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Although the life expectancy of patients with type 1 diabetes mellitus (T1DM) has improved since the introduction of insulin therapy, the acute life-threatening and long-term complications from diabetes mellitus are significant causes of both mortality and morbidity. Percutaneous intra-portal pancreatic islet transplantation (PIPIT) is a minimally invasive, repeatable procedure which allows a β-cell replacement therapy through a liver islet engraftment, leading to insulin release and glycaemic control restoration in patients with diabetes. Allo-PIPIT, in which isolated and purified islets from cadaveric donor are used, does not require major surgery, and is potentially less expensive for the recipient. In case of long-term T1DM, islet-after-kidney (IAK) transplantation can simultaneously cure diabetes and chronic renal failure, while islet-transplant-alone (ITA) is performed in brittle, short-term T1DM, based on the infusion of an adequate islet mass and on a steroid-free immunosuppressive regimen according to the Edmonton protocol. Results of the Collaborative Islet Transplant Registry (CITR) demonstrate that allo-PIPIT reduces episodes of hypoglycemia and diabetic complications, and improves quality of life of diabetic patients. Auto-PIPIT, in which the own patient’s islets are used, has been investigated as a preventive treatment for pancreatogenic diabetes in patients who undergo extensive pancreatectomy for malignant and non-malignant disease. This Review outlines the role of imaging and interventional radiology in allo- and auto-PIPIT.

The factors that determine whether disseminated transformed cells in vivo yield neoplastic lesions have only been partially identified. We established an ad hoc model of peritoneal carcinomatosis by injecting colon carcinoma cells in mice. Tumor cells recruit inflammatory leukocytes, mostly macrophages, and generate neoplastic peritoneal lesions. Phagocyte depletion via clodronate treatment reduces neoplastic growth. Colon carcinoma cells release a prototypic damage-associated molecular pattern (DAMP)/alarmin, High Mobility Group Box1 (HMGB1), which attracts leukocytes. Exogenous HMGB1 accelerates leukocyte recruitment, macrophage infiltration, tumor growth and vascularization. Lentiviral-based HMGB1 knockdown or pharmacological interference with its extracellular impair macrophage recruitment and tumor growth. Our findings provide a preclinical proof of principle that strategies based on preventing HMGB1-driven recruitment of leukocytes could be used for treating peritoneal carcinomatosis.

Islet transplantation is one of the most promising and effective therapies for restoring normoglycemia in type 1 diabetes (T1D) patients, but islet engraftment is one of the main obstacles hampering long-term success. Monitoring graft loss, caused either by immunological or nonimmunological events, occurring in the first phase after transplantation and at later stages of a patient's life is a very important issue. Among the imaging approaches previously applied, magnetic resonance imaging (MRI) monitoring of islet fate following labeling with superparamagnetic iron oxide agents yielded promising results. The aim of this study was to translate into patients the method of islet labeling and MRI monitoring developed in our preclinical setting and to compare imaging results with graft clinical outcome. Three T1D patients and one nondiabetic patient undergoing autotransplantation following subtotal pancreatectomy received Endorem®-labeled islets. Patients were monitored by MRI and metabolically (HbA1c, exogenous insulin requirement, and C-peptide, TEF) at 1, 3, and 7 days following transplantation and once a month up to 10 months. Labeled transplanted islets appeared as hypointense areas scattered within the liver parenchyma, whose absolute number at 24 h after transplantation reflected the labeling efficiency. In patients #1 and #3 with good midterm graft function, MRI follow-up showed an important early loss of hypointense spots followed by a slow and progressive disappearance at later timepoints. Graft loss of function in patient #2 4 weeks after transplantation was associated with the complete disappearance of all hypointense signals. The autotransplanted patient, stably insulin free, showed no significant signal reduction during the first 3 days, followed by loss of spots similar to a patient with good midterm graft function. These results suggest that MRI monitoring of islet transplantation at early time points could represent a meaningful readout for helping in predicting transplant failure or success, but its relevance for mid/long-term islet function assessment appears evanescent.

Inflammatory myopathies comprise heterogeneous disorders. Their etiopathogenesis is poorly understood, because of the paucity of informative experimental models and of approaches for the noninvasive study of inflamed tissues. Magnetic resonance imaging (MRI) provides information about the state of the skeletal muscle that reflects various facets of inflammation and remodeling. This technique has been scarcely used in experimental models of inflammatory myopathies. We characterized the performance of MRI in a well-established mouse model of myositis and the antisynthetase syndrome, based on the immunization of wild-type mice with the amino-terminal fragment of histidyl-tRNA synthetase (HisRS). Over an eight-week period following myositis induction, MRI enabled precise identification of pathological events taking place in muscle tissue. Areas of edema and of active inflammation identified by histopathology paralleled muscle modifications detected noninvasively by MRI. Muscles changes were chronologically associated with the establishment of autoimmunity, as reflected by the development of anti-HisRS antibodies in the blood of immunized mice. MR imaging easily appreciated muscle damage and remodeling even if actual disruption of myofiber integrity (as assessed by serum concentrations of creatinine phosphokinase) was limited. Thus, MR imaging represents an informative and noninvasive analytical tool for studyingin vivoimmune-mediated muscle involvement.

Aims We present clinical, electroanatomical mapping (EAM), imaging, and catheter ablation (CA) strategies in patients with myocarditis-related ventricular tachycardia (VT). Methods and results Between January 2010 and July 2012, 26 consecutive patients underwent imaging-guided CA of myocarditis-related ventricular arrhythmias, 23 of 26 using a combined endo–epicardial approach. Segment per segment correspondence of late enhanced (LE) scar localization with EAM scar was assessed in all patients with available uni/bipolar maps ( n = 19). Induced VTs were targeted prior to substrate modification. Late potentials (LPs) abolition constituted a procedural endpoint independently from VT inducibility. Clinical monomorphic VT was induced in 15 of 26 patients (57.7%) and was associated with epicardial LPs in 10 of 15, completely abolished in 7 of 10 patients. Of the 10 patients rendered non-inducible VTs were ablated epicardially in 7. Late potentials were also detected in 7 of 11 initially non-inducible patients and completely abolished in 4. After a median follow-up of 23 (15–31) months, 20 of 26 patients (76.9%) remained free from VT recurrence. Bipolar mapping revealed low-voltage scar (

The aim of this study was to investigate liver microvascular adaptation following the intraportal infusion of pancreatic islets (pancreatic islet transplantation [islet-tx]) in diabetic patients using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI was performed before and 7 days after islet-tx in six diabetic patients. Initial area under curve (AUC60) and volume transfer coefficient (Ktrans) were assessed as markers of liver perfusion. Clinical and metabolic monthly follow-up was performed in all patients, considering fasting C-peptide and β-score as main indices of graft function. High variability in the response of liver microvasculature to islet infusion was observed: two patients showed a significant reduction in liver perfusion after transplantation (pt.2: AUC60 = −23.4%, Ktrans = −31.7%; pt.4: AUC60 = −23.7%, Ktrans = −27.9%); three patients did not show any significant variation of liver perfusion and one patient showed a significant increase (pt.3: AUC60 = +31%, Ktrans = +42.8%). Interestingly, a correlation between DCE-MRI parameters and indices of graft function was observed and, in particular, both patients with DCE-MRI evidence of posttransplantation liver perfusion reduction experienced premature graft failure. Our preliminary study demonstrated that DCE-MRI may identify different adaptive responses of liver microvasculature in patients submitted to islet-tx. These different responses could have an impact on islet engraftment, although reported findings need confirmation from larger studies.

