Adjuvant chemotherapy for sarcomas and carcinomas

The use of adjuvant chemotherapy appears to offer many advantages to the patient with cancer. However, objective information is difficult to compile. Clinical trials all too often have only a small number of patients. In order to best demonstrate the usefulness of adjuvant chemotherapy, many of the cases discussed here had bulky disease. Based on the known principles of chemotherapy, animals with minimal residual disease following surgery would most likely benefit from adjuvant chemotherapy. By using the principles discussed at the beginning of this article and information from clinical trials, veterinarians will better be able to inform clients of possible benefits and risks in treating their pets with chemotherapy.     

Multimodality therapy for head and neck cancer.

The refinement of radiation therapy techniques should result in a decrease in morbidity in canine and feline nasal carcinoma patients and should further allow for the addition of adjuvant therapies. Patients with large oral tumors that are incompletely excised should have radiation therapy added to their treatment regimen. Tumors with significant metastatic potential, such as melanoma, should be considered for addition of chemotherapy. Carboplatin has activity in melanomas and is being added at several institutions, but trial results are not yet available. Chemoradiation has become the treatment of choice for human head and neck squamous cell carcinomas but remains largely unexplored in veterinary medicine. Hopefully, development of chemoradiation will benefit feline squamous cell carcinoma patients, because current treatment regimens are largely ineffective. Immunotherapy agents and targeted biologic therapeutics seem to hold promise for the future.     

The effect of low reactive-level laser therapy (LLLT) with helium-neon laser on operative wound healing in a rat model

The effect of low reactive-level laser therapy (LLLT) with a He-Ne laser on operative wound healing was investigated in a rat model. 10-millimeter surgical wounds were created on the backs of Sprague Dawley rats, and animals were assigned to one of eleven groups (n=5). Ten groups received either 8.5 mW or 17.0 mW irradiation of 15 seconds LLLT a day with one of five different irradiation frequencies, i.e. daily (from the 1st to 6th day following surgery), every other day (the 1st, 3rd, and 5th day), on only the 1st day, on only the 3rd day, and on only the 5th day; the 1st day was the day following the surgery. The control group received no irradiation. A skin specimen was harvested from the dorsal thoracic region on the 7th day to measure the rupture strength. The control group had the lowest rupture strength (5.01 N), and the 17.0 mW every other day irradiation group had the highest rupture strength (13.01 N). Statistical differences were demonstrated in the 8.5 mW irradiation setting between the every other day irradiation group and the control group (p<0.05); and in 17.0 mW irradiation setting between the every day irradiation, the every other day, and the 1st day only groups vs. the control group (p<0.01). Histological examination demonstrated that wound healing in the 17.0 mW every other day irradiation group was promoted most significantly such as the prevention of excessive inflammation, increased formation of collagen fibers, and recovery in continuity of tissues. The control group showed poor wound healing and the other experimental groups showed intermediate healing. Thus LLLT with a He-Ne laser was found to promote the healing of operative wounds in the present rat model, in which the most favorable application of LLLT was the 17.0 mW setting of 15 seconds a day with a frequency of every other day.     

Principles of wound healing

Wound healing can be divided into immediate (zero to 1 hour), early (1 to 24 hours), intermediate (1 to 7 days), and late (greater than 7 days) stages. Many physical and physiologic events occur simultaneously and sequentially during these stages to produce the final wound scar. The processes of skin retraction, scab formation, would debridement, wound contraction, epithelial migration and proliferation, fibroplasia, and collagen maturation all must occur for healing to be successful. Many factors affect the size and shape of the resulting scar, including anatomic location and skin tension forces, systemic condition of the patient, blood supply to the wound, nutritional factors, environmental temperature, the presence of systemic drugs, wound infection, motion, wound oxygen gradient, wound moisture, and bandaging. Ideally, each of the factors would occur at a level compatible with optimal healing, but, in many clinical cases, one or more factors compromise normal, rapid healing. When we intervene with therapy, we probably adversely affect another factor in healing, while trying to correct the factor that is out of balance. In these decisions, the effects of our treatment on wound healing should be considered. The trade-off should be weighed and the treatment pursued only as long as necessary to allow healing to progress; then it should be discontinued or changed. With these considerations, it is hoped that we can attain healing at the most rapid physiologic rate.     

