ORCID Profile
0000-0001-7016-771X
Current Organisation
University of Melbourne
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Publisher: Wiley
Date: 19-04-2012
Publisher: Hindawi Limited
Date: 25-08-2018
DOI: 10.1002/TERM.2476
Abstract: Articular cartilage injuries experienced at an early age can lead to the development of osteoarthritis later in life. In situ three-dimensional (3D) printing is an exciting and innovative biofabrication technology that enables the surgeon to deliver tissue-engineering techniques at the time and location of need. We have created a hand-held 3D printing device (biopen) that allows the simultaneous coaxial extrusion of bioscaffold and cultured cells directly into the cartilage defect in vivo in a single-session surgery. This pilot study assessed the ability of the biopen to repair a full-thickness chondral defect and the early outcomes in cartilage regeneration, and compared these results with other treatments in a large animal model. A standardized critical-sized full-thickness chondral defect was created in the weight-bearing surface of the lateral and medial condyles of both femurs of six sheep. Each defect was treated with one of the following treatments: (i) hand-held in situ 3D printed bioscaffold using the biopen (HH group), (ii) preconstructed bench-based printed bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated (control, C group). At 8 weeks after surgery, macroscopic, microscopic and biomechanical tests were performed. Surgical 3D bioprinting was performed in all animals without any intra- or postoperative complication. The HH biopen allowed early cartilage regeneration. The results of this study show that real-time, in vivo bioprinting with cells and scaffold is a feasible means of delivering a regenerative medicine strategy in a large animal model to regenerate articular cartilage.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 08-2019
Publisher: Mary Ann Liebert Inc
Date: 08-2015
Abstract: Canine tumors are valuable comparative oncology models. This research was designed to create a sustainable biobank of canine mammary tumors for breast cancer research. The aim was to provide a well-characterized s le cohort for specimen sharing, data mining, and long-term research aims. Canine mammary tumors are most frequently managed at a local veterinary clinic or hospital. We adopted a biobank framework based on a large number of participating veterinary hospitals and clinics acting as collection centers that were serviced by a centralized storage facility. Recruitment was targeted at rural veterinary clinics. A tailored, stable collection kit (DogMATIC) was designed that was used by veterinarians in remote or rural locations to collect both fresh and fixed tissue for submission to the biobank. To validate this methodology the kit design, collection rate, and s le quality were analyzed. The Australian Veterinary Cancer Biobank was established as a network of 47 veterinary clinics and three veterinary pathology laboratories spanning over 200,000 km(2). In the first 12 months, 30 canine mammary tumor cases were submitted via the DogMATIC kit. Pure intact RNA was isolated in over 80% of s les with an average yield of 14.49 μg. A large network biobank, utilizing off-site collection with the DogMATIC kit, was successfully coordinated. The creation of the Australian Veterinary Cancer Biobank has established a long-term, sustainable, comparative oncology research resource in Australia. There are broader implications for biobanking with this very different form of collection and banking.
Publisher: Wiley
Date: 13-01-2021
DOI: 10.1111/VCO.12674
Abstract: Canine appendicular osteosarcoma is commonly treated with limb utation however, limb‐sparing options are frequently desired or necessary for a subset of patients. We evaluated 123 patients and 130 sites treated with stereotactic body radiation therapy (SBRT). Eighty‐two out of 98 dogs (84%) had maximum lameness improvement at a median of 3 weeks for a median of 6 months duration. Histopathologic evaluation of available s les from utation or necropsy revealed % tumor necrosis in 50% of limbs consistent with local disease control. Of evaluable patients, 41% fractured and 21% pursued an utation after treatment. Fine needle aspirate (n = 52) and needle core biopsy (n = 28) did not result in increased fracture risk compared to those without tumor s ling (n = 50). Median survival time (MST) was 233 days and time to first event was 143 days. Gross tumor volume and planned target volume were significantly inversely associated with survival and tumor location was significantly associated with survival. Dogs with salvage utation had a significantly longer MST compared to those without (346 vs 202 days P = .04). The presence of metastatic disease at the time of treatment in 15 dogs did not significantly impact survival time (200 vs 237 days without metastasis P = .58). Skin side effects correlated significantly with dose with 33% of patients with acute grade 3 effects developing consequential late grade 3 effects. While SBRT improves lameness in most patients, further investigation is needed to identify candidates with minimal early fracture risk prior to initiating therapy.
