Approaches and methods to study wildlife cancer.

The last few years have seen a surge of interest from field ecologists and evolutionary biologists to study neoplasia and cancer in wildlife. This contributes to the One Health Approach, which investigates health issues at the intersection of people, wild and domestic animals, together with their changing environments. Nonetheless, the emerging field of wildlife cancer is currently constrained by methodological limitations in detecting cancer using non-invasive sampling. In addition, the suspected differential susceptibility and resistance of species to cancer often make the choice of a unique model species difficult for field biologists. Here, we provide an overview of the importance of pursuing the study of cancer in non-model organisms and we review the currently available methods to detect, measure and quantify cancer in the wild, as well as the methodological limitations to be overcome to develop novel approaches inspired by diagnostic techniques used in human medicine. The methodology we propose here will help understand and hopefully fight this major disease by generating general knowledge about cancer, variation in its rates, tumour-suppressor mechanisms across species as well as its link to life history and physiological characters. Moreover, this is expected to provide key information about cancer in wildlife, which is a top priority due to the accelerated anthropogenic change in the past decades that might favour cancer progression in wild populations.

Evaluation of lidocaine for brachial plexus blockade in eastern box turtles (Terrapene carolina carolina).

OBJECTIVE: To evaluate latency and duration of a brachial plexus block technique in eastern box turtles performed with 2% lidocaine at three dose rates. STUDY DESIGN: Prospective, randomized, blinded crossover study. ANIMALS: Adult eastern box turtles, two for drug dose evaluation and a group of six (three male, three female) weighing 432 ± 40 g (mean ± standard deviation) for the main study. METHODS: Animals were randomly assigned to four brachial plexus blocks with lidocaine at 5, 10 and 20 mg kg-1 or 0.9% saline (treatments LID5, LID10, LID20 and CON, respectively), separated by 1 week. Treatment side was randomized and blocks were performed unilaterally. Baseline observations of mentation, heart rate (HR), respiratory rate (fR), skin temperature and limb response to manipulation or toe pinch were evaluated. Assessments were made every 10 minutes until 1 hour of normal sensory and motor function to the treated thoracic limb, or for a total of 2 hours if no block was evident. RESULTS: Motor and sensory blockade was achieved in treatments LID10 and LID20 in one turtle, with a latency of 10 minutes and duration of 50 minutes for both doses. Raising of the ipsilateral lower palpebra occurred with both blocks. Turtles administered lidocaine experienced higher HR compared with CON, and HR decreased over time for all individuals. Mentation and fR were not changed with any lidocaine dose. CONCLUSIONS: The technique was unreliable in producing brachial plexus motor and sensory blockade at the lidocaine doses evaluated in this study. HR was higher in lidocaine-administered turtles but remained within normal limits for the species. No change in mentation or fR was observed among treatments. CLINICAL RELEVANCE: General anesthesia with systemic analgesia is recommended for surgical procedures involving the chelonian thoracic limb. Further studies are needed to optimize a brachial plexus block in this species.

HYPERKALEMIA IN FOUR ANESTHETIZED RED WOLVES (CANIS RUFUS).

Four clinically healthy red wolves (Canis rufus) developed hyperkalemia during routine anesthetic procedures. All cases were anesthetized using a combination of dexmedetomidine (10-24 mcg/kg), ketamine (2-3 mg/kg), and either midazolam (0.25-0.5 mg/kg) or butorphanol (0.2-0.48 mg/kg). Additional anesthetics were given to effect. Total anesthetic time ranged from 60 to 420 min. Three out of four cases were treated using terbutaline (0.01 mg/kg SC), which successfully resolved the hyperkalemia. No bradyarrhythmias were seen in any cases where electrocardiography (ECG) was monitored (3/4). All cases recovered from anesthesia, with one prolonged recovery. All animals are clinically healthy at the time of writing. Factors including anesthetic duration, the use of α-2 agonists, hyperthermia, and genetics are discussed as possible triggers for hyperkalemia. Serial blood gases, with electrolyte measurements, are recommended during anesthesia of red wolves, particularly when anesthetic time may be prolonged or the patient suffers from hyperthermia. Terbutaline appears to be a successful treatment should hyperkalemia arise.

