Τετάρτη 22 Νοεμβρίου 2017
Leveraging Mega-trends in Medicine Today to Enhance Patient Care in Radiology Tomorrow
Source:Academic Radiology
Author(s): Andrew B. Rosenkrantz
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Selecting Cases for Resident Interpretation to Enhance the Teaching Experience
Source:Academic Radiology
Author(s): Ronald L. Eisenberg
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Performance of Ultrafast DCE-MRI for Diagnosis of Prostate Cancer
Source:Academic Radiology
Author(s): Aritrick Chatterjee, Dianning He, Xiaobing Fan, Shiyang Wang, Teodora Szasz, Ambereen Yousuf, Federico Pineda, Tatjana Antic, Melvy Mathew, Gregory S. Karczmar, Aytekin Oto
Rationale and ObjectivesThis study aimed to test high temporal resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for different zones of the prostate and evaluate its performance in the diagnosis of prostate cancer (PCa). Determine whether the addition of ultrafast DCE-MRI improves the performance of multiparametric MRI.Materials and MethodsPatients (n = 20) with pathologically confirmed PCa underwent preoperative 3T MRI with T2-weighted, diffusion-weighted, and high temporal resolution (~2.2 seconds) DCE-MRI using gadoterate meglumine (Guerbet, Bloomington, IN) without an endorectal coil. DCE-MRI data were analyzed by fitting signal intensity with an empirical mathematical model to obtain parameters: percent signal enhancement, enhancement rate (α), washout rate (β), initial enhancement slope, and enhancement start time along with apparent diffusion coefficient (ADC) and T2 values. Regions of interests were placed on sites of prostatectomy verified malignancy (n = 46) and normal tissue (n = 71) from different zones.ResultsCancer (α = 6.45 ± 4.71 s−1, β = 0.067 ± 0.042 s−1, slope = 3.78 ± 1.90 s−1) showed significantly (P < .05) faster signal enhancement and washout rates than normal tissue (α = 3.0 ± 2.1 s−1, β = 0.034 ± 0.050 s−1, slope = 1.9 ± 1.4 s−1), but showed similar percentage signal enhancement and enhancement start time. Receiver operating characteristic analysis showed area under the curve for DCE parameters was comparable to ADC and T2 in the peripheral (DCE 0.67–0.82, ADC 0.80, T2 0.89) and transition zones (DCE 0.61–0.72, ADC 0.69, T2 0.75), but higher in the central zone (DCE 0.79–0.88, ADC 0.45, T2 0.45) and anterior fibromuscular stroma (DCE 0.86–0.89, ADC 0.35, T2 0.12). Importantly, combining DCE with ADC and T2 increased area under the curve by ~30%, further improving the diagnostic accuracy of PCa detection.ConclusionQuantitative parameters from empirical mathematical model fits to ultrafast DCE-MRI improve diagnosis of PCa. DCE-MRI with higher temporal resolution may capture clinically useful information for PCa diagnosis that would be missed by low temporal resolution DCE-MRI. This new information could improve the performance of multiparametric MRI in PCa detection.
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Sonographic Criteria Predictive of Malignant Thyroid Nodules
Source:Academic Radiology
Author(s): Carlos Miguel Oliveira, Rui Alves Costa, Miguel Patrício, Amélia Estêvão, Bruno Graça, Filipe Caseiro-Alves
Rationale and ObjectivesThe objective of this study was to evaluate the ultrasound features of thyroid nodules and their association with malignancy, focusing on establishing feature-oriented ultrasound criteria to determine proper management of a thyroid nodule.Materials and MethodsA sample of 379 thyroid nodules were biopsied (from a total of 357 patients aged 59.8 ± 14.8 years) and 300 were included in the final study (271 benign nodules and 29 malignant ones). Ultrasound features were recorded for each nodule: size, echogenicity, homogeneity, contours, shape, texture, peripheral halo, calcifications, and the presence of adenopathy. Statistical analysis of the data was performed using the Mann-Whitney U test and chi-square test. The sensitivity and the specificity of variables seen to have a statistically significant association with the malignancy of nodules were assessed and a logistic regression was performed.ResultsA taller-than-wide shape, an ill-defined contour, the presence of a halo, microcalcifications, and adenopathy were found to have a statistically significant relationship (P < 0.05) with malignancy, although with a low sensitivity and a high specificity. The presence of at least one suspicious feature yields great sensitivity (89.7%) in detecting malignant disease.ConclusionsThe ultrasound features of thyroid nodules alone do not allow the radiologist to make a confident diagnosis regarding the malignancy of a nodule without performing a biopsy. However, a nodule showing a taller-than-wide shape, microcalcifications, a peripheral halo, an ill-defined contour, or associated adenopathy should be considered for cytology.
