Morphologic, phenotypic, and genotypic similarities between primary tumors and corresponding 3D cell cultures grown in a repeatable system-preliminary results.

BACKGROUND: Three-dimensional (3D) cell cultures are the new frontier for reproducing the tumor micro-environment in vitro. The aims of the study were (1) to establish primary 3D cell cultures from canine spontaneous neoplasms and (2) to demonstrate the morphological, phenotypic and genotypic similarities between the primary canine neoplasms and the corresponding 3D cultures, through the expression of tumor differentiation markers. RESULTS: Seven primary tumors were collected, including 4 carcinomas and 3 soft tissue sarcomas. 3D cell cultures reproduced the morphological features of the primary tumors and showed an overlapping immunophenotype of the primary epithelial tumors. Immunohistochemistry demonstrated the growth of stromal cells and macrophages admixed with the neoplastic epithelial component, reproducing the tumor microenvironment. Mesenchymal 3D cultures reproduced the immunophenotype of the primary tumor completely in 2 out of 3 examined cases while a discordant expression was documented for a single marker in one case. No single nucleotide variants or small indel were detected in TP53 or MDM2 genes, both in primary tumors and in 3D cell cultures specimens. In one sample, MDM2 amplicons were preferentially increased in number compared to TP53 ones, indicating amplification of MDM2, detectable both in the primary tumor and in the corresponding cell culture specimen. CONCLUSION: Here we demonstrate a good cell morphology, phenotype and genetic profile overlap between primary tumors and the corresponding 3D cultures grown in a repeatable system.

Metabolic Bile Acid Profile Impairments in Dogs Affected by Chronic Inflammatory Enteropathy.

Bile acids (BAs), endogenous acidic steroids synthetized from cholesterol in the liver, play a key role in the gut-liver axis physiopathology, including in hepatotoxicity, intestinal inflammatory processes, and cholesterol homeostasis. Faecal Oxo-BAs, relatively stable intermediates of oxidation/epimerization reactions of the BA hydroxyls, could be relevant to investigating the crosstalk in the liver-gut axis and the relationship between diseases and alterations in microbiota composition. A paucity of information currently exists on faecal BA profiles in dogs with and without chronic inflammatory enteropathy (CIE). Comprehensive assessment of 31 molecules among faecal BAs and related microbiota metabolites was conducted with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Odds ratios (ORs) for associations of BAs with CIE were estimated using logistic regression. Principal component analysis was performed to find differences between the control and pathological dogs. Higher levels of primary BAs and muricholic acids, and lower levels of secondary BAs were found in pathological dogs. Higher concentrations in faecal oxo-metabolites were associated with the absence of CIE (OR < 1). This study shows a marked difference in faecal BA profiles between dogs with and without CIE. Further research will be needed to better understand the role of oxo-BAs and muricholic acids in CIE dogs.

Skeletal muscle dissemination in a dog with T-cell lymphoma.

A 5-year-old spayed female American Staffordshire was referred for weakness, reluctance to move and distension of the abdomen. Three weeks before, the dog underwent surgery for excision of a nodular mass suspected to be a non-epitheliotropic cutaneous T-cell lymphoma (NE-CTCL). Computed tomography revealed heterogeneous enhancing mesenteric masses and nodular lesions of soft tissue density, and infiltration of the abdominal muscular wall. Moreover, a pattern of diffuse muscle nodules in the skeletal muscles was visible, with lesions showing homogenous, heterogeneous or ring enhancement. Necrosis was histologically observed and these lesions were infiltrated by CD3-positive and CD20-, CD79a- and Iba1-negative neoplastic lymphocytes. On the basis of the immunopathological features metastatic NE-CTCL was suspected. Skeletal muscle metastasis has been rarely reported in small animals and this case report further confirms that this possibility should be considered in dogs with lymphoma.

The Role of Fine Needle Aspiration of Liver and Spleen in the Staging of Low-Grade Canine Cutaneous Mast Cell Tumor.

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.

