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Objective: To outline a practical method of performing prostate cancer radiotherapy in patients with bilateral metal hip prostheses with the standard resources available in a modern general hospital. The proposed workflow is based exclusively on magnetic resonance imaging (MRI) to avoid computed tomography (CT) artifacts. Case description: This study concerns a 73-year-old man with bilateral hip prostheses with an elevated risk prostate cancer. Magnetic resonance images with assigned electron densities were used for planning purposes, generating a synthetic CT (sCT). Imaging acquisition was performed with an optimized Dixon sequence on a 1.5T MRI scanner. The images were contoured by autosegmentation software, based on an MRI database of 20 patients. The sCT was generated assigning averaged electron densities to each contour. Two volumetric modulated arc therapy plans, a complete arc and a partial one, where the beam entrances through the prostheses were avoided for about 50° on both sides, were compared. The feasibility of matching daily cone beam CT (CBCT) with MRI reference images was also tested by visual evaluations of different radiation oncologists. Conclusions: The use of magnetic resonance images improved accuracy in targets and organs at risk (OARs) contouring. The complete arc plan was chosen because of 10% lower mean and maximum doses to prostheses with the same planning target volume coverage and OAR sparing. The image quality of the match between performed CBCTs and MRI was considered acceptable. The proposed method seems promising to improve radiotherapy treatments for this complex category of patients.

Background Radiomics is expected to improve the management of metastatic colorectal cancer (CRC). We aimed at evaluating the impact of liver lesion contouring as a source of variability on radiomic features (RFs). Methods After Ethics Committee approval, 70 liver metastases in 17 CRC patients were segmented on contrast-enhanced computed tomography scans by two residents and checked by experienced radiologists. RFs from grey level co-occurrence and run length matrices were extracted from three-dimensional (3D) regions of interest (ROIs) and the largest two-dimensional (2D) ROIs. Inter-reader variability was evaluated with Dice coefficient and Hausdorff distance, whilst its impact on RFs was assessed using mean relative change (MRC) and intraclass correlation coefficient (ICC). For the main lesion of each patient, one reader also segmented a circular ROI on the same image used for the 2D ROI. Results The best inter-reader contouring agreement was observed for 2D ROIs according to both Dice coefficient (median 0.85, interquartile range 0.78–0.89) and Hausdorff distance (0.21 mm, 0.14–0.31 mm). Comparing RF values, MRC ranged 0–752% for 2D and 0–1567% for 3D. For 24/32 RFs (75%), MRC was lower for 2D than for 3D. An ICC > 0.90 was observed for more RFs for 2D (53%) than for 3D (34%). Only 2/32 RFs (6%) showed a variability between 2D and circular ROIs higher than inter-reader variability. Conclusions A 2D contouring approach may help mitigate overall inter-reader variability, albeit stable RFs can be extracted from both 3D and 2D segmentations of CRC liver metastases.

Quantitative metrics in lung computed tomography (CT) images have been widely used, often without a clear connection with physiology. This work proposes a patient-independent model for the estimation of well-aerated volume of lungs in CT images (WAVE). A Gaussian fit, with mean (Mu.f) and width (Sigma.f) values, was applied to the lower CT histogram data points of the lung to provide the estimation of the well-aerated lung volume (WAVE.f). Independence from CT reconstruction parameters and respiratory cycle was analysed using healthy lung CT images and 4DCT acquisitions. The Gaussian metrics and first order radiomic features calculated for a third cohort of COVID-19 patients were compared with those relative to healthy lungs. Each lung was further segmented in 24 subregions and a new biomarker derived from Gaussian fit parameter Mu.f was proposed to represent the local density changes. WAVE.f resulted independent from the respiratory motion in 80% of the cases. Differences of 1%, 2% and up to 14% resulted comparing a moderate iterative strength and FBP algorithm, 1 and 3 mm of slice thickness and different reconstruction kernel. Healthy subjects were significantly different from COVID-19 patients for all the metrics calculated. Graphical representation of the local biomarker provides spatial and quantitative information in a single 2D picture. Unlike other metrics based on fixed histogram thresholds, this model is able to consider the inter-and intra-subject variability. In addition, it defines a local biomarker to quantify the severity of the disease, independently of the observer., 31 pages, 7 figures, accepted in EJMP

In a kidney transplant recipient, bladder and graft ureter displacement into a groin hernia is a highly unusual cause of obstructive uropathy that may lead to graft dysfunction or graft loss. We report the case of a White man, 56 years old, who had previously, at the age of 19 years, undergone a kidney transplant from a deceased donor, to mitigate chronic glomerulonephritis. The patient presented to us with a reducible left inguinal hernia with worsening kidney function, and we used the Lichtenstein hernioplasty technique to surgically repair the hernia, which was followed by an uneventful postoperative course. Existing literature has identified few cases of kidney graft dysfunction due to inguinal hernias. Groin hernia repair of this type in this specific circumstance remains a subject of debate. However, in our opinion, with attention to appropriate reductions of immunosuppressive therapy, the Lichtenstein technique is safe for transplant recipients and the use of mesh greatly reduces the risk of hernia recurrence.

To determine whether torso CT can be avoided in patients who experience high-energy blunt trauma but have normal vital signs. High-energy blunt trauma patients with normal vital signs were retrieved retrospectively from our registry. We reviewed 1317 patients (1027 men and 290 women) and 761 (57.8%) fulfilled the inclusion criteria. All patients were initially evaluated at the emergency room (ER), with a set of tests, part of a specific protocol. Patients with at least one altered exam at initial examination or after six-hour observation received a torso CECT. Sensitivity, specificity, accuracy, positive (PPV) and negative predictive values (NPV), and likelihood ratio (LH) of the protocol were evaluated. Of 761 patients, 354 (46.5%) received torso CECT because of the positive ER test, with 330 being true positive and 24 being false positive. The remaining 407 patients were negative at ER tests and did not receive torso CECT, showing a significantly (P

Objective: To describe a left epididymitis and para-aortical involvement caused by Mycobacterium tuberculosis hominis reactivation after bacillus Calmette-Guérin instillation for non-muscle-invasive bladder cancer. Patient and methods: A Caucasian male, aged 76 years, exposed to bacillus Calmette-Guérin for a high-grade non-muscle-invasive bladder cancer in 2015, reported painful and progressive left scrotal swelling with purulent discharge from a cutaneous fistulous track that yielded, on liquid culture, a pan-susceptible Mycobacterium tuberculosis hominis strain. Moreover, after 6 months of anti-tuberculosis treatment, an abdominal peri-aortic mass, sized 4 cm, was found and a surgical biopsy showed necrotizing granulomas; however, although smear microscopy and Xpert MTB/Rif™ performed on fresh biopsy sample were positive, liquid cultures resulted negative, indicating treatment efficacy. Results: Numerous peculiar and multi-organ involvement due to BCGitis after intravesical immunotherapy have been previously described, including 17 scientific articles about epididymitis, however, no reports so far showed reactivation of Mycobacterium tuberculosis hominis after bacillus Calmette-Guérin treatment. Conclusion: Although BCGitis is more prevalent in patients undergoing bacillus Calmette-Guérin instillation for non-muscle-invasive bladder cancer, tuberculosis by other species of Mycobacterium tuberculosis should be always ruled out by molecular and conventional microbiology in patients with a history of Mycobacterium tuberculosis hominis exposure.

