Oral Flashcards
Nemec et al. 2012. Histological subtype of oral non-tonsillar SCC in dogs
82% SCC were conventional SCC (CSS), 47.8% well-differentiated, 44.9% moderately-differrentiated and 7.3% poorly differentiated, 5.95% papillary SCC and basiloid SCC, 3.6% adenosquamous carcinoma, and 2.4% spindle cell carcinoma
Neutered female dogs, dogs aged 10-<15 years, English springer spaniel and Shetland Sheepdogs were overrepresentted
78% were proliferative with or without ulceration
71.4% located in dentate jaws, well differentiated CSCC more affected the tongue and othr non-dentate mucosal surfaces
No association was found between subtypes and TAI, perineural or lymphovascular invasion, or brtween gross appearance and tumor location
Frazier et al. Outcome in dogs with surgically resected oral FSA (1997-2008)
Oral FSA treated with surgical excision with or without adjuvant RT
21 dogs treated with surgery alone and 8 dogs with surgery and RT
Median PFI?
MST?
1- and 2- year survival rates?
Local recurrence rate?
Metastasis?
>653 days (1.8 yr)
743 days (2.0 yr)
88% and 58%
- 1%
- 1%
Gardner et al. Canine oral FSA: a retrospective analysis of 65 cases (1998-2010)
6 significant predictors of median survival were?
2 significant predictors of PFS were?
A combination of ___ and ___ was the strongest predictor of prolonged MS and PFS at ___ and ____ days
Location, tumor size and oral stage, type of surgery, margins, grade
Location, RT protocol
surgery and RT, 505 and 301 days
Culp et al. Results of surgical excision and evaluation of factors associated with survival time in dogs with lingual neoplasia: 97 cases
Rate of tumor recurrence?
Most common histopath diagnosis?
Rate of metastatic disease? Overall MST?
MST for SCC? MM?
Which dogs had shorter survival time?
28%
SCC (32%) and malignant melanoma (30%)
19%, 483 days (16 months)
216 days (7.2 mo), 241 days (8 mo)
Lingual tumors >2 cm
Fulton et al. Risk factors associated with survival in dogs with nontonsillar oral squamous cell carcinoma (OSCC):
Risk of death for the 21 dogs treated with surgery was?
1-year survival rate for dogs treated and not treated with surgery?
Risk of death increased with?
Tumor location, stage, and histologic subtype and survival time?
Decreased by 91.4% compared to dogs not treated with surgery
94% and 0%
Increasing TAI and increasing risk score (combination of TAI, PNI, LVI)
No association
Martin et al. Combined zoledronic acid and meloxicam reduced bone loss and tumor growth in an orthotopic mouse model of bone-invasinve oral SCC
___ inhibited osteoclastic bone resorption at tumor-bone interface
____ was more effective than ___ at reducing xenograft growth but did not affect bone resorption
Synergistic effect betwen meloxicam and ZOL?
ZOL
Meloxicam than ZOL
Not observed - combination was well tolerated
Delanet et al. Immunohistochemical and biochemical evidence of ameloblastic origin of amyloid-producing odeontogenic tumors (APOT) in cats
APOT are rare in cats
Antiameloblastine antibodies labeled neoplastic epithelial cells and amyloid in call cases
Neoplastic epithelial cells had strong, diffuse immunoreactivity to antibodies against AE1/AE3, cytokeratin 14, cytokeratin 19 and focal immunoreactivity to nerve growth factor receptor in 2 of 3 cases
Amyloid and some stromal cells weakly positive for laminin
Calretin, amelogenin, S100, GFAP did not label neoplastic epithelial cells
Feline APOTs and the amyloid are of ameloblastic lineage
Nemec et al. Oral papillary SCC in 12 dogs
PSCC is a histological subtype of oral SCC
Considered oral tumor of young animals
Majority (>75%) were what age?
All tumors were derived from?
What % were advanced tumors (T2 and T3)?
