David S. Wang, MD

All Publications

• Deep-Learning for Automated Classification of Inferior Vena Cava Filter Types on Radiographs. Journal of vascular and interventional radiology : JVIR Ni, J. C., Shpanskaya, K., Han, M., Lee, E. H., Do, B. H., Kuo, W. T., Yeom, K. W., Wang, D. S. 2019

  Abstract

  PURPOSE: To demonstrate the feasibility and evaluate the performance of a deep-learning convolutional neural network (CNN) classification model for automated identification of different types of inferior vena cava (IVC) filters on radiographs.MATERIALS AND METHODS: In total, 1,375 cropped radiographic images of 14 types of IVC filters were collected from patients enrolled in a single-center IVC filter registry, with 139 images withheld as a test set and the remainder used to train and validate the classification model. Image brightness, contrast, intensity, and rotation were varied to augment the training set. A 50-layer ResNet architecture with fixed pre-trained weights was trained using a soft margin loss over 50 epochs. The final model was evaluated on the test set.RESULTS: The CNN classification model achieved a F1 score of 0.97 (0.92-0.99) for the test set overall and of 1.00 for 10 of 14 individual filter types. Of the 139 test set images, 4 (2.9%) were misidentified, all mistaken for other filter types that appear highly similar. Heat maps elucidated salient features for each filter type that the model used for class prediction.CONCLUSIONS: A CNN classification model was successfully developed to identify 14 types of IVC filters on radiographs and demonstrated high performance. Further refinement and testing of the model is necessary before potential real-world application.

  View details for DOI 10.1016/j.jvir.2019.05.026

  View details for PubMedID 31542278

• A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma. Hepatology Banerjee, S., Wang, D. S., Kim, H. J., Sirlin, C. B., Chan, M. G., Korn, R. L., Rutman, A. M., Siripongsakun, S., Lu, D., Imanbayev, G., Kuo, M. D. 2015; 62 (3): 792-800

  Abstract

  Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is an independent predictor of poor outcomes subsequent to surgical resection or liver transplantation (LT); however, MVI currently cannot be adequately determined preoperatively. Radiogenomic venous invasion (RVI) is a contrast-enhanced computed tomography (CECT) biomarker of MVI derived from a 91-gene HCC "venous invasion" gene expression signature. Preoperative CECTs of 157 HCC patients who underwent surgical resection (N = 72) or LT (N = 85) between 2000 and 2009 at three institutions were evaluated for the presence or absence of RVI. RVI was assessed for its ability to predict MVI and outcomes. Interobserver agreement for scoring RVI was substantial among five radiologists (κ = 0.705; P < 0.001). The diagnostic accuracy, sensitivity, and specificity of RVI in predicting MVI was 89%, 76%, and 94%, respectively. Positive RVI score was associated with lower overall survival (OS) than negative RVI score in the overall cohort (P < 0.001; 48 vs. >147 months), American Joint Committee on Cancer tumor-node-metastasis stage II (P < 0.001; 34 vs. >147 months), and in LT patients within Milan criteria (P < 0.001; 69 vs. >147 months). Positive RVI score also portended lower recurrence-free survival at 3 years versus negative RVI score (P = 0.001; 27% vs. 62%).RVI is a noninvasive radiogenomic biomarker that accurately predicts histological MVI in HCC surgical candidates. Its presence on preoperative CECT is associated with early disease recurrence and poor OS and may be useful for identifying patients less likely to derive a durable benefit from surgical treatment.

  View details for DOI 10.1002/hep.27877

  View details for PubMedID 25930992

• A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma HEPATOLOGY Banerjee, S., Wang, D. S., Kim, H. J., Sirlin, C. B., Chan, M. G., Korn, R. L., Rutman, A. M., Siripongsakun, S., Lu, D., Imanbayev, G., Kuo, M. D. 2015; 62 (3): 792-800

  Abstract

  Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is an independent predictor of poor outcomes subsequent to surgical resection or liver transplantation (LT); however, MVI currently cannot be adequately determined preoperatively. Radiogenomic venous invasion (RVI) is a contrast-enhanced computed tomography (CECT) biomarker of MVI derived from a 91-gene HCC "venous invasion" gene expression signature. Preoperative CECTs of 157 HCC patients who underwent surgical resection (N = 72) or LT (N = 85) between 2000 and 2009 at three institutions were evaluated for the presence or absence of RVI. RVI was assessed for its ability to predict MVI and outcomes. Interobserver agreement for scoring RVI was substantial among five radiologists (κ = 0.705; P < 0.001). The diagnostic accuracy, sensitivity, and specificity of RVI in predicting MVI was 89%, 76%, and 94%, respectively. Positive RVI score was associated with lower overall survival (OS) than negative RVI score in the overall cohort (P < 0.001; 48 vs. >147 months), American Joint Committee on Cancer tumor-node-metastasis stage II (P < 0.001; 34 vs. >147 months), and in LT patients within Milan criteria (P < 0.001; 69 vs. >147 months). Positive RVI score also portended lower recurrence-free survival at 3 years versus negative RVI score (P = 0.001; 27% vs. 62%).RVI is a noninvasive radiogenomic biomarker that accurately predicts histological MVI in HCC surgical candidates. Its presence on preoperative CECT is associated with early disease recurrence and poor OS and may be useful for identifying patients less likely to derive a durable benefit from surgical treatment.

  View details for DOI 10.1002/hep.27877

  View details for Web of Science ID 000360375100017

  View details for PubMedCentralID PMC4654334

• Cationic versus Neutral Microbubbles for Ultrasound-mediated Gene Delivery in Cancer RADIOLOGY Wang, D. S., Panje, C., Pysz, M. A., Paulmurugan, R., Rosenberg, J., Gambhir, S. S., Schneider, M., Willmann, J. K. 2012; 264 (3): 721-732

  Abstract

  To test whether plasmid-binding cationic microbubbles (MBs) enhance ultrasound-mediated gene delivery efficiency relative to control neutral MBs in cell culture and in vivo tumors in mice.Animal studies were approved by the institutional animal care committee. Cationic and neutral MBs were characterized in terms of size, charge, circulation time, and DNA binding. Click beetle luciferase (CBLuc) reporter plasmids were mixed with cationic or neutral MBs. The ability of cationic MBs to protect bound plasmids from nuclease degradation was tested by means of a deoxyribonuclease (DNase) protection assay. Relative efficiencies of ultrasound-mediated transfection (ultrasound parameters: 1 MHz, 1 W/cm(2), 20% duty cycle, 1 minute) of CBLuc to endothelial cells by using cationic, neutral, or no MBs were compared in cell culture. Ultrasound-mediated gene delivery to mouse hind limb tumors was performed in vivo (n = 24) with insonation (1 MHz, 2 W/cm(2), 50% duty cycle, 5 minutes) after intravenous administration of CBLuc with cationic, neutral, or no MBs. Tumor luciferase activity was assessed by means of serial in vivo bioluminescence imaging and ex vivo analysis. Results were compared by using analysis of variance.Cationic MBs (+15.8 mV; DNA binding capacity, 0.03 pg per MB) partially protected bound DNA from DNase degradation. Mean CBLuc expression of treated endothelial cells in culture was 20-fold higher with cationic than with neutral MBs (219.0 relative light units [RLUs]/µg protein ± 92.5 [standard deviation] vs 10.9 RLUs/µg protein ± 2.7, P = .001) and was significantly higher (P < .001) than that in the no MB and no ultrasound control groups. Serial in vivo bioluminescence of mouse tumors was significantly higher with cationic than with neutral MBs ([5.9 ± 2.2] to [9.3 ± 5.2] vs [2.4 ± 0.8] to [2.9 ± 1.1] × 10(4) photons/sec/cm(2)/steradian, P < .0001) and versus no MB and no ultrasound controls (P < .0001). Results of ex vivo analysis confirmed these results (ρ = 0.88, P < .0001).Plasmid-binding cationic MBs enhance ultrasound-mediated gene delivery efficiency relative to neutral MBs in both cell culture and mouse hind limb tumors.

  View details for DOI 10.1148/radiol.12112368

  View details for Web of Science ID 000308645500013

  View details for PubMedID 22723497

  View details for PubMedCentralID PMC3426857

• Identification of noninvasive imaging surrogates for brain tumor gene-expression modules PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Diehn, M., Nardini, C., Wang, D. S., McGovern, S., Jayaraman, M., Liang, Y., Alclape, K., Cha, S., Kuo, M. D. 2008; 105 (13): 5213-5218

  Abstract

  Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor in adults. We combined neuroimaging and DNA microarray analysis to create a multidimensional map of gene-expression patterns in GBM that provided clinically relevant insights into tumor biology. Tumor contrast enhancement and mass effect predicted activation of specific hypoxia and proliferation gene-expression programs, respectively. Overexpression of EGFR, a receptor tyrosine kinase and potential therapeutic target, was also directly inferred by neuroimaging and was validated in an independent set of tumors by immunohistochemistry. Furthermore, imaging provided insights into the intratumoral distribution of gene-expression patterns within GBM. Most notably, an "infiltrative" imaging phenotype was identified that predicted patient outcome. Patients with this imaging phenotype had a greater tendency toward having multiple tumor foci and demonstrated significantly shorter survival than their counterparts. Our findings provide an in vivo portrait of genome-wide gene expression in GBM and offer a potential strategy for noninvasively selecting patients who may be candidates for individualized therapies.