Publisher: Informa UK Limited
Date: 15-03-2018
Publisher: Elsevier
Date: 2013
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JCPA.2017.07.005
Abstract: Osteosarcoma (OS) originates from bone-forming mesenchymal cells and represents one of the primary bone tumours. It is the most common primary bone tumour in dogs and man. The characterization of an appropriate natural disease animal model to study human OS is essential to elucidate the pathogenesis of the disease. This study aimed to validate canine OS as a model for the human disease by evaluating immunohistochemically the expression of markers known to be important in human OS. The immunohistochemical panel included vimentin, alkaline phosphatase (ALP), desmin, S100, neuron-specific enolase (NSE), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 4 (BMP4). Immunohistochemistry was conducted on formalin-fixed, paraffin wax-embedded tissue sections from 59 dogs with confirmed primary OS. Vimentin, ALP, Runx2 and BMP4 were highly expressed by all tumours, while desmin, S100 and NSE were expressed variably. The findings were similar to those described previously for human OS and suggest that canine OS may represent a useful model for the study of the human disease.
Publisher: American Veterinary Medical Association (AVMA)
Date: 09-2020
Abstract: To compare the bursting strength of the uterine horns (UHs) and cervical-vestibule junction (CVJs) of rabbits following sealing with a vessel-sealing device (VSD) or encircling ligatures. UHs and CVJs collected from 30 rabbit ( Oryctolagus cuniculus ) cadavers. UHs and CVJs were randomly assigned to sealing with encircling Miller knot ligatures (LIG n = 10 CVJs and 20 UHs) or a VSD (12 CVJs and 24 UHs). Lumens were infused with saline (0.9% NaCl) solution under pressure until seals burst or to a maximum pressure of 300 mm Hg. For CVJs, median (range) bursting pressure of the LIG and VSD groups was 300 mm Hg (224 to 300 mm Hg) and 35 mm Hg (0 to 60 mm Hg), respectively. Five of 12 CVJs in the VSD group failed at pressures 33 mm Hg. For UHs, median (range) bursting pressure of the LIG and VSD groups was 255 mm Hg (120 to 300 mm Hg) and 154 mm Hg (range, 44 to 202 mm Hg), respectively. The evaluated VSD was effective in sealing UHs at bursting pressures well in excess of expected physiologic pressures, indicating that the VSD may be useful for ovariectomy procedures in rabbits. However, CVJ seals created with the VSD were ineffective and could potentially burst at low pressures, which could predispose to urine entering the abdomen. Given these results, we do not recommend sealing of the CVJ with a VSD for ovariohysterectomy in rabbits.
Publisher: American Society of Mechanical Engineers
Date: 22-06-2011
Abstract: Distal radius osteosarcoma accounts for nearly 10% of all cancer-related maladies within the canine population. Traditional methods of treatment include utation and/or chemotherapy. A major increase in survival rates (from 10% to 60%) with the combined use of these two techniques has now directed research towards saving the limbs of these patients. Massive cortical bone allografts, metal endoprosthesis and distraction osteogenesis are some of the available limb sparing approaches that have been investigated. Distraction osteogenesis requires surgeon expertise and significant post-operative intervention. Cortical allografts require the maintenance of a bone bank. Furthermore, they are associated with increased infection rates and ultimately result in utation of the affected limb. Metal endoprostheses are a viable alternative to these methods. A metal endoprosthesis has previously been developed for limb sparing of distal radius osteosarcoma patients. However, a clinical trial of this device demonstrated failure rates of approximately 40%. The major causes of failure were screw pullout and shear failure of the proximal radius screws. A computational finite element study conducted in our laboratory corroborated these findings and provided critical information as regards to the structural causes of failure for these implants.
