Somatic activating BRAF variants cause isolated lymphatic malformations.

Somatic activating variants in PIK3CA, the gene that encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been previously detected in ∼80% of lymphatic malformations (LMs).1 , 2 We report the presence of somatic activating variants in BRAF in individuals with LMs that do not possess pathogenic PIK3CA variants. The BRAF substitution p.Val600Glu (c.1799T>A), one of the most common driver mutations in cancer, was detected in multiple individuals with LMs. Histology revealed abnormal lymphatic channels with immunopositivity for BRAFV600E in endothelial cells that was otherwise indistinguishable from PIK3CA-positive LM. The finding that BRAF variants contribute to low-flow LMs increases the complexity of prior models associating low-flow vascular malformations (LM and venous malformations) with mutations in the PI3K-AKT-MTOR and high-flow vascular malformations (arteriovenous malformations) with mutations in the RAS-mitogen-activated protein kinase (MAPK) pathway.3 In addition, this work highlights the importance of genetic diagnosis prior to initiating medical therapy as more studies examine therapeutics for individuals with vascular malformations.

Computational fluid dynamics modeling aiding surgical planning in a toddler with Parkes Weber syndrome.

Parkes Weber syndrome is a fast-flow and slow-flow vascular anomaly with limb overgrowth that can lead to congestive heart failure and limb ischemia. Current management strategies have focused on symptom management with focal embolization. A pediatric case with early onset heart failure is reported. We discuss the use of computational fluid dynamics (CFD) modeling to guide a surgical management strategy in a toddler with an MAP2K1 mutation.

Transforaminal intrathecal delivery of nusinersen for older children and adults with spinal muscular atrophy and complex spinal anatomy: an analysis of 200 consecutive injections.

BACKGROUND: Nusinersen is the only approved treatment for all spinal muscular atrophy (SMA) subtypes and is delivered intrathecally. Distorted spinal anatomy and instrumentation preclude standard approaches for intrathecal access, necessitating alternative techniques for delivery. The purpose of this study is to report technical success and adverse events of transforaminal intrathecal delivery of nusinersen. METHODS: 28 patients, mean age 24.1±9.8 years (range 10.0-51.0 years), with intermediate or late onset SMA, underwent a combined 200 transforaminal nusinersen injections. All patients had osseous fusion or spinal instrumentation precluding standard posterior access routes. Patients who underwent nusinersen injections using a technique other than transforaminal lumbar puncture (n=113) were excluded. Technical success, adverse events (AEs) and radiation exposure were recorded. RESULTS: 200 (100%) procedures were technically successful; 6 (3%) required a second level of attempt for access. 187 (93.5%) interventions were completed using cone beam computed tomography (CBCT) with two-axis fluoroscopic navigational overlay. 13 (6.5%) procedures were performed with fluoroscopic-guidance only at subsequent sessions. There were 8 (4.0%) mild AEs and 2 (0.5%) severe AEs; one patient received antibiotics for possible traversal of the large bowel but did not develop meningitis, and one patient developed aseptic meningitis. Mean air kerma was 74.5±161.3 mGy (range 5.2-1693.0 mGy). CONCLUSION: Transforaminal intrathecal delivery of nusinersen is feasible and safe for gaining access in patients with distorted spinal anatomy. The use of CBCT delineates anatomy and optimizes needle trajectory during the initial encounter, and may be used selectively for subsequent procedures.

Intrahepatic veno-venous collateralization and misrepresentative hepatic venous pressure gradients in children.

