Comparison of Different Pneumorrhaphy Methods after Partial Pulmonary Lobectomy in Dogs.

Pulmonary loborraphy can be performed using manual sutures and staples, although other methods, such as tissue adhesives, are also cited in the veterinary literature. Although the surgery is well tolerated in the canine species, failure in pulmonary aerostasis is still a reality since all the methods described so far eventually lead to air leakage after the use of the partial lobectomy technique in the lungs. Within this context, the aim of this research was to compare the effectiveness of different hermetic sealing methods after partial lobectomy of the right caudal lung lobe (RCLL) in dogs. 30 cadavers models were divided in 6 groups: G1-cobbler suture associated with simple continuous; G2-overlapping continuous suture associated with simple continuous suture; G3-Ford interlocking suture; G4-Stapling device; G5-Tissue glue (cyanoacrylate). After performing the sealing techniques, the lungs were submerged in water and inflated with oxygen at positive ventilatory pressures at physiological (up to 14.7 mmHg, which is equivalent to up to 20 cmH2O) and supraphysiological levels (above 14.7 mmHg) to evaluate the performance of the sealing methods. At physiological ventilatory pressure levels, there was no difference between groups. Sealing with surgical glue was superior to interlocking sutures and stapling devices at supraphysiological levels of ventilatory pressure.

Molecular Profile of Canine Hemangiosarcoma and Potential Novel Therapeutic Targets.

Canine hemangiosarcoma (HSA) is a relatively common neoplasia, occurring mainly in the skin, spleen, liver and right atrium. Despite the numerous studies investigating the treatment of canine HSA, no significant improvement in survival has been achieved in the last 20 years. Advancements in genetic and molecular profiling presented molecular similarities between canine HSA and human angiosarcoma. It could therefore serve as a valuable model for investigating new and more effective treatments in people and dogs. The most common genetic abnormalities in canine HSA have been found in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and neuroblastoma RAS viral oncogene homolog (NRAS) pathways. Mutations are also found in tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN) and cyclin dependent kinase inhibitor 2A (CDKN2A). Known abnormal protein expression could be exploited to trial new target treatments that could be beneficial for both canine and human patients. Despite the high expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), no correlation with overall survival time has ever been found. In this review, we explore the most recent developments in molecular profiling in canine HSA and discuss their possible applications in the prognosis and treatment of this fatal disease.

Comparison of surgical resection of Axillary Lymph Nodes in Dogs with Mammary Gland Tumors with or without sentinel lymph node visualization with patent blue dye.

Introduction: Dogs' axillary lymph node (ALN) is often difficult to locate before surgical resection. The anatomical location of ALN often discourages Veterinarians from surgical lymphadenectomy. Considering the limited literature available, the actual incidence of metastases and the prognostic relevance are poorly understood. Methods: A non-randomized, prospective clinical study was conducted with female dogs (n = 41) with mammary gland tumor (MGT) in the thoracic or cranial abdominal mammary glands. The study investigated the risks of ALN metastasis based on tumors clinical findings, tumor size, histopathological diagnosis and grade. The main aim of this study was to compare ALN resection with or without patent blue 2.5% (PB) dye injection for sentinel lymph node visualization. A total of 46 mastectomies were performed and five animals underwent two mastectomies. In the first group, 17 patients underwent a mastectomy and lymphadenectomy without PB injection (G1). In contrast, in the second group, 24 patients also received PB injections for sentinel lymph node mapping (G2). The ALN was identified in 38/46 cases (82%). The ALN was identified and excised in only 58% of surgeries in G1(19/46), while in group 2, the lymph node was identified in 92% of the cases and resected in 100% of the cases. The use of PB improves ALN's identification and reduces the surgical resection time in dogs with MGT. Results and discussion: Surgical time differed between the two groups, as it was significantly shorter in the PB injection group compared to group 1 (80 vs. 45 min) (p < 0.0001). The overall frequency of ALN metastasis was 32%. Macroscopic abnormalities in the lymph nodes, tumor size (>3 cm), and diagnosis of anaplastic carcinoma or grade II/III mammary gland tumors were associated with a higher probability of ALN metastasis. Metastases in the ALNs are more common, in dogs presenting with tumors larger than 3 cm and diagnosed with aggressive histological subtypes. The ALNs should be removed for correct staging, prognostic evaluation, and decision for adjuvant therapy.

Case report: Suspected plasmablastic lymphoma in a dog resembling the clinical presentation in humans.

