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.     

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.     

Amputation and Carboplatin for Treatment of Dogs With Osteosarcoma: 48 Cases (1991 to 1993)

Forty-eight dogs with histologically confirmed appendicular osteosarcoma (OSA) entered a prospective clinical trial evaluating treatment with amputation and up to 4 doses of carboplatin given every 21 days. The median disease-free interval (DFI) was 257 days, with 31.2% of the dogs disease-free at 1 year. The median survival time was 321 days, with 35.4% of the dogs alive at 1 year. Dogs with proximal humeral OSA had shorter DFI (P = .016) and survival (P = .037) times than dogs with OSA at other locations. Dogs with lower body weights (40 kg) had longer DFI (P = .0056) and survival (P = .007) times than larger dogs. Survival times for dogs that received carboplatin were statistically longer than those previously reported for amputation alone (P < .001). DFI and survival times are similar to those previously reported for 2 to 4 doses of cisplatin. Carboplatin appears to be a well-tolerated chemotherapeutic drug that can be given safely every 21 days at a dose of 300 mg/m². Neutropenia was the dose-limiting toxicity in this study. J Vet Intern Med 1996_;10:76–81. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

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.     

Adjuvant carboplatin and gemcitabine combination chemotherapy postamputation in canine appendicular osteosarcoma

Background: Appendicular osteosarcoma (OSA), the most common bone tumor in dogs, is typically treated by amputation and adjuvant chemotherapy. Despite numerous efforts, the median survival time (MST) for dogs receiving a platinum compound, doxorubicin, or a combination of these remains at 8–12 months. Evidence from studies in mice suggests that gemcitabine has activity against OSA in vivo. Our preliminary work demonstrated that the addition of low‐dosage (10 mM) gemcitabine to carboplatin resulted in synergistic inhibition of OSA cell viability in vitro. Objective: The purpose of the following study was to determine whether the addition of low‐dosage (2 mg/kg) gemcitabine to carboplatin chemotherapy in dogs with OSA after amputation would improve MST over carboplatin monotherapy. Animals: Fifty dogs with histologically confirmed appendicular OSA. Methods: Dogs were treated prospectively with amputation and up to 4 dosages of carboplatin and gemcitabine in combination every 3 weeks. Results: The chemotherapeutic regimen was well tolerated with only 5 episodes of grade 3 or 4 hematologic toxicity. The median disease‐free interval (DFI) was 203 days and the MST was 279 for all dogs in this study. The 1‐ and 2‐year survival rates were 29.5 and 11.3%, respectively. Dogs with proximal humeral OSA had a shorter median DFI (P= .04) compared with dogs with OSA in other locations. Conclusions and Clinical Importance: These results are comparable to those reported for carboplatin monotherapy indicating that the addition of gemcitabine to carboplatin in dogs with appendicular OSA does not appear to improve outcome.     

Marginal excision of low-grade spindle cell sarcoma of canine extremities: 35 dogs (1996-2006)

Objective— To evaluate recurrence rate and disease-free interval (DFI) of dogs with low-grade soft tissue spindle cell sarcoma of the extremities treated by marginal excision.
Study Design— Retrospective study.
Animals— Dogs (n=35) with soft tissue low-grade spindle cell sarcoma.
Methods— Medical records were reviewed and dogs that had marginal surgical resection of low-grade soft tissue spindle cell sarcoma at or distal to elbow and stifle were included.
Results— Histopathologic margins were dirty (12 dogs), clean but close (12), and clean (11). Follow-up after surgery occurred from 210 to 2202 days (minimum, 180 days). Local recurrence and metastatic rates were 10.8% and 0%, respectively. Median DFI and survival time were not reached, because <50% of dogs died of disease-related events. Mean DFI and mean survival time were 697.8 days (95% CI: 559.7–836 days) and 703.5 days (95% CI: 566.6–840.5 days), respectively. There were no significant differences among survival functions stratified by histologic margins.
Conclusion— Marginal surgical excision without adjuvant treatment of low-grade soft tissue spindle cell sarcoma of the extremities results in a low local recurrence rate.
Clinical Relevance— Low-grade spindle cell sarcomas located at or distal to the elbow and stifle joints can be excised without need for wide or radical surgery.     