Elephant Genomes Reveal Accelerated Evolution in Mechanisms Underlying Disease Defenses.

Disease susceptibility and resistance are important factors for the conservation of endangered species, including elephants. We analyzed pathology data from 26 zoos and report that Asian elephants have increased neoplasia and malignancy prevalence compared with African bush elephants. This is consistent with observed higher susceptibility to tuberculosis and elephant endotheliotropic herpesvirus (EEHV) in Asian elephants. To investigate genetic mechanisms underlying disease resistance, including differential responses between species, among other elephant traits, we sequenced multiple elephant genomes. We report a draft assembly for an Asian elephant, and defined 862 and 1,017 conserved potential regulatory elements in Asian and African bush elephants, respectively. In the genomes of both elephant species, conserved elements were significantly enriched with genes differentially expressed between the species. In Asian elephants, these putative regulatory regions were involved in immunity pathways including tumor-necrosis factor, which plays an important role in EEHV response. Genomic sequences of African bush, forest, and Asian elephant genomes revealed extensive sequence conservation at TP53 retrogene loci across three species, which may be related to TP53 functionality in elephant cancer resistance. Positive selection scans revealed outlier genes related to additional elephant traits. Our study suggests that gene regulation plays an important role in the differential inflammatory response of Asian and African elephants, leading to increased infectious disease and cancer susceptibility in Asian elephants. These genomic discoveries can inform future functional and translational studies aimed at identifying effective treatment approaches for ill elephants, which may improve conservation.

YERSINIA PSEUDOTUBERCULOSIS INFECTION IN LIONS (PANTHERA LEO) AT A ZOOLOGICAL PARK.

Two co-housed 17-yr-old male lions (Panthera leo) and one 15-yr-old female lion in an adjacent enclosure developed acute lethargy, depression, anorexia, and ataxia at a zoological park in central North Carolina, United States. One of the male lions and the female lion were found dead 5 and 4 d after the onset of clinical signs, respectively. The other male lion recovered without any clinical treatment. A third male lion housed with the female lion never developed clinical signs. Postmortem examination, microscopic evaluation, and bacterial culture of the liver from both deceased lions confirmed systemic Yersinia pseudotuberculosis infection. Susceptibility testing revealed resistance to amoxicillin-clavulanic acid and cefazolin. To investigate the extent of the outbreak, qualitative real-time polymerase chain reaction (PCR) for Y. pseudotuberculosis was performed on feces and substrate from 15 enclosures housing nondomestic felids and canids, resulting in a positive sample from one enclosure housing four asymptomatic lions. This enclosure was adjacent to housing of the deceased female lion. Enrofloxacin was administered to all animals in the vicinity at doses of 5 mg/kg in nondomestic felids and 10 mg/kg in nondomestic canids, orally q24h for 14 d. Repeated fecal PCR performed 1 wk after completing the antibiotic treatment protocol found no positive samples. The source of the infection was not identified despite PCR testing of environmental samples from all enclosures in the vicinity, the remains of a prey item fed out prior to the outbreak, and a single dead rodent found on grounds. No further clinical cases have occurred within the following year.

EVALUATION OF PROGNOSTIC INDICATORS FOR INJURED TURTLES PRESENTING TO A WILDLIFE CLINIC.

The Turtle Rescue Team (TRT) at North Carolina State University College of Veterinary Medicine currently sees over 500 chelonian cases a year. Each turtle receives a thorough physical examination as the main evaluation of its health because further diagnostics are cost prohibitive in a donation-based facility. Thus, there is a need to further understand how a few economical diagnostics can evaluate the prognosis of chelonians. The objectives were to evaluate lactate, PCV, total solids, glucose, temperature, and HR as prognostic indicators in multiple chelonian species and to determine how the change in lactate concentrations over a 24 h period affects prognosis. Eastern box turtles (Terrapene carolina carolina), yellow-bellied sliders (Trachemys scripta scripta), river cooters (Pseudemys concinna), painted turtles (Chrysemys picta), and common snapping turtles (Chelydra serpentina) were evaluated because of prevalence of presentation to the TRT, differences in habitat, and differences in physiology. Hyperlactatemia, an increased lactate over 24 h when the initial lactate concentration was greater than 5 mM/L, and anemia were determined to be significant prognostic indicators of mortality for all turtles, and hypoglycemia was a significant prognostic indicator of mortality for male turtles (P < 0.05).

