HES1, a target of Notch signaling, is elevated in canine osteosarcoma, but reduced in the most aggressive tumors.

BACKGROUND: Hairy and enhancer of split 1 (HES1), a basic helix-loop-helix transcriptional repressor, is a downstream target of Notch signaling. Notch signaling and HES1 expression have been linked to growth and survival in a variety of human cancer types and have been associated with increased metastasis and invasiveness in human osteosarcoma cell lines. Osteosarcoma (OSA) is an aggressive cancer demonstrating both high metastatic rate and chemotherapeutic resistance. The current study examined expression of Notch signaling mediators in primary canine OSA tumors and canine and human osteosarcoma cell lines to assess their role in OSA development and progression. RESULTS: Reverse transcriptase - quantitative PCR (RT-qPCR) was utilized to quantify HES1, HEY1, NOTCH1 and NOTCH2 gene expression in matched tumor and normal metaphyseal bone samples taken from dogs treated for appendicular OSA at the Colorado State University Veterinary Teaching Hospital. Gene expression was also assessed in tumors from dogs with a disease free interval (DFI) of <100 days compared to those with a DFI > 300 days following treatment with surgical amputation followed by standard chemotherapy. Immunohistochemistry was performed to confirm expression of HES1. Data from RT-qPCR and immunohistochemical (IHC) experiments were analyzed using REST2009 software and survival analysis based on IHC expression employed the Kaplan-Meier method and log rank analysis. Unbiased clustered images were generated from gene array analysis data for Notch/HES1 associated genes. Gene array analysis of Notch/HES1 associated genes suggested alterations in the Notch signaling pathway may contribute to the development of canine OSA. HES1 mRNA expression was elevated in tumor samples relative to normal bone, but decreased in tumor samples from dogs with a DFI < 100 days relative to those with a DFI > 300 days. NOTCH2 and HEY1 mRNA expression was also elevated in tumors relative to normal bone, but was not differentially expressed between the DFI tumor groups. Survival analysis confirmed an association between decreased HES1 immunosignal and shorter DFI. CONCLUSIONS: Our findings suggest that activation of Notch signaling occurs and may contribute to the development of canine OSA. However, association of low HES1 expression and shorter DFI suggests that mechanisms that do not alter HES1 expression may drive the most aggressive tumors.

Adrenocortical carcinoma in a dog with incomplete excision managed long-term with metastasectomy alone.

A 10 yr old bichon frise presented with a 3 mo history of polyuria, polydipsia, and hind limb weakness. Serum biochemistry revealed persistent hypokalemia. A left adrenal gland mass with right adrenal atrophy was detected ultrasonographically. Basal serum cortisol concentration was at the low end of normal (30 nmol/L; reference range, 30-140 nmol/L) and adrenocorticotropic hormone (ACTH)-stimulated cortisol concentration was low (199 nmol/L; reference range, 220-470 nmol/L). Basal serum 17-α-OH progesterone concentration was also low (0.03 ng/mL; reference range, 0.06-0.30 ng/mL), but the aldosterone concentration 2 hr after the ACTH stimulation was elevated (> 3,000 pmol/L; reference range, 197-2,103 pmol/L). A left adrenalectomy and nephrectomy were performed. Histopathology revealed an adrenocortical zona glomerulosa carcinoma. Surgical excision was considered incomplete; however, clinical signs resolved. Two years later, basal and ACTH-stimulated aldosterone concentrations were elevated. Computed tomography demonstrated a mass effect in the liver. The left lateral and left medial hepatic lobes were removed. Histopathology confirmed metastatic endocrine carcinoma. The patient was stable 1,353 days postsurgically (when this report was prepared). This is the first case report of a metastatic adrenal carcinoma that was successfully managed surgically for > 3 yr.

Use of a Dacron shape-memory intravascular coil to achieve slow, progressive occlusion of the jugular vein in dogs.