Background Lower muscle mass is a known predictor of unfavorable outcome, but its prognostic impact on COVID-19 patients is unknown. Purpose To investigate the contribution of CT-derived muscle status in predicting clinical outcomes in COVID-19 patients. Materials and Methods Clinical/laboratory data and outcomes (intensive care unit [ICU] admission and death) were retrospectively retrieved for patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19, who underwent chest CT on admission in four hospitals in Northern Italy from February 21 to April 30, 2020. Extent and type of pulmonary involvement, mediastinal lymphadenopathy, and pleural effusion were assessed. Cross-sectional areas and attenuation of paravertebral muscles were measured on axial CT images at T5 and T12 vertebral level. Multivariable linear and binary logistic regression, including calculation odds ratios (OR) with 95% confidence intervals (CIs), were used to build four models to predict ICU admission and death, tested and compared using receiver operating characteristic curve (ROC) analysis. Results A total 552 patients (364 men; median age 65 years, interquartile range 54-75) were included. In a CT-based model, lower-than-median T5 paravertebral muscle area showed the highest ORs for ICU admission (OR 4.8, 95% CI 2.7-8.5; P

The purpose of this study was to compare the performance of gadobenate dimeglumine–enhanced MRI and gadoxetic acid–enhanced MRI in the hepatobiliary phase (HBP) in cirrhotic patients with different degrees of liver dysfunction. In this retrospective cross-sectional study, we analyzed the unenhanced phase and the HBP of 131 gadobenate dimeglumine–enhanced MRI examinations (gadobenate dimeglumine group) and 127 gadoxetic acid–enhanced MRI examinations (gadoxetic acid group) performed in 249 cirrhotic patients (181 men and 68 women; mean age, 64.8 years) from August 2011 to April 2017. For each MRI, the contrast enhancement index of the liver parenchyma was calculated and correlated to the Model For End-Stage Liver Disease (MELD) score (multiple linear regression analysis). A qualitative analysis of the adequacy of the HBP, adjusted for the MELD score (logistic regression analysis), was performed. The contrast enhancement index was inversely related (r = − 0.013) with MELD score in both gadoxetic acid and gadobenate dimeglumine group. At the same MELD score, the contrast enhancement index in the gadoxetic acid group was increased by a factor of 0.23 compared to the gadobenate dimeglumine group (p 10, if the hepatobiliary phase is clinically indicated. • In patients with high MELD score (> 15), the administration of the hepatobiliary agent could be useless; even though, if it is clinically indicated, we recommend to use gadoxetic acid given the higher probability of obtaining clinically relevant information.

Both abdominal obesity and its visceral component are independently associated with cardiometabolic diseases. Among the non-modifiable and modifiable determinants, lifestyle plays a central role, while chronotype is an emerging factor. Evening type (E-Type), more active and efficient in the last part of the day, has been associated with a health-impairing style, resulting in a higher risk of obesity and cardiometabolic diseases than morning type (M-Type). However, no study has examined the contribution of chronotype to abdominal fat distribution, even considering adherence to the Mediterranean diet (MD). We conducted a cross-sectional study on 416 adults (69.5% females, 50 &plusmn, 13 years). Waist circumference (WC), visceral fat (VAT) using ultrasonography, chronotype through the reduced Morningness-Eveningness Questionnaire (rMEQ), and adherence to MD were studied. Our results showed no differences in WC and VAT between chronotypes. However, adherence to MD resulted significantly lower in the E-Types compared to M-Types. WC decreased with increasing Mediterranean score and rMEQ score, and VAT decreased with increasing rMEQ score, indicating that E-Types have +2 cm of WC and +0.5 cm of VAT compared to M-Types. In conclusion, these results showed that chronotype is independently associated with abdominal obesity and visceral fat, underlining the potential implications of the individual circadian typology on abdominal obesity.

There is increasing evidence that myelin disruption is related to cognitive decline in Alzheimer's disease (AD). In the CNS, myelin is produced by oligodendrocytes, which are generated throughout life by adult oligodendrocyte progenitor cells (OPCs), also known as NG2-glia. To address whether alterations in myelination are related to age-dependent changes in OPCs, we analyzed NG2 and myelin basic protein (MBP) immunolabelling in the hippocampus of 3×Tg-AD mice at 6 and 24 months of age, compared with non-Tg age-matched controls. There was an age-related decrease in MBP immunostaining and OPC density, together with a decline in the number of OPC sister cells, a measure of OPC replication. Notably, the loss of myelin and OPC sister cells occurred earlier at 6 months in 3xTg-AD, suggesting accelerated aging, although there was not a concomitant decline in OPC numbers at this age, suggesting the observed changes in myelin were not a consequence of replicative exhaustion, but possibly of OPC disruption or senescence. In line with this, a key finding is that compared to age-match controls, OPC displayed marked morphological atrophy at 6 months in 3xTg-AD followed by morphological hypertrophy at 24 months, as deduced from significant changes in total cell surface area, total cell volume, somata volume and branching of main processes. Moreover, we show that hypertrophic OPCs surround and infiltrate amyloid-β (Aβ) plaques, a key pathological hallmark of AD. The results indicate that OPCs undergo complex age-related remodeling in the hippocampus of the 3xTg-AD mouse model. We conclude that OPC disruption is an early pathological sign in AD and is a potential factor in accelerated myelin loss and cognitive decline., Graphical abstract, Highlights • Life-long generation of myelin is the function of adult oligodendrocyte progenitor cells (OPCs). • Age-related loss of myelin is accelerated in the 3xTg-AD mouse model of Alzheimer's disease (AD). • OPCs are disrupted at an early stage of 3xTg-AD. • Dysregulation of OPC and myelin loss are important biomarkers for AD-like pathology.

The aim of this study was to develop and validate a machine learning algorithm to predict response of individual HER2-amplified colorectal cancer liver metastases (lmCRC) undergoing dual HER2-targeted therapy. Twenty-four radiomics features were extracted following 3D manual segmentation of 141 lmCRC on pre-treatment portal CT scans of a cohort including 38 HER2-amplified patients; feature selection was then performed using genetic algorithms. lmCRC were classified as non-responders (R-), if their largest diameter increased more than 10% at a CT scan performed following 3 months of treatment, responders (R+) otherwise. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values in correctly classifying individual lesion and overall patient response were assessed on a training dataset and then validated on a second dataset using a Gaussian naive bayesian classifier. Per-lesion sensitivity, specificity, NPV and PPV were 89%, 85%, 93%, 78% and 90%, 42%, 73%, 71% respectively in the testing and validation datasets. Per-patient sensitivity and specificity were 92% and 86%. Heterogeneous response was observed in 9 of 38 patients (24%). Five of the 9 patients were carriers of non-responder lesions correctly classified as such by our radiomics signature, including 4 of 7 harboring only one non-responder lesion. The developed method has been proven effective in predicting behavior of individual metastases to targeted treatment in a cohort of HER2 amplified patients. The model accurately detects responder lesions and identifies non-responder lesions in patients with heterogeneous response, potentially paving the way to multimodal treatment in selected patients. Further validation will be needed to confirm our findings. This article is protected by copyright. All rights reserved.

Background The aim of this study was to determine the relative frequency of primary cutaneous lymphoma (PCL) in Argentina according to the new World Health Organization (WHO)-European Organization for the Research and Treatment of Cancer (EORTC) classification system. Methods A total of 416 patients from 21 dermatology services were included during a 5-year period (2010-2015); these patients were classified using WHO-EORTC criteria. Results There were 231 (55.2%) males and 185 (44.8%) females; the male-to-female ratio was 1.35. The median age of the patients was 57 years (range, 0-90 years). Most patients were Caucasian (79%), and only 16% of patients were registered as Amerindian. Most patients (387/416, 93%) had cutaneous T-cell lymphoma (CTCL); 28 patients (6.7%) were diagnosed with cutaneous B-cell lymphoma (CBCL). The most frequent CTCL subtypes, in decreasing order of prevalence, were mycosis fungoides (MF), including its variants (75.7%); CD30+ primary cutaneous lymphoproliferative disorders (7.2%); and Sezary syndrome (SS) (3.1%). Cutaneous follicle center lymphoma was the most common CBCL subtype (2.9%). In the subset of patients ≤20 years of age, the most common condition was MF (57%), followed by extranodal NK-T nasal-type lymphoma (14%). Conclusions This study revealed relatively higher rates of MF and lower rates of CBCL in Argentinean patients that have been reported in American and European countries.