Feasibility of a blind perineural injection technique for brachial plexus blockade in eastern box turtles (Terrapene carolina carolina): a cadaver study.

OBJECTIVE: To describe the anatomy of the brachial plexus in eastern box turtles (Terrapene carolina carolina), develop a blind perineural injection technique for brachial plexus blockade and evaluate the distribution of three volumes of new methylene blue dye for injection in cadavers. STUDY DESIGN: Prospective, randomized, blinded cadaveric study. ANIMALS: A total of 24 frozen-thawed box turtle cadavers; two turtles identified with shoulder injuries were subsequently excluded from the study. The remaining 22 turtles weighed 397 (190-581) g, median (range). METHODS: The brachial plexus and regional anatomy were identified by dissection of seven cadavers to determine anatomic landmarks for a perineural injection technique. This technique was tested by randomizing 15 cadavers into one of three groups to be injected bilaterally with one of three volumes (0.1, 0.2 or 0.3 mL) of methylene blue dye 1% aqueous solution. Investigators blinded to the assigned group dissected cadavers 15 minutes after injection and used staining of the four cervical spinal nerves (C5-C8; 25% for each nerve) to record a staining score of the brachial plexus (0-100%). RESULTS: Based on descriptions of the anatomy of the brachial plexus, an injection technique was designed. Injections of 0.1 mL methylene blue dye resulted in nine/10 injections with 100% nerve stained, and one/10 injection with 50% (two) nerves stained. All injections of 0.2 or 0.3 mL of methylene blue dye resulted in 100% nerves stained. CONCLUSIONS AND CLINICAL RELEVANCE: Perineural injection of the brachial plexus with 0.1, 0.2 or 0.3 mL methylene blue dye was successful in 29/30 injections in box turtle cadavers weighing 190-581 g. Further studies are needed to determine the minimum volume of injectate that can be successfully used for this technique, and to evaluate its application and efficacy in live turtles.

DIFFERENTIATING ENTEROPATHY-ASSOCIATED T-CELL LYMPHOMA TYPE 2 FROM INFLAMMATORY BOWEL DISEASE IN A SNOW LEOPARD (UNCIA UNCIA).

After a history of intermittent vomiting, endoscopic biopsies of stomach and duodenum were collected from a 13-yr-old male snow leopard (Uncia uncia). On microscopic examination, monomorphic small lymphocytes expanded the duodenal mucosa and occasionally formed intraepithelial nests. Immunohistochemistry of the infiltrating small lymphocytes in the mucosa and within the epithelium had strong, perimembranous labeling for CD3e, with few CD79a-positive lymphocytes located at the base of the villi. Polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR) of feline T-cell receptor gamma (TCRG) detected a monoclonal cell population. The sequence of the PCR product was 100% homologous with the feline TCRG gene. By histology, immunophenotyping, and PARR testing, a final diagnosis of enteropathy-associated T-cell lymphoma, small cell type, was made. Homology in the nucleotide sequence between U. uncia and the domestic cat (Felis catus) indicates that feline PARR testing for TCRG may be diagnostic in snow leopards.

EVALUATION OF ACUPUNCTURE POINTS GOVERNING VESSELS 1 AND 26 ON ANESTHETIC RECOVERY OF EASTERN BOX TURTLES ( TERRAPENE CAROLINA CAROLINA).

