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The cannabinoid 2 receptor (CB2R) is a crucial element of the endocannabinoid system (ECS), which is predominantly expressed on cells of the reticuloendothelial system. Alterations in CB2R expression have shown a prognostic role in various human neoplastic diseases and its expression has been studied in canine mast cell tumours (MCT). Canine diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in dogs and has a variable clinical behaviour. Expression of CB2R was assessed by means of immunohistochemistry in fifteen dogs with proven histological diagnosis of DLBCL. A semiquantitative and quantitative assessment of immunoreactivity (IR) by digital analysis was performed in all cases. Our results indicate that CB2R expression is conserved in canine DLBCL but does not correlate with clinical outcome., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Vinorelbine (VRL), a semi-synthetic vinca alkaloid commonly used in humans with advanced lung cancer, reaches high concentrations in the lung tissue, has proven antineoplastic activity and a low toxicity profile in dogs. Treatment-naïve, client-owned dogs with a cyto/histological diagnosis of advanced pulmonary carcinoma, selected from a laboratory database and previously subjected to imaging, were enrolled in the study. Vinorelbine (15 mg/m 2 ) was administered weekly for 4 weeks and then fortnightly until progressive disease was documented. Staging work-up was repeated by means of diagnostic imaging after the fourth VRL (i.e., 28 days) and monthly thereafter; response to treatment was evaluated according to the RECIST. Toxicity was graded following the VCOGC group. Ten dogs met the inclusion criteria. Partial response was documented in eight dogs. Median time to progression was 88 days (range: 7-112) and median survival time for all dogs was 100 days (range 7-635). The most common side effect was neutropenia. The main limitations of the study were the absence of histological diagnosis in eight cases and the limited number of treated dogs. VRL is well tolerated with an adequate toxicity profile and may be useful in the management of advanced lung tumours if used as a first-line treatment strategy.

Neoadjuvant chemotherapy can be used in canine mast cell tumours (MCTs) to optimise surgical margins or to enable marginal excision in challenging locations. The objective of this study was to describe the outcome of dogs with cutaneous and subcutaneous MCTs treated with neoadjuvant vinblastine-prednisolone (NA-VP). Records of treatment-naïve dogs with cutaneous/subcutaneous MCT that received NA-VP were reviewed including signalment, indication for NA-VP, staging results, clinical response, surgical data and histopathology reports. For dogs with post-operative follow-up ≥365 days, predictive factors for local recurrence (LR) were evaluated. Forty-four dogs were included. NA-VP was indicated to optimise surgical margins (group MARG) in 19 dogs (43.2%) and to enable surgery (group MORB) in 25 dogs (56.8%). Complete and partial response were documented in 40.9% of dogs and 30 dogs (68.2%) underwent surgery. The indication for NA-VP was significantly associated with undergoing surgery (p < .001) on multivariable analysis. Twelve (48%) and 18 dogs (94.7%) underwent surgery in the group MORB and MARG, respectively. Five dogs (16.7%) experienced wound dehiscence. Complete excision was achieved in 14 dogs (46.7%). In dogs undergoing surgery with ≥365 days of follow-up, LR was documented in five cases (20.8%). None of the factors analysed including mitotic count, completeness of excision and response to NA-VP were associated with LR; notably, LR occurred in 3/11 (27.2%) completely excised MCTs. In a pre-operative setting, NA-VP appears safe and could be beneficial in selected cases. Prognostic factors such as clinical response, mitotic count and completeness of excision should be interpreted with caution following NA-VP., (© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Cyclooxygenase (COX) inhibitors have been demonstrated to have antitumour activity in canine urothelial cell carcinoma (UCC), given as a sole treatment or in combination with chemotherapy. The purpose of this retrospective multi-institutional study was to assess the efficacy of meloxicam in combination with mitoxantrone or vinblastine as a first-line treatment for non-resectable canine UCC. Gastrointestinal adverse effects (AEs) of these treatment combinations were also assessed. A total of 28 dogs met the inclusion criteria, 21/28 dogs received mitoxantrone and meloxicam, and 7/28 received vinblastine and meloxicam. Tumour response (TR) and AE were evaluated according to Veterinary Co-Operative Oncology Group (VCOG) criteria. The endpoint of the study was the time to tumour progression (TTP). The mitoxantrone-group induced 24% partial response and 62% stable disease, while the vinblastine-group induced 14% and 86%, respectively. Median TTP was 84 days (mitoxantrone and meloxicam, 70 days; and vinblastine and meloxicam, 178 days). The presence of metastatic disease significantly decreased TTP ( p = 0.007). Gastrointestinal AEs were reported in 21.4% of the patients, with the most common being VCOG grade 1-2 diarrhoea. Meloxicam is a well-tolerated NSAID when combined with mitoxantrone or vinblastine as first-line treatment for non-resectable canine UCC.

