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Background: Sporadic venous malformation (VM) and angiomatosis of soft tissue (AST) are benign, congenital vascular anomalies affecting venous vasculature. Depending on the size and location of the lesion, symptoms vary from motility disturbances to pain and disfigurement. Due to high recurrence of the lesions more effective therapies are needed. Methods: As targeting stromal cells has been an emerging concept in anti-angiogenic therapies, here, by using VM/AST patient samples, RNA-sequencing, cell culture techniques and a xenograft mouse model, we investigated the crosstalk of endothelial cells (EC) and fibroblasts and its effect on vascular lesion growth. Results: We report, for the first time, expression and secretion of transforming growth factor A (TGFA) in ECs or intervascular stromal cells in AST and VM lesions. TGFA induced secretion of VEGF-A paracrinally, and regulated EC proliferation. Oncogenic PIK3CA variant in p.H1047R, a common somatic mutation found in these lesions, increased TGFA expression, enrichment of hallmark hypoxia, and in a mouse xenograft model, lesion size and vascularization. Treatment with afatinib, a pan-ErbB tyrosine-kinase inhibitor, decreased vascularization and lesion size in mouse xenograft model with ECs expressing oncogenic PIK3CA p.H1047R variant and fibroblasts. Conclusions: Based on the data, we suggest that targeting of both intervascular stromal cells and ECs is a potential treatment strategy for vascular lesions having a fibrous component. Funding: Academy of Finland, Ella and Georg Ehnrooth foundation, the ERC grants, Sigrid Jusélius Foundation, Finnish Foundation for Cardiovascular Research, Jane and Aatos Erkko Foundation, and Department of Musculosceletal and Plastic Surgery, Helsinki University Hospital.

Background Velopharyngeal insufficiency (VPI) often results from palatal shortening or insufficient levator function after cleft palate repair. Aims To assess the efficacy of palatal re-repair with Z-plasty in treatment of VPI for patients with isolated cleft palate (ICP). Methods This retrospective analysis comprised 130 consecutive patients who had ICP with VPI that required Z-plasty as secondary surgery between 2008 and 2017. Pre- and post-operative evaluation of velopharyngeal function was done perceptually and instrumentally by Nasometer. Results Median patient age at Z-plasty was 6.8 years (range 3.0-20.1). Of the 130 patients, preoperatively VPI was severe in 73 (56%), mild-to-moderate in 55 (42%), and borderline in 2 (2%). Postoperatively, 105 (81%) of patients achieved adequate (normal or borderline) velopharyngeal competence and 16 (12%) required second operation for residual VPI. The success rate was 84% in nonsyndromic patients, 79% in nonsyndromic Pierre Robin sequence patients, and 58% in syndromic patients. In syndromic children, the speech outcome was significantly worse than in nonsyndromic children (P = 0.014). Complications included wound healing problems in 3 patients (2%), mild infection in 1 patient (1%), postoperative bleeding in 1 (1%), and postoperative fistula in 2 (2%). Conclusion Palatal re-repair with Z-plasty is a safe operation for VPI correction in patients with ICP with a success rate of 81%. In syndromic patients, the procedure did not seem to work as well as in nonsyndromic patients.

OBJECTIVES/HYPOTHESIS Facial functional restoration is one of the main goals in face transplantation. We report the oromyofacial function outcomes of two bimaxillary face transplantation (FT) patients in Helsinki. STUDY DESIGN Outcome Study. METHODS Two male patients, aged 34 and 59, had severe functional facial disabilities following self-inflicted gunshot injuries sustained to their mid and lower faces several years earlier. Both underwent tooth-bearing maxillomandibular face transplantation in 2016 and 2018. We collected data regarding speech, swallowing, sensory recovery, motor recovery, and olfaction prior to transplantation. Patient charts were reviewed from the follow-up period of 4 and 2 years, respectively. RESULTS Speech intelligibility, acceptability, and articulation continued to improve during follow-up for both patients. Voice quality and resonance were mainly normal at last follow-up. Swallowing improved once lip occlusion was regained, with only minor aspiration evident on videofluorography. Both patients had significant improvement in facial mimic muscle function after FT. The first patient who only had buccal sensory nerves connected has only recovered protective facial sensation, whereas our second patient with buccal, infraorbital, and alveolar nerves connected has almost complete facial two-point discrimination. CONCLUSION Both patients have regained satisfactory facial sensory and motor function. Sensory recovery seems to be faster and more precise if multiple sensory nerve coaptations are performed. Swallowing and speech have continued to improve over time although not reaching the level of the normal population. We demonstrate how speech-corrective surgery can safely be performed in a FT patient and can improve speech recovery. LEVEL OF EVIDENCE 4 Laryngoscope, 131:E2643-E2649, 2021.

