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1.
Acta Neuropathol ; 142(3): 565-590, 2021 09.
Article in English | MEDLINE | ID: mdl-34283254

ABSTRACT

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that frequently harbor genetic alterations in polycomb repressor complex 2 (PRC2) components-SUZ12 and EED. Here, we show that PRC2 loss confers a dedifferentiated early neural-crest phenotype which is exclusive to PRC2-mutant MPNSTs and not a feature of neurofibromas. Neural crest phenotype in PRC2 mutant MPNSTs was validated via cross-species comparative analysis using spontaneous and transgenic MPNST models. Systematic chromatin state profiling of the MPNST cells showed extensive epigenomic reprogramming or chromatin states associated with PRC2 loss and identified gains of active enhancer states/super-enhancers on early neural crest regulators in PRC2-mutant conditions around genomic loci that harbored repressed/poised states in PRC2-WT MPNST cells. Consistently, inverse correlation between H3K27me3 loss and H3K27Ac gain was noted in MPNSTs. Epigenetic editing experiments established functional roles for enhancer gains on DLX5-a key regulator of neural crest phenotype. Consistently, blockade of enhancer activity by bromodomain inhibitors specifically suppressed this neural crest phenotype and tumor burden in PRC2-mutant PDXs. Together, these findings reveal accumulation of dedifferentiated neural crest like state in PRC2-mutant MPNSTs that can be targeted by enhancer blockade.


Subject(s)
Nerve Sheath Neoplasms/drug therapy , Nerve Sheath Neoplasms/genetics , Peripheral Nervous System Neoplasms/drug therapy , Peripheral Nervous System Neoplasms/genetics , Polycomb Repressive Complex 2/genetics , Animals , Biomarkers, Tumor , Cell Cycle Proteins/antagonists & inhibitors , Cell Differentiation/genetics , Cell Line, Tumor , Dogs , Enhancer Elements, Genetic/genetics , Epigenesis, Genetic/genetics , Homeodomain Proteins/genetics , Humans , Mice , Mice, Transgenic , Mutation , Nerve Sheath Neoplasms/pathology , Neural Crest/pathology , Peripheral Nervous System Neoplasms/pathology , Species Specificity , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics , Xenograft Model Antitumor Assays , Zebrafish
2.
Vet Surg ; 49(4): 659-667, 2020 May.
Article in English | MEDLINE | ID: mdl-32170778

ABSTRACT

OBJECTIVE: To report outcomes of dogs treated for lung lobe torsion (LLT) and to determine prognostic factors for survival. STUDY DESIGN: Retrospective multicenter study from four veterinary teaching hospitals. ANIMALS: Dogs (n = 80) with LLT. METHODS: Medical records were reviewed for clinical and histopathological findings. Long-term outcome was assessed with an owner questionnaire. Lung lobe torsion was classified as idiopathic or secondary on the basis of the etiology. RESULTS: The most represented breeds were pugs (47.5%) and sighthounds (16.2%). The cause of the LLT was considered primary in 77%, secondary in 21%, and unknown in 2% of dogs. Postoperative complications were recorded in 14% of dogs. Overall, 95% of dogs survived to discharge, and median follow-up was 1095 days (range, 7-3809). Owners assessed outcomes and quality of life as excellent in 93% and 89% of dogs, respectively. Primary LLT was associated with a longer survival (median not reached in the study) compared with secondary LLT (921 days; range, 7-2073; P = .001). CONCLUSION: Overall long-term survival after lung lobectomy for LLT was excellent. Primary LLT was associated with longer survival compared with secondary LLT. Long-term owner evaluation of clinical outcome for dogs undergoing lung lobectomy for LLT was considered excellent. CLINICAL IMPACT: Dogs with primary LLT undergoing lung lobectomy have a longer survival time compared with dogs with secondary LLT and have an excellent postoperative outcome.


Subject(s)
Dog Diseases/surgery , Lung Diseases/veterinary , Postoperative Complications/veterinary , Torsion Abnormality/veterinary , Animals , Dogs , Female , Longevity , Lung Diseases/surgery , Male , Quality of Life , Retrospective Studies , Torsion Abnormality/etiology , Torsion Abnormality/surgery , Treatment Outcome
3.
Vet Surg ; 48(8): 1490-1499, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31179557

