Spirocercosis-associated esophageal sarcomas in dogs. A retrospective study of 17 cases (1997-2003)

Seventeen client-owned dogs diagnosed with spirocercosis-associated esophageal sarcomas were retrospectively reviewed. The most common clinical signs noticed were vomiting and/or regurgitation (94%), lethargy and depression (59%), pyrexia and anorexia (41% each). Leukocytosis (82%) and microcytic hypochromic anemia (30%) were the most common hematological abnormalities. Caudal thoracic masses were demonstrated on survey radiographs of 13/15 of the dogs and thoracic spondylitis was detected in 12/15 dogs. Spirocerca lupi eggs were detected in 2/8 patients and worms were demonstrated on 1/11 at necropsy. Ten cases underwent surgical attempt to remove the tumors. In six of them partial esophagectomy (PE) was performed and all of them survived the immediate postoperative hospitalization. Five of the cases that underwent PE also received chemotherapy after surgery (doxorubicin (Adriamycin, Upjohn)) with an average survival time of 267 days. The histopathological results of the esophageal tumors were osteosarcoma (9), fibrosarcoma (5) and undifferentiated sarcoma (1). In areas endemic to spirocercosis, regurgitation or vomiting in dogs and microcytic hypochromic anemia and neutrophilia warrant ruling out esophageal sarcomas. Proper surgical treatment could prolong the dogs' lifespan for months, and improve their quality of life.     

Soft tissue sarcoma in dogs: A treatment review and a novel approach using electrochemotherapy in a case series

Canine soft tissue sarcomas (STSs) are locally invasive mesenchymal neoplasms. Electrochemotherapy (ECT) is an antitumour local ablative treatment that uses electric pulses to enhance the intracellular delivery of cytotoxic drugs. The aim of this retrospective study was to review the current treatment for STSs and to evaluate the efficacy and safety of ECT with bleomycin in canine STSs. Fifty‐two dogs with 54 STSs were included. Three groups were arranged: (a) ECT alone, (b) intra‐operative ECT and (c) adjuvant ECT. Signalment, tumour size, location, histological grade and margins and ECT parameters were collected. Recurrence rate (RR) and disease‐free interval (DFI) were calculated. Treatment toxicity was assessed using a 6‐point scale. STSs were mostly located on limbs (77.8%). Median tumour size was 4.3 cm (range 0.4‐17.0 cm). Most STSs were grade I (47.7%) and II (50.0%), and histological margins were incomplete in 94.5% of cases. Two complete remissions, one partial remission and one stable disease were recorded in group 1. Group 2 and 3 were similar for tumour location, size and grade, histological margins, treatment toxicity, pulse frequency and voltage. Moreover, RR and DFI were similar between group 2 and 3 (23% and 25%, 81.5 and 243 days, respectively). Local toxicity post ECT was mild (score ≤ 2) in 66.7% of cases. Higher toxicity score was associated with higher pulse voltage (1200 vs 1000 V/cm) (P = 0.0473). ECT coupled with bleomycin resulted safe and efficient in tumour local control and should be considered as an option for treatment of canine STSs.     

Canine intranasal tumours treated with alternating carboplatin and doxorubin in conjunction with oral piroxicam: 29 cases

Few veterinary studies have evaluated the response to chemotherapy treatment of canine intranasal tumours, while many have focused on the efficacy of radiation therapy. Given the higher costs and limited access to radiation therapy, alternative treatment options are needed. The study describes a cohort of dogs with histologically confirmed intranasal tumours treated with chemotherapy as a sole therapy. This retrospective study was conducted using data from the Melbourne Veterinary Specialist Centre (MVSC) database between 2004 and 2017. Dogs with a histologically confirmed intranasal tumour who received chemotherapy treatment were included. Signalment, presenting signs, tumour type, chemotherapy details, adverse events (AEs) and survival times were reviewed. Twenty‐nine dogs met the inclusion criteria. Overall median survival time for dogs in the study was 234 days (range 12‐1698 days). Median survival for dogs with adenocarcinoma or carcinoma (n = 12) was 280 days, transitional cell carcinoma (n = 6) 163 days, squamous cell carcinoma, anaplastic carcinoma or undifferentiated carcinoma (n = 7) 59 days and all sarcomas (n = 4) 448 days. Adverse events were reported following 28% of treatments and 69% of dogs experienced at least one AE. Twenty four per cent of all dogs experienced grade 3 or 4 toxicities. The chemotherapy protocol was generally well tolerated. The study suggests potential benefit in the use of chemotherapy for dogs with adenocarcinoma, carcinoma and sarcoma.     