  View details for DOI 10.1073/pnas.0801279105

  View details for Web of Science ID 000254723700047

  View details for PubMedID 18362333

  View details for PubMedCentralID PMC2278224

• Molecular imaging: A primer for interventionalists and imagers JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Wang, D. S., Dake, M. D., Park, J. M., Kuo, M. D. 2006; 17 (9): 1405-1423

  Abstract

  The characterization of human diseases by their underlying molecular and genomic aberrations has been the hallmark of molecular medicine. From this, molecular imaging has emerged as a potentially revolutionary discipline that aims to visually characterize normal and pathologic processes at the cellular and molecular levels within the milieu of living organisms. Molecular imaging holds promise to provide earlier and more precise disease diagnosis, improved disease characterization, and timely assessment of therapeutic response. This primer is intended to provide a broad overview of molecular imaging with specific focus on future clinical applications relevant to interventional radiology.

  View details for DOI 10.1097/01.RVI.0000235746.86332.DF

  View details for Web of Science ID 000240883100004

  View details for PubMedID 16990461

• ACR Appropriateness Criteria® Pulsatile Abdominal Mass, Suspected Abdominal Aortic Aneurysm: 2023 Update. Journal of the American College of Radiology : JACR Wang, D. S., Shen, J., Majdalany, B. S., Khaja, M. S., Bhatti, S., Ferencik, M., Ganguli, S., Gunn, A. J., Heitner, J. F., Johri, A. M., Obara, P., Ohle, R., Sadeghi, M. M., Schermerhorn, M., Siracuse, J. J., Steenburg, S. D., Sutphin, P. D., Vijay, K., Waite, K., Steigner, M. L. 2023; 20 (11S): S513-S520

  Abstract

  Abdominal aortic aneurysm (AAA) is defined as abnormal dilation of the infrarenal abdominal aortic diameter to 3.0 cm or greater. The natural history of AAA consists of progressive expansion and potential rupture. Although most AAAs are clinically silent, a pulsatile abdominal mass identified on physical examination may indicate the presence of an AAA. When an AAA is suspected, an imaging study is essential to confirm the diagnosis. This document reviews the relative appropriateness of various imaging procedures for the initial evaluation of suspected AAA. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

  View details for DOI 10.1016/j.jacr.2023.08.010

  View details for PubMedID 38040468

• ACR Appropriateness Criteria® Sudden Onset of Cold, Painful Leg: 2023 Update. Journal of the American College of Radiology : JACR Browne, W. F., Sung, J., Majdalany, B. S., Khaja, M. S., Calligaro, K., Contrella, B. N., Ferencik, M., Gunn, A. J., Kapoor, B. S., Keefe, N. A., Kokabi, N., Kramer, C. M., Kwun, R., Shamoun, F., Sharma, A. M., Steenburg, S. D., Trout, A. T., Vijay, K., Wang, D. S., Steigner, M. L. 2023; 20 (11S): S565-S573

  Abstract

  Acute onset of a cold, painful leg, also known as acute limb ischemia, describes the sudden loss of perfusion to the lower extremity and carries significant risk of morbidity and mortality. Acute limb ischemia requires rapid identification and the management of suspected vascular compromise and is inherently driven by clinical considerations. The objectives of initial imaging include confirmation of diagnosis, identifying the location and extent of vascular occlusion, and preprocedural/presurgical planning. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

  View details for DOI 10.1016/j.jacr.2023.08.012

  View details for PubMedID 38040470

• Automatic Detection of Perilunate and Lunate Dislocations on Wrist Radiographs Using Deep Learning. Plastic and reconstructive surgery Pridgen, B., von Rabenau, L., Luan, A., Gu, A. J., Wang, D. S., Langlotz, C., Chang, J., Do, B. 2023

  Abstract

  Delayed or missed diagnosis of perilunate or lunate dislocations can lead to significant morbidity. Advances in computer vision provide an opportunity to improve diagnostic performance. In this study, a deep learning algorithm was utilized for detection of perilunate and lunate dislocations on lateral wrist radiographs. A total of 435 lateral wrist radiographs were labeled as normal or pathologic (perilunate or lunate dislocation). The lunate in each radiograph was segmented with a rectangular bounding box. Images were partitioned into training and test sets. Two neural networks, consisting of an object detector followed by an image classifier, were applied in series. First, the object detection module was used to localize the lunate. Next, the image classifier performed a binary classification for normal or pathologic. The accuracy, sensitivity, and specificity of the overall system were evaluated. A receiver operating characteristic (ROC) curve and the associated area under the curve (AUC) were used to demonstrate the overall performance of the computer vision algorithm. The lunate object detector was 97.0% accurate at identifying the lunate. Accuracy was 98.7% among the sub-group of normal wrist radiographs, and 91.3% among the sub-group of wrist radiographs with perilunate/lunate dislocations. The perilunate/lunate dislocation classifier had a sensitivity (recall) of 93.8%, specificity of 93.3%, and accuracy of 93.4%. The AUC was 0.986. We have developed a proof-of-concept computer vision system for diagnosis of perilunate/lunate dislocations on lateral wrist radiographs. This novel deep learning algorithm has potential to improve clinical sensitivity to ultimately prevent delayed or missed diagnosis of these injuries.

  View details for DOI 10.1097/PRS.0000000000010928

  View details for PubMedID 37467052

• Monitoring sarcoma response to immune checkpoint inhibition and local cryotherapy with circulating tumor DNA analysis. Clinical cancer research : an official journal of the American Association for Cancer Research Bui, N. Q., Nemat-Gorgani, N., Subramanian, A., Torres, I. A., Lohman, M., Sears, T. J., van de Rijn, M., Charville, G. W., Becker, H. C., Wang, D. S., Hwang, G. L., Ganjoo, K. N., Moding, E. J. 2023

  Abstract

  Immune checkpoint inhibition has led to promising responses in soft tissue sarcomas (STSs), but the majority of patients do not respond and biomarkers of response will be crucial. Local ablative therapies may augment systemic responses to immunotherapy. We evaluated circulating tumor DNA (ctDNA) as a biomarker of response in patients treated on a trial combining immunotherapy with local cryotherapy for advanced STSs.We enrolled 30 patients with unresectable or metastatic STS to a phase 2 clinical trial. Patients received ipilimumab and nivolumab for 4 doses followed by nivolumab alone with cryoablation performed between cycles 1 and 2. The primary endpoint was objective response rate (ORR) by 14 weeks. Personalized ctDNA analysis using bespoke panels was performed on blood samples collected prior to each immunotherapy cycle.ctDNA was detected in at least one sample for 96% of patients. Pre-treatment ctDNA allele fraction was negatively associated with treatment response, progression-free survival (PFS), and overall survival (OS). ctDNA increased in 90% of patients from pre-treatment to post-cryotherapy, and patients with a subsequent decrease in ctDNA or undetectable ctDNA after cryotherapy had significantly better PFS. Of the 27 evaluable patients, the ORR was 4% by RECIST and 11% by irRECIST. Median PFS and OS were 2.7 and 12.0 months, respectively. No new safety signals were observed.ctDNA represents a promising biomarker for monitoring response to treatment in advanced STS, warranting future prospective studies. Combining cryotherapy and immune checkpoint inhibitors did not increase the response rate of STSs to immunotherapy.

  View details for DOI 10.1158/1078-0432.CCR-23-0250

  View details for PubMedID 37130154

• Multi-center validation of an artificial intelligence system for detection of COVID-19 on chest radiographs in symptomatic patients. European radiology Kuo, M. D., Chiu, K. W., Wang, D. S., Larici, A. R., Poplavskiy, D., Valentini, A., Napoli, A., Borghesi, A., Ligabue, G., Fang, X. H., Wong, H. K., Zhang, S., Hunter, J. R., Mousa, A., Infante, A., Elia, L., Golemi, S., Yu, L. H., Hui, C. K., Erickson, B. J. 2022

  Abstract

  OBJECTIVES: While chest radiograph (CXR) is the first-line imaging investigation in patients with respiratory symptoms, differentiating COVID-19 from other respiratory infections on CXR remains challenging. We developed and validated an AI system for COVID-19 detection on presenting CXR.METHODS: A deep learning model (RadGenX), trained on 168,850 CXRs, was validated on a large international test set of presenting CXRs of symptomatic patients from 9 study sites (US, Italy, and Hong Kong SAR) and 2 public datasets from the US and Europe. Performance was measured by area under the receiver operator characteristic curve (AUC). Bootstrapped simulations were performed to assess performance across a range of potential COVID-19 disease prevalence values (3.33 to 33.3%). Comparison against international radiologists was performed on an independent test set of 852 cases.RESULTS: RadGenX achieved an AUC of 0.89 on 4-fold cross-validation and an AUC of 0.79 (95%CI 0.78-0.80) on an independent test cohort of 5,894 patients. Delong's test showed statistical differences in model performance across patients from different regions (p < 0.01), disease severity (p < 0.001), gender (p < 0.001), and age (p = 0.03). Prevalence simulations showed the negative predictive value increases from 86.1% at 33.3% prevalence, to greater than 98.5% at any prevalence below 4.5%. Compared with radiologists, McNemar's test showed the model has higher sensitivity (p < 0.001) but lower specificity (p < 0.001).CONCLUSION: An AI model that predicts COVID-19 infection on CXR in symptomatic patients was validated on a large international cohort providing valuable context on testing and performance expectations for AI systems that perform COVID-19 prediction on CXR.KEY POINTS: An AI model developed using CXRs to detect COVID-19 was validated in a large multi-center cohort of 5,894 patients from 9 prospectively recruited sites and 2 public datasets. Differences in AI model performance were seen across region, disease severity, gender, and age. Prevalence simulations on the international test set demonstrate the model's NPV is greater than 98.5% at any prevalence below 4.5%.

