Gulraiz Chaudry

Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies.

BACKGROUND AND OBJECTIVES: Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days. METHODS: Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m2 per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths. RESULTS: Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred. CONCLUSIONS: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.

Abdominal manifestations of cystic fibrosis in children

Pulmonary complications remain the main cause of mortality in cystic fibrosis, but the presenting symptoms in children are often related to gastrointestinal or pancreaticobiliary disease. Furthermore, abdominal manifestations are now seen throughout childhood, from infancy to adolescence. The child might present in the neonatal period with meconium ileus or its attendant complications. The older child might present with distal intestinal obstruction syndrome or colonic stricture secondary to high doses of pancreatic enzyme replacement. Less-common gastrointestinal manifestations include intussusception, duodenitis and fecal impaction of the appendix. Most children also show evidence of exocrine pancreatic deficiency. Radiologically, the combination of fat deposition and pancreatic fibrosis leads to varying CT and MR appearances. A higher than normal incidence of pancreatic cysts and calcification is also seen. Decreased transport of water and chloride also increases the viscosity of bile, with subsequent obstruction of the biliary ductules. If extensive, this can progress to obstructive cirrhosis, portal hypertension and esophageal varices. Diffuse fatty infiltration, hypersplenism and gallstones are also commonly seen in these patients. We present a pictorial review of the radiological appearance of these abdominal manifestations. The conditions are dealt with individually, together with typical appearances in various imaging modalities.

Swine-Origin Influenza A (H1N1) Viral Infection in Children: Initial Chest Radiographic Findings

PURPOSE To evaluate initial chest radiographic findings of swine-origin influenza A (S-OIV) (also known as H1N1) viral infection in children. MATERIALS AND METHODS This was an institutional review board-approved, HIPAA-compliant retrospective study of 108 patients who had microbiologically confirmed S-OIV infection and available initial chest radiographs obtained between April 2009 and October 2009. The final study group was divided on the basis of clinical course (group 1, outpatients without hospitalization [n = 72]; group 2, inpatients with brief hospitalization [n = 22]; group 3, inpatients with intensive care unit admission [n = 14]). Two pediatric radiologists blinded to patient group and lung parenchymal, airway, pleural, hilar, and mediastinal abnormalities systematically reviewed initial chest radiographs. Lung parenchyma and airways were evaluated for pattern (peribronchial markings, consolidation, and ground-glass, nodular, and reticular opacity), distribution, and extent of abnormalities. Radiographs were assessed for presence of pleural effusions or lymphadenopathy. Medical records were reviewed for underlying medical conditions and patient outcomes. Association between frequency of underlying medical conditions and clinical course of S-OIV infection among study groups was evaluated with the Pearson chi(2) test. RESULTS The frequency of normal chest radiographs was significantly higher in group 1 (n = 48) than in groups 2 (n = 1) and 3 (n = 0) (P < .001, Pearson chi(2) test). Among patients with abnormal radiographs, the most common finding in group 1 was prominent peribronchial markings with hyperinflation (n = 17), whereas the most common findings in groups 2 (n = 12) and 3 (n = 12) were bilateral, symmetric, and multifocal areas of consolidation, often associated with ground-glass opacities. Nodular opacities, reticular opacities, pleural effusion, or lymphadenopathy were not observed in any patient. An increased frequency of underlying medical conditions was observed in patients with greater severity of illness due to S-OIV infection (group 3, 71%; group 2, 59%; group 1, 31%) (P = .003, Pearson chi(2) test). All 84 patients with available follow-up information have fully recuperated from S-OIV infection. CONCLUSION Initial chest radiographs in children with a mild and self-limited clinical course of S-OIV infection are often normal, but they may demonstrate prominent peribronchial markings with hyperinflation. Bilateral, symmetric, and multifocal areas of consolidation, often associated with ground-glass opacities, are the predominant radiographic findings in pediatric patients with a more severe clinical course of S-OIV infection. (c) RSNA, 2009.

Gorham-Stout disease and generalized lymphatic anomaly--clinical, radiologic, and histologic differentiation.

