Wireless Measurements Using Electrical Impedance Spectroscopy to Monitor Fracture Healing.

There is an unmet need for improved, clinically relevant methods to longitudinally quantify bone healing during fracture care. Here we develop a smart bone plate to wirelessly monitor healing utilizing electrical impedance spectroscopy (EIS) to provide real-time data on tissue composition within the fracture callus. To validate our technology, we created a 1-mm rabbit tibial defect and fixed the bone with a standard veterinary plate modified with a custom-designed housing that included two impedance sensors capable of wireless transmission. Impedance magnitude and phase measurements were transmitted every 48 h for up to 10 weeks. Bone healing was assessed by X-ray, µCT, and histology. Our results indicated the sensors successfully incorporated into the fracture callus and did not impede repair. Electrical impedance, resistance, and reactance increased steadily from weeks 3 to 7-corresponding to the transition from hematoma to cartilage to bone within the fracture gap-then plateaued as the bone began to consolidate. These three electrical readings significantly correlated with traditional measurements of bone healing and successfully distinguished between union and not-healed fractures, with the strongest relationship found with impedance magnitude. These results suggest that our EIS smart bone plate can provide continuous and highly sensitive quantitative tissue measurements throughout the course of fracture healing to better guide personalized clinical care.

Regenerative medicine 2.0: extracellular vesicle-based therapeutics for musculoskeletal tissue regeneration.

In recent years, extracellular vesicles (EVs) have emerged as prominent mediators of the homeostasis, repair, and regeneration of musculoskeletal tissues including bone, skeletal muscle, and cartilage. Accordingly, the therapeutic potential of EVs for regenerative medicine applications has not gone unnoticed. The use of EVs for the treatment of musculoskeletal injury and disease in veterinary species is a nascent but rapidly expanding area of research. Recent studies in this area have demonstrated the safety and feasibility of EV products in dogs and horses. While early clinical responses to EV-based therapeutics in companion animals have been favorable, more rigorously designed, sufficiently powered, and placebo-controlled clinical trials are required to fully elucidate the clinical benefits and best-use scenarios for EV therapeutics in veterinary medicine. Additionally, clinical translation of EV-based therapeutics will require Good Manufacturing Practice-compliant methods to scale up and purify EV products. Despite these challenges, EVs hold great promise in the regenerative medicine landscape, particularly in the treatment of musculoskeletal injury and disease in companion animals.

The platelet-rich plasma and mesenchymal stem cell milieu: A review of therapeutic effects on bone healing.

Platelet-rich plasma is autologous plasma that contains concentrated platelets compared to whole blood. It is relatively inexpensive to produce, can be easily isolated from whole blood, and can be administered while the patient is in the operating room. Further, because platelet-rich plasma is an autologous therapy, there is minimal risk for adverse reactions to the patient. Platelet-rich plasma has been used to promote bone regeneration due to its abundance of concentrated growth factors that are essential to wound healing. In this review, we summarize the methods for producing platelet-rich plasma and the history of its use in bone regeneration. We also summarize the growth factor profiles derived from platelet-rich plasma, with emphasis on those factors that play a direct role in promoting bone repair within the local fracture environment. In addition, we discuss the potential advantages of combining platelet-rich plasma with mesenchymal stem cells, a multipotent cell type often obtained from bone marrow or fat, to improve craniofacial and long bone regeneration. We detail what is currently known about how platelet-rich plasma influences mesenchymal stem cells in vitro, and then highlight the clinical outcomes of administering platelet-rich plasma and mesenchymal stem cells as a combination therapy to promote bone regeneration in vivo.

Analysis of outcome in dogs that undergo secondary amputation as an end-point for managing complications related to limb salvage surgery for treatment of appendicular osteosarcoma.

