Keijiro Shiomitsu

Intratumoral bleomycin and IL-12 electrochemogenetherapy for treating head and neck tumors in dogs.

Bleomycin and Interleukin 12 have been used clinically to treat tumors; however, the co-administration of Bleomycin and Interleukin 12 followed by electroporation has not been tested clinically. In this study, dogs with spontaneous head and neck tumors were treated with one co-administration of Bleomycin and Interleukin 12 plasmid DNA followed by electroporation. The regression of the recurrent papillary tumor and the adjacent metastatic bone tumor was analyzed by multiple CT scans. The papillary tumor was completely eradicated in less than 2 weeks, and the bone tumor was not visible 23 weeks after the administration.

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma.

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkins) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance.

Evaluation of a ferret-specific formula for determining body surface area to improve chemotherapeutic dosing

OBJECTIVE To use CT-derived measurements to create a ferret-specific formula for body surface area (BSA) to improve chemotherapeutic dosing. ANIMALS 25 adult ferrets (19 live and 6 cadavers). PROCEDURES Live subjects were weighed, and body measurements were obtained by each of 3 observers while ferrets were awake and anesthetized. Computed tomography was performed, and a 3-D surface model was constructed with open-source imaging software, from which BSA was estimated. The CT-derived values were compared with BSA calculated on the basis of the traditional tape method for 6 cadavers. To further validate CT analysis software, 11 geometric shapes were scanned and their CT-derived values compared with those calculated directly via geometric formulas. Agreement between methods of surface area estimation was assessed with linear regression. Ferret-specific formulas for BSA were determined with nonlinear regression models. RESULTS Repeatability among the 3 observers was good for all measurements, but some measurements differed significantly between awake and anesthetized ferrets. Excellent agreement was found between measured versus CT-derived surface area of shapes, traditional tape- versus CT-derived BSA of ferret cadavers, and CT-derived BSA of cadavers with and without monitoring equipment. All surface area formulas performed relatively similarly. CONCLUSIONS AND CLINICAL RELEVANCE CT-derived BSA measurements of ferrets obtained via open-source imaging software were reliable. On the basis of study results, the recommended formula for BSA in ferrets would be 9.94 × (body weight)(2/3); however, this represented a relatively minor difference from the feline-derived formula currently used by most practitioners and would result in little practical change in drug doses.

Comparison of Calculated Radiation Delivery Versus Actual Radiation Delivery in Military Macaws (Ara militaris)

Abstract The skin and oral cavity are common sites of neoplasia in avian species. Radiation therapy has been described for the treatment of these tumors in birds; however, its observed effectiveness has been variable. One possible explanation for this variability when radiation is used to treat the head is the unique anatomy of the avian skull, which contains an elaborate set of sinuses not found in mammalian species. To compare a calculated dose of radiation intended to be administered and the actual amount of radiation delivered to the target area of the choana in 3 adult military macaws (Ara militaris), computed tomography scans were obtained and the monitor unit was calculated to deliver 100 cGy (1Gy) by using radiation planning software. The birds received 3–4 radiation treatments each from a megavoltage radiation therapy unit. A thermoluminescent dosimetry chip (TLD) placed in the choana of the birds was used to measure the amount of ionizing radiation delivered at each treatment. The TLDs were kept in place using Play-Doh as a tissue analog. The actual dose of radiation delivered was lower than the 100-cGy calculated dose, with the 95% confidence limits of predicted bias values between 2.35 and 5.39 (radiation dose from 94.61 to 97.65 cGy). A significant difference was identified between the actual amount of radiation delivered and the calculated radiation goal (P < .001). None of the TLDs received the intended dose of 100 cGy of radiation. The results revealed that the amount of radiation delivered did not reach intended levels. Because the combination of the significance of this discrepancy and the standard dose inhomogeneity could lead to greater than 10% dose inhomogeneity, future investigation is warranted for accurate dose calculation and efficacy of radiation therapy for neoplasia at the lumen of the choana in birds.

