Palliative Radiation Therapy for Treatment of Cutaneous T-cell Lymphoma in a Double Yellow-headed Amazon Parrot (Amazona oratrix).

A 17-year-old captive female double yellow-headed Amazon parrot (Amazona oratrix) was presented to the Kansas State University Zoological Medicine Service (Manhattan, KS, USA) for a 2-month history of a left sided facial swelling. On examination, a red, raised mass was noted on the left side of the face. A whole-body computed tomography scan of the bird was performed to assess the extent of the mass and evaluate the patient for obvious evidence of disseminated disease. No systemic involvement was detected, and the swelling was localized to the cutaneous and subcutaneous tissues overlying the left rhamphotheca. Two punch biopsies were collected, and histopathology was consistent with cutaneous lymphoma, with strong positive CD3 staining congruous with a T-cell origin. Because of a lack of evidence for disseminated disease, the authors elected to pursue localized radiation therapy, and a single fraction of 8 Gray was administered. The swelling had resolved by the time of the recheck examination 4 weeks post-radiation therapy, and the patient remained clinically normal 52 weeks after radiation therapy.

Diagnosis and management of a peripheral T-cell lymphoproliferative disease in an American pine marten (Martes americana).

A 9-year-old neutered male American pine marten (Martes americana) was referred for further evaluation of suspected lymphoproliferative disease. On physical examination, the pine marten was determined to be in an underconditioned state with an enlarged right mandibular lymph node. Hematology revealed a marked leukocytosis characterized by a lymphocytosis. Flow cytometry performed on peripheral blood was suggestive of a CD4+ T-cell lymphoproliferative disease. Whole-body radiographs demonstrated a large cranial mediastinal mass and splenomegaly. These findings were confirmed using ultrasound, which also identified intra-abdominal lymphadenopathy and splenic nodules. Cytologic evaluation of aspirates from the mediastinal mass was interpreted as possible lymphoma. The pine marten was treated with chlorambucil and prednisolone and achieved a durable partial remission. Twelve months after initial diagnosis, progressive disease was noted and treatment with lomustine was initiated as a rescue protocol until euthanasia, which was carried out 15 mo after the initial diagnosis. Based on a literature search, this is the first case report describing the management of peripheral T-cell lymphoproliferative disease, presumably peripheral lymphoma, in a pine marten; this neoplasm should be considered as a differential diagnosis in pine martens that have abnormal complete blood cell count findings and enlarged lymph nodes. Key clinical message: This report describes the diagnosis and management of a peripheral T-cell lymphoproliferative disease, presumably peripheral lymphoma, in an American pine marten (Martes americana). This is the first report of this disease and its successful treatment in a pine marten.

Diagnostic et prise en charge d'une maladie lymphoproliférative à cellules T périphériques chez une martre d'Amérique ( Martes americana ). Une martre d'Amérique (Martes americana) mâle castré âgé de 9 ans a été référée pour une évaluation plus approfondie d'une suspicion de maladie lymphoproliférative. À l'examen physique, il a été déterminé que la martre était dans un état sous-optimal avec un ganglion lymphatique mandibulaire droit élargi. L'hématologie a révélé une hyperleucocytose marquée caractérisée par une lymphocytose. La cytométrie en flux réalisée sur le sang périphérique était évocatrice d'une maladie lymphoproliférative des lymphocytes T CD4+. Les radiographies du corps entier ont montré une importante masse médiastinale crânienne et une splénomégalie. Ces résultats ont été confirmés par échographie, qui a également identifié une lymphadénopathie intra-abdominale et des nodules spléniques. L'évaluation cytologique des aspirations de la masse médiastinale a été interprétée comme un possible lymphome. La martre d'Amérique a été traitée avec du chlorambucil et de la prednisolone et une rémission partielle durable a été obtenue. Douze mois après le diagnostic initial, une progression de la maladie a été notée et un traitement par lomustine a été initié comme protocole de sauvetage jusqu'à l'euthanasie, qui a été réalisée 15 mois après le diagnostic initial. Sur la base d'une recherche documentaire, il s'agit du premier rapport de cas décrivant la prise en charge d'une maladie lymphoproliférative périphérique à cellules T, vraisemblablement un lymphome périphérique, chez une martre d'Amérique; ce néoplasme doit être considéré comme un diagnostic différentiel chez les martres d'Amérique qui présentent des résultats anormaux de numération globulaire complète et des ganglions lymphatiques hypertrophiés.Message clinique clé :Ce rapport décrit le diagnostic et la prise en charge d'une maladie lymphoproliférative à cellules T périphériques, vraisemblablement un lymphome périphérique, chez une martre d'Amérique (Martes americana). Il s'agit du premier signalement de cette maladie et de son traitement réussi chez une martre d'Amérique.(Traduit par Dr Serge Messier).

