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Objectives To assess the effects of acupuncture and dry-needling for the treatment of nonspecific low back pain. Background Low back pain is usually a self-limiting condition that tends to improve spontaneously over time. However, for many people, back pain becomes a chronic or recurrent problem for which a large variety of therapeutic interventions are employed. Search strategy We updated the searches from 1996 to February 2003 in CENTRAL, MEDLINE, and EMBASE. We also searched the Chinese Cochrane Centre database of clinical trials and Japanese databases to February 2003. Selection criteria Randomized controlled trials of acupuncture (that involved needling) or dry-needling for adults with nonspecific acute/subacute or chronic low back pain. Data collection and analysis Two reviewers independently assessed methodologic quality (using the criteria recommended by the Cochrane Back Review Group) and extracted data. The trials were combined using meta-analysis methods or levels of evidence when the data reported did not allow statistical pooling. Results Thirty-five randomized clinical trials were included: 20 were published in English, 7 in Japanese, 5 in Chinese, and 1 each in Norwegian, Polish, and German. There were only 3 trials of acupuncture for acute low back pain. These studies did not justify firm conclusions because of their small sample sizes and low methodologic quality. For chronic low back pain, there is evidence of pain relief and functional improvement for acupuncture compared to no treatment or sham therapy. These effects were only observed immediately after the end of the sessions and in short-term follow-up. There is also evidence that acupuncture, added to other conventional therapies, relieves pain and improves function better than the conventional therapies alone. However, the effects are only small. Dry-needling appears to be a useful adjunct to other therapies for chronic low back pain. No clear recommendations could be made about the most effective acupuncture technique. Conclusions The data do not allow firm conclusions regarding the effectiveness of acupuncture for acute low back pain. For chronic low back pain, acupuncture is more effective for pain relief and functional improvement than no treatment or sham treatment immediately after treatment and in the short-term only. Acupuncture is not more effective than other conventional and "alternative" treatments. The data suggest that acupuncture and dry-needling may be useful adjuncts to other therapies for chronic low back pain. Because most of the studies were of lower methodologic quality, there is a clear need for higher quality trials in this area.

To perform an intra-individual comparison of the frequency of respiratory-motion artefacts on magnetic resonance imaging (MRI) in cirrhotic patients following injection of gadoxetate disodium and gadobenate dimeglumine.Ninety-five cirrhotic patients (61 men and 34 women, mean age 58 years) underwent liver MRI with intravenous administration of gadoxetate disodium and gadobenate dimeglumine at different times (interval between studies, 189±83 days). Three readers scored the severity of respiratory-motion artefacts on the three-dimensional (3D) gradient-echo (GRE) images acquired before and after contrast medium injection. McNemar's test was used to assess the difference in frequency of new respiratory-motion artefacts and transient severe motion (TSM) artefacts between gadoxetate disodium and gadobenate dimeglumine MRI studies. The association between clinical and technical features and the occurrence of TSM on gadoxetate disodium MRI studies was investigated.On arterial phase images, new respiratory-motion artefacts were present in 32/95 (34%) cases after injection of gadoxetate disodium, while only seen in 2/95 (2%) cases after injection of gadobenate dimeglumine (p0.0001). TSM was present in 6/95 (6%) cases after injection of gadoxetate disodium, and in 0/95 (0%) case after injection of gadobenate dimeglumine. No clinical or technical features were associated with the occurrence of TSM.In cirrhotic patients, respiratory-motion artefacts on arterial phase 3D GRE images are more frequently seen after injection of gadoxetate disodium than after injection of gadobenate dimeglumine.

International audience; Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that plays integral roles in eliminating mRNAs with premature termination codons to prevent the synthesis of truncated proteins that could be pathogenic. One response to the accumulation of detrimental proteins is apoptosis, which involves the activation of enzymatic pathways leading to protein and nucleic acid cleavage and culminating in cell death. It is not clear whether NMD is required to ensure the accurate expression of apoptosis genes or is no longer necessary since cytotoxic proteins are not an issue during cell death. The present study shows that caspases cleave the two NMD factors UPF1 and UPF2 during apoptosis impairing NMD. Our results demonstrate a new regulatory pathway for NMD that occurs during apoptosis and provide evidence for role of the UPF cleaved fragments in apoptosis and NMD inhibition.

In 1984, the Met receptor and its ligand, the HGF/SF, were discovered thanks to their ability to induce cell transformation and proliferation. Thirty years of research highlighted their crucial role in the development and homeostasis of various structures, including many epithelial organs. This period also allowed unraveling the structural basis of their interaction and their complex signaling network. In parallel, Met was shown to be deregulated and associated with a poor prognosis in many cancers. Met involvement in resistance to current therapies is also being deciphered. Based on these data, pharmaceutical companies developed a variety of Met inhibitors, some of which are evaluated in phase III clinical trials. In this review, we trace the exemplary track record of research on Met receptor, which allowed moving from bench to bedside through the development of therapies targeting its activity. Many questions still remain unanswered such as the involvement of Met in several processes of development, the mechanisms involving Met in resistance to current therapies or the likely emergence of resistances to Met-targeted therapies., En 1984, le récepteur à activité tyrosine kinase Met et son ligand l’HGF (hepatocyte growth factor)/SF (scatter factor) sont découverts grâce à leur aptitude à induire la transformation et la prolifération cellulaires. Trois décennies ont permis de mettre en évidence leur rôle fondamental dans le déve­loppement et l’homéostasie de nombreuses structures, notamment des organes épithéliaux. Cette même période a permis de décrypter les bases structurales de leur interaction, ainsi qu’un réseau de signalisation complexe. Parallèlement, l’implication de la dérégulation de Met dans la tumorigenèse, supposée dès sa découverte, a été démontrée ; elle est associée à un mauvais pronostic dans de nombreux cancers. Le rôle de cette dérégulation dans des phénomènes de résistance aux thérapies actuelles commence également à être déchiffré. Sur la base de ces données, des compagnies pharmaceutiques ont développé une grande diversité d’inhibiteurs ciblant l’HGF/SF ou le récepteur Met, dont certains sont actuellement évalués dans des essais cliniques de phase III. Nous proposons dans cette revue de retracer le parcours exemplaire des recherches sur le récepteur Met, qui auront permis en trente ans de passer de la découverte fondamentale d’un oncogène au développement de thérapies ciblant son action. Cependant, de nombreuses questions restent en suspens. Par exemple, l’implication de Met dans plusieurs étapes du développement reste à préciser, de même que les mécanismes faisant de ce récepteur un facteur de résistance aux traitements actuels ou le développement probable de résistances aux thérapies ciblant sa propre activité.

