Role of Interventional Radiology in Children with Biliary and Gallbladder Diseases.

Biliary and gallbladder diseases in infants and children often present unique diagnostic and therapeutic challenges that require a fundamental understanding of notable biliary diseases and anatomical variations. Surgical and endoscopic approaches that are often the gold standard in adult biliary treatment may be technically challenging and are associated with a high morbidity that may warrant a multidisciplinary treatment approach. This article will provide a comprehensive overview of the biliary conditions where interventional radiology can play a vital role in the diagnosis, management, and treatment. Differences in approach or technique between children and adults will be highlighted.

Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach.

Fed-batch cultures of Chinese Hamster Ovary cells have been used to produce high quantities of biotherapeutics, particularly monoclonal antibodies. However, a growing number of next-generation biotherapeutics, such as bi-specific antibodies and fusion proteins, are difficult to express using standard fed-batch processes. Decoupling cell growth and biotherapeutic production is becoming an increasingly desired strategy for the biomanufacturing industry, especially for difficult-to-express products. Cells are grown to a high cell density in the absence of recombinant protein production (the growth phase), then expression of the recombinant protein is induced and cell proliferation halted (the production phase), usually by combining an inducible gene expression system with a proliferation control strategy. Separating the growth and production phases allows cell resources to be more efficiently directed toward either growth or production, improving growth characteristics and enhancing the production of difficult to express proteins. However, current mammalian cell proliferation control methods rely on temperature shifts and chemical agents, which interact with many non-proliferation pathways, leading to variable impacts on product quality and culture viability. Synthetic biology offers an alternative approach by strategically targeting proliferation pathways to arrest cell growth but have largely remained unused in industrial bioproduction. Due to recent developments in microbial decoupling systems and advances in available mammalian cell engineering tools, we propose that the synthetic biology approach to decoupling growth and production needs revisiting.

24/7 pediatric radiology attending coverage: times are changing.

The job of the pediatric radiologist long ago ceased to be an 8-to-5 role. Many practices have adopted evening shifts of in-house attending radiologists to cover the busy evening activity. With the ever-increasing role of imaging in clinical decisions and patient management, there is a need - if not a demand - to further extend attending pediatric radiology coverage. In this article, we discuss the needs and justification for extending pediatric radiology coverage at a tertiary-care children's hospital. We also describe the approach we took toward implementing 24/7 attending in-house coverage of pediatric radiology.

Quantitative MRI for hepatic fat fraction and T2* measurement in pediatric patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The gold standard for diagnosis is liver biopsy. MRI is a non-invasive imaging method to provide quantitative measurement of hepatic fat content. The methodology is particularly appealing for the pediatric population because of its rapidity and radiation-free imaging techniques. OBJECTIVE: To develop a multi-point Dixon MRI method with multi-interference models (multi-fat-peak modeling and bi-exponential T2* correction) for accurate hepatic fat fraction (FF) and T2* measurements in pediatric patients with NAFLD. MATERIALS AND METHODS: A phantom study was first performed to validate the accuracy of the MRI fat fraction measurement by comparing it with the chemical fat composition of the ex-vivo pork liver-fat homogenate. The most accurate model determined from the phantom study was used for fat fraction and T2* measurements in 52 children and young adults referred from the pediatric hepatology clinic with suspected or identified NAFLD. Separate T2* values of water (T2*W) and fat (T2*F) components derived from the bi-exponential fitting were evaluated and plotted as a function of fat fraction. In ten patients undergoing liver biopsy, we compared histological analysis of liver fat fraction with MRI fat fraction. RESULTS: In the phantom study the 6-point Dixon with 5-fat-peak, bi-exponential T2* modeling demonstrated the best precision and accuracy in fat fraction measurements compared with other methods. This model was further calibrated with chemical fat fraction and applied in patients, where similar patterns were observed as in the phantom study that conventional 2-point and 3-point Dixon methods underestimated fat fraction compared to the calibrated 6-point 5-fat-peak bi-exponential model (P < 0.0001). With increasing fat fraction, T2*W (27.9 ± 3.5 ms) decreased, whereas T2*F (20.3 ± 5.5 ms) increased; and T2*W and T2*F became increasingly more similar when fat fraction was higher than 15-20%. Histological fat fraction measurements in ten patients were highly correlated with calibrated MRI fat fraction measurements (Pearson correlation coefficient r = 0.90 with P = 0.0004). CONCLUSION: Liver MRI using multi-point Dixon with multi-fat-peak and bi-exponential T2* modeling provided accurate fat quantification in children and young adults with non-alcoholic fatty liver disease and may be used to screen at-risk or affected individuals and to monitor disease progress noninvasively.

Renal Doppler evaluation in the child with hypertension: a reasonable screening discriminator?