Spontaneous oral tumours in 18 rabbits (2005–2015)

This retrospective study of a series of 18 cases aimed to describe the clinical and pathological findings of oral tumours in rabbits, as there have been few reports detailing spontaneous oral tumours in this species. A total of 13 different tumour types were diagnosed: squamous cell carcinoma (three), ameloblastoma (two), fibrosarcoma (two), osteosarcoma (two), cementoma (one), complex odontoma (one), giant cell epulis (one), sarcoma (one), chondrosarcoma (one), trichoepithelioma (one), papilloma (one), malignant melanoma (one) and basal cell carcinoma (one). Odontogenic tumours were relatively common in this study as compared to the oral tumours typically identified in dogs and cats. The most common clinical sign in this study was feeding abnormalities. Surgical excision and radiation therapy were found to be effective in rabbits.     

Biological behaviour of canine mandibular osteosarcoma. A retrospective study of 50 cases (1999–2007)

The purpose of this retrospective study was to describe the biological behaviour of canine mandibular osteosarcoma (OSA) and to examine factors for their impact on metastasis‐free interval (MFI) and survival time (ST). Records from dogs treated with mandibulectomy for OSA (1999–2007) were reviewed. Archived tumour samples were evaluated for mitotic index (MI) and tumour grade. Fifty dogs were included, 21 received chemotherapy. Twenty‐nine dogs (58%) developed metastatic disease. The median MFI was 627 days, and median ST was 525 days. In univariate analysis MI > 40 was prognostic for decreased MFI and ST. Grade also influenced MFI and ST, with 5/21 (24%) dogs with grade II/III tumours metastasis‐free at one year versus 16/22 (72%) dogs with grade I tumours (P = 0.002); and 5/21 (24%) dogs with grade II/III tumours alive versus 17/22 (77%) dogs with grade I tumours (P = 0.001). In multivariate analysis, histological grade and adjuvant chemotherapy were prognostic for MFI and ST.     

Oesophageal leiomyosarcoma in dogs: surgical management and clinical outcome of four cases

Oesophageal leiomyosarcoma has yet to be reported in dogs. This retrospective case series describes the case management and clinical outcome of four dogs with oesophageal leiomyosarcoma treated by marginal excision alone. Histological features used to determine tumour grade included capsular invasion, percent necrosis, pleomorphism and mitotic rate. All tumours were designated grade 1 leiomyosarcoma. Excision of all grossly evident tumour tissue was achieved in two of the four cases; however, histopathologic evaluation showed tumour cells at the surgical margins in one of these two cases. Two dogs had grossly incomplete excision. Two dogs died from unrelated conditions, one 3 years and 5.5 months after surgery, the other at 65 days. One dog had persistent mega‐oesophagus and was lost to follow‐up 388 days after surgery and one dog is still alive (last follow‐up 405 days after surgery). Despite large tumour size and incomplete excision, surgical removal of low‐grade leiomyosarcomas can result in long‐term resolution of clinical signs.     

