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Purpose: Lower intestinal venous malformations are rare anomalies resulting from errors in vascular morphogenesis. These lesions may cause significant chronic and acute gastrointestinal hemorrhage. Venous malformations are unresponsive to angiogenesis inhibitors. Though these anomalies are generally incompletely resectable due to diffuse pelvic and mesenteric involvement, we sought to abate bleeding by excluding the lesion from the gastrointestinal lumen. Methods: Three patients with circumferential transmural venous malformations of the colorectum, pelvis and mesentery were identified. Imaging findings were similar among the patients, and included circumferential septated bright signal on T-2 weighted MRI, contrast enhancement, and multiple phleboliths, seen best on CT. The lesion extended from the anus to the splenic flexure in two patients and throughout the entire colorectum in the other. Each had daily hematochezia for many years and required transfusions (estimated over 100 units in one case) and chronic iron therapy. Though bleeding began in early childhood in each patient, no therapy was successful until ages 7,24, and 45. Colectomy, anorectal mucosectomy (through the pelvic venous malformation), and endorectal pull-through and anastomosis was performed (coloanal in two and ileoanal in one). Results: Bleeding has been essentially eradicated in all three patients with 5 to 52 month follow-up. One patient received a three unit transfusion intraoperatively and the other two received none. The most recently operated patient, who has residual venous malformation in the remaining 1 cm of anal mucosa, has some mild difficulty with fecal control if her diet results in loose stool. Conclusion: Colectomy with mucosectomy and endorectal pull-through should be considered for diffuse venous malformations of the colorectum prior to the development of large transfusion requirements., SJ Fishman MD, FAAP; RC Shamberger MD, FAAP; V Fox MD, PE Burrows MD; Children's Hospital, Boston, MA [...]

Hereditary hemorrhagic telangiectasia (HHT) is associated with defective capillary network, leading to dilated superficial vessels and arteriovenous malformations (AVMs) in which arteries connect directly to the veins. Loss or haploinsufficiency of components of TGF-β signaling, ALK1, ENG, SMAD4, and BMP9, have been implicated in the pathogenesis AVMs. Emerging evidence suggests that the inability of endothelial cells to detect, transduce and respond to blood flow, during early development, is an underpinning of AVM pathogenesis. Therefore, components of endothelial flow detection may be instrumental in potentiating TGF-β signaling in perfused blood vessels. Here, we argue that endothelial cilium, a microtubule-based and flow-sensitive organelle, serves as a signaling hub by coupling early flow detection with potentiation of the canonical TGF-β signaling in nascent endothelial cells. Emerging evidence from animal models suggest a role for primary cilia in mediating vascular development. We reason, on recent observations, that endothelial cilia are crucial for vascular development and that embryonic loss of endothelial cilia will curtail TGF-β signaling, leading to associated defects in arteriovenous development and impaired vascular stability. Loss or dysfunction of endothelial primary cilia may be implicated in the genesis of AVMs due, in part, to inhibition of ALK1/SMAD4 signaling. We speculate that AVMs constitute part of the increasing spectrum of ciliopathy-associated vascular defects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Eisa-Beygi, Burrows and Link.)

Background: Central conducting lymphatic anomalies (CCLA) may cause chylous leaks and protein-losing enteropathy (PLE) owing to dysfunction of the central lymphatic channels. Most of the treatment strategies for these conditions are palliative and provide transient improvement., Methods: We treated 14 patients with intractable chylous leak and/or PLE using a novel technique of lymphaticovenous bypass of the terminal portion of the thoracic duct. Chylous leaks occurred in multiple different anatomic sites. All patients had CCLA and failure of thoracic duct emptying demonstrated by preoperative intranodal lymphangiography., Results: Five patients had complete resolution of symptoms, and two patients had partial improvement. There were no major complications. Of 5 patients with PLE, only one improved after lymphaticovenous bypass. Repeat traditional lymphangiography was performed in 4 patients who did not improve, demonstrating patency of the bypass in all cases with persistent sluggish drainage. One patient had repeat MR lymphangiography that did not show the thoracic duct well., Conclusions: Bypass of the terminal thoracic duct is a novel procedure that offers improvement and a chance of cure for some patients with devastating manifestations of CCLA who lack other effective therapeutic options., Level of Evidence: IV., (Copyright © 2018. Published by Elsevier Inc.)

Objective- Endothelial cells (ECs) sense and respond to flow-induced mechanical stress, in part, via microtubule-based projections called primary cilia. However, many critical steps during vascular morphogenesis occur independent of flow. The involvement of cilia in regulating these stages of cranial vascular morphogenesis is poorly understood because cilia have not been visualized in primary head vessels. The objective of this study was to investigate involvement of cilia in regulating the early stages of cranial vascular morphogenesis. Approach and Results- Using high-resolution imaging of the Tg(kdrl:mCherry-CAAX) y171 ;(bactin::Arl13b:GFP) zebrafish line, we showed that cilia are enriched in the earliest formed cranial vessels that assemble via vasculogenesis and in angiogenic hindbrain capillaries. Cilia were more prevalent around the boundaries of putative intravascular spaces in primary and angiogenic vessels. Loss of cardiac contractility and blood flow, because of knockdown of cardiac troponin T type 2a ( tnnt2a) expression, did not affect the distribution of cilia in primary head vasculature. In later stages of development, cilia were detected in retinal vasculature, areas of high curvature, vessel bifurcation points, and during vessel anastomosis. Loss of genes crucial for cilia biogenesis ( ift172 and ift81) induced intracerebral hemorrhages in an EC-autonomous manner. Exposure to high shear stress induced premature cilia disassembly in brain ECs and was associated with intracerebral hemorrhages. Conclusions- Our study suggests a functional role for cilia in brain ECs, which is associated with the emergence and remodeling of the primary cranial vasculature. This cilia function is flow-independent, and cilia in ECs are required for cerebral-vascular stability.

