Biomechanical Comparison of a 3-Loop Pulley and a 4-Loop Pulley Suture for Tenorrhaphy in the Canine Gastrocnemius Tendon.

OBJECTIVE: The aim of this study was to compare a 3-loop pulley (3LP) suture pattern with a 4-loop pulley (4LP) suture pattern for the tenorrhaphy of the canine gastrocnemius tendon STUDY DESIGN: Randomized, cadaveric, biomechanical study of 30 canine gastrocnemius tendons. Tendons were transected and repaired with either 3LP or 4LP suture pattern with 2-0 polypropylene. A tensile load was applied at 25 mm/min until construct failure. The load required to form a 1 mm gap, 3 mm gap and maximum load at failure was recorded and compared between groups. RESULTS: The estimated mean load to form a 1 mm gap for the 3LP and 4LP was 28.4 N (95% confidence interval [CI]: 24.0-32.6N) and 45.5 N (95% CI: 40.7-50.1N) respectively. The 4LP mean load to form a 1 mm gap was 17.1 N (95% CI: 11.7-22.5N) greater than the 3LP. The estimated mean load to form a 3mm gap for the 3LP and 4LP was 39.7 N (95% CI: 34.1-45.4N) and 55.0 N (95% CI: 49.3-60.9N) respectively. The mean load to form a 3mm gap was 15.3 N (95% CI: 8.5-21.9N) greater in the 4LP than the 3LP. The estimated mean load for failure in the 3LP and 4LP was 41.2 N (95% CI: 35.6-46.9 N) and 54.3 N (95% CI: 48.7-60.3 N) respectively. CONCLUSION: A 4LP pattern was biomechanically superior to a 3LP pattern, as demonstrated by a greater load required to form both a 1 and 3 mm gap and a greater load for failure CLINICAL SIGNIFICANCE: A 4LP suture pattern better resists gap formation and requires greater load prior to construct failure compared with a 3LP, in this canine gastrocnemius model.

Outcome and prognosis for canine appendicular osteosarcoma treated with stereotactic body radiation therapy in 123 dogs.

Canine appendicular osteosarcoma is commonly treated with limb amputation; however, limb-sparing options are frequently desired or necessary for a subset of patients. We evaluated 123 patients and 130 sites treated with stereotactic body radiation therapy (SBRT). Eighty-two out of 98 dogs (84%) had maximum lameness improvement at a median of 3 weeks for a median of 6 months duration. Histopathologic evaluation of available samples from amputation or necropsy revealed >80% tumor necrosis in 50% of limbs consistent with local disease control. Of evaluable patients, 41% fractured and 21% pursued an amputation after treatment. Fine needle aspirate (n = 52) and needle core biopsy (n = 28) did not result in increased fracture risk compared to those without tumor sampling (n = 50). Median survival time (MST) was 233 days and time to first event was 143 days. Gross tumor volume and planned target volume were significantly inversely associated with survival and tumor location was significantly associated with survival. Dogs with salvage amputation had a significantly longer MST compared to those without (346 vs 202 days; P = .04). The presence of metastatic disease at the time of treatment in 15 dogs did not significantly impact survival time (200 vs 237 days without metastasis; P = .58). Skin side effects correlated significantly with dose with 33% of patients with acute grade 3 effects developing consequential late grade 3 effects. While SBRT improves lameness in most patients, further investigation is needed to identify candidates with minimal early fracture risk prior to initiating therapy.

Comparison of the use of a vessel-sealing device versus ligatures for occlusion of uterine tissues during ovariohysterectomy or ovariectomy in rabbits (Oryctolagus cuniculus).