Appendicular osteosarcoma (OSA) remains a prevalent musculoskeletal cancer in dogs and definitive local control followed by adjuvant cytotoxic chemotherapy is considered the gold standard approach. Several studies support surgical limb salvage as a means of local control with similar outcomes compared with limb amputation. Complications are well described for limb salvage but little is known of dogs that undergo secondary amputation as a result of complications and outcomes specific to this group. A retrospective analysis of dogs in an institutional primary bone tumour registry was performed to identify dogs diagnosed with histologically confirmed OSA treated with surgical limb salvage with a technique that required an implant to reconstruct the osseous defect. A total of 192 dogs were identified with 31 dogs undergoing secondary amputation representing a limb preservation rate of 84%. A total of 111 dogs were analysed: 31 secondary amputation cases and 80 controls were selected for comparison. The most common reasons for secondary amputation were local recurrence (LR) and surgical site infection (SSI), with odds ratios of 3.6 and 1.7, respectively. Dogs that underwent secondary amputation had a significantly (P = .05) longer median disease specific survival time (ST) (604 days) compared with the control group (385 days). Dogs lived for a median of 205 days beyond secondary amputation and 97% had good functional outcome. Significant independent factors that positively influenced ST were secondary amputation, moderate SSI, severe SSI and age.

Bilateral caudal maxillectomy for resection of tumors crossing palatal midline and use of the angularis oris axial pattern flap for primary closure or dehiscence repair in two dogs.

OBJECTIVE: To describe the technique and outcomes for bilateral caudal maxillectomy for resection of large caudal maxillary tumors crossing palatal midline in two dogs. STUDY DESIGN: Clinical case report. ANIMALS: Two client-owned dogs. METHODS: Two client-owned dogs with primary caudal maxillary tumors, a poorly differentiated sarcoma, and a multilobulated osteochondrosarcoma. Bilateral caudal maxillectomies were performed for curative-intent resection of these tumors. The angularis oris axial pattern flap was used for primary closure in one dog and for dehiscence repair in the other. RESULTS: Both tumors were resected with complete histologic margins. The defects were closed with local buccal mucosal flaps, with or without a unilateral angularis oris flap. Esophagostomy tubes were placed at time of surgery to bypass oral feeding. Incisional dehiscence and subsequent oronasal fistula formation occurred as a postoperative complication in both dogs (3 and 10 days, respectively). Both were successfully repaired with a combination of local buccal mucosal flaps and the angularis oris flap. Both dogs had good functional outcome and quality of life after recovery from revision surgery. CONCLUSION: Bilateral caudal maxillectomy allowed resection of caudal maxillary tumors crossing palatal midline, with good function and quality of life after recovery in 2 dogs. CLINICAL SIGNIFICANCE: Good outcomes including complete resections are achievable with bilateral caudal maxillectomy despite complications. Local mucosal and axial pattern flaps can be used for dehiscence repair.

Prognosis for dogs with stage III osteosarcoma following treatment with amputation and chemotherapy with and without metastasectomy.

OBJECTIVE To determine survival times of selected dogs with metastatic (stage III) osteosarcoma, whether disease-free interval (DFI) was associated with survival time after diagnosis of stage III disease (ie, stage III survival time), and whether a survival benefit of metastasectomy existed. DESIGN Retrospective case series with nested cohort study. ANIMALS 194 client-owned dogs treated for histologically confirmed appendicular osteosarcoma from 1997 through 2009. PROCEDURES Dogs were included if they had stage I or II osteosarcoma at the time of initial evaluation, had amputation of the affected appendage and ≥ 1 dose of chemotherapy afterward, and developed metastasis within the follow-up period or prior to death. Data collected from the medical records included signalment, primary tumor location, clinical and laboratory findings, whether metastasectomy was performed, and outcome. Various factors were examined for associations with outcome. RESULTS Dogs that received no treatment for the metastasis had a median survival time between 49 and 57 days after diagnosis of stage III osteosarcoma. Duration of the preceding DFI had no association with this period. Metastasectomy alone was associated with a longer median stage III survival time (232 days) than no metastasectomy (49 days). Among all dogs identified as qualifying for pulmonary metastasectomy on the basis of < 3 pulmonary nodules visible on thoracic radiographs and a DFI > 275 days (n = 21), a survival advantage was also identified for those that actually received pulmonary metastasectomy (6). CONCLUSIONS AND CLINICAL RELEVANCE Preceding DFI had no influence on survival time of dogs with stage III osteosarcoma. Metastasectomy was associated with an increase in survival time for selected dogs.

Outcome and complications in dogs with appendicular primary bone tumors treated with stereotactic radiotherapy and concurrent surgical stabilization.