ABSTRACT

OBJECTIVE: To describe the technique and outcomes for bilateral caudal maxillectomy for resection of large caudal maxillary tumors crossing palatal midline in two dogs. STUDY DESIGN: Clinical case report. ANIMALS: Two client-owned dogs. METHODS: Two client-owned dogs with primary caudal maxillary tumors, a poorly differentiated sarcoma, and a multilobulated osteochondrosarcoma. Bilateral caudal maxillectomies were performed for curative-intent resection of these tumors. The angularis oris axial pattern flap was used for primary closure in one dog and for dehiscence repair in the other. RESULTS: Both tumors were resected with complete histologic margins. The defects were closed with local buccal mucosal flaps, with or without a unilateral angularis oris flap. Esophagostomy tubes were placed at time of surgery to bypass oral feeding. Incisional dehiscence and subsequent oronasal fistula formation occurred as a postoperative complication in both dogs (3 and 10 days, respectively). Both were successfully repaired with a combination of local buccal mucosal flaps and the angularis oris flap. Both dogs had good functional outcome and quality of life after recovery from revision surgery. CONCLUSION: Bilateral caudal maxillectomy allowed resection of caudal maxillary tumors crossing palatal midline, with good function and quality of life after recovery in 2 dogs. CLINICAL SIGNIFICANCE: Good outcomes including complete resections are achievable with bilateral caudal maxillectomy despite complications. Local mucosal and axial pattern flaps can be used for dehiscence repair.


Subject(s)
Bone Neoplasms/veterinary , Dog Diseases/surgery , Postoperative Complications/veterinary , Sarcoma/veterinary , Surgical Flaps/veterinary , Animals , Bone Neoplasms/surgery , Craniotomy , Dogs , Female , Male , Maxilla/surgery , Postoperative Complications/surgery , Reoperation , Sarcoma/surgery , Surgical Wound Dehiscence/veterinary
4.
Vet Surg ; 48(6): 923-932, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31140634

ABSTRACT

OBJECTIVE: To describe the clinical characteristics, perioperative complications, and outcomes in dogs surgically treated for gastric carcinoma. STUDY DESIGN: Multi-institutional retrospective case series. ANIMALS: Forty client-owned dogs with histologically confirmed gastric carcinoma. METHODS: Medical records were reviewed for preoperative diagnostics, surgery, histopathology, postoperative complications, adjuvant chemotherapy, disease progression, and survival. Variables were assessed for associations with outcome by using Cox proportional hazards regression analysis. RESULTS: Surgical treatment included partial gastrectomy (28 dogs), Billroth I (9 dogs), subtotal gastrectomy (2 dogs), and submucosal resection (1 dog). Major postoperative complications occurred in 8 of 40 dogs, including septic peritonitis secondary to dehiscence in 4 dogs. The median progression free interval was 54 days, and the median survival time (MST) was 178 days (range, 1-1902). According to multivariable analysis results, experiencing an intraoperative complication was associated with an increased risk of death (hazard ratio [HR] 3.5, 95% CI 1.1-9.8, P = .005), and administration of adjuvant chemotherapy correlated with an improved survival (HR 0.4, 95% CI 0.2-0.9, P = .03). CONCLUSION: In this population of dogs, MST exceeded historically reported data, major postoperative complication rates were comparable to established literature, and administration of adjuvant chemotherapy was associated with improved survival. CLINICAL SIGNIFICANCE: Results from this study may be used to counsel owners more accurately regarding prognosis for dogs undergoing surgical excision for gastric carcinoma.


Subject(s)
Carcinoma/veterinary , Dog Diseases/surgery , Intraoperative Complications/veterinary , Postoperative Complications/veterinary , Societies, Veterinary , Stomach Neoplasms/veterinary , Animals , Carcinoma/surgery , Chemotherapy, Adjuvant , Dogs , Female , Male , Retrospective Studies , Stomach Neoplasms/surgery , Treatment Outcome
5.
Vet Surg ; 47(6): 802-808, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30051470

ABSTRACT

OBJECTIVE: To report modification of the endoprosthesis surgical limb-salvage technique to treat a locally extensive osteosarcoma in a dog and associated functional outcome. STUDY DESIGN: Clinical case report. ANIMALS: One client-owned dog. METHODS: A 9-year-old dog was presented for treatment of a locally extensive distal radial osteosarcoma. A limb-salvage surgery was performed with a second-generation Veterinary Orthopedic Implants (VOI) endoprosthesis to reconstruct the radial segmental and carpal osseous defect. The endoprosthesis was stabilized with a 16-mm-wide locking VOI limb-salvage plate. The level of the osteotomy of the radius/ulna was 3 cm proximal to the periosteal reaction seen on radiographs, and the distal osteotomy extended through the proximal metacarpal bones (II-V), 3 cm from the distal extent of the soft tissue component of the tumor. A 3.5-mm SOP (String of Pearls) plate was used as adjunct fixation. RESULTS: The postoperative functional outcome was classified as acceptable. Ambulation was normal, with mild subjective lameness on the treated limb at examinations 20, 43, and 63 days after surgery. The dog was euthanized 92 days after surgery because of progressive metastatic disease. CONCLUSION: The modified endoprosthetic technique allowed complete excision of the carpal joint, which resulted in acceptable functional outcomes in the dog described here. CLINICAL SIGNIFICANCE: Distal ostectomies may include part of the manus during limb salvage surgery of locally extensive distal radial osteosarcoma and using an endoprosthesis implant to reconstruct the defect.


