Zoledronic acid for the treatment of appendicular osteosarcoma in a dog

A 10-year-old male intact Corso dog was referred for lameness and for a large neoplasm affecting the right foreleg. Physical examination of the patient revealed a 5 × 5 × 3 cm mass in the distal right foreleg. Histopathology was consistent with a diagnosis of appendicular osteosarcoma. The staging process found no evidence of metastasis. Because of the large size of the patient, the owners elected to treat their dog with antiresorptive therapy. The patient was treated with an infusion of zoledronic acid every 28 days. The tumour remained stable for 16 months and the lameness of the dog greatly improved. At that time, the patient returned for evaluation of a large rapidly growing prescapular mass. Biopsy confirmed lymph node metastasis and the dog was euthanased. Zoledronic acid showed remarkable palliation in our patient and possibly anti-tumour action and warrants further investigation.     

Cutaneous metastasis of primary appendicular osteosarcoma in a dog

A 6-year-old, neutered male Rottweiler was presented to the University of Illinois Veterinary Teaching Hospital because of a lytic bone lesion involving the distal portion of the right radius and possible pulmonary metastases on thoracic radiographs. Results of serum biochemical analysis were unremarkable. Aspiration and cytologic examination of the bone lesion indicated likely sarcoma with reactive bone. Cutaneous masses were found on the left thigh, interscapular region, and dorsal lumbar region, 4 weeks after initial presentation. Neoplastic spindle cells were found in aspirates from 2 of the masses. The neoplastic cells stained positive for alkaline phosphatase activity using cytochemistry. Re-evaluation of serum biochemical values at this time revealed a marked increase in alkaline phosphatase activity (413 U/L, reference interval 12-110 U/L) compared with the initial value (26 U/L). Due to progressive disease, the dog was euthanized and a necropsy was performed. Histologic findings included primary osteosarcoma of the distal portion of the right radius, with metastases in the lungs, spleen, left fourth and fifth ribs, soft tissue of the right medial thigh, and T1-T3/interscapular region. Cutaneous metastasis of primary appendicular osteosarcoma has been reported rarely in animals and humans. Increased serum alkaline phosphatase activity may be a potential indicator of poor prognosis for this neoplasm.     

Carboplatin and doxorubicin combination chemotherapy for the treatment of appendicular osteosarcoma in the dog

Twenty-four client-owned dogs with histologically diagnosed appendicular osteosarcoma (OSA) and no evidence of gross metastatic disease were treated with amputation or limb salvage followed by combination chemotherapy consisting of carboplatin (175mg/ m2 IV, day 1) and doxorubicin (15 mg/m2 IV, day 2) given on a 21-day cycle for a maximum of 4 cycles. Hematologic and gastrointestinal adverse effects were graded according to National Cancer Institute guidelines. Thoracic radiographs were obtained before the 3rd chemotherapy cycle and then every 2 months. Median disease-free interval was 195 days (95% confidence interval 111-228 days) and median survival was 235 days (95% confidence interval 150-283 days). Two patients required dose reductions: 1 for grade 3 thrombocytopenia and 1 for grade 3 adverse gastrointestinal effects. Patients with a longer duration of clinical signs before definitive diagnosis and surgery (greater than 30 days) were more likely to develop progressive disease and to die or be euthanized because of progressive disease on any day; hazard ratios were 3.0 (P = .02) and 3.7 (P .02), respectively. In conclusion, although this combination chemotherapy protocol was well tolerated, it did not provide any improvement over historical single-agent protocols.     

Intraoperative radiation for limb sparing of the distal aspect of the radius without transcarpal plating in five dogs

Objectives— To evaluate intraoperative irradiation (IORT) as a method of limb spare with preservation of the radiocarpal joint.
Study Design— Prospective case series.
Animals— Dogs (n=5) with stage II sarcoma of the distal aspect of the radius.
Methods— A bone segment containing the tumor was isolated surgically, treated by IORT, reimplanted, and secured by internal fixation. In 1 dog, the postradiation tumor bed was curetted and filled with bone cement. Dogs were administered alternating adriamycin and carboplatin starting 2 weeks after IORT and monitored at regular intervals.
Results— Four dogs had osteosarcoma and 1 had undifferentiated sarcoma. Implant failure (n=3), deep tissue infection (3), and pathologic fracture (3) resulted in amputation (3) or pancarpal plating (2). The dog with undifferentiated sarcoma was euthanatized because of suspected tumor recurrence 4 months postoperatively. Osteotomy healing was documented by radiography (1), histopathology (2), or by direct observation (2).
Conclusions— A technique for limb-sparing surgery of the distal portion of the radius in dogs using IORT had advantages include healing of the autograft and a source for a perfectly fitting autograft but did not appear to offer any advantage with respect to infection rate. Long-term preservation of the radiocarpal joint was not successful.
Clinical Relevance— It was not possible to preserve the function of the radiocarpal joint and so this technique cannot be recommended currently. Further study is needed to evaluate whether or not IORT can be considered in combination with pancarpal plating and possibly curettage and cementation of the tumor to prevent subchondral bone collapse.     

