Carbon dioxide laser photoablation adjunctive therapy following superficial lamellar keratectomy and bulbar conjunctivectomy for the treatment of corneolimbal squamous cell carcinoma in horses: a review of 24 cases

Objective To determine the complications and nonrecurrence rates following superficial lamellar keratectomy, bulbar conjunctivectomy, and adjunctive carbon dioxide (CO₂) photoablation for corneolimbal squamous cell carcinoma (SCC) in the horse. Study design Retrospective study. Sample population Twenty‐four horses with corneolimbal SCC. Procedure Medical records of horses diagnosed with corneolimbal SCC that was surgically excised and where CO₂ photoablation was used as an adjunctive therapy from 2000 to 2007 were reviewed. Signalment, prior therapy, tumor location and size, complications, and recurrence of SCC were recorded. Results The Thoroughbred was the most commonly (25%) represented breed. Lesions were >10 mm in diameter in 70.8% of cases. Eight horses (33.3%) had neoplastic cells extending to the deep margin of the keratectomy. All horses were available for follow‐up for an average ± standard deviation of 40.7 ± 25 months. Four horses (16.7%) developed a recurrence of SCC. Three of these four horses underwent repeat keratectomy and CO₂ photoablation, one each, at 4 months, 1, and 2 years following the initial procedure. One horse underwent enucleation 8 months following the initial procedure. Conclusions and clinical relevance As an adjunctive therapy, CO₂ photoablation was successful in 87.5% of the horses following a single procedure and in a total of 91.7% following a second therapeutic application. CO₂ photoablation appears to be effective as an adjunctive therapy following removal of large corneolimbal SCC in the horse and in cases in which all tumor cells were not excised.     

Photodynamic therapy for the treatment of periocular squamous cell carcinoma in horses: a pilot study

Objective  Local photodynamic therapy (PDT) is a novel cancer therapy in veterinary ophthalmology. A prospective pilot study seeking to demonstrate proof of principle and safety for the treatment of equine periocular squamous cell carcinoma (PSCC) was therefore conducted. We hypothesized that surgical excision with adjunctive local PDT is an effective and safe treatment for equine PSCC.
Procedures  Nine horses (10 eyes) with PSCC were treated with surgical resection, local infiltration of resulting wound beds with 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and irradiation with 665-nm wavelength diode laser. Regular follow-up ophthalmic examinations were performed.
Results  Surgical resection and PDT yielded disease-free intervals of 25–68 months in our study horses as of January, 2008. These results were obtained following a single treatment in seven horses and two treatments in one horse. In one horse, carcinoma in situ developed 2.5 months after partial surgical excision and PDT, requiring local excision under standing sedation.
Conclusions  Preliminary results suggest that surgical resection and adjunctive local PDT is a safe and effective novel treatment for PSCC in horses. More research is needed before PDT for the treatment of equine PSCC can be adequately compared with other current modalities. Important to future investigations regarding PDT, tumor recurrence rate, length of hospitalization, number of treatment episodes required to effect tumor remission, and total treatment costs should be examined in a controlled manner. Our present results and experiences suggest that this treatment may be useful in the treatment of equine PSCC.     

Initial experience of ultrapurified bovine haemoglobin use in horses

Ultrapurified bovine haemoglobin solutions such as Oxyglobin are rarely used in equine medicine due to their relatively high cost and concerns over their safety. Four foals and a mature horse were administered Oxyglobin as part of their treatment regime to good clinical effect, and no adverse clinical signs were noted. All 5 animals went on to make a full recovery from the various disease processes that necessitated treatment with blood and blood products. Oxyglobin appears to be a useful adjunctive treatment for acute, life‐threatening anaemia in the horse.     

A Review of Current Treatment Options in the Treatment of Ocular and/or Periocular Squamous Cell Carcinoma in Horses: Is There a Definitive “Best” Practice?

