A chimeric human/dog-DNA vaccine against CSPG4 induces immunity with therapeutic potential in comparative preclinical models of osteosarcoma.

The high mortality rate of osteosarcoma (OSA) patients highlights the requirement of alternative strategies. The young age of patients, as well as the rarity and aggressiveness of the disease, limits opportunities for the robust testing of novel therapies, suggesting the need for valuable preclinical systems. Having previously shown the overexpression of the chondroitin sulfate proteoglycan (CSPG)4 in OSA, herein the functional consequences of its downmodulation in human OSA cells were evaluated in vitro, with a significant impairment of cell proliferation, migration, and osteosphere generation. The potential of a chimeric human/dog (HuDo)-CSPG4 DNA vaccine was explored in translational comparative OSA models, including human xenograft mouse models and canine patients affected by spontaneous OSA. The adoptive transfer of HuDo-CSPG4 vaccine-induced CD8+ T cells and sera in immunodeficient human OSA-bearing mice delayed tumor growth and metastasis development. HuDo-CSPG4 vaccination resulted safe and effective in inducing anti-CSPG4 immunity in OSA-affected dogs, which displayed prolonged survival as compared to controls. Finally, HuDo-CSPG4 was also able to induce a cytotoxic response in a human surrogate setting in vitro. On the basis of these results and the high predictive value of spontaneous OSA in dogs, this study paves the way for a possible translation of this approach to humans.

Diagnostic Findings and Surgical Management of Three Dogs Affected by Osseous Metaplasia Secondary to a Salivary Mucocele.

Saliva is an irritant of the subcutaneous tissue, thus causing the development of a non-epithelial reactive pseudocapsule. Metaplastic ossification of the pseudocapsule is a condition rarely described in the veterinary literature. The main causes of calcification are trauma, tumours, various chronic inflammatory conditions and fibrodysplasia ossificans progressiva. The aim of the present case series was to describe three dogs affected by a calcified salivary mucocele. The medical records of dogs affected by a cervical sialocele were retrospectively evaluated, and three cases met the inclusion criteria. All the dogs in this study were referred to the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Sciences of the University of Turin (Turin, Italy) for a large solid mass in the intermandibular region. The diagnosis of a mucocele was confirmed clinically by centesis and by radiography or CT. Complete excision of both the pseudocyst and the ipsilateral mandibular/monostomatic sublingual salivary gland was performed in all cases. The histological report showed large areas of bone metaplasia within the pseudocapsule and chronic sialadenitis. Based on this limited case series, complete excision of the pseudocyst and a concurrent sialoadenectomy provided an effective treatment for this rare salivary mucocele disorder.

Sentinel lymph node mapping with computed tomography lymphography for mast cell tumours and a comparison between regional and sentinel lymph node histological status: Sixty-two cases.

It is known that the regional lymph node (RLN) may not correspond to the sentinel lymph node (SLN) (the first lymph node draining the tumour), and many diagnostic techniques have recently been aimed at its detection. Although lymphoscintigraphy is the gold standard in both human and veterinary medicine for SLN mapping, it is relatively unavailable in veterinary medicine due to costs and difficult management of the radiotracer. This prospective study evaluated, as a first aim, the feasibility and sensitivity of the computed tomography lymphography (CTL) in detecting the SLN in 62 mast cell tumours (MCTs). The second aim was to evaluate the accuracy of the CTL in identifying the most representative lymph node of the patient's lymphatic status; the histological status of the SNL was compared with that of the RLN, to see in how many cases the patient's stage would have changed according to the RLN. When the RLN turned out to be also the SLN it was decided to excise, as a control LN, the one localised in the neighbourhood of the MCT (neighbouring lymph node; NLN). The detection rate was 90%, with failure of SLN identification in six cases. In 18 (32%) of 56 MCTs with a diagnostic CTL, the SLN did not correspond to the RLN. Forty-five MCTs were surgically removed, together with their corresponding SLN and RLN/NLN. Since the clinical stage of the patient would have changed in only 7% of cases, CTL is a reliable method of detecting the SLN and, for staging purposes, there is no need to remove other LNs.