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Shear Wave Elastography (SWE) for Monitoring of Treatment of Tendinopathies
Source:Academic Radiology
Author(s): Timm Dirrichs, Valentin Quack, Matthias Gatz, Markus Tingart, Björn Rath, Marcel Betsch, Christiane K. Kuhl, Simone Schrading
Rationale and ObjectivesWe aimed to investigate the diagnostic accuracy with which shear wave elastography (SWE) can be used to monitor response to treatment of tendinopathies, and to compare it to conventional ultrasound (US)-imaging methods (B-mode US (B-US) and power Doppler US (PD-US)).Materials and MethodsA prospective Institutional Review Board-approved longitudinal study on 35 patients with 47 symptomatic tendons (17 Achilles-, 15 patellar-, and 15 humeral-epicondylar) who underwent standardized multimodal US and standardized clinical assessment before and after 6 months of treatment (tailored stretching exercise, sport break, and local Polidocanol) was carried out. All US studies were performed by radiologists blinded to the clinical symptoms on both tendon sides to avoid biased interpretations, by B-US, PD-US, and SWE, conducted in the same order, using a high-resolution linear 15 MHz probe (Aixplorer). Orthopedic surgeons who were in turn blinded to US imaging results used established orthopedic scores (Victorian Institute of Sports Assessment questionnaire for Achilles, Victorian Institute of Sports Assessment questionnaire for patellar tendons, and Disability Arm Shoulder Hand scoring system) to rate presence, degree, and possible resolution of symptoms. We analyzed the diagnostic accuracy with which the different US imaging methods were able to detect symptomatic tendons at baseline as well as treatment effects, with orthopedic scores serving as reference standard.ResultsB-US, PD-US, and SWE detected symptomatic tendons with a sensitivity of 66% (31 of 47), 72% (34 of 47), and 87.5% (41 of 47), respectively. Positive predictive value was 0.67 for B-US, 0.87 for PD-US, and 1 for SWE. After treatment, clinical scores improved in 68% (32 of 47) of tendons. Treatment effects were observable by B-US, PD-US, and SWE with a sensitivity of 3.1% (1 of 32), 28.1% (9 of 32), and 81.3% (26 of 32), respectively. B-US was false-positive in 68.8% (20 of 32), PD-US in 46.9% (15 of 32), and SWE in 12.5% (4 of 32) (SWE). Clinical scores and B-US, PD-US, and SWE findings correlated poorly (r = 0.24), moderately (r = 0.59), and strongly (r = 0.80).ConclusionUnlike B-US or PD-US, SWE is able to depict processes associated with tendon healing and may be a useful tool to monitor treatment effects.
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The Current State of Radiology Call Assistant Triage Programs Among US Radiology Residency Programs
Source:Academic Radiology
Author(s): Jennifer Shaffer Ngo, Charles M. Maxfield, Gary R. Schooler
Rationale and ObjectivesGiven increasing volume and workflow interruptions in radiology, we sought to identify and characterize radiology call assistant triage (RCAT) programs among US radiology residency programs.Materials and MethodsA survey was created using Qualtrics survey software and emailed to all members of the Association of Program Directors in Radiology listserv. A total of 296 active members belong to this listserv, including program directors and assistant program directors. The survey included questions about the existence and specifics of a call triage assistant program.ResultsData were obtained from 88 active members of the Association of Program Directors in Radiology (30% response rate). Of those, 20 programs (23%) have an RCAT program. Triage assistant staffing includes nonmedical or clerical staff (60%), medical students (30%), first-year radiology residents (5%), and technologists (5%). All respondents with RCAT programs report satisfaction with their program and plan to continue. A significant majority (75%) have no plans to change, whereas the remaining 25% are considering program expansion and pay increases. Among residency programs without RCAT programs, none reported termination of their triage program. The most common reasons for not having triage assistants include cost, lack of awareness, differing opinions on utility, and the presence of 24/7 attending coverage.ConclusionTwenty US radiology residency programs report having an RCAT program. All report satisfaction with their program despite different staffing models. RCAT programs may represent an effective measure in limiting interruptions and potentially decreasing interpretative errors made by residents on call.
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Extreme widening of asymmetric giant cystic Virchow-Robin spaces
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Effect of Age on High T1 Signal Intensity of the Dentate Nucleus and Globus Pallidus in a Large Population Exposed to Gadodiamide.
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Effect of Age on High T1 Signal Intensity of the Dentate Nucleus and Globus Pallidus in a Large Population Exposed to Gadodiamide.
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Editorial Board
Source:Radiotherapy and Oncology, Volume 125, Issue 2
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Contents
Source:Radiotherapy and Oncology, Volume 125, Issue 2
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Global impact of radiotherapy in oncology: Saving one million lives by 2035
Source:Radiotherapy and Oncology, Volume 125, Issue 2
Author(s): Yolande Lievens, Mary Gospodarowicz, Surbhi Grover, David Jaffray, Danielle Rodin, Julie Torode, Mei Ling Yap, Eduardo Zubizarreta
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Added diagnostic value of respiratory-gated 4D 18F–FDG PET/CT in the detection of liver lesions: a multicenter study
Abstract
Purpose
The aim of the present study was to evaluate the added diagnostic value of respiratory-gated 4D18F–FDG PET/CT in liver lesion detection and characterization in a European multicenter retrospective study.
Methods
Fifty-six oncological patients (29 males and 27 females, mean age, 61.2 ± 11.2 years) from five European centers, submitted to standard 3D–PET/CT and liver 4D–PET/CT were retrospectively evaluated. Based on visual analysis, liver PET/CT findings were scored as positive, negative, or equivocal both in 3D and 4D PET/CT. The impact of 4D–PET/CT on the confidence in classifying liver lesions was assessed. PET/CT findings were compared to histology and clinical follow-up as standard reference and diagnostic accuracy was calculated for both techniques. At semi-quantitative analysis, SUVmax was calculated for each detected lesion in 3D and 4D–PET/CT.
Results
Overall, 72 liver lesions were considered for the analysis. Based on visual analysis in 3D–PET/CT, 32/72 (44.4%) lesions were considered positive, 21/72 (29.2%) negative, and 19/72 (26.4%) equivocal, while in 4D–PET/CT 48/72 (66.7%) lesions were defined positive, 23/72 (31.9%) negative, and 1/72 (1.4%) equivocal. 4D–PET/CT findings increased the confidence in lesion definition in 37/72 lesions (51.4%). Considering 3D equivocal lesions as positive, sensitivity, specificity, and accuracy were 88.9, 70.0, and 83.1%, respectively, while the same figures were 67.7, 90.0, and 73.8% if 3D equivocal findings were included as negative. 4D–PET/CT sensitivity, specificity, and accuracy were 97.8, 90.0, and 95.4%, respectively, considering equivocal lesions as positive and 95.6, 90.0, and 93.8% considering equivocal lesions as negative. The SUVmax of the liver lesions in 4D–PET (mean ± SD, 6.9 ± 3.2) was significantly higher (p < 0.001) than SUVmax in 3D–PET (mean ± SD, 5.2 ± 2.3).