OBJECTIVE To compare prospective electrocardiogram (ECG)-triggered high-voltage coronary computed tomography (CT) angiography (CTA; 140-kVp P-cCTA) with retrospective ECG-gated standard-voltage cCTA (120-kVp R-cCTA), in patients with coronary stents. METHODS Fifty-two patients with coronary stents were studied with 64-slice multidetector scanner. Ninety-three stents were analyzed: 55 with 140-kVp P-cCTA and 38 with 120-kVp R-cCTA. Image quality (IQ), diagnostic confidence (DC), in-stent assessable lumen, artificial narrowing, and effective radiation dose were compared between techniques. RESULTS Image quality and DC were significantly better for the 140-kVp P-cCTA in comparison with the 120-kVp R-cCTA (IQ, 1.1 ± 0.36 vs 1.7 ± 0.60, respectively; P < 0.00001. Diagnostic confidence: 1.1 ± 0.29 vs 1.5 ± 0.65 respectively; P < 0.0001). In-stent assessable lumen and artificial narrowing were comparable between the techniques. Effective dose was lower for the 140-kVp P-cCTA (6.7 ± 2.07 mSv vs 15.8 ± 6.89 mSv; P < 0.0001). CONCLUSIONS High voltage combined with axial prospective ECG-triggered scan improved IQ and DC in stent cCTA imaging but failed to improve the diameter of in-stent assessable lumen and to reduce the artificial narrowing compared with the 120-kVp R-cCTA. Effective dose was 60% lower for the 140-kVp P-cCTA.

"Skeletal muscle remodeling in response to various noxae physiologically includes structural changes and inflammatory events. The possibility to study those phenomena in-vivo has been hampered by the lack of validated imaging tools. In our study, we have relied on multiparametric magnetic resonance imaging for quantitative monitoring of muscle changes in mice experiencing age-related sarcopenia or active regeneration after sterile acute injury of tibialis anterior muscle induced by cardiotoxin (CTX) injection. The extent of myofibrils' necrosis, leukocyte infiltration, and regeneration have been evaluated and compared with parameters from magnetic resonance imaging: T2-mapping (T2 relaxation time; T2-rt), diffusion-tensor imaging (fractional anisotropy, F.A.) and diffusion weighted imaging (apparent diffusion coefficient, ADC). Inflammatory leukocytes within the perimysium and heterogeneous size of fibers characterized aged muscles. They displayed significantly increased T2-rt (P

Purpose: To prospectively compare clinical breast examination (CBE), mammography, ultrasonography (US), and contrast material-enhanced magnetic resonance (MR) imaging for screening women at genetic-familial high risk for breast cancer and report interim results, with pathologic finding as standard. Materials and Methods: Institutional review board of each center approved the research; informed written consent was obtained. CBE, mammography, US, and MR imaging were performed for yearly screening of BRCA1 or BRCA2 mutation carriers, first-degree relatives of BRCA1 or BRCA2 mutation carriers, or women enrolled because of a strong family history of breast or ovarian cancer (three or more events in first-or second-degree relatives in either maternal or paternal line; these included breast cancer in women younger than 60 years, ovarian cancer at any age, and male breast cancer at any age). Results: Two hundred seventy-eight women (mean age, 46 years ± 12 [standard deviation]) were enrolled. Breast cancer was found in 11 of 278 women at first round and seven of 99 at second round (14 invasive, four intraductal; eight were ≤10 mm in diameter). Detection rate per year was 4.8% (18 of 377) overall; 4.3% (11 of 258) in BHCA1 or BRCA2 mutation carriers and first-degree relatives of BRCA1 or BRCA2 mutation carriers versus 5.9% (seven of 119) in women enrolled because of strong family history; and 5.3% (nine of 169) in women with previous personal breast and/or ovarian cancer versus 4.3% (nine of 208) in those without. In six (33%) of 18 patients, cancer was detected only with MR imaging. Sensitivity was as follows: CBE, 50% (95% confidence interval [CI]: 29%, 71%); mammography, 59% (95% CI: 36%, 78%); US, 65% (95% CI: 41%, 83%); and MR imaging, 94% (95% CI: 82%, 99%). Positive predictive value was as follows: CBE, 82% (95% CI: 52%, 93%); mammography, 77% (95% CI: 50%, 92%); US, 65% (95% CI: 41%, 83%); and MR imaging, 63% (95% CI: 43%, 79%). Conclusion: Addition of MR imaging to the screening regimen for high-risk women may enable detection of otherwise unsuspected breast cancers. © RSNA, 2007.

Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.

In myocarditis patients, persisting inflammation is associated with arrhythmias and unfavorable remodeling ([1][1]). Novel therapeutic strategies may counteract chronic myocardial inflammation, but their use is strictly dependent on the ability to detect and monitor myocardial inflammation.

Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis. The wall of inflamed arteries contains an abundant infiltrate of lymphocytes and macrophages and undergoes substantial remodeling, with hyperplasia of the intimal layer, luminal occlusion and potentially aneurysm formation and

The prolonged, gonadotoxic effect of chemotherapy can finally lead to infertility in female cancer survivors. There is controversial evidence regarding the protective role of gonadotropin-releasing hormone analogue (GnRH-a) on chemotherapy-induced ovarian damage. In the present study on a murine model, ultrasound (US) and contrast-enhanced US (CEUS) were firstly used to characterise ovarian glands in normal conditions to validate a preclinical model. In addition, preliminary findings were obtained on anatomical and vascular ovarian changes induced by GnRH-a based on decapeptyl administration. Ovaries were accurately assessed with US and CEUS in a murine model placed in prone position, providing quantitative and reproducible information. Ovaries were identified in 40/40 cases and CEUS analysis was successfully performed in 20/20 cases with 100% technical success. A statistically significant increase of the diameter of the dominant follicle at US and a statistically significant reduced vascularisation at CEUS in decapeptyl-treated mice compared to untreated control mice were recorded. Further studies using US and CEUS in the murine model combining GnRH-a and chemotherapeutic agents will be needed to obtain more translational information useful for clinical practice.

Background Hyperemia is a key component of acute myocarditis (AM). Early gadolinium uptake because of myocardial hyperemia may be quantified by using T1 mapping. Purpose To evaluate the value of early enhanced T1 shortening for the diagnosis of acute myocarditis. Materials and Methods Study participants suspected of having AM and healthy control (HC) participants were prospectively enrolled from September 2016 to May 2019. Participants underwent 1.5-T cardiac MRI including Lake Louise criteria, T2 mapping, native T1, and extracellular volume, with the addition of early enhanced T1 mapping (2 minutes after intravenous administration of 0.15 mmol/kg gadobutrol). Color-coded maps of the percentage of T1 shortening from precontrast to early postcontrast were generated. Optimal early T1 shortening cut-off value and its diagnostic performance in the identification of acute myocarditis were calculated. Results Forty-five study participants with AM (median age, 40 years; interquartile range [IQR], 20-46 years; 22 women) diagnosed according to multidisciplinary clinical evaluation, electrocardiography, laboratory test, echocardiography, cardiac MRI, and coronary CT and/or invasive angiography. Findings were confirmed by endomyocardial biopsy in 64% (29 of 45) of participants. MRI parameters were compared with 19 HC participants (median age, 39 years; IQR, 28-46 years; seven women). Median early T1 shortening was 75% (IQR, 72%-78%) in participants with AM versus 65% (IQR, 61%-66%) in HC participants (P < .001). Early T1 shortening showed high diagnostic performance (area under the receiver operating characteristic curve [AUC], 0.97; 95% confidence interval [CI]: 0.94, 1.00) and excellent interobserver reproducibility (intraclass correlation coefficient: 0.98; 95% CI: 0.96, 1.00). Early T1 shortening of 70% or greater identified acute myocarditis with 93% sensitivity, 100% specificity, and 95% diagnostic accuracy. Early T1 shortening had better diagnostic performance than late percentage T1 shortening (AUC, 0.97 vs 0.90, respectively; P = .03) and extracellular volume (AUC, 0.97 vs 0.88, respectively; P = .046), and similar to native T1 (AUC, 0.97 vs 0.93, respectively; P = .63) and T2 mapping (AUC, 0.97 vs 0.97, respectively; P > .99). Conclusion In this proof-of-concept study, percentage of T1 shortening at early enhanced T1 mapping showed high accuracy for the diagnosis of acute myocarditis. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by De Cecco and Monti in this issue.