  View details for DOI 10.1007/s00330-022-08969-z

  View details for PubMedID 35779089

• Efficacy and Safety of Trans-Arterial Yttrium-90 Radioembolization in Patients with Unresectable Liver-Dominant Metastatic or Primary Hepatic Soft Tissue Sarcomas. Cancers Testa, S., Bui, N. Q., Wang, D. S., Louie, J. D., Sze, D. Y., Ganjoo, K. N. 2022; 14 (2)

  Abstract

  Patients with liver-dominant metastatic or primary hepatic soft tissue sarcomas (STS) have poor prognosis. Surgery can prolong survival, but most patients are not surgical candidates, and treatment response is limited with systemic chemotherapy. Liver-directed therapies have been increasingly employed in this setting, and Yttrium-90 trans-arterial radioembolization (TARE) is an understudied yet promising treatment option. This is a retrospective analysis of 35 patients with metastatic or primary hepatic STS who underwent TARE at a single institution between 2006 and 2020. The primary outcomes that were measured were overall survival (OS), liver progression-free survival (LPFS), and radiologic tumor response. Clinical and biochemical toxicities were assessed 3 months after the procedure. Median OS was 20 months (95% CI: 13.9-26.1 months), while median LPFS was 9 months (95% CI: 6.2-11.8 months). The objective response rate was 56.7%, and the disease control rate was 80.0% by mRECIST at 3 months. The following correlated with better OS post-TARE: liver disease control (DC) at 6 months (median OS: 40 vs. 17 months, p = 0.007); LPFS ≥ 9 months (median OS: 50 vs. 8 months, p < 0.0001); ECOG status 0-1 vs. 2 (median OS: 22 vs. 6 months, p = 0.042); CTP class A vs. B (median OS: 22 vs. 6 months, p = 0.018); and TACE post-progression (median OS: 99 vs. 16 months, p = 0.003). The absence of metastases at diagnosis was correlated with higher median LPFS (7 vs. 1 months, p = 0.036). Two grade 4 (5.7%) and ten grade 3 (28.6%) laboratory toxicities were identified at 3 months. There was one case of radioembolization-induced liver disease and two cases of radiation-induced peptic ulcer disease. We concluded that TARE could be an effective and safe treatment option for patients with metastatic or primary hepatic STS with good tumor response rates, low incidence of severe toxicity, and longer survival in patients with liver disease control post-TARE.

  View details for DOI 10.3390/cancers14020324

  View details for PubMedID 35053486

• Safety and Feasibility of Cryoablation during Immunotherapy in Patients with Metastatic Soft Tissue Sarcoma. Journal of vascular and interventional radiology : JVIR Doshi, A., Zhou, M., Bui, N., Wang, D. S., Ganjoo, K., Hwang, G. L. 2021

  Abstract

  PURPOSE: Patients with metastatic soft tissue sarcoma (STS) undergo a wide array of treatments, including surgery, radiation, chemotherapy, immunotherapy, and ablative therapies, to control their disease. The combination of cryoablation and immunotherapy may lead to an enhanced anti-tumor immune response via the abscopal effect. It is hypothesized that the combination of cryoablation and immunotherapy in patients with metastatic STS is safe and feasible.MATERIALS/METHODS: A single-center retrospective analysis was performed on patients with metastatic STS who underwent cryoablation. Sixteen patients were treated with 27 cryoablation procedures while receiving ipilimumab and nivolumab from April 2017 to July 2020. RECIST 1.1 criteria was used to determine outcomes of non-target tumors. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of first cryoablation after initiating immunotherapy until progression or death.RESULTS: Thirty-four tumors were cryoablated, 23 of which were intentionally subtotal. Most common tumor subtype was liposarcoma (n = 4). Thirteen patients (81%) had previously demonstrated disease progression on multiple lines of chemotherapy. All tumors cryoablated with complete intention demonstrated complete response. Seven patients had clinical benefit, including 1 complete response, 1 partial response, and 5 with stable disease. The median OS was 14.1 months, with a median PFS of 2.3 months (95% CI 1.8-14.3). Five patients had post-cryoablation pneumothoraces, two of whom required chest tube placement. Eleven patients experienced adverse events related to immunotherapy, 10 of which were grade 1 or 2.CONCLUSION: Cryoablation in patients with metastatic soft tissue sarcoma undergoing immunotherapy is feasible and safe.

  View details for DOI 10.1016/j.jvir.2021.08.017

  View details for PubMedID 34478852

• ACR Appropriateness Criteria Nontraumatic Aortic Disease. Journal of the American College of Radiology : JACR Expert Panel on Vascular Imaging, Gunn, A. J., Kalva, S. P., Majdalany, B. S., Craft, J., Eldrup-Jorgensen, J., Ferencik, M., Ganguli, S., Kendi, A. T., Khaja, M. S., Obara, P., Russell, R. R., Sutphin, P. D., Vijay, K., Wang, D. S., Dill, K. E. 2021; 18 (5S): S106–S118

  Abstract

  Nontraumatic aortic disease can be caused by a wide variety of disorders including congenital, inflammatory, infectious, metabolic, neoplastic, and degenerative processes. Imaging examinations such as radiography, ultrasound, echocardiography, catheter-based angiography, CT, MRI, and nuclear medicine examinations are essential for diagnosis, treatment planning, and assessment of therapeutic response. Depending upon the clinical scenario, each of these modalities has strengths and weaknesses. Whenever possible, the selection of a diagnostic imaging examination should be based upon the best available evidence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. The purpose of this document is to assist physicians select the most appropriate diagnostic imaging examination for nontraumatic aortic diseases.

  View details for DOI 10.1016/j.jacr.2021.02.004

  View details for PubMedID 33958105

• Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative. Radiology Puijk, R. S., Ahmed, M., Adam, A., Arai, Y., Arellano, R., de Baère, T., Bale, R., Bellera, C., Binkert, C. A., Brace, C. L., Breen, D. J., Brountzos, E., Callstrom, M. R., Carrafiello, G., Chapiro, J., de Cobelli, F., Coupé, V. M., Crocetti, L., Denys, A., Dupuy, D. E., Erinjeri, J. P., Filippiadis, D., Gangi, A., Gervais, D. A., Gillams, A. R., Greene, T., Guiu, B., Helmberger, T., Iezzi, R., Kang, T. W., Kelekis, A., Kim, H. S., Kröncke, T., Kwan, S., Lee, M. W., Lee, F. T., Lee, E. W., Liang, P., Lissenberg-Witte, B. I., Lu, D. S., Madoff, D. C., Mauri, G., Meloni, M. F., Morgan, R., Nadolski, G., Narayanan, G., Newton, I., Nikolic, B., Orsi, F., Pereira, P. L., Pua, U., Rhim, H., Ricke, J., Rilling, W., Salem, R., Scheffer, H. J., Sofocleous, C. T., Solbiati, L. A., Solomon, S. B., Soulen, M. C., Sze, D., Uberoi, R., Vogl, T. J., Wang, D. S., Wood, B. J., Goldberg, S. N., Meijerink, M. R. 2021: 203715

  Abstract

  There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

  View details for DOI 10.1148/radiol.2021203715

  View details for PubMedID 34581627

• Genomic biomarkers to determine survival in Multicenter Study of RAS mutations (MURAS) in patients with colorectal liver metastases receiving Y90 radioembolization treatment. Case, M., Ghodadra, A., Novelli, P. M., Wu, V., Ganguli, S., Wildgruber, M., Kohler, M., Robinson, C., Kim, C., Wang, D. S., Sze, D. Y., Kolbeck, K., Russell, L., Ludwig, J. M., Uhlig, J., Kim, K. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368305473

• KRAS status and survival in multicenter study of RAS mutations (MURAS) in patients with colorectal liver metastases receiving Y90 radioembolization treatment Case, M., Ghodadra, A., Novelli, P. M., Wu, V., Ganguli, S., Wildgruber, M., Kohler, M., Robinson, C., Kim, C., Wang, D. S., Sze, D. Y., Kolbeck, K., Russell, L., Uhlig, J., Ludwig, J. M., Kim, H. S. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000530922700228

• Lower Extremity Venous Stent Placement: A Large Retrospective Single-Center Analysis. Journal of vascular and interventional radiology : JVIR Mabud, T. S., Cohn, D. M., Arendt, V. A., Jeon, G., An, X., Fu, J., Souffrant, A. D., Sailer, A. M., Shah, R., Wang, D., Sze, D. Y., Kuo, W. T., Rubin, D. L., Hofmann, L. V. 2019

  Abstract

  PURPOSE: To study short-term and long-term outcomes of lower extremity venous stents placed at a single center and to characterize changes in vein diameter achieved by stent placement.MATERIALS AND METHODS: A database of all patients who received lower extremity venous stents between 1996 and 2018 revealed 1,094 stents were placed in 406 patients (172 men, 234 women; median age, 49 y) in 513 limbs, including patients with iliocaval stents (9.4% acute thrombosis, 65.3% chronic thrombosis, 25.3% nonthrombotic lesions). Primary, primary assisted, and secondary patency rates were assessed for lower extremity venous stents at 1, 3, and 5 years using Kaplan-Meier analyses and summary statistics. Subset analyses and Cox regression were performed to identify risk factors for patency loss. Vein diameters and Villalta scores before and up to 12 months after stent placement were compared. Complication and mortality rates were calculated.RESULTS: Primary, primary assisted, and secondary patency rates at 5 years were 57.3%, 77.2%, and 80.9% by Kaplan-Meier methods and 78.6%, 90.3%, and 92.8% by summary statistics. Median follow-up was 199 days (interquartile range, 35.2-712.0 d). Patency rates for the subset of patients (n= 46) with ≥ 5 years of follow-up (mean ± SD 9.1 y ± 3.4) were nearly identical to cohort patency rates at 5 years. Patients with inferior vena cava stent placement (hazard ratio 2.11, P < .0001) or acute thrombosis (hazard ratio 3.65, P < .0001) during the index procedure had significantly increased risk of losing primary patency status. Vein diameters were significantly greater after stent placement. There were no instances of stent fracture, migration, or structural deformities. In patients with chronic deep vein thrombosis, Villalta scores significantly decreased after stent placement (from 15.7 to 7.4, P < .0001). Perioperative mortality was < 1%, and major perioperative complication rate was 3.7%.CONCLUSIONS: Cavo-ilio-femoral stent placement for venous occlusive disease achieves improvement of vein disease severity scores, increase in treated vein diameters, and satisfactory long-term patency rates.

