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Oral squamous cell carcinoma (oSCC) is a highly invasive malignant neoplasm in cats. Recently, tumor stroma, known as tumor microenvironments, have been considered to play an essential role in tumor progression. However, their role in feline squamous cell carcinoma (SCC) remains unclear. This study aimed to reveal the cancer microenvironment of feline oSCC and evaluate the pathological mechanisms of progression. We used 19 samples from 17 cats with oSCC, which were examined using light microscopy, immunohistochemistry, and in situ hybridization (RNAscope ® ). Feline oSCCs had two types of stroma, namely fibrotic and myxoid stromal reaction patterns, which were easily distinguished using hematoxylin-eosin staining. The myxoid stroma was rich in hyaluronic acid, which seems to be produced by neoplastic cells. Furthermore, the presence of myxoid stroma was correlated with histological parameters, including the appearance of cancer-associated fibroblasts and tumor budding. Periostin protein expression was also frequently observed in the stroma of feline oSCC and was significantly more common in the myxoid stromal reaction pattern group than in the fibrotic group. Positive signals for periostin mRNA were detected in stromal cancer-associated fibroblasts. This study indicates that the interaction between neoplastic cells and stromal reaction pattern components, such as hyaluronic acid and periostin, may be involved in tumor malignancy. Therefore, we propose that focus be placed not only on the tumor tissue but also on the characterization of the stroma for analyzing feline oSCC.

Feline oral squamous cell carcinoma (FOSCC) is characterised by invasive and metastatic behaviour and is poorly responsive to current treatments, hence the need for new therapeutic strategies. FOSCC shares molecular targets with human head and neck squamous cell carcinoma (HNSCC), among these the epidermal growth factor receptor. Cetuximab is an anti-epidermal growth factor receptor monoclonal antibody employed in the therapy of HNSCC and, interestingly, previous work in vitro suggested that it displays cytostatic and cytotoxic properties also against FOSCC. With the present study, we aimed at further investigating the effects of cetuximab on invasion and metastasis pathways proven to be relevant in human patients. To this purpose, FOSCC cell lines SCCF1, SCCF2 and SCCF3 were treated with cetuximab for 48/72 h and subjected to Western blot for matrix metalloproteinases-2/9 (MMP-2/9) and epithelial-mesenchymal transition markers vimentin, E-, P- and N-cadherin. Treatment with cetuximab resulted in downregulation of MMP-2/-9 in all of the three cell lines in a dose-dependent manner. Moreover, cetuximab downregulated vimentin and P-cadherin in SCCF1, upregulated E-cadherin whilst downregulating P-/N-cadherins in SCCF2, and impaired P-/N-cadherins in SCCF3. An in vitro scratch test also demonstrated that cetuximab delayed cell migration in SCCF3. These data suggest that cetuximab mitigates invasion and metastasis processes by impairing MMPs and epithelial-mesenchymal transition pathways in FOSCC, indicating that this monoclonal antibody may help to counteract malignant progression and improve the management of locally invasive disease., (© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

A 14-year-old cat presented with right-sided epistaxis, right facial swelling, hyporexia, and sneezing. A right nasal mass was diagnosed based on dental radiography and computed tomography (CT), and nasal angiofibroma was diagnosed based on histopathology. Treatment consisted of stereotactic body radiation therapy in three consecutive daily doses. Self-limiting grade 3 oral mucositis developed which resolved within 6 weeks. Recheck CT 169 days after treatment confirmed a partial response by RECIST(1) based on digital CT measurements . Disease progression was confirmed on CT 642 days after treatment, per RECIST criteria, with the longest tumor diameter measuring 3.4 cm., (© 2023 American College of Veterinary Radiology.)

Feline oral squamous cell carcinoma (FOSCC) is an aggressive cancer in domestic cats that has no effective treatment option when advanced. Preventative or early diagnostic measures are thus crucial. FOSCC is also a model for human head and neck SCC (HNSCC); strong risk factors in HNSCC include exposure to alcohol, tobacco, areca nut, and high-risk human papillomavirus. Previous studies have identified flea collar and tobacco smoke exposure, feeding canned tuna, canned cat food and cat foods with chemical additives, living in a rural environment, and having outdoor access as risk factors for FOSCC but there was no overlap in the risk factors between studies. In our study, risks for FOSCC were evaluated in an online epidemiologic survey study in 67 cats with FOSCC and 129 control cats. Clumping clay cat litter and flea collar use were significant risk factors for FOSCC on multiple logistic regression with odds ratios of 1.66 (95% CI 1.20-2.30) and 4.48 (95% CI 1.46-13.75) respectively. Crystalline silica is a carcinogen that may be present in all clay cat litters and tetrachlorvinphos is a carcinogen that is present in the most commonly used flea collars in our study. We recommend further investigation into the association between FOSCC and clay-based litter and/or flea collars containing tetrachlorvinphos., (© 2023 John Wiley & Sons Ltd.)

