3D Printing in alloy design to improve biocompatibility in metallic implants.

3D Printing (3DP) or additive manufacturing (AM) enables parts with complex shapes, design flexibility, and customization opportunities for defect specific patient-matched implants. 3DP or AM also offers a design platform that can be used to innovate novel alloys for application-specific compositional modifications. In medical applications, the biological response from a host tissue depends on a biomaterial's structural and compositional properties in the physiological environment. Application of 3DP can pave the way towards manufacturing innovative metallic implants, combining structural variations at different length scales and tailored compositions designed for specific biological responses. This study shows how 3DP can be used to design metallic alloys for orthopedic and dental applications with improved biocompatibility using in vitro and in vivo studies. Titanium (Ti) and its alloys are used extensively in biomedical devices due to excellent fatigue and corrosion resistance and good strength to weight ratio. However, Ti alloys' in vivo biological response is poor due to its bioinert surface. Different coatings and surface modification techniques are currently being used to improve the biocompatibility of Ti implants. We focused our efforts on improving Ti's biocompatibility via a combination of tantalum (Ta) chemistry in Ti, the addition of designed micro-porosity, and nanoscale surface modification to enhance both in vitro cytocompatibility and early stage in vivo osseointegration, which was studied in rat and rabbit distal femur models.

Additively manufactured calcium phosphate reinforced CoCrMo alloy: Bio-tribological and biocompatibility evaluation for load-bearing implants.

Cobalt-chromium-molybdenum (CoCrMo) alloys are widely used in load-bearing implants; specifically, in hip, knee, and spinal applications due to their excellent wear resistance. However, due to in vivo corrosion and mechanically assisted corrosion, metal ion release occurs and accounts for poor biocompatibility. Therefore, a significant interest to find an alternative to CoCrMo alloy exists. In the present work we hypothesize that calcium phosphate (CaP) will behave as a solid lubricant in CoCrMo alloy under tribological testing, thereby minimizing wear and metal ion release concerns associated with CoCrMo alloy. CoCrMo-CaP composite coatings were processed using laser engineered net shaping (LENS™) system. After LENS™ processing, CoCrMo alloy was subjected to laser surface melting (LSM) using the same LENS™ set-up. Samples were investigated for microstructural features, phase identification, and biocompatibility. It was found that LSM treated CoCrMo improved wear resistance by 5 times. CoCrMo-CaP composites displayed the formation of a phosphorus-based tribofilm. In vitro cell-material interactions study showed no cytotoxic effect. Sprague-Dawley rat and rabbit in vivo study displayed increased osteoid formation for CoCrMo-CaP composites, up to 2 wt.% CaP. Our results show that careful surface modification treatments can simultaneously improve wear resistance and in vivo biocompatibility of CoCrMo alloy, which can correlate to a reduction of metal ion release in vivo.

Effects of MgO and SiO2 on Plasma-Sprayed Hydroxyapatite Coating: An in Vivo Study in Rat Distal Femoral Defects.

Plasma-sprayed hydroxyapatite (HA)-coated titanium implants have been widely used in orthopedic applications due to their inheritance of an excellent mechanical property from titanium and great osteoconductivity from HA. However, the lack of osteoinductivity limits their further applications. In this study, 1 wt % MgO and 0.5 wt % SiO2 were mixed with HA for making plasma-sprayed coatings on titanium implants. Plasma-sprayed HA- and MgO/SiO2-HA-coated titanium implants showed adhesive bond strengths of 25.73 ± 1.92 and 23.44 ± 2.89 MPa, respectively. The presence of MgO and SiO2 significantly increased the osteogenesis, osseointegration, and bone mineralization of HA-coated titanium implants by the evaluation of their histomorphology after 6, 10, and 14 weeks of implantation in rat distal femoral defects. Implant pushout tests also showed a shear modulus of 149.83 ± 3.69 MPa for MgO/SiO2-HA-coated implants after 14 weeks of implantation, compared to 52.68 ± 10.41 MPa for uncoated implants and 83.92 ± 3.68 MPa for pure HA-coated implants; These are differences in the shear modulus of 96% and 56.4%, respectively. This study assesses for the first time the quality of the bone-implant interface of induction plasma-sprayed MgO and SiO2 binary-doped HA coatings on load-bearing implants compared to bare titanium and pure HA coatings in a quantitative manner. Relating the osseointegration and interface shear modulus to the quality of implant fixation is critical to the advancement and implementation of HA-coated orthopedic implants.

Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.

Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors.

There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors, and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need.

SrO- and MgO-doped microwave sintered 3D printed tricalcium phosphate scaffolds: mechanical properties and in vivo osteogenesis in a rabbit model.

The presence of interconnected macro pores allows guided tissue regeneration in tissue engineering scaffolds. However, highly porous scaffolds suffer from having poor mechanical strength. Previously, we showed that microwave sintering could successfully be used to improve mechanical strength of macro porous tricalcium phosphate (TCP) scaffolds. This study reports the presence of SrO and MgO as dopants in TCP scaffolds improves mechanical and in vivo biological performance. We have used direct three dimensional printing (3DP) technology for scaffold fabrication. These 3DP scaffolds possessed multiscale porosity, that is, 3D interconnected designed macro pores along with intrinsic micro pores. A significant increase in mechanical strength, between 37 and 41%, was achieved due to SrO and MgO doping in TCP as compared with pure TCP. Maximum compressive strengths of 9.38 ± 1.86 MPa and 12.01 ± 1.56 MPa were achieved by conventional and microwave sintering, respectively, for SrO-MgO-doped 3DP scaffolds with 500 µm designed pores. Histomorphological and histomorphometric analysis revealed a significantly higher osteoid, bone and haversian canal formation induced by the presence of SrO and MgO dopants in 3DP TCP as compared with pure TCP scaffolds when tested in rabbit femoral condyle defect model. Increased osteon and thus enhanced network of blood vessel formation, and osteocalcin expression were observed in the doped TCP scaffolds. Our results show that these 3DP SrO-MgO-doped TCP scaffolds have the potential for early wound healing through accelerated osteogenesis and vasculogenesis.

Dysregulated microRNA clusters in response to retinoic acid and CYP26B1 inhibitor induced testicular function in dogs.

Spermatogenesis is a multistep synchronized process. Diploid spermatogonia differentiate into haploid spermatozoa following mitosis, meiosis and spermiogenesis. Division and differentiation of male germ cells is achieved through the sequential expression of several genes. Numerous mRNAs in the differentiating germ cells undergo post-transcriptional and translational regulation. MiRNAs are powerful negative regulators of mRNA transcription, stability, and translation and recognize their mRNA targets through base-pairing. Retinoic acid (RA) signaling is essential for spermatogenesis and testicular function. Testicular RA level is critical for RA signal transduction. This study investigated the miRNAs modulation in an RA- induced testicular environment following the administration of all-trans RA (2 µM) and CYP26B1- inhibitor (1 µM) compared to control. Eighty four canine mature miRNAs were analyzed and their expression signatures were distinguished using real-time PCR based array technology. Of the miRNAs analyzed, miRNA families such as miR-200 (cfa-miR-200a, cfa-miR-200b and cfa-miR-200c), Mirlet-7 (cfa-let-7a, cfa-let-7b, cfa-let-7c, cfa-let-7g and cfa-let-7f), miR-125 (cfa-miR-125a and cfa-miR-125b), miR-146 (cfa-miR-146a and cfa-miR-146b), miR-34 (cfa-miR-34a, cfa-miR-34b and cfa-miR-34c), miR-23 (cfa-miR-23a and cfa-miR-23b), cfa-miR-184, cfa-miR-214 and cfa-miR-141 were significantly up-regulated with testicular RA intervention via administration of CYP26B1 inhibitor and all-trans-RA and species of miRNA such as cfa-miR-19a, cfa-miR-29b, cfa-miR-29c, cfa-miR-101 and cfa-miR-137 were significantly down-regulated. This study explored information regarding chromosome distribution, human orthologous sequences and the interaction of target genes of miRNA families significantly distinguished in this study using prediction algorithms. This study importantly identified dysregulated miRNA species resulting from RA-induced spermatogenesis. The present contribution serves as a useful resource for further elucidation of the regulatory role of individual miRNA in RA synchronized canine spermatogenesis.

Use of single-agent carboplatin as adjuvant or neoadjuvant therapy in conjunction with amputation for appendicular osteosarcoma in dogs.

