BACKGROUND:Splenic artery aneurysm (SAA) is a rare but potentially fatal condition. Rupture results in 25% mortality up to 75% in pregnant women with 95% fetal mortality. Brief reports suggest an increased risk of developing SAA in patients with HHT.METHODS:We analyzed enhanced multidetector CT data in 186 HHT patients matched (gender and ± 5 year old) with 186 controls. We screened for SAA and recorded diameter of splenic and hepatic arteries and hepatic, pancreatic and splenic parenchymal involvements. We determined by univariate and multivariate analysis, the relationship with age, sex, genetic status, cardiovascular risk factors (CVRF) and visceral involvement.RESULTS:SAA concerned 24.7% of HHT patients and 5.4% of controls, p<0.001. Factors associated with increased risk of SAA in HHT were female gender (p = 0.04, OR = 2.12, IC 95% = 1.03-4.50), age (p = 0.0003, OR = 1.04, 95% CI = 1.02-1.06) and pancreatic parenchymal involvement (p = 0.04, OR = 2.13, 95% CI = 1.01-4.49), but not type of mutation, hepatic or splenic parenchymal involvements, splenic size or splenic artery diameter or CVRF.CONCLUSIONS:We found a 4.57 higher rate of SAA in HHT patients without evidence of splenic high output related disease or increased CVRF. These results suggest the presence of a vascular intrinsic involvement. It should lead to screening all HHT patients for SAA. The vasculopathy hypothesis could require a change in management as screening of all systemic arteries and even the aorta and to further research in the field.

Poster: ECR 2019 / C-3595 / Place of imaging in the management of acute upper gastrointestinal bleedings by: D. Kontogom 1, D. CABRAL2, N. ZHANG3, S. Binsse4, J. Sellier5, M. Sirol6, R. Y. Carlier1, P. Lacombe4, M. El Hajjam4; 1Garches/FR, 2Poissy/FR, 3Caen/FR, 4Boulogne-Billancourt/FR, 5Poitiers/FR, 6Paris/FR

Hereditary hemorrhagic telangiectasia (HHT) is an autosomic dominant disorder, which is characterized by the development of multiple arterio-venous malformations in the skin, mucous membranes, and/or visceral organs. Pulmonary Arterio-Venous Malformation (PAVM) is an abnormal connection where feeding arteries shunt directly into draining veins with no intervening capillary bed. This condition may lead to paradoxical embolism and hemorrhagic complications. PAVMs patients should systematically be screened as the spontaneous complication rate is high, reaching almost 50%. Chest enhanced contrast CT scanner is the reference screening and follow-up examination. When performed by experienced operators as the prime treatment, percutaneous embolization of PAVMs is a safe, efficient and sustained therapy. The accuracy of PAVM detection and quantification of its progression over time is the key of embolotherapy success. In this paper, we propose an automatic method for PAVM detection and quantification relying on a modeling of vessel deformation, i.e. local caliber increase, based on mathematical morphology. The pulmonary field and vessels are first segmented using geodesic operators. The vessel caliber is estimated by means of a granulometric measure and the local caliber increase is detected by using a geodesic operator, the h-maxdomes. The detection sensitivity can be tuned up according to the choice of the h value which models the irregularity of the vessel caliber along its axis and the PAVM selection is performed according to a clinical criterion of >3 mm diameter of the feeding artery of the PAVM. The developed method was tested on a 20 patient dataset. A sensitivity study allowed choosing the irregularity parameter to maximize the true positive ratio reaching 85.4% in average. A specific false positive reduction procedure targeting the vessel trunks of the arterio-venous tree near mediastinum allows a precision increase from 13% to 67% with an average number of 1.15 false positives per scan.

