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Multi‐modality treatment strategies are more becoming commonplace in veterinary oncology practice yet the evidence base is far inferior to what has been generated in people. Surgery is unquestionably the cornerstone of most solid tumour treatment plans but certain scenarios dictate combining surgery with systemic chemotherapy and radiation therapy as an adjunct. By using these in the neoadjuvant setting, one can leverage certain effects of the treatment to improve local disease control, improve overall survival, gain insight into drug efficacy, reduce surgical morbidity and reduce long‐term complications. An unintended consequence of combining therapies is an increased flow of information between members of the care team upfront that in almost all cases leads to improved patient outcomes albeit a difficult metric to quantify. This review sets out to explore some of the principles of neoadjuvant therapies and discuss potential opportunities to expand the evidence base in veterinary medicine. [ABSTRACT FROM AUTHOR]

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Griffin, Mastorakis, Wustefeld-Janssens, Martin, Duda, Seguin and Tremolada.)

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.

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.

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.

Local recurrence after surgical excision of canine massive hepatocellular carcinoma (HCC) has been poorly studied in veterinary medicine with scant information published regarding risk factors for and outcome following recurrence. The aim of this case-control study was to describe the time to recurrence, evaluate potential risk factors for recurrence, and report the outcome in dogs with massive HCC. Medical records for 75 dogs who developed recurrence and 113 dogs who did not develop recurrence were reviewed. Statistical analyses were performed to determine risk factors for recurrence as well as the median time to develop recurrence and overall survival time (OS). None of the risk factors evaluated were significant for the development of recurrence. The median time to develop recurrence was 367 days (range 32-2096 days). There was no significant difference in median OS for dogs who developed recurrence vs. those who did not (851 vs. 970 days). For dogs with recurrent HCC, treatment at recurrence trended toward prolonged OS but was not significantly different from dogs not undergoing treatment at recurrence. There was no significant difference in median OS for dogs with histologically complete vs. incomplete tumour excision (990 vs. 903 days). Although specific risk factors for recurrence were not identified, elevations in liver values were noted in patients with recurrent disease and could act as a noninvasive surveillance tool. Recurrence was noted earlier in dogs who had routine post-operative surveillance (228 vs. 367 days). Routine surveillance for recurrence is recommended especially in dogs where further intervention is possible and should extend beyond 1 year. Patients with massive HCC have a good long-term prognosis regardless of incomplete excision, pulmonary metastasis, or recurrent local disease., (© 2022 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Sertoli cell tumours are one of the most common canine testicular neoplasia. These tumours are significantly more likely to arise in cryptorchid dogs and are often functional, oestrogen-secreting tumours which can lead to fatal myelotoxicity. The goal of this study was to describe the outcome of dogs with oestrogen-induced bone marrow suppression secondary to Sertoli cell tumours in seven client-owned dogs. Medical records from April 1, 2011 through April 1, 2021 were reviewed to identify dogs that underwent surgical management of a Sertoli cell tumour with documented bone marrow suppression. Overall, 5/7 dogs required transfusion of blood products peri-operatively. Cases 1 and 6 received a transfusion of packed red blood cells (RBC) prior to surgery and case 5 required a transfusion of whole blood. Case 1 also required a transfusion of platelets before surgery. Post-operatively, cases 1 and 2 received packed RBC's and case 6 received two transfusions of whole blood. Case 3 required transfusions of both fresh frozen plasma and platelets post-operatively. All dogs survived to discharge and 6/7 dogs had documented improvement in haematopoietic values. Two dogs remained chronically thrombocytopenic. The median hospital stay was 4 days. One dog died within 4 weeks of surgery from worsening pancytopenia. Survival for greater than 1 year was documented in 4/7 dogs, and one dog was lost to follow-up 4 months post-operatively. One dog remained severely pancytopenic 4 weeks post-operatively and received oral lithium treatment. Improvements in all blood cell lines were observed within the 4 weeks and resolution of pancytopenia within 6 weeks. Historically, the prognosis for dogs with bone marrow suppression secondary to Sertoli cell tumours was guarded to poor. This report documented improved outcomes for dogs that underwent surgery, including one dog that received lithium chloride as treatment for Sertoli cell tumour-induced bone marrow suppression., (© 2021 John Wiley & Sons Ltd.)

The invasive, locally aggressive nature of feline injection-site sarcomas (FISSs) poses a unique challenge for surgeons to obtain complete margins with surgical excision. Optical coherence tomography (OCT), an imaging technology that uses light waves to generate real-time views of tissue architecture, provides an emerging solution to this dilemma by allowing fast, high-resolution scanning of surgical margins. The purpose of this study was to use OCT to assess surgical margins of FISS and to evaluate the diagnostic accuracy of OCT for detecting residual cancer using six evaluators of varying experience. Five FISSs were imaged with OCT to create a training set of OCT images that were compared with histopathology. Next, 25 FISSs were imaged with OCT prior to histopathology. Six evaluators of varying experience participated in a training session on OCT imaging after which each of the evaluators was given a dataset that included OCT images and videos to score on a scale from cancerous to non-cancerous. Diagnostic accuracy statistics were calculated. The overall sensitivity and specificity for classification of OCT images by evaluators were 78.9% and 77.6%, respectively. Correct classification rate of OCT images was associated with experience, while individual sensitivities and specificities had more variation between experience groups. This study demonstrates the ability of evaluators to correctly classify OCT images with overall low levels of experience and training and also illustrates areas where increased training can improve accuracy of evaluators in interpretation of OCT surgical margin images., (© 2021 John Wiley & Sons Ltd.)

