Prognostic Significance of Computed Tomography Findings in Pulmonary Vein Stenosis.

(1) Pulmonary vein stenosis (PVS) can be a severe, progressive disease with lung involvement. We aimed to characterize findings by computed tomography (CT) and identify factors associated with death; (2) Veins and lung segments were classified into five locations: right upper, middle, and lower; and left upper and lower. Severity of vein stenosis (0-4 = no disease-atresia) and lung segments (0-3 = unaffected-severe) were scored. A PVS severity score (sum of all veins + 2 if bilateral disease; maximum = 22) and a total lung severity score (sum of all lung segments; maximum = 15) were reported; (3) Of 43 CT examinations (median age 21 months), 63% had bilateral disease. There was 30% mortality by 4 years after CT. Individual-vein PVS severity was associated with its corresponding lung segment severity (p < 0.001). By univariate analysis, PVS severity score >11, lung cysts, and total lung severity score >6 had higher hazard of death; and perihilar induration had lower hazard of death; (4) Multiple CT-derived variables of PVS severity and lung disease have prognostic significance. PVS severity correlates with lung disease severity.

Outcomes in Establishing Individual Vessel Patency for Pediatric Pulmonary Vein Stenosis.

The purpose of this study was to determine what patient and pulmonary vein characteristics at the diagnosis of intraluminal pulmonary vein stenosis (PVS) are predictive of individual vein outcomes. A retrospective, single-center, cohort sub-analysis of individual pulmonary veins of patients enrolled in the clinical trial NCT00891527 using imatinib mesylate +/- bevacizumab as adjunct therapy for the treatment of multi-vessel pediatric PVS between March 2009 and December 2014 was performed. The 72-week outcomes of the individual veins are reported. Among the 48 enrolled patients, 46 patients and 182 pulmonary veins were included in the study. Multivariable analysis demonstrated that patients with veins without distal disease at baseline (odds ratio, OR 3.69, 95% confidence interval, CI [1.52, 8.94], p = 0.004), location other than left upper vein (OR 2.58, 95% CI [1.07, 6.19], p = 0.034), or veins in patients ≥ 1 y/o (OR 5.59, 95% CI [1.81, 17.3], p = 0.003) were at higher odds of having minimal disease at the end of the study. Veins in patients who received a higher percentage of eligible drug doses required fewer reinterventions (IRR 0.76, 95% CI [0.68, 0.85], p < 0.001). The success of a multi-modal treatment approach to aggressive PVS depends on the vein location, disease severity, and drug dose intensity.

Adjunct Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel Intraluminal Pediatric Pulmonary Vein Stenosis.

OBJECTIVE: To evaluate the use of imatinib mesylate with or without bevacizumab targeting neoproliferative myofibroblast-like cells with tyrosine kinase receptor expression, as adjuncts to modern interventional therapies for the treatment of multivessel intraluminal pulmonary vein stenosis (PVS). We describe the 48- and 72-week outcomes among patients receiving imatinib mesylate with or without bevacizumab for multivessel intraluminal PVS. STUDY DESIGN: This single-arm, prospective, open-label US Food and Drug Administration approved trial enrolled patients with ≥2 affected pulmonary veins after surgical or catheter-based relief of obstruction between March 2009 and December 2014. Drug therapy was discontinued at 48 weeks, or after 24 weeks of stabilization, whichever occurred later. RESULTS: Among 48 enrolled patients, 5 had isolated PVS, 26 congenital heart disease, 5 lung disease, and 12 both. After the 72-week follow-up, 16 patients had stabilized, 27 had recurred locally without stabilization, and 5 had progressed. Stabilization was associated with the absence of lung disease (P = .03), a higher percentage of eligible drug doses received (P = .03), and was not associated with age, diagnosis, disease laterality, or number of veins involved. Survival to 72 weeks was 77% (37 of 48). Adverse events were common (n = 1489 total), but only 16 were definitely related to drug treatment, none of which were serious. CONCLUSION: Survival to 72 weeks was 77% in a referral population with multivessel intraluminal PVS undergoing multimodal treatment, including antiproliferative tyrosine kinase blockade. Toxicity specific to tyrosine kinase blockade was minimal.