BACKGROUND: Accurate and reproducible means of measuring the portosystemic gradient are essential for risk stratification and treatment of portal hypertension. OBJECTIVE: To report the reliability of hepatic venous pressure gradients in children with intrahepatic veno-venous collateralization. MATERIALS AND METHODS: Between January 2012 and December 2019 (96 months), 39 patients with native livers underwent wedge hepatic venography and hepatic venous pressure gradient measurements at a tertiary pediatric center. All archived images were reviewed for balloon isolation of the hepatic vein and hepatic vein-to-hepatic vein (HV-HV) collaterals. HV-HV collaterals were categorized as present on the basis of non-catheterized segmental venous opacification despite appropriate balloon isolation. Hepatic venous pressure gradient was defined as the difference of wedge and free hepatic venous pressures. Wedge portosystemic gradient was defined as the difference between wedge hepatic venous pressure and right atrial (RA) pressures. For patients subsequently undergoing portal venous catheterization, portosystemic gradient was defined as the difference between main portal vein and RA pressures. RESULTS: Thirteen of 39 (33.3%) patients demonstrated HV-HV collaterals on wedge hepatic venography. The mean hepatic venous pressure gradient was 5.2±3.8 mmHg (range: 0-15 mmHg). The mean hepatic venous pressure gradient was 3.6±2.6 mmHg (range: 0-9 mmHg) in the presence of HV-HV collaterals and 5.9±4.2 mmHg (range: 1-15 mmHg) in the absence of HV-HV collaterals (P=0.043). Twelve (30.8%) patients were found to have varices: 10 gastroesophageal, 1 rectal and 1 stomal. The mean hepatic venous pressure gradient in patients with varices was 5.4±47 mmHg (range: 0-15 mmHg). For patients with varices, mean hepatic venous pressure gradient was 3.0±2.7 mmHg (range: 0-9 mmHg) in the presence of HV-HV collaterals and 10.3±4.1 mmHg (range: 5-15 mmHg) in the absence of HV-HV collaterals (P=0.004). Four (10.3%) patients had extrahepatic portal vein occlusion: 3 with cavernous transformation and 1 with type Ib Abernethy malformation. All patients with extrahepatic portal vein occlusion demonstrated HV-HV collaterals compared with 8 of 35 (22.9%) patients without extrahepatic portal vein occlusion (P=0.002). Four of 39 (10.3%) patients underwent direct portal pressure measurements: 3 via transhepatic and 1 via trans-splenic portal access. All had demonstrated HV-HV collaterals on wedged imaging. One had extrahepatic portal vein occlusion. The mean time between wedge portosystemic gradient and portosystemic gradient measurement was 3.75 days (range: 0-8 days). The mean wedge portosystemic gradient was 4.5±3.1 mmHg (range: 2-9 mmHg) and the mean portosystemic gradient was 14.5±3.7 mmHg (range: 12-20 mmHg) (P=0.006). CONCLUSION: HV-HV collateralization is frequently observed in children undergoing wedged portal venography and leads to misrepresentative hepatic venous pressure gradients. All patients undergoing hepatic venous pressure gradient measurement should have wedged venography to identify HV-HV collaterals and to qualify measured pressures. Additional techniques to obtain representative pressures in the presence of HV-HV collaterals warrant further investigation.

Microwave ablation of osteoid osteoma: initial experience and efficacy.

BACKGROUND: Image-guided percutaneous microwave ablation has been used to treat adult osteoid osteomas but has not been thoroughly evaluated in the pediatric population. OBJECTIVE: To evaluate the technical feasibility and clinical efficacy of microwave ablation to treat osteoid osteomas in pediatric patients. MATERIALS AND METHODS: The electronic medical record and imaging archive were reviewed for 24 consecutive patients who had undergone microwave ablation of osteoid osteomas between January 1, 2015, and May 31, 2018, at a single tertiary care pediatric hospital. All patients were diagnosed by clinical and imaging criteria, and referred by a pediatric orthopedic surgeon after failing conservative management with pain medication. The average age of the patients was 13.3 years (range: 3-18 years), and the average size of the osteoid osteoma nidus was 8.8 mm (range: 5-22 mm). Technical success was defined as placement of the microwave antenna at the distal margin of the lesion nidus and achievement of the target ablation temperature. Clinical findings were assessed pre- and post-ablation and clinical success was defined as complete relief of pain without pain medication at 1-month follow-up. The number and severity of complications were also documented. RESULTS: Clinical success was achieved in 100% of patients (24/24), with all reporting complete cessation of pain medication use 1 week after treatment and 0/10 pain at 1 month. There were 4 minor complications (17%) including access site numbness and a minor soft-tissue infection. There were no major complications. CONCLUSION: Microwave ablation is a technically feasible and clinically effective treatment for pediatric osteoid osteomas.

Benefits and risks of protocol biopsies in pediatric renal transplantation.

Protocol biopsies are defined as sampling of allograft tissue at predetermined times regardless of function. This procedure can be justified due to the lack of non-invasive methods to reliably diagnose rejection (acute or subclinical). Changes in creatinine are not seen with subclinical rejection or early acute rejection and do not always correlate with efficacy of treatment. Parents and providers are still hesitant to pursue protocol biopsy due to the potential complications and lack of definitive evidence of a benefit from doing this procedure. Importantly, the rate of transplant renal biopsy complications requiring additional intervention is low. It is unclear if detection and treatment of subclinical rejection detected on protocol biopsy will lead to improved graft survival. Our goal is to review the literature on this topic and share some of the experience in our center. Definition, indications, and complications of diagnostic transplant renal biopsies are not included in this review.

Cone-beam computed tomography guidance with navigational overlay for percutaneous lung nodule biopsy.