Measurement of Cyclooxygenase Products in Plasma as Markers for Inhibition of Cyclooxygenase Isoforms by Oral Meloxicam in New Zealand White Rabbits (Oryctolagus cuniculus ).

Pain management in rabbits is a challenging task that is complicated by the rabbit's ability to hide signs of distress and the limited pharmacologic data available for this species. Pharmacokinetic data has shown that in rabbits, meloxicam, a nonsteroidal anti-inflammatory NSAID, reaches plasma concentrations that are known to provide analgesia in dogs and cats; these concentrations could theoretically alleviate pain in rabbits. However, the inhibitory effects of meloxicam on cyclooxygenase (COX) isoforms have not been studied in rabbits. In this study, we measured the products of COX-1 and COX-2 after the oral administration of a single 1 mg/kg dose of meloxicam to New Zealand White rabbits (n = 6). Blood samples were collected before drug administration (T0) and then at predetermined time points over 48 h. Plasma prostaglandin E2 (PGE2 ) and thromboxane (TxB2) concentrations were measured as surrogate markers for COX-1 and COX-2, respectively, by using commercial ELISA kits. After meloxicam administration, both TxB2 and PGE2 plasma concentrations fell significantly below baseline, with maximal mean reductions to 80% and 60% of baseline at 8 h, respectively. The reduction in PGE2 concentrations was followed by a significant increase that moved its mean plasma concentrations toward baseline between 8 and 24 h. Adverse effects such as lethargy, inappetence, or changes in fecal production were not observed in any rabbits. In conclusion, meloxicam appeared to significantly inhibit both COX-1 and COX-2 with a time course similar to previously reported meloxicam plasma concentration-time profiles in rabbits. Our data suggest that a dosage of 1 mg/kg given orally could provide analgesia to rabbits, but a more frequent dosing interval than the currently recommended daily dosing may be required to maintain clinical efficacy.

Examination of the pharmacokinetics and differential inhibition of cyclooxygenase isoenzymes in New Zealand white rabbits (Oryctolagus cuniculus) by the Non-Steroidal anti-inflammatory Robenacoxib.

Effective rabbit analgesia is challenging, and there are few studies available on the newer COX-2 selective NSAIDs, such as robenacoxib. This study aimed to establish the pharmacokinetics of oral and subcutaneous robenacoxib, describe its inhibitory actions on COX enzymes, and develop dosing, using six healthy New Zealand white rabbits. Pharmacokinetics were determined from plasma concentrations after oral administration of robenacoxib (0.83-0.96 mg/kg) and also after subcutaneous administration (2 mg/kg). The inhibitory actions of robenacoxib were evaluated by measuring plasma concentrations of thromboxane B2 (TBX2 ) and prostaglandin E2 (PGE2 ) as surrogate markers of cyclooxygenase enzyme isoform inhibition. The mean maximum concentration for oral and subcutaneous administration was 0.23 µg/ml and 5.82 µg/ml, respectively. Oral robenacoxib administration did not demonstrate a significant difference between any time point for PGE2 or TBX2 , though subcutaneous administration did for both. There was no significant difference in PGE2 or TBX2 concentrations at any time point when comparing subcutaneous versus oral routes. Although the results support that plasma robenacoxib exceeds the therapeutic levels compared to dogs and cats, there was little significance in the difference in the changes associated with COX-1 and COX-2 inhibition. Further studies are warranted to determine appropriate dosing, safety, and efficacy in rabbits.