  View details for DOI 10.1016/j.jvir.2019.06.011

  View details for PubMedID 31542273

• Contemporary management of metastatic soft tissue sarcoma. Current problems in cancer Bui, N. Q., Wang, D. S., Hiniker, S. M. 2019

  Abstract

  Soft tissue sarcoma (STS) is a rare, heterogeneous cancer that can have high rates of distant metastases. Optimal treatment planning requires detailed knowledge of distinct sarcoma histologies as well as the wide array of therapeutic options through surgical, medical, radiation, and interventional oncology. In this review article, we discuss the contemporary management of metastatic STS and the underlying data behind these recommendations. All patients with metastatic STS should be discussed in a multidisciplinary tumor board at an experienced sarcoma center. For patients with oligometastatic disease, there should be strong consideration for definitive local therapy such as surgical resection, stereotactic body radiation therapy, or ablative procedures. In cases with widespread metastases, cytotoxic chemotherapy represents the standard treatment for STS patients with traditional chemotherapies, such as anthracyclines, gemcitabine/docetaxel, ifosfamide, and dacarbazine, still being the most commonly used drugs today. The recent approvals of trabectedin, eribulin, and pazopanib have expanded the therapeutic armamentarium for metastatic STS. Histology-directed treatment is crucial for certain subtypes of STS which are highly sensitive to targeted therapy and relatively insensitive to chemotherapy. Despite the significant progress that has been made in metastatic STS in the past decade, overall prognosis is poor and there is a critical need for novel therapeutics.

  View details for DOI 10.1016/j.currproblcancer.2019.06.005

  View details for PubMedID 31248634

• Evidence-Based Integration of Yttrium-90 Radioembolization in the Contemporary Management of Hepatic Metastases from Colorectal Cancer. Techniques in vascular and interventional radiology Wang, D. S., Louie, J. D., Sze, D. Y. 2019; 22 (2): 74–80

  Abstract

  Hepatic metastases are common in patients with metastatic colorectal cancer and are frequently the most life-threatening source of morbidity and mortality. The contemporary management of patients with liver-dominant or liver-only metastatic colorectal cancer is characterized by resection of metastases when feasible and successive lines of systemic treatment regimens consisting of chemotherapy drugs and/or targeted biological agents. Yttrium-90 radioembolization has emerged as a promising liver-directed therapy for patients with unresectable colorectal cancer liver metastases (CLM). The integration of radioembolization into the current treatment algorithm for unresectable CLM is dependent on the line of therapy it is being considered and whether it is to be used alone or in combination with systemic treatment options. This article provides background information on the current management of CLM and uses this framework to discuss the existing data that define when and how radioembolization can benefit patients with CLM.

  View details for PubMedID 31079714

• Quantification of Activity Lost to Delivery-System Residual and Decay in Yttrium-90 Radioembolization JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Hoang, N. S., Khalaf, M. H., Rosenberg, J. K., Kwofie, J., Reposar, A. L., Wang, D. S., Louie, J. D., Sze, D. Y. 2018; 29 (12): 1672–77

  View details for DOI 10.1016/j.jvir.2018.07.011

  View details for Web of Science ID 000453341200007

• Albumin-Bilirubin Score: An Accurate Predictor of Hepatic Decompensation in High-Risk Patients Undergoing Transarterial Chemoembolization for Hepatocellular Carcinoma JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Mohammed, M., Khalaf, M. H., Liang, T., Wang, D. S., Lungren, M. P., Rosenberg, J., Kothary, N. 2018; 29 (11): 1527–34

  View details for DOI 10.1016/j.jvir.2018.06.016

  View details for Web of Science ID 000450542400005

• A Role for Virtual Reality in Planning Endovascular Procedures JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Mohammed, M., Khalaf, M. H., Kesselman, A., Wang, D. S., Kothary, N. 2018; 29 (7): 971–74

  View details for DOI 10.1016/j.jvir.2018.02.018

  View details for Web of Science ID 000438179300010

• Phase II study of epacadostat with pembrolizumab in metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma requiring paired biopsies. Kardosh, A., Tseng, D., Sahaf, B., Zomet, A., Krupa, J., Fisher, G. A., Wang, D. S., Mackall, C., Kunz, P. L. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.4_suppl.TPS191

  View details for Web of Science ID 000436174100183

• Authors' Reply: Letter to the Editor Regarding "Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular-Cholangiocarcinoma". Cardiovascular and interventional radiology Wang, D. S., Sze, D. Y. 2017

  View details for DOI 10.1007/s00270-017-1708-z

  View details for PubMedID 28550513

• Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular-Cholangiocarcinoma. Cardiovascular and interventional radiology Chan, L. S., Sze, D. Y., Poultsides, G. A., Louie, J. D., Abdelrazek Mohammed, M. A., Wang, D. S. 2017

  Abstract

  Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare mixed cell type primary liver cancer with limited data to guide management. Transarterial radioembolization with yttrium-90 microspheres (RE) is an emerging treatment option for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. This study explored the safety and efficacy of RE for unresectable cHCC-CC.Patients with histopathologically confirmed cHCC-CC treated with RE were retrospectively evaluated. Clinical and biochemical toxicities were assessed using the Common Toxicity Criteria for Adverse Events v4.03. Radiological response was analyzed using the Response Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST criteria. Survival times were calculated and prognostic variables identified.Ten patients (median age 59 years; six men, four women) with unresectable cHCC-CC underwent 14 RE treatments with resin (n = 6 patients) or glass (n = 4 patients) microspheres. Clinical toxicities were limited to grade 1-2 fatigue, anorexia, nausea, or abdominal pain. No significant biochemical toxicities were observed. Median overall survivals from the first RE treatment and from initial diagnosis were 10.2 and 17.7 months, respectively. Six of seven patients with elevated tumor biomarker levels before RE showed decreased levels after treatment (median decrease of 72%, range 13-80%). Best hepatic radiological response was 60% partial response and 40% stable disease by modified RECIST, and 100% stable disease by RECIST v1.1. Poor performance status and the presence of macrovascular invasion were identified as predictors of reduced survival after RE.RE appears to be a safe and promising treatment option for patients with unresectable cHCC-CC.Level 4.

  View details for DOI 10.1007/s00270-017-1648-7

  View details for PubMedID 28432387

• Ultrasound-guided therapeutic modulation of hepatocellular carcinoma using complementary microRNAs. Journal of controlled release Mullick Chowdhury, S., Wang, T., Bachawal, S., Devulapally, R., Choe, J. W., Abou Elkacem, L., Yakub, B. K., Wang, D. S., Tian, L., Paulmurugan, R., Willmann, J. K. 2016; 238: 272-280

  Abstract

  Treatment options for patients with hepatocellular carcinoma (HCC) are limited, in particular in advanced and drug resistant HCC. MicroRNAs (miRNA) are non-coding small RNAs that are emerging as novel drugs for the treatment of cancer. The aim of this study was to assess treatment effects of two complementary miRNAs (sense miRNA-122, and antisense antimiR-21) encapsulated in biodegradable poly (lactic-co-glycolic acid) nanoparticles (PLGA-NP), administered by an ultrasound-guided and microbubble-enhanced delivery approach in doxorubicin-resistant and non-resistant human HCC xenografts. Proliferation and invasiveness of human HCC cells after miRNA-122/antimiR-21 and doxorubicin treatment were assessed in vitro. Confocal microscopy and qRT-PCR were used to visualize and quantitate successful intracellular miRNA-loaded PLGA-NP delivery. Up and down-regulation of miRNA downstream targets and multidrug resistance proteins and extent of apoptosis were assessed in vivo in treated human HCC xenografts in mice. Compared to single miRNA therapy, combination therapy with the two complementary miRNAs resulted in significantly (P<0.05) stronger decrease in cell proliferation, invasion, and migration of HCC cells as well as higher resensitization to doxorubicin. Ultrasound-guided delivery significantly increased in vivo miRNA-loaded PLGA-NP delivery in human HCC xenografts compared to control conditions by 5-9 fold (P<0.001). miRNA-loaded PLGA-NP were internalized in HCC cells and anti-apoptotic proteins were down regulated with apoptosis in ~27% of the tumor volume of doxorubicin-resistant human HCC after a single treatment with complementary miRNAs and doxorubicin. Thus, ultrasound-guided delivery of complementary miRNAs is highly efficient in the treatment of doxorubicin- resistant and non-resistant HCC. Further development of this new treatment approach could aid in better treatment of patients with HCC.