Microscopically 2 patterns seen: 1) invasion of bone forming a cup-shaped indentation in bone or deeply cavitating cyst (cavitating pattern)
2) Histologically malignant growth but lack of bone invasion (non-cavitating pattern)
Features suggest 2 distinct biological behaivours of COPSCC
> 6 years (median 9 years)
Gingiva of dentate jaws with 67% affecting rostral location
92%
Fulton et al. The expression of calretinin and cytokeratins in canine acanthomatous ameloblastoma and oral SCC
15 OSCC and 15 CAA, 6 tooth buds and 2 normal gingival tissues
CK expression?
Calretinin?
OSCC consistent with CAA and canine tooth bud tissue
10/15 OSCC and 2/15 CAA
Armory et al. 2013. CT characteristics of odontogenic neoplasms of dogs
All tumor types were a direct association with or in the region of multiple teeth in 96.4% (27/28), contrast enhancement in 96.3% (26/27), alveolar bone lysis in 93.1% (27/29), and mass-associated tooth displacement in 85.2% (23/27).
Canine acanthomatous ameloblastomas (n = 15) appeared as extra-osseous (10/15) or intra-osseous (5/15) masses. Intra-osseuouc more aggressive.
Amyloid-producing odontogenic tumors (n = 3) had subjectively uniform CT imaging characteristics and consisted of round soft tissue and mineral attenuating masses with multiple associated cyst-like structures.
Fibromatous epulides of periodontal ligament origin (n = 4) were contrast enhancing extra-osseous masses that were rarely referred for CT examinations and 25% (1/4) were not visible with CT.
Broome et al. Clincial feature and treatment outcomes of 41 dogs with sublingual ectopic thyroid neoplasia
Dogs with sublingual tumors were ___ and less likely to have ____ compared to eutopic thyroid carcinomas
21 dogs treated with surgery (partial hyoidectomy) 7 with radioiodine alone, 13 with surgery followed by radioiodine (radioiodine recommended for multifocal disease)
Overall MST?
Younger, metastatic disease (15% vs. 30%)
562 days (19 months)
Suzuki et al. The origin and role of autophagy in the formation of cytoplasmic granules in canine lingual granular cell tumors
GCTs are characterized by polygonal neoplastic cells with eosinophilic cytoplasmic granules
Derived from Scwann cells in humans
Canine lingual GCT originate from ___ and develop cytoplasmic granules via ___
Neural crest, autophagy
Soltero-Rivera et al. Benign and malignant proliferative fibro-osseous and osseous lesions of the oral cavity of dogs
Mestrinho et al. PCNA and grade in 13 canine oral SCC: association with prognosis
Median DFS for grade 3 tumors? grade 2?
Grade __ tumors and PCNA labeling index ___ were related with shorter DFST
Mean PCNA labeling index was ___ in recurrent cases
Grade and PCNA may be important prognostic factors in canine OSCC
138 days, not reached
Grade 3 and >65%
Significantly higher
Mestrinho et al. 2015. p63 and E-cadherin expression in canine oral SCC
All tumor cell has enhanced p63 expression
77% showed decreased E-cadherin immunoreactivity and 59% was cytoplasmic
Neither p63 nor E-cad were associated with tumor size, bone invasion, LN mets
p63 score was related to PCNA proliferative index
Aytpical p63 and cytoplasmic E-cad were related with higher tumor grade
Sabhlok et al. 2014. Palliative RT outcomes for cats with oral SCC (1999-2005)
Overall mean and median ST?
Mean and median ST receiving palliative RT alone?
Mean and median ST receiving RT and chemotherapy?
MST for sublingual tumors? mandibular tumors?
4 months (127d) and 3 months (92d)
157 and 113 days
116 and 80 days
135 days and 80 days
Munday et al. 2015. Molecular and IHC studies do not support a role for papillomavirus in canine oral SCC development
None of the primers amplified PV DNA but 4 had intense p16 staining - not due to PV infection
PVs are not significant cause of canine OSCCs
Bonfanti et al. 2015. Diagnostic value of cytological analysis of tumors and tumor-like lesions of the oral cavity in dogs and cats: a prospective study on 114 cases
The diagnostic accuracy of FNA, FNI, IS for dogs were?