Pasteurized tumoral autograft as a novel procedure for limb sparing in the dog: A clinical report

OBJECTIVE: To evaluate use of a pasteurized tumoral autograft prepared from the resected primary bone neoplasm for limb sparing in a dog with distal radial osteosarcoma (OSA). STUDY DESIGN: Clinical case report. ANIMALS: A 9-year-old male Maremma shepherd dog. METHODS: After right distal radial OSA removal, the tumoral autograft was pasteurized. The excised bone segment was placed in a sterile watertight box containing sterile saline solution preheated to 65 degrees C in a water bath. The box was kept immersed in the water bath at 65 degrees C for 40 minutes to kill the tumor cells. The autograft was then fixed in the host with a plate and screws based on standard AO/ASIF technique for carpal arthrodesis. Three doses of cisplatin (70 mg/m(2) intravenously) were administered, 3 weeks apart; the initial dose was administered the day after surgery. RESULTS: The autograft was incorporated in a manner comparable to an allograft, and after 708 days, the metallic implants were removed. A 1-month activity restriction as well as spoon splint to protect the leg from a full loading were used thereafter. Limb function was fair to good, and the dog remains disease free after 56 months. CONCLUSIONS: A pasteurized autograft consisting of the resected primary bone neoplasm is a valid alternative to a cortical bone allograft for limb sparing in dogs with appendicular OSA in terms of feasibility and pattern of healing. CLINICAL RELEVANCE: This procedure can be an alternative method of limb sparing when difficulties are encountered in establishing and maintaining a canine bone allograft bank.     

Acute shortening and subsequent lengthening of the radius and ulna for the treatment of an infected nonunion in a dog

A 3-year-old, male crossbred dog with osteomyelitis of the radius and ulna was treated using Ilizarov's method. Two centimeters of infected bone was resected, then acute bone shortening and subsequent lengthening of a healthy bone site were performed. The infection was eradicated, but a residual leg-length discrepancy was present.     

Use of cisplatin for treatment of appendicular osteosarcoma in dogs

Nineteen dogs were treated for osteosarcoma of the appendicular skeleton. Eleven dogs treated by amputation and adjunctive cisplatin chemotherapy had a significantly longer (P less than 0.003) median survival time of 43 weeks (range, 20 to 108 weeks) than did 8 dogs whose median survival time was 14.5 weeks (range, 8 to 46 weeks) after amputation alone. All 11 dogs given cisplatin were evaluated for signs of drug toxicosis. Transient episodes of vomiting were recorded in 9 of 11 dogs. Additional toxic effects included gradual decreases in endogenous creatinine clearance in 3 dogs and thrombocytopenia in 1 dog. On the basis of prolonged survival times and minimal adverse effects, we concluded that cisplatin has promise as an effective and relatively nontoxic agent, when combined with amputation, for treatment of dogs with osteosarcoma of the appendicular skeleton.     

Toxicity and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of canine appendicular osteosarcoma following limb amputation

Objective To evaluate the safety and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of dogs with appendicular osteosarcoma following limb amputation. Design Retrospective study. Procedure Dogs diagnosed with appendicular osteosarcoma, with no evidence of metastatic disease, treated with amputation and adjuvant chemotherapy consisting of two doses of doxorubicin given 14 days apart, followed by four doses of carboplatin at 3‐weekly intervals between September 2003 and December 2009 were identified from the medical records of Perth Veterinary Oncology. Haematological and gastrointestinal toxicities were assessed based on information in the medical records and recorded complete blood count results. The efficacy of the protocol was assessed by determining the median disease‐free interval (DFI) and overall survival time (OST) using the Kaplan‐Meier product‐limit method. Results In total, 33 dogs met the inclusion criteria. The median DFI was 231.5 days and the median OST was 247 days. With regard to haematological toxicity, 56% of dogs had a grade 1–2 neutropenia recorded as their highest marrow toxicity and 9% of dogs experienced a grade 3–4 neutropenia, all subsequent to doxorubicin administration. The highest gastrointestinal toxicity was grade 1–2 in 15 dogs (47%) and 5 dogs (16%) experienced grade 3–4 gastrointestinal toxicity. Conclusion This chemotherapy protocol did not result in a longer time to disease recurrence or OST in this population of dogs. Dual‐agent protocols have failed to improve survival times and therefore we conclude that a single‐agent protocol using carboplatin may be equally effective with less toxicity.     

