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Veterinary Resources

Oral eosinophilic granuloma in three cavalier King Charles spaniels. Bredal WP, Gunnes G, Vollset I, Ulstein TL. J Small Anim Pract. Octobeer 1996;37(10):499-504. Quote: Oral eosinophilic granuloma is a rare and enigmatic disease in dogs. The clinical, haematological, cytological and histopathological features of three unrelated Cavalier King Charles spaniels with oral ulcers are presented. The disease was characterised by granuloma or plaque formation in the oral cavity. Common clinical signs were clearing the throat, swallowing problems, coughing during and after meals, reduced appetite and difficulty in eating. Haematological findings were not specific. Cytology was considered easier to perform than tissue biopsy due to friability of the tissue, but could not be used to confirm a granuloma diagnosis. The diagnosis of oral eosinophilic granuloma was verified histopathologically in each case. Response to glucocorticoid therapy varied, from complete remission to lack of any visible effect, leading to a guarded prognosis. The aetiology of the disease was not determined; however, the gross and microscopic morphologies of the lesions, their location and the response to corticosteroid therapy was suggestive of hypersensitivity.

Chromosome aberrations in canine multicentric lymphomas detected with comparative genomic hybridisation and a panel of single locus probes. R Thomas, K C Smith, E A Ostrander, F Galibert, and M Breen. Brit J Cancer; Oct. 2003;89(8):1530–1537.  Quote: "Malignant lymphoma (lymphosarcoma) represents one of the most frequently encountered canine neoplasms, most commonly affecting middle-aged to older dogs of a wide range of breeds. The disease originates from the malignant transformation of developing lymphocytes, and in the absence of chemotherapy, survival beyond one month after diagnosis is uncommon. Although generally considered a chemoresponsive form of malignancy in the dog, .. the disease is highly heterogeneous at both the clinical and histological level. A proportion of cases demonstrate more favourable response to therapy, and longer overall survival time, than others receiving the same initial diagnosis. ... Since humans and dogs demonstrate extensive genome homology, it is likely that canine lymphoma will also be associated with recurrent chromosome aberrations. However, few reports exist describing chromosome abnormalities detected in canine lymphoma and at present insufficient data are available from which to draw significant conclusions on their findings. ... The development of comparative genomic hybridisation (CGH) as a technique for indirect analysis of chromosomal copy number changes in human tumour cells now provides a means by which imbalanced genomic aberrations can be identified accurately and efficiently without the need to generate tumour chromosome preparations. The application of CGH to the dog, the advent of novel molecular cytogenetic resources for this species, the development of comparative cytogenetic maps and the generation of an integrated canine genome map now provide a means by which to overcome prior practical difficulties and embark on more comprehensive studies of tumour karyotypes in this species. ... We have used CGH analysis to identify chromosome imbalances in 25 cases [including one cavalier King Charles spaniel] of canine multicentric lymphoma. The resulting range and distribution of aberrations observed indicates that, as with the human counterpart of this disease, the cytogenetic profiling of canine lymphoma as a potential aid to diagnosis and clinical management warrants more detailed investigation."

New aspects of canine pyometra. R. Hagman, Doctoral thesis, Swedish University of Agricultural Sciences, Uppsala, 2004. Quote: "Breeds with high risk of the development of pyometra in the present study were Collie (rough-haired), Rottweiler, Cavalier King Charles Spaniel, Bernese Mountain Dog and Golden Retriever. ... The interactions with biological age could be interpreted as that in some breeds (e.g. Rottweiler, rough-haired Collie, Golden Retriever, and Cavalier King Charles Spaniel), the risk of pyometra actually increases more and at an earlier age compared with other breeds. These breeds may carry a higher genetic predisposition for pyometra than other breeds."

Anal sac tumours of the dog and their response to cytoreductive surgery and chemotherapy. S.G. Emms. Austr Vet J; June 2005;83(6):340-343. Quote: "A retrospective study of anal sac tumours without pulmonary metastases, from the author's clinical records for the period July 1989 to July 2002, was conducted to establish the response to treatment with surgery and melphalan chemotherapy. Of 21 dogs [including cavalier King Charles spaniels] with tumours of the anal sacs 19 had apocrine gland adenocarcinomas of anal sac origin, one had a benign papillary cystadenoma and another had a malignant melanoma. Two of the 19 dogs had bilateral anal sac adenocarcinomas. Ten of the 19 dogs with apocrine gland adenocarcinomas of anal sac origin had sublumbar lymphadenopathy. Five dogs were excluded by their owners from recommended treatment. Fourteen dogs with apocrine gland adenocarcinomas of anal sac origin were treated by surgical cytoreduction and chemotherapy with melphalan. Seven of the 14 dogs had regional lymph node metastases. Cytoreduction was by local excision of the anal sac in all 14 dogs and concurrent removal of the sublumbar retroperitoneal lymph nodes in the seven dogs with regional lymph node metastases. The median survival time of dogs with sublumbar nodal metastasis was 20 months and for dogs with tumour localised to the anal sac the median survival time was 29.3 months. There was no difference in median survival of those dogs with sublumbar metastases compared to those without. This study suggests there is a role for melphalan in the treatment of dogs with anal sac adenocarcinoma when combined with cytoreductive surgery, with treatment survival times and the local recurrence rate of the primary tumour comparing favourably with previously published treatment regimes."

Primary Renal Neoplasia of Dogs. Jeffrey N. Bryan, Carolyn J. Henry, Susan E. Turnquist, Jeff W. Tyler, Julius M. Liptak, Scott A. Rizzo, Gabriella Sfiligoi, Steven J. Steinberg, Annette N. Smith, and Tarraca Jackson. J Vet Intern Med 2006;20:1155–1160. Quote: "Background: Primary renal tumors are diagnosed uncommonly in dogs. Hypothesis: Signs and survival will differ among different categories of primary renal tumors. Animals: Data were collected from the medical records of 82 dogs [including a cavalier King Charles spaniel] with primary renal tumors diagnosed by examination of tissue obtained by ultrasound-guided biopsy, needle aspiration, surgery, or at postmortem examination. Results: Forty-nine dogs had carcinomas, 28 had sarcomas, and 5 had nephroblastomas. The dogs were geriatric (mean 8.1 years; range: 1–17) with a weight of 24.9 kg (range: 4.5–80). Tumors occurred with equal frequency in each kidney with 4% occurring bilaterally. Initial signs included one or more of hematuria, inappetance, lethargy, weight loss, or a palpable abdominal mass. Pain was reported more frequently in dogs with sarcomas (5/28). The most common hematologic abnormalities were neutrophilia (22/63), anemia (21/64), and thrombocytopenia (6/68). Polycythemia was present in 3 dogs and resolved with treatment. Hematuria (28/49), pyuria (26/49), proteinuria (24/50), and isosthenuria (20/56) were the most frequently observed abnormalities on urinalysis. Pulmonary metastases were noted on thoracic radiographs in 16% of dogs at diagnosis. Seventy-seven percent of dogs had metastatic disease at the time of death. Median survival for dogs with carcinomas was 16 months (range 0–59 months), for dogs with sarcomas 9 months (range 0–70 months), and for dogs with nephroblastomas 6 months (range 0–6 months). Conclusions and Clinical Importance: Primary renal tumors in dogs are generally highly malignant with surgery being the "only treatment that improves survival."

Canine conjunctival hemangioma and hemangiosarcoma: a retrospective evaluation of 108 cases (1989–2004). Chris G. Pirie, Amy M. Knollinger, Chet B. Thomas, Richard R. Dubielzig. Vet Ophth; July 2006;9(4):215-226. Quote: "Canine conjunctival tumors of vascular endothelial origin are common, although under-reported. The purpose of this study was to evaluate the epidemiology of and potential risk factors for these tumors. This study evaluated 108 cases [including cavalier King Charles spaniels] (70 hemangiomas, 38 hemangiosarcomas) from 8300 canine submissions between 1989 and 2004. Signalment, location, pigmentation, size, duration, diagnosis, margins, ancillary therapy, and geographic location were recorded. Follow-up information was available for 49 cases. Each case was matched with two unaffected controls and compared using logistic regression analysis. Average age upon presentation was 8.6 years; there was no sex predilection. Risk of conjunctival tumors was statistically different among breed groups (P = 0.0010), demonstrating a propensity to occur in groups likely to have increased outdoor activity. Primary involvement occurred within nonpigmented epithelium along the leading edge of the nictitating membrane (41/108) and temporal bulbar conjunctiva (33/108). The etiology remains unknown; however, the strong site predilection, involvement of nonpigmented epithelium, and development within specific breed classes strongly suggest ultraviolet (UV) light as a significant risk factor. In a full-logistic model including breed, gender, age, and UV exposure, UV was not a statistically significant variable (P = 0.1215). In a reduced-model including UV only, significance was approached (P = 0.0696) and posthoc contrast demonstrated a significant linear trend with increasing UV exposure (P = 0.0147). In separate analysis of risks associated with hemangiosarcoma, compared with hemangioma, breed was not significant while increasing UV exposure was significant (P = 0.0381). Early surgical therapy is recommended and may be curative; however, recurrence is possible and more likely with hemangiosarcomas (11/20)."

Combined Use of Surgery and Radiation in the Treatment of an Intradural Myxoid Liposarcoma in a Dog. Sergio Rodenas, Isabel Valin, Patrick Devauchelle, Françoise Delisle, Michel Baron. J. AAHA. September 2006;42(5):386-391. Quote: An intradural-extramedullary myxoid liposarcoma of the high cervical spine was diagnosed in a 9-year-old, spayed female Cavalier King Charles spaniel that was presented for a 2-month history of cervical pain and tetraparesis. Radiation therapy applied after surgery resulted in complete remission of the neurological deficits. The tumor recurred 18 months after surgical excision. A second surgery and another course of radiotherapy again resulted in complete remission of the clinical signs. The dog was euthanized 11 months after the second surgery because of tumor recurrence.

Breed, gender and neutering status of British dogs with anal sac gland carcinoma. G. A. Polton, V. Mowat, H. C. Lee, K. A. Mckee, T. J. Scase. Vet. & Comparative Onocology. September 2006; doi: 10.1111/j.1476-5829.2006.00100.x. Quote: This study details the breed, gender and neutering status of a large cohort of British canine patients suffering from histologically confirmed anal sac gland carcinoma [ASGC]. Estimates of the relative risk for the development of this disease attributable to these factors are calculated. To reduce the impact of sampling errors, cases were selected from veterinary histopathology laboratories rather than referral hospital databases, and multiple estimates of the general British canine population were used. The weaknesses of the statistical assumptions made are discussed. There was no evidence to support a gender predisposition for the development of this condition. English cocker spaniels are significantly over-represented, with a mean relative risk estimate of 7.3. ... The data indicated that English cocker spaniels, springer spaniels and cavalier King Charles spaniels exhibited statistically significant probabilities of an increased incidence of ASGC; the cocker spaniels demonstrated absolute consistency across the reference populations, P < 0.001. These three breeds were distinguished and the Fisher’s exact tests repeated so that ‘at-risk’ breeds were excluded from the ‘not-at-risk’ groups. Odds ratios and their 95% confidence intervals were then calculated for the at-risk breeds using the modified groupings (Table 3). The data indicate a marked predisposition for the development of ASGC in English cocker spaniels, with an average odds ratio of 7.3; average odds ratios for springer spaniels and cavalier King Charles spaniels were 2.2 and 2.6, respectively. ... The mean relative risk estimate associated with being neutered was 1.4; the effect of neutering appeared to be more significant in male dogs compared with that in female dogs.

A population study of neutering status as a risk factor for canine prostate cancer. Jeffrey N. Bryan, Matthew R. Keeler, Carolyn J. Henry, Margaret E. Bryan, Allen W. Hahn, Charles W. Caldwell. The Prostate; August 2007;67(11):1174–1181. Quote: "Background: Prostate cancer has been reported to occur more commonly in neutered than intact male dogs in several case series. This study was undertaken to evaluate risk of prostate cancer in a large population database. The hypothesis was that castration is a risk factor for prostate cancer in male companion dogs. Methods: Data were derived from recorded visits to North American veterinary teaching hospitals. The Veterinary Medical Databases (VMDB) were queried to yield male dogs with urinary bladder transitional cell carcinoma (TCC), prostate adenocarcinoma (ACA), prostate TCC, prostate carcinoma (CA), and prostate tumors. A second query yielded all male dogs over the age of 4 years without a diagnosis of urinary tract cancer. These populations were compared to determine relative risks for developing each disease, singly and collectively, associated with neutering status. Odds ratios were calculated for breed as a risk factor. Results: Neutered males had a significantly increased risk for each form of cancer. Neutered males had an odds ratio of 3.56 (3.02–4.21) for urinary bladder TCC, 8.00 (5.60–11.42) for prostate TCC, 2.12 (1.80–2.49) for prostate adenocarcinoma, 3.86 (3.13–4.16) for prostate carcinoma, and 2.84 (2.57–3.14) for all prostate cancers. Relative risks were highly similar when cases were limited to those with a histologically confirmed diagnosis. Conclusions: Breed predisposition suggests that genetic factors play a role in the development of prostate cancer. The risk associated with being neutered is highest for TCC, supporting previous work identifying the urothelium and ductular rather than acinar epithelium as the source of these tumors."

Corneal squamous cell carcinoma in dogs with a history of chronic keratitis. R. R. Dubielzig, C. S. Schobert and J. Dreyfus. Vet Ophth; 2008;11(6):413–429 (Abstract 101). Quote: "Purpose: Corneal squamous cell carcinoma (SCC) is a rare tumor in dogs. The COPLOW has seen a recent increase in primary SCC in the axial cornea. We report here on 25 cases. Methods: Twenty-five cases of primary axial corneal SCC were selected from the COPLOW collection which includes more that 6000 neoplastic specimens. ... Results: The number of canine corneal SCC has risen in the past several years from 1 case per year from 1998 to 2004, jumping to 6 cases in 2005, 8 cases in 2006, and 7 cases in 2007. Brachycephalic breeds are overrepresented. The breed distribution included 8 Pugs, 5 Bulldog, 2 Boxers, 2 Greyhound, 2 Shi Tzu, 2 Border Collie, 2 Pekinese, 1 Bassett, 1 Chow, 1 Cocker, and 1 Cavalier King Charles Spaniel. No correlation to sex was found. Out of the 25 cases, 21 showed signs of chronic keratitis prior to developing SCC. In the remaining 4 cases the prior corneal history was unknown. Within the group of 25, 10 cases had been treated with cyclosporine alone, 4 with tacrolimus alone, 5 with both cyclosporine and tacrolimus, and 6 treated with other drugs or unknown. Follow-up information was obtained from 23 cases with a follow-up interval of between 5 days and 31 months (mean: 7.9 months). Three dogs had died for reasons unrelated to the ocular disease. One dog had recurrent disease extending deeply into the cornea. Conclusions: Brachycephalic dogs with a background of chronic keratitis that are treated with nonsteroidal antiinflammatory drugs are at risk to develop axial corneal SCC. The increase in annual cases of SCC suggests that this phenomenon is a developing problem."

Examining the heritability of anal sac gland carcinoma in cocker spaniels. Gerry Polton. J Sm Animal Prac; Jan 2009;50(1):57. Quote: English cocker spaniels, and to a lesser extent springer and cavalier King Charles spaniels, are at higher risk of developing anal sac gland tumours than other dogs. ... If colleagues have encountered this tumour in an English cocker spaniel, a springer spaniel or a cavalier King Charles spaniel, it would be of great value to this project if a blood sample and/or the affected patient’s pedigree certificate could be submitted for inclusion in the analyses. ... For further information or to submit blood or pedigrees please contact Gerry Polton at North Downs Specialist Referrals, Friesian Building 3&4, Brewerstreet Dairy Business Park, Brewer Street, Bletchingley, Surrey RH1 4QP, UK. Tel: +44 (0) 1883 741440, Fax: +44 (0) 1883 347030. E-mail: gerrypolton@gmail.com website: www.ndsr.co.uk

Multi-focal cerebral oligoastrocytoma in a puppy. G. L. Walmsley, K. Chandler, E. S. Davies, C. R. Lamb, B. Smyth, B. A. Summers. J. Sm. Anim. Pract. August 2009; doi: 10.1111/j.1748-5827.2009.00761.x. Quote: A nine-month-old entire male cavalier King Charles spaniel presented with cluster seizures, which had been preceded by behaviour changes for approximately 24 hours. ... The Neurological deficits were found localising to the prosencephalon, mesencephalon and myelencephalon. Magnetic resonance imaging identified multiple, large lesions involving both cerebral hemispheres. Management with antiepileptic and immunomodulatory drugs was instituted; however, the seizures became progressively refractory and the puppy was euthanased. Histopathology following post-mortem examination found a mixed glial cell tumour with discrete areas where neoplastic cells appeared oligodendroglial or astrocytic. Primary intracranial neoplasia is a rare cause of neurological disease in young dogs. Moreover, this case is unusual in terms of both the mixed glial nature of the neoplasm and also its multi-focal distribution.

