Use of Photodynamic Therapy Against Squamous Cell Carcinoma in the Casque of a Great Indian Hornbill (Buceros bicornis)
Squamous cell carcinomas are uncommonly encountered neoplasms in avian species.2,4,8,9 Squamous cell carcinomas of the mandibular and maxillary areas have been infrequently reported.5,8 Treatment, when initiated, has generally been unsuccessful.8 Photodynamic therapy has been used with success in humans and dogs with squamous cell carcinomas,10 and was elected in this case. Photodynamic therapy involves the use of an IV photosensitizing agent that is subsequently activated by a light source. Upon activation, photochemical generation of cytotoxic oxygen radicals destroys neoplastic cells. Ease of application, minimal side effects, and post-operative care were prime considerations in electing this form of therapy, as opposed to standard treatment modalities such as chemotherapy, cryosurgery and radiation therapy.
A 33-yr-old, male great Indian hornbill (Buceros bicornis) weighing 3.1 kg was presented for having a roughened rostral aspect to his casque. A pervasive “yeast-like” odor was noted when staff entered the bird’s holding stall. Physical examination revealed a softened rostral casque. Aerobic and anaerobic cultures revealed Candida albicans, Staphylococcus epidermidis and Proteus mirabilis. A CBC and select serum profile revealed no abnormalities. A biopsy was obtained from the keratinized layers of the casque and placed in 10% neutral buffered formalin. The initial biopsy contained only stratum corneum, and there was marked orthokeratotic hyperkeratosis and heavy pigmentation. Based on culture results, treatment was initiated with 5 mg/kg enrofloxacin (Baytril®, Bayer Corp., Shawnee Mission, KS, USA) and 250 mg/kg flucytosine (Ancobon, Roche Pharmaceuticals, Paramus, NJ, USA) PO, BID. After 20 days of therapy, a noticeable decrease in odor was noted. A second biopsy was performed and a squamous cell carcinoma was diagnosed. Histologically, the tumor was composed of anastomosing cords and fronds of neoplastic squamous epithelial cells. The cells were polygonal to spindle-shaped with moderately anisokaryotic, round to oval, hypochromic nuclei, one to three prominent nucleoli that varied in size and shape and moderate amounts of eosinophilic cytoplasm with distinct cell boundaries. Desmosomes were prominent. There were up to 16 mitoses per 400x field, and mitotic atypia was frequent. There were rare dyskeratotic cells. Survey radiographs of the head and casque demonstrated radiopaque material within the rostral aspect of the casque with a slight osteolysis of the crista7 on the left side.
One injection of 0.3 mg/kg hexylether pyropheophorbide-a (Photochlor, Roswell Park Cancer Institute, Buffalo, NY, USA) warmed to the bird’s body temperature was administered in the basilic vein.
The next day, the bird was anesthetized by preoxygenation with 100% oxygen for 2 min, followed by incremental increases in isoflurane (Aeranne, Anaquest, Madison, WI, USA) until a surgical plane of anesthesia was achieved. The bird was placed on a heated surgery table, intubated and maintained on 2.5% isoflurane during the procedure. A 20-ga intraosseous spinal catheter was placed in the right ulna, and 35 cc of warmed physiologic fluids (LRS, Abbott laboratories, Chicago, IL, USA) was administered every 30 min during therapy. Respiratory excursions, cardiac rate and rhythm were constantly monitored during therapy.
Portions of the casque were mechanically removed to provide better visualization and access to the tumor. Necrotic dermal papillae were also removed. A diode laser (AOC Medical Systems, South Plainfield, NJ, USA) fitted with a 400 μm microlens optic fiber (PDT Systems Inc., Santa Barbara, CA, USA) was used to deliver 665 nm of light to the tissue. The tissue dose was 100 joules/cm2. To prevent thermal effects, the fiber output was maintained at 100 mW/cm2. The treatment time was 16 min, 49 sec for each 3-cm focal spot. After each period of therapy, the laser was adjusted to treat adjacent neoplasia. After 3.5 h, therapy was complete. The bird was placed in an incubator, recovered uneventfully, and began eating the same day. Butorphanol tartrate (Torbugesic, Fort Dodge Laboratories, Overland Park, KS, USA) at 3 mg/kg was administered IM daily for 2 days. The bird was kept indoors for 3 wk, as severe skin photosensitization from direct sunlight has been noted in human patients with similar photosensitizing agents.1
Within 72 h, a firm, dark eschar was noted over the treated tissue. Over the course of the next 5 wk, 20 biopsies were obtained from various areas of the treated tissues. Initial histopathologic evaluations were encouraging, as necrosis of the neoplastic tissue was noted. However, later biopsies confirmed the presence of a viable, well-differentiated squamous cell carcinoma. Rapid growth of the tumor was noted clinically, with a concomitant massive increase in the bird’s appetite observed.
A second therapy session was performed 8 wk after the first therapy. The bird had lost 0.5 kg in weight, and was not as active as before, according to the keeper. The anesthetic protocol was the same. During the second session, aggressive debulking of the dermal papillae and tumor was performed. Laser therapy was performed as before. The bird went into respiratory arrest at the culmination of the procedure, but responded to one injection of 5 mg/kg doxapram hydrochloride (Dopram, Fort Dodge Laboratories, Overland Park, KS, USA) IV, positive pressure ventilation, and discontinuance of anesthesia. Paralysis of the left leg was noted upon recovery. Survey radiographs of the leg and acetabular area revealed no abnormalities. The foot was splinted in a natural position. Butorphanol tartrate was administered as before and appeared to alleviate pain associated with the vasoconstrictive effects of therapy on the neoplasia.1 The bird was ataxic for 4 days but gradually improved in attitude and strength over the course of the next several days. One week after surgery, the splint was removed, with a full return to normal strength and mobility noted. A very firm, blackened eschar was noted at the treatment site. Biopsy at that time revealed destruction of a substantial amount of the squamous cell carcinoma. However, 1 wk later, an additional biopsy revealed recurrence of the neoplasm. Upon further assessment and discussion, additional treatment options were not pursued. Upon failing appetite and lethargy of several days’ duration, the bird was euthanatized. Survey radiographs demonstrated progression of the neoplasia to the deeper layers of the rhamphotheca, destruction of cancellous bone and keratin layers of the maxilla.
Photodynamic therapy is currently being used in experimental trials to treat various neoplastic processes in people and animals, including esophageal squamous cell carcinomas.1,3,6 Photodynamic therapy has been used infrequently in exotic animals, with varying results.10 As a precaution, the bird was kept indoors for 3 wk, even though this newer class of photosensitizing agents has not demonstrated the severe skin sensitization observed with other agents. In this case, the large size and depth of the initial tumor, combined with accessibility and a paucity of information on normal anatomy may have hampered efforts to eliminate the neoplasia. The apparent high occurrence of this specific type of neoplasia in a specific location of great Indian hornbill casques (personal communications) warrants additional investigation.
The authors would like to thank the Kansas City Zoological Gardens keeper staff, and Mrs. Debbie Tate, oncology technician, for their efforts in caring for the hornbill.
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