Survival following amputation and administration of single-agent carboplatin for treatment of appendicular osteosarcoma (OSA) in dogs was retrospectively examined. Records of 155 dogs with appendicular OSA treated with amputation and single-agent carboplatin were included from 14 centers. Any carboplatin dosage, number of doses, and protocol schedule were eligible for inclusion. The median disease-free interval (DFI) was 256 days. The median overall survival time was 307 days. Similar prognostic survival factors were identified in this study as reported in prior studies of canine appendicular OSA. Median DFI and survival were comparable to those reported in the original Bergman et al publication. Carboplatin treatment improves the survival probability in dogs with appendicular OSA compared to amputation alone and remains an acceptable alternative to adjuvant treatment with cisplatin.

Reconstruction of chest wall defects after rib tumor resection: a comparison of autogenous, prosthetic, and composite techniques in 44 dogs.

OBJECTIVE: To compare short- and long-term outcome and complications of chest wall reconstruction in dogs using autogenous, prosthetic, and composite autogenous-prosthetic techniques. STUDY DESIGN: Historical cohort. ANIMALS: Dogs (n=44) with spontaneous tumors arising from or involving the chest wall. METHODS: Medical records were reviewed for dogs with rib and/or sternal tumors treated by chest wall resection and reconstruction. Signalment, preoperative clinical features, intraoperative findings and complications, reconstruction technique (autogenous muscle flap, prosthetic mesh, or composite autogenous-prosthetic technique), and short- (< or =14 days) and long-term (>14 days) postoperative complications were determined from the medical records and telephone contact with owners and referring veterinarians. Associations between chest wall reconstruction technique and postoperative complications were tested with Cox proportional hazards. RESULTS: Chest wall defects were reconstructed with autogenous muscle flaps (29 dogs), prosthetic mesh (3), and a composite technique of prosthetic mesh and either autogenous muscle or omental pedicle flap (12). Early postoperative complications were recorded in 8 dogs (18.2%) and included seroma (5) and pleural effusion and peripheral edema (3). One dog had a late complication (2.3%) with a mesh-related infection 767 days postoperatively. Overall, complications occurred in 10.3% of autogenous, 25.0% of composite, and 66.7% of prosthetic reconstructions. Chest wall reconstruction with Marlex mesh alone was associated with a significantly increased risk of postoperative complications compared with autogenous reconstruction (P=.027). Reconstruction of sternal defects (3), 2 of which were performed with Marlex mesh alone, was associated with a significantly increased risk of complications compared with lateral chest wall reconstructions (P=.037). CONCLUSIONS: Large chest wall defects can be reconstructed with autogenous and composite techniques, but prosthetic mesh should be covered with well-vascularized autogenous muscle or omentum to decrease the risk of postoperative complications. Sternal defects should be reconstructed with rigid techniques. CLINICAL RELEVANCE: Chest wall reconstruction with autogenous muscle flaps or a combination of autogenous techniques with prosthetic mesh is associated with a low rate of infection and other complications.

Oncologic outcome after curative-intent treatment in 39 dogs with primary chest wall tumors (1992-2005).

OBJECTIVE: To describe the clinical features and determine oncologic outcome and prognostic factors for dogs with primary tumors of the osseous chest wall. STUDY DESIGN: Historical cohort. ANIMALS: Dogs (n=39) with spontaneous tumors involving the chest wall. METHODS: Medical records were reviewed for dogs with rib and/or sternal tumors treated by chest wall resection and reconstruction. Signalment, preoperative clinical features, reconstruction technique, and oncologic outcome (local tumor recurrence, metastasis, and survival time) were determined from medical records and by telephone contact with owners and referring veterinarians. Oncologic outcome and prognostic factors were determined using Kaplan-Meier survival analysis and Cox proportional hazards. Logistic regression was used to determine if increased serum alkaline phosphatase (ALP) concentration was associated with tumor type. RESULTS: Of the 39 dogs with tumors arising from the chest wall, 25 had osteosarcoma, 12 had chondrosarcoma, and 2 dogs had hemangiosarcoma. Median survival time (MST) for dogs with rib osteosarcoma was 290 days. Increased activity of total ALP significantly decreased survival in dogs with osteosarcoma (210 days versus 675 days, P=.0035). MST for dogs with rib chondrosarcoma was not reached (mean 1301 days) and survival was significantly greater than all other types of rib tumors (P=.0321). CONCLUSION: Rib tumors should be resected with wide margins to decrease the risk of incomplete excision, because local tumor recurrence has a significant impact on the survival time. The prognosis for dogs with rib chondrosarcoma is very good, but guarded for other types of tumors. CLINICAL RELEVANCE: Osteosarcoma and chondrosarcoma are the most common primary tumors of the chest wall. Prognosis for dogs with primary rib chondrosarcoma is very good with surgery alone, but surgery and adjunctive chemotherapy is recommended for dogs with primary rib osteosarcoma and the prognosis remains guarded.