Sentinel Lymph Node Mapping with Indirect Lymphangiography for Canine Mast Cell Tumour.

Mast cell tumour (MCT) is a common cutaneous and subcutaneous neoplasia in dogs. It can metastasise to lymph nodes (LNs), and this adversely affects the prognosis and treatment. The study aims to evaluate the SLN mapping of MCTs with radiographic indirect lymphography. Dogs that underwent clinical staging were prospectively enrolled. Lipiodol was injected around the MCT or the surgical scar. After 24 h, LNs that picked up contrast were radiographically assessed. Twenty-six dogs with 29 MCTs were included. MCTs were confirmed histologically, while SLNs were evaluated either by cytology and/or histology. SLNs were detectable in 23 dogs with 26 MCTs. Lymphatic vessels were visible in 19 MCTs. In nine MCTs, at least two SLNs picked up contrast. In particular, seven MCTs involved two SLNs, and two MCTs involved three different SLNs. In nine MCTs, at least a SLN was metastatic. This study indicates that the lymph drainage pattern of the MCTs may be different for each MCT, and more than one SLN can be involved. Indirect lymphangiography with Lipiodol allowed the detection of the SLN in 90% of MCTs. This provided clinically relevant information to remove the LN and stage the patient.

Imaging and Endoscopic Diagnosis of Lung Diseases in Small Animals. A Review.

Diagnostic imaging plays a fundamental role in the diagnosis of pulmonary diseases. Radiography, ultrasound, computed tomography, and endoscopy are important tools for achieving a diagnosis. The choice of diagnostic procedure varies according to the patient, the suspected diagnosis and the risk/benefit ratio. Culture, cytology and histology are nearly always necessary to obtain a definitive diagnosis. Several biopsy sampling techniques are described. Surgical biopsies are the gold standard for the diagnosis of bronchiolitis or interstitial lung diseases but often not performed due to the high risk. In humans, the introduction of transbronchial cryobiopsies has led to excellent results in the study of interstitial lung diseases.

Comparison between Image-Guided Transbronchial Cryobiopsies and Thoracoscopic Lung Biopsies in Canine Cadaver: A Pilot Study.

To date, the only method of sampling lung tissue with a high diagnostic yield is represented by surgical lung biopsies (SLB), which are highly invasive and have a high risk/benefit ratio. In humans, transbronchial lung cryobiopsies (TBLC) have recently been introduced, which are described to be less invasive and able to significantly increase diagnostic confidence in most patients with interstitial lung diseases. The aim of this study was to evaluate the feasibility and diagnostic yield of TBLC compared to SLB in small animals. A total of 21 pulmonary cryobiopsies under fluoroscopic and real-time CT fluoroscopic guidance and 21 video-assisted thoracoscopic surgery (VATS) lung biopsies were collected from three dog cadavers. Upon histological examination, cryobiopsy samples were smaller than VATS biopsies, but were still large enough to reach a specific diagnosis or to allow pattern recognition. Morphological features on TBLC and SLB were concordant in all cases. Cryobiopsy samples showed fewer artifacts and a higher percentage of alveolar tissue than VATS samples. TBLC is a feasible and useful alternative to SLB for lung histopathological examination in dogs. The effectiveness and reduced invasiveness of TBLC compared to SLB could represent many advantages in the diagnosis of diffuse lung diseases in small animals.

Potential Role of Hepatozoon canis in a Fatal Systemic Disease in a Puppy.