Hematological indices play a prognostic role in human osteosarcoma (OSA), but data are limited in dogs. The aim of this retrospective multicentric cohort study was to investigate the prognostic significance of pre-operative hematological/inflammatory indices in a cohort of client-owned dogs with appendicular OSA receiving standardized treatment. Cut-offs associated with progression-free survival (PFS) for pre-operative hematological values/ratios were established using the minimal p -value approach. Historical prognostic factors were also assessed. Statistical analyses were performed for the whole population and after the exclusion of sighthounds. Fifty-nine dogs were included (13 were sighthounds). Multivariable analysis revealed that a low neutrophil count (<4.37 × 10 9 /L, HR0.28, CI 95% 0.13-0.61, p = 0.001), a high red blood cell count (≥7.91, HR3.5, CI 95% 1.56-7.9, p = 0.002), and a proximal humerus location (HR3.0, CI 95% 1.48-6.1, p = 0.002) were associated with shorter PFS. In the sighthound-only population, only OSA location was significantly associated with PFS in univariable analysis. When sighthounds were excluded, a low neutrophil count, a low monocyte count, and a proximal humerus location were associated with shorter PFS, in multivariable analysis. Neutrophil count and possibly monocyte and red blood cell counts can be useful prognostic markers in canine OSA treated with amputation and adjuvant carboplatin. However, not all indices are appropriate in sighthounds.

Canine cutaneous mast cell tumours (cMCTs) of the pinna have been associated with an aggressive biological behaviour, although data remain scarce. The knowledge acquired over the past years on histologic gradings, and the value of lymph node (LN) staging, may help in better characterizing this anatomical presentation. The first aim was to describe the frequency, location, and histologic appearance of LN metastases in cMCT of the pinna. A second aim was to evaluate prognosis. Medical records of dogs with cMCT of the pinna, that underwent tumour and sentinel (SLN) or regional LN (RLN) excision, were reviewed. The influence of potential prognostic variables on time to progression (TTP) and tumour-specific survival (TSS) was investigated. Thirty-nine dogs were included: 19 (48.7%) had Kiupel high-grade (K-HG) and 20 (51.3%) had low-grade (K-LG) MCTs. Eighteen (46.1%) dogs underwent SLN mapping: the superficial cervical LN was at least one of SLN in 17 (94.4%) cases. Twenty-two (56.4%) dogs had LN metastases; the superficial cervical LN was always involved. On multivariable analysis, only K-HG was associated with increased risk of progression (p = .043) and tumour-related death (p = .021). Median TTP and TSS were 270 and 370 days in K-HG, respectively; these were not reached in dogs with K-LG tumours (p < .01). cMCTs of the pinna are often K-HG and are also associated with a higher frequency of LN metastasis; however, we confirmed the independent prognostic value of histologic grading. A multimodal treatment may lead to favourable long-term outcome. Moreover, the superficial cervical LN is most often the SLN., (© 2023 John Wiley & Sons Ltd.)

Cannabinoid receptors (CB1 and CB2) belong to endocannabinoid system (ECS), which is also composed from endocannabinoids and the enzymatic systems involved in their biosynthesis and degradation. The expression of CB1 and CB2 have been previously identified in normal canine mast cell and in atopic dermatitis. Canine cutaneous mast cell tumours (cMCTs) are among the most common cutaneous neoplasms in dogs and have a highly variable clinical behaviour. Expression of CB1-CB2 was assessed by means of immunohistochemistry in thirty-seven dogs (from 2019 to 2021) with proven histological diagnosis of cMCT. Dogs were divided in two groups according to the Kiupel's grading system: high-grade (HG) cMCT and low-grade (LG) cMCT. A semiquantitative (score 0-3) and quantitative assessment of immunoreactivity (IR) was performed for each case. Our results show that there CB1 and CB2 are highly expressed in LG- cMCT, in contrast to HG- cMCT., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Historically, the prognosis for dogs with stage II Kiupel high-grade cutaneous mast cell tumours has been considered poor., Objectives: The aim of this study was to explore the impact of lymphadenectomy on outcome in dogs with Kiupel high-grade cutaneous mast cell tumours and overt regional lymph node metastasis., Material and Methods: Data from dogs with completely staged Kiupel high-grade cutaneous mast cell tumours with overt and/or certain regional lymph node metastasis undergoing excision of the primary tumours and adjuvant medical treatment were extracted. Dogs with a cytological diagnosis of regional lymph node metastasis that did not undergo lymphadenectomy were compared with dogs that underwent lymphadenectomy and had a histological diagnosis of overt lymph node metastasis., Results: Forty-nine dogs were included, 18 did not undergo lymphadenectomy while 31 underwent lymphadenectomy. Median time to progression was significantly shorter in dogs that did not undergo lymphadenectomy (150 days, 95% confidence interval: 129 to 170) compared to the other dogs (229 days, 95% confidence interval: 191 to 266). Median survival time was also shorter in dogs that did not undergo lymphadenectomy (250 days, 95% confidence interval: 191 to 308) compared to dogs that underwent lymphadenectomy (371 days, 95% confidence interval: 311 to 430). On multivariable analysis, lack of lymphadenectomy was associated with higher risk of overall tumour progression (hazard ratio: 2.05, 95% confidence interval: 1.02 to 4.13), nodal progression (hazard ratio: 3.4, 95% confidence interval: 1.65 to 7.02) and tumour-related death (hazard ratio 3.63, 95% confidence interval: 1.72 to 7.66), whereas tumour size was associated with higher risk of local recurrence (hazard ratio: 3.61, 95% confidence interval: 1.06 to 13)., Clinical Significance: Regional lymphadenectomy may improve outcome in dogs with biologically aggressive cutaneous mast cell tumours., (© 2022 British Small Animal Veterinary Association.)