Pharmacokinetics and ex vivo pharmacodynamics of oral firocoxib administration in New Zealand White rabbits (Oryctolagus cuniculus).

OBJECTIVE: To examine the pharmacokinetics and ex vivo pharmacodynamics of oral firocoxib administration in New Zealand White rabbits (Oryctolagus cuniculus). ANIMALS: 6 healthy New Zealand White rabbits. PROCEDURES: Pharmacokinetics were determined from plasma concentrations measured via ultra performance liquid chromatography-tandem mass spectrometry after oral administration of firocoxib at a dose of 3.74 to 4.20 mg/kg. Pharmacokinetic analysis was performed using non compartmental methods. Pharmacodynamics of firocoxib were evaluated by measuring plasma concentrations of thromboxane and prostaglandin via ELISAs as surrogate markers of cyclooxygenase enzyme isoform inhibition. RESULTS: The terminal rate constant was 0.07 hours (range, 0.05 to 0.11 h). The mean maximum concentration (Cmax) and time to Cmax were 0.16 µg/mL and 3.81 hours (range, 2.0 to 8.0 h), respectively. Mean residence time was 15.02 hours. Mean elimination half-life was 9.12 hours. For the pharmacodynamic analysis, firocoxib administration did not demonstrate a significant difference between any time point for prostaglandin E2 and only a significant difference between 24 and 48 hours for thromboxane B2. CLINICAL RELEVANCE: Although the pharmacokinetic research supports that plasma firocoxib concentrations that would be therapeutic in dogs are achieved in rabbits, the pharmacodynamic results do not demonstrate a significant difference in levels of cyclooxygenase-2 inhibition, which indirectly reflects the anti-inflammatory effects of the drug. Further pharmacodynamic studies and multidose studies are warranted to determine the efficacy and safety of this drug in rabbits.

Hypofractionated radiation therapy of a thyroid tumor in a pet raccoon (Procyon lotor).

Thyroid neoplasia has been documented in raccoons; however, successful management and treatment has not been well-described. A 15-year-old, intact female pet raccoon (Procyon lotor) was examined for evaluation of a right-sided ventral cervical mass and a cough of 4 to 5 mo duration. Cytology and computed tomography (CT) findings of the mass were most consistent with a thyroid tumor. The raccoon was treated with a hypofractionated external beam radiation protocol (8 Gy/fraction for 4 once/wk fractions). Treatments were well-tolerated and no radiation-induced side effects were detected. This is the first report of radiation treatment of thyroid neoplasia in a raccoon, presenting the challenges of animals that are difficult to handle or medicate.

Radiothérapie hypofractionnée d'une tumeur thyroïdienne chez un raton-laveur ( Procyon lotor ). La néoplasie thyroïdienne a été documentée chez les ratons-laveurs; cependant, la gestion et le traitement réussis n'ont pas été bien décrits. Un raton-laveur femelle intact de 15 ans (Procyon lotor) a été examiné pour l'évaluation d'une masse cervicale ventrale droite et d'une toux d'une durée de 4 à 5 mois. Les résultats de la cytologie et de la tomodensitométrie (CT) de la masse étaient les plus compatibles avec une tumeur thyroïdienne. Le raton-laveur a été traité avec un protocole de rayonnement externe hypofractionné (8 Gy/fraction pour quatre fractions 1 fois/semaine). Les traitements ont été bien tolérés et aucun effet secondaire radio-induit n'a été détecté. Il s'agit du premier rapport de radiothérapie d'une néoplasie thyroïdienne chez un raton-laveur, présentant les défis des animaux difficiles à manipuler ou à soigner.(Traduit par Dr Serge Messier).

Clinical presentation and treatment of lymphoma in companion rats (Rattus norvegicus; 2008-2020).