OBJECTIVE: To document the outcome of dogs with appendicular primary bone tumors treated with stereotactic radiotherapy (SRT) and concurrent stabilization. STUDY DESIGN: Multi-institutional retrospective case series. ANIMALS: Eighteen dogs with presumptive or definitive diagnosis of appendicular osteosarcoma. METHODS: Medical records of dogs with appendicular primary bone tumors treated with SRT and stabilization were reviewed for signalment, preoperative staging and diagnostics, radiation dose, stabilization method, and outcome. RESULTS: The distal radius was affected in 13/18 cases. Osteosarcoma or sarcoma was confirmed cytologically or histologically in 15/18 cases. Seven dogs were diagnosed with a pathological fracture at the time of treatment, and 11 were considered at high risk for pathological fracture. Dogs received a single dose (n = 5) or 3 doses (n = 13) of SRT. Surgical stabilization was performed under the same anesthetic event as the final dose of SRT in 10 dogs. Stabilization was achieved with a bone plate (n = 15) or interlocking nail (n = 3). Seventeen dogs received adjuvant chemotherapy. Complications occurred in 16/17 dogs, 15/17 of those being considered major complications. Four dogs experienced more than one complication. Infection was the most common complication, diagnosed in 15/17 cases, and considered as a major complication in 13/15 cases. Postoperative fracture was recorded as a major complication in 3 cases. Nine dogs were amputated at a median of 152 days. The median survival time was 344 days. CONCLUSION: Treatment of bone tumors with SRT and concurrent stabilization was associated with a prohibitively high complication rate in dogs. Alternative methods for limb salvage should be considered for dogs at risk for pathologic fracture.

Combined delivery of FGF-2, TGF-ß1, and adipose-derived stem cells from an engineered periosteum to a critical-sized mouse femur defect.

Critical-sized long bone defects suffer from complications including impaired healing and non-union due to substandard healing and integration of devitalized bone allograft. Removal of the periosteum contributes to the limited healing of bone allografts. Restoring a periosteum on bone allografts may provide improved allograft healing and integration. This article reports a polysaccharide-based tissue engineered periosteum that delivers basic fibroblast growth factor (FGF-2), transforming growth factor-ß1 (TGF-ß1), and adipose-derived mesenchymal stem cells (ASCs) to a critical-sized mouse femur defect. The tissue engineered periosteum was evaluated for improving bone allograft healing and incorporation by locally delivering FGF-2, TGF-ß1, and supporting ASCs transplantation. ASCs were successfully delivered and longitudinally tracked at the defect site for at least 7 days post operation with delivered FGF-2 and TGF-ß1 showing a mitogenic effect on the ASCs. At 6 weeks post implantation, data showed a non-significant increase in normalized bone callus volume. However, union ratio analysis showed a significant inhibition in allograft incorporation, confirmed by histological analysis, due to loosening of the nanofiber coating from the allograft surface. Ultimately, this investigation shows our tissue engineered periosteum can deliver FGF-2, TGF-ß1, and ASCs to a mouse critical-sized femur defect and further optimization may yield improved bone allograft healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 900-911, 2017.

Treatment of extraskeletal osteosarcoma at a previous injection site resulting in prolonged survival in 1 dog.

A rare presentation of an extraskeletal osteosarcoma at a previous interscapular injection site in a dog is described. Treatment included surgical excision of the tumor followed by 6 rounds of intravenous carboplatin, oral toceranib, and cyclophosphamide. The dog survived for 20.5 months after diagnosis despite early development of pulmonary metastases.

Traitement d'un ostéosarcome extrasquelettique à un site d'injection antérieur produisant une survie prolongée chez un chien. Ce rapport décrit une rare présentation d'un ostéosarcome extrasquelettique à un site d'injection interscapulaire antérieur chez un chien. Le traitement a inclus l'excision chirurgicale de la tumeur suivie de six séries de traitement de carboplatine intraveineuse, de tocéranib oral et de cyclophosphamide. Le chien a survécu pendant 20,5 mois après le diagnostic malgré le développement précoce de métastases pulmonaires.(Traduit par Isabelle Vallières).

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

Outcomes of Limb-Sparing Surgery Using Two Generations of Metal Endoprosthesis in 45 Dogs With Distal Radial Osteosarcoma. A Veterinary Society of Surgical Oncology Retrospective Study.

