Oncology Flashcards
Screening for bovine papillomavirus type 13 (BPV13) in a European population of sarcoid-bearing equids
Flawed study: Focused only on previously BPV1/2-positive sarcoid samples, potentially overlooking mixed BPV infections in sarcoid-negative populations.
Absence of BPV13:
• None of the 135 sarcoid DNA samples tested positive for BPV13.
• Negative results were consistent across: Horses in Austria (n = 99). Donkeys in Italy and the UK (n = 36).
The absence of BPV13 DNA suggests:
• BPV13 may not play a significant role in sarcoid development in Europe.
• Its presence in Brazilian horses may indicate regional or geographic variation.
• The primers previously used for BPV1/2 detection can recognize BPV13, reducing the likelihood that BPV13 infections have been overlooked in earlier studies.
• Large-scale studies, including equids from other European regions, are required to further explore BPV13 prevalence.
• BPV13 was first identified in bovine papillomas in Brazil and later in Brazilian equine sarcoids.
• Studies in Southern Italy and Iraq demonstrated BPV13 presence in bovine and ovid papillomas, supporting its non-regional confinement.
Histological evidence of superficial inflammation is associated with lower recurrence of equine sarcoids following surgical removal
Recurrence Rate:
• 40.6% of sarcoids recurred at the surgical site. Median time to follow up 56 months
• Median time to recurrence: 6.8 months post-excision.
• The presence of superficial inflammation (within the upper third of the lesion) significantly reduced the odds of sarcoid recurrence. Adjusted odds ratio (OR): 0.32 (95% CI: 0.10–0.96; P = 0.04).
• Anatomical Location: Sarcoids on limbs had the lowest recurrence rates compared to other locations (P = 0.05), as shown by Kaplan-Meier analysis.
• Sex: Mares were more likely to develop sarcoids at new, distant sites compared to geldings and stallions (P = 0.03).
Role of Inflammation in Prognosis
• Superficial inflammation may act as a protective factor against sarcoid recurrence, possibly due to:
-Recruitment of immune cells (e.g., CD8+ lymphocytes) to eliminate residual tumor cells.
-Cytotoxic effects of neutrophils or macrophages leading to tumor modulation.
• Sarcoids with a lack of superficial inflammation may require more aggressive follow-up and adjunctive therapies to reduce recurrence risk.
• Combining surgical excision with treatments that induce localized inflammation (e.g., topical chemotherapeutics like 5-fluorouracil or immunostimulatory agents) may improve outcomes.
Cross-sectional comparison of superficial swab and fine-needle aspiration: Improving the diagnostic workup of horses with sarcoids
Overall BPV Detection:
• FNA: Detected BPV in 98% of sarcoids (95% CI: 95.3–100%).
• Swabs: Detected BPV in 70% of sarcoids (95% CI: 58.5–81.2%).
• Significant difference in favor of FNA (P = 0.0001).
Non-Ulcerated Sarcoids:
• FNA: BPV detected in 98% (95% CI: 91.4–100%).
• Swabs: BPV detected in 63% (95% CI: 50.4–76.6%).
• Difference was significant (P = 0.0001).
Ulcerated Sarcoids:
• Both methods detected BPV in 100% of cases, as swabs had direct access to lesion tissue.
Test Performance Metrics
Sensitivity:
• FNA: 98%.
• Swabs: 70%.
Specificity:
• FNA: 100%.
• Swabs: 92%.
Negative Predictive Value (NPV):
• FNA: 93% (improved likelihood of accurate exclusion of sarcoids).
• Swabs: 46%.
Accuracy:
• FNA: 98%.
• Swabs: 75%.
Advantages of FNA
• Consistently more accurate for all sarcoid types, especially those with intact epidermis.
• Lower risk of false positives due to superficial contamination or latent BPV presence in keratinocytes.
• Reduced likelihood of improper sampling compared to swabs.