Detection and characterization of focal lesions in the cirrhotic liver may pose a diagnostic dilemma. Several benign and malignant lesions may be found in a cirrhotic liver along with hepatocellular carcinoma (HCC), and may exhibit typical or atypical imaging features. In this pictorial essay, we illustrate computed tomography and magnetic resonance imaging findings of lesions such as simple bile duct cysts, hemangioma, focal nodular hyperplasia-like nodules, peribiliary cysts, intrahepatic cholangiocarcinoma, lymphoma, and metastases, all of which occur in cirrhotic livers with varying prevalences. Pseudolesions, such as perfusion anomalies, focal confluent fibrosis, and segmental hyperplasia, will also be discussed. Imaging characterization of non-HCC lesions in cirrhosis is important in formulating an accurate diagnosis and triaging the patient towards the most appropriate management.

To compare sodium ((23)Na) characteristics between native and transplanted kidneys using dual-tuned proton ((1)H)/sodium MRI.Six healthy volunteers and six renal transplant patients (3 normal function, 3 acute allograft rejection) were included. Proton/sodium MRI was obtained at 3 T using a dual-tuned coil. Signal to noise ratio (SNR), sodium concentration ([(23)Na]) and cortico-medullary sodium gradient (CMSG) were measured. Reproducibility of [(23)Na] measurement was also tested. SNR, [(23)Na] and CMSG of the native and transplanted kidneys were compared.Proton and sodium images of kidneys were successfully acquired. SNR and [(23)Na] measurements of the native kidneys were reproducible at two different sessions. [(23)Na] and CMSG of the transplanted kidneys was significantly lower than those of the native kidneys: 153.5 ± 11.9 vs. 192.9 ± 9.6 mM (P = 0.002) and 8.9 ± 1.5 vs. 10.5 ± 0.9 mM/mm (P = 0.041), respectively. [(23)Na] and CMSG of the transplanted kidneys with normal function vs. acute rejection were not statistically different.Sodium quantification of kidneys was reliably performed using proton/sodium MRI. [(23)Na] and CMSG of the transplanted kidneys were lower than those of the native kidneys, but without a statistically significant difference between patients with or without renal allograft rejection.Dual-tuned proton/sodium RF coil enables co-registered proton and sodium MRI. Structural and sodium biochemical property can be acquired by dual-tuned proton/sodium MRI. Sodium and sodium gradient of kidneys can be measured by dual-tuned MRI. Sodium concentration was lower in transplanted kidneys than in native kidneys. Sodium gradient of transplanted kidneys was lower than for native kidneys.

Ets-1 overexpression in human breast cancers is associated with invasiveness and poor prognosis. By overexpressing Ets-1 or a dominant negative mutant in MMT breast cancer cells, we previously highlighted the key role of Ets-1 in coordinating multiple invasive features of these cells. Interestingly, we also noticed that Ets-1 decreased the density of breast cancer cells cultured in three-dimensional extracellular matrix gels. The 3D context was instrumental to this phenomenon, as such downregulation was not observed in cells grown on two-dimensional plastic or matrix-coated dishes. Ets-1 overexpression was deleterious to anchorage-independent growth of MMT cells in soft agar, a standard model for in vitro tumorigenicity. The relevance of this mechanism was confirmed in vivo, during primary tumor growth and in a metastatic assay of lung colonization. In these models, Ets-1 was associated with epithelial-to-mesenchymal transition features and modulated the ratio of Ki67-positive cells, while hardly affecting in vivo apoptotic cell death. Finally, siRNA-mediated knockdown of Ets-1 in human breast cancer cell lines also decreased colony growth, both in anchorage-independent assays and 3D extracellular matrix cultures. These in vitro and in vivo observations shed light on an unsuspected facet of Ets-1 in breast tumorigenesis. They show that while promoting malignancy through the acquisition of invasive features, Ets-1 also attenuates breast tumor cell growth and could therefore repress the growth of primary tumors and metastases. This work also demonstrates that 3D models may reveal mechanisms of tumor biology that are cryptic in standard 2D models.

Acute conditions affecting the mesenteric vessels can cause abdominal pain and result in significant morbidity and mortality if not diagnosed and treated quickly. As bowel viability depends on patency of the mesenteric vessels, prompt diagnosis is essential. Helical multidetector computed tomography (MDCT) provides a rapid, widely available, non-invasive method to promptly evaluate the mesenteric arteries, veins, and abdominopelvic viscera. Given the value of MDCT in diagnosing vascular disease, it is important the radiologist understand technical and imaging findings of mesenteric vascular injury. Therefore, successful diagnosis hinges on familiarity with MDCT angiography and the extended capabilities of volume rendering and multiplanar reformation. In this review, we illustrate and describe key MDCT findings of congenital, inflammatory, traumatic, infectious, and thromboembolic conditions affecting the mesenteric vasculature in adult patients.

The sympathetic nervous system relies on distinct populations of neurons that use noradrenaline or acetylcholine as neurotransmitter. We show that fating of the sympathetic lineage at early stages results in hybrid precursors from which, genetic cell-lineage tracing reveals, all types progressively emerge by principal mechanisms of maintenance, repression and induction of phenotypes. The homeobox transcription factor HMX1 represses Tlx3 and Ret, induces TrkA and maintains tyrosine hydroxylase (Th) expression in precursors, thus driving segregation of the noradrenergic sympathetic fate. Cholinergic sympathetic neurons develop through cross-regulatory interactions between TRKC and RET in precursors, which lead to Hmx1 repression and sustained Tlx3 expression, thereby resulting in failure of TrkA induction and loss of maintenance of Th expression. Our results provide direct evidence for a model in which diversification of noradrenergic and cholinergic sympathetic neurons is based on a principle of cross-repressive functions in which the specific cell fates are directed by an active suppression of the expression of transcription factors and receptors that direct the alternative fate.