OBJECTIVE: To report outcomes in dogs with distal radial osteosarcoma (OSA) treated with metal endoprosthesis limb-sparing surgery and compare outcomes between 2 generations of endoprosthesis. STUDY DESIGN: Multi-institutional retrospective case series. ANIMALS: Forty-five dogs with distal radial OSA treated with endoprosthesis and chemotherapy. METHODS: Data of dogs treated with either first-generation endoprosthesis (GEN1) or second-generation endoprosthesis (GEN2) were sourced from medical records and radiographs. Surgical outcomes included postoperative lameness assessment and the presence, severity, and time to onset of complications. Oncologic outcomes included presence of local recurrence or metastasis, time to onset of local recurrence, metastasis-free interval (MFI), and survival time. Results for surgical and oncologic outcomes were compared between GEN1 and GEN2. RESULTS: Twenty-eight dogs received GEN1 and 17 dogs received GEN2. There were 39 complications (96%, 14 minor, 29 major) including infection (78%), implant-related complication (36%), and local recurrence (24%). Metastatic frequency was 67% and median MFI was 188 days (95% confidence interval [CI]: 126-250 days). Survival time ranged from 34 days to 6.1 years with a median of 289 days (95% CI: 207-371 days). There was no significant difference in complication severity, frequency, time to complication, MFI, or survival time between dogs receiving GEN1 and GEN2. CONCLUSION: There was no significant difference in outcomes between dogs receiving GEN1 and GEN2 for limb-sparing surgery of the radius. Metastatic frequency and survival time for metal endoprosthesis were similar to that of amputation with curative intent chemotherapy.

Do Mesenchymal Stromal Cells Influence Microscopic Residual or Metastatic Osteosarcoma in a Murine Model?

BACKGROUND: Mesenchymal stromal cells (MSCs) have been shown in rodent models to promote primary and pulmonary metastatic sarcoma growth when injected in the presence of gross tumor. In theory, this would limit their use in a clinical setting after limb salvage treatment for osteosarcoma. Although concerning, these models do not translate to the clinical setting wherein MSCs could be used after primary tumor resection to aid in bone healing and incorporation of tumor endoprostheses. If we can determine whether the use of MSCs in this setting is safe, it might improve our ability to augment bone healing in patients undergoing limb salvage. QUESTIONS/PURPOSES: The purpose of this study was to determine (1) whether MSCs promote pulmonary metastatic disease progression in a murine osteosarcoma model; and/or (2) whether they affect local disease recurrence in the presence of microscopic residual osteosarcoma. METHODS: An orthotopic model of luciferase-expressing osteosarcoma was developed. At 10 days, resection of the primary tumor was performed. One hundred fourteen female C3H mice were inoculated with DLM8-luc osteosarcoma in the proximal tibia. Ninety-four mice developed orthotopic osteosarcoma with luciferase expression. Mice with bioluminescent evidence of a primary tumor received either a microscopically "clean" amputation at a time when residual microscopic metastatic disease was present in the lungs (pulmonary metastasis group; n = 65) or a "dirty" amputation (local recurrence group; n = 29). Mice were randomized to receive intravenous MSCs, MSCs at the surgical site, or no MSCs. Mice were monitored for development and progression of pulmonary metastasis and local recurrence by bioluminescence imaging and daily measurements at the surgical site. The number of pulmonary nodules, time to first evidence of metastasis, and size of recurrent tumor were compared using Kruskal-Wallis, analysis of variance, Welch's, t-tests, or Mann-Whitney tests as appropriate for the specific data sets with p < 0.05 considered significant. RESULTS: Mice receiving intravenous MSCs had a faster time to first detection of pulmonary metastasis (2.93 ± 1.90 days) compared with mice with local injection of MSCs (6.94 ± 6.78 days) or no MSCs (5.93 ± 4.55 days) (p = 0.022). MSC treatment did not influence whether mice developed local recurrence (p = 0.749) or size of recurrent tumors (p = 0.221). CONCLUSIONS: MSCs delivered to the surgical site did not promote local recurrence or size of recurrent tumors, but intravenous injection of MSCs did hasten onset of detection of pulmonary metastatic disease. Although local administration of MSCs into a surgical site does not appear to promote either pulmonary metastatic disease or local recurrence, large variation within groups and small numbers diminished statistical power such that a Type II error cannot be ruled out. CLINICAL RELEVANCE: If MSCs are to be used to augment bone healing in the postlimb salvage setting in patients with osteosarcoma, it will be important to understand their influence, if any, on pulmonary micrometastsis or residual microscopic local disease. Although murine models do not completely recapitulate the clinical scenario, these results suggest that intravenous delivery of MSCs may promote micrometastatic pulmonary disease. Local administration into a surgical wound, even in the presence of residual microscopic disease, may be safe, at least in this murine model, but further investigation is warranted before considering the use of MSCs for clinical use in patients with osteosarcoma.