Magnetic resonance lymphography of the thoracic duct after interstitial injection of gadofosveset trisodium: a pilot dosing study in a porcine model.

UNLABELLED: BACKGROUND-RATIONALE: To investigate whether interstitial injection of gadofosveset trisodium (Ablavar®, Lantheus Medical, North Billerica, MA) would be suitable for thoracic duct (TD) imaging in a pig model. METHODS AND RESULTS: Gadofosveset trisodium alone or premixed with 10% human serum albumin (HSA) was administered intradermally in the extremities of pigs at varying doses to visualize the TD by MRI. Two blinded readers evaluated MRIs for TD visibility. The inter-observer variability for all MR imaging sessions was assessed using the Spearman rank correlation test. MR lymphography using gadofosveset trisodium premixed with HSA yielded superior visualization of the TD compared to gadofosveset trisodium alone, with a high inter-observer agreement (correlation coefficient of 0.88 (p=0.00000115)). CONCLUSIONS: We demonstrate that gadofosveset trisodium (premixed with 10%HSA) can be injected intradermally in order to perform MR lymphography of the thoracic duct. Since this agent is already FDA approved for MR imaging, the off-label use of it for imaging of the thoracic duct in humans is feasible, and the approach may prove to be beneficial for patients with TD abnormalities.

Outcome predictors and implications for management of scimitar syndrome.

BACKGROUND: Scimitar syndrome is a rare congenital anomaly. We evaluated risk factors for postoperative pulmonary vein stenosis or death and predictive factors for survival without scimitar vein surgery in patients with scimitar syndrome. METHODS: The records of patients with scimitar syndrome evaluated at our medical center between 1964 and 2011 were reviewed. RESULTS: Scimitar syndrome was identified in 80 patients, with a median follow-up of 4.5 years. Patients presenting less than 1 year of age had a higher incidence of symptoms, aortopulmonary collaterals, coexisting congenital heart disease (CHD), extracardiac anomalies, and pulmonary hypertension. Of 36 patients having scimitar vein surgery, 18 had postoperative pulmonary vein obstruction that occurred with similar frequency after baffle or reimplantation procedures, early or late in the study period, and tended to be more common in infants (P = .10). Overall, 19 (24%) of 80 died. Multivariate risk factors for death included systolic pulmonary pressure >0.5 systemic level (P = .007) and left pulmonary vein stenosis (P = .009). Pulmonary artery systolic pressure <0.5 systemic level (P = .01) and absence of CHD excluding atrial septal defect (P = .01) were predictive factors in 28 patients who survived and did not have scimitar vein surgery; these patients had no or mild right ventricular dilation and a ratio of pulmonary-to-systemic flow <1.6 either at baseline, after coiling aortopulmonary collaterals or nonscimitar vein intervention. CONCLUSIONS: Postoperative pulmonary vein obstruction is common after scimitar vein surgery regardless of redirection technique. Pulmonary hypertension and left pulmonary vein stenosis are risk factors for death, whereas patients without significant pulmonary hypertension or associated CHD did well without scimitar vein surgery. These observations may guide management decisions in patients with scimitar syndrome.

Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations.

Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and subspecialty providers.

A prospective phase II trial of vinblastine and methotrexate in multivessel intraluminal pulmonary vein stenosis in infants and children.

OBJECTIVE: To determine the safety and efficacy of the chemotherapeutic agents vinblastine and methotrexate in the treatment of children with progressive multivessel intraluminal pulmonary vein stenosis (PVS). METHODS: Children received weekly vinblastine and methotrexate for a period of 1 year. Outcomes (for patients receiving ≥1 month of chemotherapy) were classified separately for patients with isolated PVS and PVS with congenital heart disease (CHD). Primary efficacy outcome was "response to treatment" categorized by echocardiographic criteria of response. Survival to 1 year was also evaluated. All adverse events were classified according to Cancer Therapy Evaluation Program, Common Terminology Criteria version 3.0. Events were further classified as related to chemotherapy, cardiac, or other causes. RESULTS: Among 29 patients enrolled, 28 received at least one dose of chemotherapy and were evaluable for toxicity, while 23 were evaluable for response (21 CHD, 2 isolated). Both patients in the isolated group had progressive disease and died. Overall, 33% (7/21) of patients with PVS and CHD had stable disease; 1-year survival of 38%; and four patients continue in remission (93, 96, 124, and 125 months after treatment initiation). While both cardiac-related (19%) and chemotherapy-related (53%) toxicities were common, most were asymptomatic laboratory changes. Grade 3 (13%) and grade 4 (4%) toxicities were reversible, and no treatment-related grade 5 toxicities were observed. CONCLUSION: We report on the first prospective trial of chemotherapy for infants and children targeting the presence of myofibroblastic cells within the lesions of PVS based on myofibroblastic proliferation associated with desmoid tumors of infancy. The toxicity profile resulted in numerous treatment delays and interruptions that, combined with limited information on the natural history of PVS in this patient population, hampered our ability to determine the true efficacy of this approach. These results will be important as a baseline for clinical trials in this patient population.