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.MEDDOS.2011.07.003
Abstract: Accurate calculation of absorbed dose to the skin, especially the superficial and radiosensitive basal cell layer, is difficult for many reasons including, but not limited to, the build-up effect of megavoltage photons, tangential beam effects, mixed energy scatter from support devices, and dose interpolation caused by a finite resolution calculation matrix. Stereotactic body radiotherapy (SBRT) has been developed as an alternative limb salvage treatment option at Colorado State University Veterinary Teaching Hospital for dogs with extremity bone tumors. Optimal dose delivery to the tumor during SBRT treatment can be limited by uncertainty in skin dose calculation. The aim of this study was to characterize the difference between measured and calculated radiation dose by the Varian Eclipse (Varian Medical Systems, Palo Alto, CA) AAA treatment planning algorithm (for 1-mm, 2-mm, and 5-mm calculation voxel dimensions) as a function of distance from the skin surface. The study used Gafchromic EBT film (International Specialty Products, Wayne, NJ), FilmQA analysis software, a limb phantom constructed from plastic water™ (fluke Biomedical, Everett, WA) and a canine cadaver forelimb. The limb phantom was exposed to 6-MV treatments consisting of a single-beam, a pair of parallel opposed beams, and a 7-beam coplanar treatment plan. The canine forelimb was exposed to the 7-beam coplanar plan. Radiation dose to the forelimb skin at the surface and at depths of 1.65 mm and 1.35 mm below the skin surface were also measured with the Gafchromic film. The calculation algorithm estimated the dose well at depths beyond buildup for all calculation voxel sizes. The calculation algorithm underestimated the dose in portions of the buildup region of tissue for all comparisons, with the most significant differences observed in the 5-mm calculation voxel and the least difference in the 1-mm voxel. Results indicate a significant difference between measured and calculated data extending to average depths of 2.5 mm, 3.4 mm, and 10 mm for the 1-mm, 2-mm, and 5-mm dimension calculation matrices, respectively. These results emphasize the importance of selecting as small a treatment planning software calculation matrix dimension as is practically possible and of taking a conservative approach for skin treatment planning objectives. One suggested conservative approach is accomplished by defining the skin organ as the outermost 2-3 mm of the body such that the high dose tail of the skin organ dose-volume histogram curve represents dose on the deep side of the skin where the algorithm is more accurate.
Publisher: Wiley
Date: 30-12-2008
Publisher: American Veterinary Medical Association (AVMA)
Date: 03-2013
Abstract: Objective —To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. Animals —26 athymic nude rats. Procedures —3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10 6 Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Results —Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. Conclusions and Clinical Relevance —The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.
Publisher: American Society of Mechanical Engineers
Date: 17-06-2009
Abstract: Orthopaedic extremity injuries present a large medical and financial burden to the United States and world-wide communities [1]. Approximately six million long bone fractures are reported annually in the United States and approximately 10% of these fractures do not heal properly. Though the exact mechanism of impaired healing is poorly understood, many of these non-unions result when there is a communited condition that does not proceed through a stabilized healing pathway [2]. Currently, clinicians may monitor healing visually by radiographs, or via manual manipulation of the bone at the fracture [3]. Unfortunately, the course of aberrant fracture healing is not easily diagnosed in the early period when standard radiographic information of the fracture is not capable of discriminating the healing pathway. Manual assessment of fracture healing is also an inadequate diagnostic tool in the early stages of healing [4].
Publisher: Cold Spring Harbor Laboratory
Date: 10-03-2023
DOI: 10.1101/2023.03.08.531678
Abstract: Angiogenesis is essential for skeletal development, bone healing and regeneration. Various research areas, especially implantology and tissue engineering, would benefit from improved three-dimensional (3D) imaging of the vasculature within bone tissue. X-ray microtomography (microCT) is a well-suited non-destructive 3D imaging technique for bone morphology. For the detection of vessels, a contrast-enhanced microCT-imaging must be used. Limited contrast between perfusion agents and mineralized bone has been the major drawback of this approach, making their distinct segmentation problematic. A decalcification step resolves this issue but inhibits simultaneous assessment of intracortical bone microstructure and vascular morphology. Moreover, the problem of contrasting becomes further compounded in s les with metal implants. This study describes μAngiofil-enhanced microCT-based visualization of vasculature within bone tissue in various small and large animal models, with and without decalcification. We present simultaneous microvascular and bone imaging in murine tibia, murine bone metastatic model, pulp chamber, gingiva and periodontal ligaments. In a large animal model (minipig) we perform visualization and segmentation of different tissue types and vessels in the hemimandible containing metal implants. Our manuscript introduces the first non-destructive approach for 3D imaging of the vasculature within soft and hard tissues in the vicinity of metal implants in a large animal model.