Objective: Children with Pierre Robin sequence (PRS) and cleft palate have a high rate of velopharyngeal insufficiency (VPI) following primary palatoplasty. Our purpose was to determine the long-term incidence of speech-correcting surgeries (SCSs) and fistula rates in PRS after primary palatoplasty and the influence of possible causal factors. Design: A retrospective single-center, observational chart review study. Participants: After exclusion, the study cohort comprised 78 nonsyndromic PRS children (48 females) born between 1990 and 2009 and treated at the Cleft Palate and Craniofacial Center of Helsinki University Hospital, Finland. Causal factors included gender, surgeon, age at primary palatoplasty, surgical technique, airway obstruction in infancy, and cleft severity. We analyzed the outcome at age 8 years and at data retrieval, with a median follow-up of 14 years (range: 8-27 years). Results: Thirty-four (43.6%) children received SCS by age 8 years, and of the 19 (24.4%) postoperative fistulas, 6 (7.7%) underwent closure. At data retrieval, 37 (47.4%) children had undergone SCS and 8 (10.3%) had a fistula closure. Median age at SCS was 6 years. The results showed no significant association for gender, surgeon, age at primary palatoplasty, surgical technique, cleft severity, or airway obstruction in infancy regarding incidence of SCS, fistulas, or repaired fistulas. Conclusion: Pierre Robin sequence in children is associated with a high incidence of SCS and fistula formation, which necessitates accurate clinical follow-up and observation of speech development. The development of VPI in PRS is complex and most likely involving multiple factors.

The aim of this study is to compare the length of synostosis and segmented intracranial volume (SIV) with age in children with non-syndromic sagittal synostosis. Thirty-three consecutive patients (22 boys) who had been operated by cranial vault remodeling because of sagittal synostosis were compared retrospectively from 3D-CT imaging data sets obtained from volumetric CT. The mean age of the patients at preoperative CT imaging was 0.49 (range 0.13-1.3) years and at 1-year postoperative imaging 1.8 (range 1.3-3) years. The mean interval between preoperative CT imaging and surgery was 0.25 (range 0-0.8) years. Pearson's correlation and Student's t test were used in the statistical analyses. Length of sagittal synostosis correlated positively with age at preoperative CT (r = 0.688, p

Background Sclerotherapy is often the primary treatment for peripheral venous malformations. It is mostly sufficient alone, but can be combined with other endovascular techniques. Despite its mini-invasiveness, it is not without potentially severe complications. Here, we systematically report sclerotherapy complications in trunk and extremity venous malformations. Methods We retrospectively assessed the complications of 127 consecutive patients who had received sclerotherapy for peripheral venous malformation in our tertiary care unit (January 2007–August 2013). We applied the Clavien–Dindo classification to grade the severity of complications. We mostly used detergent sclerosants (85.7%), and less often ethanol (5.7%) or bleomycin (4.2%). In 4.2% of the procedures, we combined glue, coils, endovascular laser or particles to sclerotherapy. Results The overall complication rate per procedure was 12.5%. Most complications (83.3%) were local and managed conservatively. We encountered four severe complications, all related to blood coagulopathy. Subcutaneous lesion location and use of ethanol significantly increased the risk of local complications. Conclusion Sclerotherapy alone or combined with other endovascular techniques is a safe method for local venous malformations with moderate risk for conservatively manageable complications. Blood coagulopathy constitutes a risk for, otherwise rare, severe complications.

Structured Abstract Objectives To evaluate cephalometrically craniofacial morphology in children with operated sagittal synostosis and to compare the findings with age- and sex-matched controls. Setting and Sample Population Forty-two children (37 boys) with operated primary sagittal synostosis were compared retrospectively with age- and sex-matched controls from lateral cephalograms taken at a mean age of 8.1 (range 7.0–8.9) years. Material and Methods The operations had been performed between the ages of 2 months and 6.3 years at three Finnish hospitals. The surgical methods included strip craniectomy, pi-plasty and cranial vault expansion. A paired Student's t-test and Pearson's correlation analysis were used in the statistical analyses. Results Children with operated sagittal synostosis had wide cranial base angles and their mandibles were retrognathic with labially inclined lower incisors relative to the controls. Age at craniosynostosis operation did not correlate with the cranial base angle. Conclusion This study suggests that children with operated sagittal synostosis have minor distinctive morphological features in the cranial base and mandible. Orthodontic evaluation of craniofacial growth is recommended.