OBJECTIVE: To investigate the ability of shape memory Dacron polymer vascular coils to induce the complete, gradual occlusion of the canine jugular vein. STUDY DESIGN: Observational pilot study. ANIMALS: Nine purpose-bred dogs. METHODS: Eighteen coils were deployed in nine dogs using fluoroscopic-guided percutaneous transvenous coil implantation. Individual coil formulations varied around a Dacron polymer base. Jugular vein diameter, percent vessel occlusion, and thrombus echogenicity were monitored at weekly intervals using ultrasonography. Affected jugular veins were harvested at 6 weeks post-implantation and histopathological analysis was performed to assess adventitial fibrosis, intimal layer thickening, and inflammation. RESULTS: Ten coils migrated from the jugular veins to the pulmonary vasculature within 0-2 weeks following implantation. Three jugular veins achieved at least 90% occlusion at six weeks. Histopathology of these jugular veins revealed marked perivascular thickening and fibrovascular proliferation, increased infiltration of macrophages, neutrophils and lymphocytes, and abundant fibroplasia. CONCLUSIONS: Complete, gradual occlusion of a jugular vein was achieved in three dogs. Significant vessel wall reaction and inflammation can induce gradual vessel occlusion when a Dacron coil remains implanted within the jugular vein. Dacron polymer coils could be a feasible treatment option for the gradual occlusion of congenital portosystemic shunts in dogs using minimally invasive, percutaneous transvenous implantation.

Evaluation of novel serological markers and autoantibodies in dogs with inflammatory bowel disease.

BACKGROUND: The use of serological markers to diagnose inflammatory bowel disease (IBD) in humans is well-established. Because of the frequency of IBD in dogs and resources required for its diagnosis with current methods, new approaches are desired. OBJECTIVE: The goal is to evaluate novel serologic markers to differentiate clinical cohorts in dogs with gastrointestinal (GI) disease and assess their potential to develop a serum-based IBD diagnostic test. ANIMALS: Seventy dogs diagnosed with biopsy-confirmed IBD, 23 dogs with non-IBD predominantly acute GI diseases, and 58 normal dogs. METHODS: Prospective control study. ELISA methods were developed to detect autoantibodies to polymorphonuclear leukocytes (APMNA) and calprotectin (ACNA), antibodies against gliadins (AGA), microbial outer membrane porin C (ACA), and flagellins (AFA) isolated from diseased dogs based on clinical and histopathological scoring. RESULTS: IBD dogs displayed a 39%-76% prevalence of seropositivity against selected serologic markers that markedly decreased to 0%-13% in non-IBD and normal dogs. ROC analysis showed statistical significance in differentiating the cohorts, with seropositivity against OmpC being the highest single performance marker. The combination of markers such as OmpC and APMNA reached specificities of 93%-99% and 79%-98% and sensitivities of 76%-97% and 66%-86% when comparing IBD versus normal cohorts and non-IBD cohorts, respectively. CONCLUSION AND CLINICAL IMPORTANCE: Seropositivity of canine immunoglobulins A against selected serologic markers in dogs appears promising in the detection and differentiation of IBD versus other acute GI conditions. Among them, antibody reactivity to Escherichia coli OmpC and canine autoantibodies against polymorphonuclear leukocytes displayed the highest single marker discriminating performance.

Alimentary-associated carcinomas in five Vietnamese potbellied pigs.

CASE DESCRIPTION: 5 Vietnamese potbellied pigs were evaluated for abdominal distress that had not responded to medical treatment (4 pigs) or a draining tract of the cranial abdomen of unknown duration (1 pig). CLINICAL FINDINGS: Clinical signs in the pigs included anorexia, vomiting, and constipation. Physical examination revealed a palpable abdominal mass in all pigs. Radiography revealed distended loops of small intestine in 2 pigs. TREATMENT AND OUTCOME: 3 pigs were treated successfully with wide-margin excision of the abdominal masses, and 2 were euthanized. Primary tumors were diagnosed at necropsy or through histologic evaluation of biopsy specimens obtained during surgery. Types of tumor included cholangiocellular carcinoma, transmural gastric carcinoma, small intestinal adenocarcinoma, metastatic hepatocellular carcinoma, and carcinoma. The tumors involved the stomach, small intestine, spiral colon, liver, and gall bladder. All 3 surgically treated pigs survived at least 9 months after surgery. CLINICAL RELEVANCE: Although rare, neoplasia of the alimentary system should be considered among the differential diagnoses for potbellied pigs with signs of abdominal distress. Wide-margin excision of the neoplastic tissue may result in a good outcome in affected pigs.