Cold atmospheric plasma (CAP) has shown promising results against squamous cell carcinoma (SCC) in both in vivo and in vitro assays, mainly in humans and mice. Its applicability for treatment of feline tumors, however, remains unknown. This study aimed to evaluate the anticancer effects of CAP on a head and neck squamous cell carcinoma (HNSCC) cell lineage and against a clinical case of cutaneous SCC in a cat. Control and treatment groups employing the HNSCC cell line (SCC-25) were used, the latter exposed to CAP for 60 seconds, 90 seconds, or 120 seconds. The cells were subjected to the MTT assay nitric oxidation assay and thermographic in vitro analyses. The clinical application was performed in one cat with cutaneous SCC (3 sites). The lesions were treated and evaluated by thermographic, histopathological, and immunohistochemical examinations (caspase-3 and TNF-alpha). Treatment of the SCC-25 cells for 90 seconds and 120 seconds resulted in a significant nitrite concentration increase. Decreased cell viability was observed after 24 hours and 48 hours, regardless of exposure time. However, the cell viability reduction observed at 72 hours was significant only in the 120 seconds treatment. In vitro, the temperature decreased for all treatment times, while the plasma induced a slight increase in mean temperature (0.7°C) in the in vivo assay. Two of the 3 clinical tumors responded to the treatment: one with a complete response and the other, partial, while the third (lower lip SCC) remained stable. Both remaining tumors displayed apoptotic areas and increased expression of caspase-3 and TNF-alpha. Adverse effects were mild and limited to erythema and crusting. The CAP exhibited an in vitro anticancer effect on the HNSCC cell line, demonstrated by a dose-dependent cell viability reduction. In vivo, the therapy appears safe and effective against feline cutaneous SCC. The treatment did not result in a clinical response for 1 of 3 lesions (proliferative lower lip tumor), however, a biological effect was still demonstrated by the higher expression of apoptosis indicators., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Feline oral squamous cell carcinoma (FOSCC) is the most common oral tumour diagnosed in pet cats and carries a poor prognosis with <10% one-year survival despite multi-modal therapies. Tumours of the mandible or maxilla are frequently osteo-invasive and pain can result from osteolysis. Zoledronate is a bisphosphonate that inhibits osteoclasts and reduces bone resorption. Radiation therapy (RT) is used to treat FOSCC due to anti-cancer activity and ability to improve quality of life. We hypothesized RT can be safely combined with zoledronate, and that this combinatory therapy would be efficacious, well tolerated, and result in decreased bone resorption in cats with FOSCC. SCCF1 cell line was treated with zoledronate before, concurrently, or after RT, and clonogenic assays were performed to determine if an optimal dosing schedule would be identified. Nine cats with osteoinvasive FOSCC were recruited for treatment with 4 weekly doses of 8 Gy RT combined with zoledronate administered at the first and fourth treatments. Serial CT scans were performed to assess tumour response. Safety and tolerability were monitored with hematologic and biochemical parameters, and acute radiation effects were characterized. Serum c-telopeptide (CTx) and relative bone mineral density (rBMD) by dual -energy X-ray absorptiometry (DEXA) quantified bone resorption. In vitro studies showed no clear benefit to timing of zoledronate with RT, therefore all zoledronate was administered concurrently with RT in FOSCC patients. Based on tumour volume, 4/9 (44.4%) cats achieved partial remission, 4/9 (44.4%) stable disease and 1/9 (11.1%) had progressive disease. The combinatory therapy was well-tolerated based on biochemical measurements, and all patients experienced decreased serum CTx. Combining RT with zoledronate in tumour-bearing cats is safe, well-tolerated, results in a partial remission rate of up to 44%, and decreases serum CTx, a marker of bone resorption., (© 2022 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Background: Intensity-modulated radiotherapy (IMRT), which allows generating steep dose gradients, is a beneficial treatment for companion animals with adjacent target and risk organs. IMRT is essential for high setup accuracy for avoiding overdose to risk organs, and optimal radiotherapy is important for evaluating the setup accuracy of companion animals., Aim: To use an immobilization device to evaluate setup errors in radiotherapy for companion animals., Methods: We calculated setup errors in radiotherapy for 386 animals (dogs and cats; 3,261 registration images) that underwent radiotherapy between 2016 and 2022. The companion animals were immobilized with a customized bite block and vacuum lock device. A quantile-quantile plot with 95% confidence interval (CI) was used to evaluate the histogram of the setup errors, and the systematic and random setup errors were calculated for each region (brain, head and neck, chest and abdomen, pelvis, and spine)., Results: The setup error in each direction presented an extremely narrow-interval histogram, with the following lower and upper 95% CIs: cranial-caudal (-0.08, -0.06 cm); left-right (-0.04, -0.02 cm); and dorsal-ventral (-0.13, -0.11 cm). The mean systematic setup error was 0.16 cm (range: 0.12-0.36 cm), and the random error was 0.15 cm (range: 0.08-0.34 cm). The pelvis showed the highest systematic and random setup errors (mean: 0.36 and 0.23 cm, respectively)., Conclusion: The use of an immobilization device enables highly accurate radiotherapy for companion animals (95% CI < 0.15 cm)., Competing Interests: The authors declare that they have no conflict of interest.

