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Successful treatment of equine sarcoids with cisplatin electrochemotherapy: A retrospective study of 48 cases
Equine Veterinary Journal
Abstract
Sarcoids are the commonest form of equine skin tumour. Several therapeutic measures have been described but none is considered to be universally effective. Electrochemotherapy (ECT) is a new anticancer therapy that utilises electrical field pulses to induce increased cell membrane permeability to antitumour hydrophilic drugs, such as cisplatin. The increased intracellular concentration of the drugs has a significant therapeutic benefit. The procedure has not been previously reported in a large number of horses.
To validate ECT as a novel alternative treatment for equine sarcoids.
A retrospective study evaluating the efficacy of cisplatin ECT in the treatment of equine sarcoids was performed. Electrochemotherapy treatments were applied under general anaesthesia at 2 week intervals with or without prior excision or debulking. Electric pulses were directly applied to the lesions following intra-tumoural injections of an aqueous solution of cisplatin.
One-hundred-and-ninety-four sarcoids on 34 horses, 2 ponies, 11 donkeys and one mule were treated with ECT. The 4 year nonrecurrence rate was 97.9% for animals (47/48) and 99.5% (193/194) for tumours. When ECT was used as a single treatment, a significant influence of tumour size (ρ= 0.55) on the number of treatments required for cure was shown. When prior surgery was performed, there was a significant influence (P<0.001) of the excision quality (complete or incomplete) and the healing mode (closed or open wound) on the number of treatments. The most common adverse effect was a slight oedematous reaction for lesions located on thin skin regions.
Results demonstrate that ECT, with or without concurrent tumour debulking, is an effective alternative for treatment of equine sarcoids.
... [5][6][7]18 Further techniques, such as interstitial brachytherapy or plesiotherapy and local electrochemotherapy, are commonly reported but may have limited practical availability. [19][20][21][22][23][24][25] The range in treatment modalities is primarily due to widely variable lesion clinical behaviour. Traditionally, selection of treatment modality for this condition has often been based on clinical experience, or anecdotal evidence and case series. ...
... 5 Cisplatin electrochemotherapy, either as a sole treatment or in combination with surgical excision of the mass, gave complete regression rates of 91%-100%. 25 Electrochemotherapy has the advantage of increasing a cytotoxic drug's intracellular concentration and cytotoxicity when compared with intralesional injection alone. 41 Surgical debulking did not significantly influence sarcoid regression rate, but for medium and large-sized tumours significantly reduced the number of treatments needed. ...
... 41 Surgical debulking did not significantly influence sarcoid regression rate, but for medium and large-sized tumours significantly reduced the number of treatments needed. 25 Surgical debulking should therefore be considered prior to ECT in cases with large or invasive tumours. Though this study examined the use of cisplatin with ECT, the most commonly used chemotherapeutic agent in other veterinary species receiving ECT is bleomycin. ...
Background
The sarcoid is the most common equine cutaneous neoplasm. Evidence‐based treatment of this condition is often lacking, and selection of treatment modality based on clinical experience or anecdotal evidence.
Objectives
To assess the quality of the currently available best evidence regarding the treatment of the equine sarcoid.
Study design
Systematic review.
Methods
In compliance with PRISMA guidelines, literature searches were performed in PUBMED, Web of Science, CAB Abstracts, EMBASE (Ovid) and Scopus in April 2021. Included papers were required to describe an interventional study examining sarcoid treatment strategy, of level 4 evidence or greater. The case definition required confirmation of at least some included lesions on histopathology, and a minimum of 6 months of follow‐up was required on treated cases. Studies were assessed by two independent reviewers (KO, CD). Data extraction was performed manually, followed by risk of bias assessment. Methodological quality was assessed using the GRADE system.
Results
In total, 10 studies were included in the review. Case definition was confirmed via histopathology in all included lesions in 60% of papers. Time to follow‐up was variably reported. Overall risk of bias ranged from ‘some concerns’ to ‘critical’. Reported sarcoid regression rate ranged from 28% to 100% on an individual sarcoid level, and 9%–100% on a whole horse level. Transient local inflammation was reported following most treatment strategies, with further adverse events reported infrequently.
Main limitations
Review methodology excluded a large proportion of available literature regarding the equine sarcoid. Significant heterogeneity between included studies prevented quantitative synthesis and most included papers were at significant risk of bias, indirectness, and imprecision.
Conclusions
There is insufficient evidence currently available to recommend one sarcoid treatment over another. There is an urgent need for sufficiently powered, randomised, placebo‐controlled trials in order to allow more definitive comparison of the efficacy of different treatment strategies.
... But nowadays, it can be used as a first-line treatment, alone or in combination with other therapies. It has been used to treat tumors in different anatomical regions, aided by the electrodes specially designed for veterinary and human medicine (5)(6)(7)(8)(9)(10)(11). ...
... Tumors of any histology can be treated with very good results, with an objective response rate of around 70-100%. This high response rate can be observed in dogs, cats, horses, and of course in human patients as well (11,16,17). In particular, in malignant melanoma, the objective response rate in early stages is around 90% (9), in squamous cell carcinomas is around 80% (18), in sarcoids is around 97% (11), and in mast cell tumors of less than 2 cm 3 is around 100% (19). ...
... This high response rate can be observed in dogs, cats, horses, and of course in human patients as well (11,16,17). In particular, in malignant melanoma, the objective response rate in early stages is around 90% (9), in squamous cell carcinomas is around 80% (18), in sarcoids is around 97% (11), and in mast cell tumors of less than 2 cm 3 is around 100% (19). ...
Electrochemotherapy (ECT) consists in the application of electric pulses to increase chemotherapeutic drug intake (bleomycin, cisplatin, or calcium) into the tumor cells. It has become a very valuable treatment option in veterinary oncology. It is an effective and safe treatment modality, which is not only beneficial as a palliative treatment, but also for a curative approach. Performing the treatment adequately will ensure the best results possible, in the minimum number of sessions, and reduce complications. Usually, only one session is enough to achieve excellent results, but the treatment can be repeated. Several sessions can be necessary in the case of incompletely treated or very extended lesions, as well as in the occurrence of new lesions. ECT is effective for superficial or oral tumors of any histology that are accessible to the electrodes. Intravenous bleomycin is the preferred drug and route of administration, leaving other ways of administration and drugs for selected cases. The guidelines presented here are destined to veterinarians who want to develop their understanding of the basis of ECT and wish to perform it adequately and effectively. In this paper, we also discuss common problems and how to solve them, and we include practical tips to improve the treatment results based on common questions and mistakes of beginner users.
... All types of sarcoids responded to the treatment with a 4-year recurrence-free interval for tumors of 99.5%. The treatment was well tolerated by all the animals; the most common adverse effect was a slight edematous reaction for lesions located on thin skin regions (Tamzali et al. 2012). ...
... Also here, ECT was used as a single treatment (18 animals with 52 tumor nodules) or as an adjuvant treatment to marginal surgical excision (14 animals with 18 tumor nodules). In contrast to Tamzali et al. (2012), who performed ECT in 2 weeks' interval, here the authors used a 4-week interval between treatments. Most cases (28/31) were treated with 1-3 sessions, two were treated four times, and one animal was treated with 5 ECT treatments. ...
... Define the treatment plan: for T 2 -T 4 tumors, surgical debulking prior to ECT is recommended for optimal results (Tamzali et al. 2012). Depending on the characteristics of the tumor, an incomplete tumor resection with evidence of gross residual disease or an incomplete resection with microscopically "dirty" tumor margins can be performed. ...
Electrochemotherapy (ECT) has been used in veterinary medicine since the late 1990s and has become increasingly established as a treatment modality for various cutaneous and subcutaneous tumors in dogs. For some tumor types, such as mast cell tumors and perianal tumors, an excellent response can be achieved, while for others, such as oral tumors, palliation of the disease with improvement in quality of life can be expected. In addition to dogs, various tumor types in cats, horses, and exotic pets can be treated with ECT. In this chapter, we have reviewed all the currently available literature describing the use of ECT in different animal species and tumor types. In addition, the treatment procedure for different tumor types in dogs, cats, and horses is presented, describing the selection of appropriate patients, the treatment procedure, and guidelines for follow-up examinations, aftercare, or possible retreatment.
... Sarcoids are the most common skin tumors in equids. Numerous treatments have been described, but none of them manages to cure the tumors and avoid relapses in all types of sarcoids [1]. The choice of the treatment mainly depends on the size and the localization of the tumor, the behaviour of the horse, the financial resources and availability of the owner, the equipment of the veterinarian and the regulations of the country. ...
... This technique allows a considerable increase of the intracellular concentration of the active compound, and therefore a significantly increased therapeutic effect [3][4][5]. It has been shown that ECT with cisplatin was very effective for treatment of equine sarcoids [1,[6][7][8][9][10][11]. However, the use of cisplatin is currently limited due to very restrictive regulations on anticancer drugs in veterinary medicine in many countries [12][13][14]. ...
... Moreover, only the verrucous, nodular, fibroblastic and mixed types were selected [1]. Occult and malignant sarcoids were excluded from the study. ...
Electrochemotherapy (ECT) is an anticancer bioelectrochemical therapy where electrical field pulses (electropermeabilization) increase intracellular concentration of antitumor drugs. The procedure is very effective against skin tumors. The restrictive regulations concerning anticancer drugs in veterinary medicine limit use of ECT. Electroporation with calcium (Electroporation Calcium Therapy)(ECaT) was proved to be effective in vivo on induced tumors in laboratory animals. This study evaluated the effects of ECaT in equine sarcoids (spontaneous skin tumors) on an animal cohort. Pulse parameters for ECaT were choosen for using skin contact electrodes. ECaT was applied under general anesthesia. The tumors were removed at different days after the treatment and analyzed by histology. The study assessed the volume fraction of necrosis that was >50% for 9 of 13 sarcoids. Sixteen sarcoids in 10 horses were treated with ECaT. Macroscopic changes (a crust) were observed in 14/16 tumors. The main microscopic changes were necrosis, ulceration,hemorrhages, calcifications and thrombosis. The adverse effect was an inflammatory local reaction. Surrounding tissues were not affected. This targeted effect can be explained by its control by the field distribution in the tissue and on the interstitial diffusion of the injected Ca²⁺.
... Currently no uniformly effective therapy for its treatment has been reported despite publication of numerous treatment protocols (Byam-Cook et al., 2006;Carstanjen et al., 1997;Compston et al., 2016;Hollis, 2020;Hollis & Berlato, 2018;Klein et al., 1986;Knottenbelt et al., 2020;Knottenbelt & Kelly, 2000;Lane, 1977;Martens, De Moor, Vlaminck, et al., 2001;McCauley et al., 2002;McConaghy et al., 1994;Stadler et al., 2011;Stewart et al., 2006;Tamzali et al., 2012;Theon et al., 2006). Laser excision, either by CO 2 or diode laser, is widely used for the surgical removal of sarcoids (Carstanjen et al., 1997;Compston et al., 2016;Martens, De Moor, Demeulemeester, & Peelman, 2001;Martens, De Moor, Vlaminck, et al., 2001;McCauley et al., 2002). ...
... Though thermal injury secondary to laser excision extends beyond the surgical field, this is variable and difficult to predict (Knottenbelt, 2019;Tate & Tate, 2019). A multimodal approach to sarcoid treatment has frequently been suggested to reduce sarcoid recurrence rates (Klein et al., 1986;Knottenbelt, 2019;Spoormakers et al., 2003;Tamzali et al., 2012), likely due to greater destruction of remaining neoplastic cells in situations where complete tumour excision has not been achieved. ...
Background
Laser excision is used routinely in the treatment of sarcoids but may be ineffective in cases where complete excision cannot be achieved. A multimodal approach is warranted in these cases. 5‐FU may improve the lethal effect of cryosurgery as an adjunct to laser excision.
Objectives
To compare two treatment protocols for equine sarcoids, laser excision alone versus a combination protocol of laser excision, cryosurgery and 5‐FU chemotherapy. Factors associated with sarcoid recurrence are also investigated.
Study design
Retrospective case controlled study.
Results
Eighty‐four horses with 168 histologically confirmed sarcoids were included, with a median follow‐up time of 39 months (IQR 21–62 months). Sarcoid recurrence at the treated site was reported in 38% of cases and in 23% of any individual sarcoid. No significant difference was demonstrated between treatment categories in either rate of sarcoid recurrence ( p = 0.45 for any treated horse, p = 0.63 for individual sarcoid) or time to sarcoid recurrence ( p = 0.73). Sarcoid recurrence was higher in horses with a greater number of sarcoids (OR 1.2 (1.0–1.5), p = 0.03); when treatment had been received prior to admission (OR 7.6 (2.0–33), p = 0.004). Horses with urogenital sarcoids or >1 mixed sarcoid experienced more rapid recurrence (HR 3.6 (1.3–10), p = 0.02 and HR 9.9 (3.3–30), p < 0.001) and recurrence was less rapid following the treatment of a horse's first sarcoid (HR 0.3 (0.1–0.7), p = 0.009).
Main limitations
Significant differences in case populations in each treatment category. Treatment selection was neither blinded nor randomised and missing data and recall bias limit the study's power. Sarcoid recurrence was owner reported.
Conclusions
When assessing the likelihood of sarcoid recurrence, characteristics of both the individual patient and sarcoid phenotype must be considered carefully when selecting a specific treatment protocol.
... For instance, Yildirim et al. demonstrated that the inclusion of 1 wt.% of SWCNT in an alginate scaffold was enough to improve the tensile strength close to that displayed by natural tissues, as well as increasing cell attachment and proliferation [80]. Mechanical and electrical properties of scaffolds can be tuned by modifying the CNT concentration [81] and/or orientation inside the hydrogel [82]. Ahadian et al. reported a tuneable gelatine methacyoyl (GelMA)/aligned MWCNT scaffold which enhanced the differentiation of embryoid bodies into cardiac cells, meaning this could represent a suitable support for any tissue regeneration based on stem cells therapy [82,83]. ...
... Biosensors [15][16][17][18][19][20][21][22][23] Diagnostic [72][73][74][75][76][77][78] Imaging [24][25][26][27][28][29][30][31][32][33][34] Cells guidance and tissue scaffolds [35][36][37][38][39][40][41] Cells guidance and tissue scaffolds [79][80][81][82][83][84][85][86][87][88][89] Drugs and gene delivery [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] Drugs delivery [71,[90][91][92][93][94][95][96][97][98][99] Anticancer therapies [44,[57][58][59][60][61] Skin delivery [100][101][102][103][104] ...