Subject(s)
Bone Neoplasms/veterinary , Dog Diseases/surgery , Limb Salvage/veterinary , Osteosarcoma/veterinary , Prostheses and Implants/veterinary , Animals , Bone Neoplasms/surgery , Carpus, Animal/pathology , Dogs , Female , Limb Salvage/methods , Osteosarcoma/surgery , Treatment Outcome
6.
Vet Surg ; 45(1): 60-5, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26547378

ABSTRACT

OBJECTIVE: To compare the peak vertical force (PVF) and vertical impulse (VI) in dogs with naturally occurring cranial cruciate ligament (CCL) disease with or without concurrent meniscal injury. STUDY DESIGN: Prospective case series. STUDY POPULATION: Client-owned dogs with naturally occurring CCL disease. METHODS: Dogs with hind limb lameness because of CCL disease that required surgery underwent force plate gait analysis. Force plate analysis was performed at a walking gait (speed 1-1.3 m/s; acceleration ± 0.5 m/s(2)) and data were analyzed using commercial proprietary software. Meniscal injury was diagnosed either by mini-arthrotomy or arthroscopy. The primary outcome was PVF and the secondary outcome was VI. Comparisons were made between dogs with or without meniscal injury, and dogs with partial or complete CCL rupture. RESULTS: Forty dogs were included. Meniscal injury was present in 18/40 dogs (45%). PVF (P = .003) and VI (P = .01) were significantly lower in dogs with meniscal injury than in dogs without meniscal injury. CONCLUSION: Dogs with CCL disease and medial meniscal injury had significantly reduced PVF and VI.


Subject(s)
Anterior Cruciate Ligament Injuries , Dog Diseases/surgery , Rupture/veterinary , Tibial Meniscus Injuries , Animals , Anterior Cruciate Ligament/pathology , Anterior Cruciate Ligament/surgery , Arthroscopy/veterinary , Biomechanical Phenomena , Dogs , Fascia , Menisci, Tibial/pathology , Menisci, Tibial/surgery , Prospective Studies
7.
Vet Surg ; 44(1): 70-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24708556

ABSTRACT

OBJECTIVE: To describe and compare a large population of dogs that had pancarpal arthrodesis (PCA) using either a hybrid dynamic compression plate (HDCP) or a CastLess Plate (CLP). STUDY DESIGN: Multicenter, retrospective, cohort study. ANIMALS: Dogs (n = 240; 261 PCA). METHODS: Medical records (2000-2012) from 12 UK orthopedic centers were reviewed for dogs that had PCA to document signalment, diagnosis, arthrodesis method, and complication rates. Follow-up data were used to compare outcome (lameness evaluation and radiographic healing) after use of HDCP and CLP plates. RESULTS: PCA was performed with HDCP in 125 cases, CLP in 105, and by other techniques in 31. Carpal hyperextension injury was the most common diagnosis in HDCP and CLP groups. Surgical site infection (18.3%) was the most common postoperative complication. There was no difference in intra- (11% HDCP, 21% CLP) or postoperative (34% HDCP, 41% CLP) complication rates. Use of external coaptation did not affect postoperative complication rates or outcome. External coaptation related complications occurred in 32% HDCP and 18% CLP (P = .02). At median follow-up, most dogs were classified as having no or mild lameness (73% HDCP, 83% CLP) and there was radiographic healing in 40% HDCP and 46% CLP (P = .8) cases. CONCLUSIONS: CLP and HDCP may both be used successfully to achieve pancarpal arthrodesis. Adjunctive external coaptation does not appear to have a measurable clinical benefit but is associated with morbidity.


Subject(s)
Arthrodesis/veterinary , Bone Plates/veterinary , Carpus, Animal/surgery , Animals , Cohort Studies , Dogs , England , Female , Gait , Male , Postoperative Period , Retrospective Studies , Surgical Wound Infection/veterinary , Surveys and Questionnaires , Wound Healing
8.
J Am Vet Med Assoc ; 262(7): 1-9, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38382204

ABSTRACT

OBJECTIVE: To report the clinical characteristics, treatments, and outcomes in a cohort of dogs with histologically confirmed retroperitoneal sarcoma (RPS) and to identify potential variables of prognostic significance. ANIMALS: 46 client-owned dogs from 10 clinics with histopathologic diagnosis of a sarcoma originating from the retroperitoneal space. METHODS: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed to report descriptive data for all cases and overall survival time. Multivariate analysis was utilized to evaluate prognostic factors for overall survival. RESULTS: Hemangiosarcoma was the most common histologic subtype diagnosed (76.1%). Cytoreductive and curative intent surgical excision of the RPS was attempted in 12 and 22 dogs, respectively; 12 dogs underwent no surgery or had an exploratory laparotomy with incisional biopsy only. Nineteen dogs received adjuvant chemotherapy, either injectable or metronomic, and 1 dog received adjuvant radiation therapy. Fourteen of the 34 (41.2%) surgically treated dogs developed evidence of local recurrence, but there was no difference in local recurrence when comparing dogs categorized as curative intent versus cytoreductive surgery. The median overall survival time was 238 days. On multivariable analysis, treatment approach was associated with survival with surgical excision (vs palliative treatment) and adjuvant chemotherapy following surgery being protective against death. A diagnosis of hemangiosarcoma was associated with a greater hazard of death. CLINICAL RELEVANCE: This study demonstrates a substantially greater survival time than previously published and suggests a survival benefit from surgical excision and adjuvant chemotherapy.