Plasmablastic lymphoma (PBL) is a rare form of lymphoma in people. PBL originates from plasmablasts and usually presents with swelling/mass in the mouth/neck. A 7-year-old Mongrel dog was presented for a large oral and neck mass. Cytology and histopathology were suggestive of a round cell tumor that was suspected to be lymphoma. An immunohistochemical (IHC) stain panel showed positive for CD18, thus supporting the diagnosis of round cell tumor, but negative for T- and B-cell lymphomas, CD3, CD20, and PAX-5. Other markers including cytokeratin AE1/3 (for epithelial cell origin), CD31 (for endothelial cells), SOX10 (for melanoma), IBa-1 (for histiocytic sarcoma), and CD117 (for mast cell tumor) were all negative. MUM-1 (for plasma cell differentiation) was strongly positive and CD79a (B cell and plasma cells) was also scantly positive. Based on the histopathology and immunohistochemistry results in combination with the clinical presentation, a suspected diagnosis of PBL was made. As per available literature, this is perhaps the first highly suspected case of PBL in a dog.

Extreme lymphocytosis in a dog with T-zone lymphoma.

Background: Canine T-zone lymphoma (TZL) is recognized as an indolent CD45-T cell lymphoma, with low aggressiveness and high overall survival. The diagnosis is obtained by histopathology and immunohistochemistry, but also by cytological examination of the lymph node associated with immunophenotyping. Lymphocytosis is commonly identified as around 10,000 cells/µl and may reach 30,760 cells/µl. Case Description: The present report describes a case of a female Golden Retriever, nine years old, with generalized lymphadenopathy. In the cytological examination of the superficial cervical lymph node, a monomorphic population of small, "clear cells" and "hand mirror" lymphocyte shape was suggestive of TZL. The leukogram showed intense leukocytosis (160,050 cells/µl) due to small clear cell lymphocytosis (152,048 cells/µl). The myelogram showed a myeloid:erythroid ratio of 2:3; with a pyramidal distribution of cell types and the presence of 22.8% of lymphocytes in the differential count. Bone marrow, peripheral blood, and lymph node immunophenotyping resulted in lymphocyte gates with 97.3% to 99.5% CD5+, predominantly CD4-, CD8-, and CD45- confirming the diagnosis of TZL with associated leukemia. Treatment with chlorambucil and prednisolone was started. During the first month, the lymphocytosis remained above 200,000 cells/uL. After four months of treatment, there was a decrease in lymphocytes, which progressively reached a count of 10,800 cells/ul in the eleventh month. Conclusion: In the literature, lymphocytosis above 30,760 cells/µl has not been observed in TZLs. Thus, it is believed that this is the first report of extreme lymphocytosis with a slow response to chemotherapy.

Retrospective Evaluation of a Combination of Carboplatin and Bleomycin for the Treatment of Canine Carcinomas.

Carboplatin is a chemotherapy agent widely used in veterinary oncology to treat various types of tumors including carcinomas. Carboplatin has previously been used in combination with 5-Fluoro uracil (5-FU) or gemcitabine for the treatment of various carcinomas. Bleomycin is a chemotherapy drug commonly used in humans, but its use has been uncommonly reported in dogs. The combination of carboplatin and bleomycin chemotherapy treatment has never been reported in dogs. Dogs diagnosed with carcinoma and treated with a combination of carboplatin and bleomycin, at a single veterinary referral center, were retrospectively evaluated. Thirty patients met the inclusion criteria. The dose of carboplatin ranged from 200-250 mg/m2 (median 240 mg/m2) and the dose of bleomycin from 15-20 IU/m2 (median 15 IU/m2). The treatment with carboplatin and bleomycin was well tolerated, with sixteen patients (53%) developing side effects. Thirteen patients (46%) developed gastrointestinal signs and nine dogs (30%) developed hematological abnormalities. The most common side effects were grade-1 hyporexia and grade-1 neutropenia. Grade-2 neutropenia was rarely observed, and only one patient developed grade-3 neutropenia. None of the dogs developed grade-4 adverse events, or required hospitalization, or died due to the treatment. No signs of chronic side effects, including pulmonary toxicity, were observed. Objective response was observed in 24% of the cases (six partial responses) and 76% of cases achieved clinical benefit (partial response+ stable disease). Clinical signs improved in 24 of the 30 cases (80%). The main aim of this study was to evaluate the safety of bleomycin and carboplatin in combination for the treatment of various types of carcinomas. The combination of bleomycin and carboplatin appears safe and potentially effective for some types of carcinomas. Larger prospective studies are needed to confirm the safety and efficacy of combined carboplatin and bleomycin.