This review examines the most commonly reported treatment options for ocular squamous cell carcinoma (OSCC) and periocular squamous cell carcinoma (POSCC) in horses and proposes to conclude on the most viable method based on available published studies in terms of treatment outcome, known side effects, advantages, disadvantages, and reliability of available evidence. After a literature search for peer-reviewed published articles, seven most commonly reported on treatments for OSCC and/or POSCC were identified: surgery, photodynamic therapy, carbon dioxide (CO₂) laser ablation, radiofrequency hyperthermia, cryotherapy, chemotherapy, and radiation therapy. Combination therapies were supported as a most successful recommendation; however, when considering site-specific outcomes, the following conclusions may be drawn: limbal squamous cell carcinoma (SCC) was most effectively treated with surgery and adjunctive therapy including CO₂ laser ablation, mitomycin C, and brachytherapy; third eyelid SCC reported good outcomes when treated with surgery alone (clear margins) and in combination with brachytherapy for unclear margins; eyelid SCC, surgical resection was usually limited and most reports supported the use of adjunctive brachytherapy, although photodynamic therapy appeared to be a promising new treatment. It was deemed unreasonable to conclude on the best treatment for cornea, conjunctivae (palpebral and bulbar), and medial canthi in isolation because of lack of evidence. A consistently favored treatment for OSCC and/or POSCC in horses does not currently exist. The presentation of data in the literature and its lack of consistency make it impossible to statistically analyze and make comparative conclusions on treatment outcomes. This review provides a basis for further research to establish a best-practice protocol.     

Local photodynamic therapy for equine squamous cell carcinoma: evaluation of a novel treatment method in a murine model

The objective of this study was to evaluate the effect of local photodynamic therapy (PDT) with verteporfin on tumor growth inhibition of squamous cell carcinoma (SCC) in a murine model. SCC was implanted in 85 nude mice by subcutaneous injection of A-431 SCC cells. Treatment groups (10 mice/group) received an intra-tumoral injection of verteporfin dissolved in dimethyl sulfoxide (DMSO) or 5% dextrose solution at a dose of 0.01 or 0.1mg/cm3. Controls received only solvent, or no injectate. All groups received identical light illumination (100J/cm2). Relative change in tumor volume (RCTV) at day 30 was compared between groups using the Wilcoxon rank sum test (P< 0.05). Local PDT with verteporfin at a dose of 0.1mg/cm3 resulted in significantly lower RCTV at day 30 compared to controls. Choice of solvent (DMSO versus D5W) did not affect the results. Local PDT may be an effective adjunctive therapy for the treatment of periocular equine SCC.     

A review of equine mucocutaneous squamous cell carcinoma

Squamous cell carcinoma (SCC) accounts for approximately 20% of all equine mucocutaneous (MC) tumours and continues to present a therapeutic challenge to practitioners. Most MC‐SCC are locally invasive and slow to metastasise, but metastasis to local lymph nodes is not uncommon. The most common location for MC‐SCC is the periorbital region, with the eyelid most commonly affected. Although only 13% of MC‐SCC involves the external genitalia, MC‐SCC is the most common neoplasm of male genitalia. Equine caballus papillomavirus‐2 has recently been linked to MC‐SCC and may prove to be necessary for tumour development. Risk factors may include chronic exposure to ultraviolet light and chronic skin irritation. Horses developing genital MC‐SCC tend to be older compared to those with periorbital MC‐SCC. Histopathology is required for definitive diagnosis of MC‐SCC, although horse phenotype and lesion location may suggest MC‐SCC. Several treatment modalities have been successful in eliminating or managing MC‐SCC, with surgical excision and intratumoural chemotherapy yielding the best results. Other treatment options including cryotherapy, hyperthermia, radiotherapy and photodynamic therapy are often used as adjunctive therapies. Early recognition of tumours and prompt intervention are associated with a positive outcome.     

