High intensity focused ultrasound for the treatment of solid tumors: a pilot study in canine cancer patients.

PURPOSE: To investigate the safety, feasibility, and outcomes of High-Intensity Focused Ultrasound (HIFU) for the treatment of solid tumors in a spontaneous canine cancer model. METHODS: Dogs diagnosed with subcutaneous solid tumors were recruited, staged and pretreatment biopsies were obtained. A single HIFU treatment was delivered to result in partial tumor ablation using a commercially available HIFU unit. Tumors were resected 3-6 days post HIFU and samples obtained for histopathology and immunohistochemistry. Total RNA was isolated from paired pre and post treated FFPE tumor samples, and quantitative gene expression analysis was performed using the nCounter Canine IO Panel. RESULTS: A total of 20 dogs diagnosed with solid tumors were recruited and treated in the study. Tumors treated included Soft Tissue Sarcoma (n = 15), Mast Cell Tumor (n = 3), Osteosarcoma (n = 1), and Thyroid Carcinoma (n = 1). HIFU was well tolerated with only 1 dog experiencing a clinically significant adverse event. Pathology confirmed the presence of complete tissue ablation at the HIFU targeted site and immunohistochemistry indicated immune cell infiltration at the treated/untreated tumor border. Quantitative gene expression analysis indicated that 28 genes associated with T-cell activation were differentially expressed post-HIFU. CONCLUSIONS: HIFU appears to be safe and feasible for the treatment of subcutaneous canine solid tumors, resulting in ablation of the targeted tissue. HIFU induced immunostimulatory changes, highlighting the canine cancer patient as an attractive model for studying the effects of focal ablation therapies on the tumor microenvironment.

Risk factors and outcome in dogs with recurrent massive hepatocellular carcinoma: A Veterinary Society of Surgical Oncology case-control study.

Local recurrence after surgical excision of canine massive hepatocellular carcinoma (HCC) has been poorly studied in veterinary medicine with scant information published regarding risk factors for and outcome following recurrence. The aim of this case-control study was to describe the time to recurrence, evaluate potential risk factors for recurrence, and report the outcome in dogs with massive HCC. Medical records for 75 dogs who developed recurrence and 113 dogs who did not develop recurrence were reviewed. Statistical analyses were performed to determine risk factors for recurrence as well as the median time to develop recurrence and overall survival time (OS). None of the risk factors evaluated were significant for the development of recurrence. The median time to develop recurrence was 367 days (range 32-2096 days). There was no significant difference in median OS for dogs who developed recurrence vs. those who did not (851 vs. 970 days). For dogs with recurrent HCC, treatment at recurrence trended toward prolonged OS but was not significantly different from dogs not undergoing treatment at recurrence. There was no significant difference in median OS for dogs with histologically complete vs. incomplete tumour excision (990 vs. 903 days). Although specific risk factors for recurrence were not identified, elevations in liver values were noted in patients with recurrent disease and could act as a noninvasive surveillance tool. Recurrence was noted earlier in dogs who had routine post-operative surveillance (228 vs. 367 days). Routine surveillance for recurrence is recommended especially in dogs where further intervention is possible and should extend beyond 1 year. Patients with massive HCC have a good long-term prognosis regardless of incomplete excision, pulmonary metastasis, or recurrent local disease.

Intestinal dehiscence and mortality in cats undergoing gastrointestinal surgery.