Use of alternating administration of carboplatin and doxorubicin in dogs with microscopic metastases after amputation for appendicular osteosarcoma: 50 cases (1999-2006).

OBJECTIVE: To evaluate the efficacy and toxicity of an alternating carboplatin and doxorubicin chemotherapy protocol in dogs with putative microscopic metastases after amputation for appendicular osteosarcoma and assess patient-, tumor-, and treatment-related factors for associations with prognosis. DESIGN: Retrospective case series. ANIMALS: 50 client-owned dogs. PROCEDURES: Records of dogs that underwent amputation for appendicular osteosarcoma and received an alternating carboplatin and doxorubicin chemotherapy protocol were reviewed. Dogs had full staging and were free of detectable metastases prior to chemotherapy. Data on disease-free interval (DFI), survival time, and toxicoses were retrieved from medical records and owner or referring veterinarian communications. RESULTS: Median DFI was 202 days. Median survival time was 258 days. Twenty-nine (58%) dogs completed the protocol as planned, and the rest were withdrawn typically because of metastases or toxicoses. Grade 3 or 4 myelosuppression was reported in 9 of 50 (18%) dogs and grade 3 or 4 gastrointestinal toxicosis in 6 of 50 (12%) dogs. There were no chemotherapy-related fatalities. Univariate factors associated with significant improvement in DFI included tumor location (radius), receiving doxorubicin as the first drug, starting chemotherapy more than 14 days after amputation, and no rib lesions on preamputation bone scans. Multivariate factors associated with a significant improvement in survival time were tumor location (radius) and completing chemotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Alternating administration of carboplatin and doxorubicin resulted in DFI and survival time similar to those reported for single-agent protocols. Clients should be counseled regarding the likelihood of toxicoses. Relevance of sequence and timing of starting chemotherapy should be further evaluated.

Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study.

BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.

Evaluation of primary re-excision after recent inadequate resection of soft tissue sarcomas in dogs: 41 cases (1999-2004).

OBJECTIVE: To determine the efficacy of primary re-excision alone for treatment of soft tissue sarcomas after recent incomplete resection, the frequency and clinical importance of detecting residual tumor in resected scars, and prognostic factors associated with the procedure. DESIGN: Retrospective case series. ANIMALS: 41 dogs. PROCEDURES: Medical records of dogs that had undergone recent incomplete excision of a soft tissue sarcoma at a referring veterinary practice and subsequent re-excision of the scar at the Colorado State University Veterinary Medical Center were reviewed. Owners and referring veterinarians were contacted for follow-up information. Slides from re-excised specimens were reviewed. Dogs that underwent radiation therapy after the re-excision procedure were excluded. RESULTS: 41 dogs met the inclusion criteria, and long-term follow-up information was available for 39 dogs. Median follow-up time was 816 days. Local recurrence of tumor developed in 6 of 39 (15%) dogs, and distant metastasis occurred in 4 of 39 (10%) dogs. Healthy tissue margins of 0.5 to 3.5 cm were achieved at re-excision. Residual tumor was identified in 9 of 41 (22%) resected scars. No tumor-, patient-, or treatment-related variables were associated with local recurrence except for the presence of liposarcoma or fibrosarcoma or whether fine-needle aspiration had been performed prior to surgery. CONCLUSIONS AND CLINICAL RELEVANCE: After incomplete resection of soft tissue sarcomas, resection of local tissue should be performed, even if excisable tissue margins appear narrow. A long-term favorable prognosis is achievable without radiation therapy or amputation. The presence of residual tumor in resected scar tissue should not be used to predict local recurrence.

Mechanical characteristics of cortical bone pins designed for fracture fixation.