PurposeGorham-Stout disease (GSD) is a rare vascular disorder of lymphatic origin characterized by progressive osteolysis. Generalized lymphatic anomaly (GLA) is a multisystem disorder that also commonly affects bone. We hypothesized that Gorham-Stout disease is different from other osseous lymphatic anomalies. We proposed to discriminate these entities by analyzing findings on skeletal imaging.MethodsClinical data, imaging studies, and histopathologic findings were retrospectively reviewed in patients presenting to our Vascular Anomalies Center with lymphatic anomalies of bone.FindingsWithin a cohort of 51 patients with lymphatic disorder and radiological evidence of bony involvement, two distinct categories emerged. Nineteen patients met the imaging criteria for GSD: progressive osteolysis with resorption and cortical loss. Thirty-two were categorized as GLA: Discrete radiolucencies and increasing numbers of bone affected over time, but without evidence of progressive osteolysis. The ribs were the most common site in both groups, followed by the cranium, clavicle, and cervical spine in GSD, and thoracic spine, humerus, and femur in GLA. Fewer bones were involved in GSD, with relative sparing of the appendicular skeleton. Associated infiltrative soft tissue abnormality was seen in 18 in GSD, but only six with GLA. Macrocystic lymphatic malformations were identified in 14 with GLA, but none with GSD.ConclusionsThere are significant radiological differences between GSD and GLA, although there are some overlapping features. The major distinguishing characteristic is the progressive osteolysis seen in GSD. Findings suggestive of GLA are more extensive involvement, particularly of the appendicular skeleton, presence of discretemacrocystic lymphatic malformations and visceral organ lesions.

Intranodal Lymphangiography: Feasibility and Preliminary Experience in Children

PURPOSE To review an initial experience studying the lymphatic system using direct injection of ethiodized oil contrast medium into lymph nodes (ie, intranodal lymphangiography) in children with chylous disorders. MATERIALS AND METHODS Children with chylous disorders who underwent intranodal lymphangiography were included in this retrospective study. Under general anesthesia, ultrasonography was used to guide the placement of a small-bore (22-25-gauge) needle into an inguinal lymph node. Ethiodized oil contrast medium was very slowly injected into the node. Opacification of the lymphatic system was documented with fluoroscopic and digital substraction imaging and videofluoroscopic clips. RESULTS Five children (age range, 6 wk to 17 y) with chylous vaginorrhea (n = 1), postoperative chylothorax (n = 2), or spontaneous chylothorax (n = 2) underwent intranodal lymphangiography. The amount of ethiodized oil injected was 0.5-4.5 mL. Intranodal lymphangiography was successfully completed in four patients. One procedure was terminated because of patient motion and extravasation of contrast medium. Lymphangiographic findings included a spectrum of lymphatic channel disorders including incompetence, obstruction, collateralization, chylous reflux, and chylous leak. There were no complications. CONCLUSIONS The simplified technique of injecting contrast medium into a lymph node to opacify the lymphatic system in children can be an alternative to the more elaborate conventional lymphangiography.

Complex lymphatic anomalies

Complex lymphatic anomalies include several diagnoses with overlapping patterns of clinical symptoms, anatomic location, imaging features, hematologic alterations, and complications. Lymphatic malformations likely arise through anomalous embryogenesis of the lymphatic system. Analysis of clinical, imaging, histologic, and hematologic features is often needed to reach a diagnosis. Aspiration of fluid collections can readily define fluid as chylous or not. The presence of chyle indicates dysfunction at the mesenteric or retroperitoneal level or above the cisterna chyli due to reflux. The imaging patterns of generalized lymphatic anomaly (GLA) and Gorham-Stout disease have been segregated with distinctive bone lesions and peri-osseous features. More aggressive histology (spindled lymphatic endothelial cells), clinical progression, hemorrhage, or moderate hematologic changes should raise suspicion for kaposiform lymphangiomatosis. Biopsy may be needed for diagnosis, though avoidance of rib biopsy is advised to prevent iatrogenic chronic pleural effusion. Lymphangiography can visualize the anatomy and function of the lymphatic system and may identify dysfunction of the thoracic duct in central conducting lymphatic anomalies. Local control and symptom relief are targeted by resection, laser therapy, and sclerotherapy. Emerging data suggest a role for medical therapies for complications of complex lymphatic anomalies. Outcomes include recurrent effusion, infection, pain, fracture, mortality, and rarely, malignancy. Complex lymphatic anomalies present significant diagnostic and therapeutic challenges. Results from a phase 2 study of sirolimus in these and other conditions are expected in 2014. Improved characterization of natural history, predictors of poor outcomes, responses to therapy, and further clinical trials are needed for complex lymphatic anomalies.