Association between anal sac gland carcinoma and dog leukocyte antigen-DQB1 in the English Cocker Spaniel. J Aguirre-Hernández; G Polton; L J Kennedy; D R Sargan. Tissue antigens 2010;76(6):476-81. Quote: "Anal sac gland carcinomas occur frequently in English Cocker Spaniels and, to a lesser extent, in other spaniel breeds. The disease typically presents in dogs aged 8 years or older and frequently metastasises to the local lymph nodes. The association between anal sac gland carcinoma in English Cocker Spaniels and the major histocompatibility complex class II loci (the dog leukocyte antigen loci DLA-DRB1, -DQA1, -DQB1) was investigated in 42 cases and 75 controls. Based on a corrected error rate of 0.017 for each test, the allele distribution in DLA-DRB1 showed no significant difference between cases and controls (P value = 0.019), while a significant difference was obtained for DLA-DQA1 and -DQB1 alleles (P values are 0.010 and 3.3 × 10⁻⁵). The DLA-DQB1*00701 allele was the most common in both cases and controls, but it had a higher frequency among the former (0.89) than in the latter (0.61), while the second most common allele had a higher frequency in the controls (0.23) than in the cases (0.07). Haplotype distributions were also significantly different between the two groups (P value = 1.61 × 10⁻⁴). This is the second disease in English Cocker Spaniels for which the most common DLA-DQB1 allele in the breed has been shown to have a higher frequency in cases than controls, while the second most common allele in the breed (*02001) has a significantly higher frequency in the controls, compared with the cases."

The development of multiple cutaneous inverted papilloma following ovariohysterectomy in a dog. Munday, J.S.; French, A.F.; MacNamara, A.R. N.Zeal. Vet. J.; June 2010;58(3):168-171(4). Quote: "Case History: Ovariohysterectomy was performed on an adult Cavalier King Charles Spaniel. The skin that had been clipped for surgery was noticed to be erythematous 8 days later. Clinical and Pathological Findings: Poorly defined patches containing multiple papules were visible bilaterally within the clipped skin. These became larger over the following 2 weeks, and samples were collected for histology. Seven days later, the lesions were multiple raised masses, up to 5 cm in diameter. Histology revealed numerous cup-shaped epidermal proliferations extending into the dermis. The presence of keratin ocytes with increased quantities of blue-grey cytoplasm, and koilocytosis suggested papillomaviral infection; Canis familiaris papillomavirus (CfPV-2) DNA was amplified from two separate samples. Complete regression was observed 8 weeks after the lesions had been initially observed. Diagnosis: Multiple inverted papilloma confined to skin that had been clipped for surgery. Clinical Relevance: This is the first time that the development of canine cutaneous papillomas has been associated with surgery. The nature of the association between surgery and development of the papillomas is uncertain. However, it is possible that damage to superficial skin could promote the formation of papillomas. This is the first identification of CfPV-2 in New Zealand."

Microchip-induced tumors in laboratory rodents and dogs: A review of the literature 1990–2006. Katherine Albrecht. IEEE Int'l Symposium. June 2010;337-349. Quote: This paper reviews literature published in oncology and toxicology journals between 1990 and 2006 addressing the effects of implanted radio-frequency (RFID) microchips on laboratory rodents and dogs. Eleven articles were reviewed in all, with eight investigating mice and rats, and three investigating dogs. In all but three of the articles, researchers observed that malignant sarcomas and other cancers formed around or adjacent to the implanted microchips. The tumors developed in both experimental and control animals, and in two household pets. In nearly all cases, researchers concluded that the microchips had induced the cancers. Possible explanations for the tumors are explored, and a set of recommendations for policy makers, human patients and their doctors, veterinarians, pet owners, and oncology researchers is presented in light of these findings.

Unilateral facial myokymia in a dog with an intracranial meningioma. Holland, CT; Holland, JT; Rozmanec, M. Austr Vet J; Sept 2010;88(9):357-361(5). Quote: "A 23-month-old castrated male Cavalier King Charles spaniel was evaluated because of a 6-month history of unusual rippling/undulating movements of the right facial muscles that were continuous and persisted during sleep. Neurological examination revealed narrowing of the right palpebral fissure and unilateral right-sided facial myokymia that was characterised by myokymic, and to a lesser degree, neuromyotonic discharges on concentric needle electromyographic examination. After persisting unchanged for almost 2.5 years from its onset, the facial myokymia gradually disappeared over a 6-month period concomitant with the emergence of a persistent ipsilateral facial paralysis and head tilt. At 5 years and 9 months after the first examination, signs of ipsilateral lacrimal, pharyngeal and laryngeal dysfunction became evident and the dog was euthanased. Postmortem examination identified a malignant (WHO grade III) meningioma in the right cerebellopontomedullary angle that compressed the ventrolateral cranial medulla, effaced the jugular foramen and internal acoustic meatus and extended into the facial canal of the petrous temporal bone. Novel findings were the unique observation of isolated unilateral facial myokymia preceding diagnosis of a meningioma affecting facial nerve function within the caudal cranial fossa and the remarkably long duration of neurological signs (75 months) attributable to the neoplasm."

Discovery and Canine Preclinical Assessment of a Nontoxic Procaspase-3–Activating Compound. Quinn P. Peterson, Danny C. Hsu, Chris J. Novotny, Diana C. West, Dewey Kim, Joanna M. Schmit, Levent Dirikolu, Paul J. Hergenrother, Timothy M. Fan. J.CancerRes. Sept. 2010;70:7232-7241. Quote: "A critical event in the apoptotic cascade is the proteolytic activation of procaspases to active caspases. The caspase autoactivating compound PAC-1 induces cancer cell apoptosis and exhibits antitumor activity in murine xenograft models when administered orally as a lipid-based formulation or implanted s.c. as a cholesterol pellet. However, high doses of PAC-1 were found to induce neurotoxicity, prompting us to design and assess a novel PAC-1 derivative called S-PAC-1. Similar to PAC-1, S-PAC-1 activated procaspase-3 and induced cancer cell apoptosis. However, S-PAC-1 did not induce neurotoxicity in mice or dogs. Continuous i.v. infusion of S-PAC-1 in dogs led to a steady-state plasma concentration of ∼10 μmol/L for 24 to 72 hours. In a small efficacy trial of S-PAC-1, evaluation of six pet dogs with lymphoma revealed that S-PAC-1 was well tolerated and that the treatments induced partial tumor regression or stable disease in four of six subjects. Our results support this canine setting for further evaluation of small-molecule procaspase-3 activators, including S-PAC-1, a compound that is an excellent candidate for further clinical evaluation as a novel cancer chemotherapeutic."

Syncope in a Cavalier King Charles dog. C Fina, F Stambouli. Point Vétérinaire, 2011;42(316):9-10. Quote: The clinical signs, diagnosis and surgical treatment of chemodectoma in a Cavalier King Charles Spaniel dog in France are described. Clinical presentation: A 7-year-old Charles Charles male dog is presented for consultation for the exploration of a heart murmur. The owners report an episode of syncope 2 months before the consultation and the appearance of a dry cough for 1 week. The clinical examination confirms left apexal systolic systolic murmur (IV / VI) without any other abnormality. X-rays of front and thorax profile are made (photos 1 and 2) .Quality of the image → The density, the contrast, the sharpness and the fineness of the details are ...

Superficial corneal squamous cell carcinoma occurring in dogs with chronic keratitis. Jennifer Dreyfus, Charles S. Schobert, Richard R. Dubielzig. Vet Ophth; May 2011;14(3):161-168. Quote: "Objective: Canine corneal squamous cell carcinoma (SCC) is a rare tumor, with only eight cases previously published in the veterinary literature. The Comparative Ocular Pathology Lab of Wisconsin (COPLOW) has diagnosed 26 spontaneously occurring cases, 23 in the past 4 years [three of which were cavalier King Charles spaniels]. This retrospective study describes age and breed prevalence, concurrent therapy, biologic behavior, tumor size and character, and 6-month survival rates after diagnosis. Results: A search of the COPLOW database identified 26 corneal SCC cases diagnosed from 1978 to 2008. There is a strong breed predilection (77%) in brachycephalic breeds, particularly those prone to keratoconjunctivitis sicca. The mean age was 9.6 years (range 6–14.5 years). Follow-up information >6 months was available for 15 of 26 cases. Recurrence occurred in the same eye in nine cases, seven of which were incompletely excised at the time of first keratectomy. No cases were known to have tumor growth in the contralateral eye and no cases of distant metastases are known. Where drug history is known, 16 of 21 dogs had a history of treatment with topical immunosuppressive therapy (cyclosporine or tacrolimus) at the time of diagnosis. Conclusion: Chronic inflammatory conditions of the cornea and topical immunosuppressive therapy may be risk factors for developing primary corneal SCC in dogs. SCC should be considered in any differential diagnosis of corneal proliferative lesions. Superficial keratectomy with complete excision is recommended, and the metastatic potential appears to be low."

Canine tonsillar squamous cell carcinoma - a multi-centre retrospective review of 44 clinical cases. A. Mas, L. Blackwood, P. Cripps, S. Murphy, J. De Vos, N. Dervisis, M. Martano, G. A. Polton. J. Sm. Anim. Pract. July 2011; doi: 10.1111/j.1748-5827.2011.01075.x. Quote: Objectives: To review the presenting clinical signs, treatment and survival of dogs with tonsillar squamous cell carcinoma and, if possible, to identify useful prognostic indicators. Methods: Medical records of 44 dogs were reviewed retrospectively [including 4 cavalier King Charles spaniels (9.1%)]. Clinical signs, clinical stage, time of diagnosis, treatment and outcome were recorded. Data were analysed using the Kaplan-Meier, log-rank, Student's t test, Kruskal-Wallis test and Chi-square/Fisher Exact test as appropriate. Results: The most frequent clinical signs were cough (12 dogs, 27%), enlarged lymph nodes (11 dogs, 25%) and dysphagia (11 dogs, 25%). Anorexia and lethargy were less common but were significantly associated with a poor outcome. No matter what treatment modalities were used, survival times were short and median survival time for all the dogs in the study was 179 days. However, there were a small number of long-term survivors. Clinical Significance: Dogs with tonsillar squamous cell carcinoma that suffered anorexia and lethargy had shorter survival times than patients without these clinical signs. Although surgery, chemotherapy and radiotherapy seem to increase the median survival time of dogs diagnosed with tonsillar squamous cell carcinoma, there is no highly effective treatment for canine tonsillar squamous cell carcinoma.

Dog models of naturally occurring cancer. Jennie L. Rowell, Donna O. McCarthy, Carlos E. Alvarez. Trends in Molecular Med. July 2011;17(7):380-388. Quote: "Studies using dogs provide an ideal solution to the gap in animal models for natural disease and translational medicine. This is evidenced by approximately 400 inherited disorders being characterized in domesticated dogs, most of which are relevant to humans. There are several hundred isolated populations of dogs (breeds) and each has a vastly reduced genetic variation compared with humans; this simplifies disease mapping and pharmacogenomics. Dogs age five- to eight-fold faster than do humans, share environments with their owners, are usually kept until old age and receive a high level of health care. Farseeing investigators recognized this potential and, over the past decade, have developed the necessary tools and infrastructure to utilize this powerful model of human disease, including the sequencing of the dog genome in 2005. Here, we review the nascent convergence of genetic and translational canine models of spontaneous disease, focusing on cancer."

Pharmacokinetics and derivation of an anticancer dosing regimen for PAC-1 in healthy dogs. Pamela W. Lucas, Joanna M. Schmit, Quinn P. Peterson, Diana C. West, Danny C. Hsu, Chris J. Novotny, Levent Dirikolu, Daniel R. Deorge, Laura D. Garrett, Paul J. Hergenrother, and Timothy M. Fan. Invest New Drugs. 2011 October; 29(5): 901–911. Quote: "PAC-1 [procaspase-3 activating compound 1]  is a preferential small molecule activator of procaspase-3 and has potential to become a novel and effective anticancer agent. The rational development of PAC-1 for translational oncologic applications would be advanced by coupling relevant in vitro cytotoxicity studies with pharmacokinetic investigations conducted in large mammalian models possessing similar metabolism and physiology as people. In the present study, we investigated whether concentrations and exposure durations of PAC-1 that induce cytotoxicity in lymphoma cell lines in vitro can be achievable in healthy dogs through a constant rate infusion (CRI) intravenous delivery strategy. Time- and dose-dependent procaspase-3 activation by PAC-1 with subsequent cytotoxicity was determined in a panel of B-cell lymphoma cells in vitro. The pharmacokinetics of PAC-1 administered orally or intravenously was studied in 6 healthy dogs using a crossover design. The feasibility of maintaining steady state plasma concentration of PAC-1 for 24 or 48 hours that paralleled in vitro cytotoxic concentrations was investigated in 4 healthy dogs. In vitro, PAC-1 induced apoptosis in lymphoma cell lines in a time- and dose-dependent manner. The oral bioavailability of PAC-1 was relatively low and highly variable (17.8 ± 9.5%). The achievement and maintenance of predicted PAC-1 cytotoxic concentrations in normal dogs was safely attained via intravenous CRI lasting for 24 or 48 hours in duration. Using study, we investigated whether concentrations and exposure durations of PAC-1 that induce cytotoxicity in lymphoma cell lines in vitro can be achievable in healthy dogs through a constant rate infusion (CRI) intravenous delivery strategy. Time- and dose-dependent procaspase-3 activation by PAC-1 with subsequent cytotoxicity was determined in a panel of B-cell lymphoma cells in vitro. The pharmacokinetics of PAC-1 administered orally or intravenously was studied in 6 healthy dogs using a crossover design. The feasibility of maintaining steady state plasma concentration of PAC-1 for 24 or 48 hours that paralleled in vitro cytotoxic concentrations was investigated in 4 healthy dogs. In vitro, PAC-1 induced apoptosis in lymphoma cell lines in a time- and dose-dependent manner. The oral bioavailability of PAC-1 was relatively low and highly variable (17.8 ± 9.5%). The achievement and maintenance of predicted PAC-1 cytotoxic concentrations in normal dogs was safely attained via intravenous CRI lasting for 24 or 48 hours in duration. Using the dog as a large mammalian model, PAC-1 can be safely administered as an intravenous CRI while achieving predicted in vitro cytotoxic concentrations."

Malocclusion associated with macroglossia in a dog. Gerhard Putter. Comp. Anim. Nov/Dec 2011;16(9):12-19. Quote: "Macroglossia (defined as enlargement of the tongue but not indicating the cause) is a rare condition in dogs. The association with malocclusion has not been described before. It has been reported that resection of as much as 60% of the body of the tongue is well tolerated by dogs. Although the tongue is a very vascular organ, intraoperative haemorrhage during tongue amputation can be effectively controlled by a tourniquet at the base of the tongue. Healing of the amputation wound is usually rapid and uneventful. ... A five year old, 12 kg neutered male Cavalier King Charles Spaniel was presented with a complaint of an excessively long tongue."

Identification of genetic variation in 11 candidate genes of canine mammary tumour. K. S. Borge, A. L. Børresen-Dale, F. Lingaas. Vet. & Comp. Oncology; Dec 2011;9(4):241-250. Quote: "The incidence of canine mammary tumours (CMTs) differs significantly between breeds [cavalier King Charles spaniels are identified as being at low-risk for CMT], strongly supporting an influence of genetic risk factors. We aimed at identifying germline genetic variations in mammary tumour-associated genes in dogs and survey whether these might alter the encoded proteins. We sequenced 11 genes (BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EGFR, ESR1, HER2, PTEN, STK11 and TP53) and screened for genetic variations. Sixty-four single nucleotide polymorphisms (SNPs) were identified. Nine of the coding SNPs were non-synonymous, of which four were located in gene regions conserved across four species. Three of the non-synonymous SNPs might be damaging according to PolyPhen predictions. One of the indels identified has previously been associated with CMTs. Because of the founder effects, genetic drift and inbreeding in many dog breeds the allele frequencies of the genes studied are likely to vary significantly between breeds and contribute to the considerable difference in genetic risk associated with cancer."

Thymidine kinase assay in canine lymphoma. J. W. Elliott, P. Cripps, L. Blackwood. Vet. & Comp. Oncology; Dec 2011. Quote: "The aim of the study was to evaluate if thymidine kinase (TK) correlated with duration of first remission (DFR) or survival in dogs with lymphoma and if initial TK levels correlated with stage and substage; and also to assess if TK level at diagnosis correlated with immunophenotype. TK was assayed in 73 dogs with treatment naïve lymphoma, then again after treatment; 47% had an initial TK above the reference interval. Dogs with B-cell lymphoma had higher initial TK activities than dogs with T-cell lymphoma. TK levels were not higher in dogs with higher stage disease and TK activity prior to treatment was not associated with DFR or survival. Where TK was elevated at diagnosis, it fell into the reference range during remission. TK was normal in 53% dogs at diagnosis, which is higher than previously reported. Further studies are warranted to assess the utility of TK in dogs with lymphoma."

Parallel Synthesis and Biological Evaluation of 837 Analogues of Procaspase-Activating Compound 1 (PAC-1). Danny C. Hsu, Howard S. Roth, Diana C. West, Rachel C. Botham, Chris J. Novotny, Steven C. Schmid, Paul J. Hergenrother. ACS Comb Sci. 2012 January; 14(1):44–50. Quote: "Procaspase-Activating Compound 1 (PAC-1) is an ortho-hydroxy N-acyl hydrazone that enhances the enzymatic activity of procaspase-3 in vitro and induces apoptosis in cancer cells. An analogue of PAC-1, called S-PAC-1, was evaluated in a veterinary clinical trial in pet dogs with lymphoma and found to have considerable potential as an anticancer agent. With the goal of identifying more potent compounds in this promising class of experimental therapeutics, a combinatorial library based on PAC-1 was created, and the compounds were evaluated for their ability to induce death of cancer cells in culture. For library construction, 31 hydrazides were condensed in parallel with 27 aldehydes to create 837 PAC-1 analogues, with an average purity of 91%. The compounds were evaluated for their ability to induce apoptosis in cancer cells, and through this work, six compounds were discovered to be substantially more potent than PAC-1 and S-PAC-1. These six hits were further evaluated for their ability to relieve zinc-mediated inhibition of procaspase-3 in vitro. In general, the newly identified hit compounds are two- to four-fold more potent than PAC-1 and S-PAC-1 in cell culture, and thus have promise as experimental therapeutics for treatment of the many cancers that have elevated expression levels of procaspase-3.