Magnetic resonance lymphangiography with a nano-sized gadolinium-labeled dendrimer in small and large animal models.

AIM: Imaging of the lymphatic system is critical in preoperative planning of resections of complex lymphatic malformations. However, safe, effective imaging methods with sufficient resolution to identify the lymphatics have been lacking. In this study, we demonstrate the use of gadolinium-labeled dendrimers to image the lymphatics in small and large animal models during magnetic resonance lymphangiography. METHODS: Polyamidoamine G6-Gd_1B4M_N-hydroxysuccinimide was synthesized and administered intradermally in the extremities of normal mice and pigs at several doses. RESULTS: The lymphatics were well demonstrated in both animal models and there was rapid uptake in the deep lymphatic system, including the thoracic duct. A significant dose reduction was achieved (1 µmol Gd/kg) in the 35-kg pig compared with mice, while still producing excellent results. No toxicity was observed and only minor inflammatory changes were observed at the injection site 30 days later. CONCLUSION: We demonstrate that a low dose of a macromolecular magnetic resonance contrast agent can provide rapid imaging of the deep lymphatic system in both small and large animals. This data provides a basis to consider a similar agent in clinical trials.

Neonatal hemochromatosis and patent ductus venosus: clinical course and diagnostic pitfalls.

BACKGROUND: Neonatal hemochromatosis is a rare metabolic disorder characterized by excessive iron deposition within the liver leading to hepatic failure and portal hypertension. OBJECTIVE: We describe the clinical course and imaging findings in three infants with neonatal hemochromatosis associated with patent ductus venosus. We paid special attention to the diagnostic challenges encountered in these patients in order to emphasize some of the potential diagnostic pitfalls. MATERIALS AND METHODS: We conducted a comprehensive search of our radiology database of the last 10 years (1999-2008) for the keywords "neonatal hemochromatosis." Medical records and imaging studies of various modalities were reviewed. RESULTS: Three neonates were found to have neonatal hemochromatosis; all of them were associated with patent ductus venosus. Two of these patients were referred to our tertiary center for embolization of an inaccurately diagnosed hepatic vascular malformation. Two patients underwent successful liver transplantation and one died shortly after referral. CONCLUSION: The awareness and inclusion of neonatal hemochromatosis in the differential diagnosis of newborns with liver failure and patent ductus venosus has critical treatment implications.

MDCT evaluation of pulmonary embolism in children and young adults following a lateral tunnel Fontan procedure: optimizing contrast-enhancement techniques.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening thromboembolic complication in patients who have undergone a Fontan procedure for augmenting pulmonary blood flow in the setting of single-ventricle physiology. In patients following a Fontan procedure, lack of proper contrast agent mixing in the right atrium and sluggish, low-velocity blood flow within the Fontan circulation often results in suboptimal contrast enhancement within the pulmonary artery for evaluating PE. Unfortunately, there is a paucity of information describing the optimal contrast-enhancement technique with multidetector CT (MDCT) for evaluating PE in children and young adults following a Fontan procedure. OBJECTIVE: We illustrate the MDCT imaging findings of suboptimal contrast enhancement within the pulmonary artery, which can be mistaken for PE, in patients following a lateral Fontan procedure, and we discuss MDCT techniques to optimize contrast enhancement within the pulmonary artery in these patients for evaluating PE. MATERIALS AND METHODS: The MDCT imaging findings in pediatric and young adult patients following a lateral Fontan procedure and with clinically suspected PE are illustrated. We describe intravenous contrast agent injection techniques that can be used to optimize the contrast enhancement in the pulmonary artery in patients following a lateral Fontan procedure. RESULTS: The use of a suboptimal contrast-enhancement technique led to initial misdiagnosis and incomplete evaluation of PE in the three patients following a lateral Fontan procedure. Imaging in two patients showed that optimal evaluation of thrombosis in the Fontan pathway and PE in the pulmonary arteries can be successfully achieved with simultaneous upper- and lower-limb injections of contrast agent. CONCLUSION: This series demonstrates that suboptimal contrast enhancement can result in misdiagnosis or incomplete evaluation of PE in children and young adults following a lateral Fontan procedure. Careful attention to optimizing contrast enhancement during MDCT examination for evaluation of PE in these patients is essential to prevent misdiagnosis and incomplete evaluation.

