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BackgroundNonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.Hypothesis/objectivesThe primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse-administered toceranib phosphate (TOC) combined with lomustine.AnimalsForty-seven client-owned dogs with measurable MCT.MethodsToceranib phosphate was given PO on days 1, 3 and 5 of a 21-day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m(2) . All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.ResultsThe MTD of lomustine was established at 50 mg/m(2) when combined with pulse-administered TOC; the dose-limiting toxicity was neutropenia. Forty-one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression-free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.Conclusions and clinical importanceCombined treatment with pulse-administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT.

BackgroundSurvival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered.ObjectiveTo describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC).AnimalsClient-owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11).MethodsRetrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically.ResultsIntraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024).Conclusion and clinical importanceThis study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow-up time was short and the impact on long-term outcome and survival was not determined.

Abstract P‐glycoprotein (P‐gp, MDR1) is expressed at the blood–brain barrier (BBB) and restricts penetration of its substrates into the central nervous system (CNS). In vitro MDR1 assays are frequently used to predict the in vivo relevance of MDR1‐mediated efflux at the BBB. It has been well established that drug candidates with high MDR1 efflux ratios (ERs) display poor CNS penetration. Following a comparison of MDR1 transporter function between the MDR1‐MDCKI cell line from National Institutes of Health (NIH) and our internal MDR1‐MDCKII cell line, the former was found to provide better predictions of in vivo brain penetration than our in‐house MDR1‐MDCKII cell line. In particular, the NIH MDR1 assay has an improved sensitivity to differentiate the compounds with ERs of

Introduction. Spontaneous intramural oesophageal haematoma is a rare condition that usually occurs secondary to an acute or chronic coagulation disorder. The presenting complaint is often with retrosternal chest pain and most patients are initially investigated to exclude more common causes in the differential diagnosis, such as acute coronary syndromes. Severe life-threatening bleeding or perforation seldom, if ever, arises. Case Presentation. We present a case of spontaneous oesophageal haematoma which appears to have developed gradually in a 69-year-old female with uncontrolled hypertension and antiplatelet medication use. The diagnosis was made on computed tomography imaging and was further evaluated with upper gastrointestinal endoscopy. Management was conservative and a follow-up endoscopy two weeks later showed almost complete resolution of the lesion. Discussion. Spontaneous oesophageal haematomas are very rare and usually result in the separation of the mucosal layer from the underlying muscle, presenting with chest pain, haematemesis, and dysphagia. Usually the diagnosis is one of exclusion, based on computed tomography imaging and endoscopy. Conservative management is almost always successful.

Funding under Title IV-E has historically not been available to American Indian communities, therefore, tribes have had to develop agreements with states to access these funds for child care services. This study analyzes Title IV-E intergovernmental provisions to help tribes and states strengthen Title IV-E agreements. A nationwide content analysis of existing Title IV-E documents, phone interviews, and focus groups revealed that Title IV-E tribal/state agreements vary widely, with most tribes not receiving full access to state services. These agreements focus on foster care maintenance payments and services. This article includes recommendations to help facilitate tribal access to Title IV-E funding for foster care and adoption services. [ABSTRACT FROM AUTHOR]

The expanding number of specialized oncology therapeutics available in veterinary oncology can make staying updated on the most recent advances challenging. This article summarizes the mechanism of action, available supporting data, and clinical use of three key veterinary cancer/supportive care therapeutics: Laverdia-CA1, Canalevia-CA1, and Stelfonta. This information will help guide clinical use within your practice and can be incorporated into discussions with clients regarding the newest available options for their dogs with cancer., Competing Interests: Disclosure C. Mullin: No disclosures to report. C.A. Clifford: Speaker, advisory board member and consultant with Jaguar Animal Health and Anivive. C.M. Johannes: Speaker, advisory board member and consultant with QBiotics Group; advisory board member with Jaguar Animal Health., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Melanoma of the dog and cat poses a clinical challenge to veterinary practitioners across the globe. As knowledge evolves, so too do clinical practices. However, there remain uncertainties and controversies. There is value for the veterinary community at large in the generation of a contemporary wide-ranging guideline document. The aim of this project was therefore to assimilate the available published knowledge into a single accessible referenced resource and to provide expert clinical guidance to support professional colleagues as they navigate current melanoma challenges and controversies. Melanocytic tumors are common in dogs but rare in cats. The history and clinical signs relate to the anatomic site of the melanoma. Oral and subungual malignant melanomas are the most common malignant types in dogs. While many melanocytic tumors are heavily pigmented, making diagnosis relatively straightforward, melanin pigmentation is variable. A validated clinical stage scheme has been defined for canine oral melanoma. For all other locations and for feline melanoma, TNM-based staging applies. Certain histological characteristics have been shown to bear prognostic significance and can thus prove instructive in clinical decision making. Surgical resection using wide margins is currently the mainstay of therapy for the local control of melanomas, regardless of primary location. Radiotherapy forms an integral part of the management of canine oral melanomas, both as a primary and an adjuvant therapy. Adjuvant immunotherapy or chemotherapy is offered to patients at high risk of developing distant metastasis. Location is the major prognostic factor, although it is not completely predictive of local invasiveness and metastatic potential. There are no specific guidelines regarding referral considerations for dogs with melanoma, as this is likely based on a multitude of factors. The ultimate goal is to provide the best options for patients to extend quality of life and survival, either within the primary care or referral hospital setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Polton, Borrego, Clemente-Vicario, Clifford, Jagielski, Kessler, Kobayashi, Lanore, Queiroga, Rowe, Vajdovich and Bergman.)

