Anti-Ro/SSA Antibodies Blocking Calcium Channels as a Potentially Reversible Cause of Atrioventricular Block in Adults.

BACKGROUND: In ∼50% of severe atrioventricular blocks (AVBs) occurring in adults <50 years, the underlying etiology remains unknown. Preliminary evidence from case reports suggests that autoimmunity, specifically the presence of circulating anti-Ro/SSA antibodies in the patient (acquired form), in the patient's mother (late-progressive congenital form), or in both (mixed form), could be involved in a fraction of idiopathic AVBs in adults by possibly targeting the L-type calcium channel (Cav1.2) and inhibiting the related current (ICaL). OBJECTIVES: The purpose of this study was to evaluate whether anti-Ro/SSA antibodies are causally implicated in the development of isolated AVBs in adults. METHODS: Thirty-four consecutive patients with isolated AVB of unknown origin and 17 available mothers were prospectively enrolled in a cross-sectional study. Anti-Ro/SSA antibodies were assessed by fluoroenzyme-immunoassay, immuno-Western blotting, and line-blot immunoassay. Purified immunoglobulin-G (IgG) from anti-Ro/SSA-positive and anti-Ro/SSA-negative subjects were tested on ICaL and Cav1.2 expression using tSA201 and HEK293 cells, respectively. Moreover, in 13 AVB patients, the impact of a short course of steroid therapy on AV conduction was evaluated. RESULTS: Anti-Ro/SSA antibodies, particularly anti-Ro/SSA-52kD, were found in 53% of AVB-patients and/or in their mothers, most commonly an acquired or mixed form (two-thirds of cases) without history of autoimmune diseases. Purified IgG from anti-Ro/SSA-positive but not anti-Ro/SSA-negative AVB patients acutely inhibited ICaL and chronically down-regulated Cav1.2 expression. Moreover, anti-Ro/SSA-positive sera showed high reactivity with peptides corresponding to the Cav1.2 channel pore-forming region. Finally, steroid therapy rapidly improved AV conduction in AVB-patients with circulating anti-Ro/SSA antibodies but not in those without. CONCLUSIONS: Our study points to anti-Ro/SSA antibodies as a novel, epidemiologically relevant and potentially reversible cause of isolated AVB in adults, via an autoimmune-mediated functional interference with the L-type calcium channels. These findings have significant impact on antiarrhythmic therapies by avoiding or delaying pacemaker implantation.

Left Ventricular Mass with Delayed Enhancement as a Predictor of Major Events in Patients with Myocarditis with Preserved Ejection Fraction.

Background: Cardiac Magnetic Resonance (CMR) has a key role in subjects presenting with acute myocarditis, independent from left ventricular ejection fraction; it is widely used as a non-invasive imaging test for both diagnostic and prognostic purposes. However, poor data is available about the CMR-derived prognostic parameters of acute myocarditis with preserved ejection fraction (AMpEF). The aim of this study was to investigate the role of CMR in predicting outcomes in patients followed up for AMpEF, using a composite endpoint of all-cause mortality and hospitalization for heart failure (HF). Methods: We retrospectively enrolled 61 patients with diagnosed AMpEF. All patients underwent biohumoral, echocardiographic and CMR evaluation in the acute phase. Myocarditis was confirmed by Lake-Louis criteria assessed on CMR images. Mean follow-up was 4.8 ± 0.6 years during which a composite endpoint of all-cause mortality and hospitalization for HF was investigated. Results: The population was fairly homogeneous regarding baseline clinical features. In particular, no significant differences in age and main cardiovascular risk factors were found between patients with and without events at follow-up. Seven patients met the endpoint. They had significantly higher levels of circulating neutrophils in the acute phase (76 ± 7% vs. 61 ± 11%, p = 0.014) and a higher amount of left ventricular mass with delayed enhancement (DE-LVM, 18 (14-29.5) vs. 12 (8-16) g, p = 0.028). At Cox univariate analysis, DE-LVM was the only significant predictor of endpoint, regardless of the site of inflammation. Conclusions: DE-LVM can predict the composite endpoint of all-cause mortality and hospitalization for HF in a population of patients with AMpEF, representing a new added tool for prognostic stratification.