Canine hepatozoonosis caused by Hepatozoon canis is an emerging disease in Europe. Clinical pictures vary from subclinical to life-threatening and non-specific clinical signs are predominantly reported. A 2-month-old female puppy originating from Southern Italy was adopted and moved to Northern Italy. Then, the dog was brought to a local veterinary practice for gastrointestinal signs, migrating lameness and pruritic dermatitis, and then tested positive for Hepatozoon spp. gamonts at the blood smear. After treatment with imidocarb dipropionate and doxycycline, the dog showed an initial clinical improvement. However, gastrointestinal signs recurred, and diffuse superficial pyoderma appeared on the thoracolumbar region, along with fever, lethargy, and weight loss. Eight months from the first onset of clinical signs, the dog was referred to a veterinary clinic and subjected to complete blood count, urine and fecal analysis, along with abdominal ultrasonography, whole-body CT and gastroduodenal endoscopy. Skin biopsies and blood samples were subjected to a PCR-coupled sequencing protocol, which scored both positive for H. canis. Alterations were consistent with a pre-existing cholangiohepatitis and multiple acquired extrahepatic shunts secondary to portal hypertension. The dog was euthanatized due to a clinical worsening two months later. The potential role of H. canis in the systemic disease observed, clinic-pathological findings and epizootiological implications are discussed.

B-Mode and Contrast Enhanced Ultrasonography Features of Gastric Inflammatory and Neoplastic Diseases in Dogs.

Canine gastric disorders are common in veterinary clinical practice and among these neoplasms require rapid identification and characterization. Standard ultrasound (US) is the imaging modality of choice for gastric wall assessment. The aim of this prospective study is to describe the specific B-mode and contrast enhanced US (CEUS) features of normal, inflammatory, and neoplastic gastric wall in dogs. B-mode US and CEUS of the stomach were performed in anesthetized dogs with or without gastric disorders. Gastric wall qualitative and quantitative parameters were evaluated on B-mode US and CEUS examination. A total of 41 dogs were included: 6 healthy (HEA) as the control group; 9 gastritis (INF); 8 adenocarcinoma (AC); 8 alimentary lymphoma (AL); 4 leiomyosarcoma (LEIS); 2 gastrointestinal stromal tumor (GIST); 2 leiomyoma; 1 undifferentiated sarcoma; 1 metastatic gastric hemangiosarcoma. Gastric tumors appear as a marked wall thickness with absent layers definition and possible regional lymphadenopathy (AC and AL) and steatitis (AC) while gastritis generally shows no/mild thickening and no other alterations on B-mode US. On CEUS, neoplasm shows a higher and faster wash in if compared to that of gastritis. B-mode and CEUS assessment may be useful in the evaluation of canine gastric disorders in the distinction between gastritis and gastric neoplasms, even if there are no specific features able to discriminate between the different tumor histotypes.

Clinical Value of CT-Guided Fine Needle Aspiration and Tissue-Core Biopsy of Thoracic Masses in the Dog and Cat.

Diagnosis of thoracic lesions on the basis of history and physical examination is often challenging. Diagnostic imaging is therefore of paramount importance in this field. Radiology has traditionally been considered the diagnostic procedure of choice for these diseases. Nevertheless, it is often not possible to differentiate inflammatory/infectious lesions from neoplastic diseases. A correct cytological and histopathologic diagnosis is therefore needed for an accurate diagnosis and subsequent prognostic and therapeutic approach. In human medicine, Computed Tomography (CT) and CT-guided biopsy are used in the presence of lesions which are not adequately diagnosed with other procedures. In the present study, thoracic lesions from 52 dogs and 10 cats of different sex, breed and size underwent both CT-guided fine-needle aspiration (FNAB) and tissue-core biopsy (TCB). Clinical examination, hematobiochemical analysis and chest radiography were performed on all animals. In this study, 59 of 62 histopathological samples were diagnostic (95.2%). Cytology was diagnostic in 43 of 62 samples (69.4%). General sensitivity, accuracy and PPV for FNAB and TCB were 67.7%, 67.7% and 100% and 96.7%, 95.2% and 98.3%, respectively. Combining the two techniques, the overall mean accuracy for diagnosis was 98.4%. Nineteen of 62 cases showed complications (30.6%). Mild pneumothorax was seen in 16 cases, whereas mild hemorrhage occurred in three cases. No major complications were encountered. CT-guided FNAB cytology can be considered a useful and reliable technique, especially for small lesions or lesions located close to vital organs and therefore dangerous to biopsy in other way.

Lymphatic Drainage Mapping with Indirect Lymphography for Canine Mammary Tumors.