  View details for DOI 10.1016/j.jconrel.2016.08.005

  View details for PubMedID 27503707

  View details for PubMedCentralID PMC5185600

• Local Stent-Based Release of Transforming Growth Factor-1 Limits Arterial In-Stent Restenosis JALA Wang, D. S., Ganaha, F., Kao, E. Y., Lee, J., Elkins, C. J., Waugh, J. M., Dake, M. D. 2016; 21 (2): 305-311

  Abstract

  The long-term success of intra-arterial stenting remains limited by in-stent restenosis (ISR). Transforming growth factor-β1 (TGF-β1) can inhibit smooth muscle cell (SMC) proliferation and migration and convert SMCs into extracellular matrix (ECM)-synthesizing cells. Here, we evaluate the effects of stent-based delivery of TGF-β1 on ISR in a rabbit model. Channeled stents loaded with TGF-β1 or control microspheres were deployed in rabbit aortas. Stented aortas were harvested at 7 and 28 d and evaluated for Ki-67-positive cells, collagenous ECM production, and intima-to-media (I/M) ratio. At 7 d, the TGF-β1 group exhibited fewer Ki-67-positive cells were found for the TGF-β1 group (17.87 ± 2.18 cells per mm(2)) relative to control (25.07 ± 2.65 cells per mm(2), p = 0.04), but increased collagen content (31.4 ± 2.5 percentage area) compared with control (29.3 ± 1.2 percentage area, p = 0.019). The I/M ratio in the TGF-β1 group was reduced by 50% and 9.1% versus control at 7 d (0.13 ± 0.02 vs. 0.26 ± 0.02, p = 0.0001) and 28 d (1.80 ± 0.05 vs. 1.98 ± 0.08, p = 0.0038), respectively. Stent-based controlled release of TGF-β1 limits ISR and is associated with inhibition of SMC proliferation but an increase in ECM production.

  View details for DOI 10.1177/2211068215611040

  View details for Web of Science ID 000372883400010

• Local Stent-Based Release of Transforming Growth Factor-β1 Limits Arterial In-Stent Restenosis. Journal of laboratory automation Wang, D. S., Ganaha, F., Kao, E. Y., Lee, J., Elkins, C. J., Waugh, J. M., Dake, M. D. 2016; 21 (2): 305-11

  Abstract

  The long-term success of intra-arterial stenting remains limited by in-stent restenosis (ISR). Transforming growth factor-β1 (TGF-β1) can inhibit smooth muscle cell (SMC) proliferation and migration and convert SMCs into extracellular matrix (ECM)-synthesizing cells. Here, we evaluate the effects of stent-based delivery of TGF-β1 on ISR in a rabbit model. Channeled stents loaded with TGF-β1 or control microspheres were deployed in rabbit aortas. Stented aortas were harvested at 7 and 28 d and evaluated for Ki-67-positive cells, collagenous ECM production, and intima-to-media (I/M) ratio. At 7 d, the TGF-β1 group exhibited fewer Ki-67-positive cells were found for the TGF-β1 group (17.87 ± 2.18 cells per mm(2)) relative to control (25.07 ± 2.65 cells per mm(2), p = 0.04), but increased collagen content (31.4 ± 2.5 percentage area) compared with control (29.3 ± 1.2 percentage area, p = 0.019). The I/M ratio in the TGF-β1 group was reduced by 50% and 9.1% versus control at 7 d (0.13 ± 0.02 vs. 0.26 ± 0.02, p = 0.0001) and 28 d (1.80 ± 0.05 vs. 1.98 ± 0.08, p = 0.0038), respectively. Stent-based controlled release of TGF-β1 limits ISR and is associated with inhibition of SMC proliferation but an increase in ECM production.

  View details for DOI 10.1177/2211068215611040

  View details for PubMedID 26464421

• Transcatheter Therapy for Hepatic Malignancy: Standardization of Terminology and Reporting Criteria. Journal of vascular and interventional radiology Gaba, R. C., Lewandowski, R. J., Hickey, R., Baerlocher, M. O., Cohen, E. I., Dariushnia, S. R., Janne d'Othée, B., Padia, S. A., Salem, R., Wang, D. S., Nikolic, B., Brown, D. B. 2016; 27 (4): 457-473

  View details for DOI 10.1016/j.jvir.2015.12.752

  View details for PubMedID 26851158

• Endovascular Stent Placement for May-Thurner Syndrome in the Absence of Acute Deep Vein Thrombosis. Journal of vascular and interventional radiology Ahmed, O., Ng, J., Patel, M., Ward, T. J., Wang, D. S., Shah, R., Hofmann, L. V. 2016; 27 (2): 167-173

  Abstract

  To assess the clinical utility of iliac vein stent placement for patients with chronic limb edema or pelvic congestion presenting with nonocclusive May-Thurner physiology.All patients (N = 45) undergoing stent placement for May-Thurner syndrome (MTS) without an associated acute thrombotic event between 2007 and 2014 were retrospectively reviewed; 11 were excluded for poor follow-up. A total of 34 patients (28 female) were studied (mean age, 44 y; range, 19-80 y). Average follow-up time was 649 days (median, 488 d; range, 8-2,499 d).The technical success rate was 100% (34 of 34). No major and two minor (5%) complications occurred, and 68% of patients (23 of 34) had clinical success with relief of presenting symptoms on follow-up visits. Technical parameters including stent size and number, stent type, concurrent angioplasty, access site, and resolution of collateral iliolumbar vessels were not found to be statistically related to clinical success (P > .05). Similarly, no significant relation to clinical success was seen for clinical factors such as the type of symptoms, presence of chronic deep vein thrombosis (DVT), or concurrent coagulopathy (P > .05). Female sex was found to correlate with clinical success (82% vs 18%; P = .04).Iliac stent placement in patients presenting with chronic limb or pelvic symptoms from MTS without acute DVT is associated with clinical success in the majority of patients.

  View details for DOI 10.1016/j.jvir.2015.10.028

  View details for PubMedID 26703783

• Quantitative Emphysema Score as a Predictor of Morbidity in Transthoracic Needle Aspiration Biopsy Gonzales, N., Wang, D., Holty, J., Kuschner, W., Raffy, P., Laeseke, P., Shah, R., Sung, A., Van Wert, R. AMER COLL CHEST PHYSICIANS. 2015

  View details for DOI 10.1378/chest.2280739

  View details for Web of Science ID 000367163100042

• A titratable two-step transcriptional amplification strategy for targeted gene therapy based on ligand-induced intramolecular folding of a mutant human estrogen receptor. Molecular imaging and biology Chen, I. Y., Paulmurugan, R., Nielsen, C. H., Wang, D. S., Chow, V., Robbins, R. C., Gambhir, S. S. 2014; 16 (2): 224-234

  Abstract

  The efficacy and safety of cardiac gene therapy depend critically on the level and the distribution of therapeutic gene expression following vector administration. We aimed to develop a titratable two-step transcriptional amplification (tTSTA) vector strategy, which allows modulation of transcriptionally targeted gene expression in the myocardium.We constructed a tTSTA plasmid vector (pcTnT-tTSTA-fluc), which uses the cardiac troponin T (cTnT) promoter to drive the expression of the recombinant transcriptional activator GAL4-mER(LBD)-VP2, whose ability to transactivate the downstream firefly luciferase reporter gene (fluc) depends on the binding of its mutant estrogen receptor (ER(G521T)) ligand binding domain (LBD) to an ER ligand such as raloxifene. Mice underwent either intramyocardial or hydrodynamic tail vein (HTV) injection of pcTnT-tTSTA-fluc, followed by differential modulation of fluc expression with varying doses of intraperitoneal raloxifene prior to bioluminescence imaging to assess the kinetics of myocardial or hepatic fluc expression.Intramyocardial injection of pcTnT-tTSTA-fluc followed by titration with intraperitoneal raloxifene led to up to tenfold induction of myocardial fluc expression. HTV injection of pcTnT-tTSTA-fluc led to negligible long-term hepatic fluc expression, regardless of the raloxifene dose given.The tTSTA vector strategy can effectively modulate transgene expression in a tissue-specific manner. Further refinement of this strategy should help maximize the benefit-to-risk ratio of cardiac gene therapy.

  View details for DOI 10.1007/s11307-013-0673-4

  View details for PubMedID 23955099

  View details for PubMedCentralID PMC4154804

• Ultrasound and microbubble-mediated gene delivery in cancer: progress and perspectives. Investigative radiology Panje, C. M., Wang, D. S., Willmann, J. K. 2013; 48 (11): 755-769

  Abstract

  Ultrasound-mediated gene delivery with microbubbles has emerged as an attractive nonviral vector system for site-specific and noninvasive gene therapy. Ultrasound promotes intracellular uptake of therapeutic agents, particularly in the presence of microbubbles, by increasing vascular and cell membrane permeability. Several preclinical studies have reported successful gene delivery into solid tumors with significant therapeutic effects using this novel approach. This review provides background information on gene therapy and ultrasound bioeffects and discusses the current progress and overall perspectives on the application of ultrasound and microbubble-mediated gene delivery in cancer.

