Association Between 18F-FDG PET Activity and HER2 Status in Breast Cancer Brain Metastases.

Purpose: The objective of this study was to evaluate whether uptake on 18F-fluorodeoxyglucose (18F-FDG) PET could help differentiate HER2-positive from HER2-negative breast cancer brain metastases. Methods: In this retrospective, cross-sectional study of a cohort of 14 histologically proven breast cancer brain metastases, we analyzed both preoperative 18F-FDG PET/CT and HER2 status of the resected/biopsied brain specimens. The maximum standardized uptake values (SUVmax) of the lesions were normalized to contralateral normal white matter and compared using Mann-Whitney U tests. Results: The study cohort was comprised of 12 women with breast cancer with a mean age of 59 years (range: 43-76 years) with a total of 14 distinct brain metastatic lesions. The SUVmax ratio of HER2-positive breast cancer brain metastases was significantly greater than that of HER2-negative lesions (3.98 vs 1.79, U = 38.00, p = 0.008). Conclusion: The SUVmax ratio may help to identify the HER2 status of breast cancer brain metastases, if validated prospectively.

Multimodal smoking cessation treatment combining transcranial magnetic stimulation, cognitive behavioral therapy, and nicotine replacement therapy in veterans with posttraumatic stress disorder: A feasibility randomized controlled trial protocol.

Tobacco-related deaths exceed those resulting from homicides, suicides, motor vehicle accidence, alcohol consumption, illicit substance use, and acquired immunodeficiency syndrome (AIDS), combined. Amongst U.S. veterans, this trend is particularly concerning given that those suffering from posttraumatic stress disorder (PTSD)-about 11% of those receiving care from the Department of Veterans Affairs (VA)-have triple the risk of developing tobacco use disorder (TUD). The most efficacious strategies being used at the VA for smoking cessation only result in a 23% abstinence rate, and veterans with PTSD only achieve a 4.5% abstinence rate. Therefore, there is a critical need to develop more effective treatments for smoking cessation. Recent studies have revealed the insula as integrally involved in the neurocircuitry of TUD, specifically showing that individuals with brain lesions involving this region had drastically improved quit rates. Some of these studies show a probability of quitting up to 5 times greater compared to non-insula lesioned regions). Altered activity of the insula may be involved in the disruption of the salience network's (SN) connectivity to the executive control network (ECN), which compromises that patient's ability to switch between interoceptive states focused on cravings to executive and cognitive control. Thus, we propose a feasibility phase II randomized controlled trial (RCT) to study a patterned form of repetitive transcranial magnetic stimulation (rTMS), intermittent theta burst stimulation (iTBS), at 90% of the subject's resting motor threshold (rMT) applied over a region in the right post-central gyrus most functionally connected to the right posterior insula. We hypothesize that by increasing functional connectivity between the SN with the ECN to enhance executive control and by decreasing connectivity with the default mode network (DMN) to reduce interoceptive focus on withdrawal symptoms, we will improve smoking cessation outcomes. Fifty eligible veterans with comorbid TUD and PTSD will be randomly assigned to two conditions: active-iTBS + cognitive behavioral therapy (CBT) + nicotine replacement therapy (NRT) (n=25) or sham-iTBS + CBT + NRT (n=25). The primary outcome, feasibility, will be determined by achieving a recruitment of 50 participants and retention rate of 80%. The success of iTBS will be evaluated through self-reported nicotine use, cravings, withdrawal symptoms, and abstinence following quit date (confirmed by bioverification) along with evaluation for target engagement through neuroimaging changes, specifically connectivity differences between the insula and other regions of interest.

Mobile health contingency management for smoking cessation among veterans experiencing homelessness: A comparative effectiveness trial.

Tobacco cessation is reduced in U.S. military veterans experiencing homelessness. Mobile contingency management (mCM) is a promising treatment for tobacco use among populations experiencing homelessness, but past CM studies have largely been small, have relied on in-person follow-up, and/or lacked long-term biochemically verified abstinence measures. Veterans who smoked and were experiencing homelessness (N = 127) were randomly assigned to mCM treatment (4 weeks of mCM, 5 weeks of telehealth counseling, and the option of 12 weeks of pharmacotherapy) or VA standard care (3 biweekly group sessions and clinically appropriate pharmacotherapy), and all participants were randomly assigned to a $100 longer-term financial incentive for abstinence at 3-month follow-up. Participants were followed at 3-, 6-, and 12-months post-randomization, with the a priori main outcome designated as biochemically verified prolonged abstinence (with lapses) at 6-month follow-up. At 6-months, participants in the mCM group were significantly more likely to meet criteria for prolonged abstinence (OR = 3.1). Across time points, veterans in the mCM group had twice the odds of prolonged abstinence as those in the standard care group. However, by the 12-month follow-up, there was no statistically significant group difference in abstinence. Cost-effectiveness analysis indicated a modest increase in cost ($1,133) associated with an increase of one quality-adjusted life year saved for the intervention compared to standard care. mCM is a cost-effective approach to smoking cessation among veterans experiencing homelessness. Considering waning potency of this and other tobacco cessation interventions at 12-month follow-up, it is crucial to implement strategies to sustain abstinence for individuals experiencing homelessness.