This Editorial is a response to the Canadian Task Force on Preventive Health Care's recent recommendation "against instrument-based depression screening using a questionnaire with cut-off score to distinguish 'screen positive' and 'screen negative' administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth)." While we acknowledge the gaps and limitations in research on perinatal mental health screening, we have concerns regarding the potential impact of a recommendation against screening and for "de-implementation" of existing perinatal depression screening practices, particularly if there is not careful attention to the specificity as well as limitations of the recommendation, or if there are not clear alternative systems put in place to support the detection of perinatal depression. In this manuscript, we highlight some of our key concerns and suggest considerations for perinatal mental health practitioners and researchers., Competing Interests: Declaration of Competing Interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Clinical studies of depression have historically excluded participants with suicidal ideation. Research participant safety protocols are critical to allow for the much-needed study of suicide risk. This report summarizes participant feedback about the safety protocol used in a national, remote study of perinatal women with suicidal ideation., Methods: Upon completion of the study, participants who had triggered the suicidality safety protocol during the study were invited to complete a brief survey with questions about their experiences with the protocol. The survey included 4 Likert-scale questions and 1 open text question where participants could provide feedback, suggestions, and comments to the research team. Participant feedback survey data were collected between October 2021 and April 2022, and this research was funded by the National Institute of Mental Health., Results: Of the 45 participants enrolled in the UPWARD-S study, 16 triggered the safety protocol. All eligible participants (N = 16) completed the survey. Among respondents, most were at least neutral to very comfortable with the call from the study psychiatrist (75% [n = 12]) and reported that the call had a "positive impact" on their well-being (69% [n = 11]). After the call with the study psychiatrist, 50% of participants (n = 8) reported that they increased engagement with treatment for depression, and the other 50% reported no change in treatment. We also report on themes from the qualitative feedback regarding suggestions of how to modify or improve the safety protocol., Conclusions: Learning from the experiences of research participants will provide unique insight into satisfaction with, and impact of, the implemented suicidality safety protocol. Findings from this study could inform the refinement and implementation of safety protocols used in depression studies as well as future research on the impact of such protocols., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Flake thickness is one of the defining properties of graphene-related 2D materials (GR2Ms), and therefore requires reliable, accurate, and reproducible measurements with well-understood uncertainties. This is needed regardless of the production method or manufacturer because it is important for all GR2M products to be globally comparable. An international interlaboratory comparison on thickness measurements of graphene oxide flakes using atomic force microscopy has been completed in technical working area 41 of versailles project on advanced materials and standards. Twelve laboratories participated in the comparison project, led by NIM, China, to improve the equivalence of thickness measurement for two-dimensional flakes. The measurement methods, uncertainty evaluation and a comparison of the results and analysis are reported in this manuscript. The data and results of this project will be directly used to support the development of an ISO standard., (Creative Commons Attribution license.)