  View details for DOI 10.1097/RLI.0b013e3182982cc1

  View details for PubMedID 23697924

• Noninvasive imaging of hypoxia-inducible factor-1a gene therapy for myocardial ischemia. Human gene therapy methods Chen, I. Y., Gheysens, O., Li, Z., Rasooly, J. A., Wang, Q., Paulmurugan, R., Rosenberg, J., Rodriguez-Porcel, M., Willmann, J. K., Wang, D. S., Contag, C. H., Robbins, R. C., Wu, J. C., Gambhir, S. S. 2013; 24 (5): 279-288

  Abstract

  Abstract Hypoxia-inducible factor-1 alpha (HIF-1α) gene therapy holds great promise for the treatment of myocardial ischemia. Both preclinical and clinical evaluations of this therapy are underway and can benefit from a vector strategy that allows noninvasive assessment of HIF-1α expression as an objective measure of gene delivery. We have developed a novel bidirectional plasmid vector (pcTnT-HIF-1α-VP2-TSTA-fluc), which employs the cardiac troponin T (cTnT) promoter in conjunction with a two-step transcriptional amplification (TSTA) system to drive the linked expression of a recombinant HIF-1α gene (HIF-1α-VP2) and the firefly luciferase gene (fluc). The firefly luciferase (FLuc) activity serves as a surrogate for HIF-1α-VP2 expression, and can be noninvasively assessed in mice using bioluminescence imaging after vector delivery. Transfection of cultured HL-1 cardiomyocytes with pcTnT-HIF-1α-VP2-TSTA-fluc led to a strong correlation between FLuc and HIF-1α-dependent vascular endothelial growth factor expression (r(2)=0.88). Intramyocardial delivery of pcTnT-HIF-1α-VP2-TSTA-fluc into infarcted mouse myocardium led to persistent HIF-1α-VP2 expression for 4 weeks, even though it improved neither CD31+ microvessel density nor echocardiographically determined left ventricular systolic function. These results lend support to recent findings of suboptimal efficacy associated with plasmid-mediated HIF-1α therapy. The imaging techniques developed herein should be useful for further optimizing HIF-1α-VP2 therapy in preclinical models of myocardial ischemia.

  View details for DOI 10.1089/hgtb.2013.028

  View details for PubMedID 23937265

• Prophylactic Topically Applied Ice to Prevent Cutaneous Complications of Nontarget Chemoembolization and Radioembolization JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Wang, D. S., Louie, J. D., Kothary, N., Shah, R. P., Sze, D. Y. 2013; 24 (4): 596-600

  Abstract

  Cutaneous complications can result from nontarget deposition during transcatheter arterial chemoembolization or radioembolization. Liver tumors may receive blood supply from parasitized extrahepatic arteries (EHAs) that also perfuse skin or from hepatic arteries located near the origin of the falciform artery (FA), which perfuses the anterior abdominal wall. To vasoconstrict cutaneous vasculature and prevent nontarget deposition, ice packs were topically applied to at-risk skin in nine chemoembolization treatments performed via 14 parasitized EHAs, seven chemoembolization treatments near the FA origin, and five radioembolization treatments in cases in which the FA could not be prophylactically coil-embolized. No postprocedural cutaneous complications were encountered.

  View details for DOI 10.1016/j.jvir.2012.12.020

  View details for PubMedID 23522163

• Intra-arterial therapies for metastatic colorectal cancer. Seminars in interventional radiology Wang, D. S., Louie, J. D., Sze, D. Y. 2013; 30 (1): 12-20

  Abstract

  Intra-arterial therapies for unresectable hepatic metastases from colorectal cancer include radioembolization (RE) with yttrium-90 microspheres, transarterial chemoembolization (TACE), hepatic arterial infusion, and percutaneous hepatic perfusion using an organ isolation system. In this article, we discuss our approach toward treatment selection, followed by details of how RE and TACE are performed at our institution.

  View details for DOI 10.1055/s-0033-1333649

  View details for PubMedID 24436513

• Heparin-induced thrombocytopenia (HIT) causing portosplenic, superior mesenteric, and splenic vein thrombosis resulting in splenic rupture and pulmonary emboli formation CLINICAL IMAGING Lammering, J. C., Wang, D. S., Shin, L. K. 2012; 36 (6): 865-868

  Abstract

  Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin administration. Of the few reported cases of HIT-associated intra-abdominal thrombosis, none to our knowledge provide multidetector-row computed tomography (MDCT) imaging findings or emphasize its utility in diagnosis. We describe a case of HIT with MDCT images demonstrating extensive intra-abdominal thrombosis and end-organ complications including splenic rupture and pulmonary emboli. This case emphasizes the potential role of MDCT in the rapid detection of HIT-related thromboembolic complications in patients with nonspecific abdominal pain.

  View details for DOI 10.1016/j.clinimag.2012.01.011

  View details for Web of Science ID 000311533800037

  View details for PubMedID 23154026

• Ultrasound-Mediated Gene Delivery with Cationic Versus Neutral Microbubbles: Effect of DNA and Microbubble Dose on In Vivo Transfection Efficiency THERANOSTICS Panje, C. M., Wang, D. S., Pysz, M. A., Paulmurugan, R., Ren, Y., Tranquart, F., Tian, L., Willmann, J. K. 2012; 2 (11): 1078-1091

  Abstract

  To assess the effect of varying microbubble (MB) and DNA doses on the overall and comparative efficiencies of ultrasound (US)-mediated gene delivery (UMGD) to murine hindlimb skeletal muscle using cationic versus neutral MBs.Cationic and control neutral MBs were characterized for size, charge, plasmid DNA binding, and ability to protect DNA against endonuclease degradation. UMGD of a codon optimized firefly luciferase (Fluc) reporter plasmid to endothelial cells (1 MHz, 1 W/cm², 20% duty cycle, 1 min) was performed in cell culture using cationic, neutral, or no MBs. In vivo UMGD to mouse hindlimb muscle was performed by insonation (1 MHz, 2 W/cm², 50% duty cycle, 5 min) after intravenous administration of Fluc combined with cationic, neutral, or no MBs. Gene delivery efficiency was assessed by serial in vivo bioluminescence imaging. Efficiency of in vivo UMGD with cationic versus neutral MBs was systematically evaluated by varying plasmid DNA dose (10, 17.5, 25, 37.5, and 50 µg) while maintaining a constant MB dose of 1x10(8) MBs and by changing MB dose (1x10(7), 5x10(7), 1x10(8), or 5x10(8) MBs) while keeping a constant DNA dose of 50 µg.Cationic and size-matched control neutral MBs differed significantly in zeta potential with cationic MBs being able to bind plasmid DNA (binding capacity of 0.03 pg/MB) and partially protect DNA from nuclease degradation while neutral MBs could not. Cationic MBs enhanced UMGD compared to neutral MBs as well as no MB and no US controls both in cell culture (P < 0.001) and in vivo (P < 0.05). Regardless of MB type, in vivo UMGD efficiency increased dose-dependently with DNA dose and showed overall maximum transfection with 50 µg DNA. However, there was an inverse correlation (ρ = -0.90; P = 0.02) between DNA dose and the degree of enhanced UMGD efficiency observed with using cationic MBs instead of neutral MBs. The delivery efficiency advantage associated with cationic MBs was most prominent at the lowest investigated DNA dose (7.5-fold increase with cationic versus neutral MBs at a DNA dose of 10 µg; P = 0.02) compared to only a 1.4-fold increase at a DNA dose of 50 µg (P < 0.01). With increasing MB dose, overall in vivo UMGD efficiency increased dose-dependently with a maximum reached at a dose of 1x10(8) MBs with no further significant increase with 5x10(8) MBs (P = 0.97). However, compared to neutral MBs, cationic MBs enhanced UMGD efficiency the most at low MB doses. Relative enhancement of UMGD efficiency using cationic over neutral MBs decreased from a factor of 27 for 1x10(7) MBs (P = 0.02) to a factor of 1.4 for 1x10(8) MBs (P < 0.01) and no significant difference for 5x10(8) MBs.Cationic MBs enhance UMGD to mouse skeletal muscle relative to neutral MBs but this is dependent on MB and DNA dose. The enhancement effect of cationic MBs on UMGD efficiency is more evident when lower doses of MBs or DNA are used, whereas the advantage of cationic MBs over neutral MBs is substantially reduced in the presence of excess MBs or DNA.

  View details for DOI 10.7150/thno.4240

  View details for Web of Science ID 000312955800005

  View details for PubMedID 23227124

  View details for PubMedCentralID PMC3516840

• Stent-grafts for thoracic aortic aneurysms and dissections. Handbook of Vascular & Interventional Radiologic Procedures Wang, D. S., Dake, M. D. Lippincott Williams & Wilkins. 2010; 4th
• Endovascular treatment for type B aortic dissection. Modern Trends in Vascular Surgery: Surgery of the Aorta & its Body Branches. Wang, D. S., Dake, M. D. People’s Medical Publishing House. 2010
• Molecular Imaging: A Primer for Interventionalists and Imagers (Reprinted from J Vasc Interv Radiol, vol 17, pg 1405-1423, 2006) JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Wang, D. S., Dake, M. D., Park, J. M., Kuo, M. D. 2009; 20 (7): S505-S522

  Abstract

  The characterization of human diseases by their underlying molecular and genomic aberrations has been the hallmark of molecular medicine. From this, molecular imaging has emerged as a potentially revolutionary discipline that aims to visually characterize normal and pathologic processes at the cellular and molecular levels within the milieu of living organisms. Molecular imaging holds promise to provide earlier and more precise disease diagnosis, improved disease characterization, and timely assessment of therapeutic response. This primer is intended to provide a broad overview of molecular imaging with specific focus on future clinical applications relevant to interventional radiology.