Recurrence of HCC reduces survival rates in patients treated with surgery, and one of the most relevant risk factors for tumour recurrence is microvascular invasion (mVI). The identification of mVI on preoperative examinations could improve surgical planning’s and techniques so as to reduce the risk of tumour recurrence. During our study, we have revised 101 CT examinations of the liver performed on patients diagnosed with solitary HCC who had surgical treatment and pathological analysis of the specimens for mVI in order to detect CT signs which could be reliable in mVI prediction. On CT examinations, the tumours were evaluated for margins, capsule, size, contrast enhancement, halo sign and Thad. From our statistical analysis, we found out that irregularity in tumour margins and defects in peritumoural capsule are the most significant characteristics predicting mVI in HCC. Every report on CT examinations performed on surgical candidate patients should include suggestions about mVI probability in order to tailor procedures, reduce tumour recurrence risk and improve survival rates.

Mycosis fungoides is the most common type of primary cutaneous T cell lymphoma. We have evaluated CDKN2A losses and MYC gains/amplifications by FISH analysis, as well as expression of miR-155 and members of the oncogenic cluster miR-17-92 (miR17, miR18a, miR19b, and miR92a) in MF patients with advanced disease. Formalin-fixed paraffin-embedded skin biopsies from 36 patients at diagnosis, 16 with tumoral MF (T-MF), 13 in histological transformation to a large T cell lymphoma (TR-MF), and 7 cases with folliculotropic variant (F-MF), were studied. Twenty cases showed genomic alterations (GAs): 8 (40 %) had CDKN2A deletion, 7 (35 %) showed MYC gain, and 5 (25 %) exhibited both alterations. GAs were more frequently observed in F-MF (p = 0.004) and TR-MF (p = 0.0001) than T-MF. GAs were significantly higher in cases presenting lesions in head, neck, and lower extremities compared to those observed in trunk and upper extremities (p = 0.03), when ≥25 % neoplastic cells were CD30 positive (p = 0.016) as well as in cases with higher Ki-67 proliferation index (p = 0.003). Patients with GAs showed bad response to treatment (p = 0.02) and short survival (p = 0.04). Furthermore, MF patients showed higher miRNA expression compared to controls (p ≤ 0.0223). T-MF showed higher miR17 and miR-18a expression compared to F-MF and TR-MF (p ≤ 0.0387) while miR19b, miR92a, and miR-155 showed increased levels in F-MF and TR-MF with respect to T-MF (p ≤ 0.0360). Increased expression of miR17 and miR19b in GA group compared to cases without alterations (p ≥ 0.0307) was also detected. Our results add new information about genomic imbalances in MF patients, particularly in F-MF, and extend the present view of miRNA deregulation in this disease.

aim: Adherence to the Mediterranean dietary pattern (MDP) is inversely related with abdominal adiposity as detected by waist circumference but the specific association to subcutaneous and visceral abdominal tissue has not been investigated. To this purpose we evaluated the association between MDP, visceral (VAT) and subcutaneous (SAT) abdominal tissue in a large sample of Italian adults.A cross-sectional study was carried out on 4388 consecutive adults (73.2% women) followed as outpatients at Nutritional Research Centre in Milan, ICANS. VAT and SAT were measured by ultrasonography. MDP was evaluated using a Mediterranean dietary score (MEDscore) obtained from a validated 14-item questionnaire.At multiple linear regression adjusted for sex, age, smoking and physical activity, a 1-unit increase in MEDscore was associated with a -0.118 kg/m(2) decrease in BMI (p0.01), a -0.292 cm decrease in waist circumference (p0.01), a -0.002 cm:cm decrease in waist to height ratio (p0.001), a -1.125 mm decrease in the sum of 4 skinfolds (p0.001), and with a -0.045 cm decrease in VAT (p0.05). MEDscore was, however, not associated with SAT. Finally, the adherence to the MDP was a protective factor for obesity (OR = 0.717, 95%CI: 0.555-0.922) and VAT excess (OR = 0.717, 95%CI: 0.530-0.971).Our study confirms the inverse association between MDP, BMI and waist circumference and adds that the association with abdominal obesity as detected by waist circumference is due to an association with VAT and not with SAT.

The aim of our study was to evaluate the sensitivity of contrast-enhanced magnetic resonance (CE-MR) with phased array coil in the diagnosis of local recurrence in patients with prostate cancer after radical prostatectomy and referred for salvage radiotherapy (SRT). This retrospective study included 73 patients treated with SRT after radical prostatectomy in the period between September 2006 and November 2017. All patients performed a CE-MRI with phased array coil before the start of SRT. A total of 213 patients treated at the ASST Grande Ospedale Metropolitano Niguarda in the period between September 2006 and November 2017 with SRT after radical prostatectomy were reviewed. Seventy-three patients with a CE-MRI with phased array coil of the pelvis before the start of SRT were included in the present study. At imaging review, recurrence local recurrent disease was diagnosed in 48 of 73 patients. By considering as reference standard the decrease in prostate-specific antigen (PSA) value after radiotherapy, we defined: 41 true positive (patients with MRI evidence of local recurrence and PSA value decreasing after SRT), 7 false positive (patients with MRI evidence of local recurrence without biochemical response after SRT), 3 true negative (patients without MRI evidence of local recurrence and stable or increased PSA value after SRT) and 22 false negative (patients without MRI evidence of local recurrence and PSA value decreasing after SRT) cases. The sensitivity values were calculated in relation to the PSA value before the start of treatment, obtaining a value of 74% for PSA above 0.2 ng/mL. The sensitivity of CE-MRI in local recurrence detection after radical prostatectomy increases with increasing PSA values. CE-MRI with phased array coil can detect local recurrences after radical prostatectomy with a good sensitivity in patients with pre-RT PSA value above 0.2 ng/mL.

To determine the relationship between multidetector computed tomography (MDCT) findings, management strategies, and ultimate clinical outcomes in patients with splenic injuries secondary to blunt trauma. This Institutional Review Board-approved study collected 351 consecutive patients admitted at the Emergency Department (ED) of a Level I Trauma Center with blunt splenic trauma between October 2002 and November 2015. Their MDCT studies were retrospectively and independently reviewed by two radiologists to grade splenic injuries according to the American Association for the Surgery of Trauma (AAST) organ injury scale (OIS) and to detect intraparenchymal (type A) or extraparenchymal (type B) active bleeding and/or contained vascular injuries (CVI). Clinical data, information on management, and outcome were retrieved from the hospital database. Statistical analysis relied on Student’s t, chi-squared, and Cohen’s kappa tests. Emergency multiphase MDCT was obtained in 263 hemodynamically stable patients. Interobserver agreement for both AAST grading of injuries and vascular lesions was excellent (k = 0.77). Operative management (OM) was performed in 160 patients (45.58% of the whole cohort), and high-grade (IV and V) OIS injuries and type B bleeding were statistically significant (p

Targeting HER2 is effective in 24% of ERBB2 amplified metastatic colorectal cancer; however, secondary resistance occurs in most of the cases. We studied the evolution of individual metastases during treatment to discover spatially resolved determinants of resistance. Circulating tumor DNA (ctDNA) analysis identified alterations associated with resistance in the majority of refractory patients. ctDNA profiles and lesion-specific radiographic reports revealed organ- or metastasis-private evolutionary patterns. When radiologic assessments documented progressive disease in target lesions, response to HER2 blockade was retained in other metastases. Genomic and functional analyses on samples and cell models from eight metastases of a patient co-recruited to a postmortem study unveiled lesion-specific evolutionary trees and pharmacologic vulnerabilities. Lesion size and contribution of distinct metastases to plasma ctDNA were correlated.

