Pain characterization and response to palliative care in dogs with naturally-occurring appendicular osteosarcoma: An open label clinical trial.

This study aimed to characterize bone cancer pain (quantitative sensory testing (QST), stance asymmetry index, actimetry, scores of pain and quality of life (QoL)) in dogs with appendicular osteosarcoma (OSA), and to evaluate a stepwise palliative analgesic treatment. The pain profile of thirteen client-owned dogs with OSA was compared with seven healthy dogs. Dogs with OSA were then enrolled in a prospective, open-label, clinical trial. Outcome measures included: primary and secondary mechanical thresholds (MT), conditioned pain modulation (CPM), stance asymmetry index, actimetry (most and least active periods), visual analog scales and QoL. After baseline assessments, stepwise treatment comprised orally administered cimicoxib (2 mg/kg q 24h), amitriptyline (1-1.5 mg/kg q 24h) and gabapentin (10 mg/kg q 8h); re-evaluations were performed after 14 (D14), 21 (D21) and 28 (D28) days, respectively. Statistics used mixed linear models (α = 5%; one-sided). Centralized nociceptive sensitivity (primary and secondary MT, and dynamic allodynia) was recorded in OSA dogs. Healthy dogs had responsive CPM, but CPM was deficient in OSA dogs. Construct validity was observed for the QST protocol. Asymmetry index was significantly present in OSA dogs. The CPM improved significantly at D14. When compared with baseline (log mean ± SD: 4.1 ± 0.04), most active actimetry significantly improved at D14 (4.3 ± 0.04), D21 and D28 (4.2 ± 0.04 for both). When compared with baseline, least active actimetry significantly decreased after treatment at all time-points indicating improvement in night-time restlessness. No other significant treatment effect was observed. Except for tactile threshold and actimetry, all outcomes worsened when gabapentin was added to cimicoxib-amitriptyline. Dogs with bone cancer are affected by widespread somatosensory sensitivity characterized by peripheral and central sensitization and have a deficient inhibitory system. This severe pain is mostly refractory to palliative analgesic treatment, and the latter was only detected by specific and sensitive outcomes.

Postsurgical Outcome in Cats with Exocrine Pancreatic Carcinoma: Nine Cases (2007-2016).

Feline exocrine pancreatic carcinoma has been reported to be an aggressive tumor with a high metastatic rate and poor prognosis. Studies reporting long-term outcome of cats after surgical removal of solitary pancreatic carcinomas are rare, due to the uncommon diagnosis and paucity of cats who undergo treatment. In this study, nine cases of feline exocrine pancreatic carcinoma from seven academic and private practice veterinary hospitals were reviewed to examine the outcome in cats undergoing surgical removal of the mass. The median postsurgical survival time for the nine cats was 316.5 days (range, 25-964 days), with three cats alive at a median follow-up time of 309 days. This study demonstrates that surgical removal of pancreatic exocrine tumors in cats with localized disease can result in survival times of over 300 days.

Outcome and clinical, pathological, and immunohistochemical factors associated with prognosis for dogs with early-stage anal sac adenocarcinoma treated with surgery alone: 34 cases (2002-2013).

OBJECTIVE To determine survival time and metastatic rate for dogs with early-stage anal sac adenocarcinoma (ASACA) treated with surgery alone and assess whether specific clinical, pathological, or immunohistochemical factors were predictive of outcome for those dogs. DESIGN Retrospective case series. ANIMALS 34 dogs with early-stage, nonmetastatic ASACA that were treated with surgery only. PROCEDURES Medical record databases of 2 referral hospitals were searched to identify dogs examined between 2002 and 2013 that had a diagnosis of nonmetastatic ASACA that was < 3.2 cm at its largest diameter. Only dogs that received surgical treatment alone were included in the study. For each dog, information extracted from the medical record included signalment, clinical and diagnostic test findings, tumor characteristics, and outcome. When available, archived tumor specimens were histologically reviewed and tumor characteristics were described; Ki-67 and E-cadherin expressions were evaluated by use of immunohistochemical methods. Clinical, pathological, and immunohistochemical factors were assessed for associations with survival time and tumor recurrence and metastasis rates. RESULTS Median survival time was 1,237 days. Seven dogs had tumor recurrence and 9 dogs developed metastatic disease at a median of 354 and 589 days, respectively, after primary tumor removal. Cellular pleomorphism was positively associated with development of metastatic disease. No other factors evaluated were associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated dogs with early-stage nonmetastatic ASACA generally had a favorable outcome following surgical removal of the primary tumor alone. Routine rectal examination may be a simple and useful method for detection of dogs with early-stage ASACA.