Prolongation of survival of dogs with oral malignant melanoma treated by en bloc surgical resection and adjuvant CSPG4‐antigen electrovaccination

Reported post‐surgery 1‐year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan‐4 (hCSPG4)‐encoded plasmid in 23 dogs with resected II/III‐staged CSPG4‐positive oral cMM compared with 19 dogs with resected only II/III‐staged CSPG4‐positive oral cMM. Vaccination resulted in 6‐, 12‐, 18‐ and 24‐month survival rate of 95.6, 73.9, 47.8 and 30.4%, respectively [median survival time (MST) 684 days, range 78–1694, 8 of 23 dogs alive] and 6‐, 12‐, 18‐ and 24‐month disease‐free interval (DFI) rate of 82.6, 47.8, 26.1 and 17.4%, respectively (DFI 477 days, range 50–1694). Non‐vaccinated dogs showed 6‐, 12‐, 18‐ and 24‐month survival rate of 63.2, 26.3, 15.8 and 5.3%, respectively (MST 200 days, range 75–1507, 1 of 19 dogs alive) and 6‐, 12‐, 18‐ and 24‐month DFI rate of 52.6, 26.3, 10.5 and 5.3%, respectively (DFI 180 days, range 38–1250). Overall survival and DFI of vaccinated dogs was longer in those <20 kg. In vaccinated and non‐vaccinated dogs local recurrence rate was 34.8 and 42%, respectively while lung metastatic rate was 39 and 79%, respectively.     

Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma

Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti‐tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post‐operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease‐free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment.     

Penile amputation and scrotal urethrostomy in 18 dogs

The objective of this study was to report the signalment, indications for surgery, postoperative complications and outcome in dogs undergoing penile amputation and scrotal urethrostomy. Medical records of three surgical referral facilities were reviewed for dogs undergoing penile amputation and scrotal urethrostomy between January 2003 and July 2010. Data collected included signalment, presenting signs, indication for penile amputation, surgical technique, postoperative complications and long-term outcome. Eighteen dogs were included in the study. Indications for surgery were treatment of neoplasia (n=6), external or unknown penile trauma (n=4), penile trauma or necrosis associated with urethral obstruction with calculi (n=3), priapism (n=4) and balanoposthitis (n=1). All dogs suffered mild postoperative haemorrhage (posturination and/or spontaneous) from the urethrostomy stoma for up to 21 days (mean 5.5 days). Four dogs had minor complications recorded at suture removal (minor dehiscence (n=1), mild bruising and swelling around the urethrostomy site and mild haemorrhage at suture removal (n=2), and granulation at the edge of stoma (n=1)). One dog had a major complication (wound dehiscence and subsequent stricture of the stoma). Long-term outcome was excellent in all dogs with non-neoplastic disease. Local tumour recurrence and/or metastatic disease occurred within five to 12 months of surgery in two dogs undergoing penile amputation for the treatment of neoplasia. Both dogs were euthanased.     

Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized,phase III trial

Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease‐free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin.     

Resection of Pulmonary Metastases in Canine Osteosarcoma: 36 Cases (1983–1992)

Thirty-six dogs underwent pulmonary metastatectomy for osteosarcoma. All patients had been treated for histologically confirmed osteosarcoma of the appendicular skeleton. Treatment for the primary tumor consisted of amputation or a limb sparing procedure in conjunction with adjuvant chemotherapy, local radiation therapy, or both.
Significant factors in determining prognosis included the disease-free interval (DFI) between treatment of the primary tumor and development of pulmonary metastases and the number of metastatic nodules present at surgery. Dogs that developed pulmonary metastases 300 days or more after diagnosis of the primary tumor had a median DFI of 128 days after metastatectomy. Dogs that developed pulmonary metastases fewer than 300 days after diagnosis had a median DFI of 58 days. Dogs with one or two metastatic nodules removed had a median DFI of 95 days, whereas dogs with three or more nodules removed had a median DFI of 53 days. The results of this study indicate that prognostic variables exist for dogs with metastatic pulmonary osteosarcoma and can help predict survival after metastatectomy. These variables are similar to the prognostic variables that have been determined for human patients undergoing pulmonary metastatectomy because of osteosarcoma. Though a controversial procedure, pulmonary metastatectomy seems to be a valid treatment option for selected dogs with metastatic pulmonary osteosarcoma.     