BACKGROUND:Epistaxis is the most frequent and disabling manifestation of hereditary hemorrhagic telangiectasia (HHT). The efficacy of intravenous bevacizumab (an anti-vascular endothelial growth factor monoclonal antibody) for epistaxis has been shown. However, the efficacy of intranasal bevacizumab has yet to be evaluated.OBJECTIVE:To evaluate the efficacy of 3 different doses of bevacizumab administered as a nasal spray in a repeated manner for the duration of nosebleeds in patients with HHT.DESIGN, SETTING, AND PARTICIPANTS:Randomized, multicenter, placebo-controlled, phase 2/3 clinical trial with dose selection at an intermediate analysis and prespecified stopping rules (nonbinding stopping for futility). Patients aged 18 years or older with a diagnosis of HHT were recruited from 5 French centers from April 2014 to January 2015 with a 6-month follow-up after the end of treatment. Participants had a history of self-reported nosebleeds with a monthly duration of more than 20 minutes in at least the 3 months prior to inclusion corroborated by epistaxis grids completed during the same preinclusion period.INTERVENTIONS:Eighty consecutive HHT patients were randomized and treated in the phase 2 study, with 4 parallel groups in a 1:1:1:1 ratio. One group received placebo (n = 21); the other 3 received bevacizumab nasal spray. Each bevacizumab group received a different dose of the drug (25 mg [n = 20], 50 mg [n = 20], or 75 mg [n = 19] per treatment) in 3 doses 14 days apart for a total treatment duration of 4 weeks, resulting in a total dose of 75 mg, 150 mg, and 225 mg in each treatment group.MAIN OUTCOMES AND MEASURES:Mean monthly epistaxis duration for 3 consecutive months immediately after the end of the treatment.RESULTS:Of the 80 patients who were randomized (mean age, 60.47 [SD, 10.61] years; 37 women [46.25%]), 75 completed the study. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 59 patients receiving bevacizumab in comparison with the placebo group (P = .57) or between the bevacizumab groups. The mean monthly epistaxis duration was 259.2 minutes (95% CI, 82.1-436.3 minutes) in the 25-mg group, 244.0 minutes (95% CI, 81.8-406.2 minutes) in the 50-mg group, 215.0 minutes (95% CI, 102.8-327.2 minutes) in the 75-mg group, and 200.4 minutes (95% CI, 109.3-291.5 minutes) in the placebo group. Toxicity was low and no severe adverse events were reported. This study was terminated prior to phase 3 for treatment futility after interim analysis on the recommendations of an independent data monitoring committee.CONCLUSIONS AND RELEVANCE:In patients with HHT, a bevacizumab nasal spray treatment of 3 administrations at 14-day intervals with doses of 25 mg, 50 mg, or 75 mg per spray, compared with a placebo, did not reduce monthly epistaxis duration in the 3 consecutive months immediately after the end of treatment.TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT02106520.

RASA1‐ related disease is a rare autosomal dominant disease characterized by capillary malformations, arteriovenous malformations (AVMs), and/or arteriovenous fistulas (AFVs). Penetrance is nearly complete and vascular malformations may cause serious complications such as organ injury due to oxygenation disorder, brain abscess, hemorrhage, and stroke. Early diagnosis is useful in order to discuss optimal management, including AVMs/AVFs embolization or surgical procedures, and try to prevent some of the complications. In this context, molecular testing of RASA1 gene mutation in relatives may help to better manage the family. All arteriovenous malformations are however not accessible to such procedures. In addition, these therapeutic procedures may result in potential side effects and complications. A couple was referred to our genetics unit and asked us for prenatal genetic testing about a RASA1 mutation. Here, we discuss about arguments that led our team to accept prenatal testing. To the best of our knowledge, no molecular prenatal diagnosis was reported until now in RASA1 ‐related diseases. This first report of prenatal diagnosis in RASA1 ‐related diseases may also offer perspectives for a more general discussion in the field of inherited arteriovenous malformations.

Pulmonary arteriovenous malformations (PAVMs) are present in approximately 15–50% individuals with hereditary hemorrhagic telangiectasia (HHT). They may be isolated but more often are multiple. The goal of this study was to evaluate the influence of PAVMs on lung mechanical properties.

