Beyond the three P's: adrenal involvement in MEN1.

Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients' clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47 ± 11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3-123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional work-up (diagnoses: pheochromocytoma (n = 2), adrenocorticotropic hormone-dependent hypercortisolism (n = 2), hyperandrogenism (n = 1), hyperaldosteronism (n = 1)); surgery was indicated for 5 (83.3%; n = 12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and two with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion's growth rate and size. A baseline hormonal work-up is recommended, and no further biochemical work-up is suggested when the initial assessment shows nonfunctioning lesions.

Major Adverse Renal and Cardiovascular Events following Intra-Arterial Contrast Media Administration in Hospitalized Patients with Comorbid Conditions.

INTRODUCTION: Several clinical studies and meta-analyses have demonstrated lower incidence of adverse renal and cardiovascular outcomes associated with the use of iso-osmolar contrast media (IOCM) than low-osmolar contrast media (LOCM) in patients with variable risk profiles undergoing intra-arterial interventional procedures. However, the association of contrast-type and major adverse renal and cardiovascular events (MARCE) has not been studied via comprehensive and robust real-world data analyses in patients with comorbid conditions considered at risk for post-procedural acute kidney injury (AKI). The objective of this study was therefore to retrospectively assess the MARCE rates comparing IOCM with LOCM in at-risk patients receiving iodinated intra-arterial contrast media using a real-world inpatient data source. METHODS: Patients who underwent a diagnostic or treatment procedure with intra-arterial IOCM or LOCM administration were identified using the Premier Healthcare Database. Patient subgroups including those with diabetes, heart failure, chronic kidney disease (CKD) stages 1-4, CKD 3-4, or diagnosis of chronic total occlusion (CTO) were formed. Subgroups with combinations of diabetes and CKD 3-4 with and without CTO were also investigated. We compared the primary endpoint of MARCE (composite of AKI, AKI requiring dialysis, acute myocardial infarction, stroke/transient ischemic attack, stent occlusion/thrombosis, or death) after IOCM versus LOCM administration via adjusted multivariable regression analyses. RESULTS: A total of 536,013 inpatient visits met the primary inclusion and exclusion criteria (IOCM = 133,192; LOCM = 402,821). After multivariable modeling, the use of IOCM was associated with a significantly lower incidence of MARCE than LOCM in patients with CKD 1-4, CKD 3-4, diabetes, or heart failure, with greatest absolute risk reduction (ARR) of 2.4% (p < 0.0001) in CKD 3-4 patients (relative risk reduction [RRR] = 13.8%, number needed to treat [NNT] = 43). Additionally, ARR associated with IOCM increased to 3.5% (p < 0.0001) in patients with combined comorbidities of diabetes and CKD 3-4 (RRR = 19.1%, NNT = 29). Statistically significant risk reduction was also found for the use of IOCM among patients who underwent revascularization for CTO (ARR = 1.6% [p < 0.0001], RRR = 22.3%, NNT = 62). CONCLUSION: Intra-arterial administration using IOCM in at-risk patients is associated with lower rates of MARCE than the use of LOCM. This difference is especially apparent in patients with a combination of CKD 3-4 and diabetes and in patients with CTO, providing real-world data validation with meaningful NNT in favor of IOCM.

Comparison of virtual to true unenhanced abdominal computed tomography images acquired using rapid kV-switching dual energy imaging.