Prognosis for acute nontraumatic hemoperitoneum in the dog: a retrospective analysis of 60 cases (2003-2006).

The complete medical records of 60 dogs with hemoabdomen were reviewed. All dogs underwent exploratory laparotomy and had a diagnosis established by a veterinary pathologist. Final diagnoses were hemangiosarcoma in 38 (63.3%) dogs, splenic hematoma in 16 (26.6%) dogs, splenic torsion in three (5%) dogs, hepatocellular carcinoma in two (3.3%) dogs, and carcinomatosis in one (1.6%) dog. Twenty-four (63.1%) dogs with hemangiosarcoma, 14 (87.5%) dogs with splenic hematoma, three (100%) dogs with splenic torsion, and two (100%) dogs with hepatocellular carcinoma were discharged from the hospital. Dogs with hemangiosarcoma were given a poor prognosis, while dogs with splenic hematoma, splenic torsion, and hepatocellular carcinoma were given a fair to good prognosis.

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

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

Apocrine gland anal sac adenocarcinoma in cats: 30 cases (1994-2015).

OBJECTIVE To describe the signalment, clinical signs, biological behavior, and outcome for cats with apocrine gland anal sac adenocarcinoma (AGASACA) that underwent surgical excision. DESIGN Retrospective case series. ANIMALS 30 client-owned cats. PROCEDURES Databases of 13 Veterinary Society of Surgical Oncology member-affiliated institutions were searched for records of cats with a histologic diagnosis of AGASACA that underwent tumor excision. For each cat, information regarding signalment, clinical signs, diagnostic test results, treatment, and outcome was extracted from the medical record. The Kaplan-Meier method was used to determine median time to local recurrence (TLR), disease-free interval (DFI), and survival time. Cox regression was used to identify factors associated with TLR, DFI, and survival time. RESULTS Perineal ulceration or discharge was the most common clinical sign in affected cats. Eleven cats developed local recurrence at a median of 96 days after AGASACA excision. Incomplete tumor margins and a high nuclear pleomorphic score were risk factors for local recurrence. Nuclear pleomorphic score was negatively associated with DFI. Local recurrence and a high nuclear pleomorphic score were risk factors for death. Median DFI and survival time were 234 and 260 days, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, in cats, perineal ulceration or discharge should raise suspicion of AGASACA and prompt rectal and anal sac examinations. Local recurrence was the most common life-limiting event in cats that underwent surgery for treatment of AGASACA, suggesting that wide margins should be obtained whenever possible during AGASACA excision. Efficacy of chemotherapy and radiation therapy for treatment of cats with AGASACA requires further investigation. (J Am Vet Med Assoc 2019;254:716-722).

Equine giant cell tumor of soft parts: a series of 21 cases (2000-2007).

In horses, giant-cell tumors of soft parts are rare neoplasms, with the majority of reported cases occurring within the hind limb muscles and soft tissues in older horses. The following article documents 21 cases of equine giant-cell tumors of soft parts clinically examined within the state of Colorado from 2000 to 2007. The majority of cases occurred in male horses aged 10 years or older. Nine (43%) arose within the hind limbs. Key histologic features included numerous multinucleated giant cells and hemosiderin-laden macrophages admixed with a spindle-cell proliferation. The majority demonstrated liposarcomatous change, variable areas of necrosis and hemorrhage, and an intermediate number of mitotic figures. Immunohistochemical results demonstrated 2 distinct cell populations: vimentin-expressing neoplastic mesenchymal cells and CD18 (histiocytic marker) expressing multinucleated giant cells. These results suggest a mesenchymal origin of the neoplasm with possible recruitment of the secondary histiocytic population. Surgical excision was attempted in the majority of horses and was considered clinically complete. A recurrence of the neoplasm was documented in 1 horse and 1 mule. In 18 horses, surgical excision, regardless of margin integrity, appeared successful with no recurrence of disease documented. Unfortunately, 10 of 21 horses were lost to follow-up within approximately 3 months of surgery. Of the 11 remaining horses that were available for follow-up evaluation, there has been no evidence of metastasis. A larger case series with more controlled follow-up is necessary to evaluate malignant potential and the importance of complete surgical excision.