OBJECTIVE: To describe the clinical presentation, treatment, and treatment outcomes for companion rats (Rattus norvegicus) diagnosed with lymphoma. ANIMALS: All rats that presented to the exotics service and underwent postmortem examination during the time period of 2008 through 2020 were evaluated. PROCEDURES: The medical records of 35 rats were evaluated for an ante- or postmortem diagnosis of lymphoma. Cases with a diagnosis of lymphoma were further reviewed for signalment, presenting complaint, clinical signs observed on physical exam, diagnostic testing performed, and treatments administered. Postmortem gross and histologic findings were reviewed. RESULTS: 7 out of 35 rats were diagnosed with lymphoma, either ante-mortem or postmortem. The most common presenting complaint that was present in all rats with lymphoma was respiratory abnormalities. Five out of 7 rats had radiographs performed, all of which had abnormalities noted in the thoracic cavity including pulmonary nodules, cranial mediastinal widening, or alteration to the cardiac silhouette. Diagnosis via cytologic aspirates was performed in 2 cases and each was diagnostic for lymphoma; however, even with treatment, survival time following initiation of chemotherapy was short (less than or equal to 24 days). The definitive diagnosis in the remainder of the cases was via necropsy. CLINICAL RELEVANCE: Results suggest that lymphoma is a common neoplastic disease in rats and a thorough diagnostic work-up is indicated in any rat that presents for general malaise or respiratory signs.

Circulating Endocannabinoids in Canine Multicentric Lymphoma Patients.

The endocannabinoid system is increasingly being implicated in the pathogenesis and progression of various human cancers. Specifically, increased levels of 2-arachidonoylglycerol (2-AG) and oleoythanolamide (OEA) have been demonstrated in human diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL) patients, respectively. The objectives of this paper were to compare 2-AG, OEA, N-arachidonoylethanolamine (AEA), and palmitoylethanolamide (PEA) levels between dogs with multicentric lymphoma and healthy control dogs. In addition, evaluate 2-AG, OEA, AEA, and PEA levels as biomarkers for progression free interval (PFI) and overall survival time (OST) in the dogs with lymphoma. The study consisted of 26 dogs with multicentric B cell lymphoma, 14 dogs with multicentric T cell lymphoma, and 12 healthy control dogs. Serum 2-AG, OEA, AEA, and PEA levels were measured using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) in dogs with lymphoma and in healthy dogs. OEA, AEA, and PEA levels were significantly elevated in dogs with lymphoma compared to healthy controls (p < 0.05). Total AG was significantly higher in healthy control dogs (p = 0.049). There was no significant difference between dogs with B cell and T cell lymphoma for any of the measured endocannabinoids. Elevated PEA was significantly associated with decreased PFI (p = 0.04) in dogs with lymphoma with a hazards ratio of 1.816 [95% Confidence Interval (CI): 1.020-3.232]. Overall, dogs with lymphoma have elevated levels of OEA, AEA, and PEA. PEA levels have the potential to be a prognostic biomarker.

Toceranib phosphate in the management of canine insulinoma: A retrospective multicentre study of 30 cases (2009-2019).

BACKGROUND: Insulinomas are the most common tumour of the endocrine pancreas in dogs. These malignant tumours have a high metastatic rate and limited chemotherapeutic options. The multi-receptor tyrosine kinase inhibitor sunitinib malate has benefit in the treatment of metastatic insulinoma in people. Toceranib phosphate, an analogous veterinary agent, may provide benefit for dogs. METHODS: A retrospective study describing the extent and duration of clinical outcomes and adverse events (AEs) in dogs diagnosed with insulinoma and receiving toceranib. RESULTS: Records for 30 dogs diagnosed with insulinoma and having received toceranib were identified from a medical record search of five university and eight referral hospitals. The median progression-free interval and overall survival time were 561 days (95% confidence interval (CI): [246, 727 days]) and 656 days (95% CI: [310, 1045 days]), respectively. Of the dogs for which the canine Response evaluation criteria for solid tumours tool could be applied, the majority (66.7%) showed either a complete response, partial response or stable disease. Time to clinical progression was associated with prior intervention and type of veterinary practice. Larger dogs were at increased risk for disease progression and death. No novel AEs were reported. CONCLUSIONS: Most dogs diagnosed with insulinoma and receiving toceranib appeared to have a clinical benefit. Randomised, prospective studies are needed to better elucidate and objectively quantify the potential effect and survival benefit of toceranib therapy for management of insulinoma in dogs.