One of the primary objectives of the Oncology Pathology Working Group (OPWG) is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for veterinary oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for the diagnosis of, and histopathologic prognostication for, canine cutaneous and oral/lip melanocytic neoplasms, suggest guidelines for reporting, provide recommendations for clinical interpretation, and discuss future directions. This document represents the opinions of the working group and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists, American College of Veterinary Internal Medicine or the Veterinary Cancer Society., (© 2022 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Background: Canine peripheral nodal T-cell lymphoma is considered chemotherapy resistant and carries a relatively poor prognosis. Prospective evaluations reporting the impact of chemotherapy on progression-free survival (PFS) and overall survival time for dogs with T-cell lymphoma are lacking. This study examined the impact of L-CHOP (L-asparaginase, doxorubicin, cyclophosphamide, vincristine, prednisone) chemotherapy or L-CHOP in combination with AT-005, a US Department of Agriculture-licensed caninised monoclonal antibody, on PFS and response rates in dogs with clinical intermediate- and high-grade peripheral nodal T-cell lymphoma., Methods: A prospective, randomised, placebo-controlled, investigator- and owner-blinded, multicentre study was completed. All dogs received a 19-week L-CHOP chemotherapy protocol with randomisation (1:1) into placebo or AT-005 groups. Response was evaluated via the Veterinary Cooperative Oncology Group criteria for canine lymphoma., Results: Forty-nine dogs were enrolled (25 received placebo and 24 received AT-005). Most demographic factors were similar between the two groups, with the exception that more dogs with stage IV and V disease were treated with AT-005 (34% vs. 8%; p = 0.03). Median PFS was 103 days (95% confidence interval [CI], 56-118) in the placebo group versus 64 days (95% CI, 36-118) in the AT-005 group. The overall response rate (ORR) for all dogs was 98% (48 of 49); complete response rate in the placebo group (64%) was not different from the AT-005 group (67%)., Conclusions: To the best of the authors' knowledge, this is the first prospective study to document that treatment with L-CHOP chemotherapy, with or without AT-005, may result in a high ORR, but relatively brief PFS in dogs with clinical intermediate- and high-grade T-cell lymphoma., Competing Interests: Chad Johannes, Laura Treml and Lydia Cook McAnulty are former employees of Aratana Therapeutics, Inc. and were employed by Aratana Therapeutics, Inc. during the study period. Elizabeth McNiel is a former employee of Elanco Animal Health. Chad Johannes, Craig Clifford and Philip Bergman are advisory board members for Elanco Animal Health and receive honoraria. Margaret Musser has not declared any conflicts of interest., (© 2022 The Authors. Veterinary Record Open published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Core-shell nanoparticles have attracted much attention in recent years due to their unique properties and their increasing importance in many technological and consumer products. However, the chemistry of nanoparticles is still rarely investigated in comparison to their size and morphology. In this review, the possibilities, limits, and challenges of X-ray photoelectron spectroscopy (XPS) for obtaining more insights into the composition, thickness, and homogeneity of nanoparticle coatings are discussed with four examples: CdSe/CdS quantum dots with a thick coating and a small core; NaYF 4 -based upconverting nanoparticles with a large Yb-doped core and a thin Er-doped coating; and two types of polymer nanoparticles with a poly(tetrafluoroethylene) core with either a poly(methyl methacrylate) or polystyrene coating. Different approaches for calculating the thickness of the coating are presented, like a simple numerical modelling or a more complex simulation of the photoelectron peaks. Additionally, modelling of the XPS background for the investigation of coating is discussed. Furthermore, the new possibilities to measure with varying excitation energies or with hard-energy X-ray sources (hard-energy X-ray photoelectron spectroscopy) are described. A discussion about the sources of uncertainty for the determination of the thickness of the coating completes this review. Graphical abstract., (© 2022. The Author(s).)

Background: Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs., Hypothesis/objectives: To determine the efficacy and safety of RAB in dogs with lymphoma., Animals: One hundred and fifty-eight client-owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019., Methods: Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression-free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected., Results: The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P < .0001, HR 6.265 [95% CI 3.947-9.945]). The BORR for RAB-treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo-treated dogs (P < .0001). One month after the last treatment, 37 RAB-treated dogs (33%) were progression free compared with no placebo-treated dogs (P < .0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB-treated (20%) and 5 placebo-treated dogs (13%)., Conclusions and Clinical Importance: Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Objective: The treatment of acne presents a major clinical and dermatological challenge. Investigating the nanomechanical properties of the microcomedone precursor lesions using atomic force microscopy (AFM) may prove beneficial in understanding their softening, dissolution and prevention. Although the exact biochemical mechanism of NaSal on microcomedones is not fully understood at present, it appears to exhibit a significant exfoliation effect on the skin via corneodesmosome dissolution., Methods: Therefore, to support this exploration, sodium salicylate (NaSal), a common ingredient employed in skin care products, is applied ex vivo to microcomedones,collected by nose strip adhesive tape, and their nanomechanical properties are assessed using AFM. Although the exact biochemical mechanism of NaSal on microcomedones is not fully understood at present, it appears to exhibit a significant exfoliation effect on the skin via corneodesmosome dissolution., Results: Herein, our findings demonstrate that when microcomedones are treated with 2% NaSal, samples appeared significantly more compliant ('softer') ((1.3 ± 0.62) MPa) when compared to their pre-treated measurements ((7.2 ± 3.6) MPa; p = 0.038). Furthermore, elastic modulus maps showed that after 2% NaSal treatment, areas in the microcomedone appeared softer and swollen in some, but not in all areas, further proving the valuable impact of 2% NaSal solution in altering the biomechanical properties and morphologies in microcomedones., Conclusion: Our results are the first of their kind to provide qualitative and quantitative mechanobiological evidence that 2% NaSal decreases the elastic modulus of microcomedones. Therefore, this study provides evidence that NaSal can be beneficial as an active ingredient in topical treatments aimed at targeting microcomedones., (© 2021 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

One of the primary objectives of the Oncology Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects and provide guidelines for oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for grading of canine cutaneous mast cell tumors, suggest guidelines for reporting, and provide recommendations for its clinical interpretation. The article mainly focuses on histologic grading, but relevant information on mitotic count and cytological grading are also discussed. This document represents the opinions of the working group and the authors but does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society.