Soft tissue sarcoma in the dog – part 1: a current review

Soft tissue sarcomas are derived from tissues of mesenchymal origin. Although local recurrence following surgical resection is the characteristic challenge in their management, 40% dogs with high‐grade tumours may also develop metastatic disease, despite successful local control. Soft tissue sarcoma is a complex disease and there are many uncertainties regarding the biology and optimal clinical management. There are currently no diagnostic tests that can reliably predict the amount of surgical margin required for a particular tumour, so there can be a mismatch between treatment and disease. Historically, the tendency has been to always recommend wide excision margins but this is not fully supported by recent evidence. A selection bias for less aggressive soft tissue sarcomas in primary care practice can account for good outcomes that are achieved despite narrow surgical excision margins. On the other hand, inappropriately conservative treatment will adversely affect outcomes for patients with more aggressive disease. This review provides an update on the current understanding of management of canine soft tissue sarcomas.     

Soft tissue sarcomas and mast cell tumours in dogs; clinical behaviour and response to surgery

OBJECTIVE: To characterise the types of canine soft tissue sarcoma and mast cell tumour treated surgically at the University Veterinary Centre, Sydney. To evaluate the success of surgical treatment of these tumours and identify variables predictive of local recurrence and survival. To establish whether conclusions drawn from previous international studies are applicable to the University Veterinary Centre, Sydney, dog population and vice versa. DESIGN: Clinical presentation and results of surgical excision of 54 soft tissue sarcomas and 70 mast cell tumours affecting the trunk and limbs of dogs at the University Veterinary Centre, Sydney, between 1989 and 2001 were reviewed retrospectively. RESULTS: Cross-bred dogs and Rhodesian Ridgebacks were at significantly greater risk of developing soft tissue sarcomas, and Boxers, Australian Cattle Dogs and Staffordshire Bull Terriers were at significantly greater risk of developing mast cell tumours than other breeds. Fine needle aspiration biopsy yielded a correct diagnosis in 62.5% of soft tissue sarcomas and 96% of mast cell tumours. Local recurrence was encountered after surgical excision in 7.4% of soft tissue sarcomas and 7.3% of mast cell tumours. Metastasis occurred in 6% of soft tissue sarcomas and 12% of mast cell tumours. The most significant risk factors for local recurrence were contaminated surgical margins (soft tissue sarcomas) and histological grade (mast cell tumours). Due to the low number of animals experiencing metastasis, no conclusions could be drawn about significant risk factors. CONCLUSIONS: Aggressive surgical management of soft tissue sarcomas and mast cell tumours is associated with a low incidence of local recurrence. The type, location and behaviour of mast cell tumours and soft tissue sarcomas in the population of dogs presented to the University Veterinary Centre, Sydney are similar to those reported by others.     

Neoadjuvant and adjuvant chemotherapy combined with anatomical resection of feline injection‐site sarcoma: results in 21 cats

This study assesses the outcome of two combined treatment strategies for the treatment of feline injection‐site sarcoma (FISS). Twenty‐one cats with primary or recurrent FISS received 3 cycles of neoadjuvant chemotherapy with epirubicin (25 mg m^?2), then an anatomical resection of the entire muscle compartment containing the tumour was performed based on the findings of co‐axial imaging. Cats then received a further 3 cycles of adjuvant chemotherapy. Follow‐up was performed by telephone contact with a median follow‐up time of 1072 days. Three cats (14%) developed local tumour recurrence at days 264, 664 and 1573 after surgery. A median survival time could not be calculated as over 80% of the study population remained alive or were censored due to death from other causes. When compared to historical controls, the results of this study demonstrate superior rates of tumour‐free survival and disease‐free interval.     

The radiological features of non-osteogenic malignant tumours of bone in the appendicular skeleton of the dog: a review of thirty-four cases

The clinical features, sites of origin and radiological changes in 34 dogs with 38 histologically proven non-osteogenic malignant tumours of the appendicular skeleton are reported. The incidence of such tumours when compared with the number of osteosarcomas recorded during the same period is much higher than in previously reported series. A wide variety of tumour types was recorded, fibrosarcomas (nine cases), metastatic deposits (eight cases) and haemangiosarcomas (five cases) being the most common. No distinctive features could be related to histological type, but only one tumour in this group demonstrated radiological signs indistinguishable from those previously classified as characteristic of osteosarcoma (Gibbs, Denny & Kelly, 1984). Lung metastases were detected radiographically in approximately 15 per cent of cases. Of eight dogs treated, either by amputation or surgical excision, three are known to have survived without recurrence for more than two years.     