Household chemical exposures and the risk of canine malignant lymphoma, a model for human non-Hodgkin’s lymphoma. Biki B. Takashima-Uebelhoer, Lisa G. Barber, Sofija E. Zagarins, Elizabeth Procter-Gray, Audra L. Gollenberg, Antony S. Moore, Elizabeth R. Bertone-Johnson. Environmental Research. Jan 2012.; 112:171-176.  Quote: "Background: Epidemiologic studies of companion animals offer an important opportunity to identify risk factors for cancers in animals and humans. Canine malignant lymphoma (CML) has been established as a model for non-Hodgkin’s lymphoma (NHL). Previous studies have suggested that exposure to environmental chemicals may relate to development of CML. Methods: We assessed the relation of exposure to flea and tick control products and lawn-care products and risk of CML in a case–control study of dogs presented to a tertiary-care veterinary hospital (2000–2006). Cases were 263 dogs with biopsy-confirmed CML. Controls included 240 dogs with benign tumors and 230 dogs undergoing surgeries unrelated to cancer. Dog owners completed a 10-page questionnaire measuring demographic, environmental, and medical factors. Results: After adjustment for age, weight, and other factors, use of specific lawn care products was associated with greater risk of CML. Specifically, the use of professionally applied pesticides was associated with a significant 70% higher risk of CML (odds ratio(OR)=1.7; 95% confidence interval (CI)=1.1–2.7). Risk was also higher in those reporting use of self-applied insect growth regulators (OR=2.7; 95% CI=1.1–6.8). The use of flea and tick control products was unrelated to risk of CML. Conclusions: Results suggest that use of some lawn care chemicals may increase the risk of CML. Additional analyses are needed to evaluate whether specific chemicals in these products may be related to risk of CML, and perhaps to human NHL as well."

The effect of neutering on the risk of mammary tumours in dogs – a systematic review. W. Beauvais, J. M. Cardwell and D. C. Brodbelt. J.Sm.Anim.Pract, June 2012; 53(6): 314-322. Quote: "A commonly-stated advantage of neutering bitches is a significant reduction in the risk of mammary tumours, however the evidence for this has not previously been assessed by systematic review. The objectives of this study were to estimate the magnitude and strength of evidence for any effect of neutering, or age of neutering, on the risk of mammary tumours in bitches. A systematic review was conducted based on Cochrane guidelines. Peer-reviewed analytic journal articles in English were eligible and were assessed for risk of bias by two reviewers independently. Of 11,149 search results, 13 reports in English-language peer-reviewed journals addressed the association between neutering/ age at neutering and mammary tumours. Nine were judged to have a high risk of bias. The remaining four were classified as having a moderate risk of bias. One study found an association between neutering and a reduced risk of mammary tumours. Two studies found no evidence of an association. One reported “some protective effect” of neutering on the risk of mammary tumours, but no numbers were presented. Due to the limited evidence available and the risk of bias in the published results, the evidence that neutering reduces the risk of mammary neoplasia, and the evidence that age at neutering has an effect, are judged to be weak and are not a sound basis for firm recommendations."

The dog as a possible animal model for human non-Hodgkin lymphoma: a review. Laura Marconato, Maria Elena Gelain, Stefano Comazzi. Hematological Oncology. 2012.  Quote: "Lymphoma represents the most frequent hematopoietic cancer in dogs, and it shows significant overlap with the human disease. ... Diffuse large B-cell lymphoma ... DLBCL is prevalent in Cavalier King Charles Spaniel and Bassethound ... Several environmental factors have been associated with canine lymphoma, suggesting that they may contribute to lymphomagenesis. Canine lymphoma often presents in advanced stage (III–V) at diagnosis and, most commonly, has an aggressive clinical course requiring prompt treatment, which relies on the use of polychemotherapy. In this review, we will summarize the state-of-the-art of canine lymphoma epidemiology, pathobiology, diagnostic work-up and therapy, and will highlight the links to the corresponding human disease, providing evidence for the use of dog as an animal model of spontaneous disease."

Squamous papilloma in an older Cavalier King Charles. Sing Kong Yuen. Aug. 2012. SinPets.com

Rectal lymphoma in 11 dogs – a retrospective study. N. Van den Steen, D. Berlato, G. Polton, J. Dobson, J. Stewart, G. Maglennon, A. M. Hayes and S. Murphy. J.Sm.Anim.Prac. Aug 2012. Quote: "Objectives: To retrospectively evaluate the clinical behaviour and immunophenotype of lymphoma of the rectum in dogs. Methods: Eleven dogs [including a cavalier King Charles spaniel] diagnosed with lymphoma of the rectum on histopathology were retrospectively reviewed. Immunohistochemistry with CD3 and CD79a antibodies was performed at diagnosis or retrospectively. Results: Treatment protocol varied with six dogs undergoing surgery and adjuvant chemotherapy, two received chemotherapy after only incisional biopsy, one had surgical resection only, one was treated symptomatically and one dog was not treated. Chemotherapy treatment consisted of either a -low-dose COP (cyclophosphamide - prednisolone - vincristine) protocol (four dogs) or a six-week CHOP-based (cyclophosphamide - vincristine - -prednisolone - anthracycline) protocol (four dogs). Dogs that received chemotherapy lived significantly longer than dogs that did not receive chemotherapy (2352 versus 70 days). Median survival time was not reached, and there was an overall mean survival time of 1697 days. Immuno-histochemistry was performed in 10 of 11 samples, and was consistent with B-cell -lymphoma in all cases. Clinical Significance: Canine lymphoma of the rectum is associated with a favourable prognosis. Immunohistochemical evaluation of these lesions was consistent with B-cell lymphoma in all cases in which it was examined."

Single Agent Polysaccharopeptide Delays Metastases and Improves Survival in Naturally Occurring Hemangiosarcoma. Dorothy Cimino Brown and Jennifer Reetz. Evidence-Based Complementary and Alternative Medicine 2012; Article ID 384301. Quote: "The 2008 World Health Organization World Cancer Report describes global cancer incidence soaring with many patients living in countries that lack resources for cancer control. Alternative treatment strategies that can reduce the global disease burden at manageable costs must be developed. Polysaccharopeptide (PSP) is the bioactive agent from the mushroom Coriolus versicolor (right). Studies indicate PSP has in vitro antitumor activities and inhibits the growth of induced tumors in animal models. Clear evidence of clinically relevant benefits of PSP in cancer patients, however, is lacking. The investment of resources required to complete large-scale, randomized controlled trials of PSP in cancer patients is more easily justified if antitumor and survival benefits are documented in a complex animal model of a naturally occurring cancer that parallels human disease. Because of its high metastatic rate and vascular origin, canine hemangiosarcoma is used for investigations in antimetastatic and antiangiogenic therapies. In this double-blind randomized multidose pilot study, high-dose PSP significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma. These data suggest that, for those cancer patients for whom advanced treatments are not accessible, PSP as a single agent might offer significant improvements in morbidity and mortality."

Breed Variations in the Incidence of Pyometra and Mammary Tumours in Swedish Dogs. S. Jitpean, R. Hagman, B. Ström Holst, O.V. Höglund, A. Pettersson, A. Egenvall. Reproduction in Domestic Animals. Dec. 2012. Quote: "Dogs enrolled in a Swedish insurance company (during 1995–2006) were studied for development of pyometra and mammary tumours (MTs), with special attention to breed and age. There were over 260 000 female dogs with over 1 000 000 dog-years at risk (DYAR) in the database, using data on bitches up to 10 years of age and 110 breeds with over 1000 DYAR. In total, 20 423 bitches were diagnosed with pyometra and 11 758 with MTs and 30 131 with either or both of the two diseases. [48% of female cavalier King Charles spaniels developed pyometra, and 15% of them developed mammary tumors, and 54% of them developed either or both pyometra and mammary tumors, by the age of ten years.] The incidence rate (IR) for pyometra was 199 (95% CI 196–202), for MTs 112 (95% CI 110–114) and for either or both of the two diseases 297 (95% CI 294–301) dogs per 10 000 DYAR. The mean age of diagnosis pyometra was 7.0 years (SD ± 2.2), MTs 8.0 years (SD ± 1.6). In all breeds, the overall proportion of the bitches that developed disease by 10 years of age was for pyometra 19%, MTs 13%, and either or both of two diseases 30%. The top 10 breeds diagnosed with either or both of the two diseases were the Leonberger (73%), Irish Wolfhound (69%), Bernese Mountain Dog (69%), Great Dane (68%), Staffordshire Bull Terrier (66%), Rottweiler (65%), Bullterrier (62%), Doberman (62%), Bouvier des Flandres (60%), Airdaleterrier (60%). These data provide information of the combined disease incidence in a large number of different breeds. Breed variations in incidence rate suggests genetic components in disease development. Our study may be valuable in the search for genetic risk-factors or protective factors."

Evaluation of an anal sac adenocarcinoma tumor in a Spitz dog. Javad Javanbakht, Abbas Tavassoli, Atefeh Sabbagh, Mehdy Aghamohammmad Hassan, Shohreh Alian Samakkhah, Radmehr Shafiee, Ali Lakzian, Vahideh Rahmani Ghalee, and Sonia Shoja Gharebagh. Asian Pac J Tropical Biomed. Jan. 2013; 3(1):74-78. Quote: "Anal Gland Adenocarcinoma is a cancer of the apocrine gland, located inside of the anal sac. Canine anal glands are scent glands that produce an oily secretion. They are found on either side of the dog's anus between the internal and external sphincter. These tumors tend to be locally invasive and can metastasize early. However, this cancer is associated with a prolonged clinical course. Breeds more commonly affected include English Cocker Spaniels, Cavalier King Charles Spaniels, German Shepherds and English Springer Spaniels. Both genders of dogs are equally affected. The cause of this tumor is unknown."

Breed-Predispositions to Cancer in Pedigree Dogs. Jane M. Dobson. ISRN Vet.Sci. 2013. Quote: "Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies. ... In our clinic (Cambridge, UK) ... cavalier King Charles spaniels ... are under-represented [for mast cell tumors]. ... Canine anal sac gland carcinoma (ASGC) is a relatively uncommon malignancy arising from the apocrine glands in the walls of the anal sacs. This tumour is invasive and metastatic in nature and is often associated with a paraneoplastic hypercalcaemia. Although ASGC [anal sac gland carcinoma] may arise in any breed of dog the English cocker spaniel and to a lesser degree other spaniel types (English springer and cavalier King Charles) have been reported to be predisposed to development of this tumour."

Neutering Dogs: Effects on Joint Disorders and Cancers in Golden Retrievers. Gretel Torres de la Riva, Benjamin L. Hart, Thomas B. Farver, Anita M. Oberbauer, Locksley L. McV Messam, Neil Willits, Lynette A. Hart. PLOSone. Feb. 2013.   Excerpt: "Hemangiosarcoma is a cancer that is affected by neutering in females. A study of cardiac tumors in dogs found that cardiac HSA for spayed females was greater than 4 times that of intact females. A study on splenic HSA found the spayed females had more than 2 times the risk of developing this tumor as intact females. Neither of these studies separated early- versus late-spayed females with regard to increased risk, and neither focused on just one breed. A study on the epidemiology of LSA (lymphoma) in dogs, for comparison with human lymphoma, found that intact females had a significantly lower risk of developing this cancer than neutered females or neutered males or intact males. Another cancer of concern is prostate cancer, which occurs in neutered males about four times as frequently as in intact males. A study on cutaneous mast cell tumors (MCT) in several dog breeds, including the Golden Retriever, examined risk factors such as breed, size, and neuter status. Although early versus late neutering was not considered, the results showed a significant increase in frequency of MCT in neutered females; four times greater than that of intact females. In contrast to the rather strong evidence for neutering males and/or females as a risk factor for OSA, HSA, LSA, MCT, and prostate cancer, evidence for neutering as protection against a dog acquiring one or more cancers is weak. The most frequently mentioned is mammary cancer (MC). However, a recent systematic review of published work on neutering and mammary tumors found the evidence that neutering reduces the risk of mammary neoplasia to be weak, at best."

Breed predispositions in canine mast cell tumour: A single centre experience in the United Kingdom. James Warland, Jane Dobson. Vet.J. April 2013. Quote: "Genetic factors play a major role in carcinogenesis. Many breeds have been reported to be predisposed to mast cell tumour (MCT) development using various methods and diverse control populations. A database of 222 dogs with MCT seen at a UK university referral hospital was compared to three control populations, namely, an insured population of UK dogs, registrations with the UK Kennel Club and other dogs seen through the same hospital. Odds ratios were calculated for each breed. Boxers, Labradors, Golden Retrievers and Staffordshire Bull Terriers appeared predisposed to MCT development. English Springer Spaniels, English Cocker Spaniels, German Shepherd Dogs, West Highland White Terriers and Cavalier King Charles Spaniels were underrepresented."

Serum thymidine kinase 1 and C-reactive protein as biomarkers for screening clinically healthy dogs for occult disease. K. A. Selting, C. R. Sharp, R. Ringold, J. Knouse. Vet. & Comparative Oncology. 2013. Quote: "Thymidine kinase (TK1) is a biomarker that correlates well with diagnosis and prognosis in certain canine cancers. Canine C-reactive protein (cCRP) is a widely accepted marker of inflammation correlated with increased risk and severity of various diseases. We evaluated serum TK1 and cCRP concentrations in apparently healthy dogs (n=360). All dogs were followed up for a minimum of 6months by health questionnaire. All dogs with cancer were identified using a proprietary dual-biomarker algorithm [termed Neoplasia Index (NI)]. Specificity of positive NI is 0.91 and high positive is 0.98. All-cause mortality was 20% in dogs with elevated cCRP and 3% in dogs with low cCRP. The performance of serum TK1 and cCRP as tools for screening for occult cancer is improved when evaluated together. Serum TK1 and cCRP (unified in the NI) are useful in the screening of occult canine cancer. cCRP is useful in screening for other serious diseases."

Canine Melanoma Vaccine. Heather Wilson-Robles. Clinicians Brief. August 2013:15-16. Quote: "Malignant melanoma is the most common malignant oral tumor in dogs, but it can also occur in other locations (eg, nail bed, eye, perineum, nasal cavity, GI tract, skin). ... Oncept (Merial, petcancervaccine.com), immunotherapy labeled for dogs with stage II or III oral melanoma, can help achieve local disease control.4 This therapy uses an orthologous DNA (different species) vaccine against tyrosinase, a melanosomal glycoprotein needed for melanin synthesis, to induce an antityrosinase immune response.5 Tyrosinase has been overexpressed in melanomas of various species.6-8 Although the human tyrosinase protein differs enough from the canine tyrosinase protein to allow human tyrosinase protein stimulation of an immune response in canine patients, in some cases the human tyrosinase protein is similar enough to the canine tyrosinase protein that the immune response is effective against canine melanoma cells."

Successful transendoscopic oesophageal mass ablation in two dogs with Spirocerca lupi associated oesophageal sarcoma. E. Yas, G. Kelmer, A. Shipov, J. Ben-Oz and G. Segev. J.Sm.Anim.Pract. Sept. 2013;54(9):495-498. Quote: "This report describes two cases of oesophageal tumours managed by transendoscopic neodymium:yttrium-aluminum-garnet laser ablation and polypectomy snare electrocautery. ... [including] A 4-year-old, neutered male, Cavalier King Charles spaniel ... In each dog oesophagoscopy revealed caudal oesophageal masses, suspected to be Spirocerca lupi-induced oesophageal neoplasia. To resect the masses, transendoscopic neodymium:yttrium-aluminum-garnet laser ablation was used in the first case and polypectomy snare electrocautery in the second. Recovery was uneventful. Histopathology was consistent with oesophageal fibrosarcoma and osteosarcoma in each case, respectively. Follow-up oesophagoscopy revealed apparently healthy oesophageal tissue except for focal scar tissue in the first case. Transendoscopic laser ablation and polypectomy snare electrocautery is a potential non-invasive, cost effective alternative for surgical oesophageal mass resection."

Canine tonsillar Squamous cell carcinoma. Isabelle Desmas. Vet. Ireland J. December 2013;3(12):654-657. Quote: Canine tonsillar squamous cell carcinoma is an uncommon disease, characterised by rapid growth and aggressive infiltration of the underlying tissues. Primary tonsillar cancer is called TSCC1. Whatever the treatment used, it is generally regarded to carry a poor prognosis. The metastatic rate is around 73%, the disease generally spreads to the regional lymph nodes and to the lungs. Treatment approach includes surgery, radiation therapy, chemotherapy and symptomatic treatment, or any combination of these approaches. Multimodality approach is indicated given the high aggressiveness of this type of cancer. All treatment confounded but keeping a multimodality treatment approach, the median survival time is around six months. Without any treatment, an absence of control of the primary disease will lead to euthanasia in one or two months. (Photo: Lymphadenopathy of the right submandibular lymph node in a Cavalier King Charles with a right-sided tonsillar squamous cell carcinoma.)

Extranodal lymphoma with peripheral nervous system involvement in a dog. Ueno H, Miyoshi K, Fukui S, Kondo Y, Matsuda K, Uchide T. J.Vet.Med.Sci. May 2014;76(5):723-727. Quote: "An 8-year-old neutered female Cavalier King Charles Spaniel was evaluated for progressing right forelimb lameness. Upon magnetic resonance imaging, the right-sided radius nerves and the caudal brachial plexus were swelled. The histological and molecular biological diagnosis of partial the C8 spinal nerve was T-cell lymphoma. Co-administration of lomustine and irradiation was started. However, this therapy was ineffective. At necropsy, neoplastic tissues were seen extending into the subarachnoid space of the spinal cord, the liver, pancreas and kidneys as gross findings. A large mass was also identified occupying the caudal thorax. Histologic findings included infiltration in these organs and mass by neoplastic lymphocytes. To date, involvement of peripheral nerves (neurolymphomatosis) is rarely reported in veterinary species."