Coating cortical bone allografts with periosteum-mimetic scaffolds made of chitosan, trimethyl chitosan, and heparin.

Bone allografts have very limited healing leading to high rates of failure from non-union, fracture, and infection. The limited healing of bone allografts is due in large part to devitalization and removal of the periosteum, which removes osteogenic cells and osteoinductive signals. Here we report techniques for directly coating cortical bone with tissue scaffolds, and evaluate the scaffolds' capacity to support osteoprogenitor cells. Three types of coatings are investigated: N,N,N-trimethyl chitosan-heparin polyelectrolyte multilayers, freeze-dried porous chitosan foam coatings, and electrospun chitosan nanofibers. The freeze-dried and electrospun scaffolds are also further modified with polyelectrolyte multilayers. All of the scaffolds are durable to subsequent aqueous processing, and are cytocompatible with adipose-derived stem cells. Alkaline phosphatase and receptor activator of nuclear factor kappa-B ligand expression at days 7 and 21 suggest that these scaffolds support an osteoprogenitor phenotype. These scaffolds could serve as periosteum mimics, deliver osteoprogenitor cells, and improve bone allograft healing.

Outcome following curative-intent surgery for oral melanoma in dogs: 70 cases (1998-2011).

OBJECTIVE: To evaluate the outcome in terms of progression-free interval (PFI) and overall survival time (ST) after curative-intent resection of oral melanoma in dogs. DESIGN: Retrospective case series. ANIMALS: 70 client-owned dogs. PROCEDURES: An electronic medical record search and review was performed for dogs that underwent curative-intent resection of oral melanoma (May 1, 1998, to December 31, 2011). Information gathered included signalment, oral location of tumor, staging results, type of surgery, type of adjuvant therapy, findings on histologic evaluation, and outcome. RESULTS: 36 (51.4%), 16 (22.9%), 13 (18.6%), and 1 (1.4%) of 70 dogs had tumors classified as stage I, II, III, and IV, respectively; tumor stage could not be determined for 4 (5.7%) dogs because of the lack of tumor size information. Fifty-one (72.9%) dogs had tumors completely excised. Twenty-nine (41.4%) dogs received adjuvant therapy. Median PFI and ST were 508 and 723 days, respectively. Thirty-two (45.7%) dogs had disease progression. Significant associations with PFI or ST were found for administration of adjuvant therapy, presence of metastatic disease at the time of diagnosis, higher tumor stage (III or IV), increased tumor size (> 3 cm), and sexually intact female dogs. Administration of adjuvant treatment was associated with a 130% increased hazard (hazard ratio, 2.3; 95% confidence interval [CI], 1.0 to 5.0) of disease progression; the presence of metastases at the time of diagnosis was associated with a 281% increased hazard (hazard ratio, 3.8; 95% CI, 1.5 to 9.6) of death. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with oral melanoma can have a long PFI and ST after resection with wide margins.

Outcome and prognostic factors for osteosarcoma of the maxilla, mandible, or calvarium in dogs: 183 cases (1986-2012).

OBJECTIVE: To describe the biological behavior, clinical outcome, and prognostic factors of osteosarcoma of the maxilla, mandible, or calvarium in dogs. DESIGN: Retrospective case series. ANIMALS: 183 client-owned dogs with osteosarcoma of the maxilla, mandible, or calvarium. PROCEDURES: Medical records for dogs treated for osteosarcoma of the maxilla, mandible, or calvarium from 1986 through 2012 were reviewed. Dogs with a histopathologic diagnosis of osteosarcoma and treated for a primary tumor arising from these bones of the head were included. RESULTS: Mean age was 9.3 years, and body weight was 31.8 kg (70.0 lb). Most dogs (124/183 [67.8%]) were purebred, and the most common primary tumor site was the maxilla (80 [43.7%]). Treatments included palliative medical treatment only (11/183 [6.0%]), coarsely fractionated radiation therapy (RT; 12 [6.6%]), fractionated or stereotactic RT (18 [9.8%]), surgery (135 [73.8%]), and both surgery and fractionated RT (7 [3.8%]). Eighty-three (45.4%) dogs received adjuvant chemotherapy. Local recurrence or progression occurred in 80 of 156 (51.3%) dogs, and 60 of 156 (38.5%) dogs developed distant metastases. Median survival time for all dogs was 239 days. Dogs that underwent surgery had a median survival time of 329 days. Histologically tumor-free surgical margins were associated with significantly decreased hazards of progression or recurrence (hazard ratio [HR], 0.4) and death (HR, 0.5). Dogs with osteosarcoma of the calvarium had a significantly greater hazard of local recurrence or progression (HR, 2.0). CONCLUSIONS AND CLINICAL RELEVANCE: In this study, tumor excision in dogs with histologically tumor-free margins resulted in better local control and longer survival time than did other treatment types.