MEASUREMENT OF TUMOR HYPOXIA IN SPONTANEOUS CANINE SARCOMAS

We used positron emission tomography (PET) with [18F]fluoromisonidazole ([18F]FMISO) to study tumor hypoxia in six dogs with spontaneous sarcomas. The tumors were regarded as hypoxic if [18F]FMISO uptake exceeded normal tissue radioactivity by 40% (tumor/muscle ratio > 1.4) or if kinetic analysis indicated a positive [18F]FMISO tissue influx rate (Ki > 0) by a Patlak plot. Using these criteria, we found hypoxia in a fibrosarcoma grade II, an undifferentiated sarcoma, and an ostoeosarcoma, but not in a fibrosarcoma grade I, another osteosarcoma, and a myxosarcoma. In three animals, the tumor oxygen partial pressure (pO2) was also measured invasively using Eppendorf needle electrodes. In these cases, the Eppendorf measurements were confirmed by the [18F]FMISO PET results. In addition, [15O]H2O PET was performed in four dogs in order to assess tumor perfusion. Comparisons of the [18F]FMISO with [15O]H2O PET images in two cases showed that tumor hypoxia occurred in the tumor center with low perfusion, whereas perfusion was heterogeneous in a nonhypoxic tumor.     

Sarcoma development after radiotherapy in two dogs

Two dogs were treated with a hypofractionated course of radiotherapy following surgical excision of an intermediate grade mast cell tumour and a round cell tumour, respectively. Both dogs developed a sarcoma of the bone, within the irradiated site, several years after the initial radiotherapy treatment. Bone tumours arising within a previously irradiated area are well‐recognized late radiotherapy side‐effect in humans but have been reported infrequently in dogs. These are the first case reports to describe bone sarcomas in the appendicular skeleton at a site, which had been previously treated by a hypofractionated course of radiotherapy for an unrelated tumour.     

Outcome after repair of a sarcoma-related pathologic fracture in dogs: a Veterinary Society of Surgical Oncology Retrospective Study

Objective: To report outcome in dogs after internal fixation of a sarcoma‐related pathologic fracture of the appendicular skeleton. Study Design: Multi‐institutional case series. Animals: Dogs (n=16). Methods: Medical records of participating VSSO members were reviewed for dogs with pathologic fracture associated with a confirmed bone sarcoma of the appendicular skeleton repaired by external or internal fixation. Dogs were included if they had a histological diagnosis of osteosarcoma or sarcoma and excluded if they had radiation before fracture. Data collected were analyzed for signalment, fracture location, staging performed, method of fracture fixation, histopathology, adjunctive treatment and outcome. Results: Signalment and fracture location of 16 dogs that met the inclusion criteria was similar to dogs with appendicular OSA without fracture. One of 14 dogs had pulmonary metastasis and 3 of 5 dogs had bone metastasis. Bone plate or interlocking nail were used for repair in 12 dogs. Limb use immediately after surgery in 13 dogs was good (4), weight‐bearing but lame (7) and non‐weight bearing (2). Adjunctive therapy was administered in 5 dogs (chemotherapy, 3; radiation, 4; pamidronate, 3). Survival time ranged from 18 to 897 days; median survival was 166 days. Conclusions: Repair of pathologic fracture can result in palliation and prolonged survival.     

Do postvaccinal sarcomas occur in Australian cats ?

SUMMARY: A soft tissue sarcoma occurred in the interscapular area of a cat, 1 to 7 months after vaccination at that site. The vaccine contained inactivated feline panleucopaenia virus combined with modified live feline herpesvirus and calicrvirus. The tumour showed histological features of both fibrosarcoma and malignant fibrous histiocytoma. The tumour was observed to evolve from the site of a presumed postvaccinal granuloma. Local recurrence 6 weeks post excision necessitated more radical resection. Euthanasia was performed 2 years later when pleural effusion developed. The cause of effusion was not determined. There was no palpable evidence of local tumour regrowth at the time of euthanasia. A causal relationship between vaccination and sarcoma formation is considered based on the temporal association between the two events, the anatomical location of the tumour and histopathology consistent with postvaccinal sarcomas reported overseas. Six other vaccine site fibrosarcomas, potentially vaccine associated using the above criteria, are summarised.     