A retrospective comparison of first and second opinion histopathology with patient outcomes in veterinary oncology cases (2011-2019).

Mandatory second opinion histopathology is common practice in human surgical pathology. It is intended to confirm the original diagnosis or identify clinically significant discrepancies, which could alter the course of disease, cost of treatment, patient management or prognosis. This retrospective analysis aimed to evaluate agreement between first and second opinion histopathology cases, examine their correlation with natural history of disease and investigate the rationale for pursuing this test. Medical records from 2011 to 2019 were reviewed, identifying 109 cases where second opinion histopathology was sought. Reasons for seeking second opinion and clinical disease course were also reviewed to determine whether case progression favoured first or second opinion findings in cases of diagnostic disagreement. Diagnostic disagreement was found in 49.5% of cases. Complete diagnostic disagreement (a change in degree of malignancy or tumour type) occurred in 15.6% cases and partial disagreement (a change in tumour subtype, grade, margins and mitotic count) occurred in 33.9%. Major disagreement (a change in diagnosis resulting in alteration of treatment recommendations) occurred in 38.5% of cases. The most common reasons for seeking second opinion were an atypical/poorly differentiated tumour (31.2%; 34/109) or a discordant clinical picture (24.8%; 27/109). Among cases with any form of disagreement, natural history of disease favoured second opinion findings in 33.3%. The first opinion was favoured over the second in a single case. These findings reinforce previous literature supporting a role for second opinion histopathology in optimizing therapy and predicting outcomes in veterinary oncology, particularly in cases where diagnosis is in question based on the overall clinical picture.

Evaluation of lymphocyte-specific programmed cell death protein 1 receptor expression and cytokines in blood and urine in canine urothelial carcinoma patients.

Urothelial carcinoma (UC) is the most common urinary tumour in dogs. Despite a range of treatment options, prognosis remains poor in dogs. In people, breakthroughs with checkpoint inhibitors have established new standards of care for muscle-invasive bladder cancer patients and elevated levels of programmed cell death protein 1 (PD-1) suggest immune checkpoint blockade may be a novel target for therapy. The goal of this study was to determine if canine UC patients express elevated levels of lymphocyte-specific PD-1 and/or urinary cytokine biomarkers compared to healthy dogs. Paired blood and urine were evaluated in 10 canine UC patients, five cystitis patients and 10 control dogs for lymphocyte-specific PD-1 expression via flow cytometry and relative cytokine expression. In UC patients, PD-1 expression was significantly elevated on CD8+ lymphocytes in urine samples. UC patients had a higher CD4:CD8 ratio in their urine compared to healthy dogs, however, there was no significant variation in the CD8:Treg ratio between any group. Cystitis patients had significantly elevated levels of CD4+ T cells, CD8+ T cells and Tregs in their blood samples compared to UC patients and healthy dogs. Cytokine analysis demonstrated significant elevations in urinary cytokines (granulocyte-macrophage colony-stimulating factor, interferon-gamma [IFN-γ], interleukin (IL)-2, IL-6 IL-7, IL-8 and IL-15, IP-10, KC-like, IL-18, monocyte chemoattractant protein-1 and tumour necrosis factor-alpha). Several of these cytokines have been previously correlated with both lymphocyte-specific PD-1 expression (IFN-γ, IL-2, IL-7 and IL-15) in muscle-invasive urothelial carcinoma in humans. Our results provide evidence of urinary lymphocyte PD-1 expression and future studies could elucidate whether veterinary UC patients will respond favourably to anti-PD-1 immune checkpoint inhibitor therapy.

Evaluation of PD-1 and PD-L1 expression in canine urothelial carcinoma cell lines.