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% CI: 1.03-3.04; P = .04), outdoor access (OR: 1.68; 95% CI: 1.07-2.63; P = .02), environmental tobacco smoke (OR: 1.77; 95% CI: 1.05-3; P = .03), and petfood containing chemical additives (OR: 1.98; 95% CI: 1.04-3.76; P = .04). Risk factors shared with CGS and PD were outdoor access and petfood containing chemical additives, respectively. A history of oral inflammation was reported in 35% of cats with OSCC but did not emerge as a risk factor., Conclusions and Clinical Importance: The study proposes novel potential risk factors for OSCC in cats. Although a history of inflammatory oral disease was not significantly more frequent compared with random age-matched controls, OSCC shared several risk factors with CGS and PD., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Recent evidence suggests a possible association of Felis catus papillomavirus type 2 (FcaPV-2) DNA with feline oral squamous cell carcinoma (FOSCC). In this study, type-specific PCR targeting two genes (L1/E6 or E1/E6) of FcaPV-1/-2/-3/-4/-5/-6 was performed to detect viral DNA in a large amount of FOSCC samples collected in Italy and Austria. FcaPV-1/-2/-3/-4/-5 were detected in 7/113 (6.2%), 7/93 (7.5%), 6/113 (5.3%), 1/113 (0.9%) and 2/113 (1.8%) specimens, respectively, with different prevalences in Italian vs. Austrian samples, whilst FcaPV-6 went undetected. Our results confirms that FcaPV-2 is the most prevalent in FOSCC, followed by FcaPV-1/-3 and suggest that FcaPVs have variable circulation rates in European countries.

It is difficult to retain tumoricidal doses of ethanol in large or unencapsulated tumours without causing intoxication or damaging surrounding tissue. Ethyl cellulose-ethanol ablation (ECEA) overcomes this limitation by trapping ethanol intratumorally. To evaluate the safety of ECEA and to develop a clinically feasible workflow, a single-arm pilot study was performed in cats with lingual/sublingual squamous cell carcinoma (SCC). Six cats underwent intratumoral injection of 6% ethyl cellulose in ethanol. Subjects were observed overnight. There was mild bleeding and transient hyperthermia, and injection site pain and swelling that improved with anti-inflammatory drugs. Serum ethanol was minimally elevated; the mean concentration peaked 1 hour after injection (129 +/- 15.1 nM). Cats were rechecked at weeks 1 and 2; booster treatments were given in cats (n = 3) with stable quality of life and partial response to therapy. Recheck examinations were then performed monthly. The longest tumour dimension increased in each animal (progressive disease via cRECIST); however, estimated tumour volume was reduced in 3 of 6 cats, within 1 week of ECEA. All cats were euthanized (median survival time 70 days) because of local tumour progression and/or lingual dysfunction that was likely hastened by ECEA. ECEA is not a viable treatment for feline lingual/sublingual SCC; tumour volume was effectively reduced in some cats, but the simultaneous loss of lingual function was poorly tolerated. Further optimization may make ECEA a useful option for SCC at other oral sites in the cat, and for head and neck malignancies in other species., (© 2021 John Wiley & Sons Ltd.)

Feline oral squamous cell carcinoma (FOSCC) is characterized by high local invasiveness and early bone lysis. The late diagnosis largely limits the efficacy of therapy and increases treatment-related morbidity. The aim of this exploratory study was to assess the methylation pattern of 10 candidate genes and TP53 mutational status in histologic samples of FOSCC. Results were compared with normal oral mucosa and oral inflammatory lesions, in order to establish a gene panel for FOSCC detection. For 10 cats, the above analyses were also performed on oral brushing samples, in order to explore the utility of these methods for screening purposes. Thirty-one FOSCC, 25 chronic inflammatory lesions and 12 controls were included. TP53 mutations were significantly more frequent in the FOSCC (68%) than in the non-neoplastic oral mucosa (3%; P <.001). Based on lasso regression analysis, a step-wise algorithm including TP53, FLI1, MiR124-1, KIF1A and MAGEC2 was proposed. The algorithm allowed to differentiate FOSCC with 94% sensitivity and 100% specificity (accuracy, 97%). When applying the proposed algorithm on 10 brushing samples, accuracy decreased to 80%. These results indicate that the altered DNA methylation of specific genes is present in FOSCC, together with a significant proportion of TP53 mutations. Such alterations are infrequent in normal oral mucosa and chronic stomatitis in cats, suggesting their involvement in feline oral carcinogenesis and their utility as diagnostic biomarkers. Further studies on a high number of brushing samples will be needed to assess the utility of a screening test for the early detection of FOSCC., (© 2020 John Wiley & Sons Ltd.)