OBJECTIVE: To compare "virtual" unenhanced (VUE) computed tomography (CT) images, reconstructed from rapid kVp-switching dual-energy computed tomography (DECT), to "true" unenhanced CT images (TUE), in clinical abdominal imaging. The ability to replace TUE with VUE images would have many clinical and operational advantages. METHODS: VUE and TUE images of 60 DECT datasets acquired for standard-of-care CT of pancreatic cancer were retrospectively reviewed and compared, both quantitatively and qualitatively. Comparisons included quantitative evaluation of CT numbers (Hounsfield Units, HU) measured in 8 different tissues, and 6 qualitative image characteristics relevant to abdominal imaging, rated by 3 experienced radiologists. The observed quantitative and qualitative VUE and TUE differences were compared against boundaries of clinically relevant equivalent thresholds to assess their equivalency, using modified paired t-tests and Bayesian hierarchical modeling. RESULTS: Quantitatively, in tissues containing high concentrations of calcium or iodine, CT numbers measured in VUE images were significantly different from those in TUE images. CT numbers in VUE images were significantly lower than TUE images when calcium was present (e.g. in the spine, 73.1 HU lower, p < 0.0001); and significantly higher when iodine was present (e.g. in renal cortex, 12.9 HU higher, p < 0.0001). Qualitatively, VUE image ratings showed significantly inferior depiction of liver parenchyma compared to TUE images, and significantly more cortico-medullary differentiation in the kidney. CONCLUSIONS: Significant differences in VUE images compared to TUE images may limit their application and ability to replace TUE images in diagnostic abdominal CT imaging.

A functional model for classifying metastatic lesions integrating scans and biomarkers.

Perfusion computed tomography is an emerging functional imaging modality that uses physiological models to quantify characteristics pertaining to the passage of fluid through blood vessels. Perfusion characteristics provide physiological correlates for neovascularization induced by tumor angiogenesis and thus a quantitative basis for cancer detection, prognostication, and treatment monitoring. We consider a liver cancer study where patients underwent a dynamic computed tomography protocol to enable evaluation of multiple perfusion characteristics derived from interrogating the time-attenuation of the concentration of the intravenously administered contrast medium. The objective is to determine the effectiveness of using perfusion characteristics to identify and discriminate between regions of liver that contain malignant tissues from normal tissue. Each patient contributes multiple regions of interest which are spatially correlated due to the shared vasculature. We propose a multivariate functional data model to disclose the correlation over time and space as well as the correlation among multiple perfusion characteristics. We further propose a simultaneous classification approach that utilizes all the correlation information to predict class assignments for collections of regions. The proposed method outperforms conventional classification approaches in the presence of strong spatial correlation. The method offers maximal relative improvement in the presence of temporal sparsity wherein measurements are obtainable at only a few time points.

Diagnostic performance of adrenal CT in the differentiation of adenoma and pheochromocytoma.

BACKGROUND: Differentiation of adenoma and pheochromocytoma on computed tomography (CT) may be problematic. PURPOSE: To investigate if adenoma and pheochromocytoma can be differentiated with adrenal CT. MATERIAL AND METHODS: A total of 147 pathologically proven adrenal masses (119 adenomas, 28 pheochromocytomas) that had undergone adrenal CT were retrospectively evaluated. Lesion attenuation on unenhanced phase (UEP), portal phase (PP), 15-min delayed phase (DP), absolute/relative percentage enhancement wash-out (APEW/RPEW), and qualitative features were recorded. Student's t-test for parametric data, Mann-Whitney U test for non-parametric data, and Fisher's exact test for categorical data were used. Diagnostic performance of CT attenuation was assessed by area under the curve (AUC) of the receiver operating characteristics. RESULTS: APEW of adenomas was not significantly different from pheochromocytomas; 68.4% and 59% (P = 0.284). Adenomas had significantly higher RPEW; 57.3% vs. 37.4% (P = 0.004). Of pheochromocytomas, 50% met APEW >60% or RPEW >40% criteria, and therefore were misclassified as adenoma on wash-out CT. Of those, 80% (4/5) were < 3 cm. UEP, PP, and DP attenuations of pheochromocytomas were significantly higher than adenomas; however, they were overlapping. AUC for UEP, PP, and DP was 0.906, 0.784, and 0.926, respectively. Larger pheochromocytomas were more likely to contain necrosis compared to smaller pheochromocytomas and adenomas; 41.6% vs. 12.5% vs. 3%. Homogeneous enhancement was seen in 25% of pheochromocytomas and 49% of adenomas (P = 0.018). No significant difference was found in terms of lesion borders and presence of fat/calcification (P > 0.05). CONCLUSIONS: A considerable percentage of pheochromocytomas, especially smaller ones, demonstrate adenoma-like wash-out on CT. Heterogeneous enhancement, higher attenuation, and necrosis are more suggestive of pheochromocytoma.