Background We aimed to improve management of extremity low-flow vascular malformations by analyzing the histology and imaging of venous malformations (VMs) not responsive to sclerotherapy. Method We reviewed patient records of 102 consecutive patients treated with sclerotherapy for extremity VM in our institution to identify patients who had undergone surgery due to insufficient response. We semi-quantitatively analysed the tissue specimens and compared histological findings to those in preoperative imaging. Result The number of patients operated on was 19 (18.6%); 15 of them had lower-extremity intramuscular lesions. The histological pattern of 13 of these 15 lesions corresponded to angiomatosis of soft tissue (AST). All other lesions treated surgically were VMs. The histology of AST was distinctive but magnetic resonance imaging findings often overlapped with those of VM. Conclusion AST is easily mixed with intramuscular VM. The differentiation of these two entities has therapeutic importance. We emphasize the role of histology in the differential diagnostics of intramuscular slow-flow vascular malformations.

The purpose of this study was to evaluate perinatal features and the rate of cesarean section in children with non-syndromic sagittal synostosis and to compare these with the official statistics. The birth data of 36 consecutive children (25 boys) operated on using cranial vault remodeling because of primary sagittal synostosis were analyzed retrospectively from hospital records. The children were born between 2007 and 2011, and the surgery was performed before the age of 1 year. The official statistics of all Finnish newborns from the year 2010 (n = 61 371) were used as a reference. Chi-square and Fisher's exact tests were used in statistical analyses. The average gestational age of the newborns with sagittal synostosis was 39.8 weeks (reference 39.7 weeks). The average birth weight was 3565.8 g (3540 g) for boys and 3197.2 g (3427 g) for girls, and the average lengths at birth are 51 cm (50.4 cm) and 49.4 cm (49.6 cm), respectively. The average head circumference was 36 cm for both sexes (35.2 and 34.6 cm for reference boys and girls). The mean age of mothers was 30.5 years (30.1 years). The rate of cesarean section was significantly increased 30.5 % (reference 16.6 %), and the rate of suction cup delivery was increased 13.9 % (9 %). In addition, a prolonged or difficult delivery was reported in three childbirths. Newborns with non-syndromic sagittal synostosis appear to be of average birth size and gestational age. The incidences of perinatal complications and cesarean sections were increased with problems occurring in more than half of the childbirths.

Correction of calvarial defects after calvarial vault reconstruction (CVR) is challenging in craniosynostosis patients of advanced age and typically employs autologous bone. Demineralized bone matrix (DBM) is a potential alternative material for autologous bone, but its use has not been extended to correct calvarial defects. CVR patients operated at the Department of Plastic Surgery, Helsinki University Hospital, during 2008-2010 were retrospectively reviewed. Inclusion criteria of the study were CVR patients who received DBM plate, with or without bone dust, on calvarial defects and who had suitable uncovered defect on the contralateral side as control. This study included 17 craniosynostosis and one positional plagiocephaly patient, whose mean age was 6.9 years (range 0.9-19 years). The mean follow-up time was 5.6 years. The fusion degree of all defects was measured from 1 week to 1 year postoperatively using three-dimensional computed tomography (3D CT) images by the OsiriX (R) method. Medical records were reviewed for DBM-related complications. A total of 26 defects were covered with a DBM plate (mean area 11.1 cm(2)) and 26 control defects were identified (mean area 7.8 cm2). The mean fusion degree of the DBM defects was 74% and 54% for the controls (p 30 months) than in younger patients or when used with bone dust. (C) 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Sclerotherapy is one treatment option for head and neck venous malformations (VMs). Evaluation of complication risks is, however, essential to improve its safety. We aimed to systematically report sclerotherapy complications by means of the Clavien-Dindo classification and to distinguish factors predisposing to complications. We identified our institution's head and neck VM patients who received sclerotherapy between 1 January 2007 and 31 August 2013, analyzed patient reports retrospectively, and applied to them the Clavien-Dindo classification. Our 75 VM patients underwent a total of 150 sclerotherapy sessions. The most common sclerosants were 3 % sodium tetradecyl sulfate and polidocanol. Complications occurred in 13 patients (17.3 %) and in 15 sessions (10.0 %); 3 complications required extensive postprocedural treatment and caused permanent morbidity, whereas 12 received conservative treatment. Patients with sclerotherapy complications underwent more treatments (p = 0.009) and more often needed further surgery (p = 0.007). We thus consider sclerotherapy a relatively safe treatment modality for head and neck VMs. To avoid complications, evaluation of VM characteristics and optimal treatment technique in a multidisciplinary team is vital.

