Treatment of an ocular squamous cell carcinoma in a stallion with atrial fibrillation

Abstract

A stallion was presented for surgical treatment of limbal squamous cell carcinoma. Excision with a conjunctival pedicle flap was done to prevent ocular invasion and preserve vision. A complication was the diagnosis of atrial fibrillation, which was not converted to sinus rhythm due to the potential complication of treatment with quinidine sulfate.

An 18-year-old, bay, warmblood stallion was presented for treatment of a limbal squamous cell carcinoma (SCC). The referring veterinarian had examined the stallion after the owners had noted a slowly growing mass in the left eye (OS) over the previous 2 mo. A biopsy was submitted for light microscopy, which confirmed the diagnosis of SCC.

On presentation, the horse’s general physical examination was unremarkable, except for an irregular arrhythmia of the heart. A neuro-ophthalmic examination, including menace, palpebral, and pupillary light reflexes, was normal. Sedation was achieved with 0.3 mg/kg body-weight (BW) of xylazine (Anased; Novopharm Animal Health, Toronto, Ontario). The auriculopalpebral nerves were blocked bilaterally with 30 mg of lidocaine (Lidocaine HCI2%; Bimeda-MTC, Cambridge, Ontario) per site to facilitate a complete ocular examination. Schirmer tear test results were 20 and 15 mm, and intraocular pressures were 19 and 20 mmHg in the right eye (OD) and OS, respectfully. The OS had a mucopurulent discharge and a pink nodular mass on the scleral conjunctiva at the lateral canthus. It was 3 cm in diameter, extended 4 mm over the cornea, and was raised 2 mm above the surface of the eye (Figure 1). The goals of treatment were tumor removal, prevention of metastasis, and maintaining an esthetically visual eye by en-bloc resection with a conjunctival pedicle flap.

Figure 1.

The left eye of a stallion with mucopurulent discharge and a pink nodular mass on the cornea, limbus, and bulbar conjunctiva.

An electrocardiogram (ECG) was conducted to determine the nature of the arrhythmia. It revealed f-waves and variable Q-Q intervals. The conclusion was atrial fibrillation. Serial ECG’s over a 2-day period demonstrated that the arrhythmia was unchanging. An echocardiogram was completed to evaluate heart size, contractility, and valvular function. Mild triscupid regurgitation was noted and considered within normal limits. Two cardiologists were consulted independently, and their recommendations were to not attempt conversion with quinidine sulfate.

The horse was premedicated, IV, with acepromazine (Acevet; Vetoquinol N-A, Lavaltrie, Quebec), 0.03 mg/kg BW; xylazine (Anased; Novopharm Animal Health), 0.5 mg/kg (BW); and butorphanol (Torbugesic; Wyeth Canada, St. Laurent, Quebec), 0.025 mg/kg BW. Anesthesia was induced with 2 mg/kg of ketamine (Vetalar; Bioniche Animal Health Canada, Belleville, Ontario) and guafenesin (WCVM Teaching Hospital, University of Saskatchewan, Saskatoon, Saskatchewan), IV, to effect. Maintenance was achieved with 2% isofluorance (Isofluorane; Abbott Laboratories, Saint-Laurent, Quebec), and a constant rate infusion of xylazine (Anased; Novopharm Animal Health), 2 mg/kg BW, ketamine (Vetalar; Bionche Animal Health Canada), 4 mg/kg BW, and diazepam (Diazepam; Sabex, Boucherville, Quebec) 0.1 mg/kg BW, IV, at a rate of 25 mL/h. Eight milliliters of dobutamine (Dobutamine; Sabex) in 500 mL of physiologic saline (Normosol R; Abbott Laboratories, Abbott Park, Illinois, USA), with a drip rate of 1 drop/ 2 s, was also used.