Publisher: Wiley
Date: 28-10-2013
Publisher: Wiley
Date: 18-09-2017
DOI: 10.1111/VRU.12406
Abstract: An 8-year-old female neutered domestic short hair cat presented for investigation of poorly controlled diabetes mellitus. Thoracic radiographs identified a soft tissue opacity in the caudoventral thorax adjacent to the diaphragm. Computed tomography (CT) then characterized a pleuroperitoneal hernia with cranial displacement of a portion of the liver within the hernia. A pleuroperitoneal hernia was confirmed and repaired via exploratory laparotomy. This is the first description of the CT features of a pleuroperitoneal hernia in a cat.
Publisher: Wiley
Date: 28-09-2018
DOI: 10.1111/VSU.12949
Abstract: To report the outcome of dogs treated with triple pelvic osteotomy (TPO) for dorsal luxation after total hip replacement (THR). Retrospective clinical case series. Seventeen client-owned animals. Medical records were searched at a single institution for dogs that had been treated with TPO for dorsal THR luxation. The angle of lateral opening (ALO), version angle (VA), and inclination angle (IA) were measured from radiographs after THR and TPO and corrected for pelvic rotation. A paired t test was performed to compare cup orientation after THR and TPO. Functional outcome was assessed at follow-up examination and during telephone interviews. Eighteen TPOs were performed in 17 dogs, and radiographs were available for 15 cases. Open and/or closed hip reduction with additional stabilization was attempted unsuccessfully in 6 dogs prior to TPO. Triple pelvic osteotomy reduced the ALO by a mean of 23.0 ° ± 10.9 ° (P ≤ .001), increased VA by 9.0 ° ± 4.9 ° (P < .001), and increased IA by 2.9 ° ± 5.8 ° (P = .126). An excellent or good outcome was achieved in 12 dogs. Ventral luxation occurred in 3 dogs, and dorsal luxation occurred in 1 dog after TPO. Triple pelvic osteotomy excessively reduced ALO in 2 dogs with ventral luxation. Triple pelvic osteotomy with cup retention is a viable alternative to cup revision for treatment of dorsal luxation of cemented and cementless THR. Triple pelvic osteotomy significantly reduces ALO and increases VA. Careful patient selection is recommended because excessive ventroversion can lead to ventral luxation. Triple pelvic osteotomy offers a revision option that preserves the implant-bone interface and significantly reduces ALO. This technique may be appropriate in dogs with high ALO, luxoid hips, and prior failed revision attempts.
Publisher: American Animal Hospital Association
Date: 03-2013
Abstract: Bilateral synchronous appendicular bone tumors, occurring in the same bone and same anatomic site within the bone are very rare. This report describes the clinical presentation and oncologic outcome for four dogs with this rare presentation. All cases presented to the authors following a history of unilateral lameness for several weeks. On presentation, case 1 had pain elicited in the contralateral proximal humerus but all the other cases had no abnormalities detectable on physical examination of the contralateral limb. All dogs had technetium 99m (99mTc) nuclear scintigraphy performed that identified bilateral lesions of the distal radii in two dogs, proximal humeri and distal tibiae in one dog each. Thoracic radiographs performed on all dogs showed no evidence of pulmonary metastases. Three dogs were treated with palliative radiation therapy (two dogs received concurrent bisphosphonates) resulting in survival times from initial presentation of 50 days, 193 days, and 523 days, respectively. One dog had stereotactic radiation therapy (SRT) and a surgical limb-salvage performed followed by carboplatin chemotherapy, resulting in a survival time of 926 days from initial presentation. Palliative and curative-intent treatments for the bilateral synchronous appendicular bone tumors resulted in survival times similar to those reported for treatment of a single primary appendicular bone tumor.