Surgical Excision of Intramuscular Sarcomas: Description of Three Cases in Dogs.

Compartmental excision consists of the complete resection of an anatomic district in which specific structures act as a barrier to local tumour invasion. It is a well-established procedure in human medicine, while only a few reports are available in veterinary medicine. The aim of this study was to describe complete muscle resection in 3 dogs affected by different intramuscular sarcomas. The clinical outcome was also reported. Medical records were searched, including preoperative diagnostic findings, compartmental excision, histologic diagnosis, and outcome. Three dogs fit the inclusion criteria, which had a sarcoma confined to a single muscular belly (semitendinosus, biceps, and splenius capitis muscles). Complete excision of the affected muscle was performed in all cases. One dog showed moderate lameness in the immediate postoperative period, resulting from the dorsal lifting of the scapula due to serratus ventralis tenotomy performed to remove the caudal insertion of the splenius capitis muscle. All the dogs recovered fully within one month, experiencing good clinical function. Histopathology showed complete tumour removal with no neoplastic fascial disruption in all cases. Compartmental excision provides effective local tumour control, representing an alternative to limb amputation or more radical excision if adjuvant radiotherapy is not an option for owners.

Improving Osteosarcoma Treatment: Comparative Oncology in Action.

Osteosarcoma (OSA) is the most common pediatric malignant bone tumor. Although surgery together with neoadjuvant/adjuvant chemotherapy has improved survival for localized OSA, most patients develop recurrent/metastatic disease with a dismally poor outcome. Therapeutic options have not improved for these OSA patients in recent decades. As OSA is a rare and "orphan" tumor, with no distinct targetable driver antigens, the development of new efficient therapies is still an unmet and challenging clinical need. Appropriate animal models are therefore critical for advancement in the field. Despite the undoubted relevance of pre-clinical mouse models in cancer research, they present some intrinsic limitations that may be responsible for the low translational success of novel therapies from the pre-clinical setting to the clinic. From this context emerges the concept of comparative oncology, which has spurred the study of pet dogs as a uniquely valuable model of spontaneous OSA that develops in an immune-competent system with high biological and clinical similarities to corresponding human tumors, including in its metastatic behavior and resistance to conventional therapies. For these reasons, the translational power of studies conducted on OSA-bearing dogs has seen increasing recognition. The most recent and relevant veterinary investigations of novel combinatorial approaches, with a focus on immune-based strategies, that can most likely benefit both canine and human OSA patients have been summarized in this commentary.

The mitotic regulator polo-like kinase 1 as a potential therapeutic target for c-Myc-overexpressing canine osteosarcomas.

Osteosarcoma is the most common primary malignant bone tumour in dogs, characterized by a locally aggressive and highly metastatic behaviour. Despite the current standards of care, most dogs succumb to the disease, indicating the need for novel treatment strategies. Polo-like kinase 1 (PLK1) is dysregulated in a variety of human cancer types, including osteosarcoma, and induces c-Myc accumulation. The crosstalk between the two molecules coordinates cell proliferation, differentiation, self-renewal and apoptosis. Therefore, PLK1 has recently emerged as a potential therapeutic target, mainly in tumours overexpressing c-Myc. BI 2536 is a selective PLK1 inhibitor promoting mitotic arrest and apoptosis in a variety of cancer cells. This research aimed at evaluating PLK1 and c-Myc protein expression in 53 appendicular canine osteosarcoma (cOSA) samples and the in vitro effects of BI 2536 on a c-Myc and PLK1-overexpressing cOSA cell line (D17). PLK1 and c-Myc expression in cOSA samples showed no correlation with clinicopathological data. However, c-Myc overexpression was associated with a significantly reduced overall survival (p = .003). Western Blot and RT-qPCR assays revealed that D17 expressed high protein and transcript levels of both PLK1 and MYC. When treated with BI 2536 (range 2.5-15 nM) for 24 h, D17 showed a substantial decrease in cell growth, inducing apoptosis and G2 /M cell cycle arrest. Interestingly, under BI 2536 treatment, D17 showed decreased c-Myc protein levels. Consistent with human OSA, these preliminary data outline the prognostic value of c-Myc expression in cOSA and highlight the potential role of PLK1 as an antiproliferative therapeutic target for tumours overexpressing c-Myc.