Forelimb amputation for the treatment of distal radius osteosarcoma in an African pygmy hedgehog (Atelerix albiventris)

Neoplasia is a common finding in African pygmy hedgehogs. Both skeletal and extraskeletal osteosarcomas have been previously reported in this species, but the only reported case of appendicular osteosarcoma was diagnosed postmortem. A 3-year-old intact female African pygmy hedgehog presented with a 10-day history of left foreleg swelling and lameness. Radiographs performed by the referring veterinarian confirmed the presence of a lytic lesion affecting the distal radius. A whole-body computed tomography scan was performed and confirmed a marked osteolytic lesion affecting the distal radius, which was consistent with bone neoplasia, however osteomyelitis could not be excluded. There was no evidence of thoracic or abdominal metastasis. Ultrasound-guided fine needle aspiration of the lesion yielded a nondiagnostic sample. The affected forelimb was amputated and along with the axillary lymph node, was submitted for histological analysis which confirmed a well differentiated osteosarcoma within the distal radius. The patient made a full recovery with no complications and remained disease free at the time of writing, 12 months after presentation. Osteosarcoma is rarely diagnosed antemortem in African pygmy hedgehogs. This case describes the management, diagnostic techniques, and successful treatment of an osteosarcoma affecting the distal radius by forelimb amputation.     

Treatment of appendicular osteosarcoma in a horse

A 14‐year‐old Arabian gelding was examined for a mass on the lateral aspect of the left tarsus and proximal lateral metatarsus. Radiography revealed a predominately osteolytic lesion involving the fourth tarsal bone and the proximal third and fourth metatarsal bone. Results of histopathological examination of the mass prior to surgery were consistent with an undifferentiated sarcoma. The mass was surgically excised and the remaining bone defect treated with absorbable beads containing cisplatin. Histology and immunohistochemistry of the mass removed at surgery revealed a telangiectatic osteosarcoma. The surgical site healed uneventfully and the horse was performing as a low level jumper 8.5 years after surgery.     

Transverse ulnar bone transport osteogenesis: a new technique for limb salvage for the treatment of distal radial osteosarcoma in dogs

Objective— To develop instrumentation and a technique for transverse ulnar bone transport osteogenesis in dogs.
Study Design— Cadaveric study and in vivo validation (1 dog).
Sample Population— Paired cadaveric antebrachii (n=10 dogs) and 1 live dog.
Methods— Circular fixator constructs were applied and fitted with reeling or linear motors designed to transport an ulnar segment transversely into a defect created by excising the distal 50% of the ipsilateral radius. A longitudinal osteotomy of the adjacent ulna was created and the segment was transported across the radial defect. Pre- and post-distraction CT scans were used to compare the efficacy of each construct. The procedure was performed unilaterally in a live dog using the reeling motor (RM) construct.
Results— Both constructs effectively transported the ulnar segment into the defect. Subjectively, the RMs were easier to apply and operate. No significant differences were observed in the objective measures of efficacy between the 2 construct types. The live dog produced viable regenerate bone after transverse ulnar bone transport.
Conclusions— Transverse ulnar bone transport should be considered a potential method for limb salvage in dogs with osteosarcoma (OSA) of the distal radius. The RMs were effective and clinically applicable.
Clinical Relevance— Transverse ulnar bone transport osteogenesis affords the benefits of longitudinal radial bone transport osteogenesis, allowing resolution of large longitudinal radial defects in a substantially less time as a result of shortening the transport distance. This would be beneficial when treating conditions such as OSA where minimizing convalescence and maximizing quality of life is a priority.     

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.     