Range of ventricular dimensions and function by steady-state free precession cine MRI in repaired tetralogy of Fallot: right ventricular outflow tract patch vs. conduit repair.

PURPOSE: To characterize the range of biventricular size and function evaluated by steady-state free precession (SSFP) cine magnetic resonance (MR) in a large cohort of patients with repaired tetralogy of Fallot (TOF), and to compare these measurements in those with a right ventricular outflow tract (RVOT) patch vs. a right ventricle-to-pulmonary artery (RV-PA) conduit. MATERIALS AND METHODS: Analysis of ventricular size and function in 300 consecutive examinations in patients with repaired TOF evaluated by SSFP cine MR. RESULTS: Of the 300 examinations performed in 256 patients, 69% had undergone repair with a RVOT patch and 31% with a RV-PA conduit. Compared to patients with RV-PA conduit, those with a RVOT patch had significantly more pulmonary regurgitation (PR) (38 +/- 17 vs. 23 +/- 16%, P < 0.0001), larger indexed RV end-diastolic volume (154 +/- 53 vs. 133 +/- 51 mL/m(2), P = 0.002), similar indexed end-systolic volume (80 +/- 39 vs. 74 +/- 46 mL/m(2), P = 0.31), higher ejection fraction (EF) (50 +/- 9 vs. 47 +/- 12%, P = 0.037), and lower mass-to-volume ratio (0.29 +/- 0.08 vs. 0.36 +/- 0.13, P < 0.0001). Pulmonary regurgitation fraction correlated positively with RV end-diastolic volume index in the RVOT patch group (r = 0.51, P < 0.0001) but not in the RV-PA conduit. CONCLUSION: This study provides the range and distribution of biventricular size and function, and PR measured by MRI in a large contemporary cohort of patients with repaired TOF, and demonstrates important variations in RV mechanics between patients repaired with a RVOT patch and those with an RV-PA conduit.

Cardiac magnetic resonance imaging evaluation of sinus venosus defects: comparison to surgical findings.

Sinus venosus defect (SVD) is an uncommon type of interatrial communication in which cardiac magnetic resonance (CMR) is increasingly used as an alternative imaging modality. The goal of this study was to determine the accuracy of CMR in patients with SVD compared with surgical findings. The diagnostic studies and operative reports of all patients who had CMR followed by surgical repair of SVD (n = 16) from 1996 to 2005 were reviewed and discrepancies were recorded. CMR studies included assessment of anatomy (evaluated by a combination of gradient echo cine, spin echo, and gadolinium-enhanced three-dimensional magnetic resonance angiography), ventricular volumes and function, and flow measurements. The median age at CMR was 14 years (range, 0.4-42). Compared with operative findings, there were no major discrepancies with CMR. The SVD was clearly imaged in all patients and 36 anomalously draining pulmonary veins were identified. The median pulmonary-to-systemic flow ratio was 2.4 (range, l.3-4.6). Patients had an average of 1.7 previous diagnostic tests (range, 1-3; 19 transthoracic echo, 5 catheterizations, and 3 transesophageal echo). Before CMR, SVD was diagnosed in 1 patient, suspected in 7, and not suspected in 8. Additional unsuspected findings identified by CMR included malposition of septum primum (n = 2), left superior vena cava to coronary sinus (n = 2), and aortic arch anomalies (n = 2). CMR accurately depicts SVD anatomy and associated anomalous pulmonary venous drainage, provides quantitative information on the hemodynamic burden, and reveals additional cardiovascular abnormalities. This experience indicates that CMR provides the information necessary for surgical planning of SVD repair.

