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OBJECTIVE:\ud We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.\ud \ud METHODS:\ud A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered.\ud \ud RESULTS:\ud The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively.\ud \ud CONCLUSIONS:\ud This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

The recent outbreak of SARS-CoV-2 greatly involves the resources of the global healthcare system, as it affects newborns, adults, and elders. This infection runs in three major stages: a mild cold-like illness, a moderate respiratory syndrome and a severe acute interstitial pneumonia. SARS-CoV-2 infection seems to have a more benign evolution in children. As a matter of fact, low susceptibility and minor aggressivity have been highlighted in most cases. There are currently no effective antiviral drugs treatment for the affected children. No sufficient results have been reached by the use of interferon (IFN), lopinavir/ritonavir, orbidol, and oseltamivir in the treatment of the coronaviruses infection. The aim of this short review is to highlight the differences existing between COVID-19 cases in adults and children.

PANDAS are known as the spectrum of autoimmune pathologies related to a previous or current infection by group A beta-hemolytic streptococcus (SBEGA), dealing with several neuropsychiatric manifestations that mainly affect pediatric age. The main features consist of behavioral disease or movement disease characterized by acute-onset, presenting especially through infant period or adolescence. Specific manifestations, occurring during the progression of the disease, are the presence of otorhinolaryngologic symptoms (ENT) and orofacial movement disorders associated with temporomandibular joint pain.We enrolled 130 children (5-15 years) with a clinical diagnosis of PANDAS between 2012 and 2018. Participants were assessed using ENT specific parameters, PSG to examine respiratory disorders and conventional audiological evaluation. Descriptive and comparative statistical analyses were performed with a control group of 51 healthy patients.The prevalence of ENT symptoms associated was significantly detected in 88 patients of 130 in Group A (relative frequency (%) 67.6; p=0.041) and in 51 patients of 130 in the control Group B (relative frequency (%) 39.2; p=0.063). In relation to prevalence of SDB, 54 subjects have presented nocturnal respiratory obstructive symptoms from mild to severe (relative frequency (%) 61.3; p=0.033) vs. 20 patients of Group B (relative frequency (%) 39.2; p=0.055). The obstructive severity average type was correlated to the consensual adenotonsillar development (size 3-4), (relative frequency (%) 45.4; p=0.047). The audiological deficits found were mostly of transmissive type with OME correlated and linked to the presence of occasional episodes of AOM. The four PANDAS patients who presented orobuccal dystonia (relative frequency (%) 4.54; p=0.091) achieved an improvement of the algic symptoms through the exercises of self-rehabilitation.Findings from our study show that respiratory diseases, characterizing a group of patients with pandas, are the direct consequences of the malformed or hypertrophic condition and suggesting in these conditions surgical therapy as an approaching tool.

To verify whether it is possible, in people with diabetes mellitus (DM) considered at very high cardiovascular (CV) risk, stratify this risk better and identify significant modifiable risk factor (including lifestyle habits) to help patients and clinicians improve CV prevention. People with DM and microvascular diseases or one or more CV risk factors (hypertension, hyperlipidemia, smoking, poor dietary habits, overweight, physical inactivity) included in the Risk and Prevention study were selected. We considered the combined endpoint of non-fatal acute myocardial infarction and stroke and CV death. A multivariate Cox proportional analysis was carried out to identify relevant predictors. We also used the RECPAM method to identify subgroups of patients at higher risk. In our study, the rate of major CV events was lower than expected (5 % in 5 years). Predictors of CV events were age, male, sex, heart failure, previous atherosclerotic disease, atrial fibrillation, insulin treatment, high HbA1c, heart rate and other CV diseases while being physically active was protective. RECPAM analysis indicated that history of atherosclerotic diseases and a low BMI defined worse prognosis (HR 4.51 95 % CI 3.04–6.69). Among subjects with no previous atherosclerotic disease, men with HbA1c more than 8 % were at higher CV risk (HR 2.77; 95 % CI 1.86–4.14) with respect to women. In this population, the rate of major CV events was lower than expected. This prediction model could help clinicians identify people with DM at higher CV risk and support them in achieving goals of physical activity and HbA1c.

Background The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool is a validated questionnaire used to assess the methodological quality of clinical guidelines (CGs). We used the AGREE II tool to assess the development process, the methodological quality, and the quality of reporting of available pediatric CGs for the management of headache in children. We also studied the variability in responses related to the characteristics of eleven Italian neuropediatric centers, showing similarities and differences in the main recommendations reported in CGs. Methods A systematic literature search was conducted from January 2002 to June 2013 on Mediline, the Cochrane database, the National Guideline Clearinghouse website and the NHS evidence search tool, using the following terms: headache, cephalalgia, guidelines and children (MESH or text words). Six CGs providing information on the diagnosis and management of headache and specific recommendations for children were selected. Eleven neuropediatric centers assessed the overall quality and the appropriateness of all available CGs using of the AGREE II instrument. Results Six CGs meeting the inclusion and exclusion criteria were identified and assessed by 11 reviewers. Our study showed that the NICE CGs was “strongly recommended” while the French and Danish CGs were mainly “not recommended”. The comparison between the overall quality score of the French CGs and the NICE CGs was statistically significant (6.54 ± 0.69 vs 4.18 ± 1.08; p =0.001). The correlation analysis between quality domain score and guideline publication date showed a statistically significant association only for the “editorial independence” domain (r = 0.842 p = 0.035). The intra-class coefficients showed that the 11 reviewers had the highest agreement for the Lewis CGs (r = 0.857), and the lowest one for the NICE CGs (r = 0.656). Statistical analyses showed that professionals from outpatient services dedicated pediatric headache assigned a higher overall quality score to the NICE CGs as compared to professionals from non-outpatient services (6.86 ± 0.38 vs 6.0 ± 0.82; p = 0.038). Conclusions CGs resulted definitely of low-moderate quality and non “homogeneous”. Further major efforts are needed to update the existing CGs according to the principles of evidence based medicine.