The purpose of this article is to quantitatively assess the rate of resolution of clot burden detected on pulmonary CT angiography (CTA) in patients with acute pulmonary embolism (PE).We evaluated 111 consecutive patients (55 men and 56 women) in a retrospective cohort who were diagnosed with PE by pulmonary CTA and had at least one follow-up pulmonary CTA within 1 year. Two radiologists in consensus measured the volume of each clot using a semiautomated quantification program. Semiquantitative measures of clot burden were also computed. The resolution rates of the total clot volume, as well as clot volumes of the central (main and lobar) and peripheral vessels (segmental and subsegmental), were analyzed.The mean (± SD) clot volume per study was 3403.3 ± 6505.6 mm(3) at baseline and 531.6 ± 2383.5 mm(3) at the follow-up pulmonary CTA. Overall, 85 patients (77% ) showed complete resolution at the follow-up pulmonary CTA. Complete resolution was seen in 17 of 30 patients (56.7%) at a follow-up interval of 1-14 days, in 24 of 31 patients (77.4%) at 29-90 days, and in 32 of 34 patients (94.1%) after 90 days. The total clot volume measurements summed for all patients decreased by 78% (central clot, 69.4%; peripheral clot, 86.0%) at 14 days, by 96.6% (central clot, 93.4%; peripheral clot, 100%) at 90 days, and by 97.7% (central clot, 95.9%; peripheral clot, 100%) after 90 days.Clot burden resolved completely in 77% of patients during the follow-up period. Our analysis showed that clots resolved faster in the peripheral arteries than in the central pulmonary arteries.

Background & Aims Steatosis is a defining feature of nonalcoholic fatty liver disease (NAFLD). However, evidence that severity of steatosis can predict adverse outcomes in NAFLD or nonalcoholic steatohepatitis (NASH) is lacking. The aim of this study was to determine whether steatosis assessed by computed tomography (CT) imaging predicts adverse outcomes in diabetic patients at risk for NAFLD/NASH. Methods We studied deaths, liver-related and cardiovascular adverse outcomes in a 5-year retrospective observational cohort of 2343 type 2 diabetic patients in a large care network who had noncontrast CT imaging for clinical indications. We measured steatosis by subtraction of spleen from liver attenuation, a method that showed low sensitivity (0.417) and high specificity (0.882) compared with histopathological scoring. We evaluated outcomes prediction using multivariate Cox proportional hazards modelling of steatosis both as a categorical (≥30%) and continuous variable. Results Steatosis ≥30% was present in 233 (9.9%) of the cohort at baseline. Over 5 years, there were 372 total deaths, 18 liver-related and 99 cardiovascular deaths, 48 liver transplants, 51 occurrences of hepatic encephalopathy, 41 hepatocellular carcinomas, 653 myocardial infarctions, 66 strokes, 180 occurrences of angina, 735 occurrences of arrhythmia and 772 occurrences of congestive heart failure. Steatosis had no predictive value for any adverse outcome. Patients with steatosis averaged 8 years younger than those without it. Age had a strong covariate influence on occurrence of total deaths, cardiovascular deaths, myocardial infarctions, arrhythmias and congestive heart failure. Conclusion Although steatosis on imaging is often the abnormality that triggers diagnosis and assessment of NAFLD/NASH, it lacks predictive value for adverse clinical outcomes.

Background & Aims: Genetic studies indicate that distinct signaling modulators are each necessary but not individually sufficient for embryonic hepatocyte survival in vivo. Nevertheless, how signaling players are interconnected into functional circuits and how they coordinate the balance of cell survival and death in developing livers are still major unresolved issues. In the present study, we examined the modulation of the p53 pathway by HGF/ Met in embryonic livers. Methods: We combined pharmacological and genetic approaches to biochemically and functionally evaluate p53 pathway modulation in primary embryonic hepatocytes and in developing livers. RT-PCR arrays were applied to investigate the selectivity of p53 transcriptional response triggered by Met. Results: Met recruits p53 to regulate the liver developmental program, by qualitatively modulating its transcriptional properties: turning on the Mdm2 survival gene, while keeping death and cell-cycle arrest genes Pmaip1 and p21 silent. We investigated the mechanism leading to p53 regulation by Met and found that Abl and p38MAPK are required for p53 phosphorylation on S 389 , Mdm2 upregulation, and hepatocyte survival. Alteration of this signaling mechanism switches p53 properties, leading to p53-dependent cell death in embryonic livers. RT-PCR array studies affirmed the ability of the Met-Abl-p53 axis to modulate the expression of distinct genes that can be regulated by p53. Conclusions: A signaling circuit involving Abl and p38MAPK is required downstream of Met for the survival of embryonic hepatocytes, via qualitative regulation of the p53 transcriptional response, by switching its proapoptotic into survival properties. 2012 European Association for the Study of the Liver. Published

Background & Aims Acute pancreatitis (AP) and chronic pancreatitis (CP) share etiologies, but AP can be more severe and is associated with a higher rate of mortality. We investigated features of CP that protect against severe disease. The amount of intrapancreatic fat (IPF) is increased in obese patients and fibrosis is increased in patients with CP, so we studied whether fibrosis or fat regulate severity of AP attacks in patients with CP. Methods We reviewed records from the University of Pittsburgh Medical Center/Presbyterian Hospital Autopsy Database (1998–2008) for patients with a diagnosis of AP (n = 23), CP (n = 35), or both (AP-on-CP; n = 15). Pancreatic histology samples from these patients and 50 randomly selected controls (no pancreatic disease) were analyzed, and IPF data were correlated with computed tomography data. An adipocyte and acinar cell Transwell coculture system, with or without collagen type I, was used to study the effects of fibrosis on acinar-adipocyte interactions. We studied the effects of nonesterified fatty acids (NEFAs) and adipokines on acinar cells in culture. Results Levels of IPF were significantly higher in nonobese patients with CP than in nonobese controls. In patients with CP or AP-on-CP, areas of IPF were surrounded by significantly more fibrosis than in controls or patients with AP. Fat necrosis–associated peri-fat acinar necrosis (PFAN, indicated by NEFA spillage) contributed to most of the necrosis observed in samples from patients with AP; however, findings of peri-fat acinar necrosis and total necrosis were significantly lower in samples from patients with CP or AP-on-CP. Fibrosis appeared to wall off the fat necrosis and limit peri-fat acinar necrosis, reducing acinar necrosis. In vitro, collagen I limited the lipolytic flux between acinar cells and adipocytes and prevented increases in adipokines in the acinar compartment. This was associated with reduced acinar cell necrosis. However, NEFAs, but not adipokines, caused acinar cell necrosis. Conclusions Based on analysis of pancreatic samples from patients with CP, AP, or AP-on-CP and in vitro studies, fibrosis reduces the severity of acute exacerbations of CP by reducing lipolytic flux between adipocytes and acinar cells.