La délivrance de molécules hydrophiles et de macromolécules à travers la peau grâce à l'électroporation est une approche alternative prometteuse à l'injection intradermique. Récemment, nous avons développé un matériau nanocomposite composé de nanotubes de carbone biparois (NTC) et d'un hydrogel d'agarose, pouvant servir à la fois d'électrode et de réservoir adapté à cet objectif. Dans ce matériau, les NTC sont piégés au sein de la matrice d'agarose afin de pouvoir exploiter leurs propriétés mécaniques et électriques, tout en s'affranchissant des questions de toxicité potentielle que leur utilisation soulève. Dans les travaux présentés ici, nous avons approfondi la caractérisation de ce dispositif deux-en-un et évalué son potentiel pour permettre la délivrance transdermique non- invasive de principes actifs par électroporation de la peau. La première partie de ces travaux détaille l'amélioration de l'élaboration du matériau nanocomposite et la caractérisation de ses propriétés. Dans un premier temps, nous avons étudié l'impact de l'ajout d'un dispersant des NTC (Carboxyméthylcellulose ou CMC) sur la préparation du nanocomposite et sur ses différentes propriétés. D'autres procédés visant à améliorer et uniformiser la mise en forme des échantillons obtenus ont aussi été explorés. Nous avons ensuite évalué et comparé la capacité de ces différents nanocomposites à stocker puis restituer un principe actif en utilisant un dextran fluorescent de 4kDa comme molécule modèle (FD4). Enfin nous avons mesuré leurs propriétés mécaniques par rhéométrie ainsi que leurs propriétés de conduction électrique. L'ensemble de ces analyses a confirmé que la présence de CMC permettait une meilleure dispersion des NTC dans les nanocomposites. Cependant, la concentration massique de NTC majoritairement utilisée lors de ces travaux s'est révélée insuffisante pour engendrer des variations significatives des propriétés du matériau. La deuxième partie de ces travaux concerne l'utilisation de ces nanocomposites comme plateforme de délivrance sur des peaux de souris " hairless " ex-vivo. Premièrement, la disposition et la configuration des électrodes utilisées étant différentes de celles de la littérature relative à l'électroporation, nous avons répondu à des questions fondamentales. Nous avons démontré l'efficacité du dispositif à perméabiliser les cellules de l'épiderme de la peau, et identifié le caractère réversible de cette perméabilité induite. Dans une seconde étape, nous avons étudié l'effet des propriétés physico-chimiques (masse et charge) des molécules, ainsi que le rôle respectif des forces motrices de délivrance que sont l'électrophorèse et la diffusion passive. Ces observations nous ont permis de mettre en évidence, pour la première fois à notre connaissance, une asymétrie entre la cathode et l'anode dans la génération des chemins de perméabilisation dans le stratum corneum lors de l'électroporation. Finalement, nous avons évalué la toxicité des NTC sur plusieurs lignées cellulaires de la peau et n'avons observé aucun effet néfaste de ces derniers, dans nos conditions expérimentales. Les travaux effectués au cours de cette thèse nous ont permis de montrer la pertinence d'un dispositif deux-en-un pour la délivrance transdermique non-invasive de molécules hydrophiles par électroporation. Nous avons pu déterminer les leviers disponibles pour l'optimisation des propriétés d'électrodes et de réservoir du nanocomposite. Enfin notre compréhension des mécanismes mis en jeu lors de la délivrance transdermique par électroporation a pu être approfondi, posant ainsi des bases solides pour de futurs travaux.
... Because it strengthens the transmission of molecules to the structure, ECT has a high potential for treating advanced solid tumors [22,23]. In the reversible electroporation (RE) zone, cell membrane permeability due to electroporation can promote drug diffusion into the cells [24][25][26][27], which may improve antitumor efficacy. On the other hand, a preclinical study has shown that IRE enhanced gemcitabine delivery into the RE zone and thereby reduced local recurrence [28]. ...
... is is consistent with findings by Shamseddine et al. that intra-arterial plasma gemcitabine peaks at 30 minutes [40]. Membrane permeation by electroporation enhances drug entry into the cell, enhancing cytotoxicity [26,27,41,42]. ese factors highlight the potential value of ECT in LAPC treatment. ...
Background:
Irreversible electroporation (IRE) is a new local ablation technique for pancreatic cancer. The aim of this study is to analyse the safety and effectiveness of simultaneous gemcitabine and percutaneous CT-guided IRE for locally advanced pancreatic cancer (LAPC).
Materials and methods:
From October 2016 to January 2018, 61 patients with LAPC who received simultaneous gemcitabine and IRE therapy (GEM-IRE group, n = 31) or IRE alone therapy (IRE group, n = 30). Routine intravenous gemcitabine chemotherapy was performed 2 weeks after IRE in both groups.
Results:
Technical success rates were 90.0% (27/30) and 93.3% (28/30) in the GEM-IRE and IRE groups. Compared with the IRE group, the GEM-IRE group exhibited longer overall survival (OS), local tumor progression free survival (LTPFS), and distant disease free survival (DDFS) from IRE (OS, 17.1 vs. 14.2 months, p=0.031; LTPFS, 14.6 vs. 10.2 months, p=0.045; DDFS, 15.4 vs. 11.7 months, p=0.071). Multivariate Cox regression analysis results suggested that tumor volume ≤37 cm3 and simultaneous gemcitabine with IRE were significant independent prognostic factors of OS, LTPFS, and DDFS. Four major adverse reactions occurred; all of them were resolved after symptomatic treatment.
Conclusions:
Simultaneous gemcitabine and percutaneous CT-guided IRE therapy model was effective and well-tolerated therapeutic strategy in LAPC patients.
... The advantages of ECT are its simplicity, short duration of treatment sessions, low chemotherapeutic doses, and no side effects, as determined by the Veterinary Cooperative Oncology Group toxicity scale (Veterinary Co-operative Oncology 2004) in follow-up examinations. The results of published clinical trials suggest a safe and effective use of ECT (Impellizeri et al. 2016;Tozon et al. 2016;Tamzali et al. 2012;Spugnini and Baldi 2019). Partial necrosis of the tumors, more frequent after bleomycin treatment, does not require additional wound healing approaches and causes minimal inflammation reactions of surrounding tissue, which seem to be painless. ...
... Furthermore, cosmetic and functional effects after treatment are excellent. For equid sarcoids, the treatment is favorably combined with surgery, which makes it effective in most cases and provides satisfactory functional and esthetic results (Tamzali et al. 2012). ...
Enormous progress has been made in pulsed electric field-based therapies since the first reports describing the occurrence of electric field-induced transient pores in phospholipid bilayer vesicles. The term electroporation took some time to anchor within the vocabulary of the scientific community. Cell and tissue electroporation, visualized at the single-cell level, can be described as a succession of different steps. By a good selection of the pulses parameters, it is possible to induce a transient or irreversible permeabilization of the cell membrane, and to transfer non-permeant or poorly permeant molecules into cells and tissues. The development and current use of electroporation in oncology practice indeed highly benefitted from the understanding of the mechanisms and underlying biological processes of this method, from the optimization of pulses generators and electrodes, and from the standardization of the operating procedures. Classical electrochemotherapy and irreversible electroporation, already proved their efficacy to treat cancer both in human and veterinary clinics. Gene electrotransfer for immunotherapy and the combination of calcium ions with high-intensity electric field pulses, on another hand, have been developed in the last years, and are emerging as two additional clinical applications of electroporation.
... ECT combines the administration of chemotherapy agents (mostly lipophobic molecules) to permeabilize electric pulses that stimulate their capitation by cancer cells. In equine oncology, most applications of ECT have been aimed at controlling cutaneous sarcoids, with good response rates and cosmetic results (Tamzali et al., 2012;Tozon et al., 2016). Conversely, only scant case reports have been published on other histotypes (Spugnini et al., 2011(Spugnini et al., , 2016(Spugnini et al., , 2017Scacco et al., 2013). ...
... ECT increases the uptake of lipophobic drugs such as cisplatin by tumor cells, obtaining a greater efficacy, and extended local control (Spugnini and Baldi, 2019). Its use in equine oncology is mostly still limited to the treatment of sarcoids (Tamzali et al., 2012;Tozon et al., 2016;Galant et al., 2019) although there are a few case reports of its adoption in the treatment of melanoma, FSA, and SCC (Spugnini et al., 2011(Spugnini et al., , 2016(Spugnini et al., , 2017Scacco et al., 2013), frequently achieving extended local control. To the best of authors' knowledge, this is the first retrospective report of ECT used to treat large solid tumors of non-viral origin in equids. ...
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.
... ECT makes it possible to use incompatible medicine topically in drug-sensitive animals [1]. Several cohort studies of animals with spontaneous neoplasm were treated with biphasic electric pulses with specific chemotherapeutic agents like bleomycin and cisplatin [2][3][4][5][6][7][8][9][10]. Melanoma, squamous cell carcinoma (SCC), various types of sarcoma, and lymphoma have been reported to be successfully treated with ECT in veterinary patients [1]. ...
... ECT is being used as an adjuvant treatment of human cutaneous and subcutaneous tumors. There are also veterinary studies that have described the efficacy of ECT in various cutaneous, oral, and inoperable tumors of dogs, cats, and horses [2][3][4][5][6][7][8][9][10][11][12]. Electrical pulses administered to the tumor changes the permeability of the cell membrane. ...
... A retrospective study from 2011, investigating the effect of treatment with a chemotherapeutic drug (cisplatin) in combination with electroporation (electrochemotherapy) on equine sarcoids, showed very low recurrence rates (1 of 194 treated sarcoids) [14]. However, due to restrictive regulations on the use of chemotherapeutic drugs in veterinary medicine, the first study investigating calcium electroporation treatment of equine sarcoids was initiated and recently published, showing the method´s safety and short-term effects of the treatment [15]. ...
... Furthermore, calcium electroporation may not be the first treatment choice for sarcoids based on these few cases since the response rate is slightly lower than after surgical removal. The response rate, in this study, was also lower than the response shown in a retrospective study of electrochemotherapy on equine sarcoids [14]; however, the use of chemotherapeutic agents requires higher safety standards and expensive handling of biological hazard waste. A great advantage of calcium electroporation treatment is, nevertheless, that it is possible in areas where surgical removal is challenging, such as sarcoids placed on the eyelid. ...
Simple Summary
Sarcoids are skin tumors on horses where better treatment options are needed. Calcium electroporation is a novel anti-cancer treatment where calcium is injected into the tumor, followed by brief electric pulses (electroporation) that transiently open the cell membrane and allow uptake of calcium. This, in turn, induces cell death. In this study, we aimed to investigate the safety and effect of calcium electroporation on sarcoids. Thirty-two sarcoids in eight horses were treated once or twice with calcium electroporation and followed for 12–38 weeks with size-measurement and clinical photographs. The study showed that calcium electroporation is a safe and feasible treatment for sarcoids, including inoperable sarcoids. Six of 27 sarcoids (22%) were completely eliminated, and six further sarcoids (22%) decreased more than 30% in size. No relation between response and location, type, nor size of the sarcoid was observed. Larger studies are needed to further investigate the effect of calcium electroporation on sarcoids.
Abstract
Sarcoids are common equine skin tumors where the risk of recurrence after treatment is high, and better treatment options are warranted. Calcium electroporation is a novel anti-cancer treatment where lethally high calcium concentrations are introduced into the cells by electroporation, a method where short high-voltage pulses induce transient permeabilization of the cell membrane. This study investigated the safety and long-term response of calcium electroporation on sarcoids. Thirty-two sarcoids in eight horses were included. The study suggested that calcium electroporation is a safe and feasible treatment for sarcoids, including inoperable sarcoids. Horses were treated once (2/8) or twice (6/8) under general anesthesia, where sarcoids were injected with 220 mM calcium chloride followed by electroporation with 8 pulses of 100 μs, 1 kV/cm, and 1 Hz. Biopsies were taken prior to treatment. The sarcoid size was monitored for 12–38 weeks after the first treatment. Complete response was observed in 22% (6/27) of treated sarcoids, and partial response in 22% (6/27), giving a 44% total response. Treatment efficacy did not appear to be related to location, type, or size. In all non-biopsied lesions, a complete response was seen (4/4). In conclusion, in this small study, 44% of sarcoids responded with 22% of sarcoids disappearing.
... The ongoing thoroughgoing studies brought about the development of a standard ESOPE protocol (8 pulses, 1000 V/cm 100 μs) (13). Moreover, the beneficial effect of ECT in increasing drug efficiency in cancer cells and decreasing the applied dose of chemotherapeutic has been shown in multiple in vitro and in vivo models (13)(14)(15)(16)(17)(18)(19)(20)(21). Some researchers indicate also thermal ablation techniques including irreversible electroporation (IRE) as appropriate methods for the treatment of lung, liver, kidney and bone tumors (22). ...
... Its antitumor efficacy was verified against several tumors and is currently used in clinical chemotherapy for the treatment of testicular, ovarian, head and neck, and small cell lung cancer (31). CPPD is also one of the drugs applied in electrochemotherapeutic protocols (17,18,(32)(33)(34)(35)(36)(37). However, CPPD has still high cytotoxic impact and undesirable side effects (36)(37)(38). ...
Background/aim:
Small cell lung cancer (SCLC) originates from neuroendocrine branchial cells (15-20%). It is regarded as distinct from other lung cancers due to its biological and clinical features. In most cases of SCLC, surgery or radiotherapy alone is not an effective cure. The aim of our study was to examine the cytotoxic effects of chemotherapy supported by electroporation (EP) on a resistant SCLC model, in vitro.
Material and methods:
The multidrug resistant small lung cell line H69AR was used to evaluate the cytotoxic effects of cisplatin (CPPD) and vinorelbine (Navirel®; NAV) at lower doses when used with EP. Cells were treated with different concentrations of CPPD and NAV, alone or in combination with the following EP parameters: 400-1200 V/cm, 8 pulses of 100 μs duration, at 1Hz. The cell viability was estimated by MTT assay after 24 and 48 h. Apoptotic cells were detected by neutral comet assay and immunofluorescence assay with PARP-6.
Results:
CPPD and NAV alone showed a dose-dependent effect on cell viability. Cytostatic drugs combined with EP revealed increased anticancer activity. Lower doses of CPPD or NAV delivered by EP were as effective as higher doses of these drugs without EP. The electrochemotherapeutic protocols increased the number of apoptotic cells and increased immunoreactivity of PARP-6. Our results indicated higher sensitivity of H69AR cells to NAV supported by EP.
Conclusion:
In SCLC cells, an increased anticancer activity was potentiated by exposure of cells to high intensity electric pulses and low drug doses. It is suggested that this method could be effectively applied in the treatment of lung cancer.
... Electrochemotherapy has proven to be an effective therapeutic modality in the treatment of various neoplasias within human and veterinary medicine. The literature includes reports of squamous cell carcinoma [16,17], melanoma [18,19], soft tissue sarcomas [19,20], injection site sarcomas (ISSs) [21], mastocytomas [22,23], localized cutaneous lymphoma [24], plasma cell tumors [25], perianal tumors [26], and sarcoid lesions [27]. ...
Captive birds of prey often exceed their wild counterparts’ lifespan, as seen in bald eagles (Haliaeetus leucocephalus, ~20 years wild vs. ~40 years captive), golden eagles (Aquila chrysaetos, ~32 years wild vs. ~46 years captive), and Andean condors (Vultur gryphus, ~50 years wild vs. ~79 years captive), highlighting the impact of controlled environments on longevity. However, recent evidence suggests a rising incidence of neoplastic processes in these species. While previous studies have indicated a higher-than-expected prevalence of neoplasia in raptors, comprehensive research on this topic remains scarce. Squamous cell carcinoma (SCC), a frequently reported neoplasm in pet birds, has been documented in birds of prey, though the literature on its prevalence and management is limited. Retrospective studies have identified SCC cases in peregrine falcons (Falco peregrinus), primarily affecting the flank or thigh, with locally invasive behavior and rare distant metastasis. Complete surgical excision is the preferred treatment for SCCs, yet its feasibility is often constrained by tumor invasiveness and anatomical limitations. Electrochemotherapy (ECT) has emerged as a promising alternative, utilizing electroporation to enhance intracellular drug uptake while minimizing systemic toxicity. Bleomycin and cisplatin have been successfully used in avian intralesional chemotherapy, offering a potentially safer and effective treatment approach. ECT has demonstrated efficacy in various exotic species, yet its application in raptors remains largely unexplored. This case report describes the use of electrochemotherapy with bleomycin in a peregrine falcon diagnosed with SCC, contributing to the growing body of evidence supporting its clinical utility in avian oncology.
... This leads to an increase in drug concentration in the sarcoid cells and an increase in its effect. Horses usually undergo the procedure under a brief general anesthesia because of the electric shock (Tamzali et al., 2012), if sedation combined with locoregional techniques is not a viable option. In equids, ear manipulation may be very painful. ...