Congenital Muscular Dystrophies (CMDs) can be considered as a heterogeneous group of diseases characterized by marked weakness, generalized hypotonia and joint contractures. They are divided into pure and classical forms, without ocular and cerebral involvement, and complex forms, which are associated with cerebral abnormalities. Seizures have rarely been described in the pure forms while they seem to occur more frequently in complex forms. The aim of our study was to evaluate the incidence of seizure in CMD. Herein, the authors describe 16 cases of congenital muscular dystrophy (CMD) associated with different kinds of epileptic events, in order to study the pathogenic connection between the two clinical manifestations. In all described patients we reviewed the clinical, neurophysiologic, and neuroimaging data to determine any associations with epilepsy. The patients were divided into two groups: 14 cases with merosin positive CMD in one group and 2 patients with Walker Warburg syndrome (WWS) in the second group. In our study we found that in the first group, one benign myoclonic epilepsy (BME), one benign febrile convulsions had occurred. Also in one patient, the EEG revealed a moderately high voltage slow background with diffuse sharp waves reaching 300mV in amplitude with no clinical signs. In the merosin positive CMD patients, the presence of two different epileptic diseases, benign myoclonic epilepsy (BME) in one and febrile convulsion with tonic clinic seizures, may represent a new expression of merosine-positive congenital muscular disease (PCMD) in which the deficiency of an undiscovered muscular protein with a cerebral isoform may be the cause of epileptic events in this group of patients.

Summary Purpose To investigate whether patients with typical absence seizures (TAS) starting in the first 3 years of life, conformed to Panayiotopoulos's definition of childhood absence epilepsy (CAE), show different electroclinical course than those not fulfilling CAE criteria. Methods In this multicenter retrospective study, we choose a fixed duration follow-up of 36 months to examine the electroclinical course of epilepsy in all children with TAS starting before 3 years of age. The probands who fulfilled Panayiotopoulos's criteria for CAE were classified as having pure early onset absence epilepsy (P-EOAE), whereas those who did not as nonpure EOAE (NP-EOAE). In addition, these two groups of patients were further stratified according to the number of antiepileptic drugs taken to obtain initial seizure control (mono-, bi-, and tritherapy). Key Findings Patients with P-EOAE (n = 111) showed earlier initial seizure control (p = 0.030) and better seizure-free survival curve (p = 0.004) than those with NP-EOAE (n = 77). No mutation in SLC2A1 gene or abnormal neuroimaging was observed in P-EOAE. Among patients with NP-EOAE, those receiving tritherapy showed increased risk of structural brain abnormalities (p = 0.001) or SLC2A1 mutations (p = 0.001) but fewer myoclonic features (p = 0.031) and worse seizure-free survival curve (p = 0.047) than those treated with mono- and bitherapy. Children with NP-EOAE had 2.134 the odds of having relapse during the follow-up compare to those with P-EOAE. Significance Children with early onset TAS who did meet Panayiotopoulos's criteria showed a favorable course of epilepsy, whereas patients not fulfilling Panayiotopoulos's criteria showed increased risk of relapse at long-term follow-up.

The ARX (Aristaless-related (X-linked) homeobox) gene is not only present in arthropods and their ancestors, but also in vertebrates including humans (ARX orthologs). The gene is composed of 5 coding exons and it is expressed predominantly in foetal and adult brain and skeletal muscle. In this review we report on our experience and review the existing literature on the genotype and phenotype heterogeneity associated with ARX abnormalities in humans ranging from severe neuronal migration defects (e.g., lissencephaly), to mild forms of X-linked mental retardation without apparent brain abnormalities. The ARX-related disorders are reviewed focusing on their clinical features and on the role of the ARX gene. It has yet to be established whether the molecular defect alone could cause a given cerebral abnormality and/or malformation or an additional or related molecular or environmental event could contribute to a given phenotype in molecularly.

Spinal neurofibromatosis (SNF) is a related form of neurofibromatosis 1 (NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4-74 years]: 9 SNF families (21/49), 1 mixed SNF/NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non-SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots (MNFSR): 4 mixed SNF/MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café-au-lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio (OR) = 6.16; confidence interval (CI) = 3.14-13.11], which were more frequent in SNF vs MNFSR (p = 0.0271).