The role of albumin replacement in the critically ill veterinary patient

Objective: To review the human and veterinary literature on the physiological role and effects of therapeutic albumin supplementation. Data sources: Data from human and veterinary literature was reviewed. Human data synthesis: Hypoalbuminemia often occurs in a variety of critical illnesses, and contributes to the development of life‐threatening complications, including pulmonary edema, delayed wound healing, feeding intolerance, hypercoaguability, and multiple organ dysfunction. Serum albumin concentration has been used as a prognostic indicator in cases of chronic hypoalbuminemia. The use of albumin replacement therapy in humans is sometimes controversial, but may be associated with improved morbidity and decreased mortality. Veterinary data synthesis: Unlike human literature, there is a paucity of controlled clinical studies in the literature regarding albumin supplementation in veterinary patients. Rather, the majority of published studies were performed in experimental animals or via retrospective analyses. One recent study evaluated the use of plasma to improve albumin concentration in dogs with hypoalbuminemia. Other older studies investigated wound healing in dogs with experimentally induced hypoalbuminemia. As in human medicine, serum albumin concentration may be helpful as a prognostic indicator in critically ill dogs. Conclusion: Albumin is one of the most important proteins in the body because of its role in maintenance of colloid oncotic pressure, substrate transport, buffering capacity, as a mediator of coagulation and wound healing, and free‐radical scavenging. Albumin replacement in veterinary medicine is difficult, but until prospective clinical trials determine the efficacy of albumin replacement are conducted, a suggested clinical guideline would be to maintain albumin concentration at or above 2.0 g/dl utilizing fresh frozen plasma.     

Do magnetic fields influence soft tissue wound healing?--A preliminary communication

Magnetic fields have been considered for treating many ailments over man's history. There have been many anecdotal unsupported claims for successful treatment of soft tissue injury although reports have been more substantive in the orthopaedic field. The widespread clinical and veterinary use of a light self-adhesive magnetic foil in Europe prompted this trial of experimental wound healing. One hundred and sixty Sprague-Dawley rats had a linear 2.5 cm incision or a circular 1 cm skin defect made over the mid-dorsal spine. Equal numbers were randomised to receive either a magnetic foil or a dummy (control) dressing. At three, seven, 10 or 14 days linear wounds were distracted using a tensiometer; open defects were measured, excised and assayed for collagen content; 14-day wounds were examined histologically. Although wound tensile strengths increased and open wounds decreased in size with increase of hydroxyproline, there were no statistically significant differences between treated or control animals. Although easy to apply the alternate magnetic foil (giving 400 Gauss at 7 mm) conferred no statistically significant effect on soft tissue healing.     

Topical therapeutic agents that modulate corneal wound healing.

In summary, corneal wound healing is a complex phenomenon that involves interplay between the cellular elements of the cornea, numerous soluble factors, and the constituents of the ECM. Unfortunately, many studies that demonstrate marked alteration on cell behavior in vitro and even in in vivo experiments are often not helpful in the diseased patient, as shown by the results of careful clinical trials. Future work that addresses the complex milieu of the corneal wound healing environment by addressing the interaction of many of these factors will be more likely to be successful than seeking a single agent that will enhance wound healing in all situations.Modulation of wound healing processes by the application of topical therapeutic agents is, however, an expanding field of study sure to produce clinically significant improvements in the management of veterinary patients with corneal defects. The judicious use of topical cytoactive compounds has a place in the clinician's armamentarium integrated into a therapeutic plan that decreases the mechanical stresses imposed on the wound bed as well as removal of any underlying inciting cause.     

Plasma haptoglobin concentration in cattle with surgically corrected torsio uteri intrapartum

In 26 cows with surgically corrected torsio uteri intra partum, severity of disease, wound healing and secondary diseases were correlated with plasma haptoglobin concentration. The objective of the investigation was to determine, if an increased plasma haptoglobin concentration indicates the severity of disease respectively expected wound healing disorders or secondary diseases. The degree of severity of disease was determined by rectally diagnosed elasticity of the uterus before the surgery. In the present investigation, the severity of a uterine torsion intra partum could not be evaluated by determining the plasma haptoglobin concentration. In 9 of 11 days of investigation there was no significant difference in the plasma haptoglobin concentration of animals with an elastic uterus (animals with good prognosis) in contrast to cows with tight uterus (patients with poor prognosis) found. The significant differences on the 6th and 7th day post surgery are related to secondary diseases in patients with poor prognosis, which develop evidently earlier and form stronger. The correlation of all cows with--to those without secondary illnesses shows, that 10 days post surgery patients with secondary diseases have a significant higher plasma haptoglobin concentration (p < 0.05) compared to animals without secondary illnesses. No correlations existed between plasma haptoglobin concentration and wound healing in the examined cattle. A postoperatively increase of haptoglobin indicates a higher risk of secondary illnesses and complications.     