Publisher: Wiley
Date: 12-2006
Publisher: American Veterinary Medical Association (AVMA)
Date: 08-2009
Abstract: Objective —To evaluate the mechanical properties of canine carpal ligaments for use in a finite element model of the canine antebrachium. S le Population —26 forelimbs obtained from cadavers of 13 dogs euthanized for reasons unrelated to this study. Procedures —6 ligaments (medial collateral, lateral collateral, palmar ulnocarpal, palmar radiocarpal, accessorometacarpal-V, and accessorometacarpal-IV) were evaluated. Quasistatic tensile tests were performed on all specimens (n = 8 specimens/ligament) by use of a servohydraulic materials testing system in conjunction with a 6- df load cell. Each specimen was preconditioned for 10 cycles by applying 2% strain by use of a Haversine waveform. Tension was subsequently applied to each specimen at a strain rate of 0.5%/s until ligament failure. Results —Significant differences in modulus of elasticity were detected among the ligaments. Elastic modulus did not differ significantly between the 2 accessorometacapal ligaments, between the 2 collateral ligaments, or between the 2 palmar carpal ligaments. Ligaments were classified into 3 groups (accessorometacarpal ligaments, intra-articular ligaments, and palmar carpal ligaments), and significant differences were detected among the 3 ligament groups. The accessorometacarpal ligaments had a relatively high elastic modulus, compared with results for the other ligaments. The medial and lateral collateral ligaments had the lowest elastic modulus of any of the ligaments tested. Conclusions and Clinical Relevance —These results indicated a strong function-elastic modulus relationship for the 6 ligaments tested. The mechanical properties described here will be of use in creating a finite element model of the canine antebrachium.
Publisher: Wiley
Date: 07-2018
DOI: 10.1111/VSU.12923
Abstract: To determine the effects of 6 types of transarticular immobilization techniques on tibiotarsal joint angles during stimulated weight bearing. Canine ex vivo biomechanical study. Canine cadaveric pelvic limbs (n = 15). A validation study was conducted to determine tibiotarsal flexion before and after transection of the superficial digital flexor tendon in 5 canine cadaveric limbs without tibiotarsal joint immobilization. Six transarticular tibiotarsal immobilization techniques were tested sequentially in 10 canine cadaveric pelvic limbs. The tibiotarsal joint angles were measured from lateral projection radiographs before and during axial loading of 200 N. Mixed linear models were applied to determine the effects of the immobilization techniques on change in tibiotarsal joint angle under loading. There was no change of tibiotarsal joint angle between extended digits and flexed digits under both unloaded and loaded conditions. Change in tibiotarsal joint angles did not differ among any of the immobilization techniques tested here (mean change 1.36°, range 0-5). The main contributor to variance in angle explained by the final model was associated with the random effect for limb. Changes in tibiotarsal joint angles during single static loading in canine cadaveric limbs for the 6 immobilization techniques were minimal. The 6 techniques appear equally effective at limiting tibiotarsal joint flexion during single axial loading of 200 N. Cyclic mechanical testing of these techniques is recommended to support our findings and validate their clinical application.
Publisher: MDPI AG
Date: 11-05-2020
Abstract: Osteosarcoma is the most common form of primary bone cancer. Over 20% of osteosarcoma patients present with pulmonary metastases at diagnosis, and nearly 70% of these patients fail to respond to treatment. Previous work revealed that human and canine osteosarcoma cell lines are extremely sensitive to the therapeutic proteasome inhibitor bortezomib in vitro. However, bortezomib has proven disappointingly ineffective against solid tumors including sarcomas in animal experiments and clinical trials. Poor tumor penetration has been speculated to account for the inconsistency between in vitro and in vivo responses of solid tumors to bortezomib. Here we show that the second-generation proteasome inhibitor ixazomib, which reportedly has enhanced solid tumor penetration compared to bortezomib, is toxic to human and canine osteosarcoma cells in vitro. We used experimental osteosarcoma metastasis models to compare the efficacies of ixazomib and bortezomib against primary tumors and metastases derived from luciferase-expressing KRIB or 143B human osteosarcoma cell lines in athymic mice. Neither proteasome inhibitor reduced the growth of primary intramuscular KRIB tumors, however both drugs inhibited the growth of established pulmonary metastases created via intravenous inoculation with KRIB cells, which were significantly better vascularized than the primary tumors. Only ixazomib slowed metastases from KRIB primary tumors and inhibited the growth of 143B pulmonary and abdominal metastases, significantly enhancing the survival of mice intravenously injected with 143B cells. Taken together, these results suggest ixazomib exerts better single agent activity against osteosarcoma metastases than bortezomib. These data provide hope that incorporation of ixazomib, or other proteasome inhibitors that penetrate efficiently into solid tumors, into current regimens may improve outcomes for patients diagnosed with metastatic osteosarcoma.