Introduction: Extensive cervicofacial venous malformations (VM) pose significant challenges to a patient's quality of life (altered breathing, dysphagia, dysarthria). Treatment options include: 1) Surgical debulking; 2) Sclerotherapy; 3) laser therapy; or 4) Combined modalities. Recent studies have demonstrated the importance of multimodality and multidisciplinary management of these patients. However, no studies have described combined single anesthetic laser and sclerotherapy treatment. We sought to demonstrate the safety and efficacy of combined Nd:YAG laser and sclerotherapy under the same anesthetic administration., Methods: Retrospective review of 8 patients (Age 6 mo -74 yrs, x͂ 31) with extensive cervicofacial VM with significant airway involvement. Patients were treated with combined suspension laryngoscopy with Nd:YAG laser of airway VM followed by image guided direct puncture sclerotherapy using bleomycin in the airway VM and sodium tetradecyl sulfate (STS) foam in the cervicofacial VM during the same anesthetic encounter., Results: All 8 patients had extensive cervicofacial VMs that were symptomatic with snoring or orthopnea. Four of the patients had previously been treated at outside institutions with residual disease or significant complications. All patients remained intubated post procedure (Avg. 1.07 days) and tolerated extubation without re-intubation or any major complications. The average length of hospital stay was 3.2 days, of which 1.9 days were spent in the ICU. Patients reported symptomatic improvement or had decreased VM disease on MRI follow up., Conclusion: Combined Nd:YAG laser therapy and sclerotherapy allows treatment of both superficial and deep components of VMs in a safe and efficient manner. In addition, suspension laryngoscopy provides improved visualization and access for the interventional radiologist in difficult to reach areas for sclerotherapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Importance: Patients with somatic overgrowth commonly require surgical intervention to preserve function and improve cosmesis. To our knowledge no observation of scarring outcomes in this population has been published to date., Objective: To observe the frequency of abnormal scarring in patients with somatic overgrowth and sequencing-verified mutations in the PIK3CA gene., Design, Setting, and Participants: This retrospective study evaluated scarring outcomes in patients with PIK3CA-related overgrowth. Samples of affected tissue were sequenced between July 2015 and October 2016. Medical records from multiple large academic tertiary care centers were reviewed for surgical history and scar descriptions, and clinical photographs were assessed by 2 surgeons (J.N.J. and D.M.K.) to confirm abnormal scarring. Analysis of medical records and photographs was performed between April 2017 and June 2017 by a multidisciplinary team from dermatology, plastic surgery, orthopedic surgery, radiology, and genetics departments. All patients considered for the study were diagnosed with somatic overgrowth and previously had affected tissue sent for next-generation sequencing. Those with pathogenic PIK3CA variants and 1 or more prior surgical procedures were reviewed., Main Outcomes and Measures: Presence of excessive scarring in patients with PIK3CA overgrowth., Results: A total of 57 patients with segmental overgrowth syndromes were sequenced. Of the 57 patients, 25 (44%) had pathogenic or likely pathogenic variants in PIK3CA. Of those with pathogenic PIK3CA variants, 6 (24%) had past surgical procedures, all with preoperative and postoperative photographs. Of 6 patients with PIK3CA-related overgrowth and a history of 1 or more surgical procedure, 4 (67%) developed excessive scarring. The cohort with abnormal scarring comprised 3 females and 1 male, with a median age of 8.5 years. All abnormal scarring occurred in affected overgrowth tissue. Three of the 4 patients developed the excessive scarring after debulking procedures for overgrowth and/or vascular malformations of the upper or lower extremity., Conclusions and Relevance: Excessive scarring occurred frequently in patients with PIK3CA-related overgrowth syndromes. The risk of abnormal scarring should therefore be discussed preoperatively. Given the activating nature of these PIK3CA variants, we suggest that the excessive scarring may be owing in part to up-regulation of the PI3K-Akt-mTOR pathway. Additional studies are needed to assess scarring outcomes in patients with other types of overgrowth.

Vascular anomalies are variably associated with overgrowth, skeletal anomalies, and abnormalities of the brain, leptomeninges, and eye. We assembled a 16-institution network to determine the range of genetic variants associated with a spectrum of vascular anomalies with overgrowth, ranging from mild to severe. Because of the overlap between cancer-associated variants and previously described somatic variants in vascular overgrowth syndromes, we employed tumor genetic profiling via high-depth next-generation sequencing using a panel to assay affected tissue from a diverse cohort of subjects with vascular anomalies with overgrowth. Seventy-five percent (43/57) harbored pathogenic or likely pathogenic variants in 10 genes. We identified two genes (mTOR, PIK3R1) and several variants previously described in the setting of cancer but that, to our knowledge, have not been described in vascular malformations. All were identified at low variant allele frequency consistent with somatic mosaic etiology. By leveraging somatic variant detection technology typically applied to cancer in a cohort inclusive of broad phenotypic severity, we demonstrated that most vascular anomalies with overgrowth harbor postzygotic gain-of-function mutations in oncogenes. Furthermore, continued interrogation of oncogenes in benign developmental disorders could provide insight into fundamental mechanisms regulating cell growth., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal dominant vascular disorder that is associated with inherited inactivating mutations of the RASA1 gene in the majority of cases. Characteristically, patients exhibit one or more focal cutaneous CM that may occur alone or together with AVM, arteriovenous fistulas or lymphatic vessel abnormalities. The focal nature and varying presentation of lesions has led to the hypothesis that somatic "second hit" inactivating mutations of RASA1 are necessary for disease development. In this study, we examined CM from four different CM-AVM patients for the presence of somatically acquired RASA1 mutations. All four patients were shown to possess inactivating heterozygous germline RASA1 mutations. In one of the patients, a somatic inactivating RASA1 mutation (c.1534C > T, p.Arg512*) was additionally identified in CM lesion tissue. The somatic RASA1 mutation was detected within endothelial cells specifically and was in trans with the germline RASA1 mutation. Together with the germline RASA1 mutation (c.2125C > T, p.Arg709*) in the same patient, the endothelial cell somatic RASA1 mutation likely contributed to lesion development. These studies provide the first clear evidence of the second hit model of CM-AVM pathogenesis., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

This article describes three hereditary conditions known to be associated with arteriovenous malformation (AVM), along with their clinical and imaging features and angiographic angioarchitecture. Hereditary hemorrhagic telangiectasia, capillary malformation-AVM (CM-AVM), and PTEN tumor hamartoma syndrome are conditions with autosomal dominant inheritance, caused by mutations in different molecular pathways, which frequently present with symptomatic AVMs. Imaging biomarkers, including sites of predilection, angioarchitecture, and tissue overgrowth patterns, are helpful in identifying these patients and selecting appropriate treatment.