Canine osteosarcoma (OSA) is an aggressive bone tumour in dogs. Standard-of-care treatment typically results in relatively short survival times; thus, alternative treatments are needed to confer a survival advantage. It has been shown that OSA is an immunogenic tumour, suggesting that immune modulation may result in superior outcomes. A cryopreserved, Listeria-based OSA vaccine was recently developed and an initial study in dogs reported prolonged survival for patients receiving the vaccine in conjunction with standard-of-care. The goal of the current observational study was to report on the safety of the lyophilized formulation of this vaccine (the canine OSA vaccine, live Listeria vector [COV-LLV]) in a group of dogs previously diagnosed with OSA. Forty-nine (49) dogs received the COV-LLV and were included for analysis. Adverse events (AEs) noted during and after vaccinations were recorded. The AEs observed were typically mild and self-limiting, with nausea, lethargy and fever being most common. Four dogs (8%) cultured positive for Listeria (three infections including an amputation site abscess, septic stifle joint and bacterial cystitis; and one dog whose lungs cultured Listeria-positive on necropsy within 24 hours of COV-LLV administration). These cases join the previously reported Listeria-positive thoracic abscess that developed in a canine following use of COV-LLV. Although uncommon, it is important to realize this clinically significant AE is possible in patients treated with live therapeutic Listeria vaccines. As Listeria is zoonotic, caution is required not only for the patient receiving the vaccine, but also for the health care workers and family caring for the patient., (© 2020 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

The objective of this retrospective study was to evaluate the effects of surgery on outcome for dogs with naturally occurring urinary bladder transitional cell carcinoma. Forty-seven dogs met the inclusion criteria. Thirty-one dogs (Group A) were treated with partial cystectomy and adjunctive medical therapy and 16 dogs (Group B) were treated with medical therapy alone. Overall survival was greater in dogs treated with partial cystectomy and adjunctive medical therapy (498 days for Group A versus 335 days for Group B, hazard ratio 2.5; 95% confidence interval: 1.1 to 5.7; P = 0.026). Progression-free survival was not different between groups (85 days for Group A versus 83 days for Group B; P = 0.663). No prognostic factors were identified for progression-free survival. Due to the many cases in Group A that were lost to follow-up, time-to-event survival analysis was performed. No significant difference in overall survival was noted, and no prognostic factors were identified in the time-to-event analysis. Prospective, randomized studies are needed to determine the role of partial cystectomy in the treatment of transitional cell carcinoma., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L-asparaginase (L-ASP) has not been studied., Hypothesis/objectives: To evaluate the safety and efficacy of L-ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma., Animals: Fifty-two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin-based chemotherapy protocol., Methods: Open-label, multicenter, prospective single-arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L-asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB., Results: The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression-free survival time (MPFS) was 63 days (range 5-428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44-428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L-ASP were negative prognostic factors on multivariate analysis., Conclusions and Clinical Importance: Concurrent RAB/L-ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Introduction: Various pressures exist for curricular change, including economic forces, burgeoning knowledge, broadening learning outcomes, and improving quality and outcomes of learning experiences. In an Australian 5-year undergraduate medical course, staff were asked to reduce teaching hours by 20% to alleviate perceived overcrowded preclinical curriculum, achieve operating efficiencies and liberate time for students' self-directed learning. Methods: A case study design with mixed methods was used to evaluate outcomes. Results: Teaching hours were reduced by 198 hours (14%) overall, lectures by 153 hours (19%) and other learning activities by 45 hours (7%). Summative assessment scores did not change significantly after the reductions: 0.4% increase, 1.5% decrease and 1.7% increase in Years 1, 2 and 3, respectively. The percentage of students successfully completing their academic year did not change significantly: 94.4% before and 93.3% after the reductions. Student evaluations from eVALUate surveys changed little, except workload was perceived to be more reasonable. Conclusions: Teaching hours, particularly lectures, can be moderately reduced with little impact on student learning outcomes or satisfaction with an undergraduate medical course.

One of the primary objectives of the Oncology-Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for oncologic pathology. Consensus is established through critical review of peer-reviewed literature relevant to a subgroup's particular focus. Subsequent acceptance and approval of the document by the OPWG membership at large establishes consensus. The intent of this publication is to help educate practitioners and pathologists on the value of diagnostics related to the KIT receptor tyrosine kinase for canine cutaneous mast cell tumours and to provide a guide for the use of these tests in veterinary medicine. This document represents the opinions of the OPWG and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society., (© 2019 John Wiley & Sons Ltd.)

