Wibke Uller

Lymphatic and Other Vascular Malformative/Overgrowth Disorders Are Caused by Somatic Mutations in PIK3CA

OBJECTIVES To test the hypothesis that somatic phosphatidylinositol-4,5-bisphospate 3-kinase, catalytic subunit alpha (PIK3CA) mutations would be found in patients with more common disorders including isolated lymphatic malformation (LM) and Klippel-Trenaunay syndrome (KTS). STUDY DESIGN We used next generation sequencing, droplet digital polymerase chain reaction, and single molecule molecular inversion probes to search for somatic PIK3CA mutations in affected tissue from patients seen at Boston Childrens Hospital who had an isolated LM (n = 17), KTS (n = 21), fibro-adipose vascular anomaly (n = 8), or congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (n = 33), the disorder for which we first identified somatic PIK3CA mutations. We also screened 5 of the more common PIK3CA mutations in a second cohort of patients with LM (n = 31) from Seattle Childrens Hospital. RESULTS Most individuals from Boston Childrens Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), fibro-adipose vascular anomaly (5/8), and congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (31/33) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for ∼ 80% of cases. Seventy-four percent of patients with LM from Seattle Childrens Hospital also were somatic mosaic for 1 of 5 specific PIK3CA mutations. Many affected tissue specimens from both cohorts contained fewer than 10% mutant cells. CONCLUSIONS Somatic PIK3CA mutations are the most common cause of isolated LMs and disorders in which LM is a component feature. Five PIK3CA mutations account for most cases. The search for causal mutations requires sampling of affected tissues and techniques that are capable of detecting low-level somatic mosaicism because the abundance of mutant cells in a malformed tissue can be low.

Overgrowth syndromes with complex vascular anomalies

Management of overgrowth syndromes with complex vascular anomalies is challenging. Careful analysis of the various clinical features by an interdisciplinary team of physicians experienced in this field is paramount to proper diagnostic and therapeutic approaches. In this article, we focus on the spectrum of the clinical presentation and the management strategies of the most common overgrowth syndromes with complex vascular anomalies.

CT Features of Early Type II Endoleaks after Endovascular Repair of Abdominal Aortic Aneurysms Help Predict Aneurysm Sac Enlargement

PURPOSE To determine computed tomographic (CT) features of early type II endoleaks associated with aneurysm sac enlargement after endovascular aortic aneurysm repair (EVAR) of abdominal aortic aneurysm. MATERIALS AND METHODS Institutional review board approval was not required for this retrospective study. The authors reviewed imaging and clinical data from 56 patients (seven women, 49 men; mean age ± standard deviation, 71 years ± 7.9; age range, 52-85 years) with early type II endoleak who had undergone EVAR between December 2002 and December 2011 and who had been followed up with imaging and clinical evaluation for at least 6 months. The number and diameter of all feeding and/or draining arteries were measured, and endoleaks were classified according to their sources into simple inferior mesenteric artery (IMA), simple lumbar artery (LA), complex LA, and complex IMA-LA type II endoleaks. Volume and attenuation of the nidus were measured. Aneurysm enlargement was defined as an increase in the aneurysm volume of more than 5% during follow-up. Simple and multivariate logistic regression analyses were performed to identify independent clinical and imaging variables associated with aneurysm enlargement. RESULTS Twenty-three of the 56 patients (41%) showed aneurysm sac enlargement during follow-up (mean follow-up, 3.0 years ± 2.0). With the multivariate model, the variables that showed the strongest indicators for aneurysm sac enlargement were complex IMA-LA type II endoleak (odds ratio [OR] = 10.29, P = .004) and the diameter of the largest feeding and/or draining artery (OR = 4.55, P = .013). Patients without complex IMA-LA type II endoleak in whom the largest feeding and/or draining artery was larger than 3.8 mm and patients with a complex IMA-LA type II endoleak in whom the largest feeding and/or draining artery was larger than 2.2 mm were at high risk for aneurysm sac enlargement. CONCLUSION The strongest indicators for aneurysm sac enlargement are complex IMA-LA type II endoleak and the diameter of the largest feeding and/or draining artery.

Gelfoam for closure of large percutaneous transhepatic and transsplenic puncture tracts in pediatric patients.

