Double level osteotomy for medial osteoarthritis and bifocal varus malalignment has excellent short-term results while maintaining physiologic radiographic joint parameters.

PURPOSE: The purpose of this study was to prospectively evaluate the clinical and radiological results of double level osteotomy (distal femoral lateral closed wedge and proximal tibial medial open wedge) in medial osteoarthritis and varus malalignment due to bifocal deformity of femur and tibia. METHODS: From 2017 to 2019 all cases of DLO in osteoarthritic varus malaligned knees with bifocal deformity (femoral and tibial deformity) were prospectively enrolled into this observational therapeutic study. Evaluation was performed preoperatively, at six, twelve, 18 and 24 months with regard to survival (not requiring arthroplasty), functional outcome [subjective International Knee Documentation Committee score (IKDC), Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome score (KOOS) and Tegner Activity Scale], pain level (numeric rating scale), subjective satisfaction (rating 1-5), radiographic parameters on a pre-and postoperative full leg x-rays (mechanical axis, mechanical proximal tibial and distal femoral angles) and complications. For statistical evaluation student's t test, Mann-Whitney U test and Wilcoxon-signed-rank test were used. RESULTS: Fifty-two consecutive cases in 48 patients were enrolled in the study. Three cases were excluded, resulting in a follow-up rate of 94%. No arthroplasties were performed within follow-up. All functional outcome scores substantially and significantly increased as early as six months after the index procedure and further increased until final follow-up (p < 0.001). Pain level significantly decreased (p < 0.001). At final follow-up all patients stated that they would retrospectively undergo the operation again, and rated the result with 4.5 ± 0.6 out of 5 (3-5). Radiographic parameters were within physiological limits postoperatively. No severe complications occurred. CONCLUSIONS: Double level osteotomy has excellent short-term results while maintaining physiological radiographic parameters. Therefore, it should be an integral part and standard procedure in realignment surgery for monocompartimental osteoarthritis. LEVEL OF EVIDENCE: IV (prospective observational therapeutic study).

Outcome comparison between radiation therapy and surgery as primary treatment for dogs with periarticular histiocytic sarcoma: An Italian Society of Veterinary Oncology study.

Localized histiocytic sarcoma may occur as a primary lesion in periarticular tissues of large appendicular joints. Treatment options for the primary lesion include radical surgical excision, radiation therapy (RT), or both, in combination with chemotherapy for potential systemic metastases. In an effort to better characterize the time to progression (TTP) following surgical vs non-surgical approaches for periarticular histiocytic sarcoma (PAHS), a contemporary European population of affected dogs was retrospectively surveyed. Medical records were queried for newly-diagnosed PAHS cases undergoing surgery (predominantly limb amputation) or RT followed by systemic chemotherapy. Of 49 dogs, 34 underwent RT and 15 underwent surgery. All dogs received adjuvant chemotherapy. There was no statistically significant difference in TTP or overall survival between groups. The median TTP was 336 days for the operated dogs and 217 days for the irradiated dogs (P = .117). The median overall survival time was 398 days for the operated dogs and 240 days for the irradiated dogs (P = .142). On multi-variable analysis, the variables significantly associated with an increased risk of both tumour progression and tumour-related death were regional lymph node and distant metastasis at admission. Survival and local control rates following RT may be comparable to radical resection. These data may better inform shared decision-making processes between multi-disciplinary care providers and owners.

Multimodality treatment including ONCEPT for canine oral melanoma: A retrospective analysis of 131 dogs.

Canine oral melanoma (OM) is an aggressive cancer with a high rate of metastasis. Surgery and/or radiotherapy (RT) are effective local treatments, yet many dogs succumb to distant metastasis. Immunotherapy represents an attractive strategy for this potentially immunogenic tumor. The objective of this multi-institutional retrospective study was to examine the clinical outcome of dogs with OM treated with ONCEPT melanoma vaccine. Most dogs also underwent surgery and/or RT (8 Gy × four weekly fractions). Dogs with distant metastasis at diagnosis and those receiving concurrent chemotherapy were excluded. One hundred thirty-one dogs treated with ONCEPT were included: 62 had adequate local tumor control defined as complete tumor excision or irradiation of residual microscopic disease; 15 were treated in the microscopic disease setting following an incomplete excision without adjuvant RT; and 54 had gross disease. Median time to progression, median progression-free survival, and median tumor-specific overall survival were 304, 260, and 510 days, respectively. In multivariable analysis, presence of gross disease correlated negatively with all measures of clinical outcome. Other negative prognostic indicators were primary tumor ≥2 cm, higher clinical stage (stages 2 and 3), presence of lymph node metastasis at diagnosis, and caudal location in the oral cavity. Radiotherapy had a protective effect against tumor progression. To date, this is the largest reported series of dogs with OM treated with ONCEPT. Several previously reported prognostic indicators were confirmed.