BACKGROUND: Hypertension is diagnosed in 1-5% of children, and 5-10% of those hypertensive children have renovascular disease. The gold standard for a diagnosis of renal artery stenosis is arteriography, and Doppler ultrasound (Doppler US) continues to be advocated as a useful screening test. OBJECTIVE: The purpose of this study was to determine the utility of Doppler US in children as a screening tool and to better define clinical features of children in whom arteriography should be performed. MATERIALS AND METHODS: This retrospective study evaluated the imaging and clinical parameters for all children who had a renal US with Doppler followed by a diagnostic arteriogram for the evaluation of hypertension during a 12-year period at a tertiary children's hospital. Sixty-two children were included. We evaluated each child's clinical parameters and placed each child into one of three categories of hypertension: mild, moderate or severe. RESULTS: Eleven of 17 kidneys with proven renal artery stenosis were detected with Doppler US (sensitivity 64%). Six children with renal artery stenosis were missed by Doppler US, four of whom had segmental artery lesions. Of the children with positive renal artery stenosis on arteriography, all but three (79%) were classified as having moderate to severe hypertension. CONCLUSION: Doppler US is a useful screening examination when evaluating children with hypertension, detecting renal artery stenosis in most affected children. The clinical risk classifications are helpful in guiding which children should proceed with arteriography regardless of the Doppler US results.

Outcomes of percutaneous interventions for managing stenosis after meso-Rex bypass for extrahepatic portal vein obstruction.

PURPOSE: To determine outcomes in children with extrahepatic portal vein obstruction who underwent percutaneous intervention for anastomotic stenosis after meso-Rex bypass. MATERIALS AND METHODS: Eighty-six patients who underwent meso-Rex bypass between 1997 and 2009 were retrospectively reviewed, and 15 who underwent transhepatic portal venography for graft stenosis were identified. Technical success and clinical outcomes were analyzed. RESULTS: Nine of 15 patients (60%) with anastomotic stenosis were successfully treated by endovascular techniques and remain symptom-free with patent shunts, three (20%) underwent technically successful interventions but currently have recurrent stenosis, and three (20%) underwent failed attempts at percutaneous intervention. All three in whom percutaneous intervention failed required surgical revision, including two with near-occlusive lesions that prevented traversal of the stenosis and one who developed postprocedure shunt thrombosis. In total, patients underwent 27 endovascular procedures, including 17 balloon venoplasties, four cutting balloon venoplasties, five stent placements, and one balloon venoplasty with thrombolysis. The mean pressure gradient across the stenosis decreased from 11 mm Hg ± 3 to 5 mm Hg ± 3 (P < .001) after technically successful intervention. Platelet count improved (from 97,000/µL ± 41,000 to 165,000 ± 67,000/µL; P = .002) and ammonia levels decreased (from 40 µmol/L ± 11 to 24 µmol/L ± 13; P = .05) after intervention. Patients were followed for a median duration of 39 months after the last intervention. CONCLUSIONS: Percutaneous interventions allow for long-term vein graft patency and clinical resolution of symptoms in the majority of patients with anastomotic stenosis after meso-Rex bypass.

Outcomes and risk factors for failure of radiologic treatment of biliary strictures in pediatric liver transplantation recipients.

Posttransplantation biliary strictures occur in 5-34% of the pediatric liver transplant patients and are conventionally managed by interventional radiological techniques. The aim of this manuscript is to assess the outcomes of patients with biliary strictures treated by percutaneous dilatation at our institution. Included in the study were 35 children with posttransplant biliary strictures that were treated with percutaneous dilatation and stenting. Initial dilation and biliary stent placement was accomplished in all patients without complications requiring surgical intervention. Recurrent strictures developed in 23 (66%) of 35 patients. The recurrence rate was 45% for anastomotic strictures, 90% for intrahepatic strictures, and 100% for those with both an anastomotic and intrahepatic component. Seven patients required revision of the choledochojejunostomy, 5 of them with a successful outcome and 2 requiring retransplant. Five patients were treated with retransplantation without surgical revision. Patients with an intrahepatic or a "combined" stricture were less likely to have a successful outcome after radiologic treatment. In conclusion, the radiological treatment of biliary strictures with balloon dilation and stenting can be performed successfully with minimal complications avoiding the need for surgical correction in many cases.

Pediatric vascular access.

Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices.

Conventional versus modified technique for percutaneous nephrostomy in newborns and young infants.

Percutaneous nephrostomy (PN) in newborns and young infants presents unique challenges. Twenty-six consecutive PN procedures in 18 patients were retrospectively reviewed. Fifteen procedures were performed with the conventional micropuncture technique. The modified technique describe herein was used in 11 procedures. Depending on whether there is obstruction and whether the obstruction is at the ureteropelvic junction level or distal to it, the technique selected will vary.

Interventional Radiology in the Pediatric Liver Transplant Patient.

Liver transplantation now plays a major role in the treatment of end-stage liver disease in children. Reduced-size liver transplant surgical techniques have allowed increasing numbers of children to undergo liver transplantation. As more children are undergoing liver transplantation, there is a growing need for radiologic diagnosis of and intervention in post-transplantation complications in these patients.