Excisional biopsy and radiotherapy for management of an olfactory neuroblastoma in an axolotl (Ambystoma mexicanum)

CASE DESCRIPTION A 4-year-old sexually intact male leucistic axolotl (Ambystoma mexicanum) was presented with a 2-week history of dysrexia and difficulty swallowing. CLINICAL FINDINGS Physical examination revealed a 1-cm-diameter intraoral mass on the rostral aspect of the palate and swelling of the left nasal fossa. Local invasion into the left nasal fossa was suspected during oral examination. The lesion was marginally excised, and an incompletely excised olfactory neuroblastoma was diagnosed histologically. Five weeks later, physical examination revealed persistent erythema, delayed healing of the rostral portion of the palate, and a mild facial deformity associated with a white mass in the nasal cavity. TREATMENT AND OUTCOME 6 weeks after excision, adjuvant electron (6-MeV) beam radiotherapy was initiated for treatment of the incompletely excised olfactory neuroblastoma and likely presence of a recurrent mass. The protocol consisted of 4 weekly fractions of 8 Gy each (total, 32 Gy) with the axolotl under anesthesia. No acute adverse radiation effects were noted following radiotherapy. The oral erythema resolved after the third session. No recurrence was observed 2 months after treatment, and the owners reported no abnormal signs at home. The axolotl died 3.5 months after radiotherapy was completed (8 months after marginal excision of the tumor) secondary to an environmental management failure. Postmortem histologic evaluation showed no evidence of neoplasia. CLINICAL RELEVANCE In axolotls, olfactory neuroblastoma should be considered in the differential diagnosis of intraoral palatal masses. This report describes the first application of radiotherapy for treatment of an olfactory neuroblastoma in an axolotl.

Geographic distribution of Pythium insidiosum infections in the United States

OBJECTIVE To describe the geographic distribution of infections caused by Pythium insidiosum in dogs, horses, and other animal species in the US. ANIMALS For the last 20 years, we have collected data from cases of pythiosis in 1,150 horses, 467 dogs, and other species (59) from various geographic locations in the US. PROCEDURES Due to lost data (from 2006 to 2016), the selected cases include years 2000 to 2005 and 2016 to 2020. The selection of cases was based on infected host clinical features, serum samples demonstrating strong positive anti–P insidiosum IgG titers in serologic assays, and positive results on ≥ 1 of the following diagnostic modalities: microbial culture on 2% Sabouraud dextrose agar, histologic evaluation, PCR assay, and wet mount cytologic evaluation (with potassium hydroxide). RESULTS Most confirmed P insidiosum infections were found in horses and dogs in the southeastern US. Interestingly, in Texas, no cases were found west of longitude 100°W. Few pythiosis cases were diagnosed in west-coast states. Equine cases were more often diagnosed during summer and fall months, but canine cases were more often diagnosed between September and February. Cases in other species were discovered in the same geographic areas as those in dogs and horses. CLINICAL RELEVANCE To our knowledge, this is the first report providing the ecological distribution of P insidiosum infection in affected species in the US. Results of this study illustrated the importance of including P insidiosum in the differential diagnostic scheme of nonhealing skin lesions or intestinal granulomatous masses, particularly in dogs and horses inhabiting or having visited endemic areas.

PET Imaging in Cardiac Sarcoidosis: A Narrative Review with Focus on Novel PET Tracers

Sarcoidosis is a multi-system inflammatory disease characterized by the development of inflammation and noncaseating granulomas that can involve nearly every organ system, with a predilection for the pulmonary system. Cardiac involvement of sarcoidosis (CS) occurs in up to 70% of cases, and accounts for a significant share of sarcoid-related mortality. The clinical presentation of CS can range from absence of symptoms to conduction abnormalities, heart failure, arrhythmias, valvular disease, and sudden cardiac death. Given the significant morbidity and mortality associated with CS, timely diagnosis is important. Traditional imaging modalities and histologic evaluation by endomyocardial biopsy often provide a low diagnostic yield. Cardiac positron emission tomography (PET) has emerged as a leading advanced imaging modality for the diagnosis and management of CS. This review article will summarize several aspects of the current use of PET in CS, including indications for use, patient preparation, image acquisition and interpretation, diagnostic and prognostic performance, and evaluation of treatment response. Additionally, this review will discuss novel PET radiotracers currently under study or of potential interest in CS.