The diagnostic accuracy of FNA, FNI, IS for cats were?
High agreement with histopathology suggets cytological examination are all appropriate to correctly diagnose lesions of the oral cavity
98%, 98%, 91%
95%, 95%, 95%
FNI - fine needle insertion
IS - impression smear
Milovancev et al. 2016. Antiproliferative effects of masitinib and imatinib against canine oral FSA in vitro
PDGFR-a and PDGFR-b
KIT and KDR?
The addition of ____ resulted in synergistic activity
Detected in neoplastic cells from most COF (5/6 and 6/6)
Not detected
Doxorubicin
Meier et al. Hypoxia-related marker GLUT-1, CAIX, Proliferative index and MVD in canine oral malignant neoplasia
Thierry et al. CT appearnce of canine tonsillar neoplasia: 14 cases
SCC>melanoma>LSA
Features associated with tonsillar neoplasia?
Medial retropharyngeal and mandibular lymphadenomegaly was ___
5 dogs had no enlargement of tonsil despit metastatic lymphadenomegaly
Consider tonsillar neoplasia with medial retropharyngeal lymphadenomegaly with normal sized tonsils
Marked enlargement, heterogeneity, loss of hypoattenuating hilus of medial retropharyngeal LN
ipsilateral to neoplastic tonsil 8/12 and 6/9 dogs
Pisamai et al. 2017. Gene expression of cell adhesion molecules, MMP and their inhibitors in canine oral tumors
Decreased CDH1, SDC1, NECTIN4 were observed in OSCC and OM
Downregulation of MMP in late-stage OM
Enhanced TIMP1 in all tumor groups
MMP14 expression in early stage OM
Higher MMP9 and TIMP1 in AA
Altered expression of adhesion molecules, MMP7 and MMP correlated wtih clininopathologic features whereas TIMP1 and MMP14 was probably associated with early stage tumors
Goldschmidt et al. 2017. Clinical characterization of canine AA in 263 dogs and the influence of postsurgical histopathological margin on local recurrence
Commonly presents where?
Breed overrepresented?
Local recurrence?
Raises question what the recommended margins should be
Rostral mandible in adult large breed dogs
Golden retrievers
None
Reiec et al. 2017. Evaluation of CBC Indices (NLR, PLR, MPV/PLT, and PLCRi) in healthy dogs with periodontis, and dogs with oropharyngeal tumors as potential biomarkers of systemic inflammatory response
Association between CBC indices and PD?
Indices in OT dogs which were significant?
None
NLR and PLCRi significantly higher in OT than HD and dogs with OD
PLCRi - platelet large cell ratio index
Cannon et al. 2017. Evaluation of protein kinase CK2 as therapeutic target for squamous cell carcinoma of cats
Expression of CK2a in feline oral mucosa samples and oral SCC samples?
Expression of CK2a and CK2a’ was downregulated with siRNA leading to?
Expressed in all mucosa samples and 7/8 SCC
decreased viability and apoptosis
Walz et al. 2017. Fatty acid synthase as a potential therapeutic target in feline oral SCC
High FASN (fatty acid synthase) expression in feline OSS
Orlistat, FASHN inhibitor, reduced cell viability in feline and human OSCC cell lines
FASN inhibition is a viable therapeutic target for feline OSCC
Antagonistic with carboplatin
van Ninwegen et al. 2017. Intratumoral injection of radioactive holmium (166 Ho) microspheres for treatment of oral SCC
Emit B-radiation
Local response rate?
MST?
