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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.

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Petos Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.

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.

Adaptive therapy, an ecologically inspired approach to cancer treatment, aims to overcome resistance and reduce toxicity by leveraging competitive interactions between drug-sensitive and drug-resistant subclones, prioritizing patient survival and quality of life instead of killing the maximum number of cancer cells. In preparation for a clinical trial, we used endocrine-resistant MCF7 breast cancer to stimulate second-line therapy and tested adaptive therapy using capecitabine, gemcitabine, or their combination in a mouse xenograft model. Dose modulation adaptive therapy with capecitabine alone increased survival time relative to MTD but not statistically significantly (HR = 0.22, 95% CI = 0.043-1.1, p = 0.065). However, when we alternated the drugs in both dose modulation (HR = 0.11, 95% CI = 0.024-0.55, p = 0.007) and intermittent adaptive therapies, the survival time was significantly increased compared to high-dose combination therapy (HR = 0.07, 95% CI = 0.013-0.42, p = 0.003). Overall, the survival time increased with reduced dose for both single drugs ( p < 0.01) and combined drugs ( p < 0.001), resulting in tumors with fewer proliferation cells ( p = 0.0026) and more apoptotic cells ( p = 0.045) compared to high-dose therapy. Adaptive therapy favors slower-growing tumors and shows promise in two-drug alternating regimens instead of being combined.

Highly effective cancer therapies often face limitations due to acquired resistance and toxicity. Adaptive therapy, an ecologically inspired approach, seeks to control therapeutic resistance and minimize toxicity by leveraging competitive interactions between drug-sensitive and drug-resistant subclones, prioritizing patient survival and quality of life over maximum cell kill. In preparation for a clinical trial in breast cancer, we used large populations of MCF7 cells to rapidly generate endocrine-resistance breast cancer cell line. We then mimicked second line therapy in ER+ breast cancers by treating the endocrine-resistant MCF7 cells in a mouse xenograft model to test adaptive therapy with capecitabine, gemcitabine, or the combination of those two drugs. Dose-modulation adaptive therapy with capecitabine alone increased survival time relative to MTD, but not statistically significant (HR: 0.22, 95% CI 0.043- 1.1 P = 0.065). However, when we alternated the drugs in both dose modulation (HR = 0.11, 95% CI: 0.024 - 0.55, P = 0.007) and intermittent adaptive therapies significantly increased survival time compared to high dose combination therapy (HR = 0.07, 95% CI: 0.013 - 0.42; P = 0.003). Overall, survival time increased with reduced dose for both single drugs (P < 0.01) and combined drugs (P < 0.001). Adaptive therapy protocols resulted in tumors with lower proportions of proliferating cells (P = 0.0026) and more apoptotic cells (P = 0.045). The results show that Adaptive therapy outperforms high-dose therapy in controlling endocrine-resistant breast cancer, favoring slower-growing tumors, and showing promise in two-drug alternating regimens.

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Peto's Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer., Competing Interests: Competing interests: JDS is co-founder, shareholder, and employed by Peel Therapeutics, Inc., a company developing evolution-inspired medicines based on cancer resistance in elephants. LMA is share-holder and consultant to Peel Therapeutics, Inc. The other authors declare that they have no competing interests (ZTC, VKH, WM, SR, DM, SEK, MW, RK, KN, CB, LR, AP, BM, SS, SA, GF, OV, MG, EGD, SS, EF, HD, AZ, TAG, BT, TMH, MT, AA, AMB, CCM)