Intramuscular administration of anesthetic agents in chelonians may result in a prolonged (≥1 hr) return of spontaneous movement and breathing, which increases the probability for peri- and postoperative complications. The acupuncture point governing vessel (GV)-26 has been demonstrated to reduce anesthetic recovery times from inhalant anesthesia in other species. In this study, 30 eastern box turtles (EBT; Terrapene carolina carolina), presented to the Turtle Rescue Team at North Carolina State University's College of Veterinary Medicine for treatment of aural abscess, were divided into four groups: control (no treatment); GV-26 acupuncture; GV-1 and GV-26 acupuncture; or GV-1 and GV-26 electroacupuncture. Turtles receiving either GV-1 and GV-26 acupuncture or GV-1 and GV-26 electroacupuncture had a significantly reduced time to return of voluntary movement ( P = 0.012 and P = 0.006, respectively), a significantly reduced time to response of limb extension ( P = 0.03 and P < 0.001, respectively), and a significantly reduced time to anesthetic recovery ( P < 0.05 and P < 0.01, respectively). Therefore, the use of either GV-1 and GV-26 acupuncture or GV-1 and GV-26 electroacupuncture produces significant reductions in anesthetic recovery time in EBTs that have received injectable anesthetics.

EVALUATION OF HUSBANDRY AND MORTALITY IN LESSER HEDGEHOG TENRECS (ECHINOPS TELFAIRI).

Causes of morbidity and mortality for various species of tenrecs have not been widely published, aside from several reports of neoplasia, and these data are crucial for advancing objectives for preventive medicine, diagnosis, and treatment. A survey on husbandry, morbidity, and mortality of lesser hedgehog tenrecs ( Echinops telfairi ) in Association of Zoos and Aquariums (AZA) institutions was conducted. Out of 32 institutions, 20 responded with data for 98 living and 93 dead animals. The most common causes of mortality among the dead animals were neoplasia (24%), hepatic lipidosis (11%), septicemia (8.6%), pneumonia (8.6%), cardiomyopathy (7.5%), renal disease (6.5%), osteomyelitis (3.2%), and trauma (3.2%). There was no statistically significant correlation between sex and neoplasia. Data about educational usage were specifically provided by survey respondents for 50 of the tenrecs, with only 42% being excluded from educational programming. Tenrecs are common to many AZA institutions as both educational and exhibit animals, and this study provides a helpful reference for expected health problems and highlights the need for future investments into medical diagnosis and treatment for these animals.

OBSTETRICAL AND POSTPARTUM COMPLICATIONS IN LESSER MADAGASCAR HEDGEHOG TENRECS (ECHINOPS TELFAIRI): FOUR CASES.

Currently, little is known about diseases and health concerns in tenrecs, family Tenrecidae. During the past 10 yr of breeding lesser Madagascar hedgehog tenrecs ( Echinops telfairi ) at a single zoological institution, a diverse range of obstetric and postpartum complications have been observed: pyometra, metritis, retained fetal membranes, retained fetus, perinatal mortality, and maternal neglect with subsequent successful hand-rearing of neonates. Treatment of these problems is complicated in tenrecs because of their small size and secretive behavior. Some of the cases reported in this article had successful resolution by ovariohysterectomy or cesarean section. The four cases described in this report overall help to disseminate options and outcomes for the diagnosis, treatment, and management of obstetric and postpartum complications in this small, secretive, nondomestic species.

Technique for venipuncture of the transverse facial vein in the black rhinoceros (Diceros bicornis).

Through the use of operant conditioning, the authors developed a technique to facilitate obtaining blood samples from a black rhinoceros diagnosed with idiopathic epilepsy. The technique involved operant conditioning to facilitate venipuncture of the transverse facial vein, at an anatomic landmark on the lateral side of the face ventral to the medial canthus of the eye, and dorsal to the lateral commissure of the mouth. The investigators used standard operant conditioning protocols to train the animal for desensitization to a needle puncture in the facial vein. Blood samples obtained from the facial location were free of excessive hemolysis and allowed for large volumes to be collected. The procedure was well-tolerated by the rhinoceros and could be performed regularly without complication. Zoo Biol. 35:570-573, 2016. © 2016 Wiley Periodicals, Inc.

Humoral response to calicivirus in captive tigers given a dual-strain vaccine.

