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.
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.
In canine cutaneous mast cell tumours (cMCTs), histologic grade and clinical stage are the most important prognostic factors, with high‐grade tumours and metastatic lymph nodes (LNs) significantly influencing the evolution of disease. However, it is uncertain whether histologic grade and clinical stage should be given equal weighting value in patient prognostication and management. Dogs with low‐ and high‐grade cMCTs and at least one overtly metastatic sentinel LN undergoing standardized treatment, consisting of surgical excision of the cMCT, lymphadenectomy and chemotherapy, were retrospectively included. The aim was to determine whether, at the same clinical stage, histologic grade retained prognostic relevance. Sixty dogs were included: 26 had a high‐grade cMCT tumour and 34 had a low‐grade cMCT. Median follow‐up was 367 days (range, 187–748) in the high‐grade group, and 1208 days (range, 180–2576) in the low‐grade group. Median time to progression was significantly shorter in the high‐grade group than in the low‐grade group (214 days versus not reached; p < .001), as well as tumour‐specific survival (545 days versus not reached; p < .001). On multivariable analysis, a high histologic grade and incomplete margins retained prognostic significance for both tumour progression and tumour‐specific death. In dogs with cMCT and at least one overtly metastatic LN undergoing multimodal treatment, histologic grade significantly correlated with outcome. Overall prognosis was not unfavourable, even in the high‐grade group, further supporting that a multimodal therapeutic approach, addressing primary tumour and sentinel LN, should be offered. Whether chemotherapy should be incorporated in the therapeutic planning of low‐grade cMCTs remains to be defined.
Background: Risk factors for oral squamous cell carcinoma (OSCC) in cats are derived from a single study dated almost 20 years ago. The relationship between inflammation of oral tissues and OSCC is still unclear. Objectives: To investigate previously proposed and novel potential risk factors for OSCC development, including oral inflammatory diseases. Animals: Hundred cats with OSCC, 70 cats with chronic gingivostomatitis (CGS), 63 cats with periodontal disease (PD), and 500 controls. Methods: Prospective, observational case-control study. Cats with OSCC were compared with an age-matched control sample of client-owned cats and cats with CGS or PD. Owners of cats completed an anonymous questionnaire including demographic, environmental and lifestyle information.Results: On multivariable logistic regression, covariates significantly associated with an increased risk of OSCC were rural environment (OR: 1.77; 95%
Lymph node (LN) metastasis in canine mast cell tumor (MCT) can affect prognosis and postsurgical treatment recommendations; however, routine histological single-section examination may underestimate the incidence of metastases. This prospective study aimed at determining whether longitudinal step-sectioning of the entire LN allows for a more reliable detection of metastases. Dogs with MCT undergoing resection of the primary tumor and regional lymphadenectomy were enrolled. Formalin-fixed LNs were bisected longitudinally, both halves were embedded in paraffin and histological sections prepared at 200 μm steps. The nodal mast cells were classified according to the Weishaar classification. First-section evaluation (FSE; ie, examination of the first section obtained from the blocks) and whole LN step-section evaluation (SSE) were compared. Fifty-eight LNs were included. The median number of sections per LN was 6 (range, 3–28). FSE with toluidine blue (TB) revealed 27 (47%) nonmetastatic (HN0), 14 (24%) premetastatic (HN1), 9 (15%) early metastatic (HN2), and 8 (14%) overtly metastatic (HN3) LNs. SSE with TB resulted in upgrading the LN status in 2 cases (HN2 to HN3; HN0 to HN1). Evaluation of the first section plus an additional step-section resulted in 100% accuracy. Compared with SSE with TB, the accuracy of FSE with HE was 98% for HN3 LNs and 74% for HN2 LNs. FSE appears to reliably allow for the detection of LN metastasis in MCT, although examination of a further parallel section at a 200 μm step may increase the accuracy. A metachromatic stain is recommended for the identification of early metastases.