Introduction The aim of the present study was to compare the confocal and clinical features of newly diagnosed glaucoma patients receiving unpreserved prostaglandins (tafluprost) versus preserved prostaglandins (latanoprost). Materials and Methods 40 patients were randomized to tafluprost 0.0015% (20 patients; 32 eyes) or latanoprost 0.005% + benzalkonium chloride 0.02% (20 patients; 35 eyes) once daily for 1 year. Inclusion criteria were new glaucoma diagnosis, and no ocular treatments for 6 months before the study. Patients were evaluated at baseline and every 3 months with a complete ophthalmologic evaluation, Schirmer’s test, break-up time test, confocal microscopy of the central cornea, and measurement of intraocular pressure (IOP). Investigators were masked to treatment. Both eyes were analyzed if they fulfilled inclusion criteria. Treatments and changes between follow-up and baseline were compared by analysis of variance (ANOVA), t test and Chi-square test. Results At baseline, the two groups had similar age, ocular surface and confocal findings; keratocyte activation was present in 40%, branching pattern in 85%, and beading in 75%, with no inter-group differences. At follow-up, no significant clinical changes were detected, apart from a drop of IOP by 3.6–4.2 mmHg in the two groups (p

Summary Background We previously found that dual HER2 blockade with trastuzumab and lapatinib led to inhibition of tumour growth in patient-derived xenografts of HER2 -amplified metastatic colorectal cancer. In this study, we aimed to assess the antitumour activity of trastuzumab and lapatinib in patients with HER2-positive colorectal cancer. Methods HERACLES was a proof-of-concept, multicentre, open-label, phase 2 trial done at four Italian academic cancer centres. We enrolled adult patients with KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive metastatic colorectal cancer refractory to standard of care (including cetuximab or panitumumab), an Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion. We defined HER2 positivity in tumour samples by use of immunohistochemistry and fluorescence in-situ hybridisation in accordance with our previously validated colorectal cancer-specific diagnostic criteria. Eligible patients received intravenous trastuzumab at 4 mg/kg loading dose followed by 2 mg/kg once per week, and oral lapatinib at 1000 mg per day until evidence of disease progression. The primary endpoint was the proportion of patients achieving an objective response (defined as complete response or partial response), which was assessed by independent central review in the intention-to-treat population. This trial is registered with EudraCT, number 2012-002128-33. Findings Between Aug 27, 2012, and May 15, 2015, we screened 914 patients with KRAS exon 2 (codons 12 and 13) wild-type metastatic colorectal cancer and identified 48 (5%) patients with HER2-positive tumours, although two died before enrolment. Of these patients, 27 were eligible for the trial. All were evaluable for response. At the time of data cutoff on Oct 15, 2015, with a median follow-up of 94 weeks (IQR 51–127), eight (30%, 95% CI 14–50) of 27 patients had achieved an objective response, with one patient (4%, 95% CI −3 to 11) achieving a complete response, and seven (26%, 95% CI 9–43) achieving partial responses; 12 (44%, 95% CI 25–63) patients had stable disease. Six (22%) of 27 patients had grade 3 adverse events, which consisted of fatigue in four patients, skin rash in one patient, and increased bilirubin concentration in one patient. No grade 4 or 5 adverse events were reported. We detected no drug-related serious adverse events. Interpretation The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive metastatic colorectal cancer. Funding Associazione Italiana Ricerca Cancro (AIRC), Fondazione Oncologia Niguarda Onlus, and Roche.

The purpose of this study is to assess the dose of ionizing radiation caused by repeated CT scans performed to investigate non-traumatic acute abdominal conditions in young adults. Over 26 months, we collected a cohort of patients aged 18 to 45 years who were subject to at least one urgent contrast-enhanced abdomen/pelvis CT. Patients affected with urolithiasis, HIV infection, tumors, and vascular and chronic inflammatory bowel diseases were excluded. All abdomen/pelvis CT scans carried out at our institution for over 6 years were retrospectively tallied, and the effective doses (EDs) were computed by multiplying the total dose-length product by the appropriate anatomic conversion factor. Examples of age- and gender-adjusted lifetime attributable cancer risks were estimated using the online calculator Radiation Risk Assessment Tool. Sixty-one patients (average age 34.2 years) received multiple CT scans (average 2.7 scans per patient). ED largely varied among single- and multi-phase acquisitions. Cumulative ED ranged from 14.1 mSv to a maximum of 436.6 mSv (average 70.1 mSv per person). Twenty-five patients (40.9%) received more than 50 mSv, 84% of them within year; 12 (19.7%) and 4 (6.6%) patients received more than 100 and 200 mSv, respectively. Young adults are subject to repetitive CT imaging to monitor urogenital, intestinal, hepatobiliary, and pancreatic disorders during non-operative management to detect and follow up abdominal emergencies requiring surgical intervention and to assess post-surgical complications. In this population, the risk of accruing high cumulative radiation exposure should be considered.

Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value. We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s). From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36–86) and the median number of previous treatment lines was five (range 2–8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%). One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63–3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0–15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80–5.03] vs. 2.13 months [95% CI 1.77–2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17–9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33–10.80] vs. 7.18 months [95% CI 5.63–9.33], respectively, p = 0.06). This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment.

A Body Shape Index (ABSI) was specifically developed as a transformation of waist circumference (WC), statistically independent of BMI to better evaluate the relative contribution of WC to central obesity and clinical outcomes. Previous studies have found ABSI is associated with total mortality and cardiovascular events. However, no study has specifically evaluated the joint contribution of ABSI and BMI to cardio-metabolic outcomes (high triglycerides, low HDL, high fasting glucose and high blood pressure). With this aim, we performed a retrospective study on 6081 Caucasian adults. Subjects underwent a medical interview, anthropometric measurements, blood sampling, measurement of blood pressure, and measurement of visceral abdominal fat thickness (VAT) by ultrasound. Generalized linear models (GLM) were used to evaluate the sex and age adjusted association of ABSI with binary and continuous cardio-metabolic risk factors. Four pre-specified GLM were evaluated for each outcome: M1 = ABSI, BMI and ABSI*BMI interaction, M2 = ABSI and BMI, M3 = ABSI alone and M4 = BMI alone. Bayesian Information Criterion (BIC) was calculated and used to identify the best predictive model. ABSI and BMI contributed independently to all outcomes. Compared to BMI alone, the joint use of BMI and ABSI yielded significantly improved associations for having high triglycerides (BIC = 5261 vs. 5286), low HDL (BIC = 5371 vs. 5381), high fasting glucose (BIC = 6328 vs. 6337) but not high blood pressure (BIC = 6580 vs. 6580). The joint use of BMI and ABSI was also more strongly associated with VAT than BMI alone (BIC = 22930 vs. 23479). In conclusion, ABSI is a useful index for evaluating the independent contribution of WC, in addition to that of BMI, as a surrogate for central obesity on cardio-metabolic risk.

Typical haemolytic uraemic syndrome (HUS) is caused by Shiga toxin (Stx)- producing Escherichia coli infections and is characterized by thrombotic microangiopathy that leads to haemolytic anaemia, thrombocytopenia and acute renal failure. Renal or neurological sequelae are consequences of irreversible tissue damage during the acute phase. Stx toxicity and the acute inflammatory response raised by the host determine the development of HUS. At present there is no specific therapy to control Stx damage. The pathogenic role of reactive oxygen species (ROS) on endothelial injury has been largely documented. In this study, we investigated the in-vivo effects of Stx on the oxidative balance and its contribution to the development of HUS in mice. In addition, we analysed the effect of anti-oxidant agents as therapeutic tools to counteract Stx toxicity.We demonstrated that Stx induced an oxidative imbalance, evidenced by renal glutathione depletion and increased lipid membrane peroxidation. The increased ROS production by neutrophils may be one of the major sources of oxidative stress during Stx intoxication. All these parameters were ameliorated by anti-oxidants reducing platelet activation, renal damage and increasing survival. To conclude, Stx generates a pro-oxidative state that contributes to kidney failure, and exogenous antioxidants could be beneficial to counteract this pathogenic pathway. Fil: Gómez, Sonia Alejandra. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Abrey Recalde, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Panek, Cecilia Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Ferrarotti, Nidia Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina Fil: Repetto, Marisa Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mejias, María Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina

