The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations.

To elaborate expert consensus patient pathways to guide patients and physicians toward efficient diagnostics and management of patients with venous malformations. Methods: VASCERN-VASCA (https://vascern.eu/) is a European network of multidisciplinary centers for Vascular Anomalies. The Nominal Group Technique was used to establish the pathways. Two facilitators were identified: one to propose initial discussion points and draw the pathways, and another to chair the discussion. A dermatologist (AD) was chosen as first facilitator due to her specific clinical and research experience. The draft was subsequently discussed within VASCERN-VASCA monthly virtual meetings and annual face-to-face meetings. Results: The Pathway starts from the clinical suspicion of a venous type malformation (VM) and lists the clinical characteristics to look for to support this suspicion. Strategies for subsequent imaging and histopathology are suggested. These aim to inform on the diagnosis and to separate the patients into 4 subtypes: (1) sporadic single VMs or (2) multifocal, (3) familial, multifocal, and (4) combined and/or syndromic VMs. The management of each type is detailed in subsequent pages of the pathway, which are color coded to identify sections on (1) clinical evaluations, (2) investigations, (3) treatments, and (4) associated genes. Actions relevant to all types are marked in separate boxes, including when imaging is recommended. When definite diagnoses have been reached, the pathway also points toward disease-specific additional investigations and recommendations for follow up. Options for management are discussed for each subtype, including conservative and invasive treatments, as well as novel molecular therapies. Conclusion: The collaborative efforts of VASCERN-VASCA, a network of the 9 Expert Centers, has led to a consensus Diagnostic and Management Pathways for VMs to assist clinicians and patients. It also emphasizes the role of multidisciplinary expert centers in the management of VM patients. This pathway will become available on the VASCERN website (http://vascern.eu/).

The VASCERN-VASCA working group diagnostic and management pathways for lymphatic malformations.

Lymphatic malformations (LMs) are developmental defects of lymphatic vessels. LMs are histologically benign lesions, however, due to localization, size, and unexpected swelling, they may cause serious complications that threaten vital functions such as compression of the airways. A large swelling of the face or neck may also be disfiguring and thus constitute a psychological strain for patients and their families. LMs are also highly immunologically reactive, and are prone to recurrent infections and inflammation causing pain as well as chronic oozing wounds. The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) is dedicated to gathering the best expertise in Europe. There are only few available guidelines on management and follow up of LMs, which commonly focus on very specific situations, such as head and neck LM (Zhou et al., 2011). It is still unclear, what constitutes an indication for treatment of LMs and how to follow up the patients. The Vascular Anomalies Working Group (VASCA-WG) of VASCERN decided to develop a diagnostic and management pathway for the management of LMs with a Nominal Group Technique (NGT), a well-established, structured, multistep, facilitated group meeting technique used to generate consensus statements. The pathway was drawn following 2 face-to-face meetings and multiple web meetings to facilitate discussion, and by mail to avoid the influence of most authoritative members. The VASCA-WG has produced this opinion statement reflecting strategies developed by experts and patient representatives on how to approach patients with lymphatic malformations in a practical manner; we present an algorithmic view of the results of our work.

The VASCERN-VASCA working group diagnostic and management pathways for severe and/or rare infantile hemangiomas.

The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN), is dedicated to gathering the best expertise in Europe and provide accessible cross-border healthcare to patients with rare vascular diseases. Infantile Hemangiomas (IH) are benign vascular tumors of infancy that rapidly growth in the first weeks of life, followed by stabilization and spontaneous regression. In rare cases the extent, the localization or the number of lesions may cause severe complications that need specific and careful management. Severe IH may be life-threatening due to airway obstruction, liver or cardiac failure or may harbor a risk of functional impairment, severe pain, and/or significant and permanent disfigurement. Rare IHs include syndromic variants associated with extracutaneous abnormalities (PHACE and LUMBAR syndromes), and large segmental hemangiomas. There are publications that focus on evidence-based medicine on propranolol treatment for IH and consensus statements on the management of rare infantile hemangiomas mostly focused on PHACES syndrome. The Vascular Anomalies Working Group (VASCA-WG) decided to develop a diagnostic and management pathway for severe and rare IHs with a Nominal Group Technique (NGT), a well-established, structured, multistep, facilitated group meeting technique used to generate consensus statements. The pathway was drawn following two face-to-face meetings and in multiple web meetings to facilitate discussion, and by mail to avoid the influence of most authoritative members. The VASCA-WG has produced this opinion statement reflecting strategies developed by experts and patient representatives on how to approach patients with severe and rare IH in a practical manner; we present an algorithmic view of the results of our work.

Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network.

