Operative Management of Intra-abdominal Lymphatic Malformations in Children: A Single Tertiary Center Experience.

BACKGROUND: Intra-abdominal lymphatic malformations (LMs) are relatively rare congenital anomalies and can be divided into intra- and retroperitoneal subgroups. This study aims to evaluate the outcomes after surgical resection of intraperitoneal LMs in children. METHODS: The records of all patients ≤16 years of age with intraperitoneal LMs managed at our tertiary center between 2007-2022 were reviewed. Patients with retroperitoneal LMs were excluded. Our preferred approach is surgical exploration for large (>5 cm), symptomatic lesions if they are potentially resectable on imaging. RESULTS: A total of 12 patients (10 males) were diagnosed with intraperitoneal LMs located in the small bowel mesentery or omentum at a median age of 6.6 (range, 0.6-14.4) years. Ten (83%) patients presented with acute symptoms, including abdominal pain (n = 8; 67%) and vomiting (n = 3; 25%). Two (17%) intraperitoneal LMs were found on imaging performed for other reasons. Surgical exploration was performed in 11/12 (92%) cases. Intestinal volvulus around a mesenteric macrocyst had occurred in 4 (36%) patients. Complete macroscopic resection was achieved in 10/11 (91%) patients. Most lesions were localized to a short intestinal segment. One mixed type LM with an extensive mesenteric involvement was biopsied as the lesion was deemed to be unresectable in preoperative imaging and the diagnosis was initially unclear. There was one recurrence (8%) during postoperative follow-up on imaging (median 3.6 (range, 1.5-6.9) years) but the patient has remained asymptomatic and not undergone interventions. 6/8 (75%) of screened intraperitoneal LMs were positive for a somatic PIK3CA mutation. CONCLUSIONS: Most large, pedunculated macrocystic LMs in the small bowel mesentery or omental location were amenable to macroscopic resection. Intraperitoneal LMs tend to present with acute symptoms including a risk for intestinal volvulus based on anatomical location. Our results suggest low recurrence rates or need for further interventions over follow-up. LEVEL OF EVIDENCE: III.

ErbB signaling is a potential therapeutic target for vascular lesions with fibrous component.

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 the 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, the expression and secretion of transforming growth factor A (TGFA) in ECs or intervascular stromal cells in AST and VM lesions. TGFA induced secretion of vascular endothelial growth factor (VEGF-A) in paracrine fashion, 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 a 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, GeneCellNano Flagship program, and Department of Musculoskeletal and Plastic Surgery, Helsinki University Hospital.

Outcomes at a Mean of 13 Years After Proximal Humeral Fracture During Adolescence.

BACKGROUND: The long-term outcomes of a proximal humeral fracture during adolescence are not well known. We investigated the course of primary treatment for these injuries and the long-term outcomes in adulthood, comparing the outcomes with those from age-matched controls. We also compared outcomes after operative and nonoperative treatment via propensity score matching. METHODS: We included children who sustained a proximal humeral fracture between the ages of 10.0 and 16.0 years and underwent treatment between 1995 and 2005. Data from primary treatment episodes were extracted from patient files. The patients were invited to a follow-up visit with outcome assessment and radiographs or to a telephone interview if unable to attend. The primary outcome was the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. The secondary outcomes were the Simple Shoulder Test (SST), pain at rest and with strenuous use, shoulder range of motion, strength measurements, health-related quality of life (15D), and harms. Participant results were compared with the normal values of an age-matched population. The effect of operative treatment was assessed using propensity score matching and the average treatment effect was calculated. RESULTS: This study included 209 patients (210 fractures). The mean follow-up (and standard deviation) was 13.1 ± 3.2 years. Outcome data were obtained from 152 participants (153 fractures); 78 participants attended the follow-up visit. The primary treatment episodes were uneventful. The mean scores were 2.5 (95% confidence interval [CI], 1.8 to 3.3 [range, 0 to 13]) for the DASH and 11.7 (95% CI, 11.5 to 11.8 [range, 8 to 12]) for the SST. Other outcomes were similarly good. There were no differences in function compared with the normal population values. Propensity matching showed no treatment effect for operative treatment compared with nonoperative treatment. CONCLUSIONS: Proximal humeral fractures of adolescents heal well and rarely result in impairments whether treated operatively or nonoperatively. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Venous Malformations and Blood Coagulation in Children.

INTRODUCTION: Venous malformations (VMs) are congenital low-flow lesions with a wide spectrum of clinical manifestations. An increasing number of studies link VMs to coagulation abnormalities, especially to elevated D-dimer and decreased fibrinogen. This condition, termed localized intravascular coagulopathy (LIC), may pose a risk for hemostatic complications. However, detailed data on the laboratory variables for coagulation and fibrinolytic activity in VM patients are limited. We addressed this question by systematically analyzing the coagulation parameters in pediatric VM patients. METHODS: We included 62 patients (median age 11.9 years) with detailed laboratory tests for coagulation and fibrinolytic activity at a clinically steady phase. We assessed clinical and imaging features of VMs and their correlations with coagulation and fibrinolysis variables using patient records and MRI. RESULTS: D-dimer was elevated in 39% and FXIII decreased in 20% of the patients, as a sign of LIC. Elevated D-dimer and decreased FXIII were associated with large size, deep location, and diffuse and multifocal VMs. FVIII was elevated in 17% of the patients and was associated with small VM size, superficial and confined location, discrete morphology, and less pain. Surprisingly, antithrombin was elevated in 55% of the patients but without associations with clinical or other laboratory variables. CONCLUSIONS: LIC was common in pediatric patients with VMs. Our results provide a basis for when evaluating the risks of hemostatic complications in children with VMs. Further research is warranted to explore the mechanisms behind coagulation disturbances and their relation to clinical complications.