Ability of Delta Radiomics to Predict a Complete Pathological Response in Patients with Loco-Regional Rectal Cancer Addressed to Neoadjuvant Chemo-Radiation and Surgery.

We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodological item able to predict the frequency of complete pathological responses and, consequently, the outcome of patients with locally advanced rectal cancer addressed to neoadjuvant chemoradiotherapy (C-RT) and subsequently, to radical surgery. In particular, we carried out a retrospective analysis including 100 patients with locally advanced rectal adenocarcinoma who received C-RT and then radical surgery in three different oncological institutions between January 2013 and December 2019. Our experimental design was focused on the evaluation of the gross tumor volume (GTV) at baseline and after C-RT by means of MRI, which was contoured on T2, DWI, and ADC sequences. Multiple texture parameters were extracted by using a LifeX Software, while D-TA was calculated as percentage of variations in the two time points. Both univariate and multivariate analysis (logistic regression) were, therefore, carried out in order to correlate the above-mentioned TA parameters with the frequency of pathological responses in the examined patients' population focusing on the detection of complete pathological response (pCR, with no viable cancer cells: TRG 1) as main statistical endpoint. ROC curves were performed on three different datasets considering that on the 21 patients, only 21% achieved an actual pCR. In our training dataset series, pCR frequency significantly correlated with ADC GLCM-Entropy only, when univariate and binary logistic analysis were performed (AUC for pCR was 0.87). A confirmative binary logistic regression analysis was then repeated in the two remaining validation datasets (AUC for pCR was 0.92 and 0.88, respectively). Overall, these results support the hypothesis that D-TA may have a significant predictive value in detecting the occurrence of pCR in our patient series. If confirmed in prospective and multicenter trials, these results may have a critical role in the selection of patients with locally advanced rectal cancer who may benefit form radical surgery after neoadjuvant chemoradiotherapy.

Combined Use of Voltage Mapping and Speckle-tracking Analysis for the Characterization of Arrhythmogenic Right Ventricular Cardiomyopathy: A Case Report.

A 38-year-old man was admitted to our hospital after ventricular tachycardia. Endocardial bipolar and unipolar voltage mapping were performed and findings were integrated with data from intracardiac echocardiography (ICE) right ventricular (RV) speckle-tracking analysis. A reduction in the strain analysis was stored in correspondence of the fragmented electrogram area. The definitive diagnosis was arrhythmogenic RV cardiomyopathy (ARVC). The integration of ICE-derived RV strain and voltage mapping could represent a successful strategy to improve the results of ablation in ARVC.

Radiomics predicts survival of patients with advanced non-small cell lung cancer undergoing PD-1 blockade using Nivolumab.

Immune checkpoint blockade is an emerging anticancer strategy, and Nivolumab is a human mAb to PD-1 that is used in the treatment of a number of different malignancies, including non-small cell lung cancer (NSCLC), kidney cancer, urothelial carcinoma and melanoma. Although the use of Nivolumab prolongs survival in a number of patients, this treatment is hampered by high cost. Therefore, the identification of predictive markers of response to treatment in patients is required. In this context, PD-1/PDL1 blockade antitumor effects occur through the reactivation of a pre-existing immune response, and the efficacy of these effects is strictly associated with the presence of necrosis, hypoxia and inflammation at the tumour sites. It has been indicated that these events can be evaluated by specific assessments using a computed tomography (CT) texture analysis (TA) or radiomics. Therefore, a retrospective study was performed, which aimed to evaluate the potential use of this analysis in the identification of patients with NSCLC who may benefit from Nivolumab treatment. A retrospective analysis was performed of 59 patients with metastatic NSCLC who received Nivolumab treatment between January 2015 and July 2017 at Siena University Hospital (35 patients, training dataset), Catanzaro University Hospital and Reggio Calabria Grand Metropolitan Hospital, Italy (24 patients, validation dataset). Pre- and post-contrast CT sequences were used to contour the gross tumour volume (GTV) of the target lesions prior to Nivolumab treatment. The impact of variations on contouring was analysed using two delineations, which were performed on each patient, and the TA parameters were tested for reliability using the Intraclass Coefficient Correlation method (ICC). All analyses for the current study were performed using LifeX Software©. Imaging, clinical and pathological parameters were correlated with progression free survival and overall survival (OS) using Kaplan Meier analysis. An external validation testing was performed for the TA Score using the validation dataset. A total of 59 patients were included in the analysis of the present study. The reliability ICC analysis of 14 TA parameters indicated a highly reproducibility (ICC >0.70, single measure) in 12 (85%) pre- contrast and 13 (93%) post-contrast exams. A specific cut-off was detected for each of the following parameters: volume (score 1 >36 ml), histogram entropy (score 1 > 1.30), compacity (score 1 <3), gray level co-occurrence matrix (GLCM)-entropy (score 1 >1.80), GLCM-Dissimilarity (score 1 >5) and GLCM-Correlation (score 1<0.54). The global texture score allowed the classification of two subgroups of Low (Score 0-1; 36 patients; 61%) and High Risk patients (Score >1; 23 patients; 39%) that respectively, showed a median OS of 26 (mean +/- SD: 18 +/- 1.98 months; 95% CI 14-21 months) and 5 months (mean +/- SD: 6 +/- 0.99 months; 95% CI: 4-8 months; P=0.002). The current study indicated that TA parameters can identify patients that will benefit from PD-1 blockage by defining the radiological settings that are potentially suggestive of an active immune response. These results require further confirmation in prospective trials.