Background Trials have shown a beneficial effect of n-3 polyunsaturated fatty acids in patients with a previous myocardial infarction or heart failure. We evaluated the potential benefit of such therapy in patients with multiple cardiovascular risk factors or atherosclerotic vascular disease who had not had a myocardial infarction. Methods In this double-blind, placebo-controlled clinical trial, we enrolled a cohort of patients who were followed by a network of 860 general practitioners in Italy. Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction. Patients were randomly assigned to n-3 fatty acids (1 g daily) or placebo (olive oil). The initially specified primary end point was the cumulative rate of death, nonfatal myocardial infarction, and nonfatal stroke. At 1 year, after the event rate was found to be lower than anticipated, the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes. Results Of the 12,513 patients enrolled, 6244 were randomly assigned to n-3 fatty acids and 6269 to placebo. With a median of 5 years of follow-up, the primary end point occurred in 1478 of 12,505 patients included in the analysis (11.8%), of whom 733 of 6239 (11.7%) had received n-3 fatty acids and 745 of 6266 (11.9%) had received placebo (adjusted hazard ratio with n-3 fatty acids, 0.97; 95% confidence interval, 0.88 to 1.08; P=0.58). The same null results were observed for all the secondary end points. Conclusions In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. (Funded by Societa Prodotti Antibiotici and others; ClinicalTrials.gov number, NCT00317707.).

Migration and HIV infection are known risk factors for methicillin-resistant Staphylococcus aureus (MRSA) carriage and infection. The aim of the study was to analyze the prevalence of MRSA nasal colonization in a high risk population of HIV-negative migrants and HIV-infected subjects. Secondary aim was to investigate over time MRSA carriage prevalence in HIV-infected subjects.During the study period (January-June 2008), nasal swabs were collected from 96 HIV-negative migrants and 63 HIV-infected patients. A group of 68 seropositive subjects was additionally screened for MRSA carriage in 2012. Subjects were evaluated for HIV status, previous antibiotic use or hospitalization, soft tissue and skin infections (SSI), nationality and work conditions. The swab specimens were plated and incubated for 24-h under static condition at 37 degrees and then identified as S. aureus by using standard methods.A total of 227 subjects, 131 HIV-infected adults (63 in 2008 and 68 in 2012) and 96 HIV-negative migrants, were analyzed. Overall, 71/227 (31.2%) were S. aureus carriers: 34 out of 131 (25.9%) among HIV infected subjects and 37 out of 96 (38.5%) among migrants. Two MRSA were detected in HIV-infected patients (2.8%). Between 2008 and 2012 there was an increase of MRSA carriage in HIV+ group (p=0.49). No statistically significant differences were found between S. aureus carriers and no-carriers in terms of CD4+ cell count, TMP/SMX prophylaxis, previous antibiotic use or hospitalization, nationality and duration of stay in Italy. Among HIV+ patients there was a higher prevalence of SSI in MSSA carriers compared with no carriers (25% vs 4%, p=0.028). In the migrants group, having a job based on a close human contact was significantly associated with S. aureus colonization (p=0.0038).Despite of the high prevalence of S. aureus isolation (31.2%), the present study showed the low rate of MRSA carriage in a high risk population. The main factor associated with S. aureus colonization was a close human contact rather than the HIV status and the condition of being migrant.

Congenital talipes equinovarus (CTEV) is a common but still not fully understood disorder of the lower limb. It is usually defined as a fixation of the foot in adduction, supination, and varus. Different treatment options exist including the Ponseti method.We report here the results obtained in infants with CTEV treated by the Ponseti method.Eighty two patients (114 clubfeet) were enrolled at the Orthopaedic Clinic of Catania University during the period of March 2004 to January 2010 and followed prospectively up to February 2011: 56 patients (68.29%) were male, the anomaly was bilateral in 32 (39%) cases, unilateral in 50 (60.9%) in the right side in 28 (56%). The mean age at initiation of treatment was 14 days (range 3-81 days), severity of the club foot deformity by the Pirani Severity score was 5.56 points (range 4.3-6 points). Total numbers of Ponseti casts before tenotomy, details of tenotomy, and compliance with CTEV brace were recorded. Clinical evaluation was performed using the functional Ponseti Scoring System. Mean follow up was 4 years: range 13-83 months.An average of 6.6 casts was necessary before performing the tenotomy. Tenotomy was performed by a single surgeon (V.P.) in a total of 68 patients (82.93%) always in an operating room under general anaesthesia by a percutaneous approach at a mean age of 106 days (range 45-213 days). Compliance with CTEV brace was satisfactory in 79 patients (96.3%). Functional Ponseti Scores were good/excellent in 79 (96.34%) patients (109 clubfeet; 95.61%). Only 3 patients; 3.7% (5 clubfeet; 4.4%) suffered relapse. Poor compliance with the Denis Browne splint was thought to be the main cause of failure.The Ponseti method provides an excellent outcome at follow up in the treatment of congenital idiopathic clubfoot.