International audience; The use of Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition permitted the synthesis of a new compound that is able to inhibit the HGF-induced scattering of MDCK (epithelial cells) and in vitro tumorigenesis of H1437 (non-small-cell lung cancer) and GTL-16 (human gastric carcinoma). In agreement with biochemical and biological results, docking studies within the ATP binding site of Met suggested for the new synthesized compound a binding mode similar to that of the active compound Triflorcas previously reported.

OBJECTIVE:To evaluate agreement between contrast-enhanced ultrasound (CEUS), multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI) for the assessment of typical and atypical enhancement patterns of small hepatocellular carcinoma (HCC); and to compare diagnostic sensitivity of 2005 and 2010 American Association for the Study of Liver Diseases (AASLD) guidelines. MATERIALS AND METHODS: Between January 2008 and December 2009, we included cirrhotic patients with newly diagnosed 10-20 mm HCC imaged at two contrast-enhanced imaging techniques among CEUS, MDCT, and MRI. Dynamic studies were reviewed by two radiologists to assess enhancement pattern. Percentage of cases with concordant findings and Cohen coefficient (k) were calculated. McNemar's test was used to compare sensitivity between 2005 and 2010 AASLD guidelines. RESULTS: There were 91 patients (69 M; 22 F; mean age, 68 years) with 96 HCCs, studied with a combination of CEUS and MDCT (n=59), CEUS and MRI (n=26), or MDCT and MRI (n=11). Intermodality agreement for assessment of tumor enhancement pattern was 67% (k=0.294, P=0.001). Typical enhancement pattern was detected coincidentally at two imaging modalities in 50 (52%) HCCs. Sensitivity for the diagnosis of HCC increased significantly using the 2010 AASLD (81/96 (84%) vs. 50/96 (52%), P

International audience; The Met receptor tyrosine kinase is a promising target in anticancer therapies for its role during tumor evolution and resistance to treatment. It is characterized by an unusual structural plasticity as its active site accepts different inhibitor binding modes. Such feature can be exploited to identify distinct agents targeting tumor dependence and/or resistance by oncogenic Met. Here we report the identification of bioactive agents, featuring a new 4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl moiety, targeting cancer cells dependent on oncogenic Met. One of these compounds (7c; Triflorcas) impairs survival, anchorageindependent growth, and in vivo tumorigenesis, without showing side effects. Our medicinal chemistry strategy was based on an in-house Met-focused library of aminoacid-amide derivatives enriched through structure-based computer modeling, taking into account the Met multiple-binding-mode feature. Altogether, our findings show how a rational structure-based drug design approach coupled to cell-based drug evaluation strategies can be applied in medicinal chemistry to identify new agents targeting a given oncogenic-dependency setting.

International audience; The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by ''RTK swapping'' by interfering with PDGFRb phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid-mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis.

Accurate diagnosis and description of the various findings in acute pancreatitis is important for treatment. The original Atlanta classification for acute pancreatitis sought to create a uniform system for classifying the severity of acute pancreatitis as well as common language to describe the various events that can occur in acute pancreatitis. The goal was to allow accurate communication between physicians using standardized language so correct treatment options could be used. Since that time, advances in the understanding of acute pancreatitis as well as improvements in both interventions and imaging have led to criticisms of the system and its abandonment by physicians. A 2007 revision of the Atlanta classifications sought to address many of these issues. This article will explain the changes to the Atlanta classification system and provide pictorial examples of the findings in acute pancreatitis as described by the Atlanta classification system.

The simplicity of BCR-ABL 'oncogene addiction' characterizing leukemia contrasts with the complexity of solid tumors where multiple 'core pathways', including receptor tyrosine kinases (RTKs) and p53, are often altered. This discrepancy illustrates the limited success of RTK antagonists in solid tumor treatment compared with the impact of Imatinib in BCR-ABL-dependent leukemia. Here, we identified c-Abl as a signaling node interconnecting Met-RTK and p53 core pathways, and showed that its inhibition impairs Met-dependent tumorigenesis. Met ensures cell survival through a new path in which c-Abl and p38-MAPK are employed to elicit p53 phosphorylation on Ser(392) and Mdm2 upregulation. We found a clinical correlation between activated Met, phospho-p53, and Mdm2 levels in human tumors, supporting the role of this path in tumorigenesis. Our findings introduce the concept that RTK-driven tumors may be therapeutically treated by hitting signaling nodes interconnecting core pathways. Moreover, they underline the importance of evaluating the relevance of c-Abl antagonists for combined therapies, based on the tumor signaling signature.

Sodium magnetic resonance (MR) imaging is a promising technique for detecting changes of proteoglycan (PG) content in cartilage associated with knee osteoarthritis. Despite its potential clinical benefit, sodium MR imaging in vivo is challenging because of intrinsically low sodium concentration and low MR signal sensitivity. Some of the challenges in sodium MR imaging may be eliminated by the use of a high-sensitivity radiofrequency (RF) coil, specifically, a dual-tuned (DT) proton/sodium RF coil which facilitates the co-registration of sodium and proton MR images and the evaluation of both physiochemical and structural properties of knee cartilage. Nevertheless, implementation of a DT proton/sodium RF coil is technically difficult because of the coupling effect between the coil elements (particularly at high field) and the required compact design with improved coil sensitivity. In this study, we applied a multitransceiver RF coil design to develop a DT proton/sodium coil for knee cartilage imaging at 3 T. With the new design, the size of the coil was minimized, and a high signal-to-noise ratio (SNR) was achieved. DT coil exhibited high levels of reflection S11 (∼-21 dB) and transmission coefficient S12 (∼-19 dB) for both the proton and sodium coils. High SNR (range 27-38) and contrast-to-noise ratio (CNR) (range 15-21) were achieved in sodium MR imaging of knee cartilage in vivo at 3-mm(3) isotropic resolution. This DT coil performance was comparable to that measured using a sodium-only birdcage coil (SNR of 28 and CNR of 20). Clinical evaluation of the DT coil on four normal subjects demonstrated a consistent acquisition of high-resolution proton images and measurement of relative sodium concentrations of knee cartilages without repositioning of the subjects during the same MR scanning session.

