Intralesional 5-fluorouracil as a therapeutic approach for ocular squamous cell carcinoma in cattle

Introduction

Bovine ocular squamous cell carcinoma (OSCC), commonly referred to as "cancer eye, " is one of the most frequently occurring malignant neoplasms in cattle and represents a significant economic problem in the livestock industry. The tumour arises from the squamous epithelium of the conjunctiva, cornea, eyelids or associated ocular tissues and is characterized by progressive local invasion with occasional metastasis to regional lymph nodes [1] . Several environmental and genetic factors have been associated with the development of OSCC including exposure to ultraviolet radiation, lack of periocular pigmentation, geographical location and age of the animal [2] . Viral agents such as bovine papilloma virus and bovine herpes virus have also been implicated in the etiopathogenesis of the tumour [3] . The incidence of bovine eye cancer increases with advancing age, and most cases are reported in cattle older than five years [4] . Breed susceptibility has also been reported, with crossbred cattle such as Holstein Friesian and Jersey crossbreds showing a higher incidence of ocular tumours compared to indigenous breeds [2,5] . Female cattle are more frequently affected than males because they are generally maintained for longer periods for breeding and milk production, which increases their exposure to environmental risk factors such as solar radiation [6] . Several treatment methods have been reported for the management of ocular squamous cell carcinoma including surgical excision, cryotherapy, radiation therapy and chemotherapy [7] . Among chemotherapeutic agents, 5-Fluorouracil (5-FU) is widely used due to its antineoplastic activity against epithelial tumours. 5-Fluorouracil is a pyrimidine analogue that inhibits thymidylate synthase, thereby interfering with DNA synthesis and preventing proliferation of rapidly dividing tumour cells [8] .

Intralesional administration of the drug enables direct delivery to the tumour mass, producing localized cytotoxic effects while minimizing systemic toxicity. Therefore, the present study was undertaken to evaluate the prevalence of bovine ocular tumours and assess the therapeutic efficacy of intralesional 5-Fluorouracil in affected cattle.

Materials and Methods

The present study was conducted on clinical cases of cattle affected with ocular tumours presented to the Department of Veterinary Surgery and Radiology, Veterinary College, Bidar. A total of fifteen cases were randomly selected for the study. Relevant data pertaining to each animal, including history, clinical signs, age, sex and breed, were systematically recorded. Diagnosis of ocular tumours was established based on clinical examination and was further confirmed through histopathological and immunohistochemical findings. All animals were subjected to detailed clinical, haematobiochemical and ophthalmic examinations prior to treatment. Intralesional therapeutic procedures were performed under proper restraint, with animals maintained in a standing position. Regional anaesthesia was achieved by administering auriculopalpebral nerve block and Peterson block using 2% lignocaine hydrochloride to ensure painless intervention. The size of the tumour was measured using a digital Vernier calliper for assessment and monitoring of treatment response. All affected cattle were treated with intralesional administration of 5-Fluorouracil (50 mg/ml). The drug was injected directly into the tumour mass until saturation was achieved, as indicated by resistance to further injection or leakage of the drug from previous injection sites due to the friable nature of the tissue. The volume of drug administered varied depending on the size of the tumour. Treatments were given at weekly intervals on day0, 7, 14 and 21, resulting in a total of four injections.

Results and Discussion

In the present study, ocular tumours appeared as raised, irregular and fleshy masses involving different parts of the eye including the limbus, third eyelid and eyelids. The lesions were typically pink to reddish in colour and were associated with lacrimation, irritation and partial loss of vision. Tumour growths varied in size and often presented as cauliflower-like proliferative masses, which is consistent with earlier reports [16,17] .

In the present study, a total of fifteen clinical cases of ocular tumours in cattle were examined, and all cases were confirmed as squamous cell carcinoma based on histopathological findings. The occurrence of OSCC in the present study supports earlier reports indicating that it is the most common malignant ocular tumour in bovines [1,2] . Moulton JE, 1961. Fazili MR et al., 2001. The age of affected animals in the present study ranged from 4 to 9 years, with the majority of cases observed in cattle above 5 years of age. The highest incidence was recorded in animals between 6-8 years. This finding is in agreement with earlier reports which state that OSCC is predominantly a disease of older cattle due to prolonged exposure to ultraviolet radiation and cumulative carcinogenic effects [3][4][5] . Histopathological examination confirmed the diagnosis of squamous cell carcinoma in all cases. Microscopic examination revealed proliferation of squamous epithelial cells arranged in nests and sheets with formation of keratin pearls, cellular pleomorphism and presence of mitotic figures. These findings are in agreement with previous studies on bovine OSCC [18,19] . Intralesional administration of 5-Fluorouracil resulted in gradual regression of tumour masses in all fifteen treated animals. The antitumour effect of the drug is attributed to its ability to inhibit DNA synthesis and induce cytotoxic effects in rapidly proliferating tumour cells [14] . Similar successful outcomes with intralesional 5-FU therapy have been reported in both veterinary and human oncology studies [15,24,25] .

The localized delivery of the drug directly into the tumour mass ensured a high drug concentration at the lesion site, enhancing its therapeutic efficacy. Furthermore, the procedure was simple, economical and suitable for field conditions when compared to more invasive surgical procedures.

On day 0, the affected bovines presented with proliferative neoplastic masses involving the corneal, limbal or third eyelid region, showed loss of vision at the tumour region, mild lacrimation, slight corneal opacity around the tumour and distortion of the palpebral fissure. From day 7 to day 14 following of intralesional 5-Fluorouracil therapy, gradual regression of the tumour mass was observed, characterized by reduction in tumour size, shrinkage of proliferative margins and improvement in ocular appearance. Mild lacrimation and corneal opacity progressively subsided during this period. By day 21, a significant healing and marked reduction in tumour volume were evident. The lesions appeared as small localized regressing nodules near the limbal or corneal margins with mild residual congestion at the treatment site. Restoration of corneal transparency was observed in the surrounding ocular tissues and vision was preserved in all the animals as evidenced by normal palpebral, corneal and pupillary reflexes. Between day 28 and day 35, complete macroscopic regression of the neoplastic mass with satisfactory healing of the ocular surface was observed in most cases.

References

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