OBJECTIVE: To compare the bursting strength of the uterine horns (UHs) and cervical-vestibule junction (CVJs) of rabbits following sealing with a vessel-sealing device (VSD) or encircling ligatures. SAMPLE: UHs and CVJs collected from 30 rabbit (Oryctolagus cuniculus) cadavers. PROCEDURES: UHs and CVJs were randomly assigned to sealing with encircling Miller knot ligatures (LIG; n = 10 CVJs and 20 UHs) or a VSD (12 CVJs and 24 UHs). Lumens were infused with saline (0.9% NaCl) solution under pressure until seals burst or to a maximum pressure of 300 mm Hg. RESULTS: For CVJs, median (range) bursting pressure of the LIG and VSD groups was > 300 mm Hg (224 to > 300 mm Hg) and 35 mm Hg (0 to 60 mm Hg), respectively. Five of 12 CVJs in the VSD group failed at pressures < 33 mm Hg. For UHs, median (range) bursting pressure of the LIG and VSD groups was 255 mm Hg (120 to > 300 mm Hg) and 154 mm Hg (range, 44 to 202 mm Hg), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The evaluated VSD was effective in sealing UHs at bursting pressures well in excess of expected physiologic pressures, indicating that the VSD may be useful for ovariectomy procedures in rabbits. However, CVJ seals created with the VSD were ineffective and could potentially burst at low pressures, which could predispose to urine entering the abdomen. Given these results, we do not recommend sealing of the CVJ with a VSD for ovariohysterectomy in rabbits.

The Proteasome Inhibitor Ixazomib Inhibits the Formation and Growth of Pulmonary and Abdominal Osteosarcoma Metastases in Mice.

Osteosarcoma is the most common form of primary bone cancer. Over 20% of osteosarcoma patients present with pulmonary metastases at diagnosis, and nearly 70% of these patients fail to respond to treatment. Previous work revealed that human and canine osteosarcoma cell lines are extremely sensitive to the therapeutic proteasome inhibitor bortezomib in vitro. However, bortezomib has proven disappointingly ineffective against solid tumors including sarcomas in animal experiments and clinical trials. Poor tumor penetration has been speculated to account for the inconsistency between in vitro and in vivo responses of solid tumors to bortezomib. Here we show that the second-generation proteasome inhibitor ixazomib, which reportedly has enhanced solid tumor penetration compared to bortezomib, is toxic to human and canine osteosarcoma cells in vitro. We used experimental osteosarcoma metastasis models to compare the efficacies of ixazomib and bortezomib against primary tumors and metastases derived from luciferase-expressing KRIB or 143B human osteosarcoma cell lines in athymic mice. Neither proteasome inhibitor reduced the growth of primary intramuscular KRIB tumors, however both drugs inhibited the growth of established pulmonary metastases created via intravenous inoculation with KRIB cells, which were significantly better vascularized than the primary tumors. Only ixazomib slowed metastases from KRIB primary tumors and inhibited the growth of 143B pulmonary and abdominal metastases, significantly enhancing the survival of mice intravenously injected with 143B cells. Taken together, these results suggest ixazomib exerts better single agent activity against osteosarcoma metastases than bortezomib. These data provide hope that incorporation of ixazomib, or other proteasome inhibitors that penetrate efficiently into solid tumors, into current regimens may improve outcomes for patients diagnosed with metastatic osteosarcoma.

Parathyroid hormone receptor 1 (PTHR1) is a prognostic indicator in canine osteosarcoma.

Osteosarcoma (OS) is the most common malignant primary bone tumour in humans and dogs. Several studies have established the vital role of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation and remodeling. In addition, these molecules play a role in the progression and metastasis of many human tumour types. This study investigated the expression of PTHR1 and PTHrP in canine OS tissues and assessed their prognostic value. Formalin-fixed, paraffin-embedded tissue samples from 50 dogs diagnosed with primary OS were immunolabeled with antibodies specific for PTHR1 and PTHrP. The immunostaining intensity of tumours from patients with OS was correlated with survival time. Both PTHR1 and PTHrP were detected in all OS samples (n = 50). Dogs with OS tumours showing high immunostaining intensity for PTHR1 (n = 36) had significantly shorter survival times (p = 0.028, Log Rank; p = 0.04, Cox regression) when compared with OS that had low immunostaining intensity for PTHR1 (n = 14).PTHrP immunostaining intensity did not correlate with survival time (p > 0.05). The results of this study indicate that increased expression of PTHR1 antigen in canine OS is associated with poor prognosis. This suggests that PTHR1 may be useful as a prognostic indicator in canine OS.

Association of tibial plateau leveling osteotomy with proximal tibial osteosarcoma in dogs.