Antigen mimicry as an effective strategy to induce CSPG4-targeted immunity in dogs with oral melanoma: a veterinary trial.

BACKGROUND: Melanoma is the most lethal form of skin cancer in humans. Conventional therapies have limited efficacy, and overall response is still unsatisfactory considering that immune checkpoint inhibitors induce lasting clinical responses only in a low percentage of patients. This has prompted us to develop a vaccination strategy employing the tumor antigen chondroitin sulfate proteoglycan (CSPG)4 as a target. METHODS: To overcome the host's unresponsiveness to the self-antigen CSPG4, we have taken advantage of the conservation of CSPG4 sequence through phylogenetic evolution, so we have used a vaccine, based on a chimeric DNA molecule encompassing both human (Hu) and dog (Do) portions of CSPG4 (HuDo-CSPG4). We have tested its safety and immunogenicity (primary objectives), along with its therapeutic efficacy (secondary outcome), in a prospective, non-randomized, veterinary clinical trial enrolling 80 client-owned dogs with surgically resected, CSPG4-positive, stage II-IV oral melanoma. RESULTS: Vaccinated dogs developed anti-Do-CSPG4 and Hu-CSPG4 immune response. Interestingly, the antibody titer in vaccinated dogs was significantly associated with the overall survival. Our data suggest that there may be a contribution of the HuDo-CSPG4 vaccination to the improvement of survival of vaccinated dogs as compared with controls treated with conventional therapies alone. CONCLUSIONS: HuDo-CSPG4 adjuvant vaccination was safe and immunogenic in dogs with oral melanoma, with potential beneficial effects on the course of the disease. Thanks to the power of naturally occurring canine tumors as predictive models for cancer immunotherapy response, these data may represent a basis for the translation of this approach to the treatment of human patients with CSPG4-positive melanoma subtypes.

Canine Melanoma Immunology and Immunotherapy: Relevance of Translational Research.

In veterinary oncology, canine melanoma is still a fatal disease for which innovative and long-lasting curative treatments are urgently required. Considering the similarities between canine and human melanoma and the clinical revolution that immunotherapy has instigated in the treatment of human melanoma patients, special attention must be paid to advancements in tumor immunology research in the veterinary field. Herein, we aim to discuss the most relevant knowledge on the immune landscape of canine melanoma and the most promising immunotherapeutic approaches under investigation. Particular attention will be dedicated to anti-cancer vaccination, and, especially, to the encouraging clinical results that we have obtained with DNA vaccines directed against chondroitin sulfate proteoglycan 4 (CSPG4), which is an appealing tumor-associated antigen with a key oncogenic role in both canine and human melanoma. In parallel with advances in therapeutic options, progress in the identification of easily accessible biomarkers to improve the diagnosis and the prognosis of melanoma should be sought, with circulating small extracellular vesicles emerging as strategically relevant players. Translational advances in melanoma management, whether achieved in the human or veterinary fields, may drive improvements with mutual clinical benefits for both human and canine patients; this is where the strength of comparative oncology lies.

Treatment of an aneurysmal bone cyst in a young dog: A case report.