‘Herbal’ preparations for equine dermal neoplasms contain large amounts of zinc chloride
All three “herbal black salve” products contained significant concentrations of zinc chloride:
• Xxterra®: 11.6% ZnCl₂
• Sarcoid Black Salve®: 13.7% ZnCl₂
• Newmarket Bloodroot Ointment®: 25% ZnCl₂
• Bloodroot (Sanguinaria canadensis) itself does not possess escharotic (tissue-destroying) properties. Claims that the products work solely through “immune stimulation” or bloodroot’s active properties are misleading.
• The observed effects, including tissue necrosis and eschar formation, are most likely due to zinc chloride.
Implications
• Efficacy and Mechanism of Action
-The caustic effect of zinc chloride likely explains the reported effectiveness of these “herbal” products in resolving sarcoids.
-While effective, this mechanism is non-selective, damaging both tumor and surrounding healthy tissues.
Risks and Side Effects
• Severe Tissue Reactions: ZnCl₂ at concentrations >10% is highly caustic, leading to: Necrosis of both neoplastic and healthy tissues.Potential for scarring and disfigurement.
• Unpredictable Outcomes: Variability in ZnCl₂ concentration between products and lack of standardization increase the risk of inconsistent results and adverse effects.
• Regulatory Concerns: “Herbal” branding is misleading, as these products contain a caustic chemical not derived from plants.
Clinical performance of a commercially available thymidine kinase 1 assay for diagnosis of lymphoma in 42 hospitalized horses
Median TK1 Levels:
• Lymphoma group: 3.0 U/L (range: 0.4–17.7).
• Non-lymphoma group: 3.9 U/L (range: 0.8–94).
No significant difference in TK1 activity between:
• Horses with lymphoma and those without (P = 0.59).
• Horses with neoplasia (any type) and non-neoplastic conditions (P = 0.69).
• Logistic regression found no association between serum TK1 activity and a diagnosis of lymphoma (Odds Ratio = 0.97; P = 0.48).
• Receiver Operating Characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.55, confirming poor predictive accuracy.
Clinical Observations
• Horses with inflammatory conditions and other neoplasia also exhibited elevated TK1 activity, indicating its non-specific nature.
• The highest TK1 value (94 U/L) occurred in a horse with a pheochromocytoma, emphasizing TK1 elevation in various proliferative or inflammatory states.
•The TK1 assay used (chemiluminescence immunoassay) differs from previously validated radioimmunoassays in horses, potentially affecting performance.
• previous study= was higher in horses with lymphoma vs clinically normal/inflam disease/ non haematopoeitic neoplasia.
• previous study had greater numbers
Strontium plesiotherapy for the treatment of sarcoids in the horse
• Complete Resolution: Achieved in all 10 lesions across 8 horses. Resolution occurred between 4 and 12 weeks post-treatment.
• No sarcoid recurrence observed at treated sites over a follow-up period of 6–30 months.
Localized and mild side effects were observed:
• Depigmentation (10/10 lesions).
• Alopecia (10/10 lesions).
• Leucotrichia (9/10 lesions).
• Mild dermatitis (5/10 lesions).
• One lesion inside a nostril developed more extensive dermatitis before healing but resolved without intervention.
Treatment Methodology
• Lesion preparation: Lesions ≤3 mm deep were suitable for treatment; deeper lesions required debulking beforehand.
• Single vs. Fractionated Treatment:
-Single Fraction: Applied for most lesions (6 lesions).
-Fractionated Protocol: Used in 4 lesions to minimize side effects, particularly for delicate areas like the eyelid or nostril.
• Delivered 100 Gy to the tumor margin, with a surface dose of approximately 250–350 Gy.
A pilot study on the use of ultra-deformable liposomes containing bleomycin in the treatment of equine sarcoid
• 44% (52/118) of all sarcoids treated achieved complete resolution at 12 months post-treatment.
• Combination therapies significantly outperformed single treatments:
-5-FU + Bleosome: 77% resolution.
-Tazarotene + Bleosome: 78% resolution.
•Single-agent treatments were less effective:
-Tazarotene: 17% resolution.
-5-FU: 27% resolution.
-Bleosome alone: 44% resolution (small sample size).
Pain and Tolerability
• Bleosome: No reported pain, discomfort, or inflammatory reactions.