OBJECTIVES: The aim of this study was to determine the incidence of and risk factors for both gastrointestinal (GI) incisional dehiscence and mortality in a large cohort of cats undergoing GI surgery. We hypothesized that cats with preoperative septic peritonitis (PSP), systemic inflammatory response syndrome (SIRS) or sepsis would have higher GI dehiscence and mortality rates than unaffected cats. METHODS: A medical records search identified cats with surgically created, full-thickness incisions into their stomach, small intestines or large intestines. Preoperative data, including signalment, clinical signs, comorbidities, surgical history, current medications, presenting physical examination findings, complete blood counts and serum biochemistry values, were collected. It was determined whether or not cats had PSP, SIRS or sepsis at admission. Intraoperative data, final diagnosis and postoperative variables such as vital parameters, bloodwork and (if applicable) the development of GI dehiscence or mortality were noted. Postoperative follow-up of at least 10 days was obtained in survivors. RESULTS: In total, 126 cats were included. One cat developed GI dehiscence following complete resection of a jejunal adenocarcinoma. Twenty-three cats (18.2%) died within 10 days of surgery. Cats with PSP (P = 0.0462) or that developed hypothermia 25-72 h postoperatively (P = 0.0055) had higher odds of mortality in multivariate analysis. Cats with PSP had 6.7-times higher odds of mortality than cats not diagnosed with PSP. CONCLUSIONS AND RELEVANCE: In cats receiving GI surgery, the incidence of GI incisional dehiscence was <1%. Cats with PSP had a higher likelihood of mortality. SIRS was a common finding in cats with septic peritonitis, but was not associated with mortality. Postoperative mortality during the home recovery period might be significant in cats. Future studies evaluating postoperative mortality in cats should consider extending the research period beyond the date of discharge.

Stiffness of a type II external skeletal fixator and locking compression plate in a fracture gap model.

OBJECTIVE: To compare the stiffness of constructs fixed with a type II external skeletal fixator (ESF) or a 3.5-mm locking compression plate (LCP) in axial compression and bending with a fracture gap model. STUDY DESIGN: Quasi-static four-point bending and axial compression tests. SAMPLE POPULATION: Ten LCP and 10 ESF immobilizing epoxy cylinders with a 40-mm fracture gap. METHODS: Five constructs of each type were tested in nondestructive mediolateral (ML) four-point bending and then rotated and tested in nondestructive craniocaudal (CC) four-point bending. Five additional constructs of each type were tested in nondestructive axial compression. Stiffness was compared between loading modes by construct type and between construct types by loading mode. RESULTS: Type II ESF were stiffer than LCP in ML bending (difference, 1474 N/mm, P < .0001) and in axial compression (difference, 458 N/mm, P = .008) but not in CC bending (P = .1673). Type II ESF were stiffer in ML bending than in CC bending (difference, 999 N/m, P < .0001), while LCP were stiffer in CC bending than in ML bending (difference, 634 N/mm, P < .0001). CONCLUSION: Type II ESF generated stiffer constructs compared with LCP in ML bending and in axial compression without a difference in CC bending. External skeletal fixator and LCP bending stiffness varied by loading direction. CLINICAL SIGNIFICANCE: A type II ESF should be considered in a comminuted fracture requiring increased stability in ML and axial directions.

Outcomes of cats treated with maxillectomy: 60 cases. A Veterinary Society of Surgical Oncology retrospective study.

Maxillectomy is poorly described for the management of oral tumours in cats and is occasionally not recommended because of the high complication rate and sub-optimal outcome reported in cats treated with mandibulectomy. The purpose of this study was to retrospectively evaluate the complications and oncologic outcome in cats treated with maxillectomy. Sixty cats were included in the study. Maxillectomy procedures included unilateral rostral (20.0%), bilateral rostral (23.3%), segmental (10.0%), caudal (20.0%) and total unilateral maxillectomy (26.7%). Intra-operative and post-operative complications were reported in 10 (16.7%) and 34 (56.7%) cats, respectively. The most common post-operative complications were hyporexia (20.0%) and incisional dehiscence (20.0%). The median duration of hyporexia was 7 days. Benign tumours were diagnosed in 19 cats (31.7%) and malignant tumours in 41 cats (68.3%). Local recurrence and metastatic rates were 18.3% and 4.9%, respectively; the median progression-free interval (PFI) was not reached. The disease-related median survival time was not reached overall or for either benign or malignant tumours. The 1- and 2-year survival rates were, respectively, 100% and 79% for cats with benign tumours, 89% and 89% for cats with malignant tumours, 94% and 94% for cats with fibrosarcomas, 83% and 83% for cats with squamous cell carcinomas, and 80% and 80% for cats with osteosarcomas. Poor prognostic factors included mitotic index for PFI, adjuvant chemotherapy for both PFI and survival time, and local recurrence for survival time. Maxillectomy is a viable treatment option for cats resulting in good local tumour control and long survival times.