Association of lesion contour and lesion composition on MR with HER2 status in breast cancer brain metastases.

BACKGROUND AND PURPOSE: With the development of HER2-directed therapies, identifying non-invasive imaging biomarkers of HER2 status in breast cancer brain metastases has become increasingly important, particularly given the risks of tissue sampling within the brain and the possibility of a change in receptor expression from the primary tumor to the brain metastasis. The purpose of this study was to evaluate whether lesion contour and composition on MR could help identify the HER2 status of breast cancer brain metastases. MATERIALS AND METHODS: We derived a cohort of 34 women with a mean age of 55 years (range: 31-81 years) with a total of 47 distinct histologically proven breast cancer brain metastases with preoperative contrast-enhanced brain MR and HER2 immunohistochemistry and/or fluorescent in-situ hybridization (FISH) of the resected/biopsied brain specimens from 2018 to 2021. Two fellowship-trained neuroradiologists evaluated the lesion contour and lesion composition of each lesion. Logistic regression analyses were performed. RESULTS: In a logistic regression model, an irregular contour had an odds ratio of 170 (p = 0.007) in differentiating HER2-positive from HER2-negative lesions. In a logistic regression model, when compared to a predominantly cystic lesion composition, a solid lesion composition had an odds ratio of 17 (p = 0.016) in differentiating HER2-positive from HER2-negative lesions. CONCLUSION: Lesion contour and lesion composition on MR were significantly associated with the HER2 status of breast cancer brain metastases. Current assessment of HER2 status requires tissue sampling and immunochemical and/or FISH analyses. A non-invasive imaging biomarker that may help predict HER2 status may be of great clinical value.

Association of Relative Cerebral Blood Volume from Dynamic Susceptibility Contrast-Enhanced Perfusion MR with HER2 Status in Breast Cancer Brain Metastases.

RATIONALE AND OBJECTIVES: With the development of HER2-directed therapies, identifying non-invasive imaging biomarkers of HER2 expression in breast cancer brain metastases has become increasingly important. The purpose of this study was to investigate whether relative cerebral blood volume (rCBV) from dynamic susceptibility contrast-enhanced (DSC) perfusion MR could help identify the HER2 status of breast cancer brain metastases. MATERIALS AND METHODS: With IRB approval for this HIPAA-compliant cross-sectional study and a waiver of informed consent, we queried our institution's electronic medical record to derive a cohort of 14 histologically proven breast cancer brain metastases with preoperative DSC perfusion MR and HER2 analyses of the resected/biopsied brain specimens from 2011-2021. The rCBV of the lesions was measured and compared using Mann-Whitney tests. Receiver operating characteristic analyses were performed to evaluate the performance of rCBV in identifying HER2 status. RESULTS: The study cohort was comprised of 14 women with a mean age of 56 years (range: 32-81 years) with a total of 14 distinct lesions. The rCBV of HER2-positive breast cancer brain metastases was significantly greater than the rCBV of HER2-negative lesions (8.02 vs 3.97, U=48.00, p=0.001). rCBV differentiated HER2-positive lesions from HER2-negative lesions with an area under the curve of 0.98 (standard error=0.032, p<0.001). The accuracy-maximizing rCBV threshold (4.8) was associated with an accuracy of 93% (13/14), a sensitivity of 100% (7/7), and a specificity of 86% (6/7). CONCLUSION: rCBV may assist in identifying the HER2 status of breast cancer brain metastases, if validated in a large prospective trial.

Performance of enhancement on brain MRI for identifying HER2 overexpression in breast cancer brain metastases.