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., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: To provide information about complication rates and the risk factors for complications with mandibulectomy and maxillectomy procedures in dogs., Animals: 459 client-owned dogs that underwent a mandibulectomy or maxillectomy between January 1, 2007, and January 1, 2018., Procedures: Inclusion criteria included a complete medical record that contained an anesthesia record, surgical report, available histopathology results, and results of CBC and serum biochemical analysis before surgery. A minimum follow-up of 90 days after surgery was required., Results: 271 complications occurred in 171 of 459 (37.3%) dogs. Eighteen complications were not given a severity description. Of the remaining 253 complications, most were considered minor (157/253 [62.1%]). Multivariable logistic regression analysis revealed that only increased surgical time had a significant (OR, 1.36; 95% CI, 1.12 to 1.54) association with the occurrence of ≥ 1 complication. For each additional hour of surgery, the odds of complications increased by 36%. Preoperative radiation therapy or chemotherapy increased the odds of incisional dehiscence or oral fistula formation (OR, 3.0; 95% CI, 1.3 to 7.2). Additionally, undergoing maxillectomy, compared with mandibulectomy, increased the odds of incisional dehiscence or oral fistula formation (OR, 1.8; 95% CI, 1.1 to 3.1). Two hundred forty-four of 271 (90.0%) complications occurred in the perioperative period (0 to 3 months after surgery)., Conclusions and Clinical Relevance: Compared with mandibulectomy, performing maxillectomy increased the risk for incisional dehiscence or oral fistula formation. Mandibulectomy and maxillectomy had a moderate risk for a complication.

Objective:  This study investigated variables associated with surgical site infection (SSI) in dogs with cranial cruciate ligament rupture managed with stifle joint examination and lateral fabellotibial suture stabilization., Study Design:  A retrospective study of dogs that had stifle arthroscopy, stifle arthrotomy, or a combination of both, followed by lateral fabellotibial suture stabilization for cranial cruciate ligament rupture. All cases had a minimum follow-up of 90 days. Lameness grades were recorded preoperatively, and at 6-week and final follow-up., Results:  One hundred fifty procedures in 130 dogs met the inclusion criteria. Overall, SSI rate was 17.3% and removal of the lateral fabellotibial suture was performed in 53% of SSI. Multivariable analysis showed significant association between SSI and bodyweight ( p  = 0.013), and induction using propofol ( p  = 0.029). Multilevel ordinal logistic regression analysis showed a greater proportion of dogs had a higher lameness grade at 6-week ( p  = 0.021) and final follow-up ( p  = 0.002) assessments in the infected compared with non-infected dogs., Conclusion:  Our study demonstrated a higher SSI incidence than previously reported in dogs undergoing a lateral fabellotibial suture for cranial cruciate ligament rupture. Bodyweight and induction with propofol were identified as significant risk factors for postoperative SSI. Owners could be advised of an increased SSI risk in larger dogs and consideration should be given to selection of induction agent. Dogs that develop an SSI have a worse lameness grade at 6-week and final follow-up., Competing Interests: None declared., (Thieme. All rights reserved.)

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., (© 2020 The American College of Veterinary Surgeons.)

Pigmented villonodular synovitis (PVNS) is a rare benign and usually monoarticular neoplastic lesion arising from the synovium, bursae and tendon sheaths in humans, horses and dogs. Categorization for PVNS in humans includes localized and diffuse forms of PVNS and tenosynovial giant cell tumour (TGCT), although histologically they are the same. The localized form is characterized by discrete nodular lesions, the diffuse form is often intra-articular, infiltrative, affecting the entire synovium with more aggressive behaviour and TGCT occurs along tendon sheaths. Computed tomography (CT) of PVNS is well described in humans but not documented in the veterinary literature. Pigmented villonodular synovitis is not a straightforward diagnosis and CT is useful to further characterize radiographic findings. A representative open surgical biopsy of the synovium is essential to obtaining the diagnosis and ruling out malignancy. Currently, there are no guidelines for the diagnosis of PVNS in dogs or long-term follow-up of these cases. This case report describes the presentation, diagnostic findings, treatment and long-term outcome of a 4-year-old male Labrador Retriever with confirmed PVNS. Clinical outcome was considered fair with the dog's lameness and symptoms remaining stable with medical management 3 years following the initial diagnosis., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

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., (© Copyright 2014 by The American College of Veterinary Surgeons.)