We show that detection, by week-2 magnetic resonance imaging, of tumor shrinkage >10% in response to therapy with cetuximab or panitumumab for metastatic colorectal carcinoma represents an early indicator of clinical outcome because it is predictive of the prolongation of progression-free survival and overall survival. Purpose: The early identification of patients with metastatic colorectal carcinoma who are likely to benefit from treatment with panitumumab or cetuximab remains of paramount importance. We evaluated whether the early tumor shrinkage assessed by magnetic resonance imaging (MRI) is predictive of long-term outcome to these epidermal growth factor receptor‐targeted therapies. Patients and Methods: Thirty-nine patients with chemorefractory metastatic colorectal carcinoma were treated with cetuximab or panitumumab. The patients were evaluated by unenhanced MRI at baseline, week 2, and week 8 after the beginning of the treatment and by contrast-enhanced computed tomography within 3 months. Early response was defined as a tumor shrinkage 10% at week-2 MRI, whereas response by contrast-enhanced computed tomography was defined according to standard Response Evaluation Criteria in Solid Tumors 1.1. Results: At week-2 MRI, 15 (38.5%) of 39 patients had an early response. Eleven (73.3%) of these 15 early responders then presented a partial response by contrast-enhanced computed tomography, whereas none of the 24 early nonresponders obtained a partial response (P .0005, Fisher exact test). Median progression-free survival (PFS) was 29.7 and 8 weeks in patients with or without early response, respectively (hazard ratio [HR] 0.156 [95% CI, 0.069-0.355]; P .0001)]. The median overall survival (OS) was 80 weeks in patients with early response and 23.3 weeks in those without early response, respectively (HR 0.154 [95% CI, 0.057-0.420]; P .00005]). Conclusions: Early detection of tumor response by week-2 MRI without contrast medium is associated with a prediction of clinical outcome in patients with metastatic colorectal carcinoma treated with cetuximab or panitumumab.

Background/Aims: Mutual interactions between portal vein and hepatic artery can be documented during hepatobiliary surgery. Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a recently introduced surgical technique which can also represent a unique living human model to investigate intrahepatic blood circulation. We report three consecutive cases in which a residual right portal branch flow was clearly detectable after first-step ALPPS, and try to further investigate this unexpected finding with intraoperative clamping tests. Methodology: Every patient was evaluated with CT scan 7 days after first-step ALPPS and Intraoperative Doppler Ultrasonography (IOUS) at both steps of the procedure. Results: In every patient, CT scan and second-step IOUS demonstrated a clear hepatopetal flow distally to the divided right portal branch. The flow was present after right biliary duct clamping and stopped after right total hilar clamping as well as after right hepatic artery occlusion. Conclusions: Neither cross-portal circulation between the two hemilivers nor trans-sinusoidal backflow from the hepatic veins can explain these findings, which are rather consistent with a refilling of the occluded portal branch through the opening of intrahepatic arterioportal shunts (APS). APS could represent the simplest homeostatic mechanism that regulate intrahepatic blood flow

Background The relative contribution of visceral (VAT) and subcutaneous (SAT) adipose tissue to cardiometabolic disease is controversial. The aim of this study was to evaluate whether dissecting abdominal fat in VAT and SAT using US may detect stronger and more specific association with MS, MS components, hyperuricemia and altered liver enzymes compared to waist circumference. Methods We performed a cross-sectional study on 2414 subjects aged 18 to 66 years (71 % women) followed at the International Center for the Assessment of Nutritional Status (ICANS, Milan, Italy). VAT and SAT were measured using ultrasonography. Multivariable logistic regression controlling for age and gender was used to evaluate the association of the parameters of interest (waist circumference (WC), VAT, SAT and VAT + SAT) with the MS (international harmonized definition), its components (high triglycerides, low HDL, high blood pressure, high glucose), high uric acid (≥7 mg/dl), high alanine transaminase (ALT, ≥ 30 U/l) and high gamma-glutamyl-transferase (GGT, ≥ 30 U/l). Results VAT was independently associated with all the outcomes of interest, while SAT was independently associated with MS and only with high blood pressure and high ALT when we considered the single parameters of MS and NAFLD. VAT had the strongest association with high triglycerides, high ALT and high GGT. The VAT + SAT association had the strongest association with MS. WC had the strongest association with low HDL and high blood pressure. VAT and WC were similarly associated to high glucose and high uric acid. Conclusion US-determined VAT and SAT are both independently associated with MS. Moreover, to our knowledge, we are the first to show that VAT, being associated to all of the MS components in addition to hyperuricemia and altered liver enzymes, performs equally or better than WC except for high blood pressure and low HDL. Electronic supplementary material The online version of this article (doi:10.1186/s12937-015-0120-2) contains supplementary material, which is available to authorized users.

To compare a contrast agent with high iodine concentration with an iso-osmolar contrast agent for coronary dual-source computed tomography angiography (DS-CTA), and to assess whether the contrast agent characteristics may affect the diagnostic quality of coronary DS-CTA.Patients were randomized to receive either 80 mL of iodixa:nol-320 (Visipaque, GE Healthcare, Chalfont St. Giles, United Kingdom) or iomeprol-400 (Iomeron, Bracco Imaging SpA, Milan, Italy) at 5 mL/s. Mean, minimum, maximum heart rate, and its variation (max-min) were assessed during calcium scoring scan and coronary DS-CTA. Three off-site readers independently evaluated the image sets in terms of technical adequacy, reasons for inadequacy, vessel visualization, diagnostic confidence (based on a 5-point scale), and arterial contrast opacification in Hounsfield units (HUs).Ninety-six patients were included in the final evaluation. No significant differences were observed for pre- and postdose heart rate values for iomeron-400 compared with iodixanol-320, and changes in heart rate variation were also not significantly different (-2.3 ± 11.7 vs. -2.5 ± 7.3 bpm, P0.1). Contrast measurements in all analyzed vessels were significantly higher for iomeprol-400 (mean, 391.5-441.4 HU) compared with iodixanol-320 (mean, 332.3-365.5 HU, all P ≤ 0.0038). There was no significant difference in qualitative visualization of coronary arteries (mean scores, 4.3-4.5 for iomeprol, 4.1-4.3 for iodixanol, P = 0.15-0.28), or in diagnostic confidence scores. HU were inversely correlated with the number of insufficiently opacified segments (all readers P ≤ 0.0006).The high-iodine concentration contrast medium iomeprol-400 demonstrated significant benefit for coronary arterial enhancement compared with the iso-osmolar contrast medium iodixanol-320 when administered at identical flow rates and volumes for coronary DS-CTA. In addition, higher enhancement levels were found to be associated with lower numbers of inadequately visualized segments. Finally, observed mean heart rate changes after intravenous contrast injection were generally small during the examination and comparable for both agents.

Interleukin (IL)-1β plays a crucial role in the mechanisms of limbic seizures in rodent models of temporal lobe epilepsy. We addressed whether activation of the IL-1β signaling occurs in rats with genetic absence epilepsy (GAERS) during the development of spike-and-wave discharges (SWDs). Moreover, we studied whether inhibition of IL-1β biosynthesis in GAERS could affect SWD activity. IL-1β expression and glia activation were studied by immunocytochemistry in the forebrain of GAERS at postnatal days (PN)14, PN20, and PN90 and in age-matched non-epileptic control Wistar rats. In PN14 GAERS, when no SWDs have developed yet, IL-1β immunostaining was undetectable, and astrocytes and microglia showed a resting phenotype similar to control Wistar rats. In 3 out of 9 PN20 GAERS, IL-1β was observed in activated astrocytes of the somatosensory cortex; the cytokine expression was associated with the occurrence of immature-type of SWDs. In all adult PN90 GAERS, when mature SWDs are established, IL-1β was observed in reactive astrocytes of the somatosensory cortex but not in adjacent cortical areas or in extra-cortical regions. An age-dependent c-fos activation was found in the somatosensory cortex of GAERS with maximal levels reached in PN90 rats; c-fos was also induced in some thalamic nuclei in PN20 and PN90 GAERS. Inhibition of IL-1β biosynthesis in PN90 GAERS by 4-day systemic administration of a specific ICE/Caspase-1 blocker, significantly reduced both SWD number and duration. These results show that IL-1β is induced in reactive astrocytes of the somatosensory cortex of GAERS at the onset of SWDs. IL-1β has pro-ictogenic properties in this model, and thus it may play a contributing role in the mechanisms underlying the occurrence of absence seizures.