PURPOSE: To investigate whether enhancement on MRI could help identify HER2 overexpression in breast cancer brain metastases. METHODS: We derived a cohort of 38 histologically proven breast cancer brain metastases with preoperative contrast-enhanced brain MRI and HER2 fluorescent in-situ hybridization of the resected/biopsied brain specimens from 2018 to 2021. Enhancement of the lesions was measured and compared using t-tests. Receiver operating characteristic and logistic regression analyses were performed to evaluate the performance of MRI enhancement in identifying HER2 overexpression. RESULTS: The study cohort was comprised of 29 women with a mean age of 55 years (range: 31-81 years) with a total of 38 distinct lesions. The HER2-positive subcohort was comprised of 17 patients, while the HER2-negative subcohort was comprised of 13 patients. The percent signal intensity change (PSIC) of HER2-positive breast cancer brain metastases was significantly greater than that of HER2-negative lesions (310 v. 153, P = 0.002). The PSIC differentiated HER2-positive lesions from HER2-negative lesions with an area under the curve of 0.88 (P < 0.001). In a model controlling for lesion size, lesion location, tumor grade, patient age, scanner magnetic field strength, and contrast agent, the PSIC had an accuracy of 92% (35/38), sensitivity of 96% (23/24), and specificity of 86% (12/14) in differentiating HER2-positive lesions from HER2-negative lesions. CONCLUSION: Enhancement on MRI may assist in identifying HER2 overexpression in breast cancer brain metastases, if validated prospectively.

Transcranial Magnetic Stimulation Treatment for Smoking Cessation: An Introduction for Primary Care Clinicians.

Tobacco use remains the number one preventable cause of death in the United States, resulting in significant public health and economic costs. Despite progress in reducing tobacco use through pharmacotherapy and psychotherapy smoking cessation interventions, additional treatment options are still needed to improve treatment effectiveness. As an adjunctive treatment, the US Food and Drug Administration recently cleared transcranial magnetic stimulation (TMS), a noninvasive brain stimulation technique, as an aid for smoking cessation in adults. Given that most smoking cessation interventions occur in the primary care setting, this article aims to introduce TMS, to provide an overview of the evidence of TMS for smoking cessation, and to outline the procedures for implementing TMS in the primary care setting when referral to an interventional psychiatrist is not possible. With growing scientific evidence and increasing regulatory approval of TMS for smoking cessation, this novel treatment option is now available for patients who want to quit smoking but have been unsuccessful with pharmacologic approaches.

Utilizing transcranial direct current stimulation to enhance laparoscopic technical skills training: A randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that delivers constant, low electrical current resulting in changes to cortical excitability. Prior work suggests it may enhance motor learning giving it the potential to augment surgical technical skill acquisition. OBJECTIVES: The aim of this study was to test the efficacy of tDCS, coupled with motor skill training, to accelerate laparoscopic skill acquisition in a pre-registered (NCT03083483), double-blind and placebo-controlled study. We hypothesized that relative to sham tDCS, active tDCS would accelerate the development of laparoscopic technical skills, as measured by the Fundamentals of Laparoscopic Surgery (FLS) Peg Transfer task quantitative metrics. METHODS: In this study, sixty subjects (mean age 22.7 years with 42 females) were randomized into sham or active tDCS in either bilateral primary motor cortex (bM1) or supplementary motor area (SMA) electrode configurations. All subjects practiced the FLS Peg Transfer Task during six 20-min training blocks, which were preceded and followed by a single trial pre-test and post-test. The primary outcome was changes in laparoscopic skill performance over time, quantified by group differences in completion time from pre-test to post-test and learning curves developed from a calculated score accounting for errors. RESULTS: Learning curves calculated over the six 20-min training blocks showed significantly greater improvement in performance for the bM1 group than the sham group (t = 2.07, p = 0.039), with the bM1 group achieving approximately the same amount of improvement in 4 blocks compared to the 6 blocks required of the sham group. The SMA group also showed greater mean improvement than sham, but exhibited more variable learning performance and differences relative to sham were not significant (t = 0.85, p = 0.400). A significant main effect was present for pre-test versus post-test times (F = 133.2, p < 0.001), with lower completion times at post-test, however these did not significantly differ for the training groups. CONCLUSION: Laparoscopic skill training with active bilateral tDCS exhibited significantly greater learning relative to sham. The potential for tDCS to enhance the training of surgical skills, therefore, merits further investigation to determine if these preliminary results may be replicated and extended.

