Takuya Maruo

Case summary: An 8-year-old spayed female Ragdoll cat presented with a several-month history of coughing and exertional dyspnoea. Initial treatment for presumed feline asthma was unsuccessful. Thoracic CT revealed an intraluminal mass at the carina and complete atelectasis of the right middle lung lobe. Endoscopy initially identified an intraluminal mass. As biopsy was considered unsafe owing to the risk of acute airway obstruction, brush cytology was performed instead; however, it was non-diagnostic. As a result of progressive obstructive respiratory failure, urgent palliative radiation therapy was initiated (6 Gy × 6 fractions weekly; total dose 36 Gy). By the fourth fraction, the cat showed marked clinical improvement, and imaging confirmed tumour shrinkage. Before the fifth fraction, endoscopic biopsies were repeated and histopathology established a diagnosis of an epithelial malignant tumour, most consistent with adenocarcinoma. Toceranib phosphate was introduced on an alternate-day schedule as adjuvant therapy. The short-term outcome was favourable, with resolution of clinical signs. The cat remained clinically well more than 150 days after the start of radiation therapy. Relevance and novel information: Primary tracheal tumours are rare in cats, and treatment protocols are not well defined. Surgical excision of masses involving the carina is technically challenging, and radiation therapy for this location has not previously been reported. In this case, a short course of hypofractionated radiation therapy rapidly alleviated airway obstruction, allowing stabilisation of ventilation and subsequent histopathological confirmation. This staged diagnostic–therapeutic approach highlights the utility of hypofractionated radiation therapy as an emergency airway-sparing treatment for cats with obstructive tracheal tumours.

The reproducibility of immobilization is critical in small animal radiotherapy, especially for the head region. We developed a reusable immobilization method using a thermoplastic mask molded with cylinders that can be universally applied, eliminating the need for individual patient‐specific masks. We aimed to compare the effectiveness of this method with two conventional techniques, namely immobilization using a cylinder and patient‐specific thermoplastic mask immobilization. Five beagle dogs underwent repeated CT scans for each method, and the positional errors of the anatomical landmarks were measured. In addition to the maxilla, we examined the mandible and lymph nodes in the head and neck region, which have rarely been considered in previous studies. The results demonstrated that the accuracy of the new universal immobilization method was comparable with that of the conventional methods, with no significant differences in the positioning of the bony landmarks. Universal immobilization outperformed cylindrical immobilization for the lymph nodes. However, large errors were observed in the positions of the lymph nodes across all tested head immobilization methods. The universal method required the shortest setup time, emphasizing its efficiency. It also eliminated the need for patient‐specific individual masks, making it simple and sustainable. Despite certain limitations, such as the exclusive use of beagle dogs and the single‐day anesthesia protocol, the study concluded that the cylindrical thermoplastic mask is a promising method that offers precision and efficiency. This study represents a model investigation rather than a validated clinical approach. Further proof‐of‐principle investigations are required to validate the clinical utility of this approach.

Background: Despite an initial favorable response to hypofractionated radiotherapy (RT), intranasal neoplasia has a poor long-term prognosis. Re-irradiation (re-RT) has been shown to result in clinical remission in dogs with recurrent intranasal tumors. Hypofractionated re-RT is indicated in cases of recurrence. Aim: This study aimed to investigate the response of patients with recurrent intranasal tumors who were initially treated with repeated hypofractionated RT. Methods: Medical records of dogs with intranasal tumors that relapsed after undergoing hypofractionated RT at Azabu University Veterinary Teaching Hospital and who underwent re-RT between 2008 and 2022 were retrospectively analyzed. Results: Among the 30 dogs included, 20 had adenocarcinomas. Eleven patients underwent second re-irradiation, and five patients underwent third re-irradiation. The median total isocenter dose and total number of fractions were 56 Gy (range, 37.5–102) and 8 fractions (range, 5–14), respectively. The first, second, and third progression-free intervals (PFI) were 315 (n = 30), 185 (n = 11), and 218 days (n = 4), respectively. Overall survival (OS) was 504 days (n = 30). Adverse events such as alopecia (n = 7), white hair (n = 8), cataracts (n = 9), pigmentation (n = 5), keratitis (n = 3), and corneal ulceration (n = 1) were limited to grades 1 and 2. The medians of the first PFI for one course and two or more courses of re-RT were 298 and 331 days, respectively, indicating no significant differences between the groups. The OS after two or more courses of re-RT (758 days) was significantly longer than after one course of re-RT alone (414 days) (P = 0.048). However, the cases were not randomized and most of the tumor types were adenocarcinomas. Conclusion: Since it is expected to prolong survival time with few life-threatening adverse events, the findings of the present study suggest that hypofractionated re-RT can be used in dogs with recurrent intranasal tumors initially treated with hypofractionated RT. Therefore, repeated hypofractionated re-RT may be a reasonable option for young dogs with a good initial response and recurrent intranasal tumors.