Conclusions
Respiratory-gated PET/CT technique is a valuable clinical tool in diagnosing liver lesions, reducing 3D undetermined findings, improving diagnostic accuracy, and confidence in reporting. 4D–PET/CT also improved the quantification of SUVmax of liver lesions.
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Metabolic activity by 18 F–FDG-PET/CT is predictive of early response after nivolumab in previously treated NSCLC
Abstract
Background
Nivolumab, an anti-programmed death-1 (PD-1) antibody, is administered in patients with previously treated non-small cell lung cancer. However, little is known about the established biomarker predicting the efficacy of nivolumab. Here, we conducted a preliminary study to investigate whether 18F–FDG-PET/CT could predict the therapeutic response of nivolumab at the early phase.
Methods
Twenty-four patients were enrolled in this study. 18F–FDG-PET/CT was carried out before and 1 month after nivolumab therapy. SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were calculated. Immunohistochemical analysis of PD-L1 expression and tumour-infiltrating lymphocytes was conducted.
Results
Among all patients, a partial metabolic response to nivolumab was observed in 29% on SUVmax, 25% on MTV, and 33% on TLG, whereas seven (29%) patients achieved a partial response (PR) based on RECIST v1.1. The predictive probability of PR (100% vs. 29%, p = 0.021) and progressive disease (100% vs. 22.2%, p = 0.002) at 1 month after nivolumab initiation was significantly higher in 18F–FDG on PET/CT than in CT scans. Multivariate analysis confirmed that 18F–FDG uptake after administration of nivolumab was an independent prognostic factor. PD-L1 expression and nivolumab plasma concentration could not precisely predict the early therapeutic efficacy of nivolumab.
Conclusion
Metabolic response by 18F–FDG was effective in predicting efficacy and survival at 1 month after nivolumab treatment.
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Prognostic value of lymph node-to-primary tumor standardized uptake value ratio in endometrioid endometrial carcinoma
Abstract
Purpose
To determine whether the relative metabolic activity of pelvic or para-aortic LN compared with that of primary tumor measured by preoperative [18F]FDG PET/CT scan has prognostic value in patients with endometrioid endometrial carcinoma.
Methods
We retrospectively reviewed patients with endometrioid endometrial carcinoma who underwent preoperative [18F]FDG PET/CT scans. Prognostic values of PET/CT-derived metabolic variables such as maximum standardized uptake value (SUV) of the primary endometrial carcinoma (SUVTumor) and LN (SUVLN), and the LN-to-endometrial carcinoma SUV ratio (SUVLN / SUVTumor) were assessed.
Results
Clinico-pathological data, imaging data, and treatment results were reviewed for 107 eligible patients. Median post-surgical follow-up was 23 months (range, 6–60), and 7 (6.5%) patients experienced recurrence. Regression analysis showed that SUVLN / SUVTumor (P < 0.001), SUVLN (P = 0.003), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.006), and tumor grade (P = 0.011) were risk factors of recurrence. Multivariate regression analysis revealed that FIGO stage (P = 0.034) was the independent risk factor of recurrence. SUVLN / SUVTumor showed significant correlation with FIGO stage (P < 0.001), LN metastasis (P < 0.001), lymphovascular space invasion (P < 0.001), recurrence (P = 0.001), tumor grade (P < 0.001), and deep myometrial invasion of tumor (P = 0.022). Patient groups categorized by SUVLN / SUVTumor showed significant difference in progression-free survival (Log-rank test, P = 0.001).
Conclusions
Preoperative SUVLN / SUVTumor measured by [18F]FDG PET/CT was significantly associated with recurrence, and may become a novel prognostic factor in patients with endometrioid endometrial carcinoma.
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Targeting angiogenesis for radioimmunotherapy with a 177 Lu-labeled antibody
Abstract
Purpose
Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy.
Methods
The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with 177Lu (t 1/2 6.65 days). Balb/c mice were implanted with 4T1 mammary carcinoma cells, and five study groups were used: 177Lu only, TRC105 only, 177Lu-DTPA-IgG (a nonspecific antibody), 177Lu-DTPA-TRC105 low-dose, and 177Lu-DTPA-TRC105 high-dose. Toxicity of the agent was monitored by body weight measurements and analysis of blood markers. Biodistribution studies of 177Lu-DTPA-TRC105 were also performed at 1 and 7 days after injection. Ex vivo histology studies of various tissues were conducted at 1, 7, and 30 days after injection of high-dose 177Lu-DTPA-TRC105.
Results
Biodistribution studies indicated steady uptake of 177Lu-DTPA-TRC105 in 4T1 tumors between 1 and 7 days after injection (14.3 ± 2.3%ID/g and 11.6 ± 6.1%ID/g, respectively; n = 3) and gradual clearance from other organs. Significant inhibition of tumor growth was observed in the high-dose group, with a corresponding significant increase in survival (p < 0.001, all groups). In most study groups (all except the nonspecific IgG group), the body weights of the mice did not decrease by more than 10%, indicating the safety of the injected agents. Serum alanine transaminase levels remained nearly constant indicating no damage to the liver (a primary clearance organ of the agent), and this was confirmed by ex vivo histological analyses.
Conclusion
177Lu-DTPA-TRC105, when administered at a sufficient dose, is able to curtail tumor growth and provide a significant survival benefit without off-target toxicity. Thus, this targeted agent could be used in combination with other treatment options to slow tumor growth allowing the other agents to be more effective.
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Comment on “Comparison of CT and PET/CT for biopsy guidance in oncological patients”
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18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start
Abstract
Purpose
The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation.