PURPOSE Evaluation of the efficacy and safety of Gelfoam for the closure of transhepatic or transsplenic parenchymal puncture tracts with large-bore sheaths in pediatric patients. MATERIALS AND METHODS Between January 2012 and May 2013, 8 percutaneous transhepatic accesses and 3 percutaneous transsplenic accesses were closed using percutaneous Gelfoam in pediatric patients. The primary study endpoints to determine treatment efficacy and safety were patient survival, technical success defined as successful closure of the puncture tract without signs of bleeding, and complication rates. The secondary study endpoints were the occurrence of local and systemic inflammation. RESULTS Overall survival was 100 % with a median follow-up of 256 days. The procedure was technically successful in 10 of 11 procedures. One patient suffered from bleeding, which was successfully managed by a single blood transfusion. No re-bleeding was detected during follow-up and no surgical interventions were necessary. No signs of local or systemic infections related to the Gelfoam application occurred. CONCLUSION Percutaneous Gelfoam application is an effective and safe technique for the closure of transhepatic or transsplenic accesses in pediatric patients. KEY POINTS Interventional closure of large transhepatic and transsplenic parenchymal accesses in children after interventional treatment is recommended to avoid bleeding. Gelfoam application does not cause artifacts in magnetic resonance imaging and does not increase the risk of local or systemic inflammation in comparison to permanent embolic agents. Thus, especially children under immunosuppressive therapy can benefit from the application of Gelfoam.

Combined Surgical and Interventional Therapy of Acute Portal Vein Thrombosis without Cirrhosis: A New Effective Hybrid Approach for Recanalization of the Portal Venous System

Acute portomesenteric venous thrombosis represents a rare event, but is associated with severe and potentially lethal complications. Portal vein thrombosis (PVT) usually develops in the main trunk reaching left or right hepatic branches and can extend to the superior mesenteric vein and/or splenic vein. Noncirrhotic, nonmalignant, or nontransplant PVT is rarely a solitary disease and mostly a consequence of hypercoagulability or hypofibrinolysis. Other underlying causes for acute PVT are abdominal trauma and septic conditions, such as pancreatitis. In addition, surgical interventions, such as splenectomy in particular, as well as other local factors can lead to acute PVT. Clinical symptoms of acute PVT are mostly unspecific and variable, which makes an accurate clinical diagnosis difficult. Most patients present with acute abdominal pain, nausea, diarrhea, or ileus symptoms, but some patients are even asymptomatic. For diagnosis of PVT, Doppler ultrasound and contrast-enhanced CT are the most common imaging techniques that detect intrahepatic and extrahepatic PVT explicitly. Additional information, for example, the extent of thrombosis (mesenteric veins) and underlying or concomitant findings, such as bowel ischemia or congestion, is provided by a contrastenhanced CT scan that also allows distinguishing acute from chronic PVT. Management of acute PVT can include anticoagulation, regional or systemic thrombolysis, thrombectomy, or a combination of these treatments, with the aim to

Percutaneous Embolization of a Chylous Leak from Thoracic Duct Injury in a Child

Postoperative chylous leak may result from thoracic duct injury during surgical procedures in the chest or neck and can be successfully treated with percutaneous embolization. We report the case of a child with persistent chylothorax and chyloperitoneum following multivisceral transplantation, which was performed due to unresectable inflammatory myofibroblastic tumor of the retroperitoneum. Intranodal lymphangiography was used to demonstrate the site of chylous leak from the lower segment of the thoracic duct and the leak resolved within days following percutaneous embolization of the thoracic duct.

Percutaneous Management of Postoperative Bile Leaks with an Ethylene Vinyl Alcohol Copolymer (Onyx)

PURPOSE The management of postoperative bile leakage is challenging especially if the leak rises from the cut surface of the liver and endoscopic treatment fails. Percutaneous transhepatic treatment of bile leaks with biliary drainage is accepted but often requires long-term placement of the drains and is associated with treatment failures. This series evaluates selective embolization of bile ducts with an ethylene vinyl alcohol copolymer (Onyx) in patients with postoperative bile leaks as an alternative treatment option. MATERIALS AND METHODS Between January and September 2012, five consecutive patients with persistent postoperative bile leaks underwent percutaneous transhepatic Onyx application and were analyzed regarding procedural management, complications and success rates. RESULTS The persistent bile leaks were situated at the cystic stump (after cholecystectomy, n = 2), at the cut surface of the liver (after extended liver resection, n = 2) and at the surface of the liver after surgical exploration and perihepatic abscess (n = 1). Bile drainage alone (endoscopic or percutaneous) failed in all patients and open redo-surgery was deemed potentially harmful. Bilomas were externally drained in all patients before Onyx application. For the closure of bile leaks, Onyx was injected through a microcatheter in a previously built coil nest to keep Onyx in place. All bile leaks were initially closed immediately. In the 2nd week after Onyx embolization, 2 patients showed recurrent small bile leaks without clinical symptoms. In the 4th week after Onyx application, all leaks were closed. No complications occurred. CONCLUSION All leaking bile ducts were initially closed immediately after Onyx application. In the 2nd week after Onyx application, 2 patients showed small bile leaks without clinical symptoms. All leaks were closed in the 4th week after Onyx application.