Clinical staging is a fundamental step in the clinical assessment of canine cutaneous mast cell tumor (cMCT), and it is recommended to evaluate the tumor draining lymph node (eTDLN), perform diagnostic imaging, and fine needle aspiration (FNA) of the spleen and liver to determine the presence of metastatic disease, thereby refining the prognosis. The aim of this retrospective study was to evaluate the prevalence of splenic and hepatic involvement in newly diagnosed canine low-grade cMCT (Patnaik grade I-II, Kiupel low-grade). Medical records of dogs that underwent a clinical staging work-up and surgical excision for a low-grade cMCT between December 2019 and December 2021 were reviewed at five veterinary centers. Only dogs with a histological diagnosis of low-grade cMCT, FNA or histology of the eTDLN, FNA of the spleen and liver, and one year of follow up were included. One hundred and thirty-six dogs met the inclusion criteria. Only 1 out of 136 dogs (0.7%) had the presence of visceral metastases at diagnosis, suggesting that the prevalence of visceral metastases in low-grade cMCT is extremely low. The results of this study are consistent with previous literature and suggest that after a diagnosis of low-grade cMCT, cytology of visceral organs may not represent an essential step in the clinical staging work-up.

The staging system commonly used in canine anal sac gland carcinoma (ASGC) is a revised Tumour-Node-Metastasis (TNM) system published in 2007. This staging system consists in four stages and, for dogs with nodal metastases, the size of the metastatic lymph node (mLN) defines the N stage. However, we hypothesise that (1) the mLN size has no prognostic significance when the mLN can be excised, (2) a high number of mLNs is associated with poorer prognosis and (3) the measurement of the mLN on imaging is not reproducible. To investigate these hypotheses, medical records and diagnostic images of dogs with ASGC and mLN, treated with sacculectomy and lymphadenectomy, with or without chemotherapy, were reviewed. Interobserver variability for mLN measurement was assessed. Prognostic factors including mLN size and number were investigated. Time to documented progression (TDP) and disease-specific survival (DSS) were evaluated. Progression-free interval (PFI) was analysed with interval-censored data analysis. Fifty-seven dogs were included. The median PFI, TDP and DSS were 110 (95%CI 61.5-185.5), 196 (95%CI 162-283) and 340 days (95%CI 321-471), respectively. For measurement of the largest mLN, interobserver agreement was excellent but limits of agreement reached 39.7%. Neither the size of the largest mLN nor the use of adjuvant chemotherapy were associated with outcome. The number of mLNs was associated with outcome and having more than four mLNs was associated with shorter PFI (p < .001), TDP (p = .004) and DSS (p < .001). While mLN size measurement was not consistently reproducible and did not influence outcome in our cohort, number of mLNs did. Further studies are required for development of a revised staging system., (© 2021 John Wiley & Sons Ltd.)

Background: Computed tomography (CT) and ultrasonography (US) may be used to assist staging in dogs with lymphoma. The imaging features of splenic and hepatic infiltration have never been directly compared in the same population of dogs., Methods: The aim of this retrospective study was to describe and compare the CT and US findings of the liver and spleen in dogs with confirmed hepatic and/or splenic lymphoma and compare imaging and cytological diagnoses., Results: CT and US studies of 18 dogs with multicentric lymphoma involving the liver and/or the spleen were retrospectively evaluated. US detected abnormalities more frequently than CT in the spleen with lymphoma, whereas CT detected abnormalities more frequently in the liver with lymphoma. The two diagnostic imaging modalities often disagreed in the findings, including the imaging classification of the organ as normal or abnormal., Conclusion: US and CT often disagree in the imaging findings present in hepatic and splenic lymphoma. The results of this study suggest that cytologic evaluation of both the liver and spleen is advisable regardless of their US or CT appearance for detection of lymphoma., (© 2021 British Veterinary Association.)

Objective: To evaluate ultrasound-guided placement of an anchor wire (AW) or injection of methylene blue (MB) to aid in the intraoperative localization of peripheral lymph nodes in dogs and cats., Animals: 125 dogs and 10 cats with a total of 171 lymphadenectomies., Procedures: Medical records of dogs and cats that underwent peripheral lymphadenectomies with or without (N) the AW or MB localization technique were reviewed. Data retrieved included clinical, surgical, and histologic findings. The proportions of successful lymphadenectomies, lymph node characteristics, and complications among the 3 groups were analyzed., Results: 143 (84%) lymph nodes were successfully excised. Lymphadenectomy success was significantly affected by the localization technique, with 94% for group AW, 87% for group MB, and 72% for group N. Lymph node size was smaller in groups AW and MB, compared with group N. Duration of lymphadenectomy was shorter in group AW, compared with groups MB and N, and in group MB, compared with group N. Intra- (7%) and postoperative (10%) complications and final diagnosis did not significantly differ among groups., Conclusions and Clinical Relevance: Both lymph node localization techniques were highly successful and reduced surgery time, compared with unassisted lymphadenectomy. Specifically, these techniques were effective for localization of normal-sized and nonpalpable lymph nodes and were efficient and practical options for peripheral lymphadenectomies, particularly for those that were small or nonpalpable.