Magnetic Resonance Imaging in Pregnancy with Intrauterine Growth Restriction: A Pilot Study.

OBJECTIVE: Intrauterine growth restriction (IUGR) is a major cause of late stillbirth, though not all compromised babies remain small or are considered growth restricted as pregnancy progresses. Fetal Magnetic Resonance Imaging (f-MRI) represents a second-line tool to study pregnancies with IUGR fetuses. The aim of our study was to evaluate the usefulness of f-MRI on predicting fetal growth and the offspring's perinatal respiratory outcome. DESIGN: All f-MRI performed between 2014 and 2016 in Siena were analysed. Pregnancies with IUGR (Study group (SG)) were recruited together with a control population (Control group (CG)), coupled for gestational age (GA) at the time of f-MRI (mean GA 31 wks). Neonatal information was collected. The f-MRI protocol consisted of T2w images. Six regions of interest (ROI) were placed as follows: 2 on the lung, 2 on the liver, and 2 on the amniotic fluid. The signal intensities (SI) of each ROI were measured. The SI lung to liver ratio (SI lung/liver) and SI lung to amniotic fluid ratio (SI lung/amniotic fluid) were obtained for each fetus. Each ratio was compared between SG and CG. Therefore, SG was divided into two subgroups: adequate and small for gestational age (AGA and SGA) newborns. All measurements were related to offspring's perinatal respiratory outcome. RESULTS: SI lung/liver was linearly related with GA at the time of f-MRI and with EFW. SI lung/amniotic fluid was significantly higher in SG than in CG (p = 0,014). In contrast, among SG, lower values of SI lung/amniotic fluid were found in the SGA compared to AGA (p = 0,036). The days of oxygen supply were higher in the SGA subgroup than in the AGA subgroup (p = 0,028). CONCLUSIONS: SI lung/liver increases with fetal lung maturation and appears to be useful to estimate intrauterine fetal growth. SI lung/amniotic fluid seems to be a reliable predictive index to distinguish the IUGR fetuses that can recover their growth from those that were born SGA. f-MRI represents a promising frontier to predict IUGR fetus outcome, thus contributing to ameliorate the perinatal management.

Magnetic-Resonance-Imaging Texture Analysis Predicts Early Progression in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiation.

BACKGROUND: We hypothesized that texture analysis (TA) from the preoperative MRI can predict early disease progression (ePD), defined as the percentage of patients who relapsed or showed distant metastasis within three months from the radical surgery, in patients with locally advanced rectal cancer (LARC, stage II and III, AJCC) undergoing neoadjuvant chemoradiotherapy (C-RT). METHODS: This retrospective monoinstitutional cohort study included 49 consecutive patients in total with a newly diagnosed rectal cancer. All the patients underwent baseline abdominal MRI and CT scan of the chest and abdomen to exclude distant metastasis before C-RT. Texture parameters were extracted from MRI performed before C-RT (T1, DWI, and ADC sequences) using LifeX Software, a dedicated software for extracting texture parameters from radiological imaging. We divided the cohort in a training set of 34 patients and a validation set of 15 patients, and we tested the data sets for homogeneity, considering the clinical variables. Then we performed univariate and multivariate analysis, and a ROC curve was also generated. RESULTS: Thirteen patients (26.5%) showed an ePD, three of whom with lung metastases and ten with liver relapse. The model was validated based on the prediction accuracy calculated in a previously unseen set of 15 patients. The prediction accuracy of the generated model was 82% (AUC = 0.853) in the training and 80% (AUC = 0.833) in the validation cohort. The only significant features at multivariate analysis was DWI GLCM Correlation (OR: 0.239, p < 0.001). CONCLUSION: Our results suggest that TA could be useful to identify patients that may develop early progression.