Histiocytic sarcoma (HS) and hemangiosarcoma (HSA) are uncommon and aggressive neoplasms that develop much more frequently in dogs than in cats. Breed-specific predispositions have been identified for both cancers. The development of novel diagnostics is underway and may aid in earlier diagnosis. Therapeutic approaches to HS and HSA depend on the stage of disease and may include surgery, radiation therapy, and chemotherapy. Such interventions improve outcome; however, aside from a small number of clinical circumstances, both diseases are considered largely incurable. Continued efforts toward the identification of driver mutations and subsequent druggable targets may lead to improvements in long-term prognosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rabacfosadine (RAB), a novel double prodrug of the acyclic nucleotide phosphonate PMEG, preferentially targets neoplastic lymphocytes with reduced off target toxicity. Historical studies have suggested that every 21-day dosing is effective with acceptable toxicity. The purpose of this study was to evaluate RAB's safety and efficacy at 2 different doses every 21 days in dogs with relapsed B-cell lymphoma. Dogs that had failed 1 doxorubicin-based chemotherapy protocol were eligible for inclusion in this prospective trial. Once enrolled, dogs were randomized to receive RAB at either 0.82 mg/kg or 1.0 mg/kg as a 30-minute IV infusion every 21 days for up to 5 treatments. Response assessment and adverse event (AE) evaluation were performed every 21 days via VCOG criteria. Fifty dogs were enrolled, with 16 treated at 0.82 mg/kg and 34 treated at 1.0 mg/kg. The overall response rate was 74%, with 45% of dogs experiencing a complete response (CR). The median progression free intervals (PFIs) were 108 days, 172 days and 203 days for all dogs, all responders, and all CRs, respectively. Response rates and PFIs were similar in both treatment groups. The incidence of AEs, dose delays, dose reductions and withdrawals were not statistically different between the 2 groups. The AEs observed were similar to those previously reported and included hematologic, gastrointestinal, dermatologic and pulmonary AEs. One dog had grade 5 pulmonary fibrosis; otherwise, AEs resolved with supportive treatment. Rabacfosadine is a generally well tolerated, effective chemotherapy option for dogs with relapsed B-cell lymphoma., (© 2017 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Background: KIT inhibitors, such as toceranib (TOC), and vinblastine (VBL) have not been prospectively compared in the treatment of macroscopic mast cell tumors (MCTs). Also, it is unknown whether VBL or TOC is superior for treating MCT without c-kit mutations., Hypothesis/objectives: To determine the value of KIT genotyping and localization in treatment decisions for dogs with macroscopic MCT. We hypothesized that c-kit mutated MCT would have a better response to TOC than VBL., Animals: Eighty-eight client-owned dogs with macroscopic MCT., Methods: Prospective, randomized trial. Dogs were randomized to TOC (2.75 mg/kg EOD) or VBL (2.5 mg/m 2 weekly × 4 then EOW) by KIT localization and c-kit mutation status using an adaptive randomization scheme., Results: Sixty dogs were allocated to TOC and 28 to VBL. Of the dogs receiving TOC, 20% had c-kit mutations, compared to 30% receiving VBL (P = 0.74). Overall response rates were 46% (TOC) and 30% (VBL) (odds ratio = 1.56 [0.62-3.92]; P = 0.28). Median progression-free survival (PFS) for dogs receiving VBL was 78 days (7-1,521) and for TOC 95.5 (14-990); hazard ratio (HR) = 1.34 [0.72-2.50]; P = 0.36. Median overall survival (OS) was 241.5 days (10-1,521) for the VBL group and 159 (20-990) for the TOC group; HR = 0.80 ([0.45-1.41]; P = 0.44)., Conclusions and Clinical Importance: Neither PFS nor OS was significantly different between treatment groups. As the proportion of dogs with c-kit mutations was not different between treatment groups in this population of dogs, c-kit mutation status did not predict treatment response., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Pamidronate is a bisphosphonate drug widely utilized in veterinary oncologic practice for the palliation of malignant osteolysis. Pamidronate has not been previously reported to cause tissue injury upon extravasation in dogs. The medical records of 11 client-owned dogs undergoing palliative treatment for primary bone tumors with known or suspected pamidronate extravasation reactions were reviewed. The majority of adverse events were low grade in nature, however in some cases, the reactions were severe and led to euthanasia in one instance. Time to complete resolution of lesions ranged from within several days to greater than one and a half months. Aside from the dog that was euthanized, no long-term sequelae of extravasation were identified. Treatments employed to address the reactions varied widely. Pamidronate extravasation reaction appears to be an uncommon, but potentially serious complication of intravenous administration., (© 2016 John Wiley & Sons Ltd.)

Sixty-four dogs were treated with single-agent doxorubicin (DOX) for presumptive cardiac hemangiosarcoma (cHSA). The objective response rate (CR + PR) was 41%, and the biologic response rate (CR + PR + SD), or clinical benefit, was 68%. The median progression-free survival (PFS) for treated dogs was 66 days. The median survival time (MST) for this group was 116 days and was significantly improved compared to a MST of 12 days for untreated control dogs (P = 0.0001). Biologic response was significantly associated with improved PFS (P < 0.0001) and OS (P < 0.0001). Univariate analysis identified larger tumour size as a variable negatively associated with PFS. The high rate of clinical benefit and improved MST suggest that DOX has activity in canine cHSA., (© 2014 John Wiley & Sons Ltd.)

This was a multi-institutional retrospective study evaluating the outcome and clinical parameters associated with the postoperative prognosis of 36 cats with splenic mast cell tumors treated with splenectomy. Clinical parameters reviewed included signalment, clinical history, results of staging tests, surgical variables, administration of blood products, presence of metastasis, postoperative complications, administration of chemotherapy postoperatively, chemotherapy protocol, and response to chemotherapy. Overall median survival time was 390 days (range, 2-1737 days). Administration of a blood product (P < .0001), metastasis to a regional lymph node (P = .022), and evidence of either concurrent or historical neoplasia (P = .037) were negatively associated with survival. Response to chemotherapy (P = .0008) was associated with an improved median survival time. Larger-scale prospective studies evaluating different chemotherapy protocols are required to elucidate the discrepancy between lack of survival benefit with administration of chemotherapy and improvement in survival time with positive response to chemotherapy.