Opinion on the Optimal Histologic Evaluation of the Bone Marrow in Nonclinical Toxicity Studies

Identification of bone marrow toxicity is an important issue in drug development and toxicologic pathologists play a critical role in that identification. Knowledge of the general components of bone marrow, relevant anatomical and species differences, and the standard approach (routine systematic histological evaluation of the bone marrow in conjunction with analysis of the peripheral complete blood count data) will be reviewed. Specific morphologic features that anatomic pathologists should look for in the various components of bone marrow as well as suggested terminology for bone marrow findings will be discussed. Finally, an opinion on the limitations of the standard approach to bone marrow evaluation will be provided including general recommendations on when additional methods (image analysis of hematoxylin and eosin stained slides, flow cytometry or Sysmex XT 2000iV analysis, cytological evaluation of bone marrow smears, in vitro models, and transmission electron microscopy) might be useful in the detection or further characterization of bone marrow toxicity. [Box: see text]

Disseminated coelomic xanthogranulomatosis in eclectus parrots (Eclectus roratus) and budgerigars (Melopsittacus undulatus)

Xanthogranulomatosis is an inflammatory lesion characterized by lipid-containing macrophages, extracellular lipid, hemorrhage, and necrosis. We describe disseminated intracoelomic xanthogranulomatosis in 5 eclectus parrots ( Eclectus roratus) and 2 budgerigars ( Melopsittacus undulatus). Postmortem, clinicopathologic, and historical case material was reviewed. Ages ranged from 3 to 24 years; there were 5 males and 2 females. Table food was included in the diet of 3/5 cases, and animal products were included in 2/3 cases. Common clinicopathologic abnormalities included leukocytosis (4/5 cases) and elevated concentrations of bile acids (3/4 cases) and cholesterol within 6 months prior to death (2/4 cases). At postmortem examination, all 7 birds had grossly visible, irregular, soft, tan to yellow, amorphous plaques distributed on the surfaces of the viscera and body wall. Histologic evaluation and oil red O stain revealed xanthogranulomatous inflammation with phagocytized and extracellular lipid, necrosis, cholesterol clefts, fibrosis, and mineralization. Infectious agents were not identified with special stains in all cases. Concurrent hepatobiliary disease was present in 6/7 cases, and 6/7 had lipid accumulation within the parenchyma of various visceral organs. Five cases had atherosclerosis of great vessels. We describe a unique form of disseminated coelomic xanthogranulomatosis in 2 psittacine species. This condition should be recognized as a differential diagnosis in cases of disseminated coelomic mass formation and coelomic distension in psittacine birds, particularly in eclectus parrots and budgerigars.