Cardiac Magnetic Resonance Normal Reference Values of Biventricular Size and Function in Male Athlete's Heart.

OBJECTIVES: The aim of this meta-analysis was to derive normal reference values of biventricular size and function estimated by cardiac magnetic resonance (CMR) in competitive athletes. BACKGROUND: Exercise-induced enlargement of cardiac chambers is commonly observed in competitive athletes. However, ventricular dilatation is also a common phenotypic expression of life-threatening cardiomyopathies. The use of CMR for the exclusion of pathology is growing. However, normal reference values have not been established for athletes. METHODS: The authors conducted a systematic review of English-language studies in the MEDLINE, Scopus, and Cochrane databases investigating biventricular size and function by CMR in athletes. Athletes were divided into endurance, combined, and mixed groups according to the sport practiced. The potential impact of training volume was also evaluated. RESULTS: Twenty-seven studies and 983 competitive athletes were included for CMR quantification of biventricular size and function. In this review, normal reference values are presented for biventricular size and function to be applied to male competitive athletes according to the disciplines practiced. A significant impact of training volume was demonstrated for the right ventricle: athletes practicing the largest number of training hours per week were those exhibiting the greatest degree of right ventricular remodeling. Notably, biventricular function was not significantly affected by training volume. CONCLUSIONS: The present meta-analysis defines the normal limits of biventricular size and function estimated by CMR in competitive athletes. The authors suggest using these normal reference values as an alternative to standard upper limits derived from the general population when interpreting CMR images in athletes.

3D bone texture analysis as a potential predictor of radiation-induced insufficiency fractures.

BACKGROUND: The aim of our work is to assess the potential role of texture analysis (TA), applied to computed tomography (CT) simulation scans, in relation to the development of insufficiency fractures (IFs) in patients undergoing radiation therapy (RT) for pelvic malignancies. METHODS: We analyzed patients undergoing pelvic RT from Jan-2010 to Dec-2016, 31 of whom had developed IFs of the pelvis. We analyzed CT simulation scans using LifeX Software©, and in particular we selected three regions of interest (ROI): L5 body, the sacrum and both the femoral heads. The ROI were automatically contoured using the treatment planning software Raystation©. TA parameters included parameters from the gray-level histogram, indices from sphericity and from the matrix of GLCM (gray level co-occurrence matrix). The IFs patients were matched (1:1 ratio) with control patients who had not developed IFs, and were matched for age, sex, type of tumor, menopausal status, RT dose and use of chemotherapy. Univariate and multivariate analyses (logistic regression) were used for statistical analysis. RESULTS: Significant TA parameters on univariate analysis included both parameters from the histogram distribution, as well from the matrix of GLCM. On logistic regression analysis the significant parameters were L5-energy [P=0.033, odds ratio (OR): 1.997, 95% CI: 1.059-3.767] and FH-Skewness (P=0.014, OR: 2.338, 95% CI: 1.191-4.591), with a R2: 0.268. A ROC curve was generated from the binary logistic regression, and the AUC was 0.741 (95% CI: 0.627-0.855, P=0.001, S.E.: 0.058). CONCLUSIONS: In our experience, 3D-bone CT TA can be used to stratify the risk of the patients to develop radiation-induced IFs. A prospective study will be conducted to validate these findings.