55% - CR and PR allowing marginal resection
113 days and 296 days for patients with local response
Giuliano et al. 2016. Quantitative expression and co-localization of Wnt signaling protein in feline SCC
Cyclin D1 (CCND1 or CD1), FRA1, c-Myc, and MMP7
Expression of CD1 was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls
There was significant change in co-localization for all permutations (CD1/FRA1 etc.) except for nuclear localization of CD1
Supsavhad et al. 2016. p16, pRb, p53 in feline oral SCC
Majority of FOSCC have low p16 immunostaining intensity, therefore inactivation of CDKN2A may play a role in pathogenesis
A subset had increased p16 protein which supports an alternate pathogenesis
Olmstead et al. 2017. Tolerability of toceranib phosphate when used in conjunction with other therapies in 35 cats with oral SCC: 2009-2013
2.75 mg/kg 3 days a week
Toxicity?
Median treatment duration
Well tolerated by majority of cats
Seen in 6 cats - grade 1 and 2 GI toxicity and 1 grade 4 metabolic toxicity
Discontinued in 1 cat and 2 cats dose reduction
77 days
Wiles et al. 2017. Retrospective evaluation of Palladia in cats with oral SCC
Biological response rate?
MST with toceranib?
Cats achieving SD or better had significantly longer PFS and MST
Administration of NSAID?
56%
123 days vs. 45 days with no toceranib
Assciaited with significantly improved survival time
Kiobukowska et al. 2016. High numbers of stromal cancer associated fibroblats are associated with shorter survival time in cats with oral SCC
CAF express a-SMA - associated with poor prognosis in human cancers such as SCC
CAF-positive stroma identified in? MST in these cats?
Median ST for oropharygeal vs. maxillary, mandibular, sublingual?
Median ST for sublingual SCC was shorter compared to maxillary SCC
75%, 35 days vs. 48.5 days (CAF-negative SCC)
Significantly longer 179 days vs. 43.5 days. vs. 42 days. vs. 22.5 days
Brown et al. 2015. Characterization of STAT3 expression, signaling and inhibition in feline oral SCC
Yoshokawa et al. 2016. Predicting clinical outcome in feline oral SCC: tumor initiating cells. telomeres, and telomerase
20 cats underwent SRT
Significant inverse correlation detected between treatment outcomes and Bmi-1 expression - negative prognostic indicator
Telomere lenght exhibited variability, many tumors had high levels of TA - correlated with high levels of Bmi-1, Ki67 and EGFR
Bmi-1 and telomerase may represent therapeutic targets
Soltero-Rivera et al. 2014. Prevalence of regional and distant metastais in cats with advanced oral SCC: 49 cases (2005-2011)
Prevealence of LN metastasis?
Thoracic metastasis?
Patients with mandibulat LN mets, where were tumors located?
Pulmonary metastasis and tumor location?
31%
10%
53% maxillary, 27% mandibular, 13% sublingual, 7% caudal pharyngeal
3 mandibular, 1 maxillary, 1 sublingual mass
Yoshikawa et al. 2016. Assessment of predictive molecular variables in feline oral SCC treated with SRT
Median ST and PFI
Overall response rate?
Patients with higher ___ or more ___ had shorter ST and PFI
Females had ___ PFI and ST than males
106 days and 87 days
38.5%
higher MVD or more keratinized SCC
significantly longer PFI and ST
Randall et al. 2016. Evaluation of 18F-FDG PET/CT as a diagnostic imaging and staging tool for feline oral SCC
Yoshikawa et al. 2013. Comparison between 18-F-FDG-PET and contrast enhanced CT for measuring gross tumors volume in cats with oral SCC
Mean gross tumor volume was significantly smaller than mean CT gross volume in mandibular/maxillary SCC but not in lingual/laryngeal group
Mismatch fraction analysis revealed that most of the lingual/laryngeal patients had large region of high 18-F-FDG activity outside of CT gross tumor volume
Mismath fraction was significantly greater in the lingual/laryngeal group than mandibular/maxillary group
Modality detected regions of possible tumor not detected on CT images
Yoshikawa et al. 2012. Immunohistochemical characterization of feline oral SCC
22 tumor samples
Wide variation in Ki67 expression, MI, MVD, and EGFR expression
Tongue SCC has higher MVD than did mandibular or maxillary SCC
Tumor expression of EGFR was inversely proportional to survival time
Poirier et al. 2013. Efficacy and toxicity of an accelerated hypofractionated RT protocol in cats with oral SCC
21 cats
10 once daily fractions of 4.8 Gy
Acute toxicity?