Mandibular squamous cell carcinoma in a 5‐year‐old Tennessee Walking Horse

Squamous cell carcinoma (SCC) is the second most common neoplasm reported in the horse, but occurs rarely in the oral cavity. Clinical signs may be insidious in onset and mimic other non‐neoplastic processes, thus delaying appropriate treatment. Timely evaluation and advanced diagnostic imaging may offer the opportunity to initiate definitive treatment. This report describes a young gelding with mandibular SCC that was evaluated for mandibular swelling failing to respond to symptomatic therapy.     

Periocular cutaneous mast cell tumors in cats: evaluation of surgical excision (33 cases)

Objective  To describe feline periocular cutaneous mast cell tumor (CMCT) clinical features, rates of local tumor recurrence and metastases, and cat survival time following surgical excision.
Animals studied  Thirty-three cats with periocular CMCTs.
Procedures  Medical records of cats diagnosed with periocular CMCTs were reviewed; cats were included if CMCTs were surgically excised and the diagnosis confirmed by histopathology. The appearance, size, location and histopathology findings of CMCTs were recorded. Rates of local recurrence, metastasis, and survival time following surgical excision were collected when available.
Results  All periocular CMCTs were restricted to the eyelids. In addition to surgical excision, three cats were treated with adjunctive therapy (strontium-90 irradiation or cryotherapy) intraoperatively. Local tumor control was achieved in 22/23 cats with a minimum follow-up of 30 days (median follow-up time of 711 days); one cat developed disseminated CMCTs but no local recurrence. Cats with periocular CMCTs had a median survival time of 945 days. Metastatic disease involving peripheral lymph nodes or abdominal viscera was not detected in any cat at any time during the study. All periocular CMCTs were classified as low-grade based on histopathology, and complete excision was achieved in approximately 50% of cases.
Conclusions  Surgical excision of periocular CMCTs in cats is an effective treatment option with rare local recurrence and metastases, even following incomplete surgical excision.     

Combined keratectomy, strontium-90 irradiation and permanent bulbar conjunctival grafts for corneolimbal squamous cell carcinomas in horses (1990-2002): 38 horses

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of postoperative beta-irradiation with strontium-90 as an adjunctive treatment to superficial keratectomy and permanent bulbar conjunctival graft for removal of equine corneolimbal squamous cell carcinoma (SCC), in decreasing recurrence rate. STUDY: The retrospective case study included 38 horses diagnosed and treated for SCC of the eye that involved the limbus and/or cornea. The patients were treated between 1990 and 2002, with strontium-90 irradiation immediately after corneal and conjunctival graft surgery. Recurrence was defined as the postoperative and postirradiation regrowth of SCC in the same site and globe that was previously treated. RESULTS: The Appaloosa was the most commonly represented breed and horses that had more than one base coat color represented the majority of the cases (53%). The coat colors of white, chestnut/sorrel and gray were the most commonly represented colors of the horses treated. Eight horses (21%) could not be assessed for tumor recurrence due to lack of two or more post-treatment examinations, and another horse was enucleated 6 days postoperatively due to progressive corneal ulceration. Twenty-four horses (63% of the entire study population; 83% of the followed cases) had a mean +/- SD of 1754 +/- 1319 days without tumor recurrence, ranging from 14 days to 5110 days. Five horses (13% of the entire study population; 17% of the assessed horses) had tumor recurrence at a mean +/- SD of 449 +/- 339 days with a range of 29 days to 900 days. For the five recurrences, treatment included local excision (n = 1), enucleation (n = 2), and additional strontium-90 therapy (n = 3). CONCLUSIONS: The combination of superficial keratectomy, beta-irradiation and permanent bulbar conjunctival grafts for limbal, corneal or corneolimbal SCC in horses is effective in at least 83% of the horses. Recurrence occurred in about 17% of the horses. Multiple biannual re-examinations are recommended to observe for tumor recurrence.     