The purpose of our study was to assess the accuracy and reproducibility of clot burden quantification with pulmonary CT angiography (CTA).A semiautomated program was developed for segmentation and volumetric quantification of pulmonary embolus with pulmonary CTA. The accuracy of this measurement method was assessed using two pulmonary embolus phantoms. Reproducibility of the measurement method was assessed using clinical pulmonary CTA in 30 patients (16 women, 14 men; mean age, 62 years) with pulmonary embolism (PE). Two observers segmented and measured the volume of blood clot from pulmonary CTA images twice at two separate sessions. Accuracy was evaluated by the relative volume measurement error. Intra- and interobserver reliability were evaluated using intraclass correlation coefficient (ICC); agreement between measurements within and between the two observers was assessed using Bland-Altman analysis.Mean relative measurement error from the two phantoms was less than 1% for both observers. A total of 60 emboli were measured from the 30 patients. The intraobserver ICC was 0.990 for observer 1 and 0.999 for observer 2; interobserver ICC was 0.994 for session 1 and 0.989 for session 2. ICC for all four clot measurements was 0.988. Mean volume measurement difference for intraobserver agreement was 0.9% for observer 1 and 0.3% for observer 2, and interobserver agreement was -5.1% for session 1 and -5.8% for session 2.Blood clot burden can be quantified with a high degree of accuracy and reproducibility from pulmonary CTA images using a semiautomated segmentation method.

Although breast lesions are commonly detected because of their hypoechogenicity, some lesions may present with hyperechogenicity due to their histological components. Hyperechogenicity has been shown to be highly predictive of benignity; however, hyperechoic lesions can occasionally be malignant. This article reviews hyperechoic lesions of the breast, describes the underlying histological causes associated with hyperechogenicity, and the sonographic features useful for the differential diagnosis between benign and malignant hyperechoic lesions.

[IT] La presentazione di Altair4 ad Arquelogica 2.0 consiste essenzialmente nella presentazione delle ultime produzioni su Roma Antica, attraverso la proiezione di alcune animazioni tratte da "How Nero Saved Rome" film in HD per National Geographic Channel e Il Foro Romano e i Fori Imperiali per la trasmissione RAI Ulisse. Queste produzioni si inquadrano nell'ambito del progetto pluriennale A.R.T. (Ancient Rome Tour). Il progetto nasce nel 1998 con il proposito di creare nuovi strumenti di comunicazione per la conoscenza della storia della costruzione della città di Roma e degli eventi ad essa collegati. Dopo dieci anni dalla prima pubblicazione si è deciso di operare un significativo aggiornamento dei contenuti della parte più monumentale della città, il palatino, il foro romano, i fori imperiali e la valle del colosseo, area un tempo in gran parte occupata dalla fastosa residenza dell'imperatore Nerone: La Domus Aurea. In questi dieci anni infatti si sono raccolti e analizzati i risultati di alcune importanti attività di scavo e ricerca svolte da diverse istituzioni e istituti di ricerca concretizzati in un impegnativo lavoro di sintesi visuale con gli strumenti della computer grafica 3D cercando di restituire una unità spaziale ad un'area che risulta oggi estremamente frammentata e di difficile lettura.

OBJECTIVES: Our aim was to compare retrospectively hepatic venous and delayed phase images for the detection of tumour washout during multiphasic multidetector row CT (MDCT) of the liver in patients with hepatocellular carcinoma (HCC). METHODS: 30 cirrhotic patients underwent multiphasic MDCT in the 90 days before liver transplantation. MDCT was performed before contrast medium administration and during hepatic arterial hepatic venous and delayed phases, images were obtained at 12, 55 and 120 s after trigger threshold. Two radiologists qualitatively evaluated images for lesion attenuation. Tumour washout was evaluated subjectively and objectively. Tumour-to-liver contrast (TLC) was measured for all pathologically proven HCCs. RESULTS: 48 HCCs were detected at MDCT. 46 of the 48 tumours (96%) appeared as either hyper- or isoattenuating during the hepatic arterial phase subjective washout was present in 15 HCCs (33%) during the hepatic venous phase and in 35 (76%) during the delayed phase (p

Neoplastic and nonneoplastic diseases may involve the liver with a regional distribution, which is defined as a non-focal process without any specific anatomic predilection. In this pictorial essay we review hepatic diseases commonly presenting with a regional distribution in the liver and describe the CT and MR imaging findings helpful for differential diagnosis. Knowledge of the characteristic imaging manifestations of neoplastic and non-neoplastic diseases affecting the liver regionally will facilitate an accurate diagnosis and result in the appropriate clinical management of these liver diseases.

The purposes of our study were to evaluate the surgical outcome of cases of radial scar without atypia diagnosed at imaging-guided percutaneous needle biopsy and to determine whether the mammographic and sonographic features are able to predict which lesions will be upgraded to malignancy at surgical excision.The records of 4,458 consecutive imaging-guided biopsies were retrospectively reviewed. Surgical excision results were available in 62 cases in which radial scar was the highest-risk lesion at stereotactically guided or sonographically guided biopsy. The mammographic and sonographic images and surgical findings were reviewed. The underestimation rate of malignancy of percutaneous biopsy was calculated. Differences in mammographic and sonographic appearances between radial scars with and without associated malignancy were evaluated using the Fisher's exact test.The percutaneous malignancy underestimation rate was 8% (5/62): 9% (4/43) for sonography guided 14-gauge biopsies and 5% (1/19) for stereotactically guided 11-gauge vacuum-assisted biopsies (p = 1.000). Mammographic and sonographic appearances were not significantly different between radial scars with and those without associated malignancy.A percutaneous diagnosis of a radial scar does not exclude associated malignancy at surgical excision. Mammographic and sonographic features of a lesion diagnosed as a radial scar at percutaneous imaging-guided biopsy do not predict which lesions will have associated malignancy at surgery. Therefore, all patients with percutaneous diagnosis of a radial scar should undergo surgical excision regardless of mammographic and sonographic appearances, until further criteria can be determined.