Background
During electrochemotherapy (ECT), a chemotherapeutic drug is injected into the tumor and then an electroporation is provided. In horses, ear manipulation may be very painful, and combining a loco-regional technique with sedation might be a good option to avoid anesthesia-related risks. A two-injection-point block of the internal and external pinna and acoustic meatus was described in horse cadavers, and it permitted complete stain of all three branches of the great auricular nerve (GAN), internal auricular nerve branch (IAB), lateral auricular branch (LAB), and caudal auricular nerve (CAN), suggesting a lower risk of intra-parotid injection during the IAB and LAB block.
Case Description
An 8-year-old Italian jumping gelding presented for ECT to treat a fibroblastic sarcoid in the left medial pinna. After intravenous sedation with acepromazine, romifidine, and butorphanol, a two-injection-point block was provided as previously described. The block of the GAN was blind, whereas an electrical nerve locator was used for the IAB, LAB, and CAN. A total of 12 ml of 0.5% ropivacaine was injected. The ECT was safely performed without any difficulties. The horse well tolerated the procedure and completely recovered 75 minutes after sedation. No complications were detected.
Conclusion
The described approach seems feasible and suitable for the blockade of the sensory innervation of the equine ear in the case of ECT.
... As lesões mais comuns são vistas em pele fina e com áreas de pouco pelo, incluindo a face, porção medial dos membros, virilha, pálpebras, orelhas e abdômen (7). Sua etiologia ainda é controversa (8), mas estudos já concluíram que o papiloma vírus bovino tipo 1 e 2 estão associados com a manifestação do sarcóide em cavalos que possuem um contato maior com bovinos (9). ...
Equine sarcoid is a cutaneous neoplasm, with fibroblast, non-metastatic origin, locally invasive, responsible for even 66% of skin tumors in equines. Among treatments alternation, the use of intratumoral cisplatin after previous surgical excision is an option, with low recurrence rate. This study aims to report the case of a sarcoid located in the left supraorbital region of a mare and its treatment with intratumoral cisplatin. A mare was seen, tordilha, SRD, 5 years old and the weight of 280 Kg, presenting non-ulcerative volume increase in the left supraorbital region, with progressive evolution of 60 days. Neoplasm was suspected and lesion complete excision was made and forwarded to histopathological examination and sarcoid was diagnosed. Due to tumor recurrence, the second procedure was excision of tumor mass followed by chemotherapy treatment wtih 1mg/cm3 cisplatin dose of tumor mass. The drug was injected through intratumoral, during 4 applications, with two weeks breaks between every application. It was observed involution of the lesion right after the first dose until tumor's complete remission at the end of the treatment. The animal was seen during 7 months after the end of therapy and it was noted complete healing without sequels and relapses. It can be concluded that prognosis was favorable, and treatment proposed on this case report trough chemotherapy with intralesional cisplatin associated to surgical excision was effective.
... These models can predict tissue volume coverage and the suitable electrode configuration. The literature recommends using static numerical models of electric field-dependent conductivity (e.g. based on Finite Element Method or Finite Difference Method) to explain the non-linear increase of the conductivity and field distribution due to pore formation (Suzuki et al 2018, Tamzali et al 2012. Yet, some deep-seated tumors are known to be challenging for ECT. ...
Electrochemotherapy success is directly related to tumor electric field coverage, and the coverage failure may result in tumor recurrence and pain. The electric field may diffract during nodule treatment due to surrounding dielectrics and non-linear dynamic response to electroporation. Computational models are used to study this complex process and optimize the treatment. Bone is characterized as a low electric conductivity material, and if located near tumor regions, it may affect the electric field distribution. This paper aims to assess the electric field distribution in cancer-infected tissue near bones. We calculated the electric field distribution using computational simulations
(COMSOL Multiphysics). Our case study was a dogs' nasal cavity tumor surrounded by bone (semi ellipsoid). We investigated whether the voltage pulses would meet electrochemotherapy electric field requirements. This is, minimizing the lack of an insufficient electrical field, the so-called indentation. We studied a range of 282.4 to 529.5 V applied to a recently ECT electrode apparatus. We also studied if a conductive gel could enhance the electrical field distribution. Results showed that high electric field application does not solve the indentation problem. The electric field indentation was detected from approximately 3 mm electrode-bone proximity region at the lowest electric fields and increased to 5 mm at 150 kV/m. The electric field indentation mostly occurred due to the bone insulator behavior. The use of the conductive gel also led to indentation. The tumor volume coverage is reduced when compared with simulations without
gel, thus it is not recommended for use in this situation.
... The prior studies have shown promising results with singular use of the technique and its use as an adjunct with other therapies. These results corroborate the need for further studies to prove that the technique can be an alternative treatment for malignant melanomas in dogs (64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80). ...
Melanoma is a prevalent, aggressive form of cancer in dogs. New treatment or preventive modalities are necessary to control this disease in dogs. On December 03, 2020, the Brazilian Association of Veterinary Oncology, ABROVET, organized the “Colloquium on Canine Melanoma” to present the newest achievements for the treatment of this disease.
Invited talks included fundamental aspects of canine melanoma, and conventional and innovative therapies. The talks were delivered online and more than 100 attendees joined the transmission. This report aims to present the most important information about canine melanoma discussed at the Colloquium.
... Electrochemotherapy (ECT) and/or gene electrotransfer of plasmid DNA encoding interleukin-12 (GET pIL-12) are effective treatments for cutaneous, subcutaneous and maxillofacial tumors in dogs (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41), superficial cell carcinoma in cats (42), cutaneous tumors in ferrets (43) and sarcoid tumors in horses (44,45). Several preclinical (46)(47)(48)(49) and clinical studies in veterinary patients (26-28, 33, 36, 50) have shown that the effect of ECT is potentiated by GET pIL-12, and ECT has become an established standard of care for a variety of human cancers: cutaneous and subcutaneous tumors, including melanoma, squamous cell carcinoma, basal cell carcinoma, and other metastases (51)(52)(53)(54)(55)(56)(57)(58); hepatocellular carcinoma and colorectal liver metastases (59)(60)(61)(62)(63); pancreatic neoplasia (64)(65)(66); and others. ...
Electrochemotherapy (ECT) and/or gene electrotransfer of plasmid DNA encoding interleukin-12 (GET pIL-12) are effective treatments for canine cutaneous, subcutaneous, and maxillofacial tumors. Despite the clinical efficacy of the combined treatments of ECT and GET, data on parameters that might predict the outcome of the treatments are still lacking. This study aimed to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) results of subcutaneous tumors differ between tumors with complete response (CR) and tumors without complete response (non-CR) in dogs treated with ECT and GET pIL-12. Eight dogs with a total of 12 tumor nodules treated with ECT and GET pIL-12 were included. DCE-US examinations were performed in all animals before and immediately after therapy as well as 8 h and 1, 3, and 7 days later. Clinical follow-up examinations were performed 7 and 14 days, 1 and 6 months, and 1 year after treatment. Numerous significant differences in DCE-US parameters were noted between tumors with CR and non-CR tumors; perfusion and perfusion heterogeneity were lower in CR tumors than in non-CR tumors. Therefore, studies with larger numbers of patients are needed to investigate whether DCE-US results can be used to predict treatment outcomes and to make effective decisions about the need for repeated therapy or different treatment combinations in individual patients.
... EP is a safe procedure because it does not affect normal pancreatic parenchyma. Additional in vitro studies showed that EP potentiates the bleomycin cytotoxicity in pancreatic tumor cell lines 54,55 . ECT was successfully used to treat nasal cavity tumors in dogs with single-needle electrodes achiev-ing 60% survival rate at 1 year and 30% at 32 months, while 0% was observed for the control group 56 . ...
Electroporation (EP) techniques, used alone (Irreversible Electroporation, IRE) or in combination with anti-cancer drugs (Electrochemotherapy, ECT), have been shown to be effective in the treatment of several types of cancers. The efficacy of ECT and IRE is well demonstrated for the treatment of non-superficial tumor metastases, and it depends on the applied electrical parameters. Particularly, ECT is an effective local therapy that uses electroporation to enhance the cytotoxic effect of bleomycin or cisplatin injected intravenously or intratumorally. Pre-clinical investigations to test alternative anti-cancer drugs, explore new combinations of treatment modalities, and evaluate different sets of pulse protocols for effective tissue electroporation, are ongoing. Further ECT developments include the treatment of deep-seated tumors with percutaneous, laparoscopy, and endoscopy approaches, with the aim of establishing a less invasive approach. ECT is highly effective in the treatment of tumors of any histology, in minimizing the damage of critical normal tissue or organs, and in reducing pain and muscular contractions. This work describes the new technological advances in the field of ECT treatment for deep-seated tumors.
... Elle est directement dépendante de l'intensité du champ appliqué , de la géométrie des électrodes (Čorović et al. , 2008) et de la composition du tissu (Čorović et al. , 2007;Miklavcic et al. , 1998). Basé sur ces preuves de concept in vitro et in vivo, l'ECT a pu être transposée en clinique humaine Rols et al. , 2002) mais aussi vétérinaire (Tamzali et al. , 2012). La standardisation des paramètres électriques pour une application clinique humaine a permis d'introduire l'ECT dans plusieurs pays européens (130 centres hospitalier et cliniques), on parle de procédures opératoire normalisées (Standard Operating Procedure, SOP) . ...
Au cours de ces dernières décennies, l'arsenal des thérapies anticancéreuses basées sur des principes physiques tels que les radiofréquences, les ultrasons, le laser, l'électroporation, la thérapie photo dynamique et les plasmas a considérablement augmenté. Ces approches permettent d'éradiquer les cellules cancéreuses, directement ou via la stimulation du système immunitaire. Elles sont aussi proposées en tant que méthodes de vectorisation pour délivrer des molécules d'intérêt thérapeutique. Plus récemment, est apparu un intérêt grandissant pour l'utilisation en thérapie anti-cancéreuse de liquides enrichis en espèces réactives de l'oxygène et de l'azote (RONS) via leur exposition au plasma froid. Les cellules cancéreuses peuvent ainsi être éradiquées, de façon sélective, après contact avec du liquide activé par plasma (PAL). Néanmoins, les mécanismes d'action de ces PAL sont encore peu connus à ce jour. C'est dans ce contexte que nous avons évalué le potentiel thérapeutique de différentes solutions salines exposées au jet de plasmas froids sur les cellules cancéreuses. Parallèlement, l'électroperméabilisation ou électroporation (EP) réversible connaît un essor important en raison du développement de ses applications cliniques notamment en électrochimiothérapie pour favoriser le transfert d'agent anti-cancéreux. Nous avons proposé une approche innovante reposant sur la combinaison des PAL et de l'EP, afin de potentialiser les effets cytotoxiques et génotoxiques des PAL, via la déstabilisation par l'EP de la tumeur, et obtenir ainsi une éradication plus efficace. Dans un premier temps, nous avons étudié l'effet du tampon phosphate salin (PBS) et du chlorure de sodium (NaCl) exposés au jet hélium de plasma froid, in vitro, sur la croissance, la viabilité/mort cellulaire et l'organisation structurelle de modèles 3D de tumeurs non-vascularisées (les sphéroïdes). Deux lignées cellulaires cancéreuses ont été utilisées : cellules de cancer colorectal humain HCT-116 et cellules de carcinose ovarienne péritonéale humaine SKOV-3. Nous avons mis en évidence que ces PAL induisent une cascade d'évènements cellulaires : fuite de l'ATP intracellulaire, dommages à l'ADN et dysfonction mitochondriale, provoquant la mort apoptotique des cellules des couches externes du sphéroïde dans les heures suivant le traitement (~6 heures). De plus, le PBS activé par plasma a montré une cytotoxicité et génotoxicité supérieure au NaCl, qui est corrélée avec la quantité de RONS présente dans les PAL. L'efficacité d'éradication des cellules cancéreuses de ces PAL se limitent aux cellules en périphérie des sphéroïdes. Il est nécessaire de faire plusieurs traitements pour avoir une éradication totale. Ainsi dans une deuxième partie, afin de pallier les problèmes de pénétration des PAL, nous avons proposé de les associer à l'EP réversible. La combinaison de ces deux approches a montré une potentialisation de la cytotoxicité et la génotoxicité des PAL, induisant la mort de toutes les cellules cancéreuses du sphéroïde. Cette augmentation de l'efficacité est en partie causée par des réarrangements des jonctions cellulaires suite à l'EP et à l'induction d'une mort cellulaire par autophagie.[...]
... 11 In another study of 194 sarcoids in 48 equids (34 horses of various breeds, 2 ponies, 11 donkeys, and 1 mule), there were 15 occult, 80 verrucous, 30 nodular, 35 fibroblastic, and 34 mixed forms. 107 Similarly, within 467 sarcoids in horses of various breeds from western Canada, the following clinical types were diagnosed: fibroblastic (145), nodular (104), occult (72), verrucous (72), and mixed (74). Malignant sarcoids are described rarely. ...
Equine sarcoid is the most common skin tumor of horses. Clinically, it occurs as a locally invasive, fibroblastic, wart-like lesion of equine skin, which has 6 clinical classes: occult, verrucose, nodular, fibroblastic, mixed, and malignant. Sarcoids may be single but multiple lesions are more frequent. The typical histological feature is increased density of dermal fibroblasts which form interlacing bundles and whorls within the dermis. Lesions are mostly persistent, resist therapy, and tend to recur following treatment. In general, sarcoids are not fatal but their location, size, and progression to the more aggressive form may lead to the withdrawal of a horse from use and serious infringement of their welfare leading to the loss of valuable animals. Bovine papillomavirus (BPV) type 1 and less commonly type 2 contribute to the development of equine sarcoid. The viral genome and proteins are detected in a high percentage of cases. Furthermore, viral oncoprotein activity leads to changes in the fibroblastic tissue similar to changes seen in other types of tumors. Equine sarcoids are characterized by a loss of tumor suppressor activity and changes allowing abnormal formation of the affected tissue, as well as y immune defense abnormalities that weaken the host’s immune response. This impaired immune response to BPV infection appears to be crucial for the development of lesions that do not spontaneously regress, as occurs in BPV-infected cows.
... Matching was done to minimize biological variation when comparing ES-affected horses to tumor-free control horses and ES-affected donkeys to tumor-free control donkeys.23 Cases and controls were not matched for comparison of ES-affected horses to horses with other skin tumors, because different breed dispositions exist for ES disease compared to melanoma or genital SCC. Furthermore, ES disease often manifests earlier in life than do the other 2 skin tumors.[24][25][26][27][28][29][30] ...
Background
MicroRNAs (miRNAs) are potential biomarkers for equine sarcoids (ES).
Objectives
To assess eca‐miR‐331, eca‐miR‐100, and eca‐miR‐1 as serum biomarkers for ES disease.
Animals
Sixty‐eight ES cases (56 horses, 12 donkeys), 69 tumor‐free controls (60 horses, 9 donkeys), and 20 horses with other skin tumors.
Methods
For this case‐control study, expression of serum eca‐miR‐331, eca‐miR‐100, and eca‐miR‐1 in ES‐affected equids was compared to tumor‐free age‐, sex‐, and breed‐matched control horses and donkeys with other skin tumors using reverse transcription quantitative PCR (polymerase chain reaction) for relative miRNA quantification. Biological, preanalytical, and clinical variable influences on miRNA expression were examined. Receiver operator characteristic (ROC) curve analyses were used to determine differences in miRNA expression between groups.