BACKGROUND: Cone-beam CT is increasingly used in pediatric interventional radiology procedures. However, the feasibility or safety of using this mode of imaging guidance for percutaneous lung nodule biopsy in children has not been assessed. OBJECTIVE: To retrospectively evaluate safety and diagnostic accuracy of percutaneous lung nodule biopsy in people treated at a pediatric hospital using cone-beam CT with navigational overlay. MATERIALS AND METHODS: Thirty-six consecutive patients from two large tertiary-care children's hospitals with lung nodules of 48 mm or smaller underwent percutaneous lung nodule biopsy using cone-beam CT with navigational overlay. We evaluated patient demographics, pre- and post-biopsy diagnoses, number of biopsy passes, complications, radiation exposure and technical success. RESULTS: Percutaneous lung nodule biopsy was performed for 37 nodules in 36 patients (23 males, 13 females, median age 15.5 years, range 8 months to 23 years). One patient underwent biopsy of two nodules at a single procedure. Median patient weight was 55 kg (range 8-97 kg). Pre-biopsy diagnoses included metastatic sarcoma or other solid tumor (n=11), leukemia/lymphoma (n=13), infection (n=10), chronic granulomatous disease (n=2) and post-transplant lymphoproliferative disorder (PTLD; n=1). Mean number of passes was 5 (range 2-15). Mean pre-procedure international normalized ratio (INR) was 1.1 and platelet count 193 × 109/L. Diagnostic specimens were obtained in 32 of 36 patients (89%). Thirteen complications were encountered in 12 patients (33% of cohort), including 9 pneumothoraces (4 requiring chest tubes); 1 hemothorax, which required a chest tube; and 3 self-limited pulmonary hemorrhages. Mean and median radiation doses were as follows: fluoroscopy time 3 min and 2.4 min, dose-area product (DAP) (recorded in 31 patients) 23,402 Gy·cm2 and 12,453 Gy·cm2, and air kerma 88 mGy and 58 mGy. CONCLUSION: Percutaneous lung nodule needle biopsy can be performed accurately using cone-beam CT with navigational overlay.

An Interventionalist's Guide to Hemoptysis in Cystic Fibrosis.

Massive hemoptysis occurs in a minority of patients with cystic fibrosis, with an annual incidence of 1%. Although rare, massive hemoptysis can be a severe and potentially fatal complication of this disease. Beyond the acute life-threatening event, hemoptysis in patients with cystic fibrosis has been associated with faster decline in lung function, accelerated need for lung transplant, and increased mortality. The bronchial arteries are the culprit vessels in over 90% of cases of hemoptysis. This normally quiescent vascular system undergoes remarkable hypertrophy, collateralization, and angiogenesis before the onset of hemoptysis, introducing numerous pitfalls for the interventionalist. However, in experienced hands, bronchial artery embolization is a safe and potentially lifesaving therapy. Preprocedural noninvasive imaging, specifically computed tomographic angiography, has been repeatedly validated for helping to localize the likely site of bleeding, characterizing pertinent arterial anatomy, and promoting efficient and effective intervention; it has been recommended for all stable patients with hemoptysis. Success in the angiographic suite requires a thorough understanding of normal and variant bronchial arterial anatomy, appropriate patient selection, and a meticulous embolization technique. A meticulous approach to imaging and intervention, conscientious of both visualized and nonvisualized collateral pathways and nontarget vessels, can minimize potentially devastating complications. This review summarizes the current literature, modern procedural techniques, and emerging controversies, serving to guide an evolving approach to management of patients with cystic fibrosis and hemoptysis. ©RSNA, 2018.

Combined glue embolization and excision for the treatment of venous malformations.

BACKGROUND: The purpose of this study was to evaluate safety, technical success, and clinical outcomes of treatment for venous malformations using n-BCA glue embolization immediately prior to excision. Sixty three patients (22 male, 41 female; mean age 12 years (range 1-25)) who underwent 70 procedures for extremity and trunk venous malformations were reviewed. Indications for treatment included pain (100%), swelling (22%), and diminished range of motion (16%). Thirty seven patients (59%) had undergone prior stand-alone interventional or surgical treatment but were persistently symptomatic. Safety, technical and clinical success were retrospectively assessed. RESULTS: Embolization was technically successful in 100% of patients. Mean lesion size was 3.0 × 2.9 × 5.7 cm. Three patients (5%) underwent planned, second stage procedures for lesions intentionally not treated at the first procedure. Four patients (6%) underwent an unplanned, second stage procedure for residual disease after the primary operation. Mean and median follow-up duration were 18 and 17 months, respectively (range 3 to 35 months). Symptomatic improvement was achieved in 58 patients (92%), of whom 41 (65%) reported complete elimination of pain. There were no recognized instances of nontarget embolization or other complications of the interventional procedure. One patient required additional surgery for wound dehiscence and one patient developed an abscess requiring incision and drainage. Minor surgical complications included surgical site skin infections (n = 5) and numbness (n = 1). Mean and median surgical blood loss volumes were 131 mL and 10 mL, respectively. One patient required perioperative blood transfusion. CONCLUSIONS: Extremity and truncal venous malformations can be safely and effectively treated in a single-stage fashion using glue embolization immediately preceding excision.