Purpose: Diffuse remodeling of myocardial extra-cellular matrix is largely responsible for left ventricle (LV) dysfunction and arrhythmias. Our hypothesis is that the texture analysis of late iodine enhancement (LIE) cardiac computed tomography (cCT) images may improve characterization of the diffuse extra-cellular matrix changes. Our aim was to extract volumetric extracellular volume (ECV) and LIE texture features of non-scarred (remote) myocardium from cCT of patients with recurrent ventricular tachycardia (rVT), and to compare these radiomic features with LV-function, LV-remodeling, and underlying cardiac disease. Procedures: Forty-eight patients suffering from rVT were prospectively enrolled: 5/48 with idiopathic VT (IVT), 23/48 with post-ischemic dilated cardiomyopathy (ICM), 9/48 with idiopathic dilated cardiomyopathy (IDCM), and 11/48 with scars from a previous healed myocarditis (MYO). All patients underwent echocardiography to assess LV systolic and diastolic function and cCT with pre-contrast, angiographic, and LIE scan to obtain end-diastolic volume (EDV), ECV, and first-order texture parameters of Hounsfield Unit (HU) of remote myocardium in LIE [energy, entropy, HU-mean, HU-median, standard deviation (SD), and mean absolute deviation (MAD)]. Results: Energy, HU mean, and HU median by cCT texture analysis correlated with ECV (rho = 0.5650, rho = 0.5741, rho = 0.5068; p < 0.0005). cCT-derived ECV, HU-mean, HU-median, SD, and MAD correlated directly to EDV by cCT and inversely to ejection fraction by echocardiography (p < 0.05). SD and MAD correlated with diastolic function by echocardiography (rho = 0.3837, p = 0.0071; rho = 0.3330, p = 0.0208). MYO and IVT patients were characterized by significantly lower values of SD and MAD when compared with ICM and IDCM patients, independently of LV-volume systolic and diastolic function. Conclusions: Texture analysis of LIE may expand cCT capability of myocardial characterization. Myocardial heterogeneity (SD and MAD) was associated with LV dilatation, systolic and diastolic function, and is able to potentially identify the different patterns of structural remodeling characterizing patients with rVT of different etiology.

Background Squid, as Onyx, is an ethylene-vinyl alcohol copolymer (EVOH)-based liquid embolic agent developed for neuroradiologic interventions with poor application in abdominal district. Our aim was to evaluate safety, complications, and efficacy of transcatheter embolization using the two available formulations Squid-18 and 12, in 30 patients affected by different abdominal diseases. Results Transcatheter embolization with Squid, combined with other embolic agents, as poly vinyl alcohol (PVA) particles, coils and amplatzer plugs, or alone (type 2 endoleak), was performed in 30 patients, as follows: 10 portal vein embolizations (PVEs), 6 arteriovenous malformations (AVMs), 5 visceral artery aneurysms (VAAs), 4 type 2 endoleaks, 3 preoperative embolizations, 1 acute arterial bleeding, 1 female varicocele. Squid was always administered using dimethyl sulfoxide (DMSO) compatible microcatheters. Technical success, 30-day clinical success and complications were assessed. Technical success was 90%. 3 patients (2 AVMs, 1 VAA) required re-intervention successfully performed in all cases. Major complications, cases of microcatheter entrapment and DMSO-related poor pain control were not recorded. 30-day clinical success was 93.3%: in 2 patients submitted to PVE a sufficient future liver remnant (FLR) hypertrophy was not achieved. Conclusion Squid was successfully used with low complication rate in many abdominal diseases showing a valid embolic action either combined with other embolic agents or alone in type 2 endoleak. The availability of different formulations (Squid-18 and Squid-12) variable for viscosity makes Squid preferable to Onyx as EVOH-based liquid embolic agent, even though comparable studies in different abdominal districts with a larger cohort of patients will be necessary.

Objectives: To investigate the association between preoperative texture analysis from multidetector computed tomography (MDCT) and overall survival in patients with gastric cancer. Methods: Institutional review board approval and informed consent were obtained. Fifty-six patients with biopsy-proved gastric cancer were examined by MDCT and treated with surgery. Image features from texture analysis were quantified, with and without filters for fine to coarse textures. The association with survival time was assessed using Kaplan–Meier and Cox analysis. Results: The following parameters were significantly associated with a negative prognosis, according to different thresholds: energy [no filter] – Logarithm of relative risk (Log RR): 3.25; p = 0.046; entropy [no filter] (Log RR: 5.96; p = 0.002); entropy [filter 1.5] (Log RR: 3.54; p = 0.027); maximum Hounsfield unit value [filter 1.5] (Log RR: 3.44; p = 0.027); skewness [filter 2] (Log RR: 5.83; p = 0.004); root mean square [filter 1] (Log RR: - 2.66; p = 0.024) and mean absolute deviation [filter 2] (Log RR: - 4.22; p = 0.007). Conclusions: Texture analysis could increase the performance of a multivariate prognostic model for risk stratification in gastric cancer. Further evaluations are warranted to clarify the clinical role of texture analysis from MDCT. Key points: • Textural analysis from computed tomography can be applied in gastric cancer. • Preoperative non-invasive texture features are related to prognosis in gastric cancer. • Texture analysis could help to evaluate the aggressiveness of this tumour.

Background Choriocarcinoma is a highly malignant tumor but with a good prognosis due to the valid response to systemic chemotherapy. We present a case of a young woman affected by a giant pelvic arterio-venous fistula following a metastatic gestational choriocarcinoma, conditioning metrorrhagia and pulmonary embolism, successfully treated by multimodal transcatheter embolization, using a simultaneous transarterial and transvenous approach. Case presentation In a young patient affected by choriocarcinoma and metrorrhagia, a computed tomography showed a giant arterio-venous fistula, pulmonary metastases and embolism. A transfemoral diagnostic arteriography showed a giant arterio-venous fistula sustained by right and left hypogastric arteries with early opacification of the right gonadal vein and of the inferior vena cava. A transarterial embolization of the distal branches of hypogastric arteries with poly-vinyl-alcohol particles, coils and Squid was performed. A transfemoral phlebography of the right gonadal vein showed multiple thrombi, responsible of the pulmonary embolism. An Amplatzer plug via trans-jugular was finally placed at the confluence of the gonadal vein in the vena cava, to reduce arterio-venous fistula out-flow and to occlude the vein, preventing further episodes of pulmonary embolism. Metrorrhagia progressively disappeared. A second transarterial embolization combined with a complete response to systemic chemotherapy determined arterio-venous fistula resolution. Conclusions This was a very rare case of a giant pelvic arterio-venous fistula following choriocarcinoma in a patient symptomatic for metrorrhagia with an accidental finding of pulmonary embolism at computed tomography. A transcatheter embolization was successfully performed with different embolic materials, using a simultaneous transarterial and transvenous approach: the goal was not only to obtain metrorrhagia resolution but also to avoid a massive pulmonary embolism, a potential life threatening condition, in a young woman affected by a highly malignant tumor but with a good prognosis.

To investigate the role of the apparent diffusion coefficient (ADC) as a potential prognostic biomarker in the evaluation of the aggressiveness of oesophageal cancer.Between November 2009 and December 2013, 43 patients with evidence of oesophageal or oesophago-gastric junction cancer were referred to our institution and prospectively entered in our database. The final study population consisted of 23 patients (18 men; 5 women; mean age, 64.62 ± 10.91 years) who underwent diffusion-weighted Magnetic Resonance before surgical intervention. Specifically, 14 were directly treated with surgery and 9 were addressed to chemo/radiotherapy beforehand. Two radiologists independently measured mean tumour ADC and inter-observer agreement (Spearman's and intraclass correlation coefficient [ICC]) was assessed. In the univariate analysis, overall survival curves related to pathological ADC, pT, pN, tumour location and histotype were fitted using the Kaplan-Meier method. Survival curves were then compared using the log-rank test.Inter-observer reproducibility was very good (Spearman's rho = 0.95; ICC = 0.94). At a total median follow-up of 19 months (2-49 months), 4 patients had died. The median follow-up was 18.50 months (5-49 months) for the surgery-only group (1/4 events, 25 %) and 24 months (2-34 months) for the chemo/radiotherapy group (3/4 events, 75 %). Survival time at 48 months for the overall population was 59 % (±0.11), while for the surgery-only group and the chemo/radiotherapy group was 90 % (±0.09) and 61 % (±0.34), respectively. In the univariate analysis, ADC values below or equal to 1.4 × 10(-3) mm(2)/s were associated with a negative prognosis both in the total population (P = 0.016) and in the surgery-only group (P 0.001).Despite the biggest limitation of our study (i.e. the small study population), we were able to show that pathological ADC could be considered a prognostic factor for oesophageal cancer. DWI might be introduced into clinical practice as a promising and reliable technique in the diagnostic pathway of this tumour.