Publisher: Mary Ann Liebert Inc
Date: 09-2009
DOI: 10.1089/TEN.TEA.2008.0476
Abstract: Concerns over utilizing autogenous cancellous bone grafts (such as donor-site morbidity, increased surgical time/complication rate, and restricted availability) as the gold-standard treatment for critical-sized defects in bone have motivated the development of a wide variety of sophisticated synthetic bone scaffolds in recent years. In this work, a novel solvent-free template synthesis technique was utilized to fabricate poly(epsilon-caprolactone) (PCL) nanowire surfaces as a building block for the development of three-dimensional bone scaffolds. Bone marrow-derived mesenchymal stem cells (MSCs) were used to characterize the short- and long-term in vitro biocompatibility and cellular response to these surfaces. A 4-week study in rats was conducted to assess in vivo biocompatibility as well. Short-term in vitro studies revealed that PCL nanowire surfaces enhanced MSC response in terms of survivability, viability, cytoskeleton changes, and morphology as compared with control surfaces (smooth PCL and polystyrene). In long-term in vitro studies, nanowire surfaces induced a rapid production of bone extracellular matrix by differentiated MSCs as indicated by accelerated calcium phosphate mineralization, and osteocalcin and osteopontin production. In vivo studies and histological analysis confirmed that nanowire surfaces are biocompatible. Preliminary biodegradation studies were conducted and indicated that rate of PCL biodegradation can, to some extent, be controlled through the inclusion of nanowires and ester-degrading enzymes. In addition to demonstrating enhanced short- and long-term MSC response to PCL nanowire surfaces, this work presents a simple technique for solvent-free fabrication and bioactive molecule encapsulation of biocompatible, biodegradable three-dimensional bone scaffold components and warrants further investigation.
Publisher: American Veterinary Medical Association (AVMA)
Date: 15-09-2018
Abstract: OBJECTIVE To assess for any association between a history of tibial plateau leveling osteotomy (TPLO) and subsequent development of proximal tibial osteosarcoma in dogs. DESIGN Matched case-control study. ANIMALS 34 client-owned dogs in which proximal tibial osteosarcoma was diagnosed between January 2005 and December 2012 (cases) and 79 dogs without osteosarcoma, matched 3:1 to cases (when possible) by age, breed, and initial examination date (controls). PROCEDURES Information on each case and control was collected from the medical records and other sources regarding date of birth, sex and neuter status, body weight, breed, and whether TPLO had been performed ≥ 1 year ago. A multivariable conditional logistic regression model was constructed to evaluate associations of body weight and history of TPLO with the outcome of proximal tibial osteosarcoma in dogs. RESULTS After adjusting for body weight in the multivariable model, dogs with a history of TPLO were 40 times as likely to develop proximal tibial osteosarcoma as were dogs with no history of TPLO. In addition, each 1-kg (2.2-lb) increase in body weight was associated with an 11% increase in the odds of proximal tibial osteosarcoma. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that dogs with a history of TPLO were at increased risk of developing osteosarcoma of the proximal region of the tibia relative to dogs with no such history. Therefore, it is important for proximal tibial osteosarcoma to be included among the differential diagnoses for new or worsening hind limb lameness in dogs that underwent TPLO ≥ 1 year previously.
