Evaluation of electrochemotherapy in the management of apocrine gland anal sac adenocarcinomas in dogs: A retrospective study.

Background: Electrochemotherapy (ECT) combines the administration of anticancer drugs with the delivery of electric pulses, thus increasing the drug uptake through the cell membranes, resulting in increased efficacy. Aim: The aim of our study was to describe the tolerability and efficacy of ECT alone or in association with other treatment modalities for the management of apocrine gland anal sac adenocarcinoma (AGASAC). Methods: Medical records of dogs with a diagnosis of AGASAC that were treated with ECT alone or in combination with surgery/chemotherapy were retrospectively evaluated. Each dog received 20 mg/m2 of bleomycin intravenously. Based on the clinician's decision, the primary tumor or tumor bed was also infiltrated with cisplatin at the dose of 0.5 mg/cm2. Trains of permeabilizing biphasic electric pulses were then applied under general anesthesia. Results: Ten dogs were enrolled in the study. Of those 10 dogs, only one received ECT for treatment of microscopic local disease, while in six cases ECT was the only treatment modality. In three dogs, ECT was followed by systemic medical treatment. Six dogs (60%) had a partial response (PR), three dogs (30%) had stable disease, and one dog treated for microscopic disease did not show any sign of local relapse for 305 days after treatment, being still alive and in complete remission at the time of writing this article. The median time to progression was 303 days and the median survival time was 365 days. The treatment was well tolerated and local side effects were minimal. No systemic effects were documented. Conclusion: This preliminary study suggests that ECT may be beneficial for dogs with AGASAC and could be a useful addition to the current therapeutic options in consideration of its low cost, limited toxicity, and ease of administration.

Combination of bleomycin and cisplatin as adjuvant electrochemotherapy protocol for the treatment of incompletely excised feline injection-site sarcomas: A retrospective study.

Background: fFeline injection-site sarcomas (FISSs) are mesenchymal tumors that can occur in cats after injections of different medical agents and are easily prone to recurrence. Aim: The aims of this study were to report treatment outcomes for cats with feline injection-site sarcomas (FISSs) treated with both bleomycin and cisplatin, per adjuvant electrochemotherapy (ECT) protocol. Methods: The medical records of cats with a diagnosis of FISS that were treated with ECT using both bleomycin and cisplatin were retrospectively evaluated. A total of 27 cats were available for statistical evaluation of their response. The cats received intravenous 20 mg/m2 bleomycin, and the tumor bed and margins were infiltrated with cisplatin at the dose of 0.5 mg/cm2. Then, the trains of permeabilizing biphasic electric pulses lasting 50 + 50 µseconds each were delivered in bursts of 1,300 V/cm using caliper electrodes under sedation. A second session was performed 2 weeks later. Results: Side effects were limited to local inflammation in three cats. Three cats developed local tumor recurrence at days 180, 180, and 545 after surgery, two cats developed recurrence and metastases at 100 and 505 days after surgery, and two cats experienced distant metastases. A median time to recurrence could not be calculated as over 80% of the study population remained disease free or were censored due to death from other causes. Mean survival time was 985 days, and median cumulative survival for all cases was 1,000 days. Conclusion: When compared to historical controls, the results of this study demonstrate the superior rates of tumor-free survival and disease-free interval. This adjuvant therapy could be a useful addition to the current options for FISS in consideration of its efficacy, limited toxicity, and ease of administration.

Ultrasound guided electrochemotherapy for the treatment of a clear cell thymoma in a cat.

A twelve-year-old male castrated domestic shorthair cat was presented for rapidly progressing respiratory distress. The cat was depressed, tachypneic and moderately responsive. Ultrasonography showed a mediastinal mass associated with a significant pleural effusion that needed tapping every five to seven days. Ultrasound guided biopsy yielded a diagnosis of clear cell thymoma upon histopathology. After complete staging procedures, the owner elected to treat the cat with electrochemotherapy (ECT) using systemic bleomycin. Two sessions of ultrasound guided ECT were performed at two week intervals with trains of biphasic electric pulses applied using needle electrodes until complete coverage of the area was achieved. The treatment was well tolerated and resulted in partial remission (PR). Additional sessions were performed on a monthly basis. The cat is still in PR after fourteen months. ECT resulted in improved local control and should be considered among the available adjuvant treatments in pets carrying visceral tumors.

Histological and Immunohistochemical Characterization of a Case of Endometriosis in a Guinea Pig (Cavia tschudii).

Endometriosis is a chronic gynecological disease characterized by the ectopic proliferation of endometrial tissue outside of the uterine cavity. The pathogenesis of this disease is still obscure, and Sampson's theory of retrograde menstruation is still the most widely accepted explanation. Endometriosis in animals has been so far described not only in baboons and a rhesus macaque but also in dogs and horses that are nonmenstruating animals. In this article, we report the histological and immunohistochemical characterization of the first case of ovarian cystic endometriosis and adenomyosis in a guinea pig. The case presented supports the hypothesis that endometriosis is a disease not at all related to the phenomenon of retrograde menstruation but is a consequence of some alterations in the morphogenesis of the female genital system and therefore it could be found in any mammal. We suggest considering endometriosis among the other pathological phenotypes in animals displaying ovarian and uterine alterations and having a history of difficulties in conceiving.

Dietary Protective Effects Against Hepatocellular Carcinoma Development in Mdr2-/- Knockout Mice.

BACKGROUND/AIM: The Mdr2(-/-) mouse develops early chronic cholestatic hepatitis and hepatocellularcarcinoma (HCC) when adult. We tested the effects of a restricted-calorie diet on HCC development in Mdr2(-/-) mice. MATERIALS AND METHODS: Mdr2(-/-) mice (n=40, divided into two groups of 20 mice each) were randomized to receive ad libitum diet or restricted-calorie diet. Two mice from each group were sacrificed at 3 and 6 months, and liver tissue samples were removed for analysis. The remaining mice were fed their respective diets until the age of 30 months, at which time they were euthanized and livers were collected for analysis. RESULTS: The restricted-calorie diet had partial chemopreventive effect on the development of HCC in Mdr2(-/-) mice. Moreover, mice with ad libitum diet had a median survival of 361 days, while the restricted-calorie group had a median survival of 500 days (p=0.0001). CONCLUSION: A restricted diet might reduce the chance of developing HCC in patients at risk and could increase the protective action of anti-inflammatory agents.

Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors.

BACKGROUND: The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI) increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. METHODS: Thirty-four companion animals (27 dogs and 7 cats) were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats) whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. RESULTS: The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6%) the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17%) experienced short lived partial responses (1-3 months duration) while all the others died of progressive disease within two months. CONCLUSIONS: high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of the quality of life in pets with down staged cancer and in the majority of the treated animals PPI were well tolerated. Further studies are warranted to assess the efficacy of this strategy in patients with advanced cancers in companion animals as well as in humans.