Arnaldo Scardapane

Hepatic involvement in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterized by mucocutaneous or visceral angiodysplastic lesions (telangiectases and arteriovenous malformations) that may be widely distributed throughout the cardiovascular system. The recognition of mucocutaneous telangiectases, the occurrence of spontaneous and recurrent episodes of epistaxis, the presence of visceral involvement, and a family history of this disease are the clinical criteria that allow diagnosis. In comparison with skin, lungs, gastrointestinal tract, and brain involvement, hepatic involvement defined by clinical criteria alone has long been considered uncommon. Our experience with a large group of HHT patients, even those asymptomatic for liver involvement, demonstrates that it is more frequent than reported and is characterized by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases, and other vascular lesions. Congestive cardiac failure, portal hypertension, portosystemic encephalopathy, cholangitis, and atypical cirrhosis have been reported as possible serious complications related to this condition. Thus, a correct diagnosis is important, and diagnostic imaging has a fundamental role in detecting alterations involving the liver. The possibilities to perform a multiphasic study and to provide high-quality multiplanar and angiographic reconstructions, gives multidetector row helical computed tomography the ability to detect and characterize the complex anatomopathologic alterations typical of this disease.

Accuracy of transvaginal sonography and contrast‐enhanced magnetic resonance‐colonography for the presurgical staging of deep infiltrating endometriosis

To investigate the accuracy of transvaginal sonography (TVS) and contrast‐enhanced magnetic resonance‐colonography (CE‐MR‐C) for the presurgical assessment of deep infiltrating endometriosis (DIE).

Prognostic value of multidetector computed tomography in bowel infarction

PurposeThis study aimed to correlate computed tomography (CT) findings and outcomes in patients affected by bowel infarction.Materials and methodsTwenty-seven patients with bowel infarction due to vascular obstruction were evaluated with multidetector CT (MDCT) to establish the prognostic value of CT findings and their correlation with the origin of the ischaemia. The chi-square test was used to analyse the results (p≤0.05).ResultsMDCT images allowed recognition of the nature of ischaemia in all cases. In particular, arterial occlusion was found in 67% of patients and venous obstruction in 33%. The overall mortality rate was 63%. Outcome closely correlated with the kind of vascular obstruction, with a mortality rate of 89% in arterial forms and 11% in venous forms. Bowel-wall hyperdensity (2/9 venous occlusions), loss of wall enhancement (1/9 venous occlusions, 2/18 arterial occlusions) and wall thickening (8/9 venous obstructions, 2/18 arterial occlusions) were predictive of good outcome. Bowel-loop dilatation (4/9 venous occlusions, 13/18 arterial occlusions), intramural pneumatosis (1/9 venous occlusions, 17/18 arterial occlusions), mesenteric venous gas (2/9 venous occlusions, 11/18 arterial occlusions), portal venous gas (1/9 venous occlusions, 4/18 arterial occlusions), pneumoperitoneum (8/18 arterial occlusions) and pneumoretroperitoneum (1/18 arterial occlusions) were predictive of poor outcome. Ascites (6/9 venous occlusions, 12/18 arterial occlusions) did not add any prognostic information.ConclusionsMDCT is able to detect the nature of bowel ischaemia and provide important prognostic information.RiassuntoObiettivoRicercare eventuali correlazioni tra informazioni ottenute con tomografia computerizzata (TC) e prognosi nell’infarto intestinale.Materiali e metodiSono state valutate le immagini TC multidetettore (TCMD) di 27 pazienti con infarto intestinale da occlusione vascolare e sono state ricercate: significatività prognostica delle alterazioni evidenziate, correlazioni con la natura dell’ischemia. È stato applicato il test statistico del χ2 (p≤0,05).RisultatiLa TCMD ha riconosciuto sempre la natura dell’ischemia, secondaria ad occlusione arteriosa nel 67% dei casi e venosa nel 33%. Il tasso di mortalità complessivo è stato del 63%. L’eziologia della patologia in rapporto alla prognosi è risultata altamente significativa, con mortalità del 89% nelle forme arteriose e del 11% in quelle venose. L’iperdensità parietale (2/9 occlusioni venose), l’assenza di enhancement (1/9 occlusioni venose, 2/18 occlusioni arteriose), l’ispessimento di parete (8/9 occlusioni venose, 2/18 occlusioni arteriose) sono risultati significativi di evoluzione benigna, mentre la dilatazione delle anse (4/9 occlusioni venose, 13/18 occlusioni arteriose), la pneumatosi parietale (1/9 occlusioni venose, 17/18 occlusioni arteriose), l’aria nelle vene mesenteriche (2/9 occlusioni venose, 11/18 occlusioni arteriose), l’aria nei rami portali (1/9 occlusioni venose, 4/18 occlusioni arteriose), lo pneumoperitoneo (8/18 occlusioni arteriose) e il retropneumoperitoneo (1/18 occlusioni arteriose) sono risultati indici prognostici sfavorevoli. L’ascite (6/9 occlusioni venose, 12/18 occlusioni arteriose) non ha fornito indicazioni di tipo prognostico.ConclusioniLa TCMD consente di definire la natura dell’ischemia intestinale e fornisce importanti valutazioni prognostiche.