Association of tumor grade, enhancement on multiphasic CT and microvessel density in patients with clear cell renal cell carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) comprises nearly 90% of all diagnosed RCC subtypes and has the worst prognosis and highest metastatic potential. The strongest prognostic factors for patients with ccRCC include histological subtype and Fuhrman grade, which are incorporated into prognostic models. Since ccRCC is a highly vascularized tumor, there may be differences in enhancement patterns on multidetector CT (MDCT) due to the hemodynamics and microvessel density (MVD) of the lesions. This may provide a noninvasive method to characterize incidentally detected low- and high-grade ccRCCs on MDCT. The purpose of our study was to determine the correlation between MDCT enhancement parameters, ccRCC MVD, and Fuhrman grade to determine its utility and value in assessing tumor vascularity and grade in vivo. METHODS: In this retrospective, HIPAA-compliant, institutional review board-approved study with waiver of informed consent, 127 consecutive patients with 89 low-grade (LG), and 43 high-grade (HG) ccRCCs underwent preoperative four-phase MDCT. A 3D volume of interest (VOI) was obtained for every tumor and absolute enhancement and the wash-in/wash-out of enhancement for each phase was assessed. Immunohistochemistry on resected specimens was used to quantify MVD. Linear regression and Pearson correlation were used to investigate the strength of the association between 3D VOI enhancement and MVD. Stepwise logistic regression analysis determined independent predictors of HG ccRCC. Cut-off values and odds Ratio (OR) with 95% CIs were reported. The clinical, radiomic, and pathologic features with the highest performance in the stepwise logistic regression analysis were evaluated using receiver operator characteristics (ROC) and area under the curve (AUC). RESULTS: Absolute enhancement in the nephrographic phase < 52.1 Hounsfield Units (HU) (HR 0.979, 95% CI 0.964-0.994, p value = 0.006), lesion size > 4.3 cm (HR 1.450, 95% CI 1.211-1.738, p value < 0.001), and an intratumoral MVD < 15% (HR 0.932, 95% CI 0.867-1.002, p value = 0.058) were independent predictors of HG ccRCC with an AUC of 0.818 (95% CI 0.725-0.911). HG ccRCCs had a significant association between 3D VOI enhancement and MVD in each post-contrast phase (r2 = 0.238 to 0.455, p < 0.05). CONCLUSIONS: Absolute enhancement of the entire lesion obtained from a 3D VOI in the nephrographic phase on preoperative MDCT can provide quantitative data that are a significant, independent predictor of a high-grade clear cell RCC and can be used to assess tumor vascularity and grade in vivo.

Deep learning and radiomics: the utility of Google TensorFlow™ Inception in classifying clear cell renal cell carcinoma and oncocytoma on multiphasic CT.

PURPOSE: Currently, all solid enhancing renal masses without microscopic fat are considered malignant until proven otherwise and there is substantial overlap in the imaging findings of benign and malignant renal masses, particularly between clear cell RCC (ccRCC) and benign oncocytoma (ONC). Radiomics has attracted increased attention for its utility in pre-operative work-up on routine clinical images. Radiomics based approaches have converted medical images into mineable data and identified prognostic imaging signatures that machine learning algorithms can use to construct predictive models by learning the decision boundaries of the underlying data distribution. The TensorFlow™ framework from Google is a state-of-the-art open-source software library that can be used for training deep learning neural networks for performing machine learning tasks. The purpose of this study was to investigate the diagnostic value and feasibility of a deep learning-based renal lesion classifier using open-source Google TensorFlow™ Inception in differentiating ccRCC from ONC on routine four-phase MDCT in patients with pathologically confirmed renal masses. METHODS: With institutional review board approval for this 1996 Health Insurance Portability and Accountability Act compliant retrospective study and a waiver of informed consent, we queried our institution's pathology, clinical, and radiology databases for histologically proven cases of ccRCC and ONC obtained between January 2000 and January 2016 scanned with a an intravenous contrast-enhanced four-phase renal mass protocol (unenhanced (UN), corticomedullary (CM), nephrographic (NP), and excretory (EX) phases). To extract features to be used for the machine learning model, the entire renal mass was contoured in the axial plane in each of the four phases, resulting in a 3D volume of interest (VOI) representative of the entire renal mass. We investigated thirteen different approaches to convert the acquired VOI data into a set of images that adequately represented each tumor which was used to train the final layer of the neural network model. Training was performed over 4000 iterations. In each iteration, 90% of the data were designated as training data and the remaining 10% served as validation data and a leave-one-out cross-validation scheme was implemented. Accuracy, sensitivity, specificity, positive (PPV) and negative predictive (NPV) values, and CIs were calculated for the classification of the thirteen processing modes. RESULTS: We analyzed 179 consecutive patients with 179 lesions (128 ccRCC and 51 ONC). The ccRCC cohort had a mean size of 3.8 cm (range 0.8-14.6 cm) and the ONC cohort had a mean lesion size of 3.9 cm (range 1.0-13.1 cm). The highest specificity and PPV (52.9% and 80.3%, respectively) were achieved in the EX phase when we analyzed the single mid-slice of the tumor in the axial, coronal and sagittal plane, and when we increased the number of mid-slices of the tumor to three, with an accuracy of 75.4%, which also increased the sensitivity to 88.3% and the PPV to 79.6%. Using the entire tumor volume also showed that classification performance was best in the EX phase with an accuracy of 74.4%, a sensitivity of 85.8% and a PPV of 80.1%. When the entire tumor volume, plus mid-slices from all phases and all planes presented as tiled images, were submitted to the final layer of the neural network we achieved a PPV of 82.5%. CONCLUSIONS: The best classification result was obtained in the EX phase among the thirteen classification methods tested. Our proof of concept study is the first step towards understanding the utility of machine learning in the differentiation of ccRCC from ONC on routine CT images. We hope this could lead to future investigation into the development of a multivariate machine learning model which may augment our ability to accurately predict renal lesion histology on imaging.