Subject(s)
Dog Diseases , Retroperitoneal Neoplasms , Sarcoma , Animals , Dogs , Dog Diseases/therapy , Dog Diseases/mortality , Dog Diseases/surgery , Dog Diseases/pathology , Sarcoma/veterinary , Sarcoma/therapy , Sarcoma/mortality , Sarcoma/surgery , Retroperitoneal Neoplasms/veterinary , Retroperitoneal Neoplasms/mortality , Retroperitoneal Neoplasms/surgery , Retroperitoneal Neoplasms/therapy , Retroperitoneal Neoplasms/pathology , Male , Female , Retrospective Studies , Treatment Outcome , Survival Analysis , Cohort Studies , Hemangiosarcoma/veterinary , Hemangiosarcoma/mortality , Hemangiosarcoma/therapy , Hemangiosarcoma/surgery , Hemangiosarcoma/pathology
9.
Vet Comp Oncol ; 21(2): 327-331, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36861227

ABSTRACT

Apocrine gland anal sac adenocarcinoma (AGASACA) is a highly relevant disease in dogs, with a high rate of lymph node (LN) metastasis during the course of disease. A recent study showed that risk for death and disease progression was significantly associated with primary tumour size less than 2 and 1.3 cm, respectively. The objective of this study was to report the proportion of dogs that have primary tumours less than 2 cm in diameter, that are diagnosed with LN metastasis at presentation. This was a single site retrospective study of dogs that underwent treatment for AGASACA. Dogs were included if physical examination primary tumour measurements were available, abdominal staging was performed, and confirmation of abnormal lymph nodes by cytology or histology was done. Over a 5-year period, 116 dogs were included for review with 53 (46%) having metastatic LN at presentation. The metastatic rate for dogs with primary tumours <2 cm was 20% (9 of 46 dogs) compared to 63% (44 of 70 dogs) in dogs with primary tumours ≥2 cm. The association between tumour size group (<2 vs. ≥2 cm) and the presence of metastasis at presentation was significant (P < .0001) with an OR of 7.0 (95% CI: 2.9-15.7). Primary tumour size was significantly associated with LN metastasis at presentation but the proportion of dogs that presented with LN metastasis in the <2 cm group was relatively high. This data suggests that dogs with small tumours may still have aggressive tumour biology.


Subject(s)
Adenocarcinoma , Anal Gland Neoplasms , Anal Sacs , Dog Diseases , Dogs , Animals , Lymphatic Metastasis/pathology , Apocrine Glands/pathology , Anal Sacs/pathology , Adenocarcinoma/veterinary , Adenocarcinoma/pathology , Retrospective Studies , Anal Gland Neoplasms/pathology , Dog Diseases/pathology , Lymph Nodes/pathology
10.
J Am Vet Med Assoc ; 261(10): 1-5, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37290758

ABSTRACT

OBJECTIVE: To report to what degree narrative operative reports for soft tissue sarcoma (STS) and mast cell tumor (MCT) resections met a predetermined template made up of essential elements. ANIMALS: 197 consecutive client-owned animals between May 1, 2017, and August 1, 2022. PROCEDURES: A consensus list of 9 elements made up the final synoptic operative report (SR) template. Consecutive narrative surgery reports (NRs) of dogs that underwent MCT or STS resection were then reviewed to determine how many of the SR elements were present in each NR. A score was then determined for each NR out of a maximum total of 9. RESULTS: Overall, 197 reports (99 MCT and 98 STS) were included. The median score was 5 (56% of elements reported). No report had all 9 elements, and 1 report had none of the elements reported. When MCT and STS were analyzed independently, the median score was 6 (67% of elements reported) for MCT and 5 (56% of elements reported) for STS. There was a trend of more cases with MCT that had a preoperative diagnosis, intraoperative measurements of the tumor, and surgeon margins marked compared to dogs with STS. More dogs with STS had an estimated Enneking dose compared to dogs with MCT. CLINICAL RELEVANCE: Our data show that essential elements of STS and MCT resection in dogs were inconsistently recorded and no case had all elements present. This mirrors data in people and presses the need for more standardization in reporting of cancer operations in veterinary medicine.