OBJECTIVE. The purpose of this study is to test the association between diffusion-weighted MRI and prostate cancer Gleason score at both biopsy and final pathologic analysis after radical prostatectomy. SUBJECTS AND METHODS. Patients with prostate cancer (n = 72) underwent diffusion-weighted MRI (b values, 0, 800, and 1600 s/mm(2)) with an endorectal coil. Apparent diffusion coefficient (ADC) and ADC ratio were obtained in normal and pathologic tissue and were correlated with transrectal ultrasound-guided biopsy (n = 72) and histopathologic (n = 39) Gleason scores using the ANOVA test. ADC accuracy was estimated using ROC curves. RESULTS. Lesions suspicious for prostate cancer were detected in 65 patients. The mean ADC was 1.47 and 0.87 × 10(-3) mm(2)/s for normal and pathologic tissue, respectively (p < 0.001). When we divided the population into four groups (normal tissue and biopsy Gleason scores of 6, 7, and 8-10), then the mean ADC value was 1.47, 0.96, 0.80, and 0.78 × 10(-3) mm(2)/s, respectively (p < 0.001). The ADC ratio decreased along with an increase in biopsy Gleason score (66.9%, 56.7%, and 51.5% for Gleason scores of 6, 7 and 8-10, respectively) (ANOVA, p = 0.003) and pathologic Gleason score (ANOVA, p < 0.001). ROC curves had an AUC of 0.94 and 0.86 for ADC and ADC ratio, respectively (p = 0.012 and 0.042, respectively). CONCLUSION. Decreasing ADC values may represent a strong risk factor of harboring a poorly differentiated prostate cancer, independently of biopsy characteristics.

To assess the role of preoperative multiparametric MRI (mpMRI) of the prostate in the prediction of nodal metastases in patients treated with radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). We retrospectively analyzed 101 patients who underwent both preoperative mpMRI of the prostate and RP with ePLND at our institution. For each patient, complete preoperative clinical data and tumour characteristics at mpMRI were recorded. Final histopathologic stage was considered the standard of reference. Univariate and multivariate logistic regression analyses were performed. Nodal metastases were found in 23/101 (22.8%) patients. At univariate analyses, all clinical and radiological parameters were significantly associated to nodal invasion (all p

OBJECTIVE To investigate the role of apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (DW-MRI) when applied to the 7th TNM classification in the staging and prognosis of gastric cancer (GC). METHODS Between October 2009 and May 2014, a total of 89 patients with non-metastatic, biopsy proven GC underwent 1.5T DW-MRI, and then treated with radical surgery. Tumor ADC was measured retrospectively and compared with final histology following the 7th TNM staging (local invasion, nodal involvement and according to the different groups - stage I, II and III). Kaplan-Meier curves were also generated. The follow-up period is updated to May 2016. RESULTS Median follow-up period was 33 months and 45/89 (51%) deaths from GC were observed. ADC was significantly different both for local invasion and nodal involvement (P

BACKGROUND: To assess feasibility, safety, and metabolic outcome of islet auto transplantation (IAT) in patients undergoing completion pancreatectomy because of sepsis or bleeding after pancreatic surgery. METHODS: From November 2008 to October 2016, approximately 22 patients were candidates to salvage IAT during emergency relaparotomy because of postpancreatectomy sepsis (n = 11) or bleeding (n = 11). Feasibility, efficacy, and safety of salvage IAT were compared with those documented in a cohort of 36 patients who were candidate to simultaneous IAT during nonemergency preemptive completion pancreatectomy through the pancreaticoduodenectomy. RESULTS: The percentage of candidates that received the infusion of islets was significantly lower in salvage IAT than simultaneous IAT (59.1% vs 88.9%, P = 0.008), mainly because of a higher rate of inadequate islet preparations. Even if microbial contamination of islet preparation was significantly higher in candidates to salvage IAT than in those to simultaneous IAT(78.9% vs 20%, P < 0.001), there was no evidence of a higher rate of complications related to the procedure. Median follow-up was 5.45 ± 0.52 years. Four (36%) of 11 patients reached insulin independence, 6 patients (56%) had partial graft function, and 1 patient (9%) had primary graft nonfunction. At the last follow-up visit, median fasting C-peptide was 0.43 (0.19-0.93) ng/mL; median insulin requirement was 0.38 (0.04-0.5) U/kg per day, and median HbA1c was 6.6% (5.9%-8.1%). Overall mortality, in-hospital mortality, metabolic outcome, graft survival, and insulin-free survival after salvage IAT were not different from those documented after simultaneous IAT. CONCLUSIONS: Our data demonstrate the feasibility, efficacy, and safety of salvage IAT after relaparotomy.

Liver thermal ablation is an alternative treatment for hepatocellular carcinoma (HCC) and secondary liver malignancies. Microwave ablation (MWA) produces large ablation zones (AZ) in short time; however, AZ prediction is based on preclinical ex vivo models, rising concerns about reproducibility and safety in humans. We aimed to investigate the effects produced by a new-generation MWA system on human liver in vivo with different approaches (percutaneous or intraoperative) and liver conditions (cirrhosis or previous chemotherapy treatment), in comparison with manufacturer-provided predictions based on ex vivo animal models. Complete tumor ablation (CA) and early clinical outcomes were also assessed. From October 2014, 60 consecutive patients (cirrhotic = 31; non-cirrhotic = 10; chemotherapy-treated = 19) with 81 liver nodules (HCC = 31; mets = 50) underwent MWA procedures (percutaneous = 30; laparotomic = 18; laparoscopic = 12), with a 2450 MHz/100 W generator with Thermosphere™ Technology (Emprint™, Medtronic). A contrast-enhanced CT or MR was performed after one month to assess CA and measure AZ. A linear correlation between AZ volumes and ablation times was observed in vivo, without differences from manufacturer-provided ex vivo predictions in all operative approaches and liver conditions. Other independent variables (sex, age, nodule location) showed no relationship when added to the model. Median (IQR) longitudinal and transverse roundness-indexes of the AZs were, respectively, 0.77(0.13) and 0.93(0.11). CA at 1 month was 93% for percutaneous and 100% for intraoperative procedures (p = 0.175). Thirty-day morbidity and mortality were 3% and 0%. MWA with Thermosphere™ Technology produces predictable AZs on human liver in vivo, according to manufacturer-provided ex vivo predictions. In our experience, this new-generation MWA system is effective and safe to treat liver malignancies in different operative and clinical settings.

Purpose An accurate prediction of tumour response to therapy is fundamental in oncology, so as to prompt personalised treatment options if needed. The aim of this study was to investigate the ability of preoperative texture analysis from multi-detector computed tomography (MDCT) in the prediction of the response rate to neo-adjuvant therapy in patients with gastric cancer. Material and methods Thirty-four patients with biopsy-proven gastric cancer were examined by MDCT before neo-adjuvant therapy, and treated with radical surgery after treatment completion. Tumour regression grade (TRG) at final histology was also assessed. Image features from texture analysis were quantified, with and without filters for fine to coarse textures. Patients with TRG 1–3 were considered responders while TRG 4–5 as non- responders . The response rate to neo-adjuvant therapy was assessed both at univariate and multivariate analysis. Results Fourteen parameters were significantly different between the two subgroups at univariate analysis; in particular, entropy and compactness (higher in responders ) and uniformity (lower in responders ). According to our model, the following parameters could identify non-responders at multivariate analysis: entropy (≤6.86 with a logarithm of Odds Ratio − Log OR −: 4.11; p = 0.003); range (>158.72; Log OR: 3.67; p = 0.010) and root mean square (≤3.71; Log OR: 4.57; p = 0.005). Entropy and three-dimensional volume were not significantly correlated ( r = 0.06; p = 0.735). Conclusion Pre-treatment texture analysis can potentially provide important information regarding the response rate to neo-adjuvant therapy for gastric cancer, improving risk stratification.