Objectives: The aim of this study was to evaluate the efficacy, long-term outcome and prognostic factors of feline squamous cell carcinoma (SCC) treated with photodynamic therapy (PDT)., Methods: Cats with histologically verified SCC of the head and neck received an intravenous injection of liposomal phosphorylated meta-tetra(hydroxylphenyl)chlorine (mTHPC) and 4 h later 652 nm light was delivered by a diode laser. One group received ⩽10 J/cm 2 , the other 20 J/cm 2 . Tumour response and duration were analysed with stage, tumour diameter, location and treatment intensity as prognostic factors., Results: In total, 63 lesions in 38 cats underwent treatment with ⩽10 J/cm2 (n = 22) and 20 J/cm 2 (n = 41). Overall response rate was 84% (complete remission 61%, partial remission 22%) with a mean progression-free interval of 35 months (median not reached) and a median overall survival time of 40 months (95% confidence interval 33-47). With regard to tumour stage, invasiveness yielded a highly significant worse outcome ( P <0.017). All patients with invasive tumours showed progression at less than 6 months. Larger lesions were associated with inferior control and treatment intensity, and tumour location did not influence response and duration., Conclusions and Relevance: PDT using a systemic photosensitiser leads to excellent long-term tumour control in the majority of cats. However, invasive and large tumours had a clearly inferior outcome, even if treated with the higher-dose intensity. This suggests that advanced lesions are not indications for PDT.

Background: Squamous cell carcinoma (SCC) is the most common nonodontogenic oral tumor in cats. In the jaw, it usually presents as an ulceroproliferative lesion associated with enlargement of the affected bone., Case Presentation: This report describes the case of a cat in which clinical and radiographic findings of a mandibular swelling were suggestive of an aggressive process, but the oral mucosa was unaffected. The results of histopathological and immunohistochemical examination of the samples obtained from the intraosseous lesion were consistent with SCC. The animal was euthanized 5 months after initial presentation as a result of the severe progression of the disease, and no other primary tumors were identified at necropsy., Conclusions: Based on the clinicopathological, microscopic, and immunohistochemical staining features, as well as the absence of a primary tumor at a distant site, we propose that the term, solid type primary intraosseous SCC (PIOSCC), be used to describe this neoplasia, as it shares similar features with human PIOSCC.

Repeatable head immobilization is important for minimizing positioning error during radiation therapy for veterinary patients with head neoplasms. The purpose of this retrospective cross-sectional study was to describe a novel technique for head immobilization (Device II) and compare this technique with a previously described technique (Device I). Device II provided additional support by incorporating three teeth (vs. two teeth with Device I). Between 2011 and 2013, both devices were applied in clinically affected cats (Device I, n = 17; Device II, n = 11) and dogs (Device I, n = 85; Device II, n = 22) of various breeds and sizes. The following data were recorded for each included patient: variability in the angle of the skull (roll, yaw, and pitch), coordinates of the isocenter, and distance from the reference mark to the tumor. Devices I and II differed for skull angle variability during the treatment of dogs (roll, P = 0.0007; yaw, P = 0.0018; pitch, P = 0.0384) and for yaw of during the treatment of cats (P < 0.0001). In each case, Device II was superior to Device I. The distance from the reference mark to the center of the tumor was significantly decreased for Device II vs. Device I (dogs, P < 0.0001; cats, P = 0.0002). Device II also provided more accurate coordinates for the isocenter. Authors recommend the use of, Device II for future clinical patients., (© 2015 American College of Veterinary Radiology.)

Background: Advanced carcinoma of the head represents a substantial health problem in cats for local control and overall survival., Objectives: Evaluate the capability of electrochemotherapy (ECT) to improve bleomycin efficacy in cats with periocular carcinoma and advanced carcinoma of the head., Animals: Twenty-one cats with periocular carcinoma (17 squamous cell carcinoma [SCC] and 4 anaplastic carcinoma) and 26 cats with advanced SCC of the head., Methods: Nonrandomized prospective controlled study. Periocular carcinoma cohorts: 12 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT under anesthesia; 9 cats were treated with bleomycin alone. Advanced head SCC cohorts: 14 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT administered under sedation; 12 control cats were treated with bleomycin alone. ECT treatments (2-8) were performed every other week until complete remission (CR) or tumor progression occurred., Results: Toxicities were minimal and mostly treated symptomatically. Overall response rate in the ECT treated animals was 89% (21 Complete Response [CR] and 2 Partial Response [PR]) whereas controls had response rate of 33% (4 CR and 3 PR). Median time to progression in ECT group was 30.5 months, whereas in controls it was 3.9 months (P < .0001). Median time to progression for ECT cohorts was 24.2 months for periocular cohort and 20.6 in advanced head SCC cohort, respectively., Conclusions: Electrochemotherapy is well tolerated for advanced SCC of the head in cats; its use may be considered among loco-regional strategies for cancer therapy in sensitive body regions such as periocular region., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Setup variability affects the appropriate delivery of radiation and informs the setup margin required to treat radiation patients. Twenty-four veterinary patients with head and neck cancers were enrolled in this prospective, cross-sectional study to determine the accuracy of an indexed board immobilization device for positioning. Couch position values were defined at the first treatment based on setup films. At subsequent treatments, patients were moved to the previously defined couch location, orthogonal films were acquired, table position was modified, and displacement was recorded. The mean systematic displacement, random displacement, overall displacement, and mean displacement values of the three-dimensional (3D) vector were calculated. Three hundred thirty-two pairs of orthogonal setup films were analyzed for displacement in cranial-caudal, lateral, and dorsal-ventral directions. The mean systematic displacements were 0.5, 0.8, and 0.5 mm, respectively. The mean random displacements were 1.0, 1.1, and 0.7 mm, respectively. The overall displacements were 1.1, 1.4, and 0.9 mm, respectively. The mean 3D vector value was 1.6 mm with a standard deviation of 1.2 mm. Ninety-five percent of the vectors were <3.6 mm. These values were compared to data obtained with a previously used immobilization device. A t-test was used to compare the two devices. The 3D vector, random displacement in all directions, and overall displacement in the cranial-caudal and dorsal-ventral directions were significantly smaller than displacements with the previous device. The precision and accuracy of the indexed board device was superior to the historical head and neck device., (© 2015 American College of Veterinary Radiology.)