BACKGROUND: An aneurysmal bone cyst (ABC) is a rare benign lytic lesion affecting the medullary canal of long bones. It has been widely reported in human medicine, but rarely described in domestic animals. OBJECTIVE: To report the surgical treatment and long term follow-up of a dog affected by ABC. METHODS: An 8-month-old, intact female Weimaraner was presented with lameness affecting the left front limb and progressive swelling of the mid-distal radius. Survey radiographs revealed a mid-distal diaphyseal radial lesion. Fine needle aspirates, biopsy, CT scan and histopathology results supported the diagnosis of ABC. Treatment consisted of partial corticotomy of the affected radius, filling of the cystic cavity with demineralised bone matrix and autologous bone graft and stabilisation using lag screws and a neutralisation plate. RESULTS: The long-term follow-up, at 36 post-operative months, showed no recurrence of the cyst and bone modelling. Comparing preoperative radiographs with those at 36 months, bone modelling reduced the radial area by 23.3% in the craniocaudal radiographic view and 30% in the mediolateral projection. CONCLUSIONS: This treatment was sucessful in the case here described, with a 3 years follow-up.

Prognostic impact of bone invasion in canine oral malignant melanoma treated by surgery and anti-CSPG4 vaccination: A retrospective study on 68 cases (2010-2020).

Prognosis of canine oral malignant melanoma encompasses clinical, histological and immunohistochemical parameters. The aim of this study was to evaluate the prognostic impact of bone invasion in oral canine melanoma. Sixty-eight dogs bearing oral melanoma staged II and III that underwent surgery and anti-CSPG4 electrovaccination, with available histological data and a minimum follow up of minimum 1 year, were retrospectively selected. Bone invasion was detected on imaging and/or histology. Median survival time of dogs with evidence of bone invasion (group 1) was 397 days and significantly shorter compared with dogs with oral melanomas not invading the bone (group 2, 1063 days). Dogs with tumours localised at the level of the cheek, lip, tongue and soft palate (soft tissue - group 3) lived significantly longer compared with dogs having tumours within the gingiva of the maxilla or mandible (hard tissue - group 4) with a median survival time of 1063 and 470 days, respectively. Within group 4, the subgroup of dogs with tumours not invading the bone (group 5) showed a significant prolonged survival time (972 days) in comparison with dogs of group 1 (bone invasion group). Similar results were obtained for the disease-free intervals amongst the different groups. Statistical analysis showed that Ki67 and mitotic count were correlated with shorter survival in patients of group 1 (with bone invasion). Bone invasion should always be assessed since it appears to be a negative prognostic factor.

Canine Epithelial Thymic Tumors: Outcome in 28 Dogs Treated by Surgery.

Thymoma is a tumor rarely reported in dogs and should be differentiated from mediastinal lymphoma. Clinical signs may have a late onset, and thymoma is often diagnosed when symptoms related to the space-occupying effect or paraneoplastic syndromes occur. CT and fine-needle aspirates or core biopsies are helpful in differential diagnosis, but flow cytometry may improve the pre-operative diagnostic ability. Concurrent paraneoplastic syndromes such as myasthenia gravis and hypercalcemia have been reported; however, their role as prognostic factors is not well determined. Surgical excision is the treatment of choice; adjuvant radiotherapy and/or chemotherapy may prolong survival in cases of incomplete excision or when a thymic carcinoma is diagnosed. Local recurrence and metastasis are infrequently reported; therefore, a long survival time is expected if the tumor is completely excised or if adjuvant therapy is undertaken. This article reports the authors' experience with 28 dogs affected by 18 thymomas and 10 thymic carcinomas. The median overall survival in this series was 1173 days, and the median disease-free interval was 903 days. Dogs with thymic carcinoma had significantly shorter disease-free intervals and shorter, although not statistically significant, survival times. Dogs with Masaoka Stage III tumors had worse outcomes.

Timing of adjuvant chemotherapy after limb amputation and effect on outcome in dogs with appendicular osteosarcoma without distant metastases.

OBJECTIVE: To determine an optimal time interval between amputation and initiation of adjuvant chemotherapy (TIamp-chemo) in dogs with appendicular osteosarcoma without distant metastases and whether TIamp-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 TIamp-chemo. RESULTS: Median TIamp-chemo was 14 days (range, 1 to 210 days). Median time to tumor progression for dogs with a TIamp-chemo ≤ 5 days (375 days; 95% CI, 162 to 588 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (202 days; 95% CI, 146 to 257 days). Median overall survival time for dogs with a TIamp-chemo ≤ 5 days (445 days; 95% CI, 345 to 545 days) was significantly longer than that for dogs with a TIamp-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.