Purpose: To retrospectively report a large single-center experience of visceral artery aneurysms (VAAs) and pseudoaneurysms (VAPAs) treated with covered stenting (CS) as the first therapeutic option vs transcatheter embolization (TE). Methods: One hundred patients (mean age 59±14 years; 58 men) underwent 59 elective and 41 emergent endovascular procedures to treat 51 VAAs and 49 VAPAs. Seventy patients had TE and 30 received CS (27 Viabahn and 3 coronary stent grafts). Both TE and CS were performed in 10 cases. Results: Technical success was 96% (97% CS, 96% TE), and 30-day clinical success was 83% (87% CS, 81.4% TE). Four major complications occurred; 30-day mortality was 7%, mainly due to septic shock following pancreatic surgery. The midterm follow-up was 20.8 months in the total population and 32.8 months in the CS group. More than 6 months after CS all aneurysms remained excluded; stent patency was achieved in 88%. Twelve CS patients with >3 years’ follow-up had maintained stent patency. Conclusion: In endovascular treatment of visceral aneurysms, covered stenting was feasible in 30%. CS showed a slightly better efficacy than TE and good midterm patency. The Viabahn covered stent seems to be suitable for endovascular repair of tortuous visceral arteries affected by true or false aneurysms.

PURPOSE:To assess whether changes in diffusion-weighted MRI (DW-MRI) and (18) F-fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18) F-FDG PET/CT), correlate with treatment response to neoadjuvant therapy (NT), as expressed by tumor regression grade (TRG), from locally advanced gastric adenocarcinoma (GA).MATERIALS AND METHODS:Seventeen patients underwent both DW-MRI and (18) F-FDG-PET/CT scans before and after the end of NT. Apparent diffusion coefficient (ADC) and mean standardized uptake value (SUV) corrected for partial volume effect (PVC-SUVBW-mean ) were evaluated and compared with histopathological TRG.RESULTS:Pre- and post-NT and percentage changes for ADC and PVC-SUVBW-mean were assessed. Post-NT ADC and ΔADC showed a significant inverse correlation with TRG (r = -0.71; P = 0.0011 and r = -0.78; P = 0.00020, respectively) and significant differences in their mean values were found between responders (TRG 1-2-3) and nonresponders (TRG 4-5) (P = 0.0009; P = 0.000082, respectively). No correlations with TRG were found for pre-NT ADC and for all PVC-SUVBW-mean values as well as between ΔADC and Δ PVC-SUVBW-mean .CONCLUSION:DW-MRI seems more accurate than (18) F-FDG-PET/CT and ADC modifications may represent a reproducible tool to assess tumor response for GA. PurposeTo assess whether changes in diffusion-weighted MRI (DW-MRI) and 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), correlate with treatment response to neoadjuvant therapy (NT), as expressed by tumor regression grade (TRG), from locally advanced gastric adenocarcinoma (GA).Materials and MethodsSeventeen patients underwent both DW-MRI and 18F-FDG-PET/CT scans before and after the end of NT. Apparent diffusion coefficient (ADC) and mean standardized uptake value (SUV) corrected for partial volume effect (PVC-SUVBW-mean) were evaluated and compared with histopathological TRG.ResultsPre- and post-NT and percentage changes for ADC and PVC-SUVBW-mean were assessed. Post-NT ADC and ΔADC showed a significant inverse correlation with TRG (r = −0.71; P = 0.0011 and r = −0.78; P = 0.00020, respectively) and significant differences in their mean values were found between responders (TRG 1–2-3) and nonresponders (TRG 4–5) (P = 0.0009; P = 0.000082, respectively). No correlations with TRG were found for pre-NT ADC and for all PVC-SUVBW-mean values as well as between ΔADC and Δ PVC-SUVBW-mean.ConclusionDW-MRI seems more accurate than 18F-FDG-PET/CT and ADC modifications may represent a reproducible tool to assess tumor response for GA

Objectives The aim of this study was to investigate the contribution of smoking and alcohol intake and pancreas divisum on the risk of developing chronic pancreatitis (CP). Methods Consecutive patients with CP who underwent secretin-enhanced magnetic resonance cholangiopancreatography were compared with consecutive patients without pancreatic disease who underwent secretin-enhanced magnetic resonance cholangiopancreatography for irritable bowel syndrome. Results We enrolled 145 consecutive CP patients and 103 irritable bowel syndrome patients from 2010 to 2014. In a univariate analysis, statistically significant differences in sex, mean age, and the duration and amount of cigarette and alcohol use were found. Per a receiver operating characteristic curve analysis, thresholds for cigarette and alcohol consumption were, respectively, 5.5 cigarettes and 13.5 g daily. In a multivariate analysis, independent risk factors for CP were male sex (odds ratio [OR], 2.05), smoking more than 5.5 cigarettes per day (OR, 2.72), and drinking more than 13.5 g/d (OR, 6.35). Conclusions In an Italian population, we confirmed smoking and alcohol as cofactors in the development of CP. This study shows that alcohol intake and smoking habits are 2 of the most important risk factors for the development of CP.

An accurate detection of myocardial scar using Cardiac CT may have a strong clinical impact; however, the main drawback is the insufficient contrast to noise ratio of delayed iodine enhanced (DIE) CT images, which makes its accurate segmentation (manual as well as automatic) difficult. In this work, we investigate texture parameters applied on the different scans in order to obtain the scans and features that best differentiates normal from scarred myocardium. The experiments on 7 cases of myocarditis show the accuracy of the parameter energy in all scans, as well as the good performance of the angiographic scan (having higher spatial resolution) with different parameters for the segmentation propose. Moreover, the best performance was obtained on the baseline scan for the energy feature, with an accuracy of 94%.

Background Chromogranin-A (CgA) is a secretory protein processed into peptides that regulate angiogenesis and vascular cells activation, migration and proliferation. These processes may influence arterial inflammation and remodelling in Takayasu arteritis (TA). Methods Plasma levels of full-length CgA (CgA439), CgA fragments lacking the C-terminal region (CgA-FRs) and the N-terminal fragment, CgA1–76 (vasostatin-1, VS-1) were analysed in 42 patients with TA and 20 healthy age-matched controls. Vascular remodelling was longitudinally assessed by imaging. CgA peptides were related to markers of systemic and local inflammation, disease activity and vascular remodelling. Results Levels of CgA-FRs and VS-1 were increased in TA. Treatment with proton-pump inhibitors (PPIs) and arterial hypertension partially accounted for CgA levels and high inter-patient variability. CgA439, CgA-FRs and VS-1 levels did not reflect disease activity or extent. Markers of systemic or local inflammation correlated with higher CgA-FRs and VS-1 in normotensive patients and with higher CgA439 in hypertensive patients. Treatment with non-biologic anti-rheumatic agents was associated with increased CgA-FRs and a distinctive regulation of CgA processing. Reduced blood levels of anti-angiogenic CgA peptides were associated with vascular remodelling in the groups of patients on PPIs and with arterial hypertension. Conclusions The plasma levels of CgA fragments are markedly increased in TA as a consequence of disease- and therapy-related variables. Anti-angiogenic forms of CgA may limit vascular remodelling. Given the effect of the various CgA peptides, it is advisable to limit the therapeutic prescriptions that might influence CgA-derived peptide levels to clearly agreed medical indications until further data become available. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-1082-2) contains supplementary material, which is available to authorized users.