The aim of this article was to review and conduct a meta-analysis of the paediatric literature on the neurology of coeliac disease.We conducted a review of paediatric studies published in English assessing neurological illness in coeliac disease identified through a MEDLINE search (1950-2009). Calculation of computed relative risk, odds ratio, and risk difference was performed using the fixed effect method if applicable.Fifteen studies were analysed (11 772 participants). The meta-analysis showed that (1) the relative risk of epilepsy in individuals with coeliac disease, and of coeliac disease in individuals with epilepsy, compared with the general population, was 2.1 and 1.7, respectively, and the risk difference was close to zero, indicating that it was probably a chance association; and (2) the relative risk of headache in individuals with the disease compared with comparison groups was 3.2. In two studies, cerebellar ataxia was documented in 2.7 to 5.4% of participants; in two further studies, the risk of cerebellar dysfunction was zero. Two studies found an association between coeliac disease and peripheral neuropathy. Brain white matter lesions were recorded in two other studies. An association between autism and coeliac disease is disputed. Interpretation Children with coeliac disease are at risk of developing neurological complications, but the risk is lower than in adulthood. The discrepancy might be due to short disease duration, early elimination of gluten from the diet, stricter adherence to diet, or different susceptibility to immune-mediated disorders.

Vitamin D deficiency is the most common cause of rickets mainly in breast-fed dark-skinned, African or Asian children receiving inadequate sunlight exposure. We report a case of a 1.5 year-old Afro-Italian male infant living in South Italy who came to our observation with the typical clinical picture of vitamin D deficiency rickets. The child was exclusively breast-fed for 8 months without vitamin D supplements. Owing to the rarity of vitamin D deficiency rickets in the South of Italy he underwent several investigations, which demonstrated the association with an abdominal ganglioneuroblastoma. To our knowledge, ganglioneuroblastoma has never been reported in association with vitamin D deficiency rickets. Although the association between these 2 rare conditions may be coincidental, the protective action of vitamin D against cancer suggests that vitamin D deficiency might have contributed to the development of ganglioneuroblastoma in our patient.

Recently, an atypical form of celiac disease (CD) has been identified, in which gastrointestinal symptoms are less pronounced. Other organs can be more or less severely affected, and the disease might be unrecognized and undiagnosed. In some cases, hypertransaminasemia has been indicated as the first symptom of CD in infancy. A direct relationship between liver damage and glutensensitivity has been proven by the disappearance of biochemical signs and histological lesions of the liver after the initiation of the gluten-free diet. The present case report is of a 14-year-old girl affected by CD and severe hepatic failure who underwent a liver transplant. To our knowledge, this case is the first report of liver involvement related to CD which is so severe as to require a liver transplant in a child. Because most patients with CD remain undiagnosed, and, as observed in the present report, untreated CD with subclinical hepatic involvement can lead to more serious liver disease, a more aggressive diagnostic work-up for CD in the general population is warranted.

Three-dimensional reconstruction techniques have been used since the development of computed tomography. In skeletal radiology they have been used to better visualize fractures and spatial relationships between fragments in maxillo-facial surgery. Aim of this paper is to illustrate the most important reconstruction techniques and their application in skeletal radiology. Images can be obtained by means of a Spiral CT scanner with the following parameters: collimation/pitch/reconstruction interval 2/1/1. Acquired images are sent to a workstation with a software running on a Window NT platform Vitrea 2.01 (Vital Images, USA) equipped with Volume Rendering algorithm. SSD as well as MPR and curved reformatted reconstruction algorithms is available at the CT console. Three-dimensional reconstruction have been shown to be useful for the diagnosis and for a preoperative planning. Other applications of three-dimensional reconstruction techniques are prosthesis engineering and biomechanic research. 3D images help the communication between radiologist and surgeons. Technical advances in acquisition methods and in reconstruction algorithms are needed to improve image quality and use in skeletal radiology.

The role of MR imaging in the assessment of pancreatic adenocarcinoma is in identification, characterization and staging of the neoplastic lesion. Technique optimization is required in order to obtain high qualities images competitive with spiral CT. The choice of imaging protocol is strictly related to the available equipment as well as fast imaging capabilities. Contrast-enhanced study using breath-hold sequences is required if working at high field strength with high gradient performance; on mid-low field strength nonbreath-hold acquisition techniques, using respiratory compensation techniques, can be implemented. The use of fat saturation pulses may increase the sensitivity of MR in detecting pancreatic lesions. Other advantages of MR imaging are represented by the availability of additional noninvasive techniques for the evaluation of the biliary tree (MR-cholangiopancreatography) and splanchnic vessels (MR-angiography). Lesion identification is based on TIw sequences where the lesion appears hypointense compared with the surrounding pancreas; increased lesion-pancreas contrast is obtained when fat suppression is used. On dynamic studies following gadolinium injection, pancreatic tumors are hypovascular compared with surrounding normal pancreatic gland. Problems in correctly defining the size of the lesions may be encountered in patients presenting with inflammatory changes of the pancreatic parenchyma surrounding the carcinoma (epineoplastic pancreatitis). For lesion characterization MRI is not able to characterize focal pancreatic lesions, allowing a differential diagnosis between pancreatic cancer and focal hypertrophic chronic pancreatitis. Even the use of MR-cholangiopancreatography is not helpful for characterizing focal pancreatic masses. MR imaging is accurate in local staging (assessment of peripancreatic fat infiltration) thanks to the higher contrast resolution, but in vascular staging and in the evaluation of lymphnodal involvement it suffers the same limitations as computed tomography. Future perspective are represented by the use of magnetic resonance angiography for the evaluation of vascular encasement and the use of specific contrast agents for lymphadenopathy. Identification of hepatic metastases with MRI has been proven to be high, with sensitivity and specificity comparable to CT. The use of liver-specific contrast agents (either positive or negative) is becoming almost routine and it is proving to further improve the diagnostic value of MRI.