A 9 yr old castrated male golden retriever weighing 36 kg was presented for evaluation of progressive left pelvic limb paresis and fecal and urinary incontinence. MRI demonstrated an extradural, ovoid mass compressing the lumbar spinal cord. Surgical excision of the mass was performed. Histologically, the mass was consistent with hemangiosarcoma with no involvement of the adjacent vertebrae. The dog underwent a doxorubicin-based chemotherapy protocol with the addition of oral cyclophosphamide. After completion of chemotherapy, the dog was evaluated q 4 mo for restaging. Clinicopathological evidence of primary tumor recurrence or metastatic disease was not detected for 15 mo after initial diagnosis and treatment. To the authors' knowledge, this is the first report of a primary extradural hemangiosarcoma in the lumbar vertebral column in a dog. The clinical presentation, diagnosis, treatment, and outcome are also discussed.

Background: We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy., Methods and Findings: This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib., Conclusions: The addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.

Quantitative determination of the geometry of an atomic force microscope (AFM) probe tip is critical for robust measurements of the nanoscale properties of surfaces, including accurate measurement of sample features and quantification of tribological characteristics. Blind tip reconstruction, which determines tip shape from an AFM image scan without knowledge of tip or sample shape, was established most notably by Villarrubia [J. Res. Natl. Inst. Stand. Tech. 102 (1997)] and has been further developed since that time. Nevertheless, the implementation of blind tip reconstruction for the general user to produce reliable and consistent estimates of tip shape has been hindered due to ambiguity about how to choose the key input parameters, such as tip matrix size and threshold value, which strongly impact the results of the tip reconstruction. These key parameters are investigated here via Villarrubia's blind tip reconstruction algorithms in which we have added the capability for users to systematically vary the key tip reconstruction parameters, evaluate the set of possible tip reconstructions, and determine the optimal tip reconstruction for a given sample. We demonstrate the capabilities of these algorithms through analysis of a set of simulated AFM images and provide practical guidelines for users of the blind tip reconstruction method. We present a reliable method to choose the threshold parameter corresponding to an optimal reconstructed tip shape for a given image. Specifically, we show that the trend in how the reconstructed tip shape varies with threshold number is so regular that the optimal, or Goldilocks, threshold value corresponds with the peak in the derivative of the RMS difference with respect to the zero threshold curve vs. threshold number., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To determine features of lymphoma of the tarsus in cats., Design: Multi-institutional retrospective study., Animals: 23 cats with cutaneous lymphoma of the tarsus., Procedures: Veterinary oncologists were requested to submit cases fitting the following criteria: histologically or cytologically confirmed lymphoma with a location at or near the tarsus and described as subcutaneous or mass-like. Data regarding breed, sex, age, FeLV and FIV status, and reason for evaluation were collected. Results of staging tests, location of the tumor, immunophenotype, and histopathologic description were recorded. Type of treatments, outcome, survival time, presence or absence of progressive disease, and cause of death or reason for euthanasia were also recorded., Results: Most cats were older, with a median age of 12 years (range, 7 to 18 years). No association with positive retroviral status was found. Popliteal lymph node involvement at diagnosis was reported in 5 cats, and a suspicion of lymphoma at a different site on the basis of results of abdominal ultrasonography was reported in 4 cats. Treatments were variable and included corticosteroids alone (n = 2), chemotherapy (9), radiation and chemotherapy (7), or surgery with or without chemotherapy (5). Thirteen cats were reported to have lymphoma at a different site at the time of last follow-up, death, or euthanasia. Median survival time for all cats in the study was 190 days (range, 17 to 1,011 days)., Conclusions and Clinical Relevance: Results suggested that tarsal lymphoma is an uncommon manifestation of lymphoma in cats, and in this study was most commonly nonepitheliotropic and of high grade as determined on histologic evaluation. Systemic involvement was identified; therefore, thorough staging is recommended prior to initiating treatment. Future studies are warranted to evaluate effective treatment protocols.

Thirty-four cases were reviewed in this retrospective study for information on clinical presentation, prognostic indicators, survival time and response to various therapies. The most common presenting clinical signs were weight loss, decreased appetite, vomiting, palpable abdominal mass and diarrhoea. Metastatic disease was confirmed in 11 cats. The overall median survival was 97 days. The median survival times for patients who received chemotherapy or had their masses surgically removed was 165 days. Those patients who had an abdominal effusion present at the time of diagnosis survived a median of 30 days. Cats that received non-steroidal anti-inflammatory drug therapy had a median survival of 26 days. This study confirms that exocrine pancreatic carcinoma in cats is an aggressive tumour with a high metastatic rate and poor prognosis, although three patients survived over 1 year. Fifteen percent of the patients were diabetic, which raises the question as to what the link between diabetes and pancreatic cancer in people and cats may be., (© 2012 John Wiley & Sons Ltd.)

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.

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.