Metastasis or delayed local extension of ocular squamous cell carcinoma in four horses

Four horses treated for ocular squamous cell carcinoma (SCC) that subsequently developed local tumour extension or local metastases without ocular recurrence are included in this study. Medical records were examined and long‐term follow‐up obtained through contact with owners and referring veterinarians. In 2 horses, SCC developed in the nasolacrimal duct and maxillary sinus one and 3.5 years, respectively, after treatment for SCC in the medial canthus of the eye. No recurrence of the SCC was noted in the ocular structures. Both were treated successfully with surgery and radiation therapy. Two additional horses had delayed metastasis of SCC to the parotid lymph node one and 2 years after excision of the ipsilateral third eyelid for SCC. No recurrence of the SCC was noted in the ocular structures. One was treated with surgery and radiation without success and one was not treated. Ocular SCC can spread to local tissues or lymph nodes without recurrence in the eye. The clinical manifestation of tumour recurrence may be delayed. Delayed local extension or local metastasis in horses after ocular SCC without recurrence in the eye itself has not been previously reported. Clinical signs of ocular squamous cell carcinoma should prompt immediate treatment and local recurrence despite successful treatment of the ocular disease is a possibility.     

Penile and preputial squamous cell carcinoma in the horse and proposal of a classification system

Squamous cell carcinoma (SCC) is the most common tumour of the penis and prepuce of the horse and is found mainly in older animals. Reports on breed predilection for penile tumour formation are equivocal but castration, coat colour, poor genital hygiene and various infectious agents have been suggested to predispose to the development of SCC. Careful assessment of the primary tumour is an important first step in the design of an optimal treatment protocol. Tumour size, invasiveness, differentiation grade and presence of metastases are relevant to the decision to pursue additional diagnostic procedures or specific treatment options. Complete elimination of the neoplasm and, therefore, risk of recurrence is highly dependent on the type of therapy chosen. However, the size and histopathological features of the primary tumour are also important factors with respect to prognosis. This review describes the clinical and pathological features of penile and preputial SCC in the horse and proposes a standard staging system.     

Radiotherapy for the treatment of periocular tumours in the horse

Periocular tumours are a relatively common problem in the horse, and present some unique challenges. Radiotherapy has long been considered the ‘gold standard’ for the treatment of periocular tumours in the horse, and there are various techniques of delivering this treatment. Although teletherapy and plesiotherapy are occasionally used, the most commonly used technique is interstitial brachytherapy. Low-dose rate interstitial brachytherapy has reported success rates of between 74 and 100% for the treatment of periocular sarcoids, and other tumours can also be successfully treated using this technique. There are significant disadvantages to the low-dose rate brachytherapy approach, and recently, a technique using high-dose rate brachytherapy has been described with a reported success rate of 100% for periocular sarcoid treatment. Electronic brachytherapy is a technique which may provide an alternative to high-dose rate brachytherapy, but its use for the treatment of periocular tumours has not been reported, and the requirement for general anaesthesia is a significant disadvantage.     

Skeletal metastasis from a squamous cell carcinoma of the nictitating membrane in a Haflinger horse

A 12-year-old Haflinger gelding with a history of a persistent cough was referred for evaluation of a severe lameness of the left forelimb. An excision of the right nictitans had been performed 2 years prior to presentation, and a squamous cell carcinoma (SCC) with embolic neoplastic cells in several blood vessels had been confirmed by histopathology. The origin of the lameness could not be localised with regional analgesia; therefore, a nuclear scintigraphic examination was performed. This revealed an area of marked increased radiopharmaceutical uptake at the level of the caudodorsal border of the left scapula. Further examination, including ultrasound-guided biopsy of the suspect region, confirmed the presence of SCC invading the scapula. Due to poor a prognosis, the horse was subjected to euthanasia. Prior to euthanasia, the gelding was tested homozygous for the missense variant in the damage-specific DNA-binding protein 2 (DDB2) gene, which is reported as a risk factor for the development of nictitans SCC in Haflinger horses. Post-mortem evaluation revealed multiple SCC metastasis, affecting the scapula, the liver and the lungs. To the authors' knowledge, this is the first reported case of bone metastasis following a primary periocular SCC in a horse.     

