Cross-species evaluation of fibroblast activation protein alpha as potential imaging target for soft tissue sarcoma: a comparative immunohistochemical study in humans, dogs, and cats.

Introduction: Complete surgical tumor resection is paramount in the management of soft tissue sarcoma (STS) in humans, dogs, and cats alike. Near-infrared targeted tracers for fluorescence-guided surgery (FGS) could facilitate intraoperative visualization of the tumor and improve resection accuracy. Target identification is complicated in STS due to the rarity and heterogeneity of the disease. This study aims to validate the expression of fibroblast activation protein alpha (FAP) in selected human, canine, and feline STS subtypes to assess the value of FAP as a target for FGS and to validate companion animals as a translational model. Methods: Formalin-fixed and paraffin-embedded tissue samples from 53 canine STSs (perivascular wall tumor (PWT), canine fibrosarcoma (cFS), and STS not further specified (NOS)), 24 feline fibrosarcomas, and 39 human STSs (myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dermatofibrosarcoma protuberans, and malignant peripheral nerve sheath tumor) as well as six canine and seven feline healthy controls and 10 inflamed tissue samples were immunohistochemically stained for their FAP expression. FAP labeling in tumor, peritumoral, healthy skin, and inflamed tissue samples was quantified using a visually assessed semiquantitative expression score and digital image analysis. Target selection criteria (TASC) scoring was subsequently performed as previously described. Results: Eighty-five percent (85%) of human (33/39), 76% of canine (40/53), and 92% of feline (22/24) STSs showed FAP positivity in over 10% of the tumor cells. A high expression was determined in 53% canine (28/53), 67% feline (16/24), and 44% human STSs (17/39). The average FAP-labeled area of canine, feline, and human STSs was 31%, 33%, and 42%, respectively (p > 0.8990). The FAP-positive tumor area was larger in STS compared to healthy and peritumoral tissue samples (p < 0.0001). TASC scores were above 18 for all feline and human STS subtypes and canine PWTs but not for canine STS NOS and cFS. Conclusion: This study represents the first cross-species target evaluation of FAP for STS. Our results demonstrate that FAP expression is increased in various STS subtypes compared to non-cancerous tissues across species, thereby validating dogs and cats as suitable animal models. Based on a TASC score, FAP could be considered a target for FGS.

Performance of two clinical fluorescence imaging systems with different targeted and non-targeted near-infrared fluorophores: a cadaveric explorative study.

Introduction: Near-infrared (NIR) fluorescence-guided surgery is increasingly utilized in humans and pets. As clinical imaging systems are optimized for Indocyanine green (ICG) detection, the usage of targeted dyes necessitates the validation of these systems for each dye. We investigated the impact of skin pigmentation and tissue overlay on the sensitivity of two NIR cameras (IC-FlowTM, VisionsenseTM VS3 Iridum) for the detection of non-targeted (ICG, IRDye800) and targeted (AngiostampTM, FAP-Cyan) NIR fluorophores in an ex vivo big animal model. Methods: We quantitatively measured the limit of detection (LOD) and signal-to-background ratio (SBR) and implemented a semi-quantitative visual score to account for subjective interpretation of images by the surgeon. Results: VisionsenseTM VS3 Iridum outperformed IC-FlowTM in terms of LOD and SBR for the detection of all dyes except FAP-Cyan. Median SBR was negatively affected by skin pigmentation and tissue overlay with both camera systems. Level of agreement between quantitative and semi-quantitative visual score and interobserver agreement were better with VisionsenseTM VS3 Iridum. Conclusion: The overlay of different tissue types and skin pigmentation may negatively affect the ability of the two tested camera systems to identify nanomolar concentrations of targeted-fluorescent dyes and should be considered when planning surgical applications.

Long-term outcome after total scapulectomy for the treatment of osteosarcoma in a cat.

Case summary: A 10-year-old neutered female domestic shorthair cat was presented for acute lameness of the right forelimb after a pathological fracture caused by scapular osteosarcoma. Total scapulectomy was performed, including the glenoid, and the humerus was sutured to the second rib via a bone tunnel in the humeral head. Two months postoperatively, the cat showed mild lameness without any other impairment or signs of pain. The owner reported that the cat was back to normal activity, including climbing and running. Follow-up checks 6 and 18 months after surgery were unremarkable. At the final follow-up, 33 months postoperatively, the cat showed mild lameness, but the orthopaedic examination was still non-painful. Walking fluoroscopy revealed a failure of the fixation of the humeral head, which was now travelling along ribs 1-4 with each step. The owner still rated the cat's quality of life and leg function as excellent. Relevance and novel information: Suture fixation of the humerus to the second rib via a bone tunnel in the humeral head after performing total scapulectomy, and the long-term outcome of the procedure, has so far not been described in cats. While the technique initially led to full return of limb function, the fixation was found to have failed at 33 months after surgery, resulting in a gait alteration that did not impair activity or quality of life.

Biomechanical comparison of ex vivo lumbar vertebral fracture luxations stabilized with tension band or polymethylmethacrylate in cats.