The current feline vaccine with a single strain of calicivirus has been used for captive tigers, yet it may not protect against virulent systemic calicivirus infections. A cross-institutional study investigated the humoral response to a new dual-strain, killed-virus calicivirus vaccine for nine captive tigers. The subspecies of these tigers were Amur (Panthera tigris altaica), Bengal (Panthera tigris tigris), and Malayan (Panthera tigris jacksoni). Serum neutralization titers for virulent feline calicivirus strain FCV-DD1 were higher following dual-strain vaccine administration. There were no reports of adverse vaccine reactions. Dual-strain vaccination may afford broadened cross-protection against different calicivirus strains and is desirable to reduce the risk of virulent systemic calicivirus disease in tigers.

Calculation of body surface area of corn snakes (Pantherophis guttatus) utilizing computed tomography.

OBJECTIVE: To determine the K-constant for body surface area calculation from body weight in corn snakes (Pantherophis guttatus) through the use of computed tomography (CT) measurements. ANIMALS: 12 adult corn snakes held by North Carolina State University for research purposes underwent CT between November 2022 and January 2023. METHODS: Each snake had a CT scan, physical examination, and body weight measurement. CT images were uploaded into software able to perform 3-D reconstruction and measure body surface area. The species-specific K-constant was determined using nonlinear regression analysis between body surface area and (body weight in grams)2/3. RESULTS: The mean body weight of the 12 adult corn snakes was 228 g, with a mean body surface area of 505.1 cm2. The calculated K-constant was 13.6 (P < .001). The resulting formula for body surface area in corn snakes is BSA in cm2 = 13.6 X (body weight in grams)2/3. CLINICAL RELEVANCE: The body surface area formula developed for corn snakes will allow for improved dosing accuracy for medications with low therapeutic safety margins. Additional pharmacokinetic and pharmacodynamic studies are necessary to determine the safety and efficacy of individual medications.

SARS-CoV-2 morbidity, treatment interventions, and vaccination practices in tigers (Panthera tigris ssp) in North American zoos.

OBJECTIVE: Evaluate SARS-CoV-2 morbidity, mortality, clinical signs, treatment interventions, and vaccination practices in tigers under professional care. ANIMALS: Amur (Panthera tigris altaica), Sumatran (Panthera tigris sumatrae), and Malayan (Panthera tigris jacksoni) tigers managed under the Tiger Species Survival Plan (SSP). METHODS: A retrospective, voluntary online survey was sent to all North American zoos holding SSP tigers between January 2020 and June 2023. RESULTS: Responses were received from 55 of 108 institutions (51%) housing 162 tigers in total, and SARS-CoV-2 infection was diagnosed in 39 tigers from 15 institutions (20 Amur, 8 Sumatran, and 11 Malayan [1 to 18 years old; 17 males and 22 females]). This corresponds to a minimum study group infection incidence of 24% over 42 months. Clinical signs included dry cough (82%), inappetence (64%), lethargy (62%), nasal discharge (46%), wheezing (31%), wet cough (18%), and ocular discharge (15%). Most cases were characterized as mild (n = 22) or moderate (14). A single case was characterized as severe. Two cases were asymptomatic. Seventeen positive tigers had been vaccinated once (n = 8) or twice (9) for SARS-CoV-2 prior to infection. No deaths due to SARS-CoV-2 were reported in the study group. Treatment interventions included antibiotics (49%), NSAIDs (18%), antiemetics (15%), and fluids (13%). No treatments were administered in 19 of 39 cases (49%). Amongst participating institutions, 69% reported fully vaccinating tigers for SARS-CoV-2 (≥ 2 doses). CLINICAL RELEVANCE: Most SARS-CoV-2-infected tigers presented with mild to moderate clinical signs and recovered with limited to no treatment interventions. Asymptomatic SARS-CoV-2 infections can occur in tigers and may be underreported. Tigers vaccinated for SARS-CoV-2 remain susceptible to infection.

The Impact of Dermal Characteristics on Low-Level Laser Power Measurement in Postmortem Zoological Species.