The parakeet auklet ( Aethia psittacula ) is a piscivorous seabird with a natural diet of various invertebrate and teleost species, which is challenging to replicate in a managed collection. A high prevalence of early onset cataracts was observed in a managed collection of parakeet auklets at the North Carolina Zoo (Asheboro, NC, USA), which was hypothesized to be related to inappropriate vitamin A and E levels. From 1994 to 2002, these parakeet auklets were offered dietary supplementation comprising Vita-Zu small bird tablets. In June 2002, the birds were transitioned to only Thiamin-E paste (vitamin E and thiamin only). Plasma samples were collected from birds with and without cataracts from 1998 to 2005 and submitted for vitamin A (retinol) and vitamin E (α-tocopherol) analysis. Food items comprising the birds' diet were also evaluated for vitamin content. This information was combined with clinical and necropsy data from medical records from 1994 to 2015. A total of 78% of birds (39/50) developed cataracts, with a median age of onset of 7 years (range, 2-12 years). Cataracts ranged from incipient to hypermature during both routine ophthalmic examinations and postmortem evaluations. The median (range) of plasma retinol and α-tocopherol values were 1.99 µg/mL (0.20-6.68 µg/mL) and 15.39 µg/mL (3.40-96.27 µg/mL), respectively. There were no significant differences in plasma concentrations of vitamins based on the animals' sex, origin, presence of cataracts, or administered vitamin supplementation product. No other etiologies for cataract development were identified in the population. Further research in free-ranging parakeet auklet nutrition and cataract occurrence is warranted for continued species collection management.

Current recommendations for wound management in amphibians are based primarily on clinical experience and on extrapolation from other taxa, whereas controlled clinical studies are lacking. Low-level laser therapy, also termed photobiomodulation, has gained popularity in veterinary medicine and may represent a valuable adjunct therapy for wound care in amphibians, though dosing and safety evaluations have not been previously reported. Silver sulfadiazine (SSD), a topical antimicrobial, is commonly utilized in amphibian medicine but little is known about its effects on wound healing in this class of animals. This pilot study evaluated the effects of repeated treatments of low-level laser therapy or topical SSD on second-intention healing characteristics of surgically induced full-thickness dermal wounds in 33 adult wild-caught marine toads. Toads were anesthetized, and a 6 mm cutaneous biopsy was performed over the right dorsum. They were then randomly assigned to one of three groups: laser therapy (LT) at 5 Hz (905 nm wavelength on a super pulsed sequence), topical SSD (SD), or control sham treatment (CT). Treatments were administered at 24 hrs after biopsy and then every 72 hrs thereafter, concurrent with a visual assessment of the wound. Toads were euthanized at one of five timepoints (day 4, 7, 13, 19, or 28) to permit scoring of histologic criteria, including lymphocytic inflammation, granulomatous inflammation, heterophilic inflammation, granulation tissue, fibrosis, and reepithelialization. Visual assessments and histologic scoring did not identify a benefit of laser therapy or SSD as compared to controls. Laser therapy and SSD, at the doses and dosing schedule utilized in this pilot study, appear to be safe and well-tolerated treatments in marine toads, but may not be warranted for uncomplicated skin wounds in this species., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Kate E. Archibald et al.)

A 0.34 kg adult female Massasauga rattlesnake ( Sistrurus catenatus ) was presented for evaluation of a subcutaneous mass affecting the ventral scales. The mass was diagnosed as a sarcoma via punch biopsy with no evidence of metastasis on diagnostic imaging. Surgical margins of 1-2 cm were planned to achieve complete excision of the neoplasm. A technique for tissue expansion was employed due to concerns regarding the ability to close the surgical site without excess tension or dehiscence. Two 27 mm diameter × 5 mm hygroscopic self-inflating tissue expanders were placed subcutaneously under the lateral scales adjacent to the mass. Maximum skin expansion occurred over a four-week period, and no direct negative effects were noted. Excision of the primary mass was performed routinely five weeks after implant placement. Primary closure of the defect was achieved with minimal tension by incorporating the expanded skin. While the surgery was successful with no evidence of metastasis, the snake died of sepsis two weeks postoperatively. This is the first report of the use of self-inflating hygroscopic tissue expanders to help close a surgical defect in a reptile., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Kate E. Archibald et al.)