Finite element analysis (FEA) is used to model nanoindentation by a rigid, spherically shaped indenter, axially indenting an elastic two phase polymer system comprised of a cylindrical nanoparticle of compliant polymer set in a semi-infinite matrix of stiffer polymer. The cylindrical nanoparticle is normal to the sample surface. An axisymmetric finite element model is used to determine the reduced modulus measured as a function of the indentation depth for various nanoparticle radii and extensions below the surface. We show how the previous simple analytical equations may be extended to describe these situations with accuracy. This gives excellent agreement with the FEA and provides a clear guide to the maximum indentation depth as a function of both the nanoparticle radius and its thickness consistent with a choice of either computation from the analytical equations or direct measurement with a maximum of 10% error in the measured reduced modulus.

The characterisation of nanoscale surface properties of textile and hair fibres is key to developing new effective laundry and hair care products. Here, we develop nanomechanical methods to characterise fibres using an atomic force microscope (AFM) to give their nanoscale modulus. Good mounting methods for the fibre that are chemically inert, clean and give strong mechanical coupling to a substrate are important and here we detail two methods to do this. We show, for elastic nanoindentation measurements, the situation when the tip radius significantly affects the result via a function of the ratio of the radii of the tip and fibre and indicate the importance of using an AFM for such work. A valid method to measure the nanoscale modulus of fibres using AFM is thus detailed and exampled on hair to show that bleaching changes the nanoscale reduced modulus at the outer surface., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)

OBJECTIVE-To determine outcome of dogs with presumed primary hepatic lymphoma treated with various multiagent, doxorubicin-based chemotherapeutic protocols and identify factors associated with prognosis. DESIGN-Retrospective case series. ANIMALS-18 dogs with presumed primary hepatic lymphoma. PROCEDURES-Medical records were reviewed for information on signalment, treatment, and outcome. RESULTS-8 dogs had a complete remission (CR), with a median remission duration of 120 days. Dogs with leukocytosis, neutrophilia, hypoalbuminemia, hyperbilirubinemia, or a combination of hypoalbuminemia and hyperbilirubinemia were less likely to achieve a CR. Overall median survival time (MST) was 63 days (range, 2 to 402 days). In a multivariate analysis, response to treatment and serum albumin concentration were associated with MST. Dogs that did not achieve a CR had a significantly shorter MST than did dogs that did achieve a CR (13 vs 283 days, respectively). Dogs with serum albumin concentration < 2.5 g/dL at the time treatment was initiated had a significantly shorter MST than did dogs with serum albumin concentration within reference limits (10 vs 128 days, respectively). There was also a positive correlation between serum albumin concentration and survival time (r = 0.74). CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that dogs with primary hepatic lymphoma that underwent chemotherapy had a poor prognosis, with a low response rate. Dogs that responded to treatment had a better prognosis, and dogs with hypoalbuminemia had a poorer prognosis.

Eighteen dogs with measurable subcutaneous haemangiosarcoma (SQHSA) were treated with doxorubicin-based chemotherapy. Response assessment was evaluated and compared using World Health Organization (WHO), Response Evaluation Criteria in Solid Tumours (RECIST) and tumour volume criteria. The overall response rate for all dogs was 38.8% using WHO criteria, 38.8% using RECIST criteria and 44% using tumour volume criteria. One dog had a complete response. The median response duration for all dogs was 53 days (range 13-190 days). Four dogs had complete surgical excision after neoadjuvant chemotherapy. The median progression-free interval for dogs with complete surgical excision after neoadjuvant chemotherapy was significantly longer than those not having surgical excision (207 days versus 83 days, respectively) (P = 0.003). No significant difference in metastasis-free interval or survival time was found between the groups. Doxorubicin-based chemotherapy appears to be effective for non-resectable canine SQHSA, although the response duration is relatively short.

Histiocytic sarcoma (HS) is associated with a poor prognosis owing to the presence of metastasis at the time of diagnosis in most dogs. Improved outcome has been reported in several dogs with localized HS following local therapy, however, distant metastasis occurs in 70-91% of dogs suggesting that adjuvant systemic therapy is necessary. The purpose of this retrospective study was to describe clinical characteristics and outcome in dogs with localized HS treated with aggressive local therapy plus adjuvant CCNU chemotherapy. Data from 16 dogs were evaluated. The median disease-free interval was 243 days. Two dogs had local recurrence and eight dogs developed metastatic disease with a median time to relapse of 201 days in these 10 dogs. The median survival time for all 16 dogs was 568 days. These results support the recommendation for aggressive local therapy combined with adjuvant CCNU chemotherapy in dogs with localized HS.

Finite element analysis (FEA) is used to investigate the effect of the Poisson's ratios of both the overlayer and the substrate on the nanoindentation of an elastic two-phase system where the elastic overlayer is more compliant than the underlying elastic substrate. A rigid spherical indenter is used as a probe. It is found that nanoindentation results may be expressed analytically using a simple extension of the previously described equation (Clifford and Seah 2006 Nanotechnology 17 5283). This simple function describes the reduced modulus value measured using Oliver and Pharr's method (1992 J. Mater. Res. 7 1564) for any modulus values or Poisson's ratio values of the overlayer and substrate, overlayer thickness or indenter tip radius. This equation and the FEA behind it are tested using experimental published data for the nanoindentation of a silicon dioxide layer on silicon.