Pulmonary embolism (PE) is a medical condition defined as the obstruction of pulmonary arteries by a blood clot, usually originating in the deep veins of the lower limbs. PE is a common but elusive illness that can cause significant disability and death if not promptly diagnosed and effectively treated. CT Pulmonary Angiography (CTPA) is the first line imaging study for the diagnosis of PE. While clinical prediction rules have been recently developed to associate short-term risks and stratify patients with acute PE, there is a dearth of objective biomarkers associated with the long-term prognosis of the disease. Clot (embolus) burden is a promising biomarker for the prognosis and recurrence of PE and can be quantified from CTPA images. However, to our knowledge, no study has reported a method for segmentation and measurement of clot from CTPA images. Thus, the purpose of this study was to develop a semi-automated method for segmentation and measurement of clot from CTPA images. Our method was based on Modified Seeded Region Growing (MSRG) algorithm which consisted of two steps: (1) the observer identifies a clot of interest on CTPA images and places a spherical seed over the clot; and (2) a region grows around the seed on the basis of a rolling-ball process that clusters the neighboring voxels whose CT attenuation values are within the range of the mean ± two standard deviations of the initial seed voxels. The rollingball propagates iteratively until the clot is completely clustered and segmented. Our experimental results revealed that the performance of the MSRG was superior to that of the conventional SRG for segmenting clots, as evidenced by reduced degrees of over- or under-segmentation from adjacent anatomical structures. To assess the clinical value of clot burden for the prognosis of PE, we are currently applying the MSRG for the segmentation and volume measurement of clots from CTPA images that are acquired in a large cohort of patients with PE in an on-going NIH-sponsored clinical trial.

Objective: To retrospectively compare portal venous phase (PVP) and delayed phase (DP) for the detection of tumor washout at gadobenate dimeglumine-enhanced liver magnetic resonance imaging (MRI) in cirrhotic patients with hypervascular hepatocellular carcinoma (HCC). Methods: Thirty-three patients with 55 HCCs underwent 1.5-T MRI by means of fat-suppressed T1-weighted sequence obtained before and after gadobenate dimeglumine administration, during early and late arterial phases, PVP (70 seconds), and DP (180 seconds). Detection rates of contrast washout of hypervascular HCCs and tumor-to-liver contrast on PVP and DP were measured and compared. Results: Among 54 hypervascular HCCs, washout was present in 24 (44%) of 54 tumors on PVP and in 44 (82%) of 54 on DP (P < 0.001). In 20 (37%) of 54 tumors, washout was deemed present only on DP. Delayed phase images yielded significantly higher mean tumor-to-liver contrast absolute values compared with PVP images (—24.5 [56.1] vs -9.3 [52.6], P = 0.001). Conclusions: Delayed phase is superior to PVP for the washout detection of hypervascular HCC at gadobenate dimeglumine-enhanced MRI of cirrhotic liver.

Renal cystic disease is a heterogeneous entity, including developmental (simple and complex cysts, localized cystic diseases, extraparenchymal sinus cysts, medullary sponge kidney, and multicystic dysplastic kidney), acquired (acquired cystic kidney disease), and heritable (autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, tuberous sclerosis complex, von Hippel–Lindau disease) disorders. Various imaging modalities are used for the diagnosis and clinical evaluation of renal cystic diseases. While ultrasound is more commonly used as a screening modality, CT and MR imaging are more widely used in clinical settings for characterizing renal cystic lesions, assessing cysts complications, and differentiating benign from malignant cystic lesions. The diagnosis of a specific renal cystic disease can be made by a review of the patient’s clinical history in conjunction with radiographic findings. Key imaging features useful for the diagnosis of renal cystic disease include the location, distribution, size, and composition of renal cysts as well as other coexisting noncystic renal lesions and characteristic extrarenal findings.

The purpose of this study was to evaluate the reliability of volumetric magnetic resonance imaging (MRI) in breast cancer size assessment before, during and after neoadjuvant chemotherapy (NAC). Volumetric MRI measures performed on 15 patients with breast cancer were compared with volumes reckoned upon mean lesional diameters, using the same MRI data. Concordance correlation coefficient (CCC), Bland & Altman plots, RECIST evaluation and Cohen's Kappa were assessed, to evaluate the agreement between the two methods. CCC was computed before (0.9357), during (0.8053) and after (0.7499) NAC, in all examinations pooled together (0.8617), and on final tumor volume as a percentage of baseline volume (0.9224). In 2/15 (13.3%) cases RECIST assessment was different. Cohen's Kappa was 0.787 (CI95% = 0.513–1.062). In summary, volumetric MRI is a reliable tool to assess breast cancer size before, during and after NAC. Further investigations are needed to understand whether improvements in surgical planning are feasible.

OBJECTIVE. The purpose of this article is to review the epidemiology, multimodality imaging findings, differential diagnosis, pathologic staging, and current treatment options of gallbladder carcinoma.CONCLUSION. Understanding the characteristic appearances of primary gallbladder carcinoma at multiple imaging modalities can facilitate diagnosis and enable more accurate staging for triage to extended resection or an alternate therapy.

OBJECTIVE. The objective of our study was to investigate the relationship between hepatic adenoma and liver steatosis. MATERIALS AND METHODS. Radiology and pathology records from January 1999 to March 2007 were reviewed to identify 24 patients (22 women and two men; mean age, 40 years) with a pathology-proven diagnosis of hepatic adenoma (mean size ± SD, 7.2 ± 3.7 cm) who underwent helical contrast-enhanced CT (n = 23) and/or gadolinium-enhanced MRI (n = 8). The control group was composed of 24 patients of similar age and sex (21 women and three men; mean age, 43 years) with hepatic hemangioma who underwent CT or MR evaluation during the same time period. Two radiologists independently interpreted the imaging studies to determine the number of lesions and whether steatosis was present. The difference in prevalence of steatosis between the adenoma group versus the control group and the difference between patients with a single hepatic adenoma versus those with multiple hepatic adenomas were assessed (chi-square test). RESULTS. Hepatic steatosis was present in 14 of 24 patients (58%) with hepatic adenoma versus seven of 24 patients (29%) with hemangioma (p = 0.042). Steatosis was more common in patients with multiple hepatic adenomas (9/11, 82%) than in those with a single hepatic adenoma (5/13, 38%) (p = 0.047). CONCLUSION. Hepatic adenomas occur more frequently and more often are multiple in patients with hepatic steatosis.