Pins constructed from cortical bone may provide a reasonable alternative to other fracture-fixation devices by circumventing some of the complications associated with stainless steel and synthetic biodegradable implants. However, it is unknown whether cortical bone pins provide comparable strength compared to conventional pins. Using four-point bending, we compared the mechanical characteristics of 1.2-mm allogeneic cortical bone pins milled from specific regions of human tibiae and femora to commercially available 1.1-mm diameter stainless steel pins and 1.3-mm diameter polydioxanone pins. We used impact testing to identify mechanical differences in cortical bone pins between gender and harvest site. Cortical bone pins had better mechanical properties in four-point bending compared with polydioxanone pins, but not stainless steel pins. Pins milled from the right tibiae of males had the best bending characteristics. The mechanical performance of 1.2-mm cortical bone pins was comparable to those of stainless steel and polydioxanone pins regardless of site, bone, and gender. The clinical investigation of cortical bone pins as an implant for fracture fixation is warranted based on mechanical testing and comparison to commercially available polydioxanone and stainless steel pins.

Cortical allograft and endoprosthesis for limb-sparing surgery in dogs with distal radial osteosarcoma: a prospective clinical comparison of two different limb-sparing techniques.

OBJECTIVE: To compare surgical and oncologic outcome in dogs with osteosarcoma (OSA) of the distal aspect of the radius treated with limb-sparing surgery, using either a cortical allograft or endoprosthesis, and postoperative chemotherapy; and to evaluate predictive factors for outcome. STUDY DESIGN: Prospective cohort study. ANIMALS: Dogs (n = 20) with spontaneous, non-metastatic OSA of the distal aspect of the radius. METHODS: Dogs were prospectively randomized for limb-sparing surgery with either a cortical allograft (n = 10) or endoprosthesis (10) and full-course adjuvant chemotherapy using single or dual agent protocols of cisplatin, carboplatin, and/or doxorubicin. Surgical (intraoperative findings, postoperative infection, construct failure) and oncologic (local tumor recurrence, metastasis, survival) outcomes were compared. The influence of intraoperative and postoperative variables on surgical and oncologic outcome were evaluated. RESULTS: No clinically significant differences in surgical and oncologic outcome were detected between groups. The percentage of radius replaced by the implant was significantly greater in the endoprosthesis group (60.9% compared with 48.6%, P = .008). Median survival time (MST) for dogs with construct failure, regardless of implant type, was 685 days and significantly greater than MST of dogs without construct failure (322 days, P = .042; hazard ratio [HR] 16.82). Median metastasis-free interval and MST (685 days versus 289 days; P = .034, HR 24.58) were significantly greater in dogs with postoperative infection. Disease-free and overall limb-salvage rates were 70% and 85%, respectively. Overall MST was 430 days. CONCLUSIONS: For dogs with OSA of the distal aspect of the radius, a cortical allograft or endoprosthesis can be used for limb-sparing surgery. Construct failure and postoperative infection significantly improve survival time regardless of implant type. CLINICAL RELEVANCE: An endoprosthesis is an attractive alternative to cortical allografts for limb-salvage of the distal aspect of the radius in dogs because surgical and oncologic outcomes are similar, but the endoprosthesis is an immediately available off-the-shelf implant which is not complicated by the bone harvesting and banking requirements associated with cortical allografts. Mechanisms whereby postoperative infection improves survival time requires further investigation and, if elucidated, may provide the opportunity to improve the outcome of dogs and humans with OSA.

Evaluation of survival time in dogs with stage III osteosarcoma that undergo treatment: 90 cases (1985-2004).

OBJECTIVE-To assess survival time in dogs that underwent treatment for stage III osteosarcoma and evaluate factors affecting survival. DESIGN-Retrospective case series. ANIMALS-90 dogs with stage III osteosarcoma. PROCEDURES-Records in the osteosarcoma database at the Animal Cancer Center at Colorado State University from 1985 to 2004 were searched for dogs with metastatic disease at the time of evaluation. Dogs were included in the study if they had metastasis to any site and if treatment was initiated. A Kaplan-Meier survival analysis was performed, and the influences of age, sex, breed, primary tumor site, metastatic sites, and treatment on outcome were analyzed via log-rank analysis. RESULTS-Median survival time was 76 days, with a range of 0 to 1,583 days. No significant differences in survival times on the basis of age, sex, breed, or primary site were observed. Breeds and primary tumor sites were typical of those usually associated with osteosarcoma in dogs. Dogs treated palliatively with radiation therapy and chemotherapy had a significantly longer survival time (130 days) than dogs in all other treatment groups. Dogs treated with surgery alone had a significantly shorter survival time (3 days) than dogs treated with surgery and chemotherapy (78 days). Dogs with bone metastases had a longer survival time than dogs with soft tissue metastases. CONCLUSIONS AND CLINICAL RELEVANCE-Treatment of dogs with stage III osteosarcoma can result in various survival times. Dogs with metastasis to bone and dogs that were treated palliatively with radiation and chemotherapy had the longest survival times.