Hereditary hemorrhagic telangiectasia: arteriovenous malformations in children.

OBJECTIVE To evaluate the clinical features in a large cohort of pediatric patients with genetically confirmed hereditary hemorrhagic telangiectasia (HHT) and to identify possible predictors of arteriovenous malformation (AVM) onset or clinical significance. STUDY DESIGN Prospective cross-sectional survey of all children subjected to screening for AVMs in the multidisciplinary HHT center. All patients proved to be carriers of endoglin mutations or activin A receptor type-II-like kinase 1 mutations, defined as HHT1 and HHT2, respectively. A full clinical-radiological protocol for AVM detection was adopted, independent from presence or absence of AVM-related symptoms. RESULTS Forty-four children (mean age, 10.3 years; range, 1-18) were subjected to a comprehensive clinical-radiologic evaluation. This investigation disclosed cerebrovascular malformations in 7 of 44 cases, pulmonary AVMs in 20 of 44 cases, and liver AVMs in 23 of 44 cases. Large visceral AVMs were found in 12 of 44 children and were significantly more frequent in patients with HHT1. Only large AVMs were associated with symptoms and complications. CONCLUSIONS Children with HHT have a high prevalence of AVMs; therefore, an appropriate clinical and radiological screening protocol is advisable. Large AVMs can be associated with complications in childhood, whereas small AVMs probably have no clinical risk.