Methods
Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t0, base-line), two weeks (t1, study examination) and three months after treatment initiation (t2, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients.
Results
Three patients with partial metabolic response in PET at t1 turned out to have complete response at t2. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t2, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t1. OS in patients with PMD at t2 varied between 148 and 814 days. SMD at both t1 and t2 was seen in one patient, tumor progress was observed after 308 days.
Conclusion
Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future.
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Improving quality of life in patients with pancreatic neuroendocrine tumor following peptide receptor radionuclide therapy assessed by EORTC QLQ-C30
Abstract
Introduction
Neuroendocrine tumors (NETs) have proven to be appropriate neoplasms for peptide receptor radionuclide therapy (PRRT), as the majority of these slow-growing malignancies overexpress somatostatin receptors. The aim of this study was to evaluate changes in quality of life (QoL) of patients with P-NET following PRRT.
Methods
Sixty-eight patients with P-NET (31 female, mean age 61.4 y) underwent PRRT: 12 with NET of grade 1, 40 of grade 2, 8 of grade 3 (grade non-available n = 8). Prior to treatment, 39 patients showed ECOG 0, 26 patients ECOG 1, and three patients ECOG 2. Clinical assessment included evaluation of QoL and symptom changes using a standardized questionnaire (EORTC QLQ-C30) and was performed at baseline and every three months following each therapy cycle up to 12 months. Primary analysis compared QoL at baseline and after the fourth treatment cycle (N = 53).
Results
Up to four treatment cycles PRRT were performed for each patient. The median cumulative administered activity was 28.2 GBq. Primary analysis revealed that compared to baseline QoL was significantly improved revealing increased global health status (p = 0.008) and social functioning (p = 0.049) at the end of the study. Furthermore, fatigue and appetite loss showed a significant improvement after the last PRRT cycle (fatigue: p = 0.029, appetite loss p = 0.015). Sub-analyses showed that QoL was improved revealing increased global health status (3 months after first, second, and third treatment cycle p = 0.048, p = 0.002, and p < 0.001, respectively), emotional functioning (3 months after first-third cycle p = 0.003, p = 0.049, and p = 0.001, respectively) and social functioning (3 months after the first and second p < 0.001, and after the third cycle p = 0.015, respectively). Furthermore, some symptoms were significantly alleviated compared with baseline: fatigue (after first-third cycle p = 0.026, p = 0.050, and p = 0.008, respectively), nausea and vomiting (after first and second cycle p = 0.006 and p = 0.001, respectively), dyspnea (after third cycle p = 0.025), appetite loss (after first-third cycle p = 0.010, p = 0.001, and p = 0.009, respectively), constipation (after first-third cycle p = 0.050, p = 0.003, and p = 0.060, respectively).
Conclusion
PRRT is an effective treatment of P-NET improving QoL of patients in terms of increasing global health and mitigation of physical complaints.
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Targeted alpha therapy of mCRPC: Dosimetry estimate of 213 Bismuth-PSMA-617
Abstract
Purpose
PSMA-617 is a small molecule targeting the prostate-specific membrane antigen (PSMA). In this work, we estimate the radiation dosimetry for this ligand labeled with the alpha-emitter 213Bi.
Methods
Three patients with metastatic prostate cancer underwent PET scans 0.1 h, 1 h, 2 h, 3 h, 4 h and 5 h after injection of 68Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions. The imaging nuclide 68Ga was extrapolated to the half-life of 213Bi. The residence times of 213Bi were forwarded to the instable daughter nuclides. OLINDA was used for dosimetry calculation. Results are discussed in comparison to literature data for 225Ac-PSMA-617.
Results
Assuming a relative biological effectiveness of 5 for alpha radiation, the dosimetry estimate revealed equivalent doses of mean 8.1 Sv RBE5/GBq for salivary glands, 8.1 Sv RBE5/GBq for kidneys and 0.52 Sv RBE5/GBq for red marrow. Liver (1.2 Sv RBE5/GBq), spleen (1.4 Sv RBE5/GBq), bladder (0.28 Sv RBE5/GBq) and other organs (0.26 SvRBE5/GBq) were not dose-limiting. The effective dose is 0.56 Sv RBE5/GBq. Tumor lesions were in the range 3.2–9.0 SvRBE5/GBq (median 7.6 SvRBE5/GBq). Kidneys would limit the cumulative treatment activity to 3.7 GBq; red marrow might limit the maximum single fraction to 2 GBq. Despite promising results, the therapeutic index was inferior compared to 225Ac-PSMA-617.
Conclusions
Dosimetry of 213Bi-PSMA-617 is in a range traditionally considered reasonable for clinical application. Nevertheless, compared to 225Ac-PSMA-617, it suffers from higher perfusion-dependent off-target radiation and a longer biological half-life of PSMA-617 in dose-limiting organs than the physical half-life of 213Bi, rendering this nuclide as a second choice radiolabel for targeted alpha therapy of prostate cancer.
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Clinical impact of PSMA-based 18 F–DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy
Abstract
Purpose
The purpose of our study was to assess 18F–DCFBC PET/CT, a PSMA targeted PET agent, for lesion detection and clinical management of biochemical relapse in prostate cancer patients after primary treatment.
Methods
This is a prospective IRB-approved study of 68 patients with documented biochemical recurrence after primary local therapy consisting of radical prostatectomy (n = 50), post radiation therapy (n = 9) or both (n = 9), with negative conventional imaging. All 68 patients underwent whole-body 18F–DCFBC PET/CT, and 62 also underwent mpMRI within one month. Lesion detection with 18F–DCFBC was correlated with mpMRI findings and pre-scan PSA levels. The impact of 18F–DCFBC PET/CT on clinical management and treatment decisions was established after 6 months' patient clinical follow-up.