Early diagnosis may hold the key to the successful treatment of nasal and paranasal sinus neoplasia in the horse

Intrasinus neoplasia remains a rare but difficult condition to diagnose and treat in the horse, comprising approximately 8–19% of sinonasal disorders. There are, however, only a few case series upon which to base an approach to diagnosis and management ( Cotchin 1967, 1977 ; Madewell et al. 1976 ; Stunzi and Hauser 1976 ; Sundberg et al. 1977 ; Priester and McKay 1980 ; Boulton 1985 ; Hilbert et al. 1988 ; Dixon and Head 1999 ; Head and Dixon 1999 ; Tremaine and Dixon 2001a,b ). Squamous cell carcinoma (SCC) is the most common neoplasm observed in the equine paranasal sinuses. Evidence from other species would indicate that early recognition of SCC is crucial to the success of treatment and the ideal treatment remains complete excision with margins. Sinus involvement generally precludes this and we must often settle for surgical debulking, with or without adjunctive radio‐ or chemotherapy. In horses, as in other species, early recognition is difficult because clinical signs are nonspecific. Treatment is, therefore, often not attempted due to the extensive nature of lesions at presentation and the limited surgical access. The accompanying article by Kowalczyk et al. (2011 ) showed how 3‐dimensional (3D) imaging can identify the hallmark changes associated with aggressive neoplasia in the equine sinuses ( Kowalczyk et al. 2011 ). The value of computed tomography (CT) and magnetic resonance imaging (MRI) lies in noninvasive early diagnosis as well as lesion monitoring post intervention. Where CT can be performed with the horse in the standing position, avoidance of general anaesthesia offers further value, especially as standing surgical techniques now allow thorough, minimally invasive evaluation and biopsy of the equine sinuses. In combination, standing CT and minimally invasive sinus surgery allow accurate and early diagnosis and monitoring of disease progression, opening the door for advances in surgical and adjunctive treatments for this complex condition.     

Differential diagnoses,investigation, and management of a periocular swelling close to the nasolacrimal duct in a horse – A case report of Dacryops

To describe the differential diagnoses, investigation, and management of a periocular swelling close to the nasolacrimal duct in a horse that was consistent with a nasolacrimal duct dacryops (lacrimal cyst). A 16‐year‐old gelding, Connemara cross presented with a history of a periocular swelling rostroventral medial to the right eye that had been sampled by the referring veterinary surgeon. A cystic lesion was diagnosed following standing computed tomography. Surgical removal of the cystic lesion was performed, and the tissue was submitted for histopathologic and immunohistochemical examination. Surgical removal of the cyst was curative, and there was no recurrence of clinical signs 7 months later. There was a small amount of mineralized material in the center of the cyst. Histopathologic and immunohistochemical examination confirmed a nasolacrimal duct cyst. Dacryops can form in horses as well as other species and appears to have a favorable outcome if surgically removed.     

Clinical observations on the use of BCG cell wall fraction for treatment of periocular and other equine sarcoids

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.     

Penile and preputial tumours in the horse: literature review and proposal of a standardised approach

Penile and preputial tumours are not uncommon in the horse, but can cause discomfort and lead to serious complications. Several types of tumour of the male external genitalia have been described. The most common type is the squamous cell carcinoma (SCC), which is found mainly in older horses. Reports of a breed predilection for penile tumour formation are equivocal, but castration, coat colour, poor hygiene and various infectious agents have all been suggested to predispose to the development of some types of tumour (e.g. SCC, papilloma and melanoma). Careful assessment of the primary tumour is an important first step in the design of an optimal treatment protocol. Invasiveness, differentiation grade, tumour size and presence of metastases are all relevant to the decision to pursue additional diagnostic procedures or specific treatment options. To date, no standard protocol has been reported for the approach to penile tumours in the horse and treatments range from minimally invasive therapies (e.g. topical use of 5-fluorouracil) to radical surgical interventions (e.g. en bloc penile and preputial resection with penile retroversion). Completeness of removal of the neoplasm and therefore risk of recurrence is highly dependent on the type of therapy chosen. However, the size and histopathological features of the primary tumour are also important factors with respect to the likelihood of recurrence. This review describes the most common penile and preputial neoplasms in the horse, and outlines a standard protocol aimed at arriving at a specific diagnosis and tailoring the therapeutic approach accordingly.     