In veterinary radiotherapy, highly reproducible immobilization is important for accurate irradiation. Consequently, we developed a new reusable head‐immobilization method for dogs using cylinders. This study aimed to compare the accuracy of our novel immobilization method using cylinders with that of bite‐block type immobilization methods. Three immobilization methods were compared: bite‐block only, bite‐block combined with torso immobilization, and immobilization using cylinders. Five beagles with canine teeth underwent CT five times for each of the three immobilization methods. One beagle without canine teeth underwent CT 15 times using each method. Three maxillary landmarks (maxillary incisor, frontal sinus, and occipital bone) and one mandibular landmark (mandibular incisor) were established, and the errors in each immobilization method were measured. For all head landmarks, the error in the immobilization method using cylinders was the most reproducible, with the smallest errors. No significant differences were observed in the time required for immobilization. Although there were limitations (such as the use of dogs from a single breed, a single episode of anesthesia, no disassembly of the immobilization system between scans, and the same person performing the positioning on the same day), we found our new reusable immobilization method using cylinders was the most accurate among the three compared methods. This was a proof‐of‐principle study to evaluate head immobilization using cylinders, and further investigations are needed to confirm its clinical utility.

Intranasal tumors in dogs are malignant solid tumors that are primarily treated with radiotherapy and often recur post-treatment. Combination therapy is pivotal in cancer therapy. Effective drugs include fluoropyrimidine 5-fluorouracil (5-FU) and toceranib phosphate. TS-1, an oral formulation containing the 5-FU prodrug tegafur and enzyme modulators gimeracil and oteracil, is proven to be safe in dogs with solid tumors. While the oral drug toceranib phosphate (Palladia®) is safely administered, the combined toxicity with TS-1 is unknown. We aimed to determine the dosage of this combination in dogs. In the preclinical/clinical trials conducted here, we used a standard 3+3 cohort design with fixed doses of toceranib phosphate (2.4 mg/kg) administered thrice weekly. TS-1 administration was initiated at a dose of 0.5 mg/kg (upper limit 2.0 mg/kg) thrice weekly. Four cohorts were included to confirm the safety of TS-1 and toceranib phosphate. Each cohort was followed up for 1 month. The intranasal tumor types included in the clinical trial (n=13) were adenocarcinoma (n=7), squamous cell carcinoma (n=1), non-epithelial malignancy (n=2), undifferentiated carcinoma (n=1), and transitional carcinoma (n=2). The TS-1 dosage could be increased up to its dose limit in the preclinical/clinical trials. The TS-1 dose to combine with toceranib phosphate thrice weekly was 2.0 mg/kg. This regimen was well-tolerated in dogs. Thus, combined TS-1 and toceranib phosphate therapy is safe for dogs with intranasal tumors.

Background: Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the number of moles of ethylene oxide (EO). HCO ethoxylates have the potential to cause anaphylactoid reactions. There is little published information about these types of reactions in dogs.Objective: To determine the potential for HCO‐ethoxylate‐containing drugs to cause anaphylactoid reactions in dogs, employing intradermal testing (IDT) with various concentrations of HCO ethoxylates (HCO‐25, ‐40, ‐60 and ‐80).Animals: Four healthy male laboratory dogs.Materials and Methods: We performed IDT with drugs containing HCO ethoxylates and HCO ethoxylates alone to determine threshold concentrations. The IDT scores and threshold concentrations were compared. Analysis of skin biopsies from IDT sites was used to measure the percentage of degranulated mast cells. The effect of histamine at IDT sites was investigated by pre‐treatment with an antihistamine.Results: All HCO‐ethoxylate‐containing drugs caused a wheal‐and‐flare reaction. The threshold concentrations (0.001% and 0.00001%) of each HCO‐ethoxylate depended on the number of moles of EO (p < 0.05). Mast cell degranulation was enhanced by all HCO ethoxylates. The HCO‐60‐induced reaction was suppressed by an oral antihistamine.Conclusions and Clinical Relevance: The threshold concentration can serve as a consideration for developing safe new drug formulations and for clinical decision‐making around using drugs containing PEG derivatives. IDT is useful to predict the risk of adverse effects. Antihistamines could demonstrate a prophylactic effect.