Comparison of enhancement quantification from virtual unenhanced images to true unenhanced images in multiphase renal Dual-Energy computed tomography: A phantom study.

Multiphase computed tomography (CT) exams are a commonly used imaging technique for the diagnosis of renal lesions and involve the acquisition of a true unenhanced (TUE) series followed by one or more postcontrast series. The difference in CT number of the mass in pre- and postcontrast images is used to quantify enhancement, which is an important criterion used for diagnosis. This study sought to assess the feasibility of replacing TUE images with virtual unenhanced (VUE) images derived from Dual-Energy CT datasets in renal CT exams. Eliminating TUE image acquisition could reduce patient dose and improve clinical efficiency. A rapid kVp-switching CT scanner was used to assess enhancement accuracy when using VUE compared to TUE images as the baseline for enhancement calculations across a wide range of clinical scenarios simulated in a phantom study. Three phantoms were constructed to simulate small, medium, and large patients, each with varying lesion size and location. Nonenhancing cystic lesions were simulated using distilled water. Intermediate (10-20 HU [Hounsfield units]) and positively enhancing masses (≥20 HU) were simulated by filling the spherical inserts in each phantom with varied levels of iodinated contrast mixed with a blood surrogate. The results were analyzed using Bayesian hierarchical models. Posterior probabilities were used to classify enhancement measured using VUE compared to TUE images as significantly less, not significantly different, or significantly higher. Enhancement measured using TUE images was considered the ground truth in this study. For simulation of nonenhancing renal lesions, enhancement values were not significantly different when using VUE versus TUE images, with posterior probabilities ranging from 0.23-0.56 across all phantom sizes and an associated specificity of 100%. However, for simulation of intermediate and positively enhancing lesions significant differences were observed, with posterior probabilities < 0.05, indicating significantly lower measured enhancement when using VUE versus TUE images. Positively enhancing masses were categorized accurately, with a sensitivity of 91.2%, when using VUE images as the baseline. For all scenarios where iodine was present, VUE-based enhancement measurements classified lesions with a sensitivity of 43.2%, a specificity of 100%, and an accuracy of 78.1%. Enhancement calculated using VUE images proved to be feasible for classifying nonenhancing and highly enhancing lesions. However, differences in measured enhancement for simulation of intermediately enhancing lesions demonstrated that replacement of TUE with VUE images may not be advisable for renal CT exams.

A Phase II Trial of Ziv-Aflibercept in Patients With Advanced Pancreatic Neuroendocrine Tumors.

OBJECTIVES: Therapies for patients with advanced well-differentiated pancreatic neuroendocrine tumors (pNETs) are insufficient, with patients succumbing to disease despite recent treatment advances. Ziv-aflibercept is a fusion protein of portions of the vascular endothelial growth factor (VEGF) receptors 1 and 2, fused to the Fc portion of immunoglobulin G1, forming a VEGF trap. Perfusion computed tomography (CT) has previously defined hyperperfused neuroendocrine tumors, potentially predicting antiangiogenic benefit. METHODS: We performed a single-arm open-label study, using the Simon optimal 2-stage design, of 6 mg/kg ziv-aflibercept in patients with advanced pNETs. The primary end point was objective radiographic response, with a hierarchically tested co-primary end point of response prediction by baseline hyperperfusion, defined as blood volume greater than 5.25 mL/100 g and permeability surface area product greater than 25 mL/min per 100 g. RESULTS: Between July 3, 2014, and September 28, 2016, 21 patients were treated. Two patients (9.5%; 95% confidence interval, 1.1%-30.4%) demonstrated objective response, satisfying criteria to open the second stage, but the study was terminated for accrual. Perfusion CT could not be confirmed to predict radiographic response. Toxicities include 1 grade 5 gastrointestinal hemorrhage and 5 incidents of proteinuria requiring treatment discontinuation. CONCLUSIONS: Responses with ziv-aflibercept were consistent with other VEGF inhibitors in pNET, but perfusion CT could not be confirmed to predict outcome.