Kaposiform Lymphangiomatosis: A Distinct Aggressive Lymphatic Anomaly

OBJECTIVE To describe the clinical and imaging characteristics of a new lymphatic disorder with a unique histological pattern and poor prognosis. STUDY DESIGN An observational, retrospective study identified and characterized 20 patients with distinct lymphatic histopathology referred to the Vascular Anomalies Center at Boston Childrens Hospital between 1995 and 2011. RESULTS The median age at onset was 6.5 years (range, birth to 44 years). Clinical and radiologic findings suggested a generalized process. The most common presentations were respiratory symptoms (50%), hemostatic abnormalities (50%), and an enlarging, palpable mass (35%). All patients had mediastinal involvement; 19 patients developed pericardial (70%) and/or pleural effusions (85%). Extrathoracic disease manifested in bone and spleen and less frequently in abdominal viscera, peritoneum, integument, and extremities. Despite aggressive procedural and medical therapies, the 5-year survival was 51% and the overall survival was 34%. Mean interval between diagnosis and death was 2.75 years (range, 1-6.5 years). CONCLUSIONS We describe a clinicopathologically distinct lymphatic anomaly. We propose the term kaposiform lymphangiomatosis (KLA) because of characteristic clusters or sheets of spindled lymphatic endothelial cells accompanying malformed lymphatic channels. The intrathoracic component is most commonly implicated in morbidity and mortality; however, extrathoracic disease is frequent, indicating that KLA is not restricted to pulmonary lymphatics. The mortality rate of KLA is high despite aggressive multimodal therapy.

Fibro-adipose vascular anomaly: clinical-radiologic-pathologic features of a newly delineated disorder of the extremity.

Background: The diagnosis and management of vascular anomalies of the extremities can be challenging as these disorders are uncommon and may clinically overlap. The aim of this paper is to describe the clinical, radiologic, and histopathologic features of fibro-adipose vascular anomaly (FAVA), a previously unrecognized disorder of the limb. Methods: The clinical, imaging, operative, and histopathologic data from patients with a unique intramuscular lesion of the extremities comprising dense fibrofatty tissue and slow-flow vascular malformations were retrospectively reviewed. Results: Sixteen patients diagnosed with FAVA of the extremity (3 male and 13 female individuals) met the clinical, radiologic, and histopathologic inclusion criteria. The age at presentation ranged from the time of birth to 28 years. The locations of the lesions were: calf (n=10), forearm/wrist (n=3), and thigh (n=3). Fourteen patients presented with severe pain. Seven of the patients with calf lesions had limited ankle dorsiflexion. On imaging, the complex intramuscular lesions replaced muscle fibers with fibrofatty overgrowth and phlebectasia (dilation of the veins). The extrafascial component comprised fatty overgrowth, phlebectasia, and an occasional lymphatic malformation. The histopathologic features comprised dense fibrous tissue, fat, and lymphoplasmacytic aggregates within atrophied skeletal muscle. Adipose tissue also infiltrated skeletal muscle at the periphery of the lesion. There were large, irregular, and sometimes excessively muscularized venous channels and smaller, clustered channels. Other findings include organizing thrombi, a lymphatic component, and dense fibrous tissue–encircled nerves. Conclusions: The constellation of clinical, radiologic, and histopathologic features constitutes a distinct entity comprising fibrofatty infiltration of muscle, unusual phlebectasia with pain, and contracture of the affected extremity. The clinical and radiologic findings permit the diagnosis of FAVA with major therapeutic implications. Level of Evidence: Level III.

Diagnostic Imaging of Vascular Anomalies

Medical imaging has become critically important in the diagnosis and treatment planning of vascular anomalies. The classification of lesions into fast-flow and slow-flow categories, the identification of a soft tissue mass, and the determination of the extent of the lesions are all facilitated by the use of magnetic resonance imaging, ultrasonography, catheter angiography, and other imaging studies. The use of these imaging techniques in the diagnosis and assessment of vascular tumors, malformations, and combined malformation syndromes is discussed in this article.

Imaging of congenital mesoblastic nephroma with pathological correlation

BackgroundThere are a variety of imaging findings for congenital mesoblastic nephroma (CMN) and two main pathological variants: classic and cellular.ObjectiveTo determine whether imaging findings in children can predict the likely pathological variant.Materials and methodsWe reviewed imaging in children with pathology-proven CMN. Imaging findings correlated with gross and histological appearance.ResultsIn 15 boys and 15 girls with CMN, US was performed in 27, CT in 19, and MRI in 7. Cystic components were readily identified on US; central hemorrhage was better differentiated on CT. MRI demonstrated high sensitivity for both. Histology confirmed classic CMN in 13 children, cellular CMN in 14 and “mixed” CMN in 3. Age at presentation was significantly higher in children with the cellular variant. Of 15 solid or predominantly solid tumors and 10 lesions with a hypoechoic ring, 12 and 7, respectively, had pathology consistent with classic CMN. In contrast, five of seven with intratumoral hemorrhage and all with a large cystic/necrotic component had pathology consistent with the cellular variant.ConclusionThe imaging appearance of CMN is often determined by the pathological type of tumor. Findings suggestive of the classic variant include a peripheral hypoechoic ring or large solid component. In comparison, cystic/necrotic change and hemorrhage is much more common in cellular CMN.