Intraoperative acridine orange-photodynamic therapy (AO-PDT) and cribriform plate irradiation are used to treat canine intranasal tumors. The purpose of this study was to evaluate the effects of AO-PDT on intranasal tumors and the recurrence rate of tumors after this treatment. Treatments with AO-PDT were performed on 38 dogs through a narrow window of the dorsal nasal cavity. The median progression-free interval was 12 mo and recurrence was detected in 21 dogs. Based on computed tomography, recurrence in 16 dogs was biased to the following areas: lateral (n = 10), medial (n = 2), ventral (n = 0), rostral (n = 0), and caudal (n = 8). Side effects were mild and included subcutaneous emphysema and rhinitis. The median survival time was 24 mo. Although AO-PDT with cribriform irradiation is an effective treatment for intranasal tumors, AO-PDT techniques should be improved to treat the nasal cavity more uniformly and thoroughly.

Tegafur is a prodrug of fluoropyrimidine 5-fluorouracil (5-FU), while TS-1^TM is an oral fixed-dose combination of three active drugs, tegafur, gimeracil, and oteracil. This pilot study evaluated the safety of tegafur/gimeracil/oteracil in the treatment of cancers in dogs. Tegafur/gimeracil/oteracil was administered orally at a mean dose of 1.1 mg/kg twice daily on alternate days, Monday-Wednesday-Friday, every week to 11 dogs with tumors. Partial response and stable disease were observed in one dog each, whereas six exhibited progressive disease. Three dogs were not assessed. Adverse events, the most serious being grade 2, were noted in seven dogs. Adverse events were acceptable, and the drug was effective in some dogs. Therefore, tegafur/gimeracil/oteracil may be useful for treating malignant solid tumors in canines.

Carboplatin is used to treat certain cancers in dogs and cats and is routinely administered via intravenous drip (IVD). Subcutaneous (SC) administration has also been described. However, the toxicity, serum concentrations, and area under blood concentration-time curves (AUCs) of SC carboplatin are unknown. This study aimed to compare serum carboplatin concentrations in dogs after SC and IVD and to monitor any adverse events. In this crossover study, five dogs received SC or IV carboplatin (300 mg/m2). After a minimum of 3 weeks, each dog received the other treatment. No gross skin toxicity or abnormal clinical signs were observed in any of the dogs. Blood test abnormalities were detected in most dogs. Decreased neutrophil and platelet counts, and increased C-reactive protein (CRP) levels were found. There was no significant difference in the neutropenia, thrombocytopenia, and CRP scores between the groups. Systemic toxicities of SC carboplatin were comparable to those of IVD carboplatin. The time to maximum carboplatin concentration after SC was longer than that after IVD (P<0.001). SC carboplatin remained in the serum longer than IVD carboplatin (P=0.008). The AUC of SC was less than that of IVD (P=0.002). The AUC and time taken to reach the maximum concentration of SC carboplatin were lower than those of IVD carboplatin. This study suggests that SC carboplatin may be an efficacious option for the treatment of tumors in dogs, particularly where IVD administration is challenging.

The preparation of modified Mohs paste, commonly used for malignant wounds, requires time and effort. Moreover, metal-containing liquid waste is generated when malignant wounds are scrubbed. Therefore, we previously changed the base material of the modified Mohs paste from zinc oxide starch powder to carboxymethyl cellulose (CMC). The novel modified Mohs paste based on CMC (moM-CMC sol) may reduce these disadvantages. In the present study, the moM-CMC sol was applied to malignant tumors in three dogs to manage bleeding and malodor. The moM-CMC sol transitioned into a gel on the tumors within an hour of application and could be easily removed. The symptoms resolved within a few days. The moM-CMC sol could be beneficial for dogs with malignant wounds.