Subject(s)
Dog Diseases , Sarcoma , Soft Tissue Neoplasms , Dogs , Animals , Mast Cells/pathology , Dog Diseases/surgery , Dog Diseases/pathology , Sarcoma/surgery , Sarcoma/veterinary , Soft Tissue Neoplasms/surgery , Soft Tissue Neoplasms/veterinary , Retrospective Studies
11.
J Am Vet Med Assoc ; 261(9): 1-8, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37257826

ABSTRACT

OBJECTIVE: To determine the incidence of histologic grade shift (alteration of grade relative to the original tumor) in recurrent canine soft tissue sarcoma (STS) and mast cell tumor (MCT), and to determine the level of agreement between blinded pathologist review and original histology interpretation of STS and MCT grades. ANIMALS: 15 dogs with recurrent cutaneous/subcutaneous STS and 5 dogs with recurrent cutaneous MCT. All included dogs underwent excision of both the primary and recurrent tumors and had tumor samples available for review. PROCEDURES: The medical records and histology database from a single institution were reviewed, and data were recorded and analyzed. A single board-certified veterinary pathologist performed blinded evaluation of all excisional tumor samples, including both primary and recurrent disease, and these were evaluated independently and in conjunction with initial pathologic diagnoses. RESULTS: Based on single pathologist review, 7 of 15 (46.7%) dogs with recurrent STS had grade shift characterized by a higher or lower recurrent tumor grade in 4 of 7 and 3 of 7 cases, respectively, and 1 of 5 dogs with recurrent MCT had grade shift characterized by an increased grade of the recurrent tumor. Variability in reported grade between original histology report and pathologist review occurred for 13 of 30 (43.3%) STS excisional biopsy samples and 0 of 10 MCT excisional biopsy samples. CLINICAL RELEVANCE: Grade shift has been reported in multiple tumor types in people and has the potential to alter prognosis and treatment recommendations. This is the first study to document this phenomenon in dogs. Additional large-scale studies are needed to determine factors associated with grade shift as well as prognostic significance of grade shift for recurrent canine STS and MCT.


Subject(s)
Dog Diseases , Sarcoma , Soft Tissue Neoplasms , Animals , Dogs , Female , Male , Dog Diseases/epidemiology , Dog Diseases/pathology , Incidence , Recurrence , Retrospective Studies , Soft Tissue Neoplasms/veterinary , Sarcoma/veterinary
12.
Article in English | MEDLINE | ID: mdl-37436906

ABSTRACT

OBJECTIVE: To describe the appearance of lesions noted on abdominal computed tomography (CT) in dogs with spontaneous hemoperitoneum and determine the utility in using CT to differentiate benign from malignant lesions. DESIGN: Retrospective case series. SETTING: Single-center, university veterinary teaching emergency service. ANIMALS: Twenty-six dogs presented between 2015 and 2020 with spontaneous hemoperitoneum confirmed via abdominocentesis with pre- and postcontrast abdominal CT performed prior to surgery or euthanasia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: On histopathological diagnosis, 20 of 26 lesions were found to be malignant, and 6 of 26 were benign. Two radiologists reviewed the CTs. Radiologist 1 correctly identified 5 of 6 (83.3%) benign cases and 18 of 20 (90%) malignant cases. Radiologist 2 correctly identified 2 of 6 (33.3%) benign lesions and 18 of 20 (90%) malignant cases. Of the 10 imaging descriptors evaluated, none were significantly associated with the histological diagnosis. CONCLUSIONS: Results from the current study suggest that abdominal CT imaging of spontaneous hemoperitoneum cases is not a reliable indicator of malignancy versus benignancy. As such, prognosis should not be defined using this modality alone prior to emergency surgery and instead should be concluded based on the clinical course of the patient and histopathological findings of the resected tissues after surgery.


Subject(s)
Dog Diseases , Hemoperitoneum , Dogs , Animals , Hemoperitoneum/diagnostic imaging , Hemoperitoneum/veterinary , Retrospective Studies , Tomography, X-Ray Computed/veterinary , Dog Diseases/diagnostic imaging
13.
Vet Comp Oncol ; 21(1): 82-90, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36271481

ABSTRACT

Surgical resection of solid tumours, especially in early stages of disease, remains a cornerstone of cancer treatment in dogs and cats. There are numerous publications that show a strong association between local tumour control and outcome. To achieve local control in some cases radiation therapy and surgery are combined, with radiation therapy being delivered in the neoadjuvant or adjuvant setting. The objective of the study was to report acute toxicity and surgical site complication data in dogs that received a short-course pre-operative (SCPO) radiation therapy protocol, followed by surgical excision for various solid tumours. Medical records were reviewed, and data was analysed retrospectively. Dogs were included if a dermal or subcutaneous solid tumour was treated with SCPO radiation therapy and then was resected on the last day of radiation or 2-3 weeks later. A total of 34 dogs with 35 primary tumours were included. Acute radiation toxicity was diagnosed in 14 sites (40%). VRTOG scores were grade 1 in 50%, grade 2 in 43%, and grade 3 in 7%. Surgical site complications were identified in 17% of dogs with an overall surgical site infection rate of 11%. According to the Clavien-Dindo classification, two dogs required medical intervention (grade 2), 1 dog required surgical intervention under general anaesthesia (grade 3b), and 1 dog died as a result of complications (grade 5). Logistic regression analysis found that anatomic site was significantly associated with complications, where tumours located on the extremity was protective (P = .02; OR 0.06).