Retrobulbar malignant peripheral nerve sheath tumor in a golden retriever dog: A challenging diagnosis.

A 9-year-old golden retriever dog was diagnosed with a left retrobulbar mass. Fine-needle aspirations and incisional biopsies resulted in discordant diagnoses: myxosarcoma/myxoma or rhadomyosarcoma, respectively. Immunohistochemistry following exenteration allowed definitive diagnosis of malignant peripheral nerve sheath tumor with fibromyxomatous differentiation. Fifteen weeks after surgery, an aggressive recurrence resulted in euthanasia.

Tumeur rétrobulbaire maligne des gaines nerveuses périphériques chez un Golden Retriever : un défi diagnostique. Une masse rétrobulbaire gauche a été diagnostiquée chez une Golden Retriever de 9 ans. Des aspirations à l'aiguille fine et des biopsies incisionnelles ont établi des diagnostics discordants : un myxosarcome/myxome ou un rhabdomyosarcome, respectivement. Suite à l'exentération, l'immunohistochimie a permis un diagnostic définitif de tumeur maligne des gaines nerveuses périphériques avec différenciation fibro-myxomateuse. Quinze semaines après la chirurgie, une récidive agressive a conduit à l'euthanasie de la chienne.(Traduit par les auteurs).

Presumptive primary pulmonary mast cell tumor in 2 dogs.

Two dogs were presented, each with a large solitary pulmonary mass, and cytology confirmed mast cell tumor (MCT) in each dog. One dog was euthanized following diagnosis. Thoracic computed tomography scan and exploratory thoracotomy of the second dog revealed a right pulmonary mass that would require a radical lung resection. The patient was euthanized and histopathology confirmed a poorly granulated MCT with characteristics suggestive of epitheliotropism, an uncommon finding with MCT. These represent the first reported cases of presumptive primary pulmonary MCT in dogs.

Mastocytome primaire pulmonaire présumé chez deux chiens. Deux chiens ont été présentés avec une volumineuse masse pulmonaire dont l'analyse cytopathologique confirma le diagnostic de mastocytome (MCT). L'un des chiens a été euthanasié suite au diagnostic. Un CT scan thoracique et une thoracotomie exploratrice du second chien ont révélé une masse pulmonaire droite nécessitant une résection pulmonaire radicale; le chien fut euthanasié. L'histopathologie a confirmé un MCT peu granulé avec des caractéristiques suggestives d'épithéliotropisme, une trouvaille inhabituelle lors de MCT. Il s'agit des premiers cas rapportés de MCT pulmonaires primaires présumés chez le chien.(Traduit par les auteurs).

Primary nodal hemangiosarcoma in four dogs.

CASE DESCRIPTION 4 dogs with a slow-growing mass in the cervical region were evaluated. CLINICAL FINDINGS All dogs had no clinical signs at the time of the evaluation. There was no apparent evidence of visceral metastases or other primary tumor based on available CT or MRI data for any dog. TREATMENT AND OUTCOME For each dog, surgery to remove the mass was performed. Histologic examination of the excised tissue revealed a completely excised grade 1 or 2 lymph node hemangiosarcoma. All dogs received adjuvant chemotherapy; 2 dogs underwent curative intent chemotherapy, 1 dog underwent metronomic treatment with cyclophosphamide, and 1 dog underwent metronomic treatment with chlorambucil. The survival time was 259 days in 1 dog; 3 dogs were still alive 615, 399, and 365 days after surgery. CLINICAL RELEVANCE Primary nodal hemangiosarcoma in dogs is a rare and, to the authors' knowledge, previously undescribed disease that appears to develop in the cervical lymph nodes as a slow-growing mass or masses. Surgical excision and adjunct treatment resulted in long survival times for 3 of the 4 dogs of the present report. Given the aggressive biologic behavior of hemangiosarcomas in other body locations, adjunct chemotherapy should be considered for affected dogs, although its role in the cases described in this report was unclear. Additional clinical information is required to further characterize the biologic behavior of this tumor type and determine the expected survival times and associated risk factors in dogs.

Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: a pilot study.

Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA.

Traitement adjuvant à la doxorubicine et au déracoxib pour l'angiosarcome splénique canin : étude pilote. L'angiosarcome canin est une tumeur hautement maligne pour laquelle la chimiothérapie standard a peu fait pour améliorer substantiellement la survie. La cyclooxygénase-2 (Cox-2) joue un rôle dans la formation, la croissance et la métastase des tumeurs et des inhibiteurs ont démontré des bienfaits thérapeutiques pour certains cancers canins. Dans cette étude prospective, 21 chiens ont reçu un traitement adjuvant combinant l'inhibiteur de la Cox-2 sélectif déracoxib avec la doxorubicine, après la splénectomie pour l'angiosarcome. La combinaison a été bien tolérée et seulement des toxicités gastro-intestinales et hématologiques de faible intensité ont été signalées. Une survie médiane globale de 150 jours (écart de 21 à 1506 jours) a été signalée. Même s'il n'y a pas eu de différence significative dans la survie si l'on se base sur le stade de la maladie, les chiens avec un angiosarcome de stade III (n = 11) ont eu une survie médiane de 149 jours, ce qui semble plus long que ce qui avait déjà été signalé. De nouvelles études sont justifiées afin d'évaluer le bienfait potentiel des inhibiteurs de la Cox-2 pour le traitement de l'angiosarcome canin.(Traduit par Isabelle Vallières).

Ulnar osteosarcoma in dogs: 30 cases (1992-2008).

OBJECTIVE: To examine the biological behavior of ulnar osteosarcoma and evaluate predictors of survival time in dogs. DESIGN: Retrospective case series. ANIMALS: 30 dogs with primary ulnar osteosarcoma. PROCEDURES: Medical records were reviewed. Variables recorded and examined to identify predictors of survival time were signalment, tumor location in the ulna, tumor length, serum alkaline phosphatase activity, surgery type, completeness of excision, tumor stage, tumor grade, histologic subtype, development of metastases, and use of chemotherapy. RESULTS: 30 cases were identified from 9 institutions. Eleven dogs were treated with partial ulnar ostectomy and 14 with amputation; in 5 dogs, a resection was not performed. Twenty-two dogs received chemotherapy. Median disease-free interval and survival time were 437 and 463 days, respectively. Negative prognostic factors for survival time determined via univariate analyses were histologic subtype and development of lung metastases. Telangiectatic or telangiectatic-mixed subtype (n = 5) was the only negative prognostic factor identified via multivariate analysis (median survival time, 208 days). Dogs with telangiectatic subtype were 6.99 times as likely to die of the disease. CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis for ulnar osteosarcoma in this population was no worse and may have been better than the prognosis for dogs with osteosarcoma involving other appendicular sites. Partial ulnar ostectomy was associated with a low complication rate and good to excellent function and did not compromise survival time. Telangiectatic or telangiectatic-mixed histologic subtype was a negative prognostic factor for survival time. The efficacy of chemotherapy requires further evaluation.

Surgery and radiation therapy for extramedullary plasmacytoma of the penile mucosa in a dog.

A 10-year-old neutered male Italian greyhound dog was presented because it had a penile plasmacytoma. Surgery followed by radiation therapy resulted in local control and survival for 1688 days. This is the first report of surgery and definitive radiation therapy for curative intent therapy of extramedullary penile plasmacytoma in a dog.A 10-year-old neutered male Italian greyhound dog was presented because it had a penile plasmacytoma. Surgery followed by radiation therapy resulted in local control and survival for 1688 days. This is the first report of surgery and definitive radiation therapy for curative intent therapy of extramedullary penile plasmacytoma in a dog.