Deep pelvic endometriosis: accuracy of pelvic MRI completed by MR colonography

PurposeThis study assessed the diagnostic accuracy of pelvic magnetic resonance (MR) imaging completed by MR colonography for the preoperative evaluation of deep pelvic endometriosis in patients undergoing laparoscopic surgery.Materials and methodsA total of 143 patients (mean age 34.3±5.1 years) with a clinical suspicion of deep pelvic endometriosis were assessed by pelvic MR and MR colonography. All patients underwent laparoscopic surgery 3–10 weeks after the MR examination. The presence, location, number and extent of endometriotic lesions were evaluated. Data obtained with MR were compared with surgical findings. MR sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and diagnostic accuracy values were calculated for each site by considering the laparoscopic and histological findings as the reference standard.ResultsLaparoscopy confirmed the presence of endometriosis in 119/143 patients (83%); in 76/119 (64%) deep pelvic endometriosis was diagnosed, whereas in the remaining 43/119 (36%), superficial peritoneal implants and endometriomas were found. In 32/119 (27%) patients, intestinal lesions were detected. MR had sensitivity, specificity, PPV, NPV and diagnostic accuracy values of 67–100%, 85–100%, 83–100%, 84–100% and 84–100%, respectively, in recognising lesions located in different pelvic sites.ConslucionsMR imaging combined with colonography is a highly accurate tool for characterising deep endometriotic lesions in patients scheduled for laparoscopic surgery. In particular, MR colonography has very high accuracy in detecting colorectal involvement.RiassuntoObiettivoScopo del presente lavoro è stato valutare l’accuratezza diagnostica della risonanza magnetica (RM) pelvica associata a colonografia-RM nella valutazione preoperatoria della endometriosi pelvica profonda in pazienti sottoposte ad intervento per via laparoscopica.Materiali e metodiCentoquarantatre pazienti (età media 34,3±5,1 anni) con sospetto clinico di endometriosi pelvica profonda sono state valutate mediante RM pelvica completata con colonografia-RM. Tutte le pazienti sono state sottoposte a laparoscopia con un intervallo di 3–10 settimane dall’esame RM. Sono stati valutati presenza, sede, numero ed estensione delle lesioni endometriosiche. I dati ottenuti dalla RM sono stati confrontati con quelli chirurgici. Sensibilità, specificità, valore predittivo positivo (VPP) e negativo (VPN) ed accuratezza diagnostica della RM sono stati calcolati per ciascuna sede esaminata, considerando i reperti laparoscopici e istologici quale gold standard.RisultatiLa laparoscopia ha confermato la presenza di endometriosi in 119/143 pazienti (83%); in 76/119 (64%) era evidente endometriosi pelvica profonda, mentre nelle rimanenti 43/119 (36%) erano presenti endometriomi e impianti peritoneali superficiali. In 32/119 (27%) pazienti, sono state riscontrate lesioni intestinali. La RM ha presentato valori di sensibilità, specificità, VPP, VPN e accuratezza diagnostica rispettivamente compresi tra 67%–100%, 85%–100%, 83%–100%, 84%–100%, 84%–100% nel riconoscimento delle diverse sedi di impianto della patologia.ConclusioniLa RM associata a colonografia rappresenta una metodica accurata per lo studio delle pazienti con endometriosi pelvica profonda da sottoporre ad intervento chirurgico laparoscopico e per la caratterizzazione delle lesioni endometriosiche. In particolare la colonografia-RM consente elevati valori di accuratezza nell’identificazione delle lesioni intestinali.

Clinical and functional characterization of a novel mutation in lamin a/c gene in a multigenerational family with arrhythmogenic cardiac laminopathy.

Mutations in the lamin A/C gene (LMNA) were associated with dilated cardiomyopathy (DCM) and, recently, were related to severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). Both genetic and phenotypic overlap between DCM and ARVC was observed; molecular pathomechanisms leading to the cardiac phenotypes caused by LMNA mutations are not yet fully elucidated. This study involved a large Italian family, spanning 4 generations, with arrhythmogenic cardiomyopathy of different phenotypes, including ARVC, DCM, system conduction defects, ventricular arrhythmias, and sudden cardiac death. Mutation screening of LMNA and ARVC-related genes PKP2, DSP, DSG2, DSC2, JUP, and CTNNA3 was performed. We identified a novel heterozygous mutation (c.418_438dup) in LMNA gene exon 2, occurring in a highly conserved protein domain across several species. This newly identified variant was not found in 250 ethnically-matched control subjects. Genotype-phenotype correlation studies suggested a co-segregation of the LMNA mutation with the disease phenotype and an incomplete and age-related penetrance. Based on clinical, pedigree, and molecular genetic data, this mutation was considered likely disease-causing. To clarify its potential pathophysiologic impact, functional characterization of this LMNA mutant was performed in cultured cardiomyocytes expressing EGFP-tagged wild-type and mutated LMNA constructs, and indicated an increased nuclear envelope fragility, leading to stress-induced apoptosis as the main pathogenetic mechanism. This study further expands the role of the LMNA gene in the pathogenesis of cardiac laminopathies, suggesting that LMNA should be included in mutation screening of patients with suspected arrhythmogenic cardiomyopathy, particularly when they have ECG evidence for conduction defects. The combination of clinical, genetic, and functional data contribute insights into the pathogenesis of this form of life-threatening arrhythmogenic cardiac laminopathy.