Complications after two transphyseal bridging techniques for treatment of angular limb deformities of the distal radius in 568 Thoroughbred yearlings

Reasons for performing study: Surgical correction of carpal angular limb deformities by growth retardation is commonly undertaken with a screws and tension band wire loop technique (S&W) or a single transphyseal screw (STS). This study compares complications after S&W and STS bridging in the distal radius of Thoroughbred yearlings. Objective: To compare the prevalence of complications serious enough to require follow‐up radiographs following either S&W or STS surgery for growth manipulation in the distal radius of Thoroughbred yearlings. Methods: Medical records and radiographs from Thoroughbred yearlings (age range 261–457 days) treated for carpal angular limb deformities at a single hospital over 2 years were reviewed. Each of the techniques was used exclusively during a single year. The complication threshold criterion for inclusion was the need for nonroutine radiographs of the operated site anytime after implant insertion or removal. Results: Of 568 horses, 253 received S&W and 315 received STS. Horses were of similar age at the time of surgery for STS and S&W. Single transphyseal screws were left in place for a significantly shorter amount of time (16 days). Sex, the limb(s) treated and medial vs. lateral placement were not significantly different between techniques. Complications included physitis post implant removal, metaphyseal collapse post implant removal, infection, overcorrection and seroma formation severe enough to require radiography. Physitis and metaphyseal collapse occurred significantly more frequently with STS compared with S&W. Infection, overcorrection and seromas were not significantly different between techniques. Conclusion: The STS and S&W techniques are both viable treatment options for correction of carpal angular limb deformities. However, horses treated with the STS technique have a significantly increased risk of developing physitis or metaphyseal collapse. Potential relevance: Horses treated with STS bridging have a significantly increased risk of developing the post correction complications of moderate to severe physitis and metaphyseal collapse compared with horses treated with S&W bridging.     

Bone allografts and adjuvant cisplatin for the treatment of canine appendicular osteosarcoma in 18 dogs

The results achieved in 18 dogs following the use of frozen bone cortical allografts for limb-sparing resection of non-metastatic canine appendicular osteosarcoma are presented. Three to five cisplatin doses (70 mg/m2) were administered, starting the day after surgery. The mean and median survival times were 478 and 266 days (range 80 to 2,611 days), respectively. The survival rate was 94 per cent at three months, 78 per cent at six months, 35 per cent at 12 months, 23 per cent at 18 months and 19 per cent at 24 months; the disease-free interval was 80 to 1,246 days (mean 365 days, median 266 days). Lung metastasis developed in 55 per cent of the dogs within one year. Complications were observed in 14/18 dogs (78 per cent), comprising local recurrence (28 per cent), allograft infection (39 per cent) and implant failure (11 per cent). Despite complications, limb sparing is a useful alternative to amputation in selected cases of appendicular osteosarcoma.     

Curative-intent radiation therapy as a treatment modality for appendicular and axial osteosarcoma: a preliminary retrospective evaluation of 14 dogs with the disease

Canine osteosarcoma is a common bone malignancy associated with aggressive local disease and rapid metastasis. Current local therapeutic modalities do not provide curative‐intent options for dogs with significant orthopaedic or neurologic disease, dogs which are denied amputation or dogs with non‐resectable lesions. The goals of this retrospective study included the evaluation of local control, survival, and time to the development of metastases in 14 dogs treated with curative‐intent radiation therapy and chemotherapy. Median local disease control was 202 days (79–777). Median survival was 209 days (79–781). Median time to metastasis was 314 days (7–645). No significant correlation was found between the outcome and pre‐treatment alkaline phosphatase levels, radiographic appearance, tumour site, radiation dose or chemotherapeutics administered. In these dogs, full‐course radiation therapy in conjunction with chemotherapy was not found to yield equivalent results to the standard of care options.     

Ipsilateral vascularised ulnar transposition autograft for limb-sparing surgery of the distal radius in 2 dogs with osteosarcoma

Canine osteosarcoma is the most commonly diagnosed primary bone tumour in the dog, affecting mainly large and giant breed dogs with the predilection site being the metaphysis of long bones, specifically the distal radius, proximal humerus, distal femur and proximal tibia and fibula. Treatment options are either palliative or curative intent therapy, the latter limb amputation or limb-sparing surgery together with chemotherapy. This article describes the use of an ipsilateral vascularised ulnar transposition autograft as well as chemotherapy in 2 dogs with osteosarcoma of the distal radius. Both dogs showed minimal complications with the technique and both survived over 381 days following the surgery. Complications seen were loosening of the screws and osteomyelitis. The procedure was well tolerated with excellent limb use. This technique is indicated for use in cases with small tumour size that have not broken through the bone cortex.