Association of qualitative and quantitative imaging features on multiphasic multidetector CT with tumor grade in clear cell renal cell carcinoma.

PURPOSE: The purpose of the study was to determine if enhancement features and qualitative imaging features on multiphasic multidetector computed tomography (MDCT) were associated with tumor grade in patients with clear cell renal cell carcinoma (ccRCC). METHODS: In this retrospective, IRB approved, HIPAA-compliant, institutional review board-approved study with waiver of informed consent, 127 consecutive patients with 89 low grade (LG) and 43 high grade (HG) ccRCCs underwent preoperative four-phase MDCT in unenhanced (UN), corticomedullary (CM), nephrographic (NP), and excretory (EX) phases. Previously published quantitative (absolute peak lesion enhancement, absolute peak lesion enhancement relative to normal enhancing renal cortex, 3D whole lesion enhancement and the wash-in/wash-out of enhancement within the 3D whole lesion ROI) and qualitative (enhancement pattern; presence of necrosis; pattern of; tumor margin; tumor-parenchymal interface, tumor-parenchymal interaction; intratumoral vascularity; collecting system infiltration; renal vein invasion; and calcification) assessments were obtained for each lesion independently by two fellowship-trained genitourinary radiologists. Comparisons between variables included χ2, ANOVA, and student t test. p values less than 0.05 were considered to be significant. Inter-reader agreement was obtained with the Gwet agreement coefficient (AC1) and standard error (SE) was reported. RESULTS: No significant differences were observed between the LG and HG ccRCC cohorts with respect to absolute peak lesion enhancement and relative lesion enhancement ratio. There was a significant inverse correlation between low and high grade ccRCC and tumor enhancement the NP (71 HU vs. 54 HU, p < 0.001) and EX (52 HU vs. 39 HU, p < 0.001) phases using the 3D whole lesion ROI method. The percent wash-in of 3D enhancement from the UN to the CM phase was also significantly different between LG and HG ccRCCs (352% vs. 255%, p = 0.003). HG lesions showed significantly more calcification, necrosis, collecting system infiltration and ill-defined tumor margins (p < 0.05). Overall agreement between the two readers had a mean AC1 of 0.8172 (SE 0.0235). CONCLUSIONS: Quantitatively, high grade ccRCC had significantly lower whole lesion enhancement in the NP and EX phases on MDCT. Qualitatively, high grade ccRCC were significantly more likely to be associated with calcifications, necrosis, collecting system infiltration, and an ill-defined tumor margin.

Association of the Gross Appearance of Intratumoral Vascularity at MDCT With the Carbonic Anhydrase IX Score in Clear Cell Renal Cell Carcinoma.

OBJECTIVE: The purpose of this study was to determine whether qualitative MDCT features are associated with the carbonic anhydrase IX (CAIX) score of clear cell renal cell carcinoma (RCC). The CAIX score has been previously found to have prognostic significance for disease-free survival, overall survival, and lymph node involvement. MATERIALS AND METHODS: A cohort of 105 histologically proven clear cell RCCs in patients who underwent preoperative four-phase renal mass MDCT was derived from 2001 to 2013. Two genitourinary radiologists evaluated each lesion for the gross appearance of intratumoral vascularity, calcification, enhancement pattern, necrosis, margin, collecting system invasion, and renal vein invasion. Immunohistochemical analysis was used to determine the CAIX score (defined as the positive staining percentage multiplied by the staining intensity). Logistic and linear regression analyses were performed. RESULTS: In a linear regression model controlled for lesion size and stage, the gross appearance of intratumoral vascularity had a significant positive association with CAIX score (ß = 38.33, p = 0.010). In a logistic regression model controlled for lesion size and stage, the gross appearance of intratumoral vascularity had an odds ratio of 2.85 (p = 0.019) in differentiating clear cell RCCs with a CAIX score of 200-300 from clear cell RCCs with a CAIX score of 0-199. CONCLUSION: In clear cell RCCs, the gross appearance of intratumoral vascularity at MDCT was significantly associated with CAIX score, a prognostically significant molecular marker. Current assessment of CAIX score requires pathologic tissue sampling and immunohistochemical analysis. A noninvasive imaging biomarker that may help predict CAIX score may be of great clinical value.