Diagnostic imaging in the study of visceral involvement of hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterised by mucocutaneous or visceral angiodysplastic lesions. Its diagnosis is exclusively based on clinical criteria. The brain, lungs and liver, in growing order of prevalence, are the most frequently involved organs. Diagnostic imaging based on ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and digital subtraction angiography (DSA) has a fundamental role in detecting visceral involvement in HHT patients and is therefore crucial for the prognostic assessment and therapeutic approach. Arteriovenous shunts are the most common cerebrovascular malformations (CVMs). MRI and CT angiography are the methods of choice for diagnosing cerebral involvement, and it is debated whether MRI could be considered as a screening examination on account of its noninvasiveness. Pulmonary arteriovenous malformations, diffuse telangiectases or high-flow, low-pressure shunts between pulmonary arteries and veins can be studied with contrast-enhanced US, but multidetector CT seems to provide the most comprehensive evaluation of their angioarchitecture, whereas angiography has a predominant role in treatment. Liver involvement is frequent and characterised by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases and other vascular lesions. US is useful for detecting hepatic lesions but should be completed by more accurate imaging methods such as multidetector CT and MRI.RiassuntoLa telangiectasia emorragica ereditaria (HHT), o malattia di Rendu-Osler-Weber, è un disordine vascolare ereditario, caratterizzato dalla comparsa di lesioni angiodisplasiche mucocutanee e viscerali, la cui diagnosi si basa esclusivamente su criteri clinici. L’encefalo, i polmoni ed il fegato sono, in ordine crescente di prevalenza, le sedi viscerali più frequentemente coinvolte. La diagnostica per immagini, mediante gli ultrasuoni (US), la tomografia computerizzata (TC), la risonanza magnetica (RM) e la angiografia (DSA), ha un ruolo cruciale nella diagnosi del coinvolgimento viscerale nei pazienti affetti da HHT ed è, pertanto, fondamentale nella valutazione prognostica e nella impostazione terapeutica. Tra le malformazioni vascolari cerebrali gli shunt arterovenosi costituiscono l’alterazione più frequente. La RM e la angio-TC sono le metodiche di scelta nella diagnosi dell’interessamento cerebrale, ed è dibattuto se, per la scarsa invasività, la RM sia da proporre come metodica di screening. Le malformazioni arterovenose polmonari, telangiectasie diffuse o fistole tra arterie e vene polmonari, possono essere ricercate con US con MdC, ma la TC multidetettore appare l’indagine più completa per la valutazione della loro angioarchitettura mentre l’angiografia mantiene un ruolo prevalentemente terapeutico. L’interessamento epatico è frequente e caratterizzato dalla comparsa di fistole arterovenose, telangiectasie intraparenchimali ed altre alterazioni vascolari. Gli US sono utili nella ricerca delle lesioni epatiche, ma devono essere integrati da indagini più accurate quali la TC multidetettore e la RM.

Hepatic nodular regenerative lesions in patients with hereditary haemorrhagic telangiectasia: computed tomography and magnetic resonance findings