We analyze the peculiar technical features of virtual endoscopy obtained with volume rendering.Our preliminary experience is based on virtual endoscopy images from volumetric data acquired with spiral CT (Siemens, Somatom Plus 4) using acquisition protocols standardized for different anatomic areas. Images are reformatted at the CT console, to obtain 1 mm thick contiguous slices, and transferred in DICOM format to an O2 workstation (Silicon Graphics, Mountain View CA, USA) with processor speed of 180 Mhz, 256 Mbyte RAM memory and 4.1 Gbyte hard disk. The software is Vitrea 1.0 (Vital Images, Fairfield, Iowa), running on a Unix platform. Image output is obtained through the Ethernet network to a Macintosh computer and a thermic printer (Kodak 8600 XLS).Diagnostic quality images were obtained in all the cases. Fly-through in the airways allowed correct evaluation of the main bronchi and of the origin of segmentary bronchi. In the vascular district, both carotid strictures and abdominal aortic aneurysms were depicted, with the same accuracy as with conventional reconstruction techniques. In the colon studies, polypoid lesions were correctly depicted in all the cases, with good correlation with endoscopic and double-contrast barium enema findings. In a case of lipoma of the ascending colon, virtual endoscopy allowed to study the colon both cranially and caudally to the lesion. The simultaneous evaluation of axial CT images permitted to characterize the lesion correctly on the basis of its density values.The peculiar feature of volume rendering is the use of the whole information inside the imaging volume to reconstruct three-dimensional images; no threshold values are used and no data are lost as opposite to conventional image reconstruction techniques. The different anatomic structures are visualized modifying the reciprocal opacities, showing the structures of no interest as translucent. The modulation of different opacities is obtained modifying the shape of the opacity curve, either using pre-set curves or in a completely independent way. Other technical features of volume rendering are the perspective evaluation of the objects, color and lighting. In conclusion, volume rendering is a promising technique to elaborate three-dimensional images, offering very realistic endoscopic views. At present, the main limitation is represented by the need of powerful and high-cost workstations.

MR cholangiopancreatography (MRCP) is a new noninvasive imaging technique for the study of biliopancreatic disorders, providing projectional images of the biliary tree and pancreatic duct without any contrast agent.We used different sequences, with both breath-hold and nonbreath-hold techniques, to acquire MRCP images, first based on GE and then on FSE sequences. FSE images provide higher SNR and are less susceptible to artifacts (metal objects, motion and blood flow artifacts). At the Department of Radiology of the University of Rome La Sapienza, we acquired MRCP images with non breath-hold, 3D fat-suppressed TSE sequences (TR = 3000-2000, TE 700, turbo factor 128) optimized on a .5T magnet with 15 mT/m gradients. No patient preparation or sedation was required, although antiperistaltic drugs and oral administration of tap water were preferred. Four hundred and thirty patients were examined, all of them with an indication to conventional cholangiography.MRCP depicted the whole common bile duct and the first-order intrahepatic branches in all the normal cases. Its accuracy in identifying biliary obstruction level and site was 100%, versus 94.6% in characterizing its cause. MRCP had 96.3% diagnostic accuracy in choledocholithiasis, with some false positives and false negatives caused by: 1) small stones missed on MIP reconstructions; 2) signal loss due to complete CBD obstruction by stones; 3) pneumobilia; 4) differential diagnosis between small stones and air bubbles. The main role of MRCP in benign strictures is to provide a detailed map of the biliary tract for better treatment planning. In particular, MRCP is extremely useful in hepaticojejunostomy patients, where ERC is not indicated because of postoperative anatomical changes. Both conventional MRI and MRCP are important in malignant strictures to identify the lesion and to characterize and stage it. Finally, MR pancreatography is very useful to follow up chronic pancreatitis patients because it shows Wirsung duct strictures and dilatations, intraductal filling defects and, in some cases, the communication between the pseudocyst and the pancreatic duct.MRCP combined with conventional MRI can completely replace CT and ERCP in bilio-pancreatic disorders.

We investigated MR cholangiopancreatography (MRCP) findings in patients with pancreatic conditions, which are mainly diagnosed based on US and CT morphologic findings. Sixty-three patients were submitted to MRCP using a .5T magnet. MRCP was performed with non-breath-hold fat-suppressed 3D turbo spin echo sequences (TR = 3000 ms, TE = 700 ms, ETL = 128, NEX = 6) with 3 min acquisition time. For better depiction of Wirsung duct and secondary ducts in the last 11 patients, a high resolution technique with a 128 x 256 matrix, 8 NEX and 8 min 36 s acquisition time was developed. MRCP images were studied both on MIP reconstructions and on single slices as well as T1- and T2-weighted TSE axial images. The diagnosis was compared with endoscopy, percutaneous procedure or CT findings in all cases. A hypointense focal mass was observed on T1-weighted TSE images in 39 pancreatic carcinoma patients (100%) and parenchymal atrophy was shown in 13 patients (33%); a sudden obstruction of the Wirsung duct was observed in 16 cases (41%) with homogeneous dilatation in 11 cases (28%). A tapered appearance of the distal Wirsung duct was demonstrated in 19 chronic pancreatitis patients, with diffuse patchy signal changes in 12 patients (63%); bead-like appearance of the Wirsung duct was shown in 6 cases (32%) and pseudocysts in 7 cases (37.3%). MRCP is the only imaging method demonstrating pancreatic conditions between carcinoma and pancreatitis, similarly to ERCP.