OBJECTIVE: To evaluate spinal stabilization with tension band stabilization (TS) in cats compared to screw and polymethylmethacrylate fixation (SP). STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Sixteen feline thoracolumbar spinal specimens. METHODS: The intact specimens were mounted in a six-degree-of-freedom biaxial testing machine for nondestructive testing to obtain the neutral zones (NZ) and range of motion (ROM) in flexion and extension. Thereafter, nondestructive testing was consecutively performed after destabilization by disc fenestration and partial L1 corpectomy and after treatment with either TS or SP. Load to failure was compared after surgical treatment in flexion. Significance was assessed by Student's t test or Wilcoxon signed-rank test. RESULTS: Range of motion was 26.4° ± 2.2° in TS constructs and 13.4° ± 2.1° in SP constructs (P = .0005). When flexion and extension were analyzed separately, no difference was found for ROM in flexion (SP, 7.0° ± 3.7°; TS, 8.3° ± 2.1°; P = .38). In extension, the mean displacement was 6.4° ± 2.7° and 18.1° ± 5.1° in SP and TS constructs, respectively (P = .0001). Neutral zone was 2.9° ± 0.6° and 7.5° ± 0.8° for the SP and TS groups, respectively (P = .0003). Screw and polymethylmethacrylate fixation constructs were two times stiffer (P = .045). CONCLUSION: Tension band stabilization provided stability comparable to SP in flexion. In extension, ROM of SP constructs was half that of TS constructs. The mode of failure of TS was related to the limited dorsal bone stock of feline lumbar vertebrae. CLINICAL SIGNIFICANCE: Surgeons should be aware of the limited stability in extension provided by TS when it is used to stabilize thoracolumbar spinal injuries. Our results provide evidence to justify additional studies to clarify the type of fractures amenable to TS.

Influence of a customized three-dimensionally printed drill guide on the accuracy of pedicle screw placement in lumbosacral vertebrae: An ex vivo study.

OBJECTIVE: To compare the accuracy of pedicle screw insertion (PSI) into canine lumbosacral vertebrae with custom-made three-dimensionally (3D)-printed drill guides or freehand insertion. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Nineteen canine lumbosacral specimens. METHODS: Drill guides for PSI were designed on the basis of safe screw insertion trajectories by using preoperative computed tomography (CT) and produced by 3D printing of templates. Right and left sides of the specimens were randomly allocated to two groups; 4-mm pedicle screws were inserted in L5-L6 and L7-S1 spinal segments either freehand (control group) or with custom-made drill guides (guide group). Sixty-six screws were inserted with each method. Insertion angles (α, ß), bone stock, and vertebral canal breach were assessed according to postoperative CT. χ2 Tests were used to compare vertebral canal breach between groups and vertebrae. RESULTS: Breaches in the vertebral canal were less common (P < .001) when screws were placed with a guide in the guide group (9/66, 14%) than without a guide (30/66, 45%). The rate of vertebral canal breach differed at L5 (P = .021) but not at L6 (P = .05), L7 (P = .075) or S1 (P = .658). The angle of insertion (α) did not differ between specimens with and without breaches (guide, P = .068; control, P = .394). CONCLUSION: The use of a customized 3D-printed guide generally improved the accuracy of PSI in canine lumbosacral vertebrae, although statistical significance was reached only at L5. CLINICAL SIGNIFICANCE: The use of customized drill guides may be considered as an alternative to freehand PSI in the lumbosacral area, especially for L5-L6 vertebrae.

Tibial plateau leveling osteotomy and tibial tuberosity advancement - a systematic review.

OBJECTIVE: The optimal surgical technique for treatment of cranial cruciate ligament rupture in canine has been scientifically discussed for decades. Despite the continuous debate, proximal tibial osteotomies such as tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA) are increasingly common. The objective of this review was to systematically evaluate the literature reporting outcome and complications associated with TPLO and TTA. MATERIALS AND METHODS: A systematic search of literature databases identified articles published from August 2004 to February 2016 describing evaluations of short- or longterm outcomes as well as complications following TPLO or TTA. RESULTS: Ninety-one studies were included in this review and assigned to one out of four evidence levels. Of those, 89 studies provided the lowest evidence level and only two were assigned to the third-best evidence level. A comparison of subjective gait analyses could not detect differences in the decrease of lameness between TPLO and TTA, while objective gait analysis supports the superiority of TPLO. Fewer patients treated with TPLO were diagnosed with postoperative joint instability and TPLO had a lower percent increase of osteoarthritis (OA) after surgery. Owner satisfaction was high for both techniques. For TPLO and TTA the average total, minor, major and catastrophic complication rates were 15.9 % and 20.8 %, 7.9 % and 11.6 %, 5.2 % and 13.2 % as well as 0.8 % and 5.6 %, respectively. CONCLUSION AND CLINICAL SIGNIFICANCE: The assessed literature supports the hypothesis that TPLO is associated with lower complication rates, an improved clinical-functional outcome and less increase of OA compared to TTA. The results are indicative for a long-term restoration of normal limb function after TPLO. However, the strength of available evidence and the comparability of each study's results were poor and more comparative studies are needed to draw strong conclusions towards the superiority of the TPLO over the TTA.