Mammary gland tumors are the most common canine neoplasms. They account for 25-50% of all tumors diagnosed in bitches. Metastases and recurrences develop in about 35-70% of bitches following excision. The presence of regional lymph node metastases is a relevant factor affecting prognosis and treatment in cases of mammary gland tumors. The sentinel lymph node (SLN) is the first lymph node (or nodes) in the regional lymphatic basin that receives lymphatic flow from the primary neoplasm. The aim of this study is to investigate the SLN with indirect lymphography for a mammary tumor in dogs. The knowledge of the precise drainage pattern and SLN of the neoplastic mammary glands would provide clinically relevant information to the surgeon and to the oncologist, and it would be of high importance for the surgeon not only for performing the most adequate surgical excision but also for determining an accurate post-surgical prognosis.

Triple-Phase Multidetector Computed Tomography in Distinguishing Canine Hepatic Lesions.

The liver has a unique vascular supply, and triple-phase contrast-enhanced computed tomography examinations are being performed in order to characterize liver lesions. This study aimed to look for any associations between the attenuation values of liver lesions and their histological classification. The inclusion criteria for this retrospective study were focal or multifocal liver lesions and histological diagnosis. All of the dogs underwent pre-contrast and triple-phase postcontrast computed tomography (CT) examinations with identical timings of the postcontrast series. Thirty-one dogs were included in the study, and various benign and malignant pathologies were identified. The results did not identify any significant differences between the benign and malignant liver lesions, nor between the individual histological diagnoses. Inflammatory lesions were significantly different compared to the normal liver parenchyma, and significant hypoattenuation was found in the portal and delayed venous phases. Hemangiosarcomas were significantly hypoattenuating to the normal liver parenchyma in the pre-contrast and arterial phases, and also to all of the benign lesions in the arterial phase. The other pathologies showed variable attenuation patterns in the different postcontrast phases, and differentiation was not possible. On the basis of this study, triple-phase contrast-enhanced computed tomography cannot differentiate between benign and malignant liver lesions, and biopsy and further histological analysis are necessary.

B-Mode and Contrast Enhanced Ultrasonography Features of Gastric Inflammatory and Neoplastic Diseases in Cats.

Alimentary lymphoma (AL) is the most common malignancy of the feline gastrointestinal tract and may cause variable mild to severe alteration of the gastric wall on ultrasonography (US) that can be very similar to those caused by inflammation (INF). The aim of this prospective study is to establish the value of B-mode and contrast-enhanced US (CEUS) in describing specific features of normal, inflammatory, and neoplastic gastric diseases in feline species. B-mode US and CEUS of the stomach were performed in anesthetized cats with or without gastric disorders. Gastric wall qualitative and quantitative parameters were evaluated on B-mode US and CEUS examination. A total of 29 cats were included: six healthy (HEA) cats as the control group; nine INF; three low-grade lymphoma (LGAL); 10 high-grade lymphoma (HGAL). On B-mode US, there were significant differences in thickness, the wall's layer definition and echogenicity between HGAL and all the other groups (<0.001). For CEUS, statistical differences between groups were found in the following: HGAL vs. HEA, HGAL vs. INF; HGAL vs. LGAL; INF vs. HEA. Diagnostic accuracy (AUC) and cut-off value were calculated and found to be significant for thickness (3.8 mm) for INF vs. LGAL (AUC > 0.70) and "benign" vs. "malignant" (AUC > 0.90) as well as peak enhancement (34.87 dB) for "benign" vs. "malignant" (AUC > 0.70). INF and LGAL showed an overlap of qualitative and quantitative parameters both on B-mode and CEUS, while HGAL usually appears as a severe wall thickening with absent layer definition, high-contrast uptake, a specific enhancement pattern, regional lymphadenopathy and local steatitis. Thickness and peak enhancement can be useful parameters in the characterization of gastric infiltrates in cats.

Evaluation of the Spirotome Device for Nasal Tumors Biopsy in Eleven Dogs.