Prognostic Value of Ki67 and Other Clinical and Histopathological Factors in Canine Apocrine Gland Anal Sac Adenocarcinoma.

Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear.

Genomic and Transcriptomic Characterization of Canine Osteosarcoma Cell Lines: A Valuable Resource in Translational Medicine.

Osteosarcoma (OSA) represents the most common primary bone tumor in dogs and is characterized by a highly aggressive behavior. Cell lines represent one of the most suitable and reproducible pre-clinical models, and therefore the knowledge of their molecular landscape is mandatory to investigate oncogenic mechanisms and drug response. The present study aims at determining variants, putative driver genes, and gene expression aberrations by integrating whole-exome and RNA sequencing. For this purpose, eight canine OSA cell lines and one matched pair of primary tumor and normal tissue were analyzed. Overall, cell lines revealed a mean tumor mutational burden of 9.6 mutations/Mb (range 3.9-16.8). Several known oncogenes and tumor suppressor genes, such as ALK, MYC, and MET, were prioritized as having a likely role in canine OSA. Mutations in eight genes, previously described as human OSA drivers and including TP53, PTCH1, MED12, and PI3KCA, were retrieved in our cell lines. When variants were cross-referenced with human OSA driver mutations, the E273K mutation of TP53 was identified in the Wall cell line and tumor sample. The transcriptome profiling detected two possible p53 inactivation mechanisms in the Wall cell line on the one hand, and in D17 and D22 on the other. Moreover, MET overexpression, potentially leading to MAPK/ERK pathway activation, was observed in D17 and D22 cell lines. In conclusion, our data provide the molecular characterization of a large number of canine OSA cell lines, allowing future investigations on potential therapeutic targets and associated biomarkers. Notably, the Wall cell line represents a valuable model to empower prospective in vitro studies both in human and in dogs, since the TP53 driver mutation was maintained during cell line establishment and was widely reported as a mutation hotspot in several human cancers.

Benign or Low-Grade Malignant Masses Occupying the Pelvic Canal Space in 11 Dogs.

Dogs with benign intra-pelvic rectal or vaginal masses show symptoms indicating compression on the adjacent organs. Clinical signs usually develop late when the lesion is large enough to interfere functionally. The dogs were referred for severe fecal and/or urinary tenesmus. The data collected included signalment, clinical signs, results of physical examination, pre-surgical diagnostic tests, surgical technique used, surgical complications and histological findings. Digital rectal and vaginal examination allowed the detection of a mass occupying space in the pelvic cavity in all patients. Abdominal ultrasonography and/or total body computed tomography (CT) were used to better characterize the lesion and to exclude a metastatic spread of the tumor in case of malignancy. A dorsal approach to the rectum, a dorsal episiotomy, a midline celiotomy, and a combined perineal and abdominal approach were performed to remove the mass. No postoperative complications were observed. Benign and well-differentiated malignant mesenchymal neoplasms were histologically diagnosed. As a consequence of the chronic urethral compression caused by the mass, urinary incontinence and/or urinary retention were observed for a few postoperative days. Fecal tenesmus resolved in all cases in the immediate postoperative period. The dogs' quality of life quickly improved after surgery, especially considering the serious and life-threatening pre-surgical clinical conditions. Both the recovery time after surgery and overall survival were also evaluated.

Surgical treatment and outcome of sterile prostatic cysts in dogs.