  View details for DOI 10.1016/j.jvir.2009.04.042

  View details for Web of Science ID 000267613200041

  View details for PubMedID 19560036

• Monitoring of the biological response to murine Hindlimb ischemia with Cu-64-labeled vascular endothelial growth factor-121 positron emission tomography CIRCULATION Willmann, J. K., Chen, K., Wang, H., Paulmurugan, R., Rollins, M., Cai, W., Wang, D. S., Chen, I. Y., Gheysens, O., Rodriguez-Porcel, M., Chen, X., Gambhir, S. S. 2008; 117 (7): 915-922

  Abstract

  Vascular endothelial growth factor-121 (VEGF121), an angiogenic protein secreted in response to hypoxic stress, binds to VEGF receptors (VEGFRs) overexpressed on vessels of ischemic tissue. The purpose of this study was to evaluate 64Cu-VEGF121 positron emission tomography for noninvasive spatial, temporal, and quantitative monitoring of VEGFR2 expression in a murine model of hindlimb ischemia with and without treadmill exercise training.64Cu-labeled VEGF121 and a VEGF mutant were tested for VEGFR2 binding specificity in cell culture. Mice (n=58) underwent unilateral ligation of the femoral artery, and postoperative tissue ischemia was assessed with laser Doppler imaging. Longitudinal VEGFR2 expression in exercised and nonexercised mice was quantified with 64Cu-VEGF121 positron emission tomography at postoperative day 8, 15, 22, and 29 and correlated with postmortem gamma-counting. Hindlimbs were excised for immunohistochemistry, Western blotting, and microvessel density measurements. Compared with the VEGF mutant, VEGF121 showed specific binding to VEGFR2. Perfusion in ischemic hindlimbs fell to 9% of contralateral hindlimb on postoperative day 1 and recovered to 82% on day 29. 64Cu-VEGF121 uptake in ischemic hindlimbs increased significantly (P < 0.001) from a control level of 0.61+/-0.17% ID/g (percentage of injected dose per gram) to 1.62+/-0.35% ID/g at postoperative day 8, gradually decreased over the following 3 weeks (0.59+/-0.14% ID/g at day 29), and correlated with gamma-counting (R2 = 0.99). Compared with nonexercised mice, 64Cu-VEGF121 uptake was increased significantly (P < or = 0.0001) in exercised mice (at day 15, 22, and 29) and correlated with VEGFR2 levels as obtained by Western blotting (R2 = 0.76). Ischemic hindlimb tissue stained positively for VEGFR2. In exercised mice, microvessel density was increased significantly (P<0.001) compared with nonexercised mice.64Cu-VEGF121 positron emission tomography allows longitudinal spatial and quantitative monitoring of VEGFR2 expression in murine hindlimb ischemia and indirectly visualizes enhanced angiogenesis stimulated by treadmill exercise training.

  View details for DOI 10.1161/CIRCULATIONAHA.107.733220

  View details for PubMedID 18250264

• Comparative evaluation of noninvasive compression adjuncts for hemostasis in percutaneous arterial, venous, and arteriovenous dialysis access procedures JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Wang, D. S., Chu, L. F., Olson, S. E., Miller, F. J., Valji, K., Wong, W. H., Rose, S. C., Austin, M., Kuo, M. D. 2008; 19 (1): 72-79

  Abstract

  To assess the relative efficacy of three compression adjuncts -- D-Stat Dry (D-Stat), QR Powder (QR), and XS Powder (XS) -- for reducing time to hemostasis in patients who underwent diagnostic and interventional percutaneous procedures.D-Stat, QR, or XS was applied in 176 percutaneous diagnostic arterial, therapeutic arterial, venous, and arteriovenous dialysis access (AVDA) procedures in 138 patients. The mean time to hemostasis and application-related complications were retrospectively assessed.Mean time to hemostasis was significantly reduced in all applications of QR (3.1 minutes +/- 1.1) and XS (3.7 minutes +/- 1.1) relative to D-Stat (6.2 minutes +/- 1.1, P < .001 vs both). For therapeutic arterial procedures, mean time to hemostasis for QR and XS was 3.6 minutes +/- 1.1 and 4.8 minutes +/- 1.1, respectively, and this was significantly less than that of D-Stat (10.0 minutes +/- 1.2; P < .001 vs QR, P < .01 vs XS). Mean times to hemostasis for QR and XS were also shorter than that with D-Stat in diagnostic arterial and AVDA procedures (P < .05). For venous procedures, mean time to hemostasis for QR (1.9 minutes +/- 1.2) was significantly shorter than that with both D-Stat (4.0 minutes +/- 1.2, P < .05) and XS (3.7 minutes +/- 1.2, P < .05). Minor immediate complications (hematoma <5 cm) occurred in 2.8% of applications. No access site infections were observed.All three agents effectively reduced time to hemostasis with minimal associated complications. QR was found to be more effective than D-Stat in all four procedure types.

  View details for DOI 10.1016/j.jvir.2007.08.028

  View details for Web of Science ID 000252853200012

  View details for PubMedID 18192470

• Will stent-graft repair emerge as treatment of choice for acute type B dissection? SEMINARS IN VASCULAR SURGERY Dake, M. D., Wang, D. S. 2006; 19 (1): 40-47

  Abstract

  Endovascular stent grafts are now accepted globally and approved by the US Food and Drug Administration as an alternative to open surgical repair for patients with descending thoracic aortic aneurysm. However, as opposed to the abdominal aorta, application of this technology to manage thoracic aortic disease is not limited to degenerative aneurysms. In fact, international registries and surveys estimate that only 60% of the thoracic cases managed currently with stent-graft placement are aneurysms. The remainder of this experience includes acute dissection, chronic dissection, traumatic aortic injury, penetrating ulcer, intramural hematoma, aortic fistula, anastomotic pseudoaneurysm, and an embolizing lesion. In this regard, it is important to keep in mind that the present devices used in these nonaneurysmal applications are not designed to address the unique anatomical and pathological features that these lesions present. Consequently, in the future, it is possible that we will see stent-graft designs that focus specifically on the challenges of some of the nonaneurysmal thoracic aortic pathologies.

  View details for DOI 10.1053/j.semvascsurg.2005.11.007

  View details for Web of Science ID 000242239900007

  View details for PubMedID 16533691

• Neuroimaging characteristics reflect tumor gene expression signatures and predict survival in glioblastoma multiforme 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Diehn, M., Nardini, C., Wang, D. S., Hsiao, A., Cha, S., Kuo, M. D. ELSEVIER SCIENCE INC. 2006: S18–S18

  View details for Web of Science ID 000241221600036

• Endovascular treatment for type B aortic dissection. Trends in Vascular Surgery Wang, D. S., Dake, M. D. Greenwood Academic. 2006
• Directed migration of smooth muscle cells to engineer plaque-resistant vein grafts JOURNAL OF ENDOVASCULAR THERAPY Amabile, P. G., Wang, D. S., Kao, E. Y., Lee, J., Elkins, C. J., Yuksel, E., Hilfiker, P. R., Waugh, J. M., Dake, M. D. 2005; 12 (6): 667-675

  Abstract

  To test the hypothesis that controlled perivascular release of tissue plasminogen activator (tPA) can generate cleaved extracellular matrix (ECM) chemotactic gradients to guide the migration of vascular smooth muscle cells (SMCs) away from the lumen, thereby limiting neointima formation.This hypothesis was tested in rabbit models in which the perivascular surface of vein bypass grafts was treated with microspheres releasing tPA (MS-tPA), microspheres containing no drug (MS-blank), or phosphate buffered saline (PBS). Vein graft segments harvested after 7 days were then evaluated for elastin content, proliferating SMCs, intima-to-media (I/M) ratio, and inflammation; late impact on neointima formation was also examined.The 7-day results demonstrated cleaved elastin gradients and proliferating SMCs that assumed a more peripheral distribution in the MS-tPA group than MS-blank and PBS controls (p<0.05). At 28 days, vein grafts treated with MS-tPA showed a mean I/M ratio (0.35+/-0.04) that was 63.5% lower than PBS controls (0.96+/-0.07, p<0.005) and 43.5% lower than MS-blank specimens (0.62+/-0.08, p<0.05).Perivascular release of tPA modifies ECM gradients, directionally guides SMC migration away from the lumen, and limits neointima formation.

  View details for PubMedID 16363896

• Endovascular repair of abdominal and thoracic aortic aneurysms CIRCULATION Katzen, B. T., Dake, M. D., MaClean, A. A., Wang, D. S. 2005; 112 (11): 1663-1675

  View details for DOI 10.1161/CIRCULATIONAHA.105.541284

  View details for Web of Science ID 000231821200021

  View details for PubMedID 16157785

• Endovascular stent-grafts for treatment of thoracic aortic diseases. Abrams’ Angiography: Interventional Radiology Wang, D. S., Dake, M. D. Little, Brown and Company. 2005; 5th
• Local resistance to oxidative stress by overexpression of copper-zinc superoxide dismutase limits neointimal formation after angioplasty JOURNAL OF ENDOVASCULAR THERAPY Kuo, M. D., Bright, I. J., Wang, D. S., Ghafouri, P., Yuksel, E., Hilfiker, P. R., Miniati, D. N., Dake, M. D. 2004; 11 (6): 585-594

  Abstract

  To examine the effects of oxidative stress on neointimal hyperplasia through local overexpression of human copper-zinc superoxide dismutase (Cu-Zn SOD).The left common femoral arteries (CFA) of 18 New Zealand white rabbits were subjected to balloon overdilation injury. Each dilated CFA was then incubated with either a nonviral (buffer) or viral (adenovirus overexpressing beta-galactosidase) control or an adenovirus overexpressing Cu-Zn SOD. Animals were then sacrificed at 3, 7, or 28 days (3 arteries per group per time point) and the treated CFA segments were harvested for analysis of esterase-positive inflammatory cells and extracellular matrix elements. The intima-to-media ratio (I/M) was measured to assess the degree of neointimal formation.At 3 days, local SOD levels in the Cu-Zn SOD-treated group were significantly elevated relative to both controls (p<0.01). Significant reductions in lipid peroxidation byproducts were also seen in the SOD group relative to viral and nonviral controls (p<0.05). Mean I/M at 28 days was 0.582+/-0.088 for the nonviral control group versus 0.565+/-0.133 for the viral control group. The SOD-treated group had a significant reduction relative to both controls: 0.259+/-0.045 (p<0.05). Statistically significant reductions in I/M were also demonstrated in the SOD group relative to control groups at 7 days (p<0.05). The SOD-treated group demonstrated significant preservation of elastin relative to controls, as well as a significant reduction in esterase-positive granulocytes relative to controls (p<0.05).Direct buffering of oxidative stress in balloon-injured vessels can significantly alter postinjury response and limit neointimal hyperplasia.

