Descriptive analysis and prognostic factors in cats with myeloma-related disorders: A multicenter retrospective study of 50 cases.

BACKGROUND: Myeloma-related disorders (MRDs) are rare and poorly documented neoplasms of cats. HYPOTHESIS/OBJECTIVES: To describe clinical, clinicopathologic, and imaging findings, response to treatment, and survival time and to identify factors associated with shorter outcomes in cats with MRD. ANIMALS: Fifty cats with a diagnosis of MRD. METHODS: Cats with paraproteinemia confirmed by serum protein electrophoresis (SPE) and either intramedullary plasmacytosis >10%, marked cytonuclear atypia with intramedullary plasmacytosis that ranged between 5% and 10%, or cytologically or histologically confirmed visceral infiltration were retrospectively included from several veterinary referral centers. RESULTS: Bone marrow plasmacytosis and splenic or hepatic involvement were present in 17/27 cats (63%), 36/42 cats (86%), and 27/38 cats (71%), respectively. Anemia was reported in 33/49 cats (67%) and thrombocytopenia in 16/47 cats (34%). Some of the treatments that the cats received included melphalan and prednisolone (n = 19), cyclophosphamide and prednisolone (n = 10), chlorambucil and prednisolone (n = 4), prednisolone (n = 4), or other (n = 4). The overall response rates to melphalan, cyclophosphamide, and chlorambucil in combination with prednisolone were 87%, 90%, and 100%, respectively. Adverse events to melphalan or cyclophosphamide occurred in 65% and 23% of cats, respectively. Median survival time was 122 days (range, 0-1403) and was not significantly associated with chemotherapy protocol. Anemia (hazard ratio [HR], 3.1; 95% confidence interval [CI], 1.0-9.8) and thrombocytopenia (HR, 2.7; 95% CI, 1.2-6.0) were risk factors for shorter survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study confirmed the guarded prognosis of MRD in cats and identified risk factors for shorter survival times.

Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma.

Circulating tumor DNA (ctDNA) has become an attractive biomarker in human oncology, and its use may be informative in canine cancer. Thus, we used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. We detected ctDNA in 21/23 (91.3%) of histiocytic sarcoma (HS), 2/8 (25%) of oral melanoma, and 12/13 (92.3%) of lymphoma cases. The utility of ctDNA in diagnosing HS was explored in 133 dogs, including 49 with HS, and the screening of recurrent PTPN11 mutations in plasma had a specificity of 98.8% and a sensitivity between 42.8 and 77% according to the clinical presentation of HS. Sensitivity was greater in visceral forms and especially related to pulmonary location. Follow-up of four dogs by targeting lymphoma-specific antigen receptor rearrangement in plasma showed that minimal residual disease detection was concordant with clinical evaluation and treatment response. Thus, our study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a promising biomarker for diagnosis and clinical follow-up. ctDNA detection appears to be useful in comparative oncology research due to growing interest in the study of natural canine tumors and exploration of new therapies.

Case Report: Intramedullary Intervertebral Disk Extrusion in a Cat: Clinical, Computed Tomographic, High-Field Magnetic Resonance Imaging, and Outcome Findings.

Background: Intramedullary disk extrusions has rarely been described in veterinary medicine, more especially in cats, with only two cases are reported in the veterinary literature. Diagnosis may be difficult, even though clinical presentation and imaging studies, such as MRI or CT, can present specific features. Treatment and prognosis are not clearly described. Case presentation: A 10-year-old domestic shorthair female cat was evaluated for a 12 h-history of peracute-onset of paraparesis with flaccid tail and urinary and fecal incontinence. The patellar reflexes were normal, the pelvic flexor reflexes were decreased (more markedly on the right limb) and the perianal reflex was absent. The tail was flaccid, without nociception. Abdominal palpation revealed a small urinary bladder, easily expressed. Manipulation of the lumbar vertebral column elicited marked pain. Neurological examination was consistent with a L7-caudal segments lesion. A lumbosacral MRI and CT evaluations were performed and revealed a focal intramedullary hemorrhagic lesion, with an associated vertical linear tract communicating with the L5-L6 intervertebral disk space, and a suspected intramedullary focus of mineralization. These imaging findings were highly suggestive of an L5-L6 intramedullary disk extrusion. A dorsal L5-L6 laminectomy confirmed the presence of intramedullary degenerative nucleus pulposus fragments, which were surgically removed. Rapid and progressive neurological improvement was observed post-surgery. At the 1-year follow-up, right plantigrade stance and mild paraparesis were still noticed, but jumps and voluntary tail movements were observed. Occasional urinary and fecal incontinence episodes remained. Conclusions: This is the first feline case report of an intramedullary disk herniation with long-term follow-up available. Clinical description, CT and High-Field MRI findings, surgical procedure and histological results are reported, and help describing the characteristics of this rare non-compressive category of peracute intervertebral disk extrusion. Surgical management may be considered in feline cases of intramedullary disk herniation and may be associated with a good outcome.