Feline head and neck squamous cell carcinoma (SCC) is a loco-regional disease harbouring a poor prognosis. The complex anatomic location precludes aggressive surgical resection and tumours recur within weeks to few months. Response to chemotherapy and local control after radiation therapy has been disappointing. In this study, a multimodal approach including medical treatment (thalidomide, piroxicam and bleomycin), radiation therapy (accelerated, hypofractionated protocol) and surgery was attempted in six cats. Treatment was well tolerated. Three cats with sublingual SCC were alive and in complete remission at data analysis closure after 759, 458 and 362 days. One cat with laryngeal SCC died of renal lymphoma after 51 days and the other with maxillary SCC died of a primary lung tumour 82 days after diagnosis. In both cats, the SCC was in complete remission. Only one cat developed metastases after 144 days. These encouraging preliminary results merit further evaluation in future trials., (© 2012 John Wiley & Sons Ltd.)

For canine and feline patients with head tumors, simultaneous irradiation of the primary tumor and mandibular and retropharyngeal lymph nodes (LNs) is often indicated. The purpose of this study was to assess the repeatability of a planning target volume (PTV) expansion protocol for these LNs. Two CT image sets from 44 dogs and 37 cats that underwent radiation therapy for head tumors were compared to determine LN repositioning accuracy and precision; planning-CT (for radiation therapy planning) and cone-beam CT (at the time of actual treatment sessions). Eleven percent of dogs and 65% of cats received treatment to their LNs. In dogs, the mandibular LNs were positioned more caudally (P = 0.0002) and the right mandibular and right retropharyngeal LNs were positioned more to the left side of the patient (P = 0.00015 and P = 0.003, respectively). In cats, left mandibular LN was positioned higher (toward roof) than the planning-CT (P = 0.028). In conclusion, when the patient immobilization devices and bony anatomy matching are used to align the primary head target and these LNs are treated simultaneously, an asymmetrical PTV expansion that ranges 4-9 mm (dogs) and 2-4 mm (cats), depending on the directions of couch movement, should be used to include the LNs within the PTV at least 95% of the time., (© 2012 Veterinary Radiology & Ultrasound.)

A 9-year-old, neutered male cat was presented for a subcutaneous mass on the neck. After surgical removal of the mass, a pet identification microchip was found within the tumour. Histological examination of the mass revealed typical features of the feline postinjection sarcoma. The cat had never received injections at the tumour site; all routine vaccinations were administered in the hindlimbs. Few cases of sarcomas developing at the site of microchip application have been reported in animals, although the contributory role of vaccine administrations has not been ruled out. This is the first report of a microchip-associated fibrosarcoma in a cat. Adherence to American Association of Feline Practitioners vaccination guidelines, avoiding the interscapular area, enabled confirmation of the definitive aetiology of the neoplasia., (© 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.)

Polyamines are essential for cell proliferation. Their production is dysregulated in many cancers and polyamine depletion leads to tumour regression in mouse models of squamous cell carcinoma (SCC). The purpose of this study was to determine the maximally tolerated dose of the polyamine transport inhibitor, MQT 1426, when combined with the ornithine decarboxylase (ODC) inhibitor, DFMO, and to determine whether this therapy results in reduction in tumour polyamine levels. Thirteen cats with oral SCC received both drugs orally and serial tumour biopsies were obtained for polyamine measurement. Cats were monitored for response to therapy and toxicity. A maximum tolerated dose (MTD) of MQT 1426 when combined with DFMO was determined. Dose-limiting toxicity was vestibular in nature, but was fully reversible. Spermidine and total polyamine levels decreased significantly in tissues, two cats experienced objective tumour regression and six cats had stable disease. These results suggest that further study of polyamine depletion therapies is warranted., (© 2011 Blackwell Publishing Ltd.)

Ethical Issues: Caring for cancer patients presents many ethical issues for veterinarians and other veterinary health workers. The issues that most veterinarians think of relate to management of the patient when the owners' preferences for treatment do not appear to be in the animal's best interest, as well as concerns about toxicities and about costs of veterinary services (advanced imaging, surgery, radiation therapy and chemotherapy). While not limited to the veterinary profession, we are more often faced with dilemmas about the appropriateness of palliative care and decisions about euthanasia than our medical colleagues. Equally important are the ethics of not treating patients, and the integration of unproven and alternative strategies into conventional care. A separate ethical issue arises from investigational therapies and research. Less often considered, but nonetheless relevant, are the ethics of suboptimal evaluation (staging) of patients prior to treatment, or of not informing owners about all the options available., Client Communication: Ethical veterinary care is intertwined with good client communication. Without good communication, it is impossible, for example, to gain informed consent; and without informed consent, the ethics of cancer treatment are uncertain., Goal: This article, which draws in part on published research, where stated, and otherwise on the author's personal experiences/opinions and those of veterinary colleagues, is intended to provoke further thought and discussion on the ethics of caring for our cancer patients., (Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