OBJECTIVE: Islet allotransplantation is a less invasive alternative to surgical pancreas transplantation for Type 1 diabetes, while percutaneous intraportal islet autotransplantation (PIPIAT) is usually performed after pancreatic surgery to prevent diabetes. Our aim was to assess the feasibility, radiological aspects, complications and clinical outcome of PIPIAT following pancreatic surgery for not only chronic pancreatitis but also benign and malignant nodules. METHODS: From 2008 to 2012, 41 patients were enrolled for PIPIAT 12-48 h after pancreatic surgery (extended pancreatic surgery for chronic pancreatitis and benign/malignant neoplasms). PIPIAT was performed using a combined ultrasonography and fluoroscopy-guided technique (4-F catheter). PIPIAT feasibility, median follow-up and metabolic (insulin independence rate, graft function based on C-peptide levels) and oncologic outcomes were recorded. RESULTS: PIPIAT was not performed in 7/41 patients (4 cases for an inadequate islet mass, 2 cases for haemodynamic instability and 1 case for islet culture contamination), while it was successfully performed in 34/34 patients. Procedure-related major complications occurred in four patients: two bleedings requiring transfusions, one patient with left portal vein thrombosis and one patient with sepsis. Median follow-up duration was 546 days. Insulin independence was achieved in 15/34 (44%) patients, partial graft function in 16/34 (47%) patients and no function in 3/34 (9%) patients. None of the 17 patients with malignant nodules developed liver metastases during follow-up. CONCLUSION: PIPIAT, performed under ultrasound and fluoroscopy combined guidance and not requiring immunosuppression, is feasible, with a relatively low complication rate and a better metabolic outcome than allotransplantation. ADVANCES IN KNOWLEDGE: PIPIAT can prevent pancreatogenic diabetes. Ultrasound is a useful tool for the guidance and monitoring of PIPIAT.

Background The aim of this study was to prospectively compare the diagnostic performance of magnetic resonance imaging (MRI), multidetector computed tomography (MDCT) and endoscopic ultrasonography (EUS) in the preoperative locoregional staging of gastric cancer. Methods This study had Institutional Review Board approval, and informed consent was obtained from all patients. Fifty-two patients with biopsy-proven gastric cancer underwent preoperative 1.5-T MRI, 64-channel MDCT and EUS. All images were analysed blind, and the results were compared with histopathological findings according to the seventh edition of the TNM classification. After the population had been divided on the basis of the local invasion (T1-3 vs T4a-b) and nodal involvement (N0 vs N+), sensitivity, specificity, positive and negative predictive value, and accuracy were calculated and diagnostic performance measures were assessed using the McNemar test. Results For T staging, EUS showed higher sensitivity (94 %) than MDCT and MRI (65 and 76 %; p = 0.02 and p = 0.08). MDCT and MRI had significantly higher specificity (91 and 89 %) than EUS (60 %) (p = 0.0009 and p = 0.003). Adding MRI to MDCT or EUS did not result in significant differences for sensitivity. For N staging, EUS showed higher sensitivity (92 %) than MRI and MDCT (69 and 73 %; p = 0.01 and p = 0.02). MDCT showed better specificity (81 %) than EUS and MRI (58 and 73 %; p = 0.03 and p = 0.15). Conclusions Our prospective study confirmed the leading role of EUS and MDCT in the staging of gastric cancer and did not prove, at present, the value of the clinical use of MRI.

Objectives The aim of this study is to develop a nomogram of clinical utility based on apparent diffusion coefficient (ADC) from diffusion-weighted imaging to predict extracapsular extension (ECE), and to validate externally its clinical utility. Materials and methods A total of 101 men (70 for the creation and 31 for external validation of the nomogram) underwent 1.5T multiparametric magnetic resonance imaging followed by radical prostatectomy at 2 different institutions. ADC values were assessed for normal and pathological tissue. Clinical and pathological variables were investigated by univariate and multivariate logistic regression analyses on 70 patients and logistic regression coefficients were used to develop our nomogram. Receiver operating characteristic curve analysis was performed to determine the optimal ADC cut off for ECE. The nomogram was then externally validated on 31 patients at another institution. Results At univariate analysis, the following variables were associated with ECE: pathological ADC and Gleason at biopsy (P

The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell-depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+-cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31(+) recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution. (Blood. 2012;120(9):1820-1830) The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially-incompatible Hematopoietic Stem Cell Transplantation (HSCT). In the TK007 clinical trial 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell-depleted HSCT and serial infusions of purified donor T cells expressing the Herpes Simplex Virus Thymidine Kinase suicide gene (TK(pos) cells). After a first wave of circulating TK(pos) cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naïve lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK(pos) cell engraftment. Accordingly, after the infusions we documented an increase in circulating T cell Receptor Excision Circles and CD31+ recent thymic emigrants, and a substantial expansion of the active thymic tissue at chest tomography scans. Interestingly, a peak in the serum level of interleukin-7 was observed after each infusion of TK(pos) cells, anticipating the appearance of newly generated T cells. Taken together, our data show that the infusion of genetically modified donor T cells after transplantation can drive the recovery of thymic activity in adults, leading to immune reconstitution.

This study evaluated the methods, technical aspects and impact of preoperative radiological guidance in radioguided occult lesion localisation (ROLL) for single nonpalpable breast lesions.A total of 288 patients underwent ROLL before surgery. Human serum albumin macroaggregates labelled with 3.7-7.4 MBq of technetium(99) were injected into the lesion. In the case of ultrasonographic guidance (221/288 patients), inoculum positioning resulted in a change of echogenicity at the lesion site. In the case of mammographic guidance (67/288 patients), iodinated contrast medium was injected following the radiotracer for subsequent mammographic evaluation. Patients underwent surgery within 24 h from ROLL. A gamma-detecting probe was used to locate the lesion during surgery and guide its removal. After excision, the specimen was examined by either ultrasonography or mammography to verify complete lesion removal before histological evaluation.The lesion was correctly localised in 281/288 patients (97.5%). One ROLL procedure failed because surgery could not be performed within 24 h and the radioactivity decayed. Of the six incorrect localisations, 2 were due to the radiological guidance and 4 to technetium(99) dispersion.Radiological guidance in ROLL ensured the outcome of the procedure of localisation and removal of single, nonpalpable breast lesions in the majority of cases.

OBJECTIVE: To evaluate the feasibility of the Adamkiewicz artery (AKA) detection by multidetector computed tomography (CT) data analysis without the need of a dedicated workstation, using low-cost hardware and the freeware OsiriX. METHODS: CT scans of 67 patients undergoing a thoracic or thoraco-abdominal aortic procedure between April 2006 and August 2008 were evaluated with respect to detection rate and AKA level and side using the OsiriX software version 3.2 on Mac OS X computer and compared to results obtained by standard workstation analysis, in a fully blinded analysis. The results were also compared with data compiled from a review of the English-language literature on this topic. RESULTS: (1) AKA identification showed a substantial agreement of 85.07% between the methods (k=0.636). (2) The comparison of AKA level showed a substantial agreement (weighted k=0.661), with consensus in 70.14%. (3) From the literature review, we found that recognition of the AKA was achieved in 466 of 555 cases (83.96%). (4) In 384 (83.3%) cases the AKA originated from a left intercostal artery. (5) The proposed method and literature-compiled data showed a similar AKA level distribution. CONCLUSIONS: Noninvasive AKA location with open-source software and low-cost hardware is feasible. The OsiriX software allows to effectively navigate through CT data not only to study the aorta, but also to detect the AKA, as in the case of the standard method and the literature data. Its availability and ease of use may contribute to make identification of the AKA part of the routine evaluation of CT scans in patients with aortic disease, even where dedicated workstations are not available, with potential benefits for planning therapeutic procedures. Objective: To evaluate the feasibility of the Adamkiewicz artery (AKA) detection by multidetector computed tomography (CT) data analysis without the need of a dedicated workstation, using low-cost hardware and the freeware OsiriX. Methods: CT scans of 67 patients undergoing a thoracic or thoraco-abdominal aortic procedure between April 2006 and August 2008 were evaluated with respect to detection rate and AKA level and side using the OsiriX software version 3.2 on Mac OS X computer and compared to results obtained by standard workstation analysis, in a fully blinded analysis. The results were also compared with data compiled from a review of the English-language literature on this topic. Results: (1) AKA identification showed a substantial agreement of 85.07% between the methods (k = 0.636). (2) The comparison of AKA level showed a substantial agreement (weighted k = 0.661), with consensus in 70.14%. (3) From the literature review, we found that recognition of the AKA was achieved in 466 of 555 cases (83.96%). (4) In 384 (83.3%) cases the AKA originated from a left intercostal artery. (5) The proposed method and literature-compiled data showed a similar AKA level distribution. Conclusions: Noninvasive AKA location with open-source software and low-cost hardware is feasible. The OsiriX software allows to effectively navigate through CT data not only to study the aorta, but also to detect the AKA, as in the case of the standard method and the literature data. Its availability and ease of use may contribute to make identification of the AKA part of the routine evaluation of CT scans in patients with aortic disease, even where dedicated workstations are not available, with potential benefits for planning therapeutic procedures.