A new MR technique is proposed to study the renal collecting system and the proximal ureteral portion in patients without obstructive uropathy, using fat-suppressed Turbo Spin Echo sequences, after drug-induced distension of the urinary tract. Nine normal volunteers and 16 patients (11 with renal stones, 1 with bilateral pyeloureteral junction stenosis, 1 with renal ptosis, 1 with ureteral hyperkinesia, 1 with renal tumor and 1 with a symptomatic renal cyst) were submitted to MR-Urography, performed with a 3D non-breath-hold fat-suppressed Turbo SE sequence (TR = 3000 ms, TE = 800 ms, 6 acquisitions, Turbo Factor = 128, Matrix = 128 x 256 or 256 x 256, acquisition time = 5 min 15 sec or 10 min 36 sec) on the coronal plane. With these acquisition parameters, parenchymal signal can be completely suppressed while enhancing fluid signal. These acquisitions were post-processed with the MIP algorithm to obtain very similar images to those of conventional urography. The maximum filling of the renal collecting system was obtained with the i.v. administration of 250 ml saline solution within 2-3 minutes and then the i.v. injection of 20 mg furosemide. The renal collecting system was optimally depicted in all the volunteers and the patients, except for 2 cases because of malfunctioning respiratory gating. Anatomical detailing was really improved after the diuretic administration, especially in the study of the major caliceal systems. To conclude, MR-Urography permits accurate morphological detailing of the renal collecting system also in patients without obstructive uropathy.

The aim of our work was to investigate Magnetic Resonance Cholangiography (MRC) capabilities in detecting common bile duct (CBD) stones in patients to be submitted to laparoscopic cholecystectomy. MRC was performed as the only preoperative imaging modality in 45 selected patients (16 men and 29 women; age range: 28-72 years, mean age: 54.4 years) before laparoscopic cholecystectomy. MRC images were obtained with 3D Turbo Spin-Echo sequences (TR = 3000 ms, TE = 700 ms, echo train length = 128) with an acquisition time of 5 min 48 sec. Diagnostic confirmation was obtained in all the patients at intraoperative cholangiography. When a stone was detected, it was removed by transcystic or transcholedochal approach. Eighteen of 45 patients (40%) had CBD stones. MRC correctly demonstrated 16 of 18 stones, with 88.9% sensitivity, 100% specificity, 100% positive predictive value, 90% negative predictive value and 95.6% accuracy. Despite the good results we obtained with MRC, this technique cannot be proposed as a screening method to be performed in all the patients candidate to laparoscopic cholecystectomy because of its high cost and of the limited number of MR units available. In conclusion, only selected patients should be submitted to MRC before laparoscopic cholecystectomy.

This study investigated the accuracy of phase contrast MRI in blood flow measurements; both in vitro and in vivo studies were carried out. Five normal volunteers (3 women and 2 men, age range: 24 to 30 years) were examined with MR angiography (MRA) and a flow measurement sequence. A 2D phase contrast sequence, with retrospective cardiac gating was also acquired with the following imaging parameters: TR/TE/FA (26/9.3/20 degrees ), field of view 150 mm, matrix 96 x 128; 4 averages. VENC value (cm/s) was chosen according to the examined region. The total acquisition time ranged 3 min 25 sec to 4 min 38 sec. The sequences were acquired on a plane perpendicular to the vessel direction, using MIP-reconstructed MRA images as a scout view. The results are the same as those obtained with other techniques, in the common carotid artery (Vmax = 70.7 cm/s; Vmin = 18.8 cm/sec; flow = 348 ml/min), internal carotid artery (Vmax -54.4 cm/sec; Vmin = 18 cm/sec; flow = 236 ml/min) and vertebral artery (Vmax = 51.7 cm/sec; Vmin = 17.5 cm/sec). The resistance index could always be calculated and exceeded 0.7 in all cases. In conclusion, MRA is an accurate technique for blood flow measurements, in particular with cardiac gating, which permits measurement optimization according to the different cardiac cycles.

Our study was aimed at investigating the role of MR-cholangiography (MRC) in the examination of patients treated with biliary-enteric anastomosis. MRC was performed in 15 patients (8 men and 7 women, mean age: 64.7 years) operated on for biliary-enteric anastomoses (13 hepaticojejunostomies and 2 choledochoduodenostomies) whose symptoms were as follows: persistent jaundice in 4 patients; cholangitis and abnormal liver function tests in 2 patients; associated transient jaundice, epigastric pain, abnormal liver function tests in 2 patients. The remaining 7 patients were asymptomatic and examined during their follow-up. MRC was performed with a non-breath-hold, fat-suppressed 3D turbo spin echo sequence (TR = 3000 msec, TE = 700 msec, ETL = 128) with an acquisition time ranging 4 min 24 sec to 5 min 48 sec. Six patients were subsequently submitted to Percutaneous Transhepatic Cholangiography (PTC) to confirm the diagnosis and to perform a therapeutical procedure. Two patients, submitted to choledochoduodenostomy were examined with ERCP. The remaining seven patients, examined during their surgical follow-up and who presented no major symptoms or dilation of the bile ducts, were not submitted to any invasive procedure. Image quality was graded as good to fair in 12/15 cases (80%) and poor in 3/15 cases (20%). The degree of bile ducts dilation was correctly assessed with complete inter observer agreement in 8/8 patients. MRCP correctly showed: bile ducts irregularities in 2 of 4 patients with cholangitis (k = 0.59), anastomosis stenosis in 8 of 8 patients (k = 0.86), and 5-15 mm stones in 5 of 5 patients (k = 0.95). In conclusion, MRCP is a safe, noninvasive technique in the study of biliary-enteric anastomoses with high accuracy in assessing the cause of jaundice. MRCP images can be used as a guide for subsequent interventional procedures. Its main disadvantages are the lack of functional information and the high cost which limits its its use to the screening of symptomatic patients.