Radiation therapy planning using MRI-CT fusion in dogs and cats with brain tumors.

INTRODUCTION: Volume definition is a delicate step within the radiation treatment planning process and the precision of defining the volumes to irradiate is important for the success of the radiation treatment. Traditionally, radiation plans are created using computed tomography (CT) studies. Due to its different mechanism of action, magnetic resonance imaging (MRI) is more sensitive for detection of brain lesions. Therefore, using fused images of both imaging modalities should result in a more precise definition of the volumes to irradiate. The feasibility to fuse CT and MRI studies performed at different institutions was tested to subsequently analyse the influence of the fused images on target volume definition. MATERIALS AND METHODS: Fourteen dogs and four cats with brain lesions having MR- and CT-imaging were included. Contrast-enhanced radiotherapy planning CT scans were fused to T1-weighted post-contrast and T2-weighted MRI scans. The gross tumor volume (GTV), the clinical tumor volume (CTV) and the planning target volume (PTV) were delineated on CT- and MRI studies. CT and MRI volumes were compared with regard to volumetric and spatial differences. RESULTS: The mean GTV was larger on MRI than on CT (2.15 vs.1.54 cm3). Also the mean CTV was larger on MRI than on CT (5.34 vs. 4.38 cm3). Consequently, the mean PTV was larger on MRI than on CT (14.20 vs. 10.82 cm3) as well. None of the differences in defined volumes were significant. Fusion images were accepted showing mean errors of 1.32 mm (mean error) and 1.73 mm (maximal error). CONCLUSION: CT-MRI fusion was feasible especially when defined, reliable, and consistent anatomic landmarks were used as registration points. Volumetric differences between CT and MRI were insignificant. In general, GTV and CTV were easier identified on MRI.

Evaluation of Ki-67 expression in feline non-ocular melanocytic tumours.

BACKGROUND: Melanomas are rare in cats. The eye is the most commonly involved site, whereas few data are available about feline non-ocular melanomas (NOMs). Ki-67 thresholds with prognostic relevance have been established for canine melanomas, but not in cats. This study was undertaken to investigate the relationship between Ki-67 index, tumour characteristics, and clinical outcome in feline NOMs. Histologic samples were retrospectively reviewed. Amelanotic tumours were admitted upon immunohistochemical positivity for Melan A or S100. Evaluated parameters included morphological diagnosis, histotype, junctional activity, degree of pigmentation, vascular invasion, lymphocytic infiltrate, necrosis, mitotic count (MC) and Ki-67 index. Pigmented tumours were bleached before evaluation. Clinical and follow-up information were retrieved via telephone interviews with the referring veterinarians. RESULTS: Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P < 0.001, Fisher's exact test) and presented a spindle cell morphology (P = 0.002; Fisher's exact test). MC and Ki-67 index were significantly correlated (P < 0.001; R = 0.67; Spearman's rank correlation); median values were 15 (range, 0-153) and 28% (range, 1-78%), respectively. Both were significantly higher in spindle cell melanomas, in tumours lacking junctional activity and in poorly-pigmented tumours. Follow-up information was available for 33 cats (66%). Variables related with a poor clinical outcome included mucosal location, tumour size, spindle, balloon and signet ring cell histotypes, low pigmentation, MC > 5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. CONCLUSIONS: Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker.

RETROSPECTIVE COMPARISON OF THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY VS. PREDNISOLONE ALONE IN 30 CASES OF CANINE INFRATENTORIAL BRAIN TUMORS.

Infratentorial tumors are relatively infrequent in dogs and a lack of data makes it difficult to offer prognostic information. Untreated, dogs with these neoplasms have shorter survival times than those with supratentorial tumors. The role of radiation therapy (RT) in the management of infratentorial tumors is poorly defined and tumoral/peritumoral swelling in this site is a potential cause of serious acute side effects. The aim of this retrospective, cohort study was to describe cases of infratentorial tumors treated with fractionated three-dimensional conformal RT (3D CRT) and glucocorticoids (GC), and compare outcomes and survival with dogs affected by tumors in the same location that received GC alone. Thirty patients with a MRI diagnosis of infratentorial tumors were recruited (15 received RT and GC and 15 GC alone). None had mentation changes at presentation. For both groups, MRI and medical records were reviewed; and factors associated with survival were evaluated with Kaplan-Meier product limit survival and Cox regression analysis. Overall median survival time (MST) was 294 days (95% CI 42-545). The MST in the RT group was 756 days (95% CI 209-1302) vs. 89 days (95% CI 34.7-143.3 days) for those dogs treated palliatively with GC alone. This difference was statistically significant (P = 0.001). No other factors (including neurological signs, MRI features, tumor volume and total RT dose) were statistically associated with survival in the RT group. This study suggests that 3D CRT offers a survival advantage for dogs with infratentorial tumors compared to GC alone, and significant complications are uncommon.