Results
Forty-one patients (60.3%) showed at least one positive 18F–DCFBC lesion, for a total of 79 lesions, 30 in the prostate bed, 39 in lymph nodes, and ten in distant sites. Tumor recurrence was confirmed by either biopsy (13/41 pts), serial CT/MRI (8/41) or clinical follow-up (15/41); there was no confirmation in five patients, who continue to be observed. The 18F–DCFBC and mpMRI findings were concordant in 39 lesions (49.4%), and discordant in 40 lesions (50.6%); the majority (n = 32/40) of the latter occurring because the recurrence was located outside the mpMRI field of view. 18F–DCFBC PET positivity rates correlated with PSA values and 15%, 46%, 83%, and 77% were seen in patients with PSA values <0.5, 0.5 to <1.0, 1.0 to <2.0, and ≥2.0 ng/mL, respectively. The optimal cut-off PSA value to predict a positive 18F–DCFBC scan was 0.78 ng/mL (AUC = 0.764). A change in clinical management occurred in 51.2% (21/41) of patients with a positive 18F–DCFBC result, generally characterized by starting a new treatment in 19 patients or changing the treatment plan in two patients.
Conclusions
18F–DCFBC detects recurrences in 60.3% of a population of patients with biochemical recurrence, but results are dependent on PSA levels. Above a threshold PSA value of 0.78 ng/mL, 18F–DCFBC was able to identify recurrence with high reliability. Positive 18F–DCFBC PET imaging led clinicians to change treatment strategy in 51.2% of patients.
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From fixed activities to personalized treatments in radionuclide therapy: lost in translation?
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18F–FDG PET/CT in solitary plasmacytoma: metabolic behavior and progression to multiple myeloma
Abstract
Purpose
Solitary plasmacytoma (SP) is a rare plasma-cell neoplasm, which can develop both in skeletal and/or soft tissue and frequently progresses to multiple myeloma (MM). Our aim was to study the metabolic behavior of SP and the role of 18F–FDG-PET/CT in predicting progression to MM.
Materials and methods
Sixty-two patients with SP who underwent 18F–FDG-PET/CT before any treatment were included. PET images were qualitatively and semiquantitatively analyzed by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and compared with age, sex, site of primary disease, and tumor size.
Results
Fifty-one patients had positive 18F–FDG-PET/CT (average SUVbw was 8.3 ± 4.7; SUVlbm 5.8 ± 2.6; SUVbsa 2 ± 1; MTV 45.4 ± 37; TLG 227 ± 114); the remaining 11 were not 18F–FDG-avid. Tumor size was significantly higher in patients avid lesions compared to FDG not avid; no other features are associated with FDG-avidity. Progression to MM occurred in 29 patients with an average of 18.3 months; MM was more likely to develop in patients with bone plasmacytoma and in patients with 18F–FDG avid lesion. Time to transformation in MM (TTMM) was significantly shorter in patients with osseous SP, in 18F–FDG avid lesion, for SUVlbm > 5.2 and SUVbsa > 1.7.
Conclusions
18F–FDG pathological uptake in SP occurred in most cases, being independently associated with tumor size. PET/CT seemed to be correlated to a higher risk of transformation in MM, in particular for 18F–FDG avid plasmacytoma and SBP. Among semiquantitative features, SUVlbm > 5.2 and SUVbsa > 1.7 were significantly correlated with TTMM.
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Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma
Abstract
Aim
The aim of this bicentric retrospective study was to assess the diagnostic performance, the prognostic value, the incremental prognostic value and the impact on therapeutic management of 18F-FDG PET/CT in patients with suspected recurrent germinal cell testicular carcinoma (GCT).
Materials and methods
From the databases of two centers including 31,500 18F-FDG PET/CT oncological studies, 114 patients affected by GCT were evaluated in a retrospective study. All 114 patients underwent 18F-FDG PET/CT for suspected recurrent disease. Diagnostic performance of visually interpreted 18F-FDG PET/CT and potential impact on the treatment decision were assessed using histology (17 patients), other diagnostic imaging modalities (i.e., contrast enhanced CT in 89 patients and MRI in 15) and clinical follow-up (114 patients) as reference. Progression-free survival (PFS) and overall survival (OS) rates were computed by means of Kaplan-Meier survival analysis. The progression rate (Hazard Ratio-HR) was determined using univariate Cox regression analysis by considering various clinical variables.
Results
Recurrent GCT was confirmed in 47 of 52 patients with pathological 18F-FDG PET/CT findings, by means of histology in 18 patients and by other diagnostic imaging modalities/follow-up in 29. Sensitivity, specificity, accuracy, positive and negative likelihood ratio (LR+ and LR-, respectively), pre-test Odds-ratio and post-test Odds-ratio of 18FDG PET/CT were 86.8%, 90.2%, 88.4%, 8.85, 0.14, 0.85, 8.85, respectively.18F-FDG PET/CT impacted significantly on therapeutic management in 26/114 (23%) cases (from palliative to curative in 12 patients, from "wait and watch" to new chemotherapy in six patients and the "wait-and-watch" approach in eight patients with unremarkable findings). At 2 and 5-year follow-up, PFS was significantly longer in patients with a negative than a pathological 18F-FDG PET/CT scan (98% and 95% vs 48% and 38%, respectively; p = 0.02). An unremarkable scan was associated also with a longer OS (98% after 2 years and 95% after 5 years, p = 0.02). At univariate Cox regression analysis, a pathological 18F-FDG PET/CT scan was associated with an increased risk of disease progression (HR = 24.3, CI 95% 14.1-40.6; p = 0.03) and lower OS (HR = 17.3 CI 95% 4,9-77; p < 0.001). Its prognostic value was confirmed also if tested against advanced disease at diagnosis and rising Human Chorionic Gonadotropin Beta (HCGB) or Alpha-Fetoprotein (AFP) (HR = 7.3 for STAGE III-PET+, p = 0.03; HR = 14.3 elevated HCGB-PET+, p = 0.02; HR 10.7 elevated AFP-PET+, p = 0.01) At multivariate analysis, only a pathological 18F-FDG PET/CT scan and advanced disease in terms of TNM staging were predictors of disease progression and OS. 18F-FDG PET/CT showed incremental value over other variables both in predicting PFS (chi-square from 24 to 40, p < 0.001) and OS (chi-square from 32 to 38, p = 0.003).