This work was aimed at investigating the CT anatomy in patients submitted to Nissen's fundoplication. Forty patients (mean age: 61 years) with peptic esophagitis (9 patients), refractory gastroesophageal (GE) reflux (11 patients) and hiatal hernia (20 patients) were examined. CT studies were performed with a third generation unit (CT Pace, General Electric, USA) with the patients in the prone position, after Gastrovison (Schering) and barium paste administration. In 34 patients, CT demonstrated surgery-related anatomical changes, such as the presence of a soft tissue mass at the distal third of the esophagus. In 4 patients, functional incompetence of the fundoplication (3 patients) and a recurrent hyatal hernia (1 patient) were demonstrated. In conclusion, CT studies performed with a dedicated technique permitted the accurate assessment of the anatomy of the GE junction after Nissen's fundoplication. In our study, CT demonstrated the presence of postoperative fluid collections and specific signs related to fundoplication incompetence. Our results suggest a possible application of CT to the postoperative follow-up of the patients submitted to Nissen's fundoplication, with a complementary role that of to endoscopy and functional exams.

Magnetic resonance pyelography (MRP) is a new noninvasive method which demonstrates dilated urinary tracts with no need of contrast agent injection. This study was aimed at technique optimization, using new fast sequences with high intrinsic contrast, to demonstrate the urinary tract in obstructive uropathy patients. Twelve consecutive patients and 4 healthy volunteers were included in this prospective study; all the exams were performed with a high gradient power 0.5-T unit using T2- weighted turbo SE sequences, acquired three-dimensionally on the coronal plane. Obstructive uropathy was caused in 9 patients by neoplastic lesions, in 2 by postoperative strictures and in 1 by inflammatory tissue. In all patients MRP depicted the dilated urinary tract optimally, with good morphological detailing and the accurate assessment of both level and cause of obstruction. In the healthy volunteers, the absence of dilatation did not permit the complete visualization of the urinary tract. To conclude, MRP is a new technique which permits high-quality imaging of the urinary tract. Further studies are needed to assess its actual potentials and clinical role.

This work was aimed at investigating the diagnostic accuracy of Magnetic Resonance Angiography (MRA) in the study of the portal vein in liver transplant recipients. Ten patients (7 men and 3 women; mean age: 45 years) were examined 7-180 days after transplantation. The indications to liver transplant follow: post-infective active chronic hepatitis (4 patients), post-alcoholic chronic hepatitis (2 patients), HCC (2 patients), sclerosing cholangitis (1 patient) and primary biliary cirrhosis (1 patient). MRA images were acquired with the 2D TOF technique (TR 50 ms, TE 6.9 ms; FA 30 degrees, 40 slices; 6-mm thickness with 1-mm overlapping; 2 averages; 7.06 TA; matrix: 192 x 256). Axial scans were reconstructed with the MIP technique. Phase contrast sequences with retrospective cardiac triggering were also acquired for flow quantitation (TR/TE/FA: 26/9.3/20 degrees; FOV 150; matrix: 96 x 128; 4 averages, VENC = 20 cm/s). MRA yielded good quality images of the anatomy of the main portal vein and of the bifurcation in all cases, while a signal loss was observed in the peripheral branches. In all cases, the anastomosis could be studied at the portal vein. On MIP reconstructed images, the anastomosis appeared as a relative stenosis (4), while on 2D images it appeared as a small hypodense area on the vessel margin, because of the slight paramagnetic effect of the vascular suture. No thrombi were depicted in any patient and flow was hepatopetal in all cases. In conclusion, MRA is a useful tool for portal system studies in liver transplant recipients, because it permits the panoramic depiction of the portal system and the quantitation of flow (10).

Magnetic Resonance cholangiopancreatography (MRCP) is a new noninvasive imaging technique for the visualization of the biliary ducts with cholangiographic images similar to those obtained with ERCP and PTC, but with no contrast agent injection. In this paper, we report on our preliminary experience with a mild-field strength magnet (0.5T) and TSE sequences, acquired with respiratory compensation. The images were compared with ERCP images to compare diagnostic quality. Eighteen patients were examined: the biliary tract was dilated because of chronic pancreatitis in 3 patients, because of choledochal stones in 9, of carcinoma of the pancreatic head in 4, of lymphadenopathy in one patient. A patient submitted to choledochoduodenostomy and waiting for cholecystectomy was also examined. MRCP was performed with a superconductive magnet at 0.5T. Volumetric images on coronal planes were acquired; a T2-weighted TSE sequence (TR = 5000, TE = 244, Nex = 4, ETL = 45; acquisition time = 14 min 10 s) with respiratory compensation was also performed. The images were reconstructed on coronal planes at different angles with the MIP algorithm. All patients were then submitted to ERCP and one to PTC. In all patients, the intrahepatic biliary tracts, hepatic ducts and choledochus were completely demonstrated, with very good image quality in 16 cases and good in 2. The Wirsung duct was always visualized in all the 9 patients with mild to severe dilation. In conclusion, MRCP can be considered a valuable alternative to diagnostic ERCP. Further studies are necessary for better assessment of the potential advantages and pitfalls of this technique.