OBJECTIVE To assess for any association between a history of tibial plateau leveling osteotomy (TPLO) and subsequent development of proximal tibial osteosarcoma in dogs. DESIGN Matched case-control study. ANIMALS 34 client-owned dogs in which proximal tibial osteosarcoma was diagnosed between January 2005 and December 2012 (cases) and 79 dogs without osteosarcoma, matched 3:1 to cases (when possible) by age, breed, and initial examination date (controls). PROCEDURES Information on each case and control was collected from the medical records and other sources regarding date of birth, sex and neuter status, body weight, breed, and whether TPLO had been performed ≥ 1 year ago. A multivariable conditional logistic regression model was constructed to evaluate associations of body weight and history of TPLO with the outcome of proximal tibial osteosarcoma in dogs. RESULTS After adjusting for body weight in the multivariable model, dogs with a history of TPLO were 40 times as likely to develop proximal tibial osteosarcoma as were dogs with no history of TPLO. In addition, each 1-kg (2.2-lb) increase in body weight was associated with an 11% increase in the odds of proximal tibial osteosarcoma. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that dogs with a history of TPLO were at increased risk of developing osteosarcoma of the proximal region of the tibia relative to dogs with no such history. Therefore, it is important for proximal tibial osteosarcoma to be included among the differential diagnoses for new or worsening hind limb lameness in dogs that underwent TPLO ≥ 1 year previously.

Management of total hip replacement luxation with triple pelvic osteotomy.

OBJECTIVE: To report the outcome of dogs treated with triple pelvic osteotomy (TPO) for dorsal luxation after total hip replacement (THR). STUDY DESIGN: Retrospective clinical case series. ANIMALS: Seventeen client-owned animals. METHODS: Medical records were searched at a single institution for dogs that had been treated with TPO for dorsal THR luxation. The angle of lateral opening (ALO), version angle (VA), and inclination angle (IA) were measured from radiographs after THR and TPO and corrected for pelvic rotation. A paired t test was performed to compare cup orientation after THR and TPO. Functional outcome was assessed at follow-up examination and during telephone interviews. RESULTS: Eighteen TPOs were performed in 17 dogs, and radiographs were available for 15 cases. Open and/or closed hip reduction with additional stabilization was attempted unsuccessfully in 6 dogs prior to TPO. Triple pelvic osteotomy reduced the ALO by a mean of 23.0 ° ± 10.9 ° (P ≤ .001), increased VA by 9.0 ° ± 4.9 ° (P < .001), and increased IA by 2.9 ° ± 5.8 ° (P = .126). An excellent or good outcome was achieved in 12 dogs. Ventral luxation occurred in 3 dogs, and dorsal luxation occurred in 1 dog after TPO. Triple pelvic osteotomy excessively reduced ALO in 2 dogs with ventral luxation. CONCLUSION: Triple pelvic osteotomy with cup retention is a viable alternative to cup revision for treatment of dorsal luxation of cemented and cementless THR. Triple pelvic osteotomy significantly reduces ALO and increases VA. Careful patient selection is recommended because excessive ventroversion can lead to ventral luxation. CLINICAL SIGNIFICANCE: Triple pelvic osteotomy offers a revision option that preserves the implant-bone interface and significantly reduces ALO. This technique may be appropriate in dogs with high ALO, luxoid hips, and prior failed revision attempts.

Biomechanical evaluation of 6 transarticular tibiotarsal immobilization methods in canine cadaveric limbs.

OBJECTIVE: To determine the effects of 6 types of transarticular immobilization techniques on tibiotarsal joint angles during stimulated weight bearing. STUDY DESIGN: Canine ex vivo biomechanical study. SAMPLE POPULATION: Canine cadaveric pelvic limbs (n = 15). METHODS: A validation study was conducted to determine tibiotarsal flexion before and after transection of the superficial digital flexor tendon in 5 canine cadaveric limbs without tibiotarsal joint immobilization. Six transarticular tibiotarsal immobilization techniques were tested sequentially in 10 canine cadaveric pelvic limbs. The tibiotarsal joint angles were measured from lateral projection radiographs before and during axial loading of 200 N. Mixed linear models were applied to determine the effects of the immobilization techniques on change in tibiotarsal joint angle under loading. RESULTS: There was no change of tibiotarsal joint angle between extended digits and flexed digits under both unloaded and loaded conditions. Change in tibiotarsal joint angles did not differ among any of the immobilization techniques tested here (mean change 1.36°, range 0-5). The main contributor to variance in angle explained by the final model was associated with the random effect for limb. CONCLUSION: Changes in tibiotarsal joint angles during single static loading in canine cadaveric limbs for the 6 immobilization techniques were minimal. CLINICAL SIGNIFICANCE: The 6 techniques appear equally effective at limiting tibiotarsal joint flexion during single axial loading of 200 N. Cyclic mechanical testing of these techniques is recommended to support our findings and validate their clinical application.