Evaluation of the risk and age of onset of cancer and behavioral disorders in gonadectomized Vizslas. M. Christine Zink, Parvene Farhoody, Samra E. Elser, Lynda D. Ruffini, Tom A. Gibbons, Randall H. Rieger. JAVMA Feb. 2014;244(3):309-319. Quote: "Objective: To investigate associations between age at gonadectomy and estimated risk or age at diagnosis of neoplastic and behavioral disorders in Vizslas. Design: Retrospective cohort study. Animals: 2,505 Vizslas born between 1992 and 2008. Procedures: Data on demographics, gonadectomy status, and age at diagnosis of disease or disorder were obtained with an anonymous online survey and analyzed. Results: Dogs gonadectomized at ≤ 6 months, between 7 and 12 months, or at > 12 months of age had significantly increased odds of developing mast cell cancer, lymphoma, all other cancers, all cancers combined, and fear of storms, compared with the odds for sexually intact dogs. Females gonadectomized at ≤ 12 months of age and males and females gonadectomized at > 12 months of age had significantly increased odds of developing hemangiosarcoma, compared with the odds for sexually intact dogs. Dogs gonadectomized at ≤ 6 months of age had significantly increased odds of developing a behavioral disorder. The younger the age at gonadectomy, the earlier the mean age at diagnosis of mast cell cancer, cancers other than mast cell, hemangiosarcoma, lymphoma, all cancers combined, a behavioral disorder, or fear of storms. (Mast cell cancer: 3.5 times higher incidence in neutered male and female dogs, independent of age at the time of neutering. Hemangiosarcoma: 9.0 times higher incidence in neutered females compared to nonneutered females, independent of age at the time spaying was performed. No difference in incidence of this disease was found for neutered versus nonneutered males. Lymphoma (lymphosarcoma): 4.3 times higher incidence in neutered male and female dogs, independent of age at the time of neutering. Other types of cancer: 5.0 times higher incidence in neutered male and female dogs. The younger a dog was at the time of neutering the younger the age of the dog at the time the cancer was diagnosed. All cancers combined: 6.5 times higher incidence of cancer in neutered females compared to nonneutered females; 3.6 times higher incidence of cancer in neutered males compared to nonneutered males.) Conclusions and Clinical Relevance: Additional studies are needed on the biological effects of removing gonadal hormones and on methods to render dogs infertile that do not involve gonadectomy. Veterinarians should discuss the benefits and possible adverse effects of gonadectomy with clients, giving consideration to the breed of dog, the owner's circumstances, and the anticipated use of the dog."

Acupuncture and Herbals for Cancers: Evidence-Based Clinical Application. Huisheng Xie. Chi Institute. October 2014. Quote: "Cancer is the most common natural cause of death in dogs and cats in the United States. About 45% of dogs that live to 10 years or older die of cancer. The most common cancers in pets are lymphoma, mammary tumors/cancer, mast cell tumor (MCT), hemangiosarcoma, soft tissue sarcomas, melanoma, squamous cell carcinoma (SCC) and osteosarcoma. Traditional Chinese Medicine (TCM) has been used for the diagnosis and treatment of tumors since the Warring States Period (475 to 221 BC), when 'Ling Shu Jing' (Miraculous Pivot) stated 'the tumor was caused by the pathological factors which had stayed in the body over a long time'. Clinical evidence indicates that acupuncture and herbal medicine can benefit for the treatment of cancer in dogs and people. This paper reviews the acupuncture and Chinese herbals for the treatment or adjunct treatment of cancers, and the possible mechanism of actions."

Clinical systemic lupeol administration for canine oral malignant melanoma. Inoru Yokoe, Kazuo Azuma, Keishi Hata, Toshiyuki Mukaiyama, Takahiro Goto, Takeshi Tsuka, Tomohiro Imagawa, Norihiko Itoh, Yusuke Murahata, Tomohiro Osaki, Saburo Minami, Yoshiharu Okamoto. Molecular & Clinical Oncology. Jan. 2015;3(1):89-92. Quote: "Canine oral malignant melanoma (COMM) is the most common and aggressive malignant tumor in dogs. Lupeol is a triterpene extracted from various fruits and vegetables that reportedly inhibits melanoma cell proliferation in vitro and in vivo. In this study, the efficacy of subcutaneous lupeol for spontaneous COMM was evaluated. A total of 11 dogs (3, 5 and 3 dogs diagnosed with clinical stage I [including a 17 year old cavalier King Charles spaniel], II and III melanoma, respectively) were evaluated. Subcutaneous lupeol (10 mg/kg) was administered postoperatively at various time points to treat these 11 COMM cases. Of the 11 subjects, 7 [including the CKCS] exhibited no local recurrence 180 days postoperatively and no severe adverse effects were observed in any of the cases. Furthermore, no distant metastasis was observed during the experimental period. Therefore, systemic lupeol may prevent local tumor progression and distant metastasis and may be a novel adjuvant treatment for the treatment of COMM.

Before & After: Cavalier King Charles Gets Second Chance After Extensive Surgery to Remove Tumors. Sharon Ostermann. Tails of a Shelter Vet. March 2014. Quote: An adorable 12-year-old Cavalier King Charles Spaniel came to us at San Jose Animal Care & Services with multiple problems. The most obvious problem was the large mass that was on the front right of her chest. Though her long locks covered and concealed much of her body, we also found another mass on her belly and a large umbilical hernia. Like many Cavalier King Charles Spaniels, this little girl also had a heart murmur. ... The small mass was a benign mixed tumor that was completely removed and not likely to come back. The larger mass was a mammary adenocarcinoma (mammary tumor) (see photo at right) that was completely removed but showed evidence that it might regrow in the future. I was definitely concerned about this given how large and involved the mass was.

Management of canine corneal squamous cell carcinoma with lamellar keratectomy and strontium 90 plesiotherapy: 3 cases. Jessica C. Nevile, Simon D. Hurn, Andrew G.Turner, Christina McGowan. Vet. Ophth. May 2015;18(3):254-260. Quote: "Purpose: To report three cases of canine corneal squamous cell carcinoma (SCC) treated with strontium 90 beta radiation as an adjunct to surgical excision. A 15-year-old Cavalier King Charles Spaniel was presented with a 4 mm diameter axial whitish pink raised corneal mass OS. Methods: Corneal SCC was excised with lamellar keratectomy. This was followed by local application of strontium 90 beta radiation. Results: Available case follow-up times range from 3 to 50 months. One case suffered a recurrence 5 months following initial excision and strontium 90 treatment. Conclusion and discussion: Strontium 90 beta radiation has been used extensively as an adjunctive treatment for equine corneal SCC and in other canine ocular tumors; however, there is a paucity of information regarding use in canine corneal SCC. The cases presented here suggest its use following keratectomy may be helpful in preventing disease recurrence. At the dosage used, severe adverse effects were not observed."

Allogeneic hematopoietic cell transplantation in a dog with acute large granular lymphocytic leukemia. Suter SE, Hamilton MJ, Sullivan EW, Venkataraman GM. J Am Vet Med Assoc. May 2015;246(9):994-997. Quote: "Case Description: A 3-year-old 10-kg (22-lb) neutered male Cavalier King Charles Spaniel was referred because of an episode of acute vomiting and diarrhea. Clinical Findings: On physical examination, mild splenomegaly and prominent submandibular and popliteal lymph nodes were detected. Complete blood cell count revealed a high WBC count, characterized by a moderate lymphocytosis with 62% unclassified cells and severe thrombocytopenia with macroplatelets. On cytologic evaluation, the unclassified cells were described as large, neoplastic lymphoid cells containing a large nucleus with lacy chromatin and a large amount of blue vacuolated cytoplasm containing sparse, very fine azurophilic granules. A diagnosis of acute large granular lymphocytic leukemia of splenic origin was made. Treatment and Outcome: Following induction chemotherapy, the affected dog underwent allogeneic hematopoietic cell transplantation with dog leukocyte antigen-matched CD34+ cells harvested from a sibling of the same litter. Chimerism analysis revealed full donor engraftment within 2 weeks after transplantation that remained stable for at least 2 years, with the dog remaining apparently healthy at home. Clinical Relevance: Acute leukemias in dogs are rapidly fatal diseases. If an appropriate donor can be located, allogeneic hematopoietic cell transplantation may offer a feasible treatment, although peripheral blood CD34+ cell harvesting requires the availability of cell separator machines and management of graft-versus-host disease with immunosuppressive agents."

Partial retraction: Allogeneic hematopoietic cell transplantation in a dog with acute large granular lymphocytic leukemia. JAVMA August 2015;247(3):299. Quote: The article “Allogeneic hematopoietic cell transplantation in a dog with acute large granular lymphocytic leukemia” describes successful (ie, full donor chimerism approximately 2 weeks after transplantation and survival for > 2 years) allogeneic hematopoietic cell transplantation (HCT) in a 3-year-old Cavalier King Charles Spaniel in which a clinical diagnosis of acute large granular lymphocytic (LGL) leukemia had been made. At the time of case management, the authors made a diagnosis of acute LGL leukemia on the basis of clinical signs, initial CBC results (ie, WBC count of 24,200 WBCs/μL, consisting of 23% neutrophils, 12% lymphocytes, 2% monocytes, 1% eosinophils, and 62% unclassified, large, mononuclear cells with lightly vacuolated cytoplasm, a large nucleus, lacy chromatin, and a large indistinct nucleolus), and response to induction chemotherapy. In retrospect and following a full review of the medical record, it appears that a definitive diagnosis could not be reached in this case. Therefore, the conclusions that this case provides evidence that “allogeneic HCT is a realistic treatment option for dogs with acute leukemia,” that the report documents the first use of allogeneic HCT “for the treatment of a client-owned dog with acute LGL leukemia,” and that the report suggests that “use of allogeneic HCT to treat acute leukemias in dogs will provide a considerable clinical benefit over chemotherapy alone” are retracted by agreement of the editors, authors, and university. The conclusion that allogeneic HCT may be a feasible treatment in dogs remains unchanged.

Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background. Ingegerd Elvers, Jason Turner-Maier, Ross Swofford, Michele Koltookian, Jeremy Johnson, Chip Stewart, Cheng-Zhong Zhang, Steven E Schumacher, Rameen Beroukhim, Mara Rosenberg, Rachael Thomas, Evan Mauceli, Gad Getz, Federica Di Palma, Jaime F Modiano, Matthew Breen, Kerstin Lindblad-Toh, Jessica Alföldi. Genome Res. September 2015. Quote: "Lymphoma is the most common hematological malignancy in developed countries. Outcome is strongly determined by molecular subtype, reflecting a need for new and improved treatment options. Dogs spontaneously develop lymphoma, and the predisposition of certain breeds indicates genetic risk factors. Using the dog breed structure, we selected three lymphoma predisposed breeds developing primarily Tcell (boxer), primarily B-cell (cocker spaniel), and with equal distribution of B and T-cell lymphoma (golden retriever), respectively. We investigated the somatic mutations in B- and T-cell lymphomas from these breeds by exome sequencing of tumor and normal pairs. Strong similarities were evident between B-cell lymphomas from golden retrievers and cocker spaniels, with recurrent mutations in TRAF3-MAP3K14 (28% of all cases), FBXW7 (25%), and POT1 (17%). The FBXW7 mutations recurrently occur in a specific codon; the corresponding codon is recurrently mutated in human cancer. In contrast, T-cell lymphomas from the predisposed breeds, boxers and golden retrievers, show little overlap in their mutation pattern, sharing only one of their 15 most recurrently mutated genes. Boxers, which develop aggressive T-cell lymphomas, are typically mutated in the PTEN-mTOR pathway. T-cell lymphomas in golden retrievers are often less aggressive and their tumors typically showed mutations in genes involved in cellular metabolism. We identify genes with known involvement in human lymphoma and leukemia, genes implicated in other human cancers, as well as novel genes that could allow new therapeutic options."

Canine indolent and aggressive lymphoma: clinical spectrum with histologic correlation. L. Aresu, V. Martini, F. Rossi, M. Vignoli, M. Sampaolo, A. Aricò, P. Laganga, A. Pierini, P. Frayssinet, R. Mantovani, L. Marconato. Vet. & Comp. Oncology. December 2015;13(4):348-362. Quote: "Sixty-three dogs with newly diagnosed lymphoma underwent complete staging and received the same chemotherapy. Diffuse large B-cell lymphoma was the leading histotype (44.4%), followed by peripheral T-cell lymphoma (20.6%). Indolent lymphomas accounted for 30.2% of cases. Most dogs with aggressive B-cell lymphoma had stage IV disease. Dogs with indolent and aggressive T-cell lymphoma had more often stage V disease and were symptomatic. Liver and bone marrow were predominantly involved in B-cell and T-cell lymphoma, respectively. The clinical stage was significantly related to substage, sex and total lactic dehydrogenase (LDH) levels. Aggressive B-cell lymphomas were more likely to achieve remission. Median survival was 55 days for aggressive and indolent T-cell lymphoma, 200 and 256 days for indolent and aggressive B-cell lymphoma, respectively. The prognosis of advanced indolent lymphoma does not appear to be appreciably different from that of aggressive disease. Familiarity with the various histotypes is critical to make the correct diagnosis and drive therapy."

High-throughput mRNA and miRNA profiling of epithelial-mesenchymal transition in MDCK cells. Priyank Shukla, Claus Vogl, Barbara Wallner, Doris Rigler, Mathias Müller, Sabine Macho-Maschler. BMC Genomics. November 2015;16:944. Quote: "Background: Epithelial-mesenchymal transition (EMT) is an important process in embryonic development, especially during gastrulation and organ formation. Furthermore EMT is widely observed in pathological conditions, e.g., fibrosis, tumor progression and metastasis. Madin-Darby Canine Kidney (MDCK) cells are widely used for studies of EMT and epithelial plasticity. MDCK cells show an epithelial phenotype, while oncogenic Ras-transformed MDCK (MDCK-Ras) cells undergo EMT and show a mesenchymal phenotype. Methods: RNA-Seq and miRNA-Seq analyses were performed on MDCK and MDCK-Ras cells. Data were validated by qRT-PCR. Gene signature analyses were carried out to identify pathways and gene ontology terms. For selected miRNAs target prediction was performed. Results: With RNA-Seq, mRNAs of approximately half of the genes known for dog were detected. These were screened for differential regulation during Ras-induced EMT. We went further and performed gene signature analyses and found Gene Ontology (GO) terms and pathways important for epithelial polarity and implicated in EMT. Among the identified pathways, TGFβ1 emerged as a central signaling factor in many EMT related pathways and biological processes. With miRNA-Seq, approximately half of the known canine miRNAs were found expressed in MDCK and MDCK-Ras cells. Furthermore, among differentially expressed miRNAs, miRNAs that are known to be important regulators of EMT were detected and new candidates were predicted. New dog miRNAs were discovered after aligning our reads to that of other species in miRBase. Importantly, we could identify 25 completely novel miRNAs with a stable hairpin structure. Two of these novel miRNAs were differentially expressed. We validated the two novel miRNAs with the highest read counts by RT-qPCR. Target prediction of a particular novel miRNA highly expressed in mesenchymal MDCK-Ras cells revealed that it targets components of epithelial cell junctional complexes. Combining target prediction for the most upregulated miRNAs and validation of the targets in MDCK-Ras cells with pathway analysis allowed us to identify two novel pathways, e.g., JAK/STAT signaling and pancreatic cancer pathways. These pathways could not be detected solely by gene set enrichment analyses of RNA-Seq data. Conclusion: With deep sequencing data of mRNAs and miRNAs of MDCK cells and of Ras-induced EMT in MDCK cells, differentially regulated mRNAs and miRNAs are identified. Many of the identified genes are within pathways known to be involved in EMT. Novel differentially upregulated genes in MDCK cells are interferon stimulated genes and genes involved in Slit and Netrin signaling. New pathways not yet linked to these processes were identified. A central pathway in Ras induced EMT is TGFβ signaling, which leads to differential regulation of many target genes, including miRNAs. With miRNA-Seq we identified miRNAs involved in either epithelial cell biology or EMT. Finally, we describe completely novel miRNAs and their target genes."

Mutation of p53 Gene and Its Correlation with the Clinical Outcome in Dogs with Lymphoma. A. Koshino, Y. Goto-Koshino, A. Setoguchi, K. Ohno, H. Tsujimoto. J. Vet. Intern. Med. December 2015. Quote: "Background: p53 plays a key role in the apoptotic event induced by chemotherapeutic agents. Mutation of p53 gene has been observed in various spontaneous tumors in humans and is associated with a poor prognosis. p53 abnormalities have been evaluated in several tumors in dogs; however, the association of p53 gene mutation with clinical outcome in dogs with lymphoma has not been documented. Hypothesis/Objectives: The aim of this study was to examine p53 mutation in canine lymphoma cells and its association with the clinical outcome. Animals: Forty-three dogs [including 2 cavalier King Charles spaniels] with previously untreated high-grade lymphoma referred to the University of Tokyo were included in this study. Methods: Prospective cohort study. We examined p53 gene (exon 4–8) mutation in the tumor tissues from 43 dogs with lymphoma using PCR-SSCP (polymerase chain reaction – single-strand conformational polymorphism) analysis, followed by nucleotide sequencing of the abnormal bands. Results: Of the 43 dogs, 7 dogs (16%) had p53 mutation, whereas 36 dogs (84%) were devoid of p53 mutation. Overall response rate after remission induction was significantly lower (33% versus 88%, P = .002) in dogs with lymphomas having p53 mutation than those with lymphomas devoid of p53 mutation. Overall survival time was significantly shorter (67 days versus 264 days, P = .004) in dogs with lymphoma with p53 mutation than those with lymphoma retaining wild-type p53. Conclusion and Clinical Importance: Mutations of p53 gene were detected in a proportion of canine lymphoma cells from untreated dogs and can be associated with a poor prognosis."

