William Eward

Overview:

I am an Orthopaedic Oncologist, with dual clinical degrees (MD and DVM).  I treat complex sarcomas in people and animals.  My laboratory studies comparative oncology - discoveries we can make about cancer by analyses across different species.

Positions:

Frank H. Bassett III, M. D. Associate Professor of Orthopaedic Surgery

Orthopaedic Surgery
School of Medicine

Associate Professor of Orthopaedic Surgery

Orthopaedic Surgery
School of Medicine

Associate Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2006

University of Vermont, College of Medicine

Grants:

Bortezomib: A novel treatment to improve outcomes in dogs with osteosarcoma

Awarded By
Orthopaedic Research and Education Foundation
Role
Co-Principal Investigator
Start Date
End Date

Intraoperative detection and ablation of microscopic residual cancer in the tumor bed

Administered By
Orthopaedic Surgery
Awarded By
Lumicell Diagnostics
Role
Principal Investigator
Start Date
End Date

A Prospective Observational Study of Intraoperative Angiography for Predicting Wound Complications in Irradiated Soft Tissue Sarcoma of the Extremities

Administered By
Orthopaedic Surgery
Awarded By
Piedmont Orthopedic Foundation
Role
Co-Principal Investigator
Start Date
End Date

SCH: Overcoming the Intraoperative Data Desert: Biophotonics, Advanced Sensing, and Control for Automated Surgery

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Phase 1 Study of X-PACT (X-ray Psoralen Activated Cancer Therapy)

Awarded By
Immunolight, LLC
Role
Principal Investigator
Start Date
End Date

Publications:

Evaluating the relevance of surgical margins. Part one: The problems with current methodology.

The goal of cancer surgery is to achieve a "clean" microscopic resection, with no residual tumour remaining in the wound. To achieve that goal, the surgeon typically incorporates a measured buffer of grossly normal tissue about the entire circumference of the tumour. Microscopic analysis of the resection boundaries is then performed to determine if all traces of the tumour have been completely removed. This analysis is thought to provide a surrogate indication as to the likelihood for that tumour to recur after surgery. However, it is recognised that tumour recurrence may not occur even when microscopic evidence of tumour has been identified at the resection margins, and recurrence can also occur when conventional histology has considered the tumour to have been completely removed. The explanations for this dichotomy are numerous and include technical and practical limitations of the processing methodology, and also several surgeon-related and tumour-related reasons. Ultimately, the inability to confidently determine when a tumour has been removed sufficiently to prevent recurrence can impact on the ability to provide owners with confident treatment advice. In this article, the authors describe the challenges with defining the true extent of the tumour margin from the perspective of the surgeon, the pathologist and the tumour. The authors also provide an analysis of why our current efforts to ensure that all traces of the local tumour have been successfully removed may provide an imperfect assessment of the risk of recurrence.
Authors
Bray, J; Eward, W; Breen, M
MLA Citation
Bray, Jonathan, et al. “Evaluating the relevance of surgical margins. Part one: The problems with current methodology.Vet Comp Oncol, Oct. 2022. Pubmed, doi:10.1111/vco.12865.
URI
https://scholars.duke.edu/individual/pub1555234
PMID
36308442
Source
pubmed
Published In
Vet Comp Oncol
Published Date
DOI
10.1111/vco.12865

Juxtametallic Bipolar Bone Radiofrequency Ablation: Thermal Monitoring in an Ex-Vivo Model with Specimen MRI and Histopathologic Correlation.

PURPOSE: To measure the ablation zone temperature and nontarget tissue temperature during radiofrequency (RF) ablation in bone containing metal instrumentation versus no metal instrumentation (control group). MATERIALS AND METHODS: Ex vivo experiments were performed on 15 swine vertebrae (control, n = 5; titanium screw, n = 5; stainless steel screw, n = 5). Screws and RF ablation probe were inserted identically under fluoroscopy. During RF ablation (3 W, 5 minutes), temperature was measured 10 mm from RF ablation centerpoint and in muscle contacting the screw. Magnetic resonance (MR) imaging, gross pathologic, and histopathologic analyses were performed on 1 specimen from each group. RESULTS: Ablation zone temperatures at 2.5 and 5 minutes increased by 12.2 °C ± 2.6 °C and 21.5 °C ± 2.1 °C (control); 11.0 °C ± 4.1 °C and 20.0 °C ± 2.9 °C (juxta-titanium screw), and 10.0 °C ± 3.4 °C and 17.2 °C ± 3.5 °C (juxta-stainless steel) screw; differences among groups did not reach significance by analysis of variance (P = .87). Mixed-effects linear regression revealed a statistically significant increase in temperature over time in all 3 groups (4.2 °C/min ± 0.4 °C/min, P < .001). Compared with the control, there was no significant difference in the temperature change over time for titanium (-0.3 °C/min ± 0.5 °C/min, P = .53) or steel groups (-0.4 °C/min ± 0.5 °C/min, P = .38). The mean screw temperature at the final time point did not show a statistically significant change compared with baseline in either the titanium group (-1.2 °C ± 2.3 °C, P = .50) or steel group (2.6 °C ± 2.9 °C, P = .11). MR imaging and pathologic analyses revealed homogeneous ablation without sparing of the peri-hardware zones. CONCLUSIONS: Adjacent metallic instrumentation did not affect the rate of or absolute increase in temperature in the ablation zone, did not create peri-metallic ablation inhomogeneities, and did not result in significant nontarget heating of muscle tissue in contact with the metal instrumentation.
Authors
Sag, AA; Sperduto, WAL; Eward, W; Ronald, J; Davis, H; Jiang, XS; Enterline, DS; Visgauss, J; Brigman, B; Goodwin, CR; Qadri, YJ; Kim, CY
MLA Citation
Sag, Alan A., et al. “Juxtametallic Bipolar Bone Radiofrequency Ablation: Thermal Monitoring in an Ex-Vivo Model with Specimen MRI and Histopathologic Correlation.J Vasc Interv Radiol, vol. 33, no. 12, Dec. 2022, pp. 1594–600. Pubmed, doi:10.1016/j.jvir.2022.08.019.
URI
https://scholars.duke.edu/individual/pub1533606
PMID
36007783
Source
pubmed
Published In
J Vasc Interv Radiol
Volume
33
Published Date
Start Page
1594
End Page
1600
DOI
10.1016/j.jvir.2022.08.019

