Treatment of necrotizing fasciitis using negative pressure wound therapy in a puppy

A two-month-old German shepherd dog was presented with anorexia, lethargy and left hind limb lameness associated with swelling of the thigh. Clinical findings combined with cytology led to the presumptive diagnosis of necrotizing fasciitis (NF). Extensive debridement was performed and silver-foam-based negative pressure wound therapy (NPWT) was applied. During the first 48 hours, a negative pressure of -75 mmHg was used. Evaluation of the wound demonstrated no progression of necrosis and a moderate amount of granulation tissue formation. A new dress- ing was placed and a second 48-hour cycle of NPWT was initiated at -125 mmHg. At removal, a healthy wound bed was observed and surgical closure was performed. The prompt implementation of NPWT following surgical debridement led to accelerated wound healing without progression of necrosis in this case of canine NF. Negative pressure wound therapy could become an integral part of the management strategy of canine NF, improving the prognosis of this life-threatening disease

De hond als kankermodel in de zoektocht naar nieuwe therapeutische alternatieven

In cancer research, rodent cancer models are a standard research tool. However, translation of cancer research data from rodent to man is far from optimal. Hence, it is recommended that the efficacy of novel cancer drugs is confirmed in higher animal species before human trials are initiated. Pet dogs with spontaneous cancer are the perfect candidates in every respect. Dogs share a similar histologic, biologic and genetic cancer background significantly closer than the relationship between rodent and man. Furthermore, the development and interaction between tumor, host and tumor microenvironment is comparable to those in humans. There are corresponding diagnostic and treatment options available for dogs and humans, while the progression of cancer in dogs is fast enough to obtain results within a reasonable period of time. Lastly, pet dogs have a broader access to clinical trials than humans, enabling extensive research opportunities. Moreover, the dog also benefits from participation in clinical studies, since these studies offer an additional treatment option, and hence an additional chance of being cured

Negative pressure wound therapy : the past and the future

Negative pressure wound therapy (NPWT) involves the application of negative pressure on a wound bed for its positive effects on wound healing. Indications for NPWT concern various types of wounds, skin grafts and flaps, partial-thickness burns, open abdomen management and closed incisions. Negative pressure wound therapy has been used for centuries in human medicine. Its first use dates back to the Roman era (around 27 BCE) when human generated pressures were used. Later, European and Russian physicians developed various advanced methods and systems to apply negative pressure on wounds or other injuries. The on-going positive findings in human medicine triggered researchers in veterinary medicine to apply this technique on animal patients. However, much still has to be investigated regarding NPWT, especially in veterinary medicine, as there are many factors playing a role in the mechanisms of this treatment. New methods and techniques are continuously being developed and the existing studies show great potential for NPWT

Treatment of a malignant peripheral nerve sheath tumor by intravenous administration of combretastatin A4-phosphate in a dog

A fifteen-year-old, male, castrated American Staffordshire terrier was presented with a subcutaneous, ulcerated mass on the right carpal joint. Thoracic radiographs and abdominal ultrasound were both negative for metastatic disease. Punch biopsies revealed the histopathological diagnosis of a malignant peripheral nerve sheath tumor. Due to the extent of the primary mass, local excision was not possible, and amputation of the limb was not an option for the owner. The dog was treated with intravenous administration of combretastatin A4-phosphate, a vascular disrupting agent. A biopsy was taken before and after treatment and power-Doppler ultrasound and contrast-enhanced ultrasound were performed to assess pre- and posttreatment evaluation of the tumor vasculature. The treatment resulted in massive necrosis of the tumor

OncoCiDia: An innovative cancer treatment combining a vascular disrupting agent with targeted radiotherapy: Preliminary results in dogs At Ghent University, Belgium

The use of vascular targeting agents (VTAs) as treatment for cancer was first introduced in the 1990’s, when tumour vascularisation came into focus as a potential target. The morphologic differences between immature tumour vessels and quiescent, mature vessels of healthy tissue permit a high specificity, opening doors for drugs with high efficacy and little toxicity. One of the best known VTAs is combretastatin A4-phosphate (CA4P), which selectively shuts down blood supply in tumours, resulting in extensive tumour necrosis. Combretastatin A4- phosphate has been included in many (pre-)clinical trials and has been found to be safe and effective in human cancer patients. While monotherapy with CA4P has been FDA approved for clinical trials on several types of cancer, the overall success rate is low, due to surviving cancer cells typically in the periphery of the tumour, which are nutritionally supported by mature vasculature of adjacent normal tissue. These surviving tumour cells regrow and lead to tumour relapse if no complementary treatment is installed. Subsequently, a variety of studies combining CA4P with 131I-hypericin have been performed. As a necrosis avid compound, hypericin transports 131I to the necrotic areas of the tumour, where 131I can irradiate the remaining tumour cells. This strategy was found to be very successful in rodent tumour models and further investigation of this combination in larger animal models is certainly warranted. The general aim of this work was to explore the safety and efficacy of both compounds (CA4P and 131I-hyp) of this combination strategy in cancer-bearing pet dogs. In the first chapter, the potential side effects and toxicity of CA4P were assessed in ten healthy experimental dogs. In the following chapters Chapters 2 and 3) CA4P was administered to eight dogs with various pontaneous cancers, to assess its efficacy and safety and, additionally, on-invasive imaging modalities were evaluated as assessment tools for vesselperfusion after CA4P-administration. In the last chapter, the biodistribution and the tolerance of 131I-hyp were investigated in three healthy experimental dogs. A dose-escalation study of CA4P in healthy dogs Because literature on the adverse events (AEs) of CA4P in dogs was inexistent, a doseescalation study was needed to determine both a dose deemed safe for canine cancer patients, and to assess possible side effects. Escalating doses of CA4P (ranging from 50 to 100 mg m-2 were infused intravenously in ten healthy beagles over a time-span of 30 or 120 minutes. All dogs were monitored during and after injection for aematological, biochemical, gastro-intestinal (GI), cardiovascular, and neurological toxicity. As seems to be the case in human patients, CA4P was generally well tolerated with high-grade AEs only occurring at the highest dose level (100 mg m-2). In our dogs, the most common side effects were neutropenia and mild GI toxicities (i.e., nausea and iarrhoea), occurring at all dose levels. Additional mild GI side effects (i.e., anorexia and vomiting) arose only at higher dose levels (³75 mg m-2), as did cardiovascular toxicity (i.e., mild cTnI elevation). Neurologic dose imiting toxicities (i.e., severe ataxia and motor neuropathy) and mild hypertension occurred at a dose of 100 mg m-2, irrespective of infusion time. Based on these results, the dose recommended for treating canine cancer patients was 52 - 75 mg m2 Administration of CA4P to canine cancer patients. To assess the toxicity and efficacy of CA4P in dogs with various spontaneous cancer types, eight pet dogs bearing spontaneous tumours were selected and treated IV with 75 mg m-2 CA4P. All dogs were screened and monitored before, during, and after injection for haematological, biochemical, GI, cardiovascular, and neurological toxicity, and quality-of-lifenrpages: 250status: publishe

