were observed. Current 3-years follow-up shows no recurrence of BCC whilst the residual VM is stable and clinically silent. CONCLUSIONS: Mechanisms leading to the onset of skin cancers over venous malformations are still unclear. However, association between these 2 conditions may be underestimated with possible catastrophic consequences. Thorough knowledge of vascular malformations and a multidisciplinary approach is of the uttermost importance when dealing with such clinical challenges.

Vascular malformations of the orbit (lymphatic, venous, arteriovenous): Diagnosis, management and results.

Vascular malformations are often found inside the orbit. Isolated venous malformations (frequently misnamed as cavernous hemangiomas) are the most frequent among these. However, also lymphatic and arteriovenous malformations can affect the orbit. The complex anatomy of the orbit and the fact that its content easily suffers from compartmental syndrome explain why treating orbital vascular malformations can be challenging and technically demanding. In this study, two institutions have retrospectively collected their cases, consisting in a total of 69 vascular malformations of the orbit. Each type of malformation has been evaluated separately in terms of diagnosis, indications for treatment, techniques and outcomes. Moreover, the authors have analyzed in detail venous malformations, identifying three different types, named orbital venous malformation (OVM) 1, 2 and 3. These behave differently from each other, and a prompt differential diagnosis is mandatory to pose correct indications, minimize risks and improve results. Overall, surgery was the technique of choice for OVM1, microcystic lymphatic malformations (LM) and arteriovenous malformations (AVM). A pure transnasal approach with mass removal and reconstruction of the medial wall with polyethylene sheets was chosen for OVM1 (intra- or extraconal) located in the medial or superomedial compartment. Sclerotherapy had a role in treating macrocystic LM and OVM3.

Surgical correction of hypertrophic upper lip in vascular malformations.

Capillary malformations (CMs) and Lymphatic malformations (LMs) are vascular malformations that share a common tendency to cause soft and hard tissue hypertrophy, expressed in the three dimensions of the space. The middle third of the face is the most commonly involved area, with a predominance of the upper lip. To our knowledge, no paper has previously focused on the surgical technique to correct such deformities. We propose and illustrate a surgical protocol, consisting in merging an asymmetric bikini upper lip reduction and a unilateral bull horn resection technique, that allowed to reduce the overall volume of the hypertrophied lip thus restoring lip symmetry. We adopted this technique in 2 patients affected by CMs and 4 patients with LMs, with satisfactory results.