Conclusion
18F-FDG PET/CT has a very good diagnostic performance in patients with suspected recurrent GCT and has an important prognostic value in assessing the rate of PFS and OS. Furthermore, 18F-FDG PET/CT impacted the therapeutic regimen in 23% of patients, thus providing a significant impact in the restaging process.
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Comparison of 18 F-FDG PET/MRI and MRI for pre-therapeutic tumor staging of patients with primary cancer of the uterine cervix
Abstract
Purpose
The aim of the present study was to assess and compare the diagnostic performance of integrated PET/MRI and MRI alone for local tumor evaluation and whole-body tumor staging of primary cervical cancers. In addition, the corresponding impact on further patient management of the two imaging modalities was assessed.
Methods
A total of 53 consecutive patients with histopathological verification of a primary cervical cancer were prospectively enrolled for a whole-body 18F-FDG PET/MRI examination. Two experienced physicians analyzed the MRI data, in consensus, followed by a second reading session of the PET/MRI datasets. The readers were asked to perform a dedicated TNM staging in accordance with the 7th edition of the AJCC staging manual. Subsequently, the results of MRI and PET/MRI were discussed in a simulated interdisciplinary tumor board and therapeutic decisions based on both imaging modalities were recorded. Results from histopathology and cross-sectional imaging follow-up served as the reference standard.
Results
PET/MRI allowed for a correct determination of the T stage in 45/53 (85%) cases, while MRI alone enabled a correct identification of the tumor stage in 46/53 (87%) cases. In 24 of the 53 patients, lymph node metastases were present. For the detection of nodal-positive patients, sensitivity, specificity and accuracy of PET/MRI were 83%, 90% and 87%, respectively. The respective values for MRI alone were 71%, 83% and 77%. In addition, PET/MRI showed higher values for the detection of distant metastases than MRI alone (sensitivity: 87% vs. 67%, specificity: 92% vs. 90%, diagnostic accuracy: 91% vs. 83%). Among the patients with discrepant staging results in the two imaging modalities, PET/MRI enabled correct treatment recommendations for a higher number (n = 9) of patients than MRI alone (n = 3).
Conclusion
The present results demonstrate the successful application of integrated PET/MRI imaging for whole-body tumor staging of cervical cancer patients, enabling improved treatment planning when compared to MRI alone.
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Heat shock protein (hsp70) in brown trout epidermis after sudden temperature rise
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Antibiotics, Vol. 6, Pages 29: Activity In Vitro of Clotrimazole against Canine Methicillin-Resistant and Susceptible Staphylococcus pseudintermedius
Antibiotics, Vol. 6, Pages 29: Activity In Vitro of Clotrimazole against Canine Methicillin-Resistant and Susceptible Staphylococcus pseudintermedius
Antibiotics doi: 10.3390/antibiotics6040029
Authors: Sian-Marie Frosini Ross Bond
Emergence of multidrug-resistance in Staphylococcus pseudintermedius (SP) has increased interest in topical therapy as an alternative to systemic antibiotics in canine pyoderma. The antifungal imidazole, clotrimazole, is contained in numerous licensed canine ear preparations. Its in vitro activity against SP has not been evaluated, although previous studies have shown that the related imidazole, miconazole, has significant anti-staphylococcal efficacy. We therefore determined minimum inhibitory concentrations (MICs) of clotrimazole amongst 50 SP isolates (25 methicillin-resistant [MR]SP and susceptible [MS]SP) collected from dogs in Germany during 2010–2011 using an agar dilution method (CLSI VET01-A4). MICs amongst MRSP and MSSP were comparable (MIC50 and MIC90 = 1mg/L for both groups, p = 0.317); overall, 49 isolates had MIC = 1 mg/L and one had MIC = 0.5 mg/L. The relatively low MICs obtained in this study are likely to be exceeded by topical therapy and thus further clinical evaluation of clotrimazole use in canine superficial pyoderma and otitis externa caused by MRSP and MSSP is now warranted.
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International Bullous Diseases Group - Consensus on Diagnostic Criteria for Epidermolysis Bullosa Acquisita
Summary
Background
Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests making an international consensus on diagnosis of EBA needed.
Objectives
To obtain an international consensus on the clinical and diagnostic criteria for EBA.
Methods
The international bullous diseases group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When more than 30% disagreed with a proposal, a discussion was held and revoting occurred.
Results
48/50 proposals achieved consensus after discussion. This included 9 diagnostic criteria that are summarized in a flow chart. The IBDG was unable to determine one procedure which would be applicable worldwide.
Limitations
Differential diagnosis of bullous systemic lupus erythematosus has not been addressed.
Conclusion
This first international consensus conference established generally agreed upon clinical and laboratory criteria defining the clinical classification and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting.
This article is protected by copyright. All rights reserved.