Primary angiocentric/angioinvasive T-cell lymphoma of the tympanic bulla in a feline leukaemia virus-positive cat.

Case summary A 5-year-old neutered female feline leukaemia virus (FeLV)-positive domestic shorthair cat with a 5 month history of otitis media was referred for head tilt, stertor and dyspnoea. Computed tomography scan revealed soft tissue opacities inside the right tympanic bulla, with bone remodelling, and concurrent nasopharyngeal and intracranial invasion. Endoscopically guided bioptic samples were collected from the nasopharynx and middle ear. Histology revealed dense sheets of round, large, neoplastic cells, often surrounding or invading vascular walls. Neoplastic cells expressed CD3, FeLV p27 and gp70 antigens. A middle ear angiocentric/angioinvasive T-cell lymphoma was diagnosed. After improvement of clinical conditions following radiation therapy, the cat died unexpectedly. At necropsy, hepatic and splenic spread was detected. Relevance and novel information Primary middle ear tumours are rare and their diagnosis is often delayed as clinical signs mimic more common otological conditions. Multiple bioptic specimens are pivotal for a definitive diagnosis. The young age of the cat, serology and immunohistochemistry revealed a possible transforming role of FeLV.

Veterinary photodynamic therapy: a review.

Whereas in human medicine photodynamic therapy represents a well-known and recognized treatment option for diverse indications, it is still little known and unfortunately not yet established treatment option for pets. Various photosensitizers and light sources have been used and clinical results have been published. The main indication is a frequently occurring skin tumor in cats: in situ carcinoma/squamous cell carcinoma, mainly found in not or only slightly pigmented areas of the head. For early stages of this tumor, promising results have been published, partly using new, selective drugs to decrease light sensitivity after systemic administration and to increase response rates. Other possible indications are urinary tract neoplasia of dogs and equine sarcoids, the latter representing very common tumors in horses where no effective treatment is known so far. This review article summarizes the role of photodynamic therapy in veterinary medicine.

Chemotherapy and radiation therapy in 4 dogs with muscle-invasive transitional cell carcinoma of the urinary tract.

Four dogs with T(2)N(0)M(0) transitional cell carcinoma of the lower urinary tract underwent multimodal treatment consisting of neoadjuvant chemotherapy, external-beam radiotherapy, and adjuvant chemotherapy. No significant toxicity was documented. All dogs showed clinical improvement and reduction of tumor volume based on computed tomography (CT).

RésuméChimiothérapie et radiothérapie comme traitement pour carcinomes à cellules transitionnelles urothéliaux avec infiltration du muscle dans 4 chiens. Quatre chiens avec des carcinomes à cellules transitionnelles du bas tractus urinaire (TNM) ont été traités avec une approche multimodale consistent en chimiothérapie néodjuvante, radiothérapie externe et chimiothérapie adjuvante. Nous n'avons pas observé une toxicité signifiante. Tous les chiens ont répondu à ce traitement multimodale, défini comme amélioration des symptômes cliniques et réduction des dimensions de la tumeur, indiqué au scanner.(Traduit par Julia Buchholz).

3D conformal radiation therapy for palliative treatment of canine nasal tumors.

We evaluated the response of 38 dogs treated with a coarsely fractionated, palliative radiation protocol based on CT-based 3D treatment planning. Dogs with histologically confirmed malignant nasal tumors were studied. Treatment prescriptions consisted of 3-4 x 8 Gy, 4-5 x 6 Gy, or 10 x 3 Gy fractions. Selected patient and tumor factors were evaluated for an effect on outcome. Resolution of clinical signs was reported after irradiation in all dogs. Acute toxicities were mild and short lived. Thirty-seven of 38 dogs died or were euthanized due to tumor-related disease. Overall median progression-free interval (PFI) was 10 months. Tumor stage affected response, with modified stage 1 patients having a median PFI 21.3 months vs. a median PFI of 8.5 months for modified stage 2 patients (P = 0.0006). Modified stage was the only factor significantly related to outcome. Based on these findings, a palliative radiation prescription based on computerized treatment planning may be justified in some canine nasal tumor patients.