Clear cell renal cell carcinoma: identifying PTEN expression on multiphasic MDCT.

PURPOSE: To investigate whether multiphasic MDCT enhancement profiles can help to identify PTEN expression in clear cell renal cell carcinomas (ccRCCs). Lack of PTEN expression is associated with worsened overall survival, a more advanced Fuhrman grade, and a greater likelihood of lymph mode metastasis. METHODS: With IRB approval for this retrospective study, we derived a cohort of 103 histologically proven ccRCCs with preoperative 4-phase renal mass MDCT from 2001-2013. Following manual segmentation, a computer-assisted detection algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase; a 0.5-cm-diameter region of interest was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as [(Maximal lesion attenuation - cortex attenuation)/cortex attenuation] × 100. Absolute and relative attenuation in each phase were compared using t tests. The performance of multiphasic enhancement in identifying PTEN expression was assessed with logistic regression analysis. RESULTS: PTEN-positive and PTEN-negative ccRCCs both exhibited peak enhancement in the corticomedullary phase. Relative corticomedullary phase attenuation was significantly greater for PTEN-negative ccRCCs in comparison to PTEN-positive ccRCCs (33.7 vs. 9.5, p = 0.03). After controlling for lesion stage and size, relative corticomedullary phase attenuation had an accuracy of 84% (86/103), specificity of 100% (84/84), sensitivity of 11% (2/19), positive predictive value of 100% (2/2), and negative predictive value of 83% (84/101) in identifying PTEN expression. CONCLUSION: Relative corticomedullary phase attenuation may help to identify PTEN expression in ccRCCs, if validated prospectively.

Utility of multiphasic multidetector computed tomography in discriminating between clear cell renal cell carcinomas with high and low carbonic anhydrase-IX expression.

PURPOSE: To investigate if multiphasic multidetector computed tomography (MDCT) enhancement profiles can distinguish clear cell renal cell carcinomas (ccRCCs) with high carbonic anhydrase-IX (CA-IX) expression from ccRCCs with low CA-IX expression. METHODS: With IRB approval for this retrospective study, we derived a cohort of 105 histologically proven ccRCCs with preoperative 4-phase renal mass MDCT from 2001 to 2013. Following manual segmentation, the computer-assisted detection algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase. CA-IX expression level was determined by immunohistochemical staining of tumor specimens. In the high and low CA-IX expression subgroups, the magnitude of enhancement and washout were compared using t tests; the performance of contrast washout in differentiating between subgroups was assessed with logistic regression analysis. RESULTS: ccRCCs with high and low CA-IX expression both exhibited peak enhancement in the corticomedullary phase. ccRCCs with high CA-IX expression demonstrated significantly greater relative nephrographic washout than those with low CA-IX expression (18.4% vs. 7.8%, p = 0.03). ccRCCs with high CA-IX expression had greater relative excretory washout than ccRCCs with low CA-IX expression with a trend toward significance (33.4% vs. 25.2%, p = 0.05). After controlling for tumor size and stage, for distinguishing ccRCCs with high and low CA-IX expression, relative excretory washout had a sensitivity, negative predictive value, accuracy, and positive predictive value of 99% (65/66), 88% (7/8), 69% (72/105), and 67% (65/97), respectively. CONCLUSION: Relative nephrographic and excretory washout may have the potential to help distinguish ccRCCs with high and low CA-IX expression, but this requires further validation.

Clear Cell Renal Cell Carcinoma: Identifying the Loss of the Y Chromosome on Multiphasic MDCT.

OBJECTIVE: The objective of our study was to investigate whether multiphasic MDCT enhancement can help identify clear cell renal cell carcinomas (RCCs) with the loss of the Y chromosome. MATERIALS AND METHODS: We derived a cohort of 43 clear cell RCCs in men who underwent preoperative four-phase renal mass MDCT from October 2000 to August 2013. Each lesion was segmented in its entirety on axial images. A computer-assisted detection algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase. A 0.5-cm-diameter ROI was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as follows: [(maximal lesion attenuation - cortex attenuation) / cortex attenuation] × 100. Absolute attenuation and relative attenuation in each phase were compared using t tests. RESULTS: Both clear cell RCCs with the loss of the Y chromosome and clear cell RCCs without the loss of the Y chromosome exhibited peak enhancement in the corticomedullary phase. However, relative nephrographic attenuation of clear cell RCCs with the loss of Y was significantly less than that of clear cell RCCs without the loss of Y (mean, -8.9 vs 8.4 respectively; p = 0.013). A relative nephrographic attenuation threshold of -1.6 identified the loss of Y with an accuracy of 70% (30/43), sensitivity of 73% (16/22), and specificity of 67% (14/21). CONCLUSION: Multiphasic MDCT enhancement may assist in identifying the loss of the Y chromosome in clear cell RCCs; this result should be validated in a large prospective trial.

