Evaluation of the results of a L‐asparaginase‐based continuous chemotherapy protocol versus a short doxorubicin‐based induction chemotherapy protocol in dogs with malignant lymphoma

Summary

The results of an L‐asparaginase‐based continuous chemotherapy protocol (n = 52) versus a short doxorubicin‐based induction chemotherapy protocol (n = 65) were evaluated in 117 dogs with malignant lymphoma. There were no differences between the two groups in patient characteristics or incidence of protocol‐related toxicity. Complete remission was induced in 71.2% of the dogs treated with the Lasparaginase protocol and in 67.7% of the dogs treated with the doxorubicin‐plus protocol. The calculated Kaplan‐Meier one‐ and two‐year survival fractions in the L‐asparaginase group were 48% and 26%, and in the doxorubicin‐plus group 35%, and 22%, respectively. Differences in remission and survival between the two treatment groups were not significant. A multivariate Cox proportional hazards survival analysis revealed that elevated pretreatment plasma creatinine concentration and prior treatment with prednisolone were associated with shorter survival times. An elevated pretreatment plasma creatinine concentration and total leucocyte count were associated with a decrease in the disease‐free period. Differences in efficacy and toxicity between the two protocols were not significant. There is no apparent advantage in using the continuous L‐asparaginase protocol, and the shorter doxorubicin‐plus protocol is less expensive and less time consuming.     

Prevalence and anatomopathological characterization of cutaneous squamous cell carcinomas with regional and distant metastases in dogs and cats: 20 cases (1985–2020)

The aim of this study was to assess the prevalence of regional and distant metastases from cutaneous squamous cell carcinomas (SCCs) in dogs (n = 11) and cats (n = 9) in a retrospective case series over 36 years (1985–2020), as well as to characterize its macroscopic aspects (location and size), degree of differentiation (well, moderately and poorly differentiated [WD, MD and PD, respectively]) and the rate of cell proliferation, by counting the AgNORs. Immunohistochemistry (IHC) was used to identify patterns of tumour migration and invasion (islands, ribbons, cords, small aggregates, individual cells [fusiform and amoeboid]) and to evaluate the intensity of desmoplasia and the amount of myofibroblasts. The prevalence of metastatic SCCs was 4.39% (21/478), being 3.8% in dog (12/309) and 5.3% in cat (9/169). Metastases affected lymph nodes in all dogs and 66% (6/9) of cats, and less frequently distant organs. Primary tumours predominantly affected the abdominal skin in dogs and the nasal planum in cats. Among the 20 cases, 52% were MDs, 34% were WDs, and 14% were PDs. Histological lesions suggestive of exposure to chronic solar radiation were present in 57% (8/14). The main patterns of tumour migration and invasion were islands for WD SCCs and individual cells for PD SCCs. MD SCCs had a mix of patterns. In cats, individual spindle cells were restricted to PDs. A marked desmoplastic reaction was more associated with PD SCCs and often with MDs. This study highlights that the prevalence of SCC metastases in dogs and cats is predominantly regional. The IHC was essential in the identification of individual fusiform keratinocytes, whose presence in surgical margins may represent a greater risk of recurrence. Although the presence of myofibroblasts was observed in all infiltrative and metastatic tumours, further studies evaluating these cells may be important to better understand their role in the tumour microenvironment of cutaneous SCCs with metastasis in dogs and cats.     

Laparoscopic ovariectomy in dogs: a comparison of the LigaSure™ and the SonoSurg™ systems

Objectives : The objective of this study was to evaluate the surgical times for removal of ovaries, and the frequency of intra‐operative complications with two different instruments used for canine laparoscopic ovariectomy. Methods : A randomised prospective clinical study. Laparoscopic ovariectomy was performed under general anaesthesia on 10 healthy female dogs admitted for elective ovariectomy. Each ovary was randomly assigned to removal by use of either a SonoSurg? ultrasonic surgical device (Olympus), or a LigaSure? vessel‐sealing system (Valleylab/Covidien). Surgical time for removal of each ovary was measured and the frequency of intra‐operative complications was recorded. A follow‐up was made by interview with the owners, 2·5 years after surgery. Results : The two techniques did not statistically differ with regard to surgical time, or frequency of complications. All owners were very satisfied with the procedure. Clinical Relevance : Both the SonoSurg? and the LigaSure? devices appear to be effective, safe and easy to use when performing laparoscopic ovariectomy in dogs.     

Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour-bearing dogs (excluding mast cell tumours): a phase I dose-finding study

Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non-steroidal anti-inflammatory therapy is often warranted in aged cancer-bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour-bearing (non-mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose-escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose-limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg(-1), every other day; piroxicam, 0.3 mg kg(-1) daily) is generally safe. Several antitumour responses were observed. As with single-agent toceranib, label-indicated treatment holidays and dose reductions (e.g. 2.5-2.75 mg kg(-1)) may occasionally be required owing to gastrointestinal events.     

Clinical characteristics of horses and foals diagnosed with cleft palate in a referral population: 28 cases (1988–2011)

The objective of this case series was to characterize the population, case presentations, and outcomes of 28 equids diagnosed with cleft palate over a 25-year period. The incidence of cleft palate was 0.04%. The median age at presentation was 2 mo (range: 1 d to 3 y). Fifty percent of the animals were < 2 mo old, 21% were ≥ 2 mo but < 1 y old, and 29% were 1 y of age or older. Males and females were nearly equally represented. Short-term outcomes included euthanasia in 50%, surgical repair in 11%, supportive care in 4%, and no treatment in 32% of cases; 46% of the animals survived to discharge. Defects involving both the hard and soft palate and/or aspiration pneumonia generally had less favorable outcomes. Though cleft palate is rare in horses, it should be considered as a differential diagnosis in horses of all ages with nasal discharge, a cough, a history of recurrent respiratory infections, poor growth, or chronic submandibular lymphadenopathy. Endoscopic evaluation of the pharynx may aid in earlier diagnosis and prognostication for owners.     

Safety evaluation of combination vinblastine and toceranib phosphate (Palladia®) in dogs: a phase I dose-finding study

Combining drugs with known single-agent activity that lack overlapping dose-limiting toxicities (DLT) and exert antitumour activity through different mechanisms could improve clinical outcome. As toceranib and vinblastine meet these requisites, a phase I trial was performed in combination in dogs with mast cell tumours. The DLT for the simultaneous combination was neutropenia and the maximally tolerated dose was vinblastine (1.6 mg m(-2) every other week) concurrent with toceranib (3.25 mg kg(-1) PO, every other day). This represents greater than a 50% reduction in dose intensity for vinblastine (compared with single-agent use) and as such does not support this combination based on current drug combination paradigms. Although a strict adherence to dose paradigms speaks against the combination, evidence of significant activity (71% objective response) and enhanced myelosuppression suggest additive or synergistic activity. A prospective randomized evaluation comparing this combination with standard single-agent treatments would seem prudent to interrogate this potential.