In vivo stem cell tracking using scintigraphy in a canine model of DMD.

One of the main challenges in cell therapy for muscle diseases is to efficiently target the muscle. To address this issue and achieve better understanding of in vivo cell fate, we evaluated the relevance of a non-invasive cell tracking method in the Golden Retriever Muscular Dystrophy (GRMD) model, a well-recognised model of Duchenne Muscular Dystrophy (DMD). Mesoangioblasts were directly labelled with 111In-oxine, and injected through one of the femoral arteries. The scintigraphy images obtained provided the first quantitative mapping of the immediate biodistribution of mesoangioblasts in a large animal model of DMD. The results revealed that cells were trapped by the first capillary filters: the injected limb and the lung. During the days following injection, radioactivity was redistributed to the liver. In vitro studies, performed with the same cells prepared for injecting the animal, revealed prominent cell death and 111In release. In vivo, cell death resulted in 111In release into the vasculature that was taken up by the liver, resulting in a non-specific and non-cell-bound radioactive signal. Indirect labelling methods would be an attractive alternative to track cells on the mid- and long-term.

Symptomatic lateral ventricular cystic lesion in a young cat.

CASE SUMMARY: A 1.5-year-old male neutered Persian cat was referred for acute deterioration of chronic left head tilt and ataxia. A lateral intraventricular cystic lesion, closely associated with the left choroid plexus, was identified on MRI. The intralesional signal intensity and cytological analysis of the fluid revealed a liquid similar to cerebrospinal fluid. After trepanation, an endoscopic-assisted fenestration and aspiration of the cyst were performed to temporally relieve the high intracranial pressure while waiting for surgical cystoperitoneal shunt placement. Three weeks after surgery, clinical relapse and recurrence of the lesion were noted on the pre-cystoperitoneal shunting MRI. During anaesthesia, the cat arrested. Cardiac resuscitation was successfully performed and cystoperitoneal shunting was postponed. Global brain ischaemia was then suspected, based on major forebrain clinical signs and MRI abnormalities. During a 6-month recovery period, a further three fine-needle CT-guided aspirations of the lesion were required, owing to clinical recurrence and increased cyst size. Cystoperitoneal shunting was eventually performed, allowing persistent reduction of the lesion and long-term improvement of the cat's neurological status. RELEVANCE AND NOVEL INFORMATION: This is the first report of a symptomatic lateral intraventricular cystic lesion in a cat. A left lateral intraventricular choroid plexus cyst was suspected based on the MRI features. Our case suggests that endoscopic fenestration and CT-guided aspiration are not adequate treatments for long-term management. Cystoperitoneal shunting may be a safe procedure, allowing significant and stable reduction of the cystic lesion, associated with improvement in the cat's neurological status by preventing high intracranial pressure.

In Vivo Myoblasts Tracking Using the Sodium Iodide Symporter Gene Expression in Dogs.

Stem cell-based therapies are a promising approach for the treatment of degenerative muscular diseases; however, clinical trials have shown inconclusive and even disappointing results so far. Noninvasive cell monitoring by medicine imaging could improve the understanding of the survival and biodistribution of cells following injection. In this study, we assessed the canine sodium iodide symporter (cNIS) reporter gene as an imaging tool to track by single-photon emission computed tomography (SPECT/CT) transduced canine myoblasts after intramuscular (IM) administrations in dogs. cNIS-expressing cells kept their myogenic capacities and showed strong 99 mTc-pertechnetate (99 mTcO4 -) uptake efficiency both in vitro and in vivo. cNIS expression allowed visualization of cells by SPECT/CT along time: 4 h, 48 h, 7 days, and 30 days after IM injection; biopsies collected 30 days post administration showed myofiber's membranes expressing cNIS. This study demonstrates that NIS can be used as a reporter to track cells in vivo in the skeletal muscle of large animals. Our results set a proof of concept of the benefits NIS-tracking tool may bring to the already challenging cell-based therapies arena in myopathies and pave the way to a more efficient translation to the clinical setting from more accurate pre-clinical results.