Objective: Ageing of the human heart is characterised by morphological, functional and metabolic changes. Short-term interventions and cross-sectional studies in older individuals questioned the possibility that physical exercise may reverse these alterations. In this study we aimed to assess whether in middle-aged men involved in regular and long lasting physical activity these alterations were attenuated. Design: Left ventricular (LV) magnetic resonance imaging (MRI) and three-dimensional image selected in-vivo spectroscopy (3D-ISIS) 31 P magnetic resonance spectroscopy (MRS) were performed using a 1.5T scanner in 20 healthy, young and 25 healthy middle-aged non-obese men with a sedentary lifestyle (11 young and 14 middle-aged) or undergoing regular aerobic oxidative training (9 young and 11 middle-aged). Insulin sensitivity was estimated by the homeostatic model assessment 2 (HOMA-2) model. Results: Sedentary young and middle-aged men were not different with respect to LV morphological parameters and systolic function. The phosphocreatine/ATP (PCr/ATP) ratio (marker of high energy phosphates metabolism) and the LV E-peak filling rate/A-peak filling rate ratio (E/A ratio) were lower in sedentary middle-aged than physically active subjects. Parameters of LV systolic function and the PCr/ATP ratio were not different in the middle-aged compared with the young trained men; the E/A peak flow ratio was higher in the middle-aged trained men than in the middle-aged sedentary men. Within the entire population, the PCr/ATP ratio and the E/A peak flow ratio were associated with insulin sensitivity. Conclusions: Trained middle-aged subjects showed a better pattern of LV energy metabolism and of diastolic function than their sedentary counterparts. At this age the exercise-related cardiac benefits were detectable when physical exercise was performed regularly and for a long period of time.

Fatty liver is characterized by metabolic abnormalities at the liver, but also at skeletal muscle and adipose tissue sites. It is hypothesized that the heart may be suffering metabolic alterations, and this study was undertaken to ascertain whether individuals with fatty liver have left ventricular (LV) alterations of energy metabolism, structure, and function and abnormal amounts of epicardial fat as a specific marker of visceral fat accumulation. To this end we studied young, nondiabetic men matched for anthropometric features with (n = 21) or without (n = 21) fatty liver by means of (1) cardiac magnetic resonance imaging (MRI); (2) cardiac 31P-MR spectroscopy (MRS); and (3) hepatic 1H-MRS to assess quantitatively the intrahepatic fat (IHF) content. Insulin sensitivity was determined by the updated HOMA-2 computer model. Individuals with fatty liver showed reduced insulin sensitivity, increased serum free fatty acid (FFA), and E-selectin, abnormal adipokine concentrations, and higher blood pressure. LV morphology and systolic and diastolic functions were not different; however, in the scanned intrathoracic region, the intrapericardial (7.8 ± 3.1 versus 5.9 ± 2.5 cm2; P < 0.05) and extrapericardial (11.7 ± 6.1 versus 7.8 ± 3.2 cm2; P < 0.03) fat was increased in men with fatty liver compared with those without fatty liver. 1The phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio, a recognized in vivo marker of myocardial energy metabolism, was reduced in men with fatty liver in comparison with normals (1.85 ± 0.35 versus 2.11 ± 0.31; P < 0.016). In conclusion, in newly found individuals with fatty liver, fat was accumulated in the epicardial area and despite normal LV morphological features and systolic and diastolic functions, they had abnormal LV energy metabolism. Copyright © 2007 by the American Association for the Study of Liver Diseases

OBJECTIVE—Perturbations in cardiac energy metabolism might represent early alterations in diabetes preceding functional and pathological changes. We evaluated left ventricular (LV) structure/geometry and function in relation to energy metabolism and cardiovascular risk factors in overweight/obese men using magnetic resonance techniques. RESEARCH DESIGN AND METHODS—We studied 81 healthy men (aged 22–55 years, with BMI between 19 and 35 kg/m2) by means of cardiac magnetic resonance imaging and 31P-magnetic resonance spectroscopy in the resting and fasted conditions and stratified them in quartiles of BMI (cut offs: 23.2, 25.5 and 29.0 kg/m2). RESULTS—LV mass increased across quartiles of BMI; meanwhile, the volumes did not differ. Parameters of LV systolic and diastolic function were not different among quartiles. The phosphocreatine-to-ATP ratio was reduced across increasing quartiles of mean ± SD BMI (2.25 ± 0.52, 1.89 ± 0.26, 1.99 ± 0.38, and 1.79 ± 0.29; P < 0.006) in association with insulin sensitivity (computer homeostasis model assessment 2 model); this relation was independent of age, BMI, blood pressure, wall mass, HDL cholesterol, triglycerides, smoking habits, and metabolic syndrome. CONCLUSIONS—Abnormal LV energy metabolism was detectable in obese men in the presence of normal function, supporting the hypothesis that metabolic remodeling in insulin resistant states precedes functional and structural/geometrical remodeling of the heart regardless of the onset of overt hyperglycemia.

Purpose: To prospectively investigate the role of apparent diffusion coefficient (ADC) calculated from diffusion-weighted magnetic resonance (MR) imaging as a potential prognostic biomarker in the evaluation of the aggressiveness of gastric cancer. Materials and Methods: This prospective study had institutional review board approval. Informed consent was obtained from all patients. Between October 2009 and December 2013, a total of 99 patients (65 men, 34 women; mean age, 62.02 years; age range, 32.33-85.15 years) with biopsy-proved cancer (28 esophagogastric junction and 71 gastric cancers) were examined with a 1.5-T MR imaging system, including T1-, T2-, and diffusion-weighted sequences. ADC measurements were obtained. Seventy-one patients were directly treated with surgery, while 28 underwent neoadjuvant chemotherapy beforehand. Pathologic ADC, pathologic T and N stages, tumor location, surgical approach, and histologic subtype were investigated with univariate and multivariate analyses by using the Cox regression model. Results: At a total median follow-up period of 21 months, 31 patients had died. The median follow-up was 25 months for the surgery-only group (19 of 31 events [61%]) and 28 months for the chemotherapy group (12 of 31 events [39%]). In the multivariate analysis, ADC values of 1.5 x 10(-3) mm(2)/sec or lower were associated with a negative prognosis, both in the total population (log-relative risk, 1.73; standard error, 0.56; P = .002) and in the surgery-only (log-relative risk, 1.97; standard error, 0.66; P = .003) and chemotherapy (log-relative risk, 2.93; standard error, 1.41; P = .03) groups, along with other significant prognostic factors (in particular, pathologic T and N stages). Conclusion: Pathologic ADC represents a strong independent prognostic factor in the evaluation of the aggressiveness of gastric cancer, in addition to clinical and surgical variables. (C) RSNA, 2015