OBJECTIVE: To describe the surgical treatment and outcome of a large cohort of dogs with sterile prostatic cysts (PCs). STUDY DESIGN: Retrospective study. ANIMALS: Forty-four client-owned dogs. METHODS: Dogs with sterile PCs with at least 6 months of follow-up were included. Clinical variables, type of surgery, complications, recurrences, and outcomes (telephonic interviews or rechecks) were recorded. RESULTS: Extra- and intraparenchymal cysts were diagnosed in 29 and 11 dogs, respectively. Four dogs had both types. Extraparenchymal cysts were treated by partial resection and omentalization (n = 22) and complete resection (n = 7). Drainage and intracapsular omentalization were performed in all dogs with intraparenchymal cysts. The four dogs with both types of cyst were treated by omentalization. Resolution was documented in 39/44 dogs (88.6%). Intraoperative complications occurred in one dog (urethral tear). Major complications resulting in death occurred in three dogs (oliguric kidney injury, cardiac arrhythmia, and persisting urinary tract obstruction). Minor complications (n = 10) consisted of temporary urinary incontinence (n = 2), permanent urinary incontinence (n = 5), urinary retention (n = 2), and dysuria (n = 1). Recurrence occurred in two dogs with extraparenchymal cysts. Median long-term follow-up was 528 days (range, 250-730 days). Thirty-nine dogs had no signs associated with prostatic disease at long-term follow-up. CONCLUSION: Partial or complete resection and/or omentalization of sterile PCs led to resolution of clinical signs in most dogs, although postoperative urinary incontinence was frequent. IMPACT: This study is the largest case series relative to canine sterile PCs treated surgically and provides evidence on the prognosis and rate of complications.

Transoral approach for mandibular and sublingual sialoadenectomy in a cat.

Sialocele is an uncommon condition in cats. The treatment of choice for sublingual sialocele is excision of the ipsilateral mandibular and sublingual salivary gland/duct complex. Lateral and ventral cervical approaches have been described for mandibular-sublingual sialoadenectomy; however, the transoral approach, described here, has never been reported in cats. Ranula in the present case was likely caused by an inadvertent trauma of the sublingual duct during resection of a sublingual lesion performed by the referring veterinarian. The definitive surgery consisted of mass removal and sialoadenectomy through a unique oral approach. The surgery was effective without complications encountered after 6 months of follow-up. Key clinical message: This article reports a novel, transoral approach, for mandibular and sublingual sialoadenectomy in the cat. This approach decreases the surgical time and prevents recurrence of the mucocele.

Approche trans-orale pour la sialo-adénectomie mandibulaire et sublinguale chez un chat. La sialocèle est une maladie rare chez les chats. Le traitement de choix pour la sialocèle sublinguale est l'excision du complexe glandes salivaires/canal salivaire ipsilatéral mandibulaire et sublingual. Des approches cervicales latérales et ventrales ont été décrites pour la sialo-adénectomie mandibulaire-sublinguale; cependant, l'approche trans-orale, décrite ici, n'a jamais été rapportée chez les chats. Dans le cas présent, la ranula a probablement été causée par un traumatisme involontaire du canal sublingual lors de la résection d'une lésion sublinguale réalisée par le vétérinaire référent. La chirurgie définitive consistait en un enlèvement de masse et une sialo-adénectomie par une approche orale unique. La chirurgie a été efficace sans complications rencontrées après 6 mois de suivi.Message clinique clé :Cet article rapporte une nouvelle approche trans-orale pour la sialo-adénectomie mandibulaire et sublinguale chez le chat. Cette approche diminue le temps chirurgical et empêche la récidive de la mucocèle.(Traduit par Dr Serge Messier).

Difference in outcome between curative intent vs marginal excision as a first treatment in dogs with oral malignant melanoma and the impact of adjuvant CSPG4-DNA electrovaccination: A retrospective study on 155 cases.