Results
The expression of eca‐miR‐100 was affected by age (P = .003) and expression of eca‐miR‐100 and eca‐miR‐1 were affected by hemolysis (both P < .001). Eca‐miR‐331 was unaffected by biological variation, hemolysis, ES type, and disease severity. Eca‐miR‐331 concentrations were higher in ES‐affected compared to tumor‐free controls (P = .002). The ROC curve analysis indicated an area under the curve of 0.65 (P = .002) with a sensitivity of 60%, specificity of 71%, and positive and negative likelihood ratios of 2.1 and 0.56, respectively, to diagnose ES. Eca‐miR‐331 expression did not discriminate between horses with ES and other skin tumors. Expression of eca‐miR‐100 and eca‐miR‐1 was not different between groups.
Conclusions and Clinical Importance
Serum eca‐miR‐331 expression is neither sensitive nor specific enough as a single ES biomarker. If combined with other miRNAs, it may be helpful for ES diagnosis.
... In veterinary medicine, ECT is used for the treatment of cutaneous, subcutaneous and oral tumors in dogs (31-35) and (still mostly) cutaneous tumors in cats (36) and horses (37,38). In mast cell tumors (MCT) in dogs, up to a 70% complete response rate can be achieved with no major local or systemic side effects (31). ...
Electroporation is a method of inducing an increase in permeability of the cell membrane through the application of an electric field and can be used as a delivery method for introducing molecules of interest (e.g., chemotherapeutics or plasmid DNA) into cells. Electroporation-based treatments (i.e., electrochemotherapy, gene electrotransfer, and their combinations) have been shown to be safe and effective in veterinary oncology, but they are currently mostly recommended for the treatment of those solid tumors for which clients have declined surgery and/or radiotherapy. Published data show that electroporation-based treatments are also safe, simple, fast and cost-effective treatment alternatives for selected oral and maxillofacial tumors, especially small squamous cell carcinoma and malignant melanoma tumors not involving the bone in dogs. In these patients, a good local response to treatment is expected to result in increased survival time with good quality of life. Despite emerging evidence of the clinical efficacy of electroporation-based treatments for oral and maxillofacial tumors, further investigation is needed to optimize treatment protocols, improve clinical data reporting and better understand the mechanisms of patients' response to the treatment.
... 7 ECT consists in the application of an electric field to a tumor in order to increase the uptake of bleomycin that was previously administered (locally or intravenously) at a very low dose 8,9 ; alternatively, cisplatin can be used locally with equally good results. 10 ECT is primarily indicated for cutaneous and subcutaneous tumors of any histology. After the electric field is applied, a cell membrane permeabilization is produced by a physical phenomenon known as electroporation, affecting all tumor cells, regardless of the histological tissue. ...
Background
Oral malignant melanoma is the most common, but aggressive oral cancer in dogs with poor prognosis. Electrochemotherapy (ECT) has therapeutic potential in such tumors as effective local treatment. Therefore, the aim of this prospective clinical study was to evaluate treatment effectiveness of ECT in as first line treatment for canine oral malignant melanoma, and search for factors influencing treatment outcome.
Methods
Sixty-seven canines with primary oral malignant melanoma, non-candidates for first-line therapy, were enrolled. All dogs received ECT and follow-up exams for the span of two years.
Results
Based on RECIST criteria, the objective response rate was 100%, 89.5%, 57.7%, and 36.4%, in stage I, II, III and IV, respectively. Only patients in stage I, II and III with partial or complete response improved their quality of life. The median time to progression was 11, 7, 4 and 4 months, and median survival time after the treatment was 16.5, 9.0, 7.5 and 4.5 months, for patients in stage I, II, III and IV, respectively. Significantly better was local response in stage I and II disease (p = 0.0013), without the bone involvement (p = 0.043)
Conclusions
Electrochemotherapy is effective local treatment of oral canine malignant melanoma when no alternative treatment is available. Better response is expected in stage I and II patients with tumors without bone involvement.
... Recently, a new study on 31 horses and 1 donkey was published, confirming the excellent results obtained previously, with a 100% complete response rate. 102,103 Electrochemotherapy with cisplatin can be used alone, when tumors are small, or it can be used together with debulking surgery in cases of larger tumors. ...
Electrochemotherapy is gaining recognition as an effective local therapy that uses systemically or intratumorally injected bleomycin or cisplatin with electroporation as a delivery system that brings drugs into the cells to exert their cytotoxic effects. Preclinical work is still ongoing, testing new drugs, seeking the best treatment combination with other treatment modalities, and exploring new sets of pulses for effective tissue electroporation. The applications of electrochemotherapy are being fully exploited in veterinary oncology, where electrochemotherapy, because of its simple execution, has a relatively good cost-benefit ratio and is used in the treatment of cutaneous tumors. In human oncology, electrochemotherapy is fully recognized as a local therapy for cutaneous tumors and metastases. Its effectiveness is being explored in combination with immunomodulatory drugs. However, the development of electrochemotherapy is directed into the treatment of deep-seated tumors with a percutaneous approach. Because of the vast number of reports, this review discusses the articles published in the past 5 years.
... [46] In addition, ECT is also used in veterinary oncology, for the treatment of metastases as well as primary tumors. [47][48][49][50] The success rate of primary tumor treatment with ECT also provides good evidence for translation of ECT into the treatment of less-advanced tumors in humans. ...
... Chemotherapeutics in particular are able to more readily pass through the membranes of electroporated cells, increasing their efficacy when delivered alongside electroporation treatments [35]. These electrochemotherapies have combined electroporation with bleomycin [200], cisplatin [290,291], and most recently calcium [32] to successfully treat tumors. If the applied electric field is sufficiently strong and applied over enough time, electroporation may also be used directly as an effective tumor ablation modality [16]. ...
Electroporation-based treatments are motivated by the response of biological membranes to high- intensity pulsed electric fields. These fields rearrange the membrane structure to enhance the membrane's diffusive permeability, or the degree to which a membrane allows molecules to diffuse through it, is impacted by the structure, composition, and environment in which the cell resides. Tracer molecules have been developed that are unable to pass through intact cell membranes yet enter permeabilized cells. This dissertation investigates the hypothesis that the flow of such molecules may be used to quantify the effects of the electrical stimulus and environmental conditions leading to membrane electroporation. Specifically, a series of electrical pulses that alternates between positive and negative pulses permeabilizes cells more symmetrically than a longer pulse with the same total on-time. However, the magnitude of this symmetric entry decreases for the shorter alternating pulses. Furthermore, a method for quantitatively measuring the permeability of the cell membrane was proposed and validated. From data near the electroporation threshold, the response of cells varies widely in the manner in which cells become permeabilized. This method is applied to study the transient cell membrane permeability induced by electroporation and is used to demonstrate that the cell membrane remains permeable beyond 30 min following treatment. To analyze these experimental findings in the context of physical mechanisms, computational models of molecular uptake were developed to simulate electroporation. The results of these simulations indicate that the cell's local environment during electroporation facilitates the degree of molecular uptake. We use these models to predict how manipulating both the environment of cells during electroporation affects the induced membrane permeability. These experimental and computational results provide evidence that supports the hypothesis of this dissertation and provide a foundation for future investigation and simulation of membrane electroporation.
... 7 ECT consists in the application of an electric field to a tumor in order to increase the uptake of bleomycin that was previously administered (locally or intravenously) at a very low dose 8,9 ; alternatively, cisplatin can be used locally with equally good results. 10 ECT is primarily indicated for cutaneous and subcutaneous tumors of any histology. After the electric field is applied, a cell membrane permeabilization is produced by a physical phenomenon known as electroporation, affecting all tumor cells, regardless of the histological tissue. ...
Electrochemotherapy is a treatment modality which has been increasingly used in veterinary and human medicine for treating cutaneous and subcutaneous tumors. In this prospective work we evaluated the outcome of using electrochemotherapy as a first-line treatment for canine oral melanoma in different stages, with the aim of determining predictive factors of response to the treatment. Mucosal melanoma is the most common cause of oral cancer in dogs. Canine oral malignant melanoma is very similar to human oral melanoma in many aspects, being a very good translational model for studying response to this treatment. Sixty-seven canine patients were treated. Intravenous bleomycin was the preferred drug, and the standard operating procedures for electrochemotherapy were followed. The patients were followed-up for two years. According to WHO criteria, the objective response per stage was: stage I 100%, stage II 89.5%, stage III 57.7% and, stage IV 36.4%. The overall median survival was 7.5 months (2-30 months, mean 9.1 months). Median overall survival of patients in stage I was 16.5 months, in stage II was 9 months, in stage III 7.5 months, and in stage IV 4.5 months. The average number of electrochemotherapy sessions was 1.5 for every stage. The incidence of new metastases among treated patients was 28.4%. Patients in advanced stages, with bone involvement, and caudal location of the tumor had poorer response rates and shorter overall survival times. The treatment greatly improved the quality of life of the patients. Electrochemotherapy is an important technique in the oncological armamentarium against melanoma, and these results can be used to predict human response to this therapy in each stage.
El carcinoma de células escamosas (CCE) es uno de los tumores cutáneos más frecuentes en la clínica equina, la presentación a nivel de globo ocular y anexos es de complejo abordaje terapéutico. Existen varios factores asociados al riesgo de desarrollar este tipo de neoplasia, como la exposición a los rayos UV, la despigmentación y la predisposición genética de ciertas razas. La recurrencia tumoral es frecuente luego de la cirugía oncológica y en ocasiones debe optarse por un tratamiento paliativo. El objetivo de este trabajo fue presentar el caso clínico de un padrillo paint horse con CCE palpebral, el cual fue tratado con electroquimioterapia (ECT) como monoterapia. El procedimiento fue realizado bajo anestesia general a campo y se llevaron a cabo controles clínicos a los 7, 15 y 45 días pos ECT para evaluar la respuesta a esta. Se observó una remisión completa del tumor a los 45 días después del procedimiento. En la actualidad, 24 meses después de la aplicación de la ECT, no se ha observado recidiva en el animal. Sin embargo, el pronóstico es reservado, debido a las características biológicas inherentes al tipo tumoral y a las posibilidades de recurrencia reportadas para esta neoplasia. El caso clínico presentado nos brinda a la ECT como una técnica alternativa a la cirugía oncológica en el CCE palpebral equino.
Introduction
Integrated time nanosecond pulse irreversible electroporation (INSPIRE) is a novel tumor ablation modality that employs high voltage, alternating polarity waveforms to induce cell death in a well-defined volume while sparing the underlying tissue. This study aimed to demonstrate the in vivo efficacy of INSPIRE against spontaneous melanoma in standing, awake horses.
Methods
A custom applicator and a pulse generation system were utilized in a pilot study to treat horses presenting with spontaneous melanoma. INSPIRE treatments were administered to 32 tumors across 6 horses and an additional 13 tumors were followed to act as untreated controls. Tumors were tracked over a 43–85 day period following a single INSPIRE treatment. Pulse widths of 500ns and 2000ns with voltages between 1000 V and 2000 V were investigated to determine the effect of these variables on treatment outcomes.
Results
Treatments administered at the lowest voltage (1000 V) reduced tumor volumes by 11 to 15%. Higher voltage (2000 V) treatments reduced tumor volumes by 84 to 88% and eliminated 33% and 80% of tumors when 500 ns and 2000 ns pulses were administered, respectively.
Discussion
Promising results were achieved without the use of chemotherapeutics, the use of general anesthesia, or the need for surgical resection in regions which are challenging to keep sterile. This novel therapeutic approach has the potential to expand the role of pulsed electric fields in veterinary patients, especially when general anesthesia is contraindicated, and warrants future studies to demonstrate the efficacy of INSPIRE as a solid tumor treatment.
Sarcoids are common mesenchymal neoplasms of horses. Although there are few studies in which sarcoids have been followed over a long period of time, sarcoids are considered locally invasive and have been reported to frequently recur following surgical excision. Currently, no histological features have been identified to predict which sarcoids will recur after excision. The present study comprised 49 sarcoids for which histology sections were available and in which the recurrence status of the case was known. Each sarcoid was excised from a different horse. Overall, 12 of the 49 (24%) sarcoids recurred after surgical excision. Mitotic count (MC), cellularity, necrosis, nuclear pleomorphism, and inflammation of the sarcoids were evaluated histologically. Of these, MC correlated with recurrence. Four of 5 (80%) sarcoids with an MC ≥ 20 in 2.37 mm ² recurred, which was a significantly higher recurrence rate than that of sarcoids with an MC < 20, 8 of 44 cases recurred (18%), P = .0051. Clinical type was also found to correlate with recurrence. Three of 4 (75%) fibroblastic types recurred, which was a significantly higher recurrence rate than that of sarcoids with other clinical types, 9 of 45 cases (18%), P < .001. In addition, univariate Cox regression analysis confirmed fibroblastic type and MC ≥ 20 as significant predictors for recurrence ( P = .016 and P = .005, respectively). To the authors’ knowledge, this is the first large study examining recurrence rates in sarcoids, and the first time that histological features have been correlated with recurrence.
The field of bioelectrics lies at the intersection of biomedical engineering, biophysics, pulsed power technology, and bioscience, guided by the underlying theme of using electric pulses of varying waveforms and durations to drive and manipulate desired biological responses and outcomes in cells and tissues. The ever-growing list of applications includes tumor treatment, wound healing, neurostimulation, decontamination and inactivation of microorganisms and pathogens, cardiac ablation for the treatment of arrhythmias, and many more. Here, we present a broad review of the various advances in the field, the state of the hardware that drives the successful implementation of bioelectric systems, and some of the underlying biophysics and modeling efforts that help quantify and unravel the underlying mechanisms for eventual optimization of outcomes and their successful modulation. The primary focus is on the achievements over the past 50 years and the promise for future directions.
Sarcoids are the most common cutaneous neoplasm of the horse, arising as a result of a neoplastic proliferation of fibroblasts associated with infection with bovine papillomavirus, most notably types 1 and 2. Although they do not metastasise, they are locally invasive and aggressive, and can lead to important welfare concerns, interfere with tack and therefore impede athleticism, and undoubtedly lead to a reduction in the value of affected horses. This review discusses the evidence behind the most commonly used treatments for equine sarcoids. The most commonly used treatments are discussed. No one treatment is universally successful, and there are many treatments with varying level of scientific evaluation and reported success rates.
Equine sarcoids are the most common form of equine skin neoplasia, they can be challenging and expensive to treat. There are many different treatment options available to the equine clinician, with no one treatment suitable for all lesions in all locations. There is a lack of published evidence allowing direct comparison between different treatment within the literature. The use of laser surgery to remove sarcoids has become more popular in recent years and it provides a simple cost-effective way of managing many cases, with results similar to other treatments available. Histopathological analysis of any tissue removed is advisable, although the behaviour of sarcoids following removal is unpredictable and careful monitoring of the surgical site following any form of surgery is essential. If sarcoids recur following removal, then there are a variety of adjunctive therapies available to reduce the risk of further recurrence.
Özet: Elektrokemoterapi, doksanlı yılların başından itibaren beşeri hekimlikte kullanılmaya başlanan, son yıllarda da veteriner hekimlikte kullanılan önemli ve yeni bir lokal antitümöral tedavi yöntemidir. Elektroporasyon ile kemoterapinin birleşimi, hem kemoterapinin yüksek düzeydeki yan etkilerini minimuma indirmiş hem de elektroporasyon sayesinde, kullanılan kemoterapötik ilaçların sitotoksik etkinliğini maksimum seviyede tutmayı başarmıştır. Elektrokemoterapi uygulamaları 2006 yılından itibaren hem beşeri hekimlikte hem de veteriner hekimlikte Avrupa standartlarında belirlenmiş prosedürlere göre uygulanmaktadır. Veteriner hekimlikte elektrokemoterapi kedi, köpek, at ve son yıllarda egzotik hayvanlarda özellikle kutanöz tümörlerin tedavisinde kullanım alanı bulmuştur. Bu derlemenin amacı, elektrokemoterapinin çalışma mekanizmasını ve veteriner hekimlikte yer bulan uygulamalarını sunarak bu yeni teknik hakkında genel bir bilgi oluşmasına yardımcı olmaktır.