Background: While lymphadenectomy of metastatic lymph nodes (LNs) has been associated with improved outcome, the clinical utility of prophylactic lymphadenectomy in dogs with stage I cutaneous mast cell tumors (cMCTs) remains a controversial topic. To assess the therapeutic role of lymphadenectomy of uninvolved regional LNs, the long-term outcome of cMCT-bearing dogs with cytologically negative and surgically unresected regional LNs (observation only, OO) was compared with that of dogs with surgically resected and histologically negative regional LNs (prophylactic regional lymphadenectomy, PRL)., Results: A retrospective analysis of 64 dogs with a low-grade, completely resected stage I cMCT was performed: 35 (54.7%) dogs were subjected to OO and 29 (45.3%) underwent PRL. Dogs were monitored for a median of 813 and 763 days in the OO group and PRL group, respectively. The number of dogs undergoing MCT progression was significantly higher in the OO group (P = 0.028) and curve comparison revealed a tendency to a better time to progression in the PRL group (P = 0.058). No significant difference in survival time (P = 0.294) was observed between dogs in the OO and PRL groups., Conclusions: Our results showed that lack of immediate lymphadenectomy was associated with a higher risk for tumor progression. This preliminary judgement, reinforced by the findings that lymphadenectomy was well tolerated in all cases, and that histopathology provides the definitive assessment of the nodal pathological status, may suggest that prophylactic lymphadenectomy is indicated in the management of stage I MCTs. Larger prospective studies are warranted for generating clinical evidence of this latter hypothesis., (© 2021. The Author(s).)

Objective: To determine an optimal time interval between amputation and initiation of adjuvant chemotherapy (TI amp-chemo ) in dogs with appendicular osteosarcoma without distant metastases and whether TI amp-chemo was associated with outcome., Animals: 168 client-owned dogs treated at 9 veterinary oncology centers., Procedures: Data were collected from the dogs' medical records concerning potential prognostic variables and outcomes. Dogs were grouped as to whether they received chemotherapy within 3, 5, 7, 10, 15, 20, 30, or > 30 days after amputation of the affected limb. Analyses were performed to identify variables associated with time to tumor progression and survival time after limb amputation and to determine an optimal TI amp-chemo ., Results: Median TI amp-chemo was 14 days (range, 1 to 210 days). Median time to tumor progression for dogs with a TI amp-chemo ≤ 5 days (375 days; 95% CI, 162 to 588 days) was significantly longer than that for dogs with a TI amp-chemo > 5 days (202 days; 95% CI, 146 to 257 days). Median overall survival time for dogs with a TI amp-chemo ≤ 5 days (445 days; 95% CI, 345 to 545 days) was significantly longer than that for dogs with a TI amp-chemo > 5 days (239 days; 95% CI, 186 to 291 days)., Conclusions and Clinical Relevance: Findings indicated that early (within 5 days) initiation of adjuvant chemotherapy after limb amputation was associated with a significant and clinically relevant survival benefit for dogs with appendicular osteosarcoma without distant metastases. These results suggested that the timing of chemotherapy may be an important prognostic variable.

Canine oral malignant melanoma (COMM) is considered a chemo-resistant cancer with a poor long-term prognosis. The melanoma-associated antigen A (MAGE-A) genes, which belong to the cancer-testis antigen family, are expressed in several different canine cancers but not in normal somatic tissue. This study evaluates the expression of MAGE-A proteins and their prognostic role in COMM. The study was conducted in 2 parts. During the first part, biopsies from oral malignant melanomas from 43 dogs were examined and immunohistochemically assessed for expression of MAGE-A proteins. For the second part, the association between MAGE-A expression and outcome was assessed using follow-up data which was available for 20 dogs whose primary tumour had been controlled with surgery +/- radiation therapy. MAGE-A proteins were expressed in 88.4% (38/43) of oral malignant melanomas and had a predominantly cytoplasmic expression pattern. Immunopositivity was observed in more than 50% of the cells in 21 dogs (48.8%). Immunostaining intensity was classified as weak, moderate and intense in 16 (37%), 16 (37%) and 6 (14%) cases, respectively. No staining for MAGE-A was seen in 5 dogs (11%). Dogs whose COMM had weak MAGE-A staining intensity had a median survival time (MST) of 320 days while this was 129 days for dogs with moderate and intense immunostaining (p = 0.161). Dogs whose COMM had >50% of positive staining neoplastic cells had an MST of 141 days and dogs with a staining <50% had an MST of 320 days (p = 0.164). MAGE-A expression did not influence survival in our cohort., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Carcinomatosis and sarcomatosis describe the widespread dissemination of metastatic neoplastic cells throughout the body. Studies describing their clinical and imaging features in veterinary patients are limited. The objective of this retrospective, multicenter, cross-sectional study is to describe the clinical, ultrasonographic, and CT features of pleural and peritoneal carcinomatosis and sarcomatosis in dogs and cats to aid detection and differentiation of these lesions. Medical records and CT and ultrasonographic images were reviewed. Although a large degree of overlap was observed between the imaging features and clinical signs of canine and feline carcinomatosis and sarcomatosis, some distinguishing features were observed. Dogs were significantly more likely to present with abdominal pain compared to cats (P = .022), whereas cats more commonly presented with inappetence (P = .019). Dogs with sarcomatosis had a significantly heavier bodyweight than dogs with carcinomatosis (P = .005), largely due to a higher prevalence of splenic hemangiosarcoma in this patient cohort. Peritoneal effusion was more frequently observed in dogs with carcinomatosis compared to dogs with sarcomatosis (P = .021). Imaging and clinical features observed in this study may help to distinguish sarcomatosis and carcinomatosis lesions. Due to the large degree of overlap observed, cytological or histopathological analysis is recommended for definitive diagnosis., (© 2021 American College of Veterinary Radiology.)