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.

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n = 100), common CM(s) (port-wine stain; n = 100), Sturge-Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the "second-hit" hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up., (© 2013 WILEY PERIODICALS, INC.)

Mutations in gene RASA1 have been historically associated with capillary malformation-arteriovenous malformation, but sporadic reports of lymphatic involvement have yet to be investigated in detail. To investigate the impact of RASA1 mutations in the lymphatic system, we performed investigational near-infrared fluorescence lymphatic imaging and confirmatory radiographic lymphangiography in a Parkes-Weber syndrome (PKWS) patient with suspected RASA1 mutations and correlated the lymphatic abnormalities against that imaged in an inducible Rasa1 knockout mouse. Whole-exome sequencing (WES) analysis and validation by Sanger sequencing of DNA from the patient and unaffected biological parents enabled us to identify an early-frameshift deletion in RASA1 that was shared with the father, who possessed a capillary stain but otherwise no overt disease phenotype. Abnormal lymphatic vasculature was imaged in both affected and unaffected legs of the PKWS subject that transported injected indocyanine green dye to the inguinal lymph node and drained atypically into the abdomen and into dermal lymphocele-like vesicles on the groin. Dermal lymphatic hyperplasia and dilated vessels were observed in Rasa1-deficient mice, with subsequent development of chylous ascites. WES analyses did not identify potential gene modifiers that could explain the variability of penetrance between father and son. Nonetheless, we conclude that the RASA1 mutation is responsible for the aberrant lymphatic architecture and functional abnormalities, as visualized in the PKWS subject and in the animal model. Our unique method to combine investigatory near-infrared fluorescence lymphatic imaging and WES for accurate phenoptyping and unbiased genotyping allows the study of molecular mechanisms of lymphatic involvement of hemovascular disorders.

Symptomatic slow-flow vascular malformations include venous malformations and lymphatic malformations, as well as combined anomalies. Endovascular therapy, consisting mainly of intralesional sclerosant injection, is now accepted as the primary treatment for most of these lesions. Magnetic resonance imaging and ultrasonography supplement physical examination for diagnosis and assessment of the extent of malformation. Endovascular treatment is usually carried out under general anesthesia. Sclerosants for venous malformations include ethanol, 3% sodium tetradecyl sulfate, and bleomycin. Lymphatic malformations can be injected with doxycycline, bleomycin, OK-432, or other sclerosants. Complications of sclerotherapy include tissue necrosis, peripheral nerve injury, hemoglobinuria, deep vein thrombosis, and pulmonary embolism. Although most vascular malformations are not cured, the majority of patients benefit from endovascular treatment., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The purpose of this article is to study the incidence, risk factors, and treatment of gross hemoglobinuria and oliguria following sclerotherapy for venous malformations., Materials and Methods: The clinical records and imaging studies of 131 patients with venous malformations (57 male and 74 female patients; age range, 2-58 years) who underwent sclerotherapy at our institution between July 1993 and August 2007 were reviewed. Demographic data, the location and estimated size of the malformation, the type and dose of the sclerosing agents, development of postprocedural hemoglobinuria and oliguria, and the treatment given were documented and analyzed., Results: Four hundred seventy-five sclerotherapy procedures were performed on 131 patients, with the number of procedures per patient ranging from 1 to 21 (mean, 3.6 procedures). Sodium tetradecyl sulfate was used in 47% of the procedures, ethanol in 27%, and both agents in 26%. Transient hemoglobinuria occurred after 34% of the sclerotherapy procedures, and 57% of these were associated with transient oliguria, with increased risk with higher adjusted doses (sclerosant volume/weight of patient) for both agents. Resolution of the hemoglobinuria and oliguria with hydration, alkalinization, and diuretics occurred in all patients. The risk of hemoglobinuria increased with higher adjusted dose (sclerosant volume/weight of patient) for both agents and with sclerotherapy of venous malformations affecting the lower extremities and multiple locations., Conclusion: Transient hemoglobinuria and oliguria are common complications of sclerotherapy for venous malformation. Nevertheless, with proper fluid management, all the patients promptly recovered. The risk correlates with the volume of sclerosant (adjusted to patient's weight) and is higher for lower extremity and multiple locations.

The clinical implications of venous cerebrovascular maldevelopment remain poorly understood. We report on the association of cerebrofacial venous anomalies (including sinus pericranii), ocular abnormalities and mild developmental delay in two children. In addition, one child had a seizure disorder. Complex cerebrofacial slow-flow vascular anomalies may herald an underlying developmental aberration affecting the cerebrofacial and orbital regions.

PTEN hamartoma tumor syndrome (PHTS) presents in a spectrum that encompasses the eponymous disorders Cowden and Bannayan-Riley-Ruvalcaba. Herein, we delineate the distinctive histopathology of a predominantly intramuscular lesion in PHTS, often called "arteriovenous malformation," because of certain imaging and histopathologic features. Cases were identified by review of lesions resected from patients with PHTS registered at our Vascular Anomalies Center and of unusual intramuscular vascular anomalies in our pathology database from 1985 to 2008. Thirty-four patients with this lesion were identified: 20 had a clinical diagnosis of, or were suspected to have, PHTS (genetically confirmed in 16). In 4 patients without clinical manifestations of PHTS, 2 had PTEN mutations, 1 did not, and in 1 the mutation was intronic. In the remaining 10, there was insufficient clinical information to fully assess whether they had manifestations of PHTS. Lesions manifested by 15 years of age, normally with pain and swelling, and were most often located in the lower extremity. The major mass was usually intramuscular, but often there were fascial and subcutaneous components and not infrequently a cutaneous vascular stain. Magnetic resonance imaging generally showed an infiltrative soft tissue lesion involving the muscle, fascia, and subcutis with frequently enlarged, serpiginous vessels, small arteriovenous fistulae with disproportionately dilated draining veins, and a prominent adipocytic component. Some lesions involved contiguous muscles, and 20% were multifocal. Resected specimens ranged in size from 1.2 to 25 cm; in 1 patient, amputation was necessary. Histopathologically, these unencapsulated masses, often with a nodular appearance at scanning magnification, consisted of: (1) a variable admixture of mature adipocytic and dense and/or myxoid fibrous tissues (50% to 90% of surface area); (2) a vascular component (10% to 50% of surface area) with: (a) clusters of venous channels, some with excessively and irregularly muscularized complex walls and lumens, and others with thin walls resembling pulmonary alveoli, (b) tortuous, thick-walled arteries with concentric muscular hyperplasia and relatively small lumens, (c) numerous small vessels (arteries, veins, and indeterminate channels), and (d) occasional arteriovenous communications; (3) lymphoid follicles (50%); (4) foci of bone (20%); and (5) hypertrophic nerves with "onion bulb" proliferation of periaxonal spindled cells (9%). We designate this disorganized overgrowth of essentially mesenchymal elements as PTEN hamartoma of soft tissue. It differs from other vascular and connective tissue lesions that occur in patients with PHTS. PTEN hamartoma of soft tissue is histopathologically distinctive, and its identification should prompt a thorough investigation for PHTS.