Anahtar Kelimeler: Elektrokemoterapi, Elektroporasyon, Veteriner hekimlik
Diseases affecting the equine nasolacrimal (NL) system and adnexa (that is, appendages of the globe, including the superior, inferior, and third eyelid) are commonly encountered in veterinary practice. This chapter covers congenital and acquired diseases commonly affecting the equine NL system and adnexa with the aim of providing diagnostic and therapeutic approaches for treatment. Obstruction of the NL duct can be congenital or acquired and result in various degrees of epiphora and/or ocular discharge. Congenital adnexal diseases reported in horses include ankyloblepharon, eyelid agenesis, colobomas, conjunctival and limbal dermoids, aberrant hairs along the third eyelid, and palpebral cilia abnormalities. Surgical excision is almost always indicated to obtain a definitive diagnosis of any periocular/eyelid mass and to debulk total tumor size prior to administration of ancillary therapy. Additional research is warranted for a wide variety of diseases affecting the equine eyelid, conjunctiva, and NL system.
Clinical use of electroporation in combination with chemotherapeutic drugs, Electrochemotherapy (ECT), has gained acceptance and its effectiveness has been widely demonstrated in several cutaneous pathologies including metastatic melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi sarcoma, and cutaneous recurrence from breast cancer. Overall, the body of clinical evidence available provided the support needed to expand clinical investigation and application of the therapy to pathologies and tumor nodules not confined to the skin or immediate subcutaneous tissues.
Cutaneous tumours continue to present a significant clinical challenge in equine practice. There are a large number of treatment options and selecting the appropriate modality requires careful consideration of a number of factors. While sarcoids are the most commonly diagnosed cutaneous tumour, their clinical appearance can have considerable overlap with other types of lesion, so biopsy should be performed where the diagnosis is uncertain. New treatment options for sarcoids include electrosurgery, electrochemotherapy and novel intralesional treatments. Melanomas still have relatively limited treatment options beyond surgical resection, but there are now limited data to support the use of a xenogenic DNA vaccination protocol. Squamous cell carcinomas are generally best treated via surgical excision, but a novel intralesional treatment may prove to be a useful option for further treatment.
Veterinary ophthalmic surgery is a field that is growing, and novel techniques and devices are being implemented. To combat the anesthesia recovery risk, the equine surgical field has adapted to perform more surgeries standing. While this provides an added challenge for the surgeon, it is far safer for the horse and the increasing willingness of surgeons to perform more standing surgeries is advancing the equine ophthalmic surgery field. This chapter presents the definition, risk factors, pathogenesis, prevention, diagnosis, treatment, and expected outcome for the complications associated with equine ophthalmic surgery. Nearly all ophthalmologic surgical procedures have the potential postoperative complications of dehiscence, hemorrhage, swelling/inflammation, and infection.
Electrochemotherapy is an effective strategy for the treatment of solid tumors by exposing tumor cells to electric fields to enhance the bioactivity of non‐permeable or low permeable anticancer drugs, such as cisplatin. To understand the improved efficiency of cisplatin in the electrochemotherapy, the effects of oriented external electric fields (OEEFs) on the geometric structure and relevant electronic properties of cisplatin have been systemically investigated by density functional theory (DFT) computations in this work. Our results reveal that the presence of selective OEEFs on cisplatin can not only weaken its Pt‐Cl bonds, but also enhance the intramolecular charge transfer in it, which effectively accelerates the critical hydrolysis step involved in the mechanism of biological activity for this drug. Moreover, the chosen OEEFs can facilitate the attack of the singly aquated cis‐[Pt(NH3)2(H2O)Cl]⁺ on DNA, and enlarge the water solubility of cisplatin and its aquated product. These OEEF‐induced geometric and electronic modifications can indeed help to improve the antitumor activity of cisplatin, which provides a deeper insight into the higher efficacy of electrochemotherapy than traditional chemotherapy from a molecular point of view.
A reformulation of Mycobacterium cell wall fraction immunotherapeutic can be used to successfully treat sarcoids in horses. Sarcoids are reported to be the most common equine skin tumors with tumor type and location influencing the choice of treatment. Wide surgical excision is curative for many tumors, but may not always be feasible. Previous studies have reported sarcoid regression after injection with mycobacterial cell wall immunotherapeutics. A new formulation of the Mycobacterium phlei cell wall fraction immunostimulant (Immunocidin® Equine) was utilized to treat cutaneous tumors in horses. Equids with skin tumors diagnosed as sarcoids were enrolled in the study. Sarcoids were injected at the initial visit with Immunocidin® Equine and subsequently at approximately 2-week intervals. Of 17 cases, 9 cases were completely resolved at the end of the study period evaluation or at time of final follow up (52.9%). Three cases were reported as improved (smaller), but not resolved (17.6%). Three cases were discontinued from the study as the respective masses were growing larger or not resolving (17.6%). One case (5.8%) with two masses had resolution of one mass, whereas the other tumor had a small regrowth 5 months after the last treatment. One case (5.8%) was lost to follow up. All cases had mild to moderate swelling of the injection site, and some cases had discharge after the second, third, or fourth injections. No serious systemic side effects or complications were encountered during the study.
A periocular nodular sarcoid was diagnosed on the right upper eyelid and medial canthus of a 12-year-old Thoroughbred mare. Enucleation was performed and during the procedure the mass was noted to be firmly adhered to the underlying frontal bone. Partial ostectomy of the dorsal orbital rim was performed. Histopathology revealed invasion of the cortical lamellar bone and the bone marrow by neoplastic spindle cells and extension of these cells to multiple surgical margins. Recurrence at the level of the surgical site and its surroundings occurred 3 months after the procedure. The horse was euthanized 12 months later. Key clinical message: Invasion of the underlying bone occurs in some cases of equine periocular sarcoids. The case highlights how this bone invasion might affect the surgical planning and shows potential aggressiveness of this type of tumor.
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Primary cell cultures are challenging, but reliable model reflecting tumor response in vitro. The study was designed to examine if the increased electropermeabilization can overcame initial drug insensitivity in chondrosarcoma cells from lung metastasis. We established a primary cell culture and evaluated the cytotoxic impact of four drugs – cisplatin, camptothecin, 2‐metoxyestratiol and leucovorin calcium. After determination of parameters allowing for electropermeabilization we performed ECT (electrochemotherapy) in vitro with the least toxic drugs ‐ cisplatin and leucovorin calcium. Although combining cisplatin and leucovorin together increased their toxicity and supported apoptosis, application of pulsed electric fields brought no advantage for their efficacy. The study emphasizes the need for introduction of primary cell cultures into studies on pulse electric fields as model frequently less sensitive to PEF‐based treatments than continuous cell lines. Primary cell culture from metastasis of chondrosarcoma to lungs showed poor response to cisplatin and leucovorin calcium, but drug combination enhanced their toxicity Chondrosarcoma cells were sensitive to electropermeabilization Pulsed electric fields combined with drugs occurred similarly effective as CT or EP Primary cultures are a demanding model, but can be employed in experimental anticancer protocols This article is protected by copyright. All rights reserved
Irreversible electroporation is a proven ablation modality for local ablation of soft tissue tumors in animals and humans. However, the strong muscle contractions associated with the electrical impulses (duration, 50–100 μs) requires the use of general anesthesia and, in most situations, application of neuromuscular blockade. As such, this technology is not used in an outpatient setting for ablating common cutaneous tumors (e.g., squamous cell carcinoma or melanoma) in humans or animals. Recently, high-frequency irreversible electroporation (H-FIRE) technology has been developed to enable electroporation of tumors without stimulation of nearby skeletal muscle. H-FIRE administers bursts of electrical pulses (duration, 0.5–2 μs) through bipolar electrodes placed in tumor parenchyma. We hypothesized that H-FIRE could be used to safely ablate superficial tumors in standing, awake horses without the need for general anesthesia. Here, we describe the treatment of superficial tumors in five horses using this novel ablation therapy without the need for general anesthesia. In each case, H-FIRE therapy predictably ablated tumor volume. All patients tolerated the procedure, no complications developed, and veterinary personnel safety was maintained. The H-FIRE treatment may be useful for treatment in veterinary and human patients in an outpatient setting without the need for hospitalization, general anesthesia, and advanced monitoring techniques.
All gray horses inherited a single gene mutation, STX17G, that unbalances melanocyte behavior to cause graying and propensities to develop vitiligo and melanoma. The coat color genes ASIPa and MC1RE add risk such that relative likelihood of melanoma based on pregraying coat color is black > bay > chestnut. Melanomas begin at about 4 years. Locoregional control of melanoma masses depends on surgical removal and/or intralesional chemotherapy (possibly with adjunctive hyperthermia or electroporation). Systemic treatment is not evidence based but immunomodulators (cimetidine, levamisole) and vaccines can be tried.
Based on the anecdotally reported eradication of a sarcoid using aciclovir cream, the curative potential of this ointment was investigated in 22 sarcoid-affected horses referred to the Equine Clinic Tillysburg, Austria, between 2006 and 2009. Sarcoid disease was diagnosed by clinical examination and bovine papillomavirus types 1 and 2 from intact skin and tumour tissue. As nine horses had more than one lesion, a total of 47 sarcoids were treated by daily topical application of aciclovir 5 per cent cream for a period of two to six months; in four horses, surgical tumour ablation was performed before treatment. Disease parameters, including the tumour type, number, location and size, were recorded before and after aciclovir therapy. All 47 (100 per cent) of the sarcoids responded to treatment, with complete tumour regression observed for 32 (68 per cent) lesions and no recurrences reported thus far. Incomplete resolution was observed for 15 (32 per cent) lesions, probably due to their thickness. Aciclovir is proposed to be routinely used for the treatment of mild-type sarcoids and as an adjuvant therapeutic agent in combination with surgery.
Electrochemotherapy (ECT) is a new antitumor treatment which consists in delivering electric pulses to the tumor some minutes after an intravenous injection of bleomycin. We report here the first clinical trial of ECT, applied to patients with permeation nodules of head and neck squamous carcinomas. ECT was well tolerated by patients, no serious incident occurred and a clear antitumor efficiency was found.
Electrochemotherapy combines bleomycin and local electric pulses that allow cell permeabilization and free access of bleomycin to its intracellular target. We report the first veterinarian clinical trial of electrochemotherapy in 12 cats with spontaneous large soft-tissue sarcomas that suffered relapse after treatment with conventional therapies. Permeabilizing electric pulses were delivered using external surface electrodes, as well as new needle-shaped electrodes that were designed to be inserted in tumours for more effective treatment of several-centimetre-thick tumour nodules. The electric pulses were applied to the tumours several times from 4 to 15-30 min after a bolus intravenous injection of 0.5 mg kg(-1) bleomycin. Tolerance to treatment was excellent without general side-effects. The cats showed local inflammatory reactions for a few days and disease stabilization lasted from 2 weeks to 7 months. One partial regression was observed, and the general absence of nodule volume decrease can be explained by local fibrotic reactions. Histological analysis of biopsies also revealed massive tumour cell death. The cats' lifespan increased (P<<0.001), with a mean survival time of 6.1 months (maximum 18 months) compared with 0.8 months (maximum 1.5 months) for a group of 11 untreated control cats displaying similar carcinological features. Electrochemotherapy is clearly effective as a salvage treatment for large spontaneous solid tumours in adverse clinical situations and this is promising for future applications.
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Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents by administering the drug in combination with short intense electric pulses. ECT is effective because electric pulses permeabilize tumour cell membranes and allow non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on cutaneous and subcutaneous tumours. This article summarizes results obtained in independent clinical trials performed by five cancer centres. A total of 291 cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated in 50 patients. Short and intense electric pulses were applied to tumours percutaneously after intravenous or intratumour administration of bleomycin. The tumours were measured and the response to the treatment evaluated 30 days after the treatment. Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed. ECT was shown to be an effective local treatment. ECT was effective regardless of the histological type of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous and subcutaneous tumours in patients with minimal adverse side-effects and with a high response rate.
Electrochemotherapy is an anti-tumour treatment that utilizes locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. The aim of our study was to determine whether anti-tumour effectiveness of electrochemotherapy with cisplatin is a consequence of increased plasma membrane permeability caused by electroporation that enables cisplatin binding to DNA. For this purpose, anti-tumour effectiveness of electrochemotherapy was evaluated on SA-1 tumours treated with electric pulses 3 min after intravenous injection of cisplatin (4 mg kg(-1)). Anti-tumour effectiveness was correlated with platinum accumulation in tumours and the amount of platinum bound to DNA, as determined by atomic absorption spectrometry. In tumours treated with electrochemotherapy, cell kill was increased by a factor of 20 compared with treatment with cisplatin only, as determined from tumour growth curves. The amount of platinum bound to DNA and platinum content in the tumours treated by electrochemotherapy was approximately two times higher than in cisplatin-treated tumours. Based on our results, we conclude that in vivo application of electric pulses potentiates anti-tumour effectiveness of cisplatin by electroporation that consequently results in cisplatin increased delivery into the cells. In addition, besides electroporation, immune system and tumour blood flow changes could be involved in the observed anti-tumour effectiveness of electrochemotherapy.
The aim of this study was to introduce electrochemotherapy with cisplatin into veterinary medicine, where there is a need for inexpensive and effective treatment of cutaneous and subcutaneous tumours of various histological types. The response to treatment was assessed on tumour nodules in 3 cats with mammary adenocarcinoma and fibrosarcoma, and in 7 dogs with mammary adenocarcinoma, cutaneous mast cell tumour, hemangioma, hemangiosarcoma, adenocarcinoma glandulae paranalis and neurofibroma. Twenty-four tumour nodules of different size were treated; 5 with cisplatin injected intratumourally and 19 with electrochemotherapy, i.e. intratumoural administration of cisplatin followed by delivery of electric pulses to the tumour nodule. Electrochemotherapy with cisplatin had a good antitumour effect on all tumours treated. Their average size 4 weeks after treatment was also greatly reduced (0.01 cm3) compared to those treated by intratumoural cisplatin injection alone (3.0 cm3). Altogether, electrochemotherapy- treated tumours responded with 84% objective responses, whereas only one tumourpartially responded to cisplatin treatment alone. Evaluated by contingency table, the response to treatment with electrochemotherapy was significantly better than that of the cisplatin treated group (p=0.014). Furthermore, there was a significant prolongation of the duration of response in electrochemotherapy treated tumours (p = 0.046). This study showed that electrochemotherapy with cisplatin is an effective, safe and simple local treatment of different histological types of cutaneous and subcutaneous tumours in cats and dogs.
Ninety-five horses with sarcoids were subjected to three types of treatment: surgical excision (conventional or carbon dioxide laser), cryotherapy or local BCG vaccination. The type of treatment was selected on the basis of the size, location and clinical appearance of the tumours. The choice between conventional and laser excision was empirical. A successful outcome was obtained in 11 of 14 (79 per cent) of the horses treated by cryosurgery, 18 of 27 (67 per cent) treated by BCG vaccination, 18 of 22 (82 per cent) treated by conventional excision, and 20 of 28 (71 per cent) treated with a carbon dioxide laser. For both excision methods, rigorous measures were taken to avoid autoinoculation and to ensure a wide margin of normal skin. The probability of local recurrence after excision was significantly higher for large sarcoids and sarcoids which had previously failed to respond to treatment. In 10 of the 31 horses with remaining sarcoids, some or all of the untreated sarcoids were observed to regress spontaneously.