Postoperative management of the exotic animal patient.

Careful postoperative management is crucial for the success of any orthopedic surgical repair. The special needs of the exotic animal must be met during the immediate postoperative period and during hospitalization. Many exotic animals require a quiet, stress-free environment and careful attention to housing parameters, such as perching, temperature, and visual security. To provide adequate pain relief in these patients, analgesia should be given before, during, and after surgery. The drugs most often used for pain relief are NSAIDs and opioid analgesics. After surgery, monitor the healing process carefully with regular examinations and radiographs while remaining vigilant for potential problems such as osteomyelitis or nonunion. Physical therapy prevents the development of fracture disease, which includes joint or ligament contracture and bone or muscle mass loss. Because physical therapy affords the patient full use of the affected limb, it is considered a helpful practice in all patients. Physical therapy, however, is critical for free-ranging exotic animals that will be released back into the wild, such as birds of prey.     

Bone- and non-bone-derived growth factors and effects on bone healing.

In the future, it may be possible to manipulate the fracture site with exogenous growth factors to allow successful union of the bone ends without additional surgery. The complex interaction of growth factors, the timing of their appearance and disappearance at the wound site, and the concentrations necessary to achieve specific effects must be studied more thoroughly. For growth factors to find widespread clinical use, there must be evidence that healing is enhanced. It may be difficult to enhance the healing of fresh fractures in normal animals, and it may also be difficult to demonstrate the healing of nonunion fractures. Because of the great variability in fractures of clinical patients, studies designed to determine the effect of growth factors on bone healing must be carefully designed with appropriate attention given to randomizing patients based on the risk of delayed healing and other patient characteristics.     

Wound healing and management in psittacine birds.

Psittacines and other companion avian species often develop wounds requiring some form of medical or surgical therapy. Advancing technology in the field of wound care and management continues to evolve for use by the veterinary clinician. Although not all wounds can be successfully treated, many can be reduced and minimized with therapy. Consideration of the overall health, management, and nutrition of the avian patient will also aid in wound management. The avian patient with normal immune function and optimal nutrition will have improved wound healing compared with an immunocompromized or malnourished patient. The duration of treatment and potential stress of the wound-management program should also be taken into consideration when selecting a treatment program for the avian patient.     

Negative-Pressure Wound Therapy as Management of a Chronic Distal Limb Wound in the Horse

Wound healing in distal limb wounds with tissue loss in horses may be an expensive and long process due to prolonged inflammatory phase. Negative pressure wound therapy (NPWT) (also known as vacuum-assisted closure) is well established method of wound therapy in human plastic and reconstructive surgery for many years. It consists of a leak free bandage and a pump that applies subatmospheric pressure to the wound area. This report describes the successful use of the NPWT intended for the suppression of exuberant granulation tissue development of the wound on distal limb in a horse.     

Clinical indications and applications of radiotherapy and hyperthermia in veterinary oncology

The response of dogs and cats with neoplasia to radiation therapy has improved significantly during the past 10 years. This has largely been due to more aggressive radiation therapy treatment schedules, more accurate planning, and refinement of clinical indications. Sufficient numbers of dogs and cats irradiated with curative intent have not been accumulated to yet define the full impact of more aggressive therapy. However, many tumors will likely remain resistant to irradiation because of concomitant normal tissue injury that must be minimized. Systematic investigation of combination therapy (surgery, radiation, chemotherapy, and hyperthermia) should succeed in reducing local tissue side effects and increased local tumor control. A comprehensive approach to tumor management begins with decisions thoughtful of optimal treatment for suspected malignant tumors even at the time of initial examination and client counseling. An incisional biopsy provides essential information to determine the therapeutic course and should be considered prior to initial excision. More aggressive treatment, of even small tumors, early in the clinical course will lead to prolonged tumor control. Radiation therapy should be considered fundamental in the comprehensive treatment plan of many solid tumors.     