Sarcomatoid Renal Cell Carcinoma and Collecting Duct Carcinoma: Discrimination From Common Renal Cell Carcinoma Subtypes and Benign RCC Mimics on Multiphasic MDCT.

RATIONALE AND OBJECTIVES: To investigate whether imaging features on multiphasic multidetector computed tomography (MDCT) can help discriminate sarcomatoid renal cell carcinoma (RCC) and collecting duct carcinoma (CDC) from other solid renal masses. MATERIALS AND METHODS: With institutional review board approval for this HIPAA-compliant study, we derived a cohort of 7 sarcomatoid RCCs, 4 CDCs, 165 clear cell RCCs, 56 papillary RCCs, 22 chromophobe RCCs, 49 oncocytomas, and 16 lipid-poor angiomyolipomas with preoperative multiphasic MDCT with up to four phases (unenhanced, corticomedullary, nephrographic, and excretory). Each lesion was reviewed for contour, spread pattern, pattern of enhancement, neovascularity, and calcification. RESULTS: Sarcomatoid RCCs and CDCs were more likely than other solid renal masses to have an irregular contour (64% vs 2%, P < 0.001) and an infiltrative spread pattern, defined as infiltration into adjacent renal parenchyma, collecting system, or neighboring structures (82% vs 7%, P < 0.001). When used to discriminate sarcomatoid RCC and CDC from other solid renal masses, an infiltrative spread pattern had a specificity of 93% (287/308) and sensitivity of 82% (9/11), and an irregular contour had a specificity of 98% (303/308) and sensitivity of 64% (7/11). CONCLUSIONS: Solid renal lesions with an irregular contour or an infiltrative spread pattern are suspicious for sarcomatoid RCC or CDC.

Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor angiomyolipoma on multiphasic multidetector computed tomography.

OBJECTIVE: To evaluate the performance of a novel, quantitative computer-aided diagnostic (CAD) algorithm on four-phase multidetector computed tomography (MDCT) to detect peak lesion attenuation to enable differentiation of clear cell renal cell carcinoma (ccRCC) from chromophobe RCC (chRCC), papillary RCC (pRCC), oncocytoma, and fat-poor angiomyolipoma (fp-AML). MATERIALS AND METHODS: We queried our clinical databases to obtain a cohort of histologically proven renal masses with preoperative MDCT with four phases [unenhanced (U), corticomedullary (CM), nephrographic (NP), and excretory (E)]. A whole lesion 3D contour was obtained in all four phases. The CAD algorithm determined a region of interest (ROI) of peak lesion attenuation within the 3D lesion contour. For comparison, a manual ROI was separately placed in the most enhancing portion of the lesion by visual inspection for a reference standard, and in uninvolved renal cortex. Relative lesion attenuation for both CAD and manual methods was obtained by normalizing the CAD peak lesion attenuation ROI (and the reference standard manually placed ROI) to uninvolved renal cortex with the formula [(peak lesion attenuation ROI - cortex ROI)/cortex ROI] × 100%. ROC analysis and area under the curve (AUC) were used to assess diagnostic performance. Bland-Altman analysis was used to compare peak ROI between CAD and manual method. RESULTS: The study cohort comprised 200 patients with 200 unique renal masses: 106 (53%) ccRCC, 32 (16%) oncocytomas, 18 (9%) chRCCs, 34 (17%) pRCCs, and 10 (5%) fp-AMLs. In the CM phase, CAD-derived ROI enabled characterization of ccRCC from chRCC, pRCC, oncocytoma, and fp-AML with AUCs of 0.850 (95% CI 0.732-0.968), 0.959 (95% CI 0.930-0.989), 0.792 (95% CI 0.716-0.869), and 0.825 (95% CI 0.703-0.948), respectively. On Bland-Altman analysis, there was excellent agreement of CAD and manual methods with mean differences between 14 and 26 HU in each phase. CONCLUSION: A novel, quantitative CAD algorithm enabled robust peak HU lesion detection and discrimination of ccRCC from other renal lesions with similar performance compared to the manual method.

Type 1 papillary renal cell carcinoma: differentiation from Type 2 papillary RCC on multiphasic MDCT.