Electrochemotherapy is an antitumor therapy that utilizes locally-delivered, short intense direct current electric pulse to the tumor nodule plus chemotherapy. The aim of the present study was to evaluate the electrochemotherapy treatment of perianal tumors of different sizes in dogs.
In 12 dogs, 26 tumor nodules of perianal tumors of different size, and clinically expected to be of different histological type, were treated with electrochemotherapy. Electrochemotherapy consisted of intratumoral injection of cisplatin (1 mg/cm3) or bleomycin (3 mg/cm3), followed by application of electric pulses (8 electric pulses; amplitude, 910 V, duration, 100 micros, frequency, 1 Hz) to the tumor nodule.
Responses to treatment were assessed 4 weeks after the therapy; 82% of all tumors treated with electrochemotherapy responded with objective response (OR) (complete response (CR)=41%, partial response (PR)=41%), 16% responded with no change (NC) and 1 tumor (2%) went to progressive disease (PD). At the end of the observation period for each tumor, ranging from 1 to 34 months, 92% OR (CR=65%, PR=27%), 8% NC and no PD were obtained. No major local or general side-effects were noted.
Electrochemotherapy with cisplatin or bleomycin is an effective treatment of perianal tumors in dogs. The advantages of this therapy are its simplicity, short duration of treatment sessions, low chemotherapeutic doses and insignificant side-effects, as well as the fact that the subject does not have to stay in hospital.
To determine outcome for equids with cutaneous neoplasms treated with cisplatin-containing biodegradable beads, alone or in conjunction with debulking.
Retrospective case series.
56 horses, 1 zebra, 1 donkey, and 1 mule.
Medical records were reviewed. Follow-up information was obtained through telephone conversations with owners and trainers of the animals.
22 tumors were sarcoids, 6 were fibrosarcomas, 1 was a fibroma, 2 were peripheral nerve sheath tumors, 11 were squamous cell carcinomas, 14 were melanomas (13 gray horses and 1 bay horse), 1 was a lymphosarcoma, 1 was an adenocarcinoma, and 1 was a basal cell tumor. Forty-five (76%) animals underwent conventional or laser debulking of the tumor prior to bead implantation. Forty of 48 (83%) animals for which long-term follow-up information was available were relapse free 2 years after treatment. This included 20 of 22 animals with spindle cell tumors (including 11/13 horses with sarcoids), 6 of 10 animals with squamous cell carcinomas, 13 of 14 animals with melanomas, and 2 of 3 animals with other tumor types. Adverse effects were minimal.
Results suggest that implantation of cisplatin-containing biodegradable beads, with or without tumor debulking, may be an effective treatment for equidae with various cutaneous neoplasms.
Electrochemotherapy is an anti-tumour treatment that utilizes locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. The aim of our study was to determine whether anti-tumour effectiveness of electrochemotherapy with cisplatin is a consequence of increased plasma membrane permeability caused by electroporation that enables cisplatin binding to DNA. For this purpose, anti-tumour effectiveness of electrochemotherapy was evaluated on SA-1 tumours treated with electric pulses 3 min after intravenous injection of cisplatin (4 mg kg(-1)). Anti-tumour effectiveness was correlated with platinum accumulation in tumours and the amount of platinum bound to DNA, as determined by atomic absorption spectrometry. In tumours treated with electrochemotherapy, cell kill was increased by a factor of 20 compared with treatment with cisplatin only. as determined from tumour growth curves. The amount of platinum bound to DNA and platinum content in the tumours treated by electrochemotherapy was approximately two times higher than in cisplatin-treated tumours. Based on our results, we conclude that in vivo application of electric pulses potentiates anti-tumour effectiveness of cisplatin by electroporation that consequently results in cisplatin increased delivery into the cells. In addition, besides electroporation, immune system and tumour blood flow changes could be involved in the observed anti-tumour effectiveness of electrochemotherapy.
Electrochemotherapy is a new anticancer therapy where the transient permeabilization of cells by electric field pulses induces a significant increase of antitumoral drug concentration and toxicity in tumor cells. It has been successfully applied to the treatment of tumors in animals and humans by using antimitotic drugs. This report describes its first use in the treatment of horse sarcoids. Several horses have been enrolled. They had several tumors located at different positions. Treatment was performed under short duration general anesthesia. Intra tumoral injections of cisplatin were followed by short and intense electric pulses directly applied on the skin at the tumor sites. Two to four successive treatments were applied at two-week intervals. Antitumor effect was obtained. To date, three horses have a two-years period of surveillance. Objective responses were obtained in 100 % of the treated lesions. All horses tolerated the treatment well. No adverse effect from the electric pulses was observed even in the case of a high number of pulses, or when several consecutive treatments were applied.
Objective Diagnosis and management of periorbital sarcoids in horses is a significant clinical challenge for the practicing veterinary surgeon and pathologist. The purpose of this study was to investigate the response of various types of sarcoids to different therapeutic methods.
Animals studied Medical records of 445 clinical patients.
Procedures This paper retrospectively examines the clinical and histological features of periorbital sarcoids and the treatment of 445 cases. Treatment by surgical excision, cryosurgery, Bacillus—Calmette—Gaérin (BCG) immunomodulation, topical cytotoxic applications, and radiation are described.
Results Six types of sarcoid can be found in the immediate periorbital region and each has some characteristics of other disorders of the skin with which they can be confused. The diagnosis of sarcoids is, however, relatively simple in most cases. The lesions are not necessarily restricted to the dermis and epidermis, but commonly invade into the subcutis and the deeper muscular structures around the eye. Treatment with radiation is expensive and difficult to manage but resulted in the best outcome with almost 100% resolution in 66 cases. By contrast, surgical excision has serious potential complications that arise primarily as a result of the infiltrative nature of periorbital sarcoids. The value of BCG immunomodulation therapy for fibroblastic and nodular lesions described by previous workers is confirmed in this paper, with a good overall response (69%), provided that the material was injected intralesionally. Perilesional injection did not appear to carry a significant benefit. However, treatment of verrucose or occult lesions by this method gave generally poor results. The results of intralesional injection of cisplatin emulsions suggest that this may be an effective method of treatment in cases where other modalities are not feasible. In common with previous reports, failure to resolve the lesions frequently resulted in regrowth of the tumor, and in most cases this recurrence appeared to be more aggressive, with extensive local infiltration and faster growth.
Conclusion The periorbital tissues are less tolerant of damage than those at many other sites and therefore certain treatment methods may be contraindicated. This suggests that it is important to select the best possible treatment at the first‐opportunity. It is a wise precaution to warn owners of horses with periorbital sarcoids of the dangers of leaving them and the particular risks associated with the currently available treatments.
Electrochemotherapy provides effective local control of cutaneous and subcutaneous tumour nodules of different malignancies. High objective response rate of ∼80% treated nodules was reported in the majority of clinical studies, with 30–100% long lasting complete responses. This high level of local tumour control was obtained with either systemic drug injection (bleomycin) or local drug injection (cisplatin or bleomycin) with subsequent application of electric pulses to the tumour nodules. The treatment is mostly used for palliation and has in case of in transit metastases of melanoma significant clinical benefit and impact on the quality of life. Furthermore, other clinical uses of electrochemotherapy are: neoadjuvant treatment in form of cytoreductive treatment before conventional treatments, organ and function sparing treatment and treatment of choice of painful and haemorrhagic nodules. Intraoperative treatment of tumours and development of endoluminal electrodes will bring new indications for electrochemotherapy.
The equine sarcoid, a fibroblastic tumor, is the most prevalent equine skin tumor and can affect all equidae. The sarcoid should be regarded as a tumor of fibroblasts. Involvement of the epidermis is a feature of most types but is not an obligatory feature. There are six visually recognizable types that correlate closely with the histology. The occult (superficial) type features alopecia, scaling, and skin thickening. The verrucose type has a prominent warty or verrucous appearance. There are two subtypes of the nodular form. Type A nodules are usually isolated individual or lobulated congregations of spherical subcutaneous masses. Type B nodules have cutaneous involvement that precludes independent movement of the overlying skin. Fibroblastic sarcoids have a fleshy fibrovascular appearance, often closely resembling granulation tissue. Type 1 fibroblastic sarcoids are pedunculated, whereas type 2 have a broad locally invasive base. The malignant sarcoid is an aggressive locally invasive form that extends widely into adjacent skin and subcutis. Mixed forms are common, and it is probably true that the large majority of sarcoid lesions have mixed components of two or more types.
THE term ‘sarcoid’ is derived from the apparent sarcomatous appearance of the lesions as well as their tendency to recur following excision. The numbers of sarcoid (previously called 'warts') on any individual case, their character, distribution and extent, have a major bearing on the selection of the available treatment options. Clearly, the frustrations felt by many generations of veterinary surgeons have continued up to the present time; the equine sarcoid is probably the most common cutaneous reason for euthanasia and the loss to the equine industry is considerable. Horses in which there are few localised superficial lesions are usually amenable to any of the treatment options, although inadequate application will yield a poor result with a high rate of recurrence at the site and possible extension to other sites. No effective means of treating the malevolent type of sarcoid has yet been found and interfering with this particularly aggressive form merely exacerbates the signs.
Electrochemotherapy (ECT) is a non-thermal tumour ablation modality, safe and effective on any type of solid tumour. Its use is presently standardized to skin and subcutaneous localisations. ECT is based on the use of non-permeant drugs possessing high intrinsic cytotoxicity (such as bleomycin), or low-permeant drugs with known efficacy (such as cisplatin), which act directly on the cellular DNA. ECT is also based on the achievement of in vivo tumor cell electropermeabilization by means of electric pulses locally delivered to the tumors after bleomycin or cisplatin injection. Cell electropermeabilisation, a physical procedure that affects all tumor cell types, allows these anticancer drugs to enter the cells, thus magnifying their cytotoxicity by orders of magnitude. Efficacy is also sustained by a response of the host immune system, probably due to the type of cell death caused by the ECT. At least for the bleomycin injected intravenously, treatment causes a mitotic cell death that rapidly kills the dividing tumor cells and spares the neighboring non-dividing normal cells, explaining selectivity towards the dividing tumour cells and safety of the procedure. Safety is also due to the vascular effects of the electric pulses: ECT provokes a transient vascular lock which prevents further bleeding, and even stops previous bleeding in the case of hemorrhagic nodules. These bases explain why ECT is safe and very well tolerated by the patients, and why its efficacy is very high on the treated nodules, whatever the tumour histological origin.
Purpose: To evaluate and confirm efficacy and safety of electrochemotherapy with bleomy- cin or cisplatin on cutaneous and subcutaneous tumour nodules of patients with malig- nant melanoma and other malignancies in a multicenter study. Patients and methods: This was a two year long prospective non-randomised study on 41 patients evaluable for response to treatment and 61 evaluable for toxicity. Four cancer cen- ters enrolled patients with progressive cutaneous and subcutaneous metastases of any his- tologically proven cancer. The skin lesions were treated by electrochemotherapy, using application of electric pulses to the tumours for increased bleomycin or cisplatin delivery into tumour cells. The treatment was performed using intravenous or intratumoural drug injection, followed by application of electric pulses generated by a Cliniporator TM using plate or needle electrodes. Tumour response to electrochemotherapy as well as possible side- effects with respect to the treatment approach, tumour histology and location of the tumour nodules and electrode type were evaluated. Results: An objective response rate of 85% (73.7% complete response rate) was achieved on the electrochemotherapy treated tumour nodules, regardless of tumour histology, and drug used or route of its administration. At 150 days after the treatment (median follow up was 133 days and range 60-380 days) local tumour control rate for electrochemotherapy was 88% with bleomycin given intravenously, 73% with bleomycin given intratumourally and 75% with cisplatin given intratumourally, demonstrating that all three approaches were
Twenty-three equine sarcoids in 22 horses were treated, using an afterloading technique, with iridium-192 (192Ir) interstitial radiation therapy. Previously unsuccessful treatment in 14 horses included surgical excision, cryosurgery, hyperthermia, and nonspecific immunotherapy. Twenty tumors were located in the skin of the head, and three were in the skin of the extremities. Before implantation, surgical debulking was done in six tumors, and hyperthermia (43°C, 30 min) was done in three tumors. Total implantation time varied from 4 to 14 days to give radiation doses of 52–93 Gy. The criteria for assessment of therapy were tumor response, tumor-free incidence at one year, and complications. Follow-up times ranged from six to 41 months (mean, 20 months). All tumors of the head and two tumors of the extremities had complete response to therapy. One sarcoid of the extremity had partial response to treatment. Tumor recurence was seen in the head of one horse. Of 16 horses followed for one year, the tumor-free incidence was 94% (15/16). Complications were severe local necrosis in two horses and deep infection in one horse. It was concluded that 192Ir interstitial brachytherapy was an effective treatment of recurrent and difficult-to-manage equine sarcoid.
Equine sarcoids are common tumours of the equine skin, and about 1/3 of the affected horses have multiple lesions. Nearly 1/2 of the tumours recur within 3 years of surgical removal, most of the recurrent tumours appearing within 6 months. Spontaneous recovery is rare. Epizootics have been observed in large herds. Equine sarcoids may be divided into verrucous and fibroblastic types or a combination of the two, and each type may be sessile or pedunculated. Equine sarcoids are locally aggressive, fibroblastic tumours of the dermis, and, though they are usually fibropapillomas, epithelial hyperplasia may not always be present. A virus is presumed to be the cause of equine sarcoid and, even though the bovine papilloma virus produces lesions similar to equine sarcoid in young horses, it probably is not a common cause of the tumour. Wide excision plus electrocautery is currently the treatment of choice.
Résumé
Les tumeurs sarcoides de la peau du Cheval sont fréquentes et le tiers environ des Chevaux atteints l'est par des lésions multiples. Environ cinquante pour cent de ces tumeurs réapparaissent dans les trois ans qui suivent leur élimination chirurgicale, mais la plupart réapparaissent en moins de six mois. La guèrison spontanée est rare.
Des épizooties ont été constatées dans des effectifs importants. Les sarcoides du Cheval peuvent être divisés en sarcoides verruqueux, sarcoides fibroblastiques, sarcoides mixtes verruco‐fibroblastiques; chacun de ces types peut être soit pédiculé soit sessile.
Les sarcoides du Cheval sont des tumeurs du derme, de caractère aggressif, et, quoiqu'elles soient généralement des fibropapillomes, la présence d'une hyperplasie épithéliale n'est point constante. Un virus est l'agent étiologique probable: bien que le virus des papillomes du boeuf produise des lésions similaires à celles des sarcoides du jeune Cheval, il n'est sans doute point souvent responsable des sarcoides équins. Une excision large complétée par l'électrocautèrisation parait être le traitement de choix.
Zusammenfassung
Das Equine Sarcoid ist ein häufiger Tumor der Pferdehaut. Ungefähr ein Drittel der befallenen Tiere zeigen multiple Tumore. Ungefähr die Hälfte aller Sarcoide recidivieren innert drei Jahren nach ihrer chirurgischen Entfernung, meistens schon innerhalb der ersten sechs Monaten nach dem Eingriff. Spontanheilungen sind selten. Epizootien konnten in grossen Beständen beobachtet werden.
Das Equine Sarcoid kann in einer verrukösen und in einer fibroblastischen Form oder als Kombination beider Formen auftreten. Die Tumoren beider Formen können flächenhaft oder gestielt auftreten. Es handelt sich beim Equinen Sarcoid um einen lokal aggressiven, fibroblastischen Tumor der Dermis der—obgleich gewöhnlich ein Fibropapillom—nicht immer mit Epithelhyperplasie verbunden auftritt. Als Ursache kommt ein Virus in Frage. Es ist unwahrscheinlich, dass das Virus des bovinen Papilloms mit demjenigen des Sarcoids identisch ist, trotzdem es bei jungen Pferden ähnliche Läsionen hervorrufen kann.