Subclinical bacteriuria and surgical site infections in dogs with cranial cruciate ligament disease.

OBJECTIVE: To determine the prevalence of subclinical bacteriuria (SBU) in dogs with cranial cruciate ligament (CCL) disease, the clinical variables and clinicopathologic data associated with SBU, and the incidence of surgical site infections (SSI) in dogs with and without SBU. STUDY DESIGN: Prospective, clinical cohort study. ANIMALS: One hundred fifty-five dogs with CCL disease. METHODS: Dogs had a urinalysis, sediment examination, and aerobic urine culture performed. Age, breed, sex, body weight, body condition score, clinical history, and physical examination findings were recorded. Dogs with SBU were not treated for bacteriuria or with postoperative antibiotics. Standard perioperative antimicrobials were provided for all dogs. Dogs that received nonsteroidal anti-inflammatory drugs were not excluded. Dogs that underwent an osteotomy were followed for at least 1 year to determine incidence of SSI. Outcomes and variables associated with SBU were assessed. RESULTS: In 155 dogs with CCL disease, the prevalence of SBU was 6.5%, and SBU occurred exclusively in female dogs (11.4%). The incidence of SSI was 22.3% (25/112). Two of six dogs with SBU and 23/106 dogs without SBU developed SSI. Organisms isolated from SSI were different from those isolated from urine. CONCLUSION: The prevalence of SBU in dogs with CCL disease was similar to that in other studies in which SBU was evaluated in various populations of dogs. CLINICAL SIGNIFICANCE: Screening for and treatment of SBU may not be beneficial prior to tibial osteotomy for CCL disease. Additional studies are required to determine whether dogs with SBU have a greater risk of SSI.

High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular Carcinoma.

PURPOSE: To determine the safety and feasibility of percutaneous high-frequency irreversible electroporation (HFIRE) for primary liver cancer and evaluate the HFIRE-induced local immune response. MATERIALS AND METHODS: HFIRE therapy was delivered percutaneously in 3 canine patients with resectable hepatocellular carcinoma (HCC) in the absence of intraoperative paralytic agents or cardiac synchronization. Pre- and post-HFIRE biopsy samples were processed with histopathology and immunohistochemistry for CD3, CD4, CD8, and CD79a. Blood was collected on days 0, 2, and 4 for complete blood count and chemistry. Numeric models were developed to determine the treatment-specific lethal thresholds for malignant canine liver tissue and healthy porcine liver tissue. RESULTS: HFIRE resulted in predictable ablation volumes as assessed by posttreatment CT. No detectable cardiac interference and minimal muscle contraction occurred during HFIRE. No clinically significant adverse events occurred secondary to HFIRE. Microscopically, a well-defined ablation zone surrounded by a reactive zone was evident in the majority of samples. This zone was composed primarily of maturing collagen interspersed with CD3+/CD4-/CD8- lymphocytes in a proinflammatory microenvironment. The average ablation volumes for the canine HCC patients and the healthy porcine tissue were 3.89 cm3 ± 0.74 and 1.56 cm3 ± 0.16, respectively (P = .03), and the respective average lethal thresholds were 710 V/cm ± 28.2 and 957 V/cm ± 24.4 V/cm (P = .0004). CONCLUSIONS: HFIRE can safely and effectively be delivered percutaneously, results in a predictable ablation volume, and is associated with lymphocytic tumor infiltration. This is the first step toward the use of HFIRE for treatment of unresectable liver tumors.

Key Ring Fixator: A Novel External Fixation Technique for Avian Long Bone Stabilization.

A 12-year-old blue-fronted Amazon parrot (Amazona aestiva) of unknown sex (case 1) and a 14-year-old female hybrid Catalina macaw (Ara ararauna × Ara macao) (case 2) were evaluated and treated for an open tarsometatarsal fracture and a tibiotarsal fracture, respectively. In case 1, 1 month of external coaptation resulted in a delayed union, significant osteolysis, and presumptive osteomyelitis, which led to the decision to treat with a key ring fixator. In case 2, a key ring fixator was chosen for fracture repair because of presumed resistance to destruction by the bird. In both cases, fractures were stabilized with makeshift circular external fixators composed of key rings, K-wires, orthopedic wire, and acrylic resin. After key ring fixator removal, radiographs confirmed complete bone healing. Both patients had acceptable function of the affected limbs 5 years (case 1) and 2 years (case 2) after their procedures. The key ring fixator described in this report is a viable option for fracture repair in pelvic limbs of moderately sized birds (300-1500 g).