In dogs, digit squamous cell carcinoma (SCC) is uncommon. Clinical signs are frequently underestimated, leading to a diagnostic delay. The purpose of this retrospective study was to report our experience regarding the clinical presentation, diagnostic work-up, treatment and outcome of 79 client-owned dogs with SCC of the digit. The greatest majority (84.8%) of dogs was dark-coated. Schnauzers represented approximately one third of the study population, and had a poorer outcome compared with other breeds. The majority of SCCs occurred in the front limbs (61%), and bone lysis was frequently observed (92.4%). Approximately 9% of dogs had involvement of multiple digits, and this was associated with a shorter time to progression (TTP; P = 0.047). Similarly, a duration of clinical signs >90 days was associated with a shorter TTP ( P = 0.02). Regional lymph node metastases were documented in 17.7% of dogs at admission and were significantly associated with tumor-related death ( P < 0.001). At presentation, none of the dogs had evidence of distant metastasis. Digit amputation achieved adequate local tumor control in the majority of cases. Adjuvant chemotherapy and radiation therapy were carried out in 21.5% of cases, with uncertain benefit. Due to the relatively non-aggressive clinical behavior of digit SCC, chemotherapy should only be offered in the case of metastatic disease. Approximately one fourth of dogs developed de novo SCCs during the follow-up. Careful examination of the digits should be encouraged in breeds considered at high risk and in dogs with a previous history of digital SCC., 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 © 2021 Marconato, Murgia, Finotello, Meier, Morello, Pisoni, Foglia, Guerra, Chalfon, Aralla, Mesto, Annoni, Albanese, Bettini and Sabattini.)

Tumour-associated macrophages (TAMs) are an important part of the tumour microenvironment but knowledge of their distribution in canine soft tissue sarcomas (STSs) is limited to absent. We analysed 38 STSs retrieved from the veterinary pathology archive; oral and visceral STSs, synovial cell sarcoma, tumours of histiocytic origin, haemangiosarcoma, carcinosarcomas, and undifferentiated tumours were excluded. Iba-1 positive, non-neoplastic tumour infiltrating cells (morphologically indicative of macrophages) were classified as TAMs and were counted in 10 consecutive tumours areas, where no necrosis or other inflammatory cells could be identified. Associations between numbers of TAMs and mitoses, differentiation, and necrosis scores or grade were investigated. TAMs were evident in all STSs and ranged between 6% to 62% of the cells in the microscopic field. The number of TAMs positively correlated with the STSs' histologic grade. When the components of the grade were analysed separately, TAMs were statistically correlated with mitoses, but not with differentiation or necrosis score. The present findings suggest that TAMs are present in higher numbers when STS proliferation is the predominant feature that drives tumour grade. The abundant presence of TAMs in high-grade STSs may also increase the likelihood of a pathologist misdiagnosing STS for histiocytic sarcoma.

The evaluation of loco-regional lymph nodes (LN) plays an important prognostic role and assists the clinical decision making in canine cancer patients. Excision of non-palpable LN can be challenging. The aim of the study was to evaluate surgical time, successful excision rate and surgical complications associated with the use of an ultrasound-guided hook-wire (UGHW) LN localization method for non-palpable superficial inguinal LN (SILN) in dogs. Dogs that presented for excision of non-palpable SILN, performed with the aid of an UGHW placement, were enrolled. Information including signalment, SILN width, UGHW placement and surgical procedure time, hook-wire position, successful excision and intra- and post-operative complications were reviewed. Seventeen dogs were enrolled. Median LN width was 3 mm (range 2-11). Median time of preoperative UGHW placement and surgical LN excision was 8 min and 15 min, respectively. Successful SILN excision was achieved in all cases. Two minor intra-operative (hook migration and wire fragmentation) and one minor post-operative complications (seroma) were observed. No major intraoperative or post-operative complications occurred. The UGHW LN localization method is safe and effective and may allow a high rate of successful SILN excisions in dogs. This method has the potential to facilitate LN excision for other superficial LN locations.

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., (© 2020 John Wiley & Sons Ltd.)

Temozolomide is a novel oral alkylating agent that has schedule-dependent clinical activity in human malignant glioma and metastatic melanoma. Little is known about the efficacy of temozolomide in the treatment of canine solid cancers, where broad range of dosages have been used but no maximally tolerated dose (MTD) had been established. The aim of this this open-label, dose-escalating study was to determine MTD and dose-limiting toxicity (DLT) of a single temozolomide cycle in dogs with advanced solid tumours. Temozolomide was administered as a 5-days course starting at 70 mg/m 2 , using escalation of 10 mg/m 2 increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Safety evaluation was performed 10 days after dosing. Thirty-three client-owned dogs were enrolled. MTD was established at 150 mg/m 2 and the most frequent adverse events (AEs) were hematologic and hepatic, followed by gastrointestinal, with the majority being self-resolving and of mild grade. VCOG grade 3 hepatic toxicity and grade 4 thrombocytopenia were defined as DLTs at 160 mg/m 2 . A subcohort of dogs received multiple temozolomide doses on a 4-week cycle and no cumulative toxicity was documented. Conclusions of this study define temozolomide MTD at 150 mg/m 2 when given once daily over 5 days. Future trials on the efficacy of temozolomide administered at its MTD are warranted., (© 2020 John Wiley & Sons Ltd.)