Nasal Lymphoma with Low Mitotic Index in Three Cats Treated with Chlorambucil and Prednisolone.

Lymphoma is the most common tumor of the nasal cavity in cats. Commonly used treatment modalities are radiotherapy and chemotherapy, or both. Typical chemotherapy protocols used in cats with nasal lymphoma are COP (cyclophosphamide, vincristine prednisolone) and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone). Thus far, the use of single-agent chlorambucil in nasal lymphoma has been evaluated in a single case report. We report a case series of three cats with B cell nasal lymphoma, two cats with intermediate cell, and one large cell, all with a low mitotic index (MI) of less than 5 mitotic figures per ×400 field, treated with chlorambucil and prednisolone. Two of the cases achieved a long disease-free interval, while the one with the highest MI did not. Protocols using chlorambucil and prednisolone may have potential as a first-line therapy for feline nasal lymphoma cases with a very low mitotic index.

Successful Treatment of Vertebral Osteosarcoma in a Cat Using Marginal Surgical Excision and Chemotherapy.

A three-year-old male neutered Norwegian Forest cat was referred for bilateral ambulatory paraparesis and spinal pain. On magnetic resonance imaging (MRI), a mass involving the right epaxial muscles with vertebral canal invasion and causing marked extradural spinal cord compression was identified. At surgery, the mass was debulked and a right hemilaminectomy was performed. Histopathology was diagnostic of fibroblastic osteosarcoma. Residual osteolytic lesions of the osteosarcoma were present at the level of the spinous process of the second lumbar vertebra. Four cycles of adjuvant doxorubicin chemotherapy were administered followed by oral toceranib phosphate. Neurological signs improved gradually over weeks to months and the lesion in the spinous process was no longer visible on radiographs. At one year from diagnosis, an MRI of the T3-L3 (3rd thoracic vertebra to the 3rd lumbar vertebra) spinal region and a whole-body computer tomography (CT) scan found no evidence of the osteosarcoma in the spine or of any metastasis. All medications were stopped and, at the time of writing 16 months later, the patient is neurologically normal with no signs of cancer recurrence. This is the first case report documenting the complete resolution of vertebral osteosarcoma lesions after treatment with doxorubicin followed by toceranib phosphate. The treatment also prevented tumor recurrence and was associated with an exceptionally long-term survival time.

Eosinophilic pulmonary granulomatosis resembling a pulmonary carcinoma in a dog in Hong Kong.

Background: Canine Eosinophilic Pulmonary Granulomatosis (EPG) is a severe form of eosinophilic pulmonary disease that carries a guarded prognosis, responds poorly to therapy and recurs frequently. Most studies have reported a caudal lobar pulmonary distribution and a poorer prognosis in idiopathic cases. Case Description: A 7-year-old dog was presented for persistent cough, hyporexia, and weight loss. Eosinophilia and basophilia were transiently present, and an antigen test for heartworm disease was negative. Radiographic studies, followed by a computed tomography (CT) scan revealed nodular lesions and a large mass in the left cranial lobar region suggestive of neoplasia. Cytological and histopathological evaluation was consistent with EPG. The dog responded positively to corticosteroids and has since remained free of disease. Conclusion: EPG in dogs can resemble primary pulmonary neoplasia with secondary intra-pulmonary metastasis. Contrary to previous reports, idiopathic EPG can present with a cranial pulmonary distribution and respond positively to therapy.

Repurposing Drugs in Small Animal Oncology.

Repurposing drugs in oncology consists of using off-label drugs that are licensed for various non-oncological medical conditions to treat cancer. Repurposing drugs has the advantage of using drugs that are already commercialized, with known mechanisms of action, proven safety profiles, and known toxicology, pharmacokinetics and pharmacodynamics, and posology. These drugs are usually cheaper than new anti-cancer drugs and thus more affordable, even in low-income countries. The interest in repurposed anti-cancer drugs has led to numerous in vivo and in vitro studies, with some promising results. Some randomized clinical trials have also been performed in humans, with certain drugs showing some degree of clinical efficacy, but the true clinical benefit for most of these drugs remains unknown. Repurposing drugs in veterinary oncology is a very new concept and only a few studies have been published so far. In this review, we summarize both the benefits and challenges of using repurposed anti-cancer drugs; we report and discuss the most relevant studies that have been previously published in small animal oncology, and we suggest potential drugs that could be clinically investigated for anti-cancer treatment in dogs and cats.