The evaluation of defense mechanisms represents one of the most promising fields in the psychodynamic-oriented empirical research on personality disorders (PDs). This study examines the association between DSM-IV PDs and defense mechanisms. We evaluated a sample of 50 adult outpatients seeking personality assessment and psychotherapeutic treatment. PDs have been assessed using the Structured Clinical Interview for DSM-IV Personality Disorder, version 2.0. Defense mechanisms have been evaluated by a group of trained clinical psychologists and psychiatrists (interrater reliability from .61 to .95) using Perry's Defense Mechanism Rating Scale. Our results support the hypothesis that some defense mechanisms underlie PDs and that defenses call for further attention as we assess PDs.

Objective: To verify whether features of CNS involvement can be detected in SLE patients without overt neuropsychiatric manifestations.Methods: 114 SLE patients who had never received a diagnosis of neuropsychiatric lupus (never NPSLE) were studied and compared to 65 SLE patients with known neuropsychiatric involvement (NPSLE). The study relied on evaluation of neurocognitive functions by means of a battery of neuropsychological tests, on psychiatric and neuropsychological assessments and on neuroimaging studies (computed tomography, magnetic resonance, single photon emission computed tomography (SPECT)).Results: Clinical features, including disease duration/activity and pharmacological therapy, of never-NPSLE and NPSLE patients were similar. Short-term and long-term memory, visuo-spatial and verbal information processing were similarly compromised in never-NPSLE and in NPSLE patients; only attention was significantly more compromised in NPSLE patients. Psychiatric morbidity was higher than expected in never-NPSLE patients, although less than in the control neuropsychiatric group. Ischemic lesions, multiple small high intensity lesions and cortical atrophy, detected by CT and MR scans, as well as abnormal SPECT were also frequently detected in never NPSLE patients. Interestingly, left parietal and occipital area hypoperfusion by SPECT was significantly more frequent in the patients with impaired visuo-spatial intelligence and short-term memory.Conclusions: Most abnormalities detected by available diagnostic tools and characteristics of neuropsychiatric SLE are also present in non-symptomatic patients. They may derive from an unexpected widespread involvement of the CNS and are not per se sufficient, in the absence of clinical manifestations, for a diagnosis of neuropsychiatric SLE.

A common clinical practice during single-point Doppler analysis is to measure the centerline maximum velocity and to recover the time-averaged flow rate by exploiting an assumption on the shape of velocity profile (a priori formula), either a parabolic or a flat one. In a previous study, we proposed a new formula valid for the peak instant linking the maximum velocity and the flow rate by including a well-established dimensionless fluid-dynamics parameter (the Womersley number), in order to account for the hemodynamics conditions (Womersley number-based formula). Several in silico tests confirmed the reliability of the new formula. Nevertheless, an in vivo confirmation is missing limiting the clinical applicability of the formula. An experimental in vivo protocol using cine phase-contrast MRI (2-D PCMRI) technique has been designed and applied to ten healthy young volunteers in three different arterial districts: the abdominal aorta, the common carotid artery, and the brachial artery. Each PCMRI dataset has been used twice: 1) to compute the value of the blood flow rate used as a gold standard and 2) to estimate the flow rate by measuring directly the maximum velocity and the diameter (i.e., emulating the intravascular Doppler data acquisition) and by applying to these data the a priori and the Womersley number-based formulae. All the in vivo results have confirmed that the Womersley number-based formula provides better estimates of the flow rate at the peak instant with respect to the a priori formula. More precisely, mean performances of the Womersley number-based formula are about three times better than the a priori results in the abdominal aorta, five times better in the common carotid artery, and two times better in the brachial artery.

OBJECTIVE: The aim of our study was to assess the accuracy of color Doppler imaging in diagnosing the involvement of peripancreatic vessels by pancreatic carcinoma. SUBJECTS AND METHODS: We prospectively evaluated the color Doppler images of 61 patients with pancreatic carcinoma. Our evaluations occurred before surgery and focused on vascular involvement. Absence of contact or a short contiguity (< or = 2 cm) between tumors and peripancreatic vessels was considered to be a sign of resectability on color Doppler imaging; a long contiguity (> 2 cm), compression, encasement, or thrombosis was considered to be a sign of unresectability. In all patients, the sonographic diagnosis was compared with the surgical results. RESULTS: With color Doppler imaging, we detected signs of vascular involvement in 26 of 33 patients in whom vascular involvement was found at surgery. We detected no vascular involvement in 25 of 28 patients in whom no vascular involvement was found at surgery. No false-positive diagnoses occurred when vascular encasement was revealed by color Doppler imaging. For diagnosis of vascular involvement, the sensitivity, specificity, and overall accuracy of color Doppler imaging were 79%, 89%, and 84%, respectively; positive and negative predictive values were 89% and 79%, respectively. CONCLUSION: Color Doppler imaging is a sensitive and highly specific technique in assessing vascular involvement by pancreatic cancer when absence of contact or vascular encasement is seen. When vascular encasement is detected by color Doppler imaging, a definitive diagnosis of unresectability can be made, and further diagnostic procedures can be avoided. When sonography is used in the initial evaluation of pancreatic cancer, color Doppler imaging can improve the selection of patients for further diagnostic examinations or surgical exploration.

Purpose We evaluated the usefulness of dynamic enhanced magnetic resonance imaging (MRI) in the staging of superficial tumors following a bolus administration of gadopentetate dimeglumine. Materials and Methods In 48 patients with proved bladder tumors the results of preoperative plain spin echo T1 (repetition time/echo time 500/20 msec.) and T2 (repetition time/echo time 2,000/40 to 100 msec.)-weighted MRI, dynamic gadolinium-enhanced MRI (repetition time/echo time 200/15 msec.) and late gadolinium-enhanced MRI (repetition time/echo time 500/20 msec.) were compared and correlated with the histopathological findings. Results Unenhanced spin echo T1 and T2-weighted MRI sequences were able to stage correctly 14 (56 percent) and 17 (68 percent) of 25 superficial bladder cancers, respectively. Muscular infiltration (stages pT2 and pT3a) was correctly depicted in 3 (27 percent) and 6 (54 percent) of 11 cases respectively, with over staging being the most frequent error. On the basis of the dynamic gadolinium-enhanced T1-weighted MRI appearance, superficial involvement of the bladder wall was correctly assessed in 21 of 25 cases (84 percent) and muscular infiltration (stages pT2 to pT3a) in 7 of 11 (63 percent). Delayed enhanced T1-weighted sequences showed a low accuracy rate in staging superficial tumors (44 percent). The overall accuracy of T1 and T2-weighted, dynamic T1-weighted and delayed T1-weighted MRI in staging bladder cancer was 58, 71, 81 and 56 percent, respectively. Conclusions The use of gadolinium improved the accuracy of dynamic enhanced MRI in staging superficial bladder cancer. On the contrary, delayed enhanced MRI was not useful for staging superficial bladder cancer. The degree of bladder distension was a determinant factor in staging superficial tumors.

The purpose of this study was to evaluate the sensitivity of percutaneous computed tomography (CT)-guided lung biopsy in the early diagnosis of fungal pulmonary infections. Between 1997 and 2003, 18 haematologically immunodeficient patients with suspected filamentous fungi infection and negative bronchoalveolar lavage (BAL) underwent percutaneous pulmonary biopsy to diagnose the nature of the infection. In all cases, infection developed during the post-chemotherapy bone marrow aplasia period. Thirteen out of 18 patients had histologic findings positive for fungal infection: 8 Aspergillus and 5 Mucor. In 3 cases, biopsy was not specific, and in one case, the tissue sample was inadequate for a diagnosis; however, clinical course and response to drugs were compatible with fungal infection. In one patient, biopsy was positive for bronchoalveolar carcinoma. The sensitivity of percutaneous CT-guided biopsy was 80% and its positive predictive value was 100%. We only had one pneumothorax as a complication. Percutaneous CT-guided lung biopsy is an easy, safe and reliable procedure to obtain diagnostic material. Histological discrimination between Aspergillus and Mucor is important in order to plan the correct therapeutic protocols, as Mucor is usually resistant to azoles.