Epidermal Growth Factor Receptor Expression Predicts Time and Patterns of Recurrence in Patients with Glioblastoma After Radiotherapy and Temozolomide.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the potential role of epidermal growth factor receptor (EGFR) protein expression in predicting the modality of treatment failure in glioblastoma (GB). METHODS: Patients with unifocal GB undergoing surgery and postoperative radiochemotherapy from February 2008 to July 2015 were included into the study. The EGFR protein expression level was assessed by immunohistochemistry in GB tissues and classified into high and low expression. Time to progression (TTP) and pattern of recurrence (PR) were evaluated. PRs were classified as central, in-field, marginal, or distant recurrences. RESULTS: After a median follow-up time of 13 months (range, 6-67 months), 102 patients (79.1%) showed recurrences that were detectable on magnetic resonance imaging. Median TTP was 9 months after the completion of radiochemotherapy. EGFR expression was significantly correlated with TTP (log-rank test, P = 0.003) and PR (Fisher exact test, P = 0.01). The low-EGFR group had a median TTP of 13 months and a prevalence of central/in-field recurrences (accounting to a total 81%). The high-EGFR group had a shorter median TTP (6 months) and a higher rate of marginal/distant recurrences (55.6%). CONCLUSIONS: Different modality of recurrence related to EGFR expression in patients with GB envisages implication for target contouring of radiotherapy volumes and other therapeutic strategies.

Perilesional edema in brain metastasis from non-small cell lung cancer (NSCLC) as predictor of response to radiosurgery (SRS).

Radiosurgery (SRS) is widely used in the treatment of brain oligo-metastases from NSCLC. The aim of present study is to evaluate the extent of perilesional edema in brain metastases as predictive factor of treatment response. This single center retrospective study included 42 consecutive patients (January 2011-December 2014) with 1-2 brain metastasis from NSCLC treated with Radiosurgery (SRS). Extent of perilesional edema was measured as maximal extension from the edge of lesion and classified as minor (<10 mm) or major (≥10 mm). We analyzed Modality of Brain Recurrence (MBR), classified as in-field or out-of- field, and Brain Progression Free-Survival (BPFS) after treatment stratified according to extent of perilesional edema. Analyzing modality of brain recurrence and BPFS, after a median follow-up of 6 months, we found that patients with minor edema had a better radiological response to SRS with none in-field recurrences and a lower risk of the onset of new brain lesions (out-of-field recurrence). Instead, patients group with major edema had a worse response rate of lesions treated, further, a higher risk of out-of-field brain relapse. Extent of perilesional edema in brain metastasis from NSCLC could be a predictive factor of response and brain progression after SRS treatment alone.

Phase I trial of thymidylate synthase poly-epitope peptide (TSPP) vaccine in advanced cancer patients.

Thymidylate synthase (TS) poly-epitope peptide (TSPP) is a 27-mer peptide vaccine containing the amino acidic sequences of three epitopes with HLA-A2.1-binding motifs of TS, an enzyme overexpressed in cancer cells, which plays a crucial role in DNA repair and replication. Based on the results of preclinical studies, we designed a phase Ib trial (TSPP/VAC1) to investigate, in a dose escalation setting, the safety and the biological activity of TSPP vaccination alone (arm A) or in combination with GM-CSF and IL-2 (arm B) in cancer patients. Twenty-one pretreated metastatic cancer patients, with a good performance status (ECOG ≤ 1) and no severe organ failure or immunological disease, were enrolled in the study (12 in arm A, nine in arm B) between April 2011 and January 2012, with a median follow-up of 28 months. TSPP resulted safe, and its maximal tolerated dose was not achieved. No grade 4 toxicity was observed. The most common adverse events were grade 2 dermatological reactions to the vaccine injection, cough, rhinitis, fever, poly-arthralgia, gastro-enteric symptoms and, to a lesser extent, moderate hypertension and hypothyroidism. We detected a significant rise in auto-antibodies and TS-epitope-specific CTL precursors. Furthermore, TSPP showed antitumor activity in this group of pretreated patients; indeed, we recorded one partial response and seven disease stabilizations (SD) in arm A, and three SD in arm B. Taken together, our findings provide the framework for the evaluation of the TSPP anti-tumor activity in further disease-oriented clinical trials.

Traditional and innovative echocardiographic parameters for the analysis of right ventricular performance in comparison with cardiac magnetic resonance.