CT and 18F- FDG-PET-CT Findings in Secondary Adrenal Lymphoma with Pathologic Correlation.

RATIONALE AND OBJECTIVE: To evaluate computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) imaging manifestations of lymphomas secondarily involving the adrenal gland. MATERIALS AND METHODS: Seven patients (Five men, two women; median age [range], 66 years [34-75 years]) with pathologically proven adrenal lymphoma were assessed retrospectively. Clinical findings, prior history of lymphoproliferative malignancy, CT (n = 7) and fludeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) (n = 6) features were analyzed. RESULTS: Six cases were diffuse large B-cell lymphoma, and one case was peripheral T-cell lymphoma. The longest diameter of the lesions ranged from 3.2 to 6.6 cm (median 4.3 cm). Six lesions were well-defined and one lesion was ill-defined. In five cases, an adreniform shape was preserved. No lesions contained fat, calcification or hemorrhage. Two lesions had necrosis on CT. Median (range) unenhanced CT density of six lesions was 31.8 (29.2-35.2) Hounsfield units. Following administration of IV contrast media (n = 6), three lesions enhanced homogenously whereas three enhanced heterogeneously. The median increase in attenuation was 35.1 Hounsfield units. Two patients had 15-minute delayed CT and they both demonstrated limited wash-out consistent with nonadenoma. Six patients had fludeoxyglucose positron emission tomography-computed tomography(18-F-FDG-PET-CT) and all lesions were fludeoxyglucose (FDG) avid with a median SUVmax of 18.6 (range: 10.3-49.2). CONCLUSION: Secondary adrenal lymphomas usually manifest as, large (>3 cm), well-defined, homogenously or slightly heterogeneously enhancing masses on CT with preserved adreniform shape. These lesions tend to show limited wash-out and high fludeoxyglucose (FDG) uptake.

Operation duration and adrenal gland size, but not BMI, are correlated with complication rate for posterior retroperitoneoscopic adrenalectomy for benign diseases.

BACKGROUND: We sought to determine whether obesity is correlated with complications after posterior retroperitoneoscopic adrenalectomy for benign diseases and to develop surrogate markers of abdominal fat in preoperative computed tomography. METHODS: We conducted a retrospective chart review of all patients who had undergone posterior retroperitoneoscopic adrenalectomy and preoperative computed tomography between January 1, 2008 and December 31, 2015. The cross-sectional components of fat assessed by computed tomography included total fat area, subcutaneous fat area, retroperitoneal fat area, and peritoneal fat area. The patients were grouped into 2 categories according to the absence or presence of a postoperative complication (the no-complications group and the complications group, respectively). RESULTS: Of 116 study patients, 20 patients (17%) had a postoperative complication. Operations of greater duration and smaller adrenal gland size were significantly correlated with complications both in univariate and multivariate analyses. Body mass index, total fat area, subcutaneous fat area, retroperitoneal fat area, peritoneal fat area, and distance of skin to muscle (in axial and sagittal images) correlated with complications in univariate analysis but not in multivariate analysis. In the no-complications group, the removed adrenal gland was larger than that removed in the complications group (6 vs 4 cm, respectively, P = .001), whereas the complications group had a greater operative duration (139 vs 104 min, respectively, P = .001) and a greater duration of hospital stay (3 days vs 1 day, respectively, P = .001). CONCLUSION: In this study, operations of greater duration and smaller adrenal gland size were better predictors of complications after posterior retroperitoneoscopic adrenalectomy for benign disease than measures of obesity, including body mass index.

Conditional survival of patients with small renal masses undergoing active surveillance.