This study evaluated the accuracy and diagnostic quality of histological samples obtained with the Spirotome device on biopsies from dogs affected by canine nasal tumors. Eleven dogs were included in this study. The mean age was 10 years. All biopsies were successfully performed within 15 minutes. All dogs showed nasal bleeding after the biopsies, which was quickly managed by applying intranasal compression with sterile cotton swabs. Bleeding stopped within 10 minutes after sampling. All biopsy samples were considered satisfactory by the pathologist, allowing a proper histological assessment.

A Case of Adenocarcinoma of Uterus Masculinus in a Pomeranian Dog.

Introduction: Persistent Müllerian duct syndrome (PMDS), or uterus masculinus, is a rare autosomal recessive form of male pseudohermaphroditism due to the failure of paracrine anti-Müllerian hormone (AMH) secretion by Sertoli cells or failure of the Müllerian ducts to respond to AMH secretion. The malignant degeneration of persistent Müllerian remnants is rare. In human medicine, few related reports exist. In veterinary medicine, this is the first report describing adenocarcinoma of the uterus masculinus involving the prostate in a dog. Clinical history: An 11-year-old, male, neutered Pomeranian dog was referred for computed tomography due to the suspicion of prostatic carcinoma based on ultrasound and cytological examinations. The computed tomography findings were consistent with a uterus masculinus mass with possible prostatic infiltration. Uterus masculinus removal and total prostatectomy were performed; termino-terminal urethral anastomosis was carried out. Dehiscence of the anastomosis was observed 3 days after surgery. The owner declined any further procedures, and the dog was euthanized 5 days after surgery. Histopathological evaluation revealed adenocarcinoma of the uterus masculinus. Conclusion: Adenocarcinoma of the uterus masculinus may occur, suggesting that patients with PMDS should be evaluated for malignant changes of Müllerian remnants.

Prevalence, distribution, and clinical characteristics of hemangiosarcoma-associated skeletal muscle metastases in 61 dogs: A whole body computed tomographic study.

BACKGROUND: Skeletal muscle metastases (SMMs) have been described sporadically in canine oncology. HYPOTHESIS/OBJECTIVES: To determine the prevalence, localization, and clinical signs of SMMs associated with hemangiosarcoma (HSA) in a population of dogs presented for whole body computed tomography (CT). ANIMALS: Dogs with a histologically confirmed HSA and a tissue core specimen or fine needle aspirate of suspected metastatic lesions were included in the study. METHODS: Retrospective study. Dogs with a final diagnosis of visceral or muscular HSA that underwent whole body CT scan were enrolled in the study. Final diagnosis of primary tumor and SMMs was reached by histology, cytology, or both. Signalment, clinical signs, localization of the primary lesion, and metastases characteristics were reviewed. RESULTS: Sixty-one dogs met the inclusion criteria. Skeletal muscle metastases were detected in 15 dogs (24.6%) and all of these dogs had also metastases in ≥1 sites. Presence of SMMs was significantly higher in males but was not significantly related to age, neuter status, breed, localization, and dimensions of the primary tumor. Nine of 15 (60.0%) dogs with SMMs showed lameness or reluctance to move whereas these signs were not recorded in any of the 42 dogs without SMMs (P < .001). CONCLUSION AND CLINICAL IMPORTANCE: Prevalence of SMMs in our population of dogs with HSA was higher in comparison to previous studies in the human and veterinary medical literature. Whole body CT is recommended for staging of dogs with HSA, because SMMs could be missed by clinical examination and traditional diagnostic imaging modalities.

Comparison of clinical and imaging findings in cats with single and mixed lungworm infection.