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Adam Kay: Mirth partner
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Janet McLelland
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Robert Cleghorn Robb
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Pathological Roles of Neutrophil-Mediated Inflammation in Asthma and Its Potential for Therapy as a Target
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SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV
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Diagnosis and Treatment of Esophageal Granular Cell Tumor: A Case Report and Review of the Literature
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Skin Hyperpigmentation as the Presenting Symptom of Subacute Combined Degeneration of the Spinal Cord
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Methanol Extract of Holarrhena antidysenterica Inhibits the Growth of Human Oral Squamous Cell Carcinoma Cells and Osteoclastogenesis of Bone Marrow Macrophages
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Cognitive Impact of Deep Brain Stimulation on Parkinson’s Disease Patients
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Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Mice
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JCDD, Vol. 4, Pages 20: Growth and Morphogenesis during Early Heart Development in Amniotes
JCDD, Vol. 4, Pages 20: Growth and Morphogenesis during Early Heart Development in Amniotes
Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd4040020
Authors: Kenzo Ivanovitch Isaac Esteban Miguel Torres
In this review, we will focus on the growth and morphogenesis of the developing heart, an aspect of cardiovascular development to which Antoon Moorman and colleagues have extensively contributed. Over the last decades, genetic studies and characterization of regionally regulated gene programs have provided abundant novel insights into heart development essential to understand the basis of congenital heart disease. Heart morphogenesis, however, is inherently a complex and dynamic three-dimensional process and we are far from understanding its cellular basis. Here, we discuss recent advances in studying heart morphogenesis and regionalization under the light of the pioneering work of Moorman and colleagues, which allowed the reinterpretation of regional gene expression patterns under a new morphogenetic framework. Two aspects of early heart formation will be discussed in particular: (1) the initial formation of the heart tube and (2) the formation of the cardiac chambers by the ballooning process. Finally, we emphasize that in addition to analyses based on fixed samples, new approaches including clonal analysis, single-cell sequencing, live-imaging and quantitative analysis of the data generated will likely lead to novel insights in understanding early heart tube regionalization and morphogenesis in the near future.
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IJMS, Vol. 18, Pages 2487: Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report
IJMS, Vol. 18, Pages 2487: Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report
International Journal of Molecular Sciences doi: 10.3390/ijms18112487
Authors:Marcella NunziatoFlavio StarnoneBarbara LombardoMatilde PensabeneCaterina CondelloFrancesco VerdescaChiara CarlomagnoSabino De PlacidoLucio PastoreFrancesco SalvatoreValeria D’Argenio
The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible BRCA mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with early onset breast cancer and a family history of diverse cancers. BRCA molecular analysis was performed by NGS, and sequence data were analyzed using two software packages. Comparative genomic hybridization (CGH) array was used as confirmatory method. A novel large duplication, involving exons 4–26, of BRCA2 was directly detected in the patient by NGS workflow including quantitative analysis of copy number variants. The duplication observed was also found by CGH array, thus confirming its extent. Large genomic rearrangements can affect the BRCA1/2 genes, and thus contribute to germline predisposition to familial breast and ovarian cancers. The frequency of these mutations could be underestimated because of technical limitations of several routinely used molecular analysis, while their evaluation should be included also in these molecular testing. The NGS-based strategy described herein is an effective procedure to screen for all kinds of BRCA mutations.
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Chirurgie maligner hormonaktiver neuroendokriner Pankreastumoren
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Kalorimetricheskoe izuchenie perekhoda spiral'-klubok v DNK pri vzaimodeistvii s ionami Cu2+
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Strukturnye i fiziko-khimicheskie kharakteristiki DNK iz tkaneǐ zhivotnykh, podvergavshikhsia dlitel'nomu khronicheskomu oblucheniiu v zone chernobylia
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Izuchenie metodami IK- i Ramanovskoǐ spektroskopii vzaimodeǐstviia DNK s ionami medi
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Active biomonitoring with brown trout and rainbow trout in diluted sewage plant effluents
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Intersex in feral brown trout from Swiss midland rivers
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Waste water management plant effluents cause cellular alterations in the skin of brown trout
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Lectin-histochemistry of rainbow trout (Oncorhynchus mykiss) gill and skin
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Gesucht: Indikatoren für die Qualität von Fliessgewässern. Ein Beispiel zur Schaffung von Synergien zwischen Forschung und Lehre
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How disposable diapers can improve measurements of tumour growth
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Women prefer annual mammograms to bi-annual screening
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Researchers discover specific tumour environment that triggers cells to metastasise
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Chemo brain starts during cancer's progression, not just after chemotherapy
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New study points the way to therapy for rare cancer that targets the young
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People willing to trade treatment efficacy for reduced side effects in cancer therapies
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Down-top nanofabrication of binary (CdO)x (ZnO)1-x nanoparticles and their antibacterial activity
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Testosterone elevates expression of tenascin-R and oligomannosidic carbohydrates in developing male zebra finches
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Exogenous testosterone alters expression pattern of cell recognition molecules in brains of juvenal zebra finches
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Naturschutz in der Lehre der Allgemeinen Ökologie an der Universität Bern
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Regenbogenforelle und Zebrabärbling, zwei Modelle für verlängerte Toxizitätstests: Relative Empfindlichkeit, Art- und Organspezifität in der cytopathologischen Reaktion von Leber und Darm auf Atrazin
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Armut in Basel – Sozialräumliche Ausrichtung des niederschwelligen Hilfsangebots
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Grenzüberschreitende Zusammenarbeit in der Region Basel - Institutionen und Infrastrukturprojekte im Dreiländereck
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Das Life Sciences-Cluster in der trinationalen Region Basel - Auszüge aus einer Befragungs- und GIS-gestützten Studie
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Geomorphologische Exkursion in Basel – Einblick in den natürlichen quartären und anthropogenen Formenschatz zwischen dem Basler Münster und der Birsmündung
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Die Beurteilung der TSH-Suppression mit einem TSH-Assay der 3. Generation: diagnostische und therapeutische Konsequenzen
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Prediction of metabolism-induced hepatotoxicity on three-dimensional hepatic cell culture and enzyme microarrays
Abstract
Human liver contains various oxidative and conjugative enzymes that can convert nontoxic parent compounds to toxic metabolites or, conversely, toxic parent compounds to nontoxic metabolites. Unlike primary hepatocytes, which contain myriad drug-metabolizing enzymes (DMEs), but are difficult to culture and maintain physiological levels of DMEs, immortalized hepatic cell lines used in predictive toxicity assays are easy to culture, but lack the ability to metabolize compounds. To address this limitation and predict metabolism-induced hepatotoxicity in high-throughput, we developed an advanced miniaturized three-dimensional (3D) cell culture array (DataChip 2.0) and an advanced metabolizing enzyme microarray (MetaChip 2.0). The DataChip is a functionalized micropillar chip that supports the Hep3B human hepatoma cell line in a 3D microarray format. The MetaChip is a microwell chip containing immobilized DMEs found in the human liver. As a proof of concept for generating compound metabolites in situ on the chip and rapidly assessing their toxicity, 22 model compounds were dispensed into the MetaChip and sandwiched with the DataChip. The IC50 values obtained from the chip platform were correlated with rat LD50 values, human C max values, and drug-induced liver injury categories to predict adverse drug reactions in vivo. As a result, the platform had 100% sensitivity, 86% specificity, and 93% overall predictivity at optimum cutoffs of IC50 and C max values. Therefore, the DataChip/MetaChip platform could be used as a high-throughput, early stage, microscale alternative to conventional in vitro multi-well plate platforms and provide a rapid and inexpensive assessment of metabolism-induced toxicity at early phases of drug development.