  View details for PubMedID 15615548

• Correlation between global gene expression patterns and magnetic resonance imaging findings in glioblastoma multiforme 9th Annual Meeting of the Society-for-Neuro-Oncology Wang, D. S., Cha, S., Nardini, C., Diehn, M., Chan, B. K., Kuo, M. D. OXFORD UNIV PRESS INC. 2004: 340–40

  View details for Web of Science ID 000224332400139

• In-stent restenosis limitation with stent-based controlled-release nitric oxide: Initial results in rabbits RADIOLOGY Do, Y. S., Kao, E. Y., Ganaha, F., Minamiguchi, H., Sugimoto, K., Lee, J., Elkins, C. J., Amabile, P. G., Kuo, M. D., Wang, D. S., Waugh, J. M., Dake, M. D. 2004; 230 (2): 377-382

  Abstract

  To evaluate effect of controlled stent-based release of an NO donor to limit in-stent restenosis in rabbits.Bioerodable microspheres containing NO donor or biodegradable polymer (polylactide-co-glycolide-polyethylene glycol) were prepared and loaded in channeled stents. Daily concentrations of NO release from NO-containing microspheres were assayed in vitro. NO- and polymer-containing (control) microsphere-loaded stents were deployed in aortas of New Zealand white rabbits (n = 8). Aortas with stents were harvested at 7 (n = 5) and 28 days (n = 3) and evaluated for cyclic guanosine monophosphate (cGMP) levels (7 days), number of proliferating cell nuclear antigen-positive cells (7 days), and intima-to-media ratio (7 and 28 days), with statistical significance evaluated by using one-way analysis of variance.NO-containing microspheres released NO with an initial bolus in the 1st week, followed by sustained release for the remaining 3 weeks. Significant increase in cGMP levels and decrease in proliferating cell nuclear antigen-positive cells were found at 7 days for the NO-treated group relative to controls (P <.05). Intima-to-media ratio in the NO-treated group was reduced by 46% and 32% relative to controls at 7 and 28 days, respectively (mean, 0.14 +/- 0.01 [standard error] vs 0.26 +/- 0.02 at 7 days, P <.01; 1.34 +/- 0.05 vs 1.98 +/- 0.08 at 28 days, P <.01).Stent-based controlled release of NO donor significantly reduces in-stent restenosis and is associated with increase in vascular cGMP and suppression of proliferation.

  View details for DOI 10.1148/radiol.2302020417

  View details for PubMedID 14699187

• Translating nanotechnology to vascular disease. Nanoscale Technology in Biomedical Systems Kuo, M. D., Waugh, J. M., Elkins, C. J., Wang, D. S. CRC Press. 2004
• NOS inhibition accelerates atherogenesis: reversal by exercise AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Niebauer, J., Maxwell, A. J., Lin, P. S., Wang, D., Tsao, P. S., Cooke, J. P. 2003; 285 (2): H535-H540

  Abstract

  In this study, we assessed the effects of chronic exercise training (12 wk) on atherosclerotic lesion formation in hypercholesterolemic apolipoprotein E-deficient mice (n = 31). At the age of 9 wk, mice were assigned to the following groups: sedentary (Sed; n = 9); exercise (Ex; n = 12); sedentary and oral NG-nitro-L-arginine (L-NNA, Sed-NA; n = 4), or exercise and oral L-NNA (Ex-NA; n = 6). Chronic exercise training was performed on a treadmill for 12 wk (6 times/wk and twice for 1 h/day) at a final speed of 22 m/min, and an 8 degrees grade. L-NNA was discontinued 5 days before final treadmill testing. The farthest distance run to exhaustion was observed in Ex-NA mice (Sed: 306 +/- 32 m; Ex: 640 +/- 87; Sed-NA: 451 +/- 109 m; Ex-NA: 820 +/- 49 m; all P < 0.05). Lesion formation was assessed in the proximal ascending aorta by dissection microscopy after oil red O staining. The aortas of Sed-NA mice manifested a threefold increase in lesion formation compared with the other groups. This L-NNA-induced lesion formation was reduced by chronic exercise training (Sed, 786 +/- 144; Ex, 780 +/- 206; Sed-NA, 2,147 +/- 522; Ex-NA, 851 +/- 253; Sed-NA vs. all other groups: P < 0.001). In conclusion, treatment with oral L-NNA (an nitric oxide synthase antagonist) leads to accelerated atherogenesis in genetically determined hypercholesterolemic mice. This adverse effect can be overcome by chronic exercise training.

  View details for DOI 10.1152/ajpheart.00360.2001

  View details for PubMedID 12598230

• Airway management after maxillectomy: Routine tracheostomy is unnecessary Meeting of the Middle Section of the Triological-Society Lin, H. S., Wang, D., Fee, W. E., Goode, R. L., Terris, D. J. LIPPINCOTT WILLIAMS & WILKINS. 2003: 929–32

  Abstract

  There is a paucity of data to guide the optimal management of the airway in patients after maxillectomy. The decision on whether a concomitant tracheostomy is needed is often dictated by the surgeon's training and experience. We reviewed our experience with maxillectomy to assess the need for tracheostomy in postoperative airway management.Retrospective analysis at a university hospital.We identified 121 patients who underwent 130 maxillectomies between October 1990 and September 2001. Twenty-four of these were total (all six walls removed), 45 were subtotal (two or more walls removed), and 61 were limited (only one wall removed). Reconstruction ranged from none to microvascular free flap, with split-thickness skin graft being the most common reconstructive option.Only 10 tracheostomies (7.7%) were performed at the time of maxillectomy. These included four tracheostomies in patients who underwent bulky flap reconstruction, two tracheostomies in patients who underwent both flap reconstruction and mandibulectomy, one tracheostomy in a patient who underwent mandibulectomy, one tracheostomy in a patient with mucormycosis in anticipation of prolonged ventilatory support postoperatively, and two tracheostomies at the surgeons' discretion because of concern for upper airway edema. Among the 111 patients who underwent 120 maxillectomies without concomitant tracheostomy, 1 patient (0.9%), a 74 year-old man with oxygen-dependent chronic obstructive pulmonary disease, required repeat intubation on day 3 and again on day 10 after the surgery, because of respiratory failure; fiberoptic examination confirmed the absence of upper airway compromise.The routine performance of tracheostomy in patients undergoing maxillectomy is unnecessary. Selective use of tracheostomy may be indicated in situations in which mandibulectomy or bulky flap reconstruction is performed or a concern for postoperative oropharyngeal airway obstruction because of edema or packing exists.

  View details for Web of Science ID 000183391900002

  View details for PubMedID 12782798

• Mechanotransduction of endothelial oxidative stress induced by cyclic strain ENDOTHELIUM-JOURNAL OF ENDOTHELIAL CELL RESEARCH Wang, D. S., Proffit, D., Tsao, P. S. 2001; 8 (4): 283-291

  Abstract

  Atherosclerotic lesions display a nonuniform distribution throughout the vascular tree. Mechanical forces produced by local alterations in blood flow may play an important role in the localization of atherosclerosis. One such force, cyclic strain, has been hypothesized to promote atherogenesis by inducing oxidative stress in endothelial cells, resulting in enhanced endothelial adhesiveness for monocytes. To investigate the signal transduction systems involved, human aortic endothelial cells were plated on flexible silicone strips that were either non-coated or adsorbed with poly-L-lysine, vitronectin, fibronectin, or collagen I. Cells were then subjected to uniform sinusoidal stretch (10%) for 6 h. Endothelial superoxide anion production was increased in cells exposed to cyclic strain compared to static conditions. Furthermore, endothelial oxidative response to stretch was matrix protein-dependent, whereas cells grown on fibronectin and collagen I produced significantly more superoxide. The oxidative response to cyclic strain was reduced by coincubation with RGD peptides, blocking antibodies to alpha2- and beta-integrins antibodies, as well as inhibitors of protein kinase C. To investigate the effect of oxidative stress on gene transcription, endothelial cells grown on collagen I were transfected with an NFkappaB-sensitive luciferase construct. Cells that underwent cyclic strain displayed a tenfold induction of NFkappaB activation compared to static controls. Strain-induced luciferase activity was blunted by coincubation with RGD peptides or calphostin C. Thus, exposure of endothelial cells to cyclic strain led to integrin activation of a PKC-sensitive pathway that results in increased superoxide anion production and mobilization of NFkappaB.

  View details for Web of Science ID 000173063400007

  View details for PubMedID 11824481