Lymph node (LN) metastasis is a negative prognostic factor in dogs with cutaneous mast cell tumours (cMCTs). While elective lymphadenectomy of metastatic LNs improves outcome, the benefit of adjuvant medical therapy in dogs with early metastatic (HN2) LNs is debated. The aim of this retrospective multicentre study was to evaluate the therapeutic benefit of adjuvant medical therapy following surgical removal of the primary low-grade cMCT (Patnaik grade 1-2 and Kiupel low-grade) and lymphadenectomy of HN2 LNs by analysing survival rates and patterns of recurrence. Seventy-three dogs were included: 42 received adjuvant medical treatment (chemotherapy and/or kinase inhibitors), and 31 did not. The median follow-up time for medically treated dogs was 619 days: two experienced local recurrence, three nodal relapse and four distant relapse. For dogs undergoing surgery only, the median follow-up time was 545 days. None of them experienced local recurrence, nodal, or distant relapse. Time to progression was significantly shorter in dogs receiving adjuvant medical treatment (P = .021). A similar tendency was observed for overall survival (P = .056). The current study shows that dogs with low-grade cMCTs, that undergo surgical excision of the primary tumour and elective lymphadenectomy of the HN2 regional LN harbour a good prognosis. The use of adjuvant medical treatment in these dogs does not seem to provide any benefit in terms of progression and survival., (© 2020 John Wiley & Sons Ltd.)

Objectives: To describe the clinicopathological and genetic characteristics of mast cell tumours in dogs less than 12 months old., Materials and Methods: Retrospective review of dogs aged less than 12 months when diagnosed with mast cell tumours at three referral hospitals in the UK., Results: Sixteen pure-bred dogs were included, of which 11 were female. The median age at first presentation and diagnosis were 7.6 and 9 months, respectively. In 13 dogs the mast cell tumours were cutaneous and in three they were subcutaneous. Four cutaneous mast cell tumours were described as high-grade (Patnaik or Kiupel) and nine were Patnaik grade II; three had mitotic index of >5 in 10 high-power fields. Of the three subcutaneous tumours, two had an infiltrative growth pattern and one had mitotic index of 10 per 10 high-power fields. Of 10 tested dogs, seven had c-kit mutations in exon 11 and Ki-67 score was above the cut-off value in nine. Four of 12 cases showed evidence of metastasis in the regional lymph nodes. After varying treatment protocols, all patients were alive and disease free at a median of 1115 days after diagnosis., Clinical Significance: The prognosis of mast cell tumours in dogs less than a year old appears better than the adult counterparts, even without extensive treatment., (© 2020 British Small Animal Veterinary Association.)

Objective: Cytarabine, a cell-cycle phase-specific antimetabolite, has been reported to improve outcomes in dogs with bone marrow (BM) or central nervous system (CNS) lymphoma involvement receiving combination chemotherapy. The objective of this study was to evaluate the incidence and severity of toxicity of cytarabine constant rate infusion (CRI) in dogs with high-grade non-Hodgkin lymphoma., Methods: Medical records of canine lymphoma patients with confirmed or suspected BM (group 1) or CNS (group 2) involvement, treated with a modified cyclophosphamide, epirubicin, vincristine and prednisolone protocol, including a single dose of cytarabine given as CRI, were reviewed and adverse events graded., Results: Twenty-six dogs were included. Gastrointestinal toxicity occurred in 17 dogs (65.3%), with 5 (19.2%) experiencing grade III or IV toxicity. Neutropenia occurred in nine dogs (34.6%), but was grade I or II in most cases. Three dogs (11.5%) had thrombocytopenia: one grade III and two grade IV. Four dogs (15.3%) experienced increases in alanine amino transferase: one each grade I and II and two grade III. Five dogs (19.2%) required hospitalisation to manage toxicity after completing cytarabine CRI, and haematological toxicity resulted in treatment delays in five dogs (median delay of 4 days, range: 3-7 days)., Conclusion: Our findings suggest that gastrointestinal toxicity should be expected in lymphoma patients undergoing cytarabine CRI., (© 2019 Australian Veterinary Association.)

Splenectomy followed by adjuvant chemotherapy is commonly used to treat canine splenic haemangiosarcoma (HSA), although it is unclear if different treatment protocols may have a similar efficacy. The objective of this retrospective study was to assess outcome in dogs with stage I and II splenic HSA treated with either first-line adjuvant anthracycline (AC) or metronomic (MC)-based chemotherapy protocols, by comparing median time to progression (TTP) and median survival time (MST). Medical records of nine institutions were searched for dogs diagnosed with stage I and II splenic HSA that underwent adjuvant treatment with AC- or MC-based protocols following splenectomy. Patients treated with MC following AC were included in an additional group (AMC). Ninety-three dogs were included: 50 in the AC group, 23 in the AMC group and 20 in the MC group. The overall MST was 200 days (range 47-3352) and the overall median TTP was 185 days (range 37-1236). The median TTP of stage I dogs was significantly longer compared to stage II dogs (338 vs 151 days, respectively, P = .028). When adjusting for treatment type, the MST was 154 days for the AC group (range 47-3352 days), 338 days for the AMC group (range 79-1623 days) and 225 days for the MC group (range 57-911 days). The difference in MST and median TTP was not found to be statistically significant between treatment groups. This study suggests that adjuvant MC in canine splenic HSA may result in a similar outcome when compared to other treatment protocols. Further studies are warranted to confirm these findings., (© 2019 John Wiley & Sons Ltd.)