Should we be discouraging use of 'anticancer' supplements in dogs and cats with cancer?

Antonio Giuliano and colleagues argue that 'anticancer' supplements could be harmful and hinder chemotherapy and radiotherapy treatment, and so their use should be discouraged in cancer patients.

A possible role of coarse fractionated radiotherapy in the management of gingival squamous cell carcinoma in dogs: A retrospective study of 21 cases from two referral centers in the UK.

Surgery with or without the addition of radiotherapy is the treatment of choice for canine oral squamous cell carcinoma (SCC). Fractionated radiotherapy alone is also effective in the long-term control of the disease, however coarse fractionated radiotherapy (CF-RT) for gingival SCC has not been extensively reported. The aim of this study was to describe side effects, clinical response, and median survival time (MST) of dogs with gingival SCC treated with CF-RT in the palliative and adjuvant setting. Twenty-one cases from two referral centres in the UK treated with CF-RT for gingival SCC between July 2013 and June 2019 were retrospectively evaluated. Of the 21 dogs, 11 developed mild acute adverse effects. Oral mucositis was the most common radiation induced toxicity. Three dogs developed chronic severe adverse effects (oro-nasal fistula, bone necrosis and gum recession). Overall clinical response rate was 77% in dogs receiving palliative treatment with MST of 365 days (60-1,095 days). MST was not reached for dogs treated in the adjuvant setting with a mean of 466 days (121-730 days). In cases of advanced gross disease CF-RT might have a role in short term palliation of clinical signs. However, it carries a significant risk of late toxicity for cases with unexpectedly long survival times and further investigations are required to identify an optimal CF-RT protocol. Randomized controlled trials are needed to confirm the role of CF-RT as adjuvant treatment of incompletely resected gingival SCC.

Companion Animal Model in Translational Oncology; Feline Oral Squamous Cell Carcinoma and Canine Oral Melanoma.

Companion animals with naturally occurring cancers can provide an advantageous model for cancer research and in particular anticancer drug development. Compared to commonly utilized mouse models, companion animals, specifically dogs and cats, share a closer phylogenetical distance, body size, and genome organization. Most importantly, pets develop spontaneous, rather than artificially induced, cancers. The incidence of cancer in people and companion animals is quite similar and cancer is the leading cause of death in dogs over 10 years of age. Many cancer types in dogs and cats have similar pathological, molecular, and clinical features to their human counterparts. Drug toxicity and response to anti-cancer treatment in dogs and cats are also similar to those in people. Companion animals share their lives with their owners, including the environmental and socioeconomic cancer-risk factors. In contrast to humans, pets have a shorter life span and cancer progression is often more rapid. Clinical trials in companion animals are cheaper and less time consuming compared to human trials. Dogs and cats with naturally occurring cancers are an ideal and unique model for human cancer research. Model selection for the specific type of cancer is of pivotal importance. Although companion animal models for translational research have been reviewed previously, this review will try to summarize the most important advantages and disadvantages of this model. Feline oral squamous cell carcinoma as a model for head and neck squamous cell carcinoma and canine oral melanoma as a model for mucosal melanoma and immunotherapy in people will be discussed as examples.

Anisakiasis: The Importance of Prevention and the Role of Diet Therapy in Allergic Patients.

INTRODUCTION: Anisakiasis is a zoonosis of parasitic origin whose diffusion seems to be continuously increasing. OBJECTIVE: The aim of this study was to evaluate the benefits of a fish-free diet in patients allergic to Anisakis simplex as well as underlining the importance of awareness and prevention. Furthermore, we aimed to investigate the critical issues related to the spread of anisakiasis in relation to eating habits. METHODS: Patients were assessed by means of skin prick tests (SPTs) and targeted laboratory testing, with an 18-month-long fish-free diet being recommended in cases of severe sensitization. The degree of awareness about anisakiasis was evaluated from interviews. Patients were subjected to follow-up visits after 18 months. RESULTS: A total of 70 cases of sensitization to A. simplex were evaluated. The Interview answers highlighted a general state of misinformation among patients and healthy subjects along with a remarkable underestimation of anisakiasis-related risks. An overall lack of care regarding eating habits and diet plans also emerged. In 21 patients affected by severe sensitization, clinical and laboratory evaluations were repeated after 18 months of the subjects being on a fish-free diet. There was a remarkable improvement in serum IgE levels and clinical symptoms. CONCLUSION: Data analysis proved the need to implement new and more effective awareness-raising and prevention campaigns in order to reduce the incidence of anisakiasis. It is crucial to establish an adequate diet therapy for sensitized patients. Evaluation of cytokine patterns suggests how a polyphenol-rich regime can activate regulatory T cell function and possibly reduce the allergic and inflammatory components of the disease.