CLOVES syndrome is a complex disorder of congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/scoliosis/spinal anomalies. We report the occurrence of spinal-paraspinal fast-flow lesions within or adjacent to the truncal overgrowth or a cutaneous birthmark in 6 patients with CLOVES syndrome.

Purpose: To assess the safety and efficacy of percutaneous image-guided sclerotherapy with doxycycline as primary treatment of intraabdominal lymphatic malformations (LMs)., Materials and Methods: Retrospective review was performed of all cases of abdominal, mesenteric, or retroperitoneal LMs referred to a single center that were subsequently treated with image-guided percutaneous sclerotherapy., Results: Ten patients were included, of whom six were male. The mean age was 13 years (range, 2-28 y). Preprocedural cross-sectional imaging demonstrated a macrocystic malformation in nine patients and a mixed macrocystic/microcystic malformation in one. The malformation was accessed under sonographic guidance, followed by injection of opacified sclerosant agent under fluoroscopic guidance. A drainage catheter was placed in eight cases, in which sclerotherapy was repeated through the catheter for another 1 day (n = 2) or 2 days (n = 6). Doxycycline was reconstituted at 10 mg/mL, with a mean per-session dose of 608 mg (range, 80-1,000 mg) and a mean total dose of 1,230 mg (range, 80-3,000 mg). Peritoneal spill was identified in one case, but the patient remained asymptomatic. No other complications were encountered. Follow-up imaging was available in eight patients: complete resolution was seen in seven, with partial resolution in one. There was no recurrence of clinical symptoms in the follow-up period., Conclusions: Initial results indicate that percutaneous image-guided sclerotherapy of macrocystic intraabdominal LMs with doxycycline is a safe and effective procedure., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Bannayan-Riley-Ruvacalba syndrome (BRRS) belongs to the PTEN hamartoma tumor syndromes and is characterized by a high risk of malignancy in early adulthood added to local destructive effects of hamartomas in childhood. There is no standard treatment for this condition and patients are usually offered symptomatic surgical relief. Rapamycin has been reported to be effective in the management of other conditions associated with PTEN mutation. We report here a case of BRRS in a 6-year-old male with progressive loss of function of left hand and forearm associated with pain. He was treated with oral rapamycin and regained pain-free full mobility., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: To define the clinical spectrum of regional congenital anomalies associated with large cutaneous hemangiomas of the lower half of the body, clarify risk for underlying anomalies on the basis of hemangioma location, and provide imaging guidelines for evaluation., Study Design: We conducted a multi-institutional, retrospective case analysis of 24 new patients and review of 29 published cases., Results: Hemangiomas in our series tended to be "segmental" and often "minimal growth" in morphology. Such lesions were often extensive, covering the entire leg. Extensive limb hemangiomas also showed potential for extracutaneous anomalies, including underlying arterial anomalies, limb underdevelopment, and ulceration. The cutaneous hemangioma and underlying anomalies demonstrated regional correlation. Myelopathies were the most common category of associated anomalies., Conclusions: We propose the acronym "LUMBAR" to describe the association of Lower body hemangioma and other cutaneous defects, Urogenital anomalies, Ulceration, Myelopathy, Bony deformities, Anorectal malformations, Arterial anomalies, and Renal anomalies. There are many similarities between LUMBAR and PHACE syndrome, which might be considered regional variations of the same. Although guidelines for imaging are suggested, prospective studies will lead to precise imaging recommendations and help determine true incidence, risk and long-term outcomes., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background and Purpose: KTS is a rare limb overgrowth disorder with slow-flow vascular anomalies. This study examines the presumed association between KTS and spinal AVMs., Materials and Methods: We performed a MEDLINE search of articles and reviewed textbooks of spinal diseases to study the association between KTS and spinal AVM. Our goal was to ascertain the basis on which the diagnosis of KTS was established and to evaluate the evidence of its association with spinal AVMs. In addition, the data base of the Vascular Anomalies Center at Children's Hospital Boston was queried for patients with KTS, and the association with spinal AVM was investigated., Results: Twenty-four published reports on spinal AVMs in 31 patients with KTS were reviewed. None of these references provided solid evidence of the diagnosis of KTS in any patient. Clinical data were either incompatible with the diagnosis of KTS or were inadequate to establish the diagnosis. Alternative possible diagnoses (CLOVES syndrome and CM-AVM) were suggested by the first author for 9 of the patients reported in these articles. The medical records of 208 patients with the diagnosis of KTS were analyzed; not a single patient had clinical or radiologic evidence of a spinal AVM., Conclusions: An association between KTS and spinal AVM, as posited in numerous references, is most likely erroneous. The association has neither been reliably proved in the limited published literature nor encountered in a large cohort.