Clinical assessment of repeated propofol-associated anesthesia in cats.

OBJECTIVE: To assess the effects of repeated episodes of propofol-associated anesthesia on quality of recovery from anesthesia, clinical status, and erythrocyte physiology in cats. DESIGN: Original study. ANIMALS: 37 cats undergoing short-duration anesthesia for radiotherapy. PROCEDURES: Twice daily on 5 consecutive days, 13 cats with squamous cell carcinoma of the nasal planum (group 1) underwent anesthesia: first via administration of propofol or a midazolam (0.2 mg/kg [0.09 mg/lb])-propofol combination and then via administration of ketamine and midazolam each day (latter data were not analyzed). During a 19-day period, 24 cats with vaccine associated sarcoma (group 2) were anesthetized 12 times with propofol or a midazolam-propofol combination. Anesthesia was maintained with propofol in both groups. Hematologic analysis was performed before, during, and on completion of radiotherapy; changes in Hct and hemoglobin concentration between groups were compared. RESULTS: Mean duration of anesthesia was 8.1 minutes (range, 5 to 20 minutes); no adverse events were detected during recovery. Total dose of propofol administered did not differ between groups 1 (6.34 mg/kg [2.88 mg/lb]) and 2 (4.71 mg/kg [2.14 mg/lb]). Midazolam administration decreased the propofol dose by 26%. Overall decreases from baseline in Hct and hemoglobin concentration were not significantly different between the 2 groups, nor clinically important; however, compared with baseline, values in group 2 were significantly lower after 6 and 12 anesthetic episodes for both protocols. Heinz bodies were identified in low numbers in both groups during radiotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that repeated propofol-associated short-duration anesthesia does not lead to clinically relevant hematologic changes in cats undergoing short-duration radiotherapy.

Photodynamic therapy of feline cutaneous squamous cell carcinoma using a newly developed liposomal photosensitizer: preliminary results concerning drug safety and efficacy.

BACKGROUND: Squamous cell carcinomas are common skin tumors in cats. We investigated photodynamic therapy (PDT) using a new liposomal photosensitizer as a minimally invasive, effective treatment that can be easily performed while achieving good cosmetic results. AIM: The goal of this study was to assess and describe possible toxicities using a liposomal formulation of the photosensitizer meta-(Tetrahydroxyphenyl)Chlorin (m-THPC) and investigate if favorable pharmacokinetics translate into favorable tumor response and control. ANIMALS: Eighteen client-owned cats with 20 spontaneous cutaneous squamous cell carcinomas were included in the study. METHODS: PDT was performed using a new, liposomal formulation of the photosensitizer. Toxicity, tumor response, and tumor control were evaluated retrospectively. RESULTS: No general adverse effects were observed in cats treated with the new liposomal formulation. Mild local toxicity such as erythema and edema were seen in 15% of the patients. All cats responded to therapy, with a complete response rate of 100%. The overall 1-year control rate was 75%. The tumor recurrence rate was 20% with a median time to recurrence of 172.25 +/-87.1) days. CONCLUSIONS AND CLINICAL IMPORTANCE: A new liposomal photosensitizer was successfully used for squamous cell carcinoma in cats and was well tolerated. There were no systemic adverse effects observed with the liposomal formulation. The favorable pharmacokinetics of the liposomal drug resulted in a favorable tumor response.

Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonography.

BACKGROUND AND OBJECTIVES: One principal mechanism of photodynamic therapy (PDT) in tumors is destruction of tumor-associated vasculature. In the present study, the vascular effects of PDT in tumors were investigated with power Doppler ultrasonography. MATERIALS AND METHODS: Seven cutaneous squamous cell carcinomas in cats were treated. Tumors were examined via power Doppler ultrasonography before, 5 minutes, 1 hour, and 24 hours after PDT. Images were digitized for computer-aided assessment of vascularity and blood volume. RESULTS: Mean baseline tumor vascularity and blood volume were moderate. During PDT, a significant decrease in vascularity and blood volume was noted. Lowest values were found 24 hours after PDT. CONCLUSIONS: Power Doppler ultrasonography represents a non-invasive modality to successfully monitor the vascular effects and thus, treatment efficacy, of PDT.

Performance of a contact textile-based light diffuser for photodynamic therapy.