The horse was placed in right lateral recumbency and prepared for surgery with betadine. An incision was made around the tumor, with 2 mm margins on the corneal surface and 5 mm margins on the scleral surface. Care was taken not to touch the tumor with the instruments. A beaver blade was used to incise below the tumor to a depth of 650 μm. A pedicle flap was harvested from the bulbar and palpebral conjunctiva and sutured over the defect with 9-0 vicryl (Figure 2). The tumor was formalin-fixed and sent for light microscopic examination. Edges were evaluated for neoplastic cells (Prarie Diagnostic Service, Saskatoon, Saskatchewan). Postoperatively, bacitracin-neomycin-polymyxin ointment (BNP ointment; Vetcom, Upton, Quebec) was applied to his left eye, 98 h for 5 d.

Figure 2.

The left eye of the stallion noted in Figure 1, 1 mo post-keratectomy. The defect was repaired with a conjunctival pedicle flap.

A follow-up examination was done 4 wk postsurgery. The owners reported no complications until 3 d prior to the recheck, when the stallion began excessive rubbing of the OS and a mass reappeared. The mass, located above the pedicle flap, was 1 cm in diameter, pink, fleshy, and raised. The horse was sedated with xylazine (Anased; Novopharm Animal Health), 0.5 mg/kg BW, and the auriculopalpebral nerve was blocked with 30 mg of lidocaine (Lidocaine HCI 2%; bimeda-MTC). Menace, palpebral, and papillary light reflexes were normal. Schirmer tear test was > 35 mm OD and 15 mm OS. Intraocular pressure was 21 mmHg OD and 19 mmHg OS. The mass was sharply excised, impression smears were made, and the formalin-fixed tissue was sent for histopathologic examination (Prairie Diagnostic Services). The mass was determined to be a mixed population of inflammatory cells and fibroblasts — typical of granulation tissue. Six months postoperatively, the horse continues to do well, and no signs of tumor reoccurrence have been reported by the owners (Figures 1, 2).

Squamous cell carcinoma is the most common tumor of the eye and surrounding structures. It most commonly originates in the bulbar conjunctiva or the edge of the nictitating membrane. Those located at the limbus and eyelids are often raised, pink, fleshy in appearance, and localized to these tissues. In contrast, when SCC occurs on the palpebral conjunctiva or nictitating membrane, the lesions tend to invade the local adnexa and appear ulcerative or exuberant (1). Multicentric involvement occurs in 15% to 25.9% of cases (1,2). Squamous cell carcinoma has a low rate of metastasis, but late in the course of the disease, spread can occur to local and regional lymph nodes (1). Horses most predisposed to SCC are those exposed to increased mean annual solar radiation, draft horses or those with white or light markings around there eyes (3). Breeds such as the Appaloosa, American paints, and pinto, or colors such as palomino or creamello have an increased prevalence of SCC. Average age at time of diagnosis is between 8.0 and 11.8 y (3). Definitive diagnosis is based on light microscopic examination, which differentiates SCC from granulation tissue, papillomas, sarcoids, and other neoplasms.

There are many supplemental treatment options to surgical removal. They include cryotherapy, irradiation therapy, radiofrequency hyperthermia, immunotherapy, and laser ablation.

Surgical excision is the most common therapy. It is often combined with the other techniques if clear surgical margins are not obtained. A cure rate of at least 90% can be expected when surgical excision alone is used (3). Exenteration or enucleation are used when extensive ocular involvement and complete tumor resection is not possible.

Cryotherapy involves serial treatments of repeated freeze thaw cycles with nitrous oxide or liquid nitrogen. This is a technically simple procedure that rarely requires general anesthesia. Side effects include local edema and depigmentation of hair and skin in adjacent areas. An 86.6% cure rate in 15 horses using cryotherapy on ocular SCC has been reported (4).

