A Novel Imaging System Distinguishes Neoplastic from Normal Tissue During Resection of Soft Tissue Sarcomas and Mast Cell Tumors in Dogs

Overview

Journal Vet Surg

Specialties General Surgery
Veterinary Medicine

Date 2016 Jun 10

PMID 27281113

Citations 8

Authors

Suzanne Bartholf DeWitt

William C Eward

Cindy A Eward

Alexander L Lazarides

Melodi Javid Whitley

Jorge M Ferrer

Brian E Brigman

David G Kirsch

John Berg

Affiliations

Soon will be listed here.

Abstract

Objective: To assess the ability of a novel imaging system designed for intraoperative detection of residual cancer in tumor beds to distinguish neoplastic from normal tissue in dogs undergoing resection of soft tissue sarcoma (STS) and mast cell tumor (MCT).

Study Design: Non-randomized prospective clinical trial.

Animals: 12 dogs with STS and 7 dogs with MCT.

Methods: A fluorescent imaging agent that is activated by proteases in vivo was administered to the dogs 4-6 or 24-26 hours before tumor resection. During surgery, a handheld imaging device was used to measure fluorescence intensity within the cancerous portion of the resected specimen and determine an intensity threshold for subsequent identification of cancer. Selected areas within the resected specimen and tumor bed were then imaged, and biopsies (n=101) were obtained from areas that did or did not have a fluorescence intensity exceeding the threshold. Results of intraoperative fluorescence and histology were compared.

Results: The imaging system correctly distinguished cancer from normal tissue in 93/101 biopsies (92%). Using histology as the reference, the sensitivity and specificity of the imaging system for identification of cancer in biopsies were 92% and 92%, respectively. There were 10/19 (53%) dogs which exhibited transient facial erythema soon after injection of the imaging agent which responded to but was not consistently prevented by intravenous diphenhydramine.

Conclusion: A fluorescence-based imaging system designed for intraoperative use can distinguish canine soft tissue sarcoma (STS) and mast cell tumor (MCT) tissue from normal tissue with a high degree of accuracy. The system has potential to assist surgeons in assessing the adequacy of tumor resections during surgery, potentially reducing the risk of local tumor recurrence. Although responsive to antihistamines, the risk of hypersensitivity needs to be considered in light of the potential benefits of this imaging system in dogs.

Citing Articles

Machine learning approaches in non-contact autofluorescence spectrum classification.

Raman A, Zachem T, Plumlee S, Park C, Eward W, Codd P PLOS Digit Health. 2024; 3(10):e0000602.

PMID: 39383196 PMC: 11463826. DOI: 10.1371/journal.pdig.0000602.

Progresses in Fluorescence Imaging Guidance for Bone and Soft Tissue Sarcoma Surgery.

Chen Z, Huang H, He S, Wang Y, Cai L, Xie Y Front Oncol. 2022; 12:879697.

PMID: 35860548 PMC: 9289289. DOI: 10.3389/fonc.2022.879697.

The feasibility and utility of optical coherence tomography directed histopathology for surgical margin assessment of canine mast cell tumours.

Dornbusch J, Cocca C, Jennings R, Samuelson J, Vieson M, Huang P Vet Comp Oncol. 2020; 19(4):616-623.

PMID: 32951309 PMC: 9720908. DOI: 10.1111/vco.12654.

Diagnostic accuracy of optical coherence tomography for assessing surgical margins of canine soft tissue sarcomas in observers of different specialties.

Dornbusch J, Selmic L, Huang P, Samuelson J, McLaughlin E, Wavreille V Vet Surg. 2020; 50(1):111-120.

PMID: 32916007 PMC: 9744383. DOI: 10.1111/vsu.13510.

Near-infrared imaging and optical coherence tomography for intraoperative visualization of tumors.

Holt D, Singhal S, Selmic L Vet Surg. 2019; 49(1):33-43.

PMID: 31609011 PMC: 11059208. DOI: 10.1111/vsu.13332.

References

Seguin B, Besancon M, McCallan J, Dewe L, Tenwolde M, Wong E . Recurrence rate, clinical outcome, and cellular proliferation indices as prognostic indicators after incomplete surgical excision of cutaneous grade II mast cell tumors: 28 dogs (1994-2002). J Vet Intern Med. 2006; 20(4):933-40. DOI: 10.1892/0891-6640(2006)20[933:rrcoac]2.0.co;2. View

Kuntz C, Dernell W, Powers B, Devitt C, Straw R, Withrow S . Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996). J Am Vet Med Assoc. 1997; 211(9):1147-51. View

Dennis M, McSporran K, Bacon N, Schulman F, Foster R, Powers B . Prognostic factors for cutaneous and subcutaneous soft tissue sarcomas in dogs. Vet Pathol. 2010; 48(1):73-84. DOI: 10.1177/0300985810388820. View