In situ handheld three-dimensional bioprinting for cartilage regeneration.

Articular cartilage injuries experienced at an early age can lead to the development of osteoarthritis later in life. In situ three-dimensional (3D) printing is an exciting and innovative biofabrication technology that enables the surgeon to deliver tissue-engineering techniques at the time and location of need. We have created a hand-held 3D printing device (biopen) that allows the simultaneous coaxial extrusion of bioscaffold and cultured cells directly into the cartilage defect in vivo in a single-session surgery. This pilot study assessed the ability of the biopen to repair a full-thickness chondral defect and the early outcomes in cartilage regeneration, and compared these results with other treatments in a large animal model. A standardized critical-sized full-thickness chondral defect was created in the weight-bearing surface of the lateral and medial condyles of both femurs of six sheep. Each defect was treated with one of the following treatments: (i) hand-held in situ 3D printed bioscaffold using the biopen (HH group), (ii) preconstructed bench-based printed bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated (control, C group). At 8 weeks after surgery, macroscopic, microscopic and biomechanical tests were performed. Surgical 3D bioprinting was performed in all animals without any intra- or postoperative complication. The HH biopen allowed early cartilage regeneration. The results of this study show that real-time, in vivo bioprinting with cells and scaffold is a feasible means of delivering a regenerative medicine strategy in a large animal model to regenerate articular cartilage.

Outcomes of Limb-Sparing Surgery Using Two Generations of Metal Endoprosthesis in 45 Dogs With Distal Radial Osteosarcoma. A Veterinary Society of Surgical Oncology Retrospective Study.

OBJECTIVE: To report outcomes in dogs with distal radial osteosarcoma (OSA) treated with metal endoprosthesis limb-sparing surgery and compare outcomes between 2 generations of endoprosthesis. STUDY DESIGN: Multi-institutional retrospective case series. ANIMALS: Forty-five dogs with distal radial OSA treated with endoprosthesis and chemotherapy. METHODS: Data of dogs treated with either first-generation endoprosthesis (GEN1) or second-generation endoprosthesis (GEN2) were sourced from medical records and radiographs. Surgical outcomes included postoperative lameness assessment and the presence, severity, and time to onset of complications. Oncologic outcomes included presence of local recurrence or metastasis, time to onset of local recurrence, metastasis-free interval (MFI), and survival time. Results for surgical and oncologic outcomes were compared between GEN1 and GEN2. RESULTS: Twenty-eight dogs received GEN1 and 17 dogs received GEN2. There were 39 complications (96%, 14 minor, 29 major) including infection (78%), implant-related complication (36%), and local recurrence (24%). Metastatic frequency was 67% and median MFI was 188 days (95% confidence interval [CI]: 126-250 days). Survival time ranged from 34 days to 6.1 years with a median of 289 days (95% CI: 207-371 days). There was no significant difference in complication severity, frequency, time to complication, MFI, or survival time between dogs receiving GEN1 and GEN2. CONCLUSION: There was no significant difference in outcomes between dogs receiving GEN1 and GEN2 for limb-sparing surgery of the radius. Metastatic frequency and survival time for metal endoprosthesis were similar to that of amputation with curative intent chemotherapy.

DogMATIC--A Remote Biospecimen Collection Kit for Biobanking.