BACKGROUND: Medical textiles offer a unique contact opportunity that could provide value-added comfort, reliability, and safety for light or laser-based applications. We investigated a luminous textile diffuser for use in photodynamic therapy. METHODS: Textile diffusers are produced by an embroidery process. Plastic optical fibers are bent and sewn into textile to release light by macrobending. A reflective backing is incorporated to improve surface homogeneity, intensity, and safety. Clonogenic assay (MCF-7 cells) and trypan blue exclusion (NuTu19 cells) tests were performed in vitro using 0.1µg/ml m-THPC with three textile diffusers and a standard front lens diffuser. Heating effects were studied in solution and on human skin. PDT application in vivo was performed with the textile diffuser on equine sarcoids (three animals, 50mW/cm(2), 10-20J) and eight research animals. Lastly, computer simulations were performed to see how the textile diffuser might work on a curved object. RESULTS: At low fluency rate, there is a trend for the textile diffuser to have lower survival rates than the front lens diffuser for both cell lines. The textile diffuser was observed to retain more heat over a long period (>1min). All animals tolerated the treatments well and showed similar initial reactions. The simulations showed a likely focusing effect in a curved geometry. CONCLUSIONS: The initial feasibility and application using a textile-based optical diffuser has been demonstrated. Possibilities that provide additional practical advantages of the textile diffuser are discussed.

Horizontal fixation disparity measures with nonius lines.

PURPOSE: It has been reported that changes in visual direction and retinal correspondence may limit the validity of nonius lines as a subjective measure of vergence, at least in particular viewing conditions, e.g., dynamic or forced vergence. Nonius lines may be valid at larger spatial separation between fusion contour and nonius lines. Therefore, we measured fixation disparity varying the amount of a vertical gap between nonius lines. METHODS: A static central fusion stimulus was given at a 100-cm viewing distance. The nonius lines were presented with various vertical gaps either continuously (and adjusted to subjective alignment) or flashed in a series of trials (in adaptive testing). Twelve subjects with normal binocular vision were tested repeatedly to identify individual vergence characteristics. RESULTS: When the vertical gap between nonius lines was increased up to 7.9 deg, the amount of subjective fixation disparity tended to increase in part of the subjects, predominantly in those with an exo fixation disparity. Most subjective fixation disparity measures were correlated with each other and with tonic vergence (i.e., dark vergence tested subjectively without fusion stimulus); however, flashed nonius lines at larger nonius gaps were an exception. CONCLUSIONS: We found physiologically plausible measures of idiosyncratic fixation disparity with continuous nonius lines at any amount of nonius gap or with flashed nonius lines at small gaps. In these conditions, the intersubject variability of fixation disparity was much larger than effects of the spatial separation between fusion stimulus and nonius lines.

Optimizing photodynamic therapy: in vivo pharmacokinetics of liposomal meta-(tetrahydroxyphenyl)chlorin in feline squamous cell carcinoma.

PURPOSE: The aim of the present study was to optimize and simplify photodynamic therapy using a new liposomal formulation of the photosensitizer meta-(tetrahydroxyphenyl)chlorin [m-THPC (Foscan); liposomal m-THPC (Fospeg)] and to reduce systemic reactions to the photosensitizer. EXPERIMENTAL DESIGN: To examine the pharmacokinetics of liposomal m-THPC, we determined tissue and plasma variables in feline patients with spontaneous squamous cell carcinoma. In vivo fluorescence intensity measurements of tumor and skin were done with a fiber spectrophotometer after i.v. injection of m-THPC or liposomal m-THPC in 10 cats. Blood samples, drawn at several time points after photosensitizer administration, were analyzed by high-performance liquid chromatography. RESULTS: None of the liposomal m-THPC-treated cats showed side effects during or after drug injection. Fluorescence intensities, fluorescence ratios (tumor fluorescence divided by skin fluorescence), and bioavailability in the tumor were 2 to 4 times higher with liposomal m-THPC compared with m-THPC. Liposomal m-THPC concentration in the tumor increased constantly to reach a maximum at 4 hours after injection. Plasma concentration and bioavailability were approximately 3 times higher with liposomal m-THPC compared with m-THPC measured at the time points of highest plasma concentration. The distribution half-life was shorter with liposomal m-THPC, resulting in maximal tumor accumulation up to 5.5 times earlier. Maximal tumor accumulation and maximal fluorescence ratio with liposomal m-THPC occurred at the same time point, indicating maximal selectivity. In both groups, all cats responded to therapy. CONCLUSIONS: Liposomal m-THPC was well tolerated by all cats and seems to have superior pharmacokinetic properties compared with m-THPC. The efficacy of the drug warrants further study.