The use of mitomycin C as an adjunctive treatment for equine ocular squamous cell carcinoma

OBJECTIVE: To assess the effectiveness of topical mitomycin C application as an alternative adjunctive therapy to CO2 laser ablation in the treatment of equine ocular squamous cell carcinoma. DESIGN: A retrospective clinical study of eight client owned horses in which 10 affected eyes were treated for ocular squamous cell carcinoma over a 17 month period. (March 2003 to August 2004). PROCEDURE: Each horse was given a general anaesthetic to allow CO2 laser ablation of the lesion(s). Mitomycin C at a concentration of 0.4 mg/mL was then applied intraoperatively to the affected areas for 1 or 5 minutes. Postoperatively a triple antibiotic eye ointment was applied to the eye twice daily and each horse was treated with systemic non-steroidal anti-inflammatory drugs for 7 days. RESULTS: Recurrence following treatment was noted in three eyes. Two of these were retreated and no further signs developed. The remaining eye was enucleated at the request of the owner. Overall 90% of treated eyes appeared free of tumour a minimum of 11 months post treatment. CONCLUSION: In this case series mitomycin C appeared to offer a valid alternative to other adjunctive therapies currently employed in the treatment of equine ocular squamous cell carcinoma.     

Penile and preputial squamous cell carcinoma in the horse: a retrospective study of treatment of 77 affected horses

Reasons for performing study: The most common penile and preputial neoplasm in the horse is the squamous cell carcinoma (SCC), but no large surveys of treatment and effects of the grade of the tumour, based on the degree of differentiation, on outcome of affected horses are available. Objectives: Analysis of treatment of male horses affected with SCC of the external genitalia and long‐term results of treatment. Methods: Seventy‐seven cases of SCC were evaluated. Data recorded included treatment, outcome, post operative histopathology and retrospective tumour grading. Results: Treatments included: cryosurgery, excision, partial phallectomy, partial phallectomy and sheath ablation, and en bloc penile and preputial resection with penile retroversion and removal of inguinal lymph nodes. The incidence of recurrence after partial phallectomy was 25.6% (10/39) and following incomplete removal was 17.9% (7/39). The incidence of recurrence after en bloc resection with retroversion was 12.5% (1/8). In horses with confirmed inguinal lymph node metastasis, the incidence of recurrence was 25.0% (1/4). Poorly differentiated SCCs were more likely to metastasise than well differentiated SCCs, and there was a greater chance that the treatment would be unsuccessful. The success of treatment, complete removal and in preventing recurrence of the tumour, of male horses with SCC of the external genitalia was 55.7%. Conclusions: Horses that receive only partial phallectomy for treatment for SCC of the external genitalia have a high incidence of recurrence in contrast to horses that receive an en bloc resection. Tumour grading of SCC can help predict prognosis and guide selection of treatment.     

Alternaria species infection in nine domestic cats

A case series of nine domestic cats with culture-confirmed Alternaria species infection is presented, with conclusions drawn regarding signalment, clinical signs, treatment and outcome. Middle aged neutered males were over-represented and all presented with cutaneous lesions involving the extremities (nose, pinnae and digits). Lesions were mainly slow-growing, poorly circumscribed nodules or plaques but some also presented as non-healing wounds. A combination of surgical excision with adjunctive medical therapy appeared to be the most successful treatment option but long courses of medical therapy were generally required and recurrence was common.