Objective: CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/scoliosis and spinal abnormalities) is a rare, complex overgrowth syndrome with serious morbidity. In this communication we studied the presence of central and thoracic phlebectasia in patients with CLOVES syndrome and its clinical implications., Methods: We conducted a comprehensive search of our databases at Children's Hospital Boston over the last 10 years (1999-2008) for patients with CLOVES syndrome and central and thoracic phlebectasia. Medical records, clinical photographs, and imaging studies of varying modalities were reviewed., Results: Review of the clinical data and imaging studies of 12 patients with CLOVES syndrome documented the presence of central and thoracic phlebectasia in 11 patients. Two patients had serious perioperative pulmonary embolism, and 1 died., Conclusions: Central and thoracic phlebectasia in patients with CLOVES syndrome is common and increases the risk of pulmonary embolism. Aggressive prophylactic measures should be considered before major interventions., (Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Purpose: We report thrombosis of portal and mesenteric veins in patients with a pattern of rectal venous malformations (VMs) and ectatic major mesenteric veins., Methods: Eight patients having rectal VMs with either ectatic mesenteric veins and/or evidence of portomesenteric venous thrombosis (PVT), evaluated from 1995-2009, were reviewed., Results: Portomesenteric venous thrombosis was evident in 5 patients at presentation. Three had patent ectatic mesenteric veins, 2 with demonstrated reversal of flow, and 2 of whom went on to thrombosis during observation. Six patients developed portal hypertension. Five remain on long-term anticoagulation. After recognizing this pattern, one patient underwent preemptive proximal ligation of the inferior mesenteric vein (IMV) to enhance antegrade portal vein flow and prevent propagation or embolization of venous thrombus from the IMV to the portal vein., Conclusion: Rectal VMs should be evaluated for associated ectatic mesenteric veins. The ectatic vein siphons flow from the portal vein down to the rectal VM, leading to stagnation of blood in the portal vein and resultant thrombosis. Primary thrombosis in the stagnant rectal VM and/or mesenteric vein can also predispose to embolization up into the portal vein. This pattern of rectal VM and ectatic mesenteric vein should be considered a risk factor for devastating PVT., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background and Purpose: CM-AVM is a recently recognized autosomal dominant disorder associated with mutations in RASA1. Arteriovenous lesions have been reported in the brain, limbs, and the face in 18.5% of patients. We report a novel association between RASA1 mutations and spinal arteriovenous anomalies., Materials and Methods: In a collaborative study, 5 index patients (2 females, 3 males) with spinal AVMs or AVFs and cutaneous multifocal capillary lesions were investigated for the RASA1 gene mutation., Results: All 5 patients were found to have RASA1 mutation (2 de novo, 3 familial), and all had multifocal capillary malformations at birth. Neurologic deficits developed at ages ranging from infancy to early adulthood. All spinal anomalies (2 AVMs at the conus, 1 AVM at the lumbosacral junction, and 1 cervical and 1 cervicothoracic AVF) were complex, extensive, and fast-flow lesions. All patients required treatment based on the clinical and/or radiologic appearance of the lesions., Conclusions: To our knowledge, an association of RASA1 mutation and spinal AVM/AVF has not been described. MR imaging screening of patients with characteristic CMs and neurologic symptoms presenting at a young age may be useful in detecting the presence of fast-flow intracranial or intraspinal arteriovenous anomalies before potentially significant neurologic insult has occurred.

Background and Purpose: The neuroradiology and neurosurgery literature is replete with references to "hemangioma" involving the central nervous system (CNS). However, the number of cases of true infantile hemangiomas in the CNS reported to date is 15. Our purpose was to delineate the definition of infantile hemangiomas, determine their prevalence in the neuraxis, and describe their imaging characteristics and associations in this location., Materials and Methods: We reviewed our Vascular Anomalies Center data base from 1999 through May 2008 to assess the prevalence of intracranial or intraspinal involvement within the total cohort of infantile hemangiomas. Fifteen patients were identified with infantile hemangiomas that involved the neuraxis. Two board-certified neuroradiologists reviewed the available imaging of these 15 patients, and a board-certified pathologist reviewed the available histopathology. Clinical records of all 15 patients were reviewed to identify the type of treatment and the treatment response., Results: Of the 1454 patients listed with infantile hemangioma, 15 (approximately 1.0%) had involvement of the CNS. Eight patients had intracranial infantile hemangioma, 6 had intraspinal hemangioma, and 1 had both. In most instances, there was continuous extension into the neuraxis from an extracranial or extraspinal lesion. There were no cases of a CNS hemangioma without an accompanying extra-CNS tumor. Two patients had findings consistent with posterior fossa anomalies, cervicofacial hemangioma, arterial anomalies, cardiac defects, ocular abnormalities, and associated sternal or ventral defect. Of note, there were no brain or spinal parenchymal signal-intensity abnormalities, and there was no evidence of parenchymal invasion., Conclusions: CNS involvement by infantile hemangiomas is an unusual occurrence, which, when recognized, can help optimize patient management.

We present a young girl with a diffuse, macrocystic lymphatic malformation with associated venous dilation involving the left lower pulmonary lobe and mediastinum. Recurrent hemoptysis necessitated left lower lobectomy. This is the first reported case of a macrocystic lymphatic lesion with venous anomalies located within the parenchyma of the lung.

A young girl with an arteriovenous malformation involving the right upper extremity developed rapidly progressive bony destruction that did not respond to embolization. Treatment with marimastat, starting at 3 years of age, resulted in rapid resolution of pain and gradual healing of bony destruction, associated with regression of the intraosseous arteriovenous shunts. New arteriovenous shunts with bony destruction developed over the years and responded to an increase in the dose of marimastat. Interruption of therapy resulted in recurrence of pain and formation of new lesions. The patient has been treated in this way for 12 years with no adverse effects from the drug.

Vascular malformations (VM) are classified by flow characteristics and channel content. They can involve any organ and tissue plane, and occur in focal and diffuse forms. Slow-flow vascular malformations (venous and lymphatic malformations) are typically treated by sclerotherapy, whereas fast-flow lesions (arteriovenous malformations) are managed with embolizations. Some VMs, such as VMs of the rectum or uterus, are best dealt with surgically. This review will present a summary of the conditions, their imaging features, and some useful endovascular therapeutic techniques.