CASE DESCRIPTION A 22-year-old male gorilla (Gorilla gorilla gorilla) housed in a zoo was evaluated for signs of lethargy, head-holding, and cervical stiffness followed by development of neurologic abnormalities including signs of depression, lip droop, and tremors. CLINICAL FINDINGS Physical examination under general anesthesia revealed a tooth root abscess and suboptimal body condition. A CBC and serum biochemical analysis revealed mild anemia, neutrophilia and eosinopenia consistent with a stress leukogram, and signs consistent with dehydration. Subsequent CSF analysis revealed lymphocytic pleocytosis and markedly increased total protein concentration. TREATMENT AND OUTCOME Despite treatment with antimicrobials, steroids, and additional supportive care measures, the gorilla's condition progressed to an obtunded mentation with grand mal seizures over the course of 10 days. Therefore, the animal was euthanized and necropsy was performed. Multifocal areas of malacia and hemorrhage were scattered throughout the brain; on histologic examination, these areas consisted of necrosis and hemorrhage associated with mixed inflammation, vascular necrosis, and intralesional amoebic trophozoites. Tan foci were also present in the kidneys and pancreas. Immunohistochemical testing positively labeled free-living amoebae within the brain, kidneys, eyes, pancreas, heart, and pulmonary capillaries. Subsequent PCR assay of CSF and frozen kidney samples identified the organism as Balamuthia mandrillaris, confirming a diagnosis of amoebic meningoencephalitis. CLINICAL RELEVANCE Infection with B mandrillaris has been reported to account for 2.8% of captive gorilla deaths in North America over the past 19 years. Clinicians working with gorillas should have a high index of suspicion for this diagnosis when evaluating and treating animals with signs of centrally localized neurologic disease.

Over a 25-mo span from a single zoologic collection, two bufflehead ducklings (Bucephala albeola) presented with pelvic limb paresis and were euthanized. On postmortem examination, the first duckling had intralesional fungal hyphae consistent with Aspergillus sp. in the spinal vertebrae and within pulmonary granulomas. In the second duckling, evidence of a thoracic spinal lesion was detected antemortem by using thermographic imaging. At postmortem examination, fungal hyphae consistent with Mucor sp. were found within the vertebrae. Although fungal infections of the respiratory system are commonly reported in waterfowl, infections that involve the spinal cord and vertebrae are unusual. These cases highlight the importance of consideration of axial skeleton fungal disease in neurologic presentations and the use of thermography for noninvasive diagnostic screening.

A 40 yr-old female white rhinoceros (Ceratotherium simum) suffered from chronic nail-bed abscesses. Due to worsening of clinical signs, the animal's nonsteroidal anti-inflammatory treatment was switched to firocoxib. Approximately 7 days after this change, the animal developed multifocal vesicles and bullae along the lateral aspects of the thorax and abdomen, the dorsum, and the proximal limbs. Cytology and culture did not identify an infectious etiology. Histologically, the lesions consisted of a severe, subacute vesiculobullous dermatitis with intraepidermal to subepidermal clefting with areas of individual keratinocyte necrosis and minor neutrophilic epidermal infiltrates. These findings are similar to those seen in some drug reactions in people; therefore an adverse drug reaction to the firocoxib was suspected.

Background: Reports of female reproductive tract neoplasia are infrequent in great apes., Methods: Two captive-born, female western lowland gorillas (Gorilla gorilla gorilla) housed at the North Carolina Zoological Park were diagnosed with reproductive neoplasia., Results: The first gorilla had uterine endometrial thickening and uterine fibroids diagnosed during a routine annual examination. Subsequently, the animal underwent several uterine curettage procedures in an attempt to debulk the uterine mass. Biopsy results indicated uterine adenocarcinoma. The animal was treated with an ovariohysterectomy followed by a combination of megestrol acetate and medroxyprogesterone acetate. The second gorilla was diagnosed with squamous cell carcinoma of the vagina, cervix, and uterus after presenting for intermittent vaginal bleeding of 1-month duration. This animal underwent palliative radiation therapy, receiving two rounds of radiation treatment 8 weeks apart., Conclusions: The following report describes the diagnosis and management of the two cases., (© 2010 John Wiley & Sons A/S.)