The potent anti-cancer agent doxorubicin (DOX) induces apoptosis of rapidly proliferating cells by inhibiting cellular proteasomes. The aim of the present study was to determine whether DOX modulates the level of expression and function of proteasomes in feline injection-site sarcoma (FISS). Tissue extracts from primary sarcoma lesions and the related healthy subcutis of 18 cats affected by FISS were investigated. Nine of these cats had received neoadjuvant DOX treatment and nine cats did not receive this therapy. There was enhanced proteasome expression in FISS, but this was not affected by administration of DOX. This finding may account for the low clinical effectiveness of DOX therapy in FISS and provides the rationale for developing new therapeutic protocols aimed at achieving better proteasomal inhibition in FISS and other tumours that respond poorly to DOX therapy., (Copyright 2010 Elsevier Ltd. All rights reserved.)

A 4-month-old kitten was presented with a large mass over the temporal area involving the base of the left ear. Cytological evaluation of a fine-needle aspirate was not diagnostic. Computed tomography was used to determine tumor extent. Surgical resection was performed, which included parts of the orbital rim, masticatory muscles, the complete ear canal, and the pinna. Reconstruction of the ocular muscles was performed, and the skin defect was reconstructed using a single pedicle advancement flap. Despite unilateral facial paralysis, postoperative clinical function was excellent and aesthetics were good. Histological examination revealed the tumor to be a teratoma. After a follow-up period of 3 years, no signs of recurrence were evident. Extragonadal teratomas should be considered in the differential diagnosis when young animals are presented with a growing mass located outside the abdominal cavity. Surgical excision of a mature teratoma can be considered curative.

We examined the utility of a bite block-type head immobilization device, hereafter referred to as "head immobilization device", in order to improve the ease of immobilization and accuracy when performing radiotherapy for cranial tumors in animals. The head immobilization apparatus was a rectangular-shaped bite block-type device. We examined 55 cases in 46 dogs that underwent head CT scans between June 2005 and May 2006. The head immobilization device was used for 26 cases (immobilization group) and was not used for 29 cases (control group). Head stability was maintained in the control group by placing a towel under the head. We measured the angle of rotation of the xy, yz and xz planes for each group. The angles of rotation of the xy plane for the control and immobilization groups were 3.69 +/- 2.28 (mean +/- SD) and 1.39 +/- 1.50, respectively. The t-test demonstrated that the difference was statistically significant (p<0.001). These results indicate that there was reduced tilting to the left or right. We conclude that use of this head immobilization device was extremely easy and that it improved the accuracy of radiotherapy for cranial tumors in dogs and cats.

A 14-year-old spayed female domestic shorthair cat presented with an interscapular mass. A computed tomography scan, biopsy, and histological examination revealed a fibrosarcoma adjacent to a pet identification microchip. Because the cat was previously vaccinated at this site, it is not possible to establish definitive causation of the fibrosarcoma, but this is the first report of a tumor in the vicinity of a microchip in a cat. Microchip-associated tumors have been reported in rodents and dogs. Veterinarians should be aware that because inflammation may predispose felines to tumor formation, separation and observation of vaccination and implantation sites are indicated. Adherence to American Association of Feline Practitioners (AAFP) vaccination guidelines and monitoring of microchip implantation sites are recommended.

Having demonstrated BPA-BNCT induced control of experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa with no damage to normal tissue we explored the feasibility and safety of treating spontaneous head and neck tumors, with particular focus on SCC, of terminal feline patients with low dose BPA-BNCT employing the thermal beam of the RA-1 Reactor within a preclinical context. The biodistribution studies showed that, in all three cases evaluated, BPA delivered absolute boron values to tumor in the range that proved therapeutically useful in the experimental model of SCC. BPA-BNCT studies showed no radiotoxic effects, partial tumor control in terms of impaired growth and partial necrosis, an improvement in clinical condition and prolonged survival beyond the terminal condition of the feline patients at the time of recruitment.

Gemcitabine (2',2'-difluorodeoxycytidine) was given intravenously twice weekly to 10 cats with oral squamous cell carcinoma and 15 dogs with nasal carcinoma undergoing radiotherapy as a radiosensitizing agent. The average total radiation dose was 50 Gy for dogs and 54 Gy for cats given Monday-Friday (planned dose of 54 and 57 Gy, respectively). Dogs received an average of five doses of gemcitabine beginning at 50 mg/m2, and cats received an average of five doses of gemcitabine beginning at 25 mg/m2. Twelve of 15 dogs and five of 10 cats required chemotherapy dose reduction or postponement because of hematologic or normal tissue toxicity. The results herein do not support the use of gemcitabine at the studied dose and schedule, as significant hematologic and local tissue toxicity was observed in the studied patients. Pharmacokinetic data are necessary to best define the efficacy and optimal dose and schedule of gemcitabine in combination with traditional radiotherapy.