Histologic examination of hepatic biopsy samples as a prognostic indicator in dogs undergoing surgical correction of congenital portosystemic shunts: 64 cases (1997-2005).

OBJECTIVE: To determine whether results of histologic examination of hepatic biopsy samples could be used as an indicator of survival time in dogs that underwent surgical correction of a congenital portosystemic shunt (PSS). DESIGN: Retrospective case series. ANIMALS: 64 dogs that underwent exploratory laparotomy for an extrahepatic (n = 39) or intrahepatic (25) congenital PSS. PROCEDURES: All H&E-stained histologic slides of hepatic biopsy samples obtained at the time of surgery were reviewed by a single individual, and severity of histologic abnormalities (ie, arteriolar hyperplasia, biliary hyperplasia, fibrosis, cell swelling, lipidosis, lymphoplasmacytic cholangiohepatitis, suppurative cholangiohepatitis, lipid granulomas, and dilated sinusoids) was graded. A Cox proportional hazards regression model was used to determine whether each histologic feature was associated with survival time. RESULTS: Median follow-up time was 35.7 months, and median survival time was 50.6 months. Thirty-eight dogs were alive at the time of final follow-up; 15 had died of causes associated with the PSS, including 4 that died immediately after surgery; 3 had died of unrelated causes; and 8 were lost to follow-up. None of the histologic features examined were significantly associated with survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that results of histologic examination of hepatic biopsy samples obtained at the time of surgery cannot be used to predict long-term outcome in dogs undergoing surgical correction of a PSS.

Nasopharyngeal turbinates in brachycephalic dogs and cats.

This retrospective study reports the presence and incidence of nasal turbinates in the nasopharynx (nasopharyngeal turbinates) in a population of brachycephalic dogs and cats exhibiting signs of upper respiratory disease. Medical records were reviewed for 53 brachycephalic dogs and 10 brachycephalic cats undergoing upper airway endoscopy. Nasopharyngeal turbinates were identified in 21% of brachycephalic animals, including 21% of dogs and 20% of cats. Pugs accounted for 32% of all dogs in the study population and 82% of dogs with nasopharyngeal turbinates. The presence of nasopharyngeal turbinates may play a role in upper airway obstruction in the brachycephalic airway syndrome.

Safety of an Oncolytic Myxoma Virus in Dogs with Soft Tissue Sarcoma.

Many oncolytic viruses that are efficacious in murine cancer models are ineffective in humans. The outcomes of oncolytic virus treatment in dogs with spontaneous tumors may better predict human cancer response and improve treatment options for dogs with cancer. The objectives of this study were to evaluate the safety of treatment with myxoma virus lacking the serp2 gene (MYXVΔserp2) and determine its immunogenicity in dogs. To achieve these objectives, dogs with spontaneous soft tissue sarcomas were treated with MYXVΔserp2 intratumorally (n = 5) or post-operatively (n = 5). In dogs treated intratumorally, clinical scores were recorded and tumor biopsies and swabs (from the mouth and virus injection site) were analyzed for viral DNA at multiple time-points. In all dogs, blood, urine, and feces were frequently collected to evaluate organ function, virus distribution, and immune response. No detrimental effects of MYXVΔserp2 treatment were observed in any canine cancer patients. No clinically significant changes in complete blood profiles, serum chemistry analyses, or urinalyses were measured. Viral DNA was isolated from one tumor swab, but viral dissemination was not observed. Anti-MYXV antibodies were occasionally detected. These findings provide needed safety information to advance clinical trials using MYXVΔserp2 to treat patients with cancer.

Dedifferentiated Chondrosarcoma in the Dog and Cat: A Case Series and Review of the Literature.