Treatment options for dogs with metastatic (stage III) splenic hemangiosarcoma are limited. A doxorubicin-based chemotherapy regimen is commonly administered; however, there are no published data to support this practice. The aim of this study was to investigate the impact of maximum-tolerated-dose chemotherapy (MTD), metronomic chemotherapy (MC) and no adjuvant treatment on outcome in dogs with stage III splenic hemangiosarcoma undergoing splenectomy. Medical records of dogs with stage III splenic hemangiosarcoma that underwent splenectomy followed by MTD chemotherapy, MC or no adjuvant treatment were retrieved. Time to progression (TTP), survival time (ST) and toxicity were evaluated. One hundred three dogs were identified: 23 received adjuvant MTD, 38 MC and 42 were not medically treated. Overall median TTP and ST were 50 (95% confidence interval [CI], 39-61) and 55 days (95% CI, 43-66), respectively. Dogs treated with adjuvant MTD had a significantly longer TTP and ST compared with dogs receiving MC (median TTP, 134 vs 52 days, P = .025; median ST, 140 vs 58 days, P = .023, respectively). Dogs treated by splenectomy only had the shortest median TTP (28 days) and ST (40 days). However, treatment-related adverse events (AEs) were significantly more frequent in the MTD group (P = .017). The outcome for dogs with metastatic splenic hemangiosarcoma is poor. While MTD showed greater efficacy compared to MC, toxicity was higher in this group. Treatment-related AEs need to be carefully balanced against this modest survival prolongation when offering adjuvant MTD to dogs with advanced stage hemangiosarcoma., (© 2019 John Wiley & Sons Ltd.)

Objectives: To characterise the presentation, clinicopathologic data and outcome of 29 dogs with presumed primary renal lymphoma., Materials and Methods: Retrospective analysis of medical records of dogs with suspected primary renal lymphoma from 11 institutions., Results: All dogs were substage b, and lethargy and gastrointestinal signs were common presenting complaints, as were azotaemia (n=25; 86%) and erythrocytosis (n=15; 51%) on biochemical testing. Ultrasonography typically revealed bilateral renal lesions (n=23; 79%), renomegaly (n=22; 76%) and abdominal lymphadenopathy (n=14; 48%). Chemotherapy was the only treatment in 23 dogs, of which 11 responded, all considered partial responses. For all dogs the median progression-free survival and median overall survival times were 10 days (range: 1 to 126) and 12 days (range: 1 to 212), respectively, and for dogs that responded to chemotherapy 41 days (range: 10 to 126) and 47 days (range: 10 to 212), respectively., Clinical Significance: Primary renal lymphoma in dogs appears to be associated with a poor prognosis and short-lived response to chemotherapy., (© 2019 British Small Animal Veterinary Association.)

MicroRNAs (miRNAs) are a class of small, noncoding RNA that post-transcriptionally regulate protein expression. miRNAs are emerging as clinical biomarkers of many diseases, including tumors. The aim of this study was to investigate whether miRNA expression could vary in melanoma samples derived from formalin-fixed, paraffin-embedded (FFPE) tissues. The study included 4 groups: (1) 9 samples of oral canine malignant melanoma, (2) 10 samples of cutaneous malignant melanoma, (3) 5 samples of healthy oral mucosa, and (4) 7 samples of healthy skin. The expression levels of 6 miRNAs-miR-145, miR-146a, miR-425-5p, miR-223, miR-365, and miR-134-were detected and assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) using TaqMan probes. Cutaneous canine malignant melanoma showed a decrease of the expression level of miR-145 and miR-365 and an increase of miR-146a and miR-425-5p compared to control samples. MiR-145 was also downregulated in oral canine malignant melanoma. The miRNAs with decreased expression may regulate genes involved in RAS, Rap1, and transforming growth factor β (TGF-β) signaling pathways, as well as upregulated genes associated with phosphatidylinositol signaling system, adherens junction, and RAS signaling pathways. In conclusion, miR-145, miR-365, miR-146a, and miR-425-5p were differentially expressed in canine malignant melanoma and healthy FFPE samples, suggesting that they may play a role in canine malignant melanoma pathogenesis.