IRIDIUM 192 (192-Ir) HIGH DOSE RATE BRACHYTHERAPY IN A CENTRAL BEARDED DRAGON (POGONA VITTICEPS) WITH ROSTRAL SQUAMOUS CELL CARCINOMA.

A 0.5-kg, 9-yr-old, male central bearded dragon (Pogona vitticeps) presented with a proliferative mass (0.4 × 0.2 inches) on the left rostral aspect of the lower lip. Physical examination, blood work, and whole-body radiography did not reveal any other abnormalities. Histopathology confirmed squamous cell carcinoma. Considering the small size of the tumor, absence of deep tissue infiltration, and its radioresponsive characteristics, iridium 192 high dose rate brachytherapy was attempted. The dragon initially received three doses of 4 Gy/site at days 0, 7, and 17. Recurrence developed 3 mo later. Three more fractions of 6 Gy/site at days 0, 7, and 14 were delivered according to the same procedure. A second recurrence appeared after 2 mo. Surgical excision was then performed, followed by four fractions of 6 Gy/site on the surgical site at 2-wk intervals. Sixteen months posttreatment, no recurrence of the mass was observed.

The Advantage of FLASH Radiotherapy Confirmed in Mini-pig and Cat-cancer Patients.

PURPOSE: Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. EXPERIMENTAL DESIGN: Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called "FLASH-RT" and irradiation delivered at a conventional dose rate called "Conv-RT." A clinical, phase I, single-dose escalation trial (25-41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT. RESULTS: Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%. CONCLUSIONS: Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients.See related commentary by Harrington, p. 3.

Effects of radiotherapy on pituitary corticotroph macrotumors in dogs: a retrospective study of 12 cases.

The efficacy of low doses of radiotherapy for the treatment of pituitary corticotroph macrotumors in dogs is evaluated retrospectively. Twelve dogs with pituitary-dependent hyperadrenocorticism and a large pituitary tumor treated with 36 Gy of radiation were included. Radiation was delivered in 12 fractions of 3 Gy over a 4- to 6-week period. Effects of radiation therapy on tumor size were assessed by computed tomography scans; a decrease was observed in 11 dogs (decrease > 50% in 6 dogs). Three dogs were reirradiated due to major tumor regrowth or a lack of tumor decrease (mean total dose: 22 Gy given in 3-Gy fractions over 3 or 4 weeks). The mean and median survival times following the initiation of radiotherapy were 22.6 months (688 days) and 17.7 months (539 days), respectively. These data are consistent with previous findings, based on high-dose radiation, showing that radiotherapy is a useful option for treating pituitary corticotroph macrotumors in dogs. Furthermore, computed tomography follow-up of the treated dogs demonstrates objectively the efficacy of radiotherapy against corticotroph tumors in dogs.

Plasma pro-opiomelanocortin, pro-adrenocorticotropin hormone, and pituitary adenoma size in dogs with Cushing's disease.

It is difficult to predict the size of pituitary corticotroph tumors in dogs with Cushing's disease (pituitary-dependent hyperadrenocorticism [PDH]) without pituitary imaging techniques. The purpose of this study was to examine the relationship between plasma adrenocorticotropin hormone (ACTH) precursor concentration and pituitary size in dogs with Cushing's disease. Plasma concentrations of ACTH precursors (pro-opiomelanocortin [POMC]/pro-ACTH) and pituitary tumor height/brain area were measured in 36 dogs with pituitary corticotroph adenomas of various sizes. There was a correlation between tumor size (measured as the pituitary tumor height/brain area ratio [P/B]) and POMC/pro-ACTH concentration (r = .70; P < .0001). Dogs with P/B > or = 0.40 x 10(-2) mm(-1) had higher concentrations of ACTH precursors than dogs with P/B < 0.40 x 10(-2) mm(-1) (median concentration 85 pmol/L, range 15-1,350 pmol/L, n = 14 versus 15 pmol/L, range 15-108 pmol/L, n = 22; P < .0001). With a threshold of 35 pmol/L of POMC/pro-ACTH concentration, the estimated sensitivity and specificity of the kit were 93% (95% confidence interval [CI], 79-100%) and 86% (95% CI, 73-100%), respectively. We interpret these data as indicating that measurement of POMC and pro-ACTH might be of value in the characterization of tumor size in dogs with Cushing's disease. Low POMC/pro-ACTH concentrations make it unlikely that a large pituitary tumor exists in dogs with PDH.