Reverse Saphenous Conduit Flap in 19 Dogs and 1 Cat.

The purpose of this retrospective study was to report the outcomes of 19 dogs and 1 cat undergoing reverse saphenous conduit flap between 1999 and 2016. Reverse saphenous conduit flap was used to treat traumatic wounds and wounds resulting from tumor excision in the hind limb; the majority of cases had medial shearing injuries. All animals had complete flap survival. In five animals (20%), minor donor site dehiscence occurred, which did not require surgery. Other postoperative complications included signs of severe venous congestion in one dog. Reverse saphenous conduit flap is a useful technique to repair skin defects of the distal hind limb.

Effect of a single intra-articular injection of bupivacaine on synovial fluid prostaglandin E2 concentrations in normal canine stifles.

OBJECTIVE: To identify if synovial fluid prostaglandin E2 increases in response to a single intra-articular dose of bupivacaine in the normal canine stifle. RESULTS: There were no significant differences in synovial fluid prostaglandin E2 (PGE2) concentrations between treatment groups or over time within bupivacaine or saline groups. Samples requiring ≥ 3 arthrocentesis attempts had significantly higher PGE2 concentrations compared to samples requiring 1 or 2 attempts. Following correction for number of arthrocentesis attempts, PGE2 concentrations were significantly higher than baseline at 24 and 48 h in the bupivacaine group; however there were no significant differences between the bupivacaine and saline groups. In normal dogs, a single bupivacaine injection did not cause significant synovial inflammation, as measured by PGE2 concentrations, compared to saline controls. Future research should minimize aspiration attempts and include evaluation of the synovial response to bupivacaine in clinical cases with joint disease.

Cytokine and Growth Factor Concentrations in Canine Autologous Conditioned Serum.

OBJECTIVE: To compare cytokine and growth factor concentrations in canine autologous conditioned serum (ACS) to canine plasma. STUDY DESIGN: Experimental in vivo study. ANIMALS: Client-owned, adult dogs (n=22). METHODS: Blood collected from 16 medium to large breed dogs was used to produce ACS (Orthokine(®) vet irap 10 syringes) and citrated plasma (control). Canine-specific ELISA assays were run per manufacturers' instructions for interleukin (IL)-10, IL-4, tumor necrosis factor (TNF)-α, insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-2, transforming growth factor (TGF)-ß1, IL-1ß, and interleukin-1 receptor antagonist (IL-1ra). Serum, in addition to plasma and ACS, was collected from an additional 6 dogs for TNF-α, IL-1ß, and IL-1ra analysis (total of 22 dogs). Data were analyzed for differences in each cytokine concentration using pairwise comparisons between ACS, plasma, and serum using Wilcoxon signed-rank tests. Significance was set at P<.05. RESULTS: There was a large variability in growth factor and cytokine concentrations in ACS and plasma for individual dogs. There were no significant differences in IL-10, TNF-α, IGF-1, FGF-2, and TGF-ß1 concentrations between ACS, plasma, and serum. The IL-1ß concentrations in ACS (median, range 46.3 pg/mL, 0-828.8) and IL-4 (0.0 pg/mL, 0-244.1) were significantly higher than plasma (36.6 pg/mL, 0-657.1 and 0.0 pg/mL, 0-0, respectively). The IL-1ra concentration in ACS (median, range 3,458.9 pg/mL, 1,243.1-12,089.0) was significantly higher than plasma (692.3 pg/mL, 422.5-1,475.6). The IL-1ra:IL-1ß ratio in ACS was significantly higher than plasma (39.9 vs. 7.2). CONCLUSION: IL-1ra concentrations in canine ACS were comparable to those published for people and horses and pro-inflammatory cytokines remained low in canine ACS.