This retrospective case series describes seven dogs and one cat diagnosed with dedifferentiated chondrosarcoma, an uncommon, aggressive variant of chondrosarcoma. The purpose of the study is to describe clinical, imaging, and histopathological findings of this tumor. Medical records and the diagnostic laboratory database at Colorado State University from 2000 to 2015 were reviewed and complete medical records were available for the eight animals in this report. Similar to what has been reported in people, poor long-term survival and high metastatic rate, particularly to the lungs, was observed in our case series. A bimorphic pattern on imaging (radiographs, computed tomography, and MRI) consisting of mineralized and nonmineralized areas was seen mirroring the high-grade sarcomatous component adjacent to a low-grade chondroid component seen histopathologically. A review of the human literature including suspected etiology, imaging findings, histopathology, and survival times with various treatment options is presented. This article describes the first reported cases of dedifferentiated chondrosarcoma in the veterinary literature. Early accurate recognition could lead to treatment plans tailored to this variant.

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High-risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting. OBJECTIVES: To review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value. ANIMALS: Twenty-seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib. METHODS: Retrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs. RESULTS: Five of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression-free interval (PFI) in dogs with gross disease was 110 weeks (range, 36-155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9-257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib-treated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Biological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib-treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.

Agreement among surgical pathologists evaluating routine histologic sections of digits amputated from cats and dogs.

Agreement among pathologists interpreting histologic specimens is an area of interest within human pathology, but little work in this area has been reported in the veterinary literature. Agreement among pathologists evaluating routine histologic sections of amputated digits from cats and dogs submitted to multiple diagnostic centers was examined. Histologic sections from surgical specimens were reviewed in a blinded fashion by two pathologists, and a comparison to the original diagnosis, as stated in the diagnostic report, was recorded. A total of 513 cases were reviewed, and complete agreement was reached in 409 (79.7%). Of the 104 instances of disagreement, 77 (74.0%) were considered to be of clinical significance. The diagnosis of keratoacanthoma was disagreed with in 19 of 21 diagnoses (90.4%). No other individual diagnosis was similarly disputed. The overall level of disagreement is large and is similar to that reported in human pathology and suggests that further study of this issue would be useful in veterinary pathology.

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

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

A natural case of chronic wasting disease in a free-ranging moose (Alces alces shirasi).

Chronic wasting disease (CWD) was diagnosed in a free-ranging moose (Alces alces shirasi) killed by a hunter in Jackson County, Colorado, USA, in September 2005. The diagnosis was based upon immunohistochemistry (IHC) demonstrating the presence of accumulations of CWD-associated prion protein (PrP(CWD)) in tissue sections of medulla oblongata at the level of the obex (dorsal motor nucleus of the vagus) and in retropharyngeal lymph node (RPLN); additional testing by IHC revealed deposits of PrP(CWD) in multiple sections of medulla oblongata and cervical spinal cord as well as palatine tonsil and submandibular lymph node tissues. Western blot confirmed the presence of PrP(CWD) in RPLN and tonsil tissue. The PrP(CWD) also was detected via enzyme-linked immunosorbent assay of RPLN tissue. Spongiform encephalopathy was observed in sections of the brainstem and cervical spinal cord, although no clinical signs were noted by the hunter who killed the animal. The affected moose was homozygous for methionine at codon 209 of the prion protein coding region. In October 2006, two additional free-ranging moose were diagnosed with CWD. Epidemiology and implications of CWD in moose remain to be determined.

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

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

Malignant collision tumors in two dogs.