Urothelial carcinoma (UC) is the most common urinary tumor in dogs and despite combinational therapies, only modest improvements in survival have been achieved in recent years. Given the utility of monoclonal antibodies against PD-1 and PD-L1 in human UC, we evaluated the protein and mRNA expression in three established canine urothelial carcinoma cell lines. Flow cytometry and western blot analysis confirmed cell line expression of both molecules in varying degrees. Reverse transcription PCR (RT-PCR) documented mRNA expression in all three cell lines for both PD-1 and PD-L1. Fluorescence microscopy was consistent with strong PD-1 and PD-L1 expression in the canine cell lines and was in line with previous human literature. Importantly, the flow cytometry work described in this study revealed higher cell intrinsic PD-1 expression in these cell lines which may have implications for tumor behavior and potential treatment opportunities in the future. Further work is necessary to determine the expression patterns in canine UC and potential for benefit with immunotherapy directed against PD-1 and PD-L1.

Combination therapy with cannabidiol and chemotherapeutics in canine urothelial carcinoma cells.

BACKGROUND: Canine urothelial carcinoma is the most common form of canine bladder cancer. Treatment with chemotherapy has variable response rates leading to most dogs succumbing to their disease within a year. Cannabidiol is an emerging treatment within the field of oncology. In reported in vivo studies, cannabidiol has induced apoptosis, reduced cell migration, and acted as a chemotherapy sensitizer in various human tumor types. The aim of this study was to characterize the effects of cannabidiol on canine urothelial carcinoma cell viability and apoptosis as both a single agent and in combination with chemotherapy in vitro. RESULTS: Cannabidiol reduced cell viability and induced apoptosis in canine urothelial cells as determined by crystal violet viability assay and annexin V/propidium iodide flow cytometry. Furthermore, combinations of cannabidiol with mitoxantrone and vinblastine chemotherapy yielded significantly reduced cell viability and increased apoptosis compared to single agent treatment alone. The drug interactions were deemed synergistic based on combination index calculations. Conversely, the combination of cannabidiol and carboplatin did not result in decreased cell viability and increased apoptosis compared to single agent treatment. Combination index calculations suggested an antagonistic interaction between these drugs. Finally, the combination of the non-steroidal anti-inflammatory drug piroxicam with cannabidiol did not significantly affect cell viability, although, some cell lines demonstrated decreased cell viability when mitoxantrone was combined with piroxicam. CONCLUSIONS: Cannabidiol showed promising results as a single agent or in combination with mitoxantrone and vinblastine for treatment of canine urothelial carcinoma cells. Further studies are justified to investigate whether these results are translatable in vivo.

Outcomes after transperitoneal laparoscopic ureteronephrectomy for the treatment of primary renal neoplasia in seven dogs.

OBJECTIVE: To describe the perioperative characteristics and outcomes in dogs that underwent transperitoneal laparoscopic ureteronephrectomy (TLU) for primary renal neoplasia. STUDY DESIGN: Short case series. ANIMALS: Seven client-owned dogs. METHODS: Medical records were reviewed and data extracted regarding perioperative characteristics and animal outcomes. TLU was performed using a single-port + 1 or multiple port techniques. Hemostatic clips or a vessel-sealing device were used for occlusion of renal hilar vessels. The ureter was occluded and transected close to the ureterovesicular junction and the tumor was placed in a specimen retrieval bag for extraction from the abdomen. RESULTS: Preoperative contrast enhanced computed tomography (CECT) was performed in 6/7 dogs. Median estimated tumor volume measured from abdominal CECT removed by TLU was 32.42 cm3 (interquartile range [IQR] 14.76-94.85). Median surgery time for TLU was 90 minutes (IQR 85-105). In one dog, elective conversion to open laparotomy was performed due to large tumor size. Median time to discharge was 31 hours (IQR 24-48). No major perioperative complications occurred and all dogs survived to discharge. Progression free survival in four dogs was 422 days (IQR 119-784). CONCLUSION: TLU was performed for the extirpation of modest sized primary renal tumors with acceptable perioperative outcomes and a low complication rate. CLINICAL RELEVANCE: TLU may be considered for the treatment of selected cases of primary renal neoplasia in dogs.

Primary bone marrow T-cell lymphoma in a Golden Retriever.