OBJECTIVES: To determine conditional survival for patients with small renal masses (SRMs) undergoing active surveillance (AS). MATERIALS AND METHODS: Patients were enrolled in a prospective AS protocol at our institution between May 2005 and January 2016. Patients with SRMs ≤4 cm with serial cross-sectional imaging available in-house for review were included. Overall survival (OS) was estimated using the Kaplan-Meier method and modelled via Cox proportional hazards models. The primary endpoints analysed were the conditional probability of survival and tumour growth over time. Landmark analysis was used to evaluate survival outcomes beyond the 2-year mark after the initial scan. The relative conditional survival of patients on AS was compared to those undergoing partial nephrectomy (PN) using inverse probability of treatment weighting. RESULTS: A total of 272 patients were included in this analysis. The mean initial SRM size was 1.74 ± 0.77 cm, and the mean mass size closest to the 2-year mark was 1.97 ± 0.83 cm. The likelihood of continued survival to 5 years improved after the 2-year landmark. Patients with masses <3 cm who survived the first 2 years on AS had a 0.84-0.85 chance of surviving to 5 years, and if they survived 3 years, the probability of surviving to 5 years improved to 0.91. A slow tumour growth (ß: 0.12; P < 0.001) with parallel growth rates was found for tumours <3 cm. Patients on AS and those who underwent PN had similar OS for ~7 years, beyond which PN demonstrated a trend of lower risk of death compared with AS (hazard ratio 0.57; P = 0.07). CONCLUSIONS: The conditional survival probability of patients with SRMs <3 cm on AS increased after 2 years. This information may prove useful to urologists and patients who are considering continuing AS vs intervention after the first 2 years on AS.

Risk of renal events following intravenous iodinated contrast material administration among inpatients admitted with cancer a retrospective hospital claims analysis.

BACKGROUND: There is little published evidence examining the use of contrast material (CM) and the risk of acute renal adverse events (AEs) in individuals with increasingly common risk factors including cancer and chronic kidney disease (CKD). The objective of this study was to use real world hospital data to test the hypothesis that inpatients with cancer having CT procedures with iodinated CM would have higher rates of acute renal AEs in comparison to inpatients without cancer. METHODS: Inpatient hospital visits in the Premier Hospital Database from January 1, 2010 through September 30, 2015 were eligible for inclusion. The outcome of interest was a composite of acute renal AEs including: acute kidney injury, acute renal failure requiring dialysis, contrast induced-acute kidney injury and renal failure. Multivariable models, adjusted for differences in patient demographics and comorbid conditions, were used to estimate the incremental risk of acute renal AEs by CT (with or without iodinated CM), CKD stage and type of cancer. RESULTS: Among 29,850,475 inpatient visits across 611 hospitals, 7.4% had record of a CT scan, 5.9% had CKD, and 3.4% had the primary diagnosis of cancer. The baseline risk for an acute renal AE in patients without cancer or CKD and no CT or CM was 0.5%. The absolute risk increases from baseline by 0.2% with a CT and by 0.8% with iodinated CM. Patients with CKD having a CT scan with iodinated CM have an absolute risk of 4.1 to 9.7% depending on the stage of CKD. For patients with cancer, the absolute risk increases, varying from 0.3 to 2.3% depending on the type of cancer. CONCLUSIONS: Inpatients with cancer are at higher likelihood of developing acute renal AEs following CT with iodinated CM compared to those without a cancer. Understanding the underlying risks of acute renal AEs among complex inpatient admissions is an important consideration in treatment choices for oncology patients.

Utility of Intermediate-Delay Washout CT Images for Differentiation of Malignant and Benign Adrenal Lesions: A Multivariate Analysis.