Capillary malformation-arteriovenous malformation (CM-AVM) is a newly recognized autosomal dominant disorder, caused by mutations in the RASA1 gene in six families. Here we report 42 novel RASA1 mutations and the associated phenotype in 44 families. The penetrance and de novo occurrence were high. All affected individuals presented multifocal capillary malformations (CMs), which represent the hallmark of the disorder. Importantly, one-third had fast-flow vascular lesions. Among them, we observed severe intracranial AVMs, including vein of Galen aneurysmal malformation, which were symptomatic at birth or during infancy, extracranial AVM of the face and extremities, and Parkes Weber syndrome (PKWS), previously considered sporadic and nongenetic. These fast-flow lesions can be differed from the other two genetic AVMs seen in hereditary hemorrhagic telangiectasia (HHT) and in phosphatase and tensin homolog (PTEN) hamartomatous tumor syndrome. Finally, some CM-AVM patients had neural tumors reminiscent of neurofibromatosis type 1 or 2. This is the first extensive study on the phenotypes associated with RASA1 mutations, and unravels their wide heterogeneity.

Background: Lymphatic malformations (LMs) can be effectively treated by percutaneous intralesional injection of a variety of sclerosant drugs. This study aims to evaluate the efficacy of doxycycline in the treatment of LMs., Methods and Results: We reviewed the medical records of all patients with LMs who underwent sclerotherapy with doxycycline between January 1, 2003 and September 1, 2004 at Children's Hospital Boston. Follow-up imaging was performed to assess for change in lesion size. Surveys were sent to all study patients, to assess perceived improvements in symptoms and satisfaction with the results. Sixty sclerotherapy procedures were performed on 41 patients in the 20-month study period. The median age was 6.9 years (3 mo-31 y). The most common location was cervicofacial (66%), followed by truncal (19%) and extremity (15%). The most common lesion type was macrocystic (49%), followed by combined (44%) and microcystic (7%). The major and minor complication rates were 2% and 10%, respectively. The mean outcome score by imaging was 4.41/5 with a 95% CI of [4.13-4.68] corresponding to about an 83% reduction in lesion size, and by patient survey was 4.47/5 with a 95% CI of [4.15-4.79] corresponding to between a good to complete response. Higher complication rates were associated with microcystic and combined lesions (p = 0.03), and greater doxycycline dose (p = 0.05)., Conclusions: Doxycycline is a safe and effective sclerosant for LMs. Greater follow-up is necessary to quantify long-term outcomes and assess the risks of lesion recurrence.

We describe six patients with an uncommon variant of infantile hemangioma that we have termed reticular, occurring in the extremity, which were associated with intractable ulceration, anogenito-urinary-sacral anomalies, and sometimes cardiac overload. The extreme end of the spectrum is exemplified by a male neonate who presented with a stained, enlarged, pulsatile lower extremity, and cardiac failure. He also had hepatic hemangiomas and ambiguous genitalia. Progressive soft tissue necrosis and bony destruction necessitated amputation. The histopathologic features differed from those of typical infantile hemangioma: infiltrative (not lobular) and involving fascia, muscle, and bone. The mid-spectrum is illustrated by five females with reticular infantile hemangioma of the lower limb, buttock, and perineum. Four of these infants had a ventral-caudal anomaly, including omphalocele, recto-vaginal fistula, solitary/duplex kidney, imperforate anus, and tethered cord; one infant also had hepatic hemangiomas. Deep ulcerations healed following corticosteroid therapy; one patient required skin graft for closure of a thigh wound. The minor end of the spectrum is exemplified a patchy lesion in the distal limb. The reticular variant of infantile hemangioma can be confused with other vascular anomalies in the limb, such as capillary malformation, cutis marmorata telangiectasia congenita, diffuse arteriovenous malformation (Parkes Weber syndrome) and capillary-lymphatico-venous malformation (Klippel-Trenaunay syndrome). The macular network-like appearance of the tumor and coexisting ventral-caudal structural anomalies is analogous to the association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities association in the craniofacial region.

Background and Purpose: The purpose of this study was to determine the nature, incidence, and radiologic appearance of intracranial vascular anomalies that occur in association with periorbital lymphatic malformation (LM) and lymphaticovenous malformation (LVM)., Materials and Methods: We retrospectively reviewed clinical records and imaging studies of 33 patients ranging in age from the neonatal period to 39 years (mean age, 5.1 years; median age, 1.0 year) who were evaluated for orbital LM or LVM at our institution between 1953 and 2002. Imaging studies, including CT, MR imaging, and cerebral angiograms, were evaluated by 2 radiologists to determine morphologic features of orbital LM and to identify associated noncontiguous intracranial vascular and parenchymal anomalies, including arteriovenous malformations (AVM), cerebral cavernous malformations (CCM), developmental venous anomalies (DVA), dural arteriovenous malformations (DAVM), and sinus pericranii (SP)., Results: The malformation was left-sided in 70% of patients. Twenty-two patients (70%) had intracranial vascular anomalies: DVA (n = 20; 61%), CCM (n = 2; 6%), DAVM (n = 4; 12%), pial AVM (n = 1; 3%), and SP (n = 1; 3%). Arterial shunts were present in the soft tissues in 2 patients (6%). Three patients had jugular venous anomalies. Three patients (9%) had cerebral hemiatrophy, 2 (6%) had focal cerebral atrophy, and 2 had Chiari I malformation., Conclusions: Intracranial vascular anomalies, some of which are potentially symptomatic and require treatment, are present in more than two thirds of patients with periorbital LM. Initial imaging of patients with orbital LM should include the brain as well as the orbit.

Purpose: Hepatic hemangiomas, though histologically benign, may be associated with significant morbidity and mortality in afflicted infants. The literature presents much confusion regarding the natural history and treatment options for hepatic hemangiomas. Clinical manifestations range from asymptomatic self-limiting lesions to congestive heart failure associated with high-volume vascular shunting to fulminant hepatic failure with hypothyroidism, abdominal compartment syndrome, and death. There has been little rationale to choose among observation, corticosteroid, other pharmacologic agents, arterial embolization, hepatic artery ligation, resection, or liver transplantation for any given patient., Methods: We analyzed several recent retrospective radiologic analyses and pathologic studies to determine whether hepatic hemangiomas could be categorized, allowing prediction of their natural history and rational choice of therapies based upon their clinical presentation and radiographic appearance., Results: We propose that hepatic hemangiomas do not represent a single entity but, rather, 3 principle categories of lesions: focal, multifocal, and diffuse. Because these 2 categories represent different anatomical and physiologic variants, so, too, may they respond differently to previously anecdotally applied treatment regimens. With input from international multidisciplinary authorities on hemangiomas, we developed and proposed a clinical practice algorithm for the evaluation and management of hepatic hemangiomas. Toward that end, we propose a plan to institute a web-based international hepatic hemangioma registry. Participants in the registry could obtain no-cost centralized review of imaging studies (and histology if available) and guidance regarding the management algorithm from an established multidisciplinary team. In exchange, the registry will facilitate the acquisition of systematic clinical and imaging information., Conclusion: Longitudinal observation of response to more directed treatment protocols may contribute greatly to the understanding of these potentially fatal tumors.