Outcome and prognostic factors following adjuvant prednisone/vinblastine chemotherapy for high-risk canine mast cell tumour: 61 cases

The medical records of 61 dogs with MCT at high risk for metastasis that were treated with prednisone and VBL following excision+/-radiation therapy were reviewed, and median disease-free interval (DFI), median overall survival time (OS) and prognostic factors assessed. Adverse effects, mostly mild, were noted in 26% of patients, usually after the first VBL dose. 6.5% experienced severe neutropenia. The DFI was 1305 days, and the OS was not reached, with 65% alive at 3 years. 100% of dogs with "high-risk" grade II MCT were alive at 3 years. The OS for dogs with grade III MCT was 1374 days. Histologic grade, location (mucous membrane vs. skin) and use of prophylactic nodal irradiation predicted outcome. Prednisone and VBL chemotherapy is well tolerated, and results in good outcomes following surgery in dogs with MCT at high risk for metastasis. High-grade and mucocutaneous tumors had a worse outcome, and the use of prophylactic nodal irradiation appeared to improve outcome in this group of dogs.     

Retrospective outcome evaluation for dogs with surgically excised,solitary Kiupel high‐grade,cutaneous mast cell tumours

Published outcomes for dogs with specifically high‐grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high‐grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2‐year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow‐up 980 days) and 2 dogs were lost to follow‐up. Death was considered MCT‐related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.     

Evaluation of outcome associated with subcutaneous and intramuscular hemangiosarcoma treated with adjuvant doxorubicin in dogs: 21 cases (2001-2006)

OBJECTIVE: To evaluate outcome associated with subcutaneous and intramuscular hemangiosarcomas treated with adjuvant doxorubicin in dogs. DESIGN: Retrospective case series. ANIMALS: 21 dogs. PROCEDURES: Records of dogs with histologically confirmed hemangiosarcoma, no detectable metastasis at initial evaluation, and adequate local tumor control were included. Age, sex, number of treatments, treatment interval, radiation therapy, and concurrent use of cyclophosphamide or deracoxib were evaluated for associations with disease-free interval (DFI) or survival time. Three to 6 cycles of doxorubicin were planned. Disease-free interval was defined as time of definitive surgery to time of local recurrence, metastasis, or both. Survival time was defined as the beginning of the DFI to time of death. RESULTS: 17 tumors were subcutaneous, and 4 were intramuscular. Median age was 9 years. Median weight was 31.1 kg (68.4 lb). Five dogs received adjuvant radiation therapy. Median DFI for subcutaneous tumors was 1,553 days (95% confidence interval [CI], 469 days to not estimable). Median DFI for intramuscular tumors was 265.5 days (95% CI, 123 to 301 days). Median survival time for subcutaneous tumors was 1,189 days (95% CI, 596 days to not estimable). Median survival time for intramuscular tumors was 272.5 days (95% CI, 123 to 355 days). For dogs with subcutaneous tumors, younger age (< 9 years) was associated with longer DFI and survival time. Dogs with subcutaneous tumors that did not receive radiation therapy had longer DFI. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with subcutaneous hemangiosarcoma had a more favorable outcome, compared with dogs with intramuscular hemangiosarcoma, when treated with adequate local control and adjuvant doxorubicin.     

Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma

The purpose of this study was to compare a maintenance-free chemotherapy protocol based on CHOP (H from hydroxydaunorubicin = doxorubicin, O from Oncovin = vincristine) to a similar protocol with a maintenance phase for the treatment of canine lymphoma. Fifty-three dogs with multicentric lymphoma were treated with a 6-month modified version of the University of Wisconsin (UW)-Madison chemotherapy protocol (UW-25). Disease-free interval (DFI) and survival were compared to a historical control group of 55 dogs treated with a similar protocol with a prolonged maintenance phase. Remission rate for the study dogs was 94.2% (complete remission = 92.3%, partial remission = 1.9%). DFI and survival between the 2 groups did not differ significantly, with median DFI and survival of the study dogs equal to 282 and 397 days compared to 220 and 303 days for the control dogs (P = .2835 and .3365, respectively). Univariate analysis identified substage b (P = .0087), German Shepherd breed (P = .0199), and body weight > 18 kg (P = .0016) as significant for worse survival. Longer survival was associated with thrombocytopenia (P = .0436). Multivariate analysis revealed that substage (P = .0388) and weight (P = .0125) retained significance for DFI, whereas substage (P = .0093), thrombocytopenia (P = .0150), and weight (P = 0 .0050) retained significance for survival. Overall, the protocol was well tolerated by the dogs, with 41.5% (22/53) requiring a treatment delay or dose modification, but only 9.4% (5/53) needing hospitalization. The 6-month chemotherapy protocol based on CHOP with no maintenance phase provides similar DFI and survival times when compared to a similar protocol with a prolonged maintenance phase.     