OBJECTIVES: This study has compared clinical and imaging features in 52 cats naturally infected by respiratory nematodes Aelurostrongylus abstrusus, Troglostrongylus brevior and Capillaria aerophila, and in both monospecific and mixed infections. METHODS: Medical records of cats with a lungworm disease were retrospectively reviewed. Cats with clinical examination findings, haematobiochemical analysis and thoracic radiography were included in the study and clinical and radiographic scores were assigned. For eight cats CT of the thorax was also available and analysed. A statistical analysis was performed to investigate the potential correlation between clinical and radiographic score, and to evaluate the effect of age, sex and infection on clinical and radiographic severity. RESULTS: Monospecific infections by A abstrusus (32/52), T brevior (6/52) and C aerophila (5/52) and coinfections by T brevior/ A abstrusus (7/52), T brevior/ C aerophila (1/52) and A abstrusus/ C aerophila (1/52) were diagnosed. Cats with mixed infections showed higher clinical scores compared with cats with monospecific parasitoses ( P <0.05), while no differences were observed for radiographic scores. No correlation between clinical and radiographic scores was found (rs = 0.50), and these scores were not affected by patient age or sex. CT, performed on cats infected with A abstrusus, T brevior or A abstrusus/T brevior, provided additional information in cats with mild radiographic signs. CONCLUSIONS AND RELEVANCE: This study indicates that clinical parameters may be more severe in mixed infections than in monospecific parasitoses. A significant correlation between clinical and radiographic score was not detected, while several subclinically infected cats showed radiographic changes. In cats with mild-to-moderate lung patterns, the ventrodorsal/dorsoventral projection showed lesions that are not visible in the lateral projections, especially in the caudal lobes.

Is Serum Total LDH Evaluation Able to Differentiate between Alimentary Lymphoma and Inflammatory Bowel Disease in a Real World Clinical Setting?

CONTEXT: An increase in enzyme lactate dehydrogenase (LDH) in serum is a negative prognostic factor for survival in cats affected by lymphoma. Measuring LDH at the time of diagnosis has been studied for differentiating neoplastic disease from non-neoplastic disease in dogs. Inflammatory bowel disease (IBD) and alimentary lymphoma are common diseases in cats. OBJECTIVE: The aim of this study was to determine whether elevation of total LDH occurred in cats with alimentary lymphoma and non-neoplastic gastrointestinal disease, such as IBD, and to evaluate whether this enzyme is useful in supporting the differential diagnosis of these specific diseases. MATERIALS AND METHODS: A prospective non-randomized controlled study was carried-out in a real world setting of three Italian private veterinary clinics. Seventy-one client-owned cats with a history of chronic gastrointestinal symptoms were enrolled; 33 cats were histologically diagnosed as having alimentary lymphoma and 38 cats as having IBD. Serum samples of total LDH analysis were measured. RESULTS: Gender (P = 0.016) and age (P = 0.046) were found to be significant factors influencing the differentiation of serum total LDH between cats with alimentary lymphoma and those with IBD. Despite low diagnostic accuracy in the overall population (63%), a cut-off value of serum total LDH ranging from 0.85- to 1.04-times the upper reference limit showed good capability (accuracy >80%) of differentiating these two conditions in neutered males and cats younger than 8 years of age (AUC: 0.805, 0.833; sensitivities: 76.9%, 83.3%; specificities: 80.0%, 76.5%; PPV: 76.9%, 55.6%; NPV: 80.0%, 92.9%; respectively). CONCLUSIONS: Although our study showed that gender and age are significant factors in differentiating serum total LDH between cats with alimentary lymphoma and those with IBD, this test had poor diagnostic accuracy in differentiating between these two conditions in the overall population.

Combination of radiation therapy and firocoxib for the treatment of canine nasal carcinoma.

Carcinomas represent two-thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase-isoform-2 (COX-2) is expressed in 71-95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX-2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX-2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality-of-life questionnaire. Twenty-four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression-free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression-free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression-free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas.

EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

Epidermal growth factor receptor (EGFR or HER-1) and its analog c-erbB-2 (HER-2) are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas) were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7%) carcinomas were classified as intestinal-type and 9 (64.3%) as diffuse-type. EGFR was overexpressed (≥ 1+) in 8 (42.1%) cases and HER-2 (3+) in 11 (57.9%) cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80%) than in the diffuse-type (11.1%, p = 0.023). KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R). EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.