A neutered female domestic shorthaired cat was presented for a rapidly growing left cervical mass and a 6-month history of primary hyperthyroidism. Cytological examination of the mass was consistent with a sarcoma. Due to poor clinical response the cat was humanely destroyed and a post-mortem examination was performed. This revealed a markedly enlarged, irregularly shaped left thyroid gland with signs of infiltration of the trachea. The contralateral (right) thyroid was also moderately enlarged and irregularly shaped. Histopathological examination of the cervical masses indicated bilateral thyroid carcinosarcomas, evidenced by positive immunohistochemical labelling for vimentin, pan-cytokeratin and thyroid transcription factor-1 of the appropriate cell populations. The cat also had a concurrent pulmonary adenocarcinoma (papillary-lepidic type), unrelated to the thyroid neoplasm. Thyroid carcinosarcoma is an uncommonly recorded canine and human neoplasm and this is the first case of this entity to be reported in a cat., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Transitional cell carcinoma (TCC) is the most common canine urinary tract tumour and mimics human invasive TCC. Human TCCs overexpress lipoxygenase (LOX)-5 and the use of target inhibitors has proven effective in inhibiting neoplastic growth. In this study, we investigated the immunohistochemical expression of LOX-5 in normal canine urinary bladder, cystitis and TCC. The comparative expression of LOX-5, cyclo-oxygenase (COX)-1 and COX-2 among the three tissue groups was also examined. Biopsy samples from cases of cystitis and TCC were reviewed from 2012 to 2016; samples of histologically normal bladder were used as controls. Dogs were excluded if they had received glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs) and/or chemotherapy prior to tissue collection. LOX-5 was expressed in 95% of TCCs, 23% of cases of cystitis and 10% of controls. LOX-5 and COX-2 immunohistochemistry scores were significantly (P <0.01) higher in TCCs versus cystitis and normal bladders. Results of this study support the rationale for further investigation of the use of NSAIDs with dual anti COX-2 and LOX-5 effect for the treatment of canine TCC., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The DMAC protocol (dexamethasone, melphalan, actinomycin-D, cytarabine) has been evaluated in American studies for the treatment of relapsed canine lymphoma, comparing similarly to other rescue protocols. The aim of this study was to evaluate efficacy and toxicity of DMAC, in a larger UK cohort of resistant canine lymphomas. Medical records of dogs with resistant non-Hodgkin high-grade lymphomas that received DMAC as a rescue protocol were reviewed from 2007 to 2017. Response, time from initiation to discontinuation (TTD) and toxicity (Veterinary Cooperative Oncology Group criteria) were assessed. One hundred dogs were included; 86 received CEOP (modified CHOP including epirubicin) as first-line treatment. Thirty-five dogs (35%) responded: 21 complete responders (CRs) and 14 partial responders (PRs). Responders had significantly longer TTD (P < 0.001) compared with non-responders: 62 days (range 28-952) for CR vs 32 days (range 20-70) for PR. Six CR received more than six cycles of DMAC (range 7-36 cycles) and experienced a longer TTD (median 508, range 126-952 days). Thrombocytopenia occurred in 45% (24 grade 1-2, 21 grade 3-4) and neutropenia in 36% of cases (29 grade 1-2, 7 grade 3-4). Gastrointestinal toxicity occurred in 42% of dogs (40 grade 1-2, 2 grade 3-4). Owing to chemotherapy toxicity, treatment was discontinued in five, and hospitalization required in six cases. In this study, response to DMAC was lower and of generally shorter duration than previously reported. Toxicity was high, but infrequently led to hospitalization or discontinuation of treatment., (© 2019 John Wiley & Sons Ltd.)

Mast cell tumours (MCTs) are commonly treated with radiation therapy, most often in a microscopic disease setting. Poorer outcomes are expected in patients with gross disease, and irradiation of gross disease may be associated with greater toxicity. The aim of this study was to compare acute radiation adverse events (AE) in dogs with gross and microscopic MCTs receiving radiotherapy. Fifty-seven dogs were included, 28 with gross disease and 29 with microscopic. In order to assess mucosal and skin toxicity, patients were assigned to 2 groups: head (29 patients, 14 patients with gross and 15 microscopic) and other sites (28 patients, 14 each). All were treated with external beam radiotherapy, and toxicity assessed at the end of treatment and 10 to 14 days later (first recheck). All patients developed some acute radiation toxicity by the end of the course. However, there was no difference in the severity of toxicity between gross and microscopic disease in either site group at either time point. The only variable associated with an increased frequency of grade 2 or 3 toxicity at the first recheck was the use of prednisolone prior to radiotherapy (P = .05). No other factors were identified which were associated with increased toxicity. For the head group, the site of highest grade toxicity was mucosa or, if included in the field, nasal planum, which was often more severely affected than the mucosa. No significant late toxicity was identified. Two dogs developed acute haematemesis during the radiotherapy course, but both completed the course without further events., (© 2018 John Wiley & Sons Ltd.)

Unresectable or metastatic (advanced) primary pulmonary carcinoma (PPC) represents a therapeutic challenge where surgery may be contraindicated and the therapeutic role of maximum-tolerated dose (MTD) chemotherapy remains uncertain. This study was undertaken to explore the impact of metronomic chemotherapy (MC) in dogs with advanced PPC. Previously untreated dogs with advanced (T3 or N1 or M1) PPC, with complete staging work-up and follow-up data, receiving MC (comprising low-dose cyclophosphamide, piroxicam and thalidomide), surgery, MTD chemotherapy or no oncologic treatment were eligible for inclusion. For all patients, time to progression (TTP) and survival time (ST) were evaluated. Quality-of-life (QoL) was only evaluated in patients receiving MC. To assess QoL, owners of dogs receiving MC were asked to complete a questionnaire before and during treatment. Ninety-one dogs were included: 25 received MC, 36 were treated with surgery, 11 with MTD chemotherapy and 19 received no treatment. QoL was improved in dogs receiving MC. Median TTP was significantly longer in patients receiving MC (172 days) than patients undergoing surgery (87 days), receiving MTD chemotherapy (22 days), or no oncologic treatment (20 days). Median ST was similarly longer in patients receiving MC (139 days) than those undergoing surgery (92 days), MTD chemotherapy (61 days) and no oncologic treatment (60 days). In dogs with advanced PPC, MC achieved a measurable clinical benefit without significant risk or toxicity. This makes MC a potential alternative to other recognized management approaches., (© 2018 John Wiley & Sons Ltd.)