Lazarides A, Whitley M, Strasfeld D, Cardona D, Ferrer J, Mueller J . A Fluorescence-Guided Laser Ablation System for Removal of Residual Cancer in a Mouse Model of Soft Tissue Sarcoma. Theranostics. 2016; 6(2):155-66. PMC: 4729765. DOI: 10.7150/thno.13536. View

Weisse C, Shofer F, Sorenmo K . Recurrence rates and sites for grade II canine cutaneous mast cell tumors following complete surgical excision. J Am Anim Hosp Assoc. 2002; 38(1):71-3. DOI: 10.5326/0380071. View

Kirsch D, Dinulescu D, Miller J, Grimm J, Santiago P, Young N . A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med. 2007; 13(8):992-7. DOI: 10.1038/nm1602. View

Mito J, Ferrer J, Brigman B, Lee C, Dodd R, Eward W . Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging. Cancer. 2012; 118(21):5320-30. PMC: 3532657. DOI: 10.1002/cncr.27458. View

Stefanello D, Morello E, Roccabianca P, Iussich S, Nassuato C, Martano M . Marginal excision of low-grade spindle cell sarcoma of canine extremities: 35 dogs (1996-2006). Vet Surg. 2008; 37(5):461-5. DOI: 10.1111/j.1532-950X.2008.00408.x. View

Olson T, Harter J, Munoz A, Mahvi D, Breslin T . Frozen section analysis for intraoperative margin assessment during breast-conserving surgery results in low rates of re-excision and local recurrence. Ann Surg Oncol. 2007; 14(10):2953-60. DOI: 10.1245/s10434-007-9437-1. View

10.

Thurber G, Figueiredo J, Weissleder R . Detection limits of intraoperative near infrared imaging for tumor resection. J Surg Oncol. 2010; 102(7):758-64. PMC: 3758114. DOI: 10.1002/jso.21735. View

11.

McSporran K . Histologic grade predicts recurrence for marginally excised canine subcutaneous soft tissue sarcomas. Vet Pathol. 2009; 46(5):928-33. DOI: 10.1354/vp.08-VP-0277-M-FL. View

12.

Scarpa F, Sabattini S, Marconato L, Capitani O, Morini M, Bettini G . Use of histologic margin evaluation to predict recurrence of cutaneous malignant tumors in dogs and cats after surgical excision. J Am Vet Med Assoc. 2012; 240(10):1181-7. DOI: 10.2460/javma.240.10.1181. View

13.

Ozaki K, Yamagami T, Nomura K, Narama I . Prognostic significance of surgical margin, Ki-67 and cyclin D1 protein expression in grade II canine cutaneous mast cell tumor. J Vet Med Sci. 2007; 69(11):1117-21. DOI: 10.1292/jvms.69.1117. View

14.

Ehrhart N . Soft-tissue sarcomas in dogs: a review. J Am Anim Hosp Assoc. 2005; 41(4):241-6. DOI: 10.5326/0410241. View

15.

Weissleder R, Tung C, Mahmood U, Bogdanov Jr A . In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol. 1999; 17(4):375-8. DOI: 10.1038/7933. View

16.

Mito J, Riedel R, Dodd L, Lahat G, Lazar A, Dodd R . Cross species genomic analysis identifies a mouse model as undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma. PLoS One. 2009; 4(11):e8075. PMC: 2779485. DOI: 10.1371/journal.pone.0008075. View

17.

Allweis T, Kaufman Z, Lelcuk S, Pappo I, Karni T, Schneebaum S . A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery. Am J Surg. 2008; 196(4):483-9. DOI: 10.1016/j.amjsurg.2008.06.024. View

18.

Eward W, Mito J, Eward C, Carter J, Ferrer J, Kirsch D . A novel imaging system permits real-time in vivo tumor bed assessment after resection of naturally occurring sarcomas in dogs. Clin Orthop Relat Res. 2012; 471(3):834-42. PMC: 3563778. DOI: 10.1007/s11999-012-2560-8. View

19.

Schultheiss P, Gardiner D, Rao S, Olea-Popelka F, Tuohy J . Association of histologic tumor characteristics and size of surgical margins with clinical outcome after surgical removal of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc. 2011; 238(11):1464-9. DOI: 10.2460/javma.238.11.1464. View

20.

Haid A, Knauer M, Dunzinger S, Jasarevic Z, Koberle-Wuhrer R, Schuster A . Intra-operative sonography: a valuable aid during breast-conserving surgery for occult breast cancer. Ann Surg Oncol. 2007; 14(11):3090-101. DOI: 10.1245/s10434-007-9490-9. View