Irradiation therapy can be applied by using beta irradiation or brachytherapy implants. Beta irradiation works best in lesions less than 2 mm in depth, as 75% of rays are absorbed by this depth (3). It is commonly used after surgical debulking. Side effects of this therapy include keratitis and anterior uveitis. Brachytherapy, the implantation of radiotherapeutic gold implants, is another alternative. These implants release a continuous source of radiation and do not need to be removed, because they are inactive after 10 half lives. Success rates of tumors treated this way are 80% no reoccurrence in 1 y, and 70% in 2 y. With this therapy, there are risks are driving neoplastic cells into normal surrounding tissue during implantation, corneal opacity, local necrosis, and radiation hazard to personnel (3,5).

Radiofrequency hyperthermia works on the premise that neoplasic cells are more susceptible to thermal energy passed between 2 electrodes than normal cells. This therapy is recommended on tumors that are less than 3 mm deep and 4 cm in diameter, as these are the limits of radiofrequency (5). It is used most often to potentiate other therapies (3,5). Potential complications include ulcerative keratitis, conjunctivitis, and anterior uveitis (3).

Immunotherapy with mycobacterium cell wall extracts of bacille Calmette-Guérin (BCG) remains popular as a treatment for periocular SCC and sarcoids. Tumor regression is due to specific and nonspecific immune response to the inoculation. This therapy results in minimal scarring. One report describes a horse that went into remission with this therapy after metastases were seen in regional lymph nodes (6). However, multiple treatments are needed and necrosis can occur at the injection site.

Carbon dioxide laser ablation involves flash boiling and vaporizing the cells. This therapy has specific advantages, including control of intraoperative hemorrhage, minimal postoperative discomfort, precision of tumor removal, ease of application, and production of a sterile incision (7). Disadvantages include longer healing time, increased cost of equipment and protection for personnel, and increased occurrence of corneal scarring (7). More work is required to assess the frequency of tumor reoccurrence.

In the case presented, the goals of treatment were to remove the primary tumor, stop invasion of the eye, and maintain vision. Due to the location and size of the tumor, the surgical expertise, and availability of equipment, surgical excision was method of choice. A pedicle flap was used to protect the keratotomy site. Light microscopic examination of the edge of the biopsies confirmed clear surgical margins.

A challenging complication of the case was the atrial fibrillation. The increased anesthetic risk associated with this arrhythmia made conversion to a sinus rhythm prior to surgery a consideration. The longer atrial fibrillation is present, the less likely that therapy with quinidine sulfate will be effective. It is also likely that such horses will reconvert (8). Side effects of therapy include depression, mucosal edema, anorexia, urticaria, diarrhea, laminitis, colic, tachycardia, convulsions, and sudden death. It was unknown how long this horse had had the arrhythmia prior to presentation. Since risks of therapy are significant, and conversion unpredictable, it was decided not to treat the atrial fibrillation.

The biggest risk associated with horses in atrial fibrillation undergoing anesthesia is hypotension. This results from decreased cardiac output due to inadequate ventricular filling. Acepromazine is recommended for premedication for its protective effects against ventricular dysrhythmias. If α2-adrenoceptor agonists are used, low doses are indicated, since they cause bradycardia and decreased cardiac output. Ketamine is a preferable induction agent, since it decreases cardiovascular depression. Isoflurane is recommended over halothane, since it causes less myocardial depression and does not sensitize the horse to catecholamine induced dysrhythmias. If fluid loading alone cannot maintain blood pressure, dobutamine is indicated (9). Dobutamine increases cardiac contractility with no effect on heart rate. Blood pressures averaging 75/45 mmHg and a heart rate between 55 and 62 beats/min were maintained. Hypercarbia was the only complication of anesthesia.

The excessive tissue growth that was seen on follow-up was over the middle of the pedicle flap and had appeared suddenly after an episode of self-trauma, making it more typical of granulation tissue than tumor reccurrence. The biopsy report confirmed the tentative diagnosis.

This case was a reminder that it is important to do a thorough physical examination on every patient. Finding the atrial fibrillation was incidental, but it could have severely affected the case, if it had not been detected.