Use of 3D reconstruction cloacagrams and 3D printing in cloacal malformations.

INTRODUCTION: Cloacal anomalies are complex to manage, and the anatomy affects prognosis and management. Assessment historically includes examination under anesthesia, and genitography is often performed, but these do not consistently capture three-dimensional (3D) detail or spatial relationships of the anatomic structures. Three-dimensional reconstruction cloacagrams can provide a high level of detail including channel measurements and the level of the cloaca (<3 cm vs. >3 cm), which typically determines the approach for surgical reconstruction and can impact long-term prognosis. Yet this imaging modality has not yet been directly compared with intra-operative or endoscopic findings. OBJECTIVES: Our objective was to compare 3D reconstruction cloacagrams with endoscopic and intraoperative findings, as well as to describe the use of 3D printing to create models for surgical planning and education. STUDY DESIGN: An IRB-approved retrospective review of all cloaca patients seen by our multi-disciplinary program from 2014 to 2016 was performed. All patients underwent examination under anesthesia, endoscopy, 3D reconstruction cloacagram, and subsequent reconstructive surgery at a later date. Patient characteristics, intraoperative details, and measurements from endoscopy and cloacagram were reviewed and compared. One of the 3D cloacagrams was reformatted for 3D printing to create a model for surgical planning. RESULTS: Four patients were included for review, with the Figure illustrating 3D cloacagram results. Measurements of common channel length and urethral length were similar between modalities, particularly with confirming the level of cloaca. No patient experienced any complications or adverse effects from cloacagram or endoscopy. A model was successfully created from cloacagram images with the use of 3D printing technology. DISCUSSION: Accurate preoperative assessment for cloacal anomalies is important for counseling and surgical planning. Three-dimensional cloacagrams have been shown to yield a high level of anatomic detail. Here, cloacagram measurements are shown to correlate well with endoscopic and intraoperative findings with regards to level of cloaca and Müllerian development. Measurement discrepancies may be due to technical variation indicating a need for further evaluation. The translation of the cloacagram images into a 3D printed model demonstrates potential applications of these models for pre-operative planning and education of both families and trainees. CONCLUSIONS: In our series, 3D reconstruction cloacagrams yielded accurate measurements of urethral length and level of cloaca common channel and urethral length, similar to those found on endoscopy. Three-dimensional models can be printed from using cloacagram images, and may be useful for surgical planning and education.

Standardized outcome and reporting measures in pediatric head and neck lymphatic malformations.

OBJECTIVE: To develop general and site-specific treatment effect and outcome measures to standardize the reporting of head and neck lymphatic malformation (HNLM) treatments. STUDY DESIGN: Consensus statement/expert opinion. SETTING: Multiple tertiary academic institutions. SUBJECTS AND METHODS: The modified Delphi method is an iterative process of collecting expert opinions, refining opinions through discussion and feedback, statistically aggregating opinions, and using these aggregates to generate consensus opinion in the absence of other data. The modified Delphi method was used by a multi-institutional group of otolaryngology and interventional radiology experts in the field of vascular anomalies to formulate a list of recommended reporting outcomes for the study and treatment of head and neck lymphatic malformations. RESULTS: Through 3 rounds of iteration, 10 expert panelists refined 98 proposed outcome measures and 9 outcome categories to a final consensus set of 50 recommended outcome measures in 3 global categories (general, demographics, and treatment complications) and 5 site-specific categories (orbit, oral cavity, pharynx, larynx, and neck). CONCLUSIONS: We propose the first consensus set of standardized reporting measures for clinical and treatment outcomes in studies of HNLMs. Consistent outcome measures across future studies will facilitate comparison of treatment options and allow systematic review. We hope that these guidelines facilitate the design and reporting of subsequent HNLM studies.

Temporal progression of skeletal cystic angiomatosis.

Cystic angiomatosis is a rare, benign, multifocal disorder of bone and viscera, in which angiomatous deposits of both vascular and lymphatic elements result in bone lysis and organ dysfunction. We report on a case of late-onset cystic angiomatosis in a Caucasian woman who first presented at age 35 years with a lytic expansile lesion of the proximal humerus, initially diagnosed as low-grade hemangio-endothelioma. This was treated with injection of cement and prophylactic pinning. However, the lesion continued to grow, and, 5 years later, she was discovered to have disseminated bony involvement, initially thought to represent metastatic disease. However, further investigation revealed a diagnosis of cystic angiomatosis, and the patient was treated with bisphosphonates. Follow-up over a 15-year period since her initial presentation at age 35 years has shown osteosclerotic conversion of many of the lesions, with development of numerous pathologic stress fractures that have failed to heal, despite operative intervention.