OncoCiDia : an innovative cancer treatment combining a vascular disrupting agent with targeted radiotherapy : preliminary results in dogs

The use of vascular targeting agents (VTAs) as treatment for cancer was first introduced in the 1990’s, when tumour vascularisation came into focus as a potential target. The morphologic differences between immature tumour vessels and quiescent, mature vessels of healthy tissue permit a high specificity, opening doors for drugs with high efficacy and little toxicity. One of the best known VTAs is combretastatin A4-phosphate (CA4P), which selectively shuts down blood supply in tumours, resulting in extensive tumour necrosis. Combretastatin A4- phosphate has been included in many (pre-)clinical trials and has been found to be safe and effective in human cancer patients. While monotherapy with CA4P has been FDA approved for clinical trials on several types of cancer, the overall success rate is low, due to surviving cancer cells typically in the periphery of the tumour, which are nutritionally supported by mature vasculature of adjacent normal tissue. These surviving tumour cells regrow and lead to tumour relapse if no complementary treatment is installed. Subsequently, a variety of studies combining CA4P with 131I-hypericin have been performed. As a necrosis avid compound, hypericin transports 131I to the necrotic areas of the tumour, where 131I can irradiate the remaining tumour cells. This strategy was found to be very successful in rodent tumour models and further investigation of this combination in larger animal models is certainly warranted. The general aim of this work was to explore the safety and efficacy of both compounds (CA4P and 131I-hyp) of this combination strategy in cancer-bearing pet dogs. In the first chapter, the potential side effects and toxicity of CA4P were assessed in ten healthy experimental dogs. In the following chapters Chapters 2 and 3) CA4P was administered to eight dogs with various pontaneous cancers, to assess its efficacy and safety and, additionally, on-invasive imaging modalities were evaluated as assessment tools for vesselperfusion after CA4P-administration. In the last chapter, the biodistribution and the tolerance of 131I-hyp were investigated in three healthy experimental dogs. A dose-escalation study of CA4P in healthy dogs Because literature on the adverse events (AEs) of CA4P in dogs was inexistent, a doseescalation study was needed to determine both a dose deemed safe for canine cancer patients, and to assess possible side effects. Escalating doses of CA4P (ranging from 50 to 100 mg m-2 were infused intravenously in ten healthy beagles over a time-span of 30 or 120 minutes. All dogs were monitored during and after injection for aematological, biochemical, gastro-intestinal (GI), cardiovascular, and neurological toxicity. As seems to be the case in human patients, CA4P was generally well tolerated with high-grade AEs only occurring at the highest dose level (100 mg m-2). In our dogs, the most common side effects were neutropenia and mild GI toxicities (i.e., nausea and iarrhoea), occurring at all dose levels. Additional mild GI side effects (i.e., anorexia and vomiting) arose only at higher dose levels (³75 mg m-2), as did cardiovascular toxicity (i.e., mild cTnI elevation). Neurologic dose imiting toxicities (i.e., severe ataxia and motor neuropathy) and mild hypertension occurred at a dose of 100 mg m-2, irrespective of infusion time. Based on these results, the dose recommended for treating canine cancer patients was 52 - 75 mg m2 Administration of CA4P to canine cancer patients. To assess the toxicity and efficacy of CA4P in dogs with various spontaneous cancer types, eight pet dogs bearing spontaneous tumours were selected and treated IV with 75 mg m-2 CA4P. All dogs were screened and monitored before, during, and after injection for haematological, biochemical, GI, cardiovascular, and neurological toxicity, and quality-of-lifenrpages: 250status: publishe

Combretastatin A4-phosphate and its potential in veterinary oncology : a review

For many years, research on anticancer therapy has focussed almost exclusively on targeting cancer cells directly, to selectively kill them or restrict their growth. But limited advances in this strategy have led researchers to shift their attention to other potential targets. Active research is now on-going on targeting tumour stroma. Vascular disrupting agents (VDAs) appear a promising class of anticancer drugs that are currently under investigation as a sole or combined therapy in human cancer patients. This article will briefly touch on the history and biology of Combretastatin A4-Phosphate (CA4P) as a typical example of VDAs and will concentrate on the side effects that can be expected when used in veterinary patients. Particularly, the pathogenesis of these side effects and how they may be prevented and/or treated will be discussed. The purpose of this article is to illustrate the potentials of CA4P as anticancer therapy in veterinary oncology patients