Review of local extravascular delivery systems for chemotherapeutic agents in small animals and horses.

Background: Tumors of various sizes and locations can create a treatment dilemma in achieving adequate surgical margins when sufficient free tissue is not available for closure. Extravascular local adjunctive chemotherapy has been investigated clinically to aid in achieving local tumor control in animals with naturally occurring neoplastic disease. Local chemotherapy can be an alternative primary or a local adjunctive treatment. Objectives and procedures: This is a summary of relevant findings of in vitro and in vivo studies on local chemotherapeutic delivery through carrier media, together with a summary of outcomes of clinical use of local delivery of chemotherapeutic agents in small animals and Equidae. Literature from 1990 to 2022 was evaluated via searches of PubMed, Google Scholar, and CAB Abstracts databases for studies of local extravascular delivery of chemotherapeutic agents and chemotherapeutic-impregnated delivery systems in research and clinical settings in veterinary medicine. Results: Chemotherapeutic-impregnated calcium sulfate hemihydrate beads with carboplatin are currently favored for extravascular delivery and are associated with minimal wound complications. The ideal delivery system may vary depending on the chemotherapeutic agent used, commercial availability, targeted tumor type, and location. Conclusion and clinical relevance: Future investigations might focus on the required dose, the rate of sustained release, and enhancing nodal uptake.

Examen des systèmes d'administration extravasculaire locaux d'agents chimiothérapeutiques chez les petits animaux et les chevaux. Contexte: Des tumeurs de tailles et emplacements différents peuvent créer un dilemme thérapeutique pour obtenir des marges chirurgicales adéquates lorsqu'il n'y a pas suffisamment de tissu libre disponible pour la fermeture. La chimiothérapie d'appoint extravasculaire locale a été étudiée cliniquement pour aider à obtenir une limitation locale de la tumeur chez les animaux atteints d'une maladie néoplasique naturelle. La chimiothérapie locale peut être une alternative primaire ou un traitement local d'appoint. Objectifs et procédures: Il s'agit d'un résumé des résultats pertinents d'études in vitro et in vivo sur l'administration locale de chimiothérapie par le biais de transporteurs, ainsi que d'un résumé des résultats de l'utilisation clinique de l'administration locale d'agents chimiothérapeutiques chez les petits animaux et les équidés. La littérature de 1990 à 2022 a été évaluée via des recherches dans les bases de données PubMed, Google Scholar et CAB Abstracts pour des études sur l'administration extravasculaire locale d'agents chimiothérapeutiques et de systèmes d'administration chimiothérapeutiques imprégnés dans des contextes de recherche et cliniques en médecine vétérinaire. Résultats: Les billes de sulfate de calcium hémihydratée chimiothérapeutique imprégnées de carboplatine sont actuellement privilégiées pour l'administration extravasculaire et sont associées à des complications minimes des plaies. Le système d'administration idéal peut varier en fonction de l'agent chimiothérapeutique utilisé, de la disponibilité commerciale, du type de tumeur ciblé et de l'emplacement. Conclusion et pertinence clinique: Les recherches futures pourraient se concentrer sur la dose requise, le taux de libération prolongée et l'amélioration de l'absorption nodale.(Traduit par Dr Serge Messier).

Repeatability of in vitro carboplatin elution from carboplatin-impregnated calcium sulfate hemihydrate beads made in a clinic setting.