A survey of veterinary radiation therapy facilities in the United States was done in 2001 to determine the type of equipment available, radiation protocols used, case load, tumor types irradiated, as well as other details of the practice of radiation oncology. A total of 42 sites were identified and included 17 (40%) academic institutions, and 25 (60%) private practice external beam radiation facilities. The overall response rate was 79% (33/42 responded). Based on this survey there is substantial variation between facilities in all aspects ranging from equipment and personnel to radiation protocols and caseloads. American College of Veterinary Radiology boarded radiation oncologists direct 76% of the radiation facilities at academic institutions and 60% of the private practice facilities. Three facilities had orthovoltage radiation units only, and 30 facilities had mega-voltage equipment: cobalt 60 or linear accelerator. A total of 18 facilities had linear accelerators with three of these off site at a human radiation facility. Patient load information was available from 31 sites (74% of the radiation facilities in the United States), and based on the responses 2790 dogs and 1081 cats were irradiated in 2001. Canine mast cell tumors were the most frequently irradiated tumor. This represents the first survey of veterinary radiation facilities in the United States and provides information on the specialty of veterinary radiation oncology.

A retrospective study was performed to report the histologic examination results of regional lymph nodes of dogs and cats with oral or maxillofacial neoplasms. Twenty-eight dogs and 3 cats were evaluated. Histologic examination results of standard and serial tissue sectioning of regional lymph nodes were recorded. When available, other clinical parameters including mandibular lymph node palpation, thoracic radiographs, and pre- and postoperative fine needle aspiration of lymph nodes were compared with the histologic results. Squamous cell carcinoma, fibrosarcoma, and melanoma were the most common neoplasms diagnosed in dogs. Squamous cell carcinoma and fibrosarcoma were diagnosed in cats. Of the palpably enlarged mandibular lymph nodes, 17.0% had metastatic disease histologically. Radiographically evident thoracic metastatic disease was present in 7.4% of cases. Preoperative cytologic evaluation of the mandibular lymph node based on fine needle aspiration concurred with the histologic results in 90.5% of lymph nodes examined. Postoperative cytologic evaluation of fine needle aspirates of regional lymph nodes concurred with the histologic results in 80.6% of lymph nodes examined. Only 54.5% of cases with metastatic disease to regional lymph nodes had metastasis that included the mandibular lymph node. Serial lymph node sectioning provided additional information or metastasis detection. Cytologic evaluation of the mandibular lymph node correlates positively with histology, however results may fail to indicate the presence of regional metastasis. Assessment of all regional lymph nodes in dogs and cats with oral or maxillofacial neoplasms will detect more metastatic disease than assessing the mandibular lymph node only.

Variants of lipoma are uncommon, although fibrolipoma and infiltrative lipoma have been well documented. This report describes two cases of rare angiolipoma in dogs and the first documentation of angiofibrolipoma and infiltrating angiolipoma in a cat and a dog, respectively. Tumors were solitary, and most were located on the thorax of middle-aged patients. Angiolipomas were composed of mature adipose tissue mixed with variable numbers of blood vessels. In addition to the adipose and vascular components, the angiofibrolipoma contained bundles of collagenous connective tissue. The infiltrative angiolipoma had a primary mass external to the muscle and was histologically similar to a mixed intramuscular hemangioma that was confined to the muscle. Both disrupted bundles of striated muscle and were associated with segmental degeneration and loss of myofibers.

The purpose of this retrospective study was to evaluate the repositioning accuracy of different positioning devices in order to determine their applicability for potential use in conformal radiation therapy for animals. Forty-four animals with spontaneous tumors of the head were included. The animals were divided into 3 groups determined according to the positioning device used. Group 1 animals were positioned using a thermoplastic mask. Group 2 animals were positioned using a head holder. Group 3 animals were positioned using the head holder and an inflatable pillow. The time of presentation determined which position device was used. Port films of the 44 patients were reviewed retrospectively, and the repositioning precision was recorded by measurements in three orthogonal planes. Groups 2 and 3 had significantly better repositioning accuracy (P < or = 0.05) compared to Group 1. The position variation was not significantly different (P < or = 0.05) between Groups 2 and 3 in the lateral and longitudinal direction. Group 3 had a median reposition variation of 0.5 to 1.0 mm, with a standard deviation of 1.0 to 1.5 mm.

A report of a cat with a cranial tumor of nerve sheath origin is presented. The cranial mass, with a cyst-like character on presentation to the referring veterinarian suggested a benign lesion, but the clinical course was rapid and indicative of central nervous system involvement. The tumor was poorly differentiated by histologic examination, but immunohistochemistry was consistent with Schwann cell origin. Features of peripheral nerve sheath tumors in cats and other species are briefly discussed.