PurposeThis study was done to evaluate the prevalence of regenerative hepatic nodules in patients with hereditary haemorrhagic telangiectasia (HHT).Materials and methodsBetween February 2001 and December 2010, 171 consecutive HHT patients (95 men and 76 women) were studied with triphasic multidetector computed tomography (MDCT) in 91 cases, magnetic resonance imaging (MRI) in 34 cases and both in the remaining 46 cases. The presence of diffuse vascular abnormalities and focal liver lesions were recorded.ResultsHepatic arteriovenous malformations (HAVMs) were found in 126/171 (74%) patients. Arteriovenous shunts were found in 24/171 (14%) cases, arterioportal shunts in 52/171 (30%), mixed shunts in 26/171 (15%), telangiectases in 84/171 (49%) and transient hepatic attenuation differences (THADs) in 70/171 (41%). Hepatic nodular lesions were found in 6/171 (3.5%) patients (three men; three women). In 5/6 cases, vascular abnormalities were also evident. Two patients had a single lesion; four had multiple lesions. No lesion showed a central scar.ConclusionsHyperenhancing hepatic regenerative lesions have a high prevalence in HHT patients, representing the response of liver parenchyma to hypoperfusion caused by HAVMs. These lesions are often multiple and may lead to nodular regenerative hyperplasia.RiassuntoObiettivoScopo del presente lavoro è valutare la frequenza di lesioni nodulari rigenerative nei pazienti affetti da telangiectasia emorragica ereditaria (HHT).Materiali e metodiNel periodo compreso tra febbraio 2001 e dicembre 2010 sono stati arruolati consecutivamente 171 pazienti (95 uomini, 76 donne) affetti da HHT. La presenza di alterazioni epatiche è stata ricercata in 91 casi con TCMD trifasica (fase arteriosa precoce, tardiva e fase venosa) e in 34 con angio-risonanza magnetica (RM) dinamica, i rimanenti 46 pazienti sono stati sottoposti ad entrambi gli esami.RisultatiIn 126/171 (74%) pazienti sono state diagnosticate alterazioni vascolari epatiche costituite da fistole artero-venose (24/171, 14%), fistole artero-portali (52/171, 30%), fistole miste (26/171, 15%), telangiectasie (84/171, 49%) e disordini di perfuzione (THADs) (70/171, 41%). In 6/171 casi (3 donne e 3 uomini, 3,5%) sono state descritte lesioni nodulari epatiche ipervascolarizzate associate in 5 pazienti ad altre lesioni vascolari. Due pazienti erano portatori di una lesione singola mentre in quattro casi sono state dimostrate lesioni multiple. In nessun caso è stata riconosciuta una cicatrice centrale.ConclusioniLe lesioni epatiche rigenerative hanno un’elevata prevalenza nei pazienti affetti da HHT e costituiscono una risposta del fegato all’ipoperfusione determinata dagli shunt artero-venosi intraparenchimali. Tali lesioni si presentano spesso in forma multipla e possono determinare un quadro di iperplasia nodulare rigenerativa diffusa.

Preoperative local staging of colosigmoideal cancer: air versus water multidetector-row CT colonography

PurposeThe authors sought to evaluate the diagnostic accuracy of multidetector-row computed tomography (MDCT) performed with two different hypodense endoluminal contrast agents for the preoperative staging of colosigmoideal cancer.Materials and methodsSeventy consecutive patients with an endoscopically and histologically proven diagnosis of colosigmoideal cancer underwent MDCT examination. Thirty-five patients were evaluated with water MDCT colonography and the remaining 35 with air MDCT colonography. Patients were randomly assigned to the air or water groups for staging. Transverse images and multiplanar reconstructions (MPR) were retrospectively examined by two blinded expert radiologists in order to assess T and N parameters, and the results were compared with histological findings.ResultsThe overall diagnostic accuracy of MDCT was 68.6% for water and 62.8% for air colonography. In the evaluation of the T parameter, the accuracy values were 88.6% for water and 80% for air colonography. In staging of the N parameter, the accuracy values were 77.1% and 74.3% for water and air MDCT colonography, respectively.ConclusionsMDCT examination can be proposed for the local staging of colosigmoideal cancer. Water is more accurate than air in evaluation of the T parameter, whereas the kind of endoluminal contrast material does not influence the definition of the N parameter.RiassuntoObiettivoScopo del presente lavoro è stato valutare l’accuratezza diagnostica della tomografia computerizzata multidetettore (TCMD) nella stadiazione preoperatoria del carcinoma del colon-sigma utilizzando due differenti mezzi di contrasto ipodensi endoluminali.Materiali e metodiSettanta pazienti consecutivi con diagnosi endoscopica ed istologica di carcinoma del colon-sigma sono stati sottoposti a TCMD. Trentacinque sono stati valutati mediante colonografia TC con acqua e i restanti trentacinque mediante colonografia TC con aria. I pazienti sono stati assegnati in maniera random ai gruppi di stadiazione con aria o acqua. Le immagini assiali e le ricostruzioni multiplanari (MPR) sono state esaminate in cieco retrospettivamente da due radiologi esperti al fine di determinare i parametri T e N ed i risultati sono stati confrontati con i reperti istologici.RisultatiL’accuratezza diagnostica complessiva della TCMD è risultata del 68,6% per la colonografia con acqua e del 62,8% per quella con aria. Nella valutazione del parametro T, i valori di accuratezza per la colonografia con acqua e aria sono risultati rispettivamente pari a 88,6% e 80%. Nella stadiazione del parametro N, sono stati ottenuti valori di accuratezza del 77,1% e 74,3% rispettivamente per la colonografia con acqua e aria.ConclusioniLa TCMD rappresenta una metodica proponibile per la stadiazione locoregionale del carcinoma del colon-sigma. L’impiego dell’acqua nella valutazione del parametro T risulta più accurata rispetto all’aria. Il tipo di mezzo di contrasto endoluminale non sembra influenzare la definizione del parametro N.