PURPOSE To investigate the relevance of increasing b-values in evaluating liver fibrosis through the agreement of two diffusion-weighted (DW) sequences. MATERIALS AND METHODS A total of 29 cirrhotic patients and 29 healthy volunteers were studied on a 1.5T system. Two single-shot spin-echo echo-planar sequences were acquired using sets of increasing b-values: 0, 150, 250, and 400 seconds/mm(2) (first sequence: DW1a) and 0, 150, 250, 400, 600, and 800 seconds/mm(2) (second sequence: DW2a). Apparent diffusion coefficients (ADCs) of the hepatic parenchyma were calculated on ADC maps. Noise-scaled single-point ADCs were calculated for each sequence from b = 400 seconds/mm(2). RESULTS ADCs resulted significantly lower in cirrhotic patients compared to controls using both DW1a (mean 1.14 +/- 0.20 x 10(-3)mm(2)/second vs. 1.54 +/- 0.12 x 10(-3)mm(2)/second; P < 0.0001) and DW2a (mean 0.91 +/- 0.18 x 10(-3)mm(2)/second vs. 1.04 +/- 0.18 x 10(-3)mm(2)/second; P = 0.0089). DW1 and DW2, respectively significantly differed in diagnostic performance at receiver operating characteristic (ROC) curve analysis (P = 0.003), showing AUCs of 0.93 (sensitivity 89.7%, specificity 100%) and 0.73 (sensitivity 62.1%, specificity 79.3%), respectively. Noise-scaled single-point ADCs showed a progressive convergence to similar values in cirrhotic and healthy livers at b = 800 seconds/mm(2) (1.12 +/- 0.27 x 10(-3)mm(2)/second vs. 1.13 +/- 0.17 x 10(-3)mm(2)/second). CONCLUSION A DW sequence is accurate in assessing liver fibrosis using intermediate (400 seconds/mm(2)) rather than high (800 seconds/mm(2)) maximum b-values, but after proper recalculation of ADCs the effects of perfusion rather than diffusion should be considered responsible for the higher accuracy at lower b-values.

OBJECTIVE. The purpose of this study was to evaluate the incidence of nonobstructing renal stones on unenhanced CT in patients presenting to the emergency department with renal colic and to determine whether this finding might be the cause of patients' symptoms.CONCLUSION. Nonobstructing renal stones on unenhanced CT are a frequent finding in patients evaluated in the emergency department for suspected renal colic. These stones are usually not recognized as the cause of pain by physicians and may be responsible for multiple clinical and radiologic evaluations. In the absence of other clinical or CT evidence of a separate cause, these stones are likely to be the cause of a patient's acute pain.

The purpose of this study is to assess the positive predictive value (PPV) for malignancy of core needle biopsy (CNB) demonstrating lobular neoplasia (LN). From 3920 CNBs, 35 (0.89%) LNs (14 atypical lobular hyperplasia - ALH - and 21 lobular carcinoma in situ - LCIS) were identified. Twenty-eight patients underwent surgical excision and seven radiologic follow-up. We describe the imaging findings and excision histology outcomes. We report the PPV for malignancy based on excision histology (n=28) and on excision or follow-up (n=35), and according to the histologic type, biopsy probe and guidance, lesion diameter, and BI-RADS category. PPV for malignancy (based on excision histology) was 46.4% (13/28) and PPV (based on excision or follow-up) was 37.1% (13/35). The overall rate of malignancy for LN was 37.1% (13/35), with a PPV for malignancy of ALH and LCIS of 7.1% (1/14) and 57.1% (12/21), respectively (p=0.003). Estimates of the PPV for malignancy were: stereotactic-guided vacuum-assisted biopsy (22.7%) versus ultrasound-guided automated CNB (61.5%), p=0.053; lesions20mm (31.2%) versus lesions20mm (100%), p=0.043; lesions classified as BI-RADS 3 (16.7%) versus BI-RADS 4 or 5 (41.4%), p=0.377. Underestimation of malignancy was therefore more likely in cases of LCIS, US-guided CNB, and lesions that were large and suspicious on imaging. Nevertheless, the absence of these features does not spare the need for surgical excision in lobular neoplasia diagnosed on CNB.

The purpose of this study is to assess whether magnetic resonance mammography (MRM) can exclude associated malignancy in case of diagnosis of borderline breast lesions (B3) at core needle biopsy (CNB). Retrospective analysis of MRM findings of 79 borderline breast lesions (26 benign papillomas, 29 radial sclerosing lesions, 6 atypical ductal hyperplasias, 18 lobular neoplasias) diagnosed at CNB was performed. Lesions were classified as “non-suspicious” or “suspicious” according to Fischer score. These findings were compared to the results of histological analysis of the excisional specimens. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of MRM in predicting the presence of malignancy were calculated. Out of 24 (30.4%) lesions classified as “suspicious”, 8 (33.3%) proved to be malignant and 16 (66.7%) benign. Among the 55 (69.6%) “non-suspicious” lesions, only 1 (1.8%) was malignant (low-grade ductal carcinoma in situ), while the remaining 54 (98.2%) proved to be benign. MRM sensitivity, specificity, PPV, and NPV were 88.9%, 77.1%, 33.3%, and 98.2%, respectively. When a borderline lesion is diagnosed on CNB, in case of mild or no enhancement at MRM, follow-up rather than excisional biopsy might be prompted.

OBJECTIVE. The purpose of this article is to review the diagnostic imaging findings, differential diagnosis, complications, and postoperative imaging appearance of urethral diverticulum.CONCLUSION. With increased clinical awareness and advanced imaging techniques, diagnoses of urethral diverticula are more frequent, and radiologists need to be aware of the pre- and postoperative imaging appearances of this disorder.

The aim of this study was to evaluate the role of ultrasound (US)-guided core biopsy in the diagnosis of ductal carcinoma in situ (DCIS) and to correlate the histological results on percutaneous biopsy and surgical excision.Out of 2,423 consecutive core biopsies performed under US guidance, we evaluated 65 lesions with a histological diagnosis of DCIS. All patients underwent mammography, high-frequency broadband US and percutaneous breast biopsy with a 14-gauge needle and a mean number of five samples (range 4-7 passes). Surgical excision was performed in all cases, and the histological results on the surgical specimen were correlated with those on core biopsy samples. The sonographic features of DCIS lesions were described, comparing pure DCIS (those confirmed by definitive histology) and DCIS with invasive component at surgical excision.Twenty-seven out of 65 DCIS at core biopsy were found to have an invasive or microinvasive component at surgical excision, leading to rate of histological underestimation of core biopsy of 41.5%. The most frequent sonographic appearances were: (a) mass without microcalcifications (47.4% of pure DCIS, 63% of DCIS with invasive component); (b) mass with microcalcifications (23.7% of pure DCIS, 22% of DCIS with invasive component); (c) isolated microcalcifications (10.5% of pure DCIS); (d) ductal abnormalities (18.4% of pure DCIS, 15% of DCIS with invasive component).Due to the high underestimation rate of core biopsy, caution is mandatory in the case of DCIS diagnosis on core biopsy. Although some histological features (such as stromal fibrosis, periductal inflammatory infiltrate, high nuclear grade) can suggest the presence of an invasive component, the sonographic appearance of DCIS cannot be used to predict the cases that are underestimated on US-guided core biopsy. Nevertheless, a sonographically detectable solid component, either inside dilatated ducts or associated with microcalcifications, and a size greater than 20 mm are frequently associated with the presence of an invasive component.