A transdisciplinary approach to reducing global plastic pollution

Authors
Diana, Z; Karasik, R; Merrill, GB; Morrison, M; Corcoran, KA; Vermeer, D; Hepler-Smith, E; Jayasundara, N; Pare, J; Virdin, J; Eward, WC; Somarelli, JA; Dunphy-Daly, MM; Rittschof, D
MLA Citation
Diana, Z., et al. “A transdisciplinary approach to reducing global plastic pollution.” Frontiers in Marine Science, vol. 9, Oct. 2022. Scopus, doi:10.3389/fmars.2022.1032381.
URI
https://scholars.duke.edu/individual/pub1554907
Source
scopus
Published In
Frontiers in Marine Science
Volume
9
Published Date
DOI
10.3389/fmars.2022.1032381

Antibiotic Prophylaxis for Megaprosthetic Reconstructions: Drug and Dosing May Matter More than Duration.

In orthopedic oncology, the implant of a megaprosthetic device is standard of care after large-scale tumor resection involving segmental removal of bone. Infection remains the leading cause of implant failure, often resulting in major morbidity. Perioperative antibiotic practices for megaprosthetic reconstructions are not standardized and are based on guidelines for conventional joint arthroplasties. This study aims to evaluate the efficacy of current prophylactic strategies for megaprosthetic reconstructions. We conducted a retrospective review of megaprosthetic reconstructions performed at Duke University from 2001 to 2021. Logistic regression with GEE was used to assess whether a prolonged course of postoperative antibiotics is associated with infection risk. We assessed the microbial profile and corresponding susceptibilities of megaprosthetic infections through record review. Additionally, we designed a pharmacokinetic subgroup analysis using liquid chromatography-tandem mass spectrometry to quantify antibiotic concentrations in surgical tissue. Wilcoxon rank-sum tests were used to correlate tissue concentrations with infection risk. Out of 184 cases, 23 (12.5%) developed infection within 1 year. Extended postoperative antibiotics were not significantly associated with infection risk (P = 0.23). Among 18 culture-positive cases, 4 (22.2%) were caused by cefazolin-susceptible organisms. Median bone and muscle concentrations of cefazolin among cases that developed postoperative infection (0.065 ng/mL and 0.2 ng/mL, respectively) were significantly lower than those of cases that did not (0.42 ng/mL and 1.95 ng/mL, P < 0.01 and P = 0.03). This study is the first to comprehensively assess aspects of perioperative prophylaxis for megaprosthetic reconstructions. Extending postoperative antibiotics did not reduce infection risk. We detected a high frequency of cefazolin nonsusceptible organisms among postoperative infections. Additionally, intraoperative antibiotic tissue concentrations may be predictive of later infection. Future studies ought to examine optimal drug choices and dosing strategies.
Authors
Byers, IS; Turner, NA; Levine, NL; Lazarides, AL; Evans, DR; Spasojevic, I; Fan, P; Jung, S-H; Gao, J; Visgauss, JD; Brigman, BE; Eward, WC
MLA Citation
Byers, Isabelle S., et al. “Antibiotic Prophylaxis for Megaprosthetic Reconstructions: Drug and Dosing May Matter More than Duration.Antimicrob Agents Chemother, vol. 66, no. 10, Oct. 2022, p. e0014022. Pubmed, doi:10.1128/aac.00140-22.
URI
https://scholars.duke.edu/individual/pub1553045
PMID
36165615
Source
pubmed
Published In
Antimicrob Agents Chemother
Volume
66
Published Date
Start Page
e0014022
DOI
10.1128/aac.00140-22

Loss of ATRX promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin binding.

Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here, we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypic changes correspond with activation of NF-κB signaling, extracellular matrix remodeling, increased integrin αvβ3 expression, and ETS family transcription factor binding. Here, we characterize these changes in vitro, in vivo, and in a data set of human OS patients. This increased aggression substantially sensitizes ATRX-deficient OS cells to integrin signaling inhibition. Thus, ATRX plays an important tumor-suppression role in OS, and loss of function of this gene may underlie new therapeutic vulnerabilities. The relationship between ATRX expression and integrin binding, NF-κB activation, and ETS family transcription factor binding has not been described in previous studies and may impact the pathophysiology of other diseases with ATRX loss, including other cancers and the ATR-X α thalassemia intellectual disability syndrome.
Authors
Bartholf DeWitt, S; Hoskinson Plumlee, S; Brighton, HE; Sivaraj, D; Martz, EJ; Zand, M; Kumar, V; Sheth, MU; Floyd, W; Spruance, JV; Hawkey, N; Varghese, S; Ruan, J; Kirsch, DG; Somarelli, JA; Alman, B; Eward, WC
MLA Citation
Bartholf DeWitt, Suzanne, et al. “Loss of ATRX promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin binding.Jci Insight, vol. 7, no. 17, Sept. 2022. Pubmed, doi:10.1172/jci.insight.151583.
URI
https://scholars.duke.edu/individual/pub1548028
PMID
36073547
Source
pubmed
Published In
Jci Insight
Volume
7
Published Date
DOI
10.1172/jci.insight.151583