Subject(s)
Dog Diseases , Neoplasms , Animals , Dogs , Dog Diseases/radiotherapy , Dog Diseases/surgery , Feasibility Studies , Neoadjuvant Therapy/veterinary , Neoplasms/radiotherapy , Neoplasms/surgery , Neoplasms/veterinary , Retrospective Studies
14.
J Am Vet Med Assoc ; 261(10): 1-9, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37257825

ABSTRACT

OBJECTIVE: To describe the clinical characteristics, procedural techniques, complications, and outcomes of dogs and cats undergoing any of the following modified hemipelvectomy techniques: concurrent partial sacrectomy and/or partial vertebrectomy, osseous excision crossing midline, and reconstruction without the use of local musculature. ANIMALS: 23 client-owned animals (20 dogs and 3 cats) that underwent modified hemipelvectomy techniques. Animals that underwent traditional (nonmodified) hemipelvectomy techniques were excluded. PROCEDURES: The medical records of 3 academic institutions were reviewed, and data were recorded and analyzed. RESULTS: Modified hemipelvectomy was performed with partial sacrectomy and/or vertebrectomy in 11 dogs, excision crossing pelvic midline with concurrent limb amputation in 5 dogs and 2 cats, and closure without use of native muscle or mesh in 4 dogs and 1 cat. Surgery was performed for tumor excision in all cases. Excision was reported as complete in 16 of 23, incomplete in 6 of 23, and not recorded in 1 of 23 animals. All animals survived to discharge. Only animals undergoing partial sacrectomy/vertebrectomy (4/11) experienced postoperative mobility concerns. Major intra- or post-operative complications (grades 3 and 4) occurred in 2 dogs that underwent partial sacrectomy/vertebrectomy, and 1 of these animals experienced a complication that resulted in death. The median time to death or last follow-up was 251 days (range, 3 to 1,642). CLINICAL RELEVANCE: The modified hemipelvectomy techniques reported in this cohort were overall well tolerated with good functional outcomes. These findings support the use of these modified hemipelvectomy techniques in dogs and cats, and previous notions regarding tolerable hemipelvectomy procedures should be reconsidered. However, additional studies with larger numbers of patients undergoing modified hemipelvectomy techniques are needed to gain more information.


Subject(s)
Cat Diseases , Dog Diseases , Hemipelvectomy , Cats , Dogs , Animals , Hemipelvectomy/veterinary , Cat Diseases/surgery , Dog Diseases/surgery , Amputation, Surgical/veterinary , Postoperative Complications/veterinary , Retrospective Studies , Treatment Outcome
15.
Genes (Basel) ; 14(3)2023 02 23.
Article in English | MEDLINE | ID: mdl-36980828

ABSTRACT

Osteosarcoma prognosis has remained unchanged for the past three decades. In both humans and canines, treatment is limited to excision, radiation, and chemotherapy. Chemoresistance is the primary cause of treatment failure, and the trajectory of tumor evolution while under selective pressure from treatment is thought to be the major contributing factor in both species. We sought to understand the nature of platinum-based chemotherapy resistance by investigating cells that were subjected to repeated treatment and recovery cycles with increased carboplatin concentrations. Three HMPOS-derived cell lines, two resistant and one naïve, underwent single-cell RNA sequencing to examine transcriptomic perturbation and identify pathways leading to resistance and phenotypic changes. We identified the mechanisms of acquired chemoresistance and inferred the induced cellular trajectory that evolved with repeated exposure. The gene expression patterns indicated that acquired chemoresistance was strongly associated with a process similar to epithelial-mesenchymal transition (EMT), a phenomenon associated with the acquisition of migratory and invasive properties associated with metastatic disease. We conclude that the observed trajectory of tumor adaptability is directly correlated with chemoresistance and the phase of the EMT-like phenotype is directly affected by the level of chemoresistance. We infer that the EMT-like phenotype is a critical component of tumor evolution under treatment pressure and is vital to understanding the mechanisms of chemoresistance and to improving osteosarcoma prognosis.