Publisher: American Veterinary Medical Association (AVMA)
Date: 05-2014
Abstract: Objective —To determine the signalment, tibial plateau leveling osteotomy (TPLO) plate type, clinical staging information, treatment, and oncological outcome in dogs that developed osteosarcoma at the proximal aspect of the tibia following TPLO and to calculate the interval between TPLO and osteosarcoma diagnosis. Design —Multi-institutional retrospective case series. Animals —29 dogs. Procedures —Medical records from 8 participating institutions were searched for dogs that developed osteosarcoma (confirmed through cytologic or histologic evaluation) at previous TPLO sites. Signalment, TPLO details, staging tests, treatment data, and outcome information were recorded. Descriptive statistics were calculated, and disease-free intervals and survival times were evaluated by means of Kaplan-Meier analysis. Results —29 dogs met the inclusion criteria. The mean age was 9.2 years and mean weight was 45.1 kg (99.2 lb) at the time of osteosarcoma diagnosis. Most dogs had swelling over the proximal aspect of the tibia (17/21) and lameness of the affected limb (28/29). The mean interval between TPLO and osteosarcoma diagnosis was 5.3 years. One type of cast stainless steel TPLO plate was used in most (18) dogs the remaining dogs had received plates of wrought stainless steel (n = 4) or unrecorded type (7). Twenty-three of 29 dogs underwent treatment for osteosarcoma. Median survival time for 10 dogs that underwent utation of the affected limb and received ≥ 1 chemotherapeutic treatment was 313 days. Conclusions and Clinical Relevance —Results supported that osteosarcoma should be a differential diagnosis for dogs with a history of TPLO that later develop lameness and swelling at the previous surgical site. Oncological outcome following utation and chemotherapy appeared to be similar to outcomes previously reported for dogs with appendicular osteosarcoma.
Publisher: Elsevier BV
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 31-01-1206
DOI: 10.1038/S41598-020-58524-3
Abstract: Osteosarcoma (OS) is the most common malignant primary bone tumour in humans and dogs. Several studies have established the vital role of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation and remodeling. In addition, these molecules play a role in the progression and metastasis of many human tumour types. This study investigated the expression of PTHR1 and PTHrP in canine OS tissues and assessed their prognostic value. Formalin-fixed, paraffin-embedded tissue s les from 50 dogs diagnosed with primary OS were immunolabeled with antibodies specific for PTHR1 and PTHrP. The immunostaining intensity of tumours from patients with OS was correlated with survival time. Both PTHR1 and PTHrP were detected in all OS s les (n = 50). Dogs with OS tumours showing high immunostaining intensity for PTHR1 (n = 36) had significantly shorter survival times (p = 0.028, Log Rank p = 0.04, Cox regression) when compared with OS that had low immunostaining intensity for PTHR1 (n = 14).PTHrP immunostaining intensity did not correlate with survival time (p 0.05). The results of this study indicate that increased expression of PTHR1 antigen in canine OS is associated with poor prognosis. This suggests that PTHR1 may be useful as a prognostic indicator in canine OS.
Publisher: Georg Thieme Verlag KG
Date: 2014
Abstract: Objectives: To evaluate the incidence and risk factors for occurrence of osteosarcoma (OSA) following tibial plateau levelling osteotomy (TPLO). Methods: Medical records of client-owned dogs that underwent consecutive TPLO procedures at two institutions were retrospectively reviewed. Referring veterinarians and owners were contacted for follow-up. Each institutional cohort was assessed separately, and the incidence density rate and median time to occurrence of OSA at the TPLO site and at other sites were calculated. Marginal Cox regression was used to calculate hazard ratios and 95% confidence intervals for potential risk factors for occurrence of OSA. Results: There were 472 CLINIC A (Colorado State University Veterinary Teaching Hospital) and 1992 CLINIC B (SAGE Centers for Veterinary Specialty and Emergency Care) TPLO cases with over one year of follow-up available. There were five and six dogs within the cohorts that developed OSA at the site of TPLO, and seven and 22 dogs that developed OSA at other anatomical sites, respectively. The incidence density rates of OSA at the TPLO site were 30.4 and 10.2 per 10,000 dog-years at risk, and other sites were 42.6 and 37.5 per 10,000 dog-years at risk. The median time to occurrence of OSA of TPLO site OSA was 4.6 and 4.4 years, which was longer than that of other site OSA of 2.9 and 3.4 years. Clinical significance: There is a low incidence of OSA following TPLO surgery. The longer time to occurrence for TPLO site OSA is similar to that for fracture-associated sarcoma, and could indicate a similar underlying pathophysiology rather than spontaneous OSA occurrence.
No related grants have been discovered for Stewart Ryan.