Late toxicity?
Response?
Metastatic disease?
Median PFS?
Median OS?
Prognostic?
Grade 2 mucositis in all cats
Alopecia (4 cats), leukotrichia (6), tongue ulceration (1), oronasal fistula
7 CR and 5 PR
19%
105 days (1 year PFS 23%)
174 days (1 year OS 29%)
Tumor stage was prognostic with PFS 590 days
Pang et al. 2012. Identification of tumor initiating cells in feline head and neck SCC and evidence of gefitinib induced epithelial to mesenchymal transition
CD133 identified cells with sphere forming ability, reduced sensitivity to radiation and conventional chemotherpay and resistant to gefitinib (EGFR targeting drug)
Culture of cells in gefitinib causes change in cell morphology and gene expression reminiscent of epithelial to mesenchymal transition
Riggs et al. 2018. Outcomes following surgical excision combined with adjunctive, hypofractionated radiotherapy in dogs with oral SCC or FSA
87 dogs undergone maxillectomy or mandibulectomy got SCC or FSA
MST for all 87 dogs? SCC? FSA?
What was signifciant predictor of survival time?
Dogs undergoing RT after incomplete excision of oral SCC?
Postoperative RT for FSA?
2,049 days and not reached for SCC, 557 for FSA
Tumor type
MST 2051 days vs. 181 with no RT
No protective value - 299 days with RT and 694 without RT
MacLellan et al. 2018. Intraoperative and postoperative complications or partial maxillectomy for the treatment of oral tumors in dogs
Most common complication
Asscoaited with tumor size and location, maxillectomy type, surgical approach
Dogs treated with dorsolateral combined intraoral surgical approach were mor elikely to have bleding (83%) and longer mean duration of surgery than those treated with intraoral approach
Complication within 48 hours after surgery included?
bleeding 53% and 42.7% received blood transfusion
Epistaxis 51%, excesive facial swelling 37%, facial pawing 11%, difficulty eating 11.4%, wound dehiscence 11% and infection 8%
Stathopoulou et al. 2018. Evaluation of analgesic effect and absorption of buprenorphine after buccal administration in cats with oral disease
Maximum buprenorphine plasma concentration was observed 30 minutes after adminitration and had low inter-individual variability
Significant difference between baseline pain scores compared with pain scores after buprenorphine
Significant effect on stomatitis index on pain score
Cats with stomatitis showed lower bioavailability and shorter half life after bucal administration
Martano et al. 2018. Canine oral FSA: changes in prognosis over the last 30 years
Overall survival 247-743 days compared to 30-540 days before 2000
High local rate of recurrence 57%
Metastasis 10-14% and occurs late in disease course
Wide surgical excision, and combination of surgery and RT is best approach
Flickinger et al. 2018. Evaluation of long-term outcome and prognostic factors of feline SCC treated with PDT using liposomal phosphorylated meta-tetra chlorine
Overall response rate
Mean PFI
MST
Invasiveness yielded significant worse outsomce
Progression at <6 months with invasive tumors
Larger lesions associated with inferior control and treatment intensity, and tumor location did not influence response and duration
Advanced lesions are not indications for PDT
84%
35 months
40 months
Wainberg et al. 2018. Venteal cervical versus bilateral lateral approach for extirpation of mandibular and medial retropharyngeal lymph nodes in dogs
Sugical time for removal of all 4 LNs did not differ between the 2 approaches
Bilateral lateral approach was preferred by 62.5% of participants for visualization of mandibular LNs and ventral cervical approach was preferred by 87.5% for visualization of anatomy
Overall, 62.5% preferred the ventral apprach and 37.5% prefreed the bilateral lateral approach
Winer et al. 2017. The application of 3-D printing for preoperative planning in oral and maxillofacial surgery in dogs and cats