OBJECTIVE: The objective of this study was to identify features that impact the diagnostic performance of intermediate-delay washout CT for distinguishing malignant from benign adrenal lesions. MATERIALS AND METHODS: This retrospective study evaluated 127 pathologically proven adrenal lesions (82 malignant, 45 benign) in 126 patients who had undergone portal venous phase and intermediate-delay washout CT (1-3 minutes after portal venous phase) with or without unenhanced images. Unenhanced images were available for 103 lesions. Quantitatively, lesion CT attenuation on unenhanced (UA) and delayed (DL) images, absolute and relative percentage of enhancement washout (APEW and RPEW, respectively), descriptive CT features (lesion size, margin characteristics, heterogeneity or homogeneity, fat, calcification), patient demographics, and medical history were evaluated for association with lesion status using multiple logistic regression with stepwise model selection. Area under the ROC curve (Az) was calculated from both univariate and multivariate analyses. The predictive diagnostic performance of multivariate evaluations was ascertained through cross-validation. RESULTS: Az for DL, APEW, RPEW, and UA was 0.751, 0.795, 0.829, and 0.839, respectively. Multivariate analyses yielded the following significant CT quantitative features and associated Az when combined: RPEW and DL (Az = 0.861) when unenhanced images were not available and APEW and UA (Az = 0.889) when unenhanced images were available. Patient demographics and presence of a prior malignancy were additional significant factors, increasing Az to 0.903 and 0.927, respectively. The combined predictive classifier, without and with UA available, yielded 85.7% and 87.3% accuracies with cross-validation, respectively. CONCLUSION: When appropriately combined with other CT features, washout derived from intermediate-delay CT with or without additional clinical data has potential utility in differentiating malignant from benign adrenal lesions.

Observer Variability in CT Perfusion Parameters in Primary and Metastatic Tumors in the Lung.

PURPOSE: Evaluate observer variability in computed tomography perfusion measurements in lung tumors and assess the relative contributions of individual factors to overall variability. MATERIALS AND METHODS: Four observers independently delineated tumor and defined arterial input function region of interests (tumor region of interest and arterial input function region of interest) on each of 4 contiguous slice levels of computed tomography perfusion images (arterial input function level), in 12 computed tomography perfusion data sets containing lung tumors (>2.5 cm size), on 2 separate occasions. Computed tomography perfusion parameters (blood flow, blood volume, mean transit time, and permeability surface area product) for tumor volumes of interest were computed for all combinations of these factors, totaling up to 1024 combinations per patient. Overall, inter- and intraobserver variability were assessed by within-patient coefficient of variation, variance components analyses, and intraclass correlation. RESULTS: Overall observer within-patient coefficient of variations for tumor blood flow, blood volume, mean transit time, and permeability surface area product were 20.3%, 11.9%, 6.3%, and 31.7%, and intraclass correlations were 0.94, 0.91, 0.82, and 0.72, respectively. Interobserver tumor volume of interest and arterial input function level were the highest contributors to overall variance for blood flow, blood volume, and mean transit time. Overall intraobserver wCVs for blood flow, blood volume, mean transit time, and permeability surface area product (4.3%, 2.4%, 0.9%, and 3.1%) were smaller than interobserver within-patient coefficient of variations (9.5%, 5.6%, 1.6%, and 7.0%), respectively. CONCLUSION: The largest contributors to observer variability were interobserver tumor volume of interest and arterial input function level. Overall variability in computed tomography perfusion studies can potentially be minimized by using a single observer and a consistent level for arterial input function, which would be important considerations in longitudinal and multicenter studies. Methods to reliably define arterial input function and delineate tumor volumes would help to reduce variability in estimations of computed tomography perfusion parameter values.

Combining Washout and Noncontrast Data From Adrenal Protocol CT: Improving Diagnostic Performance.