The presentation and management of vascular rings: an otolaryngology perspective.

OBJECTIVE: To review the presentation and natural history of children with vascular rings and present management guidelines. METHODS: Retrospective study of tertiary care pediatric medical center charts from 1991 to 2002. RESULTS: There were 37 males and 27 females with a diagnosis of vascular rings. At presentation, 91% of patients had airway symptoms and 47% had esophageal symptoms. Airway symptoms included stridor (63%), recurrent respiratory infections (47%), respiratory distress (19%), and cough (17%). The most common esophageal symptom was dysphagia (27%). Pre-operative studies included: echocardiography (96%), chest X-ray (93%), barium swallow (75%), magnetic resonance imaging (MRI) (60%), and computerized tomography (CT) scan of the chest (59%). Surgical management included open (n=25) and thoracoscopic (n=39) approach. Complications included recurrent laryngeal nerve injury in five patients (8%). CONCLUSION: Children with vascular rings present with respiratory and/or feeding difficulty. The evaluation should include chest X-ray, echocardiography, and barium swallow. Direct laryngoscopy and bronchoscopy are recommended to assess the degree of compression of the airway and/or esophagus, tracheomalacia, and vocal fold motion prior to intervention. Indication for surgical release is given when the diagnosis is made and can be assisted by advanced radiology studies. Surgical options include minimally invasive techniques involving either thoracoscopic or robotic-assisted repairs, as well as open procedures involving thoracotomy.

Crohn's jejunoileitis: the pediatrician's perspective on diagnosis and management.

Although uncommon, diffuse jejunoilietis is one of the most difficult areas in Crohn's disease (CD) to treat. Although the exact frequency is unknown, most gastroenterologists believe that its prevalence has been underestimated and that it may have an increased incidence among children and young adolescents. The clinical importance of this clinical disease phenotype is the impact diffuse small bowel disease is expected to have on a child's growth and development. Moreover, patients with jejunoileitis are more likely to experience complications, including fistulization, and most commonly, intestinal obstruction. The associated morbidity and frequent need for surgical intervention renders these patients at risk for intestinal insufficiency. Although stricturoplasty has reduced the incidence of short bowel syndrome, most patients with proximal small bowel CD still require repeated surgical intervention. Jejunoileitis represents a distinct clinical phenotype within the heterogenous family of disease phenotypes considered as CD. Whether a specific genotype will be found to associate with jejunoileitis remains to be determined. Through the development of novel diagnostic techniques, including gadolinium enhanced magnetic resonance imaging (GMRI), enteroscopy, and capsule endoscopy, the mean age at diagnosis is expected to decrease. Coupled with an increase in clinical suspicion, early diagnosis may allow physicians to consider implementing aggressive immunomodulatory therapy. Future studies are needed to determine if the early detection and use of immune modulators in patients with proximal small bowel disease will improve overall quality of life and decrease the risk of nutritional and surgical comorbidity.

Incomplete double aortic arch with atresia of the distal left arch: distinctive imaging appearance.

OBJECTIVE: We present 10 patients with double aortic arch with atresia of the distal left arch segment, a form of incomplete double aortic arch, and describe the distinct MRI and CT findings for this potentially symptomatic vascular ring. CONCLUSION: Knowledge of the distinctive imaging appearance of this congenital arch anomaly can direct the radiologist to the correct preoperative diagnosis.

Effects of metallic implants on magnetic resonance imaging evaluation of Fontan palliation.

This study examined the effects of endovascular metallic implants on the ability of magnetic resonance imaging to evaluate cardiovascular anatomy and to assess ventricular size and function in 101 consecutive patients with Fontan palliation. Compared with studies in patients without implants, in whom 100% of anatomic segments were adequately visualized and the median image quality grade for ventricular function assessment was 5 of 5, the presence of any implant (54% of studies) reduced the proportion of adequately imaged anatomy to 77% (p <0.001) and the median image quality grade for ventricular function assessment to 3 of 5 (p <0.001).