Incomplete surgery, local immunostimulation, and recurrence of some tumour types in dogs and cats

Histologically confirmed inadequate treatment resulted in a lower than expected recurrence percentage in dogs with haemangiopericytoma (38%) and mastocytoma (30%). Clinical suspicion of inadequate tumour treatment did not always correlate with the histologically assessed inadequacy, nor with the appearance of local recurrence. Local recurrence did not seem to be correlated with histological grade of malignancy and tumour size. Local injection of C. parvum vaccine did not result in a lower percentage of local recurrence or longer recurrence-free intervals in any of the three tumour groups (canine haemangiopericytoma, canine mastocytoma, feline mammary carcinoma). Nor was palliative local adjuvant injection of Cp successful in dogs and cats with soft tissue sarcomas or in dogs with gingival melanoma. Re-operation of locally recurrent tumour was successful in some dogs with haemangiopericytoma, in a few with mastocytoma, but not in cats with mammary carcinoma. A trend toward histological progression of recurrences and metastases, when compared with the primary tumours, was not evident. The possible reasons for the relatively low recurrence rate of some tumour types and for the failure of Cp-treatment are discussed.     

Establishment of a patient-derived xenograft mouse model of pleomorphic leiomyosarcoma

Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an appropriate human sarcoma animal model to accurately evaluate their efficacy, as well as the lack of an adequate technical protocol for efficient transplantation and engraftment of sarcoma specimens in patient-derived xenograft (PDX) models. Accordingly, in this study, we sought to identify the optimal type of sarcoma and develop a protocol for generating a PDX model. We characterized a PDX mouse model using histopathological and immunohistochemical analyses to determine whether it would show pathological characteristics similar to those of human sarcomas. We achieved engraftment of one of the 10 transplanted sarcoma specimens, the xenografted tumor of which exhibited massive proliferation. Histologically, the engrafted sarcoma foci resembled a primary tumor of pleomorphic leiomyosarcoma and maintained their histological structure in all passages. Moreover, immunohistochemical analysis revealed the expression of specific markers of differentiation to smooth muscle, which is consistent with the features of leiomyosarcoma. We thus demonstrated that our pleomorphic leiomyosarcoma PDX mouse model mimics at least one aspect of human sarcomas, and we believe that this model will facilitate the development of novel therapies for sarcomas.     

Feline injection site-associated sarcoma: Is it a reason to critically evaluate our vaccination policies?

Feline injection site-associated sarcoma (FISAS) or vaccination-associated sarcoma is a serious problem in cats because of the ethical and therapeutic consequences associated with the disease. The exact aetiology of FISAS is unclear; therefore, instituting preventative measures such as delaying or discontinuing vaccination schedules is questionable. This paper will give insights into the disease process, will attempt to answer the question, “what causes FISAS?”, and will discuss preventative measures to decrease the chance of occurrence.Tumours are in general uncommon in the cat, however, malignant tumours, such as sarcomas, occur relatively frequently. FISAS have stimulated interest because of their reported linkage to certain types of vaccine. FISASs are reported to have an incidence of 1–10 per 10,000 cats and often appear in conjunction with a traumatic incident (such as a vaccination). The tumour displays an extreme malignant biological behaviour, both being locally aggressive and metastasising in 25–70% of the cases. Although the pathology still remains unclear, an exaggerated inflammatory/granulomatous response seems to be the predisposing factor in the transformation to FISAS. A multi-step carcinogenesis model, including genetic, iatrogenic and local factors seems to be the most plausible explanation for the occurrence of the tumour. Multi-modal therapy, based on aggressive surgical removal of the tumour in combination with radiation and/or chemotherapy, is usually recommended but randomised clinical studies have not yet been performed to prove the efficacy of any of the modalities.The question of whether FISAS can be prevented by not injecting irritant products remains unanswered. No specific brands of vaccine, manufacturers or factors associated with vaccine administration have been significantly associated with FISAS in a multi-institutional and epidemiological study. Control and evaluation measures as recommended by the US-based taskforce include determination of risk groups, extending re-vaccination intervals, the use of single component products and the use of consistent, predetermined sites for vaccination.     