Despite efforts to develop novel treatment strategies, human and canine osteosarcomas continue to have poor prognosis and limited overall survival. The aim of this clinical trial was to test the antitumor effect and safety of multiple dermal administrations of a peptide-based anticancer vaccine in dogs with non-metastatic appendicular osteosarcoma undergoing standard of care (SOC), consisting of limb amputation and adjuvant chemotherapy. Salmonella-infected canine osteosarcoma cells were induced to release immunogenic peptides in the extracellular space via Cx43 hemichannels opening; the secretome was collected and constituted the vaccine. Dogs with non-metastatic appendicular osteosarcoma were eligible for recruitment. Following limb amputation and adjuvant carboplatin, dogs were vaccinated on a monthly basis for six times and followed up with serial thoracic radiographs. A population of dogs undergoing SOC treatment (amputation and adjuvant carboplatin) before the vaccine was available served as controls. Primary endpoints were time to metastasis (TTM) and tumor-specific survival (TSS). Secondary endpoints were feasibility, toxicity, T-cell and humoral immune responses. A total of 20 dogs were vaccinated along with SOC and 34 received SOC only. Vaccine-specific humoral and T-cell responses were observed; their amplitude correlated with TSS. Vaccine-associated toxicity was not recorded. TTM and TSS were significantly longer in vaccinated versus unvaccinated dogs (TTM: 308 vs. 240 days, respectively; p = 0.010; TSS: 621 vs. 278 days, respectively; p = 0.002). In dogs with non-metastatic osteosarcoma undergoing SOC, the addition of a bacteria-based vaccination strategy increased TTM, thereby prolonging survival, while maintaining a safe profile. Additionally, vaccinated dogs developed a long-term tumor-specific response, as documented by the immunomonitoring of these patients over time. These results hold promise for future management of canine osteosarcoma.
Timely delivery of adjuvant chemotherapy has been shown to be advantageous in many human cancers and canine osteosarcoma. Adjuvant chemotherapy has been shown to improve outcome for canine splenic hemangiosarcoma. The aim of this retrospective study was to investigate whether timely adjuvant chemotherapy administration resulted in better outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy. Medical records were searched for dogs with non-metastatic, splenic hemangiosarcoma that received splenectomy and adjuvant chemotherapy. The number of days from surgery to the first chemotherapy dose (StoC) was evaluated to identify the cut-off value associated with the best survival advantage. StoC and other possible prognostic factors were tested for influence on time to metastasis (TTM) and overall survival (OS). Seventy dogs were included.Median StoC was 20 days (range: 4-70). The time interval associated with the greatest survival benefit was 21 days. Median TTM and OS of dogs with StoC ≤ 21 days were significantly longer than those with StoC >21 days (TTM: 163 vs. 118 days, p = .001; OS: 238 vs. 146 days, p < .001). On multivariable analysis, StoC >21 days was the only variable significantly associated with increased risk of tumour progression (HR 2.1, p = .010) and death (HR 2.3; p = .008). Starting adjuvant chemotherapy within 21 days of surgery may be associated with a survival benefit in dogs with nonmetastatic splenic hemangiosarcoma, possibly due to the early targeting of newly recruited metastatic cells after surgery.
Surgery-induced stress and anesthesia-related immunosuppression are believed to play a critical role in human oncology patients. Studies have hypothesized that anesthesia influences patients' outcome, promoting tumor recurrence and metastasis. Aim of the study was to investigate whether anesthesia promoted relapse in dogs with diffuse large B-cell lymphoma (DLBCL). Medical records were searched for dogs with DLBCL, that were in complete remission (CR) after the same chemo-immunotherapy protocol. Dogs receiving anesthesia were included if the procedure was performed while in CR. Time to relapse (TTR) was obtained via Kaplan–Meier method. Association between anesthesia and relapse was assessed using a nested case-control design and estimated using conditional logistic regression. Sixty-one dogs with DLBCL were included. Overall median TTR was 329 days (95% CI, 281–377). Forty-eight (79%) dogs relapsed during the study period, while 13 (21%) were still in CR at data analysis closure. Eighteen (30%) dogs received anesthesia with opioids, propofol, and isoflurane or sevoflurane. The relative risk of lymphoma relapse for dogs undergoing anesthesia was significantly higher compared with dogs not undergoing anesthesia, with an odds ratio of 3.09 (P = 0.019) on multivariable analysis. Anesthesia may promote relapse in dogs with DLBCL treated with chemo-immunotherapy, although a role of perioperative stress cannot be ultimately excluded. Considering the high frequency of anesthetic procedures required for diagnostic and therapeutic protocols among oncology patients, it is of utmost interest to characterize the effects of single anesthetic agents on the immune system. Further prospective studies are needed to better define the impact of anesthesia on patients' outcome.
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