Canine oral malignant melanoma is locally invasive and highly metastatic. At present, the best option for local control is en bloc excision followed by radiation if excision margins are incomplete. Adjuvantly, the role of chemotherapy is dubious while immunotherapy appears encouraging. This retrospective study evaluated 155 dogs with oral malignant melanomas (24 stage I, 54 stage II, 66 stage III and 11 stage IV) managed in a single institution. The aim was to evaluate the differences in median survival time (MST) and disease-free interval (DFI) between dogs which, at presentation, were treated surgically with a curative intent (group 1) vs those marginally excised only (group 2). MST in group 1 was longer than in group 2 (594 vs 458 days), but no significant difference was found (P = .57); a statistical difference was, however, found for DFI (232 vs 183 days, P = .008). In the subpopulation of vaccinated dogs, the impact of adjuvant anti-CSPG4 DNA electrovaccination was then evaluated (curative intent, group 3, vs marginal, group 4); a significant difference for both MST (1333 vs 470 days, respectively, P = .03) and DFI (324 vs 184 days, respectively, P = .008) was found. Progressive disease was significantly more common in dogs undergoing marginal excision than curative intent excision for both the overall population (P = .03) and the vaccinated dogs (P = .02). This study pointed out that, after staging, wide excision together with adjuvant immunotherapy was an effective approach for canine oral malignant melanoma.

Complications between ventral and lateral approach for mandibular and sublingual sialoadenectomy in dogs with sialocele.

OBJECTIVE: To compare complications of dogs treated with mandibular and sublingual sialoadenectomy for sialocele using a lateral (LAT) or ventral paramedian (VPM) approach. STUDY DESIGN: Retrospective multicenter study. ANIMALS: Dogs (140) with mandibular and sublingual sialocele. METHODS: Medical records of dogs that underwent mandibular and sublingual sialoadenectomy through a LAT or VPM approach from 2004 to 2020 were reviewed. Clinical and histopathological findings were analyzed to compare the groups. RESULTS: Seventy dogs were included in each group. The most represented breed was crossbreed (26%), and males (99/140 [71%], intact/neutered) were overrepresented. Dogs in the VPM approach group were more likely to undergo digastricus tunnelization and placement of a drain or a bandage. Dogs in the LAT approach group were heavier and more likely to undergo excision of an inflammatory pseudocapsule. No difference was detected in complication rates between groups (LAT [20%], VPM [31%], P = .116). Recurrences were more likely after LAT approach (5/70 vs 0/70, respectively; P = .029), whereas wound-related complications were more likely after VPM approach (20/70 vs 9/70, respectively; P = .018). Prolonged duration of surgery was associated with an increased risk of recurrence, and none of the other variables affected the complication rate. CONCLUSION: Ventral paramedian approach for mandibular and sublingual sialoadenectomy was associated with a lower risk of recurrence but a higher risk of wound-related complications compared with LAT approach. CLINICAL SIGNIFICANCE: Ventral paramedian approach for mandibular and sublingual sialoadenectomy may be preferred to reduce recurrence in dogs with sialoceles, but wound-related complications are common.

Evaluation of the neoplastic infiltration of the skin overlying canine subcutaneous soft tissue sarcomas: An explorative study.

Studies regarding the neoplastic infiltration of the skin overlying canine subcutaneous soft tissue sarcoma (sSTS) are lacking. In case of the absence of tumor infiltration, there would be the possibility of leaving this unaffected skin in place, thus simplifying surgery. The aim of the study was to investigate whether the skin overlying sSTSs is infiltrated by neoplastic cells. Dogs with sSTSs treated surgically were prospectively enrolled. After excision, the skin was dissected from the tumor along the natural surgical plane of cleavage and histologically evaluated. Twenty-nine dogs with an sSTS were included (22 grade I, 6 grade II, and 1 grade III). The sSTS-overlying skin was not tumor-infiltrated in 14/29 cases (48.3%). A higher frequency of infiltration was observed in higher grade sSTSs (grades II and III, 100%; P = .006); nevertheless, 8/22 grade I sSTSs (36%) also showed cutaneous infiltration. This infiltration involved the dermis of the skin directly in contact with the tumor (multifocal in 11 and diffuse in four cases). Although the cutaneous tumor infiltration is less frequent in grade I sSTSs and a wide excision may still be the safest treatment for any sSTS for a greater possibility of local control, this study opens the possibility to a less aggressive cutaneous excision, but still with a local curative intent, as only the skin directly in contact with the sSTS has been proven to be tumor-infiltrated. Additional studies are warranted to confirm that excision of only this skin may guarantee a complete local control, especially in lower-grade sSTSs.