OBJECTIVE: To evaluate the intra-lot and inter-lot consistency and total carboplatin elution over 25 days from carboplatin-impregnated calcium sulfate hemihydrate (C-I CSH) beads manufactured in a clinic setting. STUDY DESIGN: In vitro elution study. METHODS: Two volumes of carboplatin were mixed with CSH to yield 4 mg and 8 mg C-I CSH doses. Two lots of beads were made for each concentration and split into five doses (n = 10 per concentration). Beads hardened in molds and were placed in a covered six-well plate, submerged in phosphate-buffered saline, and incubated with samples collected at 12 time points (0, 6, 12, and 24 hours and 2, 3, 5, 7, 10, 14, 18, and 25 days). The amount of carboplatin in each sample was evaluated by high-performance liquid chromatography/mass spectrometry. Correction for carboplatin degradation and dilution was applied, and eluted carboplatin was calculated. Intra-lot and inter-lot coefficient of variation (CV) was calculated for each concentration. RESULTS: The intra-lot CV ranged between 7.9% and 23.1%, and the inter-lot CV ranged from 3.5% to 10.3%, with improvement noted in each successive lot of beads. Mean peak eluted carboplatin was 2.45 ± 0.43 mg (61%) and 3.68 ± 0.41 mg (45.9%) for the 4-mg and 8-mg C-I CSH beads, respectively, with both occurring at the 12-hour timepoint. CONCLUSION: Progressive improvement in variability with successive lots of beads indicated a learning curve with bead manufacturing with a low variation both within and between lots of C-I CSH beads. CLINICAL SIGNIFICANCE: On-site mixing of carboplatin with commercial CSH bead powder leads to a low variation of carboplatin per bead dose.

Risk factors for temporary tracheostomy tube placement following surgery to alleviate signs of brachycephalic obstructive airway syndrome in dogs.

OBJECTIVE To identify risk factors for temporary tracheostomy tube placement (TTTP) following surgery for alleviation of signs associated with brachycephalic obstructive airway syndrome (BOAS) in dogs. DESIGN Retrospective case-control study. ANIMALS 122 client-owned dogs with BOAS that underwent surgery to alleviate clinical signs (BOAS surgery). PROCEDURES The medical records database of a veterinary teaching hospital was searched to identify dogs that underwent BOAS surgery from January 2007 through March 2016. Of the 198 dogs identified, 12 required postoperative TTTP (cases); 110 of the remaining 186 dogs were randomly selected as controls. Data regarding signalment and select preoperative, intraoperative, and postoperative variables were extracted from the medical record of each dog. Variables were compared between cases and controls and evaluated for an association with the odds of postoperative TTTP. RESULTS Body condition score, tracheal diameter-to-thoracic inlet ratio, staphylectomy technique, and mortality rate did not differ significantly between cases and controls. The odds of postoperative TTTP increased approximately 30% (OR, 1.3) for each 1-year increase in patient age. Postoperative administration of corticosteroids and presence of pneumonia were also positively associated with the odds of postoperative TTTP. Median duration of hospitalization was significantly longer for cases than controls. CONCLUSIONS AND CLINICAL RELEVANCE Age was positively associated with the odds of TTTP in dogs after BOAS surgery, and TTTP led to prolonged hospitalization. Thus, early identification and intervention may be beneficial for dogs with BOAS. The associations between TTTP and postoperative corticosteroid use or pneumonia were likely not causal, but reflective of patient disease severity.

Type, duration, and incidence of pathologic findings after retroorbital bleeding of mice by experienced and novice personnel.

Retroorbital blood collection is a common technique in laboratory rodents due to the ease with which it can be performed and the sample volumes obtained for subsequent blood analyses. However, its use has been discouraged recently due to aesthetic discomfort and anecdotal reports of potential for ocular injury during blood collection. We hypothesized that a single standardized session of in-person training would be sufficient to learn the appropriate technique and minimize the likelihood for adverse outcomes. Experienced instructors (n = 2) conducted hands-on training classes to teach novice personnel (n = 40) to perform this procedure. Blood was collected from anesthetized mice (n = 40) via a capillary tube first placed at the medial canthus of the right eye and then advanced into the retroorbital space; the left retroorbital spaces served as unmanipulated controls. For comparison, the experienced instructors similarly collected blood from 40 additional mice. The tube could be inserted only once in each mouse, with the goal of obtaining 50 to 100 µL blood. Overall, 79 of 80 mice (98.8%) showed normal body condition, posture, and behavior throughout the 14-d study. Thus, any clinical observation scores pertained specifically to ocular lesions, which occurred at least once after sampling in 43 (53.8%) of the mice. Clinical and histopathologic scores of mice after bleeding did not differ between experienced and novice personnel. We conclude that a coordinated hands-on training program can provide consistent and sufficient instruction for research personnel to conduct retroorbital blood collection with competence in anesthetized laboratory mice.