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

Objective: To evaluate the performance of magnetic resonance (MR) and multidetector computed tomography (MDCT) in the assessment of living donor's vascular and biliary anatomy, having surgical findings as reference standard. Methods: Thirty-two living liver donors underwent MR cholangiography (1.5-T; standard cholangiography pulse sequences and delayed acquisitions after administration of biliary contrast agent) for biliary anatomy evaluation. MDCT (16-row multidetector scanner, multiphase protocol, 3 mm slice thickness) was also performed in all cases for the assessment of vascular anatomy before transplantation. Hepatic veins (

Background: Combined use of dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) allows a precise estimate of regional body composition and intra-abdominal adipose tissue (IAT). Data on body composition in HIV-infected children (HIV+) receiving highly active antiretroviral therapy (HAART) with (LD+) and with (LD-) lipodystrophy are lacking. Methods: DXA scans were performed in 34 HIV+: six LD+ 28 LD- and 34 pair-matched (age sex and body mass index) healthy controls (HC): six for LD+ (HC+) and 28 for LD- (HC-). MRI scans were performed in 16 HIV+: six LD+ 10 LD- and 16 pair-matched (age and sex) HC. Data were analysed by analysis of variance post hoc Fisher test and Mann-Whitney test. Results: LD+ and LD- were similar for: previous exposure to zidovudine/zidovudine + didanosine months on HAART (stavudine + lamuvidine + one protease inhibitor) CD4+ cells patients with HIV-RNA < 50 copies/ml. In HIV+ and HC fat mass and distribution were significantly different whereas lean mass was comparable. Thus LD+ and LD- as compared to HC+ and HC- respectively showed: 1. reduced fat amount and percentage; 2. lower truncal fat mass; 3. markedly reduced limbs fat mass. Within the HIV+ group 4. LD+ showed higher fat trunk/fat total (P = 0.04) and lower fat limbs/fat total ratios (P = 0.009) than LD-; 5. LD+ showed larger IAT areas than LD- and HC (P < 0.0003). Conclusions: Increased central fat and peripheral lipoatrophy are distinctive features of all HAART-treated children. Changes in body fat composition are detectable by DXA even in the absence of signs of Lipodystrophy. Only LD+ show true central obesity. (authors)

The natural history and management of gastric lymphomas of mucosa-associated lymphoid tissue (MAL Tomas) are not completely understood. Most stage I cases are now entered into prospective trials to confirm the excellent results obtained with conservative treatment, whereas current therapeutic policies are based on accumulated experience. The limits of staging work-ups may have a significant impact on prospective trials and ordinary clinical practice. The authors explore the sensitivity of computed tomography scanning in detecting perigastric adenopathy in 20 patients with gastric MALToma treated by gastrectomy. Clinical staging identified 17 patients as having stage I MALTomas and three patients as having stage II 1 MALTomas. Histopathologic staging showed that 8 of 17 patients formerly diagnosed with stage I MALToma had perigastric nodal involvement, whereas the three patients with clinical stage II 1 were confirmed as such. Computed tomography scanning has low sensitivity in detecting perigastric lymphadenopathy in gastric MAL Tomas. This leads to understaging, with a significant impact on therapeutic decision, and distorts newly acquired knowledge about the disease's natural history and management, introducing a bias in prospective clinical trials. Endoscopic ultrasonography should be tested as a staging procedure both in prospective trials and in ordinary clinical practice.

OBJECTIVE: The purpose of this study was to assess the diagnostic performance of MDCT in the detection of hepatocellular carcinoma in patients with cirrhosis undergoing orthotopic liver transplantation. MATERIALS AND METHODS: Eighty-eight consecutively registered patients who underwent MDCT 6 months before liver transplantation were evaluated. The original reports were analyzed, and the CT images were retrospectively reevaluated independently by two radiologists who made the final interpretation in consensus. The imaging findings were correlated with histopathologic findings in the explanted livers on a patient-by-patient and a lesion-by-lesion basis. RESULTS: Histopathologic examination revealed 139 hepatocellular carcinomas in 48 of the 88 patients. MDCT correctly depicted 89 of 139 hepatocellular carcinomas (sensitivity, 64%) at the original examination and 102 at reevaluation (sensitivity, 73.3%). Patient-by-patient analysis showed a specificity of 75% in the original reports and of 77.5% at reevaluation. A large number of false-positive nodules were found, most (59.2%) of them being smaller than 1 cm in diameter. CONCLUSION: MDCT has reasonable sensitivity in the detection of hepatocellular carcinoma in patients with cirrhosis who undergo liver transplantation. Attention should be paid, however, to avoiding overestimation of the extent of disease.

The highest rate of complications characterizing the adult living donor liver transplantation (ALDLT) are due to biliary problems with a reported negative incidence of 22-64%. We performed 23 ALDLT grafting segments V-VIII without the middle hepatic vein from March 2001 to September 2005. Biliary anatomy was investigated using intraoperative cholangiography alone in the first five cases and magnetic resonance cholangiography in the remaining 18 cases. In 13 cases we found a single right biliary duct (56.5%) and in 10 we found multiple biliary ducts (43.7%). We performed single biliary anastomosis in 17 cases (73.91%) and double anastomosis in the remaining six (26%) cases. With a mean follow up of 644 days (8-1598 days), patient and graft survivals are 86.95% and 78.26%, respectively. The following biliary complications were observed: biliary leak from the cutting surface: three, anastomotic leak: two, late anastomotic strictures: five, early kinking of the choledochus: one. These 11 biliary complications (47.82%) occurred in eight patients (34.78%). Three of these patients developed two consecutive and different biliary complications. Biliary complications affected our series of ALDLT with a high percentage, but none of the grafts transplanted was lost because of biliary problems. Multiple biliary reconstructions are strongly related with a high risk of complication. © 2006 The Authors

The authors describe a new CT finding associated with the hypoperfusion complex in children: complete lack of enhancement of both kidneys without renal swelling, without subcapsular cortical rim enhancement, and without peripheral wedge-shaped areas of hypoattenuation. This "black kidney sign" was found in two severely injured children who died within a few hours after the CT examination. It may help to establish a diagnosis of severe hemodynamic instability and may be a negative prognostic factor.

To investigate magnetic resonance imaging (MRI) characteristics of hepatic epithelioid hemangionendothelioma (HEH).The study was exempted from formal Ethics Committee approval due to its retrospective and noninvasive nature. Eleven patients with histology-proven HEH were collected from six different institutions in a 5-year time period. In all patients a contrast-enhanced MR study was available. Two experienced reviewers in consensus retrospectively noted potential MR findings of HEH. Reviewers separately analyzed morphological findings, tumor signal intensity, HEH contrast enhancement pattern, and tumor appearance on hepatobiliary phase and diffusion-weighted imaging (DWI). The frequency of various findings was calculated.The most frequent presentation was a peripheral distribution of the lesions (72.7%), target appearance on T2-weighted images (63.6%), low signal intensity on T1-weighted images (63.6%), ring or target-like enhancement at dynamic study (63.6%), and coalescence of nodules and capsular retraction (45.4%). Lack of hepatobiliary enhancement (5/8 patients) or "entrapment" hepatobiliary enhancement (3/8 patients) as well as target appearance at DWI (5/6 patients) was also observed in our series.Although quite variable imaging appearances were seen, a target appearance on the T2-weighted image, ring or target enhancement at dynamic study, lack of enhancement or "entrapment" at hepatobiliary phase, and target appearance on DWI are frequent findings of HEH.