Photobiomodulation therapy, also termed as low-level laser therapy, is commonly used as an adjunctive therapy for various medical conditions in veterinary practice. The ACTIVet PRO low-level laser has been used for treatment of various nondomestic species, yet the effects of dermal attributes such as pigment, feathers, or scales have not been evaluated. The effects of low-level laser therapy with the ACTIVet PRO have been investigated in laboratory animals, including a study in rats that evaluated the passage of laser light through the skin in postmortem samples. The objective of this study was to measure the power of a low-level laser (ACTIVet PRO) after penetration through dermal tissue (∼1 mm thickness) in a variety of postmortem animal tissue. This study sought to determine the impact of fur, feathers, scales, and different pigments on the ability of the laser to penetrate. Frozen and thawed skin tissue samples from various species were placed inside a light restricted laser box and exposed to a preprogrammed laser level from a Multi Radiance ACTIVet PRO photobiomodulation (PBM) device, with a power meter to measure the light penetration through the tissue samples. Light penetration measurements via power output measurements (mW) were recorded at 7 time points (range, 1-150 sec). A Friedman test was performed to evaluate the difference of the mean tissue penetration by each species at each time point. Lighter colored specimens had higher power readings than darker colored or pigmented samples, and feathers appeared to inhibit the laser, showing minimal to no power readings on bird skin covered in covert and down feathers. There was statistically significant mean tissue penetration for all time points between the rabbit and green sea turtle (p=0.0046), the red-tailed hawk and green iguana (p=0.0046), and the red-tailed hawk and green sea turtle (p=0.000034). Overall findings found that certain skin coverings, such as feathers, appear to inhibit passage of laser light through tissue to the photo meter. Darker pigmented areas of tissue appeared to absorb the laser light, which also did not allow light passage through the tissue to the photo meter. All of this illustrates that there are differences in tissue penetration between different animal species, at least in postmortem tissues. This could necessitate adjustment of machine settings for therapeutic effect in different species, though further studies would be warranted to determine the extent to which this would be necessary. Additional studies evaluating biologically active tissues would be needed as a next step, as photobiomodulation has an effect at the cellular level and the exact amount of medical benefit is not measurable in skin samples that are separate from a living organism.

Severe bronchiectasis resulting from chronic bacterial bronchitis and bronchopneumonia in a jungle cat.

Bronchiectasis is irreversible bronchial dilation that can be congenital or acquired secondary to chronic airway obstruction. Feline bronchiectasis is rare and, to our knowledge, has not been reported previously in a non-domestic felid. An ~10-y-old female jungle cat (Felis chaus) was presented for evaluation of an abdominal mass and suspected pulmonary metastasis. The animal died during exploratory laparotomy and was submitted for postmortem examination. Gross examination revealed consolidation of the left caudal lung lobe and hila of the cranial lung lobes. Elsewhere in the lungs were several pale-yellow pleural foci of endogenous lipid pneumonia. On cut section, there was severe distension of bronchi with abundant white mucoid fluid. The remaining lung lobes were multifocally expanded by marginal emphysema. Histologically, ectatic bronchi, bronchioles, and fewer alveoli contained degenerate neutrophils, fibrin, and mucin (suppurative bronchopneumonia) with rare gram-negative bacteria. Aerobic culture yielded low growth of Proteus mirabilis and Escherichia coli. There was chronic bronchitis, marked by moderate bronchial gland hyperplasia, lymphoplasmacytic inflammation, and lymphoid hyperplasia. The palpated abdominal mass was a uterine endometrial polyp, which was considered an incidental, but novel, finding. Chronic bronchitis and bronchopneumonia should be considered as a cause of bronchiectasis and a differential diagnosis for respiratory disease in non-domestic felids.

Retrospective Study of the Prevalence, Histopathology, Therapy, and Survival Time of Neoplastic Disease in Fish.