Lu-177-Labeled Zirconia Particles for Radiation Synovectomy. Andras Polyak, Lívia Naszályi Nagy, Eszter Drotár, Gabriella Dabasi, Róbert P. Jóba, Zita Pöstényi, Renata Mikolajczak, Attila Bóta, Lajos Balogh. Cancer Biotherapy and Radiopharmaceuticals. December 2015;30(10). Quote: "The present article describes the preparation of β-emitter lutetium-177-labeled zirconia colloid and its preliminary physicochemical and biological evaluation of suitability for local radionuclide therapy. ... An 11-year-old spayed Cavalier King Charles Spaniel was referred to the Institute with chronic, destructive, therapy-resistant osteoarthritis in the left hock joint. ... The new 177Lu-labeled therapeutic radiopharmaceutical candidate was based on the synthesis mode of a previously described zirconia nanoparticle system. The size and shape of the developed radiopharmaceutical compound were observed through a scanning electron microscope and dynamic light scattering methods. The radiocolloid had a 1.7 μm mean diameter and showed high in vitro radiochemical and colloid size stability at room temperature and during the blood sera stability test. After the in vitro characterizations, the product was investigated in the course of the treatment of a spontaneously diseased dog veterinary patient's hock joint completed with single-photon emission computed tomography (SPECT) imaging follow-up measurements and a dual-isotope SPECT imaging tests with conventional 99mTc-methanediphosphonic acid bone scintigraphy. In the treated dog, no clinical side-effects or signs of histopathological changes of the joints were recorded during the treatment. SPECT follow-up studies clearly and conspicuously showed the localization of the 177Lu-labeled colloid in the hock joint as well as detectable but negligible leakages of the radiocolloid in the nearest lymph node. On the basis of biological follow-up tests, the orthopedic team assumed that the 177Lu-labeled zirconia colloid-based local radionuclide therapy resulted in a significant and long-term improvement in clinical signs of the patient without any remarkable side-effects."

Lymphocytic thymoma in cavalier King Charles spaniel - case report and review. G. Simeonova, V. Nedev, R. Simeonov. Trakia J. of Sci. 2015;13(Suppl. 2):268-273. Quote: "A clinical case of thymoma in 6 month old, male, cavalier King Charles spaniel was described. The patient was brought to the Small Animal Clinic of Veterinary faculty at Trakia University, Stara Zagora in order to be evaluated by means of electroretinography (ERG) because of vision loss and difficulties in orientation in unfamiliar surroundings. Physical examination did not reveal any disturbances in vital parameters neither in retinal function. As complications occurred during recovery from general anaesthesia more detailed investigations were performed and the diagnosis thymoma was made. It was confirmed pathohistologically. Thymoma is an extremely rare tumor in dogs, especially in cavalier King Charles spaniels. The unusual manifestation of the disease as well as its very rare distribution among dogs was the reason to give a problem consideration."

Histological and immunohistochemical evaluation of stroma variations and their 4 correlation with the Ki-67 index and expressions of glucose transporter 1 and 5 monocarboxylate transporter 1 in canine thyroid C-cell carcinomas. Yoshio Kawamura, Hiroko Mizooku, Minoru Okamoto, Kazuya Matsuda, Tetsuo Omachi, Kazuko Hirayama, Tsuyoshi Kadosawa, Hiroyuki Taniyama. J. Vet. Med. Sci. January 2016. Quote: "Canine thyroid C-cell carcinomas (CTCCs) are malignant tumors derived from calcitonin-producing C-cells of the thyroid gland. This study aimed to investigate the histological diversity of CTCCs from the viewpoint of stroma variations and to investigate their components by histological and immunohistochemical analysis including semiquantitative analysis of the density of microvessels (MVs) and α-SMA-positive cell count. Moreover, we examined whether the variations correlated with the Ki-67 index and expressions of glucose transporter 1 (GLUT-1) and monocarboxylate transporter 1 (MCT-1). Three stroma types (reticular, R, nest, N, and trabecular, T) were observed in CTCCs and 21 cases were divided into 3 variations based on their combinations: mixed R and N (R/N) (n=7), simple N (n=7) and mixed T and N (T/N) (n=7). [One cavalier King Charles spaniel: female aged 10 years, tumor diameter: 4 cm., period to surgical treatment: 300 days.] Immuno-histochemically, stroma types depended on morphological features of α-SMA/fibronectin/laminin/collagen type IV-positive stroma cells. The density of MVs in R/N tended to be highest, and the density of those in N was significantly higher than the density of those in T/N (P=0.028). The α-SMA-positive cell count for N tended to be the lowest among the 3 variations. The Ki-67 index for R/N was significantly higher than those of the other variations (vs. N, P=0.007; vs. T/N, P=0.03), and that for T/N tended to be higher than that for N. Although there were no significant differences, GLUT-1 and MCT-1 expressions tended to be low in N. We concluded that stroma variations reflect tumor cell proliferation and expressions of GLUT-1 and MCT-1 in CTCCs."

Third eyelid gland neoplasms of dogs and cats: a retrospective histopathologic study of 145 cases. D. Dustin Dees, Charles S. Schobert, Richard R. Dubielzig, Timothy J. Stein. Vet. Ophthalmology. March 2016;19(2):138-143. Quote: "Purpose: To describe the various types of primary neoplasms affecting the third eyelid (TEL) gland of dogs and cats. Methods: A retrospective search of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database was performed. Veterinary ophthalmologists, primary care veterinarians, and, when appropriate, owners were contacted for patient follow-up information. Patient data points collected included species, age, sex, breed, laterality, tumor type, surgical margins, recurrence, metastasis, and length of follow-up. Results: A total of 127 canine [including a cavalier King Charles spaniel] and 18 feline cases met the inclusion criteria. The most common canine TEL gland tumor was adenocarcinoma (n = 108; 85.0%) followed by adenoma (n = 18; 14.2%) and squamous cell carcinoma (SCC) (n = 1; 0.8%). For canine cases with follow-up information available (n = 62), 8.1% had confirmed or suspected metastasis and 11.3% had confirmed or suspected local recurrence of disease. The most common feline TEL gland tumor was adenocarcinoma (n = 15; 83.3%) followed by SCC (n = 3; 16.7%). For feline cases with follow-up information available (n = 9), 40.0% had confirmed or suspected metastasis and 30.0% had confirmed or suspected local recurrence of disease. Conclusions: This study determined that adenocarcinoma was the most common third eyelid gland tumor in both dogs and cats. The overall survival times were less, and metastatic occurrence and recurrence rates appeared to be higher for feline tumors as compared to those diagnosed in dogs. This is the first report of SCC originating from glandular ductular epithelium."

Canine tumor development and crude incidence of tumors by breed based on domestic dogs in Gifu Prefecture. Satoshi Komazawa, Hiroki Sakai, Yusuke Itoh, Mifumi Kawabe, Mami Murakami, Takashi Mori, Kohji Maruo. J. Vet. Med. Sci. May 2016. Quote: We analyzed the status of tumor development in dogs by breed based on tumor cases that presented to the Department of Veterinary Pathology of the Gifu University for diagnostic examinations over eight years (2005–2012). We also calculated the crude incidence of tumors in dogs by breed based on the results of a survey conducted in 2011 in Gifu Prefecture. The most common sites of tumor development included the skin, digestive organs, and mammary glands. Smaller dogs showed a tendency to have a higher incidence of breast tumors. We thus identified dog breeds with a higher crude incidence of tumors (Bernese mountain dog, golden retriever, corgi, etc.) and those with a lower crude incidence of tumors (Pomeranian, poodle, Chihuahua, etc.). Unlike the current trends for domestic dogs in the US and Europe, Japan has a higher number of small dogs as pets; it is therefore necessary to develop a policy for canine cancer specific to Japan. ... Smaller dog breeds had greater proportion of 176 breast tumors, which accounted for ... 41.2% in Cavalier King Charles Spaniel (CK). ... Mast cell tumors have been found ... with a lower frequency for such tumors were also revealed to be CK ... [Number of cavaliers with tumors: 34].

Evaluation of the factors contributing to long-term survival in canine tonsillar squamous cell carcinoma. J Grant, S North. Australian Vet. J. June 2016;94(6):197-202. Quote: Objectives: To identify any prognostic factors that may be associated with the long-term survival of dogs diagnosed with tonsillar squamous cell carcinoma (TSCC). Methods: The medical records of 15 dogs treated for TSCC were reviewed retrospectively. The signalment, presenting signs, clinical stage, treatments and outcome were documented. Results: The overall median survival time (MST) of the dogs in the study was 243 days. There was a 1-and 2-year survival of 40% and 20%, respectively. The results of initial staging had a significant effect on survival, as dogs with only one tonsil affected and no evidence of metastatic disease had a longer MST (637.5 days) than the dogs with local (MST: 134 days) or distant (MST: 75 days) metastatic disease or bilateral tonsillar involvement at the time of initial presentation. Prolonged survival times were reported for dogs undergoing surgery and adjunctive chemotherapy (MST: 464.5 days) for treatment of their TSCC. Clinical significance This is the first veterinary study demonstrating an association between prognosis of patients with TSCC and stage at the time of presentation, with long survival times demonstrated for dogs with early-stage disease following an initial treatment protocol that included surgery and chemotherapy. There was no clear association between long survival and additional surgeries for progressive disease; however; further investigation is warranted. ... Population data: Of the 15 dogs included in the study, 11 (73%) were male and 4 (27%) were female. The median age at the time of diagnosis was 10.5 years (mean: 10.6 years; range: 7–14) (Table 2). There was a mixture of breeds: 5 collies (Border Collie, Rough Collie and Bearded Collie), 3 spaniels (Springer and Cavalier King Charles Spaniels), 2 West Highland White Terriers, 2 Bichon Frise, 1 Lowchen, 1 Staffordshire Bull Terrier and 1 Saluki. ... [details of CKCS: Age: 9 yrs; Sex: female, spayed; symptoms: gagging/dysphagia; contralateral tonsil: lymphoid hyperplasia (RHS); Stage: T3N1a; surgery: bilateral tonsillectomy; chemotherapy: Carboplatin: 300 mg/m² x 4 cycles + Postoperative adjunct Rx (hypofractionated: 9 Gy × 4 fractions): tonsils; Survival from diagnosis day: 779; Outcome: pulmonary carcinoma; intraoperative death. ... Although the diagnosis of TSCC continues to be associated with an extremely guarded prognosis, this is the first study to demonstrate an association between early clinical stage at the time of diagnosis and survival. Prolonged survival in patients with only one tonsil affected at the time of diagnosis was achieved in patients undergoing initial treatment with surgery and chemotherapy, thus providing a strong argument for multimodality treatment. Larger studies into the effects of initial staging and treatment on long-term prognosis in patients with TSCC are required in the future to verify these preliminary findings.

Top 5 Dermatoses Associated with Electromagnetic Radiation. Alexander Werner. Clinician's Brief. August 2016;93-97. Quote: Radiation Therapy: Radiation therapy uses ionizing, high-energy waves (eg, x-rays, gamma rays) to destroy cancer cells. Ionizing radiation directly damages DNA, which can cause cell death and other effects. To provide a large dose of radiation to the tumor while reducing the exposure of surrounding tissues, radiation beams are shaped—or aimed—from several angles to intersect at the tumor. Fractionation of dosing also allows normal cells to recover between treatments; cancer cells are slower to recover. Because of its rapid turnover rate, however, the epidermis is especially sensitive to acute radiation-induced dermatitis, with lesions developing in >90% of dogs receiving fractionated radiation therapy for skin and soft-tissue tumors. Lesions can develop several weeks into therapy. The skin becomes pink and tender before mild exudation and eventual alopecia with scarring (Figure 7) appear. Striking leukotrichia is common. Secondary bacterial infection may occur in the immediate posttreatment period. Scarring often persists after discontinuation of radiation treatments. (Figure 7 [left]: Scarring from radiation therapy for squamous cell carcinoma of the external ear canal in a 9-year-old Cavalier King Charles spaniel. The distinct borders indicate the treatment area.)

Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK. S. Verganti, D. Berlato, L. Blackwood, I. Amores-Fuster, G. A. Polton, R. Elders, R. Doyle, A. Taylor, S. Murphy. J. Sm. Anim. Pract. January 2017;58(1):10-16. Quote: Objectives: Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. Material and Methods: Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. Results: Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. Clinical Significance: Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease.

Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR. Antonella Borgatti, Joseph S. Koopmeiners, Aaron L. Sarver, Amber L. Winter, Kathleen Stuebner, Deborah Todhunter, Anthony E. Rizzardi, Jonathan C. Henricksen, Stephen Schmechel, Colleen L. Forster, Jong-Hyuk Kim, Jerry Froelich, Jillian Walz, Michael S. Henson, Matthew Breen, Kerstin Lindblad-Toh, Felix Oh, Kristy Pilbeam, Jaime F. Modiano, Daniel A. Vallera. Molecular Cancer Therapeutics. February 2017. Quote: Sarcomas differ from carcinomas in their mesenchymal origin. Therapeutic advancements have come slowly so alternative drugs and models are urgently needed. These studies report a new drug for sarcomas that simultaneously targets both tumor and tumor neovasculature. eBAT is a bispecific angiotoxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to epidermal growth factor (EGF) and the amino terminal fragment (ATF) of urokinase. Here, we study the drug in an in vivo "ontarget" companion dog trial since eBAT effectively kills canine hemangiosarcoma (HSA) and human sarcoma cells in vitro. We reasoned the model has value due to the common occurrence of spontaneous sarcomas in dogs and a limited lifespan allowing for rapid accrual and data collection. Splenectomized dogs with minimal residual disease were given one cycle of eBAT followed by adjuvant doxorubicin in an adaptive dose-finding, phase I-II study of 23 dogs with spontaneous, stage I-II, splenic HSA. eBAT improved 6-month survival from <40% in a comparison population to ~70% in dogs treated at a biologically active dose (50 µg/kg). Six dogs were long-term survivors, living >450 days. eBAT abated expected toxicity associated with EGFR-targeting, a finding supported by mouse studies. Urokinase plasminogen activator receptor (uPAR) and EGFR are targets for human sarcomas, so thorough evaluation is crucial for validation of the dog model. Thus, we validated these markers for human sarcoma targeting in the study of 212 human and 97 canine sarcoma samples. Our results support further translation of eBAT for human patients with sarcomas and perhaps other EGFR-expressing malignancies.

Colonoscopic and histologic features of rectal masses in dogs: 82 cases (1995-2012). Adamovich-Rippe KN, Mayhew PD, Marks SL, Selmic LE, Culp WT, Youello AM, Runge JJ, Holt DE, Kass PH, Peauroi JR. J. Am. Vet. Med. Assn. February 2017;250(4):424-430. Quote: Objective: To evaluate colonoscopic and histologic features of rectal masses in dogs. Design: Retrospective case series. Animals: 82 client-owned dogs [including two cavalier King Charles spaniels] with rectal masses that underwent colonoscopy. Procedures: Medical records of dogs with rectal masses that underwent colonoscopy were reviewed. History, signalment, clinical signs, results of physical examination, diagnostic imaging findings, and results of colonoscopy (including complications) were recorded. When available, tissue samples obtained during colonoscopy and by means of surgical biopsy were reviewed by a single board-certified pathologist. Histologic features and tumor grade (when applicable) of tissue samples obtained during colonoscopy versus surgical biopsy were compared. Results: Multiple rectal masses were observed during colonoscopy in 6 of the 82 dogs, but no lesions were visualized orad to the colorectal junction. Results of histologic evaluation of surgical biopsy specimens were consistent with a diagnosis of epithelial neoplasia in 58 of 64 dogs, of which 71% were classified as benign adenoma or polyp and 29% were classified as adenocarcinoma in situ or adenocarcinoma. Complications of colonoscopy occurred in 3 of 82 dogs but were considered minor. A discrepancy in diagnosis occurred in 5 of 16 dogs for which both colonoscopic and surgical biopsy samples were available for histologic review. Conclusions & Clinical Relevance: Results suggested that multiple rectal masses are uncommon in dogs, and secondary lesions orad to the colorectal junction were not found in this study. Colonoscopy was associated with few complications, but the need for colonoscopic assessment of the entire colon in this patient population may merit reevaluation.

Atypical cytologic presentation of a histiocytic sarcoma in a Cavalier King Charles Spaniel dog. Lorelei L. Clarke, Lisa S. Kelly, Bridget Garner, Cathy A. Brown. J. Vet. Diagnostic Investig. April 2017. Quote: An 8-year-old neutered male Cavalier King Charles Spaniel dog was presented because of a 10-d history of progressive vomiting, inappetence, and lethargy, with mild neurologic signs. Fine-needle aspirates of splenic nodules seen on ultrasound were suggestive of a carcinoma. On autopsy, a disseminated neoplasm was present in the lung, spleen, and adrenal glands. Additionally, there was a Chiari-like malformation of the skull with corresponding syringomyelia of the cranial spinal cord. Histologically, the neoplasm was comprised of a pleomorphic population of round cells with a high mitotic rate. Cells stained positive for vimentin and CD18 and negative for cytokeratin, chromogranin A, CD3, CD20, MHC II, and CD11d, and hence the tumor was diagnosed as a histiocytic sarcoma. The cytologic presentation in this case is uncommon for this type of tumor, as was the clinical presentation.