PURPOSE: To compare color Doppler ultrasonography (US) with fast, breath-hold, three-dimensional, gadolinium-enhanced magnetic resonance (MR) angiography in detecting renal arterial stenosis. MATERIALS AND METHODS: Forty-five patients with clinical suspicion of renovascular disease were prospectively examined with intra- and extrarenal color Doppler US and breath-hold, gadolinium-enhanced MR angiography. Digital subtraction arteriography (DSA) was the standard of reference in all patients for the number of renal arteries and degree of stenosis. RESULTS: DSA depicted 103 arteries and 52 stenoses. Color Doppler US was nondiagnostic in two examinations. Significantly more of 13 accessory renal arteries were detected with MR angiography (n = 12) than with color Doppler US (n = 3; P

To assess the potential role of magnetic resonance (MR) imaging in the follow-up evaluation of small hepatocellular carcinoma (HCC) treated with percutaneous ethanol injection (PEI), 31 patients with a single HCC lesion less than 3.0 cm in diameter underwent MR imaging at 0.5 T before and after treatment. Posttreatment follow-up included contrast material-enhanced computed tomography (CT) and fine-needle biopsy in all cases. The most important characteristic of the treated HCC lesions was hypointensity on T2-weighted MR images in cases (27 of 31) in which complete tumor necrosis was achieved with PEI. This feature corresponded to a nonenhanced, low-attenuation area on follow-up contrast-enhanced CT scans. Four HCCs were positive for malignant cells at 6-month fine-needle biopsy; in these lesions, residual tumor tissue was of high signal intensity on T2-weighted MR images and of high attenuation on contrast-enhanced CT scans. In each case, incomplete tumor necrosis was confirmed at pathologic examination of the surgical specimen.

Insulin resistance is the best prediction factor for the clinical onset of type 2 diabetes. It was suggested that intramuscular triglyceride store may be a primary pathogenic factor for its development. To test this hypothesis, 14 young lean offspring of type 2 diabetic parents, a model of in vivo insulin resistance with increased risk to develop diabetes, and 14 healthy subjects matched for anthropomorphic parameters and life habits were studied with 1) euglycemic-hyperinsulinemic clamp to assess whole body insulin sensitivity, 2) localized 1H nuclear magnetic resonance (NMR) spectroscopy of the soleus (higher content of fiber type I, insulin sensitive) and tibialis anterior (higher content of fiber type IIb, less insulin sensitive) muscles to assess intramyocellular triglyceride content, 3) 13C NMR of the calf subcutaneous adipose tissue to assess composition in saturated/unsaturated carbons of triglyceride fatty acid chains, and 4) dual X-ray energy absorption to assess body composition. Offspring of diabetic parents, notwithstanding normal fat content and distribution, were characterized by insulin resistance and increased intramyocellular triglyceride content in the soleus (P < 0.01) but not in the tibialis anterior (P = 0.19), but showed a normal content of saturated/unsaturated carbons in the fatty acid chain of subcutaneous adipocytes. Stepwise regression analysis selected intramyocellular triglyceride soleus content and plasma free fatty acid levels as the main predictors of whole body insulin sensitivity. In conclusion, 1H and 13C NMR spectroscopy revealed intramyocellular abnormalities of lipid metabolism associated with whole body insulin resistance in subjects at high risk of developing diabetes, and might be useful tools for noninvasively monitoring these alterations in diabetes and prediabetic states.

Objective: Pulmonary emphysema is frequently associated with lung cancer and, because of the impaired pulmonary function involved, it may contraindicate surgical treatment. However, improvement of pulmonary function has been observed after surgical resection in patients with advanced emphysema. The aim of this study was to evaluate whether pulmonary emphysema, as assessed by pulmonary function tests and radiological evaluation, can influence postoperative respiratory function after lobectomy for non-small cell lung cancer (NSCLC). Methods: Respiratory function was evaluated before and after lobectomy for NSCLC, Radiological evaluation of emphysema was performed on chest X-ray and CT scan. Patients that had undergone chemo- or radiotherapy or had segmental or lobar atelectasis were excluded from the study. Results: Thirty-five patients entered the study. A decrease in static lung volumes was observed after surgery. Total lung capacity (TLC) decreased from 6.58 +/- 0.92 to 5.46 +/- 0.77 1; functional residual capacity (FRC) from 3.70 +/- 0.88 to 2.96 +/- 0.73 1 and residual volume (RV) from 2.93 +/- 0.78 to 2.2 +/- 0.53 1. However, in a subgroup of 10 patients (Group 1), dynamic volumes after surgery were unchanged or slightly increased (forced vital capacity (FVC) from 3.23 +/- 0.65 to 3.3 +/- 0.68 1; forced expiratory volume in 1 s (FEV 1) from 2.14 +/- 0.51 to 2.25 +/- 0.54 1), and airway resistances (sRaw) decreased from 15.58 +/- 5.18 to 11.42 +/- 5.25 cm H2O/s. Preoperative data showed that these patients had a greater obstruction, with FEV1 changing from 69 +/- 12.42 to 72.70 +/- 13.72% of predicted, as compared with a change from 87 +/- 12.7 to 72.08 +/- 13.10% in the other group of 25 patients (Group 2). Correlation analysis reached statistical significance between FEV1% variation (Delta FEV1%) and preoperative FEV1 and FVC% (r = -0.49, P = 0.002 and r = -0.5, P = 0.001, respectively) and between Delta (FEV1)% and radiological scores for 3-level CT (r = 0.39, P = 0.04) and the sum of chest X-ray, single and 3-level CT scores (r = 0.49, P = 0.01). Conclusions: Pulmonary function may remain unchanged or even increase after lobectomy in patients with a pronounced emphysematous component of airway obstruction. The identification of preoperative parameters that identify this group of patients could extend the indications for the treatment of lung cancer in patients with pulmonary emphysema. (C) 1999 Published by Elsevier Science B.V. All rights reserved.

Purpose: To prospectively compare the image quality and diagnostic performance achieved with doses of gadobenate dimeglumine and gadopentetate dimeglumine of 0.1 mmol per kilogram of body weight in patients undergoing contrast material-enhanced magnetic resonance (MR) angiography of the pelvis, thigh, and lower-leg (excluding foot) for suspected or known peripheral arterial occlusive disease. Materials and Methods: Institutional review board approval was granted from each center and informed written consent was obtained from all patients. Between November 2006 and January 2008, 96 patients (62 men, 34 women; mean age, 63.7 years +/- 10.4 [standard deviation]; range, 39-86 years) underwent two identical examinations at 1.5 T by using three-dimensional spoiled gradient-echo sequences and randomized 0.1-mmol/kg doses of each agent. Images were evaluated on-site for technical adequacy and quality of vessel visualization and offsite by three independent blinded readers for anatomic delineation and detection/exclusion of pathologic features. Comparative diagnostic performance was determined in 31 patients who underwent digital subtraction angiography. Data were analyzed by using the Wilcoxon signed-rank, McNemar, and Wald tests. Interreader agreement was determined by using generalized k statistics. Differences in quantitative contrast enhancement were assessed and a safety evaluation was performed. Results: Ninety-two patients received both agents. Significantly better performance (P < .0001; all evaluations) with gadobenate dimeglumine was noted on-site for technical adequacy and vessel visualization quality and offsite for anatomic delineation and detection/exclusion of pathologic features. Contrast enhancement (P < .0001) and detection of clinically relevant disease (P < .0028) were significantly improved with gadobenate dimeglumine. Interreader agreement for stenosis detection and grading was good to excellent (k = 0.749 and 0.805, respectively). Mild adverse events were reported for four (six events) and five (eight events) patients after gadobenate dimeglumine and gadopentetate dimeglumine, respectively. Conclusion: Higher- quality vessel visualization, greater contrast enhancement, fewer technical failures, and improved diagnostic performance are obtained with gadobenate dimeglumine, relative to gadopentetate dimeglumine, when compared intraindividually at 0.1-mmol/kg doses in patients undergoing contrast-enhanced MR angiography for suspected peripheral arterial occlusive disease. (c) RSNA, 2010