AIMS: Right ventricle fractional area change (RVFAC), tissue Doppler and M-mode measurements of tricuspid systolic motion [tricuspid Sm and tricuspid annular plane systolic excursion (TAPSE)], and 3D echocardiography are the current non-invasive methods for the quantification of RV systolic function; RV deformation analysis by speckle-tracking echocardiography (STE) has recently allowed the analysis of RV performance. Using cardiac magnetic resonance (CMR) as the reference standard, this study aimed at exploring the correlation between the traditional (fractional shortening, s'RV, TAPSE) and innovative (strain) echocardiographic parameters and RV ejection fraction (RVEF) measured by CMR. METHODS AND RESULTS: CMR and transthoracic echo-Doppler were performed in 63 patients referred for clinical assessment. Twenty-one presented the suspicion of myocarditis, 8 presented idiopathic dilated cardiomyopathy, 10 hypertrophic cardiomyopathy, 10 arrhythmogenic right ventricular dysplasia (ARVD), 5 infiltrative cardiomyopathy, and 9 other reasons. RVEF was measured by magnetic resonance imaging (MRI). RVFAC, tricuspid S', and TAPSE were calculated in all patients. RV longitudinal strain (RVLS) by STE was assessed by averaging RV free-wall segments (free-wall RVLS) and by averaging all segments (global RVLS). The ROC analysis was applied for the assessment of diagnostic accuracy. Good correlations were found for TAPSE, tricuspid S', and global RVLS with RVEF (r = 0.45, r = 0.52, and r = -0.71, respectively; P = 0.01 for all). Close correlations between free-wall RVLS and RVFAC with RVEF were found (r = -0.86 and r = 0.77, respectively; P < 0.0001 for both). Furthermore, free-wall RVLS demonstrated the highest diagnostic accuracy [area under curve (AUC) 0.92] and good sensitivity and specificity of 96 and 93%, respectively, to predict reduced RVEF <45%, using a cut-off value of less than -17.0%. CONCLUSION: In a heterogeneous group of patients referred to CMR evaluation, conventional (TAPSE, FAC, and tricuspid S') and novice (2D speckle-tracking-derived longitudinal strain) parameters of RV systolic function were compared and correlated with RVEF measured by MRI. All tested parameters were found to be independent predictors of reduced RVEF (<45%), but the strongest correlation was seen for the RV free-wall longitudinal strain.

Diffusion-weighted magnetic resonance diagnosis of local recurrences of prostate cancer after radical prostatectomy: preliminary evaluation on twenty-seven cases.

OBJECTIVES: To assess the diagnostic performance of diffusion-weighted MR imaging (DWI) in patients affected by prostatic fossa (PF) relapse after radical prostatectomy (RP) for prostatic carcinoma (PC). METHODS: Twenty-seven patients showing a nodular lesion in the PF at T2-weighted MR imaging after RP, with diagnosis of PC relapse established by biopsy or PSA determinations, were investigated by DWI. Two readers evaluated the DWI results in consensus and the apparent diffusion coefficient (ADC) of the nodules, separately; a mean value was obtained (ADCm). RESULTS: Relapses did not significantly differ in size in respect of postsurgical benign nodules. The DWI qualitative evaluation showed sensitivity, specificity, accuracy, ppv, and npv values, respectively, of 83.3%, 88.9%, 85.2%, 93.7%, and 72.7% (100%, 87.5%, 95.6%, 93.7%, and 100%, for nodules >6 mm). The intraclass correlation coefficient (ICC) for ADC evaluation between the two readers was 0.852 (95% CI 0.661-0.935; P = 0.0001). The ADCm values for relapses and benign nodules were, respectively, 0.98 ± 0.21 × 10(-3) mm(2)/sec and 1.24 ± 0.32 × 10(-3) mm(2)/sec (P = 0.006). Sensitivity, specificity, accuracy, ppv and npv of ADCm were, respectively, 77.8%, 88.9%, 81.8%, 93.3%, and 66.7% (93.3%, 87.5%, 85.4%, 93.3%, and 87.5% for nodules >6 mm). CONCLUSIONS: Diffusion-weighted MR imaging is a promising tool in the management of a hyperintense nodule detected by T2-weighted sequences. This might have a relevant importance in contouring radiotherapy treatment volumes.