Clinical response and survival time of cats with carcinoma of the nasal cavity treated with palliative coarse fractionated radiotherapy.

OBJECTIVES: Carcinoma is the second most common tumour of the nasal cavity in cats. Few studies assessing the response and survival of cats with carcinoma of the nasal cavity treated with palliative coarse fractionated radiotherapy have been published. METHODS: Twenty-eight cats were diagnosed with histologically confirmed carcinoma of the nasal cavity. All patients treated with a coarse fractionated radiotherapy protocol were retrospectively reviewed. RESULTS: Improvement of the clinical signs were reported in 24 cases; median survival time (MST) was 342 days; and cats with Adams modified stage IV and facial deformity had a significantly reduced MST of 152 days (P = 0.0013) and 67 days (P = 0.0002), respectively. Severe radiotherapy-related clinical signs were not reported and alopecia and leukotrichia were the most common side effects reported in ten cases. CONCLUSIONS AND RELEVANCE: Coarse fractionated radiotherapy treatment for carcinoma of the nasal cavity in cats is effective in relieving clinical signs. Long survival times can be achieved, in particular in cases with a less advanced stage of the tumour.

Clinical, histological, immunohistochemical and genetic factors associated with measurable response of high-risk canine mast cell tumours to tyrosine kinase inhibitors.

The aim of the present prospective-retrospective study was to evaluate the response of high-risk canine mast cell tumours (MCTs) to tyrosine kinase inhibitors (TKIs) and to correlate this with prognostic factors. A total of 24 dogs presented with macroscopic cutaneous MCTs at disease stage II or III, and therefore, at high-risk of associated mortality, were included in the study and treated with masitinib (n=20) or toceranib (n=4). A total of 12/24 dogs achieved an objective response and the overall survival (OS) for all subjects was 113 days. Dogs responding to treatment had a significant increase in OS compared to non-responders (146.5 days vs. 47 days, P=0.02). Internal tandem duplications in exon 11 of the c-kit gene were identified in 6/24 cases. Ki67, KIT immunolabelling and c-kit mutation did not provide information regarding prognosis or prediction of response to TKIs in this population. Initial response to TKIs appears to be the most reliable prognostic factor for survival duration.

Complete Resolution of a Recurrent Canine Anal Sac Squamous Cell Carcinoma with Palliative Radiotherapy and Carboplatin Chemotherapy.

Anal sac squamous cell carcinoma (SCC) is a rare tumor in dogs. Only eight cases have been described in the literature, and previous reports of treatment only describe surgery or palliative treatment with non-steroidal anti-inflammatory drugs. We report a case of a 12-year-old female neutered Labrador with locally advanced anal sac SCC. The dog was treated with four cycles of carboplatin 300 mg/m² and four weekly fractions of 8.5 Gy radiation. The dog achieved a complete response, and one year later the dog is still alive and well with no evidence of tumor recurrence. Radiotherapy in combination with carboplatin chemotherapy was effective in the long-term control of this rare disease.

Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease.

Thyroid carcino-sarcoma in a dog.

An adult male greyhound was diagnosed with a thyroid carcino-sarcoma by means of histopathology and positive immuno-histochemistry staining for cytokeratin and vimentin. Surgery and radiotherapy of the area were successful in local tumour control. Adjuvant chemotherapy was recommended to treat and prevent further metastasis. The use of carboplatin, metronomic cyclophosphamide chemotherapy and toceranib failed to control the progression of distant metastasis. The survival time was seven months from the time of diagnosis. This is the eighth case of carcino-sarcoma of the thyroid documented in veterinary medicine and the first one treated with a multimodal approach based on surgery, radiotherapy and chemotherapy. As documented in human medicine, chemotherapy appeared to be ineffective to prevent or delay the progression of the metastatic disease in this case.