EXTH-36. ELECTROCONVULSIVE SEIZURE-INDUCED CHANGES IN THE TUMOR MICROENVIRONMENT PROMOTE SURVIVAL IN GLIOMA-BEARING MICE

PURPOSE Growing evidence indicates that the neurotransmitters dysregulated in psychiatric disorders are similarly dysregulated in glioblastoma (GBM) biology. GBM cells are dependent on bountiful neuronal glutamate, utilize elevated dopamine receptor expression to augment progression, and catabolize serotonin to drive proliferation and inhibit anti-tumor immunity. The clinical induction of seizure, known as electroconvulsive therapy (ECT), has been used by psychiatrists since the 1930s to correct these dysregulations and can additionally improve medication blood-brain barrier (BBB) penetrance. We hypothesized that seizure-induced changes in the glioma microenvironment occur with ECT, slowing tumor progression, increasing BBB permeability, and prolonging overall survival in glioma-bearing mice. METHODS C57BL6 mice were orthotopically injected with CT-2A-Luc mouse glioma cells. Mice were randomized to receive ECT via ear-clip electrodes or sham treatment daily up to five times per week. Intracranial progression was monitored via bioluminescent signal from CT-2A-Luc xenografts. BBB permeability was assessed by subjecting mice to ECT or sham treatment immediately following intravenous injection of sodium fluorescein. RESULTS Intracranial progression was maximally reduced in ECT-treated mice relative to sham-treated mice after 17 ECT treatments (ECT radiance 2.6 x 109 photons/second versus sham 4.7 x 109 photons/second, p=0.013), which was further confirmed by both decreased tumor weight and tumor size on histologic evaluation. This translated into an improvement in overall survival from median 29 days in sham-treated mice to 38 days in ECT-treated mice (p=0.0018). Mean seizure duration was 41.8 seconds and positively correlated with overall survival (Pearson coefficient r=0.63, p=0.028). Brain parenchymal uptake of sodium fluorescein was significantly higher in ECT-treated mice (mean relative increase in ECS to sham radiance of 1.47, p< 0.05). CONCLUSION Repeated ECT slows tumor progression and prolongs overall survival in C57BL6 mice bearing CT-2A-Luc xenografts. The BBB is compromised immediately following ECT. ECT merits further oncologic investigation as a potential therapeutic in GBM.

Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints

There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralateral joints as controls. Blood and synovial fluid were analysed for the tacrolimus concentration and biomarkers for inflammation and cartilage metabolism. After an initial burst release, sustained intra-articular tacrolimus concentrations (>20 ng/mL) were observed during the 42 days follow-up. Whole-blood tacrolimus levels were below the detectable level (<0.5 ng/mL). A transient inflammatory reaction was observed for all substances, evidenced by increases of the synovial fluid white blood cell count and total protein. Prostaglandin and glycosaminoglycan release were increased in joints injected with unloaded monospheres, which was mitigated by tacrolimus. Both tacrolimus-loaded monospheres and HA transiently increased the concentration of collagen II cleavage products (C2C). A histologic evaluation of the joints at the endpoint showed no pathological changes in any of the conditions. Together, these results indicate the good biocompatibility of intra-articular applied tacrolimus-loaded monospheres combined with prolonged local drug release while minimising the risk of systemic side effects. Further evaluation in a clinical setting is needed to determine if tacrolimus-loaded monospheres can be beneficial in the treatment of inflammatory joint diseases in humans and animals.

Clinical and Histologic Evaluation of Using Block Xenograft Combined With Leukocyte-Platelet Rich Fibrin (L-PRF) Versus Intraoral Autogenous Bone Block Graft With L-PRF in Treating Localized Ridge Defects: A Randomized Clinical Trial

Background: Augmentation of vertical bone defects remains the corner stone in periodontal tissue engineering. The amount and quality of alveolar bone available in all dimensions affects the success of dental implants for restoration of edentulous areas. Adequate and healthy bone supports the degree of osseointegration which in turn affects the long-term success of oral implants. The primary aim of the study was to histologically evaluate autogenous block grafts versus synthetic block grafts for the treatment of atrophic vertical and horizontal bony defects (Siebert Class III) in the anterior esthetic zone of the mouth. The secondary aim was to clinically and radiographically evaluate the outcomes of the procedure. Methods: This was a randomized controlled clinical study with a statistically determined sample size of 10 patients per group and a total of 20 patients in both groups. Patients with vertical and horizontal bone loss were enrolled from the Department of Oral Medicine, Periodontology, and Oral Diagnosis of Ain Shams University and Misr International University. Bone augmentation procedures were performed using two techniques: autogenous bone block graft and xenograft bone block graft both with leukocyte-platelet rich fibrin (L-PRF). Results: Both autogenous and xenograft blocks in conjunction with L-PRF had a significant effect on vertical bone augmentation in cases of atrophic ridges in the esthetic region. Conclusion: Both autogenous and xenograft bone blocks in conjunction with L-PRF have a significant effect on vertical bone augmentation in cases of atrophic ridges in the esthetic region.