Ethanol-Gel Sclerotherapy of Venous Malformations: Effectiveness and Safety

OBJECTIVE In the treatment of venous malformations, ethanol may be administered in a gelified form to increase local effects and reduce systemic ones. The purpose of this prospective study was to evaluate the efficacy and safety of a commercially available viscous ethanol gel in the treatment of venous malformations. SUBJECTS AND METHODS Thirty-one patients (mean age, 23.4 years; age range, 6.6-46.5 years) with venous malformations were prospectively scheduled for two ethanol-gel sclerotherapy sessions. Venous malformations were located at the lower extremity (n = 18), the upper extremity (n = 9), and the face (n = 4). Questionnaires to assess pain, clinical examinations, professional photographs, and contrast-enhanced MRI of the venous malformations were performed before and after therapy to measure therapy-induced changes. Two experienced radiologists blinded to the examination date and clinical status compared photographs and MR images before and after treatment. RESULTS A mean of 4.2 mL of ethanol gel were administered per session. The technical success rate was 100%. Clinical success, defined as improvement or resolution of symptoms, was noted in 81% of patients. Mean pain score decreased, and the difference was statistically significant (3.9 vs 3.1, p = 0.005). In 54 treatment sessions where follow-up was available, four minor complications occurred. Comparison of photographs and MR images before and after treatment showed improvement in 35% and 93% of patients, respectively. CONCLUSION Ethanol gel is an effective and safe sclerosing agent in the treatment of venous malformations.

Percutaneous treatment of biliary complications in pediatric patients after liver transplantation.

PURPOSE Evaluation of the efficiency and safety of the percutaneous treatment of biliary complications in pediatric liver transplant recipients. METHODS We conducted a retrospective analysis of children who underwent biliary percutaneous interventions after pediatric liver transplantation (PLT) over a 4-year period. Kind of biliary complication, interval between liver transplantation and intervention, status of the vessels, procedural interventional management, technical and clinical success, course of cholestasis, PTBD-related complications and patient survival were analyzed. RESULTS 23 percutaneous transhepatic biliary drainages (PTBD) were placed in 16 children due to 18 biliary complications. The drains were customized individually by shortening and cutting additional holes. PTBD placement was performed with technical and clinical success in all children. 4 children received PTBD to bridge the time to retransplantation and surgical revision. One child received PTBD for successful treatment of anastomotic leakage. Long-term dilation of biliary stenoses was performed in 13 children using PTBD. One of these 13 patients showed recurrent stenosis during a median follow-up of 295 days. Bilirubin values decreased significantly after PTBD placement for biliary stenosis. One patient suffered from bacteremia after PTBD replacement. CONCLUSION PTBD treatment for biliary complications after PLT is effective and safe.

Preoperative Embolization of Venous Malformations Using n-Butyl Cyanoacrylate

Purpose: The purpose of this study was to evaluate the safety and efficacy of preoperative percutaneous n-butyl cyanoacrylate (nBCA) embolization of venous malformations in children. Material and Methods: Clinical data were retrospectively reviewed in children who underwent embolization using nBCA followed by resection of venous malformations. Results: A total of 17 embolizations were performed in 14 patients (9 females, mean age: 5.5 years; median age: 3 years; range 0.1-16 years). The venous malformations involved the lower extremity and the knee joint (n = 7), the trunk (n = 4), head and neck (n = 2), and hand (n = 1). n-Butyl cyanoacrylate was diluted with iodized oil at a ratio of 1:3 to 1:5. The mean and median volume of nBCA per procedure were 2.1 and 2 mL, respectively (range: 0.5-8 mL). There were no complications associated with the procedures. The mean and median time between final embolization and resection were 3.6 and 2 days, respectively. All children underwent successful resection of the symptomatic lesions. The estimated mean and median blood loss were 75 and 50 mL, respectively (range: 5-350 mL). The postprocedure course was uneventful, the days to discharge ranged between 1 and 6 days (mean 3 days). Conclusion: Initial results suggest that preoperative percutaneous n-butyl cyanoacrylate embolization of venous malformations is safe and effective in children, with the potential for minimizing blood loss and inpatient stay.