Thrombolytic Therapy in Dogs and Cats

Objective: To review the thrombolytic agents most commonly used in humans, their mechanisms of action, potential uses, adverse effects, and reports of their use in dogs and cats.
Human data synthesis: Thrombolytic agents avaliable in human medicine include streptokinase, urokinase, tissueplasminogen activator (t-PA), single-chain urokinase plasma activator (scu-PA) and anisoylated plasminogen-strep-tokinase activator complex (APSAC). These agents were originally used for the management of proximal deep vein thrombosis and severe pulmonary embolism but more recently, use of these drugs has been extended to include the treatment of acute peripheral arterial disease, cerebrovascular disease (stroke) and acute coronary thrombosis. The most predictable side effect associated with the use of thrombolytic therapy is hemorrhage.
Veterinary data synthesis: Clinical experience with thrombolytic agents in small animals is limited to streptokinase and t-PA. It is possible, that as in humans, canine and feline patients with PTE and right ventricular dysfunction may benefit from thrombolytic therapy but there are no veterinary studies to support this theory to date. Successful use of streptokinase has been documented in a small number of canine patients with systemic thromboembolism. ⁶³ Thrombolytic therapy is relatively efficacious in cats with aortic thromboemboli but is associated with a high mortality rate. ^59,60,64 With regard to use of t-PA in veterinary medicine, the small number of animals treated with varying protocols makes it impossible to provide safe and effective dose recommendations at this time.
Conclusions: Future goals for thrombolytic therapy in veterinary medicine include determination of more specific clinical indications, as well as design of effective protocols that minimize mortality and morbidity.     

Evidence of an association between use of anti-microbial agents in food animals and anti-microbial resistance among bacteria isolated from humans and the human health consequences of such resistance

Several lines of evidence indicate that the use of anti-microbial agents in food animals is associated with anti-microbial resistance among bacteria isolated from humans. The use of anti-microbial agents in food animals is most clearly associated with anti-microbial resistance among Salmonella and Campylobacter isolated from humans, but also appears likely among enterococci, Escherichia coli and other bacteria. Evidence is also accumulating that the anti-microbial resistance among bacteria isolated from humans could be the result of using anti-microbial agents in food animals and is leading to human health consequences. These human health consequences include: (i) infections that would not have otherwise occurred and (ii) increased frequency of treatment failures and increased severity of infection. Increased severity of infection includes longer duration of illness, increased frequency of bloodstream infections, increased hospitalization and increased mortality. Continued work and research efforts will provide more evidence to explain the connection between the use of anti-microbial agents in food animals and anti-microbial-resistant infections in humans. One particular focus, which would solidify this connection, is to understand the factors that dictate spread of resistance determinants, especially resistant genes. With continued efforts on the part of the medical, veterinary and public health community, such research may contribute to more precise guidelines on the use of anti-microbials in food animals.     

Effects of phenylbutazone and indomethacin on the post-operative course following experimental orthopaedic surgery in dogs

Randomized placebo-controlled crossover studies were carried out in dogs to evaluate how two non-steroidal anti-inflammatory drugs (NSAID) might modulate an acute post-traumatic inflammatory reaction. Two "identical" surgical interventions were performed on the forelimbs of each animal with an interval of 28 days, to enable a paired comparison of the inflammatory signs and the wound/bone healing processes. At one operation 8 dogs received 300 mg phenylbutazone twice daily for 8 days starting on the day before surgery, and at the other operation matching placebo tablets were given. In a similar placebo-controlled trial another group of 8 dogs received 5 mg indomethacin twice daily. With phenylbutazone the post-operative swelling was not significantly reduced compared to placebo, but there was less pain and limping. With indomethacin the swelling was somewhat reduced, but there was no consistent difference to placebo in the pain and limping assessments. None of the drugs appeared to distinctly effect the wound or fracture healing, as evaluated by clinical inspection, comparison of radiographs and comparison of bone sections from the sites of surgery. It proved difficult to select an appropriate dosage of indomethacin due to its high potential to induce GI ulceration and bleeding in dogs. In this experimental surgical model with an acute inflammation, neither phenylbutazone nor indomethacin showed impressive anti-inflammatory or analgesic properties. In the same model paracetamol has proved to significantly and more efficiently, reduce both swelling and pain without any noticeable adverse effects, and appears to be a better alternative than the two presently tested NSAID.     

The effects of topical oxygen therapy on equine distal limb dermal wound healing

Topical oxygen therapy (TOT) has been used in human medicine to promote healing in chronic wounds. To test the efficacy and safety of TOT in horses, an experimental wound model was created by making 1 standardized dermal wound on each limb of 4 healthy horses (n = 16). Each wound was fitted with an oxygen delivery cannula and covered with a bandage. One limb of each front and hind pair was randomly assigned to the treatment group (fitted with an oxygen concentrator device), with the contralateral limb assigned to the control group (no device). Wound area, epithelial area, and contraction were measured every 3 to 4 d. Biopsy samples and culture swabs were taken on days 16 and 32 to evaluate angiogenesis, fibroplasia, epithelial hyperplasia, inflammation and bacterial growth. Mean healing time in treated wounds (45 d, range: 38 to 52 d) was not significantly different from that in the paired control wounds (50 d, range: 38 to 62 d). Topical oxygen therapy had little effect on dermal wound healing in this experimental wound model in healthy horses.     