RATIONALE AND OBJECTIVES: To determine if combination of washout and noncontrast data from delayed adrenal computed tomography (CT) improves diagnostic performance, and demonstration of an optimizing analytical framework. MATERIALS AND METHODS: This retrospective study consisted of 97 adrenal lesions, in 96 patients, with pathologically proven adrenal lesions (75 benign; 22 malignant), who had undergone noncontrast, portal- and approximate 15-minute delayed-phase CT. Lesion CT attenuations (Hounsfield units [HU]) during each phase, and "absolute" and "relative" percent enhancement washouts (APEW and RPEW) were assessed. The optimum combination of sequential parameters and thresholds was determined by recursive partitioning analysis; resultant diagnostic performance was compared to commonly applied single-parameter criteria for malignancy (noncontrast > 10 HU, APEW < 60%, RPEW < 40%). RESULTS: The above single-parameter criteria yielded sensitivities, specificities, and accuracies for malignancy of 100.0%, 41.3%, and 54.6%; 97.9%, 61.3%, and 69.1%; and 96.6%, 74.7%, and 78.4%, respectively. Recursive partitioning analysis identified noncontrast ≥24.75 HU, with subsequent APEW ≤63.49%, as the optimum sequential parameter-threshold combination, which yielded increased sensitivity, specificity, and accuracy of 100.0%, 85.3%, and 90.7%, respectively. Discrimination using the combined sequential classifier yielded statistically significant improvements in accuracy when compared to the above conventional single-parameter criteria (all P ≤ .039). CONCLUSION: Sequential application of noncontrast and washout criteria from delayed contrast-enhanced adrenal CT can improve diagnostic performance beyond that of commonly applied single-parameter criteria. Validation of the sequential ordering and refinement of the specific threshold values warrant further study.

Differentiation of Malignant and Benign Adrenal Lesions With Delayed CT: Multivariate Analysis and Predictive Models.

OBJECTIVE: The purpose of this study is to identify imaging and patient parameters that affect the diagnostic performance of delayed contrast-enhanced CT for distinguishing malignant from benign adrenal lesions larger than 1 cm in adult patients and to derive predictive models. MATERIALS AND METHODS: This retrospective study assessed 97 pathologically proven adrenal lesions that had undergone unenhanced, portal venous, and 15-minute delayed CT. Quantitatively, single-parameter evaluations of lesion attenuation (in Hounsfield units) and absolute percentage enhancement washout (APEW) and relative percentage enhancement washout (RPEW) were performed. In addition, descriptive CT features (lesion size, margin definition, heterogeneity vs homogeneity, fat, and calcification) and patients' demographic characteristics and medical history of malignancy were evaluated for association with lesion status using multiple logistic regression with stepwise model selection. Areas under the ROC curve (Az) were determined for univariate and multivariate analyses. Leave-one-lesion-out cross-validation was applied to ascertain the predictive performance of single-parameter and multivariate evaluations. RESULTS: The Az values for unenhanced attenuation, portal venous attenuation, delayed attenuation, APEW, and RPEW were 0.835, 0.534, 0.847, 0.792, and 0.871, respectively. Multivariate analyses revealed that portal venous attenuation, delayed attenuation, and APEW were significant features, with an Az of 0.923 when combined. The addition of the descriptive CT features increased the Az to 0.938; patient age and a history of malignancy were additional significant factors, increasing the Az to 0.956 and 0.972, respectively. The combined predictive classifier yielded 89% accuracy under cross-validation, compared with the best commonly applied single-parameter evaluation (77% for RPEW < 40%). CONCLUSION: Multivariate imaging evaluation applied to delayed contrast-enhanced CT alone, with or without patient characteristics, improves diagnostic performance for characterizing adrenal lesions beyond those of single-parameter evaluations. Predictive formulas assessing the probabilities of lesion benignity or malignancy are provided.

Correction: Harmonizing the pixel size in retrospective computed tomography radiomics studies.

[This corrects the article DOI: 10.1371/journal.pone.0178524.].

Spatial Bayesian modeling of GLCM with application to malignant lesion characterization.