Magnetic resonance imaging of the pancreas has been, limited by a series of artifacts with a resulting poor contrast to noise ratio. Nevertheless, technological progress has allowed to reduce not only scanning time but also the number of artifacts, by increasing the number of excitations and matrix size. Moreover, tissue contrast can now be modified. In our study performed on 5 normal volunteers and 20 patients with different pancreatic diseases conditions, fast SE sequences with and without fat suppression were used, with an overall increase in contrast to noise ratio. In all patients MR images allowed the accurate definition of the lesions: in 8 adenocarcinoma patients the lesion could be depicted, including the 2 lesions CT had poorly demonstrated. Also in the 3 patients with endocrine tumors, MRI depicted small tumors which were later confirmed at surgery. This new protocol makes MRI a very sensitive and accurate tool in the study of neoplastic and inflammatory pancreatic diseases thus, MRI is not only a complementary tool to CT but an even better study technique. In particular, its higher contrast to noise ratio allows a dramatic improvement in the depiction of small solid lesions, especially those not altering pancreatic outline. This study proves that MRI, when adequately performed, is a very accurate tool to study, in a very short time, the pancreas and peripancreatic region, yielding much better results than all the other diagnostic imaging modalities.

MR phlebography was recently proposed as a possible alternative to contrast venography in the detection of deep venous thrombosis. We focused our work on the study of the pelvic veins since it is at this level that contrast venography and the other noninvasive techniques, i.e., phlebography, impedance plethysmography and US, exhibit their major limitations. Thirty patients underwent MR phlebography: 13 of them had a diagnosis of DVT of the pelvic venous district and the other 17 had negative results for this condition. All the patients were also examined with color-Doppler US at the pelvis and legs. In all the patients submitted to MR phlebography, thrombosis site and presence were demonstrated, with diagnostic information also on its extent and adhesion to vein wall. To conclude, MR phlebography can provide contrast venography-like images in a noninvasive way, with high accuracy (100% sensitivity and 90% specificity) especially in the pelvic district where the limitations of other techniques are more apparent. Larger series of patients must be studied to assess the actual role of MR phlebography in the patients with DVT or at high risk for this condition.

In the last years, laparoscopic cholecystectomy has become the method of choice in the surgical treatment of gallbladder stones. Recently, the same laparoscopic approach has been used to remove choledochus stones. This surgical procedure needs the accurate intraoperative study of the biliary tree with diagnostic imaging modalities to better define the anatomy of the biliary ducts and the possible presence of choledochus stones. To this purpose, transcutaneous and endolaparoscopic US with dedicated probes and intraoperative cholangiography can be performed. In this study, we performed 30 laparoscopic cholecystectomies during which all the patients were submitted to intraoperative cholangiography with a digital fluoroscopic unit. The maneuvers for catheter insertion in the cystic duct and the examination as a whole took 3 to 5 minutes. Intraoperative cholangiography demonstrated choledochus stones in 3 patients, while preoperative US detected them in 2 patients only. In 8 cases the dynamic study, carried out with digital image acquisition, allowed to refer the biliary duct filling defects to artifacts caused by the presence of air bubbles. In conclusion, intraoperative cholangiography, also during endolaparoscopic cholecystectomy, plays a major role in the surgical assessment of the biliary tree. When the procedure was performed with a digital fluoroscopic unit, its diagnostic accuracy was higher and the images on the TV monitor were better visualized.

The authors have developed a hypermedia program for creating a tutorial of CT and MR anatomy of the upper abdomen. The program was created on a Mcintosh computer, with the Supercard software: it is made up of a series of windows, each of them containing images, texts, schematic representations and sound. Moreover, each window contains buttons which are activated with the mouse and allow different kinds of function, all created by the authors to be displayed. In particular, navigation buttons allow the users to move in the program either sequentially or non-linearly, according to their needs. The possibility of obtaining information and schematic representations is given by specific buttons. There are also multiple buttons hidden in the images which, when activated, allow the name of the selected organ to be displayed. In conclusion, this program can be especially helpful since it allows different data sets to be integrated to provide the user with complete information. Moreover, the program allows learning to be controlled, that is the user to be informed on timing and methods for more effective studying.

Aneurysms of the pancreaticoduodenal artery are rare. Nonoperative management of an iatrogenic superior pancreaticoduodenal artery aneurysm which ruptured into the duodenal stump of a Billroth II partial gastrectomy, is described here. Based on a literature review, both aetiology and site of rupture of this observation are very uncommon. Super-selective angiography was used for diagnosis and embolisation for definitive treatment.