Percutaneous intra-portal islet transplantation (PIPIT) is a less invasive, safer, and repeatable therapeutic option for brittle type 1 diabetes, compared to surgical pancreas transplantation. Hepatic steatosis is a consequence of the islet engraftment but it is curiously present in a limited number of patients and its meaning is controversial. The aims of this study were to assess hepatic steatosis at ultrasound (US) after PIPIT investigating its relationship with graft function and its role in predicting the clinical outcome. From 1996 to 2012, 108 patients underwent PIPIT: 83 type-1 diabetic patients underwent allotransplantation, 25 auto-transplantation. US was performed at baseline, 6, 12, and 24 months, recording steatosis prevalence, first detection, duration, and distribution. Contemporaneously, steatotic and non-steatotic patients were compared for the following parameters: infused islet mass, insulin independence rate, beta-score, C-peptide, glycated hemoglobin, exogenous insulin requirement, and fasting plasma glucose. Steatosis at US was detected in 21/108 patients, 20/83 allo-transplanted and 1/25 auto-transplanted, mostly at 6 and 12 months. Infused islet mass was significantly higher in steatotic than non-steatotic patients (IE/kg: S = 10.822; NS = 6138; p = 0.001). Metabolically, steatotic patients had worse basal conditions, but better islet function when steatosis was first detected, after which progressive islet exhaustion, along with steatosis disappearance, was observed. Conversely, in non-steatotic patients these parameters remained stable in time. Number of re-transplantations was significantly higher in steatotic than in non-steatotic patients (1.8 vs 1.1; p = 0.001). Steatosis at US seems to be related to the islet mass and local overworking activity. It precedes metabolic alterations and can predict graft dysfunction addressing to therapeutic decisions before islet exhaustion. If steatosis does not appear, no conclusion can be drawn. (C) 2015 Elsevier Ltd. All rights reserved.

OBJECTIVE—Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients. RESEARCH DESIGN AND METHODS—We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twenty-five patients did not receive a functioning islet transplant (kidney-only group). RESULTS—GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 ± 3.5% at baseline to 74.9 ± 2.1% at 3 years posttransplantation, P < 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 ± 0.25 to 4.20 ± 0.37 EDV/s, P < 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P < 0.05). The kidney-islet group also showed a reduction of both QT dispersion (53.5 ± 4.9 to 44.6 ± 2.9 ms, P < 0.05) and corrected QT (QTc) dispersion (67.3 ± 8.3 to 57.2 ± 4.6 ms, P < 0.05) with higher erythrocytes Na+-K+-ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness. CONCLUSIONS—Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft.

Intramyocellular lipid (IMCL) storage is considered a local marker of whole body insulin resistance; because increments of body weight are supposed to impair insulin sensitivity, this study was designed to assess IMCL content, lipid oxidation, and insulin action in individuals with a moderate increment of body fat mass and no family history of diabetes. We studied 14 young, nonobese women with body fat 30% (n = 7) and 14 young, nonobese men with body fat 25% (n = 7) by means of the euglycemic-insulin clamp to assess whole body glucose metabolism, with indirect calorimetry to assess lipid oxidation, by localized 1H NMR spectroscopy of the calf muscles to assess IMCL content, and with dual-energy X-ray absorptiometry to assess body composition. Subjects with higher body fat had normal insulin-stimulated glucose disposal (P = 0.80), IMCL content in both soleus (P = 0.22) and tibialis anterior (P = 0.75) muscles, and plasma free fatty acid levels (P = 0.075) compared with leaner subjects in association with increased lipid oxidation (P < 0.05), resting energy expenditure (P = 0.046), resting oxygen consumption (P = 0.049), and plasma leptin levels (P < 0.01) in the postabsorptive condition. In conclusion, in overweight subjects, preservation of insulin sensitivity was combined with increased lipid oxidation and maintenance of normal IMCL content, suggesting that abnormalities of these factors may mutually determine the development of insulin resistance associated with weight gain. Intramyocellular lipid content; lipid oxidation; insulin resistance; leptin; tumor necrosis factor-alpha; nuclear magnetic resonance spectroscopy.

Purpose: To report a novel case demonstrating the successful endovascular treatment of a right hepatic artery pseudoaneurysm using a balloon-expandable coronary stent-graft. Case Report: A 60-year-old woman underwent surgical treatment for a Klatskin tumor, but her postoperative course was complicated by serious blood loss. An emergent celiac angiogram through a right transfemoral approach demonstrated a small iatrogenic pseudoaneurysm in the proximal right hepatic artery. A 7-F guiding catheter was positioned at the origin of the celiac trunk, and a Jostent coronary stent-graft mounted on a 2.7-F, 4-mm × 30-mm balloon catheter was successfully placed across the aneurysm neck. The final angiogram demonstrated total exclusion of the pseudoaneurysm with preservation of the arterial lumen. The hemodynamic condition of the patient became stable. At 12-month follow-up, duplex scanning confirmed regular right hepatic artery patency and absence of thrombotic tissue or signs of infection around the stent-graft. Conclusions: For hepatic artery pseudoaneurysms, endovascular repair using small covered stents may be a viable alternative to transcatheter embolization. The use of coronary instruments facilitates treatment of vascular lesions in small caliber visceral vessels.

Signals of tissue necrosis, damage-associated molecular patterns (DAMPs), cause inflammation. Leukocytes migrating into injured tissues tonically release DAMPs, including the high mobility group box 1 protein (HMGB1). In the absence of suitable models, the relative role of DAMPs released because of necrosis or leukocyte activation has not, so far, been dissected. We have generated a mouse model lacking Hmgb1 in the hematopoietic system and studied the response to acute sterile injury of the skeletal muscle. Regenerating fibers are significantly less numerous at earlier time points and smaller at the end of the process. Leukocyte Hmgb1 licenses the skeletal muscle to react to hypoxia, to express angiopoietin-2, and to initiate angiogenesis in response to injury. Vascularization of the regenerating tissue is selectively jeopardized in the absence of leukocyte Hmgb1, revealing that it controls the nutrient and oxygen supply to the regenerating tissue. Altogether, our results reveal a novel nonredundant role for leukocyte Hmgb1 in the repair of injured skeletal muscle.

Introduction: Progression of arterial involvement is often observed in patients with Takayasu arteritis (TA) thought to be in remission. This reflects the failure of currently used biomarkers and activity criteria to detect smouldering inflammation occurring within arterial wall. Pentraxin-3 (PTX3) is a soluble pattern recognition receptor produced at sites of inflammation and could reveal systemic as well as localized inflammatory processes. We verified whether the blood concentrations of PTX3 and of C-reactive protein (CRP) in patients with Takayasu arteritis (TA) might reflect vascular wall involvement, as assessed by signal enhancement after contrast media administration, and the progression of arterial involvement. Methods: A cross-sectional single-centre study was carried out on 42 patients with TA that comprised assessment of PTX3, of CRP and erythrocyte sedimentation velocity (ESR). In total, 20 healthy controls and 20 patients with Systemic Lupus Erythematous (SLE) served as controls. Vascular imaging was carried out by magnetic resonance angiography, doppler ultrasonography and computed tomography angiography. Results: Patients with TA and SLE had higher plasmatic PTX3 and CRP concentrations than healthy controls (P = 0.009 and 0.017, respectively). PTX3 levels did not correlate with those of CRP. Patients with active systemic TA had significantly higher concentrations of CRP but similar levels of PTX3 than patients with quiescent disease. In contrast, patients with vascular inflammation detectable at imaging had higher PTX3 concentrations (P = 0.016) than those in which vessel inflammation was not evident, while CRP levels were similar. The concentration of PTX3 but not that of CRP was significantly higher in TA patients with worsening arterial lesions that were not receiving antagonists of tumor necrosis factor-α or interleukin-6. Conclusions: Arterial inflammation and progression of vascular involvement influence plasma PTX3 levels in TA, while levels of CRP accurately reflect the burden of systemic inflammation. These results support the contention that PTX3 reflects different aspects of inflammation than CRP and might represent a biomarker of actual arteritis in TA.

Churg–Strauss syndrome can be associated with Loeffler-like eosinophilic endocarditis. We report a case of a young woman in which the diagnosis of Churg–Strauss syndrome was made subsequently to the magnetic resonance demonstration of eosinophilic endocarditis associated to left ventricle apical thrombosis. In our report, this rare condition evolved in an unusual complication: the embolic migration of the left ventricle apical thrombus in the abdominal aorta as showed by multi-detector-computed-tomography angiography.