Clinical, macroscopic, and histologic features of 12 lymphangiosarcomas in cats are described. Nine tumors were located in the subcutaneous tissue at the caudoventral abdominal wall (eight cats) or in the neck (one cat). The remaining three cats had lymphangiosarcomas around the cranial mesenteric artery (two cats) or precardial in the mediastinum (one cat). Macroscopically, the tumors were noncircumscribed, white, edematous, and intermixed with fat tissue. Histologic features varied from cleft-forming and cavernous growth to papilliform and solid patterns. Follow-up data were available for seven cats with subcutaneous lymphangiosarcomas. All these cats died or were euthanatized within 6 months after surgery because of poor wound healing, local recurrence, or distant metastases. The cats with abdominal or thoracic masses were either euthanatized at surgery or within 6 months after the first surgery because of recurrent chylothorax, chyloperitoneum, or distant metastases.

Malignant Lymphoma is a common tumour disease in dogs and cats. In the dog lymphoma's are predominantly multicentric, while in the cat lymphoma's are mainly found in the mediastinum and intestinal tract. This article describes four cases of lymphoma found in unusual locations. Chemotherapy is briefly discussed.

Malignant tumors of the head and neck region occur commonly in veterinary medicine. Unfortunately, tumors in the head and neck can cause treatment dilemmas because many neoplastic entities at this site are locally aggressive. Additional local therapies such as radiation therapy are becoming commonplace as standardized therapies for many head and neck tumors in veterinary medicine.

This article is intended as a clinical introduction to radiation therapy as a treatment modality. It discusses the indications and contraindications for radiotherapy. Additionally, it attempts to cover the expected response of a wide variety of tumors to radiation. It should be remembered that veterinary radiotherapy is still in its infancy, and that much of the information presented in this article is, unfortunately, anecdotal in nature.

The microscopical and immunohistochemical features of a rare cutaneous leiomyoma in a cat are described. The principal characteristics of this tumour were multiple bundles of smooth muscle, either discrete or conjoined, with numerous collagen fibres between the muscle cells, and osteoid metaplasia. The tumour was designated a piloleiomyoma as it was considered to have arisen from the arrector pili muscles.

Radiation therapy may be indicated for larger invasive tumors of the head and neck that may be difficult to surgically excise or for which surgery would be significantly disfiguring. Previous studies of oral squamous cell carcinomas indicate that it should be possible to control approximately 80% of all but the most advanced local or locoregional tumors. Aggressive radiation therapy to total doses of 56 Gy or greater may be required. That can be done by using smaller doses per fraction and gradually reducing the size of the field so that the highest dose is given only to the tumor with a relatively tight margin. Malignant melanomas can be controlled locally apparently with a few large fractions. Metastatic disease limits survival; therefore, some type of systemic therapy seems to be needed to improve survival of those patients. Canine oral fibrosarcomas require a very high dose for a reasonable probability of control. It seems that a dose of 56 Gy given in 3.3 Gy fractions might provide local control of 50% of the tumors. It is likely that a combination of surgery and radiation would significantly improve the probability for control. Oral squamous cell carcinomas of cats must also be treated very aggressively to improve local control. Tumors of the nasal cavity are usually very large and invasive at the time of diagnosis. Radiation therapy has been shown to be effective in some instances. It is possible that with better definition of the tumor through computerized tomography imaging and improved treatment planning, control of these difficult to manage nasal tumors can be improved.

Squamous cell carcinoma is the fourth most common neoplasm in cats. As in man, local resective surgery of stage III and IV carcinoma often results in recurrence related to compromised margins. Radical resective procedures may be performed when reconstructive techniques are available to restore cosmesis and function. A platysma myocutaneous flap that was based on a cutaneous branch of the caudal auricular artery and vein was developed to fulfill this requirement. Control flaps, which included ligation and division of the caudal auricular artery and vein, were similarly developed on the contralateral aspect of the neck. Mean survival of all platysma myocutaneous flaps (86.7%), compared with control flaps (62.9%), was significantly different (p < .05). Flaps grouped in lengths of 6, 9, and 12 cm had mean survival lengths of 93.8%, 81.9%, and 84.4%, respectively. The mean survival length of flaps measuring 12 cm in length was significantly different (p < .05) compared with flaps measuring 6 and 9 cm. On the basis of the results of this study, the platysma myocutaneous flap based on a cutaneous branch of the caudal auricular artery and vein may be a source of tissue for reconstructive procedures of the head and neck in cats.

Ten cats with a total of 15 cancerous or precancerous lesions were examined for clinical response to and histopathologic changes after treatment with 13-cis-retinoic acid. Before treatment was started, the lesions were graded according to clinical severity and biopsied for histopathologic examination. Serum samples were prepared for determining vitamin A concentrations. For comparison, serum vitamin A concentrations in 10 clinically healthy cats were determined. 13-cis-Retinoic acid (approx 3.0 mg/kg) was given to affected cats once a day for an average of 68 days. At the completion of the therapeutic trial, additional biopsy tissues were obtained for histopathologic examination, and serum was assayed for 13-cis-retinoic acid. Of the 15 lesions examined, only 1 showed partial clinical and microscopic improvement during the therapy period. The mean serum vitamin A concentration of the affected cats was not statistically different from that of the 10 healthy cats. The results of this trial indicated that 13-cis-retinoic acid used at this dosage, daily frequency, and duration did not have therapeutic efficacy for squamous cell carcinomas or preneoplastic lesions in the cat and that the mean serum vitamin A concentration did not differ between the affected cats and clinically healthy cats.