Extensive lymphatic malformations (LMs) of the head and neck region may require tracheostomy to secure the airway. Treatment of these life-threatening LMs is usually multimodal and includes sclerotherapy and surgery, among others. Recently, systemic therapy with sirolimus has been introduced as an effective treatment for venous and lymphatic malformations; its efficacy and safety profile in patients with extensive LM requiring tracheostomy are, however, as yet not fully known. We performed a retrospective, multicenter review and identified 13 patients with an extensive LM of the head and neck region, who previously underwent placement of tracheostomy and subsequently received sirolimus treatment with the aim to improve the local respiratory situation and remove the tracheostomy. Under sirolimus therapy, tracheostomy could be reversed in 8/13 (62%) patients, a further 2/13 (15%) patients improved markedly, and removal of the tracheostomy was planned at the time of writing, while 3/13 (23%) patients showed insufficient or absent response to sirolimus, rendering tracheostomy reversal not feasible. The median duration of sirolimus treatment until removal of tracheostomy was 18 months (range, 8 months to 5.6 years). Adverse events of sirolimus therapy were common [10/13 (77%) patients], yet the majority of these were mild [9/10 (90%) patients] and only one severe adverse event was recorded, with ulceration and necrosis at a catheter insertion site. In conclusion, sirolimus can be considered an effective and safe salvage treatment in patients with extensive LM even after placement of a tracheostomy, as closure of the latter was possible in the majority of patients (62%) of our retrospective cohort. A better understanding of when to start sirolimus therapy, of the duration of treatment, and of factors allowing the prediction of treatment response will require further investigation.

Long-term health-related quality of life in children with lymphatic malformations treated with sclerotherapy generally matched age-appropriate standardised population norms.

AIM: We assessed the long-term health-related quality of life (HRQoL) of children who received sclerotherapy for lymphatic malformations. This treatment involved injecting drugs into the blood vessels to make them shrink. METHODS: Our cross-sectional study retrospectively reviewed patients who received OK-432 sclerotherapy injections at Karolinska University Hospital, Stockholm, Sweden, from 1998 to 2013. We studied 49 patients (63% female) aged 8-18 at least five years after their first injection. HRQoL was assessed with the KIDSCREEN-52 questionnaire and a study-specific questionnaire addressed disease consequences and patient satisfaction. We determined associations between HRQoL and disease and treatment and the patient's sex. RESULTS: Overall HRQoL paralleled age-appropriate norms in the general population, but some subgroups had lower levels. Regression-based estimates showed that larger numbers of injections were negatively associated with HRQoL in the dimensions autonomy, parent relations and home life, financial resources and school environment (p = 0.01-0.03). Malformations in the head and neck area were negative predictors across dimensions and were strongest for psychological well-being (p = 0.009), parent relations and home life (p = 0.017) and school environment (p = 0.006). CONCLUSION: Despite generally positive outcomes, multiple injections and malformations in the head and neck were associated with impaired HRQoL.

Surgical excision is the treatment of choice for cervical lymphatic malformations with mediastinal expansion.

BACKGROUND: Lymphatic malformations (LMs) in the mediastinum are uncommon. However, cervical LMs may expand into the mediastinum. The aim of this study was to review our experience with the management of patients with LMs involving the mediastinum and to propose a treatment algorithm to guide the management of these rare malformations. MATERIAL AND METHODS: This was a descriptive retrospective chart review of all patients with LMs involving the mediastinum treated at our Institution between 2009 and 2015. We collected demographic data, data on investigations, management, and complications of the treatment, as well as outcomes at follow-up. Complications were defined and described according to the Clavien-Dindo classification. The clinical outcome was assessed using a clinical assessment scale. RESULTS: The cohort consisted of seven patients. Airway compromise at the time of diagnosis was seen in 4 patients. Three patients had anatomical compression of the trachea and two patients had sub-total compression of the right lung. All three patients with tracheoscopy-verified compression of the trachea had compromise of the distal trachea, and a tracheostomy would not have been protective. All patients received sclerotherapy. The median time with mechanical ventilation at the neonatal intensive care unit after each sclerotherapy was eleven days (range 8-31). Each patient received sclerotherapy in median three times (range 1-9). Five of the patients (71%) were operated with excision of the LM in the mediastinum. Two of the patients were operated primarily and three patients were operated after major complications to sclerotherapy. The patients treated with sclerotherapy and the operated patients had comparable amount of mild complications, Clavien-Dindo grade I-II complications. Severe complications, Clavien-Dindo grade III-IV, were seen five times more commonly after sclerotherapy than after surgery. The clinical outcome was excellent for the operated patients and fair to good for the patients receiving only sclerotherapy. CONCLUSION: Patients with cervical LM involving the mediastinum represent a high-risk group with respect to the severity of complications following sclerotherapy. The swelling is unpredictable and requires extended observation at an intensive care unit with ventilation support. Tracheostomy does not prevent tracheal compression in mediastinal LM, as the malformation may compress trachea distal to the stoma. Surgical resection of the LM in the mediastinum is recommended, with the possibility of intra-operative sclerotherapy as an adjunctive. LEVEL OF EVIDENCE: IV.