Dynamic 4D MR angiography versus multislice CT angiography in the evaluation of vascular hepatic involvement in hereditary haemorrhagic telangiectasia

PurposeHereditary haemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is a rare autosomal dominant disorder characterised by mucocutaneous or visceral vascular abnormalities that may be widely distributed throughout the cardiovascular system. The purpose of this study was to compare multislice computed tomography angiography (MSCTA) and 4D dynamic contrast-enhanced magnetic resonance angiography (D-MRA) for evaluating vascular hepatic involvement in patients with HHT.Materials and methodsFifty-two consecutive HHT patients underwent MSCTA and D-MRA examinations for systematic analysis of vascular visceral involvement. The images from the two techniques were reviewed independently by two expert radiologists to identify the following vascular abnormalities: telangiectases or large vascular masses; perfusion disorders [transient hepatic attenuation differences (THADs)]; hepatic arteriovenous malformations (HAVMs). Data, as well as diameters of the common hepatic artery and portal vein, were compared with Cohen’s kappa statistic, Student’s t test and receiver operating characteristic (ROC) curve analysis, as appropriate.ResultsBoth MSCTA and D-MRA detected one or more of the following hepatic vascular abnormalities in 36/52 cases (telangiectases in 29/52, THADs in 23/52 and HAVMs in 25/52[CE1]). A good concordance was found between the two techniques when determining the type of hepatic shunt (κ=0.9). No statistically significant differences were found when comparing mean common hepatic artery and portal vein diameters (p=0.09 and 0.22, respectively) and their accuracy in predicting HAVMs.ConclusionsD-MRA has the same diagnostic accuracy as MSCTA and has the advantage of being less invasive due to the absence of ionising radiation.RiassuntoObiettivoLa teleangiectasia emorragica ereditaria (HHT) o malattia di Rendu-Osler-Weber è una patologia rara a trasmissione autosomica dominante caratterizzata da alterazioni vascolari mocoso-cutanee o viscerali che possono coinvolgere diversi organi e apparati. Il nostro scopo è quello di confrontare l’angio-risonanza magnetica (RM) dinamica 4D (D-MRA) e l’angio-tomografia computerizzata (TC) multidetettore (MSCTA) nella ricerca delle alterazioni vascolari epatiche dei pazienti con HHT.Materiali e metodiCinquantadue pazienti consecutivi con HHT sono stati sistematicamente sottoposti a D-MRA e a MSCTA. Le immagini di entrambi gli esami sono state valutate indipendentemente da due radiologi esperti al fine di ricercare le seguenti alterazioni vascolari epatiche: teleangiectasie, disordini di perfusione (THADs), malformazioni artero-venose (HAVMs). Tali dati ed i diametri di arteria epatica e vena porta sono stati successivamente confrontati con i test di Cohen, t di Student e con l’analisi delle curve receiver operating characteristic (ROC).RisultatiIn 36/52 pazienti le due metodiche hanno riscontrato la presenza di una o più delle seguenti alterazioni vascolari epatiche (29/52 teleangiectasie, 23/52 THADs e 25/52 HAVMs). Le due tecniche hanno dimostrato una buona concordanza nel determinare il tipo shunt epatico (κ=0,9). Non sono state trovate differenze significative nelle misurazioni dell’arteria epatica (p=0,09) e della vena porta (p=0,22) tra i due esami e nella loro predittività rispetto alla presenza di HAVMs.ConclusioniLa D-MRA e la MSCTA hanno mostrato la stessa accuratezza nella diagnosi del coinvolgimento vascolare epatico da HHT. La D-MRA presenta il vantaggio di una minore invasività legata all’assenza di radiazioni ionizzanti.