Radikale Excision verbunden mit Elektrokauterisierung ist zur Zeit die Behandlungsmethode der Wahl.
Sumario
Los sarcoides son comunes en la piel del equinos y cerca de una tercera parte de los equinos afectados tienen multiples lesiones. Cerca de la mita de los tumores recurren a los 3 años de su extirpación, la mayoría de los tumores recurre aparentemente entre los 6 meses. La recuperación expontanea es rara, hanssido observada las epizotias en grandes manadas. Los sarcoides en el equinos pueden ser divididos en: Tipo verrucoso y tipo fibroblásticos o la combinación de los dos, y en cada tipo pueden ser sesiles pedunculados los sarcoides en el equino son totalmente agresives, en la dérmis los tumores fibroblasticos y, aunque ellos son frecuentemente fibroblasticos papilomas, hiperplasiepitelial no siempre se presenta. Se presume que la causa es un virus y, a un cuando las lesiones en el bovino producidas por el virus son similares al sarcoide equino en caballos jovenes ello probablemente no es una causa común del tumor. El tratamiento escogido es una incisión amplia más electro cauterización.
Electrochemotherapy is an effective local treatment of solid tumours which combines delivery of chemotherapeutic drug and electric pulses. Electric pulses increase permeability of plasma membrane transiently and reversibly, leading to increased transport of the drug into the cell. As all clonogenic cells in the tumour need to be eradicated for effective treat-ment, all cells have to be permeabilised, i.e. all cells in the tumour have to be exposed to appropriate electric pulses. Electric pulses are delivered to tissue by electric pulses gener-ator via electrodes. In general there are two types of electrodes, plate electrodes and needle electrodes. The target tissue, i.e. tumour, is to be positioned well in-between the electrodes. The electrodes should thus fit the size of the tumour for good electric field distribution. Plate electrodes which are noninvasive are better suited for tumours on the surface on the skin, whereas needle electrodes which are used invasively with appropriate and suffi-cient depth of their insertion are more appropriate for treating tumours seeded deeper in the skin.
Electrochemotherapy is a new anticancer therapy where the transient permeabilization of cells by electric field pulses induces
a significant increase of antitumoral drug concentration and toxicity in tumor cells. It has been successfully applied to
the treatment of tumors in animals and humans by using antimitotic drugs. This report describes its first use in the treatment
of equids skin tumors, mainly sarcoids. 57 equids have been enrolled totalizing 248 tumors located at different body positions.
Treatment was performed under short duration general anesthesia. Intra tumoral injections of cisplatin were followed by short
and intense electric pulses directly applied on the skin at the tumor sites. Two to four successive treatments were applied
at two-week intervals. Objective antitumour responses were obtained in 94.7% of the treated lesions. All horses tolerated
the treatment well. No adverse effect from the electric pulses was observed even in the case of a high number of pulses, or
when several consecutive treatments were applied.
Electrochemotherapy is a new and promising approach in treatment of tumors employing locally applied high voltage d.c. electric pulses in combination with chemotherapeutic drugs. Increased permeability of the plasma membrane, induced by electric pulses, enables the chemotherapeutic drugs to enter into the cytosol, thus potentiating their anti-tumor effectiveness. In most of the studies published until now, trains of pulses were delivered via percutaneous parallel plate electrodes, so that the tumor was situated in between the electrodes. In our study the train of electric pulses was divided into two trains, the second one oriented perpendicularly to the first one. This changing of the electrode orientation resulted in improved anti-tumor efficacy of the electrochemotherapy: prolonged tumor growth delay and higher percentage of short and long term complete responses of the tumors. In this paper we also suggest a possible explanation for the observed effect, based on the knowledge of electric field distribution in the tissue and induced transmembrane potential.
Equine sarcoids (ES) are common, difficult to treat, and have high recurrence rates. Viscum album extracts (VAE) are used in human cancer treatment.
That therapy with VAE (Iscador P) is effective in the treatment of ES.
Fifty-three horses (444 ES); 42 were treated with VAE or placebo as monotherapy; 11 were treated with VAE or placebo after selective excision of ES.
Prospective, randomised, blinded, clinical trial. Horses were randomly assigned to treatment (VAE; n=32) or control group (Placebo; n=21). One milliliter of VAE (Iscador P) in increasing concentrations from 0.1 to 20 mg/mL or physiological NaCl solution was given SC 3 times a week over 105 days. Number, localization, and type of the ES were documented over 12 months. A subset of 163 clinically diagnosed equine sarcoid (CDES) lesions (95 VAE, 68 Placebo) was evaluated in detail, considering clinical findings and tumor volume.
No undesired adverse effects were observed except for mild edema at the injection site in 5 of 32 horses (16%). Complete or partial regression was observed in 13 horses of the VAE group (41%) and in 3 of the control horses (14%; P<.05). After VAE treatment, 48 of 95 CDES (67%) showed an improvement compared with 17 of 68 CDES in the control group (40%; P<.01). Twenty-seven CDES had disappeared completely in the VAE group (38%) compared with 9 CDES in the control group (13% NS).
VAE (Iscador P) represents a safe and effective treatment for CDES.
For an effective tissue controlled electropermeabilization as requested for electrochemotherapy and electrogenotherapy, it is very important to have informations about the electric field distribution provided by a defined set of electrodes. Computer simulations using the finite element models approach predicted the associated field distributions and currents. Phantoms made of gels with well-defined electrical conductance were used to measure the current responses of a new electrode geometry (wires), A good agreement between the measured and predicted currents was observed supporting the validity of the prediction for the field distribution. Field distribution was observed to be very localized and highly homogeneous with the new concept of contact wire electrodes. They allowed to focus the field effect along the surface of the tissue to induce a controlled release of drugs or plasmids. Non invasive (contact) electrodes can be moved rapidly on the body and avoid puncturing the skin and the tissue. They can be used for large surface effects, to treat the skin and subcutaneous tumors. The use of contact electrodes after drug or DNA intradermal injection were validated by clinical treatment of large surface skin tumors and by in vivo imaging of permeabilization or of gene expression.
The literature is briefly reviewed concerning the clinical features of equine cutaneous tumours. The data from 19 horses with periocular skin tumours are reported together with the results of their treatment by implantation with radioactive gold ¹⁹⁸ . The principles governing the implantation of radioactive sources are explained and a method for computing the initial activity of the sources is outlined. Five histologically different tumour types were treated in this series of 19 horses, 2 horses were bilaterally affected. The techniques of implantation using a simple needle/stillette combination and a purpose built gold grain implantation gun are described and the postoperative course of the animals is traced. The treatment was successful in ablating the tumour mass and preventing regrowth in 19 of 21 periocular tumour groups. The cosmetic effects of the treatment were found to be satisfactory. Emphasis is laid on the care needed in handling the radioactive material and on the need for a thorough understanding of the principles involved in radiotherapy. Doses received by the operator during an implantation procedure are quoted which show that the technique is safe as well as being effective.
RÉSUMÉ
On fait une brève revue de la littérature rapportant les caractères cliniques des tumeurs cutanées du cheval. Les données cliniques concernant 18 chevaux atteints de tumeurs cutanées périoculaires sont indiqués avec les résultats du traitement de ces tumeurs par l'or radioactif ¹⁹⁸ .
On explique les principes qui régissent l'implantation des sources radioactives et une méthode d'appréciation de l'activité initiale de ces sources est indiquée. Dans cette série de 19 chevaux, des tumeurs appartenant à 5 types histologiques différents furent traitées. Deux animaux étaient atteints de lésions bilatérales.
Les techniques d'implantation employant une instrumentation simple (aiguille—stylet) et un trocart à implantation élaboréà cette fin, sont décrites. Le devenir post‐opératoire des animaux est précisé. Le traitement fut efficace pour 19 des 22 groupes tumoraux traités, à la fois pour éliminer les tumeurs et pour en prévenir la réapparition.
Les résultats plastiques du traitement furent jugés satisfaisants.
On souligne le soin qu'il faut apporter aux manipulations du matériel radioactif et la nécessité d'une bonne compréhension des principes de la radiothérapie.
Les doses reĉues par l'opérateur durant la procédure d'implantation sont indiquées. Elles montrent que la technique est sûre autant qu'efficace.
ZUSAMMENFASSUNG
Die zugängliche Literatur über die klinischen Erscheinungen kutaner Tumoren des Pferdes wird kurz gestreift. Die Befunde von 19 Pferden mit periokulären Hauttumoren werden wiedergegeben, zusammen mit den Behandlungsresultaten, die erzielt werden konnten nach Implantation von radioaktivem Gold ¹⁹⁸ . Die bei der Implantation radioaktiver Quellen zu berücksichtigenden Grundsätze werden erklärt, und eine Methode zur Berechnung der initialen Aktivität wird wiedergegeben. In dieser Serie von 19 Pferden wurden 5 histologisch verschiedene Tumortypen behandelt, wobei zwei der Pferde bilateral befallen waren. Die Technik der Implantation mit einer einfachen Nadel‐Stilett‐Kombination wird beschrieben. Zur Implantation der Goldkörner wurde speziell eine Implantationspistole entwickelt. Der postoperative Verlauf der Behandlungen wird beschrieben: Die Behandlung war erfolgreich, insofern als die Tumormassen zum Verschwinden gebracht werden konnten und insofern als ein weiteres Wachstum bei 19 von 21 periokulären Tumoren verhindert werden konnte. Die kosmetischen Resultate der Behandlung wurden als befriedigend beurteilt. Unterstrichen wird die Sorgfalt, die nötig ist beim Umgang mit radioaktivem Material und auch das Bedürfnis, die Grundsätze der Radiotherapie wirklich zu verstehen. Die radioaktive Strahlenmenge, die der Operateur während einer Implantation aufnimmt, werden erwähnt; die Technik ist sowohl sicher als auch wirkungsvoll.
The literature is reviewed concerning the clinical features of equine sarcoids and mention is made of the traditional methods of treating this common skin tumour. The data from 50 horses with sarcoids are reported together with the results of their treatment by cryosurgery. Thirty‐four of the animals had earlier been unsuccessfully treated by one or more of the traditional methods, usually excision. The objectives of cryosurgery are defined and some equipment is described; the use of temperature monitors is regarded as imperative for safe and effective treatment. In this study a liquid nitrogen spray apparatus was found to be the single most useful instrument. The horses in this study were often affected by multiple lesions so that not less than 480 sarcoids were subjected to ultrafreezing. Nonetheless 33 horses were cleared of neoplasia and the majority of the remainder were rendered suitable for work. The author emphasises that a cautious prognosis must always be given for horses with sarcoids, and that the greater the number of lesions, the poorer are the prospects of a complete cure. Cryosurgery is reported to be a safe and practicable technique with few complications. Healing is not as rapid as first intention repair of surgical wounds but the absence of cicatrisation makes cryosurgery particularly suitable for tumours of the eyelids. A possible beneficial cryo‐immune response is mentioned. It is concluded that cryosurgery should be regarded as one of the treatments of choice for equine sarcoids and that the best results will be obtained from early treatment.
RÉSUMÉ
On passe en revue les signes cliniques de l'affection et les méthodes traditionnelles du traitement de ces tumeurs cutanées.
Puis on rapporte les cas de cinquante chevaux atteints par cette affection et traités par cryochirurgie. Trente six de ces animaux avaient été antérieurement l'objet d'un traitement chirurgical par excision et sans succès. Les objectifs de la cryochirurgie sont indiqués et l'équipement décrit. L'emploi de contrôles de température est regardé comme indispensable.
Dans cette étude l'utilisation d'un appareillage utilisant l'azote liquide est apparu comme particulièrement efficace. Les chevaux objets de cette étude présentaient souvent des lésions multiples si bien que 480 tumeurs différentes ont été traitées. Trente trois chevaux furent totalement guéris et la majorité des autres purent reprendre une activité utile.
L'auteur indique combien il convient de formuler un pronostic réservé et comment ce pronostic est d'autant plus sombre que le nombre de tumeurs est important sur un même individu.
La cryochirurgie est présentée comme une méthode sure et pratique entrainant peu de complications. La cicatrisation n'a point la promptitude d'une première intention chirurgicale. La méthode est indiquée spécialement pour les tumeurs de paupières. L'existence d'un éventuel processus de cryo immunité est envisagé.
On conclue en précisant que la cryochirurgie est la méthode de choix pour le traitement des sarcoïdes avec des résultats d'autant meilleurs que l'intervention est précoce.
ZUSAMMENFASSUNG
Die Literatur über die klinischen Züge des Sarcoids wird besprochen und die traditionellen Behandlungs‐methoden dieses Hauttumors werden erwähnt. Die Ergebnisse von 50 Sarcoid‐Fällen werden zusammen mit den Resultaten der Cryochirurgie wiedergegeben. 34 Tiere waren vorher erfolglos mit einer oder mehreren der traditionellen Methoden (meistens Excision) behandelt worden. Die Zielsetzung der Cryochirurgie wird definiert und die Ausrüstung beschrieben; der Gebrauch von Temperaturüberwachungsgeräten wird als Voraussetzung für eine gefahrlose und wirksame Behandlung angesehen. In dieser Untersuchung erwies sich ein Spraygerät für flüssigen Stickstoff als nützlichstes Instrument der Ausstaffung. Die behandelten Pferde litten oft an multiplen Sarcoiden, so dass 480 Tumoren mit der Tiefgefriertechnik behandelt werden konnten. 33 Pferde konnten als geheilt beurteilt werden und die Mehrzahl der restlichen Tiere wurden wieder arbeitsfähig. Der Autor streicht heraus, dass immer eine vorsichtige Prognose gestellt werden sollte, je zahlreicher die Tumoren, desto ungüstiger werden die Aussichten auf vollständige Heilung. Die Cryochirurgie wird als sichere und gut praktizierbare Technik mit seltenen Komplikationen beschrieben. Die Heilung verläuft nicht so schnell wie die Primärheilung einer Operationswunde, aber das Fehlen einer Narbe lässt die Cryochirurgie als besonders geeignet für Augenlidtumoren erscheinen. Es wird geschlossen, dass die Cryochirurgie als eine der Methoden der Wahl für das equine Sarcoid betrachtet werden sollte und dass die besten Resultate bei frühzeitiger Behandlung zu erwarten sind.
Electrochemotherapy delivers external electric pulses to the tumour site to induce local potentiation of the antitumour activity of intramuscular injections of bleomycin. C3H/Bi mice with spontaneous mammary carcinomas received weekly injections of 50 micrograms bleomycin followed by electric pulses 30 min later. All the 38 tumours treated exhibited at least a partial regression. 23 complete remissions were observed, 3 of which were cures. One difficulty in assessing the cure rate in this model is that frequent parallel or sequential tumours cause early death. Electrochemotherapy appears similarly efficient in spontaneous tumours as in previously studied transplanted tumours.
Clinical observations on the use of BCG cell wall fraction in oil for treating seven horses with periocular sarcoids and five horses with sarcoids in other regions are described. Therapy was successful when used for periocular or solitary and smaller sarcoids. For sarcoids previously treated with cryosurgery, therapy appeared to be less efficient. A horse with a sarcoid on the stifle developed a septic gonitis due to necrosis of the sarcoid tissue adjacent to the joint. Sarcoids of the axilla appeared to be more aggressive than sarcoids at other locations and did not respond favourably to this form of therapy.