CASE DESCRIPTION A 13-year-old Labrador Retriever with a 4-cm-diameter ulcerated perianal mass and a 12-year-old Golden Retriever with a 5-cm-diameter ulcerated caudolateral abdominal mass were brought to a referral oncology practice for evaluation of the dermal masses. Both masses were resected with wide margins without reported postoperative complications. For both dogs, a diagnosis of collision tumor was made. The database of the Veterinary Diagnostic Laboratories at Colorado State University was searched for other examples of collision tumors in dogs. CLINICAL FINDINGS Histologic assessment of the masses revealed collision tumors in both patients. The perianal mass was diagnosed as a perianal gland carcinoma with adjacent hemangiosarcoma. The flank mass was diagnosed as a fibrosarcoma with an adjacent mast cell tumor. The university database search of sample submissions in 2008 through 2014 for the keywords collision, admixed, or adjacent yielded 37 additional cases of dogs with malignant nontesticular collision tumors. TREATMENT AND OUTCOME Both dogs were treated with surgery alone and received no adjunctive treatments. Both tumors were completely excised. There was no evidence of either local tumor recurrence or metastasis in the Labrador Retriever and the Golden Retriever at 1,009 and 433 days after surgery, respectively. CLINICAL RELEVANCE Collision tumors are rare, and there is minimal information regarding treatment recommendations and outcome for animals with collision tumors. On the basis of the 2 cases described in this report, the outcome associated with treatment of collision tumors may be similar to the expected outcome for treatment of any of the individual tumor types in dogs.

Relation between pO2, 31P magnetic resonance spectroscopy parameters and treatment outcome in patients with high-grade soft tissue sarcomas treated with thermoradiotherapy.

PURPOSE: In a prior study, the combination of (31)P magnetic resonance spectroscopy (MRS)-based intracellular pH (pHi) and T2 relaxation time was highly predictive of the pathologic complete response (pCR) rate in a small series of patients with soft tissue sarcomas (STSs) treated with thermoradiotherapy. Changes in the magnetic resonance metabolite ratios and pO(2) were related to the pCR rate. Hypoxia also correlated with a greater likelihood for the development of metastases. Because of the limited number of patients in the prior series, we initiated this study to determine whether the prior observations were repeatable and whether (31)P MRS lipid-related resonances were related to a propensity for metastasis. METHODS AND MATERIALS: Patients with high-grade STSs were enrolled in an institutional review board-approved Phase II thermoradiotherapy trial. All tumors received daily external beam radiotherapy (1.8-2.0 Gy, five times weekly) to a total dose of 30-50 Gy. Hyperthermia followed radiotherapy by <1 h and was given two times weekly. Tumors were resected 4-6 weeks after radiotherapy completion. The MRS/MRI parameters included (31)P metabolite ratios, pHi, and T2 relaxation time. The median pO(2) and hypoxic fraction were determined using pO(2) histography. Comparisons between experimental endpoints and the pCR rate and metastasis-free and overall survival were made. RESULTS: Of 35 patients, 21 and 28 had reportable pretreatment MRS/MRI and pO(2) data, respectively. The cutpoints for a previously tested receiver operating curve for a pCR were T2 = 100 and pHi = 7.3. In the current series, few tumors fell below the cutpoints so validation was not possible. The phosphodiester (PDE)/inorganic phosphate (Pi) ratio and hypoxic fraction correlated inversely with the pCR rate in the current series (Spearman correlation coefficient -0.51, p = 0.017; odds ratio of percentage of necrosis > or =95% = 0.01 for a 1% increase in the hypoxic fraction; Wald p = 0.036). The pretreatment phosphomonoester (PME)/Pi ratio also correlated inversely with the pCR rate (odds ratio of percentage of necrosis > or =95% = 0.06 for pretreatment PME/Pi ratio >0.8 vs. < or =0.8, Wald p = 0.023). The pretreatment PME/PDE ratio correlated strongly with metastasis-free survival and overall survival (p = 0.012 and hazard ratio = 5.8, and p = 0.038 and hazard ratio = 6.75, respectively). CONCLUSION: The dual parameter model containing pHi and T2 to predict the pCR in STSs treated with thermoradiotherapy was not verified. However, other parameters were statistically significant, including the PDE/Pi ratio and hypoxic fraction. These relationships may have interfered with our ability to obtain the pCR rate predicted by thermal doses achieved in these patients. The relationship between the PME/PDE ratio and metastasis-free and overall survival was provocative, but requires additional study to verify its predictive capability. Currently, 50% of all STS patients with high-grade tumors develop distant metastasis even when excellent local control is achieved. Parameters that could help select for patients who need adjuvant chemotherapy could have significant clinical benefit.