RésuméPlasmocytome extramédullaire du pénis traité avec chirurgie et radiothérapie chez un chien. Un chien petit lévrier italien mâle castré âgé de 10 ans fut présenté suite à un diagnostic de plasmocytome extramédullaire du pénis. La chirurgie, suivie d'une radiothérapie, permit un contrôle local et une survie de plus de 1688 jours. Il s'agit du premier cas rapporté de plasmocytome extramédullaire du pénis chez un chien traité en plurimodalité avec chirurgie et radiothérapie définitive.(Traduit par les auteurs).

Biological behavior of oral and perioral mast cell tumors in dogs: 44 cases (1996-2006).

OBJECTIVE: To describe clinical outcome of dogs with mast cell tumors (MCTs) arising from the oral mucosa, oral mucocutaneous junction, or perioral region of the muzzle and evaluate the potential role of the chemokine receptor type 7 (CCR7) in the biological behavior of these tumors. DESIGN: Retrospective case series. ANIMALS: 44 dogs with MCTs of the oral mucosa (n=14), oral mucocutaneous junction (19), or perioral region of the muzzle (11). PROCEDURES: Medical records were reviewed for information on signalment, regional metastasis, treatments, cause of death, and survival time. Twenty of the 44 cases had stored histologic samples available for immunohistochemical staining for CCR7 RESULTS: For all dogs, median survival time was 52 months. Twenty-six (59%) dogs had regional lymph node metastasis on admission. Median survival time for dogs with lymph node metastasis was 14 months, whereas median survival time was not reached for dogs without lymph node metastasis. Intensity of staining for CCR7 was not significantly associated with the presence of regional lymph node metastasis or survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in dogs with MCTs arising from the oral mucosa, oral mucocutaneous junction, or perioral region of the muzzle, the presence of regional lymph node metastasis at the time of diagnosis was a negative prognostic factor. However, prolonged survival times could be achieved with treatment. In addition, CCR7 expression in the primary tumor was not significantly associated with the presence of regional lymph node metastasis or survival time.

Delayed diagnosis of fungal osteomyelitis with early scintigraphic lesions in a dog.

A 4-year-old neutered male golden retriever was diagnosed with osseous blastomycosis of the distal left forelimb by means of radiographs and histopathology. Presumptive bacterial pneumonia and left forelimb lameness had been diagnosed 2 y previously, at which time bone scintigraphy revealed increased uptake in the distal left forelimb, but radiographs showed no detectable lesion. Though not specific, bone scintigraphy appears more sensitive than radiography in identifying early lesions of fungal osteomyelitis in dogs.

In vitro cyclooxygenase-2 protein expression and enzymatic activity in neoplastic cells.

BACKGROUND: Cyclooxygenase-2 (COX-2) and its principle enzymatic metabolite, prostaglandin E2 (PGE2), are implicated in cancer progression. Based upon immunohistochemical (IHC) evidence that several tumor types in animals overexpress COX-2 protein, COX-2 inhibitors are used as anticancer agents in dogs and cats. HYPOTHESIS: IHC is inaccurate for assessing tumor-associated COX-2 protein and enzymatic activity. METHODS: Five mammalian cell lines were assessed for COX-2 protein expression by IHC and Western blot analysis (WB), and functional COX-2 activity was based upon PGE2 production. RESULTS: Detection of COX-2 protein by IHC and WB were in agreement in 4 of 5 cell lines. In 1 cell line that lacked COX-2 gene transcription because of promoter hypermethylation (HCT-116), IHC produced false-positive staining for COX-2 protein expression. Functional COX-2 enzymatic activity was dissociated from relative IHC-based COX-2 protein expression in 2 cell lines (RPMI 2650 and SCCF1). The RPMI 2650 cell line demonstrated strong COX-2 protein expression but minimal PGE2 production. CONCLUSIONS AND CLINICAL IMPORTANCE: Western blot is more accurate than IHC for the detection of COX-2 protein in the cell lines studied. Furthermore, the semiquantitative identification of COX-2 protein by IHC or WB does not necessarily correlate with enzymatic activity. Based upon the potential inaccuracy of IHC and dissociation of COX-2 protein expression from enzymatic activity, the practice of instituting treatment of tumors with COX-2 inhibitors based solely on IHC results should be reconsidered.