This study evaluated neoplasia in fish using medical records from zoos, aquariums, and exotic animal veterinarians. The parameters evaluated included geographic location, habitat type, signalment, anatomic location of neoplasia, type of neoplasia as confirmed with histologic examination, survival time, and treatments provided for each patient. These data were entered into the Exotic Species Cancer Research Alliance (ESCRA) database. Out of 455 cases from across the United States and England, most animals submitted were from zoologic parks or aquariums (62.9%), followed by private ownership (1.5%). The percent of female (19.3%) and male (17.8%) patients were similar, and the mean age at the time of diagnosis was 99.45 months, with a range of 12 to 300 months. The species with the highest neoplasia prevalence was koi (18.5%), followed by goldfish (10.8%). The eye was the most commonly reported site for a primary neoplasm (8.4%), and the most prevalent diagnosis across all organ systems was soft tissue sarcoma (26.2%). Only 13 patients in this study (2.9%) received any form of treatment, with a mean survival time of 8.85 months post-treatment. These data demonstrate that while information related to clinical therapy of cancer in fish species is lacking, surgical excision of tumors in fish, when feasible for the patient and client, may improve patient outcomes.

Evaluation of Neoplasia, Treatments, and Survival in Lizard Species.

Neoplasia has been reported in lizards, but more research is needed to accurately document the prevalence and prognosis of the various known neoplasms that affect lizards. This study reviewed medical records from an online database, the Exotic Species Cancer Research Alliance (ESCRA), and reviewed published literature to determine the prevalence of neoplasia, malignancy, metastasis, treatment strategies, and outcomes by species and sex. Records from 55 individual lizards, 20 different species, and 37 different tumors were identified. In the literature, 219 lizards, 59 species, and 86 unique tumors were identified from 72 published case reports. Potential signalment factors such as age, sex, and species were evaluated to see if they affected case outcome. Additional factors including neoplasia type, presence of metastasis, and types of pursued treatments were also evaluated. Statistical analysis was performed to determine whether a factor was significantly associated with animal death due to the identified neoplasia or with animal survival or death due to other causes (non-neoplastic outcomes). Komodo dragons and savannah monitors were more likely to die from neoplasia compared to other lizard species. Cases where the status of metastasis was unknown were significantly associated with death due to neoplasia. Having an unknown status of male versus female was significantly associated with non-neoplastic outcomes of death. Leukemia and islet cell carcinoma were significantly associated with death due to neoplastic causes. Chondrosarcoma, myxosarcoma, osteosarcoma, and squamous cell carcinoma were significantly associated with non-neoplastic outcomes of death. Surgery alone and radiation therapy alone each were significantly associated with non-neoplastic outcomes of death, while lizards not receiving treatment were significantly associated with death due to neoplasia. Benign neoplasia was significantly associated with non-neoplastic outcomes of death. These results will aid in the improved diagnosis and management of neoplasia in lizard species, as well as expanding our understanding of prognostic indicators of neoplasia in lizards.

Germline mutation rate predicts cancer mortality across 37 vertebrate species.

Background and objectives: Cancer develops across nearly every species. However, cancer occurs at unexpected and widely different rates throughout the animal kingdom. The reason for this variation in cancer susceptibility remains an area of intense investigation. Cancer evolves in part through the accumulation of mutations, and therefore, we hypothesized that germline mutation rates would be associated with cancer prevalence and mortality across species. Methodology: We collected previously published data on germline mutation rate and cancer mortality data for 37 vertebrate species. Results: Germline mutation rate was positively correlated with cancer mortality (P-value = 0.0008; R2 = 0.13). Controlling for species' average parental age, maximum longevity, adult body mass or domestication did not improve the model fit (the change (Δ) in Akaike Information Criterion (AIC) was less than 2). However, this model fit was better than a model controlling for species trophic level (ΔAIC > 2). Conclusions and implications: The increased death rate from cancer in animals with increased germline mutation rates may suggest underlying hereditary cancer predisposition syndromes similar to those diagnosed in human patients. Species with higher germline mutation rates may benefit from close monitoring for tumors due to increased genetic risk for cancer development. Early diagnoses of cancer in these species may increase their chances of overall survival, especially for threatened and endangered species.