Prolonged survival after craniectomy with skull reconstruction and adjuvant definitive radiation therapy in three dogs with multilobular osteochondrosarcoma

Multilobular osteochondrosarcoma is an uncommon canine tumor but presents a treatment challenge when arising on the skull. This retrospective case series study aimed to describe outcome of a multimodality treatment approach involving aggressive surgical resection and adjuvant definitive radiation therapy in a group of dogs with multilobular osteochondrosarcoma of the calvarium. Clinical, imaging, treatment, and outcome data were collected from retrospective review of medical records. Three dogs met inclusion criteria. The presenting clinical complaint was the presence of a mass effect of the skull in all three dogs and concurrent neurologic abnormalities in one dog. Advanced imaging revealed aggressive lytic and proliferative tumors arising from the calvarium in all three dogs. All dogs were treated surgically with a modified craniectomy, repaired with a titanium mesh—polymethyl methacrylate bone cement implant or a low prolife titanium mesh plate and followed by adjuvant definitive radiation therapy with 2.5 Gy per fraction for 22 daily fractions. There were no major immediate surgical complications and radiation was well tolerated overall. Neurologic improvement was seen in the patient that presented with neurologic disease. Survival times from surgery were 387, 422, and 730 days and from the time of radiation were 358, 397, and 677 days. Findings in this sample of three dogs supported the use of aggressive therapy with a combination of surgical craniectomy and cranioplasty utilizing a titanium mesh implant and high dose definitive radiation therapy for local control and prolonged survival times in dogs with multilobular osteochondrosarcoma of the skull.     

Cutaneous Wound Healing in Ehlers-Danlos Syndrome

Wound healing in five dogs and five cats affected with a connective tissue dysplasia resembling Ehlers-Danlos syndrome of humans was compared with wound healing in 10 nonaffected animals. Six skin incisions on the lateral aspects of the thorax and abdomen of each animal were sutured and assessed daily for 75 days for evidence of healing. All wounds in nonaffected dogs, affected cats, and nonaffected cats healed by first intention. Three incisions in affected dogs had dehiscence of all or part of the incision line and healed by granulation, contraction, and epithelialization. Biopsies taken at 3, 6, 9, 12, 15, and 75 days were compared histologically to determine if there were any differences in rates of healing between affected and nonaffected animals. Epidermal thickening and scab formation were noted at days 3 and 6 in both affected and nonaffected animals. Infiltration with mononuclear cells and fibroplasia steadily increased from day 6 to day 15 in all groups. Collagen fibril formation was evident by day 9. At day 75, incision sites were recognized by fine, more compact collagen bundles and lack of adnexal structures, as compared with the adjacent dermis in both affected and nonaffected animals. Although delayed wound healing has been reported to be a complication of Ehlers-Danlos syndrome in humans, using clinical and histologic criteria, wound healing in dogs and cats with Ehlers-Danlos syndrome appears to be similar to nonaffected animals.     

Monitoring techniques for diabetes mellitus in the dog and the cat

One of the keys to achieving glycemic control in animals with diabetes mellitus is the appropriate selection and interpretation of analytic monitoring tests. Diabetic animals are subject to many of the same problems described in human diabetics. Diabetics are more susceptible to infection, and wound healing is often impaired. Decreased insulin promotes lipolysis and moderate hyperlipidemia, which can lead to falsely lowered fructosamine levels, impaired renal circulation, and atherosclerosis. Hyperglycemic, hypoinsulinemic animals continue to lose weight despite an increased appetite and an increased intake because they are not able to use glucose. Many unregulated diabetic animals will present with vomiting and diarrhea that can exacerbate electrolyte abnormalities seen with the osmotic diuresis present in an uncontrolled state. Canine diabetics are prone to cataract formation secondary to sorbitol accumulation in the lens. Cats, on the other hand, can present with diabetic distal neuropathy, which may be reversible with appropriate treatment. With all of these potential complications, it is important to monitor these animals regularly; this is the only way that glycemic control can be properly maintained over time. This article reviews the monitoring parameters available to the modern practitioner and outlines the benefits of each test, as well as caveats, in their interpretation.