PURPOSE: To investigate whether multiphasic MDCT enhancement can help differentiate type 1 papillary renal cell carcinoma (RCC) from type 2 papillary RCC. METHODS: With IRB approval for this HIPAA-compliant retrospective study, we derived a cohort of 36 type 1 papillary RCCs and 33 type 2 papillary RCCs with preoperative multiphasic MDCT with up to four phases (unenhanced, corticomedullary, nephrographic, and excretory) from 2000 to 2013. Following segmentation, a computer-assisted detection (CAD) algorithm selected a 0.5 cm-diameter region of maximal attenuation within each lesion in each phase; a 0.5 cm-diameter region of interest was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as [(Lesion attenuation-cortex attenuation)/cortex attenuation] × 100. Absolute and relative attenuation values were compared using Mann-Whitney tests with Bonferroni correction for multiple comparisons. RESULTS: Relative excretory phase attenuation of type 2 papillary RCCs was significantly greater than that of type 1 papillary RCCs (2.0 vs. -18.3, p = 0.005). Relative excretory phase attenuation differentiated type 1 papillary RCCs from type 2 papillary RCCs with an accuracy of 73% (36/49), sensitivity of 87% (26/30), positive predictive value of 74% (26/35), and negative predictive value of 71% (10/14). CONCLUSION: Multiphasic MDCT enhancement may assist in differentiating type 1 papillary RCCs from type 2 papillary RCCs, if prospectively validated.

Performance of Relative Enhancement on Multiphasic MRI for the Differentiation of Clear Cell Renal Cell Carcinoma (RCC) From Papillary and Chromophobe RCC Subtypes and Oncocytoma.

OBJECTIVE: The objective of our study was to investigate the performance of relative enhancement on multiphasic MRI to differentiate clear cell renal cell carcinoma (RCC) from other RCC subtypes (papillary and chromophobe) and oncocytoma. MATERIALS AND METHODS: For this study, we derived a cohort of 34 clear cell RCCs, nine oncocytomas, 12 papillary RCCs, and 10 chromophobe RCCs with a preoperative multiphasic dynamic contrast-enhanced MRI study with up to four phases (i.e., unenhanced, corticomedullary, nephrographic, excretory) from 2005 to 2016. These groups were evaluated for multiphasic enhancement and were compared using Kruskal-Wallis and Mann-Whitney tests. ROC curves were constructed and logistic regression analyses were performed to evaluate the performance of multiphasic enhancement in differentiating clear cell RCCs from the other three groups. RESULTS: Clear cell RCCs exhibited significantly greater relative signal intensity compared with uninvolved renal cortex in the corticomedullary phase (mean, 2.9) than oncocytomas (-21.7, p = 0.001), papillary RCCs (-53.0, p < 0.001), and chromophobe RCCs (-21.0, p < 0.001). Relative signal intensity in the corticomedullary phase differentiated clear cell RCCs from oncocytomas with an AUC of 0.90 and with an accuracy of 84% (32/38), sensitivity of 90% (27/30), and specificity of 63% (5/8) after controlling for lesion size, patient age, and patient sex. Relative corticomedullary signal intensity differentiated clear cell RCCs from oncocytomas and other RCC subtypes with an AUC of 0.93 and with an accuracy of 90% (53/59), sensitivity of 90% (27/30), and specificity of 90% (26/29) after controlling for lesion size, patient age, and patient sex. CONCLUSION: Multiphasic MRI enhancement may assist in differentiating clear cell RCC from oncocytomas and other RCC subtypes, if validated in prospective studies.

Clear cell renal cell carcinoma: identifying the gain of chromosome 12 on multiphasic MDCT.

PURPOSE: To determine whether multiphasic MDCT enhancement can help identify the gain of chromosome 12 in clear cell renal cell carcinomas (RCCs). METHODS: With IRB approval for this HIPAA-compliant case control study, we derived a cohort of 65 clear cell RCCs with preoperative four-phase renal mass MDCT from October 2000 to August 2013. Each lesion was segmented in its entirety on axial images in all phases. A computer-assisted detection (CAD) algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase. Attenuation in each phase between clear cell RCCs with and without the gain of 12 was compared using t-tests. RESULTS: While the entire cohort of clear cell RCCs exhibited peak enhancement in the corticomedullary phase, the subcohort of lesions with the gain of 12 exhibited significantly greater enhancement in the nephrographic (179 vs. 145 HU, p = 0.004) and excretory phases (147 vs. 118 HU, p = 0.004) than the subcohort of lesions without the gain of 12. A nephrographic threshold of 186 HU identified the gain of 12 with an accuracy of 86% (56/65), specificity of 93% (51/55), and negative predictive value of 91% (51/56). CONCLUSION: Multiphasic MDCT enhancement, specifically enhancement in the nephrographic and excretory phases, may potentially assist in identifying the gain of 12 in clear cell RCCs.