Fungal pericarditis and endocarditis secondary to porcupine quill migration in a dog.

A dog evaluated for acute onset of neurologic clinical signs was discovered to have a porcupine quill traversing the left atrium with fungal endocarditis. The dog had been quilled by a porcupine one month prior to presentation and had had several quills removed from the thoracic inlet and left dorsal shoulder areas. A new murmur was identified during the initial examination. Echocardiographic changes consistent with mitral valve endocarditis were identified, in addition to a linear, hyperechoic structure in the left atrium. A thoracic CT identified a possible mediastinal migrating foreign body tract. The foreign body was surgically removed and confirmed as a porcupine quill. Routine aerobic cultures of blood and pericardial samples resulted in growth of presumptive candidal organisms. PCR amplification and sequencing of samples from pericardial cultures identified the presence of a fungal organism, Lodderomyces elongisporus. The neurologic signs were attributed to a left-sided central vestibular lesion presumed secondary to an embolic event from infective endocarditis. After 3 months of antimicrobial and antifungal therapy the valvular changes had markedly improved and the clinical signs resolved. To the authors' knowledge, this is the first description of fungal endocarditis secondary to an intracardiac foreign body in a dog.

Botulinum toxin A as a treatment for delayed gastric emptying in a dog.

A toy Australian shepherd dog was referred for bile peritonitis following excision of a biliary mucocele. Subsequent delayed gastric emptying was refractory to prokinetic therapy but responded to injection of botulinum toxin A into the muscularis layer of the pylorus; a novel therapy for delayed gastric emptying in dogs.

Toxine botulinique : Traitement de la vidange gastrique retardée chez un chien. Un chien Berger australien miniature a été référé pour une péritonite biliaire après l'excision d'une mucocèle biliaire. La vidange gastrique retardée subséquente a été réfractaire au traitement stimulant la motilité gastrique mais a répondu à l'injection de la toxine botulinique A dans la couche musculeuse du pylore; un traitement innovateur pour la vidange gastrique retardée chez les chiens.(Traduit par Isabelle Vallières).

Effect of two instrument designs on laparoscopic skills performance.

OBJECTIVE: To determine whether laparoscopic skills performance is affected by instrument design. STUDY DESIGN: Randomized crossover study. SAMPLE POPULATION: Veterinarians (n = 14) with variable laparoscopic experience. METHODS: Laparoscopic skills performance was assessed with the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS). Participants performed 3 MISTELS tasks twice during 2 sessions (4 tests total). Each set of instruments (set A, B) was used once during each session, and instrument order was switched between the first and second sessions. Surgeons were randomly allocated to either the AB-BA or the BA-AB sequence in a balanced fashion. Scores were compared between instrument sets A and B. RESULTS: Overall, participants performed better when using set A compared with set B. This difference was most striking in the pattern-cutting task (which used scissors and graspers), less convincing in the peg transfer task (which used 2 graspers), and nonexistent in the ligature loop task (which used 1 grasper and 1 pretied ligature loop). CONCLUSIONS: Laparoscopic skills performance, as assessed by MISTELS testing, is affected by instrument design.

Arthropathy caused by a lead bullet in a dog.

CASE DESCRIPTION: A 3-year-old spayed female Labrador Retriever was evaluated for progressive lameness of the left forelimb 21 months after being shot in the elbow with a lead bullet. CLINICAL FINDINGS: Physical examination findings were consistent with moderate osteoarthritis of the left elbow joint. Orthogonal radiographic views of the elbow revealed multiple metallic fragments in and around the joint space as well as signs of osteoarthritis. TREATMENT AND OUTCOME: The elbow joint was evaluated arthroscopically. A lead-based bullet fragment was seen in the lateral synovial compartment and removed in multiple pieces. Excess fibrin and synovium were removed, and microfractures were created in exposed subchondral bone to stimulate neovascularization and fibrocartilage formation. In a follow-up telephone conversation 4 months after surgery, the owner reported a marked improvement in the lameness. CLINICAL RELEVANCE: Removal of lead intra-articular foreign bodies may be indicated even if the material is not believed to mechanically interfere with joint motion.