Canine tumors are valuable comparative oncology models. This research was designed to create a sustainable biobank of canine mammary tumors for breast cancer research. The aim was to provide a well-characterized sample cohort for specimen sharing, data mining, and long-term research aims. Canine mammary tumors are most frequently managed at a local veterinary clinic or hospital. We adopted a biobank framework based on a large number of participating veterinary hospitals and clinics acting as collection centers that were serviced by a centralized storage facility. Recruitment was targeted at rural veterinary clinics. A tailored, stable collection kit (DogMATIC) was designed that was used by veterinarians in remote or rural locations to collect both fresh and fixed tissue for submission to the biobank. To validate this methodology the kit design, collection rate, and sample quality were analyzed. The Australian Veterinary Cancer Biobank was established as a network of 47 veterinary clinics and three veterinary pathology laboratories spanning over 200,000 km(2). In the first 12 months, 30 canine mammary tumor cases were submitted via the DogMATIC kit. Pure intact RNA was isolated in over 80% of samples with an average yield of 14.49 µg. A large network biobank, utilizing off-site collection with the DogMATIC kit, was successfully coordinated. The creation of the Australian Veterinary Cancer Biobank has established a long-term, sustainable, comparative oncology research resource in Australia. There are broader implications for biobanking with this very different form of collection and banking.

Osteosarcoma following tibial plateau leveling osteotomy in dogs: 29 cases (1997-2011).

OBJECTIVE: To determine the signalment, tibial plateau leveling osteotomy (TPLO) plate type, clinical staging information, treatment, and oncological outcome in dogs that developed osteosarcoma at the proximal aspect of the tibia following TPLO and to calculate the interval between TPLO and osteosarcoma diagnosis. DESIGN: Multi-institutional retrospective case series. ANIMALS: 29 dogs. PROCEDURES: Medical records from 8 participating institutions were searched for dogs that developed osteosarcoma (confirmed through cytologic or histologic evaluation) at previous TPLO sites. Signalment, TPLO details, staging tests, treatment data, and outcome information were recorded. Descriptive statistics were calculated, and disease-free intervals and survival times were evaluated by means of Kaplan-Meier analysis. RESULTS: 29 dogs met the inclusion criteria. The mean age was 9.2 years and mean weight was 45.1 kg (99.2 lb) at the time of osteosarcoma diagnosis. Most dogs had swelling over the proximal aspect of the tibia (17/21) and lameness of the affected limb (28/29). The mean interval between TPLO and osteosarcoma diagnosis was 5.3 years. One type of cast stainless steel TPLO plate was used in most (18) dogs; the remaining dogs had received plates of wrought stainless steel (n = 4) or unrecorded type (7). Twenty-three of 29 dogs underwent treatment for osteosarcoma. Median survival time for 10 dogs that underwent amputation of the affected limb and received ≥ 1 chemotherapeutic treatment was 313 days. CONCLUSIONS AND CLINICAL RELEVANCE: Results supported that osteosarcoma should be a differential diagnosis for dogs with a history of TPLO that later develop lameness and swelling at the previous surgical site. Oncological outcome following amputation and chemotherapy appeared to be similar to outcomes previously reported for dogs with appendicular osteosarcoma.

Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

OBJECTIVE: To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. ANIMALS: 26 athymic nude rats. PROCEDURES: 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. RESULTS: Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE: The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

Bilateral appendicular bone tumors in four dogs.

Bilateral synchronous appendicular bone tumors, occurring in the same bone and same anatomic site within the bone are very rare. This report describes the clinical presentation and oncologic outcome for four dogs with this rare presentation. All cases presented to the authors following a history of unilateral lameness for several weeks. On presentation, case 1 had pain elicited in the contralateral proximal humerus but all the other cases had no abnormalities detectable on physical examination of the contralateral limb. All dogs had technetium 99m ((99m)Tc) nuclear scintigraphy performed that identified bilateral lesions of the distal radii in two dogs, proximal humeri and distal tibiae in one dog each. Thoracic radiographs performed on all dogs showed no evidence of pulmonary metastases. Three dogs were treated with palliative radiation therapy (two dogs received concurrent bisphosphonates) resulting in survival times from initial presentation of 50 days, 193 days, and 523 days, respectively. One dog had stereotactic radiation therapy (SRT) and a surgical limb-salvage performed followed by carboplatin chemotherapy, resulting in a survival time of 926 days from initial presentation. Palliative and curative-intent treatments for the bilateral synchronous appendicular bone tumors resulted in survival times similar to those reported for treatment of a single primary appendicular bone tumor.