Subject(s)
Bone Neoplasms , Osteosarcoma , Animals , Dogs , Humans , Carboplatin/pharmacology , Carboplatin/therapeutic use , Transcriptome/genetics , Cell Line, Tumor , Drug Resistance, Neoplasm/genetics , Osteosarcoma/drug therapy , Osteosarcoma/genetics , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics
16.
Front Vet Sci ; 10: 1283728, 2023.
Article in English | MEDLINE | ID: mdl-38274657

ABSTRACT

Background: Information on dogs that undergo radiation therapy (RT) with non-stereotactic protocols in addition to surgical stabilization with implant placement for treatment of bone tumors is limited. Objective: Our primary objectives were to describe the clinical characteristics as well as short- and long-term outcomes, including complications, function, and disease progression, in dogs that underwent both surgical stabilization with implant placement and non-stereotactic RT for local treatment of a bone tumor. Methods: A bi-institutional retrospective case series was performed. Animals: Eight client-owned dogs that underwent both surgical stabilization with implant placement and non-stereotactic RT for local treatment of a bone tumor were included. Results: Tumor types included osteosarcoma or suspected osteosarcoma (5), plasma cell tumor (2), and grade 3 fibrosarcoma (1). Radiation protocols were hypofractionated (palliative intent) in 5 dogs and fractionated (definitive intent) in 3 dogs. Five dogs experienced complications following both RT and surgery, including grade 1 complications in two dogs, a grade 2 complication in one dog, both grade 1 and 2 complications in one dog, and both grade 2 and 3 complications in one dog. Clinical signs subjectively improved in all dogs that had outcomes relative to function documented post-surgery/RT (7). Of these 7 dogs, 4 maintained long-term improvement in function and clinical signs, whereas 3 experienced subsequent recurrence/progression of clinical signs at a median of 133 days (range 91-186) postoperatively in association with biomechanical complications (screw loosening), surgical site infection, and local disease progression in 1 dog each; subsequent treatment resulted in improved clinical signs for each of these 3 dogs, such that overall good long-term functional outcomes were experienced. No dogs required amputation or additional vertebral surgery as salvage for local disease control or palliation. The median progression free interval was 206 days (range 25-1078), and the median survival time was 253 days (range 122-1078) with 1 additional dog lost to follow-up at 575 days. Two dogs experienced local disease progression, and 6 dogs experienced systemic disease progression; both dogs that developed local disease progression received palliative intent RT protocols. Clinical relevance: In this cohort, dogs with primary bone tumors that underwent surgical stabilization with implant placement and hypofractionated or fractionated non-stereotactic RT for local treatment had a low incidence of major complications, good limb function and ambulation post-treatment, and relatively prolonged survival times despite disease progression.

17.
Vet Comp Oncol ; 21(4): 587-594, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37464904

ABSTRACT

Renal carcinomas (RC) are uncommonly encountered in feline medicine. Limited information regarding clinical presentation and postoperative outcomes is available. The purpose of this multi-institutional, retrospective study was to describe the presenting features and clinical outcomes of cats with RC undergoing nephrectomy. Thirty-six client-owned cats were included. Medical records from participating institutions were searched to identify cats that had a histopathologic diagnosis of RC and underwent nephrectomy from January 2001 to October 2021. The most common presenting complaints were weight loss (36.1%) and hyporexia (30.6%). Based on preoperative imaging and intraoperative findings, eight cats had suspected metastasis at the time of surgery (22.2%). Twenty-eight cats survived to discharge (77.8%). Median progression free interval (PFI) could not be determined, as only six cats developed suspected recurrence (16.7%) and seven cats developed suspected metastasis (19.4%). The all-cause median survival time (MST) was 203 days (95% confidence interval [CI]: 84, 1379 days). When cases that died prior to discharge were excluded, MST increased to 1217 days (95% CI: 127, 1641 days). One-year, two-year, and three-year survival rates were all 40.4%. Neither renal tumour histologic subtype nor the presence of preoperative azotemia, anaemia, erythrocytosis, haematuria, or suspected metastasis at diagnosis were found to influence survival. For cats surviving to discharge, prolonged survival times were possible. Further studies are necessary to elucidate other potential prognostic factors, the utility of postoperative adjuvant treatment, and to identify cats at-risk of mortality in the perioperative period.


Subject(s)
Carcinoma, Renal Cell , Cat Diseases , Kidney Neoplasms , Cats , Animals , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/veterinary , Retrospective Studies , Treatment Outcome , Nephrectomy/veterinary , Kidney Neoplasms/surgery , Kidney Neoplasms/veterinary , Cat Diseases/surgery
18.
Vet Comp Oncol ; 21(4): 739-747, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37727977

ABSTRACT

Malignant peripheral nerve sheath tumours (MPNST) of a plexus nerve or nerve root cause significant morbidity and present a treatment challenge. The surgical approach can be complex and information is lacking on outcomes. The objective of this study was to describe surgical complication rates and oncologic outcomes for canine MPNST of the brachial or lumbosacral plexus. Dogs treated for a naïve MPNST with amputation/hemipelvectomy with or without a laminectomy were retrospectively analysed. Oncologic outcomes were disease free interval (DFI), overall survival (OS), and 1- and 2-year survival rates. Thirty dogs were included. The surgery performed was amputation alone in 17 cases (57%), and amputation/hemipelvectomy with laminectomy in 13 cases (43%). Four dogs (13%) had an intraoperative complication, while 11 dogs (37%) had postoperative complications. Histologic margins were reported as R0 in 12 dogs (40%), R1 in 12 dogs (40%), and R2 in five dogs (17%). No association was found between histologic grade and margin nor extent of surgical approach and margin. Thirteen dogs (46%) had recurrence. The median DFI was 511 days (95% CI: 140-882 days). The median disease specific OST was 570 days (95% CI: 467-673 days) with 1- and 2-year survival rates of 82% and 22% respectively. No variables were significantly associated with recurrence, DFI, or disease specific OST. These data show surgical treatment of plexus MPNST was associated with a high intra- and postoperative complication rate but relatively good disease outcomes. This information can guide clinicians in surgical risk management and owner communication regarding realistic outcomes and complications.