Background: Pediatric patients who undergo diagnostic radiological imaging studies routinely require moderate or deep sedation to a Ramsay Sedation Score (RSS) of 4 or 5, respectively. The correlation between moderate and deep RSS and bispectral index (BIS) in children has never been validated. This study was designed to determine whether the BIS values correlate with RSS of children sedated for diagnostic imaging studies., Methods: After Institutional Review Board approval, data were prospectively collected on all children receiving pentobarbital alone for computed tomography or magnetic resonance imaging. On arrival in the recovery room, any child assigned a Ramsay score of 4 or 5 was subsequently monitored with the BIS. Receiver-operating characteristic (ROC) analysis was used to evaluate the discriminative ability of BIS in differentiating depth of anesthesia., Results: A total of 86 children over 1 year of age were enrolled. Children with Ramsay 4 (moderate) and Ramsay 5 (deep) sedation scores showed no significant difference in age or pentobarbital dose (mg.kg(-1)). BIS values followed a normal Gaussian-shaped distribution for both Ramsay scores. There was no significant difference in mean BIS values between the Ramsay groups (P = 0.64). There was a wide variation in BIS values (range of 31-90), which demonstrates that the BIS monitor does not correlate with the clinically assigned RSS depth of anesthesia in children. The ROC curve for BIS is equivalent to a line of nondiscrimination., Conclusion: BIS has limited ability to distinguish between moderate and deep Ramsay sedation levels in children who receive pentobarbital sedation for diagnostic imaging studies.

Objective: To determine the efficacy and safety of radiofrequency (RF) ablation of vesicles and the resulting symptomatic control of microcystic lymphatic malformation (LM) in the oral cavity., Design: An institutional review board-approved retrospective study with follow-up telephone interview., Setting: Tertiary pediatric medical center. Patients Eleven children (6 girls and 5 boys), aged 4 to 16 years, presenting between August 1, 2002, and December 1, 2004. Intervention Radiofrequency ablation of LM in the oral cavity., Main Outcome Measures: Symptoms related to LM, postoperative oral intake, and postoperative antibiotic requirements., Results: Eleven patients presented with microcystic LM involving the lips, tongue, floor of the mouth, or buccal mucosa. Complaints included bleeding, infection, swelling, vesicle formation, and malocclusion. Patients underwent RF ablation (coblation) of oral cavity lesions. Seven (64%) of the 11 patients were able to tolerate oral intake in the recovery room. The need for antibiotics was reduced after RF ablation. All patients related diminished bleeding, pain, infection, or vesicle formation, with more than half reporting a significant improvement (6 patients) or complete resolution (1 patient). Five (62%) of 8 parents stated that the improvement after RF ablation was superior to that following previous procedures., Conclusions: Subtotal RF ablation of LM appears to be safe, with early postoperative oral intake and minimal postoperative pain. Further studies are needed to determine long-term control of LM.

Purpose: To evaluate the midterm outcomes of percutaneous sclerotherapy of lymphatic malformations (LMs) as judged by patients., Materials and Methods: A 13-item survey questionnaire was sent to 74 patients who had undergone at least one sclerotherapy procedure in our hospital from January 1997 through January 2003. Information regarding the anatomic location, specific symptoms reported, history, treatment satisfaction, postprocedural complications, and number of treatment sessions was elicited. Four sclerosing agents (as single agents or in combination with other agents) were used: ethanol, sodium tetradecyl sulfate 3% (STS), OK-432, and doxycycline., Results: Fifty-five patients or their caregivers completed the survey. The patients' ages ranged from 6 months to 48 years at the time of the first procedure (mean, 12 y; median, 4 y). A majority of LMs were located in the cervicofacial region. The size and location of the lesion, recurrent infection, and pain were the most frequent indications for treatment. Fifty-one percent of these patients received sclerotherapy alone or in conjunction with surgery as primary treatment. Ethanol was the most common sclerosing agent used, followed by doxycycline, STS, and OK-432. Response varied with the type of LM, with 100%, 86%, and 43% of the patients reporting good to complete response for macrocystic, microcystic, and combined-type LMs, respectively. Skin blistering and ulcers were the most common complications. Permanent complications were uncommon and were largely related to ethanol use., Conclusions: Percutaneous sclerotherapy provides effective midterm primary treatment for LMs. Treatment outcomes appear to vary according to the morphology of the malformation.

Intracranial arteriovenous malformations (AVM) are a rare feature of Bannayan-Riley-Ruvalcaba syndrome (BRRS). Palencia et al reported a case of intracranial arteriovenous malformation in a child with BRRS in a Spanish journal in 1986. However, the occurrence of dural AVM in a patient with BRRS has not since been addressed in the literature. Advancements in imaging and therapeutic embolization, and the ability now to screen for phosphatase and tensin homologue (PTEN) mutations allow us to detect and manage these patients sooner. Early detection of intracranial AVMs is necessary because of the risk for progression to venous ischemia and resultant neurologic damage. We present the case of a child with headaches and periorbital venous congestion due to a dural AVM with bilateral venous outflow occlusion who was treated with multiple embolizations, now with interval remission of headache symptoms.

Dibenzofuran (DBF) is converted to a vacuum-sublimable, electron-transporting host material via 2,8-substitution with diphenylphosphine oxide moieties. Close pi-pi stacking and the inductive influence of P=O moieties impart favorable electron-transport properties without lowering the triplet energy. A maximum external quantum efficiency of 10.1% and luminance power efficiency of 25.9 lm/W are realized using this material as the host for the blue-green electrophosphorescent molecule, iridium(III) bis(4,6-(di-fluorophenyl)pyridinato-N,C(2')picolinate (FIrpic).