A case of congenital tuberculosis with a favorable outcome in a full term neonate.

This case of congenital tuberculosis (TB) emphasizes that TB should be suspected in newborns whose parents are from areas with high incidence of TB or who present with symptoms of an infection unresponsive to wide-spectrum antibiotics.

Intra-articular venous malformation of the knee in children: magnetic resonance imaging findings and significance of synovial involvement.

BACKGROUND: Intra-articular venous malformations of the knee are an uncommon cause of unilateral knee pain in children. Timely diagnosis is important because lesions with intrasynovial involvement can lead to joint space hemorrhage and secondary cartilage damage. OBJECTIVE: To describe our tertiary center's experience of diagnostics and typical magnetic resonance imaging (MRI) findings. MATERIALS AND METHODS: A retrospective review of all patients ≤16 years of age managed for intra-articular venous malformations of the knee at our institution between 2002 and 2018. RESULTS: Of 14 patients (8 male), the mean age at presentation was 6 years (range: 0-14 years). The most common clinical findings were unilateral knee pain (93%), joint swelling (79%), quadriceps atrophy (50%) and a limited range of motion (29%). Cutaneous manifestations were present in four patients (29%). Contrast-enhanced MRI was available in all cases. After initial MRI, a vascular anomaly etiology had been identified in 11 cases (79%), and correctly reported as a venous malformation in 6 (55%). Three patients received entirely different diagnoses (arthritis, tumor or pigmented villonodular synovitis). Three of seven patients with intrasynovial lesions had established chondropathy at diagnosis. Two patients with lesions of the suprapatellar fat pad had intrasynovial involvement that was not visualised on MRI. CONCLUSION: Although MRI usually permits the diagnosis, clinical awareness of these lesions is important for optimal imaging, accurate interpretation and timely diagnosis. Involvement of the intrasynovial cavity carries a risk of hemarthrosis and progressive chondropathy that may be underestimated by MRI.

Plunging ranula - patient characteristics, treatment, and comparison between different populations.

OBJECTIVES: To review our clinical experience and characteristics of Finnish patients with plunging ranula and compare our results with reports from other populations. DESIGN: A retrospective study from the electronic hospital records between 2005 and 2016. SETTING: The Department of Otorhinolaryngology and Head and Neck Surgery of Helsinki University Hospital, Finland. RESULTS: We describe the characteristics and treatment of 41 patients with MRI-confirmed plunging ranula. Most of our patients were young adults and 88% of them were male. Surgery and sclerotherapy were used for treatment. CONCLUSIONS: The vast majority of Finnish plunging ranula patients in our cohort were male, suggesting significant population-related differences in plunging ranula gender distribution. Transoral surgery seemed to result in lowest recurrence rate and was the most common treatment in our clinic.

Angiomatosis of soft tissue as an important differential diagnosis for intramuscular venous malformations.

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.

Sclerotherapy complications of peripheral venous malformations.

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.

Complications of sclerotherapy for 75 head and neck venous malformations.

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.

Testicular tumors in children and adolescents.

OBJECTIVE: To analyze the spectrum of testicular tumors in children in an unselected population-based series, as well as the results of testis-preserving surgery. PATIENTS AND METHODS: Our hospital database was analyzed for operations for testicular tumors from 1981 to 2006. The clinical data and findings during follow up (4.7 years) were recorded. RESULTS: Thirty-four patients were operated on because of testicular tumors. In 23 (68%) the tumor was benign: benign teratoma (16), Leydig-cell tumor (2), epidermoid cyst (2), Sertoli-cell tumor (1), cystic dysplasia (1), intratesticular focal fibrosis (1). Eleven patients (32%) had a malignant tumor: yolk-sac tumor (6), embryonal carcinoma (5). Twenty out of the 26 (77%) prepubertal boys had a benign tumor in contrast to only three of the eight (38%) adolescent males (P=0.079). Testis-preserving surgery was performed in 10 patients. In eight, the tumor was curatively excised and remaining testis preserved. Two patients with benign teratoma had a recurrence due to incomplete primary resection. In one patient who underwent orchiectomy for benign teratoma, two metachronous teratomas were detected in the contralateral testis 6 years after primary surgery. CONCLUSIONS: In children, most testicular tumors are benign, especially before puberty. If testis-preserving surgery is contemplated, complete excision of the tumor should be ascertained. The possibility of metachronous bilateral tumors should be considered in the follow up of testicular teratomas.