Subject(s)
Dog Diseases , Nerve Sheath Neoplasms , Neurofibrosarcoma , Dogs , Animals , Neurofibrosarcoma/veterinary , Nerve Sheath Neoplasms/surgery , Nerve Sheath Neoplasms/veterinary , Nerve Sheath Neoplasms/pathology , Retrospective Studies , Dog Diseases/surgery , Postoperative Complications/veterinary , Lumbosacral Plexus/surgery , Lumbosacral Plexus/pathology
19.
Vet Comp Oncol ; 21(4): 673-684, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37652746

ABSTRACT

Adrenalectomies for canine adrenal tumours are associated with peri-operative morbidity and mortality. Objectives of this study included assessing the prognostic value of tumour- or surgery-related variables in predicting peri-operative mortality and overall survival in dogs undergoing adrenalectomies for primary adrenal tumours as well as pre-treatment with phenoxybenzamine on survival to discharge with pheochromocytomas specifically. A multi-institutional retrospective cohort study was performed across nine institutions. Electronic medical record searches identified 302 dogs which met the inclusion criteria. Data collected included dog-related, tumour-related, treatment-related, surgery-related, and outcome variables. Univariate and multivariable logistic regression and cox proportional hazards models were used to identify variables associated with death prior to discharge and tumour-related survival. Overall, 87% of dogs survived to discharge with a tumour-related survival time of 3.96 years. Post-operative complications were reported in 25%. Increased surgical time (p = 0.002) and pre-surgical medical treatment other than phenoxybenzamine (p = 0.024) were significantly associated with increased peri-operative mortality while ureteronephrectomy (p = 0.021), post-operative pancreatitis (p = 0.025), and post-operative aspiration pneumonia (p < 0.001) were significantly associated with decreased overall survival. Phenoxybenzamine pretreatment had no effect on peri-operative mortality. Thirty-seven of 45 (82%) dogs with pheochromocytomas not pretreated survived to discharge, and 50 of 59 (85%) dogs with pheochromocytomas pretreated with phenoxybenzamine survived to discharge (p = 0.730). This study provides information on risk factors for death prior to discharge and tumour-related survival that may help guide clinical management and owner expectations. In addition, the study findings challenge the previously reported benefit of phenoxybenzamine for pretreatment of dogs undergoing adrenalectomies for pheochromocytomas.


Subject(s)
Adrenal Gland Neoplasms , Dog Diseases , Pheochromocytoma , Animals , Dogs , Adrenal Gland Neoplasms/surgery , Adrenal Gland Neoplasms/veterinary , Adrenalectomy/veterinary , Dog Diseases/drug therapy , Patient Discharge , Phenoxybenzamine/therapeutic use , Pheochromocytoma/surgery , Pheochromocytoma/veterinary , Pheochromocytoma/pathology , Retrospective Studies , Risk Factors
20.
Case Rep Vet Med ; 2022: 9428539, 2022.
Article in English | MEDLINE | ID: mdl-36213086

ABSTRACT

Four adult, client owned dogs with diagnosed bilateral elbow dysplasia undergoing elbow arthroscopy for removal of fragmented medial coronoid process were identified via a retrospective database search, who also received intra-articular administration of pentosan polysulfate sodium (PPS) (Cartrophen Vet, Biopharm Australia Pty Ltd., Bondi Junction, New South Wales). Dogs had postoperative administration of 5 ml PPS injected into each elbow joint following elbow arthroscopy. Within 1-3 hours of administration, each dog experienced hemorrhage from arthroscopy incisions that was determined to be independent of surgical trauma given lack of hemorrhage intraoperatively. Pressure bandages were placed, and the hemorrhage and elevated coagulation parameters resolved 12-18 hours following intra-articular injection. No further intervention was required, and the dogs were discharged 20-26 hours postoperatively. The purpose of this case series is to describe 4 dogs who experienced transient and focal hemorrhage following off-label intra-articular administration of pentosan polysulfate sodium (PPS). While this case series is limited due to small number of cases, results following bilateral, intra-articular injection of PPS support a transient systemic coagulopathy. Though this report represents administration of PSS via a route and at doses beyond that recommended on the label, results suggest that administration of PSS in the manner described in this report should be avoided.

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