This study was designed to establish whether the measurement of apparent diffusion coefficients (ADCs) is clinically accurate in diagnosing liver fibrosis in a selected series of cirrhotic patients.Twenty-eight cirrhotic patients (mean age 58.1 years) with histologically proven liver fibrosis and 29 healthy controls (mean age 43.8 years) underwent liver diffusion-weighted magnetic resonance (MR) using a 1.5-Tesla (T) magnet equipped with a phased-array coil. Diffusion studies with parallel imaging [generalized autocalibrating partially parallel acquisitions (GRAPPA)] were performed within a single breath-hold using a single-shot spin-echo echo-planar sequence (TE 74 ms) using four b values: b=0, 150, 250 and 400 s/mm(2). A unidirectional diffusion gradient was applied. ADCs were measured on ADC maps.Mean ADC was significantly lower in cirrhotic livers than in controls (1.11+/-0.16 vs. 1.54+/-0.12.10(-3)mm(2)/s) (p0.0001). Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.96 [confidence interval (CI) 95%:(0.87; 0.94)], demonstrating higher sensitivity and specificity (92.9% and 100%, respectively) for an ADC cutoff of 1.31.10(-3)mm(2)/s. Positive predictive value (PPV), negative predictive value (NPV) and overall accuracy were 100%, 99.9% and 96.4%, respectively.Diffusion-weighted MRI is an accurate tool in evaluating advanced liver fibrosis if an optimised single-shot spin-echo echo-planar sequence with maximum intermediate b value is used. The ADC threshold for liver fibrosis was 1.31.10(-3)mm(2)/s.

The purpose of this study was to determine whether the double arterial phase with multidetector computed tomography MDCT and high–iodine–concentration contrast material (CM) improves identification of hepatocellular carcinoma (HCC). Fifty patients with 111 HCC foci (61 confirmed histologically, 46 confirmed by percutaneous interventional procedures, four confirmed by CT follow–up of at least 6 months) underwent MDCT with a double arterial phase and a portal venous phase after administration of contrast material with a high iodine concentration (400 mgI/ml, 2 ml/kg, 5 ml/s). Two radiologists independently evaluated the images in three distinct reading sessions (early arterial phase (EAP), late arterial phase (LAP) and double arterial phase) to determine presence, number and degree of suspicion of HCC. The sensitivity and the positive predictive value (PPV) were calculated for every reading session. The following statistical evaluations were used: k statistic and McNemar’s test. Mean sensitivity and PPV in the detection of HCC were, respectively, 83.8% and 93.5% for EAP, 90.5% and 94.8% for LAP, and 94.1% and 95.1% for the double arterial phase. Sensitivity of the double arterial phase was statistically higher when compared with EAP alone but showed no statistically significant difference when compared with LAP. The k values indicated moderate–to–excellent interobserver agreement in all reading sessions. Sensitivity and PPV increase progressively when passing from EAP to LAP to double–arterial–phase images obtained with contrast material with a high iodine concentration. However, the difference in sensitivity between LAP and the double arterial phase was not statistically significant.

Sialyl-Tn is a carbohydrate antigen overexpressed in several epithelial cancers, including breast cancer, and usually associated with poor prognosis. Sialyl-Tn is synthesized by a CMP-Neu5Ac:GalNAcalpha2,6-sialyltransferase: CMP-Neu5Ac: R-GalNAcalpha1-O-Ser/Thr alpha2,6-sialyltransferase (EC 2.4.99.3) (ST6GalNAc I), which transfers a sialic acid residue in alpha2,6-linkage to the GalNAcalpha1-O-Ser/Thr structure. However, established breast cancer cell lines express neither ST6GalNAc I nor sialyl-Tn. We have previously shown that stable transfection of MDA-MB-231, a human breast cancer cell line, with ST6GalNAc I cDNA induces sialyl-Tn antigen (STn) expression. We report here the modifications of the O-glycosylation pattern of a MUC1-related recombinant protein secreted by MDA-MB-231 sialyl-Tn positive cells. We also show that sialyl-Tn expression and concomitant changes in the overall O-glycan profiles induce a decrease of adhesion and an increase of migration of MDA-MB-231. Moreover, STn positive clones exhibit an increased tumour growth in severe combined immunodeficiency (SCID) mice. These observations suggest that modification of the O-glycosylation pattern induced by ST6GalNAc I expression are sufficient to enhance the tumourigenicity of MDA-MB-231 breast cancer cells.

matched controls (GSP) were selected for each HIP case. Hospital course was then compared between the two groups, based on local/systemic complications of acute pancreatitis, management and length of stay. Statistics: Fischer's exact t-test was used and a two sided p-value was calculated; p-value of less than 0.05 was considered statistically significant. Results: There were 292 patients admitted during the study period. Etiologies were GSP (41.8%), alcoholic pancreatitis (23.3%), others (autoimmune, drugs, ERCP, idiopathic) (30.1%) and HIP (4.8%). There were 14 HIP cases (64% men)and 42 GSP controls (60% men). Mean age was 43.8 (range 24-64) and 44 (range 17-71) for cases and controls, respectively. Mean admission lipase levels were lower in HIP(638 mg/dl) than in GSP(2399 mg/dl). BISAP score on admission in all HIP cases was less than 2. As shown in the table, there was a significant difference between the two groups in the following variables: 2 or more abdominal CT scans, systemic complications (such as pleural effusions, ARDS, renal failure), transfer to the ICU (for renal failure,candidemia and respiratory distress) and use of TPN. There were no deaths in either group. Conclusions: Based on our data, HIP appears to follow a more aggressive course with greater resource utilization than GSP. Furthermore, a low BISAP score in HIP may not be predictive of in-hospital morbidity. These findings need to be confirmed in a prospective study with a larger sample size. Statistical comparison of various variables during the hospital course between cases (HIP) and controls (GSP)