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JCM, Vol. 6, Pages 107: Knee and Ankle Arthroplasty in Hemophilia
JCM, Vol. 6, Pages 107: Knee and Ankle Arthroplasty in Hemophilia
Journal of Clinical Medicine doi: 10.3390/jcm6110107
Authors: Luigi Solimeno Gianluigi Pasta
Today, major surgical procedures can be safely performed in hemophilic patients with chronic arthropathy, using available factor concentrates. In this setting, total knee replacement is considered the “gold standard”, while the use of total ankle replacement is still debated. Indeed, the unsatisfactory results obtained with the previous available design of implants did not raise enthusiasm as knee or hip replacement. Recently, the introduction of new implant designs and better reported outcomes have renewed the interest in total ankle replacement in people with hemophilia. In this review, the role of replacement surgery in the treatment of chronic hemophilic arthropathy will be described.
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ARHGEF19 interacts with BRAF to activate MAPK signaling during the tumorigenesis of non-small cell lung cancer
Abstract
Rho guanine nucleotide exchange factors (RhoGEFs) are proteins that activate Rho GTPases in response to extracellular stimuli and regulate various biologic processes. ARHGEF19, one of RhoGEFs, was reported to activate RhoA in the Wnt-PCP pathway controlling convergent extension in Xenopus gastrulation. The goal of this study was to identify the role and molecular mechanisms of ARHGEF19 in the tumorigenesis of non-small cell lung cancer (NSCLC). ARHGEF19 expression was significantly elevated in NSCLC tissues, and ARHGEF19 levels were significantly associated with lymph node status, distant metastasis and TNM stage; Patients with high ARHGEF19 levels had poor overall survival (OS) and progression-free survival (PFS). Our investigations revealed that ARHGEF19 overexpression promoted the cell proliferation, invasion and metastasis of lung cancer cells, whereas knockdown of this gene inhibited these processes. Mechanistically, ARHGEF19 activated the mitogen-activated protein kinase (MAPK) pathway in a RhoA-independent manner: ARHGEF19 interacted with BRAF and facilitated the phosphorylation of its downstream kinase MEK1/2; both the Dbl homology (DH) and Pleckstrin homology (PH) domains of ARHGEF19 were indispensable for the phosphorylation of MEK1/2. Furthermore, downregulation of miR-29b was likely responsible for the increased expression of ARHGEF19 in lung cancer tissues and, consequently, the abnormal activation of MAPK signaling. These findings suggest that ARHGEF19 upregulation, due to the low expression of miR-29 in NSCLC tissues, may play a crucial role in NSCLC tumorigenesis by activating MAPK signaling. ARHGEF19 could serve as a negative prognostic marker as well as a therapeutic target for NSCLC patients. This article is protected by copyright. All rights reserved.
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Experimental Investigation and Analysis of Dynamic Buckling of Drill String in Horizontal Well
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Theatre Is a Valid Add-On Therapeutic Intervention for Emotional Rehabilitation of Parkinson’s Disease Patients
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Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient
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TB Risk Perceptions among Medical Residents at a Tertiary Care Center in India
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State-Transition-Aware Spilling Heuristic for MLC STT-RAM-Based Registers
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Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries
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Comment on “DKA-Induced Takotsubo Cardiomyopathy in Patient with Known HOCM”
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Kinect V2 Performance Assessment in Daily-Life Gestures: Cohort Study on Healthy Subjects for a Reference Database for Automated Instrumental Evaluations on Neurological Patients
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Δημοφιλείς αναρτήσεις
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Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
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Publication date: March 2017 Source: Free Radical Biology and Medicine, Volume 104 from #AlexandrosSfakianakis via Alexandros G.Sfak...
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Dtsch med Wochenschr DOI: 10.1055/s-0043-100054 Hintergrund und Fragestellung Ein etablierter Weg, die optimale Behandlung von Tumorpatien...
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Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
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Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης A Novel Technique for Endoscopic Repair of Large Anterior Skull Base Defect...
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Antibodies, Vol. 9, Pages 21: Construction of Ant... In Vivo and In Vitro Evaluation of Bull Semen Pro... Vertebral artery fenestration mimi...
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Background Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extrac...
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Publication date: Available online 23 February 2018 Source: Experimental Cell Research Author(s): Subbiah Ramasamy, Ganesan Velmurugan, Ba...
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Abstract Coaxial electrospun fibrous membranes show favorable mechanical properties for use in guided bone regeneration (GBR). We used coa...