What is your diagnosis? Inguinal lymph node aspirate from a dog. Corry K. Yeuroukis, Jessica M. Thiman, Anne C. Avery, Melinda S. Camus, Jaime L. Tarigo. Vet. Clin. Pathol. April 2017. Quote: A 10-year-old, 9.0 kg, female spayed Cavalier King Charles Spaniel was presented ... for evaluation of an abnormal gait involving the pelvic limbs as well as difficulty posturing to urinate. ... The inguinal lymph nodes were moderately enlarged bilaterally and all other peripheral lymph nodes were of normal size and consistency. Neurologic examination revealed ambulatory paraparesis and proprioceptive ataxia with a neuroanatomic lesion localization to T3-L3. Pain was noted on deep palpation of the cervical and lumbar spine. ... Pertinent CBC results included a moderate lymphocytosis and a mild thrombocytopenia with an increased mean platelet volume. The platelet profile was consistent with macrothrombocytopenia associated with the Cavalier King Charles Spaniel breed. Serum biochemistry results and cerebrospinal fluid analysis were unremarkable. Significant magnetic resonance imaging findings included mild syringohydromyelia in the cervical spinal cord, another well documented condition in this breed, in addition to mild chronic intervertebral disk disease (IVDD) with herniation at T13-L3, and an unexpected, moderate enlargement of inguinal and splenic lymph nodes. ... Cytologic Interpretation: Lymphoma with uropodbearing lymphocytes, suggestive of T-zone lymphoma (TZL). ... For this dog, flow cytometry rather than surgical biopsy was pursued as a less invasive method to further characterize the lymphocyte population in the lymph node. ... In this case, the dog presented neurologic deficits related to IVDD and breed related syringohydromyelia. The discovery of TZL was an unexpected but significant finding which highlights the importance of investigating enlarged lymph nodes when present. Discharge instructions included monitoring of the dog’s peripheral lymphocytosis, lymphadenopathy, and clinical signs. Chemotherapy was not pursued as it has not been shown to improve the already prolonged median survival times with TZL (1.7–2.7 years).

Surgical management of primary, metastatic and recurrent anal sac adenocarcinoma in the dog: 52 cases. D. C. Barnes, J. L. Demetriou. J. Sm. Anim. Pract. May 2017;58(5):263-268. Quote: Objectives: To report the outcomes and complications of a cohort of dogs with primary and recurrent anal sac adenocarcinoma managed with surgery as the first-line treatment. To report the use of lymph node cytology for identification of metastatic disease. Methods: Retrospective review of case records of a single referral centre population of dogs diagnosed with anal sac adenocarcinoma. Results: Fifty-two clinical cases were identified [including one cavalier King Charles spaniel]. Altered ultrasonographic appearance of lymph nodes was highly consistent with metastatic disease as assessed by cytology and histopathology. Seven of 58 (12%) perineal surgeries had reported minor complications and seven (12%) others required further surgical intervention. Minor controllable intra-operative bleeding was the only complication noted associated with lymph node extirpation in two of 39 (5%) metastectomy procedures. Six dogs (12%) suffered local recurrence and 22 (42%) developed subsequent or recurrent nodal metastatic disease. From the time of detection of disease recurrence, median additional survival associated with a second surgical intervention was 283 days. Clinical Significance: Coeliotomy for lymph node metastatectomy in dogs with adenocarcinoma of the anal sac has low morbidity and should be considered in patients presenting with evidence of regional metastatic disease both at initial presentation and with recurrent disease.

Prognostic significance of Ki67 evaluated by flow cytometry in dogs with high-grade B-cell lymphoma. A. Poggi, B. Miniscalco, E. Morello, F. Gattino, A. Delaude, L. Ferrero Poschetto, L. Aresu, M. E. Gelain, V.Martini, S. Comazzi, F. Riondato. Vet. & Compara. Oncology. June 2017;15(2):431-440. Quote: Ki67 [Antigen KI-67 is a nuclear protein that is associated with and may be necessary for cellular proliferation] can discriminate between high- and low-grade canine lymphomas, but its prognostic role in specific subtypes of the neoplasm is unknown. We assessed the prognostic significance of Ki67% (percentage of Ki67-positive cells), evaluated by flow cytometry, in 40 dogs with high-grade B-cell lymphoma, treated with a modified Wisconsin–Madison protocol (UW-25). ... Data about the identification of breed were reported for 39 cases. There were 26 (66.7%) purebred dogs (3 Labrador retrievers, 2 German shepherds, 2 Dobermans, 2 Bloodhounds, 2 Pit bull terriers and 1 each of ... Cavalier King Charles Spaniel ...) and 13 (33.3%) crossbred dogs. ... The following variables were investigated for association with lymphoma specific survival (LSS) and relapse free interval (RFI): Ki67%, breed, sex, age, stage, substage, complete remission (CR). By multivariate analysis, Ki67% (P=0.009) and achievement of CR (P=0.001) were independent prognostic factors for LSS. Dogs with intermediate Ki67% (20.1–40%) presented longer LSS and RFI (median=866 and 428 days, respectively) than dogs with low (median =42 days, P<0.001; median=159 days, P=0.014) or high (median = 173 days, P=0.038; median=100 days, P=0.126) values. Determination of Ki67 is a prognostic tool that improves the clinical usefulness of flow cytometric analysis in canine high-grade B-cell lymphoma.

Epithelial and melanocytic tumors of the skin. Chapter 4. Goldschmidt MH, Goldschmidt KH. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: Wiley Blackwell; 2017:88-141. Quote: Sebaceous carcinoma: This is a malignant neoplasm with cells showing sebaceous differentation. Incidence, age, breed, and sex: Sebaceous carcinomas are uncommon in dogs and cats and rare in other species. In dogs, the peak incidence is between 10 and 13 years. Breeds at increased risk are cavalier King Charles spaniel, cocker spaniel, Siberian husky, Samoyed, and West Highland white terrier. No sex predilection has been noted.

Survival analysis of dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide, piroxicam and thalidomide. G. Polton, R. Finotello, S. Sabattini, F. Rossi, P. Laganga, M. E. Vasconi, A. Barbanera, K. Stiborova, C. Rohrer Bley, L. Marconato. Vet. & Comp. Oncol. March 2018;1-10. Quote: Unresectable or metastatic (advanced) primary pulmonary carcinoma (PPC) represents a therapeutic challenge where surgery may be contraindicated and the therapeutic role of maximum-tolerated dose (MTD) chemotherapy remains uncertain. This study was undertaken to explore the impact of metronomic chemotherapy (MC) in dogs with advanced PPC. Previously untreated dogs with advanced (T3 or N1 or M1) PPC, with complete staging work-up and follow-up data, receiving MC (comprising low-dose cyclophosphamide, piroxicam and thalidomide), surgery, MTD chemotherapy or no oncologic treatment were eligible for inclusion. For all patients, time to progression (TTP) and survival time (ST) were evaluated. Quality-of-life (QoL) was only evaluated in patients receiving MC. To assess QoL, owners of dogs receiving MC were asked to complete a questionnaire before and during treatment. Ninety-one dogs were included [including one cavalier King Charles spaniel]: 25 received MC, 36 were treated with surgery, 11 with MTD chemotherapy and 19 received no treatment. QoL was improved in dogs receiving MC. Median TTP was significantly longer in patients receiving MC (172 days) than patients undergoing surgery (87 days), receiving MTD chemotherapy (22 days), or no oncologic treatment (20 days). Median ST was similarly longer in patients receiving MC (139 days) than those undergoing surgery (92 days), MTD chemotherapy (61 days) and no oncologic treatment (60 days). In dogs with advanced PPC, MC achieved a measurable clinical benefit without significant risk or toxicity. This makes MC a potential alternative to other recognized management approaches.

The dog as an animal model for bladder and urethral urothelial carcinoma: Comparative epidemiology and histology. Simone de Brot, Brian D. Robinson, Tim Scase Llorenç Grau‑Roma, Eleanor Wilkinson, Stephen A. Boorjian, David Gardner, Nigel P. Mongan. Oncology Letters. May 2018; doi: 10.3892/ol.2018.8837. Quote: Despite the recent approval of several novel agents for patients with metastatic urothelial carcinoma (UC), survival in this setting remains poor. As such, continued investigation into novel therapeutic options remains warranted. Pre‑clinical development of novel treatments requires an animal model that accurately simulates the disease in humans. The aim of the present study was to evaluate the dog as an animal model for human UC. A total of 260 cases of spontaneous, untreated canine primary urethral and urinary bladder UC, were epidemiologically and histologically assessed and classified based on the current 2016 World Health Organization (WHO) tumor classification system. Canine data was compared with human data available from scientific literature. The mean age of dogs diagnosed with UC was 10.22 years (range, 4‑15 years), which is equivalent to 60‑70 human years. The results revealed a high association between UC diagnosis with the female sex [odds ratio (OR) 3.51; 95% confidence interval (CI) 2.57‑4.79; P<0.001], surgical neutering (OR 4.57; 95% CI 1.87‑11.12; P<0.001) and breed (OR 15.11 for Scottish terriers; 95% CI 8.99‑25.41; P<0.001). Based on the 2016 WHO tumor (T), node and metastasis staging system, the primary tumors were characterized as T1 (38%), T2a (28%), T2b (13%) and T3 (22%). Non‑papillary, flat subgross tumor growth was strongly associated with muscle invasion (OR 31.00; P<0.001). Irrespective of subgross growth pattern, all assessable tumors were invading beyond the basement membrane compatible with infiltrating UC. Conventional, not further classifiable infiltrating UC was the most common type of tumor (90%), followed by UC with divergent, squamous and/or glandular differentiation (6%). Seven out of the 260 (2.8%) cases were classified as non‑urothelial based on their histological morphology. These cases included 5 (2%) squamous cell carcinomas, 1 (0.4%) adenocarcinoma and 1 (0.4%) neuroendocrine tumor. The 2 most striking common features of canine and human UC included high sex predilection and histological tumor appearance. The results support the suitability of the dog as an animal model for UC and confirm that dogs also spontaneously develop rare UC subtypes and bladder tumors, including plasmacytoid UC and neuroendocrine tumor, which are herein described for the first time in a non‑experimental animal species. (Image (B) above is a microphotograph of a flat urothelial carcinoma in the urinary bladder in an 11-year-old male neutered Cavalier King Charles spaniel.)

Canine visceral hemangiosarcoma treated with surgery alone or surgery and doxorubicin: 37 cases (2005–2014). Karen Batschinski, Alessandra Nobre, Ernesto Vargas-Mendez, Marcello V. Tedardi, Juliana Cirillo, Greice Cestari, Rodrigo Ubukata, Maria Lucia Z. Dagli. Canadian Vet. J. September 2018;59(9):967-972. Quote: The purpose of this retrospective study was to determine survival times and prognostic factors of dogs with visceral hemangiosarcoma (HSA) treated with surgery alone or surgery and doxorubicin. Medical records from 2 hospitals from 2005 to 2014 were searched for dogs with histopathologically confirmed visceral HSA. Data relevant to patient demographics, tumor characteristics, and outcomes were abstracted. The most common primary organ affected was the spleen; however, primary tumor location had no influence on prognosis. Twenty-three dogs were treated with surgery alone, while 14 dogs were treated with surgery and doxorubicin. There was a significant difference in survival times between dogs treated with surgery alone and with surgery followed by doxorubicin (66 days versus 274 days). Dogs with stage I tumors (196 days) had a longer median survival time (MST) than dogs with stage II (117 days) and stage III (23 days) disease. The overall MST was 179 days with a 1-year survival rate of 29.2%.

Epithelial-Myoepithelial Carcinoma in a Canine Salivary Gland. C.-H. Park, N. Shiwa, J. Sumimoto, K. Kimitsuki. J. Comp. Path. October 2018;165:52-56. Quote: A 7-year-old male cavalier King Charles spaniel was presented with a cervical subcutaneous mass. The mass had a multilobular growth pattern and each individual lobule contained ductal epithelial cells and myoepithelial cells surrounding the ductal cells. Immunohistochemically, the ductal epithelial cells were positive for cytokeratin (CK) 7 and CAM5.2 and the myoepithelial cells were positive for a-smooth muscle actin and p63. Both types of cells were positive for CK14, a myoepithelial cell marker. Ultrastructurally, the ductal epithelial cells were attached by desmosomes and contained abundant intracytoplasmic tonofilaments. Some ductal epithelial cells contained myofilaments characteristic of myoepithelial cells. Based on these findings, a diagnosis of epithelial-myoepithelial carcinoma was made. It is presumed that the tumour originated from an intercalated duct in a parotid salivary gland.

Incidence and risk factors for the diagnosis of lymphoma in dogs in UK primary-care practice. C. Pittaway, I. Schofield, J. Dobson, D. G. O’Neill, D. C. Brodbelt. J. Sm. Anin. Pract. July 2019; doi: 10.1111/jsap.13054 Quote: Objectives: To identify the incidence, risk factors and presenting signs of lymphoma in dogs presenting to primary‐care practice in the UK using analysis of data within the VetCompass™ programme. Materials and Methods: Case records from the VetCompass™ programme from primary-care practices in the UK were searched for newly diagnosed lymphoma in dogs within a 1-year period: 2013. Diagnosis was based on clinical records with or without laboratory confirmation. Signalment was evaluated as risk factors for lymphoma diagnosis using multivariable logistic regression. Results: There were 286 presumed newly diagnosed cases [7 were cavalier King Charles spaniels] identified during 2013 from 455,553 dogs (overall incidence risk 63 of 100,000 dogs per year [CKCS incidence risk was 69 of 100,000]) of which 193 (67%) were laboratory confirmed (42 of 100,000 dogs per year). Advanced age, dogs older than 12 years, dogs weighing more than 30 kg and some specific breeds were significantly associated with lymphoma diagnosis. Only 18 dogs (6%) of the population identified were referred to a specialist clinic. Clinical Significance: This study concurs with others that age, bodyweight and breed are significant risk factors for lymphoma. Results of this study highlight: (1) the low number of dogs with lymphoma that are referred to specialists in the UK and (2) that few dogs undergo immunophenotyping (which can carry prognostic importance), emphasising the importance of epidemiological programmes that evaluate diseases presented to primary-care veterinarians.

What is your diagnosis? Subcutaneous inguinal mass in a Greyhound. Claudio Petterino, Ines Hoffmann. Vet. Clin. Pathol. August 2019;doi: 10.1111/vcp.12769. Quote: Although benign proliferative sebaceous gland lesions such as nodular sebaceous gland hyperplasia or sebaceous adenoma are commonly seen in the skin of dogs, the cytologic features of a poorly differentiated sebaceous gland carcinoma with fibroblastic reaction are infrequently described in the literature. ... Proliferative lesions arising from sebaceous glands are subclassified in five subtypes as follows: sebaceous gland hyperplasia, sebaceous adenoma, sebaceous gland ductal adenoma, sebaceous gland epithelioma, and sebaceous gland carcinoma. The latter is considered to occur uncommonly in dogs and cats,2 and rarely in other domestic animals. No sex predilection has been reported; however, some canine breeds (eg, Cavalier King Charles spaniel, cocker spaniel, Siberian husky, Samoyed, and West Highland white terrier) seem to be predisposed. In dogs, sebaceous gland carcinoma mostly occurs on the head and neck ... Therefore, complete surgical excision with wide margins can be curative.

Ivermectin inhibits canine mammary tumor growth by regulating cell cycle progression and WNT signaling. Hongxiu Diao, Nan Cheng, Ying Zhao, Huihao Xu, Haodi Dong, Douglas H. Thamm, Di Zhang, Degui Lin. BMC Vet. Res. August 2019; doi: 10.1186/s12917-019-2026-2. Quote: Background: Mammary gland tumor is the most common spontaneous tumor in intact female dogs, and its poor prognosis remains a clinical challenge. Ivermectin, a well-known anti-parasitic agent, has been implicated as a potential anticancer agent in various types of human cancer. However, there are no reports evaluating the antitumor effects of ivermectin in canine mammary tumor. Here, we investigated whether ivermectin was able to inhibit canine mammary tumor development and explored the related mechanisms. Results: Ivermectin inhibited the growth of canine mammary tumor cell lines in a dose- and time-dependent manner. The antitumor effects induced by ivermectin were associated with cell cycle arrest at G1 phase via downregulation of CDK4 and cyclin D1 expression, with no significant induction of apoptosis. Furthermore, significantly reduced β-catenin nuclear translocation was observed after treatment with ivermectin, resulting in the inactivation of WNT signaling. Consistent with the results in vitro, a significant suppression of tumor growth by ivermectin was observed in canine mammary tumor xenografts. Conclusion: Ivermectin, as a promising anti-cancer agent, inhibits the growth of canine mammary tumor by regulating cell cycle progression and WNT signaling.

Breed-related expression patterns of Ki67, γH2AX, and p21 during ageing in the canine liver. Laura J. A. Hardwick, Andre J. Kortum, Fernando Constantino-Casas, Penny J. Watson. Vet. Res. Commun. December 2020; doi: 10.1007/s11259-020-09784-x. Quote: Cellular senescence is a molecular hallmark of ageing that is associated with multiple pathologies, and DNA damage marker γH2AX, together with cell cycle inhibitor p21, have been used as senescence markers in multiple species including dogs. Idiopathic canine chronic hepatitis has recognised breed-related differences in predisposition and prognosis, but reasons behind this are poorly understood. This retrospective study using archived post mortem tissue aimed to provide insight into liver ageing in 51 microscopically normal canine livers across seven breed categories [including 10 cavalier King Charles spaniels (19.6%) aged from 1 to 14 years], including those with and without increased risk of chronic hepatitis. Immunohistochemistry was conducted for γH2AX, p21, and cell proliferation marker Ki67, and the mean number of positive hepatocytes per high power field was determined. All three markers were strongly correlated to each other, but no age-dependent expression was seen in the combined study population. ... Age-dependence of marker expression was analysed within each breed group and ... CKCS showed a positive correlation between Ki67 and age. ... Overall expression levels were low in most dogs, with median values representing less than 1.5% of hepatocytes, but this increased to 20–30% in individual dogs at the upper end of the range. Individual breed differences were noted in two breeds that have increased risk of chronic hepatitis, with English Springer Spaniels having lower expression of Ki67 than other dogs, and Labradors having higher expression of Ki67 and γH2AX than other dogs. These results warrant further investigation in these breeds and highlight a need to validate reliable markers of cellular senescence in dogs.

Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment of canine mast cell tumors with tigilanol tiglate (EBC-46). Thomas R. De Ridder, Justine E. Campbell, Cheryl Burke-Schwarz, David Clegg, Emily L. Elliot, Samuel Geller, Wendy Kozak, Stephen T. Pittenger, Jennifer B. Pruitt, Jocelyn Riehl, Julie White, Melissa L. Wiest, Chad M. Johannes, John Morton, Pamela D. Jones, Peter F. Schmidt, Victoria Gordon, Paul Reddell. J. Vet. Intern. Med. January 2021; doi: 10.1111/jvim.15806. Quote: Objective: To evaluate the efficacy and safety of tigilanol tiglate (TT) for local intratumoral treatment of mast cell tumors (MCTs) in dogs. Methods: A randomized controlled clinical study in 2 phases involving 123 dogs with cytologically diagnosed MCT. Phase 1 compared 81 TT-treated dogs with 42 control dogs; phase 2 allowed TT treatment of control dogs and retreatment of dogs that failed to achieve tumor resolution after TT treatment in phase 1. Tigilanol tiglate (1 mg/mL) was injected intratumorally with dose based on tumor volume. Concomitant medications were used to minimize potential for MCT degranulation. Modified response evaluation criteria in solid tumors were used to evaluate treatment response at 28 and 84 days. Adverse events and quality of life were also assessed. Results: A single TT treatment resulted in 75% complete response (CR) (95% confidence interval [CI] = 61‐86) by 28 days, with no recurrence in 93% (95% CI = 82-97) of dogs by 84 days. Eight TT‐treated dogs that did not achieve CR in phase 1 achieved CR after retreatment, increasing the overall CR to 88% (95% CI = 77-93). Control dogs had 5% CR (95% CI = 1-17) at 28 days. Wound formation after tumor slough and wound size relative to tumor volume were strongly associated with efficacy. Adverse events typically were low grade, transient, and directly associated with TT's mode of action. Conclusions: Tigilanol tiglate is efficacious and well tolerated, providing a new option for the local treatment of MCTs in dogs.

Recurrence-free interval 12 months after local treatment of mast cell tumors in dogs using intratumoral injection of tigilanol tiglate. Pamela D. Jones, Justine E. Campbell, Graham Brown, Chad M. Johannes, Paul Reddell. J. Vet. Intern. Med. January 2021; 10.1111/jvim.16018. Quote: Background: Tigilanol tiglate (TT) is a novel small molecule approved by the European Medicines Agency for intratumoral treatment of mast cell tumors (MCTs) in dogs. In a randomized controlled clinical efficacy and safety study in the United States, 85 of 116 dogs that received a single TT injection achieved complete response (CR) of the treated MCT by day 28. : Objective: To evaluate the durability of the TT treatment response achieved at day 28 in the U.S. study by assessing MCT recurrence at the treatment site 6 and 12 months after TT administration. Animals: Eighty-five dogs previously treated with TT. Methods: Dogs that achieved CR at day 28 were assessed retrospectively for the presence or absence of MCT at the treatment site using records from clinical visits and telephone interviews with owners. Dogs unavailable at an assessment time were considered lost-to-follow-up and data for their last assessment used in the final analysis. Results: By 12 months after TT treatment, 64 dogs remained evaluable, with 21 unavailable. Of evaluable patients, 57 (89%) remained tumor free at the treatment site and 7 (11%) had developed recurrence. All recurrences occurred within the first 6 months, predominantly (5/7, 71%) within the first 12 weeks. Conclusions and Clinical Importance: Tigilanol tiglate provided a durable long‐term local response for the treatment of MCT in dogs.

Non-neoplastic anal sac disorders in UK dogs: Epidemiology and management aspects of a research-neglected syndrome. Dan G. O'Neill, Anke Hendricks, Jennifer A. Phillips, Dave C. Brodbelt, David B. Church, Anette Loeffler. Vet. Rec. March 2021; doi: 10.1002/vetr.203. Quote: Background: Non-neoplastic anal sac disorders (ASD) are frequent presentations for dogs in primary-care practice but evidence-based information on disease occurrence and risk is sparse. This study estimates prevalence, breed associations and other risk factors as well as reporting on clinical management. Methods: A cohort study of dogs attending VetCompass practices between 1 January 2013 and 31 December 2013. Risk factor analysis used multivariable logistic regression methods. Results: Of 104,212 dogs attending 110 UK practices, the 1-year period prevalence of ASD was 4.40% (95% CI: 4.22–4.57). Compared to crossbreds, six breeds showed increased odds of ASD (Cavalier King Charles spaniel, King Charles spaniel, Cockapoo, Shih-tzu, Bichon Frise and Cocker spaniel), and six breeds showed reduced odds (Labrador Retriever, Border collie, Staffordshire Bull Terrier, Lurcher, German Shepherd Dog and Boxer). Brachycephalic types had 2.6 times the odds for ASD compared to dolichocephalic types. Medication prescribed for ASD included antimicrobials (n = 480, 20.24%) and analgesics (n = 284, 11.97%). Anal sacculectomy was performed in under 1% of cases. Conclusions: High prevalence, strong breed predispositions and evidence of severity suggested from the antimicrobial and analgesic therapies combined with current substantial knowledge gaps identify ASD as a key research‐neglected syndrome in dogs.

Dog breeds and body conformations with predisposition to osteosarcoma in the UK: a case-control study. Grace L. Edmunds, Matthew J. Smalley, Sam Beck, Rachel J. Errington, Sara Gould, Helen Winter, Dave C. Brodbelt, Dan G. O'Neill. Canine Med. & Genetics. March 2021; doi: 10.1186/s40575-021-00100-7. Quote: Background: Osteosarcoma is an aggressive and painful bone neoplasm in dogs. Previous studies have reported epidemiological associations suggesting that large body mass, long bone length and the genetics of certain breeds including the Rottweiler are associated with elevated osteosarcoma risk. However, these studies were often limited by selection bias and confounding factors, and have rarely offered insights into breed-associated protection for osteosarcoma. The current study includes 1756 appendicular and axial osteosarcoma cases presenting to VPG Histology (Bristol, UK) compared against a control population of 905,211 dogs without osteosarcoma from primary care electronic patient records in the VetCompass™ dataset. Methods and study design: Retrospective, case-control study. Multivariable logistic regression analysis explored associations between demographic risk factors (including breed, chondrodystrophy, age, sex/neuter status, skull-shape, and body mass) and osteosarcoma of all anatomical sites. Results: We identified several breeds with increased and reduced odds of osteosarcoma. At highest risk were the Rottweiler and Great Dane, with >10 times the odds of osteosarcoma compared with crossbreds, and the Rhodesian Ridgeback, which has not featured in previous lists of at-risk breeds for osteosarcoma, and had an odds ratio of 11.31 (95% confidence interval 7.37–17.35). Breeds at lowest risk of osteosarcoma (protected breeds) included the Bichon Frise, the French Bulldog and the Cavalier King Charles Spaniel, all with odd ratios of less than 0.30 compared with crossbreds. Body mass was strongly associated with osteosarcoma risk; dogs over 40 kg exhibited osteosarcoma odds of 45.44 (95% confidence interval 33.74–61.20) compared with dogs less than 10 kg. Chondrodystrophic breeds had an osteosarcoma odds ratio of 0.13 (95% confidence interval 0.11–0.16) compared with non-chondrodystrophic breeds. Conclusions: This study provides evidence of strong breed-associated osteosarcoma risk and protection, suggesting a genetic basis for osteosarcoma pathogenesis. It highlights that breeds selected for long legs/large body mass are generally overrepresented amongst at-risk breeds, whilst those selected for short leg length/small body mass are generally protected. These findings could inform genetic studies to identify osteosarcoma risk alleles in canines and humans; as well as increasing awareness amongst veterinarians and owners, resulting in improved breeding practices and clinical management of osteosarcoma in dogs.

Computed tomography of a spontaneous subserosal duodenal haematoma in a cavalier King Charles spaniel. K. R. Schaul, J. J. Karnia, O. T. Skinner. J. Sm. Anim. Pract. June 2021; doi: 10.1111/jsap.13376. Quote: An 8-year-old, spayed female Cavalier King Charles Spaniel, weighing 13.8 kg, was presented to her primary care veterinarian after developing anorexia, vomiting, diarrhoea and progres sive abdominal distension that did not respond to outpatient therapy over the course of 1 week. Initial supportive care at a second veterinary hospital for suspected pancreatitis resulted in no clinical improvement. Physical examination following referral to the University of Missouri revealed abdominal distension and a right-sided abdominal mass, palpable caudal to the last rib. A pre- and post-contrast (Omnipaque 350, GE Healthcare) CT scan of the abdomen demonstrated a 5.9×4.5×8 cm, soft tissue- attenuating mass (average 61.3 Hounsfield units) with peripheral contrast enhancement and well-defined borders, eccentrically surrounding the descending duodenum and causing narrowing of the duodenal lumen (Fig 1A, B). Surgical exploration revealed a 6.5×6×3.5 dark red mass along the antimesenteric aspect of the descending duodenum, extending from the major duodenal papilla to the level of the caudal portion of the pancreas (Fig 1C). Incision of the mass revealed clotted blood between the serosal and muscularis layers of the duodenal wall (Fig  1D). Follow ing debridement, an intact, viable muscularis layer was revealed (Fig 1E) and the serosal defect was omentalised before closure. Histopathology of the mass was consistent with a haematoma; immunohistochemical staining with CD31 did not identify evidence of occult hemangiosarcoma. The dog recovered unevent fully and was clinically normal 15 months post-operatively.

Intratumoural Treatment of 18 Cytologically Diagnosed Canine High-Grade Mast Cell Tumours With Tigilanol Tiglate. Graham K. Brown, Justine E. Campbell, Pamela D. Jones, Thomas R. De Ridder, Paul Reddell, Chad M. Johannes. Front. Vet. Sci. August 2021; doi: 10.3389/fvets.2021.675804. Quote: Canine high-grade mast cell tumours (HGMCT) are associated with a poor prognosis, are inherently more invasive, and have higher rates of local recurrence. The primary aim of this retrospective study was to assess the efficacy of intratumoural tigilanol tiglate (TT) as a local treatment option. Eighteen dogs with mast cell tumours (MCT) cytologically diagnosed by veterinary pathologists as either high-grade or suspected high-grade MCT were treated with TT. ... Larger breed or mixed breed dogs were over-represented with Staffordshire Bull Terriers making up over a quarter of the group and no other breed had more than one individual. ... The TT dose was based on tumour volume (0.5 mg TT/cm3 tumour volume) and delivered intratumourally using a Luer lock syringe and a fanning technique to maximise distribution throughout the tumour mass. Efficacy was assessed on the presence/absence of a complete response (CR) to therapy at days 28 and 84 using response evaluation criteria in solid tumours (RECIST). For dogs not achieving a CR after 28 days, the protocol was repeated with a second intratumoural TT injection. Ten out of 18 dogs (56%) in this study achieved and maintained a CR to at least 84 days after their first or second treatment. Six patients were alive and available for evaluation at 2 years, three of those were recurrence free, and a further three patients were recurrence free following a second treatment cycle. Tigilanol tiglate shows efficacy for local treatment of HGMCT, with higher efficacy noted with a second injection if a CR was not achieved following the first treatment. In the event of treatment site recurrence (TSR), the tumour may be controlled with additional treatment cycles. Tigilanol tiglate provides an alternative local treatment approach to dogs with HGMCT that would either pose an unacceptable anaesthetic risk or the tumour location provides a challenge when attempting surgical excision.

Lokivetmab improved pruritus in a dog with cutaneous epitheliotropic lymphoma. Kiyohiko Inai, Keita Kitagawa, Mami Murakami, Toshiroh Iwasaki. J. Vet. Med. Sci. December 2021; doi: 10.1292/jvms.21-0346. Quote: A 13-year-old spayed female Cavalier King Charles Spaniel presented with chronic swelling and pruritus on the palmar aspect of the left forepaw and on the tail. Cutaneous epitheliotropic lymphoma (CEL) was diagnosed by histopathology and immunocytochemistry. Prednisolone was initially used alone as an alternative treatment for CEL. Despite long-term corticosteroid therapy, the patient's physiological (pruritus) and dermatological signs (alopecia, erythema, erosion, and ulceration with crust) progressed and showed no evidence of improvement. To address the worsening condition of pruritus, lokivetmab was started in combination with prednisolone. Once on lokivetmab, the pruritus steadily improved and was effective in resolving and maintaining remission. ... In human medicine, it has been reported that the expression of serum IL-31 in cutaneous T-cell lymphoma (CTCL) patients is upregulated. Decreasing serum IL-31 levels are correlated with the resolution of pruritus in CTCL patients. Lokivetmab, a monoclonal antibody used to treat CAD [canine atopic dermatitis], is reported to neutralize IL-31 and mitigate canine pruritus. Although lokivetmab is not indicated for the treatment of CEL, it was used in the hope of reducing pruritus. In this case of CEL, lokivetmab decreased pruritus. Thus, anti-IL-31 therapy appears to be a potential treatment option in controlling pruritus associated with CEL in dogs. ... Further investigation on the critical role of IL-31 in the pruritus pathway of dogs with CEL is required.

Large granular lymphocyte lymphoma in the skin and urinary bladder of a dog. Mami Adachi, Hirotaka Igarashi, Minoru Okamoto, Takashi Tamamoto, Yasutomo Hori. J. Vet. Med. Sci. January 2022; doi: 10.1292/jvms.21-0201. Quote: A 10-year-old female Cavalier King Charles Spaniel presented with hematuria, pollakiuria and skin rash. Based on the histopathological and cytological examination of the skin and bladder mucosa, the dog was diagnosed with large granular lymphocytic (LGL) lymphoma of the bladder and skin. The dog responded well to the initial chemotherapy with nimustine for 3 months. Since recurrence of skin erosion and bladder wall thickening were observed, the dog was subsequently administered chemotherapy with other anticancer drugs, including chlorambucil, vincristine, doxorubicin, L-asparaginase, cytosine arabinoside, and cyclophosphamide. The dog survived for 11 months and died due to tumor-related disseminated intravascular coagulation. This is the first report of a canine case of LGL lymphoma in the skin and bladder.

Metastatic osteosarcoma tumor thrombus in a Cavalier King Charles Spaniel presenting with dyspnea. Alex Shirlow, Kieran Borgeat, Nicolette Hayward, Emma Scurrell, Jessie Rose Payne. J. Vet. Cardiol. March 2022; doi: 10.1016/j.jvc.2022.03.003. Quote: A six-year-seven-month-old female neutered Cavalier King Charles Spaniel was referred for investigation of progressive dyspnea and hyphema in the right eye with secondary glaucoma. Previous medical history included a high-grade soft tissue spindle cell sarcoma removed from the cranial sternal region one year before. On presentation at the referral hospital, the dog was tachypneic and dyspneic. The heart rhythm was regular and there was a soft left-sided systolic murmur. Echocardiography identified the presence of a mass significantly occluding left heart inflow, with no other lesions identified. Thoracic radiographs documented a localized alveolar pattern within the left caudal lung lobe. The size of the heart and pulmonary vessels were within normal limits, indicating a non-cardiogenic alveolar pattern. Given the clinical presentation of dyspnea and high index of suspicion of intra-cardiac neoplasia, the dog was considered to have a grave prognosis and therefore euthanized. Post-mortem gross and histopathologic examination revealed the presence of a metastatic osteosarcoma tumor thrombus in the left atrium and pulmonary vein, metastatic osteosarcoma infiltrating the myocardium, lungs, the uveal tract of the right eye, and both adrenal glands. Whitney grade II myxomatous changes were noted on the mitral and tricuspid valve leaflets. This report describes an unusual intra-cardiac tumor thrombus in a dog presenting with dyspnea. Cavalier King Charles Spaniels presenting with dyspnea often raise suspicion for myxomatous mitral valve disease. However as demonstrated in this case, other more unusual causes of dyspnea should also be considered in the absence of classic clinical findings.

Cutaneous epitheliotropic lymphoma (CETL) in dogs: Regarding two clinical cases. arolina Maturana Nolia. Univ. Autònoma de Barcelona. June 2022. Quote: Introduction and objectives: CETL is a neoplastic disease characterized by the infiltration of T lymphocytes into the epidermis. The object of this study is to review clinical and experimental articles and compare the information obtained to two clinicalcases. ... Case 1: Patient: Cavalier King Charles Spaniel, female, 9 years old [right]. Previous history: cutaneous problems - allergy. Progression: 8-9 months. Multifocal alopecia, generalized desquamation, pruritus, and mucocutaneous lesions. Treatment: 1st Lomustine + prednisone, 2nd rabacfosadine + prednisolone, 3rd masitinib + prednisolone, 4th CHOP, and 5th chlorambucil. Response: Complete remission for 3 months with rabacfosadine. Progression of the disease resulting in death under palliatives. ... Conclusion: Due to its low prevalence and difficulty to follow up on cases, the information concerning CETL is scarce. The cytotoxic drugs used in both cases are the most common for CETL, and likewise, the need to use more than one therapy is frequent. Radiotherapy is applied in animals with localized lesions, as in case 2. This therapy was applied after the dog showed resistance to cytotoxic drugs that are usually used. The time of survival of both dogs was within the expected considering the presentation of the lesions.