Background: Feline nasal lymphoma (NLSA) is a condition for which no standard of care exists., Hypothesis: There is no difference in survival times of cats with NLSA treated with single or multimodality therapy., Animals: Records from 97 cats diagnosed with NLSA were examined., Methods: The purpose of this retrospective study was to compare the survival times of cats with NLSA treated with radiation therapy (RT) alone, chemotherapy alone, or RT + chemotherapy and identify potential prognostic variables that affected survival. Cats were grouped according to therapy: RT + chemotherapy (n = 60), RT alone (n = 19), or chemotherapy alone (n = 18)., Results: Survival was calculated with 2 methods. The 1st survival analysis (method A) included all cats, but counted only deaths caused by progressive NLSA. The median survival time (MST), regardless of therapy modality, was 536 days. The 2nd survival analysis (method B) also included all cats and counted all deaths, regardless of cause, as events. The overall MST calculated for all deaths was 172 days. A negative independent prognostic variable identified was anemia (P < .001), and positive independent prognostic variables were a complete response to therapy (P < .001) and total radiation dose >32 Gy (P= .03)., Conclusions and Clinical Importance: There were no significant differences in survival times among the 3 treatment groups but these results suggest that the addition of higher doses of RT to a cat's treatment protocol may control local disease and therefore influence survival.

Cell-based vaccination strategies to induce functional tumor-specific T cells in cancer patients have focused on using autologous dendritic cells. An alternative approach is to use RNA-loaded CD40 activated B cells (CD40-B) that are highly efficient antigen-presenting cells capable of priming naive T cells, boosting memory T-cell responses and breaking tolerance to tumor antigens. The use of tumor RNA as the antigenic payload allows for gene transfer without viruses or vectors and permits major histocompatibility complex (MHC)-independent, multiple-antigen targeting. Here, we use CD40L transfected K562 cells to generate functional CD40-B cells from the peripheral blood of humans and dogs. Testing of RNA-loaded CD40-B cells in dogs allows not only for its development in veterinary medicine but also for determination of its safety and efficacy in a large animal model of spontaneous cancer prior to initiation of human clinical trials. We found that CD40-B cells from healthy humans, healthy dogs and tumor-bearing dogs express increased levels of immune molecules such as MHC and CCR7. Moreover, RNA-loaded CD40-B cells induce functional, antigen-specific T cells from healthy dogs and dogs with lymphoma. These findings pave the way for immunotherapy trials using tumor RNA-loaded CD40-B cells to stimulate antitumor immunity in a large animal model of spontaneous neoplasia.

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

Background: Dogs that harbor the naturally occurring ABCB1-1Delta polymorphism experience increased susceptibility to avermectin-induced neurological toxicosis as a result of deficient P-glycoprotein function. Whether or not the ABCB1-1Delta polymorphism affects susceptibility to toxicity of other P-glycoprotein substrate drugs has not been studied., Hypothesis: Dogs that possess the ABCB1-1Delta mutation are more likely to develop hematologic toxicity associated with vincristine than ABCB1 wild-type dogs., Animals: Thirty-four dogs diagnosed with lymphoma were included in this study., Methods: Cheek swab samples were obtained from dogs diagnosed with lymphoma that were to be treated with vincristine. DNA was extracted from cheek swabs and the ABCB1 genotype was determined. Hematologic adverse drug reactions were recorded for each dog and graded according to the Veterinary Comparative Oncology Group's criteria for adverse event reporting (Consensus Document). In order to avoid possible bias, ABCB1 genotype results for a particular patient were not disclosed to oncologists until an initial adverse event report had been submitted., Results: Dogs heterozygous or homozygous for the ABCB1-1Delta mutation were significantly more likely to develop hematologic toxicity, specifically neutropenia (P= .0005) and thrombocytopenia (P= .0001), after treatment with vincristine than ABCB1 wild-type dogs., Conclusions and Clinical Implications: At currently recommended dosages (0.5-0.7 mg/M(2)), vincristine is likely to cause hematologic toxicity in dogs with the ABCB1-1Delta mutation, resulting in treatment delays and unacceptable morbidity and mortality. Assessing the ABCB1-1Delta genotype before vincristine administration and decreasing the dosage may prevent toxicity and treatment delays resulting from neutropenia or thrombocytopenia.

Feline large granular lymphocyte (LGL) lymphoma is an uncommon, morphologically distinct variant of feline lymphoma. Limited information exists in the literature regarding pathological and immunohistochemical descriptions, clinical findings, treatment and survival times. The purpose of this study was to describe clinical features, treatment and outcome in feline LGL lymphoma. Medical records of 45 cats with LGL lymphoma were retrospectively evaluated. Decreased appetite/anorexia, weight loss, lethargy and vomiting were the most commonly reported clinical signs. All cats tested for feline leukaemia virus and feline immunodeficiency virus infection were negative. The mesenteric lymph nodes and small intestine were the most commonly affected organs. One complete response and six partial responses were noted in the 23 cats that received chemotherapy as their initial treatment. Median survival time for cats that were treated was 57 days. Based on these results, feline LGL lymphoma appears to be minimally responsive to chemotherapy and is associated with a grave prognosis.