Oesophageal diverticulum formation in the dog

This paper briefly reviews previously recorded cases of (epiphrenic) oesophageal diverticula in the dog and describes the clinical and radiological findings in, nine further cases. Four of the nine cases also had a broncho–oesophageal fistula; clinical and histological evidence is presented to suggest that the lesions were congenital in at least five animals.     

Diagnosing appendicular osteosarcoma with ultrasound-guided fine-needle aspiration: 36 cases

OBJECTIVES: To determine the ability to obtain diagnostic cytology samples from appendicular bone lesions using ultrasound-guided needle aspirations. Secondary objectives were to compare cytological evaluations with histopathological results and to determine the utility of staining malignant mesenchymal cells for the presence of alkaline phosphatase. METHODS: Aspirations from 36 aggressive appendicular bone lesions with histological diagnoses were included in the study. Ultrasound was used to guide the needle to the medullary cavity or the adjacent soft tissue mass. The smears stained with Wright-Giemsa and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indoyl phosphate toluidine salt (NBT/BCIP) were examined. RESULTS: A diagnostic sample was obtained in 32 of the 36 cases. Of the 32 diagnostic samples, cytology indicated sarcoma, with a sensitivity of 97 per cent (confidence interval: 83 to 100 per cent) and a specificity of 100 per cent (confidence interval: 16 to 100 per cent). When a diagnosis of sarcoma was made on cytology, alkaline phosphatase staining indicated osteosarcoma, with a sensitivity of 100 per cent (confidence interval: 87 to 100 per cent). CLINICAL SIGNIFICANCE: The results of this study indicate that ultrasound-guided needle aspiration of aggressive bone lesions is a viable technique for identifying malignant mesenchymal cells and for diagnosing sarcomas. It is cost-effective and minimally invasive. Furthermore, identifying alkaline-phosphatase-negative malignant mesenchymal cells from a bone aspiration may rule out osteosarcoma, whereas alkaline-phosphatase-positive malignant mesenchymal cells are suggestive of osteosarcoma.     

Partial esophagectomy with single layer closure for treatment of esophageal sarcomas in 6 dogs

OBJECTIVE: To report partial esophagectomy (PE) as a treatment for esophageal sarcoma in dogs. STUDY DESIGN: Retrospective study (2000-2002). ANIMALS: Six dogs with caudal thoracic esophageal tumors. METHODS: Medical records of 6 dogs that had surgical removal of esophageal tumors were reviewed. Signalment, medical history, physical examination results, complete blood count, surgical procedure, tumor classification, postoperative treatment, and complications were retrieved. RESULTS: Esophageal masses were approached by thoracotomy and esophagotomy on the side opposite the mass, removed with 1 cm margins by full thickness excision, and the defects closed with a single layer of interrupted sutures. All dogs recovered rapidly without major complications. Tumors were fibrosarcoma (3 dogs), undifferentiated sarcoma (1), and osteosarcoma (2). Five dogs were administered doxorubicin chemotherapy after surgery. Good quality of life was observed postoperatively in 5 dogs until deterioration necessitated euthanasia; survival ranged from 2-16 months. The remaining dog was alive, 20 months after surgery. CONCLUSIONS: Partial esophagectomy and closure using 1 suture layer, was an effective, simple, and safe technique for removal of sarcomas of the distal thoracic esophagus. CLINICAL RELEVANCE: Removal of esophageal masses by partial esophagectomy can be used reliably as a method of esophageal surgery.