The emerging field of cancer radiomics endeavors to characterize intrinsic patterns of tumor phenotypes and surrogate markers of response by transforming medical images into objects that yield quantifiable summary statistics to which regression and machine learning algorithms may be applied for statistical interrogation. Recent literature has identified clinicopathological association based on textural features deriving from gray-level co-occurrence matrices (GLCM) which facilitate evaluations of gray-level spatial dependence within a delineated region of interest. GLCM-derived features, however, tend to contribute highly redundant information. Moreover, when reporting selected feature sets, investigators often fail to adjust for multiplicities and commonly fail to convey the predictive power of their findings. This article presents a Bayesian probabilistic modeling framework for the GLCM as a multivariate object as well as describes its application within a cancer detection context based on computed tomography. The methodology, which circumvents processing steps and avoids evaluations of reductive and highly correlated feature sets, uses latent Gaussian Markov random field structure to characterize spatial dependencies among GLCM cells and facilitates classification via predictive probability. Correctly predicting the underlying pathology of 81% of the adrenal lesions in our case study, the proposed method outperformed current practices which achieved a maximum accuracy of only 59%. Simulations and theory are presented to further elucidate this comparison as well as ascertain the utility of applying multivariate Gaussian spatial processes to GLCM objects.

Metastatic melanoma to the testis.

This case report presents the ultrasound and positron emission tomography-computed tomography (PET-CT) imaging findings related to a patient with metastatic melanoma to the testis. We review this very rare entity and discuss the role of imaging.

CT perfusion in normal liver and liver metastases from neuroendocrine tumors treated with targeted antivascular agents.

OBJECTIVE: To assess the effects of bevacizumab and everolimus, individually and combined, on CT perfusion (CTp) parameters in liver metastases from neuroendocrine tumors (mNET) and normal liver. METHODS: This retrospective study comprised 27 evaluable patients with mNETs who had participated in a two-arm randomized clinical trial of mono-therapy with bevacizumab (Arm B) or everolimus (Arm E) for 3 weeks, followed by combination of both targeted agents. CTp was undertaken at baseline, 3 and 9 weeks, to evaluate blood flow (BF), blood volume (BV), mean transit time (MTT), permeability surface area product (PS), and hepatic arterial fraction (HAF) of mNET and normal liver, using a dual-input distributed parameter physiological model. Linear mixed models were used to estimate and compare CTp parameter values between time-points. RESULTS: In tumor, mono-therapy with bevacizumab significantly reduced BV (p = 0.05); everolimus had no effects on CTp parameters. Following dual-therapy, BV and BF were significantly lower than baseline in both arms (p ≤ 0.04), and PS was significantly lower in Arm E (p < 0.0001). In normal liver, mono-therapy with either agent had no significant effects on CTp parameters: dual-therapy significantly reduced BV, MTT, and PS, and increased HAF, relative to baseline in Arm E (p ≤ 0.04); in Arm B, only PS reduced (p = 0.04). CONCLUSIONS: Bevacizumab and everolimus, individually and when combined, have significant and differential effects on CTp parameters in mNETs and normal liver, which is evident soon after starting therapy. CTp may offer an early non-invasive means to investigate the effects of drugs in tumor and normal tissue.

Tree-based Methods for Characterizing Tumor Density Heterogeneity.

Solid lesions emerge within diverse tissue environments making their characterization and diagnosis a challenge. With the advent of cancer radiomics, a variety of techniques have been developed to transform images into quantifiable feature sets producing summary statistics that describe the morphology and texture of solid masses. Relying on empirical distribution summaries as well as grey-level co-occurrence statistics, several approaches have been devised to characterize tissue density heterogeneity. This article proposes a novel decision-tree based approach which quantifies the tissue density heterogeneity of a given lesion through its resultant distribution of tree-structured dissimilarity metrics computed with least common ancestor trees under repeated pixel re-sampling. The methodology, based on statistics derived from Galton-Watson trees, produces metrics that are minimally correlated with existing features, adding new information to the feature space and improving quantitative characterization of the extent to which a CT image conveys heterogeneous density distribution. We demonstrate its practical application through a diagnostic study of adrenal lesions. Integrating the proposed with existing features identifies classifiers of three important lesion types; malignant from benign (AUC = 0.78), functioning from non-functioning (AUC = 0.93) and calcified from non-calcified (AUC of 1).