Background Different pulmonary hypertension (PH) mechanisms are associated with hereditary haemorrhagic telangiectasia (HHT). Methods and results We conducted a retrospective study of all suspected cases of PH (echocardiographically estimated systolic pulmonary artery pressure [sPAP] ≥ 40 mmHg) in patients with definite HHT recorded in the French National Reference Centre for HHT database. When right heart catheterization (RHC) was performed, PH cases were confirmed and classified among the PH groups according to the European guidelines. Among 2,598 patients in the database, 110 (4.2%) had suspected PH. Forty-seven of these 110 patients had RHC: 38/47 (81%) had a confirmed diagnosis of PH. The majority of these had isolated post-capillary PH (n = 20). We identified for the first time other haemodynamic profiles: pre-capillary pulmonary arterial hypertension (PAH) cases (n = 3) with slightly raised pulmonary vascular resistances (PVR), and combined post- and pre-capillary PH cases (n = 4). Compared to controls, survival probability was lower in patients with PAH. Conclusion This study revealed the diversity of PH mechanisms in HHT. The description of combined post- and pre-capillary PH with/or without high cardiac output (CO) suggests either a continuum between the pre- and post-capillary haemodynamic profiles or a different course in response to high CO.

RASA1-related disease is a rare autosomal dominant disease characterized by capillary malformations, arteriovenous malformations (AVMs), and/or arteriovenous fistulas (AFVs). Penetrance is nearly complete and vascular malformations may cause serious complications such as organ injury due to oxygenation disorder, brain abscess, hemorrhage, and stroke. Early diagnosis is useful in order to discuss optimal management, including AVMs/AVFs embolization or surgical procedures, and try to prevent some of the complications. In this context, molecular testing of RASA1 gene mutation in relatives may help to better manage the family. All arteriovenous malformations are however not accessible to such procedures. In addition, these therapeutic procedures may result in potential side effects and complications. A couple was referred to our genetics unit and asked us for prenatal genetic testing about a RASA1 mutation. Here, we discuss about arguments that led our team to accept prenatal testing. To the best of our knowledge, no molecular prenatal diagnosis was reported until now in RASA1-related diseases. This first report of prenatal diagnosis in RASA1-related diseases may also offer perspectives for a more general discussion in the field of inherited arteriovenous malformations.

Also known as Rendu-Osler-Weber syndrome, hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder that leads to abnormal blood vessel formation in the skin, mucous membranes and often in organs such as lungs, liver and brain.1 At clinical inspection, patients frequently present with skin, lip and/or tongue telangiectasias. Common clinical symptoms include frequent epistaxis and less commonly acute and chronic digestive tract bleeding.1 About 15%–35% of patients with HHT will present with pulmonary arteriovenous malformations (PAVMs).2 As the spontaneous complication rate can reach up to 50%, PAVMs patients require screening on CT scan examination. PAVMs complications include spontaneous rupture and subsequent life-threatening haemoptysis/haemothorax, a right-to-left shunting leading to paradoxical embolism causing stroke or cerebral abscess or pulmonary hypertension.2 3 Treatment is based on antibiotic prophylaxy and percutaneous transcatheter embolisation of the diagnosed PAVM that are screened on imaging means.2 3 A 57-year-old female patient was referred to our institution soon after having an air flight from Bogota to Paris. She presented with severe chest pain and acute dyspnoea. Biological symptoms included anaemia and increased D-dimer serum levels. As patient was suspected for pulmonary embolism, chest X-ray was performed and showed an abundant left pleural fluid effusion (figure 1). Contrast-enhanced CT identified a high-density pleural effusion consistent with haemothorax. Multiplanar CT scan reformation showed a single PAVM located in the segment 9 that was fed by a large and tortuous afferent artery, and a bleeding aneurismal sac that was ruptured into the left pleural space (figure 2). Close clinical examination of the patient revealed numerous skin and mucous telangiectasias and patient complained of frequent epistaxis; HHT diagnosis was eventually made.

BACKGROUND:Although being classically located inside the liver parenchyma, hemangiomas may occasionally develop outside the extra-hepatic capsule, thus appearing as a pedunculated mass. CASE REPORT:We report the case of a 66-year-old anal cancer female patient presenting with an asymptomatic sub-hepatic mass. Incidental diagnosis of a pedunculated hepatic hemangioma was strongly suggested by the typical imaging features on computed tomography (CT) and magnetic resonance (MR) examinations, and was confirmed by histopathological examination. CONCLUSIONS:Exophytic pedunculated growth is a rare and atypical feature of hepatic hemangioma. Thin contrast- enhanced sections and multiplanar CT and MR scan reformations helped to the final diagnosis of hemangioma, showing its origin from the liver edge. Surgical resection is mandatory to prevent threatening mass pedicle torsion.