Initial wound management.

A wounded patient can be presented to the veterinary surgeon under a number of circumstances. The wound could result from external trauma,such as vehicle trauma or an animal fight, or it could have been created by surgical intervention, such as the removal of a mass. A wound could also be secondary to a failed initial attempt at wound closure. No matter what the cause, initial wound management often follows similar pathways. A successful wound closure and healing outcome is often dependent on adherence to basic principles of wound assessment, appropriate care, and reassessment. This article covers the approach to and specific options for the initial stages of wound management.

Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998-2004).

OBJECTIVE: To evaluate prognostic factors associated with outcome of dogs with multiple cutaneous mast cell tumors (MCTs) treated with surgery with or without adjuvant treatment. DESIGN: Retrospective case series. ANIMALS: 54 dogs with a minimum of 2 simultaneous, histologically confirmed cutaneous MCTs that had been excised and had adequate staging and follow-up data. PROCEDURE: Medical records from 1998 to 2004 were examined. Outcome was assessed with the Kaplan-Meier product-limit method and log-rank analysis. Prognostic factors evaluated included signalment; number, histologic grade, location, size, local recurrence, and de novo development of MCTs; quality of surgical margins; clinical signs at the time of diagnosis; and use of adjuvant treatment. RESULTS: Medical records of 54 dogs with 153 tumors were included. Median follow-up time was 658 days. Median disease-free interval (1,917 days; range, 11 to 1,917 days) and median survival time (1,917 days; range, 14 to 1,917 days) were not yet reached. The 1- year and 2- to 5-year survival rates were 87% and 85%, respectively. The overall rate of metastasis was 15%. Factors that negatively influenced survival time in the univariate analysis included incomplete excision, local recurrence, size > 3 cm, clinical signs at the time of diagnosis, and use of adjuvant treatment. Presence of clinical signs at the time of diagnosis was the only negative prognostic factor for disease-free interval detected in the multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that multiple cutaneous MCTs in dogs are associated with a low rate of metastasis and a good prognosis for long-term survival with adequate excision of all MCTs.

Thoracoscopic lung lobectomy for treatment of lung tumors in dogs.

OBJECTIVE: To report use of thoracoscopic lung lobectomy (TLL) for treatment of lung tumors (LT) in dogs. STUDY DESIGN: Retrospective study. ANIMALS: Nine dogs. METHODS: Dogs that had TLL for tumor removal were included. Using general anesthesia and 1-lung ventilation, TLL was performed using a 30-60 mm endoscopic gastrointestinal anastomosis stapler. If the visual field was obscured, lobe resection was completed via thoracotomy. RESULTS: Metastatic and primary LT were resected by thoracoscopic lobectomy in 9 dogs (6 male, 3 female; mean (+/-SD) weight, 29+/-7 kg; mean age, 10.7+/-1.9 years). Six dogs had a solitary mass and 3 dogs had 2 masses within a single lobe. The left caudal lobe was removed in 3 dogs. In 5 dogs, TLL was used alone whereas conversion to thoracotomy was required in 4 dogs because of poor visibility. There were 7 metastatic LT and 2 primary LT. Mean duration of thoracoscopic surgery was 108.8+/-30.3 minutes compared with 150.75+/-55.4 minutes in dogs requiring conversion to thoracotomy. Mean hospitalization was 3.1+/-1.3 days. CONCLUSION: Provided the visual field is not obscured, TLL can be performed effectively in dogs. CLINICAL RELEVANCE: Dogs with metastatic or primary LTs should be considered for TLL, particularly for small masses positioned away from the hilus in the left caudal lung lobe.