TLR4 preconditioning is associated with low success of OK-432 treatment for lymphatic malformations in children.

PURPOSE: We have recently shown that the relative TLR4 expression on monocytes of low responding pediatric patients after OK-432 treatment is significantly reduced after stimulation with lipopolysaccharide (LPS) compared with high responding children. The aim of this study was to perform further analysis to explain this observation. METHODS: Monocytes from children with high (HR, n = 5) and low response (LR, n = 6) after previous OK-432 treatment were stimulated with LPS for 20 h and analyzed with fluorescence-activated cell sorting (mean fluorescence intensity, MFI; level of significance P ≤ 0.05). RESULTS: Mean MFI after LPS stimulation was comparable in both groups (HR 1142 ± 652 units, LR 839 ± 427 units, P = 0.85). Significant changes after LPS stimulation are explained by higher pre-stimulation values in the LR group compared with the HR group (950 ± 718 vs. 477 ± 341, P = 0.25) with considerable differences of the mean expression changes after LPS stimulation (HR 665 ± 683 vs. LR -111 ± 605, P = 0.08). CONCLUSION: The previously shown reduced TLR4 upregulation on monocytes after LPS stimulation in the LR group compared with the HR group can be primarily explained by TLR preconditioning. This observation implies the use of absolute values with definite thresholds.

Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children.

BACKGROUND: Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to <50% of the original size. It has been suggested that the OK-432 effect is highly dependent on the Toll-like receptor (TLR) 4-dependent expression of TLR7 in antigen-presenting cells. We hypothesized that the ability for TLR expression in monocytes after treatment with the TLR4-ligand lipopolysaccharide (LPS) can be used to predict successful OK-432 treatment. METHODS: Blood was taken from children with low responder (LR, n = 6) and high responder (HR, n = 5) of previous OK-432 treatment. Monocytes were stimulated with LPS for 20 h. TLR expression was analyzed with fluorescence-activated cell sorting (mean fluorescence intensity). The level of significance was P ≤ 0.05. RESULTS: The mean age of patients in the HR group was 1.4 ± 0.9 y and in the LR group 2.8 ± 2.9 y (P = 0.31). The mean TLR4 upregulation after LPS stimulation in the HR group was significantly higher than in the LR group (factor 3.6 versus factor 1 compared with nonstimulated controls; P = 0.037). The mean TLR7 expression did not show significant differences between the groups. CONCLUSIONS: Dynamic TLR4 expression represents most probably a predictive parameter for the treatment of lymphatic malformations with OK-432 and should be further investigated.

Supraumbilical incision with U-u umbilicoplasty for congenital duodenal atresia: the Stockholm experience.

BACKGROUND: Minimizing scars has become a major concern in pediatric surgery. Since Tan and Bianchi introduced the minimally invasive umbilical incision for Ramstedt's pyloromyotomy, their technique has been adopted for a variety of neonatal abdominal conditions. The aim of this study was to evaluate a modification of the skin incision. MATERIAL AND METHODS: We have modified Bianchi's original technique to access the abdomen through the linea alba by introducing a novel U-to-u umbilicoplasty and compare the results with the traditional transverse incision. This new approach improves the abdominal access and is easy to perform. RESULTS: The operating time with the U-to-u umbilicoplasty is not longer than in standard transverse laparotomy, the access to the abdomen is more than adequate, the incidence of postoperative complications is similar and the cosmetic results are excellent. CONCLUSIONS: We conclude that the umbilical approach with this novel U-to-u umbilicoplasty to treat congenital duodenal obstruction in the newborn is a safe and effective method and a good alternative to the standard transverse laparotomy approach.

Single-site incision laparoscopic cholecystectomy in children: a single-center initial experience.

Laparoscopic cholecystectomy is the standard approach in most pediatric surgical centers. In an attempt to further minimize the surgical trauma and improve cosmetic outcome, new techniques with a single incision through the umbilicus have been proposed. There are still few reports concerning this technique in the pediatric population. We evaluated the feasibility of the single incision for laparoscopic cholecystectomy in children. We performed the operation in 10 patients, with a mean age of 12 years, mean operating time of 122 minutes, and mean hospital stay of 2 days. No complications occurred, and no conversion to open surgery was needed. In 1 patient, an extra 5-mm port was necessary. The cosmetic results were very satisfactory. In our experience, despite its technical difficulty and initial learning curve, single-incision laparoscopic cholecystectomy in the pediatric population is a safe and feasible method.