Associations between clinical parameters of sarcoids and the equine leucocyte antigen system (ELA) were analysed for 120 Swedish horses. Median age of affected horses was 5.2 years, and the majority presented with solitary tumors between 2 and 5 cm in diameter and ventral abdomen was a predilection site. Clinical signs first appeared at a median age of 3.5 years, and sarcoids at different locations first appeared at different ages. Lesions at different sites differed in size, and multiple tumors, early onset, long duration, and older age all had an association with large size. Clinical manifestations of sarcoids and the association between certain ELA-specificities and early onset (A5) and increased recurrence rates after surgery (W13), in addition to increased prevalence (A3W13), strengthen further that some horses are inherently predisposed to sarcoid growth. Unassociated with any clinical parameters, one third of the untreated horses became free of sarcoids due to "spontaneous" regression, perhaps as a result of immune responses against the tumors. Seventy percent of the horses were treated (mostly by excision), and large size was the main parameter promoting treatment. Excision had no significant effect on possibly remaining sarcoids. Recurrence rate after first treatment was about 35%, with the majority of tumors recurring within 4 months. Early onset, long duration, large size, and localization to distal limbs all appeared to increase risk of recurrence. Early treatment, performed under general anesthesia in recumbency which permits wide excision and measures to avoid autoinoculation, significantly reduced recurrence rates.
Electrochemotherapy is a new antitumor treatment consisting of electrical pulses administered to the tumor several minutes after intravenous injection of bleomycin. In mice, important antitumor effects were observed on subcutaneously transplanted tumors and on spontaneously occurring mammary carcinomas. Cures were obtained after one single treatment combining bleomycin and electric pulses. In humans, permeation nodules seemed an adequate oncologic situation to assay this new procedure. The authors report the first Phase I-II trial of electrochemotherapy.
Eight patients with 40 permeation nodules of head and neck squamous cell carcinomas were treated with 10 mg/m2 bleomycin intravenous bolus, followed by four or eight short (100 microseconds) and intense (1300 V/cm) pulses administered through two external electrodes located on each side of the treated nodule.
An instantaneous painless contraction of the underlying muscles was regularly observed. Neither local nor general side effects were observed, and electrochemotherapy was well tolerated. In addition, a clear local antitumor efficacy was found: 23 (57%) nodules were in clinical complete response within a few days.
The absence of toxicity, the good tolerance by the patients, and the net antitumor effects observed are encouraging for additional electrochemotherapy developments in clinical oncology.
One hundred and fifteen horses with periocular tumours were treated with iridium-192 interstitial brachytherapy. Tumours included squamous cell carcinomas (n = 52) and sarcoids (n = 63). All horses were scheduled to receive 60 Gy (minimal tumour dose) given at a low dose rate (0.034 +/- 0.010 Gy/h). The mean and median follow-up times to last contact or death were 24 and 16 months, respectively. Chronic radiation reactions included palpebral fibrosis (10.4%), cataract (7.8%), keratitis and corneal ulceration (6.9%). Cosmetic changes included permanent epilation (21.7%) and hair dyspigmentation (78.3%). The one year progression-free survival (PFS) rates for sarcoids and carcinomas were 86.6% and 81.8% and the 5 year PFS rates were 74.0% and 63.5%, respectively. The horse age and sex, histopathological type, anatomical subsite and classification (WHO T1-3) were included in the analysis of prognostic factors. The only significant prognostic factor that independently affected PFS time was the WHO T-classification (P = 0.009, relative risk = 0.85). When compared to horses with T1 lesions, horses with T2 and T3 lesions had 1.8-fold and 3.4-fold increased risks, respectively, for tumour recurrence (relative excess risk). The one year PFS rates for T1, T2 and T3 lesions were 95.2%, 89.5% and 66.2%, respectively. The 5 year PFS rates were 72.2%, 74.0% and 53.1%, respectively. The results of this study indicate that irradiation is an effective treatment option for horses with T1-2 lesions and should be part of a combined treatment modality for horses with T3 lesions.
Twenty-seven horses (and 1 mule) with 32 histologically confirmed cutaneous tumors were studied to evaluate the effects of intratumoral injection of cisplatin initiated at the time of surgery. As a result of surgery, 9 of the wounds were closed primarily (5 sarcoids, 4 carcinomas) and 23 were left open to granulate (16 sarcoids, 6 carcinomas, 1 hamartoma). Chemotherapy consisted of 4 treatment sessions of intratumoral injection of cisplatin in purified sesame oil at 2-week intervals. The first treatment session was administered intraoperatively. A controlled-release formulation of cisplatin in sesame oil was used to limit drug egress from the injection site. Dosage was 1 mg of cisplatin/cm3 of tissue. The mean relapse-free interval was 41 +/- 3.7 months. The estimates of overall relapse-free survival rates were 92 +/- 5% at 1 year and 77 +/- 11% at 4 years. Cisplatin-related local toxicosis was minimal and wound healing was not compromised. Intratumoral injection of cisplatin appears safe and effective when administered in the perioperative period for selected tumors in equidae.
Twenty horses with 30 lesions were studied to evaluate the effects of intratumoral chemotherapy with cisplatin in sesame oil on equine sarcoids (n = 19), squamous cell carcinomas (n = 7), and squamous cell papillomas (n = 4). Treatment consisted of 4 sessions of intratumoral cisplatin chemotherapy at 2-week intervals. A controlled-release formulation of cisplatin in sesame oil was used to limit drug egress from the injection site. Mean dosage per session was 0.97 (+/- 0.17, SEM) mg of cisplatin/cm3 of tumor tissue treated for tumor volumes ranging from 10 to 20 cm3. Dosage tended to be slightly higher for smaller tumors and slightly lower for larger tumors. Tumor regression was observed in all horses. Complete response was observed in 18 of the sarcoids, 5 of the squamous cell carcinomas, and 4 of the squamous cell papillomas. The mean relapse-free interval was 21.6 and 14 months in horses with sarcoid and carcinoma/papilloma, respectively. The 1-year relapse-free rates were 87 and 65% for equine sarcoid and carcinoma/papilloma, respectively. In horses with relapse, 70% had tumor recurrence outside the treated field. Cisplatin-related local toxicosis was minimal. Intratumoral cisplatin chemotherapy was found to be a practical and effective treatment of sarcoid and squamous cell carcinoma/papilloma in horses.
Electrochemotherapy has been demonstrated to be an effective treatment for cutaneous cancers. The treatment includes administering a chemotherapeutic agent followed by electric pulses which are applied directly to the tumour. The pulses facilitate delivery of drug through the plasma membrane. Enhanced delivery is restricted to the area that has been electrically treated. Currently, electrochemotherapy is administered as a single treatment. Complete response rates are high; however, partial responses are obtained in a fraction of the treated tumours. An issue associated with this is whether or not multiple treatments would result in an improved therapy for these partially responding tumours. A multiple treatment electrochemotherapy study was implemented in order to address this issue. The study utilized subcutaneously induced murine B16 melanoma tumours in C57B1/6 mice. Results showed large tumour volume reductions in multiple treatment groups. In addition, a twofold increase in tumour doubling time and greater percentages of complete responses were found as a result of multiple treatment. These results will be utilized to augment existing clinical trials with respect to retreating tumours that have partially responded to a single electrochemotherapy treatment.
The objective of this retrospective clinical study was to evaluate the carbon dioxide laser in the treatment of single and multiple sarcoids in 60 animals (44 horses, 13 donkeys, 2 mules, and 1 pony). Only animals that had been operated on 6 mo or more ago were included. Recurrence, new manifestation rate, and cosmetic outcome were determined. Recurrence was observed in 23 (38%) individuals. Animals with new sarcoid manifestation with or without recurrence of a sarcoid were observed in 35 cases (58%). Cases of scar tissue formation and, rarely, leukotrichia were observed. Animals presented with multiple sarcoids were more predisposed to recurrence. Donkeys showed a significantly lower recurrence rate than horses.
Surgery is the mainstay of treatment for equine tumors. Conservative treatment approaches which preserve function and appearance are increasingly used in clinical practice. This article covers the principles and applications of two conservative treatment modalities including local chemotherapy and immunotherapy. The therapeutic benefit of local chemotherapy is based on the direct drug delivery to tumor tissue, i.e., topical and intratumoral administration of cytotoxic agents in slow release formulation. This treatment modality is very effective for cutaneous tumors and does not result in any permanent damage to normal tissue. Immunotherapy produces antitumor effects primarily through the action of natural host defense mechanisms against tumor cells. Although the use of immunotherapy is still under investigation there are many examples of its successful application to treatment of selected equine tumors.
Sarcoids, the most common tumor of the horse, are fibroblastic, wart-like skin lesions that show variable manifestations. They are often invasive and recurrent, although they do not fulfill all criteria of malignancy. Due to their anatomic location, these tumors can sometimes cause loss of use of the horse. There is very strong evidence that sarcoids are caused by viruses closely related or identical to bovine papilloma viruses, and genetic studies have shown associations between genes in or near the equine major histocompatibility complex (MHC) and susceptibility to sarcoid. Several types of treatments have been successful in treating sarcoids, although the response to therapy is not consistent. Current treatment of sarcoids primarily involves antitumor therapy, but the development of preventative measures in the future may be directed against the causative papilloma virus. Sarcoid continues to be an important clinical entity for the equine practitioner.
The therapeutic potential of the photodynamic compound, hypericin, in the treatment of equine sarcoids was evaluated. The in vitro cytotoxicity was assessed using three equine cell lines and the observed phototoxic effect was comparable to that on different highly sensitive human cell lines and significantly influenced by the energy density used although independent of the cell type. The in vivo antitumoural action of photodynamic therapy using hypericin was evaluated on three equine sarcoids in a donkey. Four intratumoural injections were given and the tumours were illuminated daily during 25 days. An 81% reduction in tumour volume was obtained at the end of therapy and 2 months later, a 90% reduction was observed. Further experimental work should be performed, but these results suggest that photodynamic therapy using hypericin has a potential for the non-invasive treatment of equine sarcoids.
OBJECTIVE: Diagnosis and management of periorbital sarcoids in horses is a significant clinical challenge for the practicing veterinary surgeon and pathologist. The purpose of this study was to investigate the response of various types of sarcoids to different therapeutic methods. Animals studied Medical records of 445 clinical patients. Procedures This paper retrospectively examines the clinical and histological features of periorbital sarcoids and the treatment of 445 cases. Treatment by surgical excision, cryosurgery, Bacillus-Calmette-Gaérin (BCG) immunomodulation, topical cytotoxic applications, and radiation are described. RESULTS: Six types of sarcoid can be found in the immediate periorbital region and each has some characteristics of other disorders of the skin with which they can be confused. The diagnosis of sarcoids is, however, relatively simple in most cases. The lesions are not necessarily restricted to the dermis and epidermis, but commonly invade into the subcutis and the deeper muscular structures around the eye. Treatment with radiation is expensive and difficult to manage but resulted in the best outcome with almost 100% resolution in 66 cases. By contrast, surgical excision has serious potential complications that arise primarily as a result of the infiltrative nature of periorbital sarcoids. The value of BCG immunomodulation therapy for fibroblastic and nodular lesions described by previous workers is confirmed in this paper, with a good overall response (69%), provided that the material was injected intralesionally. Perilesional injection did not appear to carry a significant benefit. However, treatment of verrucose or occult lesions by this method gave generally poor results. The results of intralesional injection of cisplatin emulsions suggest that this may be an effective method of treatment in cases where other modalities are not feasible. In common with previous reports, failure to resolve the lesions frequently resulted in regrowth of the tumor, and in most cases this recurrence appeared to be more aggressive, with extensive local infiltration and faster growth. Conclusion The periorbital tissues are less tolerant of damage than those at many other sites and therefore certain treatment methods may be contraindicated. This suggests that it is important to select the best possible treatment at the first opportunity. It is a wise precaution to warn owners of horses with periorbital sarcoids of the dangers of leaving them and the particular risks associated with the currently available treatments.
Sarcoids are skin spontaneous tumours detected in horses. It can be cured by chemotherapy by using cisplatin. A multisequence treatment must be performed. Problems are present due to the poor diffusion of the hydrophilic product in the tumours. Electropulsation is known to drastically enhance the effect of antitumoral drugs in vivo. Taking into account the very successful results of the group in Ljubljana (Slovenia), we started a research clinical program where electropulsation was applied after local cisplatin injection. The size of sarcoids is large (several centimeters). A specially designed set of wire contact electrodes was built. The distance between the electrodes was 0.9 cm and their length was 0.9 cm. The contact with the skin was obtained by a conductive paste. A PS15 Jouan Electropulsator was used to deliver eight pulses of 0.1 ms at a 1-Hz frequency with a 1.3-kV voltage. The animal was anesthesized. Intratumoral cisplatin injections were operated every 0.6 cm (0.2 ml at a 1-mg/ml concentration). Five minutes after the first drug injection, multiple electrotreatments were applied by moving the electrodes between the pulse applications. This allows the treatment of all the tumour surface. Several successive treatments were performed with a delay of 2 weeks between each. All lesions completely responded. The sarcoids disappear after only 2 or 3 electrochemotherapies. Objective responses were obtained in 100% of the treated lesions. All horses tolerated the treatment well. No adverse effect from the electric pulses was observed even in the case of a high number of pulses, or when several consecutive treatments were applied. No regrowth was observed in the 18 months follow-up period.
To determine the benefits of reducing the interval between surgical cytoreduction and intratumoral administration of cisplatin.
Randomized clinical study.
70 horses with 89 incompletely resected T2- and T3-stage sarcoids (n = 64) and squamous cell carcinomas (25).
Horses were given 4 intratumoral treatments of cisplatin at 2-week intervals. The first treatment was given at the time of, or immediately after, surgical resection for horses treated in accordance with the perioperative protocol (group 1). Horses in group 2 were treated with cisplatin after the skin healed following surgical resection in accordance with the postoperative protocol.
A difference was not found in duration of overall local tumor control between the 2 groups. Patterns of treatment failures and interval to failure differed between the 2 groups. Length of the surgical scar was the only factor that affected prognosis; an increase in length was associated with a poorer prognosis. A detrimental effect of postoperative treatment was only found in tumors with a high tumor proliferative fraction. Local reactions were similar for the 2 treatment groups, and chronic reactions were not observed.
Intratumoral administration of cisplatin is beneficial for treatment of cutaneous tumors in horses. Tumor repopulation during the interval between surgery and intratumoral administration of cisplatin decreases treatment efficacy. These results provide evidence of rapid tumor repopulation following surgical resection without a lag period for tumors with a high proliferation index. When tumor proliferation index is not known, it may be prudent to use the perioperative protocol.
Imiquimod is an immune response modifier with potent antiviral and antitumour activity. The objective of this pilot study was to evaluate the efficacy of an imiquimod 5% cream (Aldaratrade mark: 3M, Saint Paul, MN, USA) as a topical treatment for equine sarcoids. Fifteen horses with a total of 19 tumours were enrolled, including mixed (7), fibroblastic (5), flat (3), verrucous (2), and nodular (2) types. Baseline data included history, physical examination, tumour location, measurement and digital photography. Imiquimod was applied by the owners three times a week until complete resolution of the tumour or 32 weeks, whichever occurred first. Tumours were measured and photographed every 4 weeks. Treatment efficacy was defined as 75% or greater reduction of tumour size by the end of the trial. Four sarcoids were withdrawn from the study. Twelve of the remaining 15 tumours (80%) showed more than 75% reduction in size and nine (60%) totally resolved between 8 and 32 weeks. The most common adverse effects of exudation, erythema, erosions, depigmentation and alopecia were limited to the tumour and adjacent areas. The results suggest that topical imiquimod is a therapeutic option for the treatment of equine sarcoids, although more detailed studies are required to corroborate these initial findings.