Evaluation of the anti-tumour activity of Coriolus versicolor polysaccharopeptide (I'm-Yunity) alone or in combination with doxorubicin for canine splenic hemangiosarcoma. Allison Gedney, Pascale Salah, Jennifer A. Mahoney, Erika Krick, Reenie Martins, Heather Scavello, Jennifer A. Lenz, Matthew J. Atherton. Vet. & Comparative Oncology. September 2022; doi: 10.1111/vco.12823. Quote: Canine splenic hemangiosarcoma (HSA) is an aggressive tumour of vascular endothelium that carries a grave prognosis following standard of care treatment with surgery and doxorubicin. A previous pilot study revealed potential anti-tumour activity of I'm-Yunity polysaccharopeptide (PSP) for canine HSA. The aim of this prospective study was to assess patient outcome when treated with PSP alone or in combination with doxorubicin post-splenectomy compared to patients treated with surgery and doxorubicin that received a placebo in place of PSP. Dogs undergoing splenectomy for splenic HSA were eligible. Following splenectomy, owners were offered treatment with PSP alone or adjuvant doxorubicin chemotherapy (unblinded). Patients with owners that selected to proceed with doxorubicin chemotherapy were blindly randomized to receive placebo or PSP. Dogs were evaluated weekly for 15 weeks, then scheduled for monthly visits until death. One hundred and one dogs were included in the final analysis: 51 PSP alone, 25 doxorubicin/placebo, and 25 combination PSP/doxorubicin. On multivariate analysis, dogs treated with single agent PSP, female dogs, decreased haematocrit at diagnosis, and stage III disease were negatively significantly associated with outcome; however, an interaction between treatment group and sex was documented. Gender-specific outcomes revealed no significant difference in survival between treatment groups for male dogs, but female dogs treated with PSP alone had significantly reduced survival compared to females receiving doxorubicin/placebo (HR 0.21; p = .004). Anaemia (HR 5.28; p < .001) and stage III disease (HR 2.9; p = .014) remained negatively associated with survival when controlling for sex and treatment group. The addition of PSP to doxorubicin post-splenectomy did not improve survival in dogs with splenic HSA.

Clinical course and MRI lesion progression over four year in a dog with final diagnosis of high-grade oligodendroglioma in the forebrain. F. Graciolli Tomazi, V. M. Stein, A. Oevermann, F. Meneses, A. Maiolini. Vet. Suisse Fakultät, Univ. Bern. September 2022. Quote: Introduction: Oligodendroglioma is a common primary intracranial tumour in dogs, that can present as cystic lesions, with possible intralesional hemorrhages, usually characterized as a well-defined mass, Dogs with oligodendroglioma can remain stable over several years without specific treatment, particularly if no radiological progression is seen. This report describes serial clinical and imaging findings of a young dog with high-grade oligodendroglioma, that has been clinically and radiologically stable for four years, before acute deterioration occurred. Signalment, Timeline, & Overview of the Clinical Case: Female intact Cavalier King Charles Spaniel, 9-monthold at time of 1st presentation. Onset of paroxysmal episodes of pain and cervical scratching at age 6 months ... At 9 months: Primary brain tumor suspected; initiation of pallative treatment with dexamethasone, omeprazole, and gabapentine. ... Acute onset of generalized tonic-clonic seizures, rapid neurological deterioration to sudden death at 4 years and 9 months. ... Final pathological diagnosis: Anaplastic oligodendroglioma (WHO grade III) with subarachnoidal and intraventricular drop metastasis. Conclusion: This is the first report describing the long-term clinical course and MRI lesion progression of a dog eventually diagnosed with high-grade oligodendroglioma. Even though it remains unclear whether this tumor was a grade III/anaplastic oligodendroglioma from the beginning or progressed to a high grade tumor, it was present at very early age (9 months) and remained relatively stable over 3 years. The solid part of the tumor only increased with the last 1.5 years. Therefore, it might be worthwhile to implement pallative therapy and do regular follow-ups in oligodendroglioma. Although oligodendroglioma is a common primary intracranial tumor in dogs, survival data are scarce because of lack of systematic and prospective follow-up studies. It is highly desirable to collect prospective follow-up data from a large oligodendroglioma cohort to identify prognostic factors.

Clinical course and MRI lesion progression over four years in a dog with final diagnosis of high-grade oligodendroglioma in the forebrain. F. Graciolli Tomazi, V. M. Stein, A. Oevermann, F. Meneses, A. Maiolini. 34th Symposium ESVN-SCVN; P84. J. Vet. Intern. Med. September 2022; doi: 10.1111/jvim.17218. Quote: A 9-month-old female intact Cavalier King Charles Spaniel was presented with a 3-month history of paroxysmal episodes of pain and cervical scratching. MRI revealed a large left frontal lobe intra-axial complex cystic lesion with faint incomplete rim enhancement, transtentorial and transforaminal brain herniation, and cervical syringomyelia. A primary brain tumor (glioblastoma or anaplastic astrocytoma), or less likely a parasitic cyst where suspected. Palliative treatment (dexamethasone, omeprazole, gabapentine) reduced the frequency of the paroxysmal episodes. On MRI recheck 30 months later, the lesion showed comparable size, evidence of hemorrhage or mineralization, and regressive signs of increased intracranial pressure and perilesional edema. Considering the clinical evolution and rather benign biological behavior, porencephaly, congenital cystic malformations or less likely a parasitic cyst where then considered as differentials for the lesion. The patient remained clinically stable for another 19 months until generalized, tonic-clonic, epileptic seizures acutely occurred. The neurological status subsequently deteriorated over 48 hours to stupor, cardiovascular arrest and eventually death. Post-mortem MRI showed lesion progression characterized by increased size, increased soft tissue component, invasion of the left lateral ventricle, transtentorial and transforaminal brain herniation. Neuropathology revealed an anaplastic oligodendroglioma (WHO grade III) with subarachnoidal and intraventricular drop metastasis. Although oligodendroglioma is a common primary intracranial tumor in dogs, survival data are scarce because of lack of systematic and prospective follow-up studies. This is the first report describing the long-term clinical course and MRI lesion progression under palliative treatment of a dog eventually diagnosed with high-grade oligodendroglioma.

Tonsillar carcinoma in dogs: Treatment outcome and potential prognostic factors in 123 cases. Elisabetta Treggiari, MacKenzie A. Pellin, Giorgio Romanelli, Gianluca Maresca, Irina Gramer, Andrew D. Yale, Evi Pecceu, Matteo Pignanelli, Juan Borrego, Katarzyna Purzycka, Davide Berlato. J. Vet. Intern. Med. January 2023; doi: 10.1111/jvim.16623. Quote: Background: Tonsillar carcinomas are rarely reported in dogs. Information on outcome after treatment is sparse and prognosis is guarded to poor. Hypothesis/Objectives: Assess treatment outcome and potential prognostic factors in a population of dogs with cytological or histopathological diagnosis of tonsillar carcinoma. Animals: A total of 123 client-owned dogs with diagnosis of tonsillar carcinoma confirmed by cytology or histopathology. Methods: Retrospective, multi-institutional study. Medical records of 12 institutions were reviewed from 2012 to 2021 [, including 17 (14%) cavalier King Charles spaniels, the most predominent breed.] ... Our study population included 123 dogs. Interestingly, some breeds seemed overrepresented, particularly [cavalier King Charles] spaniels and collies. This observation is consistent with previous studies, and these breeds could be predisposed to developing tonsillar cancer. Results: Treatment included surgery, chemotherapy (conventional, tyrosine kinasenhibitors or metronomic chemotherapy), radiotherapy, nonsteroidal anti-inflammatory drugs (NSAIDs) or a combination of these. Surgery was performed in 68 cases, chemotherapy was administered in association with NSAIDs in 64 cases, NSAIDs were used alone in 14 cases and in association with surgery in 21 cases, whereas radiotherapy was used alone or in combination with surgery or chemotherapy in 20 cases. Overall survival time (OST) was 126 days (95% confidence interval [CI], 88-164). Significantly longer survival was seen in dogs without evidence of metastatic disease (median survival time, 381 days; 95% CI, 116-646). Other significant positive prognostic factors included absence of clinicals signs at presentation, surgery (tonsillectomy), use of adjuvant chemotherapy and use of NSAIDs. Conclusion and Clinical Importance: Asymptomatic dogs, those treated with surgery, those that received adjuvant chemotherapy, and those that received NSAIDs may have a better prognosis than previously expected, but overall survival remains short for dogs with tonsillar carcinoma.

A pilot study of chemotherapy combinations in rats: Focus on mammary cancer treatment in female dogs. Pereira Silva, Priscila Akemi Yamamoto, Marilia Carneiro de Araújo Machado, Fabiane Maria Fernandes Neves, Francine Johansson Azeredo, Ana Carolyne Santana dos Santos Silva, Nicole Hlavac, Denis de Melo Soares, Ana Leonor Pardo Campos Godoy, Alessandra Estrela-Lima. Res. Vet. Sci. March 2023; doi: 10.1016/j.rvsc.2023.01.009. Quote: The use of combined chemotherapy is an essential alternative in treating breast cancer. However, knowledge of the pharmacokinetics of drugs is necessary to obtain maximum efficiency of the protocol and reduce adverse reactions. This study suggests for the first time the effect of the association of carboplatin with ivermectin and carboplatin with cyclophosphamide. This investigation was performed with 36 healthy Wistar rats, divided into four groups: group control, carboplatin (C), carboplatin preceded by ivermectin (C + IV), and carboplatin associated with cyclophosphamide (C + CI). Plasma concentrations quantification was performed using the High-Performance Liquid Chromatographic (HPLC) equipment with an Ultraviolet (UV) detector at eight different time points. Then, the animal was euthanized and necropsied. The bioanalytical method was validated for the two matrices (dogs and rats' plasma), with full validation in female dogs and partial validation in rats, as recommended by the EMA. In both matrices, the method was linear and reproducible. Here, we show the results in female rats' plasma. When comparing the experimental rats' groups (C; C + IV, and C + CI), there is a tendency to increase the bioavailability of carboplatin when used in association, a slight increase for C + IV and more evident to the C + CI group with an AUC rise higher than 2-fold (AUC0–∞ = 2983.61 for C; 4459.06 for C + CI; 7064.68 for C + CI min·mg·mL−1). The blood count, biochemistry profile, and histopathology of the organs revealed only alterations inherent to the metabolic effects of the drugs used. The carboplatin association with ivermectin appeared safe for this pilot group. We believe the carboplatin dose can be maintained without risk to the patient. However, in the carboplatin association with cyclophosphamide, a slight reduction in carboplatin's amount is suggested, seeking to avoid increased effects due to cyclophosphamide. Thus, studies with a more significant number per group must confirm the relevance of this pilot study.

Analyses of combination chemotherapy effectiveness for canine transmissible venereal tumor in 188 indigenous dogs. A Sabarinathan, Chhavi Gupta, A Thangamani, A Ganesan, M Balagangatharathilagar, Dr. V Prabaharan. Pharma Inovation J. April 2023; 12:4. Quote: Canine transmissible venereal tumor occurs in sexually active dogs of tropical and subtropical region. The tumor is of near constant karyotypic variation of 58-59 chromosomes against the normal chromosomes number of 78 in dogs. Southern district of Tamil Nadu state is well known for the pure germplasm of indigenous dog breeds namely, Chippiparai, Kanni, Rajapalayam and Kombai such indigenous breeds were more prone for the Canine Transmissible Venereal Tumor (CTVT). The study was carried out in 188 indigenous dogs confirmed with CTVT. In Group I 94 dogs were treated with Inj. Vincristine sulfate @ 0.025 mg per kg b.wt via Intravenous (IV) route at 7 days interval 4-8 doses. In group II 94 dogs were treated with Inj. Vincristine sulfate @ 0.025 mg per kg b.wt via Intravenous (IV) route along with Inj. Ivermectin @ 200 mcg per kg b.wt subcutaneous (SC) at 7 days interval 4-6 doses.

Vertebral Angiomatosis in a Dog. Teresa Gagliardo, Teresa Bruna Pagano, Silvana Lo Piparo, Veronica Bifara, Filena Bono, Salvatore Ruffino, Filippo Cinti. J. Am. Anim. Hosp. Assoc. January 2024; doi: 10.5326/JAAHA-MS-7384. Quote: A 3 yr old spayed female Cavalier King Charles spaniel was referred for insidious ataxia and paraparesis. A thoracolumbar lesion was suspected. Computed tomography showed focal osteolysis of the vertebral body and pedicles of T5. In addition, a hyperdense, extradural material within the vertebral canal, causing spinal cord compression on the right side, was present. The lesion was confirmed with magnetic resonance imaging. A T4-T5 hemi-dorsal laminectomy was performed to decompress the spinal cord. Histopathological examination was consistent with vertebral angiomatosis. After the surgery, the dog rapidly improved; however, 5 mo later the clinical signs relapsed. Vertebral angiomatosis is a vasoproliferative disorder, rarely reported as a cause of myelopathy in cats. This condition has not previously been reported in dogs. This case report describes the clinical features, the diagnostic findings, and the follow-up of a young dog with vertebral angiomatosis.

Risk factor analysis and clinicopathological characteristics of female dogs with mammary tumours from a single-center retrospective study in Poland. Izabella Dolka, Michał Czopowicz, Diana Stopka, Agata Wojtkowska, Ilona Kaszak, Rafał Sapierzyński. Sci. Rept. March 2024; doi: 10.1038/s41598-024-56194-z. Quote: This is a comprehensive retrospective study to characterize female dogs with canine mammary tumors (CMTs) using a dataset retrieved from the archives of the Division of Animal Pathology, Institute of Veterinary Medicine in Warsaw, and to identify prognostic factors. Clinical and histopathological data of 1447 dogs with CMTs were included. Malignant tumours were found in 83.3% (n = 1206), benign tumours in 11.7% (n = 169), and non-neoplastic lesions in 5.0% (n = 72) of dogs. Dogs most often had grade II carcinomas (38.2%, 215/562) of a single histological subtype (88.5%, 1281/1447), mostly simple carcinoma (35.3%, 510/1447). Dogs with a median age of 10 years significantly often had larger (≥ 3 cm) and malignant CMTs, whereas intact females had smaller tumours (median size 2.0 cm). However, the threshold value for the age of the dog in the differentiation of malignant and non-neoplastic/benign masses could not be determined. Most females were hormonally active (76.4%, 372/487). Hormonally active dogs significantly more often had multiple tumours. Multiple tumours were significantly smaller (median 2.5 cm) than single ones. Among pedigree dogs, small-breed dogs were mostly recorded (43%, 428/1006). Twelve breeds had an increased risk of CMTs, regardless of tumour behaviour, compared with the theoretical distribution of pedigree dogs in Poland. Four breeds were often affected only by malignant and other four breeds only by non-neoplastic/benign CMT. Large-breed dogs were significantly younger and affected by larger CMT (median 4 cm) compared with small- and medium-breed dogs. ... Based on the theoretical distribution of female pedigree dogs in Poland according to available registers of the Polish Kennel Club from years 2009–2019 ... fifteen breeds were significantly under-represented: ... Cavalier King Charles Spaniel. ... Cavalier King Charles Spaniel... were significantly underrepresented among dogs with malignant CMT. ... Ninety dogs with a malignant CMT and complete records were included in the full analysis of CMT-specific survival (CMT-SS) with a median follow-up time of 20.0 months. We showed that the timing of ovariohysterectomy in relation to mastectomy was significantly associated with grade, CMT-SS, and CMT-related death. We indicated the low diagnostic accuracy of palpation of regional lymph nodes (RLN) in the prediction of their metastatic involvement. By multivariable analysis, dogs with neoplastic emboli, tumour ulceration, and simple or complex carcinoma had a significantly higher risk of local recurrence. Tumour size > 3 cm was as a strong independent predictor of lung metastases. Compared with dogs with an easily separated localized tumour, dogs with a multiple/diffuse malignant CMT pattern had a fivefold higher risk of death. The risk of death was significantly higher in the presence of neoplastic emboli (~ fivefold) and tumour ulceration (~ fourfold). Furthermore, the presence of neoplastic emboli and large tumour size were independent predictors of CMT-related death.

Clinical course and MRI lesion progression over 4 years in a dog with final diagnosis of high-grade oligodendroglioma. Fabiana Graciolli Tomazi, Veronika M. Stein, Anna Oevermann, Felix Meneses, Arianna Maiolini. Vet. Rec. Case Rpts. November 2024; doi: 10.1002/vrc2.1037. Quote: A 9-month-old Cavalier King Charles Spaniel with 3-month history of paroxysmal episodes of cervical pain and scratching had a magnetic resonance imaging revealing a large intra-axial cystic lesion in the left frontal lobe, caudal transtentorial and foraminal brain herniation, and cervical syringomyelia. Despite suspected high-grade glioma, clinical signs improved under palliative treatment. Follow-up magnetic resonance imaging 2.5 years later showed a similar lesion size, with no radiological evidence of increased intracranial pressure. The differential diagnosis was reconsidered to possibly porencephaly, congenital cystic malformation or parasitic cyst. The dog remained clinically stable for 19 months before developing acute generalised, single, self-limiting seizures, deteriorating to cluster seizures, stupor, cardiovascular arrest and death. Postmortem magnetic resonance imaging revealed lesion progression with ventricle invasion. Neuropathology confirmed a high-grade oligodendroglioma with subarachnoid and intraventricular drop metastasis. This is the first report describing long-term clinical course and magnetic resonance imaging lesion progression under palliative treatment of a dog ultimately diagnosed with high-grade oligodendroglioma. (See also this September 2022 abstract report of this case.)