A 6.2-year-old 28-kg (61.7 lb) intact female Golden Retriever was referred due to persistent and multiple cytopenias noted on a routine CBC prior to a mature ovariohysterectomy procedure. The patient's physical examination was unremarkable, and staging of the thorax and abdomen identified no abnormalities. At the referral hospital, moderate hypercalcemia, borderline anemia, and neutropenia were noted. Assessment of bone marrow samples by cytology, histology, immunohistochemistry, and flow cytometry indicated a T-cell neoplasm. The patient was treated with a multi-agent chemotherapy protocol for 6 months, which induced remission. Nine months after diagnosis, she relapsed with recurrence of hypercalcemia, cytopenias, and clinical illness. Single-agent anthracycline (mitoxantrone) in combination with prednisone therapy was initiated for 3 months. Two months after completion, the patient relapsed again, and palliative therapy with prednisone was elected. The patient was euthanized 16 months after diagnosis due to progressive disease. Post-mortem histopathologic evaluation showed extensive replacement of bone marrow by neoplastic cells, and infiltrates in multiple organs. The neoplasm was diagnosed as lymphoma rather than leukemia due to the lack of abnormal circulating cells throughout the course of disease. The neoplasm was detected only in marrow at the time of initial diagnosis, and the marrow was the most extensively effaced organ at the time of death. Therefore, leukemia or stage V lymphoma was considered unlikely. In patients with a cytopenia and lack of neoplastic leukocytosis or solid tissue masses, primary bone marrow lymphoma should be considered among the differential diagnoses.

Clinical outcome in 23 dogs with exocrine pancreatic carcinoma.

Exocrine pancreatic carcinoma is uncommon in the dog and the veterinary literature surrounding the disease is minimal. Twenty-three cases of canine exocrine pancreatic carcinoma were reviewed in a retrospective manner to obtain information on clinical presentation, behaviour and survival associated with the disease. Presenting clinical signs were nonspecific and included anorexia, lethargy, vomiting and abdominal pain. The overall median survival time was only 1 day but was confounded by the large number of dogs that were euthanized shortly after diagnosis. Metastatic disease was detected in 78% of cases at the time of diagnosis, attesting to the aggressive nature of the disease. Neither lymph node metastasis, tumour size nor tumour location had an impact on overall survival. Only one patient was a previous diabetic who is contrary to reports of the disease in people and felines. This retrospective study reaffirms the need for early detection measures to optimize disease control. However, the benefits of therapy with surgery or radiation and adjuvant chemotherapy remain to be elucidated in dogs with exocrine pancreatic carcinoma.

Toceranib phosphate in the treatment of canine thyroid carcinoma: 42 cases (2009-2018).

Thyroid carcinoma is the most common endocrine malignancy in dogs. Thyroidectomy and radiation therapy control local disease, yet are not always feasible, and efficacious medical therapies need to be identified. Toceranib phosphate has been reported to provide clinical benefit (CB) in dogs with thyroid carcinoma, while its role in treatment-naïve thyroid tumours has not been well-described. The objective of this study was to describe the use of toceranib in the management of thyroid carcinomas in dogs in both the naïve-disease and prior therapy- settings. A medical record search identified 42 dogs diagnosed with thyroid carcinoma and treated with toceranib, of which 26 and 16 dogs were in settings of naïve-disease and after prior therapy, respectively. Twenty-three (88.4%) and twelve (75%) dogs experienced CB in the naïve and prior therapy settings, respectively. The median [95% confidence interval] progression free interval (PFI) for dogs in the naïve and prior therapy settings were 206 [106,740] and 1015 [92,1015] days, respectively. The median overall survival time (OST) for dogs in the naïve and prior therapy settings were 563 [246,916] and 1082 [289,1894] days, respectively. Overall, the data provided no evidence for differences in overall PFI (P > .20) or OST (P = .15) between settings. However, when asymptomatic at the time of diagnosis, dogs in the naïve setting showed poorer survival prognosis (estimated hazard ratio 17.2 [1.8, 163]) relative to dogs in the prior therapy setting. This study characterizes PFI, OST and CB with minimal AE in dogs with thyroid carcinoma treated with toceranib in both the naïve and prior therapy settings.

Extraction of Boron Nitride Nanotubes and Fabrication of Macroscopic Articles Using Chlorosulfonic Acid.

