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    Electrochemotherapy in Veterinary Oncology: State-of-the-Art and Perspectives

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    Tumor microenvironment represents a key obstacle for the effectiveness of anticancer drugs. Electrochemotherapy involves the systemic or local delivery of lipophobic drugs such as bleomycin and cisplatin, with the application of permeabilizing electric pulses having appropriate amplitude and waveforms. This greatly enhances the uptake of these drugs by an estimated factor of 700-fold for bleomycin and 4 to 8 times for cisplatin. Because of its efficacy and limited morbidity, this therapeutic option is becoming more and more available in veterinary oncology either as an adjuvant to surgery or as first line of treatment with palliative or curative purposes

    Electrochemotherapy for the treatment of cutaneous solid tumors in equids: A retrospective study

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    Background: Electrochemotherapy (ECT) promotes the increased uptake of antitumor agents through the administration of permeabilizing electric pulses, thus enhancing chemotherapy effectiveness. Aim: Our study aimed to describe the tolerability and efficacy of ECT alone or in association with surgery to manage solid neoplasms in equids. Methods: Medical records of equids with a diagnosis of malignant tumors treated with ECT alone or in combination with surgery were retrospectively evaluated. Each equid received local treatment within the tumors or the tumors’ bed with cisplatin at the dose of 0.5 mg/cm2. Trains of permeabilizing biphasic electric pulses were then applied under spinal or general anesthesia. Results: Sixteen equids were enrolled in this study. There were nine melanoma cases, four fibrosarcoma, and three squamous cell carcinoma. Of those 16 equids, 7 received ECT for treatment of intraoperative local disease, while in 9 cases, ECT was the only treatment modality. The seven equids treated with the combination of ECT and surgery still have no evidence of disease at different times ranging from 9 to 60 months. The remaining nine had the following responses: two complete remissions, five partial responses, one stable disease, and one progressive disease. The treatment was well-tolerated, and local side effects were minimal. No systemic effects were documented. Conclusion: This retrospective study suggests that ECT may be beneficial for equids with solid neoplasms and could be a useful addition to the current therapeutic options considering its low cost, limited toxicity, and ease of administration

    Electrochemotherapy for the treatment of an incompletely excised subcutaneous low-grade epithelioid hemangioendothelioma in a budgerigar parakeet (Melopsittacus undulatus)

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    Background: Cutaneous tumors are rarely described in avian and are frequently of viral origin. Solid tumors of vascular origin are seldom reported and usually result in difficult management by surgery alone. We describe the outcome of a subcutaneous low-grade epithelioid hemangioendothelioma (EHE) treated with the combination of surgery and electrochemotherapy. Case Description: A 10-year-old male budgerigar parakeet (Melopsittacus undulatus) was referred for evaluation of a 2-month non-healing exophytic mass on the left wing. The bird was bright, alert, and responsive, with a 2 × 1 cm proliferative lesion on the wing. Signs of discomfort were elicited by the clinical manipulation of the wing; no other abnormalities were detected during physical evaluation. Following hematological and imaging analysis, the parakeet was anesthetized and the mass was surgically removed. The histopathology report came back with a diagnosis of incompletely excised subcutaneous low-grade EHE. A surgical revision was not feasible due to the anatomical location and tumor extension. Adjuvant electrochemotherapy was chosen to increase the chance of tumor control. Two sessions of electrochemotherapy were performed with a 2-week interval between treatments using intralesional bleomycin followed by trains of permeabilizing electric pulses. Side effects were not observed and the parakeet was disease-free for 12 months when he died of acute renal failure. Conclusion: In lieu of the incomplete surgical excision of the tumor, electrochemotherapy resulted in good local control and cosmetic appearance and should be added to the standard oncological therapies for avian

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

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    Background: Feline 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

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Electrochemotherapy as First Line Cancer Treatment: Experiences from Veterinary Medicine in Developing Novel Protocols

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    Tumor microenvironment is one of the major obstacles to the efficacy of chemotherapy in cancer patients. The abnormal blood flow within the tumor results in uneven drug distribution. Electrochemotherapy (ECT) is a tumor treatment that adopts the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses having appropriate amplitude and waveforms. This allows the use of lipophobic drugs that frequently have a narrow therapeutic index maintaining at the same time a reduced patient morbidity and preserving appropriate anticancer efficacy. Its use in humans is addressed to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, and a standard operating procedure has been devised. On the other hand, in veterinary oncology this approach is gaining popularity, thus becoming a first line treatment for different cancer histotypes, in a variety of clinical conditions due to its high efficacy and low toxicity. This review summarizes the state of the art in veterinary oncology as a preclinical model and reports the new protocols in terms of drugs and therapy combination that have been developed.Tumor microenvironment is one of the major obstacles to the efficacy of chemotherapy in cancer patients. The abnormal blood flow within the tumor results in uneven drug distribution. Electrochemotherapy (ECT) is a tumor treatment that adopts the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses having appropriate amplitude and waveforms. This allows the use of lipophobic drugs that frequently have a narrow therapeutic index maintaining at the same time a reduced patient morbidity and preserving appropriate anticancer efficacy. Its use in humans is addressed to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, and a standard operating procedure has been devised. On the other hand, in veterinary oncology this approach is gaining popularity, thus becoming a first line treatment for different cancer histotypes, in a variety of clinical conditions due to its high efficacy and low toxicity. This review summarizes the state of the art in veterinary oncology as a preclinical model and reports the new protocols in terms of drugs and therapy combination that have been developed

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

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    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

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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