• 5-FU and Tazarotene: Both caused significant pain, discomfort, and skin exudation during application, reducing compliance.
• Ease of Application: Bleosome was easily applied by owners following veterinary instruction. The preparation was absorbed rapidly into the lesion, requiring minimal handling time.
Mechanism of Action
• Bleomycin causes DNA damage by inducing single- and double-strand breaks, leading to tumor cell death.
• Liposome encapsulation enhances skin penetration, extending bleomycin’s biological half-life and reducing systemic toxicity.
Diagnostic potential of three serum microRNAs as biomarkers for equine sarcoid disease in horses and donkeys
eca-miR-331:
• Significantly upregulated in serum of ES-affected equids compared to tumor-free controls (P = 0.002).
• Area under the curve (AUC): 0.65, with sensitivity 60% and specificity 71%.
• Not significantly different between ES-affected horses and those with other skin tumors (melanoma, squamous cell carcinoma).
eca-miR-100 and eca-miR-1:
• No significant differences in expression between ES-affected horses, tumor-free controls, and horses with other skin tumors.
• Expression was affected by hemolysis, rendering them unreliable as biomarkers.
Influence of Biological and Preanalytical Variables
eca-miR-331:
• Expression was not influenced by species, breed, age, sex, hemolysis, ES type, or disease severity.
• Demonstrated robustness across samples of varying quality and biological variability.
eca-miR-100 and eca-miR-1:
• Expression was influenced by hemolysis, reducing their diagnostic utility.
Diagnostic Utility
• eca-miR-331 improved the probability of correctly identifying an ES-affected horse from 50% to 67%.
• However, as a single biomarker, its sensitivity and specificity were insufficient for routine clinical diagnosis.
Clinical Implications
• While eca-miR-331 was significantly upregulated in ES-affected horses, it lacks sufficient diagnostic accuracy for standalone use.
• Its inclusion in a panel of multiple microRNAs could enhance diagnostic precision.
• As an adjunctive tool, eca-miR-331 may aid in confirming equivocal clinical diagnoses or supplementing BPV PCR testing.
ALVAC-fIL2, a feline interleukin-2 immunomodulator, as a treatment for sarcoids in horses: A pilot study
Overall Response Rate (ORR): 86%.
• Complete Response (CR): 50% (7/14 horses).
• Partial Response (PR): 35% (5/14 horses).
• Stable Disease (SD): 7% (1/14 horses).
• Progressive Disease (PD): 7% (1/14 horses).
Time to Response:
• Median time to first response: 89 days (range: 34–406 days).
• Median time to best response: 211 days (range: 56–406 days).
• Three sarcoids were still shrinking at the final evaluation, suggesting delayed or prolonged responses.
Progression-Free Survival:
• Median progression-free interval was not reached during the study.
Adverse Events (AEs)
•Transient inflammation at the injection site in 2 horses (mild to moderate, resolved within 1–2 days).
• Leukotrichia (localized hair depigmentation) in 1 horse following complete response.
• No systemic effects or significant changes in hematological or biochemical parameters were observed.
Evaluation of a subcutaneously implanted biodegradable matrix with and without cisplatin in horses
Matrix III with 7% cisplatin achieved sustained local therapeutic concentrations (≥5 μg/g) for 35 days, minimizing the need for repeated administrations.
• Adequate platinum diffusion up to 9–12 mm from the implant suggests its potential for small to medium-sized neoplasms.
• Minimal systemic absorption of platinum (<1 ppm) suggests the method is safe with no systemic toxicity concerns.
• Although cisplatin caused prolonged inflammation and incomplete matrix degradation, clinical signs (e.g., discomfort) were insignificant.
• Highest platinum concentrations occurred at day 7 and gradually declined by day 35.
Genomic characterisation of bovine papillomavirus types 1 and 2 identified in equine sarcoids in Japan
BPV1 sequence variability is geographically specific rather than host-specific; BPV2 showed no significant trends
Sequence analysis of equine/bovine-derived samples showed no sarcoid-associated variants in four regions (E2, E5, L1 and LCR) of either BPV1 or BPV2.