MSCT multi-criteria: a novel approach in assessment of mediastinal lymph node metastases in non-small cell lung cancer.

PURPOSE: To evaluate the accuracy of multi-slice computed tomography (MSCT) in diagnosing mediastinal lymph node metastases in patients with non-small cell lung cancer (NSCLC) using a multi-criteria approach. METHODS: We retrospectively reviewed contrast-enhanced MSCT of the chest in 86 consecutive patients with histopathologically proven NSCLC. All patients underwent surgical lymph node resection within 30 days from the CT examination. In all cases pathological and CT results were reviewed and correlated. RESULTS: The sensitivity, specificity, positive and negative predictive values, and accuracy of MSCT using a multi-criteria approach in the detection of the N2 stage were 100%, 98.5%, 100%, 94.4% and 98.8% respectively, whereas using the size criterion alone 64%, 61%, 87%, 40%, and 62% respectively. CONCLUSIONS: To improve MSCT accuracy for diagnosing N staging other criteria can be associated with lymph node size. The use of different dimensional cut-offs for each mediastinal lymph node station, the matching of positive nodal stations with tumour location, the structural characteristics and the type of enhancement allow for a high accuracy of MSCT in the staging of mediastinal nodes in NSCLC.

Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab and has strong antitumor activity in advanced non-small-cell-lung cancer patients.

BACKGROUND: We designed a translational clinical trial to investigate whether a dose/dense chemotherapy regimen is able to enhance in patients with non-small-cell-lung-cancer (NSCLC) the anti-angiogenic effects of bevacizumab, a murine/human monoclonal antibody to the vasculo-endothelial-growth-factor (VEGF). We also evaluated the antitumor activity of this combination. RESULTS: The combined treatment induced a significant decline in the blood-perfusion of primary tumor (NMR-study); in serum levels of VEGF, angiopoietin-1, thrombospondin-1; and in the number of VEGF-transporting cells. In the group of 40 patients who received bevacizumab an objective response and a disease stabilization rate of 77.5% (95% CI, 75.63-93.17) and 15%, respectively, were recorded with a time to progression of 7.6 mo. Grade I-II hematological toxicity was the most common adverse event. Four early deaths within 3 mo, three cases of pneumonia, and six cases of mood depression at higher bevacizumab dosage were observed. The most active biological and maximum tolerated dose were 5 and 7.5 mg/kg, respectively. PATIENTS AND METHODS: Forty-eight patients (42 males and six females) with stage III B/IV NSCLC, a mean age of 68 y, and ECOG

Magnetic resonance imaging in the evaluation of the gastric emptying and antral motion: feasibility and reproducibility of a fast not invasive technique.

PURPOSE: The aim of this study was to evaluate reproducibility of a fast MRI protocol to measure gastric emptying and motility of the gastric antrum. METHODS AND MATERIALS: Gastric emptying and antral speed were measured in 12 type 1 diabetic patients (mean age 43 years) and 9 healthy volunteers (mean age 31 years). Subjects, fasting from 6h, were evaluated in supine position using a 1.5T MR scanner and a eight-channels phased-array body coil after ingestion of 400 ml of a vanillas pudding mixed with 5 ml of Gd-DTPA. Axial 3D T1w sequence at 0 and 30 min for volume evaluation and cine-steady state acquisition every 5 min for a total time of 30 min for gastric wave speed assessing were acquired. Two blinded observers extrapolated T(1/2) from gastric volume assessment and speed of gastric waves. RESULTS: All the patients tolerated the examination. The T(1/2) cut-off was of 115 min with an accuracy in differentiate controls from diabetics of 96% (95% CI 0.766-0.992; p<0.001), while the antral speed cut-off was of 0.15 mm/s with an accuracy of 87% (95% CI 0.628-0.977; p<0.001). The inter-observer agreement for the volumes at time 0 and 30 min was respectively 0.983 (95% CI 0.9628-0.9929; p<0.001) and 0.9933 (95% CI 0.9847-0.9971; p<0.001) with an agreement of 0.9918 (95% CI 0.9853-0.9954; p<0.001), while for antral speed it was of 0.935 (95% CI 0.9097-0.9528; p<0.001). CONCLUSIONS: MRI is a reproducible technique for the evaluation of gastric emptying and antral motility.