Single-agent pamidronate for palliative therapy of canine appendicular osteosarcoma bone pain.

BACKGROUND: Canine appendicular osteosarcoma (OSA) causes focal bone destruction, leading to chronic pain and reduced quality-of-life scores. Drugs that inhibit pathologic osteolysis might provide additional treatment options for managing cancer-induced bone pain. Aminobisphosphonates induce osteoclast apoptosis, thereby reducing pain associated with malignant osteolysis in human patients with cancer. HYPOTHESIS: Treatment of dogs with pamidronate administered intravenously will alleviate bone pain and reduce pathologic bone turnover associated with appendicular OSA in dogs. ANIMALS: Forty-three dogs with naturally occurring appendicular OSA administered pamidronate intravenously. METHODS: Prospective study. Therapeutic responses in dogs treated with pamidronate administered intravenously and nonsteroidal anti-inflammatory drugs (NSAID) were evaluated by using a numerical cumulative pain index score (CPIS), and by quantifying urine N-telopeptide (NTx) excretion and relative primary tumor bone mineral density (rBMD) assessed with dual energy x-ray absorptiometry. In addition, variables, including pamidronate dose, skeletal mass, baseline and change for CPIS, urine NTx and rBMD during treatment, and baseline tumor volume and radiographic pattern were compared between dogs clinically responsive and nonresponsive to pamidronate therapy. RESULTS: Twelve of 43 dogs (28%) had pain alleviation for >4 months, lasting a median of 231 days. Changes in CPIS and rBMD during treatment were statistically different between responders and nonresponders (P = .046 and .03, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Substantiated by reductions in CPIS and increases in rBMD, single-agent pamidronate administered intravenously with NSAID therapy relieves pain and diminishes pathologic bone turnover associated with appendicular OSA in a subset of dogs.

Expression of receptor activator of nuclear factor kappa-B ligand (RANKL) in neoplasms of dogs and cats.

BACKGROUND: Receptor activator of nuclear factor kappa-B (RANK), RANK-ligand (RANKL), and the soluble decoy receptor osteoprotegerin (OPG) form a key axis modulating osteoclastogenesis. In health, RANKL-expressing bone stromal cells and osteoblasts activate osteoclasts through RANK ligation, resulting in homeostatic bone resorption. Skeletal tumors of dogs and cats, whether primary or metastatic, may express RANKL and directly induce malignant osteolysis. HYPOTHESIS: Bone malignancies of dogs and cats may express RANKL, thereby contributing to pathologic bone resorption and pain. Furthermore, relative RANKL expression in bone tumors may correlate with radiographic characteristics of bone pathology. ANIMALS: Forty-two dogs and 6 cats with spontaneously-occurring tumors involving bones or soft tissues were evaluated. METHODS: A polyclonal anti-human RANKL antibody was validated for use in canine and feline cells by flow cytometry and immunocytochemistry. Fifty cytologic specimens were collected from bone and soft tissue tumors of 48 tumor-bearing animals and assessed for RANKL expression. In 15 canine osteosarcoma (OSA) samples, relative RANKL expression was correlated with radiographic characteristics of bone pathology. RESULTS: Expression of RANKL by neoplastic cells was identified in 32/44 canine and 5/6 feline tumor samples. In 15 dogs with OSA, relative RANKL expression did not correlate with either radiographic osteolysis or bone mineral density as assessed by dual energy x-ray absorptiometry. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs and cats, tumors classically involving bone and causing pain, often may express RANKL. Confirming RANKL expression in tumors is a necessary step toward the rational institution of novel therapies targeting malignant osteolysis via RANKL antagonism.

Primary orbital melanoma without ocular involvement in a Balinese cat.

A 6.5-year-old spayed female Balinese cat was diagnosed with a large and locally invasive primary orbital melanoma, without ocular involvement or detectable metastatic disease. Advanced imaging and immunohistochemical studies helped in obtaining the diagnosis. Because of advanced unresectable disease and ensuing poor quality of life, the cat was euthanized.