Cutaneous epitheliotropic lymphoma with dual CD3 and c-kit expression in a dog.

An 11-year-old 8.9-kg spayed female Boston Terrier was presented for evaluation of a mucocutaneous tumor on the right side of the upper lip that had been biopsied (punch biopsy) by the referring veterinarian. The histologic diagnosis was poorly differentiated round cell tumor involving the submucosa with patchy involvement of the mucosa. On presentation of the dog to Louisiana State University, the tumor was found to involve the mucosa and haired skin surface of the right upper lip. A fine-needle aspirate of the right mandibular lymph node contained atypical poorly differentiated round cells similar to those in the histologic sections. To further characterize the tumor, immunohistochemical analysis of the tumor on the lip was performed; tumor cells were strongly immunoreactive for both CD3 and c-kit in a cytoplasmic to membranous pattern, with CD3 expression having a more intense membranous component. The diagnosis was cutaneous epitheliotropic T-cell lymphoma with co-expression of CD3 and c-kit by neoplastic lymphocytes, an unusual finding. As receptor tyrosine kinases can be attractive targets for cancer treatment, expression of these molecular targets in tumors is a promising subject of future research.

SAFETY AND TOXICITY OF AN ACCELERATED COARSELY FRACTIONATED RADIATION PROTOCOL FOR TREATMENT OF APPENDICULAR OSTEOSARCOMA IN 14 DOGS: 10 GY × 2 FRACTIONS

Coarsely fractionated radiation is commonly used as a method for pain control in dogs with appendicular osteosarcoma, however there is little published information on optimal protocols. The aim of this retrospective, descriptive study was to report safety and toxicity findings in a sample of dogs with appendicular osteosarcoma that had been treated with a radiation scheme of 10 Gy delivered over two consecutive days for a total of 20 Gy. Dogs were included in the study if they had osteosarcoma that was treated with the aforementioned protocol. Dogs were excluded if treated with the same protocol for any other bone tumor besides osteosarcoma or inadequate follow-up. Thirteen of the 14 patients received adjuvant therapy with pamidronate and a nonsteroidal anti-inflammatory. Nine dogs received adjuvant chemotherapy with carboplatin after radiation was complete. Within a median of 14 days, 92.8% of dogs subjectively had improved pain control. Median duration of response (DOR) was 80 days (range 20-365). The majority of patients developed VRTOG grade one toxicity, primarily alopecia. Five dogs (35.7%) developed pathologic fracture postradiation treatment. Timing of fracture was variable ranging from 24 to 250 days. This radiation protocol was well tolerated, with minimal toxicity, subjectively improved survival time, and had the benefit of being completed in two consecutive days.

What is your diagnosis? Abdominal fluid from a dog

A 5-year-old female spayed Dachshund was evaluated at the Louisiana State University (LSU) Veterinary Teaching Hospital and Clinics for chronic diarrhea, vomiting, weight loss, and decreased appetite for 8 weeks. On physical examination, the dog was bright, alert, and responsive and in poor body condition. Cutaneous lesions were not found, and abdominal palpation was within normal limits. A CBC and serum biochemical profile were performed (Table 1). Abdominal ultrasonographic examination revealed moderate anechoic abdominal effusion, corrugation of the small intestine, including the duodenum, and marked thickening of the muscularis layer with preserved layering of the duodenal wall. The liver was hyperechoic with rounded margins, and the spleen was diffusely heterogeneous. Fineneedle aspirates and a tru-cut biopsy of the liver were collected. Endoscopic examination revealed an irregular and thickened, ulcerated, pale duodenal mucosa, and multiple pinch biopsies of duodenum were obtained. Abdominal fluid was blood-tinged, but cleared after centrifugation, and had a total nucleated cell count of 4800/lL and refractometric total protein concentration of 4.1 g/dL. Smears of concentrated abdominal fluid were examined (Figure 1). Figure 1. Concentrated abdominal fluid from a dog. Wright–Giemsa, bar = 10 lm. Table 1. Selected CBC and serum biochemical results from a Dachshund with abdominal effusion.