Appendicular osteosarcoma in small-breed dogs: 51 cases (1986-2011).

OBJECTIVE: To describe outcomes for small-breed dogs with appendicular osteosarcoma. DESIGN: Multi-institutional retrospective case series. ANIMALS: 51 small-breed dogs. PROCEDURES: Records from participating Veterinary Society of Surgical Oncology members were searched for dogs that weighed ≤ 15 kg (33 lb) with a histologic diagnosis of appendicular osteosarcoma. The Kaplan-Meier method was used to determine median survival times (MSTs), and Cox regression was performed to identify variables associated with survival time. RESULTS: Tumors were most commonly located on the humerus (n = 15) and femur (14). Of the 51 study dogs, 9 were treated nonsurgically, 16 underwent amputation of the affected limb only, and 26 underwent curative-intent treatment, with MSTs of 112, 257, and 415 days, respectively. The MST did not differ significantly between dogs in the amputation-only and curative-intent groups. For dogs in the nonsurgical group, MST decreased significantly as the tumor histologic score increased. For dogs in the amputation-only group, MST decreased as body weight increased. CONCLUSIONS AND CLINICAL RELEVANCE: For the small-breed dogs with appendicular osteosarcoma of the present study, tumor histologic grade and mitotic index were subjectively lower and MST following amputation of the affected limb without adjuvant chemotherapy was longer, compared with those for similarly affected larger dogs. Results indicated no significant advantage in MST for dogs that underwent curative-intent treatment versus dogs that underwent amputation only, and further investigation of the importance of adjuvant chemotherapy is warranted.

In vivo assessment of absorbable knotless barbed suture for single layer gastrotomy and enterotomy closure.

OBJECTIVE: To compare the performance of an absorbable barbed suture device to absorbable monofilament suture after single layer, appositional gastrotomy and enterotomy closure. STUDY DESIGN: Experimental comparative study. ANIMALS: Purpose-bred adult mongrel hounds (n = 14). METHODS: Bursting strengths up to 250 mmHg of incisional closure with either monofilament or barbed suture in a simple continuous, appositional pattern at sites in the stomach (2), jejunum (4), and colon (4) were compared at postoperative Days 3, 7, and 14. Time for incisional closure was compared between materials. RESULTS: Bursting strength was not significantly different between gastrotomies/enterotomies closed with the monofilament suture or the barbed device. Closure time was significantly reduced with the barbed device in jejunal enterotomy closure. CONCLUSION: The barbed device compared favorably with monofilament suture for gastrotomy and enterotomy (small intestine, colon) closure. Results demonstrate comparable burst strengths between monofilament suture and the barbed device. Closure time was significantly reduced in jejunum closure using the barbed device.

Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

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.

Bilateral appendicular bone tumors in four dogs.

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 ((99m)Tc) 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.

Chitosan-heparin polyelectrolyte multilayers on cortical bone: periosteum-mimetic, cytophilic, antibacterial coatings.

Cortical bone allografts suffer from high rates of failure due to poor integration with host tissue, leading to non-union, fracture, and infection following secondary procedures. Here, we report a method for modifying the surfaces of cortical bone with coatings that have biological functions that may help overcome these challenges. These chitosan-heparin coatings promote mesenchymal stem cell attachment and have significant antibacterial activity against both S. aureus and E. coli. Furthermore, their chemistry is similar to coatings we have reported on previously, which effectively stabilize and deliver heparin-binding growth factors. These coatings have potential as synthetic periosteum for improving bone allograft outcomes.