Due to recent advances in high-throughput synthesis, research on boron nitride nanotubes (BNNTs) is moving toward applications. One future goal is the assembly of macroscopic articles of high-aspect-ratio, pristine BNNTs. However, these articles are presently unattainable because of insufficient purification and fabrication methods. We introduce a solution process for extracting BNNTs from synthesis impurities without sonication or the use of surfactants and proceed to convert the extracted BNNTs into thin films. The solution process can also be used to convert as-synthesized material-which contains significant amounts of hexagonal boron nitride ( h-BN)-into mats and aerogels with controllable structure and dimension. The solution extraction method, combined with further advances in synthesis and purification, contributes to the development of all-BNNT macroscopic articles, such as fibers and 3-D structures.

Receptor tyrosine kinase expression and phosphorylation in canine nasal carcinoma.

Preliminary studies have supported use of toceranib phosphate (Palladia®) in treatment of canine nasal carcinomas, though the mechanisms of its activity are unknown. This study evaluated sixteen canine nasal carcinoma and five normal nasal epithelium samples for expression and phosphorylation of known targets of toceranib [vascular endothelial growth factor receptor-2 (VEGR2), platelet derived growth factor alpha (PDGFR-α), platelet derived growth factor receptor beta (PDGFR-ß), and stem cell factor receptor (c-KIT)] and epidermal growth factor receptor 1 (EGFR1) using immunohistochemistry, RT-PCR and a receptor tyrosine kinase (RTK) phosphorylation panel. Protein for VEGFR2 was expressed in all carcinomas, PDGFR-α was noted in 15/16, whereas PDGFR-ß was detected in 3/16 samples, but showed significant stromal staining. Protein expression for c-KIT was present in 4/16 and EGFR1 was noted in 14/16 samples. Normal tissue showed variable protein expression of the RTKs. Messenger RNA for VEGFR2, PDGFR-ß, and c-KIT were noted in all samples. Messenger RNA for PDGFR-α and EGFR1 were detected in 15/16 samples. All normal nasal tissue detected messenger RNA. Phosphorylation of VEGFR2, PDGFR-α, PDGFR-ß and c-KIT was not observed in any carcinoma or normal nasal sample, but phosphorylation of EGFR1 was noted in 10/16 carcinoma and 3/5 normal samples. The absence of phosphorylated RTK targets of toceranib suggests any clinical effect of toceranib occurs through inhibition of alternative unidentified RTK pathways in canine nasal carcinomas. The observed protein and message expression and phosphorylation of EGFR1 in the nasal carcinoma samples merits further inquiry into EGFR1 as a therapeutic target for this cancer.

Graphene Oxide's Reduction of Hydrolytic Degradation in Polyamide-11.

Graphene oxide (GO) was incorporated into polyamide-11 (PA11) via in-situ polymerization. The GO-PA11 nano-composite had elevated resistance to hydrolytic degradation. At a loading of 1 mg/g, GO to PA11, the accelerated aging equilibrium molecular weight of GO-PA11 was higher (33 and 34 kDa at 100 and 120 °C, respectively) compared to neat PA11 (23 and 24 kDa at 100 and 120 °C, respectively). Neat PA11 had hydrolysis rate constants (kH) of 2.8 and 12 (×10-2 day-1) when aged at 100 and 120 °C, respectively, and re-polymerization rate constants (kP) of 5.0 and 23 (×10-5 day-1), respectively. The higher equilibrium molecular weight for GO-PA11 loaded at 1 mg/g was the result of a decreased kH, 1.8 and 4.5 (×10-2 day-1), and an increased kP, 10 and 17 (×10-5 day-1) compared with neat PA11 at 100 and 120 °C, respectively. The decreased rate of degradation and resulting 40 % increased equilibrium molecular weight of GO-PA11 was attributed to the highly asymmetric planar GO nano-sheets that inhibited the molecular mobility of water and the polymer chain. The crystallinity of the polymer matrix was similarly affected by a reduction in chain mobility during annealing due to the GO nanoparticles' chemistry and highly asymmetric nano-planar sheet structure.