Background/purpose: Vascular tumors and malformations are rare. This large series describes vascular anomalies of the female genitalia and their management., Methods: An international review board-approved retrospective database and a record review from 1994 through 2004 was conducted., Results: Of the 3186 female patients with a vascular anomaly, 82 (2.6%) had a lesion in the external genitalia. There were 60 malformations and 22 tumors. The most common malformations were combined capillary-lymphaticovenous, venous, and lymphatic. Tumors included 20 infantile hemangiomas, 1 kaposiform hemangioendothelioma, and 1 kaposiform lymphangioendothelioma. The referring diagnosis was incorrect in 56% of patients. Cutaneous stains, swelling, deformity, bleeding, fluid leakage, or infection were the prominent symptoms. Magnetic resonance imaging, ultrasonography, angiography, and computed tomography were used for diagnostic clarification. Malformation treatment consisted of sclerotherapy, embolization, and operative resection. Tumor management included observation, surgical excision, and antiangiogenic pharmacotherapy., Conclusions: Vascular anomalies of the female external genitalia are uncommon, and the initial diagnosis is often inaccurate. Correct diagnosis using clinical and radiographic data is feasible and leads to meaningful intervention for these frequently devastating lesions. Whereas tumors may respond to excision or antiangiogenic drugs, malformations require ablation or resection. Evaluation and management of these lesions is complex and benefits from interdisciplinary care.

Background: The extracellular dynamics after intravascular sclerotherapy with an injectable, fibroblast-based engineered construct is unknown., Methods: Rabbits underwent ethanol sclerotherapy of a jugular vein segment. Control animals (n = 40) underwent no further treatment or an acellular collagen hydrogel was injected. Experimental animals (n = 20) received a tissue-engineered construct. After 1, 2, 4, and 20 to 24 weeks, segments were evaluated for collagen, glycosaminoglycan (GAG), matrix metalloproteinase (MMP) 2 and 9, and tissue inhibitors of MMP (TIMPs) 1 and 2 and scored on a scale of 0 to 3. Groups and time points were compared using nonparametric statistical analysis., Results: Collagen content was higher in animals that received fibroblasts (P < .05). Glycosaminoglycan analysis showed a higher grade only at 1 week (P < .05). Collagen and GAG deposition were prominent at weeks 1 through 4, and decreased over time. Both MMP-2 and MMP-9 and TIMP-1 and TIMP-2 grade decreased with time (P < .01) in all groups, with no differences between groups., Conclusion: Enhancement of intravascular sclerotherapy by tissue engineering stems, at least in part, from increased local deposition of collagen and GAG. MMP and TIMPs may play a role in recanalization after experimental sclerotherapy. Tissue engineering may be a valuable adjunct for the treatment of vascular malformations.

Purpose: To retrospectively identify factors associated with an increased risk of adverse cardiovascular or respiratory events during sedation of pediatric patients for imaging examinations., Materials and Methods: This HIPAA-compliant study was institutional review board approved; the requirement for informed consent was waived. All sedation information--including patient demographics, medications (doses and routes of administration), time required to sedate and before discharge, American Society of Anesthesiologists physical status classification, adverse events, and failed sedations--was maintained in a computerized database. A review of the data on all patients sedated between 1997 and 2003 for magnetic resonance imaging, computed tomography, and interventional radiology revealed associated adverse respiratory events in 70 patients. Adverse respiratory event was defined as oxygen desaturation of at least 5%, pulmonary aspiration, and need for airway resuscitation. Adverse cardiovascular events were defined as cardiac arrest and hemodynamic changes requiring medical therapy. Adverse events were compared between sedation regimens--which included fentanyl, chloral hydrate, pentobarbital, and midazolam hydrochloride--by using the Fisher exact test. Multiple logistic regression analysis was applied to identify potential predictors of adverse events., Results: Among 16,467 sedations performed, 70 (0.4%) were associated with adverse respiratory events: 58 cases of oxygen desaturation, two pulmonary aspirations, 10 cases of airway resuscitation, and no cardiovascular events. Nearly 30% (n = 20) of the 70 patients who had an adverse event had a history of serious respiratory illness. Logistic regression analysis revealed that neither patient age, weight, or sex nor type of imaging procedure was associated with an increased risk of an adverse event. Use of a single sedation agent was associated with lower adverse event risk than was use of multiple agents (P < .001)., Conclusion: Consideration should be given to using single agents, avoiding the use of multidrug sedation regimens, and recognizing that a history of pulmonary disease could be associated with an increased risk of adverse respiratory events despite a currently stable respiratory state., (RSNA, 2005)

We describe 10 children with multiple vascular lesions of the skin and gastrointestinal tract associated with sustained, minor thrombocytopenia. In some children, there was involvement of the lung (n = 5), bone (n = 2), liver (n = 1), spleen (n = 1), and muscle (n = 1). The cutaneous lesions were congenital, multifocal, discrete, red-brown and variably blue macules and papules; in 3 children, a large dominant plaque was also present. All children developed hematemesis and/or melena and endoscopic evaluation revealed several to numerous small mucosal lesions that involved all levels of the gastrointestinal tract. Three of 5 children with pulmonary nodules had cough and 1 also had hemoptysis. Biopsies of cutaneous, gastrointestinal, and pulmonary lesions showed thin-walled, blood-filled vascular channels and variable endothelial hyperplasia. The endothelial nuclei were elongated, round, crescentic, or hobnailed. Cytoplasmic and extracellular periodic acid-Schiff positive deposits were often present in the zones of endothelial hyperplasia. The platelets were small in some children, suggesting a primary defect, possibly accounting for the thrombocytopenia. Gastrointestinal hemorrhage and hemoptysis required antiangiogenic therapy. The constellation of findings defines a congenital proliferative disorder of blood vessels with a distinctive microscopic appearance. We have termed this relatively indolent or slowly progressive disorder cutaneovisceral angiomatosis with thrombocytopenia because this designation incorporates its major clinical and histopathologic features.