Aim Patients with vascular anomalies are often misdiagnosed, leading to delayed or improper treatment. The aim of this study was to evaluate the impact of an interdisciplinary team on the diagnosis and treatment of paediatric patients with vascular anomalies. Methods We reviewed the paediatric patients evaluated by our interdisciplinary team between 2002 and 2012, analysing the referral diagnosis, final diagnosis, patient age, sex, clinical history, laboratory tests, imaging studies and treatments. Results Of the 480 patients who were evaluated, 435 (90.6%) had a vascular anomaly: 30.7% of all patients had a tumour and 55.2% had a malformation. Haemangiomas comprised 93.2% of all tumours, while malformations included capillary (9.8%), lymphatic (30.1%), venous (36.8%), arteriovenous (3.8%) and combined slow–flow (7.9%) malformations. Tumours were initially diagnosed correctly in 89.2% of the patients, but only 38.0% of the malformations were diagnosed correctly. Improper treatment was given to 1.4%, due to incorrect diagnoses. Conclusion This study showed that haemangiomas were likely to be diagnosed correctly, but other tumours and vascular malformations were likely to be misdiagnosed. Misdiagnosis seldom led to improper treatment, but probably led to delayed treatment in many cases. The interdisciplinary approach led to improved diagnostics and treatment. CI - Mattila, K. A., Kervinen, K., Kalajoki-Helmiö, T., Lappalainen, K., Vuola, P., Lohi, J., Rintala, R. J., Pitkäranta, A. and Salminen, P. (2015), An interdisciplinary specialist team leads to improved diagnostics and treatment for paediatric patients with vascular anomalies. Acta Paediatrica. Wiley Online library

BACKGROUND AND PURPOSE: Peripheral AVM is a locally aggressive disease with a high tendency to recur; its treatment is complex, especially in the anatomically delicate head and neck area. Here, we report results of ethanol sclerotherapy for head and neck AVM and discuss its potential use for peripheral AVM. MATERIALS AND METHODS: We retrospectively assessed degree of AVM eradication, complications, and clinical or imaging signs of recurrence for 19 patients treated with ethanol sclerotherapy for head and neck AVM (1 intraosseous, 18 soft-tissue AVMs). RESULTS: Of the 19 patients, 11 had complete eradication of arteriovenous shunting at DSA, with 1 recurrence (mean follow-up 15 months), and for 7 patients, treatment is ongoing. During 59 treatment sessions, 12 patients experienced 14 complications, 1 leading to permanent functional damage. CONCLUSIONS: Ethanol sclerotherapy has potential for complete eradication of head and neck AVM with low recurrence within the first year after completion of treatment. Complete eradication may require several treatment sessions during which complications should be minimized with careful techniques.

Hemangioma is the most common benign tumor in infancy. Over 90% of hemangiomas require no treatment, but there is a need to recognize those that may require even quick measures to secure vital functions or normal development of organs. Propranolol has established itself as the first-line treatment. Pulsed dye laser has proven effective in the treatment of ulcerated hemangiomas. Corticosteroid therapy is applied only rarely, but surgical treatment or angiography and embolization therapy associated with it may sometimes be indicated.

Despite multiple previous studies in the field of vascular anomalies, the mechanism(s) leading to their development, progression and maintenance has remained unclear. In this study, we have characterized the expression levels of vascular endothelial growth factors and their receptors in 33 human vascular anomalies. Analysis with quantitative real-time PCR and gene-specific assays showed higher expression of neuropilin-2 (NRP2) and VEGF-receptor-3 (VEGFR-3) mRNAs in vascular malformations (VascM) as compared to infantile hemangiomas (Hem). In addition, the expression levels of PlGF and VEGF-C mRNA were significantly higher in venous VascM when compared to the other VascM and Hem. Higher expression of NRP2 and VEGFR-3 were confirmed by immunohistochemistry. To further study the importance of NRP2 and VEGFR-3, endothelial cell (EC) cultures were established from vascular anomalies. It was found that NRP2 and VEGFR-3 mRNA levels were significantly higher in some of the VascM ECs as compared to human umbilical vein ECs which were used as control cells in the study. Furthermore, adenoviral delivery of soluble decoy NRP2 prevented the proliferation of ECs isolated from most of the vascular anomalies. Our findings suggest that NRP2 functions as a factor maintaining the pathological vascular network in these anomalies. Thus, NRP2 could become a potential therapeutic target for the diagnosis and treatment of vascular anomalies.