Clinical and imaging findings,treatments, and outcomes in 27 dogs with imaging diagnosed trigeminal nerve sheath tumors: A multi‐center study

The clinical behavior of canine trigeminal nerve sheath tumors and benefits of previously reported treatments are incompletely defined. Aims of this retrospective, multicenter, observational study were to describe clinical signs, tumor localization characteristics, treatments, and clinical outcomes in a group of dogs with this neoplasm. Databases at four hospitals were reviewed for dogs with a trigeminal nerve sheath tumor diagnosis, magnetic resonance imaging (MRI) studies, and presentation between 2004 and 2014. A single observer recorded medical record findings and two observers recorded MRI characteristics by consensus. A total of 27 dogs met inclusion criteria (15 treated with stereotactic radiation therapy and 12 unirradiated). Two unirradiated dogs were excluded from outcome analyses. The most common presenting signs were masticatory muscle atrophy (26 dogs), neurologic signs referable to intracranial disease (13), and ocular disease (12). Based on MRI findings, all dogs had disease extending centrally at the level of the brainstem. The most commonly affected trigeminal nerve branches were the mandibular (26 dogs), maxillary (22), and ophthalmic (10). Of 15 dogs treated with stereotactic radiation therapy, one had improved muscle atrophy, and six had poor ocular health after treatment. Neurologic signs improved in 4/5 dogs with intracranial signs. Overall median survival time for the 10 unirradiated dogs with available follow‐up was 12 days and 441 days for the 15 stereotactic radiation therapy dogs. Mean survival times between these groups were not significantly different (mean 95% CI for unirradiated dogs was 44–424 days and mean 95% CI for stereotactic radiation therapy dogs was 260–518 days).     

Survival analysis of one versus two treatments of local delivery cisplatin in a biodegradable polymer for canine osteosarcoma

The purpose of this study was to evaluate one versus two doses of local delivery cisplatin in a biodegradable polymer (OPLA‐Pt) for the treatment of osteosarcoma (OSA) after amputation in dogs. Medical records were reviewed retrospectively, and 105 dogs were included in the study; 39% of dogs received one treatment (surgical implantation) of OPLA‐Pt and 61% of dogs received two treatments of OPLA‐Pt after amputation. Administration of two doses of OPLA‐Pt did not have a significant effect on disease‐free interval or survival time compared to one dose. The anatomic site of the tumour was identified as a prognostic factor, and dogs with proximal humeral OSA had the shortest disease‐free interval and survival times. There was no advantage to giving a second dose of local delivery cisplatin following amputation for the treatment of OSA in dogs.     

Outcome of and postoperative complications in dogs undergoing surgical treatment of laryngeal paralysis: 140 cases (1985-1998).

OBJECTIVE: To compare outcomes of various surgical techniques for treatment of laryngeal paralysis in dogs and determine incidence and risk factors for development of postoperative complications. DESIGN: Retrospective study. ANIMALS: 140 dogs undergoing surgical treatment for laryngeal paralysis at a veterinary teaching hospital between 1985 and 1998. PROCEDURE: Data were analyzed to determine outcome and factors influencing outcome and development of complications. Kaplan-Meier curves were constructed for survival analysis. RESULTS: Postoperative complications were documented in 48 (34.3%) dogs; 20 (14.3%) dogs died of related causes. Aspiration pneumonia was the most common complication (33; 23.6%). Seven dogs died of aspiration pneumonia > 1 year after surgery. Dogs that underwent bilateral arytenoid lateralization were significantly more likely to develop complications and significantly less likely to survive than were dogs that underwent unilateral arytenoid lateralization or partial laryngectomy. Factors that were significantly associated with a higher risk of dying or of developing complications included age, temporary tracheostomy placement, concurrent respiratory tract abnormalities, concurrent esophageal disease, postoperative megaesophagus, concurrent neoplastic disease, and concurrent neurologic disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that surgical repair of laryngeal paralysis may be associated with high postoperative complication and mortality rates. Surgical technique and concurrent problems or diseases increased the risk of complications. Dogs appeared to have a life-long risk of developing respiratory tract complications following surgical correction.     

Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma

Immunotherapeutic strategies have shown promise for the treatment of canine osteosarcoma (cOSA). Very little is known about the immune microenvironment within cOSA, however, limiting our ability to identify potential immune targets and biomarkers of therapeutic response. We therefore prospectively assessed the disease‐free interval (DFI) and overall survival time (ST) of 30 dogs with cOSA treated with amputation and six doses of adjuvant carboplatin. We then quantified lymphocytic (CD3+, FOXP3+) and macrophage (CD204+) infiltrates within the primary tumours of this cohort using immunohistochemistry, and evaluated their association with outcome. Overall, the median DFI and ST were 392 and 455 days, respectively. The median number of CD3+ and FOXP3+ infiltrates were 45.8 cells/mm² (4.6‐607.6 cells/mm²) and 8.5 mm² (0‐163.1 cells/mm²), respectively. The median area of CD204+ macrophages was 4.7% (1.3%‐23.3%), and dogs with tumours containing greater than 4.7% CD204+ macrophages experienced a significantly longer DFI (P = 0.016). Interestingly, a significantly lower percentage of CD204+ macrophages was detected in cOSA arising from the proximal humerus compared to other appendicular bone locations (P = 0.016). Lymphocytic infiltrates did not appear to correlate with outcome in cOSA. Overall, our findings suggest that macrophages may play a role in inhibiting cOSA progression, as has been suggested in human osteosarcoma.     

Surgery and Doxorubicin in Dogs With Hemangiosarcoma

Forty-six dogs with histologically confirmed hemangiosarcoma of various locations other than skin were used in a prospective study to determine the efficacy of adjuvant doxorubicin (30 mg/m² IV q 3 weeks for 5 treatments) 10 to 14 days after the tumor was partially or completely excised. Analysis of the data included information on variables that were hypothesized to influence response to therapy, disease-free interval (DFI), or survival time (ST). Other information collected included age, gender, breed, weight, prior therapy, type of surgery, location of the primary tumor, presence of metastases, number of doses of doxorubicin, response to doxorubicin therapy (complete or partial response!, and the following histological criteria: overall differentiation, nuclear pleomorphism, percent necrosis, mitotic score, total histological score, and grade. Surgery outcome (complete versus incomplete surgical excision) markedly influenced survival times (P < .001). Twenty percent of the dogs rendered free of disease were alive at 1 year, whereas none of the dogs that had residual tumor after surgery were alive at 1 year. Most of the histological criteria (nuclear pleomorphism, mitotic score, grade, overall differentiation) had marked (P < .05), or close to marked, independent associations with ST for dogs that had complete tumor removal. Results from analysis of DFI were generally similar to those of ST in dogs with complete excision of the tumor. Twenty-seven of the 46 dogs (58.7%) had all clinical evidence of tumor successfully removed. Logistic regression analysis of surgical outcome (ability to remove all visible tumor) suggested that age of the subject was the only factor markedly influencing surgical outcome (P= .017). As age increased, the probability of success increased. Those dogs that had previous treatment for their hemangiosarcoma tended (P= .08) to have a shorter DFI and ST. Therefore, complete removal of all evidence of tumor followed by 5 doses of doxorubicin may be an effective treatment for dogs with hemangiosarcoma. Dogs that had all tumor successfully removed had a mean and median ST of 267 and 172 days, respectively. Dogs with incomplete tumor removal had a mean and median ST of 172 and 60 days, respectively. Similarly, prognostic variables such as the ability to completely excise all evidence of tumor, histological criteria, and age of the patient are potentially important prognostic variables for predicting outcome.